FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cros, D Drake, K AF Cros, D. Drake, K. TI Multifocal motor neuropathies with conduction block: Long-term follow-up of ten patients treated with Mg SO REVUE NEUROLOGIQUE LA French DT Article; Proceedings Paper CT 10th Conference on Diseases of the Peripheral Nervous System CY JAN 27, 2006 CL Paris, FRANCE DE multifocal motor neuropathy; intravenous immunoglobulins; conduction block ID INTRAVENOUS IMMUNOGLOBULIN TREATMENT; NERVE ROOT STIMULATION; DOUBLE-BLIND; DEMYELINATING NEUROPATHIES; THERAPY; IVIG AB Multifocal motor neuropathy (MMN) with conduction block responds to high-dose IV polyvalent immunoglobulins (IVIg) over the short term, but several studies have demonstrated a long-term increase in the degree of axonal degeneration and the number of conduction blocks, factors indicating a poor prognosis. The objective of this study was to evaluate the long-term effect of IVIg on clinical and neurophysiological parameters. Methods: We reviewed the records of ten patients who had initially responded well to IVIg and received regular long-term treatment. The parameters studied were muscular strength, motor function status (modified Rankin scale), as well as the number and progression of conduction blocks and the degree of axonal degeneration. Patients were followed up for a mean of 7.25 years (range, 3.5-12). They were all initially treated with 2 g IgIV/kg in 5 days every 4 weeks for 3 months. Maintenance therapy was administered every 4 weeks with dose adjustment to prevent muscular strength deterioration. Results: We noted a significant and persistent improvement in muscular strength and in the Rankin motor function score over the long term, with no escape phenomenon. The number of conduction blocks and the degree of axonal degeneration decreased markedly. Conclusion: IVIg treatment remains effective over the long term in MMN. These conclusions differ from those of other authors in earlier studies, but our patients were treated with significantly higher doses of IVIg. These results have important implications for long-term treatment of patients with MMN. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cros, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0035-3787 J9 REV NEUROL-FRANCE JI Rev. Neurol. PD JUN PY 2006 VL 162 SI 1 BP 3S46 EP 3S50 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 095QF UT WOS:000241322000006 PM 17075525 ER PT J AU Losina, E Anglaret, X Yazdanpanah, Y Wang, B Toure, S Seage, GR N'Dri-Yoman, T Walensky, RP Dakoury-Dogbo, N Goldie, SJ Messou, E Weinstein, MC Deuffic-Burbn, S Salamon, R Freedberg, KA AF Losina, E. Anglaret, X. Yazdanpanah, Y. Wang, B. Toure, S. Seage, G. R., III N'Dri-Yoman, T. Walensky, R. P. Dakoury-Dogbo, N. Goldie, S. J. Messou, E. Weinstein, M. C. Deuffic-Burbn, S. Salamon, R. Freedberg, K. A. TI Impact of opportunistic diseases on chronic mortality in HIV-infected adults in Cote d'Ivoire SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID COTRIMOXAZOLE PROPHYLAXIS; MORBIDITY; ABIDJAN; AFRICA; COUNT; RNA AB Objective. To estimate incidence rates of opportunistic diseases (ODs) and mortality for patients with and without a history of OD among HIV-infected patients in Cote d'Ivoire. Methods. Using incidence density analysis, we estimated rates of ODs and chronic mortality by CD4 count in patients in a cotrimoxazole prophylaxis trial in Abidjan before the highly active antiretroviral therapy (HAART) era. Chronic mortality was defined as death without a history of OD or death more than 30 days after an OD diagnosis. We used Poisson's regression to examine the effect of OD history on chronic mortality after adjusting for age, gender, and current CD4 count. Results. Two hundred and seventy patients (40% male, mean age 33 years, median baseline CD4 count 261 cells/mu l) were followed up for a median of 9.5 months. Bacterial infections and tuberculosis were the most common severe CDs. Of 47 patients who died, 9 (19%) died within 30 days of an OD, 26 (55%) died more than 30 days after an OD, and 12 (26%) died with no OD history. The chronic mortality rate was 31.0/100 person-years for those with an OD history, and 11.1/100 person-years for those with no OD history (rate ratio (RR) 2.81, 95% confidence interval (CI): 1.43-5.54). Multivariate analysis revealed that OD history remained an independent predictor of mortality (RR 2.15, 95% CI: 1.07-4.33) after adjusting for CD4 count, age and gender. Conclusions. Before the HAART era, a history of CD was associated with increased chronic HIV mortality in Cote d'Ivoire, even after adjusting for CD4 count. These results provide further evidence supporting OD prophylaxis in HIV-infected patients. C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Programme PACCI, Abidjan, Cote Ivoire. Ctr Hosp Tourcoing, Tourcoing, France. Univ Victor Segalen Bordeaux 2, Unite INSERM 593, Bordeaux, France. RP Losina, E (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. EM lenal@bu.edu RI Anglaret, Xavier/F-7333-2013; OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [K23 AI001794, K24 AI062476, K25 AI050436, P30 AI042851, R01 AI042006, R01 AI058736] NR 14 TC 12 Z9 15 U1 0 U2 0 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS PRIV BAG X1, JOHANNESBURG, SOUTH AFRICA SN 0256-9574 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD JUN PY 2006 VL 96 IS 6 BP 526 EP 529 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 061AN UT WOS:000238843700021 PM 16841136 ER PT J AU Pomerantz, SR Hirsch, JA AF Pomerantz, Stuart R. Hirsch, Joshua A. TI Intradiscal therapies for discogenic pain SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE discogenic pain; disc herniation; annular tear; percutaneous discectomy; Nucleoplasty; annuloplasty; Coblation; IDET; Dekompressor ID INTERNAL DISC DISRUPTION; LOW-BACK-PAIN; PERCUTANEOUS LUMBAR DISKECTOMY; FOLLOW-UP; TRIAMCINOLONE HEXACETONIDE; ELECTROTHERMAL THERAPY; CONTROLLED-TRIAL; CHEMONUCLEOLYSIS; CHYMOPAPAIN; EXPERIENCE AB Since the first injection of chymopapain in 1963, percutaneous intradiscal therapies have been used to treat discogenic back and leg pain. The percutaneous discectomy techniques treat contained disc herniations not by resecting the prolapsed disc material but rather through central decompression of the disc. By removing a small volume of tissue from the disc nucleus, a large reduction in overall disc pressure is achieved with consequent relief of neural compression. DISC Nucleoplasty (TM) and Dekompressor (TM) are the two leading percutaneous discectomy technologies currently. Although rigorous clinical testing of their efficacy is ongoing, there has now been a 40-year history confirming the concept of percutaneous disc decompression, and initial results are very promising. Discogenic low back pain can also arise from annular tears and other forms of internal disc derangement (IDD). Annuloplasty techniques, such as IntraDiscal Electrothermal Therapy (IDET (TM)) and discTRODE (TM), have been developed over the past decade that thermally treat the lesions of IDD. Although the therapeutic mechanisms of thermal annuloplasty have yet to be fully elucidated, research studies demonstrate that the procedure can be effective for appropriately selected patients with degenerative disc disease characterized by discographically proven painful annular fissures. Other novel intradiscal therapies are emerging for percutaneous treatment of discogenic pain and await more widespread clinical evaluation. C1 Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St,GRB 289, Boston, MA 02114 USA. NR 57 TC 10 Z9 11 U1 9 U2 9 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD JUN PY 2006 VL 10 IS 2 BP 125 EP 135 DI 10.1055/s-2006-939030 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 177KG UT WOS:000247151400004 PM 16586321 ER PT J AU Byrne, TN Borges, LF Loeffler, JS AF Byrne, TN Borges, LF Loeffler, JS TI Metastatic epidural spinal cord compression: Update on management SO SEMINARS IN ONCOLOGY LA English DT Review ID NEUROSURGICAL TREATMENT; VERTEBRAL-BODY; LUMBAR SPINE; DISEASE; STABILIZATION; RADIOTHERAPY; THERAPY; SURGERY; TUMORS; TRIAL C1 Harvard Univ, Sch Med, Dept Neurol & Hlth Sci Technol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Byrne, TN (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM tnbyrne@mit.edu NR 29 TC 9 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2006 VL 33 IS 3 BP 307 EP 311 DI 10.1053/j.seminoncol.2006.03.002 PG 5 WC Oncology SC Oncology GA 059KG UT WOS:000238731100004 PM 16769419 ER PT J AU Weisbord, SD Palevsky, PM AF Weisbord, Steven D. Palevsky, Paul M. TI Acute renal failure in the intensive care unit SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE acute renal failure; renal replacement therapy ID CRITICALLY-ILL PATIENTS; CONTRAST-INDUCED NEPHROPATHY; CONTINUOUS VENOVENOUS HEMOFILTRATION; RANDOMIZED CONTROLLED-TRIAL; ACUTE TUBULAR-NECROSIS; LOW-DOSE DOPAMINE; REPLACEMENT THERAPY; CARDIAC-SURGERY; CLINICAL-TRIAL; PROPHYLACTIC DIALYSIS AB Acute renal failure (ARF) is a common complication in critically ill patients, with ARF requiring renal replacement therapy (RRT) developing in similar to 5 to 10% of intensive care unit (ICU) patients. Epidemiological studies have demonstrated that ARF is an independent risk factor for mortality. Interventions to prevent the development of ARF are currently limited to a small number of settings, primarily radiocontrast nephropathy and rhabdomyolysis. There are no effective pharmacological agents for the treatment of established ARF. Renal replacement therapy remains the primary treatment for patients with severe ARF; however, the data guiding selection of modality of RRT and the optimal timing of initiation and dose of therapy are inconclusive. This review focuses on the epidemiology and diagnostic approach to ARF in the ICU and summarizes our current understanding of therapeutic approaches including RRT. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Rm 7E123 111F-U,Univ Dr Div, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 100 TC 14 Z9 16 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PD JUN PY 2006 VL 27 IS 3 BP 262 EP 273 DI 10.1055/s-2006-945527 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 061ZK UT WOS:000238913200007 PM 16791759 ER PT J AU Nguyen, BT Mullins, ME AF Nguyen, BT Mullins, ME TI Computed tomography follow-up imaging of stroke SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID ACUTE ISCHEMIC-STROKE; COOPERATIVE ACUTE STROKE; CT; DETERIORATION; ECASS C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02139 USA. Emory Univ Hosp, Dept Radiol, Atlanta, GA 30322 USA. RP Nguyen, BT (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Gray 273A,55 Fruit St, Boston, MA 02139 USA. EM bxnguyen@partners.org NR 24 TC 3 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD JUN PY 2006 VL 27 IS 3 BP 168 EP 176 DI 10.1053/j.sult.2006.02.002 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054YY UT WOS:000238415700002 PM 16808216 ER PT J AU Brobeck, BR Forero, NP Romero, JM AF Brobeck, BR Forero, NP Romero, JM TI Practical noninvasive neurovascular imaging of the neck arteries in patients with stroke, transient ischemic attack, and suspected arterial disease that may lead to ischemia, infarction, or flow abnormalities SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID ENHANCED MR-ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; MAGNETIC-RESONANCE ANGIOGRAPHY; SEVERE CAROTID STENOSIS; VERTEBRAL ARTERY; CT ANGIOGRAPHY; SUBCLAVIAN STEAL; CONVENTIONAL ANGIOGRAPHY; ATHEROSCLEROTIC PLAQUE; COLOR-DOPPLER C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurovasc Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brobeck, BR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Gray Bldg 2 Room 273A,55 Fruit St, Boston, MA 02114 USA. EM bbrobeck@partners.org NR 94 TC 5 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD JUN PY 2006 VL 27 IS 3 BP 177 EP 193 DI 10.1053/j.sult.2006.02.003 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054YY UT WOS:000238415700003 PM 16808217 ER PT J AU Mullins, ME AF Mullins, ME TI Stroke imaging with Xenon-CT SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID CEREBRAL BLOOD-FLOW C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mmullins@partners.org NR 8 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD JUN PY 2006 VL 27 IS 3 BP 219 EP 220 DI 10.1053/j.sult.2006.02.006 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054YY UT WOS:000238415700006 PM 16808220 ER PT J AU Gupta, R Jones, SE Mooyaart, EAQ Pomerantz, SR AF Gupta, R Jones, SE Mooyaart, EAQ Pomerantz, SR TI Computed tomographic angiography in stroke imaging: Fundamental principles, pathologic findings, and common pitfalls SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID CT ANGIOGRAPHY; SUBARACHNOID HEMORRHAGE; HELICAL CT; ISCHEMIC-STROKE; INJECTION PROTOCOL; CEREBRAL VASOSPASM; ARTERY DISSECTION; CAROTID STENOSIS; PEAK ENHANCEMENT; SALINE SOLUTION C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-216, Boston, MA 02114 USA. EM rgupta1@partners.org NR 71 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD JUN PY 2006 VL 27 IS 3 BP 221 EP 242 DI 10.1053/j.sult.2006.02.007 PG 22 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054YY UT WOS:000238415700007 PM 16808221 ER PT J AU Pomerantz, SR Harris, GJ Desai, HJ Lev, MH AF Pomerantz, SR Harris, GJ Desai, HJ Lev, MH TI Computed tomography angiography and computed tomography perfusion in ischemic stroke: A step-by-step approach to image acquisition and three-dimensional postprocessing SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID IODINATED CONTRAST AGENTS; CT ANGIOGRAPHY; PLASMINOGEN-ACTIVATOR; CEREBRAL ANEURYSMS; LEVEL SETTINGS; BOLUS GEOMETRY; CAROTID-ARTERY; ENHANCEMENT; INJECTION; ACCURACY C1 Massachusetts Gen Hosp, Neuroradiol Div, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Imaging Serv 3D, Boston, MA 02114 USA. RP Pomerantz, SR (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, Dept Radiol, 55 Fruit St,Gray 2-B285, Boston, MA 02114 USA. EM spomerantz@partner.org NR 31 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD JUN PY 2006 VL 27 IS 3 BP 243 EP 270 DI 10.1053/j.sult.2006.03.001 PG 28 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054YY UT WOS:000238415700008 PM 16808222 ER PT J AU Fan, J Levy, R Li, Y Vodovotz, Y Billiar, T Wilson, M AF Fan, J. Levy, R. Li, Y. Vodovotz, Y. Billiar, T. Wilson, M. TI TLR4 mediates hemorrhagic shock-induced NADPH oxidase activation in neutrophil. SO SHOCK LA English DT Meeting Abstract CT 29th Annual Conference of the Shock-Society CY JUN 03-06, 2006 CL Broomfield, CO SP Shock Soc, Novo Nordisk, USN, Off Naval REs, Def Adv Res Projects Agcy C1 Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD JUN PY 2006 VL 25 SU 1 BP 62 EP 62 DI 10.1097/00024382-200606001-00188 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 047AA UT WOS:000237851000189 ER PT J AU Sundaram, M McCall, IW Rosenthal, DI AF Sundaram, M McCall, IW Rosenthal, DI TI Untitled SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Robert Jones & Agnes Hunt Orthopaed & Dist Hosp, Oswestry, Shrops, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sundaram, M (reprint author), Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM sundarm@ccf.org; Iainwmmc@aol.com; dirosenthal@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUN PY 2006 VL 35 IS 6 BP 349 EP 349 DI 10.1007/s00256-006-0125-1 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 041GK UT WOS:000237442200001 ER PT J AU Mathews, RE McGuire, BM Estrada, CA AF Mathews, Ronnie E., Jr. McGuire, Brendan M. Estrada, Carlos A. TI Outpatient management of cirrhosis: A narrative review SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE cirrhosis; outpatient management; esophageal varices; ascites; hepatocellular carcinoma ID SPONTANEOUS BACTERIAL PERITONITIS; SUBCLINICAL HEPATIC-ENCEPHALOPATHY; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; HEPATORENAL-SYNDROME; VARICEAL HEMORRHAGE; HEPATOPULMONARY SYNDROME; ESOPHAGEAL-VARICES; PROGNOSTIC FACTORS; COMPENSATED CIRRHOSIS AB Cirrhosis is the 12th leading cause of death in the United States. Individuals with cirrhosis are at risk for many potential complications. Complications can be managed or detected early with proper outpatient management. The most lethal of these complications is bleeding esophageal varices. All patients with cirrhosis should be screened for the presence of varices and treated when indicated. The most common complication seen in these patients is ascites. Ascites can be treated with dietary modifications and a diuretic regimen. Other potential complications include spontaneous bacteria peritonitis, hepatocellular carcinoma, hepatic encephalopathy, hepatorenal syndrome, and hepatopulmonary syndrome. The outpatient management of these complications will be discussed in this paper, along with the use of vaccinations, educating patients about the avoidance of hepatotoxic drugs, and when to refer a patient for liver transplant. C1 Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. Univ Alabama, Div Gastroenterol & Hepatol, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP McGuire, BM (reprint author), 1530 3rd Ave S,MCLM 262A, Birmingham, AL 35294 USA. EM bmcguire@uab.edu NR 57 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JUN PY 2006 VL 99 IS 6 BP 600 EP 606 DI 10.1097/01.smj.0000220889.36995.54 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 095NW UT WOS:000241315600009 PM 16800415 ER PT J AU Haspel, RL Ballen, KK AF Haspel, Richard L. Ballen, Karen K. TI Double cord blood transplants - Filling a niche? SO STEM CELL REVIEWS LA English DT Article DE cord blood; chimerism; transplantation; adult AB Over the last decade, umbilical cord blood ( CB) has become a viable option for hematopoietic stem cell transplants. A limiting factor has been the 10-fold lower cell dose in a CB unit compared with harvested bone marrow or peripheral blood stem cells. The low cell dose leads to delayed engraftment and an increase in graft failure. Double cord blood transplants represent a novel strategy to overcome this limitation. This review will cover the rationale behind and clinical results of double cord blood transplant studies. The chimerism data from these studies reveal that typically only one CB "wins the battle" for engraftment. These results may have important scientific implications in terms of understanding the nature of the hematopoietic stem cell niche and how modulation of this niche may impact transplant outcomes. C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Haspel, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Dept Med, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM kballen@partners.org NR 40 TC 27 Z9 29 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1550-8943 J9 STEM CELL REV JI Stem Cell Rev. PD JUN PY 2006 VL 2 IS 2 BP 81 EP 86 PG 6 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA V56WX UT WOS:000203845100002 PM 17237545 ER PT J AU Rosell, A Ortega-Aznar, A Alvarez-Sabin, J Fernandez-Cadenas, I Ribo, M Molina, CA Lo, EH Montaner, J AF Rosell, A Ortega-Aznar, A Alvarez-Sabin, J Fernandez-Cadenas, I Ribo, M Molina, CA Lo, EH Montaner, J TI Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke SO STROKE LA English DT Article DE MMP-2; MMP-9; stroke ID FOCAL CEREBRAL-ISCHEMIA; MATRIX-METALLOPROTEINASE EXPRESSION; GELATINASE-A MMP-2; INTRACEREBRAL HEMORRHAGE; BARRIER DISRUPTION; ACTIVATION; INHIBITION; OCCLUSION/REPERFUSION; ARTERY; FORMS AB Background and Purpose - Abnormal expression of some matrix metalloproteinases ( MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 ( gelatinase A) and MMP-9 ( gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes. Methods - Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas ( infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity. Results - Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere ( P < 0.0001 and P = 0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere ( P = 0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas. Conclusions - Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema. C1 Vall Hebron Univ Hosp, Neurovasc Res Lab, Barcelona, Spain. Vall Hebron Univ Hosp, Neurovasc Unit, Dept Neurol, Barcelona, Spain. Univ Autonoma Barcelona, Dept Internal Med, E-08193 Barcelona, Spain. Vall Hebron Univ Hosp, Neuropathol Unit, Dept Pathol, Barcelona, Spain. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Montaner, J (reprint author), Hosp Gen Valle Hebron, Inst Recerca, Neurovasc Res Lab, Pg Vall Hebron 119-129, Barcelona 08035, Spain. EM 31862jmv@comb.es RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; OI Ribo, Marc/0000-0001-9242-043X NR 23 TC 215 Z9 243 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2006 VL 37 IS 6 BP 1399 EP 1406 DI 10.1161/01.STR.0000223001.06264.af PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 048CK UT WOS:000237925000022 PM 16690896 ER PT J AU Iadecola, C Goldman, SS Harder, DR Heistad, DD Katusic, ZS Moskowitz, MA Simard, JM Sloan, MA Traystman, RJ Velletri, PA AF Iadecola, C Goldman, SS Harder, DR Heistad, DD Katusic, ZS Moskowitz, MA Simard, JM Sloan, MA Traystman, RJ Velletri, PA TI Recommendations of the National Heart, Lung, and Blood Institute working group on cerebrovascular biology and disease SO STROKE LA English DT Article DE cerebrovascular disease; microcirculation ID ALZHEIMERS-DISEASE; STROKE; GENE; ISCHEMIA; BRAIN AB The National Heart, Lung, and Blood Institute (NHLBI) convened a conference call working group, consisting of experts in stroke and cerebrovascular biology on January 28, 2005. The purpose of this working group was to develop a prioritized set of recommendations for NHLBI to establish a focused and comprehensive set of research activities in cerebrovascular biology and disease. Three thematic areas of research emerged: (1) molecular and cellular neurobiology of cerebral blood vessels, focusing on genomics and proteomics, neurovascular signaling and cerebrovascular embryogenesis, development and plasticity; (2) resource development, involving the development of new methodological approaches for normal and altered function of the neurovascular unit, collaborative research, and training in cerebrovascular pathobiology; and (3) cerebrovascular diseases and translational approaches, addressing vascular mechanisms of disease, the role of risk factors, importance of biomarkers with the ultimate goal of developing new treatments. C1 NHLBI, Bethesda, MD 20892 USA. Weill Cornell Med Coll, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI USA. Univ Iowa, Iowa City, IA USA. Mayo Clin Coll Med, Rochester, MN USA. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. RP Goldman, SS (reprint author), NHLBI, 6701 Rockledge Dr,MSC 7956,Suite 10192, Bethesda, MD 20892 USA. EM goldmans@nhlbi.nih.gov RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [R01 HL082517-01, R01 HL082517] NR 17 TC 26 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2006 VL 37 IS 6 BP 1578 EP 1581 DI 10.1161/01.STR.0000221297.57305.8a PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 048CK UT WOS:000237925000054 PM 16627792 ER PT J AU Stahl, JE Sandberg, WS Daily, B Wiklund, R Egan, MT Goldman, JM Isaacson, KB Gazelle, S Rattner, DW AF Stahl, James E. Sandberg, Warren S. Daily, Bethany Wiklund, Richard Egan, Marie T. Goldman, Julian M. Isaacson, Keith B. Gazelle, Scott Rattner, David W. TI Reorganizing patient care and workflow in the operating room: a cost-effectiveness study SO SURGERY LA English DT Article ID SURGERY; DESIGN AB Background. Many surgeons believe that long turnover times between cases are a major impediment to their productivity. We hypothesized that redesigning the operating room (OR) and perioperative-staffing system to take advantage of parallel processing would improve throughput and lower the cost of care. Methods. A state of the art high tech OR suite equipped with augmented data collection systems served as a living laboratory to evaluate both new devices and perioperative systems Of care. The OR suite and all the experimental studies carried out in this setting were designated as the OR of the Future Project (ORF). Before constructing the ORF, modeling studies were conducted to inform the architectural and staffing design and estimate their benefit. In phase I a small prospective trial tested the main hypothesized benefits of the ORE reduced patient intra-operative flow-time, wait-time and operative procedure time. In phase H a larger retrospective study was conducted to explore factors influencing these effects. A modified process, costing method was used to estimate costs based on nationally derived data. Cost-effectiveness was evaluated using standard methods. Results. There were 385 cases matched by surgeon and Procedure type in the retrospective dataset (182 ORF, 193 standard operating room [SOR]). The median Wait Time (12.5m ORF vs 23.8 m SOR), Operative Procedure Time (561 m ORF vs 70.5 m SOR), Emergence Time (10.9 m ORF vs 14.5 m SOR) and Total Patient OR Flowtime (79.5 m ORF vs 108.9 m SOR) were all shorter in the Off (P <.05 for all comparisons). The median cost/patient was $3,165 in the OPF (interquartile range, $1,978 to $4,426) versus $2,645 in SORs (interquartile range, $1,823 to $3,908) (P = ns). The potential change in patient throughput for the ORF was 2 additional patients/day. This improved throughput was primarily attributable to a marked reduction in the non-operative time (ie, those activities commonly accounting for "turnover time") rather than facilitation of faster operations. The incremental cost-effectiveness ratio of ORF was $260 (interquartile range, $180 to $283). Conclusion. The redesigned perioperative system improves patient flow, allowing more Patients to be treated per day. Cost-effectiveness analysis suggests that the additional costs incurred by higher staffing ratios in an ORF environment are likely to be offset by increases in productivity. The benefits of this system are realized when performing multiple, short-to-medium duration procedures (eg, < 120 m). C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Adm, Boston, MA USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Dept Med, Boston, MA 02114 USA. EM drattner@parnters.org FU NCRR NIH HHS [1 R44 RR18076-01] NR 19 TC 49 Z9 49 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2006 VL 139 IS 6 BP 717 EP 728 DI 10.1016/j.surg.2005.12.006 PG 12 WC Surgery SC Surgery GA 060LS UT WOS:000238804300002 PM 16782425 ER PT J AU Briggs, SM AF Briggs, Susan M. TI Earthquakes SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID LOMA-PRIETA EARTHQUAKE; NATURAL DISASTERS; MEDICAL RESPONSE; INJURIES; ARMENIA AB Major earthquakes have the potential to be one of the most catastrophic natural disasters affecting mankind. Earthquakes of significant size threaten lives and damage property by setting off a chain of events that disrupts all aspects of the environment and significantly impacts the public health and medical infrastructures of the affected region. This article provides an overview of basic earthquake facts and relief protocol for medical personnel. C1 Massachusetts Gen Hosp, Int Trauma & Disaster Inst, Boston, MA 02114 USA. RP Briggs, SM (reprint author), Massachusetts Gen Hosp, Int Trauma & Disaster Inst, 8 Hawthorne Pl,Suite 114, Boston, MA 02114 USA. EM sbriggs@partners.rog NR 25 TC 17 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD JUN PY 2006 VL 86 IS 3 BP 537 EP + DI 10.1016/j.suc.2006.02.003 PG 9 WC Surgery SC Surgery GA 064TR UT WOS:000239112500004 PM 16781268 ER PT J AU Hopp, F Woodbridge, P Subramanian, U Copeland, L Smith, D Lowery, J AF Hopp, Faith Woodbridge, Peter Subramanian, Usha Copeland, Laurel Smith, David Lowery, Julie TI Outcomes associated with a home care telehealth intervention SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article ID HEALTH-CARE; HOSPITAL ADMISSIONS; TELEMEDICINE AB To determine whether adding telehealth technology to traditional home care services increases health-related quality of life (HRQOL) and home care satisfaction, and decreases resource utilization among home care patients. This trial included 37 home care patients receiving services in a Veterans Affairs medical center, randomized into intervention and control groups. Outcome measures included patient satisfaction and HRQOL at baseline and 6-month follow-up, and the use of inpatient and outpatient services before and during the 6-month study period. Intervention group patients reported greater improvement in the mental health component of HRQOL, (t = 2.27; df = 15; p = 0.04). Satisfaction with the telehealth equipment was high ( means exceeded 4.0 on six measures ranging from 1 - 5). However, no statistically significant differences were observed between intervention and control groups in terms of changes in physical health, inpatient admissions, bed days of care, emergency department visits, or general satisfaction with home care services. Intervention group members did show a trend ( p = 0.10) toward fewer overall outpatient visits ( mean = 29.1; standard deviation [SD] +/- 30.1) compared to those receiving traditional home care services ( mean = 38.9; SD +/- 28.9) The use of telehealth services as an adjunct to traditional home care is associated with greater improvements in mental health status and a trend toward lower use of inpatient and outpatient healthcare services. Further work, utilizing larger sample sizes, is needed to investigate the relationship between telehealth services, the use of healthcare resources, and other outcomes. C1 VA Ann Arbor Healthcare Syst, HSR&D Ctr Practice Management & Outcomes Res, Ann Arbor, MI 48113 USA. Richard L Roudebush Vet Affairs Med Ctr, Ctr Excellence Implementing Evidence Based Practi, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. Regenstrief Inst Healthcare, Indianapolis, IN USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Policy & Management, Ann Arbor, MI 48109 USA. S Texas Vet Hlth Care Syst VERDICT HSR&D, Dept Vet Affairs, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Indiana Ctr Aging Res, Indianapolis, IN USA. RP Hopp, F (reprint author), VA Ann Arbor Healthcare Syst, HSR&D Ctr Practice Management & Outcomes Res, POB 130170, Ann Arbor, MI 48113 USA. EM Faith.Hopp@med.va.gov OI Hopp, Faith/0000-0002-4536-3089; Copeland, Laurel/0000-0002-9478-0209 NR 31 TC 22 Z9 22 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD JUN PY 2006 VL 12 IS 3 BP 297 EP 307 DI 10.1089/tmj.2006.12.297 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 060XL UT WOS:000238835100019 PM 16796497 ER PT J AU Rajagopalan, P Shen, CJ Berthiaume, F Tilles, AW Toner, M Yarmush, ML AF Rajagopalan, Padmavathy Shen, Colette J. Berthiaume, Francois Tilles, Arno W. Toner, Mehmet Yarmush, Martin L. TI Polyelectrolyte nano-scaffolds for the design of layered cellular Architectures SO TISSUE ENGINEERING LA English DT Article ID QUARTZ-CRYSTAL MICROBALANCE; SANDWICH CONFIGURATION; RAT HEPATOCYTES; FILMS; ADHESION; CELLS; CULTURE; RECONSTRUCTION; MULTILAYERS; ADSORPTION AB The design of in vitro multilayered cellular architectures that resemble the stratified, lattice-like structure in tissues poses a significant challenge for tissue engineering. There is currently no generally applicable methodology to design multilayered cellular constructs that mimic the structure of tissues in vivo. We report a novel and generalizable approach to create multilayered cellular constructs that addresses these issues. These in vitro constructs comprise alternating layers of cells and nano-scale biocompatible polyelectrolyte ( PE) scaffolds. We apply this methodology to address two specific problems in hepatic tissue engineering: the design of in vitro liver sinusoidal structures and the critical need to increase viable cell mass in extracorporeal liver-assist devices. We assembled ultrathin polymer scaffolds on the top of a confluent monolayer of cells by the sequential deposition of oppositely charged PEs. The thickness of the PE scaffold lies in the nanometer range. The PE scaffold plays a dual role. First, it is a technique to culture hepatocytes in vitro that maintains their morphology, cytoskeletal structure, and liver-specific functions. Second, the nano-scaffold provides a cell-adhesive surface on which a second layer of cells can be cultured, resulting in layered architectures. We have used this approach to design layered three-dimensional hepatocyte-PE-hepatocyte constructs, hepatocyte-PE-endothelial cell constructs, and hepatocyte-PE-fibroblast constructs. As a result of its versatility, this approach can, in principle, be used to design layered cellular constructs of any tissue type, and therefore has potentially wide applications in tissue engineering, bioreactor devices, and in drug delivery. This methodology has the potential to generate realistic in vitro constructs of any tissue type. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM reis@sbi.org FU NIBIB NIH HHS [P41 EB002503, P41-EB002503]; NIDDK NIH HHS [R01-DK3371] NR 39 TC 56 Z9 57 U1 1 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUN PY 2006 VL 12 IS 6 BP 1553 EP 1563 DI 10.1089/ten.2006.12.1553 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 071AX UT WOS:000239570400015 PM 16846351 ER PT J AU Oh, WK Manola, J Babcic, V Harnam, N Kantoff, PW AF Oh, WK Manola, J Babcic, V Harnam, N Kantoff, PW TI Response to second-line chemotherapy in patients with hormone refractory prostate cancer receiving two sequences of mitoxantrone and taxanes SO UROLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID PLUS PREDNISONE; DOCETAXEL; TRIAL AB Objectives. Clinical trials have demonstrated a survival benefit with docetaxel chemotherapy, but limited data exist regarding the activity of second-line chemotherapy. Methods. We retrospectively identified all patients at one institution who received at least two chemotherapy regimens for hormone-refractory prostate cancer, one mitoxantrone-based and the other taxane-based, either including docetaxel or paclitaxel. Patients were evaluated using criteria modified from the Prostate-Specific Antigen Working Group. Results. A total of 68 patients were analyzed; 33 patients received mitoxantrone followed by taxane-based treatment, and 35 received taxane-based chemotherapy followed by mitoxantrone. The median patient age was 66 and 58 years and the median prostate-specific antigen at the start of treatment was 23 and 24 ng/mL in the mitoxantrone-first and taxane-first group, respectively. The response rates to taxane-based chemotherapy were greater whether it was used first or second (P < 0.0001). Progression-free survival (PFS) was longer with taxanes than with mitoxantrone, whether used first or second (P < 0.05). However, the corresponding total PFS from start of the first regimen to progression during the second regimen was similar at 39.9 and 38.7 weeks (P = 0.67). Overall survival was also not significantly different (15.2 and 17.1 months, P = 0.97). Neither age nor the interval from diagnosis to chemotherapy influenced the differences in PFS. Conclusions. Taxane-based chemotherapy is active before or after mitoxantrone. Although PFS was longer with taxane-based chemotherapy, the total PFS and overall survival were equivalent for both sequences in this retrospective analysis, suggesting that taxane-based chemotherapy retains activity, even if delayed. Although responses were seen with mitoxantrone after taxanes, the median PFS was short, and new agents are needed after taxane-based chemotherapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 21 TC 41 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2006 VL 67 IS 6 BP 1235 EP 1240 DI 10.1016/j.urology.2006.01.006 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 054PK UT WOS:000238390900027 PM 16765185 ER PT J AU Nelissen, K Vanduffel, W Orban, GA AF Nelissen, K Vanduffel, W Orban, GA TI Charting the lower superior temporal region, a new motion-sensitive region in monkey superior temporal sulcus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vision; cerebral cortex; functional imaging; primates; action; cortical area ID PURSUIT EYE-MOVEMENTS; OPTIC-FLOW COMPONENTS; MACAQUE VISUAL-CORTEX; EVENT-RELATED FMRI; INFEROTEMPORAL CORTEX; CORTICAL CONNECTIONS; RECEPTIVE-FIELDS; POLYSENSORY AREA; TOPOGRAPHIC ORGANIZATION; FUNCTIONAL-PROPERTIES AB Although the role of the middle temporal (MT/V5) area and its medial superior temporal (MST) satellites in motion processing has been well explored, relatively little is known about motion regions located more rostrally in the superior temporal sulcus (STS), such as the fundus of the superior temporal (FST) area, the superior temporal polysensory (STP) region, or beyond. To fill this void, we used contrast-enhanced functional magnetic resonance imaging in awake macaques and a five-step testing procedure that allowed us to identify six motion- sensitive regions within the STS. Direction adaptation tests confirmed the motion sensitivity of these six regions. Five of them [MT/V5, its three satellites, and the middle part of the STP (STPm) region in the upper bank of the STS] have been documented by previous single- cell studies. A sixth, previously unknown motion-responsive region, which we termed the lower superior temporal (LST) region, was observed on the lower bank and fundus of the STS, 6-8 mm anterior to the FST area. In contrast to the MST areas, the LST region responds to slow as well as fast speeds and is responsive to static and moving images of objects, to patterns defined by opponent motion, and to actions. These results, obtained in both group and single- subject analyses, suggest that motion information in the STS might follow a second path, in addition to the MT/V5-MST path. This ventral path including the LST region, FST area, and STPm region is likely involved in the visual analysis of actions and biological motion. C1 Katholieke Univ Leuven, Sch Med, Lab Neurofysiol Psychofysiol, B-3000 Louvain, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Orban, GA (reprint author), Katholieke Univ Leuven, Sch Med, Lab Neurofysiol Psychofysiol, Campus Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium. EM guy.orban@med.kuleuven.be NR 82 TC 97 Z9 98 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 31 PY 2006 VL 26 IS 22 BP 5929 EP 5947 DI 10.1523/JNEUROSCI.0824-06.2006 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 049TQ UT WOS:000238040400010 PM 16738235 ER PT J AU Abdullah, AR Smith, EE Biddinger, P Kalenderian, D Schwamm, LH AF Abdullah, Abdul R. Smith, Eric E. Biddinger, Paul Kalenderian, Deidre Schwamm, Lee H. TI Hospital notification by EMS in acute stroke is associated with shorter door to CT time and increased likelihood of tPA administration SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E794 EP E794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600063 ER PT J AU Buchanan, DM Jones, PG Rumsfeld, JS Amin, AA Ho, PM Masoudi, FA Havranek, EP Mallik, S Spertus, JA AF Buchanan, Donna M. Jones, Philip G. Rumsfeld, John S. Amin, Alpesh A. Ho, P. M. Masoudi, Frederick A. Havranek, Edward P. Mallik, Susmita Spertus, John A. TI Trajectories of depression severity following acute myocardial infarction: A latent-class analysis SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Mid Amer Heart Inst, Kansas City, MO USA. Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. St Lukes Hosp, Ctr Innovat & Res, Kansas City, MO USA. Univ Missouri, Kansas City, MO 64110 USA. Denver Hlth Med Ctr, Denver, CO USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E798 EP E798 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600081 ER PT J AU Fihn, S Lowy, E Rumsfeld, J Sales, A Sun, HL Fleming, B Jesse, R Maynard, C AF Fihn, Stephan Lowy, Elliott Rumsfeld, John Sales, Anne Sun, Haili Fleming, Barbara Jesse, Robert Maynard, Chuck TI The prevalence and outcomes of in-hospital acute myocardial infarction in the department of veterans affairs health system SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 VA Puget Sound HCS, Seattle, WA USA. Denver VA Med Ctr, Denver, CO USA. Dept Vet Affairs, Washington, DC USA. Richmond VA Med Ctr, Richmond, VA USA. RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E804 EP E804 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600109 ER PT J AU Green, SM Redmond, P Januzzi, JL Aleryani, S Lee-Lewandrowski, E Sluss, P Lewandrowski, KB AF Green, Sandy M. Redmond, Patrick Januzzi, James L. Aleryani, Samir Lee-Lewandrowski, Elizabeth Sluss, Patrick Lewandrowski, Kent B. TI Implementation of NT-ProBNP testing reduces hospital length of stay, morbidity and mortality in patients with acute decompensated heart failure SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E806 EP E807 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600121 ER PT J AU Greiner, G Lowy, E Maynard, C Sales, A Fihn, S AF Greiner, Gwen Lowy, Elliott Maynard, Chuck Sales, Anne Fihn, Stephan TI Comparison of six mortality risk adjustment models for acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 VA Puget Sound HCS, Seattle, WA USA. RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E807 EP E807 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600123 ER PT J AU Groeneveld, PW Kruse, GB Schwartz, JS Kimberly, JB Pauly, MV AF Groeneveld, Peter W. Kruse, Gregory B. Schwartz, J. Sanford Kimberly, John B. Pauly, Mark V. TI Small area variation in the diffusion of percutaneous coronary intervention, 1991-2003 SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E813 EP E813 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600152 ER PT J AU Groeneveld, PW Kruse, GB AF Groeneveld, Peter W. Kruse, Gregory B. TI Costs of cardiac procedures in the veterans health administration SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E789 EP E790 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600040 ER PT J AU Ho, PM Magid, DJ Masoudi, FA McClure, DL Rumsfeld, JS AF Ho, P. Michael Magid, David J. Masoudi, Frederick A. McClure, David L. Rumsfeld, John S. TI The association between cardioprotective medications, medication adherence, and mortality among patients with chronic ischemic heart disease SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Denver VA Med Ctr, Denver, CO USA. Kaiser Permanente Colorado, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E808 EP E808 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600127 ER PT J AU Lowy, E Greiner, G Sales, A Maynard, C Fihn, S AF Lowy, Elliott Greiner, Gwen Sales, Anne Maynard, Chuck Fihn, Stephan TI Race, race, and mortality among veterans with acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 VA Puget Sound HCS, Seattle, WA USA. RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E819 EP E820 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600183 ER PT J AU Mallavarapu, V Shalaby, A Raitt, M Groeneweld, P Hickey, K Kochar, A Marchlinski, F Verdino, R Callans, D Dixit, S AF Mallavarapu, Vamshi Shalaby, Alaa Raitt, Merritt Groeneweld, Peter Hickey, Kelly Kochar, Arshneel Marchlinski, Francis Verdino, Ralph Callans, David Dixit, Sanjay TI Outcomes in veterans with ischemic cardiomyopathy undergoing prophylactic implantable cardioverter defibriilator implantation SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Pittsburgh VA Med Ctr, Pittsburgh, PA USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E820 EP E821 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600187 ER PT J AU Pineros, SL Sales, AE Pineros, VM McDonell, M Maynard, C Lehmann, KG Fihn, SD AF Pineros, Sandra L. Sales, Anne E. Pineros, Vanessa M. McDonell, Mary Maynard, Charles Lehmann, Kenneth G. Fihn, Stephan D. TI An evaluation of a patient education initiative in VHA: Time is life for heart attack SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E825 EP E825 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600208 ER PT J AU Rumsfeld, JS Box, T Gethoffer, H Gillespie, B McDonell, M Ho, M Jesse, RL Fihn, SD AF Rumsfeld, John S. Box, Tamara Gethoffer, Hans Gillespie, Brian McDonell, Mary Ho, Michael Jesse, Robert L. Fihn, Stephan D. TI The VA cardiovascular assessment reporting and tracking system for cardiac catheterization laboratories (CART-CL) SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Denver VA Med Ctr, Denver, CO USA. VA Puget Sound HCS, Seattle, WA USA. Richmond VA Med Ctr, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E828 EP E828 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600220 ER PT J AU Sales, A McDermott, K Helfrich, C Lowy, E Greiner, G Lehmann, K Fihn, S AF Sales, Anne McDermott, Kelly Helfrich, Christian Lowy, Elliott Greiner, Gwen Lehmann, Kenneth Fihn, Stephan TI Factors associated with reperfusion for ST segment elevation myocardial infarction patients in VHA facilities SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 VA Puget Sound HCS, Seattle, WA USA. RI Sales, Anne/D-9678-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E816 EP E816 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600166 ER PT J AU Sales, A Maynard, C Sun, HL Fihn, S AF Sales, Anne Maynard, Chuck Sun, Haili Fihn, Stephan TI Race and the use of percutaneous coronary intervention in veterans with acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 VA Puget Sound HCS, Seattle, WA USA. RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E793 EP E793 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600056 ER PT J AU Schelbert, EB Rumsfeld, JS Krumholz, HM Canto, JG Magid, DJ Masoudi, FA Weintraub, WS Reid, KJ Spertus, JA AF Schelbert, Erik B. Rumsfeld, John S. Krumholz, Harlan M. Canto, John G. Magid, David J. Masoudi, Frederick A. Weintraub, William S. Reid, Kimberly J. Spertus, John A. TI Ischemic symptoms during acute myocardial infarction, quality of care, and subsequent mortality SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Denver VA Med Ctr, Denver, CO USA. Yale Univ, New Haven, CT 06520 USA. Watson Clin, Lakeland, FL USA. Colorado Permanente Med Grp, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. Emory Univ, Atlanta, GA 30322 USA. Mid Amer Heart Inst, Kansas City, MO USA. Univ Missouri, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E828 EP E829 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600224 ER PT J AU Schwamm, LH LaBresh, K Pan, WQ Frankel, M Fonarow, G AF Schwamm, Lee H. LaBresh, Kenneth Pan, Wenqin Frankel, Michael Fonarow, Greg CA GWTG Steering Comm TI Guideline-based selection of antihypertensive class at discharge after ischemic stroke or TIA: Analysis of the GWTG-stroke experience SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MassPRO, Waltham, MA USA. Duke Clin Rsch Inst, Durham, NC USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. GWTG Steering Com & Investigators, AHA, Dallas, TX USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E829 EP E829 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600225 ER PT J AU Smith, EE Abdullah, AR Amirfarzan, H Schwamm, LH AF Smith, Eric E. Abdullah, Abdul R. Amirfarzan, Houman Schwamm, Lee H. TI Risk factors for failure to control hyperlipidemia prior to admission for ischemic stroke and TIA SO CIRCULATION LA English DT Meeting Abstract CT 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 07-09, 2006 CL Washington, DC SP Amer Heart Assoc, Qual Care & Outcomes Res Interdisciplinary Working Grp, Amer Coll Cardiol Fdn, Ctr Dis Control & Prevent, Dept Vet Affairs C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 30 PY 2006 VL 113 IS 21 BP E830 EP E830 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 048RQ UT WOS:000237964600233 ER PT J AU Cabarrocas, J Cassan, C Magnusson, F Piaggio, E Mars, L Derbinski, J Kyewski, B Gross, DA Salomon, BL Khazaie, K Saoudi, A Liblau, RS AF Cabarrocas, J Cassan, C Magnusson, F Piaggio, E Mars, L Derbinski, J Kyewski, B Gross, DA Salomon, BL Khazaie, K Saoudi, A Liblau, RS TI Foxp3(+) CD25(+) regulatory T cells specific for a neo-self-antigen develop at the double-positive thymic stage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; immune tolerance; nervous system ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR FOXP3; EPITHELIAL-CELLS; NEGATIVE SELECTION; IMMUNE-RESPONSES; BASIC-PROTEIN; IN-VIVO; EXPRESSION; TOLERANCE; REPERTOIRE AB Thymus-derived regulatory T cells (Tregs) expressing CD4, CD25, and the transcription factor Foxp3 play major roles in preventing autoimmunity. The Treg population is enriched in T cells expressing high-avidity self-reactive T cell receptors, and thymic epithelial cells expressing self-antigens (Ag) have been implicated in their induction and/or selection. However, the thymic selection events leading to Treg lineage commitment remain unclear. We followed the thymic development of self-Ag-specific Tregs in double-transgenic mice coexpressing a neo-self-Ag, hemagglutinin (HA) under the control of a neural tissue-specific promoter, and a transgenic class II-restricted T cell antigen receptor specific for HA111-119. Our data show that the promiscuous expression of the HA transgene in thymic epithelial cells is involved in the selective induction and/or expansion of HA-specific Foxp3(+) Treg thymic precursors as early as the double-positive stage. C1 Purpan Hosp, Inst Natl Sante & Rech Med, U563, F-31000 Toulouse, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. German Res Ctr, Div Dev Immunol, D-69120 Heidelberg, Germany. Genethon, CNRS, Unite Mixte Rech 8115, F-91002 Evry, France. Hop La Pitie Salpetriere, CNRS, Unite Mixte Rech 7087, F-75013 Paris, France. RP Liblau, RS (reprint author), Purpan Hosp, Inst Natl Sante & Rech Med, U563, F-31000 Toulouse, France. EM rolandliblau@hotmail.com RI Mars, Lennart/K-7593-2014; Piaggio, Eliane/E-5260-2016; OI Salomon, Benoit/0000-0001-9673-5578; Abdelhadi, SAOUDI/0000-0001-7015-8178 NR 33 TC 74 Z9 79 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 30 PY 2006 VL 103 IS 22 BP 8453 EP 8458 DI 10.1073/pnas.0603086103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 052BX UT WOS:000238206800029 PM 16709665 ER PT J AU Desjardins, AE Vakoc, BJ Tearney, GJ Bouma, BE AF Desjardins, AE Vakoc, BJ Tearney, GJ Bouma, BE TI Speckle reduction in OCT using massively-parallel detection and frequency-domain ranging SO OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; LASER SOURCE; IMAGES; FILTER AB Speckle noise significantly limits the information content provided by coherent optical imaging methods such as optical coherence tomography and its recent derivative, optical frequency-domain imaging (OFDI). In this paper, we demonstrate a novel OFDI system that simultaneously acquires hundreds of angularly resolved images, which can be compounded to reduce speckle noise. The system comprises an InGaAs line-scan camera and an interferometer, configured so that the elements of the detector array simultaneously capture light spanning a backscattering angular range of 32 degrees. On successive read-outs of the array, the wavelength of the laser source was stepped through a range of 130 nm centered at 1295 nm to concurrently generate 400 angle-resolved OFDI images. A theory of angle-resolved OFDI and the design equations of the system are presented. Incoherent averaging of the angle-resolved data is shown to yield substantial speckle reduction (as high as an 8 dB SNR improvement) in images of a tissue phantom and esophageal tissue ex vivo. (c) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Desjardins, AE (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR-708, Boston, MA 02114 USA. EM adesjard@fas.harvard.edu FU NCI NIH HHS [R01 CA103769, R01 CA103769-03]; NHLBI NIH HHS [R01 HL076398, R01 HL076398-05] NR 14 TC 46 Z9 48 U1 3 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAY 29 PY 2006 VL 14 IS 11 BP 4736 EP 4745 DI 10.1364/OE.14.004736 PG 10 WC Optics SC Optics GA 051OL UT WOS:000238170300021 PM 19516630 ER PT J AU Whiting, JF Delmonico, F Morrissey, P Basadonna, G Johnson, S Lewis, WD Rohrer, R O'Connor, K Bradley, J Lovewell, TD Lipkowitz, G AF Whiting, James F. Delmonico, Francis Morrissey, Paul Basadonna, Giacomo Johnson, Scott Lewis, W. David Rohrer, Richard O'Connor, Kevin Bradley, James Lovewell, Tammy D. Lipkowitz, George TI Clinical results of an organ procurement organization effort to increase utilization of donors after cardiac death SO TRANSPLANTATION LA English DT Article DE organ donation; donation after cardiac death; renal transplantation ID NONHEARTBEATING DONORS; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; EXPERIENCE AB Background. To stimulate organ donation, an organ procurement organization (OPO)-wide effort was undertaken to increase donors after cardiac death (DCD) over a 5-year period. This included commonality of protocols, pulsatile perfusion of kidneys, centralization of data and a regional allocation variance designed to minimize cold ischemia times and encourage adoption of DCD protocols at transplant centers. Results. In one OPO, eight centers initiated DCD programs in 11 hospitals. A total of 52 DCD donors were procured, increasing from four in 1999 to 21 in 2003. Eleven donors had care withdrawn in the operating room, whereas 41 had care withdrawn in the ICU. In all, 91 patients received renal transplants from these 52 donors (12 kidneys discarded, one double transplant), whereas 5 patients received liver transplants. One-, two-, and three-year kidney graft survival rates were 90%, 90%, and 82%, respectively. Fifty-five percent of patients needed at least one session of hemodialysis postoperatively. Mean recipient hospital length of stay was 11.1 +/- 6 days. Mean creatinine levels at 3, 6, 12, and 24 months were 1.65, 1.40, 1.41, and 1.40, respectively. Conclusions. DCD donors can be an important source of donor organs and provide excellent overall outcomes. Regional cooperation and a prospectively considered allocation and distribution system are important considerations in stimulating DCD programs. C1 Maine Med Ctr, Dept Surg, Portland, ME 04102 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Rhode Isl Hosp, Dept Surg, Providence, RI USA. Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Lahey Clin Fdn, Dept Surg, Burlington, MA USA. Tufts Univ New England Med Ctr, Dept Surg, Boston, MA 02111 USA. New England Organ Bank Inc, Newton, MA USA. Baystate Med Ctr, Dept Surg, Springfield, MA 01107 USA. RP Whiting, JF (reprint author), 887 Congress St,Suite 400, Portland, ME 04102 USA. EM whitij@mmc.org NR 20 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 27 PY 2006 VL 81 IS 10 BP 1368 EP 1371 DI 10.1097/01.tp.0000179641.82031.ea PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 046PF UT WOS:000237822800002 PM 16732170 ER PT J AU Kim, SY Kim, DH Hyun, JW Henson, JW Kim, HS AF Kim, SY Kim, DH Hyun, JW Henson, JW Kim, HS TI Irisolidone, an isoflavone metabolite, represses JC virus gene expression via inhibition of Sp1 binding in human glial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE progressive multifocal leukoencephalopathy; JC virus; irisolidone; gene expression.; promoter; Sp1 ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; EARLY PROMOTER; ANTIRETROVIRAL THERAPY; HUMAN CYTOMEGALOVIRUS; IN-VITRO; FLAVONOIDS; GENISTEIN; CIDOFOVIR; BIOLOGY; SITES AB Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease that results from an oligodendrocyte infection caused by the JC virus. Therefore, inhibiting the expression of JC virus is important for preventing and/or treating PML. This Study found that irisoliclone, an isoflavone metabolite, significantly inhibited the JC virus expression in primary cultured human astrocytes and glial cell lines. Studies examining the underlying mechanism revealed that a mutation of the Sp1 binding site downstream of the TATA box (Sp1-11) dramatically diminished the inhibitory activity of irisolidone. In addition, an irisolidone treatment repressed Sp1 binding to Sp1-11 site, which is important for the basal JC virus promoter activity. The results Suggest that the inhibitory effect of irisolidone against the JC virus may be attributed at least in part to the Suppression of Sp1 binding to the JC virus promoter region. Therefore, the inhibition of the JC virus expression by irisolidone might provide therapeutic potential for PM L caused by the JC virus. (c) 2006 Elsevier Inc. All rights reserved. C1 Ewha Womans Univ, Coll Med, Dept Neurosci, Seoul, South Korea. Ewha Womans Univ, Coll Med, Med Res Inst, Seoul, South Korea. Kyung Hee Univ, Coll Pharm, Dept Microbial Chem, Seoul, South Korea. Cheju Natl Univ, Coll Med, Dept Biochem, Cheju, South Korea. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kim, HS (reprint author), Ewha Womans Univ, Coll Med, Dept Neurosci, Seoul, South Korea. EM hskimp@ewha.ac.kr NR 28 TC 12 Z9 12 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 26 PY 2006 VL 344 IS 1 BP 3 EP 8 DI 10.1016/j.bbrc.2006.03.165 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 040VE UT WOS:000237408000002 PM 16630573 ER PT J AU Rhee, J Ge, HF Yang, WL Fan, M Handschin, C Cooper, M Lin, JD Li, C Spiegelman, BM AF Rhee, J Ge, HF Yang, WL Fan, M Handschin, C Cooper, M Lin, JD Li, C Spiegelman, BM TI Partnership of PGC-1 alpha and HNF4 alpha in the regulation of lipoprotein metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOLIPOPROTEIN-A-IV; AIV GENE-CLUSTER; FAMILIAL COMBINED HYPERLIPIDEMIA; DEDIFFERENTIATED HEPATOMA-CELLS; DEPENDENT NUCLEAR RECEPTORS; APOC-III; TRANSCRIPTIONAL REGULATION; GAMMA COACTIVATOR-1-ALPHA; TRIGLYCERIDE-METABOLISM; VISCERAL ENDODERM AB Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a transcriptional coactivator involved in several aspects of energy metabolism. It is induced or activated under different stimuli in a highly tissue-specific manner and subsequently partners with certain transcription factors in those tissues to execute various biological programs. In the fasted liver, PGC-1 alpha is induced and interacts with hepatocyte nuclear factor 4 alpha(HNF4 alpha) and other transcription factors to activate gluconeogenesis and increase hepatic glucose output. Given the broad spectrum of liver genes responsive to HNF4 alpha, we sought to determine those that were specifically targeted by the combination of PGC-1 alpha and HNF4 alpha. Co-expression of these two molecules in murine stem cells reveals a high induction of mRNA for apolipoproteins A-IV and C-II. Forced expression of PGC-1 alpha in mouse and human hepatoma cells increases the mRNA of a subset of apolipoproteins implicated in very low density lipoprotein and triglyceride metabolism, including apolipoproteins A-IV, C-II, and C-III. Coactivation of the apoC-III/ A-IV promoter region by PGC-1 alpha occurs through a highly conserved HNF4 alpha response element, the loss of which completely abolishes activation by PGC-1 alpha and HNF4 alpha. Adenoviral infusion of PGC-1 alpha into live mice increases hepatic expression of apolipoproteins A-IV, C-II, and C-III and increases serum and very low density lipoprotein triglyceride levels. Conversely, knock down of PGC-1 alpha in vivo causes a decrease in both apolipoprotein expression and serum triglyceride levels. These data point to a crucial role for the PGC-1 alpha/HNF4 alpha partnership in hepatic lipoprotein metabolism. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Touchstone Ctr Diabet Res, Dallas, TX 75390 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK 54477, DK 61562] NR 55 TC 49 Z9 50 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 26 PY 2006 VL 281 IS 21 BP 14683 EP 14690 DI 10.1074/jbc.M512636200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 044KN UT WOS:000237671300021 PM 16574644 ER PT J AU Tarnovitski, N Matthews, LJ Sui, JH Gershoni, JM Marasco, WA AF Tarnovitski, N Matthews, LJ Sui, JH Gershoni, JM Marasco, WA TI Mapping a neutralizing epitope on the SARS coronavirus spike protein: Computational prediction based on affinity-selected peptides SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE SARS; antibody; epitope; Mapitope; computational algorithm ID ACUTE-RESPIRATORY-SYNDROME; HUMAN MONOCLONAL-ANTIBODY; ANGIOTENSIN-CONVERTING ENZYME-2; WEST-NILE-VIRUS; PHAGE DISPLAY; CONFORMATIONAL EPITOPES; POTENT NEUTRALIZATION; ENVELOPE GLYCOPROTEIN; RECEPTOR; IDENTIFICATION AB Rapid elucidation of neutralizing antibody epitopes on emerging viral pathogens like severe acute respiratory syndrome (SARS) coronavirus (CoV) or highly pathogenic avian influenza H5N1 virus is of great importance for rational design of vaccines against these viruses. Here we combined screening of phage display random peptide libraries with a unique computer algorithm "Mapitope" to identify the discontinuous epitope of 80R, a potent neutralizing human anti-SARS monoclonal antibody against the spike protein. Using two different types of random peptide libraries which display cysteine-constrained loops or linear 13-15-mer peptides, independent panels containing 42 and 18 peptides were isolated, respectively. These peptides, which had no apparent homologous motif within or between the peptide pools and spike protein, were deconvoluted into amino acid pairs (AAPs) by Mapitope and the statistically significant pairs (SSPs) were defined. Mapitope analysis of the peptides was first performed on a theoretical model of the spike and later on the genuine crystal structure. Three clusters (A, B and C) were predicted on both structures with remarkable overlap. Cluster A ranked the highest in the algorithm in both models and coincided well with the sites of spike protein that are in contact with the receptor, consistent with the observation that 80R functions as a potent entry inhibitor. This study demonstrates that by using this novel strategy one can rapidly predict and identify a neutralizing antibody epitope, even in the absence of the crystal structure of its target protein. (c) 2006 Elsevier Ltd. All rights reserved. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gershoni, JM (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. EM gershoni@tauex.tau.ac.il; wayne_marasco@dfci.harvard.edu OI SUI, JIANHUA/0000-0002-1272-9662 FU NIAID NIH HHS [AI053822, AI061318, AI28785, AI48436, AI60654] NR 40 TC 24 Z9 25 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 26 PY 2006 VL 359 IS 1 BP 190 EP 201 DI 10.1016/j.jmb.2006.03.008 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 044HU UT WOS:000237663800017 PM 16630634 ER PT J AU Weissleder, R AF Weissleder, R TI Molecular imaging in cancer SO SCIENCE LA English DT Editorial Material ID POSITRON-EMISSION-TOMOGRAPHY; ONCOLOGY DRUG DEVELOPMENT; IN-VIVO; LUNG-CANCER; END-POINTS; BREAST; REPORTERS; DISCOVERY; LOOKING; AGENTS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu NR 40 TC 575 Z9 604 U1 14 U2 121 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 26 PY 2006 VL 312 IS 5777 BP 1168 EP 1171 DI 10.1126/science.1125949 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048OW UT WOS:000237957400040 PM 16728630 ER PT J AU Ozcan, A AF Ozcan, A. TI Characterisation of nonlinear thin films using logarithmic Hilbert transform SO ELECTRONICS LETTERS LA English DT Article ID POLED FUSED-SILICA; 2ND-ORDER NONLINEARITY; GLASS AB A new technique based on logarithmic Hilbert transform processing of Maker-fringe curves to characterise second-order optical nonlinear depth profile of thin films is described and demonstrated experimentally. This technique, being analytical, is faster than its iterative alternative. This is the first time that a Hilbert transform based analytical tool has been applied to characterise nonlinear thin films. C1 Stanford Univ, Edward L Ginzton Lab, Stanford, CA 94305 USA. RP Ozcan, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aozcan@mgh.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 1 PU INSTITUTION ENGINEERING TECHNOLOGY-IET PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND SN 0013-5194 J9 ELECTRON LETT JI Electron. Lett. PD MAY 25 PY 2006 VL 42 IS 11 BP 647 EP 649 DI 10.1049/el:20060672 PG 3 WC Engineering, Electrical & Electronic SC Engineering GA 063PN UT WOS:000239032100028 ER PT J AU Janzen, V Scadden, DT AF Janzen, V Scadden, DT TI Stem cells - Good, bad and reformable SO NATURE LA English DT Editorial Material ID PROLIFERATION; QUIESCENCE C1 Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. RP Janzen, V (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu NR 9 TC 23 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 25 PY 2006 VL 441 IS 7092 BP 418 EP 419 DI 10.1038/441418a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 045YP UT WOS:000237778900029 PM 16724049 ER PT J AU Wheeler, AP Bernard, GR Thompson, BT Schoenfeld, D Wiedemann, HP deBoisblanc, B Connors, AF Hite, D Harabin, AL AF Wheeler, AP Bernard, GR Thompson, BT Schoenfeld, D Wiedemann, HP deBoisblanc, B Connors, AF Hite, D Harabin, AL CA Natl Heart Lung Blood Inst TI Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RIGHT-HEART CATHETERIZATION; CRITICALLY-ILL PATIENTS; RESPIRATORY-DISTRESS-SYNDROME; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; RISK SURGICAL PATIENTS; PATIENT SAFETY; PRESSURE; OUTCOMES; CARE AB Background: The balance between the benefits and the risks of pulmonary-artery catheters (PACs) has not been established. Methods: We evaluated the relationship of benefits and risks of PACs in 1000 patients with established acute lung injury in a randomized trial comparing hemodynamic management guided by a PAC with hemodynamic management guided by a central venous catheter (CVC) using an explicit management protocol. Mortality during the first 60 days before discharge home was the primary outcome. Results: The groups had similar baseline characteristics. The rates of death during the first 60 days before discharge home were similar in the PAC and CVC groups (27.4 percent and 26.3 percent, respectively; P=0.69; absolute difference, 1.1 percent; 95 percent confidence interval, -4.4 to 6.6 percent), as were the mean (+/-SE) numbers of both ventilator-free days (13.2+/-0.5 and 13.5+/-0.5; P=0.58) and days not spent in the intensive care unit (12.0+/-0.4 and 12.5+/-0.5; P=0.40) to day 28. PAC-guided therapy did not improve these measures for patients in shock at the time of enrollment. There were no significant differences between groups in lung or kidney function, rates of hypotension, ventilator settings, or use of dialysis or vasopressors. Approximately 90 percent of protocol instructions were followed in both groups, with a 1 percent rate of crossover from CVC- to PAC-guided therapy. Fluid balance was similar in the two groups, as was the proportion of instructions given for fluid and diuretics. Dobutamine use was uncommon. The PAC group had approximately twice as many catheter-related complications (predominantly arrhythmias). Conclusions: PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury. C1 Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Wheeler, AP (reprint author), Vanderbilt Univ, Med Ctr, T-1217 MCN, Nashville, TN 37232 USA. EM art.wheeler@vanderbilt.edu OI Wiedemann, Herbert/0000-0002-4587-4401 NR 47 TC 459 Z9 475 U1 2 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 25 PY 2006 VL 354 IS 21 BP 2213 EP 2224 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 045RF UT WOS:000237758900003 ER PT J AU Fischer, SA Graham, MB Kuehnert, MJ Kotton, CN Srinivasan, A Marty, FM Comer, JA Guarner, J Paddock, CD DeMeo, DL Shieh, WJ Erickson, BR Bandy, U DeMaria, A Davis, JP Delmonico, FL Pavlin, B Likos, A Vincent, MJ Sealy, TK Goldsmith, CS Jernigan, DB Rollin, PE Packard, MM Patel, M Rowland, C Helfand, RF Nichol, ST Fishman, JA Ksiazek, T Zaki, SR AF Fischer, SA Graham, MB Kuehnert, MJ Kotton, CN Srinivasan, A Marty, FM Comer, JA Guarner, J Paddock, CD DeMeo, DL Shieh, WJ Erickson, BR Bandy, U DeMaria, A Davis, JP Delmonico, FL Pavlin, B Likos, A Vincent, MJ Sealy, TK Goldsmith, CS Jernigan, DB Rollin, PE Packard, MM Patel, M Rowland, C Helfand, RF Nichol, ST Fishman, JA Ksiazek, T Zaki, SR CA LCMV Transplant Recipient TI Transmission of lymphocytic choriomeningitis virus by organ transplantation. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PET HAMSTER; INFECTION; OUTBREAK; DISEASE; MENINGOENCEPHALITIS; MENINGITIS; RECIPIENTS; DIAGNOSIS; PERSONNEL; ANIMALS AB Background: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. Methods: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause. Epidemiologic investigations, including interviews, environmental assessments, and medical-record reviews, were performed to characterize clinical courses and to determine the cause of the illnesses. Results: Laboratory testing revealed lymphocytic choriomeningitis virus (LCMV) in all the recipients, with a single, unique strain of LCMV identified in each cluster. In both investigations, LCMV could not be detected in the organ donor. In the 2005 cluster, the donor had had contact in her home with a pet hamster infected with an LCMV strain identical to that detected in the organ recipients; no source of LCMV infection was found in the 2003 cluster. The transplant recipients had abdominal pain, altered mental status, thrombocytopenia, elevated aminotransferase levels, coagulopathy, graft dysfunction, and either fever or leukocytosis within three weeks after transplantation. Diarrhea, peri-incisional rash, renal failure, and seizures were variably present. Seven of the eight recipients died, 9 to 76 days after transplantation. One recipient, who received ribavirin and reduced levels of immunosuppressive therapy, survived. Conclusions: We document two clusters of LCMV infection transmitted through organ transplantation. C1 Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Rhode Isl Hosp, Providence, RI USA. Brown Med Sch, Providence, RI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Rhode Isl Dept Hlth, Providence, RI 02908 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. Wisconsin Dept Hlth & Family Serv, Madison, WI USA. New England Organ Bank Inc, Newton, MA USA. RP Kuehnert, MJ (reprint author), Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, 1600 Clifton Rd,Mailstop A-30, Atlanta, GA 30333 USA. EM mkuehnert@cdc.gov RI Guarner, Jeannette/B-8273-2013 NR 42 TC 270 Z9 279 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 25 PY 2006 VL 354 IS 21 BP 2235 EP 2249 DI 10.1056/NEJMoa053240 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 045RF UT WOS:000237758900005 PM 16723615 ER PT J AU Senecal, E Thomas, SH Lev, MH Schwamm, LH Milne, LW Gordon, J Harris, NL Brown, DF AF Senecal, E Thomas, SH Lev, MH Schwamm, LH Milne, LW Gordon, J Harris, NL Brown, DF TI A 72-year-old woman admitted to the emergency department because of a sudden change in mental status - Acute ischemic stroke. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TISSUE-PLASMINOGEN ACTIVATOR; HYPERACUTE STROKE; INTRAARTERIAL THROMBOLYSIS; CT ANGIOGRAPHY; TRIAL; PERFUSION; CARE; RECOMMENDATIONS; ESTABLISHMENT; ASSOCIATION C1 Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Telestroke & Acute Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. NR 45 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 25 PY 2006 VL 354 IS 21 BP 2263 EP 2271 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 045RF UT WOS:000237758900010 PM 16723618 ER PT J AU Poulin, DL DeCaprio, JA AF Poulin, DL DeCaprio, JA TI The carboxyl-terminal domain of large T antigen rescues SV40 host range activity in trans independent of acetylation SO VIROLOGY LA English DT Article DE Simian virus 40; SV40; host range; large T Ag; SV40 replication ID LARGE TUMOR-ANTIGEN; ADENOVIRUS HELPER FUNCTION; SIMIAN VIRUS-40; 3' END; PHOSPHORYLATION SITES; DELETION MUTANTS; DNA-REPLICATION; GENE-EXPRESSION; EARLY REGION; WILD-TYPE AB The host range activity of SV40 has been described as the inability of mutant viruses with deletions in the C terminal region of large T Ag to replicate in certain types of African green monkey kidney cells. We constructed new mutant viruses expressing truncated T Ag proteins and found that these mutant viruses exhibited the host range phenotype. The host range phenotype was independent of acetylation of T Ag at lysine 697. Co-expression of the C terminal domain of T Ag (aa 627-708) in trans increased both T Ag and VP1 mRNA as well as protein levels for host range mutant viruses in the restrictive cell type. In addition, the T Ag 627-708 fragment promoted the productive lytic infection of host range mutant viruses in the nonpermissive cell type. The carboxyl-terminal region of T Ag contains a biological function essential for the SV40 viral life cycle. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Mayer 457,44 Biney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [R01CA063113] NR 40 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 2006 VL 349 IS 1 BP 212 EP 221 DI 10.1016/j.virol.2006.01.046 PG 10 WC Virology SC Virology GA 047ET UT WOS:000237863300020 PM 16510165 ER PT J AU Duraisamy, S Ramasamy, S Kharbanda, S Kufe, D AF Duraisamy, S Ramasamy, S Kharbanda, S Kufe, D TI Distinct evolution of the human carcinoma-associated transmembrane mucins, MUC1, MUC4 AND MUC16 SO GENE LA English DT Article DE mucins; transmembrane; phylogeny; MUC1; MUC4; MUC16 ID OVARIAN-CANCER ANTIGEN; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; MOLECULAR-CLONING; OXIDATIVE STRESS; TUMOR-GROWTH; GENE; PROTEIN; EXPRESSION; DOMAINS AB The MUC family of mucins consists of secreted and membrane-bound forms. Overexpression of the membrane-bound family members, MUC1 (CA15-3), MUC4 and MUC16 (CA125), is found in diverse human carcinomas. However, despite being classified in the same family, little is known about the genetic origins of the carcinoma-associated mucins. The present results show that MUC1 homologs are restricted to mammalian species. MUC1 has no sequence similarity with the other membrane-bound mucins, except for the presence of a sea urchin sperm protein-enterokinase-agrin (SEA) domain. The results indicate that the MUC1 SEA domain originated from heparin sulfate proteoglycan of basement membrane (HSPG2; perlecan), an inducer of tumor cell growth. MUC4 has no SEA domain, but does have (i) a NIDO domain that evolved from an ancestor common to nidogen, and (ii) AMOP and VWD domains that originated from an ancestor common to the Sushi-domain containing protein. MUC16 contains multiple SEA domains that are found in a chicken gene and were subsequently repeated through duplication events. The SEA domains in MUC16 appear to have evolved from agrin before the divergence of birds and mammals. These findings indicate that MUC1, MUC4 and MUC16 evolved from distinct ancestors and that the membrane-bound mucins consist of different subgroups based on their genetic backgrounds. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA097098] NR 45 TC 41 Z9 43 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 24 PY 2006 VL 373 BP 28 EP 34 DI 10.1016/j.gene.2005.12.021 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 049AP UT WOS:000237988000005 PM 16500040 ER PT J AU Kim, HJ DiBernardo, AB Sloane, JA Rasband, MN Solomon, D Kosaras, B Kwak, SP Vartanian, TK AF Kim, HJ DiBernardo, AB Sloane, JA Rasband, MN Solomon, D Kosaras, B Kwak, SP Vartanian, TK TI WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination SO JOURNAL OF NEUROSCIENCE LA English DT Article DE WASP-related protein; WAVE1; myelination; oligodendrocyte; actin cytoskeleton; CNS ID ALDRICH-SYNDROME PROTEIN; ARP2/3 COMPLEX; CELL-MIGRATION; OPTIC-NERVE; WASP; LAMELLIPODIA; RANVIER; MOLECULES; RAC; DIFFERENTIATION AB Myelin formation involves the outgrowth of an oligodendrocyte cell process that can be regarded as a giant lamellipodium because it is an actively growing structure with extruded cytoplasm. The actin cytoskeleton is critical to morphogenesis, but little is known about regulation of actin dynamics in oligodendrocytes. Wiskott-Aldrich syndrome protein family verprolin homologous (WAVE) proteins mediate lamellipodia formation; thus, we asked whether these proteins function in oligodendrocyte process formation and myelination. Here, we show that WAVE1 is expressed by oligodendrocytes and localizes to the lamella leading edge where actin polymerization is actively regulated. CNS WAVE1 expression increases at the onset of myelination. Expression of dominant-negative WAVE1 impaired process outgrowth and lamellipodia formation in cultured oligodendrocytes. Similarly, oligodendrocytes isolated from mice lacking WAVE1 had fewer processes compared with controls, whereas neurons and astrocytes exhibited normal morphology. In white matter of WAVE1(-/-) mice, we found regional hypomyelination in the corpus callosum and to a lesser extent in the optic nerve. In optic nerve from WAVE1(-/-) mice, there were fewer nodes of Ranvier but nodal morphology was normal, implicating a defect in myelin formation. Our in vitro findings support a developmentally dynamic and cell-autonomous role for WAVE1 in regulating process formation in oligodendrocytes. Additionally, WAVE1 function during CNS myelination appears to be linked to regional cues. Although its loss can be compensated for in many CNS regions, WAVE1 is clearly required for normal amounts of myelin to form in corpus callosum and optic nerve. Together, these data demonstrate a role for WAVE1 in oligodendrocyte morphogenesis and myelination. C1 Harvard Univ, Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA. Wyeth Res, Dept Neurosci, Princeton, NJ 08543 USA. RP Vartanian, TK (reprint author), Harvard Univ, Inst Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM tvartani@caregroup.harvard.edu OI Rasband, Matthew/0000-0001-8184-2477 FU NINDS NIH HHS [R01NS042317] NR 40 TC 53 Z9 53 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 24 PY 2006 VL 26 IS 21 BP 5849 EP 5859 DI 10.1523/JNEUROSCI.4921-05.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 046KG UT WOS:000237809900030 PM 16723544 ER PT J AU Pregibon, DC Toner, M Doyle, PS AF Pregibon, DC Toner, M Doyle, PS TI Magnetically and biologically active bead-patterned hydrogels SO LANGMUIR LA English DT Article ID MICROFLUIDIC CHANNELS; COLLOIDAL PARTICLES; DNA HYBRIDIZATION; SOFT LITHOGRAPHY; SURFACES; CELLS; PROTEINS; POLYMER; SYSTEMS; IMMUNOASSAY AB We present a new approach to the direct patterning of biologically and magnetically active microbeads in nonbiofouling polymer scaffolds for use in microfluidic devices. Briefly, the process involves treatment of a glass substrate, conformal contact bonding of a PDMS microchannel on the substrate, filling of the channel with beads and prepolymer solution, and UV-initiated photopolymerization of a mask-defined pattern using a standard inverted microscope. This versatile and simple method allows for the rapid fabrication of dispersed or packed bead patterns in poly(ethylene glycol) (PEG) hydrogels that are covalently linked to glass surfaces. By exploiting the relative opacity of the microbeads used, we are able to create both partially exposed and fully encapsulated bead patterns. To demonstrate the utility of this new technology, we separated magnetic bead-bound B lymphocytes from T lymphocytes on a PEG-encapsulated magnetic filtration platform and also captured B cells directly on patterned, protein-decorated beads in a flow-through microfluidic device. Beyond cell sorting, the accurate patterning of industrially standardized, chemically diverse microbeads may have significant implications for microchip-based analyte detection. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02214 USA. RP Doyle, PS (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pdoyle@mit.edu NR 38 TC 39 Z9 39 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAY 23 PY 2006 VL 22 IS 11 BP 5122 EP 5128 DI 10.1021/la0534625 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 043HZ UT WOS:000237593000038 PM 16700603 ER PT J AU Kulstad, JJ Green, PS Cook, DG Watson, GS Reger, MA Baker, LD Plymate, SR Asthana, S Rhoads, K Mehta, PD Craft, S AF Kulstad, JJ Green, PS Cook, DG Watson, GS Reger, MA Baker, LD Plymate, SR Asthana, S Rhoads, K Mehta, PD Craft, S TI Differential modulation of plasma beta-amyloid by insulin in patients with Alzheimer disease SO NEUROLOGY LA English DT Article ID DEGRADING ENZYME; PRECURSOR PROTEIN; CEREBROSPINAL-FLUID; HUMAN PLATELETS; A-BETA-42 LEVELS; APOLIPOPROTEIN-E; IN-VIVO; RECEPTOR; PEPTIDE; BRAIN AB Background: Hyperinsulinemia and insulin resistance are risk factors for memory impairment and Alzheimer disease ( AD). Insulin regulates levels of the amyloid beta-peptide (A beta) in vitro in neuronal cultures and in vivo in the CSF of normal older adults. Objective: To determine whether insulin affected plasma A beta levels and whether such effects differed for patients with AD compared with normal older adults. Methods: Fifty-nine patients with AD and 50 healthy older adults each received infusions of saline and of insulin (1.0 mU (.) kg(-1) (.) min(-1)) with accompanying dextrose to maintain euglycemia. A subset of participants (19 AD, 12 normal) received two additional conditions, in which insulin was infused at a lower (0.33 mU (.) kg(-1) (.) min(-1)) and higher (1.67 mU (.) kg(-1) (.) min(-1)) rate. Plasma insulin and A beta were measured after 120 minutes of infusion. Results: Adults with AD had higher plasma insulin vs normal adults at the two higher infusion rates, despite receiving comparable amounts of insulin. For normal adults, insulin reduced plasma A beta levels at the middle (1.0 mU (.) kg(-1) (.) min(-1)) dose, with attenuated effects at lower and higher doses. In contrast, for patients with AD, insulin raised plasma A beta levels at the two higher doses (1.0 and 1.67 mU (.) kg(-1) (.) min(-1)). Conclusions: These results suggest that patients with Alzheimer disease ( AD) have reduced insulin clearance and insulin-provoked plasma amyloid beta-peptide (A beta) elevation. Abnormal regulation of peripheral A beta by insulin may contribute to AD risk. C1 VAPSHCS, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI USA. Inst Basic Res Dev Disabil, Staten Isl, NY USA. RP Craft, S (reprint author), VAPSHCS, Geriatr Res Educ & Clin Ctr, S-182 GRECC,1600 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu FU NIA NIH HHS [R01 AG-10880] NR 41 TC 55 Z9 58 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 23 PY 2006 VL 66 IS 10 BP 1506 EP 1510 DI 10.1212/01.wnl.0000216274.58185.09 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 044XM UT WOS:000237706900010 PM 16717209 ER PT J AU Ning, M Furie, KL Koroshetz, WJ Lee, H Barron, M Lederer, M Wang, X Zhu, M Sorensen, AG Lo, EH Kelly, PJ AF Ning, M Furie, KL Koroshetz, WJ Lee, H Barron, M Lederer, M Wang, X Zhu, M Sorensen, AG Lo, EH Kelly, PJ TI Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke SO NEUROLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; MATRIX-METALLOPROTEINASE EXPRESSION; PREDICTS HEMORRHAGIC TRANSFORMATION; REPERFUSION; INHIBITION; INJURY; RATS; THROMBOLYSIS AB Background: Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models. The authors investigated plasma MMP9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP1), in tPA-treated and -untreated stroke patients. Methods: Non-stroke control subjects and consecutive ischemic stroke patients presenting within 8 hours of onset were enrolled. Blood was sampled within 8 hours and at 24 hours, 2 to 5 days and 4 to 6 weeks. MMP9 and TIMP1 were analyzed by ELISA and gel zymography. Results: Fifty-two cases (26 tPA treated, 26 tPA untreated) and 27 nonstroke control subjects were enrolled. Hyperacute MMP9 was elevated in tPA-treated vs tPA-untreated patients (medians 43 vs 28 ng/mL; p = 0.01). tPA therapy independently predicted hyperacute MMP9 after adjustment for stroke severity, volume, and hemorrhagic transformation (p = 0.01). There was a trend toward lower hyperacute TIMP1 levels in tPA-treated vs tPA-untreated patients (p = 0.06). Hyperacute MMP9 was correlated to poor 3-month modified Rankin Scale outcome (r = 0.58, p = 0.0005). Conclusion: Tissue plasminogen activator independently predicted plasma matrix metalloproteinase-9 (MMP9) in the first 8 hours after human ischemic stroke. As MMP9 may be an important mediator of hemorrhagic transformation, alternative thrombolytic agents or therapeutic MMP9 inhibition may increase the safety profile of acute stroke thrombolysis. C1 Mater Misericordiae Univ Hosp, Dept Neurol, Neurovasc Clin Sci Unit, Dublin 7, Ireland. Univ Coll Dublin, Dublin 2, Ireland. Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neuroprotect Res Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kelly, PJ (reprint author), Mater Misericordiae Univ Hosp, Dept Neurol, Neurovasc Clin Sci Unit, 71 Eccles St, Dublin 7, Ireland. EM kfurie@partners.org; pjkelly@partners.org FU NCRR NIH HHS [M01-RR-01066]; NINDS NIH HHS [K23 NS42720, R01-NS37074, R01-NS38731, R01-NS40529] NR 36 TC 89 Z9 97 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 23 PY 2006 VL 66 IS 10 BP 1550 EP 1555 DI 10.1212/01.wnl.0000216133.98416.b4 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 044XM UT WOS:000237706900019 PM 16717217 ER PT J AU Perry, GH Tchinda, J McGrath, SD Zhang, JJ Picker, SR Caceres, AM Iafrate, AJ Tyler-Smith, C Scherer, SW Eichler, EE Stone, AC Lee, C AF Perry, George H. Tchinda, Joelle McGrath, Sean D. Zhang, Junjun Picker, Simon R. Caceres, Angela M. Iafrate, A. John Tyler-Smith, Chris Scherer, Stephen W. Eichler, Evan E. Stone, Anne C. Lee, Charles TI Hotspots for copy number variation in chimpanzees and humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chimpanzee genome; human evolution; structural genomic variation ID COMPARATIVE GENOMIC HYBRIDIZATION; SEGMENTAL DUPLICATIONS; STRUCTURAL VARIATION; ANCESTRAL POPULATION; NUCLEOTIDE DIVERSITY; DEMOGRAPHIC HISTORY; ALPHA-DEFENSIN; GENE ONTOLOGY; DNA-SEQUENCE; POLYMORPHISM AB Copy number variation is surprisingly common among humans and can be involved in phenotypic diversity and variable susceptibility to complex diseases, but little is known of the extent of copy number variation in nonhuman primates. We have used two array-based comparative genomic hybridization platforms to identify a total of 355 copy number variants (CNVs) in the genomes of 20 wild-born chimpanzees (Pan troglodytes) and have compared the identified chimpanzee CNVs to known human CNVs from previous studies. Many CNVs were observed in the corresponding regions in both chimpanzees and humans; especially those CNVs of higher frequency. Strikingly, these loci are enriched 20-fold for ancestral segmental duplications, which may facilitate CNV formation through nonallelic homologous recombination mechanisms. Therefore, some of these regions may be unstable "hotspots" for the genesis of copy number variation, with recurrent duplications and deletions occurring across and within species. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. Howard Hughes Med Inst, Seattle, WA 98195 USA. Hosp Sick Children, Ctr Appl Genom, Dept Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada. RP Lee, C (reprint author), Brigham & Womens Hosp, Dept Pathol, 20 Shattuck St,Thorn Bldg,Room 6-12A, Boston, MA 02115 USA. EM clee@rics.bwh.harvard.edu RI Stone, Anne/B-5719-2009; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU NCRR NIH HHS [U42 RR015087] NR 55 TC 141 Z9 147 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2006 VL 103 IS 21 BP 8006 EP 8011 DI 10.1073/pnas.0602318103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 047BD UT WOS:000237853900015 PM 16702545 ER PT J AU Taube, C Thurman, JM Takeda, K Joetham, A Miyahara, N Carroll, MC Dakhama, A Giclas, PC Holers, VM Gelfand, EW AF Taube, C Thurman, JM Takeda, K Joetham, A Miyahara, N Carroll, MC Dakhama, A Giclas, PC Holers, VM Gelfand, EW TI Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE asthma; allergy; innate immunity; lung ID HEMOLYTIC-UREMIC SYNDROME; TH2 EFFECTOR FUNCTIONS; MURINE MODEL; C3A ANAPHYLATOXIN; ACQUIRED-IMMUNITY; PULMONARY ALLERGY; DEFICIENT MICE; RENAL-DISEASE; C5A RECEPTORS; CUTTING EDGE AB Exposure to inhaled allergens leads to increases in airway hyper-responsiveness (AHR) and inflammation, associated with increased levels of biologically active fragments derived from the complement C3 and C5 family of proteins. Further, complement activation during allergen challenge in sensitized animals is necessary for the development of AHR and airway inflammation. To define the complement pathway involved, we studied mice deficient in complement factor 4 (C4-/-), a critical component of the classical pathway, or factor B (fB-/-), an essential protein in the alternative complement pathway. WT, C4-/-, and fB-/- mice were sensitized to ovalbumin and subsequently exposed to nebulized ovalbumin (1% in saline) on 3 consecutive days. After allergen sensitization and challenge, fB-/- mice demonstrated significantly lower airway responsiveness to methacholine and less airway inflammation. In contrast, C4-/- mice showed no reduction in AHR and airway inflammation compared with WT mice. Tissue inflammation, goblet cell hyperplasia, and IL-4, IL-5, and IL-13 levels in BAL fluid were significantly reduced in fB-/- mice compared with C4-/- and WT mice. The development of AHR and airway inflammation in sensitized fB-/- mice could be restored after intranasal administration of purified factor B before the airway challenge. In addition, administration of a neutralizing anti-factor B mAb to sensitized mice before airway challenge reduced the development of AHR and airway inflammation. These results demonstrate that in sensitized hosts complement activation through the alternative pathway after allergen exposure is critical to the development of AHR and airway inflammation. C1 Natl Jewish Med & Res Ctr, Div Cell Biol, Dept Pediat, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Nephrol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Hypertens, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Rheumatol, Denver, CO 80262 USA. Harvard Univ, Sch Med, Dept Pediat & Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Gelfand, EW (reprint author), Natl Jewish Med & Res Ctr, Div Cell Biol, Dept Pediat, Denver, CO 80206 USA. EM gelfande@njc.org FU NHLBI NIH HHS [HL-36577, HL-61005, P01 HL036577, P01 HL036577-21A15977, R01 HL061005]; NIAID NIH HHS [AI-31105, R01 AI031105]; NIDDK NIH HHS [K08 DK064790-01, K08 DK064790] NR 48 TC 39 Z9 42 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 23 PY 2006 VL 103 IS 21 BP 8084 EP 8089 DI 10.1073/pnas.0602357103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 047BD UT WOS:000237853900028 PM 16702544 ER PT J AU Wang, L Larson, EB Bowen, JD van Belle, G AF Wang, L Larson, EB Bowen, JD van Belle, G TI Performance-based physical function and future dementia in older people SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; INCIDENT DEMENTIA; COGNITIVE DECLINE; AGED 65; GAIT; PREDICTORS; HEALTH; RISK AB Background: The association of physical function with progression to dementia has not been well investigated. We aimed to determine whether physical function is associated with incident dementia and Alzheimer disease (AD). Methods: We performed a prospective cohort study of 2288 persons 65 years and older without dementia. Patients were enrolled from 1994 to 1996 and followed up through October 2003. Main outcome measures included incident dementia and AD. Results: During follow-up 319 participants developed dementia (221 had AD). The age-specific incidence rate of dementia was 53.1 per 1000 person-years for participants who scored lower on a performance-based physical function test at baseline (<= 10 points) compared with 17.4 per 1000 person-years for those who scored higher (< 10 points). A 1-point lower performance-based physical function score was associated with an increased risk of dementia (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P <.001), an increased risk of AD (hazard ratio, 1.06; 95% confidence interval, 1.01-1.12; P=.01), and an increased rate of decline in the Cognitive Ability Screening Instrument scores (0.11 point per year; 95% confidence interval, 0.08-0.14; P <.001) after adjusting for age, sex, years of education, baseline cognitive function, APOE epsilon 4 allele, family history of AD, depression, coronary heart disease, and cerebrovascular disease. Conclusions: Lower levels of physical performance were associated with an increased risk of dementia and AD. The study suggests that poor physical function may precede the onset of dementia and AD and higher levels of physical function may be associated with a delayed onset. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Larson, EB (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM larson.e@ghc.org FU NIA NIH HHS [UO1 AG06781] NR 28 TC 127 Z9 135 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 22 PY 2006 VL 166 IS 10 BP 1115 EP 1120 DI 10.1001/archinte.166.10.1115 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 045CP UT WOS:000237720500011 PM 16717174 ER PT J AU Smith, GL Shlipak, MG Havranek, EP Foody, JM Masoudi, FA Rathore, SS Krumholz, HM AF Smith, GL Shlipak, MG Havranek, EP Foody, JM Masoudi, FA Rathore, SS Krumholz, HM TI Serum urea nitrogen, creatinine, and estimators of renal function - Mortality in older patients with cardiovascular disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; ACUTE MYOCARDIAL-INFARCTION; CHRONIC KIDNEY-DISEASE; DECOMPENSATED HEART-FAILURE; ACUTE CORONARY SYNDROMES; TIMI RISK SCORE; PREDICTIVE PERFORMANCE; HOSPITALIZATION; INSUFFICIENCY; TRIAL AB Background: Renal dysfunction predicts increased mortality in cardiovascular patients, but the best renal estimator for quantifying risks is uncertain. We compared admission serum urea nitrogen (SUN) level, creatinine level, Modification of Diet in Renal Disease (MDRD) rate, and Mayo estimated glomerular filtration rate (eGFR) for predicting mortality. Methods: In a retrospective cohort of Medicare patients (aged >= 65 years) hospitalized for myocardial infarction (n=44 437) and heart failure (n=56 652), renal estimators were compared for linearity with 1-year mortality risk, magnitude of risk, and relative importance for predicting risk (percentage variance explained) in proportional hazards models. Results: The SUN level, creatinine level, and Mayo eGFR had linear associations with mortality. These measures predicted steadily increased risk in patients who experienced a myocardial infarction with a SUN level greater than 17 mg/dL (> 6.1 mmol/L), a creatinine level greater than 1.0 mg/dL (> 88.4 mu mol/L), and a Mayo eGFR of less than 100 mL/min per 1.73 m(2); and in patients who experienced heart failure with a SUN level greater than 16 mg/dL (> 5.7 mmol/L), a creatinine level greater than 1.1 mg/dL (> 97.2 mu mol/L), and a Mayo eGFR of 90 mL/min per 1.73 m(2) or less. In contrast, the MDRD eGFR had a J-shaped association and failed to identify increased risks in 50.0% of patients who experienced a myocardial infarction (with an MDRD eGFR > 55 mL/min per 1.73 m(2)) and 60.0% of patients who experienced heart failure (with an MDRD eGFR > 44 mL/min per 1.73 m(2)). The SUN level and Mayo eGFR had the greatest magnitude of risks. In myocardial infarction and heart failure patients, adjusted mortality increased by 3% and 7%, respectively, per 5-U increase in SUN, and by 3% and 9%, respectively, per 10-U decrease in Mayo eGFR (P <.001), based on models including both renal measures. Of all the measures, SUN had the greatest magnitude of relative importance for predicting mortality. Conclusions: In older cardiovascular patients, SUN- and creatinine-based measures were powerful predictors of postdischarge mortality. Only MDRD eGFR was less adequate in quantifying risks for patients with mild impairment. Novel estimators, such as the Mayo eGFR, may play an important role in outcomes' prognostication for these patients. C1 Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver Hlth Med Ctr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Geriatr Med, Denver, CO 80262 USA. Colorado Fdn Med Care, Aurora, CO USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, 333 Cedar St,Sterling Hall Med,1 Wing,Suite 456, New Haven, CT 06520 USA. EM harlan.krumholz@yale.edu FU NIA NIH HHS [K08-AG01011, K08-AG20623-01]; NIGMS NIH HHS [GM07205] NR 44 TC 59 Z9 61 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 22 PY 2006 VL 166 IS 10 BP 1134 EP 1142 DI 10.1001/archinte.166.10.1134 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 045CP UT WOS:000237720500014 PM 16717177 ER PT J AU Levy, D DePalma, SR Benjamin, EJ O'Donnell, CJ Parise, H Hirschhorn, JN Vasan, RS Izumo, S Larson, MG AF Levy, Daniel DePalma, Steven R. Benjamin, Emelia J. O'Donnell, Christopher J. Parise, Helen Hirschhorn, Joel N. Vasan, Ramachandran S. Izumo, Seigo Larson, Martin G. TI Phenotype-genotype association grid: a convenient method for summarizing multiple association analyses SO BMC GENETICS LA English DT Article ID HAPLOTYPE BLOCKS; HUMAN GENOME; MAP AB Background: High-throughput genotyping generates vast amounts of data for analysis; results can be difficult to summarize succinctly. A single project may involve genotyping many genes with multiple variants per gene and analyzing each variant in relation to numerous phenotypes, using several genetic models and population subgroups. Hundreds of statistical tests may be performed for a single SNP, thereby complicating interpretation of results and inhibiting identification of patterns of association. Results: To facilitate visual display and summary of large numbers of association tests of genetic loci with multiple phenotypes, we developed a Phenotype-Genotype Association ( PGA) grid display. A database-backed web server was used to create PGA grids from phenotypic and genotypic data ( sample sizes, means and standard errors, P-value for association). HTML pages were generated using Tcl scripts on an AOLserver platform, using an Oracle database, and the ArsDigita Community System web toolkit. The grids are interactive and permit display of summary data for individual cells by a mouse click (i.e. least squares means for a given SNP and phenotype, specified genetic model and study sample). PGA grids can be used to visually summarize results of individual SNP associations, gene-environment associations, or haplotype associations. Conclusion: The PGA grid, which permits interactive exploration of large numbers of association test results, can serve as an easily adapted common and useful display format for large-scale genetic studies. Doing so would reduce the problem of publication bias, and would simplify the task of summarizing large-scale association studies. C1 NHLBI, Bethesda, MD 20892 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Dept Math & Stat, Boston, MA USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Broad Ctr, Cambridge, MA USA. MIT, Cambridge, MA USA. Novartis Res Inst, Cambridge, MA USA. RP Levy, D (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM levyd@nih.gov; depalma@receptor.med.harvard.edu; Emelia@bu.edu; codonnell@nih.gov; hparise@bu.edu; joelh@broad.mit.edu; vasan@bu.edu; seigoizumo@bidmc.harvard.edu; mlarson@bu.edu FU NHLBI NIH HHS [N01HC25195, N01-HC-25195] NR 6 TC 5 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD MAY 22 PY 2006 VL 7 AR 30 DI 10.1186/1471-2156/7/30 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 071WR UT WOS:000239635100001 PM 16716207 ER PT J AU Broom, WJ Russ, C Sapp, PC McKenna-Yasek, D Hosler, BA Andersen, PM Brown, RH AF Broom, WJ Russ, C Sapp, PC McKenna-Yasek, D Hosler, BA Andersen, PM Brown, RH TI Variants in candidate ALS modifier genes linked to Cu/Zn superoxide dismutase do not explain divergent survival phenotypes (vol 392, pg 52, 2006) SO NEUROSCIENCE LETTERS LA English DT Correction C1 Massachusetts Gen Hosp, Day Neuromusc Res Lab, Charlestown, MA 02129 USA. MIT, Howard Hughes Med Inst, Cambridge, MA USA. Umea Univ, Dept Neurol, S-90187 Umea, Sweden. RP Broom, WJ (reprint author), Massachusetts Gen Hosp, Day Neuromusc Res Lab, 114 16th St,Navy Yard, Charlestown, MA 02129 USA. EM wbroom@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 22 PY 2006 VL 399 IS 3 BP 273 EP 273 DI 10.1016/j.neulet.2006.02.032 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 046VK UT WOS:000237839000020 ER PT J AU Censor, Y Bortfeld, T Martin, B Trofimov, A AF Censor, Y Bortfeld, T Martin, B Trofimov, A TI A unified approach for inversion problems in intensity-modulated radiation therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CONVEX FEASIBILITY PROBLEMS; OPTIMIZATION; RADIOTHERAPY; PROJECTION; CONSTRAINTS; SETS AB We propose and study a unified model for handling dose constraints (physical dose, equivalent uniform dose (EUD), etc) and radiation source constraints in a single mathematical framework based on the split feasibility problem. The model does not impose on the constraints an exogenous objective (merit) function. The optimization algorithm minimizes a weighted proximity function that measures the sum of the squares of the distances to the constraint sets. This guarantees convergence to a feasible solution point if the split feasibility problem is consistent (i.e., has a solution), or, otherwise, convergence to a solution that minimally violates the physical dose constraints and EUD constraints. We present computational results that demonstrate the validity of the model and the power of the proposed algorithmic scheme. C1 Univ Haifa, Dept Math, IL-31905 Haifa, Israel. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Censor, Y (reprint author), Univ Haifa, Dept Math, IL-31905 Haifa, Israel. EM yair@math.haifa.ac.il RI Censor, Yair/H-5740-2011 FU NCI NIH HHS [1-R01-CA103904-01, 5-P01-CA21239-25]; NHLBI NIH HHS [HL70472] NR 33 TC 210 Z9 215 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 21 PY 2006 VL 51 IS 10 BP 2353 EP 2365 DI 10.1088/0031-9155/51/10/001 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 054NQ UT WOS:000238384700001 PM 16675857 ER PT J AU Court, LE Tishler, RB Petit, J Cormack, R Chin, L AF Court, LE Tishler, RB Petit, J Cormack, R Chin, L TI Automatic online adaptive radiation therapy techniques for targets with significant shape change: a feasibility study SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; RADIOTHERAPY; UNCERTAINTIES; PROSTATE; SYSTEM; HEAD AB This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (313) of planning and daily CT images gives global shifts. Slice-by-slice (213) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 degrees, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100%, 90% and 80% of the base-of-tongue, left nodes and right nodes, respectively, receiving the daily prescription dose), and kept the daily cord dose below the limit used in the original plan (65%, equivalent to 46 Gy over 35 fractions). Most of the loss of coverage was due to one shoulder being raised more superior relative to the other shoulder compared with the plan. This type of skew-like motion is not accounted for by the proposed ART technique. In conclusion, this technique has potential to correct for fairly extreme daily changes in patient setup, but some control of the daily position would still be necessary. Importantly, it was possible to combine treatments from different plans (MLC sequences) to correct for position and shape change. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Canc, Dept Radiat Oncol, Boston, MA 02115 USA. RP Court, LE (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Canc, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM lcourt@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 9 TC 40 Z9 41 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 21 PY 2006 VL 51 IS 10 BP 2493 EP 2501 DI 10.1088/0031-9155/51/10/009 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 054NQ UT WOS:000238384700009 PM 16675865 ER PT J AU Chan, TCY Bortfeld, T Tsitsiklis, JN AF Chan, TCY Bortfeld, T Tsitsiklis, JN TI A robust approach to IMRT optimization SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INCORPORATING ORGAN MOTION; DOSE-VOLUME RESTRICTIONS; 3D TUMOR MOTION; RADIATION-THERAPY; DIAPHRAGM MOTION; BEAM WEIGHTS; LUNG-TUMOR; SET-UP; RADIOTHERAPY; PROBABILITY AB Managing uncertainty is a major challenge in radiation therapy treatment planning, including uncertainty induced by intrafraction motion, which is particularly important for tumours in the thorax and abdomen. Common methods to account for motion are to introduce a margin or to convolve the static dose distribution with a motion probability density function. Unlike previous work in this area, our development does not assume that the patient breathes according to a fixed distribution, nor is the patient required to breathe the same way throughout the treatment. Despite this generality, we create a robust optimization framework starting from the convolution method that is robust to fluctuations in breathing motion, yet spares healthy tissue better than a margin solution. We describe how to generate the data for our model using breathing motion data and we test our model on a computer phantom using data from real patients. In our numerical results, the robust solution delivers approximately 38% less dose to the healthy tissue than the margin solution, while providing the same level of protection against breathing uncertainty. C1 MIT, Ctr Operat Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. RP Chan, TCY (reprint author), MIT, Ctr Operat Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM tcychan@mit.edu; tbortfeld@partners.org; jnt@mit.edu FU NCI NIH HHS [P01-CA21239, R01-CA103904] NR 43 TC 62 Z9 62 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 21 PY 2006 VL 51 IS 10 BP 2567 EP 2583 DI 10.1088/0031-9155/51/10/014 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 054NQ UT WOS:000238384700014 PM 16675870 ER PT J AU Raut, CP Posner, M Desai, J Morgan, JA George, S Zahrieh, D Fletcher, CDM Demetri, GD Bertagnolli, MM AF Raut, CP Posner, M Desai, J Morgan, JA George, S Zahrieh, D Fletcher, CDM Demetri, GD Bertagnolli, MM TI Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IMATINIB MESYLATE; ACQUIRED-RESISTANCE; TRIAL; GIST; KIT; MUTATIONS; DIAGNOSIS; SURVIVAL; DISEASE; SAFETY AB Purpose While targeted inhibitors of tyrosine kinase activity demonstrate dramatic efficacy in the majority of patients with advanced gastrointestinal stromal tumors (GISTs), cure remains elusive and resistance to systemic therapy is a challenge. To assess the role of surgery in multimodality management of GISTs, we studied postoperative outcomes in patients treated with targeted kinase inhibitors for advanced GIST. Methods We evaluated outcomes in a single institution series of 69 consecutive patients who underwent surgery for advanced GISTS while receiving kinase inhibitors. Patients were categorized based on extent of disease before surgery (stable disease, limited disease progression, generalized disease progression) and surgical result (no evidence of disease, minimal residual disease, bulky residual disease). Results Disease status before surgery was associated with surgical result (P <.0001; median follow-up, 14.6 months). After surgery, there was no evidence of disease in 78%, 25%, and 7% of patients with stable disease, limited progression, and generalized progression, respectively. Bulky residual disease remained after surgery in 4%, 16%, and 43% of the patients with stable disease, limited progression, and generalized progression. Twelve-month progression-free survival was 80%, 33%, and 0% for patients with stable disease, limited progression, and generalized progression (P <.0001). Twelve-month overall survival was 95%, 86%, and 0% for patients with stable disease, limited progression, and generalized progression (P <.0001). Conclusion Patients with advanced GISTs exhibiting stable disease or limited progression on kinase inhibitor therapy have prolonged overall survival after debulking procedures. Surgery has little to offer in the setting of generalized progression. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org NR 26 TC 215 Z9 236 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2006 VL 24 IS 15 BP 2325 EP 2331 DI 10.1200/JCO.2005.05.3439 PG 7 WC Oncology SC Oncology GA 046RK UT WOS:000237828500018 PM 16710031 ER PT J AU Cui, XY Yang, SC Sharma, S Heuze-Vourc'h, N Dubinett, SM AF Cui, XY Yang, SC Sharma, S Heuze-Vourc'h, N Dubinett, SM TI IL-4 regulates COX-2 and PGE2production in human non-small cell lung cancer SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE NSCLC; IL-4; COX-2; PGE(2); mPEGES-1; 15-PGDH ID ACTIVATED PROTEIN-KINASES; PROSTAGLANDIN-E SYNTHASE; SMOOTH-MUSCLE-CELLS; CYCLOOXYGENASE-2 EXPRESSION; KAPPA-B; E-2 BIOSYNTHESIS; UP-REGULATION; PATHWAYS; IDENTIFICATION; INTERLEUKIN-4 AB IL-4 is a type 2 cytokine that may mediate pleiotropic effects in the NSCLC microenvironment. Here, we investigated whether IL-4 regulates PGE(2) production in NSCLC cells. We found that IL-4 inhibited constitutive COX-2 expression and PGE(2) production in A427 and H2122 NSCLC cell lines, and also suppressed IL-1 beta-induced COX-2 expression in A549 and RH2 NSCLC cell lines. COX-2 mRNA was decreased in response to IL-4, and promoter analysis indicated that IL-4 inhibited both constitutive and IL-1 beta-induced COX-2 transcription. IL-4 inhibited IL-1 beta-stimulated ERK phosphorylation, which may mediate the inhibition of IL-1 beta-induced COX-2 by IL-4. IL-4 did not modulate additional arachidonic acid pathway enzymes mPGES-1 and 15-PGDH, which could potentially be responsible for regulating PGE2 production. Overall, our Studies demonstrate that IL-4 has the capacity to inhibit COX-2 mRNA transcription in NSCLC cells and the inhibition of PGE(2) appears to be predominately COX-2 dependent. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. EM sdubinett@mednet.ucla.edu RI HEUZE-VOURC'H, Nathalie/P-8081-2016 FU NCI NIH HHS [P50 CA90388, R01 CA111851] NR 32 TC 19 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 19 PY 2006 VL 343 IS 4 BP 995 EP 1001 DI 10.1016/j.bbrc.2006.03.073 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 038ZQ UT WOS:000237269000001 PM 16574063 ER PT J AU Drain, PK Baeten, JM Overbaugh, J Wener, MH D Bankson, D Lavreys, L Mandaliya, K O Ndinya-Achola, J McClelland, RS AF Drain, PK Baeten, JM Overbaugh, J Wener, MH D Bankson, D Lavreys, L Mandaliya, K O Ndinya-Achola, J McClelland, RS TI Low serum albumin and the acute phase response predict low serum selenium in HIV-1 infected women SO BMC INFECTIOUS DISEASES LA English DT Article ID VITAMIN-A-DEFICIENCY; HIV DISEASE PROGRESSION; RANDOMIZED-TRIAL; MICRONUTRIENT SUPPLEMENTATION; MORTALITY; INFECTION; PLASMA; BLOOD; RISK AB Background: Low serum selenium has been associated with lower CD4 counts and greater mortality among HIV-1-seropositive individuals, but most studies have not controlled for serum albumin and the presence of an acute phase response. Methods: A cross-sectional study was conducted to evaluate relationships between serum selenium concentrations and CD4 count, plasma viral load, serum albumin, and acute phase response markers among 400 HIV-1-seropositive women. Results: In univariate analyses, lower CD4 count, higher plasma viral load, lower albumin, and the presence of an acute phase response were each significantly associated with lower serum selenium concentrations. In multivariate analyses including all four of these covariates, only albumin remained significantly associated with serum selenium. For each 0.1 g/dl increase in serum albumin, serum selenium increased by 0.8 mu g/l ( p < 0.001). Women with an acute phase response also had lower serum selenium ( by 5.6 mu g/l, p = 0.06). Conclusion: Serum selenium was independently associated with serum albumin, but not with CD4 count or plasma viral load, in HIV-1-seropositive women. Our findings suggest that associations between lower serum selenium, lower CD4 count, and higher plasma viral load may be related to the frequent occurrence of low serum albumin and the acute phase response among individuals with more advanced HIV-1 infection. C1 Univ Washington, Dept Med, Seattle, WA 98105 USA. Univ Washington, Sch Med, Seattle, WA 98105 USA. Univ Washington, Dept Lab Med, Seattle, WA 98105 USA. Univ Washington, Clin Nutr Res Unit Lab Core, Seattle, WA 98105 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Coast Prov Gen Hosp, Dept Pathol, Mombasa, Kenya. Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya. RP McClelland, RS (reprint author), Univ Washington, Dept Med, 1959 NE Pacific,Box 356340, Seattle, WA 98105 USA. EM pkdrain@u.washington.edu; jbaeten@partners.org; joverbau@fhcrc.org; wener@u.washington.edu; daniel.bankson@med.va.gov; llavreys@africaonline.co.ke; kishor@ikenya.com; ndinya-achola@kaviuon.org; mcclell@africoonline.co.ke OI Drain, Paul/0000-0003-3300-3817 FU FIC NIH HHS [D43 TW000007, D43-TW00007]; NIAID NIH HHS [R01 AI043844, K23-AI52480, AI43844, K23 AI052480, AI39996]; NIDDK NIH HHS [P30 DK035816, DK35816] NR 28 TC 14 Z9 14 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD MAY 19 PY 2006 VL 6 AR 85 DI 10.1186/1471-2334-6-85 PG 6 WC Infectious Diseases SC Infectious Diseases GA 054IB UT WOS:000238368900001 PM 16712720 ER PT J AU Lim, J Hao, T Shaw, C Patel, AJ Szabo, G Rual, JF Fisk, CJ Li, N Smolyar, A Hill, DE Barabasi, AL Vidal, M Zoghbi, HY AF Lim, J Hao, T Shaw, C Patel, AJ Szabo, G Rual, JF Fisk, CJ Li, N Smolyar, A Hill, DE Barabasi, AL Vidal, M Zoghbi, HY TI A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration SO CELL LA English DT Article ID MEDIATES NEURODEGENERATION; INTERACTION DATABASE; CEREBELLAR-ATAXIA; INTERACTION MAP; C-ELEGANS; GENE; MOUSE; DROSOPHILA; MICE; TOXICITY AB Many human inherited neurodegenerative disorders are characterized by loss of balance due to cerebellar Purkinje cell (PC) degeneration. Although the disease-causing mutations have been identified for a number of these disorders, the normal functions of the proteins involved remain, in many cases, unknown. To gain insight into the function of proteins involved in PC degeneration, we developed an interaction network for 54 proteins involved in 23 inherited ataxias and expanded the network by incorporating literature-curated and evolutionarily conserved interactions. We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen; of 75 pairs tested, 83% of the interactions were verified in mammalian cells. Many ataxia-causing proteins share interacting partners, a subset of which have been found to modify neurodegeneration in animal models. This interactome thus provides a tool for understanding pathogenic mechanisms common for this class of neuroclegenerative disorders and for identifying candidate genes for inherited ataxias. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. RP Zoghbi, HY (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM hzoghbi@bcm.tmc.edu RI Hill, David/B-6617-2011; OI Rual, Jean-Francois/0000-0003-4465-8819; Shaw, Chad/0000-0001-7267-5398 FU NICHD NIH HHS [HD24064]; NINDS NIH HHS [NS27699] NR 56 TC 463 Z9 489 U1 5 U2 37 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 19 PY 2006 VL 125 IS 4 BP 801 EP 814 DI 10.1016/j.cell.2006.03.032 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 047NM UT WOS:000237886000023 PM 16713569 ER PT J AU Burdick, MM Chu, JT Godar, S Sackstein, R AF Burdick, MM Chu, JT Godar, S Sackstein, R TI HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVER METASTASIS; FLOW CONDITIONS; CANCER CELLS; TUMOR-CELLS; LEUKOCYTE ADHESION; DEPENDENT ADHESION; ENDOTHELIAL-CELLS; CD44S EXPRESSION; P-SELECTIN; GROWTH AB Engagement of vascular E-selectin and leukocyte L-selectin with relevant counter-receptors expressed on tumor cells contributes to the hematogenous spread of colon carcinoma. We recently demonstrated that the LS174T colon carcinoma cell line expresses the CD44 glycoform known as hematopoietic cell E-/L-selectin ligand (HCELL), which functions as a high affinity E- and L-selectin ligand on these cells. To define the contribution of HCELL to selectin-mediated adhesion on intact tumor cells, we measured the binding of LS174T cells transduced with CD44 short interfering RNA (siRNA) or with vector alone to 6-h interleukin-1 beta-stimulated human umbilical vein endothelial cells (HUVEC) and to human peripheral blood mononuclear cells (PBMC) under physiological flow conditions. LS174T cell attachment to HUVEC was entirely E-selectin-dependent, and PBMC tethering to tumor cell monolayers was completely L-selectin-dependent. At physiological shear stress, CD44 siRNA transduction led to an similar to 50% decrease in the number of LS174T cells binding to stimulated HUVEC relative to vector alone-transduced cells. CD44 siRNA-transduced cells also rolled significantly faster than vector-transduced cells on HUVEC, indicating prominent HCELL participation in stabilizing tumor cell-endothelial adhesive interactions against fluid shear. Furthermore, HCELL was identified as the principal L-selectin ligand on LS174T cells, as PBMC binding to CD44 siRNA-transduced tumor cells was reduced similar to 80% relative to vector-transduced cells. These data indicate that expression of HCELL confers robust and predominant tumor cell binding to E- and L-selectin, highlighting a central role for HCELL in promoting shear-resistant adhesive interactions essential for hematogenous cancer dissemination. C1 Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Sackstein, R (reprint author), Harvard Univ, Inst Med, 77 Ave Louis Pasteur,Rm 671, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu FU NHLBI NIH HHS [R01 HL073714, R01 HL60528] NR 39 TC 46 Z9 47 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2006 VL 281 IS 20 BP 13899 EP 13905 DI 10.1074/jbc.M513617200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042FC UT WOS:000237512300010 PM 16565092 ER PT J AU Boston-Howes, W Gibb, SL Williams, EO Pasinelli, P Brown, RH Trotti, D AF Boston-Howes, W Gibb, SL Williams, EO Pasinelli, P Brown, RH Trotti, D TI Caspase-3 cleaves and inactivates the glutamate transporter EAAT2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODEL; MOTOR-NEURON DEATH; SUPEROXIDE-DISMUTASE; CELL-DEATH; VITAL FUNCTIONS; EXPRESSION; MUTANT; DISEASE; MICE AB EAAT2 is a high affinity, Na+-dependent glutamate transporter with predominant astroglial localization. It accounts for the clearance of the bulk of glutamate released at central nervous system synapses and therefore has a crucial role in shaping glutamatergic neurotransmission and limiting excitotoxicity. Caspase-3 activation and impairment in expression and activity of EAAT2 are two distinct molecular mechanisms occurring in human amyotrophic lateral sclerosis (ALS) and in the transgenic rodent model of the disease. Excitotoxicity caused by down-regulation of EAAT2 is thought to be a contributing factor to motor neuron death in ALS. In this study, we report the novel evidence that caspase-3 cleaves EAAT2 at a unique site located in the cytosolic C-terminal domain of the transporter, a finding that links excitotoxicity and activation of caspase-3 as converging mechanisms in the pathogenesis of ALS. Caspase-3 cleavage of EAAT2 leads to a drastic and selective inhibition of this transporter. Heterologous expression of mutant SOD1 proteins linked to the familial form of ALS leads to inhibition of EAAT2 through a mechanism that largely involves activation of caspase-3 and cleavage of the transporter. In addition, we found evidence in spinal cord homogenates of mutant SOD1 ALS mice of a truncated form of EAAT2, likely deriving from caspase-3-mediated proteolytic cleavage, which appeared concurrently to the loss of EAAT2 immunoreactivity and to increased expression of activated caspase-3. Taken together, our findings suggest that caspase-3 cleavage of EAAT2 is one mechanism responsible for the impairment of glutamate uptake in mutant SOD1-linked ALS. C1 Harvard Univ, MassGen Inst Neurodegenerat Dis, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cecil B Day Lab Neuromuscular Res, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Trotti, D (reprint author), Harvard Univ, MassGen Inst Neurodegenerat Dis, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Bldg 114, Charlestown, MA 02129 USA. EM dtrotti@partners.org FU NINDS NIH HHS [NS44292] NR 38 TC 74 Z9 77 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2006 VL 281 IS 20 BP 14076 EP 14084 DI 10.1074/jbc.M600653200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042FC UT WOS:000237512300030 PM 16567804 ER PT J AU Ulvila, J Parikka, M Kleino, A Sormunen, R Ezekowitz, RA Kocks, C Ramet, M AF Ulvila, J Parikka, M Kleino, A Sormunen, R Ezekowitz, RA Kocks, C Ramet, M TI Double-stranded RNA is internalized by scavenger receptor-mediated endocytosis in Drosophila S2 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; PROTEIN; INTERFERENCE; PATHWAY; PHAGOCYTOSIS; PROTEASOME; COMPONENTS; INITIATION; CLEAVAGE; IDENTIFICATION AB Double-stranded RNA ( dsRNA) fragments are readily internalized and processed by Drosophila S2 cells, making these cells a widely used tool for the analysis of gene function by gene silencing through RNA interference (RNAi). The underlying mechanisms are insufficiently understood. To identify components of the RNAi pathway in S2 cells, we developed a screen based on rescue from RNAi-induced lethality. We identified Argonaute 2, a core component of the RNAi machinery, and three gene products previously unknown to be involved in RNAi in Drosophila: DEAD-box RNA helicase Belle, 26 S proteasome regulatory subunit 8 (Pros45), and clathrin heavy chain, a component of the endocytic machinery. Blocking endocytosis in S2 cells impaired RNAi, suggesting that dsRNA fragments are internalized by receptor-mediated endocytosis. Indeed, using a candidate gene approach, we identified two Drosophila scavenger receptors, SR-CI and Eater, which together accounted for more than 90% of the dsRNA uptake into S2 cells. When expressed in mammalian cells, SR-CI was sufficient to mediate internalization of dsRNA fragments. Our data provide insight into the mechanism of dsRNA internalization by Drosophila cells. These results have implications for dsRNA delivery into mammalian cells. C1 Tampere Univ, Inst Med Technol, FIN-30014 Tampere, Finland. Oulu Univ, Dept Pediat, FIN-90014 Oulu, Finland. Univ Oulu, Bioctr Oulu, FIN-90014 Oulu, Finland. Univ Oulu, Dept Pathol, FIN-90014 Oulu, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02115 USA. Tampere Univ Hosp, Dept Pediat, FIN-33521 Tampere, Finland. RP Ramet, M (reprint author), Tampere Univ, Inst Med Technol, FIN-30014 Tampere, Finland. EM Mika.Ramet@uta.fi RI Parikka, Mataleena/D-4364-2014; OI Parikka, Mataleena/0000-0001-5555-3815 FU NIAID NIH HHS [P01 AI 44220] NR 42 TC 135 Z9 142 U1 2 U2 24 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2006 VL 281 IS 20 BP 14370 EP 14375 DI 10.1074/jbc.M513868200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042FC UT WOS:000237512300063 PM 16531407 ER PT J AU Shibata, M Lu, T Furuya, T Degterev, A Mizushima, N Yoshimori, T MacDonald, M Yankner, B Yuan, JY AF Shibata, Mamoru Lu, Tao Furuya, Tsuyoshi Degterev, Alexei Mizushima, Noboru Yoshimori, Tamotsu MacDonald, Marcy Yankner, Bruce Yuan, Junying TI Regulation of Intracellular Accumulation of Mutant Huntingtin by Beclin 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article AB Intracellular accumulation of mutant Huntingtin with expanded polyglutamine provides a context-dependent cytotoxicity critical for the pathogenesis of Huntington disease (Everett, C. M., and Wood, N. W. (2004) Brain 127, 2385-2405). Here we demonstrate that the accumulation of mutant Huntingtin is highly sensitive to the expression of beclin 1, a gene essential for autophagy. Moreover, we show that the accumulated mutant Huntingtin recruits Beclin 1 and impairs the Beclin 1-mediated long lived protein turnover. Thus, sequestration of Beclin 1 in the vulnerable neuronal population of Huntington disease patients might further reduce Beclin 1 function and autophagic degradation of mutant Huntingtin. Finally, we demonstrate that the expression of beclin 1 decreases in an age-dependent fashion in human brains. Because beclin 1 gene is haploid insufficient in regulating autophagosome function (Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E. L., Mizushima, N., Ohsumi, Y., Cattoretti, G., and Levine, B. (2003) J. Clin. Invest. 112, 1809-1820; Yue, Z., Jin, S., Yang, C., Levine, A. J., and Heintz, N. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 15077 15082), we propose that the age-dependent decrease of beclin 1 expression may lead to a reduction of autophagic activity during aging, which in turn promotes the accumulation of mutant Htt and the progression of the disease. C1 [Shibata, Mamoru; Furuya, Tsuyoshi; Degterev, Alexei; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Shibata, Mamoru; Furuya, Tsuyoshi; Degterev, Alexei; Yuan, Junying] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lu, Tao; Yankner, Bruce] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Lu, Tao; Yankner, Bruce] Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. [MacDonald, Marcy] Massachusetts Gen Hosp East, Ctr Human Genet Res, Charlestown, MA 02129 USA. [MacDonald, Marcy] Massachusetts Gen Hosp East, Mol Neurogenet Unit, Charlestown, MA 02129 USA. [Mizushima, Noboru] Tokyo Metropolitan Inst Med Sci, Dept Bioregulat & Metab, Bunkyo Ku, Tokyo 1138613, Japan. [Yoshimori, Tamotsu] Natl Inst Genet, Dept Cell Genet, Mishima, Shizuoka 4118540, Japan. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM jyuan@hms.harvard.edu RI Shibata, Mamoru/L-8537-2013; Mizushima, Noboru/C-3635-2009 OI Shibata, Mamoru/0000-0002-2416-4259; Mizushima, Noboru/0000-0002-6258-6444 FU HighQ Foundation; NIA, National Institutes of Health [R37-12859, NS32765, NS16367]; Huntington's Disease Center FX This work was supported by the HighQ Foundation, by NIA, National Institutes of Health Grant R37-12859 (to J. Y.), by National Institutes of Health Grants NS32765 and NS16367, and by the Huntington's Disease Center Without Walls (to M. M.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 40 TC 222 Z9 230 U1 1 U2 15 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 19 PY 2006 VL 281 IS 20 BP 14474 EP 14485 DI 10.1074/jbc.M600364200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V06FK UT WOS:000207179300006 PM 16522639 ER PT J AU Close, P Hawkes, N Cornez, I Creppe, C Lambert, CA Rogister, B Siebenlist, U Merville, MP Slaugenhaupt, SA Bours, V Svejstrup, JQ Chariot, A AF Close, P Hawkes, N Cornez, I Creppe, C Lambert, CA Rogister, B Siebenlist, U Merville, MP Slaugenhaupt, SA Bours, V Svejstrup, JQ Chariot, A TI Transcription impairment and cell migration defects in elongator-depleted cells: Implication for familial dysautonomia SO MOLECULAR CELL LA English DT Article ID POLYMERASE-II HOLOENZYME; B KINASE COMPLEX; HISTONE ACETYLTRANSFERASE; IN-VIVO; RNA; MOTILITY; PROTEIN; GENES; IKAP; FIBROBLASTS AB Mutations in IKBKAP, encoding a subunit of Elongator, cause familial dysautonomia (FD), a severe neuro-developmental disease with complex clinical characteristics. Elongator was previously linked not only with transcriptional elongation and histone acetylation but also with other cellular processes. Here, we used RNA interference (RNAi) and fibroblasts from FD patients to identify Elongator target genes and study the role of Elongator in transcription. Strikingly, whereas Elongator is recruited to both target and nontarget genes, only target genes display histone H3 hypoacetylation and progressively lower RNAPII density through the coding region in FD cells. Interestingly, several target genes encode proteins implicated in cell motility. Indeed, characterization of IKAP/hELP1 RNAi cells, FD fibroblasts, and neuronal cell-derived cells uncovered defects in this cellular function upon Elongator depletion. These results indicate that defects in Elongator function affect transcriptional elongation of several genes and that the ensuing cell motility deficiencies may underlie the neuropathology of FD patients. C1 Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. Univ Liege, Lab Med Chem & Human Genet, Ctr Biomed Integrat Genoproteom, B-4000 Liege, Belgium. Univ Liege, Lab Connect Tissues Biol, Ctr Biomed Integrat Genoproteom, B-4000 Liege, Belgium. Univ Liege, Ctr Cellular & Mol Neurobiol, B-4000 Liege, Belgium. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Svejstrup, JQ (reprint author), Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. EM j.svejstrup@cancer.org.uk; alain.chariot@ulg.ac.be OI Svejstrup, Jesper/0000-0003-4964-6147 NR 31 TC 118 Z9 122 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 19 PY 2006 VL 22 IS 4 BP 521 EP 531 DI 10.1016/j.molcel.2006.04.017 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 046LO UT WOS:000237813300013 PM 16713582 ER PT J AU Wang, BB Love, TM Call, ME Doench, JG Novina, CD AF Wang, Bingbing Love, Tara M. Call, Matthew E. Doench, John G. Novina, Carl D. TI Recapitulation of short RNA-directed translational gene silencing in vitro SO MOLECULAR CELL LA English DT Article ID MESSENGER-RNA; HUMAN-CELLS; MICRORNA TARGETS; PASSENGER-STRAND; REGULATORY RNA; EXPRESSION; DROSOPHILA; INITIATION; CLEAVAGE; SIRNAS AB microRNAs (miRNAs) are a large class of endogenous short RNAs that repress gene expression. Many miRNAs are conserved throughout evolution, and dysregulation of miRNA pathways has been correlated with an increasing number of human diseases. In animals, miRNAs typically bind to the 31 untranslated region (3'UTR) of target mRNAs with imperfect sequence complementarity and repress translation. Despite their importance in regulating biological processes in numerous organisms, the mechanisms of miRNA function are largely unknown. Here, we report in vitro reactions for miRNA-directed translational gene silencing. These reactions faithfully recapitulate known in vivo hallmarks of mammalian miRNA function, including a requirement for a 5' phosphate and perfect complementarity to the mRNA target in the 5' seed region. Translational gene silencing by miRNAs in vitro requires target mRNAs to possess a 7-methyl G cap and a polyA tail, whereas increasing polyA tail length alone can increase miRNA silencing activity. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Proteom, Boston, MA 02115 USA. RP Novina, CD (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469; Doench, John/0000-0002-3707-9889 FU NCI NIH HHS [T32CA70083] NR 37 TC 127 Z9 133 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 19 PY 2006 VL 22 IS 4 BP 553 EP 560 DI 10.1016/j.molcel.2006.03.034 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 046LO UT WOS:000237813300016 PM 16713585 ER PT J AU Hu, VW Frank, BC Heine, S Lee, NH Quackenbush, J AF Hu, Valerie W. Frank, Bryan C. Heine, Shannon Lee, Norman H. Quackenbush, John TI Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes SO BMC GENOMICS LA English DT Article ID TUBEROUS SCLEROSIS GENE; BIPOLAR DISORDER; CANDIDATE GENES; NITRIC-OXIDE; ARGININOSUCCINATE SYNTHETASE; PSYCHIATRIC-DISORDERS; DNA MICROARRAYS; MESSENGER-RNA; CHROMOSOME 7Q; LINKAGE AB Background: The autism spectrum encompasses a set of complex multigenic developmental disorders that severely impact the development of language, non-verbal communication, and social skills, and are associated with odd, stereotyped, repetitive behavior and restricted interests. To date, diagnosis of these neurologically based disorders relies predominantly upon behavioral observations often prompted by delayed speech or aberrant behavior, and there are no known genes that can serve as definitive biomarkers for the disorders. Results: Here we demonstrate, for the first time, that lymphoblastoid cell lines from monozygotic twins discordant with respect to severity of autism and/or language impairment exhibit differential gene expression patterns on DNA microarrays. Furthermore, we show that genes important to the development, structure, and/or function of the nervous system are among the most differentially expressed genes, and that many of these genes map closely in silico to chromosomal regions containing previously reported autism candidate genes or quantitative trait loci. Conclusion: Our results provide evidence that novel candidate genes for autism may be differentially expressed in lymphoid cell lines from individuals with autism spectrum disorders. This finding further suggests the possibility of developing a molecular screen for autism based on expressed biomarkers in peripheral blood lymphocytes, an easily accessible tissue. In addition, gene networks are identified that may play a role in the pathophysiology of autism. C1 George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. Inst Genom Res, Rockville, MD 20850 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Hu, VW (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, 2300 Eye St,NW, Washington, DC 20037 USA. EM bcmvwh@gwumc.edu; bfrank@tigr.org; sheine@gwu.edu; nhlee@tigr.org; johnq@jimmy.harvard.edu OI Hu, Valerie/0000-0002-3357-0777 FU NIMH NIH HHS [R01 MH064547] NR 78 TC 103 Z9 105 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAY 18 PY 2006 VL 7 AR 118 DI 10.1186/1471-2164-7-118 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 071VW UT WOS:000239633000001 PM 16709250 ER PT J AU Yachimski, PS Chung, RT Sahani, DV Amrein, PC Misdraji, J Iafrate, AJ Hertl, M Harris, NL Gilliland, DG AF Yachimski, PS Chung, RT Sahani, DV Amrein, PC Misdraji, J Iafrate, AJ Hertl, M Harris, NL Gilliland, DG TI A 46-year-old woman with sudden onset of abdominal distention - Budd-Chiari syndrome, with centrilobular hepatocellular necrosis, sinusoidal dilatation, congestion, and red-cell extravasation consistent with the presence of venous outflow obstruction. Heterozygosity for factor V Leiden. V617F mutation in JAK2. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PORTAL-VEIN THROMBOSIS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; MYELOPROLIFERATIVE DISORDERS; EXPERIENCE; CULTURE; INVITRO C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Dept Hematol Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. RP Yachimski, PS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 21 TC 20 Z9 21 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 18 PY 2006 VL 354 IS 20 BP 2166 EP 2175 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 043BX UT WOS:000237575400012 ER PT J AU Shank-Calvo, JA Draheim, K Bhasin, M Kelliher, MA AF Shank-Calvo, JA Draheim, K Bhasin, M Kelliher, MA TI P16Ink4a or p19Arf loss contributes to Tal1-induced leukemogenesis in mice SO ONCOGENE LA English DT Article DE T-cell leukemia; Tal1/scl; p16(Ink4a); p19(Arf) ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ONCOGENIC TRANSCRIPTION FACTORS; LOOP-HELIX PROTEINS; T-CELL; C-MYC; TUMOR SUPPRESSION; MTS1 P16(INK4A); TRANSGENIC MICE; INK4A LOCUS; EXPRESSION AB Analysis of the INK4A/ARF locus in human T-ALL patients revealed frequent deletions in exon 2, the exon common to both p16(INK4A) and p14(ARF). Other studies have described selective deletion of exon 1 ss of p14ARF or methylation of the p16INK4A promoter. Therefore, it is unclear from these studies whether loss of p16INK4A and/or p14ARF contributes to the development of T-ALL. To elucidate the relative contribution of the ink4a/arf locus to T-cell leukemogenesis, we mated our tal1 transgenic mice to ink4a/arf-/-, p16(ink4a)-/-,and p19(arf)-/- mice and generated tal1/ink4a/arf+/-, tal1/p16(ink4a)+/-, and tal1/p19(arf) +/- mice. Each of these mice developed T-cell leukemia rapidly, indicating that loss of either p16(ink4a) or p19(arf) cooperates with Tal1 to induce leukemia in mice. Preleukemic studies reveal that Tal1 expression stimulates entry into the cell cycle and thymocyte apoptosis in vivo. Interestingly, mice expressing a DNA-binding mutant of Tal1 do not exhibit increases in S phase cells. The S phase induction is accompanied by an increase in thymocyte apoptosis in tal1 transgenic mice. Whereas apoptosis is reduced to wild-type levels in tal1/ink4a/arf-/- mice, S phase induction remains unaffected. Thus, Tal1 stimulates cell cycle entry independent of the ink4a/arf locus, but its ability to induce apoptosis is Ink4a/Arf-dependent. C1 Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01650 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA USA. Dana Faber Canc Inst, Immunobiol Lab, Boston, MA USA. Dana Faber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kelliher, MA (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, 364 Plantat St, Worcester, MA 01650 USA. EM michelle.kelliher@umassmed.edu FU NCI NIH HHS [CA096899, R01 CA096899] NR 39 TC 20 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 18 PY 2006 VL 25 IS 21 BP 3023 EP 3031 DI 10.1038/sj.onc.1209326 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 048MI UT WOS:000237950800006 PM 16407836 ER PT J AU Borbas, KE Mroz, P Hamblin, MR Lindsey, JS AF Borbas, KE Mroz, P Hamblin, MR Lindsey, JS TI Bioconjugatable porphyrins bearing a compact swallowtail motif for water solubility SO BIOCONJUGATE CHEMISTRY LA English DT Article ID 2 MESO SUBSTITUENTS; PHOTODYNAMIC THERAPY; MESOSUBSTITUTED DIPYRROMETHANES; OXIDE SURFACES; ACID TETHERS; IN-VITRO; CHLORIN; CONJUGATE; CANCER; CELLS AB A broad range of applications requires access to water-soluble, bioconjugatable porphyrins. Branched alkyl groups attached at the branching site to the porphyrin meso position are known to impart high organic solubility. Such "swallowtail" motifs bearing a polar group (hydroxy, dihydroxyphosphoryl, dihydroxyphosphoryloxy) at the terminus of each branch have now been incorporated at a meso site in trans-AB-porphyrins. The incorporation of the swallowtail motif relies on rational synthetic methods whereby a 1,9-bis(N-propylimino) dipyrromethane (bearing a bioconjugatable tether at the 5-position) is condensed with a dipyrromethane (bearing a protected 1,5-dihydroxypent-3-yl unit at the 5-position). The two hydroxy groups in the swallowtail motif of each of the resulting zinc porphyrins can be transformed to the corresponding diphosphate or diphosphonate product. A 4-(carboxymethyloxy) phenyl group provides the bioconjugatable tether. The six such porphyrins reported here are highly water-soluble (>= 20 mM at room temperature in water at pH 7) as determined by visual inspection, UV-vis absorption spectroscopy, or H-1 NMR spectroscopy. Covalent attachment was carried out in aqueous solution with the unprotected porphyrin diphosphonate and a monoclonal antibody against the T-cell receptor CD3 epsilon. The resulting conjugate performed comparably to a commercially available fluorescein isothiocyanate-labeled antibody with Jurkat cells in flow cytometry and fluorescence microscopy assays. Taken together, this work enables preparation of useful quantities of water-soluble, bioconjugatable porphyrins in a compact architecture for applications in the life sciences. C1 N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02142 USA. RP Lindsey, JS (reprint author), N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. EM jlindsey@ncsu.edu RI Lindsey, Jonathan/J-7761-2012; OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [CA/AI838801, R01 AI050875, R01 AI050875-05A1]; NIGMS NIH HHS [GM36238, R01 GM036238] NR 50 TC 41 Z9 41 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY 17 PY 2006 VL 17 IS 3 BP 638 EP 653 DI 10.1021/bc050337w PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 043CD UT WOS:000237576000011 PM 16704201 ER PT J AU Brown, JS Bradley, CS Subak, LL Richter, HE Kraus, SR Brubaker, L Lin, F Vittinghoff, E Grady, D AF Brown, JS Bradley, CS Subak, LL Richter, HE Kraus, SR Brubaker, L Lin, F Vittinghoff, E Grady, D CA Diagnost Aspects Incontinence Stu TI The sensitivity and specificity of a simple test to distinguish between urge and stress urinary incontinence SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID EPIDEMIOLOGIC SURVEY; CONFIDENCE-INTERVALS; SEVERITY INDEX; WOMEN; QUESTIONNAIRE; VALIDITY; HISTORY; PREVALENCE; COMMUNITY; DIAGNOSIS AB Background: Urinary incontinence is common in women. Because treatments differ, urge incontinence should be distinguished from stress incontinence. To make this distinction, current guidelines recommend an extensive evaluation that is too time-consuming for primary care practice. Objective: To test the accuracy of a simple questionnaire to categorize type of urinary incontinence in women. Design: Multicenter, prospective study of the accuracy of the 3 Incontinence Questions (3IQ) compared with an extended evaluation to distinguish between urge incontinence and stress incontinence. Setting: 5 academic medical centers in the United States. Participants: 301 women enrolled from April to December 2004 who were older than 40 years of age (mean age, 56 years [SD, 11]) with untreated incontinence for an average of 7 years (SD, 7) and a broad range of incontinence severity. Measurements: All participants included in the analyses answered the 31Q questionnaire, and a urologist or urogynecologist who was blinded to the responses performed the extended evaluation. Sensitivity, specificity, and likelihood ratios were determined for the 3IQ. Results: For classification of urge incontinence and with the extended evaluation as the gold standard, the 3IQ had a sensitivity of 0.75 (95% CI, 0.68 to 0.81), a specificity of 0.77 (CI, 0.69 to 0.84), and a positive likelihood ratio of 3.29 (CI, 2.39 to 4.51). For classification of stress incontinence, the sensitivity was 0.86 (CI, 0.79 to 0.90), the specificity was 0.60 (CI, 0.51 to 0.68), and the positive likelihood ratio was 2.13 (CI, 1.71 to 2.66). Limitations: Participants were enrolled by urologists and urogynecologists at academic medical centers. Conclusions: The 31Q questionnaire is a simple, quick, and noninvasive test with acceptable accuracy for classifying urge and stress incontinence and may be appropriate for use in primary care settings. Similar studies are needed in other populations. We also need a clinical trial comparing the outcomes of treatments based on the 31Q and the extended evaluation. C1 Univ Calif San Francisco, San Francisco, CA 94115 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Alabama, Birmingham, AL 35487 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Loyola Univ, Maywood, IL 60153 USA. RP Brown, JS (reprint author), Univ Calif San Francisco, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM brownj@obgyn.ucsf.edu FU FIC NIH HHS [D43 TW000909]; NCI NIH HHS [R01 CA094107]; NIDDK NIH HHS [P50 DK064538-03, P50 DK064538, P50 DK064538-04, P50 DK064538-02S1, P50 DK064538-02, P50 DK064538-010003, P50 DK064538-03S1, P50 DK064538-01] NR 30 TC 67 Z9 67 U1 2 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 16 PY 2006 VL 144 IS 10 BP 715 EP 723 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 043XO UT WOS:000237636400002 PM 16702587 ER PT J AU Chaudhry, B Wang, J Wu, SY Maglione, M Mojica, W Roth, E Morton, SC Shekelle, PG AF Chaudhry, B Wang, J Wu, SY Maglione, M Mojica, W Roth, E Morton, SC Shekelle, PG TI Systematic review: Impact of health information technology on quality, efficiency, and costs of medical care SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID PHYSICIAN ORDER ENTRY; ADVERSE DRUG EVENTS; RANDOMIZED CONTROLLED-TRIALS; COMPUTER-BASED INTERVENTION; DECISION-SUPPORT-SYSTEMS; HOSPITALIZED-PATIENTS; PREVENTIVE CARE; CLINICAL GUIDELINES; IMPROVE TREATMENT; TIME UTILIZATION AB Background: Experts consider health information technology key to improving efficiency and quality of health care. Purpose: To systematically review evidence on the effect of health information technology on quality, efficiency, and costs of health care. Data Sources: The authors systematically searched the English-language literature indexed in MEDLINE (1995 to January 2004), the Cochrane Central Register of Controlled Trials, the Cochrane Database of Abstracts of Reviews of Effects, and the Periodical Abstracts Database. We also added studies identified by experts up to April 2005. Study Selection: Descriptive and comparative studies and systematic reviews of health information technology. Data Extraction: Two reviewers independently extracted information on system capabilities, design, effects on quality, system acquisition, implementation context, and costs. Data Synthesis: 257 studies met the inclusion criteria. Most studies addressed decision support systems or electronic health records. Approximately 25% of the studies were from 4 academic institutions that implemented internally developed systems; only 9 studies evaluated multifunctional, commercially developed systems. Three major benefits on quality were demonstrated: increased adherence to guideline-based care, enhanced surveillance and monitoring, and decreased medication errors. The primary domain of improvement was preventive health. The major efficiency benefit shown was decreased utilization of care. Data on another efficiency measure, time utilization, were mixed. Empirical cost data were limited. Limitations: Available quantitative research was limited and was done by a small number of institutions. Systems were heterogeneous and sometimes incompletely described. Available financial and contextual data were limited. Conclusions: Four benchmark institutions have demonstrated the efficacy of health information technologies in improving quality and efficiency. Whether and how other institutions can achieve similar benefits, and at what costs, are unclear. C1 Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA 90095 USA. RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles Vet Affairs Syst, Los Angeles, CA 90048 USA. RP Chaudhry, B (reprint author), Univ Calif Los Angeles, Div Gen Internal Med, 911 Broxton Ave,2nd Floor, Los Angeles, CA 90095 USA. EM BChaudhry@mednet.ucla.edu RI Tao, Youyou/D-2367-2014 NR 106 TC 1142 Z9 1161 U1 23 U2 237 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 16 PY 2006 VL 144 IS 10 BP 742 EP 752 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 043XO UT WOS:000237636400005 PM 16702590 ER PT J AU Dienstag, JL AF Dienstag, JL TI Hepatitis C: A bitter harvest SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID VIRUS-INFECTION; UNITED-STATES; SEXUAL TRANSMISSION; RISK-FACTORS; HOMOSEXUAL MEN; LIVER-DISEASE; NON-A; ASSOCIATION; COHORT C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM jdienstag@partners.org NR 18 TC 11 Z9 12 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 16 PY 2006 VL 144 IS 10 BP 770 EP 771 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 043XO UT WOS:000237636400008 PM 16702593 ER PT J AU Healy, AM Pickard, MD Pradhan, AD Wang, YM Chen, ZP Croce, K Sakuma, M Shi, C Zago, AC Garasic, J Damokosh, AI Dowie, TL Poisson, L Lillie, J Libby, P Ridker, PM Simon, DI AF Healy, AM Pickard, MD Pradhan, AD Wang, YM Chen, ZP Croce, K Sakuma, M Shi, C Zago, AC Garasic, J Damokosh, AI Dowie, TL Poisson, L Lillie, J Libby, P Ridker, PM Simon, DI TI Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events SO CIRCULATION LA English DT Article DE platelets; myocardial infarction; transcriptional profiling; myeloid-related protein-14 ID TRANSENDOTHELIAL MIGRATION; MYOCARDIAL-INFARCTION; DISEASE; INFLAMMATION; ACTIVATION; MONOCYTES; ANGINA; WOMEN; SERUM; CD69 AB Background-Platelets participate in events that immediately precede acute myocardial infarction. Because platelets lack nuclear DNA but retain megakaryocyte-derived mRNAs, the platelet transcriptome provides a novel window on gene expression preceding acute coronary events. Methods and Results-We profiled platelet mRNA from patients with acute ST-segment-elevation myocardial infarction (STEMI, n=16) or stable coronary artery disease (n=44). The platelet transcriptomes were analyzed and single-gene models constructed to identify candidate genes with differential expression. We validated 1 candidate gene product by performing a prospective, nested case-control study (n=255 case-control pairs) among apparently healthy women to assess the risk of future cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) associated with baseline plasma levels of the candidate protein. Platelets isolated from STEMI and coronary artery disease patients contained 54 differentially expressed transcripts. The strongest discriminators of STEMI in the microarrays were CD69 ( odds ratio 6.2, P < 0.001) and myeloid-related protein-14 (MRP-14; odds ratio 3.3, P=0.002). Plasma levels of MRP-8/14 heterodimer were higher in STEMI patients (17.0 versus 8.0 mu g/mL, P < 0.001). In the validation study, the risk of a first cardiovascular event increased with each increasing quartile of MRP-8/14 (P-trend < 0.001) such that women with the highest levels had a 3.8-fold increase in risk of any vascular event (P < 0.001). Risks were independent of standard risk factors and C-reactive protein. Conclusions-The platelet transcriptome reveals quantitative differences between acute and stable coronary artery disease. MRP-14 expression increases before STEMI, and increasing plasma concentrations of MRP-8/14 among healthy individuals predict the risk of future cardiovascular events. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Donald W Reynolds Ctr Clin Cardiovasc Res, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Simon, DI (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St,PBB-1, Boston, MA 02115 USA. EM dsimon@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL57506, HL60942] NR 26 TC 171 Z9 180 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 16 PY 2006 VL 113 IS 19 BP 2278 EP 2284 DI 10.1161/CIRCULATIONAHA.105.607333 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 042TB UT WOS:000237551300007 PM 16682612 ER PT J AU Heller, EA Liu, E Tager, AM Yuan, Q Lin, AY Ahluwalia, N Jones, K Koehn, SL Lok, VM Aikawa, E Moore, KJ Luster, AD Gerszten, RE AF Heller, EA Liu, E Tager, AM Yuan, Q Lin, AY Ahluwalia, N Jones, K Koehn, SL Lok, VM Aikawa, E Moore, KJ Luster, AD Gerszten, RE TI Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells SO CIRCULATION LA English DT Article DE atherosclerosis; immunology; inflammation; leukocytes; chemokines ID TRANSCRIPTION FACTOR FOXP3; CORONARY-ARTERY-DISEASE; RECEPTOR-DEFICIENT MICE; E-KNOCKOUT MICE; REDUCES ATHEROSCLEROSIS; PROTECTIVE IMMUNITY; OXIDIZED LDL; IN-VIVO; EXPRESSION; CXCR3 AB Background-Studies to define the overall contribution of lymphocytes to lesion formation in atherosclerosis-susceptible mice have demonstrated relatively subtle effects; the use of lymphocyte-deficient mice, however, compromises both the effector and regulatory arms of the immune system. Here, we tested the hypothesis that deletion of CXCL10 (IP-10), a chemokine specific for effector T cells that has been localized within atherosclerotic lesions, would significantly inhibit atherogenesis. Methods and Results-Compound deficient Apoe(-/-)/Cxcl10(-/-) mice fed a Western-style diet for either 6 or 12 weeks demonstrated significant reductions in atherogenesis as compared with Apoe(-/-) controls, as assessed by both aortic en face and cross-sectional analyses. Immunohistochemical studies revealed a decrease in the accumulation of CD4(+) T cells, whereas quantitative polymerase chain reaction analysis of lesion-rich aortic arches demonstrated a marked reduction in mRNA for CXCR3, the CXCL10 chemokine receptor. Although overall T-cell accumulation was diminished significantly, we found evidence to suggest that regulatory T-cell (T-reg) numbers and activity were enhanced, as assessed by increased message for the T-reg-specific marker Foxp3, as well as increases in immunostaining for the T-reg-associated cytokines interleukin-10 and transforming growth factor-beta 1. We also documented naturally occurring Treg cells in human atherosclerotic lesions. Conclusions-We provide novel evidence for a functional role for the effector T-cell chemoattractant CXCL10 in atherosclerotic lesion formation by modulating the local balance of the effector and regulatory arms of the immune system. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp E, Div Cardiol, 149 13th St,8307, Charlestown, MA 02129 USA. EM rgerszten@partners.org OI Moore, kathryn/0000-0003-2505-2547 NR 47 TC 139 Z9 143 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 16 PY 2006 VL 113 IS 19 BP 2301 EP 2312 DI 10.1161/CIRCULATIONAHA.105.605121 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 042TB UT WOS:000237551300010 PM 16682613 ER PT J AU Rogers, JH Macoviak, JA Rahdert, DA Takeda, PA Palacios, IF Low, RI AF Rogers, JH Macoviak, JA Rahdert, DA Takeda, PA Palacios, IF Low, RI TI Percutaneous septal sinus shortening - A novel procedure for the treatment of functional mitral regurgitation SO CIRCULATION LA English DT Article DE cardiomyopathy; catheters; echocardiography; mitral valve; regurgitation ID HEART-FAILURE; DILATED CARDIOMYOPATHY; OVINE MODEL; VALVE REPAIR; ANNULAR REDUCTION; PORCINE MODEL; ANNULOPLASTY; MECHANISM; ECHOCARDIOGRAPHY; FEASIBILITY AB Background-The septal-to-lateral (SL) mitral annular diameter is increased in functional mitral regurgitation (MR). We describe a novel percutaneous technique (the percutaneous septal sinus shortening system) that ameliorates functional MR in an ovine model. Methods and Results-Sheep underwent rapid right ventricular pacing to obtain moderate to severe functional MR with SL enlargement. The percutaneous septal sinus shortening system was placed via standard interventional techniques consisting of a bridge (suture) element between interatrial septal wall and great cardiac vein anchors. Through progressive tensioning of the bridge element, direct SL shortening was achieved. Sheep underwent short-term (n=19) and long-term (n=4) evaluation after device implantation. In short-term studies, SL diameter decreased an average of 24% (32.5 +/- 3.5 to 24.6 +/- 2.4 mm; P < 0.001), and MR grade significantly improved (2.1 +/- 0.6 to 0.4 +/- 0.4; P < 0.001). Despite continued rapid pacing, chronic device implantation resulted in durable SL shortening (30.4 +/- 1.9 mm before implantation to 25.3 +/- 0.8 mm at 30 days; P=0.01) and MR reduction (1.8 +/- 0.5 before implantation to 0.2 +/- 0.1 at 30 days; P=0.01). Increased cardiac output, decreased wedge pressure, and decreased brain natriuretic peptide levels were observed in animals undergoing long-term device implantation. Conclusions-The percutaneous septal sinus shortening system is effective in ameliorating functional MR in an ovine tachycardia model. The procedure, which uses standard catheter techniques, can be deployed largely under fluoroscopic guidance. The unique bridge element appears durable and allows direct and precise SL shortening to a diameter optimal for MR reduction. C1 Univ Calif Davis, Davis Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ample Med Inc, Foster City, CA USA. RP Rogers, JH (reprint author), Univ Calif Davis, Davis Med Ctr, Div Cardiovasc Med, 4860 Y St,Suite 2820, Sacramento, CA 95817 USA. EM jason.rogers@ucdmc.ucdavis.edu NR 27 TC 43 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 16 PY 2006 VL 113 IS 19 BP 2329 EP 2334 DI 10.1161/CIRCULATIONAHA.105.601518 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 042TB UT WOS:000237551300013 PM 16682615 ER PT J AU Gelfand, EV Cannon, CP AF Gelfand, EV Cannon, CP TI Rimonabant: A cannabinoid receptor type 1 blocker for management of multiple cardiometabolic risk factors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DIET-INDUCED OBESITY; CB1 RECEPTORS; SMOKING-CESSATION; ENDOGENOUS CANNABINOIDS; OVERWEIGHT PATIENTS; INDUCED HYPOTENSION; MESENTERIC-ARTERY; WEIGHT-LOSS; ANTAGONIST; RATS AB Rimonabant is a first selective blocker of the cannabinoid receptor type 1 (CB1) being developed for the treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. In four large trials, after one year of treatment, rimonabant 20 mg led to greater weight loss and reduction in waist circumference compared with placebo. Therapy with rimonabant is also associated with favorable changes in serum lipid levels and an improvement in glycemic control in prediabetes patients and in type 2 diabetic patients. At the same dose, rimonabant significantly increased cigarette smoking quit rates as compared with placebo. Rimonabant seems to be well tolerated, with a primary side effect of mild nausea. As an agent with a novel mechanism of action, rimonabant has a potential to be a useful adjunct to lifestyle and behavior modification in treatment of multiple cardiometabolic risk factors, including abdominal obesity and smoking. (J Am Coll Cardiol 2006;47: 1919-26) (c) 2006 by the American College of Cardiology Foundation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med,Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med,Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 68 TC 59 Z9 66 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 16 PY 2006 VL 47 IS 10 BP 1919 EP 1926 DI 10.1016/j.jacc.2005.12.067 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OG UT WOS:000237750800001 PM 16697306 ER PT J AU Smith, GL Lichtman, JH Bracken, MB Shlipak, MG Phillips, CO DiCapua, P Krumholz, HM AF Smith, GL Lichtman, JH Bracken, MB Shlipak, MG Phillips, CO DiCapua, P Krumholz, HM TI Renal impairment and outcomes in heart failure - Systematic review and meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR SYSTOLIC DYSFUNCTION; SERUM CREATININE; NEUROHORMONAL ACTIVATION; PROGNOSTIC IMPORTANCE; KIDNEY-DISEASE; RISK-FACTORS; CYSTATIN-C; INSUFFICIENCY; MORTALITY; ASSOCIATION AB OBJECTIVES We estimated the prevalence of renal impairment in heart failure (HF) patients and the magnitude of associated mortality risk using a systematic review of published studies. BACKGROUND Renal impairment in HF patients is associated with excess mortality, although precise risk estimates are unclear. METHODS A systematic search of MEDLINE (through May 2005) identified 16 studies characterizing the association between renal impairment and mortality in 80,098 hospitalized and non-hospitalized HF patients. All-cause mortality risks associated with any renal impairment (creatinine > 1.0 mg/dl, creatinine clearance [CrCl] or estimated glomerular filtration rate [eGFR] < 90 ml/min, or cystatin-C > 1.03 mg/dl) and moderate to severe impairment (creatinine >= 1.5, CrCl or eGFR < 53, or cystatin-C >= 1.56) were estimated using fixed-effects meta-analysis. RESULTS A total of 63% of patients had any renal impairment, and 29% had moderate to severe impairment. After follow-up >= 1 year, 38% of patients with any renal impairment and 51% with moderate to severe impairment died versus 24% without impairment. Adjusted all-cause mortality was increased for patients with any impairment (hazard ratio [HR] = 1.56; 95% confidence interval [CI] 1.53 to 1.60, p < 0.001) and moderate to severe impairment (HR = 2.31; 95% CI 2.18 to 2.44, p < 0.001). Mortality worsened incrementally across the range of renal function, with 15% (95% CI 14% to 17%) increased risk for every 0.5 mg/dl increase in creatinine and 7% (95% CI 4% to 10%) increased risk for every 10 ml/min decrease in eGFR. CONCLUSIONS Renal impairment is common among HF patients and confers excess mortality. Renal function should be considered in risk stratification and evaluation of therapeutic strategies for HF patients. (J Am Coll Cardiol 2006;47:1987-96) (c) 2006 by the American College of Cardiology Foundation. C1 Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, SHM, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, Med Serv, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Cleveland Clin Fdn, Dept Gen Internal Med, Cleveland, OH 44195 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, SHM, I Wing,Suite 456,333 Cedar St, New Haven, CT 06510 USA. EM harlan.krumholz@yale.edu FU NIGMS NIH HHS [GM07205] NR 36 TC 378 Z9 419 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 16 PY 2006 VL 47 IS 10 BP 1987 EP 1996 DI 10.1016/j.jacc.2005.11.084 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OG UT WOS:000237750800010 PM 16697315 ER PT J AU Hoffmann, U Shapiro, M AF Hoffmann, U Shapiro, M TI Coronary multidetector computed tomography - A new standard for preoperative risk assessment? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM uhoffman@partners.org NR 3 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 16 PY 2006 VL 47 IS 10 BP 2025 EP 2026 DI 10.1016/j.jacc.2006.02.031 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OG UT WOS:000237750800015 PM 16697320 ER PT J AU Whittle, J Kressin, NR Peterson, ED Orner, MB Glickman, M Mazzella, M Petersen, LA AF Whittle, J Kressin, NR Peterson, ED Orner, MB Glickman, M Mazzella, M Petersen, LA TI Racial differences in prevalence of coronary obstructions among men with positive nuclear imaging studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID INVASIVE CARDIOVASCULAR PROCEDURES; ACUTE MYOCARDIAL-INFARCTION; ISCHEMIC-HEART-DISEASE; ASSOCIATION TASK-FORCE; ARTERY BYPASS-SURGERY; OF-VETERANS-AFFAIRS; REVASCULARIZATION PROCEDURES; CARDIAC-CATHETERIZATION; PRACTICE GUIDELINES; STABLE ANGINA AB OBJECTIVES The purpose of this research was to compare coronary obstruction between clinically similar African Americans (AA) and white persons undergoing coronary angiography. BACKGROUND African Americans have higher rates of coronary death than whites, but are less likely to undergo coronary revascularization. Although differences in coronary anatomy do not explain racial difference in revascularization rates, several studies of clinically diverse persons undergoing coronary angiography have found less obstructive coronary disease in AA than clinically similar whites. METHODS We studied 52 AA and 259 white male veterans who had both a positive nuclear perfusion imaging study and coronary angiography within 90 days of that study in five Department of Veterans Affairs hospitals. We used chart review and patient interview to collect demographics, clinical characteristics, and coronary anatomy results. Before angiography, we asked physicians to estimate the likelihood of coronary obstruction. RESULTS The treating physicians' estimates of coronary disease likelihood were similar for AA (79.5%) and whites (83.0%); AA were less likely to have any coronary obstruction (63.5% vs. 76.5%, p = 0.05) and had significantly less severe coronary disease (p = 0.01) than whites. African Americans continued to be less likely to have coronary obstruction in analyses controlling for clinical features, including the physician's estimate of the likelihood of coronary obstruction. CONCLUSIONS These results suggest that AA have less coronary obstruction than apparently clinically similar whites. Further studies are required to confirm our findings and better understand the paradox that AA are less likely to have obstructive coronary disease and more likely to suffer mortality from coronary disease. (J Am Coll Cardiol 2006;47:2034-41) (c) 2006 by the American College of Cardiology Foundation. C1 Zablocki Vet Adm Med Ctr, Primary Care Div, Milwaukee, WI 53295 USA. Med Coll Wisconsin, Dept Med, Div Gen Internal Med, Milwaukee, WI 53226 USA. Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. Univ Kansas, Med Ctr, Div Cardiol, Kansas City, KS 66103 USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Div Hlth Policy & Qual, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Whittle, J (reprint author), Zablocki Vet Adm Med Ctr, Primary Care Div, Mailstop 00 PC,5000 W Natl Ave, Milwaukee, WI 53295 USA. EM jeffirey.whittle@va.gov OI Glickman, Mark/0000-0003-3993-2801; Kressin, Nancy/0000-0003-2767-4286 NR 41 TC 18 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 16 PY 2006 VL 47 IS 10 BP 2034 EP 2041 DI 10.1016/j.jacc.2005.12.059 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OG UT WOS:000237750800017 PM 16697322 ER PT J AU Messas, E Bel, A Morichetti, MC Carrion, C Handschumacher, MD Peyrard, S Vilquin, JT Desnos, M Bruneval, P Carpentier, A Menasche, P Levine, RA Hagege, AA AF Messas, E Bel, A Morichetti, MC Carrion, C Handschumacher, MD Peyrard, S Vilquin, JT Desnos, M Bruneval, P Carpentier, A Menasche, P Levine, RA Hagege, AA TI Autologous myoblast transplantation for chronic ischemic mitral regurgitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol ID 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION; PAPILLARY-MUSCLE DYSFUNCTION; LEFT-VENTRICULAR DYSFUNCTION; HEART-FAILURE; MYOCARDIAL-INFARCTION; MECHANISM; INSIGHTS; VALVE; ANNULOPLASTY; PERFORMANCE AB OBJECTIVES This study was designed to assess whether post-myocardial infarction (MI) in-scar transplantation of skeletal myoblasts (SM) could reduce chronic ischemic mitral regurgitation (MR) by decreasing left ventricular (LV) remodeling. BACKGROUND Extensive work has confirmed the relationship between ischemic MR and post-myocardial infarction (MI) remodeling of the LV. METHODS An infero-posterior MI was created in 13 sheep, thereby resulting in increasing MR. Two months post-MI, the animals were randomized and in-scar injected with expanded autologous SM (n = 6, mean: 251 X 106 cells) or culture medium only (n = 7). Three-dimensional echocardiography was performed at baseline, before transplantation, and for two months thereafter (sacrifice), with measurements of LV end-diastolic and end-systolic volumes (ESV), ejection fraction (EF), MR stroke volume, and leaflet tethering distance; wall motion score index (NVMSi) was assessed by two-dimensional echo. RESULTS Measurements were similar between groups at baseline and before transplantation. At sacrifice, transplantation was found to have reduced MR progression (regurgitant volume change: -1.83 +/- 0.32 ml vs. 5.9 +/- 0.7 ml in control group, p < 0.0001) and tethering distance (-0.41 +/- 0.09 cm vs. 0.44 +/- 0.12 cm in control group, p < 0.001), with significant improvement of EF (2.01 +/- 0.94% vs. -4.86 +/- 2.23%, p = 0.02), WMSi (-0.25 +/- 0.11 vs. 0.13 +/- 0.03 in controls, p < 0.01) and a trend to a lesser increase in ESV (23.3 +/- 3.5 ml vs. 35.4 +/- 4.2 ml in control group, p = 0.055). CONCLUSIONS Autologous skeletal myoblast transplantation attenuates mild-to-moderate chronic ischemic MR, which otherwise is progressive, by decreasing tethering distance and improving EF and wall motion score, thereby enhancing valve coaptation. These data shed additional light on the mechanism by which skeletal myoblast transplantation may be cardioprotective. (J Am Coll Cardiol 2006,47:2086-93) (c) 2006 by the American College of Cardiology Foundation. C1 Hop Broussais, INSERM U633, Dept Cardiol, Hop Europeen Georges Pompidou, F-75014 Paris, France. Univ Paris 05, Fac Med Rene Descartes, Paris, France. INSERM U633, Paris, France. Ecole Chirurg, Paris, France. Grp Hosp Pitie Salpetriere, Inst Myol, INSERM U582, Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA USA. Clin Invest Ctr 92010 INSERM, Paris, France. INSERM U430, Dept Pathol, Paris, France. RP Messas, E (reprint author), Hop Broussais, INSERM U633, Dept Cardiol, Hop Europeen Georges Pompidou, 6 Rue Didot, F-75014 Paris, France. EM emmanuel.messas@nck.aphp.fr FU NHLBI NIH HHS [R21 HL 72353, R01 HL38176]; PHS HHS [K24 67434] NR 38 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 16 PY 2006 VL 47 IS 10 BP 2086 EP 2093 DI 10.1016/j.jacc.2005.12.063 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045OG UT WOS:000237750800024 PM 16697329 ER PT J AU Ji, HB Zhao, XJ Yuza, Y Shimamura, T Li, DN Protopopov, A Jung, BL McNamara, K Xia, HL Glatt, KA Thomas, RK Sasaki, H Horner, JW Eck, M Mitchell, A Sun, YP Al-Hashem, R Bronson, RT Rabindran, SK Discafani, CM Maher, E Shapiro, GI Meyerson, M Wong, KK AF Ji, Hongbin Zhao, Xiaojun Yuza, Yuki Shimamura, Takeshi Li, Danan Protopopov, Alexei Jung, Boonim L. McNamara, Kate Xia, Huili Glatt, Karen A. Thomas, Roman K. Sasaki, Hidefumi Horner, James W. Eck, Michael Mitchell, Albert Sun, Yangping Al-Hashem, Ruqayyah Bronson, Roderick T. Rabindran, Sriclhar K. Discafani, Carolyn M. Maher, Elizabeth Shapiro, Geoffrey I. Meyerson, Matthew Wong, Kwok-Kin TI Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE irreversible inhibitor; lung cancer; lung squamous cell carcinoma ID CONDITIONAL EXPRESSION; ACQUIRED-RESISTANCE; HUMAN GLIOBLASTOMAS; GENE-MUTATIONS; HUMAN CANCERS; EGF RECEPTOR; K-RAS; GEFITINIB; ERLOTINIB; ADENOCARCINOMAS AB The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2-7, is commonly found. In this study, we determined that EGFRvIII mutation was present in 5% (3/56) of analyzed human lung squamous cell carcinoma (SCC) but was not present in human lung adenocarcinoma (0/123). We analyzed the role of the EGFRvIII mutation in lung tumorigenesis and its response to tyrosine kinase inhibition. Tissue-specific expression of EGFRvIII in the murine lung led to the development of NSCLC. Most importantly, these lung tumors depend on EGFRvIII expression for maintenance. Treatment with an irreversible EGFR inhibitor, HKI-272, dramatically reduced the size of these EGFRvIII-driven murine tumors in 1 week. Similarly, Ba/F3 cells transformed with the EGFRvIII mutant were relatively resistant to gefitinib and erlotinib in vitro but proved sensitive to HKI-272. These findings suggest a therapeutic strategy for cancers harboring the EGFRvIII mutation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Nagoya City Univ, Sch Med, Dept Surg, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Wyeth Ayerst Res, Oncol Res, Pearl River, NY 10965 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu; kwong1@partners.org RI Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [P20 CA090578, P20 CA90578, R01 CA 90687, R01 CA090687]; NIA NIH HHS [K08AG 2400401] NR 38 TC 180 Z9 196 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 16 PY 2006 VL 103 IS 20 BP 7817 EP 7822 DI 10.1073/pnas.0510284103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 046UF UT WOS:000237835900052 PM 16672372 ER PT J AU Ligon, KL Kesari, S Kitada, M Sun, T Arnett, HA Alberta, JA Anderson, DJ Stiles, CD Rowitch, DH AF Ligon, KL Kesari, S Kitada, M Sun, T Arnett, HA Alberta, JA Anderson, DJ Stiles, CD Rowitch, DH TI Development of NG2 neural progenitor cells requires Olig gene function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cspg4; oligodendrocyte; synantocyte; glia; regeneration ID CENTRAL-NERVOUS-SYSTEM; DORSAL SPINAL-CORD; NG2-EXPRESSING CELLS; SUBVENTRICULAR ZONE; PRECURSOR CELLS; SURFACE-ANTIGEN; IN-VITRO; BRAIN; CNS; OLIGODENDROCYTES AB In the adult central nervous system, two distinct populations of glial cells expressing the chondroitin sulfate proteoglycan NG2 have been described: bipolar progenitor cells and more differentiated "synantocytes." These cells have diverse neurological functions, including critical roles in synaptic transmission, repair, and regeneration. Despite their potential importance, the genetic factors that regulate NG2 cell development are poorly understood, and the relationship of synantocytes to the oligodendroglial lineage, in particular, remains controversial. Here, we show that > 90% of embryonic and adult NG2 cells express Olig2, a basic helix-loop-helix transcription factor required for oligodendrocyte lineage specification. Analysis of mice lacking Olig function demonstrates a failure of NG2 cell development at embryonic and perinatal stages that can be rescued by addition of a transgene containing the human OLIG2 locus. These findings show a general requirement for Olig function in NG2 cell development and highlight further roles for Olig transcription factors in neural progenitor cells. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. CALTECH, Howard Hughes Med Inst, Div Biol, Pasadena, CA 91125 USA. RP Ligon, KL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM keith_ligon@dfci.harvard.edu; david_rowitch@dfci.harvard.edu RI Kesari, Santosh/E-8461-2013 FU NINDS NIH HHS [K08 NS047213, K08NS047213, R01 NS040511, R01NS40511] NR 35 TC 133 Z9 141 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 16 PY 2006 VL 103 IS 20 BP 7853 EP 7858 DI 10.1073/pnas.0511001103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 046UF UT WOS:000237835900058 PM 16682644 ER PT J AU Thompson, RR George, K Walton, JC Orr, SP Benson, J AF Thompson, RR George, K Walton, JC Orr, SP Benson, J TI Sex-specific influences of vasopressin on human social communication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE affiliation; aggression; anxiety; autism; emotion ID PAIR-BOND FORMATION; VOLES MICROTUS-OCHROGASTER; PRAIRIE VOLES; BEHAVIORAL-RESPONSE; HUMAN-BRAIN; OXYTOCIN; NEUROENDOCRINE; SEPTUM; AUTISM; NEUROPEPTIDES AB Arginine vasopressin (AVP) and related peptides affect social behaviors innumerous species, but AVP influences on human social functions have not yet been established. Here, we describe how intranasal AVP administration differentially affects social communication in men and women, and we propose a mechanism through which it may exert those influences. In men, AVIP stimulates agonistic facial motor patterns in response to the faces of unfamiliar men and decreases perceptions of the friendliness of those faces. In contrast, in women, AVP stimulates affiliative facial motor patterns in response to the faces of unfamiliar women and increases perceptions of the friendliness of those faces. AVP also affected autonomic responsiveness to threatening faces and increased anxiety, which may underlie both communication patterns by promoting different social strategies in stressful contexts in men and women. C1 Bowdoin Coll, Dept Psychol, Brunswick, ME 04011 USA. Bowdoin Coll, Neurosci Program, Brunswick, ME 04011 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. Vet Affairs Med Ctr, Manchester, NH 03104 USA. RP Thompson, RR (reprint author), Bowdoin Coll, Dept Psychol, Brunswick, ME 04011 USA. EM rthompso@bowdoin.edu RI Walton, James/F-7435-2010; chen, xuanlan/H-4158-2011 OI Walton, James/0000-0002-3049-1029; FU NIMH NIH HHS [R03 MH063996, R03MH063996-01A] NR 34 TC 162 Z9 164 U1 3 U2 20 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 16 PY 2006 VL 103 IS 20 BP 7889 EP 7894 DI 10.1073/pnas.0600406103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 046UF UT WOS:000237835900064 PM 16682649 ER PT J AU Gibson, CM Karmpaliotis, D Kosmidou, L Murphy, SA Kirtane, AJ Budiu, D Ray, KK Herrmann, HC Lakkis, N Kovach, R French, W Blankenship, J Lui, HH Palabrica, T Jennings, LK Cohen, DJ Morrow, DA AF Gibson, CM Karmpaliotis, D Kosmidou, L Murphy, SA Kirtane, AJ Budiu, D Ray, KK Herrmann, HC Lakkis, N Kovach, R French, W Blankenship, J Lui, HH Palabrica, T Jennings, LK Cohen, DJ Morrow, DA CA TIMI Study Grp TI Comparison of effects of bare metal versus drug-eluting stent implantation on biomarker levels following percutaneous coronary intervention for non-ST-elevation acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; TIMI FRAME COUNT; TROPONIN-I; ATORVASTATIN; ANGIOPLASTY; MORTALITY AB Drug-eluting stents (DESs) deliver biphasic (early and late) elution of, anti-inflammatory compounds. We therefore hypothesized that DESs would be associated with early reductions in inflammatory biomarker release after percutaneous coronary intervention (PCI). A total of 741 patients with non-ST-elevation acute coronary syndrome underwent PCI in the Randomized Trial to Evaluate the Relative PROTECTion against Post-PCI Microvascular Dysfunction and Post-PCI Ischemia among Anti-Platelet and Anti-Thrombotic Agents (PROTECT) Thrombolysis In Myocardial Infarction 30 study of eptifibatide and reduced-dose antithrombin compared with bivalirudin. Serial biomarkers C-reactive protein, troponin, creatine kinase-MB, soluble CD40 ligand, interleukin-6, prothrombin fragment F1.2, and RANTES (regulated on activation, normal T-cell expressed and secreted) were assessed through 24 hours after PCI. DES use was at the investigator's discretion. Patients treated with DESs (n = 665) versus bare metal stents (n = 139) were more likely to have patent arteries before PCI (92.0% vs 86.6%, p = 0.04), Thrombolysis In Myocardial Infarction myocardial perfusion grade 3 (57.9% vs 47.7%, p = 0.033), and the left anterior descending artery as the culprit artery (38.5% vs 18.3%, p < 0.001). The increase in C-reactive protein and troponin was lower among patients undergoing DES implantation (median 2.1 vs 3.5 mg/L for C-reactive protein, median 0.11 vs 0.41 ng/ml for troponin), even after adjustment for randomized treatment, clopidogrel before treatment, diabetes mellitus status, epicardial patency, left anterior descending artery. location, and myocardial perfusion (p = 0.036 and p = 0.039, respectively). Interleukin-6 was lower with DESs on univariate analysis but not multivariate analysis. Creatine kinase-MB, soluble sCD40 ligand, prothrombin fragment F1.2, and RANTES did not differ by DES use. In conclusion, patients undergoing DES implantation achieved more reductions in periprocedural markers of inflammation and necrosis than patients receiving bare metal stents among those with non-ST-elevation acute coronary syndrome. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Ben Taub Gen Hosp, Houston, TX 77030 USA. Associated Cardiovasc Consultants New Jersey, Cherry Hill, NJ USA. Harbor UCLA Med Ctr, Torrance, CA USA. Geisinger Med Ctr, Danville, PA 17822 USA. Apex Cardiol, Jackson, TN USA. Millennium Pharmaceut, Cambridge, MA USA. Univ Tennessee, Nashville, TN USA. RP Gibson, CM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. EM mgibson@timi.org NR 18 TC 28 Z9 33 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2006 VL 97 IS 10 BP 1473 EP 1477 DI 10.1016/j.amjcard.2005.12.037 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044YC UT WOS:000237708600011 PM 16679086 ER PT J AU Fox, CS Guo, CY Larson, MG Vasan, RS Parise, H O'Donnell, CJ D'Agostino, RB Keaney, JF Benjamin, EJ AF Fox, CS Guo, CY Larson, MG Vasan, RS Parise, H O'Donnell, CJ D'Agostino, RB Keaney, JF Benjamin, EJ TI Relations of inflammation and novel risk factors to valvular calcification SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NONRHEUMATIC AORTIC-STENOSIS; CARDIAC-VALVE CALCIFICATION; T-LYMPHOCYTE INFILTRATION; CORONARY HEART-DISEASE; STAGE RENAL-DISEASE; ASSOCIATION; EXPRESSION AB Investigators have suggested that inflammation may play a role in the pathogenesis of valve calcium. Participants in the Framingham Heart Study's offspring cohort had systemic levels of C-reactive protein, intercellular adhesion molecule-1, interleukin-6, and monocyte chemoattractant protein-1 measured at examination cycle 7. Mitral annular calcium, aortic annular calcium, aortic sclerosis, and aortic stenosis were assessed by echocardiography at examination cycle 6. Logistic regression was used to examine the odds of valvular calcium per 1 unit increase in inflammation (ISUM), a summary statistic of all normalized deviates of the individual markers. Two thousand six hundred eighty-three participants (mean age 61 +/- 10 years; 52% women) were analyzed: 8.2% (n = 216) had 1 calcified valve or annulus; 89 had mitral annular calcium, 78 had aortic annular calcium, 135 had aortic sclerosis, and 33 had aortic stenosis. Participants with valvular calcium were older and were more likely to have hypertension and diabetes mellitus. Participants with valve calcium had higher median levels of all markers. For each log unit increase in ISUM, after adjustment for age and gender, there was an associated 1.1-fold increased odds of >= 1 calcified valve (p = 0.02); the odds ratios were no longer significant after adjustment for cardiovascular disease risk factors (odds ratio 1.0, 95% confidence interval 0.9 to 1.1). Similar results were obtained for the individual markers and the odds of >= 1 calcified valve. In conclusion, inflammatory markers were elevated in patients with valvular calcium. Our findings suggest that much of the observed association between systemic inflammatory markers and valvular calcium may be due to shared risk factors. (c) 2006 Elsevier Inc. All rights reserved. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Diabet Endocrinol & Metab, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [R01 HL076784, K24-HL-04334, N01-HC-25195, R01 HL64753]; NINDS NIH HHS [6R01-NS-17950] NR 20 TC 30 Z9 33 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2006 VL 97 IS 10 BP 1502 EP 1505 DI 10.1016/j.amjcard.2005.11.086 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044YC UT WOS:000237708600018 PM 16679093 ER PT J AU Yoerger, DM Picard, MH Palacios, IF Vlahakes, GJ Lowry, PA Fifer, MA AF Yoerger, DM Picard, MH Palacios, IF Vlahakes, GJ Lowry, PA Fifer, MA TI Time course of pressure gradient response after first alcohol septal ablation for obstructive hypertrophic cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; VENTRICULAR OUTFLOW TRACT; FOLLOW-UP; TRANSCORONARY ABLATION; REDUCTION THERAPY; SERIES AB Alcohol septal ablation (ASA) causes remodeling of the upper septum and left ventricular outflow tract (LVOT) and reduction in the LVOT gradient. The time course of gradient reduction early after ASA has not been established. This study characterized the time course of gradient response early after ASA. Patients underwent clinical assessment and transthoracic echocardiography at baseline and immediately, 3 days, 3 months, and I year after ASA. Forty-seven patients underwent ASA. The baseline LVOT gradient was 98 +/- 48 mm Hg. Three-month echocardiographic success, defined as >= 50% gradient reduction from baseline, was achieved in 41 procedures (87%); thus, there were 6 failures. On the basis of percentage reduction in LVOT gradient at 3 days, 2 distinct subgroups of the success group were identified. These were monophasic success (>= 50% gradient reduction at 3 days and 3 months, n = 25) and triphasic success (< 50% gradient reduction at 3 days but >= 50% gradient reduction at 3 months, n = 16). LVOT gradient in the triphasic success group was similar to that in the failure group at 3 days (81 +/- 28 vs 99 +/- 31 mm Hg, p = NS) but similar to that of the monophasic success group at 3 months (24 +/- 20 vs 12 +/- 16 mm Hg, p = NS) and at 1 year (27 +/- 24 vs 13 +/- 20 mm Hg, p = NS). In conclusion, many patients who undergo ultimately successful ASA demonstrate triphasic LVOT gradient response patterns, with a large gradient 3 days after the procedure. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yoerger, DM (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM dyoerger@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 17 TC 29 Z9 30 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2006 VL 97 IS 10 BP 1511 EP 1514 DI 10.1016/j.amjcard.2005.12.040 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 044YC UT WOS:000237708600020 PM 16679095 ER PT J AU Bookman, EB Langehorne, AA Eckfeldt, JH Glass, KC Jarvik, GP Klag, M Koski, G Motulsky, A Wilfond, B Manolio, TA Fabsitz, RR Luepker, RV AF Bookman, EB Langehorne, AA Eckfeldt, JH Glass, KC Jarvik, GP Klag, M Koski, G Motulsky, A Wilfond, B Manolio, TA Fabsitz, RR Luepker, RV TI Reporting genetic results in research studies: Summary and recommendations of an NHLBI working group SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material DE research results; genetic testing; reporting research results ID CHILDRENS ONCOLOGY GROUP; RESEARCH PARTICIPANTS; INFORMED-CONSENT; ATTITUDES; POPULATION; TRIAL; ASSOCIATION; ISSUES; NEEDS AB Prospective epidemliologic studies aid in identifying genetic variants associated with diseases, health risks, and phhysiologic traits. These genetic variants may eventually be measured clinically for purposes of diagnosis, prognosis, and treatment. As evidence of the Potential clinical value of such information accrues, research studies face growing pressure to report these results to study participants or their physicians, even before sufficient evidence is available to support widespread screening of asymptomatic persons. There is thus a need to begin to develop consensus on whether and when genetic findings should be reported to participants in research studies. The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group on Reporting Genetic Resuls in Research Studies to discuss if, when, and how genetic information should be reported to study participants. The Working Group concluded that genetic test results should he reported to study participants when the associated risk for the disease is significant; the disease has important health inifilications such as premature death or substantial morbidity or has significant reproductive implications and proven therapeutic or preventive interventions are available. Finally, the working group recommended procedures for reporting genetic research results and encouraged increased efforts to create uniform guidelines for this activity. Published 2006 Wiley-Liss, Inc. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. NHLBI, Biomed Res Training Program Underrepresented Mino, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. McGill Univ, Dept Human Genet & Pediat, Montreal, PQ, Canada. Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Johns Hopkins Univ, Dept Internal Med, Baltimore, MD USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. RP Bookman, EB (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,Room 8166, Bethesda, MD 20892 USA. EM bookmane@mail.nih.gov RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU Intramural NIH HHS [Z99 HG999999] NR 34 TC 121 Z9 121 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY 15 PY 2006 VL 140A IS 10 BP 1033 EP 1040 DI 10.1002/ajmg.a.31195 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 037TW UT WOS:000237171100001 PM 16575896 ER PT J AU Ho, NH Weissleder, R Tung, CH AF Ho, NH Weissleder, R Tung, CH TI Development of a dual fluorogenic and chromogenic dipeptidyl peptidase IV substrate SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE dipeptidyl peptidases DPP-IV; fluorogenic; chromogenic; fluorescent assay ID INHIBITION; VIOLET; RATS; PRO AB A new far-red dual fluorogenic and chromogenic substrate, 5-glycylprolylglycylprolyl-9-di-3-sulfonyl-propylaminobenza[a]phenoxazonium perchlorate (GPGP-2SBPO), wits developed for dipeptidyl peptidase IV (DPP-IV) sensing. The glycylprolylglycylprolyl tetrapeptide was chosen as the recognition sequence due to its stability under physiological conditions. In contrast, the truncated substrate, GP-2SBPO, containing only a glycylprolyl peptide, is unstable. Proteolysis of GPGP-2SBPO was assayed by monitoring the absorbance and fluorescence signals from the released fluorochrome, 2SBPO, at 625 and 670 nm, respectively. (C) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01 CA99385, R21 CA114149] NR 12 TC 22 Z9 22 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 15 PY 2006 VL 16 IS 10 BP 2599 EP 2602 DI 10.1016/j.bmcl.2006.02.045 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 033IE UT WOS:000236839700006 PM 16517162 ER PT J AU Schulze, H Korpal, M Hurov, J Kim, SW Zhang, JH Cantley, LC Graf, T Shivdasani, RA AF Schulze, H Korpal, M Hurov, J Kim, SW Zhang, JH Cantley, LC Graf, T Shivdasani, RA TI Characterization of the megakaryocyte demarcation membrane system and its role in thrombopoiesis SO BLOOD LA English DT Article ID PHOSPHATIDYLINOSITOL PHOSPHATE KINASE; PLECKSTRIN-HOMOLOGY-DOMAIN; TRANSCRIPTION FACTOR NF-E2; PLATELET FORMATION; BLOOD-PLATELETS; ARP2/3 COMPLEX; N-WASP; PROPLATELET FORMATION; RAT MEGAKARYOCYTES; ACTIN NUCLEATION AB To produce blood platelets, megakaryocytes elaborate proplatelets, accompanied by expansion of membrane surface area and dramatic cytoskeletal rearrangements. The invaginated demarcation membrane system (DMS), a hallmark of mature cells, has been proposed as the source of proplatelet membranes. By direct visualization of labeled DMS, we demonstrate that this is indeed the case. Late in megakaryocyte ontogeny, the DMS gets loaded with PI-4,5-P-2, a phospholipid that is confined to plasma membranes in other cells. Appearance of PI-4,5-P-2 in the DMS occurs in proximity to PI-5-P-4-kinase alpha (PIP4K alpha), and short hairpin (sh) RNA-mediated loss of PIP4K alpha impairs both DMS development and expansion of megakaryocyte size. Thus, PI-4,5-P-2 is a marker and possibly essential component of internal membranes. PI-4,5-P-2 is known to promote actin polymerization by activating Rho-like GTPases and Wiskott-Aldrich syndrome (WASp) family proteins. Indeed, PI-4,5-P-2 in the megakaryocyte DMS associates with filamentous actin. Expression of a dominant-negative N-WASp fragment or pharmacologic inhibition of actin polymerization causes similar arrests in proplatelet formation, acting at a step beyond expansion of the DMS and cell mass. These observations collectively suggest a signaling pathway wherein PI-4,5-P-2 might facilitate DMS development and local assembly of actin fibers in preparation for platelet biogenesis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014; Graf, Thomas/B-4252-2015 OI Cantley, Lewis/0000-0002-1298-7653; Graf, Thomas/0000-0003-2774-4117 FU NHLBI NIH HHS [R01 HL 63143] NR 58 TC 97 Z9 100 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2006 VL 107 IS 10 BP 3868 EP 3875 DI 10.1182/blood-2005-07-2755 PG 8 WC Hematology SC Hematology GA 043FD UT WOS:000237584500018 PM 16434494 ER PT J AU Hideshima, T Catley, L Yasui, H Ishitsuka, K Raje, N Mitsiades, C Podar, K Munshi, NC Chauhan, D Richardson, PG Anderson, KC AF Hideshima, T Catley, L Yasui, H Ishitsuka, K Raje, N Mitsiades, C Podar, K Munshi, NC Chauhan, D Richardson, PG Anderson, KC TI Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells SO BLOOD LA English DT Article ID MALIGNANT PLASMA-CELLS; PROTEIN-KINASE CASCADE; RESISTANCE CAM-DR; N-TERMINAL KINASE; SIGNALING CASCADES; HEMATOLOGIC MALIGNANCIES; COMBINATION CHEMOTHERAPY; THERAPEUTIC IMPLICATIONS; MOLECULAR-MECHANISMS; INDUCED APOPTOSIS AB Perifosine is a synthetic novel alkylphos-pholipid, a new class of antitumor agents which targets cell membranes and inhibits Akt activation. Here we show that baseline phosphorylation of Akt in multiple myeloma (MM) cells is completely inhibited by perifosine [octadecyl-(1,1-d imethyl-piperidinio-4-yl)-phosphate] in a time- and dose-dependent fashion, without inhibiting phosphoinositide-dependent protein kinase 1 phosphorylation. Perifosine induces significant cytotoxicity in both MM cell lines and patient MM cells resistant-to conventional therapeutic agents. Perifosine does not induce cytotoxicity in peripheral blood mono-nuclear cells. Neither exogenous interleukin-6 (IL-6) nor insulinlike growth factor 1 (IGF-1) overcomes Perifosine-induced cytotoxicity. Importantly, Perifosine induces apoptosis even of MM cells adherent to bone marrow stromal cells. Perifosine triggers c-Jun N-terminal kinase (JNK) activation, followed by caspase-8/9 and poly (ADP)-ribose polymerase cleavage. Inhibition of JNK abrogates perifosine-induced cytotoxicity, suggesting that JNK plays an essential role in perifosine-induced apoptosis. Interestingly, phosphorylation of extracellular signal-related kinase (ERK) is increased by perifosine; conversely, MEK inhibitor syn-ergistically enhances Perifosine-induced cytotoxicity in MM cells. Furthermore, perifosine augments dexamethasone, doxorubicin, melphalan, and bortezomib-induced MM cell cytotoxicity. Finally, perifosine demonstrates significant antitumor activity in a human plasmacytoma mouse model, associated with down-regulation of Akt phosphorylation in tumor cells. Taken together, our data provide the rationale for clinical trials of perifosine to improve patient outcome in MM. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston Vet Adm VA Healthcare Syst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU NCI NIH HHS [IP50 CA 10070, R01 CA 50947]; PHS HHS [P01 78378] NR 61 TC 279 Z9 286 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2006 VL 107 IS 10 BP 4053 EP 4062 DI 10.1182/blood-2005-08-3434 PG 10 WC Hematology SC Hematology GA 043FD UT WOS:000237584500042 PM 16418332 ER PT J AU Levine, RL Belisle, C Wadleigh, M Zahrieh, D Lee, S Chagnon, P Gilliland, DG Busque, L AF Levine, RL Belisle, C Wadleigh, M Zahrieh, D Lee, S Chagnon, P Gilliland, DG Busque, L TI X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and NIMM patients with clonal hematopoiesis SO BLOOD LA English DT Article ID TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA; CHROMOSOME INACTIVATION; V617F MUTATION; PATTERNS; DISEASE; CELL; AGE AB The JAK2V617F mutation is present in most patients with polycythemia vera (PV) and in some patients with essential thrombocythemia (ET) and myelold metaplasia/myelofibrosis (MMM). We sought to investigate the relationship between granulocyte clonality and JAK2V617F allelic ratio. A total of 168 of 190 female patients were informative for a clonality assay at the HUMARA locus; 80% of MMM, 75% of PV, and 67% of ET patients demonstrated clonal granulopoiesis. The JAK2V617F allele was detected by quantitative real-time polymerase chain reaction (PCR) in 99% of PV, 72% of ET, and 39% of MMM. A correlation between clonality and JAK2V617F allelic ratio was demonstrated for PV (P < .001) but not for ET or MMM (both P > .6). These data suggest that acquisition of the JAK2V617F mutation may be sufficient for the development of PV, but additional genetic events are necessary in ET and MMM. In addition, some ET and MMM patients with clonal granulopoiesis have somatic mutations other than JAK2V617F. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Montreal, Hop Maison Neuve Rosemont, Montreal, PQ, Canada. RP Busque, L (reprint author), Hop Maison Neuve Rosemont, Dept Hematol, Ctr Rech Guy Bernier, 5415 Boul Assompt, Montreal, PQ H1T 2M4, Canada. EM lbusque.hmr@ssss.gouv.qc.ca FU NCI NIH HHS [CA 66996]; NIDDK NIH HHS [DK 50654] NR 19 TC 157 Z9 175 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2006 VL 107 IS 10 BP 4139 EP 4141 DI 10.1182/blood-2005-09-3900 PG 3 WC Hematology SC Hematology GA 043FD UT WOS:000237584500052 PM 16434490 ER PT J AU Wakelee, HA Bernardo, P Johnson, DH Schiller, JH AF Wakelee, HA Bernardo, P Johnson, DH Schiller, JH TI Changes in the natural history of nonsmall cell lung cancer (NSCLC) - Comparison of outcomes and characteristics in patients with advanced NSCLC entered in Eastern Cooperative Oncology Group trials before and after 1990 SO CANCER LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol DE nonsmall cell lung cancer; prognosis; survival; natural history; demographics; chemotherapy ID PHASE-III TRIAL; QUALITY-OF-LIFE; RANDOMIZED-TRIAL; COMBINATION CHEMOTHERAPY; ELDERLY-PATIENTS; SUPPORTIVE CARE; CLINICAL-TRIALS; PLUS CISPLATIN; SINGLE-AGENT; TIME TRENDS AB BACKGROUND. Demographic factors and treatment regimens were evaluated in relation to differences in outcome between patients with advanced nonsmall cell lung cancer (NSCLC) who were diagnosed and treated on Eastern Cooperative Oncology Group Phase II and III trials from 1981 to 1990 and from 1991 to 2000. METHODS. In this retrospective analysis, 6 advanced NSCLC trials were identified between 1981 and 1990, and 3 trials were identified after 1990. Patient characteristics (n = 3398 patients) and other clinical outcomes were analyzed, including progression-free Survival (PIPS) and overall Survival (OS). RESULTS. Patients who entered oil trials after 1990 more likely were women, received a cisplatin-containing regimen, had a performance status of 0 or 1, had Stage IIIB (vs. Stage IV) disease, had tumors with adenocarcinoma histology, had weight loss <= 10%, and had pulmonary-only metastases (although more total metastases and brain metastases) compared with patients who were diagnosed before 1990. OS was longer post-1990 than pre-1990 (8.2 months vs. 5.8 months pre-1990), and PFS was longer post-1990 (3.5 months vs. 2.6 months pre-1990; P <.001 for both). In addition, the median interval from the date of disease progression to death increased by nearly 62% in the later decade. CONCLUSIONS. improved survival in more recent NSCLC trials was explained in part by the enrollment of patients with more favorable prognostic factors. A change in the natural history of the disease was reflected by some of these changes, including increased numbers of women with the disease and changes in the patterns of metastases. Changes in eligibility criteria also accounted for some improvements in prognostic factors and improved second line therapies in the later decade. Thus, the survival improvements are likely to be multifactorial, with improved therapies also playing a major role. C1 Stanford Univ, Dept Med, Div Med Oncol, Stanford Canc Ctr, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Vanderbilt Univ, Div Med Oncol, Dept Med, Nashville, TN USA. Univ Wisconsin, Div Med Oncol, Dept Med, Madison, WI USA. RP Wakelee, HA (reprint author), Stanford Univ, Dept Med, Div Med Oncol, Stanford Canc Ctr, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM hwakelee@stanford.edu RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA-23318] NR 42 TC 42 Z9 42 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 2006 VL 106 IS 10 BP 2208 EP 2217 DI 10.1002/cncr.21869 PG 10 WC Oncology SC Oncology GA 039CR UT WOS:000237278300016 PM 16604529 ER PT J AU Wu, JY Lu, H Sun, Y Graham, DY Cheung, HS Yamaoka, Y AF Wu, JY Lu, H Sun, Y Graham, DY Cheung, HS Yamaoka, Y TI Balance between polyoma enhancing activator 3 and activator protein 1 regulates Helicobacter pylori - Stimulated matrix metalloproteinase 1 expression SO CANCER RESEARCH LA English DT Article ID GASTRIC EPITHELIAL-CELLS; COLLAGENASE MATRIX METALLOPROTEINASE-1; C-FOS; PATHOGENICITY ISLAND; INTERSTITIAL COLLAGENASE; GENE-EXPRESSION; MAP KINASE; TRANSCRIPTION FACTORS; PROMOTER ACTIVATION; SIGNAL-TRANSDUCTION AB Helicobacter pylori infection and elevated expression of tissue matrix metalloproteinase I (I IMP-l) are both associated with gastric cancer. We investigated the regulation of MMP-1 expression during H. pylori infection. Real-time reverse transcription-PCR was used to examine mucosal MMP-1 mRNA levels in 55 patients with gastric cancers and 61 control patients. Increased MMP-1 mRNA levels in the gastric mucosa and epithelial cells were observed in H. pylori infections in which both the cag pathogenicity island (PAI) and outer inflammatory protein A (OipA) were expressed. The combined induction of c-fos, c-jun, and Polyoma enhancing activator-3 (pea-3) by H. pylori caused maximal increase in MMP-1 expression. Activation of the MMP-1 promoter by H. pylori involved occupation of the activator protein 1 (AP-1) sites at -72 and -181 and, surprisingly, vacancy of the -88 PEA-3 site. Electrophoretic mobility shift, supershift, and chromatin immunoprecipitation assays showed increased binding of c-Fos and c-Jun to the -72 and -181 AP-1 sites during H. pylori infection. Importantly, during wild-type H. pylori infection, we detected increased PEA-3 binding to the -72 AP-1 site and decreased PEA-3 binding to the -88 PEA-3 site. However, during infection with the cag PAI and oipA mutants, PEA-3 binding to the-88 site was detected. MMP-1 and pea-3 activities are increased in gastric cancers. Maximal activation of MMP-1 transcription requires the cag PAI and OipA, which regulate AP-1 and PEA-3 binding. Thus, cag PAI and OipA provide a possible link between bacterial virulence factors and important host factors related to disease pathogenesis. C1 DeBakey Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Kaohsiung Med Univ Hosp, Dept Med, Kaohsiung, Taiwan. Shanghai Renji Hosp, Shanghai, Peoples R China. Shanghai Inst Digest Dis, Shanghai, Peoples R China. Miami Univ, Sch Med, Dept Med, Miami, FL USA. RP Yamaoka, Y (reprint author), DeBakey Vet Affairs Med Ctr 111D, Dept Med, Room 3A-320,2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [R01 DK062813, DK56338, R01 DK062813-03, DK62813, P30 DK056338] NR 45 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2006 VL 66 IS 10 BP 5111 EP 5120 DI 10.1158/0008-5472.CAN-06-0383 PG 10 WC Oncology SC Oncology GA 044NS UT WOS:000237679900019 PM 16707434 ER PT J AU Dohadwala, M Yang, SC Luo, J Sharma, S Batra, RK Huang, M Lin, Y Goodglick, L Krysan, K Fishbein, MC Hong, L Lai, C Cameron, RB Gemmill, RM Drabkin, HA Dubinett, SM AF Dohadwala, M Yang, SC Luo, J Sharma, S Batra, RK Huang, M Lin, Y Goodglick, L Krysan, K Fishbein, MC Hong, L Lai, C Cameron, RB Gemmill, RM Drabkin, HA Dubinett, SM TI Cyclooxygenase-2-dependent regulation of E-cadherin: Prostaglandin E-2 induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; EPITHELIAL-MESENCHYMAL TRANSITIONS; PROGNOSTIC-SIGNIFICANCE; BETA-CATENIN; GENE-EXPRESSION; DOWN-REGULATION; TUMOR-CELLS; INHIBITION; ADHESION; SENSITIVITY AB Elevated tumor cyclooxygenase-2 (COX-2) expression is associated with tumor invasion, metastasis, and poor prognosis in non-small cell lung cancer (NSCLC). Here, we report that COX-2-dependent pathways contribute to the modulation of E-cadherin expression in NSCLC. First, whereas genetically modified COX-2-sense (COX-2-S) NSCLC cells expressed low E-cadherin and showed diminished capacity for cellular aggregation, genetic or pharmacologic inhibition of tumor COX-2 led to increased E-cadherin expression and resulted in augmented homotypic cellular aggregation among NSCLC cells in vitro. An inverse relationship between COX-2 and E-cadherin was shown in situ by double immunohistochemical staining of human lung adenocarcinoma tissue sections. Second, treatment of NSCLC cells with exogenous prostaglandin E-2 (PGE(2)) significantly decreased the expression of E-cadherin, whereas treatment of COX-2-S cells with celecoxib (1 mu mol/L) led to increased E-cadherin expression. Third, the transcriptional suppressors of E-cadherin, ZEB1 and Snail, were up-regulated in COX-2-S cells or PGE(2)-treated NSCLC cells but decreased in COX-2-antisense cells. PGE(2) exposure led to enhanced ZEB1 and Snail binding at the chromatin level as determined by chromatin immunoprecipitation assays. Small interfering RNA-mediated knockdown of ZEB1 or Snail interrupted the capacity of PGE(2) to downregulate E-cadherin. Fourth, an inverse relationship between E-cadherin and ZEB1 and a direct relationship between COX-2 and ZEB1 were shown by immunohistochemical staining of human lung adenocarcinoma tissue sections. These findings indicate that PGE(2), in autocrine or paracrine fashion, modulates transcriptional repressors of E-cadherin and thereby regulates COX-2-dependent E-cadherin expression in NSCLC. Thus, blocking PGE(2) production or activity may contribute to both prevention and treatment of NSCLC. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Los Angeles Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. VA Greater Los Angeles Hlth Care Ctr, Los Angeles, CA USA. Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80202 USA. Univ Colorado, Ctr Canc, Div Med Oncol, Denver, CO 80202 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu OI Batra, Raj K./0000-0002-1126-543X FU NCI NIH HHS [P50 CA90388, CA58187] NR 51 TC 177 Z9 191 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2006 VL 66 IS 10 BP 5338 EP 5345 DI 10.1158/0008-5472.CAN-05-3635 PG 8 WC Oncology SC Oncology GA 044NS UT WOS:000237679900045 PM 16707460 ER PT J AU Meeran, SM Mantena, SK Elmets, CA Katiyar, SK AF Meeran, SM Mantena, SK Elmets, CA Katiyar, SK TI (-)-Epigallocatechin-3-gallate prevents photocarcinogenesis in mice through interieukin-12-dependent DNA repair SO CANCER RESEARCH LA English DT Article ID SUNBURN CELL-FORMATION; GREEN TEA POLYPHENOLS; SKIN-CANCER; CONTACT HYPERSENSITIVITY; ULTRAVIOLET-RADIATION; INDUCED IMMUNOSUPPRESSION; PYRIMIDINE DIMERS; TUMOR-REGRESSION; UVB RADIATION; IN-VIVO AB We have shown previously that topical application of epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, prevents photocarcinogenesis in mice. EGCG prevents UVB-induced immunosuppression by inducing interleukin-12 (IL-12). As immunosuppression is a risk factor for photocarcinogenesis, we investigated the possibility that EGCG also prevents UVB-induced photocarcinogenesis through an IL-12-dependent DNA repair mechanism. To investigate this possibility, we determined the effects of EGCG on photocarcinogenesis in IL-12 knockout (KO) mice using the formation of cyclobutane pyrimidine dimers (CPD) as an indicator of the extent of UVB-induced DNA damage. Topical application of EGCG (1 mg/cm(2) skin) prevented photocarcinogenesis in wild-type (C3H/HeN) mice in terms of tumor incidence and tumor multiplicity but did not prevent photocarcinogenesis in IL-12 KO mice. UVB-induced DNA damage, as determined by the formation of CPDs and the number of sunburn cells, was resolved more rapidly in the skin of wild-type mice treated with EGCG than untreated control mice. In contrast, the extent of UVB-induced DNA damage and the numbers of sunburn cells were not significantly different in the EGCG-treated IL-12 KO mice and untreated control mice. In addition, treatment of XPA-proficient human fibroblast cells with EGCG promoted repair of UVB-induced CPDs in a dose-dependent manner but not in an XPA-deficient cells, indicating that the nucleotide excision repair mechanism is involved in EGCG-mediated DNA repair. Taken together, these results indicate for the first time that EGCG can prevent photocarcinogenesis through an EGCG-induced IL-12-dependent DNA repair mechanism. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [1 R01 AT002536]; NCRR NIH HHS [C06 RR15490]; NIAMS NIH HHS [AR050948-01] NR 38 TC 59 Z9 65 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2006 VL 66 IS 10 BP 5512 EP 5520 DI 10.1158/0008-5472.CAN-06-0218 PG 9 WC Oncology SC Oncology GA 044NS UT WOS:000237679900066 PM 16707481 ER PT J AU Hirano, N Butler, MO Xia, ZN Berezovskaya, A Murray, AP Ansen, S Nadler, LM AF Hirano, N Butler, MO Xia, ZN Berezovskaya, A Murray, AP Ansen, S Nadler, LM TI Efficient presentation of naturally processed HLA class I peptides by artificial antigen-presenting cells for the generation of effective antitumor responses SO CLINICAL CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; HISTOCOMPATIBILITY COMPLEX-MOLECULES; DISTINCT PROTEOLYTIC PROCESSES; PROGNOSTIC-SIGNIFICANCE; PROTEIN-DEGRADATION; STANDARD PROTEASOME; TRANSFER THERAPY; DENDRITIC CELLS; CANCER; LYMPHOCYTES AB Appropriate presentation of tumor-associated antigens (TAA) by antigen-presenting cells (APC) is required for the development of clinically relevant antitumor T-cell responses. One common approach, which uses APC pulsed with synthetic peptides, can sometimes generate ineffective immune responses. This failure may, in part, be attributed to the formation of HLA/synthetic pulsed peptide complexes that possess different conformations compared with those of endogenously presented peptides. In addition, endogenous peptides may undergo post-translational modifications, which do not occur with synthetic peptides. Because our goal is to induce immunity that can recognize TAA that are endogenously presented by tumors, we designed an APC that would not only express the required immunoaccessory molecules but also naturally process and present target antigenic peptides. In this study, we generated an artificial APC (aAPC) that can endogenously present any chosen HLA-A*0201 (A2) -restricted peptide by processing a fusion protein that contains a unique "LTK" sequence linked to the antigenic peptide. Proteasome-dependent processing is so effective that the presented peptide can be directly eluted from the cell surface and identified by biochemical methods. Furthermore, we found that aAPC, engineered to endogenously present peptide derived from the melanoma antigen MART1, can be used to prime and expand antitumor CTL that target MART1-expressing tumor cells in a HLA-A2-restricted manner. Our engineered aAPC could serve as an "off-the-shelf" APC designed to constitutively express class I - restricted TAA peptides and could be used to generate effective T-cell responses to treat human disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Naoto_Hirano@dfci.harvard.edu FU NCI NIH HHS [CA87720, CA92625-04]; NHLBI NIH HHS [HL54785-08] NR 47 TC 27 Z9 28 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2006 VL 12 IS 10 BP 2967 EP 2975 DI 10.1158/1078-0432.CCR-05-2791 PG 9 WC Oncology SC Oncology GA 044PX UT WOS:000237685800005 PM 16707591 ER PT J AU Leung, WK Man, EPS Yu, J Go, MYY To, KF Yamaoka, Y Cheng, VYY Ng, EK Sung, JJY AF Leung, WK Man, EPS Yu, J Go, MYY To, KF Yamaoka, Y Cheng, VYY Ng, EK Sung, JJY TI Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-RELATED GENES; DIFFUSE GASTRIC-CANCER; PROMOTER HYPERMETHYLATION; INTESTINAL METAPLASIA; CARCINOMA; MUTATIONS; CDH1; EXPRESSION; INFECTION AB Purpose: Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori - infected individuals, we tested whether eradication of H pylori alters the methylation status of the noncancerous gastric epithelium. Experimental Design: Endoscopic biopsies were taken from the antrum and corpus of H pylori - infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H pylori eradication. Results: Among the 28 H pylori - infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001). Conclusion: Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori-infected individuals. Eradication of H pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation. C1 Chinese Univ Hong Kong, Prince Wales Hosp, Fac Med, Inst Digest Dis,Dept Med & Therapeut, Shatin, Hong Kong, Peoples R China. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Leung, WK (reprint author), Chinese Univ Hong Kong, Prince Wales Hosp, Fac Med, Inst Digest Dis,Dept Med & Therapeut, 30-32 Ngan Shing St, Shatin, Hong Kong, Peoples R China. EM wkleung@cuhk.edu.hk RI Hossain, Sarah /C-7332-2009; Leung, Wai Keung/B-8140-2011; Cheng, Yuen Yee/G-4406-2016; Yu, Jun /D-8569-2015 OI Hossain, Sarah /0000-0003-1355-0979; Cheng, Yuen Yee/0000-0001-7060-0624; NR 23 TC 72 Z9 76 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2006 VL 12 IS 10 BP 3216 EP 3221 DI 10.1158/1078-0432.CCR-05-2442 PG 6 WC Oncology SC Oncology GA 044PX UT WOS:000237685800037 PM 16707623 ER PT J AU Kawai, T AF Kawai, T TI Hypermucoviscosity: An extremely sticky phenotype of Klebsiella pneumoniae associated with emerging destructive tissue abscess syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID PYOGENIC LIVER-ABSCESS; INFECTIONS; STRAINS; GENE C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM tkawai@forsyth.org NR 18 TC 31 Z9 32 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2006 VL 42 IS 10 BP 1359 EP 1361 DI 10.1086/503429 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 038SU UT WOS:000237247400002 PM 16619145 ER PT J AU Nishimura, W Kondo, T Salameh, T El Khattabi, I Dodge, R Bonner-Weir, S Sharma, A AF Nishimura, Wataru Kondo, Takuma Salameh, Therese El Khattabi, Ilham Dodge, Rikke Bonner-Weir, Susan Sharma, Arun TI A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE MafA; MafB; Maf factors; insulin gene transcription factor; pancreatic development; endocrine differentiation; pancreatic islets ID INSULIN GENE-TRANSCRIPTION; C-MAF; LENS DEVELOPMENT; TRANSGENIC MICE; KEY REGULATOR; ALPHA-CELL; ENHANCER; SEQUENCES; GLUCAGON; BINDING AB Major insulin gene transcription factors, such as PDX-1 or NeuroD1, have equally important roles in pancreatic development and the differentiation of pancreatic endocrine cells. Previously, we identified and cloned another critical insulin gene transcription factor MafA (RIPE3b1) and reported that other Maf factors were expressed in pancreatic endocrine cells. Maf factors are important regulators of cellular differentiation; to understand their role in differentiation of pancreatic endocrine cells, we analyzed the expression pattern of large-Maf factors in the pancreas of embryonic and adult mice. Ectopically expressed large-Maf factors, MafA, MafB, or cMaf, induced expression from insulin and glucagon reporter constructs, demonstrating a redundancy in their function. Yet in adult pancreas, cMaf was expressed in both alpha- and beta-cells, and MafA and MafB showed selective expression in the beta- and alpha-cells, respectively. Interestingly, during embryonic development, a significant proportion of MafB-expressing cells also expressed insulin. In embryos, MafB is expressed before MafA, and our results suggest that the differentiation of beta-cells proceeds through a MafB(+) MafA(-) Ins(+) intermediate cell to MafB(-) MafA(+) Ins(+) cells. Furthermore, the MafB to MafA transition follows induction of PDX-1 expression (Pdx-1(high)) in MatB(+) Ins(+) cells. We suggest that MafB may have a dual role in regulating embryonic differentiation of both beta- and alpha-cells while MafA may regulate replication/survival and function of beta-cells after birth. Thus, this redundancy in the function and expression of the large-Maf factors may explain the normal islet morphology observed in the MafA knockout mice at birth. (c) 2006 Elsevier Inc. All rights reserved. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02132 USA. RP Sharma, A (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM arun.sharma@joslin.harvard.edu OI Nishimura, Wataru/0000-0002-8068-1277 FU NIDDK NIH HHS [R01 DK060127-03, DK-36836, DK060127, P30 DK036836, R01 DK060127, R01 DK060127-01A2, R01 DK060127-02, R01 DK060127-04, R01 DK060127-05] NR 42 TC 156 Z9 160 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 15 PY 2006 VL 293 IS 2 BP 526 EP 539 DI 10.1016/j.ydbio.2006.02.028 PG 14 WC Developmental Biology SC Developmental Biology GA 045BF UT WOS:000237716900021 PM 16580660 ER PT J AU Hezel, AF Kimmelman, AC Stanger, BZ Bardeesy, N DePinho, RA AF Hezel, AF Kimmelman, AC Stanger, BZ Bardeesy, N DePinho, RA TI Genetics and biology of pancreatic ductal adenocarcinoma SO GENES & DEVELOPMENT LA English DT Review ID TRANSFORMING-GROWTH-FACTOR; NF-KAPPA-B; COMPARATIVE GENOMIC HYBRIDIZATION; FACTOR-I RECEPTOR; TUMOR-SUPPRESSOR GENE; CANCER-CELL-LINES; PAPILLARY-MUCINOUS NEOPLASMS; PEUTZ-JEGHERS-SYNDROME; FACTOR-BETA RECEPTOR; K-RAS MUTATIONS AB Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the United States with a median survival of < 6 mo and a dismal 5-yr survival rate of 3%-5%. The cancer's lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biology and resistance to conventional and targeted therapeutic agents leads to a typical clinical presentation of incurable disease at the time of diagnosis. The well-defined serial histopathologic picture and accompanying molecular profiles of PDAC and its precursor lesions have provided the framework for emerging basic and translational research. Recent advances include insights into the cancer's cellular origins, high-resolution genomic profiles pointing to potential new therapeutic targets, and refined mouse models reflecting both the genetics and histopathologic evolution of human PDAC. This confluence of developments offers the opportunity for accelerated discovery and the future promise of improved treatment. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Radiat Oncol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Dana Farber Canc Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dana Farber Canc Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Belfer Inst Innovat Canc Sci, Dana Farber Canc Inst, Boston, MA 02114 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu FU NCI NIH HHS [K01 CA104647A-01A1, P01CA117969-01, U01CA84313-07]; NIDDK NIH HHS [K08 DK064136] NR 382 TC 529 Z9 548 U1 13 U2 88 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2006 VL 20 IS 10 BP 1218 EP 1249 DI 10.1101/gad.1415606 PG 32 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 044XT UT WOS:000237707600004 PM 16702400 ER PT J AU Vaquero, A Scher, MB Lee, DH Sutton, A Cheng, HL Alt, FW Serrano, L Sternglanz, R Reinberg, D AF Vaquero, A Scher, MB Lee, DH Sutton, A Cheng, HL Alt, FW Serrano, L Sternglanz, R Reinberg, D TI SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis SO GENES & DEVELOPMENT LA English DT Article ID NAD-DEPENDENT DEACETYLASE; CELL-CYCLE; LIFE-SPAN; SACCHAROMYCES-CEREVISIAE; PROTEIN SIR2; INTERACTS; YEAST; HETEROCHROMATIN; ACETYLATION; METHYLATION AB The mammalian cytoplasmic protein SirT2 is a member of the Sir2 family of NAD(+)-dependent protein deacetylases involved in caloric restriction-dependent life span extension. We found that SirT2 and its yeast counterpart Hst2 have a strong preference for histone H4K16Ac in their deacetylation activity in vitro and in vivo. We have pinpointed the decrease in global levels of H4K16Ac during the mammalian cell cycle to the G(2)/M transition that coincides with SirT2 localization on chromatin. Mouse embryonic fibroblasts (MEFs) deficient for SirT2 show higher levels of H4K16Ac in mitosis, in contrast to the normal levels exhibited by SirT1-deficient MEFs. The enzymatic conversion of H4K16Ac to its deacetylated form may be pivotal to the formation of condensed chromatin. Thus, SirT2 is a major contributor to this enzymatic conversion at the time in the cell's life cycle when condensed chromatin must be generated anew. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Howard Hughes Med Inst, Dept Biochem, Piscataway, NJ 08854 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Div Nucle Acids Enzymol, Piscataway, NJ 08854 USA. SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Genet, Waltham, MA 02154 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Genet, Waltham, MA 02154 USA. Rutgers State Univ, Inst Human Genet, Dept Genet, Piscataway, NJ 08854 USA. RP Reinberg, D (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Howard Hughes Med Inst, Dept Biochem, Piscataway, NJ 08854 USA. EM reinbedf@umdnj.edu RI Vaquero, Alejandro/I-9845-2014 OI Vaquero, Alejandro/0000-0002-8735-4156 FU NIGMS NIH HHS [GM28220, GM64844, R01 GM028220, R01 GM064844, R56 GM028220] NR 26 TC 268 Z9 280 U1 0 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2006 VL 20 IS 10 BP 1256 EP 1261 DI 10.1101/gad.1412706 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 044XT UT WOS:000237707600006 PM 16648462 ER PT J AU Arnold, JS Braunstein, EM Ohyama, T Groves, AK Adams, JC Brown, MC Morrow, BE AF Arnold, JS Braunstein, EM Ohyama, T Groves, AK Adams, JC Brown, MC Morrow, BE TI Tissue-specific roles of Tbx1 in the development of the outer, middle and inner ear, defective in 22q11DS patients SO HUMAN MOLECULAR GENETICS LA English DT Article ID FACIAL SYNDROME/DIGEORGE-SYNDROME; DIGEORGE-SYNDROME; NEURAL CREST; CARDIOVASCULAR DEFECTS; SIX1; EXPRESSION; MUTATION; MOUSE; GENE; MICE AB Most 22q11.2 deletion syndrome (22q11DS) patients have middle and outer ear anomalies, whereas some have inner ear malformations. Tbx1, a gene hemizygously deleted in 22q11DS patients and required for ear development, is expressed in multiple tissues during embryogenesis. To determine the role of Tbx1 in the first pharyngeal pouch (PPI) in forming outer and middle ears, we tissue-specifically inactivated the gene using Foxg1-Cre. In the conditional mutants, PPI failed to outgrow, preventing the middle ear bone condensations from forming. Tbx1 was also inactivated in the otic vesicle (OV), resulting in the failure of inner ear sensory organ formation, and in duplication of the cochleovestibular ganglion (CVG). Consistent with the anatomical defects, the sensory genes, Otx1 and Bmp4 were downregulated, whereas the CVG genes, Fgf3 and NeuroD, were upregulated. To delineate Tbx1 cell-autonomous roles, a more selective ablation, exclusively in the OV, was performed using Pax2-Cre. In contrast to the Foxg1-Cre mutants, Pax2-Cre conditional mutant mice survived to adulthood and had normal outer and middle ears but had the same inner ear defects as the Tbx1 null mice, with the same gene expression changes. These results demonstrate that Tbx1 has non-cell autonomous roles in PPI in the formation of outer and middle ears and cell-autonomous roles in the OV. Periotic mesenchymal markers, Prx2 and Brn4 were normal in both conditional mutants, whereas they were diminished in Tbx1-/- embryos. Thus, Tbx1 in the surrounding mesenchyme in both sets of conditional mutants cannot suppress the defects in the OV that occur in the null mutants. C1 Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. House Ear Res Inst, Dept Cell & Mol Biol, Los Angeles, CA 90057 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otoimmunol, Boston, MA 02114 USA. RP Morrow, BE (reprint author), Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM morrow@aecom.yu.edu OI Groves, Andrew/0000-0002-0784-7998 FU NIDCD NIH HHS [DC006977-02, F31 DC006977, R01 DC003929, R01 DC005186, DC003929, DC01089, R01 DC001089, DC05186-03, DC04876] NR 40 TC 47 Z9 48 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2006 VL 15 IS 10 BP 1629 EP 1639 DI 10.1093/hmg/ddl084 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 039QB UT WOS:000237320200008 PM 16600992 ER PT J AU Huang, KC Park, DC Ng, SK Lee, JY Ni, XY Ng, WC Bandera, CA Welch, WR Berkowitz, RS Mok, SC Ng, SW AF Huang, KC Park, DC Ng, SK Lee, JY Ni, XY Ng, WC Bandera, CA Welch, WR Berkowitz, RS Mok, SC Ng, SW TI Selenium binding protein 1 in ovarian cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ovarian cancer; membrane proteome profiling; 2-D PAGE; selenium binding protein 1; prognostic marker; androgen; methylselenocysteine ID HORMONE BINDING GLOBULIN; PROTEOMIC ANALYSIS; PROGESTERONE-RECEPTORS; ORAL-CONTRACEPTIVES; EPITHELIAL-CELLS; MESSENGER-RNA; ANDROGEN; PROTEIN; IDENTIFICATION; EXPRESSION AB Selenium binding protein I (SELENBP1) was identified to be the most significantly down-regulated protein in ovarian cancer cells by a membrane proteome profiling analysis. SELENBP1 expression levels in 4 normal ovaries, 8 benign ovarian tumors, 12 borderline ovarian tumors and 141 invasive ovarian cancers were analyzed with immunohistochemical assay. SELENBP1 expression was reduced in 87% cases of invasive ovarian cancer (122/141) and was significantly reduced in borderline tumors and invasive cancers (p < 0.001). Cox multivariate analysis within the 141 invasive cancer tissues showed that SELENBP1 expression score was a potential prognostic indicator for unfavorable prognosis of ovarian cancer (hazard ratio [HR], 2.18; 95% CI = L22-190; p = 0.009). Selenium can disrupt the androgen pathway, which has been implicated in modulating SELENBP1 expression. We investigated the effects of selenium and androgen on normal human ovarian surrace epithelial (HOSE) cells and cancer cells. Interestingly, SELENBP1 mRNA and protein levels were reduced by androgen and elevated by selenium treatment in the normal HOSE cells, whereas reversed responses were observed in the ovarian cancer cell lines. These results suggest that changes of SELENBP1 expression in malignant ovarian cancer are an indicator of aberration of selenium/androgen pathways and may reveal prognostic information of ovarian cancer. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Lab Gynecol Oncol,Div Gynecol Oncol,Dana Farber C, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Ctr, Boston, MA USA. Catholic Univ Korea, St Vincent Hosp, Dept Obstet & Gynecol, Suwon, South Korea. Univ Queensland, Dept Math, Ctr Stat, St Lucia, Qld, Australia. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Huang, KC (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Lab Gynecol Oncol,Div Gynecol Oncol,Dana Farber C, 221 Longwood Ave BLI-431, Boston, MA 02115 USA. EM khuang@rics.bwh.harvard.edu FU NCI NIH HHS [CA86381, CA94944, P50CA165009] NR 36 TC 55 Z9 63 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 15 PY 2006 VL 118 IS 10 BP 2433 EP 2440 DI 10.1002/ijc.21671 PG 8 WC Oncology SC Oncology GA 035VG UT WOS:000237029200009 PM 16380993 ER PT J AU Shen, L Black, ED Witkowski, ED Lencer, WI Guerriero, V Schneeberger, EE Turner, JR AF Shen, Le Black, Eric D. Witkowski, Edwina D. Lencer, Wayne I. Guerriero, Vince Schneeberger, Eveline E. Turner, Jerrold R. TI Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure SO JOURNAL OF CELL SCIENCE LA English DT Article DE epithelial; barrier; claudin; occludin; ZO-1 ID ENTEROPATHOGENIC ESCHERICHIA-COLI; NA+-GLUCOSE COTRANSPORT; TRANSEPITHELIAL ELECTRICAL-RESISTANCE; INCREASES PARACELLULAR PERMEABILITY; SMOOTH-MUSCLE MYOSIN; INTESTINAL EPITHELIA; INTERFERON-GAMMA; PROTEIN-KINASE; PHYSIOLOGICAL REGULATION; POLARIZED EPITHELIA AB Epithelial tight junctions form a barrier against passive paracellular flux. This barrier is regulated by complex physiologic and pathophysiologic signals that acutely fine-tune tight junction permeability. Although actomyosin contraction and myosin light chain phosphorylation are clearly involved in some forms of tight junction regulation, the contributions of other signaling events and the role of myosin light chain phosphorylation in this response are poorly understood. Here we ask if activation of myosin light chain kinase alone is sufficient to induce downstream tight junction regulation. We use a confluent polarized intestinal epithelial cell model system in which constitutively active myosin light chain kinase, tMLCK, is expressed using an inducible promoter. tMLCK expression increases myosin light chain phosphorylation, reorganizes perijunctional F-actin, and increases tight junction permeability. TJ proteins ZO-1 and occludin are markedly redistributed, morphologically and biochemically, but effects on claudin-1 and claudin-2 are limited. tMLCK inhibition prevents changes in barrier function and tight junction organization induced by tMLCK expression, suggesting that these events both require myosin light chain phosphorylation. We conclude that myosin light chain phosphorylation alone is sufficient to induce tight junction regulation and provide new insights into the molecular mechanisms that mediate this regulation. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Harvard Univ, Sch Med, GI Cell Biol, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp, Boston, MA 02115 USA. Univ Arizona, Dept Anim Sci, Tucson, AZ 85721 USA. Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Turner, JR (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave,MC 1089, Chicago, IL 60637 USA. EM jturner@bsd.uchicago.edu RI Shen, Le/E-7866-2010; Turner, Jerrold/A-6895-2009 OI Turner, Jerrold/0000-0003-0627-9455 FU NCI NIH HHS [CA14599]; NHLBI NIH HHS [HL25822, HL36781]; NIDDK NIH HHS [DK42086, DK48106, DK53056, DK57827, DK61931, DK68271] NR 74 TC 191 Z9 208 U1 1 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 15 PY 2006 VL 119 IS 10 BP 2095 EP 2106 DI 10.1242/jcs.02915 PG 12 WC Cell Biology SC Cell Biology GA 042FD UT WOS:000237512400013 PM 16638813 ER PT J AU Massberg, S Konrad, I Schurzinger, K Lorenz, M Schneider, S Zohlnhoefer, D Hoppe, K Schiemann, M Kennerknecht, E Sauer, S Schulz, C Kerstan, S Rudelius, M Seidl, S Sorge, F Langer, H Peluso, M Goyal, P Vestweber, D Emambokus, NR Busch, DH Frampton, J Gawaz, M AF Massberg, S Konrad, I Schurzinger, K Lorenz, M Schneider, S Zohlnhoefer, D Hoppe, K Schiemann, M Kennerknecht, E Sauer, S Schulz, C Kerstan, S Rudelius, M Seidl, S Sorge, F Langer, H Peluso, M Goyal, P Vestweber, D Emambokus, NR Busch, DH Frampton, J Gawaz, M TI Platelets secrete stromal cell-derived factor 1 alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; ADHESION MOLECULE-1; ENDOTHELIAL SELECTINS; VASCULAR ENDOTHELIUM; NEOINTIMA FORMATION; GLYCOPROTEIN IIB; DEFICIENT MICE; CRUCIAL ROLE; P-SELECTIN; CHEMOKINE AB The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow - derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34(+) bone marrow cells and c-Kit(+) Sca-1(+) Lin(-) bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34(+) and c-Kit(+) Sca-1(+) Lin-bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1 alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury. C1 Tech Univ Munich, Deutsch Herzzentrum, D-80636 Munich, Germany. Tech Univ Munich, Med Klin, D-80636 Munich, Germany. Tech Univ Munich, Klinikum Rechts Isar, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany. Tech Univ Munich, Klinikum Rechts Isar, Clin Cooperat Grp Vaccinol, Natl Res Ctr Environm & Hlth, D-81675 Munich, Germany. Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol, D-81675 Munich, Germany. Procorde GMBH, D-82152 Martinsried, Germany. Univ Munich, Inst Prophylaxe & Epidemiol Kreislaufkrankheiten, D-80336 Munich, Germany. Univ Munster, Max Planck Inst Mol Biomed, D-48149 Munster, Germany. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Univ Birmingham, Sch Med, Biomed Res Inst, Birmingham B15 2TT, W Midlands, England. Univ Tubingen, D-72076 Tubingen, Germany. RP Massberg, S (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM massberg@cbr.med.harvard.edu RI Goyal, Pankaj/C-3567-2012; Schulz, Christian/J-8545-2012; OI Schulz, Christian/0000-0003-3878-7833; Vestweber, Dietmar/0000-0002-3517-732X NR 42 TC 256 Z9 268 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 15 PY 2006 VL 203 IS 5 BP 1221 EP 1233 DI 10.1084/jem.20051772 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 046IA UT WOS:000237803700011 PM 16618794 ER PT J AU Purton, LE Dworkin, S Olsen, GH Walkley, CR Fabb, SA Collins, SJ Chambon, P AF Purton, LE Dworkin, S Olsen, GH Walkley, CR Fabb, SA Collins, SJ Chambon, P TI RAR gamma is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; GRANULOCYTIC DIFFERENTIATION; CD34 EXPRESSION; COMPETITIVE REPOPULATION; IN-VITRO; EX-VIVO; IDENTIFICATION; MOUSE; PROLIFERATION AB Hematopoietic stem cells (HSCs) sustain lifelong production of all blood cell types through finely balanced divisions leading to self-renewal and differentiation. Although several genes influencing HSC self-renewal have been identified, to date no gene has been described that, when activated, enhances HSC self-renewal and, when activated, promotes HSC differentiation. We observe that the retinoic acid receptor (RAR)gamma is selectively expressed in primitive hematopoietic precursors and that the bone marrow of RAR gamma knockout mice exhibit markedly reduced numbers of HSCs associated with increased numbers of more mature progenitor cells compared with wild-type mice. In contrast, RAR alpha is widely expressed in hematopoietic cells, but RAR gamma knockout mice do not exhibit any HSC or progenitor abnormalities. Primitive hematopoietic precursors overexpressing RAR alpha differentiate predominantly to granulocytes in short-term culture, whereas those overexpressing RAR gamma exhibit a much more undifferentiated phenotype. Furthermore, loss of RAR gamma abrogated the potentiating effects of all-trans retinoic acid on the maintenance of HSCs in ex vivo culture. Finally, pharmacological activation of RAR gamma ex vivo promotes HSC self-renewal, as demonstrated by serial transplant studies. We conclude that the RARs have distinct roles in hematopoiesis and that RAR gamma is a critical physiological and pharmacological regulator of the balance between HSC self-renewal and differentiation. C1 Peter MacCallum Canc Inst, Trescowthick Res Labs, Melbourne, Vic 3002, Australia. Univ Melbourne, Dept Med, Fitzroy, Vic 3065, Australia. Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. Coll France, ULP, CNRS, INSERM,Inst Genet & Biol Mol Cellulaire, F-67404 Illkirch Graffenstaden, CU Strasbourg, France. RP Purton, LE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med,Stem Cell Inst, Boston, MA 02114 USA. EM lpurton@partners.org OI Walkley, Carl/0000-0002-4784-9031 NR 45 TC 103 Z9 107 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 15 PY 2006 VL 203 IS 5 BP 1283 EP 1293 DI 10.1084/jem.20052105 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 046IA UT WOS:000237803700016 PM 16682494 ER PT J AU Streelman, JT Albertson, RC AF Streelman, JT Albertson, RC TI Evolution of novelty in the Cichlid dentition SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION LA English DT Article ID TUNING SPECTRAL SENSITIVITY; DEVELOPING MOUSE TOOTH; GENE-EXPRESSION; MAMMALIAN TEETH; HEMICHROMIS-BIMACULATUS; SYMPATRIC SPECIATION; 1ST-GENERATION TEETH; MURINE DENTITION; SIGNALING CENTER; ANTERIOR PART AB The shape of teeth occupies a central position in various biological disciplines, from paleo-ecology to molecular biology to cosmetic and reconstructive dentistry. Despite a long tradition of study in mammals, important questions remain regarding the genetic and developmental basis of differences in tooth shape. Here, we use natural mutants of cichlid fish from East Africa, which exhibit tremendous dental diversity, to help fill the gaps in our understanding of vertebrate odontogenesis. We employ an expanded genetic linkage map to demonstrate that cusp number segregates as a gene of major effect, which explains similar to 40% of the phenotypic variance, on cichlid chromosome 5. Furthermore, we examine patterns of Bmp4 expression in early odontogenesis to address and refine predictions of models linking tooth shape and tooth number. Mutations in the Bmp4 cistron do not control tooth shape in this mapping cross. Our data suggest that the evolution of novelty in the cichlid dentition is galvanized by a small number of genetic changes, echoing similar conclusions from recent studies of other vertebrate adaptive morphologies. C1 Georgia Inst Technol, Sch Biol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Streelman, JT (reprint author), Georgia Inst Technol, Sch Biol, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA. EM todd.streelman@biology.gatech.edu; calbertson@forsyth.org FU NIDCR NIH HHS [R03 DE014446, R03 DE 14446-01] NR 73 TC 45 Z9 45 U1 1 U2 21 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-5007 J9 J EXP ZOOL PART B JI J. Exp. Zool. Part B PD MAY 15 PY 2006 VL 306B IS 3 BP 216 EP 226 DI 10.1002/jez.a.21101 PG 11 WC Evolutionary Biology; Developmental Biology; Zoology SC Evolutionary Biology; Developmental Biology; Zoology GA 046QY UT WOS:000237827300004 PM 16555305 ER PT J AU Ancuta, P Autissier, P Wurcel, A Zaman, T Stone, D Gabuzda, D AF Ancuta, P Autissier, P Wurcel, A Zaman, T Stone, D Gabuzda, D TI CD16(+) monocyte-derived macrophages activate resting T cells for HIV infection by producing CCR3 and CCR4 ligands SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD MONOCYTES; IMMUNODEFICIENCY-VIRUS-INFECTION; CHEMOKINE RECEPTOR EXPRESSION; PLASMACYTOID DENDRITIC CELLS; BETA-CHEMOKINES; ANTIRETROVIRAL THERAPY; PRIMARY LYMPHOCYTES; TYPE-1 REPLICATION; IMMUNE-RESPONSES; AIDS DEMENTIA AB The CD16(+) monocyte (Mo) subset produces proinflammatory cytokines and is expanded in peripheral blood during progression to AIDS, but its contribution to HIV pathogenesis is unclear. In this study, we investigate the capacity of human CD16(+) and CD16(-) Mo subsets to render resting CD4(+) T cells permissive for HIV replication. We demonstrate that CD16(+) Mo preferentially differentiate into macrophages (M phi) that activate resting T cells for productive HIV infection by producing the CCR3 and CCR4 ligands CCL24, CCL2, CCL22, and CCL17. CD16(+), but not CD16(-), Mo-derived M phi from HIV-infected and -uninfected. individuals constitutively produce CCL24 and CCL2. Furthermore, these chemokines stimulate HIV replication in CD16- Mo:T cell cocultures. Engagement of CCR3 and CCR4 by CCL24 and CCL2, respectively, along with stimulation via CD3/CD28, renders T cells highly permissive for productive HIV infection. Moreover, HIV replicates preferentially in CCR3(+) and CCR4(+) T cells. These findings reveal a new pathway of T cell' costimulation for increased susceptibility to HIV infection via engagement of CCR3 and CCR4 by chemokines constitutively produced by CD16(+) Mo/Mo. Thus, expansion of CD16(+) Mo in peripheral blood of HIV-infected patients and their subsequent recruitment into tissues may contribute to chronic immune activation and establishment of viral reservoirs in resting T cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Beth Israel Deaconess Ctr, Boston, MA 02115 USA. Lemuel Shattuck Hosp, Jamaica Plain, MA 02130 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB816, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIDA NIH HHS [DA 016549] NR 73 TC 45 Z9 45 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2006 VL 176 IS 10 BP 5760 EP 5771 PG 12 WC Immunology SC Immunology GA 044WW UT WOS:000237705200011 PM 16670281 ER PT J AU Mueller, T Terada, T Rosenberg, IM Shibolet, O Podolsky, DK AF Mueller, T Terada, T Rosenberg, IM Shibolet, O Podolsky, DK TI Th2 cytokines down-regulate TLR expression and function in human intestinal epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTOR-4; INTERFERON-GAMMA; ULCERATIVE-COLITIS; MURINE MODEL; IFN-GAMMA; MONONUCLEAR PHAGOCYTES; HUMAN MONOCYTES; CROHNS-DISEASE; INTERLEUKIN-4 AB TLRs serve important immune and nonimmune functions in human intestinal epithelial cells (IECs). Proinflammatory Th1 cytokines have been shown to promote TLR expression and function in IECs, but the effect of key Th2 cytokines (IL-4, IL-5, IL-13) on TLR signaling in IECs has not been elucidated so far. We stimulated human model IECs with Th2 cytokines and examined TLR mRNA and protein expression by Northern blotting, RT-PCR, real-time RT-PCR, Western blotting, and flow cytometry. TLR function was determined by I-kappa Ba phosphorylation assays, ELISA for IL-8 secretion after stimulation with TLR ligands and flow cytometry for LPS uptake. IL-4 and IL-13 significantly decreased TLR3 and TLR4 mRNA and protein expression including the requisite TLR4 coreceptor MD-2. TLR4/MD-2-mediated LPS uptake and TLR ligand-induced I-kappa B alpha phosphorylation and IL-8 secretion were significantly diminished in Th2 cytokine-primed IECs. The down-regulatory effect of Th2 cytokines on TLR expression and function in IECs also counteracted enhanced TLR signaling induced by stimulation with the hallmark Thl cytokine IFN-gamma. In summary, Th2 cytokines appear to dampen TLR expression and function in resting and Thl cytokine-primed human IECs. Diminished TLR function in IECs under the influence of Th2 cytokines may protect the host from excessive TLR signaling, but likely also impairs the host intestinal innate immune defense and increases IEC susceptibility to chronic inflammation in response to the intestinal microenvironment. Taken together, our data underscore the important role of Th2 cytokines in balancing TLR signaling in human IECs. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Ctr Study Inflammatory Bowel Dis, 55 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [DK 043351, DK 069344, DK 07191] NR 45 TC 71 Z9 75 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2006 VL 176 IS 10 BP 5805 EP 5814 PG 10 WC Immunology SC Immunology GA 044WW UT WOS:000237705200016 PM 16670286 ER PT J AU Yang, HL Reinherz, EL AF Yang, HL Reinherz, EL TI CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALDRICH-SYNDROME PROTEIN; CYTOSKELETAL-ASSOCIATED PROTEIN; IMMUNOLOGICAL SYNAPSE; PTP-PEST; SIGNAL-TRANSDUCTION; LYMPHOCYTE-ACTIVATION; ACTIN CYTOSKELETON; ARP2/3 COMPLEX; PAPA SYNDROME; MOLECULE CD2 AB Human CD2 regulates T cell activation and adhesion via mechanisms yet to be fully understood. This study focuses on CD2BP1, a CD2 cytoplasmic tail-binding protein preferentially expressed in hematopoetic cells. Structural and functional analyses suggest that CD2BP1 acts as a scaffold protein, participating in regulation of the actin cytoskeleton. In this study, using a murine Ag-specific primary T cell transduction system to assess CD69, IL-2, and IFN-gamma expression, we provide evidence that CD2BP1 directly and negatively impacts T cell activation via isolated CD2 triggering or TCR stimulation dependent on coordinate CD2 engagement. Disruption of protein tyrosine phosphatase-PEST and/or CD2BP1 association with the CD2 signalsome rescues T cells from the inhibitory effect of CD2 crosslinking. The overexpression of CD2BP1 selectively attenuates phospholipase C gamma 1, ERK1/2, and p38 phosphorylation without abrogating CD2-independent TCR stimulation. This study provides new insight on the regulation of T cell activation and may have implications for autoimmune processes known to be associated with CD2BP1 mutations. C1 Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI 21226] NR 68 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2006 VL 176 IS 10 BP 5898 EP 5907 PG 10 WC Immunology SC Immunology GA 044WW UT WOS:000237705200027 PM 16670297 ER PT J AU Zhang, F Signore, AP Zhou, ZG Wang, SP Cao, GD Chen, J AF Zhang, F Signore, AP Zhou, ZG Wang, SP Cao, GD Chen, J TI Erythropoietin protects CA1 neurons against global cerebral ischemia in rat: Potential signaling mechanisms SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EPO; AKT; GSK-3 beta; BDNF; CA1 ID GLYCOGEN-SYNTHASE KINASE-3; OXYGEN-GLUCOSE DEPRIVATION; NEUROTROPHIC FACTOR; BRAIN-INJURY; FOREBRAIN ISCHEMIA; APOPTOSIS; EXPRESSION; PREVENTS; HYPOXIA; PATHWAY AB Erythropoietin (EPO) is a hormone that is neuroprotective in models of neurodegenerative diseases. This study examined whether EPO can protect against neuronal death in the CA1 region of the rat hippocampus following global cerebral ischemia. Recombinant human EPO was infused into the intracerebral ventricle either before or after the induction of ischemia produced by using the four-vessel-occlusion model in rat. Hippocampal CA1 neuron damage was ameliorated by infusion of 50 U EPO. Administration of EPO was neuroprotective if given 20 hr before or 20 min after ischemia, but not 1 hr following ischemia. Coinjection of the phosphoinositide 3 kinase inhibitor LY294002 with EPO inhibited the protective effects of EPO. Treatment with EPO induced phosphorylation of both AKT and its substrate, glycogen synthase kinase-3 beta, in the CA1 region. EPO also enhanced the CA1 level of brain-derived neurotrophic factor. Finally, we determined that ERK activation played minor roles in EPO-mediated neuroprotection. These studies demonstrate that a single injection of EPO ICV up to 20 min after global ischemia is an effective neuroprotective agent and suggest that EPO is a viable candidate for treating global ischemic brain injury. (c) 2006 Wiley-Liss, Inc. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM chenj2@upmc.edu FU NINDS NIH HHS [NS36736, NS38560, NS43802, NS45048] NR 67 TC 77 Z9 90 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 15 PY 2006 VL 83 IS 7 BP 1241 EP 1251 DI 10.1002/jnr.20816 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 041WY UT WOS:000237488500010 PM 16511866 ER PT J AU Meyer, MA Sokal, SM Sandberg, W Chang, YC Daily, B Berger, DL AF Meyer, MA Sokal, SM Sandberg, W Chang, YC Daily, B Berger, DL TI INCOMING! A web tracking application for PACU and post-surgical patients SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-Academic-Surgery CY FEB 07-11, 2005 CL San Diego, CA SP Assoc Acad Surg DE hospital efficiency; workflow support; patient transfer; information systems; web applications ID POSTANESTHESIA CARE-UNIT; OPERATING-ROOM; DELAYS; FLOW AB Background. Capacity constraints necessitate improving hospital efficiency. An integrated real time system facilitating patient flow between the post-anesthesia care unit (PACU) and surgical ward would ease PACU workload by reducing the effort of discharging patients. Methods. We developed INCOMING!, a web-based platform that monitors patient progress from the operating room to the PACU. INCOMING! integrates available data, automatically determining when a patient enters the PACU. An automated paging system alerts clinical unit managers to 'pull' their patients from the PACU after a set recovery period. General surgery patients were included in the INCOMING! system in late 2004 with paging added in mid-March 2005. Mean PACU length of stay was calculated for the intervention group (general surgery patients with INCOMING!) and compared to a control group (general surgery patients without INCOMING!) and an orthopedic surgery group before and after paging. Results. The system successfully gathers data and generates automated pages when events occur. After paging, there was a significant difference between the orthopedic surgery control group and the general surgery intervention group (235 min versus 185 min, P = 0.001). The mean PACU LOS decreased in the INCOMING! intervention group by 26 min while the mean LOS increased by 28 min in the general surgery control group (P = 0.27). Conclusion. Pilot implementation demonstrates that INCOMING! performs the desired integration and automatic notification. Given the minimal cost and potential large gains from a wider deployment, we plan to implement the system for all PACU patients and all post-PACU care units. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Comp Sci Lab, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, OR Business & Informat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Comp Sci Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Decis Support & Qual Management Unit, Boston, MA 02115 USA. RP Meyer, MA (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Dept Surg, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM mameyer@partners.org OI Sandberg, Warren/0000-0002-9246-777X NR 8 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 15 PY 2006 VL 132 IS 2 BP 153 EP 158 DI 10.1016/j.jss.2006.02.055 PG 6 WC Surgery SC Surgery GA 039VY UT WOS:000237337000002 PM 16647945 ER PT J AU Britton, JC Phan, KL Taylor, SF Welsh, RC Berridge, KC Liberzon, I AF Britton, Jennifer C. Phan, K. Luan Taylor, Stephan F. Welsh, Robert C. Berridge, Kent C. Liberzon, I. TI Neural correlates of social and nonsocial emotions: An fMRI study SO NEUROIMAGE LA English DT Review ID PRIMATE ORBITOFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; FUSIFORM FACE AREA; EVENT-RELATED FMRI; HUMAN AMYGDALA; FACIAL EXPRESSIONS; FUNCTIONAL NEUROANATOMY; BRAIN ACTIVITY; FOOD STIMULI; AUTOBIOGRAPHICAL MEMORY AB Common theories of emotion emphasize valence and arousal dimensions or alternatively, specific emotions, and the search for the underlying neurocircuitry is underway. However, it is likely that other important dimensions for emotional neurocircuitry exist, and one of them is sociality. A social dimension may code whether emotions are addressing an individual's biological/visceral need versus more remote social goals involving semantic meaning or intentionality. Thus, for practical purposes, social emotions may be distinguished from nonsocial emotions based in part on the presence of human forms. In the current fMRI study, we aimed to compare regional coding of the sociality dimension of emotion (nonsocial versus social) versus the valence dimension of emotion (positive versus negative). Using a novel fMRI paradigm, film and picture stimuli were combined to induce and maintain four emotions varying along social and valence dimensions. Nonsocial emotions of positively valenced appetite and negatively valenced disgust and social emotions of positively valenced joy/ amusement and negatively valenced sadness were studied. All conditions activated the thalamus. Appetite and disgust activated posterior insula and visual cortex, whereas joy/amusement and sadness activated extended amygdala, superior temporal gyrus, hippocampus, and posterior cingulate. Activations within the anterior cingulate, nucleus accumbens, orbitofrontal cortex, and amygdala were modulated by both social and valence dimensions. Overall, these findings highlight that sociality has a key role in processing emotional valence, which may have implications for patient populations with social and emotional deficits. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Michigan, Program Neurosci, Ann Arbor, MI 48109 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. RP Britton, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Room 2613, Charlestown, MA 02129 USA. EM jbritton@nmr.mgh.harvard.edu RI Berridge, Kent/C-1525-2009; Taylor, Stephan/A-1211-2007; Britton, Jennifer/J-4501-2013 OI Berridge, Kent/0000-0002-6031-2626; NR 111 TC 127 Z9 128 U1 9 U2 36 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2006 VL 31 IS 1 BP 397 EP 409 DI 10.1016/j.neuroimage.2005.11.027 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 049JK UT WOS:000238012200039 PM 16414281 ER PT J AU Lee, ECW de Boer, JF Mujat, M Lim, H Yun, SH AF Lee, ECW de Boer, JF Mujat, M Lim, H Yun, SH TI In vivo optical frequency domain imaging of human retina and choroid SO OPTICS EXPRESS LA English DT Article ID SWEPT LASER SOURCE; COHERENCE TOMOGRAPHY; RESOLUTION; FIBER; NERVE; REFLECTOMETRY; PRINCIPLES; COMPACT; IMAGES; FUNDUS AB Optical frequency domain imaging (OFDI) using swept laser sources is an emerging second-generation method for optical coherence tomography (OCT). Despite the widespread use of conventional OCT for retinal disease diagnostics, until now imaging the posterior eye segment with OFDI has not been possible. Here we report the development of a high-performance swept laser at 1050 nm and an ophthalmic OFDI system that offers an A-line rate of 18.8 kHz, sensitivity of > 92 dB over a depth range of 2.4 mm with an optical exposure level of 550 mu W, and deep penetration into the choroid. Using these new technologies, we demonstrate comprehensive human retina, optic disc, and choroid imaging in vivo. This advance enables us to view choroidal vasculature in vivo without intravenous injection of fluorescent dyes and may provide a useful tool for evaluating choroidal as well as retinal diseases. (c) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Lee, ECW (reprint author), Harvard Univ, Sch Med, 50 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 34 TC 125 Z9 125 U1 1 U2 10 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAY 15 PY 2006 VL 14 IS 10 BP 4403 EP 4411 DI 10.1364/OE.14.004403 PG 9 WC Optics SC Optics GA 043NT UT WOS:000237608600022 PM 19516592 ER PT J AU Oram, S Cai, XY Haleem, R Cyriac, J Wang, Z AF Oram, S Cai, XY Haleem, R Cyriac, J Wang, Z TI Regulation of calcium homeostasis by S100RVP, an androgen-regulated S100 protein in the rat ventral prostate SO PROSTATE LA English DT Article DE androgens; prostate; S100; calcium ID EF-HAND TYPE; BINDING PROTEINS; MODULATED PROTEINS; FUNCTIONAL ROLES; CELL-LINES; EXPRESSION; CANCER; FAMILY; ACTIVATION; CLONING AB BACKGROUND. S100RVP was previously identified as an androgen-response gene in the rat ventral prostate RVP Characterization of S100RVP is important for elucidating the function of S100 proteins in androgen action. METHODS. The expression and subcellular localization of S100RVP were determined by Northern blot, in situ hybridization, and fluorescent microscopy. Calcium overlay and calcium ionophore sensitivity assays were performed to investigate the calcium binding and function of S100RVP. RESULTS. S100RVP is abundantly expressed in the RVP epithelial cells. A green fluorescent protein(GFP)-S100RVP fusion protein is present in both the cytoplasm and nucleus of transfected cells. A GST-S100RVP fusion protein bound calcium in vitro at levels similar to known S100 proteins. Furthermore, GFP-S100RVP transfected LNCaP and PC3 cells exhibited reduced sensitivity to calcium ionophore-induced cell death, but not to UV-induced cell death. CONCLUSION. The results of this study argue for a role of S100RVP in calcium homeostasis in the prostate. C1 Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Wang, Z (reprint author), Northwestern Univ, Sch Med, Dept Urol, Tarry 16-763, Chicago, IL 60611 USA. EM wangz@northwestern.edu FU NCI NIH HHS [P50-CA90386]; NIDDK NIH HHS [R01-DK51193] NR 37 TC 1 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 2006 VL 66 IS 7 BP 768 EP 778 DI 10.1002/pros.20395 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 031ZU UT WOS:000236744500010 PM 16444689 ER PT J AU List, JF He, HL Habener, JF AF List, JF He, HL Habener, JF TI Glucagon-like peptide-1 receptor and proglucagon expression in mouse skin SO REGULATORY PEPTIDES LA English DT Article DE GLP-1; hair follicle; skin; C-peptide ID EPITHELIAL-MESENCHYMAL TRANSITIONS; INSULIN-SECRETING CELLS; EMBRYONIC STEM-CELLS; PROGENITOR CELLS; HAIR FOLLICLE; BETA-CELL; PANCREATIC ENDOCRINE; NESTIN EXPRESSION; DIABETES-MELLITUS; MURINE SKIN AB Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone expressed by alternative post-translational processing of proglucagon in the intestines, endocrine pancreas, and brain. The multiple antidiabetogenic actions of GLP-1 include stimulation of the proliferation and differentiation of the insulin-producing beta cells in the pancreas. The GLP-1 receptor is widely distributed and has been identified in the endocrine pancreas, intestinal tract, brain, lung, kidney, and heart. Here we report the expression of the GLP-1 receptor and proglucagon in the skin of newborn mice located predominantly in the hair follicles, as well as in cultures of skin-derived cells that also express nestin, a marker of cultured cells that have dedifferentiated by epithelial to mesenchymal transition. In cultured skin cells, GLP-1 activates the MAPK/ERK signal transduction pathway, associated with cellular proliferation, differentiation, and cytoprotection. No evidence was found for the activation of cAMP or Ca2+ signaling pathways. Further, redifferentiation of cultured skin-derived cells by incubation in differentiation medium containing GLP-1 induced expression of the proinsulin-derived peptide, C-peptide. These findings suggest a possible paracrine/autocrine role for GLP-1 and its receptor in skin development and possibly also in folliculogenesis. (c) 2006 Elsevier B.V All rights reserved. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St-Thier 320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK30834, 5 T32 DK07028] NR 54 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD MAY 15 PY 2006 VL 134 IS 2-3 BP 149 EP 157 DI 10.1016/j.regpep.2006.02.007 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 047OT UT WOS:000237889300012 PM 16631262 ER PT J AU Harris, MB Sethi, RK AF Harris, MB Sethi, RK TI The initial assessment and management of the multiple-trauma patient with an associated spine injury SO SPINE LA English DT Article DE spinal fracture management; poly-trauma and spinal fracture; timing of spinal fracture stabilization ID POLYTRAUMA PATIENTS; CERVICAL-SPINE; CORD INJURY; DAMAGE CONTROL; HALO VEST; FRACTURES; STABILIZATION; SURGERY; COMPLICATIONS; DECOMPRESSION AB Study Design. Review and summary of the relevant literature from multiple disciplines. Objective. Provide the readership with evidence-based guidelines on the initial assessment and treatment of the multiple-trauma patient with an associated spinal column injury. Summary of Background Data. Early operative stabilization of the isolated spinal column injury has decreased hospital and intensive care unit length of stay. Early intervention has not provided consistently improved neurologic outcomes. The timing of spinal column stabilization in the multiple-trauma patient continues to be a source of discussion. Methods. Review of published English literature from 1990 to present using key words: spinal trauma multiple-trauma with spinal injury; timing of spinal injury treatment; spinal fracture management; and Advanced Trauma Life Support. Conclusions. The treatment of the poly-trauma, patient with an associated spinal column injury requires strict adherence to Advanced Trauma Life Support principles. Once life and limb-threatening injuries have been identified and addressed, spinal column assessment and neurologic protection must be maintained at the highest priority. Early spinal stabilization can be performed safely in the multiple-trauma patient in medical centers, in which medical and ancillary staff is available on a 24-hour basis and is familiar with these procedures. C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Harris, MB (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. EM mbharris@partners.org NR 36 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 15 PY 2006 VL 31 IS 11 SU S BP S9 EP S15 DI 10.1097/01.brs.0000217924.56853.0d PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 042HL UT WOS:000237518800003 PM 16685243 ER PT J AU Kehlet, H Jensen, TS Woolf, CJ AF Kehlet, H Jensen, TS Woolf, CJ TI Persistent postsurgical pain: risk factors and prevention SO LANCET LA English DT Review ID TERM POSTTHORACOTOMY PAIN; PERIPHERAL-NERVE INJURY; PHANTOM LIMB PAIN; RANDOMIZED CONTROLLED-TRIAL; ACUTE POSTOPERATIVE PAIN; INGUINAL-HERNIA REPAIR; BREAST-CANCER SURGERY; NEUROPATHIC PAIN; HERPES-ZOSTER; DORSAL-HORN AB Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain. C1 Rigshosp, Sect Surg Pathophysiol 4074, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark. Aarhus Univ Hosp, Danish Pain Res Ctr, DK-8000 Aarhus, Denmark. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Kehlet, H (reprint author), Rigshosp, Sect Surg Pathophysiol 4074, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark. EM henrik.kehlet@rh.dk RI Jensen, Troels /A-3418-2009 OI Jensen, Troels /0000-0002-3487-6380 FU NINDS NIH HHS [NS 38253] NR 95 TC 1085 Z9 1144 U1 21 U2 96 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 13 PY 2006 VL 367 IS 9522 BP 1618 EP 1625 DI 10.1016/S0140-6736(06)68700-X PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 043JT UT WOS:000237598000034 PM 16698416 ER PT J AU Spector, M AF Spector, Myron TI Biomaterials-based tissue engineering and regenerative medicine solutions to musculoskeletal problems SO SWISS MEDICAL WEEKLY LA English DT Review DE tissue engineering; regenerative medicine; biomaterials; scaffolds; cells; collagen ID COLLAGEN-GLYCOSAMINOGLYCAN SCAFFOLDS; CULTURED AUTOLOGOUS CHONDROCYTES; CANINE MODEL; ARTICULAR CHONDROCYTES; CELL TRANSPLANTATION; EXTRACELLULAR-MATRIX; STEM-CELLS; BONE; DELIVERY; DEFECTS AB Tissue engineering and regenerative medicine offer solutions to a number of compelling clinical problems that have not been adequately addressed through the use of permanent replacement devices. The challenge will be to select the optimal combination of a biomaterial scaffold, cells, and soluble regulators for a particular clinical problem. For many connective tissues of the musculoskeletal system, with microstructures that reflect the mechanical environment, it may be more advantageous to regenerate the tissue in vivo than to fully engineer the tissue in vitro for subsequent implantation. The porous material to be used as the scaffold to facilitate this regeneration needs to have certain pore characteristics, chemical composition and mechanical properties. One approach has been to employ substances that serve as analogues of the extracellular matrix of the tissue to be regenerated. For selected indications in which the supply of endogenous,precursor cells is limited it may be more efficacious to employ a scaffold as a delivery vehicle for the cells rather than to inject the cells into the defect. Investigations of cell-scaffold interactions in vitro not only offer the opportunity for modification of scaffold composition and structure to improve the outcome in vivo, but also offer the opportunity to discover cell biological behaviour when cells grow in the three-dimensional tissue-like environment. Selected clinical applications may also require the implantation of regulatory proteins such as growth factors. That the action of such polypeptides released from biomaterials is short-lived has led to recent work wedding tissue engineering and gene therapy. Genes can be bound to certain biomaterial scaffolds to be released in vivo over extended periods (eg weeks) in order to genetically modify cells in the defect to produce the desired growth factors. Thus a new role for biomaterials is as a delivery vehicle for genes, as well as for cells and growth factors. These endeavours are notable particularly because there is a growing consensus that the challenge of developing biomaterials for tissue engineering, regenerative medicine, and gene therapy exceeds the challenge that was faced in the cell biological work that led to the proliferation of cells in vitro (in such a way that they retain their phenotypic characteristics) and in the genetic engineering that has led to the production of growth factors and cloning of their genes. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Orthopaed Res Lab, Boston, MA USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu NR 40 TC 35 Z9 36 U1 2 U2 11 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD MAY 13 PY 2006 VL 136 IS 19-20 BP 293 EP 301 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 052DD UT WOS:000238210400001 PM 16741852 ER PT J AU Podolsky, MJ Lasker, A Flaminio, MJBF Gowda, LD Ezekowitz, RAB Takahashi, K AF Podolsky, MJ Lasker, A Flaminio, MJBF Gowda, LD Ezekowitz, RAB Takahashi, K TI Characterization of an equine mannose-binding lectin and its roles in disease SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE mannose-binding lectin; MBL; horse; innate immunity; cloning; cDNA; characterization; lectin complement pathway; MBL-associated; serine proteases; MASP ID ACUTE-PHASE REACTANT; SERINE-PROTEASE; ACTIVATES COMPLEMENT; INNATE IMMUNITY; HUMAN-SERUM; RAT SERUM; RECOGNITION; MUTATIONS; INFECTION; GENE AB The mannose-binding lectin (MBL), a pattern recognition serum protein, participates in the innate immune system of mammals as ail opsonin. In humans, MBL plays a key role in first-line host defense against infection during the lag period prior to the development of a specific immune response. MBL also activates complement via the lectin pathway that requires a MBL-associated serine protease-2 (MASP-2). Homologues of human MBL (hMBL) have been identified in a variety of mammals, fish, and primitive animals such as ascidians. In this study, we report that equine MBL (eMBL) has properties that are similar to hMBL. In addition, we found low levels of MBL:MASP activity in sick horses compared to healthy horses. These results suggest that eMBL is involved in the immune response of the horse and that low MBL:MASP activity could be used to monitor immune function and clinical outcome. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. Cornell Univ, Coll Vet Med, Dept Clin Sci, Ithaca, NY 14853 USA. RP Takahashi, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, 55 Fruit St, Boston, MA 02114 USA. EM ktakahashi1@partners.org NR 48 TC 9 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 12 PY 2006 VL 343 IS 3 BP 928 EP 936 DI 10.1016/j.bbrc.2006.03.055 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 035CE UT WOS:000236976800036 PM 16574074 ER PT J AU Duke-Cohan, JS Kang, H Liu, H Rudd, CE AF Duke-Cohan, JS Kang, H Liu, H Rudd, CE TI Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-3 DOMAIN; T-CELLS; SIGNAL-TRANSDUCTION; STRUCTURAL BASIS; INTERLEUKIN-2 PRODUCTION; INTEGRIN ADHESION; SKAP55; FYN; SLP-76; RECOGNITION AB The immune cell adaptor adhesion and degranulation promoting adaptor protein ( ADAP) and its binding to T- cell adaptor Src kinase-associated protein of 55 kDa ( SKAP- 55) play a key role in the modulation of T- cell adhesion. While primary binding occurs via SKAP- 55 SH3 domain binding to a proline- rich region in ADAP, a second interaction occurs between the ADAP C- terminal SH3 domain ( ADAP-SH3c) and a non- canonical (RKXXYXXY297)-X-294 motif in SKAP- 55. Increasing numbers of non- canonical SH3 domain binding motifs have been identified in a number of biological systems. The presence of tyrosine residues in the SKAP- 55 RKXXY294XXY297 motif suggested that phosphorylation might influence this unusual SH3 domain interaction. Here, we show that the Src kinase p59(fyn) can induce the in vivo phosphorylation of the motif, and this event blocks ADAP- SH3c domain binding to the peptide motif. The importance of tyrosine phosphorylation was confirmed by plasmon resonance interaction analysis showing that phosphorylation of Tyr(294) residue plays a central role in mediating dissociation, whereas phosphorylation of the second Tyr(297) had no effect. Although loss of this secondary interaction did not result in the disruption of the complex, the Y294F mutation blocked T- cell receptor- induced up- regulation of lymphocyte function- associated antigen- 1- mediated adhesion to intercellular adhesion molecule- 1and interleukin- 2 promoter activity. Our findings identify a RKXXY294 motif in SKAP- 55 that mediates unique ADAP SH3c domain binding and is needed for LFA- 1- mediated adhesion and cytokine production. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ London Imperial Coll Sci & Technol, Mol Immunol Sect, Dept Immunol, Div Invest Sci,Div Med, London W12 0NN, England. RP Duke-Cohan, JS (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM jonathan_duke-cohan@dfci.harvard.edu; c.rudd@imperial.ac.uk OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU Wellcome Trust NR 39 TC 22 Z9 25 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 12 PY 2006 VL 281 IS 19 BP 13743 EP 13750 DI 10.1074/jbc.M508774200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 039VV UT WOS:000237336600085 PM 16461356 ER PT J AU Jatana, M Giri, S Ansari, MA Elango, C Singh, AK Singh, I Khan, M AF Jatana, Manu Giri, Shailendra Ansari, Mubeen A. Elango, Chinnasamy Singh, Avtar K. Singh, Inderjit Khan, Mushfiquddin TI Inhibition of NF-kappa B activation by 5-lipoxygenase inhibitors protects brain against injury in a rat model of focal cerebral ischemia SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REDUCES INFLAMMATION; EXPERIMENTAL STROKE; ARTERY OCCLUSION; GENE-EXPRESSION; PUTATIVE ROLE; CELL-DEATH; ALPHA; CYCLOOXYGENASE AB Background: Stroke is one of the leading causes of death worldwide and a major cause of morbidity and mortality in the United States of America. Brain ischemia-reperfusion (IR) triggers a complex series of biochemical events including inflammation. Leukotrienes derived from 5-lipoxygenase (5-LOX) cause inflammation and are thus involved in the pathobiology of stroke injury. Methods: To test the neuroprotective efficacy of 5-LOX inhibition in a rat model of focal cerebral IR, ischemic animals were either pre- or post-treated with a potent selective 5-LOX inhibitor, (N[ 3-[3-(-fluorophenoxy) phenyl]-1-methyl-2-propenyl]-N-hydroxyurea (BW-B 70C). They were evaluated at 24 h after reperfusion for brain infarction, neurological deficit score, and the expression of 5-LOX. Furthermore, the mechanism and the anti-inflammatory potential of BW-B 70C in the regulation of nuclear factor kappa B ( NF-kappa B) and inflammatory inducible nitric oxide synthase ( iNOS) were investigated both in vivo and in vitro. Results and discussion: Both pre- and post-treatment with BW-B 70C reduced infarctions and improved neurological deficit scores. Immunohistochemical study of brain sections showed IR-mediated increased expression of 5-LOX in the neurons and microglia. BW-B 70C down-regulated 5-LOX and inhibited iNOS expression by preventing NF-kappa B activation. Two other structurally different 5-LOX inhibitors were also administered post IR: caffeic acid and 2, 3, 5-trimethyl-6-[12-hydroxy-5, 10-dodecadiynyl]- 1, 4-benzoquinone (AA-861). As with BW-B 70C, they provided remarkable neuroprotection. Furthermore, in vitro, BW-B 70C inhibited lipopolysaccharide (LPS) mediated nitric oxide production, iNOS induction and NF-kappa B activation in the BV2 microglial cell line. Treating rat primary microglia with BW-B70C confirmed blockage of LPS-mediated translocation of the p65 subunit of NF-kappa B from cytosol to nucleus. Conclusion: The study demonstrates the neuroprotective potential of 5-LOX inhibition through down-regulation of NF-kappa B in a rat model of experimental stroke. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Khan, M (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. EM manujatana@gmail.com; giris@musc.edu; ansarim@musc.edu; elangoc@musc.edu; singha@musc.edu; singhi@musc.edu; khanm@musc.edu FU NCRR NIH HHS [C06 RR015455, C06 RR018823]; NINDS NIH HHS [R01 NS037766, R01 NS022576, R01 NS034741, R01 NS040144, R01 NS040810, R37 NS022576] NR 54 TC 52 Z9 57 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD MAY 11 PY 2006 VL 3 AR 12 DI 10.1186/1742-2094-3-12 PG 13 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 174US UT WOS:000246968900001 PM 16689995 ER PT J AU Feske, S Gwack, Y Prakriya, M Srikanth, S Puppel, SH Tanasa, B Hogan, PG Lewis, RS Daly, M Rao, A AF Feske, S Gwack, Y Prakriya, M Srikanth, S Puppel, SH Tanasa, B Hogan, PG Lewis, RS Daly, M Rao, A TI A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function SO NATURE LA English DT Article ID T-CELL-RECEPTOR; SEVERE COMBINED IMMUNODEFICIENCY; ANHIDROTIC ECTODERMAL DYSPLASIA; ACTIVATED CALCIUM-CHANNEL; KAPPA-B; LINKAGE ANALYSIS; PORE PROPERTIES; NUCLEAR-FACTOR; CA2+ CHANNELS; I-CRAC AB Antigen stimulation of immune cells triggers Ca(2+) entry through Ca(2+) release-activated Ca(2+) ( CRAC) channels, promoting the immune response to pathogens by activating the transcription factor NFAT. We have previously shown that cells from patients with one form of hereditary severe combined immune deficiency ( SCID) syndrome are defective in store-operated Ca(2+) entry and CRAC channel function. Here we identify the genetic defect in these patients, using a combination of two unbiased genome-wide approaches: a modified linkage analysis with single-nucleotide polymorphism arrays, and a Drosophila RNA interference screen designed to identify regulators of store-operated Ca(2+) entry and NFAT nuclear import. Both approaches converged on a novel protein that we call Orai1, which contains four putative transmembrane segments. The SCID patients are homozygous for a single missense mutation in ORAI1, and expression of wild-type Orai1 in SCID T cells restores store-operated Ca(2+) influx and the CRAC current ( I CRAC). We propose that Orai1 is an essential component or regulator of the CRAC channel complex. C1 Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Biol Chem & Mol Pharmacol, Chicago, IL 60611 USA. Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu OI Feske, Stefan/0000-0001-5431-8178; Puppel, Sven-Holger/0000-0003-2745-5120 FU NIGMS NIH HHS [R01 GM045374] NR 47 TC 1147 Z9 1176 U1 9 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 11 PY 2006 VL 441 IS 7090 BP 179 EP 185 DI 10.1038/nature04702 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040YP UT WOS:000237418800037 PM 16582901 ER PT J AU Attar, EC Hasserjian, RP Swartz, MN Harris, NL AF Attar, EC Hasserjian, RP Swartz, MN Harris, NL TI Case 14-2006: A 25-year-old woman with anemia and iron overload - delta beta-thalassemia and XmnI mutation in the G gamma hemoglobin promoter resulting in hereditary persistence of fetal hemoglobin. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DIAMOND-BLACKFAN ANEMIA; SICKLE-CELL-ANEMIA; BONE-MARROW; GENE; HYDROXYUREA C1 Massachusetts Gen Hosp, Ctr Leukemia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Ctr Leukemia, Boston, MA 02114 USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 11 PY 2006 VL 354 IS 19 BP 2047 EP 2056 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 040XA UT WOS:000237413100012 PM 16687718 ER PT J AU Hansen, JE Sohn, W Kim, C Chang, SS Huang, NC Santos, DG Chan, G Weisbart, RH Nishimura, RN AF Hansen, JE Sohn, W Kim, C Chang, SS Huang, NC Santos, DG Chan, G Weisbart, RH Nishimura, RN TI Antibody-mediated Hsp70 protein therapy SO BRAIN RESEARCH LA English DT Article DE Hsp70; protein therapy; protein transduction; Tat; neuroprotection; antibody ID RAT CORTICAL-NEURONS; INTRACELLULAR DELIVERY; IN-VIVO; CANCER-CELLS; TRANSDUCTION; HEAT-SHOCK-PROTEIN-70; MECHANISMS; INDUCTION; PEPTIDE; BRAIN AB Intracellular Hsp70 provides cytoprotection against a variety of stressful stimuli, and an effective means of increasing intracellular Hsp70 levels could prove beneficial in the prevention and treatment of a variety of human diseases. A novel protein transduction domain consisting of the single chain Fv fragment of an anti-DNA antibody known to penetrate into living cells and tissues, mAb 3E10, has recently been used to deliver functional proteins to cells. The ability of the single chain Fv fragment to deliver Hsp70 into living cells was tested by generating an Fv-Hsp70 fusion protein. Fv-Hsp70 was produced as a secreted protein in both COS-7 cells and the methylotropic yeast strain Pichia pastoris and was shown capable of penetrating into COS-7 cells and primary rat cortical neurons. Pretreatment with Fv-Hsp70 protected both COS-7 cells and primary rat cortical neurons against subsequent exposure to hydrogen peroxide. These results provide the first evidence that the Fv fragment of mAb 3E10 is capable of delivering proteins to neurons and indicate its potential in the development of Hsp70 protein therapy. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, San Fernando Valley Program, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Sepulveda, CA 91343 USA. RP Hansen, JE (reprint author), Univ Calif Los Angeles, San Fernando Valley Program, Dept Med, 16111 Plummer St, H Nills, CA 91343 USA. EM jameshansen2004@hotmail.com NR 29 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 9 PY 2006 VL 1088 BP 187 EP 196 DI 10.1016/j.brainres.2006.03.025 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 056HM UT WOS:000238512900020 PM 16630585 ER PT J AU Ay, H Koroshetz, WJ Benner, T Vangel, MG Melinosky, C Arsava, EM Ayata, C Zhu, M Schwamm, LH Sorensen, AG AF Ay, H Koroshetz, WJ Benner, T Vangel, MG Melinosky, C Arsava, EM Ayata, C Zhu, M Schwamm, LH Sorensen, AG TI Neuroanatomic correlates of stroke-related myocardial injury SO NEUROLOGY LA English DT Article ID INSULAR CORTEX STIMULATION; TROPONIN-T; SUDDEN-DEATH; CARDIAC-ARRHYTHMIAS; EUROPEAN-SOCIETY; INFARCTION; LESIONS; DAMAGE; RAT; REDEFINITION AB Background: Myocardial injury can occur after ischemic stroke in the absence of primary cardiac causes. The neuroanatomic basis of stroke-related myocardial injury is not well understood. Objective: To identify regions of brain infarction associated with myocardial injury using a method free of the bias of an a priori hypothesis as to any specific location. Methods: Of 738 consecutive patients with acute ischemic stroke, the authors identified 50 patients in whom serum cardiac troponin T (cTnT) elevation occurred in the absence of any apparent cause within 3 days of symptom onset. Fifty randomly selected, age- and sex-matched patients with ischemic stroke without cTnT elevation served as controls. Diffusion-weighted images with outlines of infarction were co-registered to a template, averaged, and then subtracted to find voxels that differed between the two groups. Voxel-wise p values were determined using a nonparametric permutation test to identify specific regions of infarction that were associated with cTnT elevation. Results: The study groups were well balanced with respect to stroke risk factors, history of coronary artery disease, infarction volume, and frequency of right and left middle cerebral artery territory involvement. Brain regions that were a priori associated with cTnT elevation included the right posterior, superior, and medial insula and the right inferior parietal lobule. Among patients with right middle cerebral artery infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). Conclusions: Infarctions in specific brain regions including the right insula are associated with elevated serum cardiac troponin T level indicative of myocardial injury. C1 Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, GCRC Biomed Imaging Core, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Sch Med, Charlestown, MA USA. Harvard MIT, Div Hlth Sci & Technol, Boston, MA USA. RP Ay, H (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, CNY149-2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013; OI Arsava, Ethem Murat/0000-0002-6527-4139; Schwamm, Lee/0000-0003-0592-9145 FU AHRQ HHS [R01-HS11392-02]; NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R01-NS38477-04] NR 29 TC 92 Z9 97 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2006 VL 66 IS 9 BP 1325 EP 1329 DI 10.1212/01.wnl.0000206077.13705.6d PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 040FS UT WOS:000237365000008 PM 16525122 ER PT J AU Gurrera, RJ Moye, J Karel, MJ Azar, AR Armesto, JC AF Gurrera, RJ Moye, J Karel, MJ Azar, AR Armesto, JC TI Cognitive performance predicts treatment decisional abilities in mild to moderate dementia SO NEUROLOGY LA English DT Article ID ASSESSING PATIENTS CAPACITIES; DIFFERENT LEGAL STANDARDS; QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; SUBSTITUTED JUDGMENT; INFORMED-CONSENT; OLDER-ADULTS; COMPETENCE AB Objective: To examine the contribution of neuropsychological test performance to treatment decision-making capacity in community volunteers with mild to moderate dementia. Methods: The authors recruited volunteers ( 44 men, 44 women) with mild to moderate dementia from the community. Subjects completed a battery of 11 neuropsychological tests that assessed auditory and visual attention, logical memory, language, and executive function. To measure decision making capacity, the authors administered the Capacity to Consent to Treatment Interview, the Hopemont Capacity Assessment Interview, and the MacCarthur Competence Assessment Tool-Treatment. Each of these instruments individually scores four decisional abilities serving capacity: understanding, appreciation, reasoning, and expression of choice. The authors used principal components analysis to generate component scores for each ability across instruments, and to extract principal components for neuropsychological performance. Results: Multiple linear regression analyses demonstrated that neuropsychological performance significantly predicted all four abilities. Specifically, it predicted 77.8% of the common variance for understanding, 39.4% for reasoning, 24.6% for appreciation, and 10.2% for expression of choice. Except for reasoning and appreciation, neuropsychological predictor (beta) profiles were unique for each ability. Conclusions: Neuropsychological performance substantially and differentially predicted capacity for treatment decisions in individuals with mild to moderate dementia. Relationships between elemental cognitive function and decisional capacity may differ in individuals whose decisional capacity is impaired by other disorders, such as mental illness. C1 VA Boston Healthcare Syst, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY USA. RP Gurrera, RJ (reprint author), VA Boston Healthcare Syst, 940 Belmont St 116A, Brockton, MA 02301 USA. EM Ronald.Gurrera@med.va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU Intramural VA [VA999999]; NIMH NIH HHS [R29 MH057104, R29 MH57104] NR 44 TC 45 Z9 46 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2006 VL 66 IS 9 BP 1367 EP 1372 DI 10.1212/01.wnl.0000210527.13661.d1 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 040FS UT WOS:000237365000016 PM 16682669 ER PT J AU Beeri, MS Rapp, M Silverman, JM Schmeidler, J Grossman, HT Fallon, JT Purohit, DP Perl, DP Siddiqui, A Lesser, G Rosendorff, C Haroutunian, V AF Beeri, MS Rapp, M Silverman, JM Schmeidler, J Grossman, HT Fallon, JT Purohit, DP Perl, DP Siddiqui, A Lesser, G Rosendorff, C Haroutunian, V TI Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E GENOTYPES; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; ATHEROSCLEROSIS; DEMENTIA; HYPERTENSION; CHOLESTEROL; POPULATION; PREVALENCE AB Objective: To examine the associations between postmortem Alzheimer disease (AD) neuropathology and autopsy-verified cardiovascular disease. Methods: The authors examined 99 subjects (mean age at death = 87.6; SD = 8.7) from the Mount Sinai School of Medicine Department of Psychiatry Brain Bank who were devoid of cerebrovascular disease-associated lesions or of non-AD-related neuropathology. Density of neuritic plaques (NPs) and neurofibrillary tangles (NFTs) as well as coronary artery and aortic atherosclerosis, left ventricular wall thickness, and heart weight were measured. Partial correlations were used to assess the associations of the four cardiovascular variables with NPs and NFTs in the hippocampus, entorhinal cortex, and multiple regions of the cerebral cortex after controlling for age at death, sex, dementia severity, body mass index, and ApoE genotype. These analyses were also repeated separately for ApoE4 carriers and noncarriers. Results: The extent of coronary artery disease and to a lesser extent atherosclerosis were significantly associated with the density of cardinal neuropathologic lesions of AD in this autopsy sample (significant correlations between 0.22 and 0.29). These associations were more pronounced for the ApoE4 allele carriers (n = 42; significant correlations between 0.34 and 0.47). Conclusions: The degree of coronary artery disease is independently associated with the cardinal neuropathological lesions of Alzheimer disease. These associations are primarily attributable to individuals with the ApoE4 allele. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Biostat, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Jewish Home & Hosp, New York, NY USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, 4F-33B,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM vahram.haroutunian@mssm.edu FU NIA NIH HHS [1 K01 AG023515-01A2, AG02219, AG05138, K01 AG023515, K01 AG023515-01A2, P01 AG002219, P50 AG005138] NR 39 TC 59 Z9 61 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2006 VL 66 IS 9 BP 1399 EP 1404 DI 10.1212/01.wnl.0000210447.19748.0b PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 040FS UT WOS:000237365000020 PM 16682673 ER PT J AU Swarztrauber, K Koudelka, C Brodsky, MA AF Swarztrauber, K Koudelka, C Brodsky, MA TI Initial pharmacotherapy in a population of veterans with Parkinson disease SO NEUROLOGY LA English DT Article ID LEVODOPA; BEGIN AB The authors analyzed patient and prescribing provider characteristics for 530 veterans identified from VA pharmacy records with Parkinson disease (PD) and initial pharmacotherapy. Neurologists prescribed 29% of initial therapy. While a patient being younger and seeing a movement disorder specialist predicted receiving dopamine agonists, only 20% of patients younger than age 65 years received dopamine agonists. Initial pharmacotherapy is strongly influenced by the provider's specialty but mostly initiated by providers without PD expertise. C1 Portland VA Med Ctr, Portland, OR USA. Parkinson Dis Res Educ & Clin Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Biostat & Bioinformat Shared Resources, Portland, OR USA. Oregon Hlth Sci Univ, Ctr Biostat Comp & Informat Biol & Med, Portland, OR USA. RP Swarztrauber, K (reprint author), P-3-PADRECC,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM swarztra@ohsu.edu NR 7 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 9 PY 2006 VL 66 IS 9 BP 1425 EP 1426 DI 10.1212/01.wnl.0000210433.49727.40 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 040FS UT WOS:000237365000025 PM 16682678 ER PT J AU Sage, C Huang, MQ Vollrath, MA Brown, MC Hinds, PW Corey, DP Vetter, DE Chen, ZY AF Sage, C Huang, MQ Vollrath, MA Brown, MC Hinds, PW Corey, DP Vetter, DE Chen, ZY TI Essential role of retinoblastoma protein in mammalian hair cell development and hearing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE differentiation; proliferation; regeneration; maturation; conditional knockout ID MOUSE INNER-EAR; NERVOUS-SYSTEM; GENE; PROLIFERATION; MICE; EXPRESSION; PATHWAY; FAMILY; ORGAN; MATH1 AB The retinoblastoma protein pRb is required for cell-cycle exit of embryonic mammalian hair cells but not for their early differentiation. However, its role in postnatal hair cells is unknown. To study the function of pRb in mature animals, we created a new conditional mouse model, with the Rb gene deleted primarily in the inner ear. Progeny survive up to 6 months. During early postnatal development, pRb(-/-) hair cells continue to divide and can transduce mechanical stimuli. However, adult pRb(-/-) mice exhibit profound hearing loss due to progressive degeneration of the organ of Corti. We show that pRb is required for the full maturation of cochlear outer hair cells, likely in a gene-specific manner, and is also essential for their survival. In addition, lack of pRb results in cell division in postnatal auditory supporting cells. In contrast, many pRb(-/-) vestibular hair cells survive and continue to divide in adult mice. Significantly, adult pRb(-/)- vestibular hair cells are functional, and pRb(-/-) mice maintain partial vestibular function. Therefore, the functional adult vestibular pRb(-/-) hair cells, derived from proliferation of postnatal hair cells, are largely integrated into vestibular pathways. This study reveals essential yet distinct roles of pRb in cochlear and vestibular hair cell maturation, function, and survival and suggests that transient block of pRb function in mature hair cells may lead to propagation of functional hair cells. C1 Massachusetts Gen Hosp, Neurol Serv, Ctr Nervous Syst Repair, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Radiat Oncol, Mol Oncol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Biomed Engn, Boston, MA 02111 USA. RP Chen, ZY (reprint author), Massachusetts Gen Hosp, Neurol Serv, Ctr Nervous Syst Repair, Boston, MA 02114 USA. EM zhengyi@helix.mgh.harvard.edu OI Corey, David/0000-0003-4497-6016 FU NIA NIH HHS [R01 AG020208, DC-AG20208]; NIDCD NIH HHS [R01 DC004546, DC- 06258, DC-02281, DC-04546, R01 DC002281, DC-01089, R01 DC001089, R01 DC006258, R01 DC006908, DC-06908] NR 40 TC 88 Z9 96 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2006 VL 103 IS 19 BP 7345 EP 7350 DI 10.1073/pnas.0510631103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043GT UT WOS:000237589000028 PM 16648263 ER PT J AU Yan, CT Kaushal, D Murphy, M Zhang, Y Datta, A Chen, CZ Monroe, B Mostoslavsky, G Coakley, K Gao, YJ Mills, KD Fazeli, AP Tepsuporn, S Hall, G Mulligan, R Fox, E Bronson, R De Girolami, U Lee, C Alt, FW AF Yan, CT Kaushal, D Murphy, M Zhang, Y Datta, A Chen, CZ Monroe, B Mostoslavsky, G Coakley, K Gao, YJ Mills, KD Fazeli, AP Tepsuporn, S Hall, G Mulligan, R Fox, E Bronson, R De Girolami, U Lee, C Alt, FW TI XRCC4 suppresses medulloblastomas with recurrent translocations in p53-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; N-MYC; HUMAN NEUROBLASTOMAS; GENOMIC STABILITY; P53; TUMORS; AMPLIFICATION; NEUROGENESIS; CELLS; DIFFERENTIATION AB Inactivation of the XRCC4 nonhomologous end-joining factor in the mouse germ line leads to embryonic lethality, in association with apoptosis of newly generated, postmitotic neurons. We now show that conditional inactivation of the XRCC4 in nestin-expressing neuronal progenitor cells, although leading to no obvious phenotype in a WT background, leads to early onset of neuronally differentiated medulloblastomas (MBs) in a p53-deficient background. A substantial proportion of the XRCC4/p53-deficient MBs have high-level N-myc gene amplification, often intrachromosomally in the context of complex translocations or other alterations of chromosome 12, on which N-myc resides, or extrachromosomally within double minutes. In addition, most XRCC4/p53-deficient MBs harbor clonal translocations of chromosome 13, which frequently involve chromosome 6 as a partner. One copy of the patched gene (Ptc), which lies on chromosome 13, was deleted in all tested XRCC4/p53-deficient MBs in the context of translocations or interstitial deletions. In addition, Cyclin D2, a chromosome 6 gene, was amplified in a subset of tumors. Notably, amplification of Myc-family or Cyclin D2 genes and deletion of Ptc also have been observed in human MBs. We therefore conclude that, in neuronal cells of mice, the nonhomologous end-joining pathway plays a critical role in suppressing genomic instability that, in a p53-deficient background, routinely contributes to genesis of MBs with recurrent chromosomal alterations. C1 Harvard Univ, Childrens Hosp, Sch Med,Dept Genet, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neuropathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana Farber Microarray Core Facil, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med,Dept Genet, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NCI NIH HHS [1P01-CA10990, T32 CA070083, T32 CA70083] NR 32 TC 67 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2006 VL 103 IS 19 BP 7378 EP 7383 DI 10.1073/pnas.0601938103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043GT UT WOS:000237589000034 PM 16670198 ER PT J AU Casola, S Cattoretti, G Uyttersprot, N Koralov, SB Segal, J Hao, ZY Waisman, A Egert, A Ghitza, D Rajewsky, K AF Casola, Stefano Cattoretti, Giorgio Uyttersprot, Nathalie Koralov, Sergei B. Segal, Jane Hao, Zhenyue Waisman, Ari Egert, Angela Ghitza, Dvora Rajewsky, Klaus TI Tracking germinal center B cells expressing germ-line immunoglobulin gamma 1 transcripts by conditional gene targeting SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE class switch recombination; Cre recombinase; memory B; plasma cells ID CLASS-SWITCH RECOMBINATION; HEAVY-CHAIN GENES; IGH LOCI; MICE; ISOTYPE; ACTIVATION; INDUCTION; RESPONSES; OCCURS; INTERLEUKIN-4 AB Germinal centers (GCs) represent the main sites for the generation of high-affinity, class-switched antibodies during T cell-dependent antibody responses. To study gene function specifically in GC B cells, we generated C gamma 1-cre mice in which the expression of Cre recombinase is induced by transcription of the Ig gamma 1 constant region gene segment (C gamma 1). In these mice, Cre-mediated recombination at the fas, Ig beta, IgH, and Rosa26 loci occurred in GC B cells as early as 4 days after immunization with T cell-dependent antigens and involved > 85% of GC B cells at the peak of the GC reaction. Less than 2% of IgM(+) B cells showed Cre-mediated recombination. These cells carried few Ig somatic mutations, expressed germ-line C gamma 1- and activation-induced cytidine deaminase-specific transcripts and likely include GC B cell founders and/or plasma cell precursors. Cre-mediated recombination involved most IgG1, but also a fraction of IgG3-, IgG2a-, IgG2b-, and IgA-expressing GC and post-GC B cells. This result indicates that a GC B cell can transcribe more than one downstream CH gene before undergoing class switch recombination. The efficient induction of Cre expression in GC B cells makes the C gamma 1-cre allele a powerful tool for the genetic analysis of these cells, as well as, in combination with a suitable marker for Cre-mediated recombination, the tracking of class-switched memory B and plasma cells in vivo. To expedite the genetic analysis of GC B cells, we have established C gamma 1-cre F-1 embryonic stem cells, allowing further rounds of gene targeting and the cloning of compound mutants by tetraploid embryo complementation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. RP Casola, S (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM stefano.casola@ifom-ieo-campus.it; rajewsky@cbr.med.harvard.edu RI Waisman, Ari/C-7383-2015 OI Waisman, Ari/0000-0003-4304-8234 FU NCI NIH HHS [P01 CA092625, P01 CA92625, R01 CA098285] NR 42 TC 67 Z9 68 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2006 VL 103 IS 19 BP 7396 EP 7401 DI 10.1073/pnas.0602353103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043GT UT WOS:000237589000037 PM 16651521 ER PT J AU Si, ZH Vandegraaff, N O'hUigin, C Song, B Yuan, W Xu, C Perron, M Li, X Marasco, WA Engelman, A Dean, M Sodroski, J AF Si, ZH Vandegraaff, N O'hUigin, C Song, B Yuan, W Xu, C Perron, M Li, X Marasco, WA Engelman, A Dean, M Sodroski, J TI Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE capsid; convergent evolution; restriction factor; retrovirus; ungulates ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; SIMIAN IMMUNODEFICIENCY; REVERSE TRANSCRIPTION; MONKEY TRIM5-ALPHA; POSTENTRY RESTRICTION; B30.2(SPRY) DOMAIN; HUMAN-CELLS; OLD-WORLD; HIV-1 AB Primate tripartite motif 5 alpha (TRIM5 alpha) proteins mediate innate intracellular resistance to retroviruses. In humans, TRIMS is located in a paralogous cluster that includes TRIM6, TRIM34, and TRIM22. Although TRIM6 and TRIM34 orthologs are found in other mammals, TRIM5 has to date been identified only in primates. Cow cells exhibit early blocks to infection by several retroviruses. We identify a cytoplasmic TRIM protein encoded by LOC505265 that is responsible for the restriction of infection by several lentiviruses and N-tropic murine leukemia virus in cow cells. Susceptibility of N-tropic murine leukemia virus to 505265-mediated restriction is determined primarily by residue 110 of the viral capsid protein. Phylogenetically, cow LOC505265 segregates with the TRIM5/TRIM6/TRIM34 group, but is not an ortholog of known TRIM genes. The B30.2/SPRY domain of 505265 exhibits long variable regions, a characteristic of the proteins encoded by this paralogous group, and shows evidence of positive selection. Apparently, cows have independently evolved a retroviral restriction factor from the same TRIM family that spawned TRIMS in primates. Particular features of this subset of cytoplasmic TRIM proteins may be conducive to the convergent evolution of virus-restricting factors. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Div AIDS, Boston, MA 02115 USA. SAIC Frederick, Ft Detrick, MD 21702 USA. Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Div AIDS, Boston, MA 02115 USA. EM joseph.sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI63987, AI52014, AI60354, P30 AI060354, R01 AI052014, R01 AI063987] NR 50 TC 60 Z9 66 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 9 PY 2006 VL 103 IS 19 BP 7454 EP 7459 DI 10.1073/pnas.0600771103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 043GT UT WOS:000237589000047 PM 16648259 ER PT J AU Armstrong, K Hughes-Halbert, C Asch, DA AF Armstrong, K Hughes-Halbert, C Asch, DA TI Patient preferences can be misleading as explanations for racial disparities in health care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CARDIAC-CATHETERIZATION; RENAL-TRANSPLANTATION; ETHNIC DISPARITIES; TRUST; RACE; COMMUNICATION; HYSTERECTOMY; SATISFACTION; INFORMATION; PHYSICIANS AB Addressing racial differences in US health care is difficult, in part because the origins of these differences are complex and poorly understood and also because only some differences may represent legitimate agendas for reform. For example, racial differences that result from differences in access or from clinician prejudices are symptoms of a problem that must be addressed; in contrast, racial differences that arise from different preferences for health care might be seen as acceptable consequences of variation in personal or cultural values that are worth respecting and preserving. However, we believe that this distinction is sometimes overstated. We present several fictitious clinical stories to illustrate how what appear to be individual or cultural preferences are often substantially shaped by modifiable practices of the health care system. True differences in preference that are worthy of respect surely exist between individuals or demographic groups, but some apparent differences in preference may actually reflect problems with the health care system that are worthy of remediation. Uncovering the hidden constraints that we impose on health care choice may help us reduce unwanted disparities in health care. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), Univ Penn, Sch Med, Dept Med, 1204 Blockley Hall, Philadelphia, PA 19104 USA. EM karmstro@mail.med.upenn.edu NR 50 TC 28 Z9 28 U1 4 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 8 PY 2006 VL 166 IS 9 BP 950 EP 954 DI 10.1001/archinte.166.9.950 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 039VF UT WOS:000237334900001 PM 16682567 ER PT J AU Valiyeva, E Russell, LB Miller, JE Safford, MM AF Valiyeva, E Russell, LB Miller, JE Safford, MM TI Lifestyle-related risk factors and risk of future nursing home admission SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MORTALITY; OBESITY; CARE AB Background: While risks of disease, hospitalization, and death attributable to lifestyle-related factors such as smoking, inactivity, and obesity have been well studied, their associations with nursing home admission are less well known. These risk factors are usually established by middle age, but nothing is known about how they relate to long-term risk of nursing home admission in this age group. Methods: Cox proportional hazards regressions were used to analyze risk of nursing home admission over 2 decades of follow-up (1971-1975 to 1992) in a nationally representative, longitudinal survey of community-dwelling adults aged 45 to 74 years at baseline. Middle-aged (45-64 years at baseline) and elderly persons ( aged 65-74 years at baseline) were analyzed separately: 230 (6.5%) of 3526 middle-aged respondents and 728 (24.7%) of 2936 elderly ones had 1 or more nursing home admissions. Baseline risk factors included smoking, inactivity, obesity, elevated blood pressure, elevated total cholesterol level, and diabetes mellitus, which were defined according to national guidelines. Results: All lifestyle-related factors, except total cholesterol level, were associated with higher risk of nursing home admission during follow-up in one or both age groups. Risk ratios were higher in middle-aged than in elderly persons. In those aged 45 to 64 years at baseline, diabetes more than tripled the risk of nursing home admission ( relative risk, 3.25; 95% confidence interval, 2.04-5.19); smoking, inactivity, and elevated systolic blood pressure had relative risks of 1.56, 1.40, and 1.35, respectively. Obesity was a risk factor for those aged 65 to 74 years at baseline, but not for the middle-aged subjects. Persons with 2 lifestyle-related factors were at greatly increased risk, especially if 1 was diabetes. Conclusions: Lifestyle factors are important contributors to the long-term risk of nursing home admission. Modifying lifestyle, especially in middle age, may reduce the risk of admission. C1 Rutgers State Univ, Inst Hlth, New Brunswick, NJ 08901 USA. Rutgers State Univ, Dept Econ, New Brunswick, NJ 08901 USA. Rutgers State Univ, Bloustein Sch Planning & Publ Policy, New Brunswick, NJ 08901 USA. Rutgers State Univ, Ernest Mario Sch Pharm, Dept Pharm Practice & Adm, Piscataway, NJ USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. Univ Alabama, Sch Med, Birmingham, AL USA. RP Russell, LB (reprint author), Rutgers State Univ, Inst Hlth, 30 Coll Ave, New Brunswick, NJ 08901 USA. EM lrussell@ifh-mail1.rutgers.edu FU AHRQ HHS [HS 11477] NR 31 TC 35 Z9 35 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 8 PY 2006 VL 166 IS 9 BP 985 EP 990 DI 10.1001/archinte.166.9.985 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 039VF UT WOS:000237334900006 PM 16682571 ER PT J AU Chen, WY Manson, JE Hankinson, SE Rosner, B Holmes, MD Willett, WC Colditz, GA AF Chen, WY Manson, JE Hankinson, SE Rosner, B Holmes, MD Willett, WC Colditz, GA TI Unopposed estrogen therapy and the risk of invasive breast cancer SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HORMONE-REPLACEMENT THERAPY; CONJUGATED EQUINE ESTROGENS; POSTMENOPAUSAL WOMEN; MEDROXYPROGESTERONE ACETATE; ENDOMETRIAL CANCER; RECEPTOR STATUS; NURSES HEALTH; BONE AB Background: Although short-term unopposed estrogen use does not seem to increase breast cancer risk, the effect of longer-term estrogen use remains unclear. We sought to assess the relationship between longer-term use of unopposed estrogen and the risk of invasive breast cancer over an extended follow-up period. Methods: Within the Nurses' Health Study, a prospective cohort study, we observed 11 508 postmenopausal women who had a hysterectomy and reported information on estrogen use at baseline ( 1980). The study population was expanded every 2 years to include women who subsequently became postmenopausal and had a hysterectomy, so that 28 835 women were included in the final follow-up period (2000-2002). Estrogen use was assessed from self-reported data on biennial questionnaires. The main outcome was invasive breast cancer. Results: A total of 934 invasive breast cancers were included in the analysis. Breast cancer risk increased with duration of unopposed estrogen use among longer-term users with the highest risk seen in cancers positive for estrogen receptor ( ER+) and progesterone receptor ( PR+). The multivariate relative risks (RRs) and 95% confidence intervals (CIs) for breast cancer with current use of unopposed estrogen for less than 5 years, 5 to 9.9 years, 10 to 14.9 years, 15 to 19.9 years, and 20 years or longer were, respectively, 0.96 ( 95% CI, 0.75-1.22), 0.90 ( 95% CI, 0.73-1.12), 1.06 ( 95% CI, 0.87-1.30), 1.18 ( 95% CI, 0.95-1.48), and 1.42 ( 95% CI, 1.13-1.77) ( P for trend < .001). The risk of ER+/PR+ breast cancers was noted to be statistically significant after 15 years of current use (RR, 1.48; 95% CI, 1.05-2.07). Conclusion: Users of unopposed estrogen were at increased risk of breast cancer but only after longer-term use. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Chen, WY (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM wendy.chen@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 87969] NR 22 TC 116 Z9 119 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 8 PY 2006 VL 166 IS 9 BP 1027 EP 1032 DI 10.1001/archinte.166.9.1027 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 039VF UT WOS:000237334900013 PM 16682578 ER PT J AU Varkonyi, A Kelsey, K Semey, K Bodell, WJ Levay, G Mark, E Wain, JC Christiani, DC Wiencke, JK AF Varkonyi, A Kelsey, K Semey, K Bodell, WJ Levay, G Mark, E Wain, JC Christiani, DC Wiencke, JK TI Polyphenol associated-DNA adducts in lung and blood mononuclear cells from lung cancer patients SO CANCER LETTERS LA English DT Article DE DNA adducts; P-32-postlabeling; lung cancer; cigarette smoke; benzene; polyaromatic hydrocarbons ID PEROXIDASE ACTIVATION; BENZENE METABOLITES; BONE-MARROW; HL-60 CELLS; SMOKING; DAMAGE AB The formation of smoking induced-DNA adducts is a critical factor in the induction of human lung cancer. As derivates of benzene and polyaromatic hydrocarbons (PAHs) are important compounds of tobacco smoke, in DNA isolated from human lung and blood mononuclear cells (MNCs) from 38 lung cancer patients, we used the P-32-postlabeling assay to detect polyphenol associated DNA adducts. Two DNA adducts were detected in blood MNCs and lung tissue that co-chromatographed with DNA modifications from HL60 cells treated with combinations of benzene metabolites (e.g., hydroquinone and benzenetriol). These adducts were designated polyphenol-associated DNA adducts. Relative adduct levels for polyphenolic adducts were five-fold higher than aromatic adducts in both lung and MNCs. A significant correlation was observed between levels of polyphenol adducts and total duration of cigarette smoking in lung (r = 0.34; P < 0.04) and MNCs (r = 0.7; P < 0.04), but no correlation between levels of polyphenol adducts and pack-years consumption of cigarettes nor time since quitting smoking in former smokers. Long term former smokers and the one non-smoker in the study had detectable levels of polyphenol adducts. Surprisingly, the levels of polyphenol adducts in MNCs were highly correlated with aromatic adduct levels (r = 0.84; P < 0.001). Individual aromatic adducts in MNCs also correlated with polyphenol adducts. Total polyphenol adduct levels had a correlation with aromatic DNA adduct levels in lung tissue (r = 0.46; P < 0.01). To our knowledge these results are the only comparison of adducts in MNCs with lung tissue, and the only data set indicating that blood MNCs are a valid surrogate for lung adduct DNA burden. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Epidemiol, Microbiol Res Grp, H-1529 Budapest, Hungary. Univ Calif San Francisco, Sch Med, Lab Mol Epidemiol, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Canc Biol Program, Boston, MA 02115 USA. RP Varkonyi, A (reprint author), Natl Inst Epidemiol, Microbiol Res Grp, Piheno 1, H-1529 Budapest, Hungary. EM andrea_varkonyi@hotmail.com NR 10 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 8 PY 2006 VL 236 IS 1 BP 24 EP 31 DI 10.1016/j.canlet.2005.04.034 PG 8 WC Oncology SC Oncology GA 044NP UT WOS:000237679600003 PM 15967573 ER PT J AU Houston, TK Person, SD Pletcher, MJ Liu, K Iribarren, C Kiefe, CI AF Houston, TK Person, SD Pletcher, MJ Liu, K Iribarren, C Kiefe, CI TI Active and passive smoking and development of glucose intolerance among young adults in a prospective cohort: CARDIA study SO BRITISH MEDICAL JOURNAL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CIGARETTE-SMOKING; RISK DEVELOPMENT; MEN; RECRUITMENT; PATTERNS; ALCOHOL AB Objective To assess whether active and passive smokers are more likely than non-smokers to develop clinically relevant glucose intolerance or diabetes. Design Coronary artery risk development in Young adults (CARDIA) is a prospective cohort study begun in 1985-6 with 15 years of follow-up. Setting Participants recruited from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California, USA. Participants Black and white men and women aged 18-30 years with no glucose intolerance at baseline, including 1386 current smokers, 621 previous smokers, 1452 never smokers with reported exposure to secondhand smoke (validated by serum cotinine concentrations 1-15 ng/ml), and 1113 never smokers with no exposure to secondhand smoke. Main outcome measure Time to development of glucose intolerance (glucose >= 100 mg/dl or taking antidiabetic drugs) during 15 years of follow-up. Results Median age at baseline was 25, 55% of participants were women, and 50% were African-American. During follow-up, 16.7% of participants developed glucose intolerance. A graded association existed between smoking exposure and the development of glucose intolerance. The 15 year incidence of glucose intolerance was highest among smokers (21.8%), followed by never smokers with passive smoke exposure (17.2%), and then previous smokers (14.4%); it was lowest for never smokers with no passive smoke exposure (11.5%). Current smokers (hazard ratio 1.65, 95% confidence interval 1.27 to 2.13) and never smokers with passive smoke exposure (1.35, 1.06 to 1.71) remained at higher risk than never smokers without passive smoke exposure after adjustment for multiple baseline sociodemographic, biological, and behavioural factors, but risk in previous smokers was similar to that in never smokers without passive smoke exposure. Conclusion These findings support a role of both active and passive smoking in the development of glucose intolerance in young adulthood. C1 Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. Kaiser Permanente, Oakland, CA USA. Northwestern Univ, Evanston, IL USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Birmingham Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. RP Houston, TK (reprint author), Univ Alabama, Div Gen Internal Med, 510 20th St S,FOT 720, Birmingham, AL 35294 USA. EM thouston@uabmc.edu RI Houston, Thomas/F-2469-2013 FU NHLBI NIH HHS [N01-HC48048, N01-HC-05187, N01-HC-45134, N01-HC-48047, N01-HC-48050, N01-HC-95095] NR 25 TC 100 Z9 108 U1 2 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD MAY 6 PY 2006 VL 332 IS 7549 BP 1064 EP 1067 DI 10.1136/bmj.38779.584028.55 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 042HI UT WOS:000237518400017 PM 16603565 ER PT J AU Ho, PM Rumsfeld, JS AF Ho, PM Rumsfeld, JS TI Cardiac risk management in severe mental illness SO LANCET LA English DT Editorial Material ID DISEASE; SCHIZOPHRENIA C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Cardiol Sect, Denver, CO 80220 USA. RP Ho, PM (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Cardiol Sect, 4200 E 9th Ave, Denver, CO 80220 USA. EM Michael.ho@uchsc.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 6 PY 2006 VL 367 IS 9521 BP 1469 EP 1471 DI 10.1016/S0140-6736(06)68628-5 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 039RJ UT WOS:000237324200009 PM 16679146 ER PT J AU He, P Shan, L Lin, NC Martin, GB Kemmerling, B Nurnberger, T Sheen, J AF He, P Shan, L Lin, NC Martin, GB Kemmerling, B Nurnberger, T Sheen, J TI Specific bacterial suppressors of MAMP signaling upstream of MAPKKK in Arabidopsis innate immunity SO CELL LA English DT Article ID PROGRAMMED CELL-DEATH; SYSTEM EFFECTOR PROTEINS; PTO-MEDIATED RESISTANCE; PSEUDOMONAS-SYRINGAE; NONHOST RESISTANCE; III EFFECTORS; DEFENSE RESPONSES; PLANT DEFENSE; FLAGELLIN PERCEPTION; KINASE AB Plants and animals possess innate immune systems to prevent infections and are effectively "nonhosts" for most potential pathogens. The molecular mechanisms underlying nonhost immunity in plants remain obscure. In Arabidopsis, nonhost/nonpathogenic Pseudomonas syringae sustains but pathogenic P. syringae suppresses early MAMP (microbe-associated molecular pattern) marker-gene activation. We performed a cell-based genetic screen of virulence factors and identified AvrPto and AvrPtoB as potent and unique suppressors of early-defense gene transcription and MAP kinase (MAPK) signaling. Unlike effectors of mammalian pathogens, AvrPto and AvrPtoB intercept multiple MAMP-mediated signaling upstream of MAPKKK at the plasma membrane linked to the receptor. In transgenic Arabidopsis, AvrPto blocks early MAMP signaling and enables nonhost P. syringae growth. Deletions of avrPto and avrPtoB from pathogenic P. syringae reduce its virulence. The studies reveal a fundamental role of MAMP signaling in nonhost immunity, and a novel action of type III effectors from pathogenic bacteria. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. Cornell Univ, Dept Plant Pathol, Ithaca, NY 14853 USA. Univ Tubingen, Zentrum Mol Biol Pflanzen, D-72076 Tubingen, Germany. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu RI Martin, Gregory/F-6262-2011; OI Martin, Gregory/0000-0003-0044-6830; LIN, NAI-CHUN/0000-0002-6485-9776; Kemmerling, Birgit/0000-0003-1174-0189 FU NIGMS NIH HHS [R01 GM70567] NR 45 TC 237 Z9 257 U1 8 U2 41 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 5 PY 2006 VL 125 IS 3 BP 563 EP 575 DI 10.1016/j.cell.2006.02.047 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 042CY UT WOS:000237506100021 PM 16678099 ER PT J AU Chen, BE Kondo, M Garnier, A Watson, FL Puettmann-Holgado, R Lamar, DR Schmucker, D AF Chen, BE Kondo, M Garnier, A Watson, FL Puettmann-Holgado, R Lamar, DR Schmucker, D TI The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila SO CELL LA English DT Article ID AXON GUIDANCE; NEURAL DEVELOPMENT; SENSORY NEURONS; ALPHA-NEUREXINS; NERVOUS-SYSTEM; BINDING; RECEPTORS; FAMILY; SUPERFAMILY; PROJECTIONS AB Alternative splicing of Dscam generates an enormous molecular diversity with maximally 38,016 different receptors. Whether this large diversity is required in vivo is currently unclear. We examined the role of Dscam in neuron-target recognition of single mechanosensory neurons, which connect with different target cells through multiple axonal branches' Analysis of Dscam null neurons demonstrated an essential role of Dscam for growth and directed extension of axon branches. Expression of randomly chosen single isoforms could not rescue connectivity but did restore basic axonal extension and rudimentary branching. Moreover, two Dscam alleles were generated that each reduced the maximally possible Dscam diversity to 22,176 isoforms. Reduction of Dscam diversity resulted in specific connectivity defects of mechanosensory neurons. Furthermore, the observed allele-specific phenotypes suggest functional differences among isoforms. Our findings provide evidence that a very large number of structurally unique receptor isoforms is required to ensure fidelity and precision of neuronal connectivity. C1 Harvard Univ, Sch Med, Dept Neurobiol, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA. RP Schmucker, D (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA. EM dietmar_schmucker@dfci.harvard.edu FU NCI NIH HHS [T32CA09361]; NINDS NIH HHS [R01-NS46747] NR 39 TC 113 Z9 118 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 5 PY 2006 VL 125 IS 3 BP 607 EP 620 DI 10.1016/j.cell.2006.03.034 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 042CY UT WOS:000237506100024 PM 16678102 ER PT J AU Yang, XH Kovalenko, OV Kolesnikova, TV Andzelm, MM Rubinstein, E Strominger, JL Hemler, ME AF Yang, XH Kovalenko, OV Kolesnikova, TV Andzelm, MM Rubinstein, E Strominger, JL Hemler, ME TI Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE 4 SUPERFAMILY; MHC CLASS-II; MONOCLONAL-ANTIBODIES; TETRASPANIN CD9; TM4SF PROTEINS; MRP-1/CD9 EXPRESSION; CD9-DEFICIENT MICE; BETA(1) INTEGRINS; GM3 GANGLIOSIDE; POOR-PROGNOSIS AB CD9, a tetraspanin protein, makes crucial contributions to sperm egg fusion, other cellular fusions, epidermal growth factor receptor signaling, cell motility, and tumor suppression. Here we characterize a low affinity anti-CD9 antibody, C9BB, which binds preferentially to homoclustered CD9. Using mAb C9BB as a tool, we show that cell surface CD9 homoclustering is promoted by expression of alpha 3 beta 1 and alpha 6 beta 4 integrins and by palmitoylation of the CD9 and beta 4 proteins. Conversely, CD9 is shifted toward heteroclusters upon expression of CD9 partner proteins (EWI-2 and EWI-F) or other tetraspanins, or upon ablation of CD9 palmitoylation. Furthermore, unpalmitoylated CD9 showed enhanced EWI-2 association, thereby demonstrating a previously unappreciated role for tetraspanin palmitoylation, and underscoring how depalmitoylation and EWI-2 association may collaborate to shift CD9 from homo- to heteroclusters. In conclusion, we have used a novel molecular probe ( mAb C9BB) to demonstrate the existence of multiple types of CD9 complex on the cell surface. A shift from homo- to heteroclustered CD9 may be functionally significant because the latter was especially obvious on malignant epithelial tumor cells. Hence, because of its specialized properties, C9BB may be more useful than other anti-CD9 antibodies for monitoring CD9 during tumor progression. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Paris 11, INSERM, U268, Inst Andre Lwoff, F-94807 Villejuif, France. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@DFCI.Harvard.edu OI Rubinstein, Eric/0000-0001-7623-9665 FU NCI NIH HHS [CA42368]; NIGMS NIH HHS [GM38903] NR 67 TC 28 Z9 28 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 2006 VL 281 IS 18 BP 12976 EP 12985 DI 10.1074/jbc.M510617200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 037GI UT WOS:000237134700093 PM 16537545 ER PT J AU Ripoll, J Ntziachristos, V AF Ripoll, J Ntziachristos, V TI From finite to infinite volumes: Removal of boundaries in diffuse wave imaging SO PHYSICAL REVIEW LETTERS LA English DT Article ID OPTICAL TOMOGRAPHY; SCATTERING; LIGHT; MEDIA AB In this Letter, we present a method that removes the contribution of the boundaries on the measurements from highly scattering media, transforming the signals captured from a bounded medium to measurements that would have been obtained if no boundary were present. This approach opens new possibilities in tomographic imaging in diffuse media as it eliminates the need for explicitly modeling boundaries and significantly simplifies reconstruction requirements. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion, Greece. Massachusetts Gen Hosp, Lab BioOpt & Mol Imaging, Ctr Mol Imaging Res, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. RP Ripoll, J (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, Iraklion, Greece. RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 15 TC 18 Z9 18 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAY 5 PY 2006 VL 96 IS 17 AR 173903 DI 10.1103/PhysRevLett.96.173903 PG 4 WC Physics, Multidisciplinary SC Physics GA 039QO UT WOS:000237321500019 PM 16712298 ER PT J AU Kaelin, WG AF Kaelin, WG TI Cell biology - Divining cancer cell weaknesses SO NATURE LA English DT Editorial Material ID RNAI C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM William_Kaelin@dfci.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 4 PY 2006 VL 441 IS 7089 BP 32 EP 34 DI 10.1038/441032a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 038TB UT WOS:000237248600021 PM 16672958 ER PT J AU Anton, RF O'Malley, SS Ciraulo, DA Cisler, RA Couper, D Donovan, DM Gastfriend, DR Hosking, JD Johnson, BA LoCastro, JS Longabaugh, R Mason, BJ Mattson, ME Miller, WR Pettinati, HM Randall, CL Swift, R Weiss, RD Williams, LD Zweben, A AF Anton, RF O'Malley, SS Ciraulo, DA Cisler, RA Couper, D Donovan, DM Gastfriend, DR Hosking, JD Johnson, BA LoCastro, JS Longabaugh, R Mason, BJ Mattson, ME Miller, WR Pettinati, HM Randall, CL Swift, R Weiss, RD Williams, LD Zweben, A CA COMBINE Study Res Grp TI Combined pharmacotherapies and behavioral interventions for alcohol dependence - The COMBINE study: A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TESTING COMBINED PHARMACOTHERAPIES; COMPULSIVE DRINKING SCALE; UNITED-STATES; NALTREXONE TREATMENT; RELAPSE PREVENTION; PRIMARY-CARE; DOUBLE-BLIND; ACAMPROSATE; DISEASE; MAINTENANCE AB Context Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. Objectives To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. Design, Setting, and Participants Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. Interventions Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d) or acamprosate ( 3 g/d), both, and/or both placebos, with or without a combined behavioral intervention ( CBI). A ninth group received CBI only ( no pills). Patients were also evaluated for up to 1 year after treatment. Main Outcome Measures Percent days abstinent from alcohol and time to first heavy drinking day. Results All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n= 302), CBI plus medical management and placebos ( n= 305), or both naltrexone and CBI plus medical management ( n= 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only ( n= 305), a significant naltrexone x behavioral intervention interaction ( P=. 009). Naltrexone also reduced risk of a heavy drinking day ( hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P=. 02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management ( n= 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone ( n= 153) or placebo plus medical management and CBI ( n= 156) (73.8 and 79.8, respectively; P <. 001). One year after treatment, these between-group effects were similar but no longer significant. Conclusions Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. C1 Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. Brown Univ, Roger Williams Med Ctr, Providence, RI 02912 USA. Boston Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA 02118 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Addict Treatment Ctr, Seattle, WA 98195 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. Univ Wisconsin, Milwaukee, WI 53201 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Yale Univ, Sch Med, Subst Abuse Treatment Unit, New Haven, CT USA. Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. Univ Penn, Treatment & Res Ctr, Philadelphia, PA 19104 USA. Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. NIAAA, Bethesda, MD USA. Univ Miami, Sch Med, Miami, FL USA. RP Anton, RF (reprint author), Med Univ S Carolina, Ctr Drug & Alcohol Programs, 67 President St,POB 250861, Charleston, SC 29425 USA. EM antonr@musc.edu RI Mason, Barbara/P-6604-2016 FU NIAAA NIH HHS [K05AA00133, K05AA014715, K23AA00329, U10AA11715]; NIDA NIH HHS [K02DA00326]; PHS HHS [11777, 11716, 11721, 11727, 11756, 11768, 11773, 11776, 11783, 11787, 11799] NR 68 TC 800 Z9 816 U1 8 U2 77 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 3 PY 2006 VL 295 IS 17 BP 2003 EP 2017 DI 10.1001/jama.295.17.2003 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 038MF UT WOS:000237225100017 PM 16670409 ER PT J AU Tice, JA Grady, D AF Tice, JA Grady, D TI Alternatives to estrogen for treatment of hot flashes - Are they effective and safe? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; POSTMENOPAUSAL WOMEN; BREAST-CANCER; DOUBLE-BLIND; SOY PHYTOESTROGENS; PLUS PROGESTIN; SYMPTOMS; FLUSHES; LIFE C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Tice, JA (reprint author), Univ Calif San Francisco, Dept Med, 1701 Divisadero St,Suite 554, San Francisco, CA 94143 USA. EM jeff.tice@ucsf.edu NR 28 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 3 PY 2006 VL 295 IS 17 BP 2076 EP 2078 DI 10.1001/jama.295.17.2076 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 038MF UT WOS:000237225100025 PM 16670417 ER PT J AU Dobie, SA Baldwin, LM Dominitz, JA Matthews, B Billingsley, K Barlow, W AF Dobie, SA Baldwin, LM Dominitz, JA Matthews, B Billingsley, K Barlow, W TI Completion of therapy by medicare patients with stage III colon cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADVANCED COLORECTAL-CANCER; ADJUVANT CHEMOTHERAPY; PROGNOSTIC-FACTORS; PROCEDURE VOLUME; PLUS LEVAMISOLE; RECTAL-CANCER; TOXICITY; FLUOROURACIL; OUTCOMES; CARCINOMA AB Background. Certain factors, such as race or age, are known to be associated with variation in initiation of adjuvant chemotherapy for stage III colon cancer, but little is known about what factors are associated with completion of adjuvant therapy. To determine whether predictors of initiation also predict completion, we analyzed Surveillance, Epidemiology, and End Results (SEER) program data linked to Medicare claims. We investigated mortality as a means to testing the validity of the completion measure that we created. Methods: We studied 3193 stage III colon cancer patients whose diagnosis was recorded in 1992-1996 SEER program data linked to 1991-1998 Medicare claims and who initiated adjuvant chemotherapy after colon cancer resection. We defined a measure of adjuvant chemotherapy completion as one chemotherapy administration claim in a month. We tested the validity of the created measure and its relation to 3-year cancer mortality adjusted for demographic, clinical, and environmental variables. We explored the association of patient characteristics and treating physician characteristics with chemotherapy completion by use of multivariable logistic regression modeling. Results: Of the 3193 patients, 2497 (78.2%) completed the course. Risk of cancer-related mortality was statistically significantly lower among those completing chemotherapy (relative risk = 0.79, 95% confidence interval = 0.69 to 0.89) than those with no adjuvant therapy. Patients who were female, widowed, increasingly elderly, rehospitalized, and living in certain regions were less likely to complete adjuvant chemotherapy than other patients. Race and other clinical, environmental, and physician characteristics were not associated with completion of therapy. Conclusions: Factors associated with incomplete adjuvant chemotherapy may represent physical frailty, treatment complications, and lack of social and psychological support. Interventions to mitigate these influences are a logical next step toward increasing chemotherapy completion rates. C1 Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. NW Ctr Outcomes Res Older Adults, Ctr Excellence, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Canc Res & Biostat, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Dobie, SA (reprint author), Univ Washington, Dept Family Med, Box 356390, Seattle, WA 98195 USA. EM dob@u.washington.edu OI Dominitz, Jason/0000-0002-8070-7086 FU NCI NIH HHS [R01 CA089544-01, R01 CA089544, R01CA089544] NR 53 TC 80 Z9 81 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 3 PY 2006 VL 98 IS 9 BP 610 EP 619 DI 10.1093/jnci/djj159 PG 10 WC Oncology SC Oncology GA 043UP UT WOS:000237628000010 PM 16670386 ER PT J AU Brander, C Ferrone, S Marincola, FM AF Brander, C Ferrone, S Marincola, FM TI Rewarding patient-directed research: Excellence in Translational Medicine Award SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Editorial Material AB The Editorial Board of Journal of Translational Medicine is pleased to announce a prize to recognize outstanding contributions in the field of translational medicine. The prize is sponsored by Pfizer Global Research and Development, Global Translational Medicine and supported by the Journal of Translational Medicine Editorial Board. C1 Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20854 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA. EM brander@helix.mgh.harvard.edu; soldano.ferrone@roswellpark.org; fmarincola@mail.cc.nih.gov NR 11 TC 6 Z9 9 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAY 3 PY 2006 VL 4 AR 19 DI 10.1186/1479-5876-4-19 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 052XT UT WOS:000238268000001 ER PT J AU Chang, JT Hays, RD Shekelle, PG MacLean, CH Solomon, DH Reuben, DB Roth, CP Kamberg, CJ Adams, J Young, RT Wenger, NS AF Chang, JT Hays, RD Shekelle, PG MacLean, CH Solomon, DH Reuben, DB Roth, CP Kamberg, CJ Adams, J Young, RT Wenger, NS TI Patients' global ratings of their health care are not associated with the technical quality of their care SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CONSUMER ASSESSMENT; VULNERABLE ELDERS; OLDER PATIENTS; OF-CARE; SATISFACTION; PLANS; COMMUNICATION; DEPRESSION; COMMUNITY; OUTCOMES AB Background: Patient global ratings of care are commonly used to assess health care. However, the extent to which these assessments of care are related to the technical quality of care received is not well understood. objective: To investigate the relationship between patient-reported global ratings of health care and the quality of providers' communication and technical quality of care. Design: Observational cohort study. Setting: 2 managed care organizations, Patients: Vulnerable older patients identified by brief interviews of a random sample of community-dwelling adults 65 years of age or older who received care in 2 managed care organizations during a 13-month period. Measurements: Survey questions from the second stage of the Consumer Assessment of Healthcare Providers and Systems program were used to determine patients' global rating of health care and provider communication. A set of 236 quality indicators, defined by the Assessing Care of Vulnerable Elders project, were used to measure technical quality of care given for 22 clinical conditions; 207 quality indicators were evaluated by using data from chart abstraction or patient interview. Results: Data on the global rating item, communication scale, and technical quality of care score were available for 236 vulnerable older patients. In a multivariate logistic regression model that included patient and clinical factors, better communication was associated with higher global ratings of health care. Technical quality of care was not significantly associated with the global rating of care. Limitations: Findings were limited to vulnerable elders who were enrolled in managed care organizations and may not be generalizable to other age groups or types of insurance coverage. Conclusions: Vulnerable elders' global ratings of care should not be used as a marker of technical quality of care. Assessments of quality of care should include both patient evaluations and independent assessments of technical quality. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RAND Hlth, Santa Monica, CA USA. RAND Hlth, Arlington, VA USA. RP Chang, JT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, 911 Broxton Ave,3rd Floor, Los Angeles, CA 90095 USA. EM johnchang@mednet.ucla.edu RI Hays, Ronald/D-5629-2013 FU BHP HRSA HHS [PE-19001]; NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20-MD00148-01] NR 38 TC 117 Z9 117 U1 2 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 2 PY 2006 VL 144 IS 9 BP 665 EP 672 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 039GJ UT WOS:000237293700006 PM 16670136 ER PT J AU Liddle, FJ Alvarez, JV Poli, V Frank, DA AF Liddle, FJ Alvarez, JV Poli, V Frank, DA TI Tyrosine phosphorylation is required for functional activation of disulfide-containing constitutively active STAT mutants SO BIOCHEMISTRY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; INTERFERON-GAMMA; PHOSPHATASE INHIBITOR; DNA; BINDING; TRANSFORMATION; TRANSCRIPTION; INACTIVATION; APOPTOSIS AB Aberrant activation of STAT transcription factors has been implicated in a variety of cancers. Constitutively active forms of STAT1 and STAT3 (STAT1C and STAT3C) have been developed to determine the effects of STAT activation in isolation from other cytokine-stimulated signaling pathways. These mutants were created by engineering cysteine residues into the carboxy terminus of each STAT molecule, allowing a hypothesized disulfide bond to form between two unphosphorylated monomers. To determine whether the presence of cysteine residues is sufficient to allow for functional activation in the absence of tyrosine phosphorylation, we developed STATIC and STAT3C mutants that are unable to be phosphorylated on the critical tyrosine residue. Without the tyrosine residue, cysteine containing constitutive STAT mutants failed to transactivate STAT target genes. Furthermore, transfection of STAT dominant negative mutants prevented the activation of STATIC and STAT3C. Cytokine-induced activation of STATIC and STAT3C was dramatically prolonged when compared to wild-type proteins and led to extended STAT-dependent gene activation. These data show that tyrosine phosphorylation is required for activation of STATIC and STAT3C. Additionally, these findings suggest the existence of basal phosphorylation that is a dynamic process that involves both phosphorylation and dephosphorylation. The constitutive STAT mutants likely show heightened activity because of the cysteine residues stabilizing these dimers and preventing dephosphorylation, resulting in the accumulation of trancriptionally active STAT dimer complexes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Room M552B,44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu RI Poli, Valeria/A-9215-2012 OI Poli, Valeria/0000-0002-3739-3966 FU NCI NIH HHS [CA79547] NR 21 TC 32 Z9 32 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 2 PY 2006 VL 45 IS 17 BP 5599 EP 5605 DI 10.1021/bi0525674 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 038MI UT WOS:000237225500022 PM 16634641 ER PT J AU Scirica, BM Morrow, DA AF Scirica, BM Morrow, DA TI Is C-reactive protein an innocent bystander or proatherogenic culprit? - The verdict is still out SO CIRCULATION LA English DT Editorial Material ID CORONARY-HEART-DISEASE; HUMAN ENDOTHELIAL-CELLS; DENSITY-LIPOPROTEIN CHOLESTEROL; E-DEFICIENT MICE; CARDIOVASCULAR-DISEASE; ARTERY-DISEASE; ATHEROSCLEROTIC LESIONS; RANDOMIZED-TRIALS; STATIN THERAPY; INFLAMMATION C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Toronto, St Michaels Hosp, Div Cardiac Surg, Toronto, ON M5B 1W8, Canada. Univ Calif Davis, Lab Artherosclerosis & Metab Res, Dept Med Pathol & Lab Med, Med Ctr, Sacramento, CA 95817 USA. Univ Calif Davis, Div Endocrinol Clin Nutr & Vasc Med, Dept Med, Med Ctr, Sacramento, CA 95817 USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 54 TC 129 Z9 138 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 2 PY 2006 VL 113 IS 17 BP 2128 EP 2134 DI 10.1161/CIRCULATIONAHA.105.611350 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 038GV UT WOS:000237208100016 PM 16651484 ER PT J AU Pritsker, M Ford, NR Jenq, HT Lemischkat, LR AF Pritsker, M Ford, NR Jenq, HT Lemischkat, LR TI Genomewide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cDNA library; differentiation; microarray; phenotype; self-renewal ID LEUKEMIA INHIBITORY FACTOR; SELF-RENEWAL; ES CELLS; EXPRESSION; PLURIPOTENCY; MAINTENANCE; MICE; COACTIVATOR; MICROARRAYS; ACTIVATION AB Embryonic stem (ES) cells hold great promise for the future of medicine. To elucidate the molecular mechanisms that control ES cell self-renewal and differentiation, a comprehensive knowledge of the molecules involved in these processes is required. Here we describe an effective approach for genomewide identification of functionally active genes in ES cells. This approach combines genetic screens based on cDNA libraries with microarray detection methods to permit high-throughput functional analyses. We implement this strategy to identify genes whose overexpression can maintain phenotypic properties of undifferentiated mouse ES cells under differentiation-inducing conditions, specifically in the absence of leukemia inhibitory factor. The identified genes encode a variety of regulatory proteins whose function in ES cells was previously unknown. Moreover, our approach is capable of detecting genes whose overexpression promote differentiation or cell death. Overall, our studies establish a methodology for highly sensitive identification of genes that confer particular phenotypes on ES cells. C1 Princeton Univ, Dept Biol Mol, Princeton, NJ 08544 USA. RP Lemischkat, LR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 50 Blossom St,EDR 410, Boston, MA 02114 USA. EM ilemischka@molbio.princeton.edu NR 44 TC 63 Z9 68 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 2 PY 2006 VL 103 IS 18 BP 6946 EP 6951 DI 10.1073/pnas.0509861103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900031 PM 16621925 ER PT J AU Scimone, ML Alfantis, I Apostolou, I von Boehmer, H von Andrian, UH AF Scimone, ML Alfantis, I Apostolou, I von Boehmer, H von Andrian, UH TI A multistep adhesion cascade for lymphoid progenitor cell homing to the thymus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell trafficking; chemokines; integrin; lymphopoiesis; selectin ID MOUSE BONE-MARROW; T-CELL; PRECURSOR CELLS; IN-VIVO; HEMATOPOIETIC STEM; POSTNATAL THYMUS; RECEPTOR CXCR4; FETAL LIVER; MIGRATION; LYMPHOPOIESIS AB Homing of bone marrow (BM)-derived progenitors to the thymus is essential for T cell development. We have previously reported that two subpopulations of common lymphoid progenitors, CLP-1 and CLP-2, coexist in the BM and give rise to lymphocytes. We demonstrate that CLP-2 migrate to the thymus more efficiently than any other BM-derived progenitors. Short-term adoptive transfer experiments revealed that CLP-2 homing involves P-selectin/ P-selectin glycoprotein ligand 1 interactions, pertussis toxin-sensitive chemoattractant signaling by CC chemokine ligand 25 through CC chemokine receptor 9, and binding of the integrins alpha 4 beta 1 and alpha 1 beta 2 to their respective ligands, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Preferential thymus-tropism of CLP-2 correlated with higher chemokine receptor 9 expression than on other BM progenitors. Thus, CLP access to the thymus is controlled by a tissue-specific and subset-selective multistep adhesion cascade. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL56949, HL48675, HL54936, P01 HL048675, P01 HL056949, R01 HL054936] NR 47 TC 94 Z9 98 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 2 PY 2006 VL 103 IS 18 BP 7006 EP 7011 DI 10.1073/pnas.0602024103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900041 PM 16641096 ER PT J AU Cohen, T Lipsitch, M Walensky, RP Murray, M AF Cohen, T Lipsitch, M Walensky, RP Murray, M TI Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV-tuberculosis coinfected populations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mathematical model; AIDS; prophylaxis ID DRUG-RESISTANT TUBERCULOSIS; SUB-SAHARAN AFRICA; MYCOBACTERIUM-TUBERCULOSIS; EXOGENOUS REINFECTION; CONTROL STRATEGIES; EPIDEMICS; IMPACT; TRANSMISSION; NETHERLANDS; EFFICACY AB In sub-Saharan Africa, where the emergence of HIV has caused dramatic increases in tuberculosis (TB) case notifications, new strategies for TB control are necessary. Isoniazid preventive therapy (IPT) for HIV-TB coinfected individuals reduces the reactivation of latent Mycobacterium tuberculosis infections and is being evaluated as a potential community-wide strategy for improving TB control. We developed a mathematical model of TB/HIV coepidemics to examine the impact of community-wide implementation of IPT for TB-HIV coinfected individuals on the dynamics of drug-sensitive and -resistant TB epidemics. We found that community-wide IPT will reduce the incidence of TB in the short-term but may also speed the emergence of drug-resistant TB. We conclude that community-wide IPT in areas of emerging HIV and drug-resistant TB should be coupled with diagnostic and treatment policies designed to identify and effectively treat the increasing proportion of patients with drug-resistant TB. C1 Brigham & Womens Hosp, Div Social Med & Hlth Inequalities, Boston, MA 02120 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis & Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA 02114 USA. RP Cohen, T (reprint author), Brigham & Womens Hosp, Div Social Med & Hlth Inequalities, 1 Brigham Circle,1620 Tremont St, Boston, MA 02120 USA. EM tcohen@hsph.harvard.edu RI Cohen, Ted/G-8101-2011; OI Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch, Marc/0000-0003-1504-9213 FU NIAID NIH HHS [K23 AI01794-05, 1R21 AI55825-01, K08 AI055985, K08 AI055985-04, K23 AI001794, R21 AI055825] NR 47 TC 66 Z9 67 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 2 PY 2006 VL 103 IS 18 BP 7042 EP 7047 DI 10.1073/pnas.0600349103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 040SE UT WOS:000237399900047 PM 16632605 ER PT J AU Mohanty, SA Washington, DL Lambe, S Fink, A Asch, SM AF Mohanty, SA Washington, DL Lambe, S Fink, A Asch, SM TI Predictors of on-call specialist response times in California emergency departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE on-call specialist; emergency department; health services research ID INCOME; CARE AB Objectives: To assess waiting times in emergency departments (EDs) for on-call specialist response and how these might vary by facility or neighborhood characteristics. Limited availability of on-call specialists is thought to contribute to ED overcrowding. Methods: Direct observational data from a random sample of 1,798 patients visiting 30 California EDs during a six-month period provided specialist waiting times. The authors used multivariate logistic regression and survival analysis to analyze predictors of time to on-call specialists' telephone response. Results: Eighty-six percent of on-call specialists who were paged responded by telephone within 30 minutes. Ten percent of specialists did not respond at all. After controlling for the annual percentage of non-urgent ED patients at each facility, near closure status, and hospital ownership status, for every $10,000 increase in hospital zip code income, the odds of on-call specialist response within 30 minutes increased by 123% (adjusted odds ratio = 2.23; 95% confidence interval = 1.24 to 4.02; p = 0.01). Conclusions: Although the majority of on-call specialists met the federal recommendation of a 30-minute response, those in poor neighborhoods were less likely to do so. One in ten on-call specialists did not respond at all. State and federal policies should focus on making more funding available for on-call specialist panels in poor areas. C1 Univ So Calif, Keck Sch Med, Dept Med & Emergency Med, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med & Publ Hlth, Los Angeles, CA USA. Univ Calif San Francisco, Dept Med, Div Emergency Med, San Francisco, CA USA. RP Mohanty, SA (reprint author), Univ So Calif, Dept Med, Div Geriatr & Gen Internal Med, 2020 Zonal Ave,IRD 627, Los Angeles, CA 90033 USA. EM samohant@usc.edu NR 28 TC 9 Z9 9 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2006 VL 13 IS 5 BP 505 EP 512 DI 10.1197/j.aem.2005.12.018 PG 8 WC Emergency Medicine SC Emergency Medicine GA 041VN UT WOS:000237484500005 PM 16609102 ER PT J AU Kabrhel, C Matts, C McNamara, M Katz, J Ptak, T AF Kabrhel, C Matts, C McNamara, M Katz, J Ptak, T TI A highly sensitive ELISA D-dimer increases testing but not diagnosis of pulmonary embolism SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 17-18, 2004 CL San Francisco, CA SP Amer Coll Emergency Phys DE D-dimer; ELISA; pulmonary embolism; venous thromboembolism ID VENOUS THROMBOEMBOLIC DISEASE; HELICAL COMPUTED-TOMOGRAPHY; EMERGENCY-DEPARTMENT; SEASONAL-VARIATION; OUTPATIENTS; ASSAY; SCAN; METAANALYSIS; SPECIFICITY; PROBABILITY AB Objectives: To determine the effect of introducing a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer on the percentage of emergency department (ED) patients evaluated for pulmonary embolism (PE), the use of associated laboratory testing, pulmonary vascular imaging, and the diagnoses of PE. Methods: Patients evaluated for PE during three 120-day periods were enrolled: immediately before (period 1), immediately after (period 2), and one year after the introduction of a rapid ELISA D-dimer in the hospital. The frequency of ED patients evaluated for PE with any test, with D-dimer testing, and with pulmonary vascular imaging and the frequency or PE diagnosis during each time period were determined. Results: The percentage of patients evaluated for PE nearly doubled; from 1.36% (328/24,101) in period I to 2.58% (654/25,318) in period 2 and 2.42% (583/24,093) in period 3. The percentage of patients Who underwent D-dimer testing increased more than fourfold; from 0.39% (93/24,101) in period 1 to 1.83%, (464/25,318) in period 2 and 1.77% (427/24,093) in period 3. The percentage of patients who underwent pulmonary vascular imaging increased from 1.02% (247/24,101) in period 1 to 1.36% (344/25,318) in period 2 and to 1.39% (334/24,093) in period 3. There was no difference in the percentage of patients diagnosed as having PE in period 1 (0.20%, [47/24,101]), period 2 (0.27% 169/25,3181), and period 3 (0.24% [58/24,093]). Conclusions: In the study's academic ED, introduction of ELISA D-dimer testing was accompanied by an increase in PE evaluations, D-dimer testing, and pulmonary vascular imaging; there was no observed change in the rate of PE diagnosis. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. Univ Illinois, Sch Med, Chicago, IL USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, 55 Fruit St, Boston, MA 02114 USA. EM ckabrhel@partners.org NR 28 TC 32 Z9 32 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2006 VL 13 IS 5 BP 519 EP 524 DI 10.1197/j.aem.2005.12.012 PG 6 WC Emergency Medicine SC Emergency Medicine GA 041VN UT WOS:000237484500007 PM 16551779 ER PT J AU Leff, B Harper, GM AF Leff, B Harper, GM TI The reading habits of medicine clerks at one medical school: Frequency, usefulness, and difficulties SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Clerkship Directors in Internal Medicine CY OCT, 2003 CL Savannah, GA ID STUDENTS AB Purpose To describe the reading habits of medicine clerks, which previously have not been well described. Understanding issues related to student reading habits may provide insights and opportunities for medical educators to develop methods to improve clerks' clinical clerkship experiences and their information literacy skills. Method The authors administered an 18-item survey tool to 120 students on their first inpatient internal medicine clerkships at the Johns Hopkins University School of Medicine in 2002-03. The questionnaire focused on issues related to what and how often they read during their basic medicine clerkship. Data were explored mainly with descriptive statistics. Results One hundred twelve of 120 (93%) medicine clerks completed the survey. Clerks reported reading for an average of 10.8 (SD 5.6) hours per week (median ten hours per week, range one to 30 hours per week). The most commonly used and useful reading sources were UpToDate(R) and test preparation textbooks. Approximately 30% of students reported substantial problems in reading about their patients. Limited data suggest that reading habits and learning methods vary by year of medical school. Clerks are given disparate advice on appropriate reading sources to consult by attending physicians, resident physicians, and fellow students. Conclusions Students spend significant amounts of time reading online sources during their medicine clerkship, especially UpToDate. Medical educators should become familiar with these sources and contribute to maximizing their effectiveness for students. Additional research focused on understanding how students build skills in information literacy and how educational programs can facilitate the development of those skills is needed. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Care Ctr, Johns Hopkins Bayview Med Ctr,Dept Med, Baltimore, MD 21224 USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Leff, B (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Care Ctr, Johns Hopkins Bayview Med Ctr,Dept Med, John R Burton Pavil,5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM bleff@jhmi.edu NR 13 TC 10 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAY PY 2006 VL 81 IS 5 BP 489 EP 494 DI 10.1097/01.ACM.0000222273.90705.a6 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 039HK UT WOS:000237296400014 PM 16639211 ER PT J AU Kontos, N Querques, J Freudenreich, O AF Kontos, N Querques, J Freudenreich, O TI The problem of the psychopharmacologist SO ACADEMIC PSYCHIATRY LA English DT Article ID MEDICAL MODEL; BIOPSYCHOSOCIAL MODEL; PSYCHIATRIC-EDUCATION; MANAGED CARE; PSYCHOTHERAPY; FUTURE; ISSUES; PHARMACOTHERAPY; ERA AB Objective: The psychopharmacologist designation currently pervades and heavily influences the practice, perception, and teaching of clinical psychiatry. The authors hope to make a case and provide the raw material for informed discussion of this role during psychiatric residency training. dress its problems, and bring a vital element to trainees' professional identity development. Method: A definition for the psychopharmacologist is sought. Historical trends in psychiatry which contributed most to its evolution are explored. Problems of the psychopharmacologist role are delineated. Extant solutions to psychiatry's problematic adaptation to an increasingly biological clinical role are critiqued, and a more effective one is pursued. Results: The term psychopharmacologist seems linked to presumed scientific and medical approaches, a goal of symptom relief through medication, and often other providers who are considered patients' "primary" treaters. The role derives largely from economic and remedicalization trends. Aspects of disengagement are determined to form the core problem of the psychopharmacologist. The authors propose that psychiatry is defined by its practice of the medical model and call attention to three areas where the psychopharmacologist role and the medical model collide. Conclusions: Engaging psychiatric residents in a new dialogue about their role as physician will challenge the previously unquestioned psychopharmacologist categorization, begin to address its problems, and bring a vital element to trainees' professional identity development. C1 Cambridge Hlth Alliance, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, First Break & Early Psychosis Program, Boston, MA 02114 USA. RP Kontos, N (reprint author), Cambridge Hosp, 1493 Cambridge St,Macht Bldg, Cambridge, MA 02139 USA. EM nkontos@challiance.org NR 70 TC 10 Z9 10 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2006 VL 30 IS 3 BP 218 EP 226 DI 10.1176/appi.ap.30.3.218 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 045US UT WOS:000237768600006 PM 16728768 ER PT J AU Schlozman, S Althoff, R Caplan, J Derenne, J Levin, H Newberry, P Rubin, D Strange, M Wood, W Beresin, E AF Schlozman, S Althoff, R Caplan, J Derenne, J Levin, H Newberry, P Rubin, D Strange, M Wood, W Beresin, E TI Choosing a child and adolescent psychiatry residency SO ACADEMIC PSYCHIATRY LA English DT Article C1 Child & Adolescent Psychiat Residency, MGH McLean Program Child Psychiat, Boston, MA USA. RP Schlozman, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM sschlozman@partners.org RI Wood, William/I-6005-2013 OI Wood, William/0000-0003-4985-3189 NR 7 TC 2 Z9 2 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2006 VL 30 IS 3 BP 248 EP 256 DI 10.1176/appi.ap.30.3.248 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 045US UT WOS:000237768600011 PM 16728773 ER PT J AU Derenne, JL Beresin, EV AF Derenne, JL Beresin, EV TI Body image, media, and eating disorders SO ACADEMIC PSYCHIATRY LA English DT Article ID ADOLESCENT OBESITY; LOSE WEIGHT; TELEVISION; GIRLS; PARENT; DRIVE; YOUTH; CHILD; MEN; OLD AB Objective: Eating disorders, including obesity, are a major public health problem today. Throughout history, body image has been determined by various factors, including politics and media. Exposure to mass media (television, movies, magazines, Internet) is correlated with obesity and negative body image, which may lead to disordered eating. The authors attempt to explain the historical context of the problem and explore potential avenues for change. Method: The authors review changes in ideal female body type throughout history, comment on current attitudes toward shape and weight in both men and women, and outline interventions aimed at increasing healthy habits and fostering self-esteem in youth. Results: Throughout history, the ideal of beauty has been difficult to achieve and has been shaped by social context. Current mass media is ubiquitous and powerful, leading to increased body dissatisfaction among both men and women. Conclusion: Parents need to limit children's exposure to media, promote healthy eating and moderate physical activity, and encourage participation in activities that increase mastery and selfesteem. Funding for high-quality, visible advertising campaigns promoting healthy life styles may increase awareness. C1 Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, Boston, MA 02114 USA. McLean Hosp, Boston, MA 02114 USA. RP Derenne, JL (reprint author), Massachusetts Gen Hosp, Div Child & Adolescent Psychiat, 55 Fruit St YAW 6900, Boston, MA 02114 USA. EM jderenne@partners.org NR 33 TC 60 Z9 64 U1 12 U2 85 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAY-JUN PY 2006 VL 30 IS 3 BP 257 EP 261 DI 10.1176/appi.ap.30.3.257 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 045US UT WOS:000237768600012 PM 16728774 ER PT J AU Lee, JM Anzai, Y Langlotz, CP AF Lee, JM Anzai, Y Langlotz, CP TI Mentoring the mentors: Aligning mentor and mentee expectations SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID ACADEMIC RADIOLOGY; MEDICINE; CAREER AB The Radiology Alliance for Health Services Research sponsored a symposium at the 2005 Annual Meeting of the Association of University Radiologists, which focused on the issue of aligning mentor and mentee expectations to foster successful mentoring relationships. This article presents a summary of the informal discussion of the panelists' individual experiences, common themes, and insights gained from the panel participants. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Lee, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM janie@mgh-ita.org NR 14 TC 30 Z9 31 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2006 VL 13 IS 5 BP 556 EP 561 DI 10.1016/j.acra.2006.01.050 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 036MO UT WOS:000237075400005 PM 16627195 ER PT J AU Liu, CF Campbell, DG Chaney, EF Li, YF McDonell, M Fihn, SD AF Liu, CF Campbell, DG Chaney, EF Li, YF McDonell, M Fihn, SD TI Depression diagnosis and antidepressant treatment among depressed VA primary care patients SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article DE primary care patients; veterans; depression; antidepressant treatment; depression diagnosis ID RANDOMIZED CONTROLLED-TRIAL; IMPROVING PRIMARY-CARE; CASE-MIX MEASURES; COLLABORATIVE CARE; MAJOR DEPRESSION; MENTAL-DISORDERS; VETERANS HEALTH; LATE-LIFE; OUTCOMES; MANAGEMENT AB This study examined the extent to which 3559 VA primary care patients with depression symptomatology received depression diagnoses and/or antidepressant prescriptions. Symptomatology was classified as mild (13%), moderate (42%) or severe (45%) based on SCL-20 scores. Diagnosis and treatment was related to depression severity and other patient characteristics. Overall, 44% were neither diagnosed nor treated. Only 22% of those neither diagnosed nor treated for depression received treatment for other psychopathology. Depression treatment performance measures dependent on diagnoses and antidepressant prescriptions from administrative databases exclude undiagnosed patients with significant, treatable, symptomatology. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. NR 48 TC 21 Z9 21 U1 1 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAY PY 2006 VL 33 IS 3 BP 331 EP 341 DI 10.1007/s10488-006-0043-5 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 055RE UT WOS:000238467200008 PM 16755394 ER PT J AU Neupert, SD Almeida, DM Mroczek, DK Spiro, A AF Neupert, SD Almeida, DM Mroczek, DK Spiro, A TI The effects of the Columbia shuttle disaster on the daily lives of older adults: Findings from the VA Normative Aging Study SO AGING & MENTAL HEALTH LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Gerontological-Society-of-America CY NOV 21-25, 2003 CL San Diego, CA SP Gerontol Soc Amer ID NEGATIVE AFFECT; GENDER-DIFFERENCES; PHYSICAL SYMPTOMS; DAILY STRESSORS; DIARY METHODS; MEMORY; MOOD; LIFE; PERSONALITY; CORTISOL AB During 2002-2003 the VA Normative Aging Study conducted an eight-day diary survey of stressors and well-being. A sub-sample of 19 men and 13 women ( mean age = 71.78) completed daily questionnaires before and after the Columbia shuttle exploded on 1st February 2003, presenting a unique look into peoples' daily lives before and after a tragic event. Results indicated no significant changes in negative affect or physical symptoms, but people reported significant decreases in both positive affect and memory failures on days following the shuttle explosion. Implications of these findings and directions for future research are discussed. C1 N Carolina State Univ, Dept Psychol, Raleigh, NC 27695 USA. Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. Purdue Univ, Dept Child Dev & Family Studies, W Lafayette, IN USA. Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Neupert, SD (reprint author), N Carolina State Univ, Dept Psychol, Box 7650, Raleigh, NC 27695 USA. EM shevaun_neupert@ncsu.edu FU NIA NIH HHS [R01-AG18436] NR 45 TC 11 Z9 11 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PD MAY PY 2006 VL 10 IS 3 BP 272 EP 281 DI 10.1080/13607860500409682 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 045FH UT WOS:000237727500009 PM 16777655 ER PT J AU Durazzo, TC Rothlind, JC Gazdzinski, S Banys, P Meyerhoff, DJ AF Durazzo, Timothy C. Rothlind, Johannes C. Gazdzinski, Stefan Banys, Peter Meyerhoff, Dieter J. TI A comparison of neurocognitive function in nonsmoking and chronically smoking short-term abstinent alcoholics SO ALCOHOL LA English DT Article DE alcoholism; alcohol dependence; chronic cigarette smoking; neurocognition; abstinence ID CEREBRAL BLOOD-FLOW; CHRONIC CIGARETTE-SMOKING; COGNITIVE PERFORMANCE; ALZHEIMERS-DISEASE; FEMALE ALCOHOLICS; MAJOR DEPRESSION; CONSUMPTION; DEPENDENCE; RISK; EFFICIENCY AB Approximately 70-90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests chronic cigarette smoking alone adversely affects neurocognition in adults. However, few studies on the neurocognitive function of short-term abstinent alcoholics have specifically considered the potential effects of chronic cigarette smoking. In this study, 20 nonsmoking recovering alcoholics (nsRA) and 22 actively smoking recovering alcoholics (sRA) participants, matched on age and education, were contrasted on a comprehensive neurocognitive battery after 34 +/- 9 days of abstinence. nsRA were superior to sRA on measures of auditory-verbal learning and memory, processing speed, cognitive efficiency, and static postural stability. These group differences were not a function of group disparities in age, education, estimated premorbid verbal intelligence, lifetime alcohol consumption, or other measured comorbid psychiatric or medical factors. In sRA, longer smoking duration was negatively correlated with executive skills, visuospatial learning, general cognitive efficiency, and static postural stability. These results indicate that greater consideration of the potential neurobiological effects of current chronic smoking on neurocognitive functioning is warranted in studies of alcoholism and other conditions where smoking is a common comorbid factor. (c) 2006 Elsevier Inc. All rights reserved. C1 San Francisco Vet Adm Med Ctr, Ctr Imaging & Neurodegenerat Dis 114M, San Francisco, CA 94116 USA. No Calif Inst Res & Educ, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging & Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94116 USA. EM timothy.durazzo@ucsf.edu FU NIAAA NIH HHS [AA10788] NR 76 TC 36 Z9 36 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAY PY 2006 VL 39 IS 1 BP 1 EP 11 DI 10.1016/j.alcohol.2006.06.006 PG 11 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 083RF UT WOS:000240475200001 PM 16938624 ER PT J AU Best, CA Laposata, M Proios, VG Szczepiorkowski, ZM AF Best, CA Laposata, M Proios, VG Szczepiorkowski, ZM TI Method to assess fatty acid ethyl ester binding to albumin SO ALCOHOL AND ALCOHOLISM LA English DT Article ID NONOXIDATIVE ETHANOL-METABOLISM; BOVINE SERUM-ALBUMIN; PANCREATIC INJURY; PLASMA-ALBUMIN; PROTEIN; CRYSTAL; MARKERS AB Aims: To develop a method to assess the relative binding of fatty acid ethyl esters (FAEE) and free fatty acids (FFA) to albumin, and to determine if binding affinity is related to fatty acid chain length and or degree of saturation. Methods: Radiolabelled ethyl-[C-14] oleate -bound to albumin was challenged with various ratios of FFA to FAEE. The displacement of ethyl-[C-14] oleate by FFA was visualized and quantitated through a combination of native-PAGE, autoradiography, and liquid scintillation counting (LSC). Results: As the ratio of FFA to FAEE increased from 0:1 to 12:1, for all fatty acids tested (myristate, palmitate, stearate, oleate, linoleate, and arachidonate), ethyl-[C-14] oleate displacement increased, when expressed as radioactivity (in DPM) as a percentage of control. In contrast, ethyl oleate did not displace stearate or oleate from albumin at molar ratios up to 5:1 (FAEE:FFA). Conclusions: The method developed gave reproducible visualization of noncovalent binding of radiolabelled FAEE to albumin. The combination of native-PAGE and autoradiography LSC works well in assessing the binding properties of albumin and radiolabelled FAEE. The data indicate preferential binding of FFA over FAEE to albumin with six different FFA displacing FAEE to an approximately equal extent. C1 Massachusetts Gen Hosp, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Northeastern Univ, Dept Biomed Sci, Boston, MA 02115 USA. Dartmouth Coll, Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Lebanon, NH 03756 USA. RP Best, CA (reprint author), Massachusetts Gen Hosp, Div Lab Med, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM cbest1@partners.org RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 30 TC 6 Z9 6 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD MAY-JUN PY 2006 VL 41 IS 3 BP 240 EP 246 DI 10.1093/alcalc/ag1009 PG 7 WC Substance Abuse SC Substance Abuse GA 037UZ UT WOS:000237174300005 PM 16554377 ER PT J AU Witt, WP Fortuna, L Wu, EJ Kahn, RS Winickoff, JP Pirraglia, PA Ferris, TG Kuhlthau, K AF Witt, WP Fortuna, L Wu, EJ Kahn, RS Winickoff, JP Pirraglia, PA Ferris, TG Kuhlthau, K TI Children's use of motor vehicle restraints: Maternal psychological distress, maternal motor vehicle restraint practices, and sociodemographics SO AMBULATORY PEDIATRICS LA English DT Article DE family preventive practices; maternal psychological distress; motor vehicle restraints ID SEAT-BELT USE; HEALTH BEHAVIORS; SCREENING SCALES; YOUNG-CHILDREN; MENTAL-HEALTH; USAGE; POPULATION; DEPRESSION; RACE; VULNERABILITY AB Objective.-To determine the relative contribution of maternal psycholosgical distress. maternal restraint use, and sociodemographic characteristics to the likelihood that a child Would not be restrained in a motor vehicle. Methods-We examined data on 6251 children aged 0-17 years from the 1998 National Health Interview Survey. The level of children's motor vehicle restraint use (low vs high) was examined by maternal psychological distress and motor vehicle restraint use. Multivariate regression analyses were used to model the odds of children's low use of motor vehicle restraints, controlling for potential confounders. Results.-According to maternal reports, more than 10% of children and nearly 13% of mothers reported low use of motor vehicle restraints. Multivariate analyses revealed that maternal use of restraints and psychological distress were both independently related to children's use of restraints, with maternal low use as the stronger correlate. Older children were more likely than Younger children to be low users of motor vehicle restraints if the mother reported that she was a low user of restraints. Families with male children, black and Hispanic mothers, and 4 or more members reported lower use of restraints for their children. Conclusions.-Children's low use of motor vehicle restraints was associated with low levels of maternal motor vehicle restraint use and maternal psychological distress. Moreover, maternal motor vehicle restraint practices become increasingly important as children age. Health care providers should consider maternal motor vehicle restraint use, maternal psychological distress, and child age in addition to sociodemographics when assessing children's motor vehicle safety. C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Harvard Univ, Cambridge Hlth Alliance Somerville, Sch Med, Ctr Multicultural Mental Hlth Res, Somerville, MA USA. Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Harvard Univ, Sch Med, MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02115 USA. Providence VA Med Ctr, Program Integrate Psychosocial & Hlth Serv Chron, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. RP Witt, WP (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med, 750 N Lake Shore Dr,Suite 601, Chicago, IL 60611 USA. EM w-witt@northwestern.edu FU AHRQ HHS [T32 HS00063]; NICHD NIH HHS [K23-HD40362] NR 46 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD MAY-JUN PY 2006 VL 6 IS 3 BP 145 EP 151 DI 10.1016/j.ambp.2005.12.004 PG 7 WC Pediatrics SC Pediatrics GA 046CK UT WOS:000237788800006 PM 16713932 ER PT J AU Allen, LA O'Donnell, CJ Camargo, CA Gitighano, RP Lloyd-Jones, DM AF Allen, LA O'Donnell, CJ Camargo, CA Gitighano, RP Lloyd-Jones, DM TI Comparison of long-term mortality across the spectrum of acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; CREATINE-KINASE-MB; UNSTABLE ANGINA-PECTORIS; TROPONIN-I; INVASIVE MANAGEMENT; RISK STRATIFICATION; PRACTICE GUIDELINES; MINOR ELEVATIONS; HEART-DISEASE AB Background Data are sparse regarding comparative long-term mortality across the spectrum of patients presenting with acute coronary syndrome (ACS). Methods We identified all patients hospitalized with suspected myocardial ischemia in an urban academic hospital from 1991 to 1992. We compared presenting characteristics, treatment, and long-term mortality between patients with unstable angina (UA), minor myocardial damage (MMD), definite non-ST-elevation myocardial infarction (NSTEMI), and STEMI. Results Of 760 patients (mean age 68 years, 35% women), 22% had UA, 35% had MMD, 26% had NSTEMI, and 17% had STEMI During a mean follow-up of 9.5 years, unadjusted mortality was highest in patients with MMD and NSTEMI (mortality for UA 43%, MMD 68%, NSTEMI 62%, STEMI 44%; P < .001). Patients with MMD and NSTEMI were older than patients with STEMI or UA, had more comorbid conditions (diabetes, prior myocardial infarction congestive heart failure), and were less likely to receive aspirin, unfractionated heparin, or revascularization therapies during;he index hospitalization. After multivariable adjustment for all significant covariates, mortality increased sequentially along the spectrum of ACS (hazards ratios for UA 1.0 [referent], MMD 1.12 [95% Cl 0.84-1.49], NSTEMI 1.28 [0.95-1.72], and STEMI 1.52 [1.06-2.19]). Conclusions Patients presenting with MMD and definite NSTEMI had a worse unadjusted long-term prognosis up to 10 years after index hospitalization than patients with STEMI This mortality excess for MMD/NSTEMI was associated with more comorbid conditions and decreased use of basic therapies for ACS. After controlling for baseline differences, STEMI patients had the highest mortality. C1 Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Div Cardiol, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [K23 HL04253] NR 29 TC 49 Z9 51 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2006 VL 151 IS 5 BP 1065 EP 1071 DI 10.1016/j.ahj.2005.05.019 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 043YF UT WOS:000237638200028 PM 16644337 ER PT J AU Cavusoglu, E Ruwende, C Chopra, V Yanamadala, S Eng, C Clark, LT Pinsky, DJ Marmur, JD AF Cavusoglu, E Ruwende, C Chopra, V Yanamadala, S Eng, C Clark, LT Pinsky, DJ Marmur, JD TI Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID SMOOTH-MUSCLE-CELLS; MATRIX METALLOPROTEINASES; ATHEROSCLEROTIC LESIONS; ENDOTHELIAL-CELLS; EXPRESSION; PLAQUE; GELATINASE; HEART; GENE; MICE AB Background Matrix metalloproteinases and their inhibitors have been implicated in both vascular and ventricular remodeling, and in atherosclerotic plaque rupture. The prognostic value of plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in patients with established or suspected coronary artery disease is unknown. Methods Tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 (MMP-9) levels, along with a number of other established biomarkers, were measured in 389 male patients undergoing coronary angiography at a Veterans Administration Medical Center. The patients were then followed prospectively for the occurrence of all-cause mortality, cardiac mortality, and myocardial infarction (MI). Results Follow-up data at 24 months were available for 97% of the patients. For the entire cohort of patients, TIMP-1 was the only biomarker to independently predict all-cause mortality and MI. In addition, the ratio of TIMP-1 to matrix metalloproteinase-9 was independently predictive of cardiac mortality at 24 months. The 24-month survival rates for patients in the lower quartile (< 66.5 ng/mL), interquartile (66.5-100 ng/mL), and upper quartile (> 100 ng/mL) of plasma TIMP-1 values were 95.3%, 89.3%, and 72.2%, respectively (P < .001). Furthermore, when patients with chest pain were risk stratified into those with and without an acute coronary syndrome, TIMP-1 remained an independent predictor of all-cause mortality in both subgroups. Conclusions In a cohort of male patients undergoing coronary angiography, a single baseline determination of plasma TIMP-1 is independently predictive of the subsequent risk of death and MI. C1 SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. Bronx Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Marmur, JD (reprint author), SUNY Hlth Sci Ctr, Dept Med, 450 Clarkson Ave,Box 1257, Brooklyn, NY 11203 USA. EM jonathan@marmur.com NR 26 TC 17 Z9 17 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2006 VL 151 IS 5 AR e8 DI 10.1016/j.ahj.2006.02.029 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 043YF UT WOS:000237638200034 ER PT J AU Pischke, CR Weidner, G Elliott-Eller, M Scherwitz, L Merritt-Worden, TA Marlin, R Lipsenthal, L Finkel, R Saunders, D McCormac, P Scheer, JM Collins, RE Guarneri, EM Ornish, D AF Pischke, CR Weidner, G Elliott-Eller, M Scherwitz, L Merritt-Worden, TA Marlin, R Lipsenthal, L Finkel, R Saunders, D McCormac, P Scheer, JM Collins, RE Guarneri, EM Ornish, D TI Comparison of coronary risk factors and quality of life in coronary artery disease patients with versus without diabetes mellitus SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID STYLE DEMONSTRATION PROJECT; CARDIAC REHABILITATION; HEART-DISEASE; DEPRESSION; STRESS; SF-36; POPULATION; MORTALITY; STANDARD; VALIDITY AB It is unclear whether patients with coronary artery disease (CAD) and diabetes mellitus (DM) can make comprehensive lifestyle changes that produce similar changes in coronary risk factors and quality of life compared with patients with CAD and without DM. We examined medical characteristics, lifestyle, and quality of life by diabetic status and gender in the Multicenter Lifestyle Demonstration Project (MLDP), a study of 440 nonsmoking patients with CAD (347 men, 55 with DM; 15.9%; 93 women, 36 with DM; 38.7%). Patients met in groups to improve lifestyle (plant-based, low-fat diet; exercise; stress management) for 1 year. Follow-ups were conducted at 3 and 12 months. At baseline, body mass and systolic blood pressure were significantly higher among patients with DM. Men with DM had a worse medical history (e.g., hypertension, hyperlipidemia, and family history of CAD) than did those without DM. Patients with DM, especially women, reported poorer quality of life than did patients without DM. The 2 groups of patients were able to adhere to the recommended lifestyle, as demonstrated by significant improvements in weight (mean -5 kg), body fat, low-density lipoprotein cholesterol, exercise capacity, and quality of life. No significant changes in triglycerides and high-density lipoprotein cholesterol were noted. By the end of 12 months, improvements in glucose-lowering medications (i.e., discontinuation or a change from insulin to oral hypoglycemic agents) were noted for 19.8% (n = 18) of patients with DM. In conclusion, patients with CAD and DM are able to follow a comprehensive lifestyle change program and show similar improvements in coronary risk factors and quality of life as those without DM. (c) 2006 Elsevier Inc. All rights reserved. C1 Res Inst Prevent Med, Sausalito, CA 94965 USA. Calif Pacific Med Ctr, Inst Hlth & Healing, San Francisco, CA 94115 USA. Univ S Carolina, Sch Med, Columbia, SC 29208 USA. Res & Educ Inc, Inst Hlth Behav, Columbia, SC USA. S Denver Cardiol Assoc, Denver, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Scripps Inst Oceanog, Scripps Ctr Integrat Med, La Jolla, CA USA. RP Weidner, G (reprint author), Res Inst Prevent Med, Sausalito, CA 94965 USA. EM gerdi.weidner@pmri.org NR 30 TC 25 Z9 27 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2006 VL 97 IS 9 BP 1267 EP 1273 DI 10.1016/j.amjcard.2005.11.051 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 041UZ UT WOS:000237483100001 PM 16635593 ER PT J AU Ellinor, PT Low, A Patton, KK Shea, MA MacRae, CA AF Ellinor, PT Low, A Patton, KK Shea, MA MacRae, CA TI C-reactive protein in lone atrial fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK-FACTORS; CARDIOVASCULAR-DISEASE; INTERLEUKIN-6; INFLAMMATION; ACTIVATION AB An inflammatory cause of atrial fibrillation (AF) has been proposed on the basis of the presence of lymphocytic infiltrates in the biopsy results of patients with lone AF, alterations of C-reactive protein (CRP) and interleukin-6 levels in subjects with AF, and the time course of postoperative AF. Many previous studies exploring inflammatory factors in AF have been confounded by concomitant medical illnesses. Subjects with lone AF provide a unique opportunity to eliminate the effects of associated conditions. We therefore sought to determine CRP levels in homogenous cohorts of patients with lone AF or AF and hypertension. One hundred twenty-one subjects with lone AF, 52 subjects with AF and hypertension, and 75 control subjects were enrolled and studied. Plasma CRP levels were determined using a commercially available immunoassay. There was no significant difference in CRP levels between subjects with lone AF and controls (1.34 vs 1.21 mg/L, p = 0.18). CRP levels in subjects with A-F and hypertension were elevated compared with those of controls and those of subjects with lone AF, although this difference was attributable to increased body mass indexes. CRP levels were not elevated in subjects with lone AF compared with controls. In conclusion, these findings clarify previous observations of elevations in CRP levels in subjects with AF and suggest that this marker of systemic inflammation is associated not with the arrhythmia per se, but rather with underlying cardiovascular disease. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM pellinor@partners.org RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 FU NHLBI NIH HHS [HL-71632, HL-075431, R01 HL075431] NR 17 TC 61 Z9 66 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2006 VL 97 IS 9 BP 1346 EP 1350 DI 10.1016/j.amjcard.2005.11.052 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 041UZ UT WOS:000237483100017 PM 16635609 ER PT J AU Dighe, AS Rao, A Coakley, AB Lewandrowski, KB AF Dighe, AS Rao, A Coakley, AB Lewandrowski, KB TI Analysis of laboratory critical value reporting at a large academic medical center SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE informatics; clinical pathology; clinical chemistry; management; administration; hematology; patient safety; critical value reporting AB Reporting of laboratory critical values has become an issue of national attention as illustrated by recent guidelines described in the National Patient Safety Goals of the Joint Commission on Accreditation of Healthcare Organizations. Herein, we report the results of an analysis of 37,503 consecutive laboratory critical values at our institution, a large urban academic medical center. We evaluated critical value reporting by test, laboratory specialty, patient type, clinical care area, time of day, and critical value limits. Factors leading to delays in critical value reporting are identified, and we describe approaches to improving this important operational and patient safety issue. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow Bldg,Room 510,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 52 Z9 61 U1 1 U2 7 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2006 VL 125 IS 5 BP 758 EP 764 DI 10.1309/R53XVC2U5CH6TNG8 PG 7 WC Pathology SC Pathology GA 035WO UT WOS:000237032600017 PM 16707379 ER PT J AU Manini, AF McAfee, AT Noble, VE Bohan, JS AF Manini, AF McAfee, AT Noble, VE Bohan, JS TI Acute cardiac ischemia time-insensitive predictive instrument predicts exercise treadmill test results in the chest pain unit SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY MAY, 2005 CL New York, NY SP Soc Acad Emergency Med ID CONTROLLED CLINICAL-TRIAL; EMERGENCY-DEPARTMENT; ACI-TIPI; GRADED-EXERCISE; RISK; MULTICENTER; MORTALITY; CENTERS; TOOL C1 Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Emergency Med, Brigham & Womens Hosp, Boston, MA 02115 USA. i3Magnifi Epidemiol, Auburndale, MA 02466 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Manini, AF (reprint author), Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Boston, MA 02115 USA. EM amanini@patners.org NR 20 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 2006 VL 24 IS 3 BP 375 EP 378 DI 10.1016/j.ajem.2005.11.006 PG 4 WC Emergency Medicine SC Emergency Medicine GA 041CS UT WOS:000237431500031 PM 16635724 ER PT J AU Fontana, RJ Sanyal, AJ Mehta, S Doherty, MC Neuschwander-Tetri, BA Everson, GT Kahn, JA Malet, PF Sheikh, MY Chung, RT Ghany, MG Gretch, DR AF Fontana, RJ Sanyal, AJ Mehta, S Doherty, MC Neuschwander-Tetri, BA Everson, GT Kahn, JA Malet, PF Sheikh, MY Chung, RT Ghany, MG Gretch, DR CA HALT-C Trial Grp TI Portal hypertensive gastropathy in chronic hepatitis C patients with bridging fibrosis and compensated cirrhosis: Results from the HALT-C trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ANTRAL VASCULAR ECTASIA; HELICOBACTER-PYLORI INFECTION; PEPTIC-ULCER DISEASE; NATURAL-HISTORY; LIVER-CIRRHOSIS; NONALCOHOLIC STEATOHEPATITIS; INSULIN-RESISTANCE; ASSOCIATION; PROGRESSION; SMOKING AB OBJECTIVES: The clinical significance of portal hypertensive gastropathy (PHG) in patients with compensated liver disease is not well established. The aim of this study was to determine the prevalence and correlates of PHG in a large cohort of patients with chronic hepatitis C virus (HCV) infection and bridging fibrosis/compensated cirrhosis entering the randomized phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial (HALT-C). METHODS: The presence and severity of PHG in 1,016 HCV patients with no prior history of gastrointestinal bleeding was determined at surveillance endoscopy using the New Italian Endoscopy Club criteria. RESULTS: Overall, 37% of HALT-C patients had PHG with 34% having mild and 3% with severe changes. The mucosal mosaic pattern was identified in 33%, red marks in 15%, and gastric antral vascular ectasia (GAVE) features in only 3%. Independent correlates of PHG included biochemical markers of liver disease severity (lower serum albumin, higher bilirubin), portal hypertension (lower platelet count), insulin resistance (higher glucose), and non-African American race. Independent correlates of GAVE included a history of smoking, nonsteroidal anti-inflammatory drugs (NSAIDs) use within the past year, and higher serum bilirubin and glucose levels. There was a strong positive association between the presence of PHG and esophageal varices ( p < 0.0001). CONCLUSIONS: PHG is associated with the histological and biochemical severity of liver disease in patients with HCV and advanced fibrosis but is mild in most patients. The clinical relevance of these findings will be further explored during the randomized phase of the HALT-C study. C1 Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Div Gastroenterol, Richmond, VA USA. Univ Massachusetts, Med Ctr, Div Gastroenterol, Worcester, MA 01605 USA. New England Res Inst, Watertown, MA 02172 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, Dept Hlth & Human Serv,NIH, Bethesda, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Fontana, RJ (reprint author), 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. FU NCRR NIH HHS [M01RR-06192, M01RR-00065, M01RR-00051, M01RR-00043, M01RR-00042, M01RR-01066, M01RR-00827, M01RR-00633]; NIDDK NIH HHS [N01-DK-9-2321, N01-DK-9-2325, N01-DK-9-2328, N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2323, N01-DK-9-2326, N01-DK-9-2324, N01-DK-9-2327, N01-DK-9-2322] NR 41 TC 22 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2006 VL 101 IS 5 BP 983 EP 992 DI 10.1111/j.1572-0241.2006.00461.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 041NQ UT WOS:000237463300013 PM 16573786 ER PT J AU Chang, L Chey, WD Harris, L Olden, K Surawicz, C Schoenfeld, P AF Chang, L Chey, WD Harris, L Olden, K Surawicz, C Schoenfeld, P TI Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: Systematic review of clinical trials and post-marketing surveillance data SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; RECEPTOR ANTAGONIST ALOSETRON; 5-HT3 ANTAGONIST; COLON ISCHEMIA; EFFICACY; WOMEN; SAFETY; IMPROVEMENT; SYNDROME/; FEMALE AB BACKGROUND: Ischemic colitis and serious complications of constipation have been reported in association with the use of alosetron, which is approved for women with severe diarrhea-predominant IBS who have failed conventional therapies. This systematic review calculated the incidence of these adverse events in alosetron-using patients in clinical trials and post-marketing surveillance. METHODS: A panel of experts in epidemiology and functional bowel disorders reviewed clinical trial report forms and FDA MedWatch forms of each reported case of ischemic colitis or serious complications of constipation. Experts were blinded about whether patients used alosetron or placebo. Using pre-specified criteria, experts rated the likelihood of an accurate diagnosis and an association between medication use and adverse events. Cases that were not consistent with the reported diagnosis or not possibly associated with medication use were eliminated from calculation of incidence rates of adverse events. RESULTS: Pooled data from clinical trials indicate an increased rate of ischemic colitis among alosetron-using patients compared to placebo-using patients (0.15% vs 0.0%, respectively, p = 0.03), but there was no significant difference in the rate of serious complications of constipation. All (19/19) alosetron-using patients with ischemic colitis had reversible colitis without long-term sequelae. Based on post-marketing surveillance data, the post-adjudication rate of ischemic colitis is 1.1 per 1,000 patient-years of alosetron use and the rate of serious complications of constipation is 0.66 per 1,000 patient-years of alosetron use. CONCLUSION: The incidence of ischemic colitis and serious complications of constipation is very low and is rarely associated with long-term sequelae or serious morbidity. C1 Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. Mayo Clin Scottsdale, Dept Gastroenterol, Scottsdale, AZ USA. Univ S Alabama, Sch Med, Div Gastroenterol, Mobile, AL 36688 USA. Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA 98195 USA. Vet Affairs Ctr Excellence Hlth Serv Res, Ann Arbor, MI USA. RP Schoenfeld, P (reprint author), VA Ann Arbor Healthcare Syst 111D, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. NR 31 TC 75 Z9 76 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2006 VL 101 IS 5 BP 1069 EP 1079 DI 10.1111/j.1572-0241.2006.00459.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 041NQ UT WOS:000237463300024 PM 16606352 ER PT J AU Sherman, SE Yano, EM York, LS Lanto, AB Chernof, BA Mittman, BS AF Sherman, SE Yano, EM York, LS Lanto, AB Chernof, BA Mittman, BS TI Assessing the structure of smoking cessation care in the veterans health administration SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE smoking cessation; health care quality assessment; practice guidelines; organizational structure; survey methods; questionnaires; structure of care; quality measurement; veterans; guidelines; prevention research; manuscript format : research; research purpose : instrument development; study design : quasi-experimental; outcome measure : behavioral; setting : clinical/health care; health focus : smoking control; strategy : policy; target population : adults in a health care system AB Purpose. National smoking cessation practice guidelines offer recommendations regarding the processes and structure of care. Facilities routinely measure the processes of care but not the structure of care. This pilot study assessed the structure of smoking cessation care at Veterans Health Administration facilities. Methods. Key informants at 18 sites completed a brief checklist survey adapted from national smoking cessation guidelines. Responses were compared with detailed, site surveys. Results. Guideline adherence was seen in identifying smokers and treating inpatient smokers. Areas of low adherence include offering incentives and defining staff responsibilities. The checklist survey showed poor correspondence with the detailed survey with low agreement on systematic screening (kappa = .21) and higher agreement on primary care prescribing authority (kappa = .53). Discussion. This pilot survey provides a potential rapid method for assessing adherence to systems recommendations from the national smoking cessation guidelines. The relatively low agreement with a more detailed. survey suggests that the two surveys may have been. measuring different aspects of smoking cessation care. C1 VA Greater Los Angeles HSR&D Ctr Excellence, Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. HealthNet, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. RP Sherman, SE (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, Vet Adm Greater Los Angeles Healthcare Syst, 16111 Plummer St,Mailstop 152, Sepulveda, CA 91343 USA. EM ssherman@ucla.edu NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAY-JUN PY 2006 VL 20 IS 5 BP 313 EP 318 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 041WL UT WOS:000237487100003 PM 16706001 ER PT J AU McMahon, FJ Buervenich, S Charney, D Lipsky, R Rush, AJ Wilson, AF Sorant, AJM Papanicolaou, GJ Laje, G Fava, M Trivedi, MH Wisniewski, SR Manji, H AF McMahon, FJ Buervenich, S Charney, D Lipsky, R Rush, AJ Wilson, AF Sorant, AJM Papanicolaou, GJ Laje, G Fava, M Trivedi, MH Wisniewski, SR Manji, H TI Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; STAR-ASTERISK-D; REPORT QIDS-SR; MAJOR DEPRESSION; PSYCHOMETRIC EVALUATION; QUICK INVENTORY; MOOD DISORDERS; MESSENGER-RNA; GLOBAL BURDEN; CITALOPRAM AB Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide-polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1 x 10(-6) to 3.7 x 10(-5) in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment, compared with those homozygous for the other allele. The A allele was over six times more frequent in white than in black participants, and treatment was less effective among black participants. The A allele may contribute to racial differences in outcomes of antidepressant treatment. Taken together with prior neurobiological findings, these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH,DHHS, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY USA. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH,DHHS, Rockville, MD 20852 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH,DHHS, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP McMahon, FJ (reprint author), NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH,DHHS, 35 Convent Dr,Room 1A202, Bethesda, MD 20892 USA. EM mcmahonf@intra.nimh.nih.gov RI McMahon, Francis/A-7290-2009; Wilson, Alexander/C-2320-2009; Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Lipsky, Robert/0000-0001-7753-1473; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NIMH NIH HHS [N01MH90003, U24 MH068457] NR 53 TC 285 Z9 307 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2006 VL 78 IS 5 BP 804 EP 814 DI 10.1086/503820 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 032EH UT WOS:000236756200007 PM 16642436 ER PT J AU Wang, XR Yano, EJ Wang, ZM Wang, MZ Christiani, DC AF Wang, XR Yano, EJ Wang, ZM Wang, MZ Christiani, DC TI Adverse effects of asbestos exposure and smoking on lung function SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE asbestos; occupational exposure; smoking effect; lungfunction tests; restrictive impairment; airway limitation ID PULMONARY-FUNCTION; WORKERS; PREVALENCE AB Background Exposure to asbestos is a well-recognized cause of both malignant and nonmalignant diseases of lung parenchyma and pleura. This study was conducted to determine the adverse effects of exposure to asbestos and smoking on pulmonary function. Methods Four hundred and sixty-eight workers who were occupationally exposed to asbestos for an average of 13 years were selected from an asbestos-product factory in China. Of them, 85 workers were diagnosed with asbestosis. Additionally, 282 workers who had no experience of exposure to industrial dust were included as a control group. A questionnaire was administered during a face-to-face interview and spirometric maneuvers and single-breath CO diffusing capacity (DLco) were performed. Results Multivariate regression analysis showed that exposure to asbestos was more strongly associated with decreased forced vital capacity (FVC) and DLco, and asbestosis more strongly associated with decreased FVC, while smoking was a major contributing factor to reduced FEV1/FVC. The results were confirmed by a further analysis where the subjects were grouped exclusively by smoking, asbestos exposure, and chest radiographic changes. No interaction or joint effect was observed between asbestos exposure and smoking. Conclusions This analysis suggested that asbestos and smoking might play independent roles, in which asbestos caused mainly a restrictive impairment, and smoking was a major causal factor for airway obstruction in the workers who were intensively exposed to asbestos. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Teikyo Univ, Sch Med, Tokyo 173, Japan. W China Univ Med Sci, Chengdu, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Lin, Sihao/A-8412-2012 NR 11 TC 8 Z9 9 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 2006 VL 49 IS 5 BP 337 EP 342 DI 10.1002/ajim.20293 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 034HD UT WOS:000236918900003 PM 16570255 ER PT J AU Sales, AE Helfrich, CD AF Sales, AE Helfrich, CD TI Value in development of complex interventions SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Editorial Material ID QUALITY IMPROVEMENT; SCIENCE C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. RP Sales, AE (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1880 S Columbia Way, Seattle, WA 98108 USA. EM ann.sales@med.va.gov RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 10 TC 1 Z9 1 U1 1 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAY PY 2006 VL 12 IS 5 BP 253 EP 254 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 041WS UT WOS:000237487800001 PM 16686581 ER PT J AU Zeng, WQ Gao, HL Brueton, L Hutchin, T Gray, G Chakrapani, A Olpin, S Shih, VE AF Zeng, WQ Gao, HL Brueton, L Hutchin, T Gray, G Chakrapani, A Olpin, S Shih, VE TI Fumarase deficiency caused by homozygous P131R mutation and paternal partial isodisomy of chromosome 1 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE fumarase deficiency; fumarate hydratase FH; uniparental disomy; chromosome 1; inborn error of metabolism ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; MATERNAL UNIPARENTAL DISOMY; CONGENITAL INSENSITIVITY; MOLECULAR ANALYSIS; NTRK1 GENE; PATIENT; ANHIDROSIS; MECHANISM; HYDRATASE; DISEASE AB We report on the first case of fumarase deficiency (FD) caused by uniparental isodisomy. An affected patient was found to be homozygous for the P131R mutation in the FH gene. In this nonconsanguineous family, the Unaffected father was found to be heterozygous for the same mutation, and the mother was found to be homozygous wild-type. Analysis of chromosome 1 markers showed that the patient inherited both paternal alleles with complete absence of the maternal homolog. The two copies of the paternal chromosome I are heterodisomic for most of the chromosome except the distal 1q region which is isodisomic for the mutant alleles of the FH gene. The genotypes of other chromosome markers are consistent with the patient inheriting alleles from both parents. Although FD is an autosomal recessive disorder, the effects of uniparental disomy (UPD) should be considered in genetic counseling since the recurrence risk of an affected child is significantly reduced when the disorder is due to UPD. (c) 2006 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Amino Acid Disorders Lab, Neurol Serv, Boston, MA 02129 USA. Massachusetts Gen Hosp, Amino Acid Disorders Lab, Serv Pediat, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. Birmingham Womens Hosp, Clin Genet Unit, Birmingham, AL USA. Birmingham Childrens Hosp, Dept Inherited Metab Dis, Birmingham, W Midlands, England. Sheffield Childrens Hosp, Neonatal Screening Lab, Sheffield, S Yorkshire, England. RP Shih, VE (reprint author), Massachusetts Gen Hosp, Amino Acid Disorders Lab, Neurol Serv, 149 13th St, Boston, MA 02129 USA. EM vshih@partners.org OI olpin, simon/0000-0001-9018-5173 NR 34 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAY 1 PY 2006 VL 140A IS 9 BP 1004 EP 1009 DI 10.1002/ajmg.a.31186 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 037HW UT WOS:000237138700012 PM 16575891 ER PT J AU Hoffman, RM Barry, MJ Stanford, JL Hamilton, AS Hunt, WC Collins, MM AF Hoffman, RM Barry, MJ Stanford, JL Hamilton, AS Hunt, WC Collins, MM TI Health outcomes in older men with localized prostate cancer: Results from the prostate cancer outcomes study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE prostatic neoplasms; prostatectomy; radiotherapy; outcome assessment; aged ID COMPARING RADICAL PROSTATECTOMY; GEOGRAPHIC-VARIATION; CO-MORBIDITY; TIME TRENDS; THERAPY; TRIAL; HISTORY AB PURPOSE: We compared health-related quality-of-life (HRQOL) outcomes and survival of men with localized prostate cancer who received aggressive treatment with those receiving conservative management. METHODS: We conducted a population-based cohort study of men aged 75 to 84 years when diagnosed with a clinically localized cancer in 1994 or 1995. We used medical record abstractions and patient surveys to obtain clinical and HRQOL data at diagnosis and 24-month follow-up. We used a propensity score method to adjust for baseline differences between men treated with radical prostatectomy or radiation therapy (n = 175) and men who received hormone therapy or no treatment (n = 290). Propensity scores were used in regression analyses comparing HRQOL outcomes between treatment groups. Overall and disease-specific survivals were estimated with multivariate proportional hazards models. RESULTS: At 24 months following diagnosis, aggressively treated men were more likely to report daily urinary leakage (odds ratio [OR] = 2.9, 95% confidence interval [CI] 1.2-7.0) and to be bothered by urinary problems (OR = 5.1, 95% CI, 1.3-9.1) and sexual problems (OR = 2.8, 95% CI, 1.2-6.3). The adjusted disease-specific mortality hazard ratio was 0.43 (95% CI, 0.15, 1.28), favoring aggressive treatment. However, the absolute 5-year disease-specific survival difference was only 6% (98% vs 92%). Over 80% of all deaths were from other causes. CONCLUSIONS: Aggressive treatment was associated with significant decreases in disease-specific HRQOL. However, men who were aggressively treated for localized cancer had a minimally reduced absolute risk of dying from prostate cancer. Physicians and older patients should consider these outcomes in making decisions about screening and treatment. (c) 2006 Elsevier Inc. All rights reserved. C1 New Mexico VA Hlth Care Syst, Med Serv, Albuquerque, NM 87108 USA. Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. Massachusetts Gen Hosp, Med Serv, Gen Med Div, Boston, MA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. RP Hoffman, RM (reprint author), New Mexico VA Hlth Care Syst, Med Serv, 111GIM,1501 San Pedro SE, Albuquerque, NM 87108 USA. EM rhoffman@unm.edu FU NCI NIH HHS [N01-PC-67005, N01-PC-67006, N01-PC-67010, N01-PC-67000, N01-PC-67007]; PHS HHS [N01-PCN-67009] NR 33 TC 24 Z9 24 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2006 VL 119 IS 5 BP 418 EP 425 DI 10.1016/j.amjmed.2005.06.072 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 038LO UT WOS:000237221900009 PM 16651054 ER PT J AU Adams, SG Pugh, JA Kazis, LE Lee, S Anzueto, A AF Adams, SG Pugh, JA Kazis, LE Lee, S Anzueto, A TI Characteristics associated with sustained abstinence from smoking among patients with COPD SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; tobacco use disorder; former and current smokers; mental health; cardiovascular disease ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; PRIMARY-CARE; VETERANS-HEALTH; MENTAL-ILLNESS; LUNG HEALTH; EX-SMOKERS; CESSATION; POPULATION; PREDICTORS AB PURPOSE: Smoking cessation is the mainstay of recommended treatment for chronic obstructive pulmonary disease (COPD), yet many continue smoking. This study seeks to understand the characteristics of patients with COPD who have quit and those who have not quit to identify important factors to evaluate in smoking-cessation interventions. SUBJECTS/METHODS: A cross-sectional survey of a random sample of 1.5 million, predominantly male Veterans Administration enrollees. Of the respondents (63% [n = 887 775]), those with at least 1 COPD visit, a smoking history, and aged more than 34 years were included in this analysis (n = 89 337). Differences in demographics, functional status, comorbidities, and provider-patient interactions were evaluated for current and former smokers. RESULTS: Ninety-seven percent of the cohort with COPD was male. Former smokers (n = 58 482) were older (mean age of 69.6 vs 62.8, P <. 001) and had more cardiac comorbidities, but better mental health ( Mean Mental Component Summary score from the Veterans Short Form-36 +/- standard deviation of 43.4 +/- 13.2 vs 39.9 +/- 13.7, P < .001) than current smokers (n = 25 595), respectively. In addition, former smokers more actively participated in their health care and had a better relationship with their provider than current smokers. CONCLUSION: Former smokers with COPD were older, had more cardiac comorbidities, better mental health, and better perceived provider - patient interactions than active smokers. This study highlights the importance of screening participants with COPD who are enrolling in forthcoming smoking cessation trials for mental illnesses. In addition, developing interventions that address psychiatric comorbidities and potentially improve provider-patient communication may be other key areas to evaluate in future smoking cessation trials in patients with COPD. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Div Pulm Div Critical Care Med, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. Boston Univ, Sch Publ Hlth, VAMC, Ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA. Boston Univ, Sch Publ Hlth, Hlth Outcomes Technol, Boston, MA USA. RP Adams, SG (reprint author), Audie L Murphys Mem Vet Hosp, Pulm Dis Sect, 111E,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM adamssg@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X NR 43 TC 6 Z9 6 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2006 VL 119 IS 5 BP 441 EP 447 DI 10.1016/jamjmed.2005.09.055 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 038LO UT WOS:000237221900012 PM 16651057 ER PT J AU Spiegel, BMR Farid, M Dulai, GS Gralnek, IM Kanwal, F AF Spiegel, BMR Farid, M Dulai, GS Gralnek, IM Kanwal, F TI Comparing rates of dyspepsia with Coxibs vs NSAID+PPI: A meta-analysis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc DE Cox-2 inhibitors; proton pump inhibitors; dyspepsia; meta-analysis ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; GASTRODUODENAL ULCERS; GASTROINTESTINAL TOXICITY; CYCLOOXYGENASE-2 INHIBITOR; REDUCED INCIDENCE; CLINICAL-TRIAL AB PURPOSE: Because dyspeptic symptoms are far more prevalent than ulcer complications in users of nonsteroidal anti-inflammatory drugs (NSAIDs), economic models indicate that dyspepsia rates (not ulcer complications) are the major determinant of cost-effectiveness in treating arthritis. We performed a meta-analysis to compare rates of dyspepsia for two common therapies in high-risk patients with arthritis: cyclooxygenase-2 inhibitor (Coxib) alone and combination therapy with a nonselective NSAID and a proton pump inhibitor (PPI) (NSAID+PPI). METHODS: We performed a systematic review to identify trials comparing either a Coxib versus NSAID or NSAID+PPI versus NSAID in chronic arthritis. We selected studies that report incident dyspepsia, defined a priori as "epigastric pain," "dyspepsia," and "nausea." We then performed meta-analysis to compare the relative risk reduction and absolute risk reduction of dyspepsia for Coxib versus NSAID and NSAID + PPI versus NSAID. RESULTS: Meta-analysis of 26 studies comparing dyspepsia between Coxibs and NSAIDs revealed a 12% relative risk reduction for Coxibs with an absolute risk reduction of 3.7%. Meta-analysis of four studies comparing dyspepsia between the NSAID + PPI combination and NSAIDs alone revealed a 66% relative risk reduction for NSAID + PPI with an absolute risk reduction of 9%. Compared with the NSAID strategy, the number needed to treat to prevent dyspepsia was 27 for Coxibs and 11 for NSAID + PPI. CONCLUSION: NSAID + PPI affords greater risk reduction for dyspepsia than Coxibs when compared with the common baseline of NSAIDs. Because there are limited head-to-head data comparing Coxibs versus NSAID + PPI, these data provide the best indirect evidence that NSAID + PPI may be superior to Coxibs in minimizing incident dyspepsia. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, CORE,Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Vet Affairs Ctr Outcomes Res & Educ, Los Angeles, CA USA. CURE, Digest Dis Res Ctr, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, CORE,Div Gastroenterol & Hepatol, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 51 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2006 VL 119 IS 5 DI 10.1016/j.amjmed.2005.11.020 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 038LO UT WOS:000237221900015 ER PT J AU O'Donnell, LJ Kubicki, M Shenton, ME Dreusicke, MH Grimson, WEL Westin, CF AF O'Donnell, LJ Kubicki, M Shenton, ME Dreusicke, MH Grimson, WEL Westin, CF TI A method for clustering white matter fiber tracts SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID HUMAN BRAIN; DIFFUSION; TRACKING; DTI AB BACKGROUND/PURPOSE: Despite its potential for visualizing white matter fiber tracts in vivo, diffusion tensor tractography has found only limited applications in clinical research in which specific anatomic connections between distant regions need to be evaluated. We introduce a robust method for fiber clustering that guides the separation of anatomically distinct fiber tracts and enables further estimation of anatomic connectivity between distant brain regions. METHODS: Line scanning diffusion tenser images (LSDTI) were acquired on a 1.5T magnet. Regions of interest for several anatomically distinct fiber tracts were manually drawn; then, white matter tractography was performed by using the Runge-Kutta method to interpolate paths (fiber traces) following the major directions of diffusion, in which traces were seeded only within the defined regions of interest. Next, a fully automatic procedure was applied to fiber traces, grouping them according to a pairwise similarity function that takes into account the shapes of the fibers and their spatial locations. RESULTS: We demonstrated the ability of the clustering algorithm to separate several fiber tracts which are otherwise difficult to define (left and right fornix, uncinate fasciculus and inferior occipitofrontal fasciculus, and corpus callosum fibers). CONCLUSION: This method successfully delineates fiber tracts that can be further analyzed for clinical research purposes. Hypotheses regarding specific fiber connections and their abnormalities in various neuropsychiatric disorders can now be tested. C1 MIT Comp Sci & Al Lab, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. VA Boston Healthcare Syst, Clin Neurosci Div, Brockton, MA USA. VA Boston Healthcare Syst, Lab Neurosci, Brockton, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,MRI Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Math Imaging, Boston, MA 02115 USA. RP O'Donnell, LJ (reprint author), MIT Comp Sci & Al Lab, 32 Vassar St,D540, Cambridge, MA 02139 USA. FU NCRR NIH HHS [P41 RR013218, P41 RR13218]; NIBIB NIH HHS [U54 EB005149, U54 EB005149-010012]; NIMH NIH HHS [K02 MH001110-10, R03 MH 068464-02, K02 MH001110, K02 MH 01110, R03 MH068464]; NINDS NIH HHS [R01 NS051826, 1-R01-NS051826-01] NR 19 TC 67 Z9 67 U1 0 U2 6 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2006 VL 27 IS 5 BP 1032 EP 1036 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 043LG UT WOS:000237602000020 PM 16687538 ER PT J AU Yoerger, DM Best, CA McQuillan, BM Supple, GE Guererro, JL Cluette-Brown, JE Hasaba, A Picard, MH Stone, JR Laposata, M AF Yoerger, DM Best, CA McQuillan, BM Supple, GE Guererro, JL Cluette-Brown, JE Hasaba, A Picard, MH Stone, JR Laposata, M TI Rapid fatty acid ethyl ester synthesis by porcine myocardium upon ethanol infusion into the left anterior descending coronary artery SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY; ALCOHOLIC CARDIOMYOPATHY; ARRHYTHMIAS; METABOLISM; ABLATION; PURIFICATION; REDUCTION; INCREASE; THERAPY; MARKERS AB Fatty acid ethyl esters (FAEEs), nonoxidative metabolites of ethanol, have been implicated in ethanol-induced heart injury. To assess the in vivo production of FAEEs by myocardial tissue, we used a modified ethanol ablation procedure in pigs. A controlled 60-minute ethanol infusion was administered into the distal left anterior descending coronary artery in seven swine; serial blood sampling of the coronary sinus and peripheral vein before, during, and after infusion allowed measurement of FAEE production and ethanol levels in the coronary sinus and the peripheral circulation. In a single animal, FAEEs were also quantified from nine different sites within the myocardium. FAEEs were produced by the heart within 5 minutes of exposure to ethanol, with very high concentrations of FAEEs detected in coronary sinus blood. Significant variability in amounts of FAEEs was detected in different regions of the heart tissue. A strong correlation was found between coronary sinus FAEEs and ethanol concentration (r = 0.9241, P < 0.00001). FAEE production by the heart after delivery of ethanol into the left anterior descending coronary artery was rapid, reaching levels in the coronary sinus blood 4 to 10 times greater than that found in peripheral blood after ethanol intake. These data demonstrate that FAEEs maybe mediators of ethanol induced cardiotoxicity. C1 Massachusetts Gen Hosp, Div Lab Med, Clin Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Lab Med, Clin Labs, 55 Fruit St,Gray 235, Boston, MA 02114 USA. EM mlaposata@partners.org RI McQuillan, Brendan/B-8271-2013; OI McQuillan, Brendan/0000-0002-2130-8114; Picard, Michael/0000-0002-9264-3243 NR 32 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2006 VL 168 IS 5 BP 1435 EP 1442 DI 10.2353/ajpath.2006.050537 PG 8 WC Pathology SC Pathology GA 039RY UT WOS:000237325700004 PM 16651611 ER PT J AU Spires, TL Orne, JD SantaCruz, K Pitstick, R Carlson, GA Ashe, KH Hyman, BT AF Spires, TL Orne, JD SantaCruz, K Pitstick, R Carlson, GA Ashe, KH Hyman, BT TI Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PAIRED HELICAL FILAMENTS; HEREDITARY FRONTOTEMPORAL DEMENTIA; ENTORHINAL CORTEX NEURONS; HUMAN TAU-ISOFORMS; ALZHEIMERS-DISEASE; P301L TAU; TANGLES; PROTEIN; PLAQUES; DEGENERATION AB Neurofibrillary tangles form in a specific spatial and temporal pattern in Alzheimer's disease. Although tangle formation correlates with dementia and neuronal loss, it remains unknown whether neurofibrillary pathology causes cell death. Recently, a mouse model of tauopathy was developed that reversibly expresses human tan with the dementia-associated P301L mutation. This model (rTg4510) exhibits progressive behavioral deficits that are ameliorated with transgene suppression. Using quantitative analysis of PHF1 immunostaining and neuronal counts, we estimated neuron number and accumulation of neurofibrillary pathology in five brain regions. Accumulation of PHF1-positive tan in neurons appeared between 2.5 and 7 months of age in a region-specific manner and increased with age. Neuron loss was dramatic and region-specific in these mice, reaching over 80% loss in hippocampal area CA1 and dentate gyrus by 8.5 months. We observed regional dissociation of neuronal loss and accumulation of neurofibrillary pathology, because there was loss of neurons before neurofibrillary lesions appeared in the dentate gyros and, conversely, neurofibrillary pathology appeared without major cell loss in the striatum. Finally, suppressing the transgene prevented further neuronal loss without removing or preventing additional accumulation of neurofibrillary pathology. Together, these results imply that neurofibrillary tangles do not necessarily lead to neuronal death. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. McLaughlin Res Inst, Great Falls, MT USA. Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Neurosci, Minneapolis, MN 55455 USA. Minneapolis VA Hosp, Ctr Geriatr Res Educ & Clin, Minneapolis, MN USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Alzheimer Unit,114 16th St, Charlestown, MA 02129 USA. EM tspires@partners.org; bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU NIA NIH HHS [AG00277, AG08487, AG26249, P50 AG005134, R01 AG008487, R01 AG026249, T32 AG000277] NR 48 TC 179 Z9 181 U1 2 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 2006 VL 168 IS 5 BP 1598 EP 1607 DI 10.2353/ajpath.2006.050840 PG 10 WC Pathology SC Pathology GA 039RY UT WOS:000237325700019 PM 16651626 ER PT J AU Chiou-Tan, FY Keng, MJ Graves, DE Chan, KT Rintala, DH AF Chiou-Tan, FY Keng, MJ Graves, DE Chan, KT Rintala, DH TI Racial/ethnic differences in FIM (TM) scores and length of stay for underinsured patients undergoing stroke inpatient rehabilitation SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE stroke; race; ethnicity; FIM; underinsured; rehabilitation ID NORTHERN MANHATTAN STROKE; WHITE; BLACK; RACE AB Objective: To explore racial/ethnic differences in FIM (TM) data from admission to discharge in underinsured patients undergoing inpatient stroke rehabilitation. Design: This is a retrospective analysis of the Uniform Data System for Medical Rehabilitation (UDSMR (R)) database of an inpatient rehabilitation unit of a county hospital in a large urban city. Data included 171 adult patients admitted to the stroke rehabilitation unit between January 2000 and October 2003. Main outcome measures included admission and discharge total FIM (TM) score, FIM (TM) gain, FIM (TM) efficiency, and length of stay (LOS). Data were analyzed using chi(2) analyses, t tests, univariate analysis of variance, binary logistic regression, and hierarchical multiple regression. Results: Data from 68 Hispanic, 83 black, and 20 white patients were included in the study. Univariate tests revealed that race/ethnicity groups differed significantly on admission FIM (TM) score (F = 5.38, P < 0.005), FIM (TM) gain (F = 4.35, P < 0.014), and FIM (TM) efficiency (F = 3.42, P < 0.035). Post hoc pairwise comparisons revealed that Hispanics had lower admission FIM (TM) scores than blacks (58.9 vs. 68.9). However, Hispanics had higher FIM (TM) gain scores than blacks (26.8 vs. 21.5). Race/ethnicity was not significantly related to age, gender, side of stroke, type of stroke, time from onset of stroke to rehabilitation admission, discharge FIM (TM) score, or LOS. Multiple regression analyses revealed that after controlling for all other available factors, race/ethnicity accounted for a significant amount of additional variance in admission FIM (TM) score (5.8%) and FIM (TM) efficiency (4.6%), but not in discharge FIM (TM) score, FIM (TM) gain, or LOS. Race/ethnicity was not predictive of discharge disposition. Conclusions: Differences in functional independence at admission to poststroke rehabilitation and the average daily improvement in function are related, in part, to patients' race/ethnicity. Differences in change in functional independence from admission to discharge (FIM (TM) gain) are not related to race/ethnicity once other factors, particularly admission FIM (TM) score, are taken into account. Future studies should identify reasons why Hispanics have lower admission FIM (TM) scores because demographic and stroke-related variables were not related to ethnicity yet have outcomes similar to blacks and whites at discharge. C1 Quentin Mease Hosp, Dept Phys Med & Rehabil, Harris Cty Hosp Dist, Ctr Trauma Rehabil Res, Houston, TX 77004 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Inst Rehabil Res, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Chiou-Tan, FY (reprint author), Quentin Mease Hosp, Dept Phys Med & Rehabil, Harris Cty Hosp Dist, Ctr Trauma Rehabil Res, Suite 240,3601 N MacGregor Way, Houston, TX 77004 USA. NR 10 TC 18 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY PY 2006 VL 85 IS 5 BP 415 EP 423 DI 10.1097/01.phm.0000214320.99729.f3 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 037QG UT WOS:000237161300001 PM 16628148 ER PT J AU Zhang, BX Ma, XY Zhang, WK Yeh, CK Lin, A Luo, J Sprague, EA Swerdlow, RH Katz, MS AF Zhang, BX Ma, XY Zhang, WK Yeh, CK Lin, A Luo, J Sprague, EA Swerdlow, RH Katz, MS TI Polyunsaturated fatty acids mobilize intracellular Ca(2+) in NT2 human teratocarcinoma cells by causing release of Ca(2+) from mitochondria SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE arachidonic acid; mitochondrial Ca(2+) uniporter; G protein-coupled receptor; IP(3) receptor ID ARACHIDONIC-ACID; PERMEABILITY TRANSITION; NADPH OXIDASE; GROWTH-FACTOR; 2-AMINOETHOXYDIPHENYL BORATE; EICOSAPENTAENOIC ACID; ENDOPLASMIC-RETICULUM; DOCOSAHEXAENOIC ACID; SYMPATHETIC NEURONS; CARDIAC MYOCYTES AB In a variety of disorders, overaccumulation of lipid in nonadipose tissues, including the heart, skeletal muscle, kidney, and liver, is associated with deterioration of normal organ function, and is accompanied by excessive plasma and cellular levels of free fatty acids (FA). Increased concentrations of FA may lead to defects in mitochondrial function found in diverse diseases. One of the most important regulators of mitochondrial function is mitochondrial Ca(2+)([Ca2(+)](m)), which fluctuates in coordination with intracellular Ca(2+)([Ca(2+)](i)). Polyunsaturated FA (PUFA) have been shown to cause [Ca(2+)](i) mobilization albeit by unknown mechanisms. We have found that PUFA but not monounsaturated or saturated FA cause [Ca(2+)](i) mobilization in NT2 human teratocarcinoma cells. Unlike the [Ca(2+)](i) response to the muscarinic G protein-coupled receptor agonist carbachol, PUFA-mediated [Ca(2+)](i) mobilization in NT2 cells is independent of phospholipase C and inositol-1,4,5-trisphospate (IP(3)) receptor activation, as well as IP(3)-sensitive internal Ca(2+) stores. Furthermore, PUFA-mediated [Ca(2+)](i) mobilization is inhibited by the mitochondria uncoupler carboxyl cyanide m-chlorophenylhydrozone. Direct measurements of [Ca(2+)](m) with X-rhod-1 and (45)Ca(2+) indicate that PUFA induce Ca(2+) efflux from mitochondria. Further studies show that ruthenium red, an inhibitor of the mitochondrial Ca(2+) uniporter, blocks PUFA-induced Ca(2+) efflux from mitochondria, whereas inhibitors of the mitochondrial permeability transition pore cyclosporin A and bongkrekic acid have no effect. Thus PUFA-gated Ca(2+) release from mitochondria, possibly via the Ca(2+) uniporter, appears to be the underlying mechanism for PUFA-induced [Ca(2+)](i) mobilization in NT2 cells. C1 GRECC 182, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol, Charlottesville, VA 22908 USA. RP Zhang, BX (reprint author), GRECC 182, S Texas Vet Hlth Care Syst, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM zhangb2@uthscsa.edu FU NHLBI NIH HHS [R01 HL 75011] NR 79 TC 16 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 2006 VL 290 IS 5 BP C1321 EP C1333 DI 10.1152/ajpcell.00335.2005 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 037JN UT WOS:000237143000006 PM 16601147 ER PT J AU Koutkia, P Berry, J Eaton, K Breu, J Grinspoon, S AF Koutkia, P Berry, J Eaton, K Breu, J Grinspoon, S TI Increased adrenal androgen secretion with inhibition of 11 beta-hydroxylase in HIV-infected women SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE human immunodeficiency virus; androgen shunting; stress; metyrapone ID HUMAN-IMMUNODEFICIENCY-VIRUS; ADRENOCORTICAL FUNCTION; ILLNESS; TESTOSTERONE; PROGRESSION; BODY; EXPRESSION; CORTISOL; SURVIVAL; ADULTS AB Adrenal androgen production is reduced in association with disease severity in HIV-infected women. This response may be maladaptive in terms of maintenance of lean body mass, functional status, and immune function. The aim of this study was to assess whether the use of an adrenal enzyme inhibitor of 11 beta-hydroxylase might increase androgen production in this population. We conducted a randomized, double-blind, placebo-controlled study of metyrapone (500 mg po qid) or placebo for 2 wk in 10 HIV-infected women with AIDS wasting [weight < 90% ideal body weight (IBW) or weight loss > 10%] and reduced androgen levels. Basal and ACTH-stimulated androgen, mineralocorticoid, and glucocorticoid levels were measured at baseline and after 14 days of treatment. Subjects were similar in age (40.9 +/- 0.9 yr), weight (91.7 +/- 3.5% IBW) and hormone concentrations at study entry. Total testosterone (84 +/- 54 vs. -0.4 +/- 2 ng/dl, P = 0.024), free testosterone (6.5 +/- 2.8 vs. 0.1 +/- 0.1 pg/ml, P = 0.024), DHEA (5.0 +/- 3.2 vs. -0.6 +/- 0.5 mu g/l, P = 0.024), and 11-deoxycortisol (2,145 +/- 820 vs. -14 +/- 22 ng/dl, P = 0.024) levels increased in response to metyrapone compared with placebo treatment. In response to ACTH, significant increases in the DHEA/cortisol ratio (174 +/- 48 vs. 3 +/- 3, P = 0.008) were seen in the metyrapone group compared with placebo. Blood pressure and electrolytes did not change, and signs of adrenal insufficiency were not apparent. These data demonstrate that inhibition of 11 beta-hydroxylase with metyrapone increases adrenal androgen secretion in HIV-infected women. Further studies are needed to assess the physiological effects of this strategy to increase anabolic hormone levels in severe stress, including detailed testing to rule out the potential risk of concomitant adrenal insufficiency. C1 Harvard Univ, Program Nutr Metab, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Neuroendocrine Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. MIT, Massachusetts Gen Hosp, Technol Gen Clin Res Ctr, Core Lab, Boston, MA USA. RP Grinspoon, S (reprint author), Harvard Univ, Program Nutr Metab, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR-01066]; NIDDK NIH HHS [R01 DK-54167] NR 28 TC 0 Z9 0 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 2006 VL 290 IS 5 BP E808 EP E813 DI 10.1152/ajpendo.00418.2005 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 036EJ UT WOS:000237053500006 PM 16303845 ER PT J AU Page, ST Plymate, SR Bremner, WJ Matsumoto, AM Hess, DL Lin, DW Amory, JK Nelson, PS Wu, JD AF Page, ST Plymate, SR Bremner, WJ Matsumoto, AM Hess, DL Lin, DW Amory, JK Nelson, PS Wu, JD TI Effect of medical castration on CD4(+) CD25(+) T cells, CD8(+) T cell IFN-gamma expression, and NK cells: a physiological role for testosterone and/or its metabolites SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE testosterone replacement; gonadotropin; releasing hormone antagonist; regulatory T cells; interferon-gamma ID NATURAL-KILLER-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNOLOGICAL FEATURES; KLINEFELTERS-SYNDROME; AUTOIMMUNE-DISEASES; HORMONE ANTAGONIST; INTERFERON-GAMMA; SEX STEROIDS; ESTROGEN; IMMUNE AB The higher prevalence of autoimmune disease among women compared with men suggests that steroids impact immune regulation. To investigate how sex steroids modulate cellular immune function, we conducted a randomized trial in 12 healthy men aged 35 - 55 yr treated for 28 days with placebo, a GnRH antagonist, acyline to induce medical castration, or acyline plus daily testosterone (T) gel to replace serum T, followed by a 28-day recovery period. Serum hormones were measured weekly and peripheral blood lymphocytes (PBLs) were collected biweekly for analyses of thymus-derived lymphocyte (T cell) subtypes and natural killer (NK) cells. Compared with the other groups and to baseline throughout the drug exposure period, men receiving acyline alone had significant reductions in serum T ( near or below castrate levels), dihydrotestosterone, and estradiol (P < 0.05). Medical castration significantly reduced the percentage of CD4(+) CD25(+) T cells (P < 0.05), decreased mitogen-induced CD8(+) T cell IFN-gamma expression, and increased the percentage of NK cells without affecting the ratio of CD4(+) to CD8(+) T cells and the expression of NK cell-activating receptor NKG2D or homing receptor CXCR1. No changes in immune composition were observed in subjects receiving placebo or acyline with replacement T. These data suggest that T and/or its metabolites may help maintain the physiological balance of autoimmunity and protective immunity by preserving the number of regulatory T cells and the activation of CD8(+) T cells. In addition, sex steroids suppress NK cell proliferation. This study supports a complex physiological role for T and/or its metabolites in immune regulation. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Natl Oregon Primate Res Ctr, Beaverton, OR USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Wu, JD (reprint author), 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM wuj@u.washington.edu FU NCI NIH HHS [K01 CA116002, P01 CA-85859, CA-97186]; NCRR NIH HHS [RR-00163]; NIA NIH HHS [K23 AG027238, K23 AG027238-01A1]; NICHD NIH HHS [U54 HD-12629, U54 HD-42454] NR 49 TC 53 Z9 58 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 2006 VL 290 IS 5 BP E856 EP E863 DI 10.1152/ajpendo.00484.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 036EJ UT WOS:000237053500012 PM 16352669 ER PT J AU Ayata, C Moskowitz, MA AF Ayata, C Moskowitz, MA TI Cortical spreading depression confounds concentration-dependent pial arteriolar dilation during N-methyl-D-aspartate superfusion SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cranial window; pial arterioles; electrophysiology ID NITRIC-OXIDE SYNTHASE; CEREBRAL-BLOOD-FLOW; ADULT-RATS; L-ARGININE; IMMATURE; ACTIVATION; RECEPTORS; GLUTAMATE; BRAIN; NMDA AB Pial arterioles do not express N-methyl-D-aspartate ( NMDA) receptors but dilate in response to topical NMDA application. We explored the mechanism underlying NMDA-mediated responses in murine pial arterioles ( 11 - 31 mu m), using a closed cranial window preparation, and found that arteriolar dilation was not concentration dependent. Pial arteriolar diameter abruptly increased within 3 min of superfusing 50 or 100 mu M NMDA. Dilation reached a peak within 1 min ( 46 +/- 14%) and then declined to a plateau ( 28 +/- 13%) for the duration of superfusion. Whereas a higher concentration ( 200 mu M) did not produce further dilation, lower concentrations ( 1 - 10 mu M) did not dilate the arterioles at all. MK-801 ( 10 mu M) abrogated the dilation response, whereas N-omega-nitro-L-arginine ( 1 mM) attenuated the peak and abolished the sustained dilation during NMDA superfusion. We determined that NMDA-induced pial arteriolar responses were evoked by cortical spreading depression, because abrupt vasodilation during 50 or 100 mu M NMDA superfusion was associated with a large negative slow potential shift and electrocorticogram suppression that spread from the superfusion window to distant cortical areas. Our data suggest that the responses of pial arterioles to NMDA are caused in part by neurovascular coupling due to cortical spreading depression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA 02129 USA. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Stroke & Neurovasc Regulat Lab, 149 13th St,Rm 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [P01-NS-35611, P50-NS-10828] NR 48 TC 18 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2006 VL 290 IS 5 BP H1837 EP H1841 DI 10.1152/ajpheart.01102.2005 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 030WD UT WOS:000236664900017 PM 16299263 ER PT J AU Hataishi, R Zapol, WM Bloch, KD Ichinose, F AF Hataishi, R Zapol, WM Bloch, KD Ichinose, F TI Inhaled nitric oxide does not reduce systemic vascular resistance in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE peripheral vasodilation; endothelial nitric oxide synthase; telemetry; tail cuff ID ISCHEMIA/REPERFUSION; HYPERTENSION; INHALATION; SYNTHASE; INJURY; GENE; NO AB Inhaled nitric oxide ( NO) is a highly selective pulmonary vasodilator. It was recently reported that inhaled NO causes peripheral vasodilatation after treatment with a NO synthase ( NOS) inhibitor. These findings suggested the possibility that inhibition of endogenous NOS uncovered the systemic vasodilating effect of NO or NO adducts absorbed via the lungs during NO inhalation. To learn whether inhaled NO reduces systemic vascular resistance in the absence of endothelial NOS, we studied the systemic vascular effects of NO breathing in wild-type mice treated without and with the NOS inhibitor N-omega-nitro-L-arginine methyl ester and in NOS3-deficient (NOS3(-/-)) mice. During general anesthesia, the cardiac output, left ventricular function, and systemic vascular resistance were not altered by NO breathing at 80 parts/million in both genotypes. Breathing NO in air did not alter blood pressure and heart rate, as measured by tail-cuff and telemetric methods, in either awake wildtype mice ( whether or not they were treated with N-omega-nitro-L-arginine methyl ester), or in awake NOS3(-/-) mice. Our findings suggest that absorption of NO or adducts during NO breathing is insufficient to cause systemic vasodilation in mice, even when endogenous endothelial NO production is congenitally absent. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM ichinose@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [HL-70896, HL-71987, HL-42397] NR 14 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2006 VL 290 IS 5 BP H1826 EP H1829 DI 10.1152/ajpheart.00938.2005 PG 4 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 030WD UT WOS:000236664900015 PM 16299267 ER PT J AU Xu, Y Lu, L Greyson, C Rizeq, M Nunley, K Wyatt, B Bristow, MR Long, CS Schwartz, GG AF Xu, Y Lu, L Greyson, C Rizeq, M Nunley, K Wyatt, B Bristow, MR Long, CS Schwartz, GG TI The PPAR-alpha activator fenofibrate fails to provide myocardial protection in ischemia and reperfusion in pigs SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nuclear receptor; fibric acid derivative; energy metabolism; cytokine; ventricular function ID RECEPTOR-ALPHA; ISCHEMIA/REPERFUSION INJURY; PEROXISOME PROLIFERATION; ENERGY-METABOLISM; GAMMA; RAT; LIGAND; CELLS; HEART; RESPONSIVENESS AB Rodent studies suggest that peroxisome proliferator-activated receptor-alpha ( PPAR-alpha) activation reduces myocardial ischemia-reperfusion (I/R) injury and infarct size; however, effects of PPAR-alpha activation in large animal models of myocardial I/R are unknown. We determined whether chronic treatment with the PPAR-alpha activator fenofibrate affects myocardial I/R injury in pigs. Domestic farm pigs were assigned to treatment with fenofibrate 50 mg . kg(-1) . day(-1) orally or no drug treatment, and either a low-fat (4% by weight) or a high-fat (20% by weight) diet. After 4 wk, 66 pigs underwent 90 min low-flow regional myocardial ischemia and 120 min reperfusion under anesthetized open-chest conditions, resulting in myocardial stunning. The high-fat group received an infusion of triglyceride emulsion and heparin during this terminal experiment to maintain elevated arterial free fatty acid (FFA) levels. An additional 21 pigs underwent 60 min no-flow ischemia and 180 min reperfusion, resulting in myocardial infarction. Plasma concentration of fenofibric acid was similar to the EC50 for activation of PPAR-alpha in vitro and to maximal concentrations achieved in clinical use. Myocardial expression of PPAR-alpha mRNA was prominent but unaffected by fenofibrate treatment. Fenofibrate increased expression of carnitine palmitoyltransferase (CPT)-I mRNA in liver and decreased arterial FFA and lactate concentrations ( each P < 0.01). However, fenofibrate did not affect myocardial CPT-I expression, substrate uptake, lipid accumulation, or contractile function during low-flow I/R in either the low-or high-fat group, nor did it affect myocardial infarct size. Despite expression of PPAR-alpha in porcine myocardium and effects of fenofibrate on systemic metabolism, treatment with this PPAR-alpha activator does not alter myocardial metabolic or contractile responses to I/R in pigs. C1 Vet Affairs Med Ctr, Cardiol Sect, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect 111B, 111B,1055 Clermont St, Denver, CO 80220 USA. EM Gregory.Schwartz@med.va.gov RI bristow, michael/G-7850-2011 FU NHLBI NIH HHS [HL-49944, HL-68606, R01 HL049944, R01 HL049944-09, R01 HL068606, R56 HL049944] NR 38 TC 13 Z9 13 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2006 VL 290 IS 5 BP H1798 EP H1807 DI 10.1152/ajpheart.00631.2005 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 030WD UT WOS:000236664900012 PM 16339839 ER PT J AU Kaunitz, JD AF Kaunitz, JD TI Membrane transport proteins: not just for transport anymore SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Editorial Material ID NA+/K+-ATPASE; OUABAIN; PLASMA; CFTR C1 Univ Calif Los Angeles, Sch Med, Dept Med, W Los Angeles Vet Affairs Med Ctr,Med Serv, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, W Los Angeles Vet Affairs Med Ctr,Med Serv, Bldg 114,Suite 217, Los Angeles, CA 90073 USA. EM jake@ucla.edu NR 16 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2006 VL 290 IS 5 BP F995 EP F996 DI 10.1152/ajprenal.00515.2005 PG 2 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 029YT UT WOS:000236601000005 PM 16601299 ER PT J AU Xu, HS Fu, Y Tian, W Cohen, DM AF Xu, HS Fu, Y Tian, W Cohen, DM TI Glycosylation of the osmoresponsive transient receptor potential channel TRPV4 on Asn-651 influences membrane trafficking SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cell volume regulation; hypotonicity; ion channel ID SHAKER POTASSIUM CHANNEL; REGULATING FACTOR NHERF2; CELL-SURFACE EXPRESSION; N-LINKED GLYCOSYLATION; SMOOTH-MUSCLE-CELLS; SODIUM-CHANNELS; CATION CHANNEL; PLASMA-MEMBRANE; XENOPUS-OOCYTES; TRPC6 CHANNEL AB We identified a consensus N-linked glycosylation motif within the pore-forming loop between the fifth and sixth transmembrane segments of the osmoresponsive transient receptor potential (TRP) channel TRPV4. Mutation of this residue from Asn to Gln (i.e., TRPV4(N651Q)) resulted in loss of a slower migrating band on anti-TRPV4 immunoblots and a marked reduction in lectin-precipitable TRPV4 immunoreactivity. HEK293 cells transiently transfected with the mutant TRPV4(N651Q) exhibited increased calcium entry in response to hypotonic stress relative to wild-type TRPV4 transfectants. This increase in hypotonicity responsiveness was associated with an increase in plasma membrane targeting of TRPV4(N651Q) relative to wild-type TRPV4 in both HEK293 and COS-7 cells but had no effect on overall channel abundance in whole cell lysates. Residue N651 of TRPV4 is immediately adjacent to the pore-forming loop. Although glycosylation in this vicinity has not been reported for a TRP channel, the structurally related hexahelical hyperpolarization-activated cyclic nucleotide-gated channel, HCN2, and the voltage-gated potassium channel, human ether-a-go-go-related ( HERG), share a nearly identically situated and experimentally confirmed N-linked glycosylation site which promotes rather than limits channel insertion into the plasma membrane. These data point to a potentially conserved structural and functional feature influencing membrane trafficking across diverse members of the voltage-gated-like ion channel superfamily. C1 Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM cohend@ohsu.edu NR 57 TC 38 Z9 40 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 2006 VL 290 IS 5 BP F1103 EP F1109 DI 10.1152/ajprenal.00245.2005 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 029YT UT WOS:000236601000017 PM 16368742 ER PT J AU Roffman, JL Simon, AB Prasad, KM Truman, CJ Morrison, J Ernst, CL AF Roffman, JL Simon, AB Prasad, KM Truman, CJ Morrison, J Ernst, CL TI Neuroscience in psychiatry training: How much do residents need to know? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Psychiatric-Association CY MAY 01-06, 2004 CL New York, NY SP Amer Psychiat Assoc ID FUNCTIONAL NEUROANATOMY; PSYCHOTHERAPY; PROGRAMS; EDUCATION; FUTURE; PSYCHOANALYSIS; REVOLUTION; DISORDERS; DIRECTORS; NEUROLOGY AB Objective: With the explosion of research in psychiatric neuroscience, the extent and means by which neuroscientific progress will translate into clinical care remains largely uncertain. The authors sought to determine how this dilemma is currently being played out in residency training programs, in which training directors must decide how best to integrate neuroscience teaching in a rapidly changing clinical landscape. Method: The authors surveyed U. S. and Canadian psychiatry residency training directors to characterize current and future trends in neuroscience education and to examine training directors' views on the relevance of neuroscience to clinical practice. Results: The amount of neuroscience in residency curricula has increased significantly over the past 5 years, and further increases are expected in each specific neuroscience content area examined. While most training directors agreed that training in neuroscience was important for all residents, even those becoming primarily psychotherapists, relevance to future (but not current) practice was consistently cited as a motivating factor. Conclusions: While psychiatric residency programs continue to increase the neuroscience content of their curricula, it remains unclear how this added training will influence clinical work. Reframing current practices, including psychotherapy, into a neuroscientific context may ultimately prove more useful to trainees. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Rhode Isl Hosp, Dept Psychiat, Providence, RI USA. McGill Univ, Fac Med, Dept Psychiat, Montreal, PQ, Canada. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Rm 2625, Charlestown, MA 02129 USA. EM jroffman@partners.org OI Prasad, Konasale/0000-0003-0245-1393 FU NIMH NIH HHS [K23 MH072995] NR 43 TC 26 Z9 26 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2006 VL 163 IS 5 BP 919 EP 926 DI 10.1176/appi.ajp.163.5.919 PG 8 WC Psychiatry SC Psychiatry GA 037GV UT WOS:000237136000030 PM 16648336 ER PT J AU Wrobel, BB Bien, AG Holbrook, EH Meyer, GE Bratney, NA Meza, J Leopold, DA AF Wrobel, Bozena B. Bien, Alexander G. Holbrook, Eric H. Meyer, George E. Bratney, Neil A. Meza, Jane Leopold, Donald A. TI Decreased nasal mucosal sensitivity in older subjects SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID AIR-FLOW; AGE; PERCEPTION; IDENTIFICATION; QUALITIES; SENSATION; STIMULI; SITE AB Background: The sensitivity of the human nasal cavity mucosa to touch is not well understood. The site of receptors and mode of action responsible for the sensation of the nasal airflow is a topic of controversy. Previous studies have suggested that the skin-lined nasal vestibule is more sensitive to airflow than the mucosa of the nasal cavity. A possible decline in nasal sensitivity to airflow in older subjects has not been studied. Methods: The threshold of the mucosal sensitivity to jets of air was assessed in 76 subjects with healthy nasal cavities. A total of 141 nostrils were tested, 67 in younger patients and 74 in older patients. Results: Statistically significant (p<0.001)increases in thresholds were found for all points tested for older patients compared with the younger patients. In general, the more sensitive locations were in the nasal vestibule. The nasal cavity mucosa in the inferior meatus was slightly more sensitive than the middle meatus. Conclusion: We have measured the threshold to touch (air jet sensitivity) in nine places in each of 141 nasal cavities and determined that the variability and sensitivity of these measurements among people varies by age and the distance from the nostril. Older subjects were found to have a higher threshold for the sensation of airflow, and the nasal vestibule was found to be more sensitive than the rest of the nasal cavity mucosa with the inferior meatus slightly more sensitive then the middle meatus. C1 Univ Nebraska, Med Ctr, Dept Otolaryngol Head & Neck Surg, Omaha, NE 68198 USA. Univ So Calif, Dept Otolaryngol Head & Neck Surg, Los Angeles, CA USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Univ Nebraska, Lincoln, NE USA. Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE USA. RP Leopold, DA (reprint author), Univ Nebraska, Med Ctr, Dept Otolaryngol Head & Neck Surg, 600 S 42nd St, Omaha, NE 68198 USA. EM dleopold@unmc.edu NR 19 TC 15 Z9 16 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD MAY-JUN PY 2006 VL 20 IS 3 BP 364 EP 368 DI 10.2500/ajr.2006.20.2862 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 062DX UT WOS:000238925900024 PM 16871945 ER PT J AU Ramappa, AJ Apreleva, M Harrold, FR Fitzgibbons, PG Wilson, DR Gill, TJ AF Ramappa, AJ Apreleva, M Harrold, FR Fitzgibbons, PG Wilson, DR Gill, TJ TI The effects of medialization and anteromedialization of the tibial tubercle on patellofemoral mechanics and kinematics SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Orthopaedic-Society-for-Sports-Medicine CY JUL 20-23, 2003 CL SAN DIEGO, CA SP Amer Orthopaed Soc Sports Med DE knee; biomechanics; patellofemoral; osteotomy ID ELMSLIE-TRILLAT PROCEDURE; CHONDROMALACIA PATELLAE; ANTERIOR DISPLACEMENT; ARTICULAR-CARTILAGE; TUBEROSITY TRANSFER; CONTACT PRESSURES; PROXIMAL TIBIA; PAIN SYNDROME; Q-ANGLE; JOINT AB Background: Medialization and anteromedialization of the tibial tubercle are used to correct patellar subluxation in adults. Purpose: To compare the effects of the 2 osteotomies on patellofemoral joint contact pressures and kinematics. Study Design: Controlled laboratory study. Methods: Tibial tubercle osteotomies were performed on 10 cadaveric human knees. The knees were tested between 0 degrees and 90 degrees of flexion while dynamic patellofemoral joint contact pressure and kinematic data were simultaneously obtained. Four conditions were tested: normal knee alignment, simulated increased Q angle, postmedialization of the tibial tubercle, and postanteromedialization of the tubercle. Results: An increased Q angle laterally translated the patella, shifted force to the lateral facet, and increased patella contact pressures. Both medialization and anteromedialization partially corrected the abnormal contact pressures. Medialization partially corrected the shift of force to the lateral facet induced by an increased Q angle, whereas the anteromedialization could not. Both medialization and anteromedialization corrected the patella maltracking. Conclusion: Medialization and anteromedialization are equivalent in their ability to correct abnormal patellar mechanics and kinematics. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Boston, MA 02215 USA. Univ British Columbia, Dept Orthopaed, Vancouver, BC V5Z 1M9, Canada. Vancouver Coastal Hlth Res Inst, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Ramappa, AJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthopaed Surg, Shapiro 2,330 Brookline Ave, Boston, MA 02215 USA. EM aramappa@bidmc.harvard.edu NR 39 TC 37 Z9 38 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAY PY 2006 VL 34 IS 5 BP 749 EP 756 DI 10.1177/0363546505283460 PG 8 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 036OK UT WOS:000237083500006 PM 16436533 ER PT J AU McCluggage, WG Young, RH AF McCluggage, WG Young, RH TI Paraganglioma of the ovary - Report of three cases of a rare ovarian neoplasm, including two exhibiting inhibin positivity SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; paraganglioma; immunohistochemistry; differential diagnosis ID SMALL-CELL CARCINOMA; CORD-STROMAL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; ADRENAL PHEOCHROMOCYTOMAS; MALIGNANT PARAGANGLIOMA; DIFFERENTIAL-DIAGNOSIS; MONOCLONAL-ANTIBODY; HYPERCALCEMIC TYPE; BROAD LIGAMENT; UTERUS AB Paraganglioma is one of the rarest neoplasms to involve the ovary, whether primary or metastatic, with only two previous reports. We describe three examples that occurred in patients 22, 58, and 68 years of age. Two patients had hypertension. Two tumors involved the left ovary and one the right ovary; they ranged from 8 to 22cm, were solid, and were tail, brown, or yellow. One tumor was confined to the ovary; in the second case, there were tumor deposits on the posterior surface of the Uterus and the contralateral ovary; in the other case, there was peri-aortic lynipli node involvement and peritoneal deposits. In all cases, however, radiologic investigations did not reveal an alternative primary site. On microscopic examination, all three tumors showed a predominantly nested "zellballen" pattern with 'groups of cells Surrounded by a vascular stroma. Tumor cells largely had abundant g-ranular eosinophilic cytoplasm with, in 2 cases, focal clear cell areas. In 1 case, bizarre tumor giant cells were present. Immunohistochemically, all neoplasms were cytokeratin negative and diffusely positive with neuroendocrine markers. In 1 case, there was an S-100-positive population of sustentacular cells. Two cases were positive for inhibin, one focal and one diffuse, and the other was focally positive for calretinin. Electron microscopy performed in 2 cases revealed dense core neuroendocrine granules. One patient has been followed up for 15 years and is alive and well. Although metastatic spread from an undetected primary outside the ovary cannot be totally excluded for the 2 cases with extraovarian disease, we think that the neoplasms most likely represent primary ovarian paragangliomas. Because various neoplasms in the sex cord-stromal and steroid categories are likely to enter into the differential diagnosis, inhibin and calretinin positivity represents a significant potential diagnostic pitfall. The differential is broad and may include many other ovarian tumors. particularly those with an oxyphilic cell type. Possible theories of histogenesis of primary ovarian paraganglioma include an origin from extra-adrenal paraganglia in the region of the ovary or unidirectional differentiation within a teratoma. C1 Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. EM glenn.mccluggage@bll.n-i.nhs.uk NR 38 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2006 VL 30 IS 5 BP 600 EP 605 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 038WZ UT WOS:000237261500006 PM 16699314 ER PT J AU Mitsuhashi, T Lauwers, GY Ban, S Mino-Kenudson, M Shimizu, Y Ogawa, F Ota, S Shimizu, M AF Mitsuhashi, T Lauwers, GY Ban, S Mino-Kenudson, M Shimizu, Y Ogawa, F Ota, S Shimizu, M TI Post-gastric endoscopic mucosal resection surveillance biopsies: Evaluation of mucosal changes and recognition of potential mimics of residual adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endoscopic mucosal resection; stomach; dysplasia; early gastric cancer; signet-ring; cell-like change; clear cell degeneration ID SIGNET-RING CELLS; LYMPH-NODE METASTASIS; PSEUDOMEMBRANOUS COLITIS; GALLBLADDER MUCOSA; CANCER; CARCINOMA AB Endoscopic mucosal resection (EMR) offers curative treatment for patients with node-negative early gastric carcinoma of less than 2cm without ulceration or ulceration scar. Follow-Lip biopsies are frequently performed to ensure the absence of residual neoplasia. We performed a retrospective analysis of post-EMR biopsies from 33 patients who underwent gastric EMR. Histologic changes included inflammation (100%), stromal edema (97.0%), foveolar hyperplasia (78.8%), ectatic vessels (66.7%), epithelial atypia (60.6%), increased glandular mitoses (57.6%), epithelial anisonucleosis (54.5%) fibrinopurulent materials (51.5%), ischemia (48.5%), stromal hemorrhage (33.3%), mucin depletion (12.1%), clear cell degeneration (15.2%), and signet-ring cell-like change (6.1%). Especially, clear cell degeneration and signet-ring cell-like change were conspicuous in the area of ischemia. Residual adenocarcinomas were noted in 4 of 33 cases, and consistently showed high nuclear-to-cytoplasirtic ratio with high glandular density. Glandular clear cell degeneration and/or signet-ring cell-like change were worrisome and sometimes difficult to be distinguished from residual neoplastic glands. However, these degenerative glands were usually embedded in a nondesmoplastic stroma and showed anisonucleosis of glandular epithelia. Mirnics of residual adenocarcinoma, namely clear cell degeneration and signet-ring cell-like change should be judiciously assessed to avoid unnecessary surgery. C1 Saitama Med Sch, Dept Pathol, Saitama, Japan. Saitama Med Sch, Dept Gastroenterol & Hepatol, Saitama, Japan. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mitsuhashi, T (reprint author), Tohoku Univ, Grad Sch Med Sci, Dept Pathol, Div Histopathol,Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan. EM mitsut@mail.tains.tohoku.ac.jp RI Mitsuhashi, Tomoko/A-6996-2012 NR 23 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 2006 VL 30 IS 5 BP 650 EP 656 DI 10.1097/01.pas.0000202162.88362.32 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 038WZ UT WOS:000237261500013 PM 16699321 ER PT J AU Wright, T Myrick, H Henderson, S Peters, H Malcolm, R AF Wright, T Myrick, H Henderson, S Peters, H Malcolm, R TI Risk factors for delirium tremens: A retrospective chart review SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Review ID ALCOHOL-WITHDRAWAL DELIRIUM; PRACTICE GUIDELINE; USE DISORDERS; DETOXIFICATION; MANAGEMENT; DIAGNOSIS; DRINKING; DRUGS AB A retrospective chart review was performed within an inpatient VA hospital setting in an attempt to identify risk factors for delirium tremens (DTs). Cases of delirium tremens were compared to cases where patients' alcohol withdrawal during hospitalization did not progress to DTs. Significant differences were found in regard to prior histories of DTs and laboratory values at admission. The amount and duration of benzodiazepine use during hospitalization, antipsychotic use during hospitalization, and length of hospitalization were also statistically different between the groups. While not reaching statistical significance, there were differences in reason for admission and relapse rate upon follow-up between the groups. C1 Med Univ S Carolina, Inst Psychiat 4N, Alcohol Res Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affiars Med Ctr, Res & Dev Serv, Charleston, SC USA. RP Wright, T (reprint author), Med Univ S Carolina, Inst Psychiat 4N, Alcohol Res Ctr, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM wright@musc.edu FU NIAAA NIH HHS [K23 AA00314, K24 AA013314, P50 AA10761] NR 36 TC 16 Z9 17 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAY-JUN PY 2006 VL 15 IS 3 BP 213 EP 219 DI 10.1080/10550490600625798 PG 7 WC Substance Abuse SC Substance Abuse GA 038LI UT WOS:000237221100003 PM 16923667 ER PT J AU Eger, EI Liao, M Laster, MJ Won, A Popovich, J Raines, DE Solt, K Dutton, RC Cobos, FV Sonner, JM AF Eger, EI Liao, M Laster, MJ Won, A Popovich, J Raines, DE Solt, K Dutton, RC Cobos, FV Sonner, JM TI Contrasting roles of the N-methyl-D-aspartate receptor in the production of immobilization by conventional and aromatic anesthetics SO ANESTHESIA AND ANALGESIA LA English DT Article ID GATED ION CHANNELS; MINIMUM ALVEOLAR CONCENTRATION; GLYCINE RECEPTORS; SPINAL-CORD; VOLATILE ANESTHETICS; NITROUS-OXIDE; DORSAL-HORN; NMDA; RAT; NEURONS AB We hypothesized that N-methyl-D-aspartate (NMDA) receptors mediate some or all of the capacity of inhaled anesthetics to prevent movement in the face of noxious stimulation, and that this capacity to prevent movement correlates directly with the in vitro capacity of such anesthetics to block the NMDA receptor. To test this hypothesis, we measured the effect of TV infusion of the NMDA blockers dizocilpine (MK-801) and (R)-4-(3-phosphonopropyl) piperazine-2-carboxylic acid (CPP) to decrease the MAC (the minimum alveolar concentration of anesthetic that prevents movement in 50% of subjects given a noxious stimulation) of 8 conventional anesthetics (cyclopropane, desflurane, enflurane, halothane, isoflurane, nitrous oxide, sevoflurane, and xenon) and 8 aromatic compounds (benzene, fluorobenzene, o-difluorobenzene, p-difluorobenzene, 1,2,4-trifluorobenzene, 1,3,5-trifluorobenzene, pentafluoro-benzene, and hexafluorobenzene) and, for comparison, etomidate. We postulated that MK-801 or CPP infusions would decrease MAC in inverse proportion to the in vitro capacity of these anesthetics to block the NMDA receptor. This notion proved correct for the aromatic inhaled anesthetics, but not for the conventional anesthetics. At the greatest infusion of MK-801 (32 mu g center dot kg(-1)center dot min(-1)) the MACs of conventional anesthetics decreased by 59.4 +/- 3.4% (mean +/- SD) and at 8 mu g center dot kg(-1)center dot min(-1) by 45.5 +/- 4.2%, a decrease not significantly different from a 51.4 +/- 19.0% decrease produced in the EC50 for etomidate, an anesthetic that acts solely by enhancing gamma-amino butyric acid (GABA) receptors. We conclude that some aromatic anesthetics may produce immobility in the face of noxious stimulation by blocking the action of glutamate on NMDA receptors but that conventional inhaled anesthetics do not. C1 Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Univ Nebraska, Dept Anesthesiol, Omaha, NE 68182 USA. RP Eger, EI (reprint author), Univ Calif San Francisco, Dept Anesthesia, S-455, San Francisco, CA 94143 USA. EM egere@anesthesia.ucsf.edu OI Solt, Ken/0000-0001-5328-2062 NR 37 TC 31 Z9 31 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2006 VL 102 IS 5 BP 1397 EP 1406 DI 10.1213/01.ANE.0000219019.91281.51 PG 10 WC Anesthesiology SC Anesthesiology GA 037RX UT WOS:000237165800019 PM 16632817 ER PT J AU Solt, K Ii, EIE Raines, DE AF Solt, K Ii, EIE Raines, DE TI Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics SO ANESTHESIA AND ANALGESIA LA English DT Article ID VOLATILE ANESTHETICS; IN-VIVO; XENON; INHIBITION; ACTIVATION; HALOTHANE; RATS AB N-Methyl-D-aspartate (NMDA) receptors have a presumed role in excitatory synaptic transmission and nociceptive pathways. Although previous studies have found that inhaled anesthetics inhibit NMDA receptor-mediated currents at clinically relevant concentrations, the use of different experimental protocols, receptor subtypes, and/or tissue sources confounds quantitative comparisons of the NMDA receptor inhibitory potencies of inhaled anesthetics. In the present study, we sought to fill this void by defining, using the two-electrode voltage-clamp technique, the extent to which diverse clinical and aromatic inhaled anesthetics inhibit the NR1/NR2B subtype of the human NMDA receptor expressed in Xenopus laevis oocytes. At 1 minimum alveolar anesthetic concentration (MAC), anesthetic compounds reversibly inhibited NMDA receptor currents by 12 +/- 6% to 74 +/- 6%. These results demonstrate that equianesthetic concentrations of inhaled anesthetics can differ considerably in the extent to which they inhibit NMDA receptors. Such differences may be useful for defining the role that this receptor plays in producing the in vivo actions of general anesthetics. C1 Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. RP Solt, K (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Edwards 505, Boston, MA 02114 USA. EM ksolt@partners.org OI Solt, Ken/0000-0001-5328-2062 FU NIGMS NIH HHS [P01-GM47818, R01-GM61927, T32-GM07592] NR 17 TC 54 Z9 54 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2006 VL 102 IS 5 BP 1407 EP 1411 DI 10.1213/01.ane.0000204252.07406.9f PG 5 WC Anesthesiology SC Anesthesiology GA 037RX UT WOS:000237165800020 PM 16632818 ER PT J AU Dutton, RC Laster, MJ Xing, YL Sonner, JM Raines, DE Solt, K Eger, EI AF Dutton, RC Laster, MJ Xing, YL Sonner, JM Raines, DE Solt, K Eger, EI TI Do N-methyl-D-aspartate receptors mediate the capacity of inhaled Anesthetics to suppress the temporal summation that contributes to minimum alveolar concentration? SO ANESTHESIA AND ANALGESIA LA English DT Article ID GLYCINE RECEPTORS; NMDA RECEPTORS; ISOFLURANE; TRANSMISSION; CURRENTS; ACTIVATION; MECHANISMS; HALOTHANE; GABA(A); POTENCY AB Antagonism of N-methyl-D-aspartate (NMDA) receptors markedly decreases the minimum alveolar concentration (MAC) of inhaled anesthetics. To assess the importance of suppression of the temporal summation NMDA receptor component of MAC, we stimulated the tail of rats with trains of electrical pulses of varying interstimulus intervals (ISIs) and determined the inhaled anesthetic concentrations (crossover concentrations) that suppressed movement at different ISIs. The slopes of crossover concentrations versus ISIs provided a measure of temporal summation for each anesthetic. We studied five anesthetics that differ widely in their in vitro capacity to block NMDA receptors. To block NMDA receptor transmission and reveal the NMDA receptor component, the NMDA receptor antagonist, MK801, was separately added during each anesthetic. Halothane, isoflurane, and hexafluorobenzene did not appreciably suppress the NMDA receptor components of temporal summation, which contributed to 21% to 29% of MAC (P < 0.05 for each). Xenon and o-difluorobenzene suppressed these components to 8% to 0%, respectively, of MAC (neither significant), consistent with their greater NMDA receptor blocking action in vitro. NMDA receptor blockade may contribute to the MAC produced by inhaled anesthetics that potently inhibit NMDA receptors in vitro but not those that have a limited in vitro effect. C1 Univ Calif San Francisco, Dept Anethesia & Perioperat Care, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Dutton, RC (reprint author), Univ Calif San Francisco, Dept Anesthesia, S-455, San Francisco, CA 94143 USA. EM dutton20@comcast.net OI Solt, Ken/0000-0001-5328-2062 FU PHS HHS [1POIGM47818] NR 25 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2006 VL 102 IS 5 BP 1412 EP 1418 DI 10.1213/01.ane.0000205759.67123.76 PG 7 WC Anesthesiology SC Anesthesiology GA 037RX UT WOS:000237165800021 PM 16632819 ER PT J AU Lecamwasam, H Mayfield, J Rosow, L Chang, YC Carter, C Rosow, C AF Lecamwasam, H Mayfield, J Rosow, L Chang, YC Carter, C Rosow, C TI Stimulation of the posterior cord predicts successful infraclavicular block SO ANESTHESIA AND ANALGESIA LA English DT Article ID BRACHIAL-PLEXUS BLOCK; MOTOR-RESPONSES; NEUROSTIMULATION; ANESTHESIA; INJECTION AB Infraclavicular (IC) block is often performed by localizing one cord within the brachial plexus sheath and placing all the local anesthetic solution at that location. We hypothesized that posterior cord stimulation would be associated with a greater likelihood of IC block success. We enrolled 369 patients scheduled for surgery to the lower arm or hand in a prospective, nonrandomized observational trial. All underwent IC blocks using a standard technique, and the cord stimulated immediately before drug injection was recorded. Motor and sensory functioning were evaluated 15 min after injection. Compared with stimulation of either the lateral or medial cord, stimulation of the posterior cord was associated with rapid onset of motor block in significantly more nerves, as well as a decreased likelihood of block failure (motor and sensory block inadequate to perform surgery). Failure rates were 5.8% for posterior cord, 28.3% for lateral (P < 0.05), and 15.4% for medial (P < 0.05). The differences were highly significant when adjusted for multiple possible confounders, such as gender, body mass index, location of the incision, and level of training of the individual performing the block (P < 0.001, lateral versus posterior; P = 0.003, medial versus posterior). A low failure rate was also predicted by stimulation of more than one cord simultaneously (P < 0.05). We conclude that injection after locating the posterior cord or multiple cords predicts successful IC block. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Dept Med, Boston, MA 02114 USA. Med Coll Georgia, Dept Anesthesiol & Perioperat Med, Augusta, GA 30912 USA. RP Rosow, C (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM crosow@partners.org NR 14 TC 26 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2006 VL 102 IS 5 BP 1564 EP 1568 DI 10.1213/07.ane.0000205750.58424.b2 PG 5 WC Anesthesiology SC Anesthesiology GA 037RX UT WOS:000237165800045 PM 16632843 ER PT J AU Xie, ZC Dong, YL Maeda, U Culley, DJ Crosby, G Tanzi, RE AF Xie, ZC Dong, YL Maeda, U Culley, DJ Crosby, G Tanzi, RE TI The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels SO ANESTHESIOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; VOLATILE ANESTHETICS; NEURONAL APOPTOSIS; PRECURSOR PROTEIN; IN-VITRO; CASPASES; CLEAVAGE; EXCITOTOXICITY; PRESENILIN-1 AB Background The common inhalation anesthetic isoflurane has previously been reported to enhance the aggregation and cytotoxicity of the Alzheimer disease-associated amyloid 13 protein (A beta), the principal peptide component of cerebral beta-amyloid deposits. Methods: H4 human neuroglioma cells stably transfected to express human full-length wild-type amyloid precursor protein (APP) were exposed to 2% isoflurane for 6 h. The cells and conditioned media were harvested at the end of the treatment. Caspase-3 activation, processing of APP, cell viability, and A beta levels were measured with quantitative Western blotting, cell viability kit, and enzyme-linked inummosorbent assay sandwich. The control condition consisted of 5% CO2 plus 21% O-2 and balanced nitrogen, which did not affect caspase-3 activation, cell viability, APP processing, or A beta generation. Results: Two percent isoflurane caused apoptosis, altered processing of APP, and increased production of A beta in H4 human neuroglioma cell lines. Isoflurane-induced apoptosis was independent of changes in A beta and APP holoprotein levels. However, isoflurane-induced apoptosis was potentiated by increased levels of APP C-terminal fragments. Conclusion: A clinically relevant concentration of isoflurane induces apoptosis, alters APP processing, and increases A beta production in a human neuroglioma cell line. Because altered processing of APP leading to accumulation of A beta is a key event in the pathogenesis of Alzheimer disease, these findings may haveimplications for use of this anesthetic agent in individuals with excessive levels of cerebral A beta and elderly patients at increased risk for postoperative cognitive dysfunction. C1 Massachusetts Gen Hosp, Dept Neurol, MassGene Inst Neurodegenerat Dis, Dept Anesthesia & Crit Care,Genet & Aging Res Uni, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol,MassGen Inst N, Genet & Aging Res Unit,Dept Anestehsiol & Crit Ca, 114 16th St C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU NIA NIH HHS [K12 AG 000294-17, AG 014713-07, P60 AG008812-15, R01 AG20253]; NIMH NIH HHS [MH 60009-03]; NINDS NIH HHS [K08 NS048140-01] NR 34 TC 157 Z9 192 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2006 VL 104 IS 5 BP 988 EP 994 DI 10.1097/00000542-200605000-00015 PG 7 WC Anesthesiology SC Anesthesiology GA 040JS UT WOS:000237375400014 PM 16645451 ER PT J AU Mavropoulos, A Sayinsu, K Allaf, F Kiliaridis, S Papadopoulos, MA Keles, AO AF Mavropoulos, A Sayinsu, K Allaf, F Kiliaridis, S Papadopoulos, MA Keles, AO TI Noncompliance unilateral maxillary molar distalization: A three-dimensional tooth movement analysis SO ANGLE ORTHODONTIST LA English DT Article DE Class II malocclusion; noncompliance treatment; unilateral distalization; three-dimensional cast superimposition; Keles slider ID DENTAL CASTS; PALATAL RUGAE; PENDULUM APPLIANCE; SKELETAL CHANGES; HEADGEAR; SYSTEM; ORTHODONTICS; STABILITY; LANDMARKS; COILS AB The aim of this prospective study was the three-dimensional (3-D) analysis of tooth movements after unilateral upper molar distalization by means of a noncompliance intraoral appliance, the Keles slider. This appliance exerts a distalizing force of 150 g at approximately the level of the center of resistance of the upper first molar. Twelve patients (six girls and six boys with a mean age of 13.1 years) with a unilateral Class II molar relationship participated in the study. Dental casts were taken immediately before placement and after removal of the appliance. The casts were digitized using a 3-D surface laser scanner and superimposed on a predefined area of the palate. The average unilateral upper first molar distal movement was 3.1 mm (range: 2.4 to 5.3 mm). Anchorage loss was expressed by a 2.1 mm (range: 0.8 to 3.8 mm) proclination of the central incisors and a 6.1 degrees mesial inclination of the ipsilateral first premolar (range: 1.7 degrees to 12.3 degrees). There was approximately 1 mm of midline deviation toward the contralateral side and a 1.6 mm (range: 0.8 to 2.3 mm) buccal displacement of the contralateral first premolar. A substantial variation was observed among patients. Noncompliance unilateral upper molar distalization was an efficient treatment approach. There was, however, a substantial anchorage loss. Case selection is strongly recommended because significant anterior crowding, ectopic canines, or spacing can lead to significant anchorage loss. C1 Univ Geneva, Dept Orthodont, CH-1205 Geneva, Switzerland. Yeditepe Univ, Dept Orthodont, Istanbul, Turkey. Aristotle Univ Thessaloniki, Sch Dent, Dept Orthodont, Thessaloniki, Greece. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Mavropoulos, A (reprint author), Univ Geneva, Dept Orthodont, Barthelemy Menn 19 Geneva, CH-1205 Geneva, Switzerland. EM anestis.mavropoulos@medecine.unige.ch RI Papadopoulos, Moschos/C-1625-2009 NR 35 TC 7 Z9 7 U1 1 U2 1 PU E H ANGLE EDUCATION RESEARCH FOUNDATION, INC PI NEWTON N PA 1615 BEACON ST, NEWTON N, MA 02468-1507 USA SN 0003-3219 J9 ANGLE ORTHOD JI Angle Orthod. PD MAY PY 2006 VL 76 IS 3 BP 382 EP 387 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 039XS UT WOS:000237342300005 PM 16637715 ER PT J AU Williams, EC Kivlaban, DR Saitz, R Merrill, JO Achtmeyer, CE McCormick, KA Bradley, KA AF Williams, EC Kivlaban, DR Saitz, R Merrill, JO Achtmeyer, CE McCormick, KA Bradley, KA TI Readiness to change in primary care patients who screened positive for alcohol misuse SO ANNALS OF FAMILY MEDICINE LA English DT Article DE alcohol drinking; alcoholism/diagnosis; patient acceptance of health care ID BEHAVIORAL-COUNSELING INTERVENTIONS; PROBLEM DRINKING; GENERAL-PRACTITIONERS; CONSUMPTION QUESTIONS; INTEGRATIVE MODEL; AUDIT; CAGE; DRINKERS; VALIDITY; HEALTH AB PURPOSE Readiness to change drinking may influence the content or effectiveness of brief alcohol counseling. This study was designed to assess readiness to change and its relationship to alcohol misuse severity among primary care patients whose screening questionnaire was positive for alcohol misuse. METHODS This study was a cross-sectional analysis of data collected from 2 consecutive mailed questionnaires. Male outpatients at 7 Veterans Affairs (VA) general medicine clinics were eligible if they returned both questionnaires, screened positive for alcohol misuse (augmented CAGE Questionnaire >= 1 point), responded to 3 readiness-to-change questions, and completed the Alcohol Use Disorders Identification Test (AUDIT). A validated algorithm based on 3 standardized questions categorized participants into 3 readiness groups (precontemplation, contemplation, action). Measures of alcohol misuse severity included AUDIT, CAGE, and the 3 consumption questions from the AUDIT (AUDIT-C). Analyses were descriptive; linear-by-linear associations between alcohol misuse severity and readiness were tested with chi(2) statistics. RESULTS Response rates to the first and second surveys were 59% and 55%, respectively. Of the 6,419 eligible outpatients who screened positive for alcohol misuse, 4,797 (75%) reported any readiness to change (contemplation 24%, action 51%). Among patients with AUDIT scores > 8, more than 90% indicated that they drank more than they should and/or had contemplated drinking less. Greater readiness was significantly associated with greater alcohol misuse severity (P <.001 for all measures). CONCLUSIONS Most primary care patients who screen positive for alcohol misuse indicate some readiness to change. Contrary to stereotypes of denial, those with greater alcohol misuse severity are more likely to report readiness to change. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98101 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA. Boston Univ, Sch Med, Dept Med, Clin Addict Res & Educ Unit, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emwilli@u.washington.edu OI /0000-0002-2535-1427 FU NIAAA NIH HHS [K23AA00313] NR 45 TC 31 Z9 31 U1 0 U2 2 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD MAY-JUN PY 2006 VL 4 IS 3 BP 213 EP 220 DI 10.1370/afm.542 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 053VT UT WOS:000238334700005 PM 16735522 ER PT J AU Jahnke, K Korfel, A O'Neill, BP Blay, JY Abrey, LE Martus, P Poortmans, PMP Shenkier, TN Batchelor, TT NeLtwelt, EA Raizer, JJ Schiff, D Pels, H Herrlinger, U Stein, H Thiel, E AF Jahnke, K Korfel, A O'Neill, BP Blay, JY Abrey, LE Martus, P Poortmans, PMP Shenkier, TN Batchelor, TT NeLtwelt, EA Raizer, JJ Schiff, D Pels, H Herrlinger, U Stein, H Thiel, E TI International study on low-grade primary central nervous system lymphoma SO ANNALS OF NEUROLOGY LA English DT Article ID PRIMARY-CNS-LYMPHOMA; NON-HODGKINS-LYMPHOMA; HIGH-DOSE METHOTREXATE; IMMUNOCOMPETENT PATIENTS; RADIOTHERAPY; CHEMOTHERAPY; MULTICENTER; SURVIVAL; MRI AB Objective: The aim of this study was to characterize the clinical presentation, course, and outcome of low-grade primary central nervous system lymphoma. Methods: Cases were assessed in a retrospective series collected from 18 cancer centers in 5 countries. Results: Forty patients (18 men, 22 women; median age, 60 years [range, 19-78]) were identified. Involvement of a cerebral hemisphere or deeper brain structures was seen in 37 patients, only leptomeningeal involvement in 2 patients, and spinal cord disease in 1 patient. Chemotherapy/radiotherapy was conducted in 15 patients, radiotherapy alone in 12, chemotherapy alone in 10, and tumor resection alone in 2, whereas 1 patient received no treatment. The median progression-free, disease-specific, and overall survival were 61.5 (range, 0-204), 130 (range, 1-204), mid 79 (range, 1-204) months, respectively. Only age 60 years or older was associated with shorter progression-free (p = 0.009), disease-specific (p = 0.015), and overall survival (p = 0.001) in multivariate analysis. Interpretation: Low-grade primary central nervous system lymphoma differs from the high-grade subtype in its pathological, clinical, and radiological features. It has a better long-term outcome than primary central nervous system lymphoma in general with age 60 years or older adversely affecting Survival. C1 Univ Med Berlin, Charite, Dept Hematol Oncol & Transfus Med, D-12200 Berlin, Germany. Oregon Hlth Sci Univ, Blood Brain Barrier & Neurooncol Program, Portland, OR 97201 USA. Mayo Clin, Ctr Canc, Neurooncol Program, Rochester, MN USA. Ctr Leon Berard, Unite Cytokines & Canc, F-69373 Lyon, France. Hop Edouard Herriot, Lyon, France. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Univ Med Berlin, Charite, Dept Clin Epidemiol & Biostat, Berlin, Germany. Dr Bernard Verbeeten Inst, Tilburg, Netherlands. British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Northwestern Univ, Davee Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Virginia, Div Neurooncol, Charlottesville, VA USA. Univ Bochum, Dept Neurol, Knappschaftskrankenhaus Bochum Langendreer, Bochum, Germany. Univ Tubingen, Ctr Neurol, Dept Gen Neurol, Tubingen, Germany. Univ Med Berlin, Charite, Dept Pathol, Berlin, Germany. RP Jahnke, K (reprint author), Univ Med Berlin, Charite, Dept Hematol Oncol & Transfus Med, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany. EM kristoph.jahnke@clarite.de RI Poortmans, P.M.P./L-4581-2015; Blay, Jean-Yves/N-3966-2016; OI Blay, Jean-Yves/0000-0001-7190-120X; O'NEILL, BRIAN PATRICK/0000-0001-7456-6152 NR 33 TC 29 Z9 30 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 2006 VL 59 IS 5 BP 755 EP 762 DI 10.1002/ana.20804 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 037RM UT WOS:000237164600009 PM 16586496 ER PT J AU Das, P Ng, AK Earle, CC Mauch, PM Kuntz, KM AF Das, P Ng, AK Earle, CC Mauch, PM Kuntz, KM TI Computed tomography screening for lung cancer in Hodgkin's lymphoma survivors: decision analysis and cost-effectiveness analysis SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 19-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol & Oncol DE cost-effectiveness; decision analysis; Hodgkin's lymphoma; lung cancer; second malignancies ID DOSE SPIRAL CT; LONG-TERM RISK; 2ND MALIGNANCY; ACTION PROJECT; NATURAL-HISTORY; CLINICAL-COURSE; EARLY-STAGE; BASE-LINE; DISEASE; RADIOTHERAPY AB Background: Hodgkin's lymphoma patients have an elevated risk of developing lung cancer and may be targeted for lung cancer screening. We used a decision-analytic model to estimate the potential clinical benefits and cost-effectiveness of computed tomography (CT) screening for lung cancer in Hodgkin's lymphoma survivors. Materials and methods: We developed a Markov decision-analytic model to compare annual low-dose CT screening versus no screening in a hypothetical cohort of patients diagnosed with stage IA-IIB Hodgkin's lymphoma at age 25, with screening starting 5 years after initial diagnosis. We derived model parameters from published studies and the Surveillance, Epidemiology and End Results (SEER) Program, and assumed that stage-shift produces a survival benefit. Results: Annual CT screening increased survival by 0.64 years for smokers and 0.16 years for non-smokers. The corresponding benefits in quality-adjusted survival were 0.58 quality-adjusted life-years (QALYs) for smokers and 0.14 QALYs for non-smokers. The incremental cost-effectiveness ratios for annual CT screening compared with no screening were $34 100/QALY for smokers and $125 400/QALY for non-smokers. Conclusions: Our analysis suggests that if early promising results for lung cancer screening hold, CT screening for lung cancer may increase survival and quality-adjusted survival among Hodgkin's lymphoma survivors, with a benefit and incremental cost-effectiveness ratio for smokers comparable to that of other recommended cancer screening strategies. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Das, P (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 97, Houston, TX 77030 USA. EM PrajDas@mdanderson.org NR 60 TC 20 Z9 20 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 2006 VL 17 IS 5 BP 785 EP 793 DI 10.1093/annonc/mdl023 PG 9 WC Oncology SC Oncology GA 037UY UT WOS:000237174200009 PM 16500905 ER PT J AU Gray, SL Odegard, PS Sales, AE Young, HM Sullivan, JH Hedrick, SC AF Gray, SL Odegard, PS Sales, AE Young, HM Sullivan, JH Hedrick, SC TI Quality of medication records and use of pharmacy resources in community residential care facilities SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE cohort study; community residential care; medication management ID DRUG; MANAGEMENT; BOARD AB BACKGROUND: In community residential care (CRC) facilities, medication administration is often performed by unlicensed personnel with minimal knowledge in medication use. Medication management is one of the top 3 quality-of-care issues facing these facilities. OBJECTIVE: To examine the type of medication assistance residents received, determine the proportion of facilities that used pharmacy resources, and examine the quality of facility medication records in CRC facilities (eg, adult family homes, adult residential care, assisted living facilities). METHODS: Baseline in-person interviews were conducted with 349 residents and 299 facility providers in the Puget Sound region of Washington. Information was also obtained from facility medication records at enrollment and state databases. A pharmacist determined quality of the records using a standardized form. RESULTS: The average resident was a 78-year-old white female taking 7 drugs. Medication records that were computer generated were significantly less likely to have misspelled names of drugs and errors in or absence of dose, directions for use, and route of administration. Overall, 26.3% of facilities reported that a consultant pharmacist reviewed residents' medication lists, 52.0% reported the use of preprinted lists, and 75.6% received prepackaged medications from the pharmacy. Adult family homes, the smallest facility type, were the least likely to use pharmacy-related services. CONCLUSIONS: The quality of handwritten medication records was a concern in CRC facilities. These facilities may benefit from services offered by pharmacies that may enhance medication management, many of which were underutilized. C1 Univ Washington, Sch Pharm, Geriatr Pharm Program, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Sch Nursing, Ashland, OR USA. RP Gray, SL (reprint author), Univ Washington, Sch Pharm, Geriatr Pharm Program, Box 357630, Seattle, WA 98195 USA. EM slgray@u.washington.edu RI Sales, Anne/D-9678-2012; OI Sales, Anne/0000-0001-9360-3334 NR 22 TC 3 Z9 3 U1 2 U2 6 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 2006 VL 40 IS 5 BP 894 EP 899 DI 10.1345/aph.1G585 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 043KW UT WOS:000237600900011 PM 16638918 ER PT J AU Hutter, MM Randall, S Khuri, SF Henderson, WG Abbott, WM Warshaw, AL AF Hutter, MM Randall, S Khuri, SF Henderson, WG Abbott, WM Warshaw, AL TI Laparoscopic versus open gastric bypass for morbid obesity - A multicenter, prospective, risk-adjusted analysis from the national surgical quality improvement program SO ANNALS OF SURGERY LA English DT Article ID ROUX-EN-Y; SURGERY; OUTCOMES; CARE AB Objective: To compare laparoscopic versus open gastric bypass procedures with respect to 30-day morbidity and mortality rates, using multi-institutional, prospective, risk-adjusted data. Summary Background Data: Laparoscopic Roux-en-Y gastric bypass for weight loss is being performed with increasing frequency, partly driven by consumer demand. However, there are no multi-institutional, risk-adjusted, prospective studies comparing laparoscopic and open gastric bypass outcomes. Methods: A multi-institutional, prospective, risk-adjusted cohort study of patients undergoing laparoscopic and open gastric bypass procedures was performed from hospitals (n = 15) involved in the Private Sector Study of the National Surgical Quality Improvement Program (NSQIP). Data points have been extensively validated, are based on standardized definitions, and were collected by nurse reviewers who are audited for accuracy. Results: From 2000 to 2003, data from 1356 gastric bypass procedures was collected. The 30-day mortality rate was zero in the laparoscopic group (n = 401), and 0.6% in the open group (n = 955) (P = not significant). The 30-day complication rate was significantly lower in the laparoscopic group as compared with the open group: 7% versus 14.5% (P < 0.0001). Multivariate logistic regression analysis was performed to control for potential confounding variables and showed that patients undergoing an open procedure were more likely to develop a complication, as compared with patients undergoing an laparoscopic procedure (odds ratio = 2.08; 95% confidence interval, 1.33-3.25). Propensity score modeling revealed similar results. A prediction model was derived, and variables that significantly predict higher complication rates after gastric bypass included an open procedure, a high ASA class (III, IV, V), functionally dependent patient, and hypertension as a co-morbid illness. Conclusions: Multicenter, prospective, risk-adjusted data show that laparoscopic gastric bypass is safer than open gastric bypass, with respect to 30-day complication rate. C1 Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Massachusetts Gen Hosp, Ernest Amory Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, 15 Parkman St,Wang ACC 335, Boston, MA 02114 USA. EM mhutter@partners.org NR 20 TC 79 Z9 82 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2006 VL 243 IS 5 BP 657 EP 666 DI 10.1097/01.sla.0000216784.05951.0b PG 10 WC Surgery SC Surgery GA 036MQ UT WOS:000237075600012 PM 16633001 ER PT J AU Butler, J Geisberg, C Howser, R Portner, PM Rogers, JG Deng, MC Pierson, RN AF Butler, J Geisberg, C Howser, R Portner, PM Rogers, JG Deng, MC Pierson, RN TI Relationship between renal function and left ventricular assist device use SO ANNALS OF THORACIC SURGERY LA English DT Article ID AMERICAN-HEART-ASSOCIATION; CARDIAC TRANSPLANTATION; INTERNATIONAL-SOCIETY; HEALTH-PROFESSIONALS; LUNG-TRANSPLANTATION; CLINICAL-CARDIOLOGY; PATIENT SELECTION; FAILURE; SUPPORT; BRIDGE AB Background. Poor renal function may affect outcomes after left ventricular assist device (LVAD) placement. Conversely, LVADs may optimize circulation and improve renal function. Methods. To assess the relationship between renal function and LVAD use, changes in creatinine clearances (CrCl, in mL/min) were assessed retrospectively in 220 patients who underwent LVAD placement. These patients were also divided into four groups based on CrCl quartiles (< 47, 48-68, 69-95, and > 95) and compared for outcomes post-LVAD placement. Results. Eighty-four patients died on LVAD support. Survival on LVAD was worse for patients with the worst baseline CrCl (42%, 52%, 63%, and 79% for 6 month and 26%, 34%, 47%, and 66% for 12 month survival for quartiles 1-4; both p < 0.01 for trend). Adjusting for other covariates, patients in the lowest CrCl quartile were at a higher risk of dying postimplant (odds ratio 1.95, 95% confidence interval 1.14-3.63). Paired sample analysis showed the following changes in CrCl: preoperative to week 1, 77.0 +/- 46.6 to 92.1 +/- 51.1 (p < 0.01; n = 202), week 1 to 2, 89.4 +/- 49.2 to 95.2 +/- 52.4 (p = 0.01, n = 171), week 2 to 3, 107.5 +/- 58.1 to 113.7 +/- 66.1 (p = 0.16, n = 74), and week 3 to 4, 111.1 +/- 56.6 to 110.5 +/- 56.8 (p = 0.87, n = 60). For the 60 patients with baseline CrCl less than 50, CrCl increased from 36.7 +/- 9.2 to 60.1 +/- 35.5 (p < 0.01; n = 55 pairs) from preimplant to week 1. In 37 of these patients (62%) on intraaortic balloon pump support preimplant, CrCl increased from 38.4 +/- 8.2 to 67.9 +/- 40.3 mL/minute (p < 0.01) during week 1 postimplant. Recovery of renal function to CrCl greater than 50 was associated with a trend towards better 30-day survival (84% vs 66%, p = 0.09). Conclusions. Baseline poor renal function is associated with worse outcomes after LVAD implantation. However, renal function improves substantially and rapidly in post-LVAD survivors and is associated with improved outcomes. These data underscore the importance of careful patient selection for LVAD therapy. C1 Vanderbilt Univ, Med Ctr, Div Cardiol, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. WorldHeart Inc, Oakland, CA USA. Stanford Univ, Dept Cardiothorac Surg, Stanford, CA 94305 USA. Duke Univ, Div Cardiol, Durham, NC USA. Univ Maryland, Dept Cardiothorac Surg, Baltimore, MD 21201 USA. Baltimore Vet Adm Med Ctr, Baltimore, MD USA. RP Butler, J (reprint author), Vanderbilt Univ, Med Ctr, Div Cardiol, 383-PRB, Nashville, TN 37232 USA. EM javed.butler@vanderbilt.edu NR 23 TC 51 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2006 VL 81 IS 5 BP 1745 EP 1751 DI 10.1016/j.athoracsur.2005.11.061 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 035LE UT WOS:000237001700029 PM 16631666 ER PT J AU O'Riordan, K Sharlin, DS Gross, J Chang, S Errabelli, D Akilov, OE Kosaka, S Nau, GJ Hasan, T AF O'Riordan, K Sharlin, DS Gross, J Chang, S Errabelli, D Akilov, OE Kosaka, S Nau, GJ Hasan, T TI Photoinactivation of mycobacteria in vitro and in a new murine model of localized Mycobacterium bovis BCG-induced granulomatous infection SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TUBERCULOSIS VACCINE; PHOTODYNAMIC THERAPY; NATURAL-RESISTANCE; MICE; MACROPHAGES; APOPTOSIS; VIRULENT; NECROSIS; VIVO AB Treatment of tuberculosis is currently hindered by prolonged antibiotic regimens and the emergence of significant drug resistance. Alternatives and adjuncts to standard antimycobacterial agents are needed. We propose that a direct attack utilizing photosensitizers and light-based treatments may be effective in curtailing Mycobacterium tuberculosis in discrete anatomical sites in the most infectious phase of pulmonary tuberculosis. To demonstrate experimental proof of principle, we have applied established photodynamic therapy (PDT) technology to in vitro cultures and an in vivo mouse model using Mycobacterium bovis BCG. We report here in vitro and in vivo PDT efficacy studies and the use of a three-dimensional collagen gel as a delivery vehicle for BCG, subcutaneously inserted, to induce specifically localized granuloma-like lesions in mice. When a benzoporphyrin derivative was utilized as the photosensitive agent, exposure to light killed extracellular and intracellular BCG in significant numbers. Collagen scaffolds containing BCG inserted in situ in BALB/c mice for 3 months mimicked granulomatous lesions and demonstrated a marked cellular infiltration upon histological examination, with evidence of caseating necrosis and fibrous capsule formation. When 105 BCG were present in the in vivo-induced granulomas, a significant reduction in viable mycobacterial cells was demonstrated in PDT-treated granulomas compared to those of controls. We conclude that PDT has potential in the treatment of localized mycobacterial infections, such as pulmonary granulomas and cavities. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 314,40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org OI Nau, Gerard/0000-0001-7921-8317 FU NCI NIH HHS [R01 CA156177] NR 31 TC 22 Z9 24 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2006 VL 50 IS 5 BP 1828 EP 1834 DI 10.1128/AAC.50.5.1828-1834.2006 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 040FV UT WOS:000237365300031 PM 16641456 ER PT J AU Molitoris, D Vaeisanen, ML Bolanos, M Finegold, SM AF Molitoris, D Vaeisanen, ML Bolanos, M Finegold, SM TI In vitro activities of DX-619 and four comparator agents against 376 anaerobic bacterial isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DES-FLUORO(6) QUINOLONE; GARENOXACIN; DES-F(6)-QUINOLONE AB The activity of DX-619 was evaluated against 376 anaerobic isolates using the reference CLSI agar dilution method. Overall, 90% of the strains were susceptible to DX-619 at <= 1 mu g/ml. It was more active than the other four compounds tested except for meropenem, which showed virtually identical overall activity. C1 VA Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. RP Finegold, SM (reprint author), Greater Los Angeles VAMC, 11301 Wilshire Blvd,Bldg 304,Rm E3-237, Los Angeles, CA 90073 USA. EM sidfinegol@aol.com NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2006 VL 50 IS 5 BP 1887 EP 1889 DI 10.1128/AAC.50.5.1887-1889.2006 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 040FV UT WOS:000237365300045 PM 16641470 ER PT J AU Morasco, BJ Gfeller, JD Chibnall, JT AF Morasco, Benjamin J. Gfeller, Jeffrey D. Chibnall, John T. TI The relationship between measures of psychopathology, intelligence, and memory among adults seen for psychoeducational assessment SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE cognitive functioning; depression; MMPI-2; WMS-III; WAIS-III; assessment ID TEST-PERFORMANCE; TEST-SCORES; DEPRESSION; METAANALYSIS; ATTENTION; ANXIETY; TESTS AB This study assessed the relationship between symptoms of psychopathology and cognitive functioning in clients completing comprehensive psychoeducational assessments at a university-based outpatient mental health clinic. Seventy clients (36 women, 34 men, mean age = 28.8) completed the Wechsler Memory Scale - Third Edition (WMS-III), Wechsler Adult Intelligence Scale - Third Edition (WAIS-III), and Minnesota Multiphasic Personality Inventory - Second Edition (MMPI-2). Partial correlations between the MMPI-2 clinical scales, WMS-III Index scores, WAIS-III Index scores, and WAIS-III IQ scores were not significant. Memory and Intelligence scores for clients with comorbid symptoms of depression and anxiety were comparable to scores for clients without comorbid symptomatology. Psychopathology factors accounted for 22% of the variance in the WAIS-III Full Scale IQ and 6.5% of the variance in the WMS-III General Memory Index. The results suggest that psychopathology as measured by the MMPI-2 may be minimally associated with intelligence and memory test performance in adults seen for psychoeducational assessment. (c) 2006 National Academy of Neuropsychology. Published by Elsevier Ltd. All rights reserved. C1 Portland VA Med Ctr, Dept Behav Hlth & Clin Neurosci, Portland, OR 97239 USA. St Louis Univ, St Louis, MO 63103 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr, Dept Behav Hlth & Clin Neurosci, 3710 SW US Vet Hosp Rd,P3MHDC, Portland, OR 97239 USA. EM benjamin.morasco@med.va.gov NR 17 TC 5 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD MAY PY 2006 VL 21 IS 4 BP 297 EP 301 DI 10.1016/j.acn.2006.03.005 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 067GI UT WOS:000239289500006 PM 16777372 ER PT J AU Ammar, SM Westreich, RW Lawson, W AF Ammar, SM Westreich, RW Lawson, W TI Fan septoplasty for correction of the internally and externally deviated nose SO ARCHIVES OF FACIAL PLASTIC SURGERY LA English DT Article ID SURGERY AB With recent exception, the history of septal surgery has predominantly been characterized by a slow progression toward conservatism. The earliest techniques used transmucosal reductions of deviations. As with all new surgical approaches, long-term complication rates and failures began to emerge. The resulting problems of septal perforation and nasal collapse prompted the development of the submucous resection technique by Freer(1) and Killian, (2) which was less radical in nature, preserving a mucoperichondrial cover. (1,2) This allowed for manipulation of the cartilaginous and bony septal framework without violating the integrity of the septal mucosa. Although this was a significant advance for intranasal surgery, limitations existed and long-term results were unsatisfactory in selected cases. In severely deviated and externally deviated noses, the submucous resection was unable to address the most dorsal component of the quadrangular plate. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. SUNY Downstate Med Ctr, Dept Otolaryngol, Boston, MA USA. Mt Sinai Hosp, New York, NY 10029 USA. RP Westreich, RW (reprint author), 144 Clinton St, Brooklyn, NY 11201 USA. EM doctor@newyorknose.com NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1521-2491 J9 ARCH FACIAL PLAST S JI Arch. Facial Plast. Surg. PD MAY-JUN PY 2006 VL 8 IS 3 BP 213 EP 216 DI 10.1001/archfaci.8.3.213 PG 4 WC Surgery SC Surgery GA 042QK UT WOS:000237543300009 PM 16702535 ER PT J AU Gurvits, TV Metzger, LJ Lasko, NB Cannistraro, PA Tarhan, AS Gilbertson, MW Orr, SP Charbonneau, AM Wedig, MM Pitman, RK AF Gurvits, TV Metzger, LJ Lasko, NB Cannistraro, PA Tarhan, AS Gilbertson, MW Orr, SP Charbonneau, AM Wedig, MM Pitman, RK TI Subtle neurologic compromise as a vulnerability factor for combat-related posttraumatic stress disorder - Results of a twin study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MENTAL-HEALTH; PREFRONTAL CORTEX; SOFT SIGNS; VETERANS; BRAIN; WAR; EXPOSURE; VOLUME; CARE; FEAR AB Context: Previous studies have demonstrated subtle neurologic dysfunction in chronic posttraumatic stress disorder (PTSD) manifest as increased neurologic soft signs (NSSs). The origin of this dysfunction is undetermined. Objective: To resolve competing origins of increased NSSs in PTSD, namely, preexisting vulnerability factor vs acquired PTSD sign. Design: Case-control study of identical twins. Setting: A Veterans Affairs and academic medical center (ambulatory). Participants: A convenience sample of male Vietnam veteran twins with (n = 25) and without (n = 24) PTSD and their combat-unexposed identical (monozygotic) cotwins. Interventions: Neurologic examination for 45 NSSs. Main Outcome Measure: Average scores for 45 NSSs, each scored on an ordinal scale from 0 to 3, masked to diagnosis and combat exposure status. Results: There was a significant between-pair main effect of PTSD diagnosis (as determined in the combat-exposed twin) on average NSS score in the absence of a significant combat exposure main effect or diagnosis x exposure interaction. Combat veterans with PTSD had significantly higher NSS scores than combat veterans without PTSD. The "high- risk," unexposed co-twins of the former also had significantly higher NSS scores than the "low-risk," unexposed co-twins of the latter. This result could not be explained by age, number of potentially traumatic lifetime noncombat events, alcoholism, or the presence of a comorbid affective or anxiety disorder. The average NSS score in unexposed co-twins was not significantly associated with combat severity in combat-exposed twins. Conclusions: These results replicate previous findings of increased NSSs in Vietnam combat veterans with PTSD. Furthermore, results from their combat-unexposed identical co-twins support the conclusion that subtle neurologic dysfunction in PTSD is not acquired along with the trauma or PTSD but rather represents an antecedent familial vulnerability factor for developing chronic PTSD on exposure to a traumatic event. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. Bekhterev Psychoneurol Res Inst, St Petersburg, Russia. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 13th St,Bldg 149,Room 2616, Charlestown, MA 02129 USA. EM roger_pitman@hms.harvard.edu FU NIMH NIH HHS [MH54636] NR 28 TC 45 Z9 47 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 2006 VL 63 IS 5 BP 571 EP 576 DI 10.1001/archpsyc.63.5.571 PG 6 WC Psychiatry SC Psychiatry GA 038JM UT WOS:000237215800011 PM 16651514 ER PT J AU Khachaturian, AS Zandi, PP Lyketsos, CG Hayden, KM Skoog, I Norton, MC Tschanz, JT Mayer, LS Welsh-Bohmer, KA Breitner, JCS AF Khachaturian, AS Zandi, PP Lyketsos, CG Hayden, KM Skoog, I Norton, MC Tschanz, JT Mayer, LS Welsh-Bohmer, KA Breitner, JCS CA Cache Cty Study Grp TI Antihypertensive medication use and incident Alzheimer disease - The Cache County Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID AGED 75 YEARS; BLOOD-PRESSURE; COGNITIVE DECLINE; SYSTOLIC HYPERTENSION; VASCULAR DEMENTIA; POPULATION; POTASSIUM; OLDER; PREVENTION; STROKE AB Background: Recent reports suggest that antihypertensive (AH) medications may reduce the risk of dementing illnesses. Objectives: To examine the relationship of AH medication use with incidence of Alzheimer disease (AD) among the elderly population (aged 65 years and older) of Cache County, Utah, and to examine whether the relationship varies with different classes of AH medications. Methods: After an initial (wave 1) multistage assessment (1995 through 1997) to identify prevalent cases of dementia, we used similar methods 3 years later (wave 2) to identify 104 incident cases of AD among the 3308 survivors. At the baseline assessment, we obtained a detailed drug inventory from the study participants. We carried out discrete time survival analyses to examine the association between the use of AH medications (including angiotensin converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics) at baseline with subsequent risk of AD. Results: Use of any AH medication at baseline was associated with lower incidence of AD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.41-0.98). Examination of medication subclasses showed that use of diuretics (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.94), and specifically potassium-sparing diuretics (adjusted hazard ratio, 0.26; 95% confidence interval, 0.08-0.64), was associated with the greatest reduction in risk of AD. Corresponding analysis with a fully examined subsample controlling for blood pressure measurements did not substantially change our findings. Conclusions: These data suggest that AH medications, and specifically potassium-sparing diuretics, are associated with reduced incidence of AD. Because the latter association is a new finding, it requires confirmation in further study. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. Khachaturian & Associates Inc, Potomac, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat, Baltimore, MD 21205 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Ctr Study Aging & Human Dev, Durham, NC USA. Univ Gothenburg, Inst Clin Neurosci, Gothenburg, Sweden. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Family Human & Consumer Sci, Logan, UT 84322 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Zandi, PP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu RI Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [AG 11380, R01 AG011380]; NIMH NIH HHS [MH 14592] NR 39 TC 186 Z9 191 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 2006 VL 63 IS 5 BP 686 EP 692 DI 10.1001/archneur.63.5.noc60013 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 041XQ UT WOS:000237490600007 PM 16533956 ER PT J AU Javier, JAD Lee, JB Oliveira, HB Chang, JH Azar, DT AF Javier, JAD Lee, JB Oliveira, HB Chang, JH Azar, DT TI Basement membrane and collagen deposition after laser subepithelial keratomileusis and photorefractive keratectomy in the leghorn chick eye SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID IN-SITU KERATOMILEUSIS; CORNEAL LIGHT-SCATTERING; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; ALCOHOL EXPOSURE; DEBRIDEMENT; MYOPIA; ETHANOL; HAZE; PRK AB Objective: To evaluate corneal scar formation and new collagen deposition after laser subepithelial keratomileusis ( LASEK) compared with photorefractive keratectomy (PRK) in the leghorn chick corneal model. Methods: Leghorn chick corneas treated with LASEK surgery ( using 20% ethanol for 30 seconds) or PRK were evaluated by indirect confocal immunofluorescence and transmission electron microscopy at 1, 2, 7, 14, and 28 days after surgery. New collagen deposition was determined by dichlorotriazinylaminofluorescein staining 2 and 4 weeks after surgery. Results: Laminin was detected around the basal layers during the immediate postoperative period and 4 weeks after LASEK surgery, and from day 2 onwards after PRK. Collagen III deposition in the cornea was about 3 times greater with PRK than with LASEK. The thickness of new collagen deposition at 4 weeks was 34 mu m +/- 2.5 mu m in the PRK group, which was significantly greater than that of the LASEK group (11 mu m +/- 1 mu m; P <.001). Conclusions: Reduced subepithelial stromal tissue deposition was observed in LASEK-treated eyes compared with PRK-treated eyes. Postoperative preservation of the epithelial basement membrane and survival of epithelial cells in LASEK and possibly in epithelial laser in situ keratomileusis may contribute to this phenomenon. Clinical Relevance: An advantage of LASEK over PRK is the reduction of postoperative haze. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU NEI NIH HHS [EY 14048, EY 10101] NR 28 TC 22 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2006 VL 124 IS 5 BP 703 EP 709 DI 10.1001/archopht.124.5.703 PG 7 WC Ophthalmology SC Ophthalmology GA 040GP UT WOS:000237367300010 PM 16682593 ER PT J AU Gulati, A Sacchetti, M Bonini, S Dana, R AF Gulati, A Sacchetti, M Bonini, S Dana, R TI Chemokine receptor CCR5 expression in conjunctival epithelium of patients with dry eye syndrome SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SJOGRENS-SYNDROME; KERATOCONJUNCTIVITIS SICCA; IMPRESSION CYTOLOGY; CELL-FUNCTION; CLASSIFICATION; LYMPHOCYTES; DISEASE; GENE AB Objective: To characterize chemokine receptor CCR5 expression on the conjunctival epithelium in dry eye syndromes. Methods: Conjunctival impression cytology samples were obtained from normal subjects ( n=15) and patients with dry eye syndrome (n=45). Cells were harvested from impression cytology samples, and flow cytometry was performed to quantitatively analyze the cell surface expression of chemokine receptor CCR5. Characterization of CCR5-positive cells was done by 2- color flow cytometry using fluorescein-conjugated anti-CCR5 and phycoerythrin-conjugated anti-CD45 antibodies ( where CD45 is a marker for bone marrow derived cells). To study CCR5 messenger RNA transcripts, real-time polymerase chain reaction was done on RNA isolated from the impression cytology samples of normal subjects (n=5) and patients with dry eye syndrome (n=14). Results: We found significant up-regulation in cell surface expression of CCR5 in patients with both aqueous tear-deficient and evaporative forms of dry eye syndrome ( P <.001). The real-time polymerase chain reaction results ( for messenger RNA) corroborated the flow cytometry data ( for protein). The majority of the cells expressing CCR5 were non-bone marrow-derived resident epithelial cells of the conjunctiva. Conclusion: Our findings suggest that CCR5 up-regulation is significantly associated with dry eye syndrome-associated ocular surface disease. Clinical Relevance: Chemokine receptor CCR5 or its ligands may serve as useful targets for modulation of tissue immunoinflammatory responses in dry eye syndromes. C1 Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Univ Rome, Dept Ophthalmol, Rome, Italy. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu RI Bonini, Stefano/A-2250-2012 OI Bonini, Stefano/0000-0002-7787-2144 NR 37 TC 38 Z9 40 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2006 VL 124 IS 5 BP 710 EP 716 DI 10.1001/archopht.124.5.710 PG 7 WC Ophthalmology SC Ophthalmology GA 040GP UT WOS:000237367300011 PM 16682594 ER PT J AU Goguen, LA Posner, MSR Tishler, RB Wirth, LJ Norris, CM Annino, DJ Sullivan, CA Li, Y Haddad, RI AF Goguen, LA Posner, MSR Tishler, RB Wirth, LJ Norris, CM Annino, DJ Sullivan, CA Li, Y Haddad, RI TI Examining the need for neck dissection in the era of chemoradiation therapy for advanced head and neck cancer SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CLINICALLY POSITIVE NECK; SQUAMOUS-CELL HEAD; ADVANCED LARYNGEAL-CANCER; INDUCTION CHEMOTHERAPY; ORGAN PRESERVATION; CONCURRENT CHEMOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; CHEMORADIOTHERAPY; MANAGEMENT AB Objectives: To (1) determine clinical factors that predict pathologic complete response (pCR) on neck dissection after sequential chemo radio therapy (SCRT) for advanced head and neck cancer and (2) compare survival parameters between those who under-went neck dissection and those who did not among those patients with a clinical complete response (cCR) in the neck after SCRT, thus assessing the benefit of neck dissection in patients with a cCR in the neck. Design: Retrospective review with a mean follow-up of 3.5 years. Setting: Regional cancer center. Patients: The study population comprised 55 patients undergoing SCRT for advanced head and neck cancer with N2 or N3 neck disease. Three patients developed progressive disease and were excluded, and 28 patients underwent neck dissection. Interventions: Patients were assessed by physical examination and radiographically after SCRT. Main Outcome Measures: Physical examination and radiographic assessments of residual neck disease were compared with pathologic findings in those patients who underwent neck dissection. Survival comparisons were made between patients with a cCR in the neck who underwent neck dissection and those who did not. Results: Of 28 patients who underwent neck dissection, 8 had persistent pathologically positive nodal disease: 5 (45%) of 11 had N3 and 3 (18%) of 17 had N2 disease. Individual clinical neck assessments after SCRT were fairly predictive of a negative pathologic finding at neck dissection. The negative predictive values were physical examination (75%), computed tomography or magnetic resonance imaging (71%), and positron emission tomography (75%). However, when physical examination, imaging studies, and positron emission tomography all indicated a complete response, this accurately predicted a pCR on neck dissection. There appeared to be no improvement in survival parameters when a neck dissection was performed on patients with a cCR in the neck. Conclusions: Patients with N3 disease are at high risk for residual neck metastasis after SCRT. Patients with N2 disease can be assessed with physical examination, imaging studies, and positron emission tomography. If these all indicate a cCR, then neck dissection is likely not needed. Neck dissection did not appear to further improve survival parameters for patients with a cCR in the neck. C1 Brigham & Womens Hosp, Div Otolaryngol, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goguen, LA (reprint author), Brigham & Womens Hosp, Div Otolaryngol, Dept Surg, 45 Francis St, Boston, MA 02115 USA. EM lgoguen@partners.org RI Enver, Necati/G-8704-2012 NR 21 TC 50 Z9 51 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAY PY 2006 VL 132 IS 5 BP 526 EP 531 DI 10.1001/archotol.132.5.526 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 041RQ UT WOS:000237473800009 PM 16702569 ER PT J AU Kradin, RL Badizadegan, K Auluck, P Korzenik, J Lauwers, GY AF Kradin, RL Badizadegan, K Auluck, P Korzenik, J Lauwers, GY TI Iatrogenic Trichuris suis infection in a patient with Crohn disease SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CAMPYLOBACTER-JEJUNI; ULCERATIVE-COLITIS; THERAPY AB We report a case of biopsy-proven iatrogenic infection by the pig whipworm Trichuris suis in a patient with Crohn disease. The deliberate therapeutic ingestion of T suis ova has been adopted as an experimental approach to the treatment of Crohn disease in an effort to promote a switch from the T helper subtype 1 to T helper subtype 2 inflammatory phenotype in vivo. This report examines the morphology of the immature and adult T suis, the effects of this intervention on the immunophenotype of the bowel mucosa, and it also raises the possibility of persistent active infection in man. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org RI Auluck, Pavan/A-1160-2010 NR 14 TC 50 Z9 53 U1 1 U2 7 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 2006 VL 130 IS 5 BP 718 EP 720 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 044LT UT WOS:000237674600024 PM 16683891 ER PT J AU Choi, H Binder, DS Oropilla, ML Bernotus, EE Konya, D Nee, MA Tammaro, EA AF Choi, H Binder, DS Oropilla, ML Bernotus, EE Konya, D Nee, MA Tammaro, EA TI Evaluation of selected laboratory components of a comprehensive periodic health evaluation for veterans with spinal cord injury and disorders SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE cross-sectional studies; preventive medicine; rehabilitation; spinal cord injuries; veterans ID CASE-FINDING TOOL; CREATININE CLEARANCE; AMBULATORY PATIENTS; PRACTICE GUIDELINES; PREVENTION; TESTS; INDIVIDUALS; PREVALENCE; SYSTEMS; OLDER AB Objective: To evaluate selected laboratory components of a comprehensive periodic health evaluation program for patients with spinal cord injury and disorders (SCI/D). Design: A retrospective study. Setting: A Department of Veterans Affairs spinal cord injury center. Participants: Community-dwelling male veterans with SCI/D (N=350). Interventions: Not applicable. Main Outcome Measures: Proportion of laboratory tests that resulted in new diagnoses (diagnostic yield) and proportion of laboratory tests that resulted in changes in management (therapeutic yield). Results: Although abnormality rates for many routine laboratory tests were high (up to 31.5%), diagnostic and therapeutic yields were low (<1.5%), with the exception of glucose (therapeutic yield. 3.4%) and lipid tests (up to a 4.1% diagnostic and 15.2% therapeutic yield). Conclusions: Our data revealed that diagnostic and therapeutic yields for many laboratory components of the annual PHE program for veterans with SCI/D were low, consistent with findings in the general ambulatory population. Further data collection, particularly prospective longitudinal data, may help optimize the selection and frequency of laboratory tests performed as part of this program. C1 VA Boston Healthcare Syst, Spinal Cord Injury Serv, W Roxbury, MA USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02111 USA. RP Choi, H (reprint author), CUNY Mt Sinai Sch Med, Dept Rehabil Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM howard.choi@mssm.edu NR 47 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 2006 VL 87 IS 5 BP 603 EP 610 DI 10.1016/j.apmr.2006.02.001 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 039UW UT WOS:000237333900001 PM 16635621 ER PT J AU Abid, MR Spokes, KC Aird, WC AF Abid, MR Spokes, KC Aird, WC TI VEGF signaling pathways bifurcate downstream of VEGFR-2 in NADPH oxidase-derived ROS-sensitive and -insensitive manner SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E50 EP E50 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400079 ER PT J AU Abid, MR Shih, SC Otu, HH Spokes, KC Okada, Y Curiel, DT Minami, T Aird, WC AF Abid, MR Shih, SC Otu, HH Spokes, KC Okada, Y Curiel, DT Minami, T Aird, WC TI A novel class of VEGF-responsive genes that require forkhead aactivity for expression SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Univ Alabama, Birmingham, AL USA. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E45 EP E45 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400052 ER PT J AU Bergmeier, W Crittenden, JR Chauhan, AK Piffath, CL Cifuni, SM Housman, DE Graybiel, AM Wagner, DD AF Bergmeier, W Crittenden, JR Chauhan, AK Piffath, CL Cifuni, SM Housman, DE Graybiel, AM Wagner, DD TI CalDAG-GEFI plays a central role in platelet activation and thrombus formation in injured arterioles and venules SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E48 EP E48 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400069 ER PT J AU Bogaert, YE Reusch, J Nemenoff, R AF Bogaert, YE Reusch, J Nemenoff, R TI Disruption of vascular calcification by PPAR gamma SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 UCHSC, Denver, CO USA. Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E97 EP E97 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400339 ER PT J AU Bogaert, YE Grippa, J Nemenoff, R Reusch, J AF Bogaert, YE Grippa, J Nemenoff, R Reusch, J TI PI-3K dependent alterations in vascular smooth muscle cell (VSMC) function in response to type 1 collagen SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 UCHSC, Denver, CO USA. Denver VAMC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E76 EP E76 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400225 ER PT J AU Chen, JQ Clark, J Noda, F Matsui, T Li, L Rosenzweig, A Huang, PL AF Chen, JQ Clark, J Noda, F Matsui, T Li, L Rosenzweig, A Huang, PL TI Neointimal formation is accelerated in common carotid artery after filament injury and intravenous adenoviral gene transfer of dN Akt SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E97 EP E97 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400338 ER PT J AU Fitzgerald, ML AF Fitzgerald, ML TI SPTLC1 binds ABCA1 and potently inhibits efflux activity and protein expression of the transporter SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology CY APR 27-29, 2006 CL Denver, CO C1 Harvard Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAY PY 2006 VL 26 IS 5 BP E45 EP E45 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 034PF UT WOS:000236942400054 ER PT J AU Green, DM Noble, PC Ahuero, JS Birdsall, HH AF Green, DM Noble, PC Ahuero, JS Birdsall, HH TI Cellular events leading to chondrocyte death after cartilage impact injury SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NITRIC-OXIDE; ARTICULAR-CARTILAGE; TNF-ALPHA; TRANSENDOTHELIAL MIGRATION; GENE-EXPRESSION; IN-VITRO; APOPTOSIS; OXYGEN; INTERLEUKIN-1-BETA; ADHESION AB Objective. We undertook this study to test our postulate that leukocytes extend the zone of injury in cartilage after acute mechanical trauma. Methods. Fresh cadaveric canine femoral condyles were subjected to 20-25-MPa impact injury. Condyle explants or dispersed chondrocytes were cultured with autologous blood mononuclear leukocytes (MNLs). Viability of chondrocytes at varying distances from the impact site was assessed by trypan blue exclusion. Results. Mechanical injury caused a significant loss of viable chondrocytes over 7 days, even in cartilage > 10 mm from the impact site. After biomechanical stress, death of cells within 10 mm of the impact could be largely prevented by addition of N-G-monomethyl-Larginine to inhibit nitric oxide (NO) generation. Chondrocytes within 10 mm of the impact were also susceptible to killing by living MNLs, but not by incubation with the supernatants of endotoxin-activated MNLs. Chondrocytes in this vulnerable zone expressed intercellular adhesion molecule 1 (ICAM-1) (CD54), facilitating attachment of MNLs that localized adjacent to the chondrocytes. Leukocytes killed dispersed chondrocytes harvested from the impact zone by generation of reactive oxygen species. Leukocyte-mediated killing could be blocked by desferoxamine or by antibodies to CD18, which prevent attachment of leukocytes to ICAM1-expressing chondrocytes. Conclusion. Our data suggest that after mechanical injury, chondrocytes distant from the site may be killed through the generation of NO. Inflammatory leukocytes further extend the zone of chondrocyte death by adhering to chondrocytes expressing ICAM-1 and by inducing the accumulation of free oxygen radicals in the chondrocyte cytoplasm. Patients may benefit from therapies that reduce infiltration of inflammatory leukocytes into acutely injured cartilage. C1 Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Res Off, Houston, TX 77030 USA. RP Birdsall, HH (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Res Off, MS 151,2002 Holcombe, Houston, TX 77030 USA. EM birdsall@bcm.tmc.edu FU NHLBI NIH HHS [HL-42550] NR 42 TC 27 Z9 29 U1 3 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 2006 VL 54 IS 5 BP 1509 EP 1517 DI 10.1002/art.21812 PG 9 WC Rheumatology SC Rheumatology GA 042MV UT WOS:000237533100020 PM 16649187 ER PT J AU Pai, JK Hankinson, SE Thadhani, R Rifai, N Pischon, T Rimm, EB AF Pai, JK Hankinson, SE Thadhani, R Rifai, N Pischon, T Rimm, EB TI Moderate alcohol consumption and lower levels of inflammatory markers in US men and women SO ATHEROSCLEROSIS LA English DT Article DE alcohol; inflammation; epidemiology; acute-phase proteins; cytokines; biological markers ID TUMOR-NECROSIS-FACTOR; CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK-FACTORS; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; MYOCARDIAL-INFARCTION; PLASMA-CONCENTRATION; BODY-COMPOSITION; TNF RECEPTORS; FACTOR-ALPHA AB Objective: Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect. Methods and results: From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake. Markers of inflammation were soluble tumor necrosis factor-alpha receptors I and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), and interleukin-6 (IL-6). We found significant inverse linear trends for sTNF-R1 (P-trend < 0.001 men; 0.03 women) and sTNF-R2 (p-trend = 0.002 men; 0.08 women) with increasing alcohol intake. Compared to non-drinkers, men who consumed on average 1-2 drinks/day had 26% lower CRP (-0.66 mg/L, p = 0.13), and 36% lower IL-6 (-1.12 pg/ml, p = 0.02) levels. Among women, a similar though stronger association was observed at half drink per day. Compared to non-drinkers, both men and women who consumed 1-2 drinks/drinking day had significantly lower sTNF-R1 (-9% in men, -6% in women) and sTNTF-R2 (-7% in men, -6% in women) levels as well as lower CRP (-10% in men, -32% in women) and IL-6 (-45% in men, -27% in women) levels. Conclusions: Alcohol in moderation is associated with lower levels of inflammatory markers and may lower risk of CVD through these mechanisms. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Med Ctr,Dept Pathol, Boston, MA 02115 USA. German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. RP Pai, JK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave,Bldg 2,Rm 315, Boston, MA 02115 USA. EM jpai@hsph.harvard.edu OI Pischon, Tobias/0000-0003-1568-767X FU NCI NIH HHS [CA55075, CA67262]; NHLBI NIH HHS [HL07575, HL35464]; NIAAA NIH HHS [AA11181] NR 36 TC 80 Z9 82 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2006 VL 186 IS 1 BP 113 EP 120 DI 10.1016/j.atherosclerosis.2005.06.037 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 036RS UT WOS:000237093400014 PM 16055129 ER PT J AU Pai, JK Kraft, P Cannuscio, CC Manson, JE Rexrode, KM Albert, CM Hunter, D Rimm, EB AF Pai, JK Kraft, P Cannuscio, CC Manson, JE Rexrode, KM Albert, CM Hunter, D Rimm, EB TI Polymorphisms in the CC-chemokine receptor-2 (CCR2) and-5 (CCR5) genes and risk of coronary heart disease among US women SO ATHEROSCLEROSIS LA English DT Article DE chemokine receptors; coronary heart disease; inflammation; atherosclerosis; genetic epidemiology ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MYOCARDIAL-INFARCTION; IMMUNODEFICIENCY-VIRUS; INFLAMMATORY MARKERS; HIV-1; PROGRESSION; PLASMA; MICE; ASSOCIATION; EXPRESSION AB Objective: Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5),and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). Method and results: We examined seven common variants in the CCR2 and CCR5 loci and risk of CHD among women in the Nurses' Health Study. During 8 years of follow-up, we documented 248 incident cases of nonfatal myocardial infarction and fatal CHD, and matched controls 2:1 based on age and smoking. The distribution of alleles was similar between cases and controls. The haplotype-specific odds ratios (ORs) were not statistically significant nor was the globally-adjusted p-value (p = 0.61). However, there was a statistically significant association for CCR5-Delta 32 and A58755G (rs2856758) between cases and controls comparing age of onset < 55 and > 55 years. For Delta 32, the OR for having the variant was 0.12 (0.02-0.76) for age < 55, and 1.14 (0.69-1.88) for age >= 55 years (p, interaction = 0.04). The CCR5-Delta 32 was in linkage disequilibriurn with 58755G, and a similar association was observed for having the 58755G. Conclusions: In this population, CCR2-CCR5 haplotypes were not associated with risk of CHD. However, our data suggest a strong inverse association for certain CCR5 variants and early age of CHD onset. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pai, JK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 665 Huntington Ave,Rm 315, Boston, MA 02115 USA. EM jpai@hsph.harvard.edu OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL34594]; NIA NIH HHS [AG000158] NR 30 TC 44 Z9 45 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2006 VL 186 IS 1 BP 132 EP 139 DI 10.1016/j.atherosclerosis.2005.06.041 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 036RS UT WOS:000237093400017 PM 16055130 ER PT J AU Reimer, B D'Ambrosio, LA Coughun, JF Kafrissen, ME Biederman, J AF Reimer, Bryan D'Ambrosio, Lisa A. Coughun, Joseph F. Kafrissen, Michael E. Biederman, Joseph TI Using self-reported data to assess the validity of driving simulation data SO BEHAVIOR RESEARCH METHODS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ON-ROAD; YOUNG-ADULTS; FOLLOW-UP; PERFORMANCE; ADOLESCENTS; VALIDATION; BEHAVIOR; CRASHES; IMPACT AB In this article, we use self-reported driving behaviors from a written questionnaire to assess the measurement validity of data derived from a driving simulation. The issue of validity concerns the extent to which measures from the experimental context map onto constructs of interest. Following a description of the experimental methods and setting, an argument for the face validity of the data is advanced. Convergent validity was assessed by regressing behaviors observed in the driving simulator on self-reported measures of driving behaviors. Significant relationships were found across six measures: accidents, speeding, velocity, passing, weaving between traffic, and behavior at stop signs. Concurrent validity was evaluated with an analysis of simulator accident involvement and attention deficit hyperactivity disorder status. Discrimmant validity was assessed using a multitrait-multimethod matrix of simulator and questionnaire data. We concluded that although the relationship between self-reported behaviors and observed responses in the simulator falls short of perfect correspondence, the data collected from the driving simulator are valid measures of the behaviors of interest. C1 MIT, AgeLab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Reimer, B (reprint author), MIT, AgeLab, 77 Massachusetts Ave,Room E40-291, Cambridge, MA 02139 USA. EM reimer@mit.edu RI Reimer, Bryan/G-6431-2010; Louza, Mario/H-8540-2013 OI Reimer, Bryan/0000-0003-4850-8738; Louza, Mario/0000-0003-1359-4111 NR 56 TC 55 Z9 55 U1 1 U2 7 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 1554-351X J9 BEHAV RES METHODS JI Behav. Res. Methods PD MAY PY 2006 VL 38 IS 2 BP 314 EP 324 DI 10.3758/BF03192783 PG 11 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 078CN UT WOS:000240078900018 PM 16956108 ER PT J AU Biederman, J Mick, E Surman, C Doyle, R Hammerness, P Harpold, T Dunkel, S Dougherty, M Aleardi, M Spencer, T AF Biederman, J Mick, E Surman, C Doyle, R Hammerness, P Harpold, T Dunkel, S Dougherty, M Aleardi, M Spencer, T TI A randomized, placebo-controlled trial of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adult; ADHD; stimulant; randomized trial; methylphenidate; psychopharmacology ID DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; COMORBIDITY; SYMPTOMS; PATTERNS; ABUSE AB Background: The objective of this study was to evaluate the safety and efficacy of once-daily OROS methylphenidate (MPH) in the treatment of adults with DSM-IV attention deficit/hyperactivity disorder (ADHD). Methods: We conducted a randomized, 6-week, placebo-controlled, parallel- design study of OROS MPH in 141 adult subjects with DSM-IV ADHD, using standardized instruments for diagnosis. OROS MPH or placebo was initiated at 36 mg/day, and titrated to optimal response, depending on efficacy and tolerability, up to 1.3 mg/kg/day. Results: Treatment with OROS MPH was associated with clinically and statistically significant reductions in DSM-IV symptoms of inattention and hyperactivity/impulsivity relative to subjects treated with placebo. At endpoint, 6696 of subjects (n = 444) receiving OROS MPH and 39% of subjects (n = 23) receiving placebo attained our a priori definition of response of much or very much improved on the Clinical Global Impression-Improvement scale plus a > 30% reduction in Adult ADHD Investigator System Report Scale score. OROS MPH was associated with small but statistically significant increases in systolic blood pressure (3.5 +/- 11.8 mm Hg), diastolic blood pressure (4.0 +/- 8.5 mm Hg), and heart rate (4.5 +/- 10.5 bpm). Conclusions: These results show that treatment with OROS MPH in daily doses of up to 1.3 mg/kg/day was effective in the treatment of adults with ADHD. Because of the potential for increases in blood pressure and heart rate, subjects receiving treatment with MPH should be monitored for changes in blood pressure parameters during treatment. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, YAW 6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 29 TC 161 Z9 164 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 2006 VL 59 IS 9 BP 829 EP 835 DI 10.1016/j.biopsych.2005.09.011 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 036DA UT WOS:000237049900008 PM 16373066 ER PT J AU Marty, FM Lowry, CM Cutler, CS Campbell, BJ Fiumara, K Baden, LR Antin, JH AF Marty, FM Lowry, CM Cutler, CS Campbell, BJ Fiumara, K Baden, LR Antin, JH TI Voriconazole and sirolimus coadministration after allogeneic hematopoietic stem cell transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE voriconazole; sirolimus; transplantation; aspergillosis; fungal infection ID VERSUS-HOST-DISEASE; INVASIVE FUNGAL-INFECTIONS; INTERSTITIAL PNEUMONITIS; THROMBOTIC MICROANGIOPATHY; RECIPIENTS; TACROLIMUS; PROPHYLAXIS; THERAPY; METHOTREXATE; METABOLISM AB Sirolimus is increasingly used in transplantation for prevention and treatment of graft-versus-host disease and organ rejection. Voriconazole is contraindicated when used concomitantly with sirolimus because of a substantial increase in sirolimus drug exposure with unadjusted dosing, but voriconazole is also considered the best initial treatment of invasive aspergillosis and other fungal infections. Patients who received voriconazole and sirolimus concomitantly were identified by a review of the medical records of all allogeneic hematopoietic stem cell recipients at our institution from September 1, 2002, to June 1, 2005. Data including baseline characteristics, indications for both drugs, and potential adverse effects were evaluated. Eleven patients received voriconazole and sirolimus concomitantly for a median of 33 days (range, 3-100 days). In 8 patients whose sirolimus dose was initially reduced by 90%, trough sirolimus levels were similar to those obtained before the administration of voriconazole; no obvious significant toxicity from either drug was observed during coadministration. Serious adverse events were observed in 2 patients in whom sirolimus dosing was not adjusted during voriconazole administration. Sirolimus and voriconazole may be safely coadministered if there is an empiric initial 90% sirolimus dose reduction combined with systematic monitoring of trough levels. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM fmarty@partners.org FU NHLBI NIH HHS [HL070149] NR 26 TC 60 Z9 65 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAY PY 2006 VL 12 IS 5 BP 552 EP 559 DI 10.1016/j.bbmt.2005.12.032 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 039MH UT WOS:000237309500007 PM 16635790 ER PT J AU Holmes, LB Wyszynski, DF Baldwin, EJ Habecker, E Glassman, LH Smith, CR AF Holmes, LB Wyszynski, DF Baldwin, EJ Habecker, E Glassman, LH Smith, CR TI Increased risk for non-syndromic cleft palate among infants exposed to lamotrigine during pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 MassGen Hosp Children, N Amer AED Pregnancy Registry, Boston, MA USA. NR 0 TC 33 Z9 33 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA 8 BP 318 EP 318 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200009 ER PT J AU Morgan, SC Relaix, F Buckingham, M Sandell, L Tilghman, S Loeken, MR AF Morgan, SC Relaix, F Buckingham, M Sandell, L Tilghman, S Loeken, MR TI Maternal diabetes and cardiac malformations: The role of Pax3, p53-dependent apoptosis, and cardiac neural crest migration SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Inst Pasteur, Paris, France. Stowers Inst, Kansas City, MO USA. Princeton Univ, Princeton, NJ 08544 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA 35 BP 332 EP 332 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200036 ER PT J AU Herbert, MR AF Herbert, MR TI Autism: Parsing heterogeneity of causes and features SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA S1 BP 342 EP 342 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200052 ER PT J AU Ungar, LDJ Baldwin, EJ Wyszynski, DF Holmes, LB AF Ungar, LDJ Baldwin, EJ Wyszynski, DF Holmes, LB TI Exclusion and inclusion criteria for major malformations: Impact on studies of potential teratogens SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. N Amer AED Pharm Registry, Boston, MA USA. Princeton Univ, Princeton, NJ 08544 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA P8 BP 373 EP 373 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200109 ER PT J AU Owen, MH Coull, BA Holmes, LB AF Owen, MH Coull, BA Holmes, LB TI Evidence for sex based differences in expression of Dominant hemimelia SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Simmons Coll, Dept Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2006 VL 76 IS 5 MA P54 BP 398 EP 398 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 048GS UT WOS:000237936200155 ER PT J AU Hemler, ME AF Hemler, ME TI Shedding of heterodimeric leukocyte integrin SO BLOOD LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2006 VL 107 IS 9 BP 3417 EP 3418 DI 10.1182/blood-2006-02-001958 PG 2 WC Hematology SC Hematology GA 038KE UT WOS:000237217600001 ER PT J AU Neufeld, EJ AF Neufeld, EJ TI Oral chelators deferasirox and defefiprone for transfusional iron overload in thalassen a major: new data, new questions SO BLOOD LA English DT Article ID SICKLE-CELL-DISEASE; RAT-HEART CELLS; MYOCARDIAL IRON; PHASE-II; BETA-THALASSEMIA; HYPERTRANSFUSED RATS; MAGNETIC-RESONANCE; DEPENDENT ANEMIAS; BODY IRON; ICL670 AB For nearly 30 years, patients with transfusional iron overload have depended on nightly deferoxamine infusions for iron chelation. Despite dramatic gains in life expectancy in the deferoxamine era for patients with transfusion-dependent anemias, the leading cause of death for young adults with thalassemia major and related disorders has been cardiac disease from myocardial iron deposition. Strategies to reduce cardiac disease by improving chelation regimens have been of the highest priority. These strategies have included development of novel oral iron chelators to improve compliance, improved assessment of cardiac iron status, and careful epidemiologic assessment of European outcomes with deferiprone, an oral alternative chelator available for about a decade. Each of these strategies is now bearing fruit. The novel oral chelator deferasirox was recently approved by the Food and Drug Administration (FDA); a randomized clinical trial demonstrates that deferasirox at 20 to 30 mg/kg/d can maintain or improve hepatic iron in thalassemia as well as deferoxamine. A randomized trial based on cardiac T2* magnetic resonance imaging (MRI) suggests that deferiprone can unload myocardial iron faster than deferoxamine. Retrospective epidemiologic data suggest dramatic reductions in cardiac events and mortality in Italian subjects exposed to deferiprone compared with deferoxamine. These developments herald a new era for iron chelation, but many unanswered questions remain. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol, 300 Longwood Ave,Karp 08210, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [U01-HL065260] NR 42 TC 162 Z9 169 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2006 VL 107 IS 9 BP 3436 EP 3441 DI 10.1182/blood-2006-02-002394 PG 6 WC Hematology SC Hematology GA 038KE UT WOS:000237217600015 PM 16627763 ER PT J AU Rooke, HM Orkin, SH AF Rooke, HM Orkin, SH TI Phosphorylation of Gata1 at serine residues 72, 142, and 3 10 is not essential for hematopoiesis in vivo SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; ERYTHROBLASTS; SURVIVAL AB Phosphorylation of transcription factors is important in posttranslational control of protein function. The indispensable zinc-finger transcription factor, Gata1, is phosphorylated constitutively at 6 serine residues (26, 49, 72, 142, 178, 187), and at a seventh (310) following induction of erythroid differentiation. However, the biologic consequences of phosphorylation with respect to function are unclear. To address this issue, we generated mice with serine-to-alanine mutations at the inducibly phosphorylated serine 310 alone or at conserved serine residues 72, 142, and 310 together. The peripheral blood parameters of the mice were normal, as was their response to acute erythropoietic stress. Analysis of hematopoietic progenitor populations during ontogeny and into adulthood showed a moderate decrease in erythroid burst-forming unit (BFU-E) and erythroid colony-forming unit (CFU-E) numbers only in the adult bone marrow of the triple mutant. Yet, later stage erythropoiesis was not perturbed. This suggests that any molecular consequences associated with loss of phosphorylation at residues 72, 142, and 310 can be compensated for in the in vivo environment. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu NR 12 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2006 VL 107 IS 9 BP 3527 EP 3530 DI 10.1182/blood-2005-10-4309 PG 4 WC Hematology SC Hematology GA 038KE UT WOS:000237217600032 PM 16391009 ER PT J AU Rubenstein, JL Fridlyand, J Shen, A Aldape, K Ginzinger, D Batchelor, T Treseler, P Berger, M McDermott, M Prados, M Karch, J Okada, C Hyun, W Parikh, S Haqq, C Shuman, M AF Rubenstein, JL Fridlyand, J Shen, A Aldape, K Ginzinger, D Batchelor, T Treseler, P Berger, M McDermott, M Prados, M Karch, J Okada, C Hyun, W Parikh, S Haqq, C Shuman, M TI Gene expression and angiotropism in primary CNS lymphoma SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; UNFOLDED PROTEIN RESPONSE; NERVOUS-SYSTEM LYMPHOMAS; TIME QUANTITATIVE PCR; POOR-PROGNOSIS; SURVIVAL; INTERLEUKIN-4; RECEPTOR; ANGIOGENESIS; DEATH AB Primary CNS lymphoma is an aggressive form of non-Hodgkin lymphoma whose growth is restricted to the central nervous system. We used cDNA microarray analysis to compare the gene expression signature of primary CNS lymphomas with nodal large B-cell lymphomas. Here, we show that while individual cases of primary CNS lymphomas may be classified as germinal center B-cell, activated B-cell, or type 3 large B-cell lymphoma, brain lymphomas are distinguished from nodal large B-cell lymphomas by high expression of regulators of the unfolded protein response (UPR) signaling pathway, by the oncogenes c-Myc and Pim-1, and by distinct regulators of apoptosis. We demonstrate that interieukin-4 (IL-4) is expressed by tumor vasculature as well as by tumor cells in CNS lymphomas. We also identify high expression in CNS lymphomas of several IL-4-induced genes, including X-box binding protein 1 (XBP-1), a regulator of the UPR. In addition, we demonstrate expression of the activated form of STAT6, a mediator of IL-4 signaling, by tumor cells and tumor endothelia in CNS lymphomas. High expression of activated STAT6 in tumors was associated with short survival in an independent set of patients with primary CNS lymphoma who were treated with high-dose intravenous methotrexate therapy. C1 Univ Calif San Francisco, Div Hematol Oncol, Canc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Canc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pathol, Canc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurosurg, Canc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, Canc Res Inst, San Francisco, CA 94143 USA. MD Anderson Canc Ctr, Dept Neuropathol, Houston, TX USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Dept Vet Affairs Med Ctr, Portland, OR USA. RP Rubenstein, JL (reprint author), Univ Calif San Francisco, Div Hematol Oncol, Canc Res Inst, M1282 Box 1270, San Francisco, CA 94143 USA. EM jamesr@medicine.ucsf.edu FU NCI NIH HHS [R01 CA101042-01] NR 43 TC 108 Z9 112 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 2006 VL 107 IS 9 BP 3716 EP 3723 DI 10.1182/blood-2005-03-0897 PG 8 WC Hematology SC Hematology GA 038KE UT WOS:000237217600057 PM 16418334 ER PT J AU Briesacher, BA Orwig, D Seton, M Omar, M Kahler, KH AF Briesacher, Becky A. Orwig, Denise Seton, Margaret Omar, Mohamed Kahler, Kristijan H. TI Medical care costs of Paget's disease of bone in a privately insured population SO BONE LA English DT Article DE reelin; association; LD; PDT; autism ID UNITED-STATES; MANAGEMENT; MANIFESTATIONS; COMORBIDITIES; COMPLICATIONS; FRACTURES; FEATURES; THERAPY; ENGLAND; HEALTH AB Introduction: Medical care costs are difficult to calculate in diseases such as Paget's disease because they have low detection rates and a wide range of clinical manifestations that commonly occur in aging patient populations. Materials and methods: Using 2001-2002 MarketScan Research databases, this study linked medical claims, prescription records, and encounter data on 2.8 million active and retired employees to create a longitudinal panel with 24 months of observation. Patients with Paget's disease were identified by ICD-9 code 731.0. Matched controls (MC) were identified through an exact match procedure using gender, age, and predicted Medicare costs estimated with a risk adjuster. Diagnostic and expenditure records were extracted for the sample and prevalence rates calculated for 20 conditions with well-documented associations to Paget's disease. Comorbidities and health care costs of Paget's disease patients were compared to those of the MCs, and the differences tested using Chi-square and t tests. Results: Our study identified 244 matched pairs. The average age was 72.7 years; 50.8% were female. Significantly higher comorbidities (P < 0.05) were detected in Paget's disease patients relative to MCs for: pathological fractures (4.9% vs. 0.4%), heart murmurs (3.3% vs. 0.4%), low back pain (19.7% vs. 8.6%), spinal stenosis (16.4% vs. 9.8%), and hearing loss (13.5% vs. 5.7%), respectively. Biannual per patient outpatient costs were significantly higher in Paget's disease patients (Paget's disease $9301 vs. MC $6339, P < 0.05), especially for services associated with physician visits and diagnostic tests. Prescription costs for antiresportive agents and analgesics were also higher (Paget's disease $1115 vs. MC $507, P < 0.05). Inpatient costs (Paget's disease $16,144 vs. MC $21.480) were comparable. Conclusion: This study is the first to describe the excessive costs of Paget's disease, based on known patterns of disease expression, evaluation, and treatment. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Med, Div Geriatr Med, Biotech 4, Worcester, MA 01605 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. RP Briesacher, BA (reprint author), Univ Massachusetts, Sch Med, Div Geriatr Med, Biotech 4, Suite 315,377 Plantat St, Worcester, MA 01605 USA. EM Becky.Briesacher@umassmed.edu; DORWIG@epi.umaryland.edu; margaret_seton@hms.harvard.edu; mohamed.omar@novartis.com; Kristijan.Kahler@novartis.com NR 34 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2006 VL 38 IS 5 BP 731 EP 737 DI 10.1016/j.bone.2005.10.015 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 043PU UT WOS:000237614400016 PM 16364708 ER PT J AU Ho, VT Kim, HT Liney, D Milford, E Gribben, J Cutler, C Lee, SJ Antin, JH Soiffer, RJ Alyea, EP AF Ho, VT Kim, HT Liney, D Milford, E Gribben, J Cutler, C Lee, SJ Antin, JH Soiffer, RJ Alyea, EP TI HLA-C mismatch is associated with inferior survival after unrelated donor non-myeloablative hematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol DE HLA mismatch; GVHD; stem cell transplantation; graft-versus-host disease; non-myeloablative transplantation ID BONE-MARROW-TRANSPLANTATION; CLASS-I; HEMATOLOGIC MALIGNANCIES; DISPARITY; ALLELES; IMPACT AB HLA-C matching is an important determinant of outcome after myeloablative unrelated donor ( URD) hematopoietic stem cell transplantation. However, its importance in non-myeloablative stem cell transplantation ( NST) is not known. We report a retrospective analysis of 111 patients who underwent URD NST, of whom 78 were 10/10 matched at HLA-A, B, C, DRB1, DQB1 and 33 were mismatched at one or more HLA-C antigen/allele ( 24 HLA-C only; nine HLA-C+ other locus mismatch). Patients were conditioned with busulfan ( 0.8 mg/kg/day i.v. x 4 days) and fludarabine ( 30 mg/m(2)/day i.v. x 4 days). Graft-versus-host disease prophylaxis included cyclosporine/prednisone- or tacrolimus/mini-methotrexate-based regimens. HLA-C disparity did not impair engraftment. Median marrow donor chimerisms were >= 90% donor at day+30 and +100 in both groups. Overall survival at 2 years was 30% in HLA-C-mismatched and 51% in 10/10-matched patients ( P=0.008). In Cox regression, HLA-C mismatch was an independent predictor of death ( hazard ratio 1.85, P=0.04). Treatment-related mortality was higher in the HLA-C-mismatched group: 48 versus 16%( P=0.0001). Cumulative relapse incidence was 35% in the HLA-C-mismatched and 55% in the 10/10-matched cohort, P=0.09. HLA-C mismatch is associated with inferior survival after URD NST. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. St Bartholomews Hosp, Dept Med Oncol, London, England. RP Ho, VT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1B20, Boston, MA 02115 USA. EM Vincent_ho@dfci.harvard.edu FU NHLBI NIH HHS [5 P01 HL070149-03] NR 17 TC 32 Z9 36 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2006 VL 37 IS 9 BP 845 EP 850 DI 10.1038/sj.bmt.1705315 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 034FQ UT WOS:000236914800006 PM 16532020 ER PT J AU Andorsky, DJ Loberiza, FR Lee, SJ AF Andorsky, DJ Loberiza, FR Lee, SJ TI Pre-transplantation physical and mental functioning is strongly associated with self-reported recovery from stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol DE quality of life; transplant outcomes; hematologic malignancy ID BONE-MARROW-TRANSPLANTATION; QUALITY-OF-LIFE; NON-HODGKINS-LYMPHOMA; LONG-TERM SURVIVORS; SHORT-FORM 36; PROGNOSTIC VALUE; LUNG-CANCER; CHEMOTHERAPY; RECIPIENTS; QUESTIONNAIRE AB Previous studies of quality of life ( QOL) note compromised QOL after stem cell transplantation ( HCT), but do not usually consider the impact of pre-transplantation deficits in QOL on post transplantation outcomes. To examine these associations, multivariate models for six self-reported QOL outcomes at 6 and 12 months were constructed, considering pre-transplantation clinical status and QOL, and subsequent clinical events. Outcomes measured overall subjective health, social functioning and agreement with statements such as 'Life has returned to normal.' Of 320 autologous and allogeneic HCT recipients who completed pre-transplantation surveys, 197 completed 6-month surveys and 175 completed 12-month surveys. Pre-transplantation overall health and mental health were independent predictors of all QOL outcomes at 6 months. Baseline physical health was also predictive of four of six outcomes at 12 months. In contrast, disease risk was predictive only of enjoying normal activities at 6 months. Relapse and chronic graft-versus-host disease were associated with poorer QOL. In conclusion, pre-transplantation self-reported physical and mental health are more strongly associated with QOL after HCT than commonly noted baseline clinical predictors such as age and disease risk. Measurement of baseline QOL can help place the effects of the transplantation procedure in context. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Nebraska, Med Ctr, Hematol Oncol Sect, Omaha, NE USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM stephanie_lee@dfci.harvard.edu FU NCI NIH HHS [CA75267] NR 34 TC 25 Z9 27 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2006 VL 37 IS 9 BP 889 EP 895 DI 10.1038/sj.bmt.1705347 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 034FQ UT WOS:000236914800012 PM 16532014 ER PT J AU Martinez-Juarez, IE Alonso, ME Medina, MT Duron, RM Bailey, JN Lopez-Ruiz, M Ramos-Ramirez, R Leon, L Pineda, G Castroviejo, IP Silva, R Mija, L Perez-Gosiengfiao, K Machado-Salas, J Delgado-Escueta, AV AF Martinez-Juarez, IE Alonso, ME Medina, MT Duron, RM Bailey, JN Lopez-Ruiz, M Ramos-Ramirez, R Leon, L Pineda, G Castroviejo, IP Silva, R Mija, L Perez-Gosiengfiao, K Machado-Salas, J Delgado-Escueta, AV TI Juvenile myoclonic epilepsy subsyndromes: family studies and long-term follow-up SO BRAIN LA English DT Article DE juvenile myoclonic epilepsy; subtypes; follow-up; classification ID IDIOPATHIC GENERALIZED EPILEPSY; ABSENCE EPILEPSY; PERSISTING ABSENCES; SEIZURES; CLASSIFICATION; LINKAGE; LOCUS; CHILDHOOD; PROGNOSIS; HETEROGENEITY AB The 2001 classification subcommittee of the International League Against Epilepsy (ILAE) proposed to 'group JME, juvenile absence epilepsy, and epilepsy with tonic clonic seizures only under the sole heading of idiopathic generalized epilepsies (IGE) with variable phenotype'. The implication is that juvenile myoclonic epilepsy (JME) does not exist as the sole phenotype of family members and that it should no longer be classified by itself or considered a distinct disease entity. Although recognized as a common form of epilepsy and presumed to be a lifelong trait, a long-term follow-up of JME has not been performed. To address these two issues, we studied 257 prospectively ascertained JME patients and encountered four groups: (i) classic JME (72%), (ii) CAE (childhood absence epilepsy) evolving to JME (18%), (iii) JME with adolescent absence (7%), and (iv) JME with astatic seizures (3%). We examined clinical and EEG phenotypes of family members and assessed clinical course over a mean of 11 +/- 6 years and as long as 52 years. Forty per cent of JME families had JME as their sole clinical phenotype. Amongst relatives of classic JME families, JME was most common (40%) followed by grand mal (GM) only (35%). In contrast, 66% of families with CAE evolving to JME expressed the various phenotypes of IGE in family members. Absence seizures were more common in family members of CAE evolving to JME than in those of classic JME families (P < 0.001). Female preponderance, maternal transmission and poor response to treatment further characterized CAE evolving to JME. Only 7% of those with CAE evolving to JME were seizure-free compared with 58% of those with classic JME (P < 0.001), 56% with JME plus adolescent pyknoleptic absence and 62% with JME plus astatic seizures. Long-term follow-up (1-40 years for classic JME; 5-52 years for CAE evolving to JME, 5-26 years for JME with adolescent absence and 3-18 years for JME with astatic seizures) indicates that all subsyndromes are chronic and perhaps lifelong. Seven chromosome loci, three epilepsy-causing mutations and two genes with single nucleotide polymorphisms (SNPs) associating with JME reported in literature provide further evidence for JME as a distinct group of diseases. C1 Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, Los Angeles, CA 90073 USA. VA Los Angeles VA Med Ctr, VA GLAHS W Los Angeles, Epilepsy Ctr Excellence, Epilepsy Genet Genom Labs,Comprehens Epilepsy Pro, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci, Los Angeles, CA 90073 USA. Mexico Gen Hosp, Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. Mexico Gen Hosp, Neurol & Neurosurg Unit, Mexico City, DF, Mexico. Angel Leanos Hosp, Guadalajara, Jalisco, Mexico. Natl Autonomous Univ Honduras, Tegucigalpa, Honduras. Univ Hosp La Paz, Madrid, Spain. Nuestra Senora La Paz Hosp, San Miguel, El Salvador. Inst Neurol Sci, Lima, Peru. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM escueta@ucla.edu OI Duron, Reyna M./0000-0002-9425-2289; Delgado-Escueta, Antonio V./0000-0002-1581-6999; Martinez-Juarez, Iris E./0000-0001-6512-5312 FU NINDS NIH HHS [R01-NS42376] NR 48 TC 69 Z9 70 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAY PY 2006 VL 129 BP 1269 EP 1280 DI 10.1093/brain/awl048 PN 5 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 035JV UT WOS:000236998000021 PM 16520331 ER PT J AU Martinez, V Wang, LX Tache, Y AF Martinez, Vicente Wang, Lixin Tache, Yvette TI Proximal colon distension induces Fos expression in the brain and inhibits gastric emptying through capsaicin-sensitive pathways in conscious rats SO BRAIN RESEARCH LA English DT Article DE proximal colon distension; Fos; brain; visceral pain; gastric emptying; capsaicin ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; NOXIOUS VISCERAL STIMULUS; LUMBOSACRAL SPINAL-CORD; LOCUS-COERULEUS NEURONS; DORSAL MOTOR NUCLEUS; C-FOS; COLORECTAL DISTENSION; RECTAL DISTENSION; SOLITARY TRACT AB We assessed brain nuclei activated during noxious mechanical distension of the proximal colon in conscious rats, using Fos as a marker of neuronal activation, and functional reflex changes in gastric emptying associated to colon distension. The role of capsaicin-sensitive afferents in Fos and gastric: responses to distension was also investigated. Compared with sham distension, isovolumetric phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) increased significantly Fos expression 1 h after distension in selective brain areas, most prominently, the paraventricular and supraoptic nuclei of the hypothalamus (13-fold and 80-fold, respectively), the locus coeruleus-Barrington's nucleus complex (2-fold), area postrema (7-fold) and the nucleus tractus solitarius (4-fold). Increased Fos expression was also observed in the cingulate cortex, posterior paraventricular nucleus of the thalamus, periaqueductal gray and ventrolateral medulla. Distension of the proximal colon significantly inhibited gastric emptying by 82% and 34%, as measured 30 and 60 min after the distension respectively, compared with control. Pretreatment with systemic capsaicin prevented both the brain increase in Fos expression and the inhibition of gastric emptying induced by the colon distension. These results show that visceral pain arising from the proximal colon activates a complex neuronal network that includes specific brain nuclei involved in the integration of autonomic, neuroendocrine and behavioral responses to pain and an inhibitory motor reflex in other gut areas (delayed gastric emptying). Capsaicin-sensitive afferent pathways are involved in mediating brain neuronal activation and functional changes associated with noxious visceral stimulation. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE,Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wang, LX (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, CURE,Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM lixinw@ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [R01 DK-33061]; PHS HHS [DDK-P30 41301] NR 78 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 2006 VL 1086 BP 168 EP 180 DI 10.1016/j.brainres.2006.02.063 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 049FN UT WOS:000238001500020 PM 16626641 ER PT J AU Zander, T Yunes, JA Cardoso, AA Nadler, LM AF Zander, T Yunes, JA Cardoso, AA Nadler, LM TI Rapid, reliable and inexpensive quality assessment of biotinylated cRNA SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE microarray; biotinylated cRNA; probe quality; 5 ' representation; 3 '/5 ' ratio ID POLYMERASE CHAIN-REACTION; GENE-EXPRESSION; B-CELLS; RNA; PREDICTION; PCR AB The interpretation of oligonucleotide array experiments depends on the quality of the target cRNA used. cRNA target quality is assessed by quantitative analysis of the representation of 5' and 3' sequences of control genes using commercially available Test arrays. ne Test array provides an economically priced means of determining the quality of labeled target prior to analysis on whole genome expression arrays. This manuscript validates the use of a duplex RT-PCR assay as a faster (6h) and less expensive (< US$10) but equally accurate alternative to the Test arrays in determining biotinylated cRNA quality. Forty-one different cRNA samples were hybridized to HG-U133A microarrays from Affymetrix. Ten cRNA samples with a beta-actin 3'/5' ratio > 6 were chosen and classified as degraded cRNAs, and 31 samples with a B-actin 3'/5' ratio < 6 were selected as good quality cRNAs. Blinded samples were then used for the RT-PCR assay. After gel electrophoresis, optical densities of the amplified 3' and 5' fragments of beta-actin were measured and the 375' ratio was calculated. There was a strong correlation (r(2) = 0.6802) between the array and the RT-PCR B-actin 375' ratios. Moreover, the RT-PCR 375' ratio was significantly different (P < 0.0001) between undegraded (mean +/- SD, 0.34 +/- 0.09) and degraded (1.71 +/- 0.83) samples. None of the other parameters analyzed, such as i) the starting amount of RNA, ii) RNA quality assessed using the Bioanalyzer Chip technology, or iii) the concentration and OD260/OD280 ratio of the purified biotinylated cRNA, correlated with cRNA quality. C1 Ctr Infantil Boldrini, BR-13083210 Campinas, SP, Brazil. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Cologne, Ctr Internal Med, Cologne, Germany. RP Yunes, JA (reprint author), Ctr Infantil Boldrini, Rua Gabriel Porto,1270, BR-13083210 Campinas, SP, Brazil. EM andres@boldrini.org.br FU NCI NIH HHS [P01-CA68484, P01-CA78378] NR 11 TC 1 Z9 1 U1 0 U2 1 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD MAY PY 2006 VL 39 IS 5 BP 589 EP 593 DI 10.1590/S0100-879X2006000500004 PG 5 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 046CX UT WOS:000237790100004 PM 16648895 ER PT J AU Pabst, T Stillner, E Neuberg, D Nimer, S Willman, CL List, AF Melo, JV Tenen, DG Mueller, BU AF Pabst, T Stillner, E Neuberg, D Nimer, S Willman, CL List, AF Melo, JV Tenen, DG Mueller, BU TI Mutations of the myeloid transcription factor CEBPA are not associated with the blast crisis of chronic myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CEBPA; chronic myeloid leukaemia; transcription factor; differentiation; mutation ID CHRONIC MYELOGENOUS LEUKEMIA; BINDING-PROTEIN-ALPHA; C/EBP-ALPHA; GENE; DIFFERENTIATION; ABSENCE AB The transcription factor CEBPA is crucial for normal myeloid differentiation. CEBPA gene mutations have been reported in patients with acute myeloid leukaemia. The inevitable evolution of chronic myeloid leukaemia (CML) in chronic phase (CP) to a fatal blast crisis (BC) is assumed to result from the acquisition of additional genetic changes in the leukaemic clone. Gain of CEBPA mutations might represent a key event causing the differentiation block observed in myeloid CML-BC, but not in CML-CP. Here, no CEBPA mutation in 95 CML-BC patients was found, suggesting a limited role, if any, of CEBPA mutations in this disorder. C1 Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Univ Hosp Bern, Inst Med Oncol, CH-3010 Bern, Switzerland. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Hammersmith Hosp, Imperial Coll, Dept Hematol, London, England. Univ Hosp Bern, Dept Internal Med, CH-3010 Bern, Switzerland. RP Tenen, DG (reprint author), Harvard Univ, Sch Med, Inst Med, 77 Ave Louis Pasteur,Room 954, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu OI Tenen, Daniel/0000-0002-6423-3888 NR 12 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2006 VL 133 IS 4 BP 400 EP 402 DI 10.1111/j.1365-2141.2006.06057.x PG 3 WC Hematology SC Hematology GA 031XH UT WOS:000236738000007 PM 16643447 ER PT J AU Kyle, RA Leong, T Li, SL Oken, MM Kay, NE Van Ness, B Greipp, PR AF Kyle, RA Leong, T Li, SL Oken, MM Kay, NE Van Ness, B Greipp, PR TI Complete response in multiple myeloma - Clinical trial E9486, an Eastern Cooperative Oncology Group study not involving stem cell transplantation SO CANCER LA English DT Article DE drug therapy; multiple myeloma; survival ID HIGH-DOSE CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; AUTOLOGOUS TRANSPLANTATION; COMPLETE REMISSION; PROGNOSTIC FACTORS; STAGING SYSTEM; MELPHALAN; PREDNISONE; INTERFERON; SURVIVAL AB BACKGROUND: The importance of obtaining a complete response (CR) in multiple myeloma (MM) treated with chemotherapy is unclear. METHODS. The Eastern Cooperative Oncology Group evaluated 653 previously 3 untreated patients with active MM randomized to vincristine, carinustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP), to VBMCP and recom binant interferon alfa-2 (INF alpha-2), or to VBMCP and high-close cyclophosphamide. RESULTS: Objective response was achieved in 420 (67%) of the 628 eligible patients, and 85 (14%) achieved a CR. Patients receiving VBMCP and recombinant INFa-2 had a significantly higher CR (18%) than those receiving VBMCP alone (10%) (P = .02). The CR rate for VBMCP and high-dose cyclophosphamide was 12%. setts. Median duration of survival was 3.5 years for all eligible patients, and the estimated 5-year survival rate was 31%. The median duration of survival from the date of objective response was 5.1 years for those who achieved a CR and 3.3 years for those with a partial response (P < .0001). The median postresponse survival was 6.6 years in the 21 patients in CR with nonclonal disease and 4.4 years in the 11 patients in CR who had persistent clonal disease. All patients with negative immunofixation results and nonclonal plasma cells in whom polymerase chain reaction was performed had a positive result (presence of tumor DNA). CONCLUSION. Patients in whom a CR was achieved had a longer survival than those who had a partial response. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. N Mem Med Ctr, Hubert H Humphrey Canc Ctr, Robbinsdale, MN USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. RP Kyle, RA (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM kyle.roberts@mayo.edu FU NCI NIH HHS [CA-13650, CA-21115] NR 40 TC 49 Z9 53 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2006 VL 106 IS 9 BP 1958 EP 1966 DI 10.1002/cncr.21804 PG 9 WC Oncology SC Oncology GA 037ZR UT WOS:000237187400012 PM 16565956 ER PT J AU Certo, M Moore, VD Nishino, M Wei, G Korsmeyer, S Armstrong, SA Letai, A AF Certo, M Moore, VD Nishino, M Wei, G Korsmeyer, S Armstrong, SA Letai, A TI Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members SO CANCER CELL LA English DT Article ID CYTOCHROME-C RELEASE; BH3 DOMAIN; BH3-ONLY PROTEINS; PROAPOPTOTIC ACTIVITY; CONFORMATIONAL-CHANGE; X-L; APOPTOSIS; BAX; BIM; BCL-X(L) AB We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decoded based on the pattern of mitochondrial sensitivity to this peptide panel, a strategy that we call BH3 profiling. Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins. Sensitivity to the cell-permeable BCL-2 antagonist ABT-737 is also related to priming of BCL-2 by activator BH3-only molecules. Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by 131143 profiling and which correlates with dependence on antiapoptotic family members for survival. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol & Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu OI Del Gaizo Moore, Victoria/0000-0002-6317-7693 FU NCI NIH HHS [K08 CA10254, P01 CA068484] NR 47 TC 619 Z9 636 U1 4 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2006 VL 9 IS 5 BP 351 EP 365 DI 10.1016/j.ccr.2006.03.027 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 044RA UT WOS:000237688800006 PM 16697956 ER PT J AU Carrasco, DR Fenton, T Sukhdeo, K Protopopova, M Enos, M You, MJJ Divicio, D Nogueira, C Stommel, J Pinkus, GS Fletcher, C Hornick, JL Cavenee, WK Furnari, FB DePinho, RA AF Carrasco, DR Fenton, T Sukhdeo, K Protopopova, M Enos, M You, MJJ Divicio, D Nogueira, C Stommel, J Pinkus, GS Fletcher, C Hornick, JL Cavenee, WK Furnari, FB DePinho, RA TI The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans SO CANCER CELL LA English DT Article ID ARF-DEFICIENT MICE; PROMOTER HYPERMETHYLATION; LYMPHOID NEOPLASMS; PROSTATE-CANCER; B-CELL; T-CELL; GENE; P16(INK4A); P19(ARF); ACTIVATION AB Histiocytic sarcoma (HS) is a rare malignant proliferation of histiocytes of uncertain molecular pathogenesis. Here, genetic analysis of coincident loss of Pten and Ink4a/Arf tumor suppressors in the mouse revealed a neoplastic phenotype dominated by a premalignant expansion of biphenotypic myelolymphoid cells followed by the development of HS. Pten protein loss occurred only in the histiocytic portion of tumors, suggesting a stepwise genetic inactivation in the generation of HS. Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS. These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, Ludwig Inst Canc Res, Sch Med, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Belfer Fdn Inst Innovat Canc Sc, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu RI Nogueira, Cristina/N-4574-2015; OI Nogueira, Cristina/0000-0002-0853-5304; Sukhdeo, Kumar /0000-0001-8725-6081; Fenton, Tim/0000-0002-4737-8233 FU NCI NIH HHS [U01 CA84313, P01 CA95616]; NIA NIH HHS [K08 AG0103] NR 52 TC 35 Z9 35 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2006 VL 9 IS 5 BP 379 EP 390 DI 10.1016/j.ccr.2006.03.028 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 044RA UT WOS:000237688800008 PM 16697958 ER PT J AU Smith, R Owen, LA Trem, DJ Wong, JS Jennifer, SW Golub, TR Lessnick, SL AF Smith, R Owen, LA Trem, DJ Wong, JS Jennifer, SW Golub, TR Lessnick, SL TI Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma SO CANCER CELL LA English DT Article ID DNA-BINDING; FUSION PROTEIN; TRANSCRIPTION FACTOR; MIC2 EXPRESSION; FAMILY TUMORS; GROWTH-FACTOR; CELLS; DOMAIN; DIFFERENTIATION; TRANSFORMATION AB Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin. To circumvent this, we analyzed the function of EWS/FLI in Ewing's sarcoma itself. By combining retroviral-mediated RNA interference with reexpression studies, we show that ongoing EWS/FLI expression is required for the tumorigenic phenotype of Ewing's sarcoma. We used this system to define the full complement of EWS/FLI-regulated genes in Ewing's sarcoma. Functional analysis revealed that NKX2.2 is an EWS/FLI-regulated gene that is necessary for oncogenic transformation in this tumor. Thus, we developed a highly validated transcriptional profile for the EWS/FL1 fusion protein and identified a critical target gene in Ewing's sarcoma development. C1 Univ Utah, Huntsman Canc Inst, Ctr Children, Salt Lake City, UT 84112 USA. Univ Utah, Dept Oncol Sci, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Univ Utah, Sch Med, Div Pediat Hematol Oncol, Salt Lake City, UT 84112 USA. RP Lessnick, SL (reprint author), Univ Utah, Huntsman Canc Inst, Ctr Children, Salt Lake City, UT 84112 USA. EM stephen.lessnick@hci.utch.edu FU NCI NIH HHS [K08 CA096755, K08 CA096755-05, K08 CA96755]; NICHD NIH HHS [T32 HD007491] NR 48 TC 170 Z9 180 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAY PY 2006 VL 9 IS 5 BP 405 EP 416 DI 10.1016/j.ccr.2006.04.004 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 044RA UT WOS:000237688800010 PM 16697960 ER PT J AU Levy, AG Micco, E Putt, M Armstrong, K AF Levy, AG Micco, E Putt, M Armstrong, K TI Value for the future and breast cancer-preventive health behavior SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TIME-PREFERENCES; RACIAL-DIFFERENCES; DELAYED REWARDS; RISK; WOMEN; MAMMOGRAPHY; RACE; AGE; ADHERENCE; OLDER AB Background: Time preference, or the extent to which people discount future benefits in favor of immediate benefits, might represent an important determinant of preventive health behavior, but the little research thus far on this association has yielded mixed results. This study examined the association between future time preference and use of genetic counseling for BRCA1/2 testing and how this association may differ from the relationship between future time preference and mammography screening and self-breast examination. Experimental Design: A health system-based case-control study with a nested cross-sectional survey. Eight hundred women who saw a primary care physician in the University of Pennsylvania Health System in the 3 years before the study, of whom 234 had undergone BRCA1/2 counseling (cases) and of whom 566 had not (controls). Results: Placing a relatively greater value on future benefits than present benefits was strongly associated with use of BRCA1/2 counseling [odds ratio (OR), 3.0 for one-point increase in future time preference; 95% confidence intervals (0), 1.9-4.9]. Future time preference was weakly associated with adherence to annual mammography (OR, 1.3; 95% Cl, 0.81-2.2), and was not associated with monthly self-breast examination (OR, 1.03; 95% Cl, 0.75-1.4). A stronger future orientation was seen in women who had higher levels of education (P = 0.0021) or income (P = 0.0011). Conclusion: Time preference is strongly associated with use of BRCA1/2 counseling. Time preference is more weakly associated with mammography adherence and is not associated with breast self-examination. This variation may reflect the degree to which the behavior is seen as related to future risk. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02446 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Levy, AG (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,253 Smith Bldg, Boston, MA 02446 USA. EM andrea_gurmankin@dfci.harvard.edu NR 36 TC 12 Z9 12 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2006 VL 15 IS 5 BP 955 EP 960 DI 10.1158/1055-9965.EPI-05-0169 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200020 ER PT J AU Haiman, CA Stram, DO Cheng, I Giorgi, EE Pooler, L Penney, K Le Marchand, L Henderson, BE Freedman, ML AF Haiman, CA Stram, DO Cheng, I Giorgi, EE Pooler, L Penney, K Le Marchand, L Henderson, BE Freedman, ML TI Common genetic variation at PTEN and risk of sporadic breast and prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MULTIETHNIC COHORT; REDUCED EXPRESSION; INACTIVATION; PTEN/MMAC1; PATHWAY AB PTEN frequently shows loss of heterozygosity in breast and prostate cancers, and mutations in this gene are responsible for Cowden disease, a rare Mendelian syndrome that includes breast cancer as part of its phenotype. Thus, PTEN serves as a candidate susceptibility gene for both breast and prostate cancer risk. Whether common inherited variation (either coding or noncoding) at the PTEN locus contribute to nonfamilial, sporadic breast and prostate cancer risk is not known. In this study, we employed a linkage disequilibrium-based approach to test for association between common genetic variation at the PTEN locus and breast and prostate cancer risk in African-American, Native Hawaiian, Japanese, Latina, and White men and women in the Multiethnic Cohort Study. We genotyped 17 common single nucleotide polymorphisms (SNP; >= 5% frequency in at least one ethnic group) spanning the PTEN gene to define the common alleles in these populations. These SNPs were in strong linkage disequilibrium, indicating that our survey captured most of the common sequence variation across this locus. Eight tagging SNPs were selected to predict the common PTEN haplotypes (>= 0.05 frequency) in these populations (two additional tagging SNPs were required for African Americans). These SNPs were evaluated in a breast cancer case-control study (cases, n = 1,615; controls, n 1,962) and prostate cancer case-control study (cases, it 2,320; controls, n = 2,290) nested within the Multiethnic Cohort Study. Multiple testing was explicitly accounted for by applying a permutation-based framework. We found no strong association with any common haplotype in relation to breast or prostate cancer risk. In summary, our results show that common variants in PTEN do not substantially influence risk of these two common cancers. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. MIT, Broad Inst, Cambridge, MA USA. Harvard Univ, Cambridge, MA USA. Univ Hawaii, Etiol Program, Canc Res Ctr Hawaii, Honolulu, HI 96822 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Haiman, CA (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Room 4441,1441 Eastlake Ave, Los Angeles, CA 90089 USA. EM Haimin@usc.edu NR 19 TC 19 Z9 22 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2006 VL 15 IS 5 BP 1021 EP 1025 DI 10.1158/1055-9965.EPI-05-0896 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 044ZU UT WOS:000237713200030 PM 16702386 ER PT J AU Young, MRI Cigal, M AF Young, MRI Cigal, M TI Tumor skewing of CD34(+) cell differentiation from a dendritic cell pathway into endothelial cells SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE angiogenesis; angiopoietins; endothelial cells; tumor; vasculogenesis; VEGF ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; IMMUNE SUPPRESSOR CELLS; LEWIS LUNG-CARCINOMA; NECK-CANCER PATIENTS; GROWTH-FACTOR; PERIPHERAL-BLOOD; CLINICAL-SIGNIFICANCE; INDUCED MOBILIZATION; HEAD AB Patients and animals bearing tumors have increased levels of CD34(+) progenitor cells, which are capable of developing into dendritic cells. However, addition of medium conditioned by murine Lewis lung carcinoma cells increases the cellularity of the CD34(+) cell cultures and redirects their differentiation into endothelial cells. The resulting cells resemble endothelial cells phenotypically as well as functionally by their capacity to reorganize into cord structures. Mechanisms by which tumors induced the increased cellularity and skewing toward endothelial cells were examined. Tumor-derived VEGF contributed to the increase in cellularity, but not to the redirection of differentiation. Differentiation into endothelial cells was blocked with sTie-2, suggesting tumor-derived angiopoietins in skewing differentiation. These studies show the capacity of tumors to skew progenitor cell development toward endothelial cells and define the mediators that contribute to endothelial cell development. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29401 USA. RP Young, MRI (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM rita.young@med.va.gov FU NCI NIH HHS [CA85266, CA97813] NR 37 TC 13 Z9 16 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAY PY 2006 VL 55 IS 5 BP 558 EP 568 DI 10.1007/s00262-005-0036-3 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 021HD UT WOS:000235973400008 PM 16025265 ER PT J AU Farazi, PA Glickman, J Horner, J DePinho, RA AF Farazi, PA Glickman, J Horner, J DePinho, RA TI Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression SO CANCER RESEARCH LA English DT Article ID ORGAN HOMEOSTASIS; DNA-DAMAGE; MICE; DEFICIENCY; GENE; CARCINOGENESIS; TUMORIGENESIS; CANCER; MOUSE; PROLIFERATION AB Hepatocellular carcinoma is among the most common and lethal cancers in humans. Hepatocellular carcinoma is commonly associated with physical or functional inactivation of the p53 tumor suppressor, high levels of chromosomal instability, and disease conditions causing chronic cycles of hepatocyte death and regeneration. Mounting evidence has implicated regeneration-induced telomere erosion as a potential mechanism fueling genome instability. In mouse models of hepatocellular carcinoma, telomere dysfunction has been shown to enhance initiation of hepatic neoplasias yet constrain full malignant progression of these neoplasms possibly due to activation of a p53-dependent checkpoint and/or intolerable levels of genomic instability. Here, in a hepatocellular carcinoma-prone model brought about through toxin-induced hepatocyte injury and regeneration, we sought to determine the cooperative interactions of germ line p53 mutation and telomere dysfunction [produced by telomerase reverse transcriptase (mTERT) gene knockout]. In the setting of intact telomeres, p53 mutation had no effect on hepatocarcinogenesis, whereas in the setting of telomere dysfunction, p53 mutation enabled advanced hepatocellular carcinoma disease. Notably, there was no evidence of deletion or mutation of the wild-type p53 allele in the late generation mTert(-/-)p53(+/-) mice, suggesting that reduced levels of p53 potently enable hepatocellular carcinoma progression in the setting of telomere dysfunction. Thus, this study supports a model that, in the face of chronic liver damage, attenuated p53 function and telomere-induced chromosomal instability play critical and cooperative roles in the progression of hepatocellular carcinoma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Med & Genet, Boston, MA 02115 USA. Harvard Univ, Dept Genet, Div Med Sci, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M413, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu FU NCI NIH HHS [U01 CA84313] NR 41 TC 58 Z9 59 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2006 VL 66 IS 9 BP 4766 EP 4773 DI 10.1158/0008-5472.CAN-05-4608 PG 8 WC Oncology SC Oncology GA 041ZS UT WOS:000237496900029 PM 16651430 ER PT J AU Andreassen, PR Ho, GPH D'Andrea, AD AF Andreassen, PR Ho, GPH D'Andrea, AD TI DNA damage responses and their many interactions with the replication fork SO CARCINOGENESIS LA English DT Review ID SISTER-CHROMATID COHESION; S-PHASE CHECKPOINT; NUCLEOTIDE EXCISION-REPAIR; XENOPUS EGG EXTRACTS; STRAND-BREAK REPAIR; HOLLIDAY JUNCTION RESOLVASE; CELL NUCLEAR ANTIGEN; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE AB The cellular response to DNA damage is composed of cell cycle checkpoint and DNA repair mechanisms that serve to ensure proper replication of the genome prior to cell division. The function of the DNA damage response during DNA replication in S-phase is critical to this process. Recent evidence has suggested a number of interrelationships of DNA replication and cellular DNA damage responses. These include S-phase checkpoints which suppress replication initiation or elongation in response to DNA damage. Also, many components of the DNA damage response are required either for the stabilization of, or for restarting, stalled replication forks. Further, translesion synthesis permits DNA replication to proceed in the presence of DNA damage and can be coordinated with subsequent repair by homologous recombination (HR). Finally, cohesion of sister chromatids is established coincident with DNA replication and is required for subsequent DNA repair by homologous recombination. Here we review these processes, all of which occur at, or are related to, the advancing replication fork. We speculate that these multiple interdependencies of DNA replication and DNA damage responses integrate the many steps necessary to ensure accurate duplication of the genome. C1 Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Andreassen, PR (reprint author), Childrens Hosp, Med Ctr, Div Expt Hematol, 3333 Burnet Ave ML 7013, Cincinnati, OH 45229 USA. EM Paul.Andreassen@cchmc.org NR 139 TC 73 Z9 75 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2006 VL 27 IS 5 BP 883 EP 892 DI 10.1093/carcin/bgi319 PG 10 WC Oncology SC Oncology GA 037UN UT WOS:000237172900001 PM 16490739 ER PT J AU Su, L Zhou, W Asomaning, K Lin, XH Wain, JC Lynch, TJ Liu, G Christiani, DC AF Su, L Zhou, W Asomaning, K Lin, XH Wain, JC Lynch, TJ Liu, G Christiani, DC TI Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cancer SO CARCINOGENESIS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; MATRIX METALLOPROTEINASE-12; PROMOTER POLYMORPHISM; UNRELATED INDIVIDUALS; EXPRESSION; SMOKING; DISEASE; SUSCEPTIBILITY; ASSOCIATIONS; CARCINOMA AB The MMPs (matrix metalloproteinases) are a family of secreted zinc metalloproteases that degrade the collagens of the extracellular matrix important in tissue remodeling and repair during development and inflammation. We investigated the associations between polymorphisms of MMP-1 (-1607 1G/2G, rs1799750), MMP-3 (-1171 5A/6A, rs3025058), and MMP-12 (-82AG, rs2276109, and 1082A/G, rs652438) and the risk of lung cancer in 2014 Caucasian lung cancer patients and 1323 healthy controls. The results were analyzed using logistic regression models, adjusting for covariates. The four polymorphisms were in Hardy-Weinberg disequilibrium. Except for the 1G-1082A, the other linkage disequilibrium tests between the four MMP polymorphisms were statistically significant (P < 0.001). There was no overall association between individual MMP polymorphism and the risk of lung cancer. The MMP polymorphisms jointly were associated with a non-statistically significant higher risk of lung cancer, with the adjusted odds ratio (AOR) of subjects with 5+ variant alleles versus zero variant allele of 1.31 [95% confidence interval (CI), 0.92-1.88]. Stronger associations were observed in never-smokers and males, with the corresponding AORs of 2.44 (95%CI, 1.10-5.43, P-trend = 0.04) in never smokers and 1.35 (95%CI, 0.79-2.30, P-trend = 0.04) in men. In haplotype analysis, the 1G-6A-82A-1082G haplotype was associated with higher risk of lung cancer among never smokers, with the AOR of 3.65 (95%CI, 1.62-8.20) when compared with the most common 1G-5A-82A-1082A haplotype. In conclusion, the combined MMP genotypes and associated haplotypes may be associated with higher risk of lung cancer, particularly among never smokers and men. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thorac Surg Unit,Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA90578, CA74386, ES/CA 06409]; NIEHS NIH HHS [ES00002] NR 29 TC 58 Z9 63 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2006 VL 27 IS 5 BP 1024 EP 1029 DI 10.1093/carcin/bgi283 PG 6 WC Oncology SC Oncology GA 037UN UT WOS:000237172900017 PM 16311244 ER PT J AU Rocco, JW Ellisen, LW AF Rocco, JW Ellisen, LW TI p63 and p73 - Life and death in squamous cell carcinoma SO CELL CYCLE LA English DT Article DE p63; p73; p53; squamous cell carcinoma; HNSCC; apoptosis; RNA interference; chemotherapy ID P53 HOMOLOG; DNA-DAMAGE; P73-DEPENDENT APOPTOSIS; TUMOR-SUPPRESSOR; GENE PROMOTERS; MUTANT P53; EXPRESSION; FAMILY; DELTA-NP63-ALPHA; TARGET AB The p53 family member p63 plays an essential role in the developing epithelium, and overexpression of the Delta Np63 alpha isoform is frequently observed in human squamous cell carcinomas (SCCs). These findings have suggested that Delta Np63 alpha might function as an oncogene within squamous epithelial cells. Nevertheless, the mechanism by which Delta Np63 alpha might promote tumorigenesis remains poorly understood, and data from mouse models implies that the p63 locus might in fact function as a tumor suppressor in these same tissues. A recent study using RNA interference in human SCC-derived cell lines shows that Delta Np63 alpha mediates an essential survival function in human SCC cells by virtue of its ability to suppress the pro-apoptotic function of the related p53 family member p73. These findings support an oncogenic role for Delta Np63 alpha and they demonstrate the existence of critical physical and functional interactions between endogenous p53 family members in human cancer. Specific chemotherapeutic agents and future targeted approaches may be able to exploit this pathway to therapeutic advantage. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, GRJ-904,55 Fruit St, Boston, MA 02114 USA. EM ellisen@helix.mgh.harvard.edu FU NIDCR NIH HHS [R01 DE015945] NR 50 TC 24 Z9 24 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2006 VL 5 IS 9 BP 936 EP 940 DI 10.4161/cc.5.9.2716 PG 5 WC Cell Biology SC Cell Biology GA 057DC UT WOS:000238575200007 PM 16687923 ER PT J AU Pasparakis, M Luedde, T Schmidt-Supprian, M AF Pasparakis, M Luedde, T Schmidt-Supprian, M TI Dissection of the NF-kappa B signalling cascade in transgenic and knockout mice SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE gene targeting; NF-kappa B signalling; transgenic mice ID TUMOR-NECROSIS-FACTOR; INDUCED INSULIN-RESISTANCE; SEVERE LIVER DEGENERATION; T-LYMPHOCYTE DEVELOPMENT; BETA LINKS INFLAMMATION; GAMMA-DEFICIENT MICE; IKK-BETA; IN-VIVO; TNF-ALPHA; CELL DEVELOPMENT AB Studies in transgenic and knockout mice have made a major contribution to our current understanding of the physiological functions of the NF-kappa B signalling cascade. The generation and analysis of mice with targeted modifications of individual components of the NF-kappa B pathway tremendously advanced our knowledge of the roles of the NF-kappa B proteins themselves, and also of the many activators and negative regulators of NF-kappa B. These studies have highlighted the complexity of the NF-kappa B system, by revealing the multiple interactions, redundancies, but also diverse functions, performed by the different molecules participating in the regulation of NF-kappa B signalling. Furthermore, inhibition or enforced activation of NF-kappa B in transgenic mice has uncovered the critical roles that NF-kappa B plays in the pathogenesis of various diseases such as liver failure, diabetes and cancer. C1 EMBL, Mouse Biol Unit, I-00016 Monterotondo, Italy. Univ Cologne, Genet Inst, Cologne, Germany. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Pasparakis, M (reprint author), EMBL, Mouse Biol Unit, Via Ramarini 32, I-00016 Monterotondo, Italy. EM pasparakis@embl-monterotondo.it RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Pasparakis, Manolis/0000-0002-9870-0966 NR 99 TC 90 Z9 92 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAY PY 2006 VL 13 IS 5 BP 861 EP 872 DI 10.1038/sj.cdd.4401870 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034OG UT WOS:000236938300019 PM 16470223 ER PT J AU Uldry, M Yang, WL St-Pierre, J Lin, JD Seale, P Spiegelman, BM AF Uldry, Marc Yang, Wenli St-Pierre, Julie Lin, Jiandie Seale, Patrick Spiegelman, Bruce M. TI Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation SO CELL METABOLISM LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; UNCOUPLING PROTEIN GENE; ADIPOSE-TISSUE; ADAPTIVE THERMOGENESIS; PPAR-GAMMA; ENERGY-METABOLISM; RETINOIC ACID; C/EBP-ALPHA; IN-VITRO; EXPRESSION AB Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1 alpha. We could then efficiently knockdown PGC-1 beta expression by shRNA expression. Loss of PGC-1 alpha did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1 alpha or PGC-1 beta coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1 alpha and PGC-1 beta were deficient. These data show that PGC-1 alpha is essential for brown fat thermogenesis but not brown fat differentiation, and the PGC-1 coactivators play an absolutely essential but complementary function in differentiation-induced mitochondrial biogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [1K01 DK 065584, DK 54477, DK 61562, R01 DK 060837] NR 37 TC 285 Z9 305 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY PY 2006 VL 3 IS 5 BP 333 EP 341 DI 10.1016/j.cmet.2006.04.002 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 044CP UT WOS:000237650200006 PM 16679291 ER PT J AU Taniguchi, CM Kondo, T Sajan, M Luo, J Bronson, R Asano, T Farese, R Cantley, LC Kahn, CR AF Taniguchi, CM Kondo, T Sajan, M Luo, J Bronson, R Asano, T Farese, R Cantley, LC Kahn, CR TI Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKC lambda/zeta SO CELL METABOLISM LA English DT Article ID PROTEIN-KINASE-C; INCREASED INSULIN SENSITIVITY; MICE LACKING; EMBRYONIC LETHALITY; SIGNALING PATHWAYS; LIVER; ACTIVATION; SUBUNIT; P85-ALPHA; RECEPTOR AB Although the class I-A phosphoinositide 3-kinase (PI3K) pathway is central to the metabolic actions of insulin, its mechanism of action is not well understood. To identify the role of the PI3K pathway in insulin regulation of hepatic function, we ablated the expression of both major regulatory subunits of PI3K by crossing mice lacking Pik3r1 in liver with Pik3r2 null mice, creating liver-specific double knockout mice (L-p85DKO). L-p85DKO mice failed to activate PI3K or generate PIP3 upon insulin stimulation or activate its two major effectors, Akt and PKC lambda/xi. Decreased Akt activation resulted in increased gluconeogenic gene expression, impaired glucose tolerance, and hyperinsulinemia, while the defective activation of PKC lambda/xi by insulin was associated with hypolipidemia and decreased transcription of SREBP-1c. These data indicate that the PI3K pathway is critical for insulin's actions in the liver in vivo, and that differential regulation by Akt and PKC lambda/xi differentially defines specific actions of insulin and PI3K on hepatic glucose and lipid metabolism. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Kumamoto Univ, Grad Sch Med Sci, Dept Metab Med, Kumamoto, Japan. Univ S Florida, Coll Med, Tampa, FL 33612 USA. Univ Tokyo, Fac Med, Dept Internal Med 3, Tokyo 113, Japan. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA 089021]; NIDDK NIH HHS [DK 33201, DK 34834, DK 55545]; NIGMS NIH HHS [GM 41890, R01 GM041890] NR 34 TC 152 Z9 162 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY PY 2006 VL 3 IS 5 BP 343 EP 353 DI 10.1016/j.cmet.2006.04.005 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 044CP UT WOS:000237650200007 PM 16679292 ER PT J AU Luo, J Sobkiw, CL Hirshman, MF Logsdon, MN Li, TQ Goodyear, LJ Cantley, LC AF Luo, Ji Sobkiw, Cassandra L. Hirshman, Michael F. Logsdon, M. Nicole Li, Timothy Q. Goodyear, Laurie J. Cantley, Lewis C. TI Loss of class I(A)PI3K signaling in muscle leads to impaired muscle growth, insulin response, and hyperlipidemia SO CELL METABOLISM LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE PATHWAY; FOXO TRANSCRIPTION FACTORS; LHERMITTE-DUCLOS-DISEASE; P85 REGULATORY SUBUNIT; MICE LACKING; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3'-KINASE; TARGETED DISRUPTION; GLUCOSE-HOMEOSTASIS; CARDIAC-HYPERTROPHY AB The evolutionarily conserved phosphoinositide 3-kinase (PI3K) signaling pathway mediates both the metabolic effects of insulin and the growth-promoting effects of insulin-like growth factor-1 (IGF-1). We have generated mice deficient in both the p85 alpha/p55 alpha/p50 alpha and the p85 beta regulatory subunits of class I-A PI3K in skeletal muscles. PI3K signaling in the muscle of these animals is severely impaired, leading to a significant reduction in muscle weight and fiber size. These mice also exhibit muscle insulin resistance and whole-body glucose intolerance. Despite their ability to maintain normal fasting and fed blood glucose levels, these mice show increased body fat content and elevated serum free fatty acid and triglyceride levels. These results demonstrate that in vivo p85 is a critical mediator of class I-A PI3K signaling in the regulation of muscle growth and metabolism. Our finding also indicates that compromised muscle PI3K signaling could contribute to symptoms of hyperlipidemia associated with human type 2 diabetes. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA 089021]; NIAMS NIH HHS [AR 42238]; NIDDK NIH HHS [DK 068626]; NIGMS NIH HHS [GM 41890, R01 GM041890] NR 51 TC 46 Z9 50 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAY PY 2006 VL 3 IS 5 BP 355 EP 366 DI 10.1016/j.cmet.2006.04.003 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 044CP UT WOS:000237650200008 PM 16679293 ER PT J AU Bradner, JE McPherson, OM Mazitschek, R Barnes-Seeman, D Shen, JP Dhaliwal, J Stevenson, KE Duffner, JL Park, SB Neuberg, DS Nghiem, P Schreiber, SL Koehler, AN AF Bradner, JE McPherson, OM Mazitschek, R Barnes-Seeman, D Shen, JP Dhaliwal, J Stevenson, KE Duffner, JL Park, SB Neuberg, DS Nghiem, P Schreiber, SL Koehler, AN TI A robust small-molecule microarray platform for screening cell lysates SO CHEMISTRY & BIOLOGY LA English DT Article ID DIVERSITY-ORIENTED SYNTHESIS; PEPTIDYL-PROLYL ISOMERASE; GLASS SLIDES; CARBOHYDRATE MICROARRAYS; IMMUNOSUPPRESSANT FK506; PROTEIN; IMMOBILIZATION; LIGANDS; ARRAYS; DISCOVERY AB Herein we report the expanded functional group compatibility of small-molecule microarrays to include immobilization of primary alcohols, secondary alcohols, phenols, carboxylic acids, hydroxamic acids, thiols, and amines on a single slide surface. Small-molecule "diversity microarrays" containing nearly 10,000 known bioactive small molecules, natural products, and small molecules originating from several diversity-oriented syntheses were produced by using an isocyanate-mediated covalent capture strategy. Selected printed bioactive compounds were detected with antibodies against compounds of interest. The new surface of the diversity microarrays is highly compatible with approaches involving cellular lysates. This feature has enabled a robust, optimized screening methodology using cellular lysates, allowing the detection of specific interactions with a broad range of binding affinity by using epitope-tagged or chimeric fluorescent proteins without prior purification. We believe that this expanded research capability has considerable promise in biology and medicine. C1 Broad Inst Harvard, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Dept Chem & Chem Biol, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Schreiber, SL (reprint author), Broad Inst Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM stuart_schreiber@harvard.edu; koehler@fas.harvard.edu RI Mazitschek, Ralph/E-3741-2013; Park, Seung Bum/N-1901-2014; Nghiem, Paul/A-9210-2011; OI Mazitschek, Ralph/0000-0002-1105-689X; Park, Seung Bum/0000-0003-1753-1433; Nghiem, Paul/0000-0003-2784-963X; Shen, John Paul/0000-0003-4588-2775 FU NIAMS NIH HHS [R01-AR049832]; NIGMS NIH HHS [GM38627] NR 37 TC 85 Z9 86 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD MAY PY 2006 VL 13 IS 5 BP 493 EP 504 DI 10.1016/j.chembiol.2006.03.004 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 049AU UT WOS:000237988600007 PM 16720270 ER PT J AU Bouazoune, K Brehm, A AF Bouazoune, Karim Brehm, Alexander TI ATP-dependent chromatin remodeling complexes in Drosophila SO CHROMOSOME RESEARCH LA English DT Review DE chromatin; DNA replication; Drosophila; nucleosome remodeling; SNF2 superfamily; transcription ID TRITHORAX GROUP PROTEINS; NOTCH SIGNALING PATHWAY; YEAST SWI/SNF COMPLEX; DNA-BINDING-PROTEIN; RNA-POLYMERASE-II; TARGET GENES; TRANSCRIPTIONAL ACTIVATION; IN-VIVO; METHYLTRANSFERASE ACTIVITY; NUCLEOSOME MOBILIZATION AB The regulation of chromatin structure is of fundamental importance for many DNA-based processes in eukaryotes. Activation or repression of gene transcription or DNA replication depends on enzymes which can generate the appropriate chromatin environment. Several of these enzymes utilize the energy of ATP hydrolysis to alter nucleosome structure. In recent years our understanding of the multisubunit complexes within which they function, their mechanisms of action, their regulation and their in-vivo roles has increased. Much of what we have learned has been gleaned from studies in Drosophila melanogaster. Here we will review what we know about the main classes of ATP-dependent chromatin remodelers in Drosophila. C1 Univ Marburg, Inst Mol Biol & Tumorforsch, D-35055 Marburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Brehm, A (reprint author), Univ Marburg, Inst Mol Biol & Tumorforsch, Emil Mannkopff Str 2, D-35055 Marburg, Germany. EM brehm@imt.uni-marburg.de NR 145 TC 47 Z9 47 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAY PY 2006 VL 14 IS 4 BP 433 EP 449 DI 10.1007/s10577-006-1067-0 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 060VQ UT WOS:000238830100009 PM 16821138 ER PT J AU Beer, TM Garzotto, M Park, B Mori, M Myrthue, A Janeba, N Sauer, D Eilers, K AF Beer, TM Garzotto, M Park, B Mori, M Myrthue, A Janeba, N Sauer, D Eilers, K TI Effect of calcitriol on prostate-specific antigen in vitro and in humans SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER CELL-LINES; VITAMIN-D ANALOGS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; ANDROGEN RECEPTOR; GROWTH-INHIBITION; LNCAP CELLS; CARCINOMA; PROLIFERATION; EXPRESSION; INDUCTION AB Background: Calcitriol, the natural ligand for the vitamin D receptor, has significant potential in Prostate cancer treatment. Measurement of its antineoplastic activity in prostate cancer clinical trials may be complicated by effects of calcitriol on prostate-specific antigen (PSA) production. We examined the effects of calcitriol at similar concentration on cell proliferation, androgen receptor (AR) expression, and PSA production in vitro and on PSA concentrations in prostate cancer patients. Experimental Design: LNCaP prostate cancer cell proliferation was examined by cell counts 6 days after exposure to a range of concentrations of calcitriol. AR and PSA protein was quantified in LNCaP cells over 96 hours after exposure to 1 nmol/L calcitriol. Serum PSA and free PSA was serially measured by immunoassay over a period of 8 days in patients with hormone-naive prostate cancer after a single dose of 0.5 mu g/kg calcitriol. Results: Calcitriol treatment resulted in dose-dependent growth inhibition of LNCaP with similar to 50% growth inhibition at the clinically achievable concentration of 1 nmol/L. Time-dependent up-regulation of AR expression and of PSA production in LNCaP cells was shown at the same concentration. No significant change in serum PSA or free PSA over 8 days was seen in eight subjects treated with a single dose of 0.5 mu g/kg calcitriol. The analysis was powered to detect a 1.23-fold change between the baseline and day 8 serum PSA. Conclusions: At clinically achievable concentrations, calcitriol inhibits growth and induces AR and PSA expression in LNCaP cells. We did not detect similar changes in serum PSA or free PSA in patients exposed to similar concentrations of calcitriol. Thus, a PSA flare, predicted by preclinical systems, is unlikely to occur in patients and therefore unlikely to complicate interpretation of clinical trial outcomes. C1 Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Div Urol, Portland, OR USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, CR-145,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM beert@ohsu.edu OI /0000-0003-3516-7516 FU NCI NIH HHS [5 R21 CA85585-02]; NCRR NIH HHS [5 M01 RR00334-33S2] NR 26 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2006 VL 12 IS 9 BP 2812 EP 2816 DI 10.1158/1078-0432.CCR-05-2310 PG 5 WC Oncology SC Oncology GA 041GI UT WOS:000237441900021 PM 16675575 ER PT J AU Varghese, S Rabkin, SD Nielsen, PG Wang, WZ Martuza, RL AF Varghese, S Rabkin, SD Nielsen, PG Wang, WZ Martuza, RL TI Systemic oncolytic herpes virus therapy of poorly immunogenic prostate cancer metastatic to lung SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; MHC CLASS-I; SIMPLEX-VIRUS; REPLICATION-COMPETENT; MALIGNANT GLIOMA; CELL CARCINOMA; GENE-THERAPY; INTERLEUKIN-12; IMMUNITY; MOUSE AB Purpose: Our goal was to evaluate whether systemic administration of NV1042, an interleukin-12 (IL-12) -expressing oncolytic herpes simplex virus, and its noncytokine parental vector NV1023 are effective against preexisting metastatic prostate cancer in an immunocompetent mice model. Experimental Design: Metastatic TRAMP-C2 lung tumors established in C57Bl/6 or nude mice were treated on day 21 with four i.v. administrations of NV1042 or NV1023 and sacrificed on day 42 to assess virus efficacy and the potential mechanism of efficacy. Results: NV1042 or NV1023 treatment was similarly effective in eliminating extrapleural and hemorrhagic tumors present in mock-treated mice. However, NV1042 was further effective compared with NV1023 in controlling the growth of lung tumors (as determined by mean surface tumor nodule number, lung weights, and surface tumor burden) and in extending survival. NV1042-treated mice exhibited a transient increase of serum IL-12 1 day posttreatment, whereas IL-12 levels in tumor bearing lungs persisted a further 2 days at least. Only splenocytes from NV1042-treated mice secreted IFN-gamma in response to TRAMP-C2 stimulation and displayed natural killer activity. The IL-12-mediated enhancement observed with NV1042 in the syngeneic model was abrogated in athymic mice treated in a similar manner, thus indicating a role for T cells in the augmented efficacy of NV1042 virus. Conclusions: Systemic administration of the IL-12-expressing NV1042 virus is more effective than its noncytokine parent, NV1023, against preestablished metastatic lung tumors. Given the clinical safety profile of NV1020, the parental vector of NV1023, and NV1042s enhanced efficacy and ability to activate the host immune system, NV1042 merits clinical consideration for treating metastatic prostate cancers. C1 Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Simches Res Ctr, 185 Cambridge St,CPZN-3800, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [1R01CA102139] NR 38 TC 21 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2006 VL 12 IS 9 BP 2919 EP 2927 DI 10.1158/1078-0432.CCR-05-1187 PG 9 WC Oncology SC Oncology GA 041GI UT WOS:000237441900035 PM 16675589 ER PT J AU Wilkinson, CW Raff, H AF Wilkinson, CW Raff, H TI Comparative evaluation of a new immunoradiometric assay for corticotropin SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE corticotropin; diagnostic techniques and procedures; immunoradiometric assay (IRMA); sensitivity and specificity AB We have characterized the performance of a commercial two-site immunoradiometric assay for manual in vitro diagnostic measurement of plasma corticotropin from Scantibodies Laboratory. We compared the results with those of a similar commonly used assay from Nichols Institute Diagnostics that has recently been withdrawn from production. The lower detection limit, range of the standard curve, cross-reactivity, and intra-assay and inter-assay imprecision of the two assays are very similar. Measurement of clinical samples and a series of samples from an experimental subject demonstrate high correlations between the two assays. These factors, together with recent clearance by the United States Food and Drug Administration for manual in vitro diagnostic measurement, make the Scantibodies corticotropin immunoradiometric assay an appropriate replacement for the Nichols assay. C1 VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Med Coll Wisconsin, St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI 53226 USA. RP Wilkinson, CW (reprint author), VA Puget Sound Hlth Care Syst, GRECC, S-182,1660 S Columbian Way, Seattle, WA 98108 USA. EM wilkinso@u.washington.edu NR 2 TC 13 Z9 13 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD MAY PY 2006 VL 44 IS 5 BP 669 EP 671 DI 10.1515/CCLM.2006.113 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 050YB UT WOS:000238125300027 PM 16681443 ER PT J AU Meyerhardt, JA Heseltine, D Ogino, S Clark, JW Enzinger, PC Ryan, DP Earle, CC Zhu, AX Fuchs, CS AF Meyerhardt, Jeffrey A. Heseltine, Denise Ogino, Shuji Clark, Jeffrey W. Enzinger, Peter C. Ryan, David P. Earle, Craig C. Zhu, Andrew X. Fuchs, Charles S. TI Efficacy of cetuximab after treatment with oral epidermal growth factor receptor tyrosine kinase inhibitor-based chemotherapy in metastatic colorectal cancer SO CLINICAL COLORECTAL CANCER LA English DT Article DE erlotinib; 5-fluorouracil; gefitinib; irinotecan; oxaliplatin ID CELL LUNG-CANCER; PHASE-II TRIAL; PREVIOUSLY TREATED PATIENTS; EGFR MUTATIONS; GEFITINIB; THERAPY; MALIGNANCIES; ERLOTINIB; TARGETS; TUMORS AB Purpose: We studied the efficacy of cetuximab therapy in patients with metastatic colorectal cancer (mCRC) previously treated with an oral inhibitor of the tyrosine kinase domain of the epidermal growth factor receptor. Patients and Methods: We reviewed the posttrial records of 73 patients with mCRC who participated in I of 3 clinical trials that examined a combination of gefitinib or erlotinib with standard cytotoxic chemotherapy. Medical and pharmacy records were used to identify patients who were subsequently treated with cetuximab-based therapy. Computed tomography scans during cetuximab-based therapy were reviewed, and the clinical activity of cetuximab was assessed by response rate using Response Evaluation Criteria in Solid Tumors and progression-free survival. Results: Twenty-four patients with mCRC previously treated with gefitinib or erlotinib and combination cytotoxic chemotherapy who subsequently received cetuximab-based therapy were identified. While receiving cetuximab-based therapy, no patient experienced a partial or complete response; however, 3 patients (16% of patients with available scans for formal measurements) had a minor response, defined as a 15%-29.9% decrease in the sum of longest dimensions of target lesions, and 72% had stable disease. The progression-free survival was 5.1 months for all patients and 6 months for patients who had documented progression of disease while previously receiving gefitinib- or erlotinib-based therapy. Conclusion: Cetuximab appears to have clinical benefit in patients with mCRC previously treated with a chemotherapy regimen that included an oral tyrosine kinase inhibitor of epidermal growth factor receptor. Whether these results apply to other cancer types is unknown but worthy of further study. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org FU NCI NIH HHS [1K07CA097992-01A1] NR 32 TC 8 Z9 9 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1533-0028 J9 CLIN COLORECTAL CANC JI Clin. Colorectal Canc. PD MAY PY 2006 VL 6 IS 1 BP 59 EP 65 DI 10.3816/CCC.2006.n.022 PG 7 WC Oncology SC Oncology GA 235NK UT WOS:000251240900008 PM 16796793 ER PT J AU Kaphingst, KA Janoff, JM Harris, LN Emmons, KM AF Kaphingst, KA Janoff, JM Harris, LN Emmons, KM TI Views of female breast cancer patients who donated biologic samples regarding storage and use of samples for genetic research SO CLINICAL GENETICS LA English DT Article DE breast cancer; genetic research; informed consent; privacy; tissue bank ID INFORMED-CONSENT; ETHICAL ISSUES; STORED TISSUE; POPULATION; DEBATE; BLOOD; BODY; DNA AB Although social and ethical issues related to the storage and use of biologic specimens for genetic research have been discussed extensively in the medical literature, few empiric data exist describing patients' views. This qualitative study explored the views of 26 female breast cancer patients who had consented to donate blood or tissue samples for breast cancer research. Participants generally did not expect personal benefits from research and had few unprompted concerns. Few participants had concerns about use of samples for studies not planned at the time of consent. Some participants did express concerns about insurance or employment discrimination, while others believed that current privacy protections might actually slow breast cancer research. Participants were generally more interested in receiving individual genetic test results from research studies than aggregate results. Most participants did not want individual results of uncertain clinical significance, although others believed that they should be able to receive such information. These data examined the range of participants' views regarding the storage and use of biologic samples. Further research with different and diverse patient populations is critical to establishing an appropriate balance between protecting the rights of human subjects in genetic research and allowing research to progress. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Kaphingst, KA (reprint author), Natl Human Genome Res Inst, Bldg 2,Room 4E30,2 Ctr Dr,MSC 0249, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU NCI NIH HHS [CA89393-02] NR 30 TC 37 Z9 37 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2006 VL 69 IS 5 BP 393 EP 398 DI 10.1111/j.1399-0004.2006.00614.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 036ZN UT WOS:000237116600002 PM 16650074 ER PT J AU Santos, DD Hatjiharissi, E Tournilhac, O Chemaly, MZA Leleu, X Xu, L Patterson, C Branagan, AR Manning, RJ Ho, AW Hunter, ZR Dimmock, EA Kutok, JL Churchill, WH Castells, MC Tai, YT Anderson, KC Treon, SR AF Santos, DD Hatjiharissi, E Tournilhac, O Chemaly, MZA Leleu, X Xu, L Patterson, C Branagan, AR Manning, RJ Ho, AW Hunter, ZR Dimmock, EA Kutok, JL Churchill, WH Castells, MC Tai, YT Anderson, KC Treon, SR TI CD52 is expressed on human mast cells and is a potential therapeutic target in Waldenstrom's macroglobulinemia and mast cell disorders SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article DE alemtuzumab; apoptosis; cytotoxicity; monoclonal antibodies; systemic mastocytosis ID LYMPHOPLASMACYTIC CELLS; GROWTH; ESTABLISHMENT; LYMPHOMA; SURVIVAL; PATIENT; LINE AB Background: Alemtuzumab is a monoclonal antibody used in the treatment of CD52-expressing B-cell malignancies, including Waldenstrom's macroglobulinemia (WM). Recent studies demonstrate high levels of alemtuzumab activity in relapsed/refractory disease. One potential target of alemtuzumab is bone marrow mast cells (BMMCs), which provide growth and survival signaling for WM lymphoplasmacytic cells. Patients and Methods: We therefore examined BMMCs (Fc epsilon RI+, CD117(+)) from WM and other mast cell (MC) disorders for expression of CD52. Results: We identified cell surface antigen expression by multicolor flow cytometric analysis and found CD52 expressed on human mast-derived cell line-1 (HMC-1) and LAD2 MC lines, on BMMC from 13 of 15 patients with WM, and on BMMCs from 4 of 4 patients with systemic mastocytosis (SM). None of 4 healthy donors expressed GD52. Reverse-transcriptase polymerase chain reaction analysis confirmed CD52 expression in the HMC-1 and LAD2 MC lines, in BMMCs from 14 of 15 patients with WM, and 3 of 3 patients with SM. CD52 transcripts were also detected in BMMCs from 6 of 6 healthy donors, despite the absence of CD52 cell surface expression. Importantly, we observed high levels of alemtuzumab-mediated, antibody-dependent, cell-mediated cytotoxicity against LAD2 MCs and BMMCs from patients with WM and SM. Conclusion: These studies demonstrate that CD52 is widely expressed on human MCs and WM bone marrow lymphoplasmacytic cells and provide the preclinical rationale for the use of alemtuzumab in the treatment of WM and possibly other MC-related disorders. C1 Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Hematol Immunol & Allergy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Treon, SR (reprint author), Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Bing Ctr Waldenstroms Macroglobulinemia, M548B,44 Binney St, Boston, MA 02115 USA. EM steven-treon@dfci.harvard.edu RI Ho, Allen/B-3017-2011; Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Branagan, Andrew/0000-0002-3868-9267 FU NCI NIH HHS [K-23CA087977-03] NR 26 TC 26 Z9 26 U1 1 U2 3 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD MAY PY 2006 VL 6 IS 6 BP 478 EP 483 PG 6 WC Oncology SC Oncology GA 052ZA UT WOS:000238271500006 PM 16796779 ER PT J AU Silbert, LC Nelson, C Holman, S Eaton, R Oken, BS Lou, JS Kaye, JA AF Silbert, LC Nelson, C Holman, S Eaton, R Oken, BS Lou, JS Kaye, JA TI Cortical excitability and age-related volumetric MRI changes SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE aging; TMS; white matter; atrophy; cortical excitability ID TRANSCRANIAL MAGNETIC STIMULATION; PRIMARY MOTOR CORTEX; INTRACORTICAL INHIBITION; ALZHEIMERS-DISEASE; CARDIOVASCULAR-HEALTH; PARKINSONS-DISEASE; DEPENDENT CHANGES; DEMENTIA; STROKE; BRAIN AB Objective: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. Methods: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. Results: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. Conclusions: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. Significance: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Oregon Hlth & Sci Univ, Layton Aging & Alheimers Dis Ctr, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Silbert, LC (reprint author), Oregon Hlth & Sci Univ, Layton Aging & Alheimers Dis Ctr, Dept Neurol, CR-131,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM silbertl@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [M01 RR000334]; NIA NIH HHS [P30 AG 08017, K23 AG 24826-01] NR 38 TC 19 Z9 19 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2006 VL 117 IS 5 BP 1029 EP 1036 DI 10.1016/j.clinph.2006.02.003 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 044DF UT WOS:000237651900013 PM 16564739 ER PT J AU Lin, AE AF Lin, AE TI Writing for scientific publication: Tips for getting started SO CLINICAL PEDIATRICS LA English DT Editorial Material AB Pediatricians in training and clinical practice may be eager to submit their first scientific publication by writing a letter to the editor, case report, review article, or short clinical series. Unfortunately, the would-be author encounters a literary developmental delay when facing the blank page or computer screen. This article is dedicated to the novice author and offers practical tips on writing the first manuscript. Authors are encouraged to draw from their extensive experience writing other materials and to approach the task in a systematic way. Computer technology and software developments should facilitate the process. C1 Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children,Genet & Teratol Unit, Boston, MA 02114 USA. RP Lin, AE (reprint author), Harvard Univ, Sch Med, Dept Pediat, MassGen Hosp Children,Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 12 TC 2 Z9 2 U1 0 U2 8 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAY PY 2006 VL 45 IS 4 BP 295 EP 300 DI 10.1177/000992280604500401 PG 6 WC Pediatrics SC Pediatrics GA 047IS UT WOS:000237873600001 PM 16703152 ER PT J AU Rhatigan, DL Street, AE Axsom, DK AF Rhatigan, DL Street, AE Axsom, DK TI A critical review of theories to explain violent relationship termination: Implications for research and intervention SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review ID INTIMATE PARTNER VIOLENCE; INVESTMENT MODEL ANALYSIS; BATTERED WOMEN; ABUSIVE RELATIONSHIP; DATING RELATIONSHIPS; DECISION; LEAVE; INTENTIONS; STAY; COMMITMENT AB The following review represents an update and extension to an influential article (see [Strube, M.J. (1988). The decision to leave an abusive relationship: Empirical evidence and theoretical issues. Psychological Bulletin, 104, 236-250.]), which evaluated empirical research and suggested potential theories to explain victimized women's decisions to terminate violent relationships. In contrast to the original review, this paper provides information on the importance of and means by which theory should be evaluated and critically determines which theoretical approach(es) might be most productive based on theoretical and atheoretical evidence. In addition, this paper discusses strengths and weaknesses of each approach, in light of certain criteria deemed to be important for the evaluation of theory (e.g., comprehensiveness, parsimony, etc.). Furthermore, this paper discusses current controversies regarding these issues, ramifications of differing theoretical approaches, and their potential impact on the field. Based on this analysis, it is determined that general approaches (e.g., reasoned action/planned behavior, investment model) may be better for understanding this complex and multifaceted decision. Suggestions for future theoretical and intervention research are discussed. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Houston, Dept Social Sci, Houston, TX 77002 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. RP Rhatigan, DL (reprint author), Univ Houston, Dept Social Sci, 1 Main St, Houston, TX 77002 USA. EM rhatigand@uhd.edu NR 103 TC 28 Z9 28 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD MAY PY 2006 VL 26 IS 3 BP 321 EP 345 DI 10.1016/j.cpr.2005.09.002 PG 25 WC Psychology, Clinical SC Psychology GA 045DU UT WOS:000237723600005 PM 16343720 ER PT J AU Biederman, J Mick, E Faraone, SV Wozniak, J Spencer, T Pandina, G AF Biederman, Joseph Mick, Eric Faraone, Stephen V. Wozniak, Janet Spencer, Thomas Pandina, Gahan TI Risperidone for the treatment of affective symptoms in children with disruptive behavior disorder: A post hoc analysis of data from a 6-week, multicenter, randomized, double-blind, parallel-arm study SO CLINICAL THERAPEUTICS LA English DT Article DE risperidone; bipolar disorder; major depression; conduct disorder; children; disruptive behavior disorder ID DEFICIT HYPERACTIVITY DISORDER; BIPOLAR DISORDER; CONDUCT DISORDER; JUVENILE MANIA; RATING FORM; OLANZAPINE; TRIAL; COMORBIDITY; ADOLESCENTS; CHILDHOOD AB Background: Despite the increasing recognition of bipolar disorder in childhood, there have been no controlled, randomized clinical trials of atypical antipsychotics in this population. Preliminary data from open-label trials in children suggest that these agents might be effective in treating pediatric bipolar disorder, however. Objective: The purpose of this post hoc analysis of data from Aman et al was to determine the effects of risperidone in the management of affective symptoms in children with disruptive behavioral disorders (DBDs). Methods: This report presents a secondary analysis of a previously reported 6-week, multicenter, double-blind, randomized, parallel-arm trial comparing 6 weeks of administration of risperidone (flexible dosing starting at 0.02 mg (.) kg(-1) (.) d(-1) and titrated up to 0.06 mg (.) kg(-1) (.) d(-1)) versus placebo in children with DBDs and subaverage intelligence. Twenty-four candidate affective symptoms of mania and depression were extracted from the 64-item Nisonger Child Behavior Rating Form (NCBRF). To define independent dimensions of mood-disorder psychopathology, these 24 symptoms were assigned 1 of 3 independent dimensions (symptoms of mania) based on loading: explosive irritability; agitated, expansive, grandiose; and depression. A fourth, nonaffective independent dimension encompassed a combination of nonaffective symptoms on the NCBRF Conduct Problem sub-scale. To assess treatment effect, each independent dimension was assigned a score derived from the sum of the symptoms that loaded on that dimension at weeks 2, 4, and 6 of study drug administration. Results: A total of 110 patients were included in the independent-dimension analysis (89 boys, 21 girls; risperidone, 49 patients; placebo, 61 patients; mean [SD] age, 8.6 [2.3] and 8.1 [2.4] years in the risperidone and placebo groups, respectively; mean [SD] weight, 33.9 [12.8] and 32.1 [12.0] kg in the risperidone and placebo groups, respectively). The treatment-effect analysis found that the mean scores of all 3 independent dimensions were significantly reduced with risperidone compared with placebo at weeks 2, 4, and 6 (all, P <= 0.03). The effect sizes of improvement in these factors ranged from 0.44 to 0.95 at end point. Conclusions: The results of this post hoc analysis of affective symptoms of DBDs using data from a previously published randomized, double-blind clinical comparison of risperidone and placebo in the treatment of children with DBDs and subaverage intelligence suggest that risperidone was effective in treating the factors of explosive irritability; agitated, expansive, grandiose; and depression. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Syracuse, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. Janssen Pharmaceut Inc, Cent Nervous Syst Clin Dev Div, Titusville, NJ USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 19 TC 17 Z9 17 U1 2 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAY PY 2006 VL 28 IS 5 BP 794 EP 800 DI 10.1016/j.clinthera.2006.05.009 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 051OC UT WOS:000238169400016 PM 16861101 ER PT J AU Cristian, A AF Cristian, A TI Geriatric rehabilitation SO CLINICS IN GERIATRIC MEDICINE LA English DT Editorial Material C1 James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY 10468 USA. RP Cristian, A (reprint author), James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Room 3D-16,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM acristianmd@msn.com NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP XIII EP XIV DI 10.1016/j.cger.2006.01.001 PG 2 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200001 ER PT J AU Cristian, A AF Cristian, A TI The assessment of the older adult with a physical disability: A guide for clinicians SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID SPINAL-CORD-INJURY; PARKINSONS-DISEASE; STROKE PATIENTS; SLEEP DISTURBANCES; SEXUAL DYSFUNCTION; FUNCTIONAL-CHANGES; FATIGUE; REHABILITATION; DEPRESSION; SPOUSES AB As the population of older adults increases, so does the number of people aging with a disability. It is more important than ever that clinicians caring for these individuals ask appropriate questions and focus on key areas of the physical examination that are pertinent to the care of this population. This article is meant to provide clinicians with a framework for evaluating the older adult aging with a physical disability in a clinic or hospital setting. C1 James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. RP Cristian, A (reprint author), James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, 3D-16,526-117,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM acristianmd@msn.com NR 41 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 221 EP + DI 10.1016/j.cger.2005.12.001 PG 19 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200002 PM 16627075 ER PT J AU Richards, S Cristian, A AF Richards, S Cristian, A TI The role of the physical therapist in the care of the older adult SO CLINICS IN GERIATRIC MEDICINE LA English DT Article AB Physical therapists play an important role in the care of older adults who have physical disabilities. Proper patient selection, a thorough medical, social, and functional history, and a physical examination emphasizing the neuromusculoskeletal system are the cornerstones of the evaluation process. Treatment is individualized and goal driven, with appropriate precautions being followed. Gait training is an integral part of the treatment process for many older adults with disabilities, and various assistive devices may be used to ensure safe mobility. C1 James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY 10468 USA. RP Richards, S (reprint author), James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Room 3D-16,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM shana.richards@med.va.gov NR 4 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 269 EP + DI 10.1016/j.cger.2005.12.003 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200005 PM 16627078 ER PT J AU Daley, T Cristian, A Fitzpatrick, M AF Daley, T Cristian, A Fitzpatrick, M TI The role of occupational therapy in the care of the older adult SO CLINICS IN GERIATRIC MEDICINE LA English DT Article AB Older adults who have physical disabilities often require the services of an occupational therapist. This article reviews the role of the occupational therapist in the care of the geriatric population. C1 James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Daley, T (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM teina.daley@bronx.va.gov NR 2 TC 0 Z9 1 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 281 EP + DI 10.1016/j.cger.2005.12.004 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200006 PM 16627079 ER PT J AU Ashley, J Duggan, M Sutcliffe, N AF Ashley, J Duggan, M Sutcliffe, N TI Speech, language, and swallowing disorders in the older adult SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID LOUDNESS MANIPULATIONS; PARKINSONS-DISEASE; IMPACT; TUBE; REHABILITATION; DYSARTHRIA; DYSPHAGIA AB The geriatric population has become a major component in the practice of medical speech-language pathology. This article discusses normal and abnormal functions of speech, voicing, language, cognition, and swallowing. Particular attention is given to disorders affecting the geriatric population. Evaluation, treatment, and ethical issues are explored in addition to the role of the speech-language pathologist on the interdisciplinary team. C1 James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Sutcliffe, N (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM natalie.sutcliffe@med.va.gov NR 44 TC 8 Z9 9 U1 1 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 291 EP + DI 10.1016/j.cger.2005.12.008 PG 21 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200007 PM 16627080 ER PT J AU Perret, DM Rim, J Cristian, A AF Perret, DM Rim, J Cristian, A TI A geriatrician's guide to the use of the physical modalities in the treatment of pain and dysfunction SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID LOW-BACK-PAIN; ELECTRICAL NERVE-STIMULATION; DOUBLE-BLIND TRIAL; ULTRASOUND THERAPY; MUSCULOSKELETAL DISORDERS; COLD THERAPY; EFFICACY; TENS; HEAT; REHABILITATION AB The use of the physical modalities in the treatment of musculoskeletal conditions has a long and rich history. This article explores the various physical modalities and their indications, precautions, and contraindications, especially in their applied use in pain management. It also highlights the role of the physical modalities as agents for the management of pain in the geriatric population. C1 James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY 10468 USA. Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA. SUNY Hlth Sci Ctr, Dept Anesthesiol, Brooklyn, NY 11203 USA. RP Cristian, A (reprint author), James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Room 3D-16,Route 526-117,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM acristianmd@msn.com NR 92 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 331 EP + DI 10.1016/j.cger.2005.12.005 PG 25 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200009 PM 16627082 ER PT J AU Sabol, TP Haley, ES AF Sabol, TP Haley, ES TI Wheelchair evaluation for the older adult SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID SPINAL-CORD-INJURY; PRESSURE; PROPULSION; MOBILITY; RELIABILITY; EFFICIENCY; CUSHION; PEOPLE; SYSTEM; USERS AB This article focuses on basic principles of seating and wheelchair evaluation for the general population. The discussion includes wheelchair options, components, and accessories. Basic principles to guide the clinician in the process of selection for maximum function are addressed. C1 James J Peters Vet Affairs Med Ctr, Spinal Cord Injury Unit, Bronx, NY 10468 USA. RP Sabol, TP (reprint author), James J Peters Vet Affairs Med Ctr, Spinal Cord Injury Unit, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM timothy.sabel@med.va.gov NR 31 TC 8 Z9 8 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 355 EP + DI 10.1016/j.cger.2005.12.013 PG 22 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200010 PM 16627083 ER PT J AU MacDonald, DE AF MacDonald, DE TI Principles of geriatric dentistry and their application to the older adult with a physical disability SO CLINICS IN GERIATRIC MEDICINE LA English DT Review ID ROOT SURFACE CARIES; SQUAMOUS-CELL CARCINOMA; ORAL LICHEN-PLANUS; SALIVARY FLOW-RATE; PERIODONTAL-DISEASE; PROSTHODONTIC TREATMENT; APHTHOUS STOMATITIS; NUTRITIONAL-STATUS; CARE UTILIZATION; OROFACIAL PAIN AB The older adult living with a physical disability faces many daily challenges. Limited hand function or impaired cognition often has profound effects on activities of daily life including oral hygiene. This article explores age-related changes in dentition and common causes of pathology of the oral cavity with special emphasis in populations with impaired hand function or cognition. This article will also assist the treating physician as it relates to oral diagnosis and patient management. C1 Columbia Univ, Sch Dent & Oral Surg, Div Periodontol, New York, NY 10032 USA. Columbia Univ, Fu Sch Grad Engn, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. Hosp Special Surg, Div Mineralized Tissue Res, New York, NY 10021 USA. James J Peters VA Med Ctr, Bronx, NY 10468 USA. RP MacDonald, DE (reprint author), Columbia Univ, Sch Dent & Oral Surg, Div Periodontol, 630 W 168th St,PH-7-E-110, New York, NY 10032 USA. EM dem14@columbia.edu NR 138 TC 5 Z9 6 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD MAY PY 2006 VL 22 IS 2 BP 413 EP + DI 10.1016/j.cger.2005.12.009 PG 23 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 044VX UT WOS:000237702200013 PM 16627086 ER PT J AU Ketter, TA Suppes, T Morrell, MJ Rasgon, N Cohen, LS Viguera, AC AF Ketter, Terence A. Suppes, Trisha Morrell, Martha J. Rasgon, Natalie Cohen, Lee S. Viguera, Adele C. TI REPRODUCTIVE HEALTH AND BIPOLAR DISORDER SO CNS SPECTRUMS LA English DT Editorial Material AB The presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting. Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women. Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-mode rate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families. C1 [Ketter, Terence A.; Rasgon, Natalie] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Ketter, Terence A.] Stanford Univ, Sch Med, Bipolar Disorders Clin, Stanford, CA USA. [Suppes, Trisha] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX USA. [Rasgon, Natalie] Stanford Univ, Sch Med, Behav Neuroendocrinol Program, Stanford, CA USA. [Rasgon, Natalie] Stanford Univ, Sch Med, Womens Wellness Clin, Stanford, CA USA. [Morrell, Martha J.] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Cohen, Lee S.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Clin Psychopharmacol Unit, Boston, MA 02114 USA. [Cohen, Lee S.; Viguera, Adele C.] Harvard Univ, Sch Med, Boston, MA USA. RP Ketter, TA (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. NR 109 TC 1 Z9 1 U1 0 U2 3 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2006 VL 11 IS 5 BP 1 EP 16 PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V04RL UT WOS:000207075400001 ER PT J AU Biederman, J Mick, E Spencer, T Surman, C Hammerness, P Doyle, R Dougherty, M Aleardi, M Schweitzer, K AF Biederman, J Mick, E Spencer, T Surman, C Hammerness, P Doyle, R Dougherty, M Aleardi, M Schweitzer, K TI An open-label trial of OROS methylphenidate,in adults with late-onset ADHD SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND AB Introduction: Many adults with current impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) do not report an age at onset before 7 years of age and cannot, therefore, be assigned the full Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of ADHD. We hypothesized that treatment with oral-release osmotic system (OROS) methylphenidate (MPH) will be safe and efficacious for the treatment of adults with late-onset ADHD. Method: This was a 6-week, open-label, prospective treatment study of OROS MPH monotherapy in 36 adult patients with late-onset ADHD (onset later than the required 7 years of age) using standardized instruments for diagnosis and a robust oral daily dose of up to 1.3 mg/kg/day. Symptom severity was assessed with the Adult ADHD Investigator Symptom Report Scale (AISRS) and the Clinical Global Impression (CGI) scale. Results: Subjects reported robust current symptoms of ADHD at pre-treatment baseline (11.1 +/- 2.8 DSM-IV symptoms), but had an atypical mean age at onset of 14.2 +/- 8.6 years.Treatment with OROS MPH at an average daily dose of 78.2 +/- 29.4 mg was associated with a statistically and clinically significant reduction in ADHD symptoms relative to baseline as assessed through the AISRS (-16.4 +/- 10.5; P <.001). Using a categorical definition of response (CGI-I much or very much improved), a majority (n=26; 72%) of subjects were rated as improved at endpoint. Conclusion: These results extend previous findings in adults with full ADHD to adults meeting criteria for late-onset ADHD and support the need for further controlled clinical trials in this population. C1 Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopahrmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Adult ADHD Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, PDD Program Pediat Psychopahrmacol Res Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, 15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 22 TC 18 Z9 19 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAY PY 2006 VL 11 IS 5 BP 390 EP 396 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 044CL UT WOS:000237649700016 PM 16641844 ER PT J AU Zhang, HW Wisniewski, SR Bauer, MS Sachs, GS Thase, ME AF Zhang, HW Wisniewski, SR Bauer, MS Sachs, GS Thase, ME CA STEP-BD Investig TI Comparisons of perceived quality of life across clinical states in bipolar disorder: data from the first 2000 Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) participants SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID ATTRIBUTIONAL STYLE; COGNITIVE STYLES; PERSONALITY; QUESTIONNAIRE; SATISFACTION; NEUROTICISM; SUBSTANCE; EVENTS; SAMPLE; IMPACT AB Background: Evidence indicates that quality Of life is Subnormal in patients with bipolar disorder and that it differs across mood states. However, the pattern of specific deficits has not been well studied, and the role of potential confounders has received no attention. Method: We investigated the self-reported quality of life, Medical Outcomes Study 36-Item Short Form (SF-36), and Quality of Life Enjoyment and Satisfaction (QLESQ) at baseline across the clinical states of the first 2000 participants enrolled in Systematic Treatment Enhancement Program for Bipolar Disorder. Results: Bivariate analyses indicated significant differences across mood state, with depressive symptoms predicting lower SF-36 mental and physical scores and QLESQ overall score. However, adjustment for relevant clinical and demographic variables erased the difference in the SF-36 physical score. Notably, covariate adjustment removed the apparently "supranormal" SF-36 mental and QLESQ scores among those with mania/hypomania compared with those euthymic. Conclusion: Depressive symptoms are a strong predictor of quality of life, yet covariate adjustment has an impact as well. Clinically, this indicates the need for addressing these factors if quality of life is to be maximized. Such factors Should also be taken into account in future naturalistic and clinical trials research on quality of life in bipolar disorder. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. Providence Vet Affairs Med Ctr, Providence, RI 02908 USA. Brown Univ, Sch Med, Providence, RI 02908 USA. Massachusetts Gen Hosp, Harvard Bipolar Disorder Res Program, Boston, MA 02114 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Zhang, HW (reprint author), Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA 15261 USA. EM zhangh@edc.pitt.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 28 TC 33 Z9 34 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2006 VL 47 IS 3 BP 161 EP 168 DI 10.1016/j.comppsych.2005.08.001 PG 8 WC Psychiatry SC Psychiatry GA 040AA UT WOS:000237349200001 PM 16635643 ER PT J AU Geller, DA Doyle, R Shaw, D Mullin, B Coffey, B Petty, C Vivas, F Biederman, J AF Geller, DA Doyle, R Shaw, D Mullin, B Coffey, B Petty, C Vivas, F Biederman, J TI A quick and reliable screening measure for OCD in youth: reliability and validity of the obsessive compulsive scale of the Child Behavior Checklist SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID REGRESSION TREES CART; DISORDER; CLASSIFICATION AB Background: the high prevalence and morbidity of obsessive compulsive disorder (OCD) ill Youth, the secretive nature of the disorder leading to under-recognition, and the lack of specialized child psychiatry services in many areas suggest that a simple, quick, and reliable screening tool to identify cases Could be very useful to clinicians who work with children. Method: We used 8 items from the Child Behavior Checklist (CBCL), an empirically derived instrument free of clinician bias, to investigate the usefulness of a previously reported CBCL-based obsessive compulsive scale (OCS) by Nelson et a] [Nelson EC, Hanna GL, Hudziak JJ, Botteron KN, Heath AC, Todd RD. Obsessive - compulsive scale of the Child Behavior Checklist: Specificity, sensitivity, and predictive power. Pediatrics 2001;108(1):E14] in a separate cohort of youth with OCD. We computed the psychometric properties of the OCS in outsample of youth with OCD and in psychiatric and normal controls, and compared these to the published values. Results: Using the recommended Cutoff between the 60th and 70th percentiles of the OCS to best predict the presence of OCD, we round p very high sensitivity (92%-78%), specificity (86%-94%), negative predictive value (96%-90%), and positive predictive value (77%-86%). Conclusions: The OC scale of the CBCL shows good reliability and validity and acceptable psychometric properties to help discriminate youth with OCD. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Obsess Compuls Disorder Program, Dept Psychiat, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NYU, Dept Psychiat, Ctr Child Study, New York, NY 10016 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat Obsess Compuls Disorder Program, Dept Psychiat, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. EM dageller@partners.org FU NIMH NIH HHS [K08 MH01481] NR 23 TC 26 Z9 26 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 2006 VL 47 IS 3 BP 234 EP 240 DI 10.1016/j.comppsych.2005.08.005 PG 7 WC Psychiatry SC Psychiatry GA 040AA UT WOS:000237349200012 PM 16635654 ER PT J AU Gamm, DM Harris, A Mehran, RJ Wood, M Foster, CS Mootha, VV AF Gamm, DM Harris, A Mehran, RJ Wood, M Foster, CS Mootha, VV TI Mucous membrane pemphigoid with fatal bronchial involvement in a seventeen-year-old girl SO CORNEA LA English DT Article DE mucous membrane pemphigoid; cicatricial pemphigoid; bronchus; pulmonary disease; anti-phospholipid antibodies; children AB Purpose: This study was designed to report a case of biopsy-proven mucous membrane pemphigoid with severe bronchial involvement in a young woman. Methods: Case report of a 17-year-old girl who presented with worsening dyspnea, skin rash, and bilateral ocular injection, symblepharon, and fornix foreshortening. Conjunctival, skin, an bronchial biopsies were performed along with imaging and serological tests in an effort to establish a diagnosis for this unusual constellation of findings. The surprising occurrence of a cerebrovascular accident during her hospitalization also prompted a search for a concurrent coagulation disorder. Results: Immunofluorescence studies of conjunctival, skin, and bronchial tissue specimens revealed deposition of multiple antibody classes at the basement membrane zone. The patient also possessed circulating basement membrane zone antibodies in her serum and a significant titer of antiphospholipid antibodies. She underwent dilation and stent placement for subglottic tracheal and left bronchial stenosis and was treated with immunosuppressive agents. After a favorable initial response, the patient experienced progressive bronchial stenosis and respiratory compromise, culminating in her death from bronchospasm and cardiopulmonary arrest. Conclusion: To our knowledge, this is the first report of mucous membrane pemphigoid involving the lower airways that was confirmed by immunofluorescence analysis. It highlights the potentially lethal, systemic nature of mucous membrane pemphigoid and underscores the need to question patients about symptoms of respiratory dysfunction. C1 SW Med Sch, Dept Ophthalmol, Dallas, TX 75390 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Div Thorac & Cardiovasc Surg, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Div Ophthalmol, Albuquerque, NM 87131 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX 75230 USA. RP Mootha, VV (reprint author), SW Med Sch, Dept Ophthalmol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM vinod.mootha@utsouthwestern.edu NR 10 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD MAY PY 2006 VL 25 IS 4 BP 474 EP 478 DI 10.1097/01.ico.0000178730.34564.c7 PG 5 WC Ophthalmology SC Ophthalmology GA 042AF UT WOS:000237498600020 PM 16670490 ER PT J AU Caplan, D AF Caplan, David TI Why is Broca's area involved in syntax? SO CORTEX LA English DT Article DE Broca's area; evolution of language; syntactic processing; neural basis of syntax ID SENTENCE COMPREHENSION; AGRAMMATISM; LANGUAGE AB It is suggested that, rather than Broca's area playing its role in syntactic comprehension because its functions are a specialization those of the dorsolateral prefrontal cortex (DLPFC) or derived from sensori-motor functions of cortex from which it is evolutionarily descended, this region may be involved in this aspect of language because of its intrinsic neural organization. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. EM dcaplan@partners.org FU NIDCD NIH HHS [DC02146] NR 27 TC 18 Z9 20 U1 2 U2 7 PU MASSON DIVISIONE PERIODICI PI MILANO PA VIA MUZIO ATTENDOLO DETTO SFORZA 79, 20141 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAY PY 2006 VL 42 IS 4 BP 469 EP 471 DI 10.1016/S0010-9452(08)70379-4 PG 3 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 066IE UT WOS:000239222100003 PM 16881251 ER PT J AU Sahin, NT Pinker, S Halgren, E AF Sahin, Ned T. Pinker, Steven Halgren, Eric TI Abstract grammatical processing of nouns and verbs in Broca's area: Evidence from fMRI SO CORTEX LA English DT Review DE morphology; language production; speech production; regular/irregular inflection; grammar; syntax; morphosyntax; morphophonology; insula; anterior cingulate ID EVENT-RELATED FMRI; INFERIOR PREFRONTAL CORTEX; WORD FORM AREA; LEFT FRONTAL-CORTEX; ENGLISH PAST TENSE; HUMAN-BRAIN; INFLECTIONAL MORPHOLOGY; AGRAMMATIC APHASICS; WORKING-MEMORY; SYNTACTIC COMPREHENSION AB The role of Broca's area in grammatical computation is unclear, because syntactic processing is often confounded with working memory, articulation, or semantic selection. Morphological processing potentially circumvents these problems. Using event-related functional magnetic resonance imaging (fMRI), we had 18 subjects silently inflect words or read them verbatim. Subtracting the activity pattern for reading from that for inflection, which indexes processes involved in inflection (holding constant lexical processing and articulatory planning) highlighted left Brodmann area (BA) 44/45 (Broca's area), BA 47, anterior insula, and medial supplementary motor area. Subtracting activity during zero inflection (the hawk; they walk) from that during overt inflection (the hawks; they walked), which highlights manipulation of phonological content, implicated subsets of the regions engaged by inflection as a whole. Subtracting activity during verbatim reading from activity during zero inflection (which highlights the manipulation of inflectional features) implicated distinct regions of BA 44, 47, and a premotor region (thereby tying these regions to grammatical features), but failed to implicate the insula or BA 45 (thereby tying these to articulation). These patterns were largely similar in nouns and verbs and in regular and irregular forms, suggesting these regions implement inflectional features cutting across word classes. Greater activity was observed for irregular than regular verbs in the anterior cingulate and supplementary motor area (SMA), possibly reflecting the blocking of regular or competing irregular candidates. The results confirm a role for Broca's area in abstract grammatical processing, and are interpreted in terms of a network of regions in left prefrontal cortex (PFC) that are recruited for processing abstract morphosyntactic features and overt morphophonological content. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. INSERM E9926, Marseille, France. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP Sahin, NT (reprint author), Harvard Univ, Dept Psychol, William James Hall,Room 964,33 Kirkland St, Cambridge, MA 02138 USA. EM sahin@post.harvard.edu FU NCRR NIH HHS [P41 RR014075, P41 RR14075]; NICHD NIH HHS [HD 18381, R01 HD018381]; NINDS NIH HHS [NS18741, R01 NS018741] NR 142 TC 61 Z9 62 U1 7 U2 18 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAY PY 2006 VL 42 IS 4 BP 540 EP 562 DI 10.1016/S0010-9452(08)70394-0 PG 23 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 066IE UT WOS:000239222100018 PM 16881266 ER PT J AU Chen, E West, WC Waters, G Caplan, D AF Chen, Evan West, W. Caroline Waters, Gloria Caplan, David TI Determinants of bold signal correlates of processing object-extracted relative clauses SO CORTEX LA English DT Article DE fMRI syntax; animacy; relative clauses ID EVENT-RELATED FMRI; HUMAN CEREBRAL-CORTEX; SENTENCE COMPREHENSION; WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; COORDINATE SYSTEM; CORTICAL SURFACE; FUNCTIONAL MRI; DEPENDENCIES; LOCALIZATION AB Event-related functional magnetic resonance imaging (fMRI) was used to investigate the determinants of blood oxygenation level-dependent (BOLD) signal correlates of processing relative clauses. Matched pairs of sentences that differed in their processing demands were compared. One member of the pair consisted of a syntactically simpler object-subject (OS) sentence, containing a subject-relativized clause attached to the object noun phrase. The second member of the pair consisted of a syntactically more complex subject-object (SO) sentence, containing an object-relativized clause attached to the subject noun phrase. Participants made plausibility judgments about the sentences in whole sentence visual presentation. Voxel-wise statistical activation maps showed increased BOLD signal in multiple cortical regions for complex compared to simple syntactic structures. This pattern was found for plausible sentences only and, within the set of plausible sentences, for SO sentences in which the head noun of the relative clause was animate and the subject noun of the relative clause was inanimate. These results require a re-interpretation of previous results with the same materials using positron emission tomography. C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, MIT, HMS, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM dcaplan@partners.org FU NCRR NIH HHS [P41RR14075]; NIDCD NIH HHS [DC02146] NR 39 TC 38 Z9 38 U1 4 U2 7 PU MASSON DIVISIONE PERIODICI PI MILANO PA VIA MUZIO ATTENDOLO DETTO SFORZA 79, 20141 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAY PY 2006 VL 42 IS 4 BP 591 EP 604 DI 10.1016/S0010-9452(08)70397-6 PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 066IE UT WOS:000239222100021 PM 16881269 ER PT J AU Villar, J Kacmarek, RM Perez-Mendez, L Aguirre-Jaime, A AF Villar, J Kacmarek, RM Perez-Mendez, L Aguirre-Jaime, A CA ARIES Network TI A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial SO CRITICAL CARE MEDICINE LA English DT Article DE mechanical ventilation; positive end-expiratory pressure; acute respiratory distress syndrome; acute lung injury; lung protection; tidal volume; airway pressure; barotrauma; multiple organ failure ID ACUTE LUNG INJURY; SYSTEM ORGAN FAILURE; MECHANICAL VENTILATION; CLINICAL-TRIAL; PULMONARY-EDEMA; ARDS; RECRUITMENT; MORTALITY; SEVERITY; MODEL AB Objective. It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (P-flex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). Design: Randomized, controlled clinical trial. Setting: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: Espana Study). Patients: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the PaO2/FiO(2) remained <= 200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pf(lex/)LTV. Interventions., In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP >= 5 cm H2O. In the P-flex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at P-flex + 2 cm H2O. In both groups, FIO2 was set to maintain arterial oxygen saturation >90% and PaO2 70-100 mm Hg, and respiratory rate was adjusted to maintain PaCO2 between 35 and 50 mm Hg. Measurements and Main Results. The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 P-flex), eight patients (five in control, three in P-flex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p =.040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p =.041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in P-flex/LTV, p =.008) all favored P-flex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p <.001). Conclusions: A mechanical ventilation strategy with a PEEP level set on day 1 above P-flex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS. C1 Canarian Inst Biomed Res, Las Palmas Gran Canaria 35003, Spain. St Michaels Hosp, Res Ctr, Toronto, ON M5B 1W8, Canada. CSIC, Ctr Invest, Madrid, Spain. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Villar, J (reprint author), Canarian Inst Biomed Res, Tomas Morales 6-1, Las Palmas Gran Canaria 35003, Spain. EM jesus.villar@canarias.org RI Bouza, Carmen/F-4626-2016 OI Bouza, Carmen/0000-0002-8089-9866 NR 34 TC 337 Z9 385 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2006 VL 34 IS 5 BP 1311 EP 1318 DI 10.1097/01.CCM.0000215598.84885.01 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 038PV UT WOS:000237235900002 PM 16557151 ER PT J AU Nozari, A Alston, TA AF Nozari, A Alston, TA TI Tuning up the compression and applying the choke for better horsepower in resuscitation SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE Claude Bernard; cardiopulmonary resuscitation; inspiratory impedance threshold valve; Muller maneuver ID CARDIOPULMONARY-RESUSCITATION; CPR C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Nozari, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2006 VL 34 IS 5 BP 1563 EP 1564 DI 10.1097/01.CCM.0000216180.02461.A8 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 038PV UT WOS:000237235900049 PM 16633262 ER PT J AU Gajic, O Dzilk, WH Toy, P AF Gajic, O Dzilk, WH Toy, P TI Fresh frozen plasma and platelet transfusion for nonbleeding patients in the intensive care unit: Benefit or harm? SO CRITICAL CARE MEDICINE LA English DT Review DE fresh-frozen plasma; platelet; transfusion; outcome study; pulmonary edema; clinical use ID ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; HEMOSTATIC ABNORMALITIES; LIVER-DISEASE; GUIDELINES; COAGULOPATHY; COAGULATION; BIOPSY; THROMBOCYTOPENIA; CRYOPRECIPITATE AB Objective: Whereas restrictive red cell transfusion has become a standard of care for the critically ill, evidenced-based indications for use of other blood components such as fresh frozen plasma (FFP) and platelet transfusions are limited. We searched the National Library of Medicine PubMed database as well as references of retrieved articles and summarized the current evidence for the use of FFP and platelet transfusions in critically ill patients. Results. Routine coagulation tests are poor determinants of bleeding risk in critically ill patients with coagulopathy. FFP transfusion has limited efficacy and is associated with significant morbidity in critically ill patients, in particular, pulmonary edema and acute lung injury. Routine minimally invasive critical care procedures can be safely performed by experienced clinicians in the setting of mildly abnormal coagulation test results, and there is no evidence that FFP transfusion alters the risk of bleeding. For platelet transfusion, the American Society of Clinical Oncology has developed practice guidelines designed for oncology patients. However, because the pathophysiology of thrombocytopenia in critically ill patients often differs from that of thrombocytopenia in oncology patients, published guidelines for oncology patients may not be applicable. Conclusion: Because the risk-benefit ratio of a liberal FFP or platelet transfusion strategy for critically ill patients may not be favorable, randomized controlled trials are warranted for evaluating a restrictive vs. liberal FFP or platelet transfusion strategy for nonbleeding patients in the intensive care unit. C1 Mayo Clin, Dept Internal Med, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Gajic, O (reprint author), Mayo Clin, Dept Internal Med, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. FU NHLBI NIH HHS [K23 HL 078743] NR 39 TC 67 Z9 70 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 2006 VL 34 IS 5 SU S BP S170 EP S173 DI 10.1097/01.CCM.0000214288.88308.26 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 040AK UT WOS:000237350400013 PM 16617262 ER PT J AU Robinson, D Hackett, M Wong, J Kimball, AB Cohen, R Bala, M AF Robinson, D Hackett, M Wong, J Kimball, AB Cohen, R Bala, M CA IMID Study Grp TI Co-occurrence and comorbidities in patients with immune-mediated inflammatory disorders: an exploration using US healthcare claims data, 2001-2002 SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE autoimmune; diseases; disorders; epidemiology; immunology; inflammation ID POPULATION-BASED COHORT; BOWEL-DISEASE; ANKYLOSING-SPONDYLITIS; AUTOIMMUNE-DISEASES; ADMINISTRATIVE DATA; CLINICAL-FEATURES; INCREASED RISK; HEART-FAILURE; PHARMACY DATA; EPIDEMIOLOGY AB Objective: Research in immune-mediated inflammatory disorders (IMIDs) suggests that several diseases share disruptions in key cytokines. A common pathogenesis may present as similar patterns of disease co-occurrence and comorbidity, which could be observed through the analysis of healthcare claims datasets. Methods: Adult patients continuously enrolled from 2001-2002 were identified in two US healthcare datasets containing medical and drug claims from health plans and self-insured employers. Patients with treatment records indicating an IMID were selected (e.g., rheumatoid arthritis, psoriasis, Crohn's disease); controls for each disorder were matched 3:1 based on age, gender, region, and previous insurance coverage. IMID cohorts and comorbidities were identified using International Classification of Diseases, 9th revision codes. Prevalence relative risk was used to assess co-occurrence and comorbidity rates in IMID cohorts and controls. Medical and drug utilization patterns were also explored. Results: Findings were similar across the two datasets. IMID patients represented about 4% of the population; specific IMID prevalence matched the epidemiology literature. Patients with at least one IMID had a higher risk for another IMID when compared to controls. The risk for infectious, renal, liver, and ulcerative comorbidities was also elevated. Selected drug utilization patterns confirmed comorbidity findings. IMID patients used more healthcare resources compared to controls; findings were robust under sensitivity analyses. Conclusions: IMID patients were generally more likely than controls to have another IMID, supporting the concept that the diseases are related. These patients also had higher comorbidity rates. Findings may be limited by the nature of claims datasets and the confounding effect of current treatments. Prospective studies are needed to determine whether IMIDs have a common pathogenesis. C1 Centocor Inc, MSPH, Malvern, PA 19355 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Chicago Hosp, Chicago, IL 60637 USA. RP Robinson, D (reprint author), Centocor Inc, MSPH, 200 Great Valley Pkwy, Malvern, PA 19355 USA. EM drobins4@cntus.jnj.com NR 50 TC 51 Z9 51 U1 0 U2 1 PU LIBRAPHARM PI NEWBURY PA 29-35 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD MAY PY 2006 VL 22 IS 5 BP 989 EP 1000 DI 10.1185/030079906X104641 PG 12 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 055JX UT WOS:000238447700020 PM 16709321 ER PT J AU Rutherford, AE Pratt, DS AF Rutherford, AE Pratt, DS TI Cholestasis and cholestatic syndromes SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE bile acid transport; biliary atresia; cholestasis; intrahepatic cholestasis of pregnancy; primary biliary cirrhosis; primary sclerosing cholangitis; pruritus ID PRIMARY BILIARY-CIRRHOSIS; PRIMARY SCLEROSING CHOLANGITIS; FARNESOID-X-RECEPTOR; URSODEOXYCHOLIC ACID; INTRAHEPATIC CHOLESTASIS; CONTROLLED-TRIAL; BILE-ACID; LIVER; ANTIBODIES; ATRESIA AB Purpose of review This review highlights recent advances in understanding the regulation of bile acid transport in cholestasis and in the pathogenesis, outcomes, epidemiology, and treatment of a variety of cholestatic liver diseases and their associated complications. Recent findings Highlights include additional understanding of the role of the nuclear receptors farsenoid X receptor, pregnane X receptor, and constitutive androstane receptor in bile acid homeostasis, new understanding of the pathogenesis of primary biliary cirrhosis, familial intrahepatic cholestasis, biliary atresia, and primary sclerosing cholangitis, and clinical trials of therapies for intrahepatic cholestasis of pregnancy, primary biliary cirrhosis, and primary sclerosing cholangitis. Summary Our understanding of the molecular mechanisms, epidemiology and pathogenesis of cholestasis continues to advance. These advances will hopefully lead to more effective therapies for specific cholestatic conditions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Pratt, DS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. EM dspratt@partners.org RI Ghavidel Parsa, Pooneh/G-5305-2012 NR 24 TC 13 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD MAY PY 2006 VL 22 IS 3 BP 209 EP 214 DI 10.1097/01.mog.0000218956.63311.47 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 036CH UT WOS:000237048000003 PM 16550034 ER PT J AU Dickerson, BC AF Dickerson, BC TI Functional magnetic resonance imaging of cholinergic modulation in mild cognitive impairment SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE acetylcholine; Alzheimer's disease; functional magnetic resonance imaging; mild cognitive impairment ID POSITRON-EMISSION-TOMOGRAPHY; ACETYLCHOLINE ESTERASE-ACTIVITY; HUMAN AUDITORY-CORTEX; ALZHEIMERS-DISEASE; SENILE DEMENTIA; OLDER-ADULTS; NEUROPSYCHIATRIC SYMPTOMS; HIPPOCAMPAL ACTIVATION; PHARMACOLOGICAL FMRI; CORTICAL ACTIVATION AB Purpose of review Mild cognitive impairment often represents the earliest clinical phase of Alzheimer's disease and is thought to involve synaptic dysfunction. Functional neuroimaging methods may I be sensitive to these early physiologic changes and may be useful in early detection, therapeutic monitoring, and prediction of treatment response and other clinical outcomes. This review will focus on functional magnetic resonance imaging and its use in measuring the effects of cholinergic modulation in mild cognitive impairment. Recent findings Functional magnetic resonance imaging has begun to be applied to measure changes in regional brain activation during cognitive task performance after pharmacologic manipulation. In mild cognitive impairment, recent reports have appeared demonstrating alterations in neocortical activation after acute and prolonged administration of acetylcholinesterase inhibitors. These functional changes may relate to both behavioral performance and measures of brain structure (e.g., hippocampal volume). Summary Pharmacologic functional magnetic resonance imaging is a rapidly emerging field, with applications in both basic human neuroscience and clinical psychiatry and neurology. Its use in mild cognitive impairment and Alzheimer's disease may provide novel insights into the cholinergic system, memory, and neurodegenerative disease. C1 Massachusetts Gen Hosp, Gerontol Res Unit, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2691, Charlestown, MA 02129 USA. EM bradd@nmr.mgh.harvard.edu NR 94 TC 10 Z9 11 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2006 VL 19 IS 3 BP 299 EP 306 DI 10.1097/01.yco.0000218602.25346.c6 PG 8 WC Psychiatry SC Psychiatry GA 035YX UT WOS:000237038800011 PM 16612217 ER PT J AU Daskivich, TJ Oh, WK AF Daskivich, TJ Oh, WK TI Recent progress in hormonal therapy for advanced prostate cancer SO CURRENT OPINION IN UROLOGY LA English DT Review DE androgen antagonists; estrogens; hormonal antineoplastic agents; hormone-dependent neoplasms; prostatic neoplasms ID TRANSDERMAL ESTRADIOL THERAPY; PHASE-II TRIAL; ANDROGEN DEPRIVATION; PC-SPES; KETOCONAZOLE; BICALUTAMIDE; NILUTAMIDE; FLUTAMIDE; HYDROCORTISONE; COMBINATION AB Purpose of review Primary androgen deprivation therapy and secondary hormonal therapy remain the cornerstones of treatment for advanced prostate cancer. This review outlines the basis evidence for use of hormonal therapy while highlighting major research developments made in the past year. Recent findings Recent research on androgen deprivation therapy has suggested that patients with high-risk features may have longer metastasis-free survival with early initiation of androgen deprivation therapy. Fracture risk has been sown to be significantly increased in patients on androgen deprivation therapy and is correlated with duration of treatment. In the treatment of androgen-independent prostate cancer, oral premarin has been shown to induce of prostate specific antigen responses more than 50% in 32% of patients, though thromboembolism remains a risk despite prophylactic low-dose warfarin. Transdermal estradiol has been asociated with virtually no cardiovascular toxicity, but induced of prostate specific antigen responses more than 50% in only 12.5% of patients. Clinical studies of nilutamide, flutamide,and ketoconazole have further clarified efficacy of these secondary hormonal treatments. Summary Optimal timing of androgen deprivation therapy awaits the results of randomized trials, but available evidence indicates that patients with high-risk features may benefit from early androgen deprivation therapy. New estrogen-based therapies have shown promising efficacy in the treatment of androgen-independent prostate cancer, with significantly less cardiovascular toxicity than traditional estrogens. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dana Bldg Room 1230,44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 29 TC 19 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0963-0643 J9 CURR OPIN UROL JI Curr. Opin. Urol. PD MAY PY 2006 VL 16 IS 3 BP 173 EP 178 DI 10.1097/01.mou.0000193392.77469.e2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 047TW UT WOS:000237902600011 PM 16679855 ER PT J AU Guldbakke, KK Schanbacher, CF AF Guldbakke, KK Schanbacher, CF TI Disseminated intravascular coagulation unmasked by Mohs micrographic surgery SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID PROSTATE-CANCER; MECHANISMS; MANIFESTATIONS; COAGULOPATHY; MANAGEMENT; DIAGNOSIS C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Dermatol, Boston, MA 02115 USA. RP Schanbacher, CF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Carl_Schanbacher@dfci.harvard.edu NR 30 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 2006 VL 32 IS 5 BP 760 EP 764 DI 10.1111/j.1524-4725.2006.32154.x PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 040ZC UT WOS:000237421300026 PM 16706778 ER PT J AU Adams, DS Robinson, KR Fukumoto, T Yuan, SP Albertson, RC Yelick, P Kuo, L McSweeney, M Levin, M AF Adams, DS Robinson, KR Fukumoto, T Yuan, SP Albertson, RC Yelick, P Kuo, L McSweeney, M Levin, M TI Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates SO DEVELOPMENT LA English DT Review DE left-right asymmetry; H+-V-ATPase; V-ATPase; Xenopus; chick; zebrafish; axial patterning; cytoplasmic pH; membrane voltage ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; 1ST CLEAVAGE PLANE; PLASMA-MEMBRANE ENERGIZATION; DEVELOPING XENOPUS-EMBRYOS; INTRACELLULAR PH; EARLY STEP; CHICK-EMBRYO; SEPARATE MECHANISMS; NODAL EXPRESSION AB Biased left-right asymmetry is a fascinating and medically important phenomenon. We provide molecular genetic and physiological characterization of a novel, conserved, early, biophysical event that is crucial for correct asymmetry: H+ flux. A pharmacological screen implicated the H+-pump H+-V-ATPase in Xenopus asymmetry, where it acts upstream of early asymmetric markers. Immunohistochemistry revealed an actin-dependent asymmetry of H+-V-ATPase subunits during the first three cleavages. H+-flux across plasma membranes is also asymmetric at the four- and eight-cell stages, and this asymmetry requires H+-V-ATPase activity. Abolishing the asymmetry in H+ flux, using a dominant-negative subunit of the H+-V-ATPase or an ectopic H+ pump, randomized embryonic situs without causing any other defects. To understand the mechanism of action of H+-V-ATPase, we isolated its two physiological functions, cytoplasmic pH and membrane voltage (V-mem) regulation. Varying either pH or V-mem, independently of direct manipulation of H+-V-ATPase, caused disruptions of normal asymmetry, suggesting roles for both functions. V-ATPase inhibition also abolished the normal early localization of serotonin, functionally linking these two early asymmetry pathways. The involvement of H+-V-ATPase in asymmetry is conserved to chick and zebrafish. Inhibition of the H+-V-ATPase induces heterotaxia in both species; in chick, H+-V-ATPase activity is upstream of Shh; in fish, it is upstream of Kupffer's vesicle and Spaw expression. Our data implicate H+-V-ATPase activity in patterning the LR axis of vertebrates and reveal mechanisms upstream and downstream of its activity. We propose a pH- and V-mem-dependent model of the early physiology of LR patterning. C1 Harvard Univ, Sch Dent Med, Forsyth Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47906 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Ctr Regenerat & Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCRR NIH HHS [C06RR11244]; NIDCR NIH HHS [1-T32-DE-08327, K22 DE016633, K22 DE016633-03, 1-K22-DE016633-01A1]; NIGMS NIH HHS [1R01-GM-0622] NR 132 TC 162 Z9 164 U1 6 U2 27 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY 1 PY 2006 VL 133 IS 9 BP 1657 EP 1671 DI 10.1242/dev.02341 PG 15 WC Developmental Biology SC Developmental Biology GA 032WO UT WOS:000236807200005 PM 16554361 ER PT J AU Hibino, T Ishii, Y Levin, M Nishino, A AF Hibino, T Ishii, Y Levin, M Nishino, A TI Ion flow regulates left-right asymmetry in sea urchin development SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE ion flux; left-right asymmetry; sea urchin; embryogenesis; adult rudiment ID ORAL-ABORAL AXIS; NODAL FLOW; CALCIUM IONOPHORE; MESSENGER-RNA; MOTOR PROTEIN; BETA-CATENIN; H+,K+ ATPASE; EARLY STEP; RIGHT SIDE; EMBRYO AB The degree of conservation among phyla of early mechanisms that pattern the left - right (LR) axis is poorly understood. Larvae of sea urchins exhibit consistently oriented LR asymmetry. The main part of the adult rudiment is formed from the left coelomic sac of larvae, the left hydrocoel. Although this left preference is conserved among all echinoderm larvae, its mechanism is largely not understood. Using two marker genes, HpNot and HpFoxFQ-like, which are asymmetrically expressed during larval development of the sea urchin Hemicentrotus pulcherrimus, we examined in this study the possibility that the recently discovered ion flux mechanism controls asymmetry in sea urchins as it does in several vertebrate species. Several ion-transporter inhibitors were screened for the ability to alter the expression of the asymmetric marker genes. Blockers of the H+/K+-ATPase ( omeprazole, lansoprazole and SCH28080), as well as a calcium ionophore (A23187), significantly altered the normal sidedness of asymmetric gene expression. Exposure to omeprazole disrupted the consistent asymmetry of adult rudiment formation in larvae. Immuno-detection revealed that H+/K+-ATPase-like antigens in sea urchin embryos were present through blastula stage and exhibited a striking asymmetry being present in a single blastomere in 32-cell embryos. These results suggest that, as in vertebrates, endogenous spatially-regulated early transport of H+ and/or K+, and also of Ca2+, functions in the establishment of LR asymmetry in sea urchin development. C1 Okazaki Inst Integrat Biosci, Sect Dev Neurophysiol, Aichi 4448787, Japan. Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, Tokyo 1130033, Japan. Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Chiba 2778562, Japan. Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev & Craniofacial Biol, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Sci, Misaki Marine Biol Stn, Misaki, Miura 2380225, Japan. Sunnybrook & Womens Coll Hlth Sci Ctr, Div Mol & Cell Biol, Toronto, ON M4N 3M5, Canada. RP Nishino, A (reprint author), Okazaki Inst Integrat Biosci, Sect Dev Neurophysiol, Aichi 4448787, Japan. EM anishino@nips.ac.jp RI 拓, 日比野/D-8115-2013; Nishino, Atsuo/F-5393-2013 FU NCI NIH HHS [CO6RR11244]; NIGMS NIH HHS [IR01-GM-06227] NR 53 TC 45 Z9 47 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD MAY PY 2006 VL 216 IS 5 BP 265 EP 276 DI 10.1007/s00427-005-0051-6 PG 12 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 034YT UT WOS:000236967500004 PM 16534626 ER PT J AU Nagy, N Goldstein, AM AF Nagy, N Goldstein, AM TI Endothelin-3 regulates neural crest cell proliferation and differentiation in the hindgut enteric nervous system SO DEVELOPMENTAL BIOLOGY LA English DT Article DE enteric nervous system; endothelin-3 (ET3); endothelin receptor B (EDNRB); GDNF; chick-quail chimeras; coelomic transplantation; Hirschsprung's disease; Cecum ID MICE LACKING GDNF; NADPH-DIAPHORASE ACTIVITY; IN-VITRO; AVIAN EMBRYO; B RECEPTOR; MOUSE GUT; EXPRESSION PATTERN; STEM-CELLS; NEURONS; MIGRATION AB Neural crest cells (NCC) migrate, proliferate, and differentiate within the wall of the gastrointestinal tract to give rise to the neurons and glial cells of the enteric nervous system (ENS). The intestinal microenvironment is critical in this process and endothelin-3 (ET3) is known to have an essential role. Mutations of this gene cause distal intestinal aganglionosis in rodents, but its mechanism of action is poorly understood. We find that inhibition of ET3 signaling in cultured avian intestine also leads to hindgut aganglionosis. The aim of this study was to determine the role of ET3 during formation of the avian hindgut ENS. To answer this question, we created chick-quail intestinal chimeras by transplanting preganglionic quail hindguts into the coelomic cavity of chick embryos. The quail grafts develop two ganglionated plexuses of differentiated neurons and glial cells originating entirely from the host neural crest. The presence of excess ET3 in the grafts results in a significant increase in ganglion cell number, while inhibition of endothelin receptor-B (EDNR-B) leads to severe hypoganglionosis. The ET3-induced hyperganglionosis is associated with an increase in enteric crest cell proliferation. Using hindgut explants cultured in collagen gel, we find that ET3 also inhibits neuronal differentiation in the ENS. Finally, ET3, which is strongly expressed in the ceca, inhibits the chemoattraction of NCC to glial-derived neurotrophic factor (GDNF). Our results demonstrate multiple roles for ET3 signaling during ENS development in the avian hindgut, where it influences NCC proliferation, differentiation, and migration. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA. Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1085 Budapest, Hungary. RP Goldstein, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Warren 1153, Boston, MA 02114 USA. EM agoldstein@partners.org FU NICHD NIH HHS [K08HD46655] NR 65 TC 67 Z9 73 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 2006 VL 293 IS 1 BP 203 EP 217 DI 10.1016/j.ydbio.2006.01.032 PG 15 WC Developmental Biology SC Developmental Biology GA 039YD UT WOS:000237343600017 PM 16519884 ER PT J AU Lopez-Avalos, MD Duvivier-Kall, VF Xu, G Bonner-Weir, S Sharma, A Weir, GC AF Lopez-Avalos, MD Duvivier-Kall, VF Xu, G Bonner-Weir, S Sharma, A Weir, GC TI Evidence for a role of the ubiquitin-proteasome pathway in pancreatic islets SO DIABETES LA English DT Article ID CARBOXYL-TERMINAL HYDROLASE; INSULIN-SECRETION; CHRONIC HYPERGLYCEMIA; PROTEIN LIGASE; PGP 9.5; NEUROENDOCRINE CELLS; BETA-CELLS; RAT; EXPRESSION; MARKER AB The ubiquitin-proteasome pathway is crucial for protein turnover. Part of the pathway involves deubiquitination, which is carried out by cystein proteases known as ubiquitin COOH-terminal hydrolases. The isoform Uch-L1 was found to be present in large amounts in rat islets by immunostaining, Western blot analysis, and RT-PCR. Culturing islets in high glucose concentrations (16.7 mmol/A) for 24 h led to decreased gene expression. Exposure to chronic hyperglycemia following 90% partial pancreatectomy also led to reduced Uch-L1 expression. Expression of other members of the ubiquitin-proteasome pathway studied after culturing islets at high glucose concentrations revealed little change except for modest declines in parkin, human ubiquitin-conjugating enzyme 5 (UbcH5), and beta-TRCP (transducin repeat- containing protein). With the pancreatectomy model, expression of polyubiquitin-B and c-Cbl were increased and E6-associated protein was reduced. Further insight about the proteasome pathway was obtained with the proteasome inhibitor lactacystin, which in short-term 2-h experiments enhanced glucose-induced insulin secretion. An important role for the ubiquitin-proteasome pathways in beta-cells is suggested by the findings that changes in glucose concentration influence expression of genes in the pathway and that blockade of the proteasome degradation machinery enhances glucose-stimulated insulin secretion. C1 Harvard Univ, Sch Med, Sect Islet Transplantat & Cell Biol, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lopez-Avalos, MD (reprint author), Univ Malaga, Fac Ciencias, Dpt Biol Celular Genet & Fisiol, Campus Teatinos, E-29071 Malaga, Spain. EM lopezavalos@unia.es OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [DK 35449, P30 DK 36836-16] NR 53 TC 32 Z9 32 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2006 VL 55 IS 5 BP 1223 EP 1231 DI 10.2337/db05-0450 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039KG UT WOS:000237303800006 PM 16644676 ER PT J AU Qi, L Doria, A Manson, JE Meigs, JB Hunter, D Mantzoros, CS Hu, FB AF Qi, L Doria, A Manson, JE Meigs, JB Hunter, D Mantzoros, CS Hu, FB TI Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes SO DIABETES LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; CORONARY-ARTERY-DISEASE; APM1 GENE; PROTEIN; ASSOCIATION; MELLITUS; ADIPOSE; CLASSIFICATION; EXPRESSION; HAPLOTYPE AB Adiponectin is an adipocyte-derived hormone that has shown anti-inflammatory and antiatherogenic effects. We assessed the associations of variants in the adiponectin gene (ADIPOQ) with circulating adiponectin levels and cardiovascular risk among women with type 2 diabetes. Of 989 diabetic women from the Nurses' Health Study, 285 developed cardiovascular disease (CVD) during follow-up through 2000. We genotyped five ADIPOQ polymorphisms in the CVD case and control subjects. A promoter polymorphism - 11365C -> G was significantly associated with lower plasma adiponectin levels (P = 0.004). The homozygotes of allele -4034C were significantly associated with similar to 60% increased cardiovascular risk (odds ratio 1.62 [95% CI 1.07-2.45]). Adjustment for age, BMI, and other covariates did not appreciably change the associations. In addition, a common haplotype possessing allele +276T (CAATT) was associated with a significantly lower CVD risk than the most common haplotype (CAATG) (0.70 [0.50-0.98]). In our meta-analysis of 827 CVD case and 1,887 CVD-free control subjects, polymorphism +276G -> T was significantly associated with similar to 45% (20-62%) decreased CVD risk under a recessive inheritance mode in diabetic patients. In conclusion, ADIPOQ promoter polymorphism -11365C -> G was associated with plasma adiponectin levels, whereas polymorphisms -4034A -> C and +276G -> T were associated with CVD risk in diabetic patients. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Res, Dept Med,Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Med Ctr, Div Endocrinol, Boston, MA 02115 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu FU NCI NIH HHS [CA 87969]; NHLBI NIH HHS [HL 65582, HL 71981, HL 34594]; NIDDK NIH HHS [DK 58845, P30 DK040561-11, P30 DK040561] NR 26 TC 82 Z9 93 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2006 VL 55 IS 5 BP 1512 EP 1516 DI 10.2337/db05-1520 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039KG UT WOS:000237303800043 PM 16644713 ER PT J AU Isasi, CR Soroudi, N Wylie-Rosett, J AF Isasi, CR Soroudi, N Wylie-Rosett, J TI Youth WAVE screener - Addressing weight-related behaviors with school-age children SO DIABETES EDUCATOR LA English DT Article ID PHYSICAL-ACTIVITY; INTERDISCIPLINARY INTERVENTION; US CHILDREN; ADOLESCENTS; OBESITY; PREVALENCE; OVERWEIGHT; STUDENTS; HEALTH; TRENDS AB Purpose This study evaluated the feasibility of using the youth Weight, Activity, Variety, and Excess (WAVE) screener in a classroom setting for assessing student weight control intentions and the extent to which they used the WAVE strategies to control their weight. Methods The Youth WAVE Screener was administered to fifth-grade students in an inner-city school located in the Bronx, New York. The study was conducted in part to increase student awareness of snack foods and sugary beverages in relation to weight. Results Of the 169 students who completed the survey, 45.5% (n = 77) were trying to lose weight. Students who were trying to lose weight were more likely to have low-fat dairy products, less likely to have sugary beverages, and less likely to eat junk foods than those who were not trying to lose weight. Students who reported exercising 3 times weekly were more likely to report healthier dietary patterns and less sedentary behaviors than were students who exercise less often. Feedback and dialogue with fifth graders addressed the relationship between TV viewing and eating behavior, advertisement, availability, and preferences of fruits and vegetables. Conclusions The Youth WAVE Screener can be used to quickly identify children who are concerned about their weight as well as those with dietary and physical activity patterns that may increase the risk of obesity. Diabetes educators can use this screener to start a dialogue with children about their weight-related behaviors. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Isasi, CR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM crisasi@aecom.yu.edu RI Chiang, Vincent, Ming-Hsien/D-4312-2016 OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863 NR 28 TC 10 Z9 10 U1 2 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2006 VL 32 IS 3 BP 415 EP 422 DI 10.1177/0145721706288763 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 047XR UT WOS:000237912500010 PM 16772657 ER PT J AU Bonora, E Corrao, G Bagnardi, V Ceriello, A Comaschi, M Montanari, P Meigs, JB AF Bonora, E Corrao, G Bagnardi, V Ceriello, A Comaschi, M Montanari, P Meigs, JB TI Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus SO DIABETOLOGIA LA English DT Article DE HbA(1c); metabolic control; post-prandial glucose; pre-prandial glucose; type 2 diabetes ID ENDOTHELIUM-DEPENDENT VASODILATION; BLOOD-GLUCOSE; CARDIOVASCULAR-DISEASE; PLASMA-GLUCOSE; MYOCARDIAL-INFARCTION; OXIDATIVE STRESS; GLYCEMIC CONTROL; IDDM PATIENTS; IN-VIVO; INSULIN AB Post-prandial glucose may be a risk factor for cardiovascular disease and chronic diabetic complications. We tested the hypothesis that post-prandial hyperglycaemia is common in type 2 diabetes, even among patients in apparently good glycaemic control, and that simple clinical characteristics identify subsets of diabetic patients with frequent post-prandial hyperglycaemia. Three self-assessed daily blood glucose profiles over a 1-week period, including 18 glucose readings before and 2 h after meals, were obtained from 3,284 unselected outpatients (men 51%; age 63 +/- 10 years) with non-insulin-treated type 2 diabetes mellitus attending 500 different diabetes clinics operating throughout Italy. A post-prandial blood glucose value > 8.89 mmol/l (160 mg/dl) was recorded at least once in 84% of patients, and 81% of patients had at least one Delta glucose >= 2.22 mmol/l (40 mg/dl). Among patients with apparently good metabolic control, 38% had > 40% of post-prandial blood glucose readings > 8.89 mmol/l (>= 4 of 9 meals in total), and 36% had > 40% Delta glucose >= 2.22 mmol/l. In multivariate analysis adjusted for pre-prandial glucose levels, older age, longer duration of diabetes, absence of obesity, hyperlipidaemia and hypertension, as well as treatment with sulfonylureas, were significantly associated with greater glucose excursions after meals. These results indicate that post-prandial hyperglycaemia is a very frequent phenomenon in patients with type 2 diabetes mellitus on active treatment; can occur even when metabolic control is apparently good; and can be predicted by simple clinical features. C1 Univ Hosp Verona, Div Endocrinol & Metab Dis, I-37126 Verona, Italy. Univ Milan, Dept Stat, Biostat Unit, Milan, Italy. Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. Arenzano Hosp, Dept Internal Med, Genoa, Italy. Novartis Italy, Med Board, Milan, Italy. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bonora, E (reprint author), Univ Hosp Verona, Div Endocrinol & Metab Dis, Piazzale Stefani 1, I-37126 Verona, Italy. EM enzobonora@virgilio.it OI Ceriello, Antonio/0000-0001-8122-3203; BONORA, Enzo/0000-0003-1074-5164 NR 45 TC 70 Z9 74 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2006 VL 49 IS 5 BP 846 EP 854 DI 10.1007/s00125-006-0203-x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 037YC UT WOS:000237182900005 PM 16532323 ER PT J AU Shin, JM Sachs, G AF Shin, Jai Moo Sachs, George TI Gastric H,K-ATPase as a drug target SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article ID PROTON-PUMP INHIBITORS; K+-COMPETITIVE INHIBITOR; GASTROESOPHAGEAL-REFLUX DISEASE; HELICOBACTER-PYLORI INFECTION; AMINO-ACID-SEQUENCE; BETA-SUBUNIT; H+/K+-ATPASE; ALPHA-SUBUNIT; PARIETAL-CELL; SUBSTITUTED BENZIMIDAZOLES C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Membrane Biol Lab, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu NR 90 TC 16 Z9 17 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2006 VL 51 IS 5 BP 823 EP 833 DI 10.1007/s10620-005-9042-8 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 061CA UT WOS:000238847600001 PM 16645899 ER PT J AU Clancy, TE Sengupta, TP Paulus, J Ahmed, F Duh, MS Kulke, MH AF Clancy, Thomas E. Sengupta, Tanya P. Paulus, Jessica Ahmed, Fawzia Duh, Mei-Sheng Kulke, Matthew H. TI Alkaline phosphatase predicts survival in patients with metastatic neuroendocrine tumors SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE neuroendocrine tumor; carcinoid tumor; chromogranin; alkaline phosphatase; prognostic factor; survival ID ENDOCRINE GASTROENTEROPANCREATIC TUMORS; NEURON-SPECIFIC ENOLASE; ZOLLINGER-ELLISON-SYNDROME; ISLET-CELL TUMORS; CHROMOGRANIN-A; CARCINOID-TUMORS; PROGNOSTIC-FACTORS; PANCREATIC TUMORS; LONG-TERM; OCTREOTIDE AB The clinical course of patients with metastatic neuroendocrine tumors is highly variable. While some patients experience an indolent clinical course over many years, other patients may rapidly succumb to their disease. Little is known about prognostic factors in these patients, making decisions regarding their management more difficult. We performed a retrospective analysis of 137 patients with metastatic neuroendocrine tumors referred to our institution for treatment. Potential prognostic factors were evaluated using multivariate survival analysis. The median overall survival of patients in our cohort was 6.0 years, although the range of survival times was broad (48 days to 23.4 years). Alkaline phosphatase levels above normal were predictive of shorter survival in both univariate and multivariate analysis. Elevated chromogranin A levels were also associated with shorter survival in univariate analysis; in a multivariate analysis, however, this correlation was no longer significant. There was no association between survival and gender, primary tumor site, or presence or absence of carcinoid syndrome. Elevated alkaline phosphatase is a robust adverse prognostic factor for survival in patients with metastatic neuroendocrine tumors and may be superior to chromogranin A in this setting. Close monitoring of alkaline phosphatase levels may be useful when considering initiation or changes of therapy in patients with metastatic neuroendocrine tumors. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. RP Clancy, TE (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM tclancy@partners.org FU NCI NIH HHS [K23 CA093401]; NHLBI NIH HHS [K30 HL04095] NR 37 TC 38 Z9 38 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 2006 VL 51 IS 5 BP 877 EP 884 DI 10.1007/s10620-006-9345-4 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 061CA UT WOS:000238847600010 PM 16758309 ER PT J AU Morasco, BJ Petry, NM AF Morasco, BJ Petry, NM TI Gambling problems and health functioning in individuals receiving disability SO DISABILITY AND REHABILITATION LA English DT Article DE disability; disordered gambling; pathological gambling; health functioning; mental health ID DISORDERS; PREVALENCE; GAMBLERS; ADULTS; CARE AB Purpose. This study evaluated the rates and correlates of disordered gambling, with a focus on gambling behavior among participants receiving disability. Method. The sample consisted of 723 patients seeking free or reduced-cost dental care. Participants completed the South Oaks Gambling Screen (SOGS), Short Form-12 Health Survey, Second Edition (SF-12v2), and questions assessing demographic characteristics and frequency and intensity of current gambling behaviors. Results. Results indicate a significantly higher prevalence of disordered gambling among participants receiving disability (26%) than in the remainder of the sample (14%; p < 0.001). Of the 135 individuals receiving disability, disordered gambling was associated with decreased physical and mental health functioning. Conclusions. These data indicate that individuals receiving disability have high rates of disordered gambling, and gambling behavior in this population is associated with poorer health functioning. Results suggest that disordered gamblers who receive disability have an increased need for interventions to reduce gambling and associated problems. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Portland VA Med Ctr, Portland, OR USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, 263 Farmington Ave, Farmington, CT 06030 USA. EM petry@psychiatry.uchc.edu FU NIAAA NIH HHS [P50-AA03510]; NIDA NIH HHS [R01-DA14618, P50-DA09241, R01-DA13444]; NIMH NIH HHS [R01-MH60417, R01-MH60417-SUPP] NR 21 TC 19 Z9 19 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PD MAY PY 2006 VL 28 IS 10 BP 619 EP 623 DI 10.1080/09638280500242507 PG 5 WC Rehabilitation SC Rehabilitation GA 041QO UT WOS:000237471000004 PM 16690574 ER PT J AU Seminara, SB DiPietro, MJ Ramaswamy, S Crowley, WF Plant, TM AF Seminara, SB DiPietro, MJ Ramaswamy, S Crowley, WF Plant, TM TI Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male rhesus monkey (Macaca mulatta): A finding with therapeutic implications SO ENDOCRINOLOGY LA English DT Article ID METASTASIS-SUPPRESSOR GENE; PITUITARY-GONADAL AXIS; LUTEINIZING-HORMONE; KISS-1 PEPTIDE; RECEPTOR GPR54; SECRETION; KISSPEPTIN; ACTIVATION; LIGAND; RAT AB The effect of continuous administration of the C-terminal fragment of metastin, the ligand for the G protein-coupled receptor, GPR54, on GnRH-induced LH secretion was examined in three agonadal, juvenile male monkeys whose responsiveness to GnRH was heightened by pretreatment with a chronic pulsatile iv infusion of synthetic GnRH. After bolus injection of 10 mu g human (hu) metastin 45-54 (equivalent to kisspeptin 112-121), the GPR54 agonist was infused continuously at a dose of 100 mu g/h and elicited a brisk LH response for approximately 3 h. This rise was then followed by a precipitous drop in LH despite continuous exposure of GPR54 to metastin 45-54. On d 4, during the final 3 h of the infusion, single boluses of hu metastin 45-54 (10 mu g), N-methyl-DL-aspartic acid (NMDA) (10 mg/kg) and GnRH (0.3 mu g) were administered to interrogate each element of the metastin-GPR54-GnRH-GnRH receptor cascade. Although the NMDA and GnRH boluses were able to elicit LH pulses, that of hu metastin 45-54 was not, demonstrating functional integrity of GnRH neurons (NMDA) and GnRH receptors (NMDA and GnRH) but desensitization of GPR54. The desensitization of GPR54 by continuous hu metastin 45-54 administration has therapeutic implications for a variety of conditions currently being treated by GnRH and its analogs, including restoration of fertility in patients with abnormal GnRH secretion (i.e. idiopathic hypogonadotropic hypogonadism and hypothalamic amenorrhea) and selective, reversible suppression of the pituitary-gonadal axis to achieve suppression of gonadal steroids (i.e. precocious puberty, endometriosis, uterine fibroids, and prostate cancer). C1 Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA 02114 USA. RP Plant, TM (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, S-828A Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM plant1@pitt.edu FU NICHD NIH HHS [R01 HD015788, U54 HD028138, U54 HD029164, U54 HD 08160, U54 HD 28138, R01 HD 13254] NR 29 TC 151 Z9 153 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2006 VL 147 IS 5 BP 2122 EP 2126 DI 10.1210/en.2005-1550 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 033EX UT WOS:000236830600010 PM 16469799 ER PT J AU Linglart, AS Mahon, MJ Kerachian, MA Berlach, DM Hendy, GN Juppner, H Bastepe, M AF Linglart, AS Mahon, MJ Kerachian, MA Berlach, DM Hendy, GN Juppner, H Bastepe, M TI Coding GNAS mutations leading to hormone resistance impair in vitro agonist- and cholera toxin-induced adenosine cyclic 3 ',5 '-monophosphate formation mediated by human XL alpha s SO ENDOCRINOLOGY LA English DT Article ID STIMULATORY G-PROTEIN; PSEUDOHYPOPARATHYROIDISM TYPE IB; PROGRESSIVE OSSEOUS HETEROPLASIA; ALBRIGHT HEREDITARY OSTEODYSTROPHY; IMPRINTING CONTROL ELEMENT; RENAL-CELL LINE; PARATHYROID-HORMONE; MATERNAL TRANSMISSION; SUBUNIT G(S)ALPHA; PARENTAL ORIGIN AB Most loss of function mutations of GNAS identified in different forms of pseudohypoparathyroidism disrupt not only the stimulatory G protein alpha-subunit (Gs alpha), but also its paternally expressed variant, XL alpha s. However, the possibility that XL alpha s deficiency contributes to disease pathogenesis has remained unexplored. We therefore examined the signaling property of human XL alpha s and the effects of one novel (XL alpha s(H7O4P) or Gs alpha(H362P)) and two previously described (XL alpha s(DelI724) and XL alpha s(Y733X) or Gs alpha(DelI382) and Gs alpha(Y391X), respectively) GNAS mutations on either XL alpha s or Gs alpha activity. Confocal immunofluorescence microscopy detected human XL alpha s immunoreactivity at the plasma membrane of transduced mouse embryonic fibroblasts null for endogenous Gs alpha and XL alpha s (Gnas(E2-/E2-) cells). Cholera toxin- and isoproterenol-induced cAMP accumulation in Gnas(E2-/E2-) cells transiently expressing wild-type human XL alpha s was similar to that in cells transiently expressing wild-type Gs alpha. Human XL alpha s, like Gs alpha, mediated PTH-induced cAMP accumulation in Gnas(E2-/E2-) cells coexpressing PTH receptor type 1 and either of these proteins. Moreover, overexpression of human XL alpha s or Gs alpha markedly enhanced the PTH-induced cAMP accumulation in opossum kidney cells that endogenously express PTH receptor type 1. In contrast, each XL alpha s mutant failed to mediate isoproterenol- and PTH-induced cAMP accumulation in transduced Gnas(E2-/E2-) cells. XL alpha s(DelI724) showed a reduced cholera toxin response over the basal level compared with wild-type XL alpha s, and XL alpha s(H704P) completely failed to respond to cholera toxin. These findings were comparable to those observed with each corresponding Gs alpha mutant transiently expressed in Gnas(E2-/E2-) cells. Thus, mutations that typically inactivate Gs alpha also impair XL alpha s activity, consistent with a possible role for XL alpha s deficiency in diseases caused by paternal GNAS mutations. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hop St Vincent de Paul, INSERM, U561, F-75674 Paris, France. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Physiol, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. Royal Victoria Hosp, Hormones & Canc Res Unit, Montreal, PQ H3A 1A1, Canada. Massachusetts Gen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, 50 Blossom St,Thier 501, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU NIDDK NIH HHS [K01 DK062973, K01-DK-062973]; PHS HHS [R01-46718-10] NR 54 TC 34 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2006 VL 147 IS 5 BP 2253 EP 2262 DI 10.1210/en.2005-1487 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 033EX UT WOS:000236830600024 PM 16484323 ER PT J AU Amatniek, JC Hauser, WA DelCastillo-Castaneda, C Jacobs, DM Marder, K Bell, K Albert, M Brandt, J Stern, Y AF Amatniek, JC Hauser, WA DelCastillo-Castaneda, C Jacobs, DM Marder, K Bell, K Albert, M Brandt, J Stern, Y TI Incidence and predictors of seizures in patients with Alzheimer's disease SO EPILEPSIA LA English DT Article DE Alzheimer's disease; seizures; cumulative incidence; predictors; prospective cohort ID ONSET UNPROVOKED SEIZURES; RISK-FACTOR; ADULTS; HYPERTENSION AB Purpose: To determine cumulative incidence and predictors of new-onset seizures in mild Alzheimer's disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients. Methods: Mild AD patients were prospectively followed at 6-month intervals to estimate incidence of unprovoked seizures, compare age-specific risk of unprovoked seizures with population norms, and identify characteristics at baseline (demographics, duration and severity of AD, physical and diagnostic test findings, and comorbid medical and psychiatric conditions) influencing unprovoked seizure risk. Review of study charts and medical records supplemented coded end-point data. Results: The cumulative incidence of unprovoked seizures at 7 years was nearly 8%. In all age groups, risk was increased compared with a standard population, with an 87-fold increase in the youngest group (age 50-59 years) and more than a threefold increase in the oldest group (age 85+ years). In multivariate modeling, independent predictors of unprovoked seizures were younger age [relative risk (RR), 0.89 per year increase in age; 95% confidence interval (CI), 0.82-0.97], African-American ethnic background (RR, 7.35; 95% CI, 1.42-37.98), more-severe dementia (RR, 4.15; 95% CI, 1.06-16.27), and focal epileptiform findings on electroencephalogram (EEG) (RR, 73.36; 95% CI, 1.75-3075.25). Conclusions: Seizure incidence is increased in people starting with mild-to-moderate AD. Younger individuals, African Americans, and those with more-severe disease or focal epileptiform findings on EEG were more likely to have unprovoked seizures. C1 Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10032 USA. Columbia Univ, Dept Neurol, Coll Phys & Surg, New York, NY USA. Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Stern, Y (reprint author), Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. EM ys11@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG 08702, AG07370]; NINDS NIH HHS [5-R01-NS32663] NR 19 TC 218 Z9 223 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2006 VL 47 IS 5 BP 867 EP 872 DI 10.1111/j.1528-1167.2006.00554.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 040AO UT WOS:000237350800008 PM 16686651 ER PT J AU Neilan, TG Yoerger, DM Douglas, PS Marshall, JE Halpern, EF Lawlor, D Picard, MH Wood, MJ AF Neilan, TG Yoerger, DM Douglas, PS Marshall, JE Halpern, EF Lawlor, D Picard, MH Wood, MJ TI Persistent and reversible cardiac dysfunction among amateur marathon runners SO EUROPEAN HEART JOURNAL LA English DT Article DE endurance sport; diastolic dysfunction; tissue Doppler ID VENTRICULAR DIASTOLIC FUNCTION; TISSUE DOPPLER-ECHOCARDIOGRAPHY; STRAIN-RATE ECHOCARDIOGRAPHY; FILLING PRESSURES; PROLONGED EXERCISE; HYPERTROPHIC CARDIOMYOPATHY; VELOCITY; RELAXATION; PRELOAD; HUMANS AB Aims Transient systolic and diastolic abnormalities in ventricular function have previously been documented during endurance sports. However, these described alterations may be limited by the techniques applied. We sought, using less load-dependent methods, to characterize both the extent and the chronology of the cardiac changes associated with endurance events. Methods and results Transthoracic echocardiography (TTE) was performed prior to, immediately after, and approximately 1 month after completion of the 2003 Boston Marathon in 20 amateur athletes. TTE included two-dimensional, spectral and tissue Doppler (TD) and flow propagation velocity (V-p). After completion of the marathon, global measures of left ventricular (LV) systolic function were unchanged (EF 59 +/- 6 vs. 61 +/- 4% post, P=0.14), whereas TD-derived measures of LV systolic function [septal strain -23 +/- 5 vs. -17 +/- 4%, P=0.007; septal strain rate (SR) -1.5 +/- 0.3 vs. -1.1 +/- 0.2 s(-1), P=0.007] and right ventricular (RV) systolic function (RV apical strain -33 +/- 4 vs. -27 +/- 5%, P=0.001; RV apical SR -2.4 +/- 0.7 vs. -1.8 +/- 0.5, P=0.002) were reduced. Significant changes in transmitral velocity (E/A ratio 2.0 +/- 0.5 vs.1.3 +/- 0.3, P=0.005) and TD indices of LV and RV diastolic function (E-a septal 9.5 +/- 1.8 vs. 8.1 +/- 1.2 cm/s post-marathon, P=0.01) were also observed, indicating an inherent alteration in LV relaxation. Although all indices of LV and RV systolic function had returned to normal on follow-up, there were persistent diastolic abnormalities (RV E-a, 11.5 +/- 1.5 cm/s pre-marathon vs. 10.0 +/- 1.6 cm/s follow-up, P=0.01). Conclusion Marathon running leads to transient systolic and more persistent diastolic dysfunction of both the LV and the RV. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Pediat Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. RP Wood, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St,VBK 508, Boston, MA 02114 USA. EM mjwood@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 28 TC 102 Z9 103 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2006 VL 27 IS 9 BP 1079 EP 1084 DI 10.1093/eurheartj/ehi813 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 037UC UT WOS:000237171800015 PM 16554314 ER PT J AU Neilan, TG Jassal, DS Scully, MF Chen, G Deflandre, C McAllister, H Kay, E Austin, SC Halpern, EF Harmey, JH Fitzgerald, DJ AF Neilan, TG Jassal, DS Scully, MF Chen, G Deflandre, C McAllister, H Kay, E Austin, SC Halpern, EF Harmey, JH Fitzgerald, DJ TI Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without compromising tumour suppression SO EUROPEAN HEART JOURNAL LA English DT Article DE doxorubicin; cardiotoxicity; cyclooxygenase; prostaglandins ID ISCHEMIA/REPERFUSION INJURY; INDUCED CARDIOMYOPATHY; MEDIATED APOPTOSIS; TRANSGENIC MICE; BREAST-CANCER; CYCLOOXYGENASE-2; RECEPTOR; CELLS; PROSTACYCLIN; ACTIVATION AB Aims The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has previously been shown to protect against DOX-induced cardiomyocyte injury in vitro. Here, we addressed whether iloprost is cardioprotective in vivo and whether it compromises the anti-tumour efficacy of DOX. Methods and results Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6 mice. DOX treatment was commenced from when tumours became visible. Iloprost was administered from prior to DOX treatment until sacrifice. Echocardiography and invasive haemodynamic measurements were performed immediately before sacrifice. As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of which were attenuated by iloprost. Also, iloprost alone had no effect on tumor growth and indeed, did not alter the DOX-induced suppression of this growth. Conclusion In a murine model, iloprost attenuated the acute cardiac injury and dysfunction induced by DOX therapy without compromising its chemotherapeutic effect. C1 Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Inst Biopharmaceut Sci, Dublin 2, Ireland. Massachusetts Gen Hosp, Dept Med, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Beaumont Hosp, Dept Surg, Dublin 9, Ireland. Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. Univ Coll Dublin, Dept Vet Med, Dublin 2, Ireland. RP Neilan, TG (reprint author), Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Inst Biopharmaceut Sci, St Stephens Green, Dublin 2, Ireland. EM tneilan@partners.org RI Harmey, Judith/C-8570-2012 NR 29 TC 23 Z9 26 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2006 VL 27 IS 10 BP 1251 EP 1256 DI 10.1093/eurheartj/ehl003 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 039PW UT WOS:000237319700021 PM 16624831 ER PT J AU George, S Desai, J Eder, JP Manola, J Ryan, DP Appleman, LJ Demetri, GD AF George, S Desai, J Eder, JP Manola, J Ryan, DP Appleman, LJ Demetri, GD TI Selective kinase inhibition with daily imatinib intensifies toxicity of chemotherapy in patients with solid tumours SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE targeted therapy; kinase inhibition; clinical trial; chemotherapy ID GROWTH-FACTOR-B; GASTROINTESTINAL STROMAL TUMORS; SOFT-TISSUE SARCOMAS; ABL TYROSINE KINASE; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; DERMATOFIBROSARCOMA PROTUBERANS; RANDOMIZED-TRIAL; BETA-RECEPTOR; PANCREATIC-CARCINOMA AB The aim of this study was to determine the safety and maximum-tolerated doses of imatinib combined with cytotoxic chemotherapy (either gemcitabine or doxorubicin). Patients with advanced solid tumours were enrolled separately in two different combinations of imatinib with chemotherapy (imatinib + gemcitabine or imatinib + doxorubicin). A standard modified Fibonacci inter-cohort dose escalation was planned for each combination. Sixteen patients were accrued. Seven patients received gemcitabine and imatinib. A separate cohort of nine patients received imatinib and doxorubicin. In both groups, dose-limiting toxicity (DLT) was observed at the initial dose level requiring dose reductions for subsequent cohorts. Further DLTs were observed necessitating closure of the protocol. Daily dosing of imatinib with concurrent administration of cytotoxic chemotherapy (either gemcitabine or doxorubicin) at standard doses was associated with toxicity that was clinically unacceptable. It remains unclear whether addition of growth factors might improve tolerability for imatininb in combination with cytotoxic chemotherapy. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dana Farber Canc Inst,Ludwid Ctr Canc Res Dana Fa, Boston, MA USA. RP George, S (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, SW530,44 Binney St, Boston, MA 02115 USA. EM Suzanne_George@dfci.harvard.edu OI Appleman, Leonard/0000-0003-4951-7388 NR 47 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAY PY 2006 VL 42 IS 7 BP 864 EP 870 DI 10.1016/j.ejca.2005.12.010 PG 7 WC Oncology SC Oncology GA 046SH UT WOS:000237830800015 PM 16503137 ER PT J AU Reilly, CM Olgun, S Goodwin, D Gogal, RM Santo, A Romesburg, JW Ahmed, SA Gilkeson, GS AF Reilly, CM Olgun, S Goodwin, D Gogal, RM Santo, A Romesburg, JW Ahmed, SA Gilkeson, GS TI Interferon regulatory factor-1 gene deletion decreases glomerulonephritis in MRL/lpr mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE interferon regulatory; factor-1; kidney; lupus; mouse; MRL ID NITRIC-OXIDE SYNTHASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AUTOIMMUNE KIDNEY-DISEASE; GAMMA-INDUCED APOPTOSIS; PERIPHERAL-BLOOD CELLS; IFN-GAMMA; T-CELLS; MRL-FAS(LPR) MICE; DEFICIENT MICE; AUTOANTIBODY PRODUCTION AB To investigate the role of interferon regulatory factor-1 (IRF-1) in the development of lupus nephritis, IRF-1(-/-) genotype mice were bred onto the MRL/1pJfas(1pr) (MRL/1pr) background. We examined kidney mesangial cell function and disease progression. Endpoints evaluated included inflammatory mediators, autoantibody production, immune complex deposition, renal pathology, T cell subset analysis, and duration of survival. Mesangial cells cultured from IRF-1(-/-) mice produced significantly lower levels of nitric oxide and IL-12 but not TNF-alpha when stimulated with LPS + IFN-gamma. IRF-/- mice showed less aggravated dermatitis compared to the wild-type mice. Anti-double-stranded DNA production and proteinuria were significantly decreased in IRF-1(-/-) mice compared to lRF-1(+/+) mice. IgG and C3 deposition as well as glomerulonephritis were decreased in IRF-1(-/-) mice at 26 wk of age compared to the IRF-1(+/+) mice. Splenic CD4(-)CD8(-)CD44(+) T cells were decreased while CD4(+)CD25(+) T cells were increased in the IRF-1(-/-) mice when compared to IRF-1(+/+) mice. Survival rates (ED50) were 22 wk for IRF-1(+/+) mice and 45 wk for IRF-1(-/-) mice. These findings suggest an important role of IRF-1 in mediating renal disease in MRL/1pr mice. C1 Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Virginia Maryland Reg Coll Vet Med, Blacksburg, VA 24060 USA. Via Coll Osteopath Med, Blacksburg, VA USA. Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Reilly, CM (reprint author), Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Virginia Maryland Reg Coll Vet Med, 2265 Kraft Dr, Blacksburg, VA 24060 USA. EM chreilly@vcom.vt.edu FU NIAMS NIH HHS [AR0493190-03] NR 71 TC 29 Z9 29 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2006 VL 36 IS 5 BP 1296 EP 1308 DI 10.1002/eji.200535245 PG 13 WC Immunology SC Immunology GA 046BB UT WOS:000237785300024 PM 16541466 ER PT J AU Tartar, JL Ward, CP McKenna, JT Thakkar, M Arrigoni, E McCarley, RW Brown, RE Strecker, RE AF Tartar, JL Ward, CP McKenna, JT Thakkar, M Arrigoni, E McCarley, RW Brown, RE Strecker, RE TI Hippocampal synaptic plasticity and spatial learning are impaired in a rat model of sleep fragmentation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE EEG; LTD; LTP; sleep disorders; water maze ID LONG-TERM POTENTIATION; POSTTRAUMATIC-STRESS-DISORDER; PERIODIC LEG MOVEMENTS; WATER MAZE TASK; REM-SLEEP; MEMORY CONSOLIDATION; DAYTIME FUNCTION; WAKE COMPLAINTS; DEPRIVATION; PERFORMANCE AB Sleep fragmentation, a symptom in many clinical disorders, leads to cognitive impairments. To investigate the mechanisms by which sleep fragmentation results in memory impairments, rats were awakened once every 2 min via 30 s of slow movement on an automated treadmill. Within 1 h of this sleep interruption (SI) schedule, rats began to sleep in the 90-s periods without treadmill movement. Total non-rapid eye movement sleep (NREM) sleep time did not change over the 24 h of SI, although there was a significant decline in rapid eye movement sleep (REM) sleep and a corresponding increase in time spent awake. In the SI group, the mean duration of sleep episodes decreased and delta activity during periods of wake increased. Control rats either lived in the treadmill without movement (cage controls, CC), or had 10-min periods of movement followed by 30 min of non-movement allowing deep/continuous sleep (exercise controls, EC). EC did not differ from baseline in the total time spent in each vigilance state. Hippocampal long-term potentiation (LTP), a long-lasting change in synaptic efficacy thought to underlie declarative memory formation, was absent in rats exposed to 24 and 72 h SI. In contrast, LTP was normal in EC rats. However, long-term depression and paired-pulse facilitation were unaltered by 24 h SI. Twenty-four hour SI also impaired acquisition of spatial learning in the hippocampus-dependent water maze test. Twenty-four hour SI elevated plasma corticosterone (CORT) to levels previously shown to enhance LTP (125 ng/mL). The results suggest that sleep fragmentation negatively impacts spatial learning. Loss of N-methyl-d-aspartate (NMDA) receptor-dependent LTP in the hippocampal CA1 region may be one mechanism involved in this deficit. C1 Harvard Univ, Sch Med, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Neurosci Lab, In Vitro Electrophysiol Sect, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA USA. Stonehill Coll, Dept Psychol, Easton, MA USA. RP Tartar, JL (reprint author), Harvard Univ, Sch Med, Res 151-C,940 Belmont St, Brockton, MA 02301 USA. EM jaime_tartar@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Ward, Christopher/0000-0001-9932-3894; Tartar, Jaime/0000-0002-3452-0579; Brown, Ritchie/0000-0002-7164-4132 FU BLRD VA [I01 BX001356]; NHLBI NIH HHS [P01 HL095491, P50 HL060292, T32 HL007901, T32 HL07901]; NIMH NIH HHS [F32 MH070156, K01 MH001798, K01 MH01798, R01 MH039683, R01 MH062522, R37 MH039683] NR 71 TC 101 Z9 104 U1 2 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2006 VL 23 IS 10 BP 2739 EP 2748 DI 10.1111/j.1460-9568.2006.04808.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 046LB UT WOS:000237812000021 PM 16817877 ER PT J AU Kim, JW Simmer, JP Lin, BPL Seymen, F Bartlett, JD Hu, JCC AF Kim, Jung-Wook Simmer, James P. Lin, Brent P. -L. Seymen, Figen Bartlett, John D. Hu, Jan C. -C. TI Mutational analysis of candidate genes in 24 amelogenesis imperfecta families SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE amelogenesis imperfecta; AMELX; ENAM; enamel; MMP20 ID AUTOSOMAL-DOMINANT; TRICHODENTOOSSEOUS SYNDROME; NONSENSE MUTATION; ECTODERMAL DYSPLASIA; SHEATH PROTEINS; TOOTH AGENESIS; CHROMOSOME 4Q; TDO SYNDROME; SEX TEST; ENAMEL AB Amelogenesis imperfecta (AI) is a heterogeneous group of inherited defects in dental enamel formation. The malformed enamel can be unusually thin, soft, rough and stained. The strict definition of AI includes only those cases where enamel defects occur in the absence of other symptoms. Currently, there are seven candidate genes for AI: amelogenin, enamelin, ameloblastin, tuftelin, distal-less homeobox 3, enamelysin, and kallikrein 4. To identify sequence variations in AI candidate genes in patients with isolated enamel defects, and to deduce the likely effect of each sequence variation on protein expression and structure, families with isolated enamel defects were recruited. The coding exons and nearby intron sequences were amplified for each of the AI candidate genes by using genomic DNA from the proband as template. The amplification products for the proband were sequenced. Then, other family members were tested to determine their genotype with respect to each sequence variation. All subjects received an oral examination, and intraoral photographs and dental radiographs were obtained. Out of 24 families with isolated enamel defects, only six disease-causing mutations were identified in the AI candidate genes. This finding suggests that many additional genes potentially contribute to the etiology of AI. C1 Univ Michigan, Dent Res Lab, Sch Dent, Ann Arbor, MI 48109 USA. Seoul Natl Univ, Coll Dent, Dept Pediat Dent, Seoul, South Korea. Dent Res Inst, Seoul, South Korea. Univ Calif San Francisco, Sch Dent, Dept Growth & Dev, San Francisco, CA 94143 USA. Istanbul Univ, Fac Dent, Dept Pedodont, Istanbul, Turkey. Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA USA. RP Hu, JCC (reprint author), Univ Michigan, Dent Res Lab, Dept Orthodont & Pediat Dent, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM janhu@umich.edu RI KIM, JUNG-WOOK/G-8992-2012 FU NIDCR NIH HHS [DE11301, DE12769, DE15846, R01 DE014084] NR 77 TC 65 Z9 68 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 3 EP 12 DI 10.1111/j.1600-0722.2006.00278.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800003 PM 16674655 ER PT J AU Margolis, H Gibson, C AF Margolis, Henry Gibson, Carolyn TI Untitled - Foreword SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Editorial Material C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. RP Margolis, H (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP X EP xi DI 10.1111/j.1600-0722.2006.00330.x PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800002 ER PT J AU Bartlett, JD Skobe, Z Lee, DH Wright, JT Li, Y Kulkarni, AB Gibson, CW AF Bartlett, John D. Skobe, Ziedonis Lee, Daniel H. Wright, J. Timothy Li, Yong Kulkarni, Ashok B. Gibson, Carolyn W. TI A developmental comparison of matrix metalloproteinase-20 and amelogenin null mouse enamel SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE ameloblast; amelogenesis imperfecta; enamelysin; knockout mouse ID IMPERFECTA PHENOTYPE; MICE DISPLAY; MATURATION; MUTATIONS; GENOTYPE AB Mutations in both the human amelogenin and human matrix metalloproteinase-20 (MMP20, enamelysin) genes cause amelogenesis imperfecta. Both genes have also been individually deleted from the mouse and each deletion results in defective dental enamel. Here, we compare the stage-specific progression of enamel development in continuously erupting mouse incisors from amelogenin null and MMP-20 null mice. Our goal was to closely examine differences in enamel and enamel organ structure between these mice that would allow a better understanding of each protein's function. The predominant feature of the amelogenin null incisors was the late onset of mineral deposition, with little or no protein present within the forming mineral. Conversely, the developing MMP-20 null incisors had a layer of protein between the apical surface of the ameloblasts and the forming enamel. Furthermore, the protein present within the enamel matrix was disorganized. An analysis of crystal structure demonstrated that the thin amelogenin null enamel was plate-like, while the MMP-20 null enamel had a disrupted prism pattern. These results suggest that amelogenin is essential for appositional crystal growth during the early to mid-secretory stage and for the maintenance of the crystal ribbon structure. They also suggest that MMP-20 is responsible for enamel matrix organization and for subsequent efficient reabsorption of enamel matrix proteins. Both genes are essential for the generation of full-thickness enamel containing the characteristic decussating prism pattern. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC USA. Univ Penn, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. NIDCR, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Wright, John/B-5390-2013 FU Intramural NIH HHS; NIDCR NIH HHS [DE014084, R01 DE014084, DE11089] NR 16 TC 25 Z9 25 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 EI 1600-0722 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 18 EP 23 DI 10.1111/j.1600-0722.2006.00292.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800005 PM 16674657 ER PT J AU Beniash, E Skobe, Z Bartlett, JD AF Beniash, Elia Skobe, Ziedonis Bartlett, John D. TI Formation of the dentino-enamel interface in enamelysin (MMP-20)-deficient mouse incisors SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE biomineralization; calcium phosphate; hydroxyapatite; proteinase ID MECHANICAL-PROPERTIES; HUMAN TEETH; EXPRESSION; JUNCTION; AMELOGENIN; ODONTOBLASTS; MINERALIZATION; AMELOBLASTIN; PROTEINASES; CRYSTALS AB An anomalous dentino-enamel junction (DEJ), manifested by delamination of the enamel layer, was reported in enamelysin [matrix metalloproteinase-20 (MMP-20)] knockout (KO) mice. To better understand the possible role of MMP-20 in the formation of the DEJ, we performed transmission electron microscopy (TEM) studies of the DEJ at early stages of tooth morphogenesis in KO mice. Our TEM analysis revealed that in the incisors from KO mice the mantle dentin is hypomineralized at the onset of enamel mineralization. At this early stage, TEM revealed no apparent differences in nascent aprismatic enamel between the KO mice and the controls. Hypomineralized mantle dentin was also observed in the incisors from KO mice, as assessed by back-scattered SEM at the secretory and early maturation stages, but not in the late-maturation stage, suggesting that the mineralization of mantle dentin is not completely arrested, but rather postponed. Histological studies indicate that the organic content in the initial enamel layer remains very high throughout amelogenesis. These results imply that MMP-20 is involved in the regulation of mineralization in mantle dentin and demonstrate the complex nature of DEJ formation. They also suggest that the structural and functional properties of the DEJ are determined during the initial mineralization stages. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Beniash, E (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM ebeniash@forsyth.org FU NIDCR NIH HHS [DE14084, R01 DE014084] NR 32 TC 21 Z9 22 U1 2 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 24 EP 29 DI 10.1111/j.1600-0722.2006.00293.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800006 PM 16674658 ER PT J AU Haruyama, N Thyagarajan, T Skobe, Z Wright, JT Septier, D Sreenath, TL Goldberg, M Kulkarni, AB AF Haruyama, Naoto Thyagarajan, Tamizchelvi Skobe, Ziedonis Wright, J. Tim Septier, Dominique Sreenath, Taduru L. Goldberg, Michel Kulkarni, Ashok B. TI Overexpression of transforming growth factor-beta 1 in teeth results in detachment of ameloblasts and enamel defects SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE ameloblast; dentin-enamel junction; enamel; gene expression; TGF-beta ID MOUSE TOOTH DEVELOPMENT; HUMAN TUFTELIN GENE; TRANSFORMING GROWTH-FACTOR-BETA-1; ODONTOBLAST DIFFERENTIATION; DENTIN SIALOPHOSPHOPROTEIN; TGF-BETA; EXPRESSION; COLLAGEN; LAMININ; MORPHOGENESIS AB Transforming growth factor-beta 1 (TGF-beta 1) is a key regulator of many cellular processes, including cell adhesion, the immune response and synthesis of extracellular matrix proteins. In the present study, we report the characterization of enamel defects in a transgenic mouse model overexpressing TGF-beta 1 in odontoblasts and ameloblasts, its expression being driven by the promoter sequences of the dentin sialophosphoprotein gene. As reported earlier, these mice develop distinct dentin defects similar to those seen in human dentin dysplasia and dentinogenesis imperfecta. A further detailed examination of enamel in these mice revealed that from the early secretory stage, ameloblasts began to detach from dentin to form cyst-like structures. A soft X-ray analysis revealed that this cyst-like structure had a disorganized and partially mineralized matrix with an abnormal mineralization pattern and a globular appearance. In the molars, the enamel was not only pitted and hypoplastic, but enamel rods were completely lost. Thus, altered TGF-beta 1 expression in the tooth seems to trigger detachment of ameloblasts and abnormal secretion and deposition of minerals in the cyst-like structures adjoining the dentin. We speculate that the altered expression of TGF-beta 1 in teeth impacts the adhesion process of ameloblasts to dentin. C1 NIDCR, Funct Genom Sect, CDBRB, NIH,DHHS, Bethesda, MD 20892 USA. Forsyth Inst, Biostruct Core Facil, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Univ Paris 05, Grp Matrices Extracellulaires & Biominerizat, Montrouge, France. RP Kulkarni, AB (reprint author), NIDCR, Funct Genom Sect, CDBRB, NIH,DHHS, Bldg 30,Room 122,30 Convent Dr, Bethesda, MD 20892 USA. EM ak40m@nih.gov RI Haruyama, Naoto/D-1993-2011 OI Haruyama, Naoto/0000-0001-6225-5816 NR 27 TC 16 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 30 EP 34 DI 10.1111/j.1600-0722.2006.00276.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800007 PM 16674659 ER PT J AU Hubbard, M Tuross Yamakoshi Robinson Brookes Veis Goldberg Snead Beniash Wright Simmer AF Hubbard, Michael Tuross Yamakoshi Robinson Brookes Veis Goldberg Snead Beniash Wright Simmer TI Enamel proteomics and protein interactions - Discussion of session 7 SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Editorial Material C1 Univ Melbourne, Dept Paediat, Melbourne, Vic 3052, Australia. Harvard Univ, Cambridge, MA 02138 USA. Univ Michigan, Ann Arbor, MI 48108 USA. Univ Leeds, Div Oral Biol, Inst Dent, Leeds LS2 9LU, W Yorkshire, England. Univ Leeds, Div Oral Biol, Leeds Dent Inst, Leeds LS2 9LU, W Yorkshire, England. Northwestern Univ, Dept Cell & Mol Biol, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Paris 05, Fac Chirurg Dent, F-92120 Montrouge, France. Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. Univ Michigan, Dent Res Lab, Ann Arbor, MI 48108 USA. RP Hubbard, M (reprint author), Univ Melbourne, Dept Paediat, Flemington Rd, Melbourne, Vic 3052, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 285 EP 286 DI 10.1111/j.1600-0722.2006.00372.x PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800048 ER PT J AU Fowler, CE Beniash, E Yamakoshi, Y Simmer, JP Margolis, HC AF Fowler, Christabel E. Beniash, Elia Yamakoshi, Yasuo Simmer, James P. Margolis, Henry C. TI Co-operative mineralization and protein self-assembly in amelogenesis: silica mineralization and assembly of recombinant amelogenins in vitro SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE amelogenesis; amelogenin; mineralization; self-assembly; silica ID DYNAMIC LIGHT-SCATTERING; TOBACCO-MOSAIC-VIRUS; TEMPLATE MINERALIZATION; MOUSE AMELOGENINS; IMPERFECTA AIH1; ENAMEL; MICROSTRUCTURES; NANOPARTICLES; NANOSPHERES; COMPOSITES AB An amorphous silica mineralization technique was used to produce inorganic/protein composites to elucidate the structure and mechanism of formation of amelogenin assemblies, which may play an important role in regulating enamel structure during the initial stages of amelogenesis. Full-length recombinant amelogenins from mouse (rM179) and pig (rP172) were investigated along with key degradation products (rM166 and native P148) lacking the hydrophilic C terminus found in parent molecules. The resulting products were examined using transmission electron microscopy and/or small-angle X-ray scattering. Using protein concentrations of 0.1-3 mg ml(-1), large monodisperse spheres of remarkably similar mean diameters were observed using rM179 (124 +/- 4 nm) and rP172 (126 +/- 7 nm). These spheres also exhibited 'internal structure', comprising nearly spherical monodisperse particles of approximate to 20 nm in diameter. In the presence of rM166, P148, and bovine serum albumin (control), large unstructured and randomly shaped particles (250-1000 nm) were observed. Without added protein, large dense spherical particles of silica (mean approximate to 500 nm) lacking internal structure were produced. These findings demonstrate that full-length amelogenins have the ability to form higher-order structures, whereas amelogenins that lack the hydrophilic C terminus do not. The results also suggest that full-length amelogenin can guide the formation of organized mineralized structures through co-operative interactions between assembling protein and forming mineral. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. GlaxoSmith Kline, Weybridge, Surrey, England. Univ Michigan, Dept Biol & Mat Sci, Sch Dent, Ann Arbor, MI 48109 USA. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM hmargolis@forsyth.org FU NIDCR NIH HHS [P01-DE 13237] NR 34 TC 10 Z9 10 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 297 EP 303 DI 10.1111/j.1600-0722.2006.00288.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800050 PM 16674702 ER PT J AU Skobe, Z AF Skobe, Ziedonis TI SEM evidence that one ameloblast secretes one keyhole-shaped enamel rod in monkey teeth SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article; Proceedings Paper CT 7th International Symposium on the Composition, Properties and Fundamental Structure of Tooth Enamel (Enamel VII) CY APR 10-14, 2005 CL Brewster, MA SP NIDCR DE ameloblast; amelogenesis; enamel; odontogenesis ID SCANNING ELECTRON-MICROSCOPY; FINE-STRUCTURE; AMELOGENESIS; PRISMS; LARVAL AB 6 Primate enamel is subdivided into inner enamel, having Hunter-Schreger bands, and outer enamel with all rods parallel to each other. Outer inter-rod enamel may surround each rod, lie between rows of rods, or be absent, as in the 'keyhole pattern', which is composed entirely of rods. One theory on the formation of the 'keyhole' pattern overlays the hexagonal cross-sectional shape of four or more ameloblasts over the keyhole shape of the enamel rod. This ignores the likelihood that Tomes processes have a different shape from the cell body, and also ignores the observation that paths of enamel rods sometimes diverge. Scanning electron microscopy (SEM) revealed the keyhole shape of the forming face of monkey enamel. These forming rods were arranged in stepped rows with the head regions in each row separated by the tails of the preceding row. Consequently, each forming face of a rod was surrounded on three sides by previously formed enamel. The apical surface of the Tomes process was shaped exactly like the forming rod face, permitting direct apposition of one rod and one Tomes process. The conclusion was that, in the monkey, each rod of the keyhole enamel configuration is produced by one ameloblast. C1 Forsyth Inst, Boston, MA USA. RP Skobe, Z (reprint author), 140 Fenway, Boston, MA 02115 USA. EM zskobe@forsyth.org NR 19 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 338 EP 342 DI 10.1111/j.1600-0722.2006.00305.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800057 PM 16674709 ER PT J AU Skobe, Z Beniash Line Gantt Smith Hammarstrom Snead Robinson Radlanski Wright AF Skobe, Ziedonis Beniash Line Gantt Smith Hammarstrom Snead Robinson Radlanski Wright TI Formation and structure of dental enamel - Discussion of session 9 SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Editorial Material C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. RP Skobe, Z (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 349 EP 350 DI 10.1111/j.1600-0722.2006.00374.x PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800059 ER PT J AU Margolis, H Gibson, C Diekwisch Moradian-Oldak Fukae Simmer Clarkson Wright Snead Beniash Goldberg Simmer Kirkham Skobe Robinson Limeback AF Margolis, Henry Gibson, Carolyn Diekwisch Moradian-Oldak Fukae Simmer Clarkson Wright Snead Beniash Goldberg Simmer Kirkham Skobe Robinson Limeback TI Highlights and remaining questions SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Editorial Material C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. RP Margolis, H (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD MAY PY 2006 VL 114 SU 1 BP 379 EP 383 DI 10.1111/j.1600-0722.2006.00341.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 082RL UT WOS:000240404800065 ER PT J AU Gruber, SA Silveri, MM Renshaw, PF Tzilos, GK Pollack, M Kaufman, MJ Yurgelun-Todd, DA AF Gruber, SA Silveri, MM Renshaw, PF Tzilos, GK Pollack, M Kaufman, MJ Yurgelun-Todd, DA TI Methadone maintenance improves cognitive performance after two months of treatment SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE methadone maintenance; opiate dependent; cognition ID OPIATE ADDICTS; COCAINE USE; ABUSE; IMPAIRMENT; USERS AB Methadone maintenance (MM) has received little scientific attention regarding neurocognitive effects. The present study examined cognitive function in 17 opiate-dependent subjects at baseline and after 2 months of MM treatment. Subjects demonstrated significant improvements from baseline on measures of verbal learning and memory, visuospatial memory, and psychomotor speed and reduced frequency of drug use (Addiction Severity Index) relative to baseline, although the total percentage of urine samples positive for additional illicit substances was slightly increased. No effect of illicit drug use was observed when the sample was stratified by urine toxicology results, suggesting that improvements in cognition were not associated with additional illicit drug use. Results suggest that opiate-dependent subjects exhibit significant improvement in cognitive function after MM treatment. Future investigations are needed to confirm these findings. C1 McLean Hosp, Brain Imaging Ctr, Cognit Neuroimaging Lab, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gruber, SA (reprint author), McLean Hosp, Brain Imaging Ctr, Cognit Neuroimaging Lab, 115 Mill St, Belmont, MA 02478 USA. EM gruber@mclean.harvard.edu NR 34 TC 37 Z9 41 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD MAY PY 2006 VL 14 IS 2 BP 157 EP 164 DI 10.1037/1064-1297.14.2.157 PG 8 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 050SW UT WOS:000238109800006 PM 16756419 ER PT J AU Tamietto, M Corazzini, LL de Gelder, B Geminiani, G AF Tamietto, M Corazzini, LL de Gelder, B Geminiani, G TI Functional asymmetry and interhemispheric cooperation in the perception of emotions from facial expressions SO EXPERIMENTAL BRAIN RESEARCH LA English DT Review DE emotion; hemispheric asymmetry; bilateral gain; interhemispheric interaction; redundant target effect; face perception ID SEPARATE-ACTIVATION MODELS; SPLIT-BRAIN; CORPUS-CALLOSUM; DIVIDED ATTENTION; REDUNDANT-SIGNALS; NEURAL SUMMATION; RIGHT-HEMISPHERE; REACTION-TIME; CEREBRAL HEMISPHERES; SPATIAL SUMMATION AB The present study used the redundant target paradigm on healthy subjects to investigate functional hemispheric asymmetries and interhemispheric cooperation in the perception of emotions from faces. In Experiment 1 participants responded to checkerboards presented either unilaterally to the left (LVF) or right visual half field (RVF), or simultaneously to both hemifields (BVF), while performing a pointing task for the control of eye movements. As previously reported (Miniussi et al. in J Cogn Neurosci 10:216-230, 1998), redundant stimulation led to shorter latencies for stimulus detection (bilateral gain or redundant target effect, RTE) that exceeded the limit for a probabilistic interpretation, thereby validating the pointing procedure and supporting interhemispheric cooperation. In Experiment 2 the same pointing procedure was used in a go/no-go task requiring subjects to respond when seeing a target emotional expression (happy or fearful, counterbalanced between blocks). Faster reaction times to unilateral LVF than RVF emotions, regardless of valence, indicate that the perception of positive and negative emotional faces is lateralized toward the right hemisphere. Simultaneous presentation of two congruent emotional faces, either happy or fearful, produced an RTE that cannot be explained by probability summation and suggests interhemispheric cooperation and neural summation. No such effect was present with BVF incongruent facial expressions. In Experiment 3 we studied whether the RTE for emotional faces depends on the physical identity between BVF stimuli, and we set a second BVF congruent condition in which there was only emotional but not physical or gender identity between stimuli (i.e. two different faces expressing the same emotion). The RTE and interhemispheric cooperation were present also in this second BVF congruent condition. This shows that emotional congruency is the sufficient condition for the RTE to take place in the intact brain and that the cerebral hemispheres can interact in spite of physical differences between stimuli. C1 Univ Turin, Dept Psychol, I-10123 Turin, Italy. Univ Turin, Ctr Cognit Sci, I-10123 Turin, Italy. Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Tamietto, M (reprint author), Univ Turin, Dept Psychol, Via Po 14, I-10123 Turin, Italy. EM tamietto@psych.unito.it OI Tamietto, Marco/0000-0002-8815-8499 NR 101 TC 29 Z9 32 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2006 VL 171 IS 3 BP 389 EP 404 DI 10.1007/s00221-005-0279-4 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 044HC UT WOS:000237662000010 PM 16374630 ER PT J AU Veiga, JP Costa, LF Sallan, SE Nadler, LM Cardoso, AA AF Veiga, JP Costa, LF Sallan, SE Nadler, LM Cardoso, AA TI Leukemia-stimulated bone marrow endothelium promotes leukemia cell survival SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; FIBROBLAST-GROWTH-FACTOR; MULTIPLE-MYELOMA; INCREASED ANGIOGENESIS; STROMAL CELLS; IN-VIVO; HEMATOLOGIC MALIGNANCIES; LYMPHOCYTIC-LEUKEMIA; TUMOR ANGIOGENESIS AB Extensive endothelial cell proliferation and marked neovascularization are the most pronounced microenvironmental changes consistently observed in the bone marrow (BM) of patients with acute lymphoblastic leukemia (ALL). It is not known whether ALL cells induce this phenotype and whether they receive critical signals from the tumor-associated BM endothelium. Here, we show that leukemia cells actively stimulate BM endothelium, promote de novo angiogenesis, and induce neovascularization in the leukemic BM. Soluble factors, present in the leukemic BM microenvironment, promote the proliferation, migration, and morphogenesis of BM endothelial cells, which are critical processes in tumor angiogenesis. We also show in vitro that leukemia cells display directional motion towards assembled BM endothelium and following adherence exhibit cell polarization, pseudopodia, and ultrastructural features that suggest the existence of leukemia-endothelium cross-talk. Finally, we show that BM endothelium promotes leukemia cell survival through a mechanism mediated through the anti-apoptotic molecule bcl-2. These studies indicate that ALL cells actively recruit BM endothelium and mediate the leukemia-associated neovascularization observed in ALL. Therefore, disruption of interactions between leukemia cells and BM endothelium may constitute a valid therapeutic strategy. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Lisbon, Sch Med, Inst Mol Med, Unit Tumor Biol, P-1699 Lisbon, Portugal. RP Cardoso, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Room D-540B,44 Binney St, Boston, MA 02115 USA. EM cardoso@mbcrr.harvard.edu FU NCI NIH HHS [P01-CA68484] NR 61 TC 28 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 2006 VL 34 IS 5 BP 610 EP 621 DI 10.1016/j.exphem.2006.01.013 PG 12 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 043QF UT WOS:000237615600011 PM 16647567 ER PT J AU Gold, J Valinski, HA Hanks, AN Ballen, KK Hsieh, CC Becker, PS AF Gold, J Valinski, HA Hanks, AN Ballen, KK Hsieh, CC Becker, PS TI Adhesion receptor expression by CD34(+) cells from peripheral blood or bone marrow grafts: Correlation with time to engraftment SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PROGENITOR CELLS; MOLECULE EXPRESSION; PLATELET RECOVERY; STEM-CELLS; L-SELECTIN; IN-VITRO; TRANSPLANTATION; CD44; MEGAKARYOCYTES; HEMATOPOIESIS AB Objective. This study was undertaken to define the pattern of cell adhesion receptor expression by the CD34(+) progenitor cells from mobilized peripheral blood and bone marrow from normal and autologous donors, and to correlate the adhesion receptor profile with time to blood cell recovery for patients undergoing autologous transplant. Methods. Blood cell recovery was determined by absolute neutrophil count (> 500/mu L), time to last red cell transfusion, and platelet count (> 50,000/mu L and > 100,000/mu L). The analysis for expression of adhesion receptors alpha(L) (CD11a), alpha(2) (CD49b), alpha(3) (CD49c), alpha(4) (CD49d), alpha(5) (CD49e), alpha(6) (CD49f), beta(1) (CD29), L-selectin (CD62L), ICAM-1 (CD54), PECAM-1 (CD31), HCAM (CD44), and P-selectin (CD62P) was performed by two-color flow cytometry. The Kruskal-Wallis test and Spearman's rank correlation were used for statistical analysis. Results. Statistical analysis of adhesion expression by the CD34(+) population for patients undergoing autologous transplant demonstrated that the higher percent expression of PECAM-1 correlated with longer time to platelet recovery (> 100,000/mu L, p = 0.049). In contrast, the higher the percent expression of alpha(6) (P = 0.013) and the increased density of expression of alpha(2) (P = 0.035), alpha(3) (P = 0.023), alpha(4) (p = 0.044), beta(1) (p = 0.027), and ICAM-1 (p = 0.010) correlated with shorter time to platelet recovery. Neutrophil recovery time decreased with increased density of expression of alpha(L) (P = 0.014) and P-selectin (p = 0.007) receptors. Increased density of expression of CD44 (HCAM) was associated with longer time to red blood cell recovery (p = 0.05). Conclusion. These data suggest that upregulation of specific adhesion receptors or selection of certain cell populations could result in earlier blood cell recovery after transplant. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Univ Washington, Div Hematol, Dept Med, Seattle, WA 98195 USA. Dana Farber Canc Inst, Seattle, WA 98195 USA. Univ Massachusetts, Dept Math, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01605 USA. RP Becker, PS (reprint author), Univ Washington, Div Hematol, Dept Med, Box 357710,1959 NE Pacific St, Seattle, WA 98195 USA. EM pbecker@u.washington.edu NR 25 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 2006 VL 34 IS 5 BP 680 EP 687 DI 10.1016/j.exphem.2006.01.016 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 043QF UT WOS:000237615600018 PM 16647574 ER PT J AU Park, KI Himes, BT Stieg, PE Tessler, A Fischer, I Snyder, EY AF Park, Kook In Himes, B. Timothy Stieg, Philip E. Tessler, Alan Fischer, Itzhak Snyder, Evan Y. TI Neural stem cells may be uniquely suited for combined gene therapy and cell replacement: Evidence from engraftment of Neurotrophin-3-expressing stem cells in hypoxic-ischemic brain injury SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CEREBRAL-ARTERY OCCLUSION; CLARKES NUCLEUS NEURONS; SPINAL-CORD-INJURY; ADULT-RAT CNS; GROWTH-FACTOR; PROGENITOR CELLS; NEUROTROPHIC FACTOR; FUNCTIONAL RECOVERY; GRANULE NEURONS AB Previously, we reported that, when clonal neural stem cells (NSCs) were transplanted into brains of postnatal mice subjected to unilateral hypoxic-ischemic (HI) injury (optimally 3-7 days following infarction), donor-derived cells homed preferentially (from even distant locations) to and integrated extensively within the large ischemic areas that spanned the hemisphere. A subpopulation of NSCs and host cells, particularly in the penumbra, "shifted" their differentiation towards neurons and oligodendrocytes, the cell types typically damaged following asphyxia and least likely to regenerate spontaneously and in sufficient quantity in the "post-developmental" CNS. That no neurons and few oligodendrocytes were generated from the NSCs in intact postnatal cortex suggested that novel signals are transiently elaborated following HI to which NSCs might respond. The proportion of "replacement" neurons was similar to 5%. Neurotrophin-3 (NT-3) is known to play a role in inducing neuronal differentiation during development and perhaps following injury. We demonstrated that NSCs express functional TrkC receptors. Furthermore, the donor cells continued to express a foreign reporter transgene robustly within the damaged brain. Therefore, it appeared feasible that neuronal differentiation of exogenous NSCs (as well as endogenous progenitors) might be enhanced if donor NSCs were engineered prior to transplantation to (over)express a bioactive gene such as NT-3. A subclone of NSCs transduced with a retrovirus encoding NT-3 (yielding > 90% neurons in vitro) was implanted into unilaterally asphyxiated postnatal day 7 mouse brain (emulating one of the common causes of cerebral palsy). The subclone expressed NT-3 efficiently in vivo. The proportion of NSC-derived neurons increased to similar to 20% in the infarction cavity and > 80% in the penumbra. The neurons variously differentiated further into cholinergic, GABAergic, or glutamatergic subtypes, appropriate to the cortex. Donor-derived glia were rare, and astroglial scarring was blunted. NT-3 likely functioned not only on donor cells in an autocrine/paracrine fashion but also on host cells to enhance neuronal differentiation of both. Taken together, these observations suggest (1) the feasibility of taking a fundamental biological response to injury and augmenting it for repair purposes and (2) the potential use of migratory NSCs in some degenerative conditions for simultaneous combined gene therapy and cell replacement during the same procedure in the same recipient using the same cell (a unique property of cells with stem-like attributes). (c) 2006 Elsevier Inc. All rights reserved. C1 Burnham Inst Med Res, La Jolla, CA 92037 USA. Yonsei Univ, Coll Med, Dept Pediat, Seoul 120749, South Korea. Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120749, South Korea. Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Cornell Univ, Weil Sch Med, Dept Neurosurg, New York, NY 10021 USA. RP Snyder, EY (reprint author), Burnham Inst Med Res, La Jolla, CA 92037 USA. EM esnyder@bumham.org RI Fischer, Itzhak/D-1080-2012 OI Fischer, Itzhak/0000-0003-3187-8740 NR 64 TC 97 Z9 119 U1 2 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2006 VL 199 IS 1 BP 179 EP 190 DI 10.1016/j.expneurol.2006.03.016 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 060KI UT WOS:000238800700020 PM 16714016 ER PT J AU Hataishi, R Rodrigues, AC Morgan, JG Ichinose, F Derumeaux, G Bloch, KD Picard, MH Scherrer-Crosbie, M AF Hataishi, R Rodrigues, AC Morgan, JG Ichinose, F Derumeaux, G Bloch, KD Picard, MH Scherrer-Crosbie, M TI Nitric oxide synthase 2 and pressure-overload-induced left ventricular remodelling in mice SO EXPERIMENTAL PHYSIOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; MITOCHONDRIAL RESPIRATION; CARDIAC DYSFUNCTION; HYPERTROPHY; DEFICIENCY; OVEREXPRESSION; INHIBITION; MORTALITY AB Nitric oxide synthase 2 (NOS2) has been reported to increase in hypertrophied cardiomyocytes; however, whether NOS2 plays a role in the development of hypertrophy is unknown. To investigate the relationship of NOS2 with left ventricular (LV) remodelling and hypertrophy following prolonged pressure overload, we studied 18 male wild-type (WT) and 20 male NOS2-deficient (NOS2(-/-)) mice before and 7, 14 and 28 days after transverse aortic constriction (TAC) using echocardiography. A subgroup of eight WT and eight NOS2(-/-) mice were studied 42 days after TAC. Haemodynamic measurements were obtained before killing. Left ventricular size and function were similar for both genotypes at baseline. After TAC for 28 days, both groups developed LV hypertrophy, with echo-derived LV mass increasing from 78 +/- 2 to 147 +/- 10 mg in WT and from 86 +/- 3 to 142 +/- 10 mg in NOS2(-/-) mice. Twenty-eight days after TAC, LV weight and cardiomyocyte width were also similar in both genotypes. Fractional shortening (FS) decreased on day 7 from 57 +/- 1 to 48 +/- 2% in WT and from 59 +/- 1 to 49 +/- 2% in NOS2(-/-) mice. Although this decrease in FS was transient in WT mice, it persisted in NOS2(-/-) mice. Invasively measured parameters of systolic and diastolic function, however, were similar in the two genotypes both 28 and 42 days after TAC. A load-independent index of contractility, E-max, was similar in both strains 42 days after TAC. In conclusion, NOS2 does not appear to have a critical role in the development of LV hypertrophy after chronic pressure overload. C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. EM marielle@crosbie.com OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-42397, HL-71987, HL-70896] NR 26 TC 9 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0958-0670 J9 EXP PHYSIOL JI Exp. Physiol. PD MAY 1 PY 2006 VL 91 IS 3 BP 633 EP 639 DI 10.1113/expphysiol.2005.033068 PG 7 WC Physiology SC Physiology GA 036HT UT WOS:000237062900015 PM 16527862 ER PT J AU Wen, PY Kesari, S Drappatz, J AF Wen, Patrick Y. Kesari, Santosh Drappatz, Jan TI Malignant gliomas: strategies to increase the effectiveness of targeted molecular treatment SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE malignant gliomas; targeted molecular therapy ID GROWTH-FACTOR RECEPTOR; FACTOR-KAPPA-B; PHASE-II TRIAL; PROGRESSIVE GLIOBLASTOMA-MULTIFORME; TYROSINE KINASE INHIBITORS; BRAIN-TUMOR CONSORTIUM; RESISTANCE IN-VITRO; CELL LUNG-CANCER; RECURRENT GLIOBLASTOMA; ANTIEPILEPTIC DRUGS AB Recently, there has been increasing interest in the use of targeted molecular agents for the treatment of malignant gliomas. These agents are generally well tolerated but have demonstrated only modest activity. In this article, the current status of targeted molecular agents for malignant gliomas will be reviewed and strategies to improve their effectiveness will be discussed. C1 Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Brigham & Womens Canc Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, SW43D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org; skesayi@partners.org; jdrappatz@partners.org RI Kesari, Santosh/E-8461-2013 NR 193 TC 32 Z9 33 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD MAY PY 2006 VL 6 IS 5 BP 733 EP 754 DI 10.1586/14737140.6.5.733 PG 22 WC Oncology SC Oncology GA 090AM UT WOS:000240923000015 PM 16759164 ER PT J AU Bowser, R Cudkowicz, M Kaddurah-Daouk, R AF Bowser, R Cudkowicz, M Kaddurah-Daouk, R TI Biomarkers for amyotrophic lateral sclerosis SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE amyotrophic lateral sclerosis; biomarker; mass spectrometry; metabolomics; proteomics; surrogate marker ID VOLUNTARY ISOMETRIC CONTRACTION; INCREASED OXIDATIVE DAMAGE; CENTRAL-NERVOUS-SYSTEM; SURROGATE END-POINTS; MOTOR-NEURON DISEASE; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE; SUPEROXIDE-DISMUTASE; GENE-EXPRESSION; CLINICAL-TRIAL AB Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. ALS is a fatal neurodegenerative disease and clinical diagnosis typically takes many months to complete. Early disease diagnosis through the use of biomarkers may aid in correct clinical management of patients and possibly delay time to ventilator and morbidity. This review explores the progress of biomarker discovery efforts for ALS and the many challenges that remain. Included are different technologies utilized in biomarker discovery efforts (proteomic, genomic and metabolomic) and putative biomarkers uncovered using these techniques. These studies have discovered genetic mutations leading to familial forms of ALS, and specific protein alterations that occur in biological fluids (cerebrospinal fluid and blood) and/or tissues of ALS subjects. More recent high-throughput technologies have revealed panels of proteomic or metabolic biomarkers that can discriminate between ALS and control groups. The identification of disease-specific biomarkers will provide opportunities to develop early diagnostic measures as well as surrogate markers to monitor disease progression and test drug efficacy in clinical trials. C1 Univ Pittsburgh, Dept Pathol, Sch Med, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. RP Bowser, R (reprint author), Univ Pittsburgh, Dept Pathol, Sch Med, ST S-420,200 Lothrop St, Pittsburgh, PA 15261 USA. EM bowserp@upmc.edu; mcudkowicz@partners.org; kaddu001@mc.duke.edu FU NIEHS NIH HHS [R21 ES013470] NR 128 TC 38 Z9 44 U1 0 U2 6 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2006 VL 6 IS 3 BP 387 EP 398 DI 10.1586/14737159.6.3.387 PG 12 WC Pathology SC Pathology GA 047ZA UT WOS:000237916000011 PM 16706741 ER PT J AU Almog, N Henke, V Flores, L Hlatky, L Kung, AL Wright, RD Berger, R Hutchinson, L Naumov, GN Bender, E Akslen, LA Achilles, EG Folkman, J AF Almog, Nava Henke, Vanessa Flores, Ludmila Hlatky, Lynn Kung, Andrew L. Wright, Renee D. Berger, Raanan Hutchinson, Lloyd Naumov, George N. Bender, Elise Akslen, Lars A. Achilles, Eike-Gert Folkman, Judah TI Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis SO FASEB JOURNAL LA English DT Article ID GROWTH-FACTOR; CANCER; THROMBOSPONDIN-1; EXPRESSION; MATRIX-METALLOPROTEINASE-9; DISEASE; SWITCH; CELLS AB The disease state of cancer appears late in tumor development. Before being diagnosed, a tumor can remain for prolonged periods of time in a dormant state. Dormant human cancer is commonly defined as a microscopic tumor that does not expand in size and remains asymptomatic. Dormant tumors represent an early stage in tumor development and may therefore be a potential target for nontoxic, antiangiogenic therapy that could prevent tumor recurrence. Here, we characterize an experimental model that recapitulates the clinical dormancy of human tumors in mice. We demonstrate that these microscopic dormant cancers switch to the angiogenic phenotype at a predictable time. We further show that while angiogenic liposarcomas expand rapidly after inoculation of tumor cells in mice, nonangiogenic dormant liposarcomas remain microscopic up to one-third of the normal severe combined immune deficiency ( SCID) mouse life span, although they contain proliferating tumor cells. Nonangiogenic dormant tumors follow a similar growth pattern in subcutaneous (s.c.) and orthotopic environments. Throughout the dormancy period, development of intratumoral vessels is impaired. In nonangogenic dormant tumors, small clusters of endothelial cells without lumens are observed early after tumor cell inoculation, but the nonangiogenic tumor cannot sustain these vessels, and they disappear within weeks. There is a concomitant decrease in microvessel density, and the nonangiogenic dormant tumor remains harmless to the host. In contrast, microvessel density in tumors increases rapidly after the angiogenic switch and correlates with rapid expansion of tumor mass. Both tumor types cultured in vitro contain fully transformed cells, but only cells from the nonangiogenic human liposarcoma secrete relatively high levels of the angiogenesis inhibitors thrombospondin-1 and TIMP-1. This model suggests that as improved blood or urine molecular biomarkers are developed, the microscopic, nonangiogenic, dormant phase of human cancer may be vulnerable to antiangiogenic therapy years before symptoms, or before anatomical location of a tumor can be detected, by conventional methods. C1 Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hamburg Hosp, Clin Hepatobiliary Surg & Visceral Transplantat, D-2000 Hamburg, Germany. RP Folkman, J (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. EM judah.folkman@childrens.harvard.edu RI Akslen, Lars /C-1202-2017; OI Akslen, Lars /0000-0003-2710-9543; Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA-78496, CA-64481] NR 24 TC 58 Z9 59 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2006 VL 20 IS 7 BP 947 EP + DI 10.1096/fj.05-3946fje PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 079EG UT WOS:000240157700017 PM 16638967 ER PT J AU Mantena, SK Katiyar, SK AF Mantena, SK Katiyar, SK TI Grape seed proanthocyanidins inhibit UV-radiation-induced oxidative stress and activation of MAPK and NF-kappa B signaling in human epidermal keratinocytes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE grape seed proanthocyanidins; oxidative stress; ultraviolet radiation; mitogen-activated protein kinases; hydrogen peroxide; glutathione peroxidase; glutathione; NF-kappa B; free radicals ID POLYPHENOL (-)-EPIGALLOCATECHIN-3-GALLATE TREATMENT; GREEN TEA POLYPHENOLS; PROTEIN-KINASE; MOUSE SKIN; ANTIOXIDANT ENZYMES; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; ULTRAVIOLET-LIGHT; SUPEROXIDE ANION; CELL-SURVIVAL AB Solar ultraviolet (UV) radiation-induced oxidative stress has been implicated in various skin diseases. Here, we report the photoprotective effect of grape seed proanthocyanidins (GSPs) on UV-induced oxidative stress and activation of mitogen-activated protein kinase (MAPK) and NF-kappa B signaling pathways using normal human epidermal keratinocytes (NHEK). Treatment of NHEK with GSPs inhibited UVB-induced hydrogen peroxide (H2O2), lipid peroxidation, protein oxidation, and DNA damage in NHEK and scavenged hydroxyl radicals and superoxide anions in a cell-free system. GSPs also inhibited UVB-induced depletion of antioxidant defense components,. such as glutathione peroxidase, catalase, superoxide dismutase, and glutathione. As UV-induced oxidative stress mediates activation of MAPK and NF-kappa B signaling pathways, we determined the effects of GSPs on these pathways. Treatment of NHEK with GSPs inhibited UVB-induced phosphorylation of ERK1/2, JNK, and p38 proteins of the MAPK family at the various time points studied. As UV-induced H2O2 plays a major role in activation of MAPK proteins, NHEK were treated with H2O2 with or without GSPs and other known antioxidants, viz. (-)-epigallocatechin-3 -gallate, silymarin, ascorbic acid, and N-acetylcysteine. It was observed that H2O2,induced phosphorylation of ERK1/2, JNK, and p38 was decreased by these antioxidants. Under identical conditions, GSPs also inhibited UVB-induced activation of NF-kappa B/p65, which was mediated through inhibition of degradation and activation Of I kappa B alpha and IKK alpha, respectively. Together, these results Suggest that GSPs could be useful in the attenuation of UV-radiation-induced oxidative stress-mediated skin diseases in human skin. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, Volker Hall 557,1670 Univ Blvd,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCI NIH HHS [CA104428] NR 56 TC 97 Z9 107 U1 4 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2006 VL 40 IS 9 BP 1603 EP 1614 DI 10.1016/j.freeradbiomed.2005.12.032 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 041DP UT WOS:000237433900012 PM 16632120 ER PT J AU Katic, M Bosnjak, B Gall-Troselj, K Dikic, I Pavelic, K AF Katic, M Bosnjak, B Gall-Troselj, K Dikic, I Pavelic, K TI A clinoptilolite effect on cell media and the consequent effects on tumor cells in vitro SO FRONTIERS IN BIOSCIENCE LA English DT Article DE clinoptilolite; cancer; treatment; cell signalling; PKB/Akt; ERK; JNK; NF kappa B; apoptosis ID NF-KAPPA-B; PROTEIN-KINASE B; ZEOLITE CLINOPTILOLITE; NATURAL CLINOPTILOLITE; CANCER PREVENTION; ACTIVATION; AKT; P53; ANTICANCER; THERAPY AB Clinoptilolite is a nontoxic natural zeolite with properties of an ion-exchanger and adsorbent. Earlier studies showed that clinoptilolite could be an adjuvant in cancer therapy. The aim of this study was to define effects of clinoptilolite in cell media on cell viability and activity of key proteins regulating cell survival, cell division and stress response. The number of viable cells, DNA synthesis and activity of EGF-R, PKB/Akt and NF.B was reduced, while apoptosis was increased in cells that were cultured in medium supplemneted with clinoptilolite. These results might be due to adsorbtion of some serum components such as EGF to clinoptilolite. In treated medium without serum the predominant role of clinoptilolite is that of cation exchange, likely affecting calcium levels and calcium-dependent signalling pathways. These results are in line with other data that confirm enhanced apoptosis in cells incubated in treated medium. Together, data presented here demonstrate that clinoptilolite affects cellular microenvironment through mechanisms that are dependent on adsorptive and ion-exchange characteristics of this material. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Frankfurt, Sch Med, UNI Klin, Inst Biochem 2, D-60590 Frankfurt, Germany. Pliva, Inst Res, HR-10000 Zagreb, Croatia. Rudjer Boskovic Inst, Div Mol Med, HR-10000 Zagreb, Croatia. RP Katic, M (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM masa.katic@joslin.harvard.edu RI Dikic, Ivan/O-4650-2015; OI Dikic, Ivan/0000-0001-8156-9511; Bosnjak, Berislav/0000-0003-3374-7488 NR 60 TC 18 Z9 20 U1 2 U2 12 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2006 VL 11 BP 1722 EP 1732 DI 10.2741/1918 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 996NG UT WOS:000234180200046 PM 16368551 ER PT J AU Hill, AE Hong, JS Wen, H Teng, LH McPherson, DT McPherson, SA Levasseur, DN Sorscher, EJ AF Hill, AE Hong, JS Wen, H Teng, LH McPherson, DT McPherson, SA Levasseur, DN Sorscher, EJ TI Micro-RNA-like effects of complete intronic sequences SO FRONTIERS IN BIOSCIENCE LA English DT Article DE intron; function; micro-RNA; regulation; transcription; gene signalling ID MESSENGER-RNA; 1ST INTRON; WILD-TYPE; GENE; DNA; EXPRESSION; DIFFERENTIATION; NETWORKS; TERMINUS; PROTEINS AB MicroRNAs (miRNAs) have been suggested as suppressors of numerous target genes in human cells. In this report, we present gene chip array data indicating that in the absence of miRNA sequences, complete human introns are similarly capable of coordinating expression of large numbers of gene products at spatially diverse sites within the genome. The expression of selected intronic sequences (6a, 14b and 23) derived from the cystic fibrosis transmembrane conductance regulator (CFTR) gene caused extensive and specific transcriptional changes in epithelial cells (HeLa) that do not normally express this gene product. Each intron initiated a distinctive pattern of gene transcription. Affected genes such as FOXF1, sucrase-isomaltase, collagen, interferon, complement and thrombospondin 1 have previously been linked to CFTR function or are known to contribute to the related processes of epithelial differentiation and repair. A possible regulatory function of this nature has not been demonstrated previously for non-coding sequences within eukaryotic DNA. The results are consistent with the observation that splicesomal introns are found only in eukaryotic organisms and that the number of introns increases with phylogenetic complexity. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Pittman Gen Clin Res Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Comp & Informat Sci, Birmingham, AL 35294 USA. Univ Alabama, Gregory Flemming James Cyst Fibrosis Ctr, Birmingham, AL 35294 USA. Univ Alabama, AIDS Res Ctr, Birmingham, AL 35294 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Sorscher, EJ (reprint author), 1918 Univ Blvd,MCLM 796, Birmingham, AL 35294 USA. EM sorscher@uab.edu NR 36 TC 22 Z9 24 U1 0 U2 2 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2006 VL 11 BP 1998 EP 2006 DI 10.2741/1941 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 996NG UT WOS:000234180200069 PM 16368574 ER PT J AU Ramaswamy, S Seminara, SB DiPietro, MJ Crowley, WF Plant, TM AF Ramaswamy, Suresh Seminara, Stephanie B. DiPietro, Meloni J. Crowley, William F., Jr. Plant, Tony M. TI Effects of continuous intravenous administration of human metastin 45-54 on the activity in the hypothalamic-pituitary-gonadal axis of intact adult male rhesus monkeys (Macaca mulatta) SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 78 EP 78 DI 10.1016/j.yfrne.2006.03.164 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300153 ER PT J AU DiPietro, MJ Ramaswamy, S Seminara, SB Crowley, WF Plant, TM AF DiPietro, Meloni J. Ramaswamy, Suresh Seminara, Stephanie B. Crowley, William F., Jr. Plant, Tony M. TI Attempts to activate a pubertal pattern of GnRH release in juvenile male rhesus monkeys (Macaca mulatta) with continuous low dose infusions of human metastin 45-54 SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 6th International Congress of Neuroendocrinology CY JUN 19-22, 2006 CL Pittsburgh, PA SP Int Neuroendocrine Federat C1 Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD MAY PY 2006 VL 27 IS 1 BP 140 EP 140 DI 10.1016/j.yfrne.2006.03.286 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 055NB UT WOS:000238456300267 ER PT J AU Anand, BS Currie, S Dieperink, E Bin, EJ Shen, H Ho, SB Wright, T AF Anand, BS Currie, S Dieperink, E Bin, EJ Shen, H Ho, SB Wright, T CA VA HCV 001 Study Grp TI Alcohol use and treatment of hepatitis C virus: Results of a national multicenter study SO GASTROENTEROLOGY LA English DT Article ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; LIVER-DISEASE; ANTIVIRAL THERAPY; UNITED-STATES; PEGINTERFERON ALPHA-2B; INITIAL TREATMENT; RANDOMIZED-TRIAL; NATURAL-HISTORY; INFECTION; VETERANS AB Background & Aims: Patients with hepatitis C virus (HCV) infection who use alcohol have been excluded from clinical trials; therefore, outcomes with antiviral therapy are unknown. The aim of the study was to determine the impact of alcohol use on HCV treatment outcomes. Methods: Subjects using alcohol were categorized as follows: no alcohol versus regular alcohol use, quantity consumed (none, < 6 drinks/ day, >= 6 drinks/day), CAGE score < 2 or >= 2, and recent alcohol use (past 12 months). Patients were treated with interferon plus ribavirin. Results: A total of 4061 subjects were enrolled, and 726 (18%) received treatment. Alcohol use (past and within 12 months) reduced treatment candidacy. Past alcohol use did not affect the end-of-treatment response, sustained virologic response (SVR), and treatment discontinuation rates. However, recent alcohol use resulted in higher treatment discontinuation (40% vs 26%; P =.0002) and tended to reduce the SVR (14% vs 20%; P =.06), but when patients who discontinued treatment were excluded from analysis, the trend in favor of nondrinkers for SVR disappeared (25% vs 23%). These findings were also consistent in subgroup analyses on race and genotype. Conclusions: Eligibility for anti-HCV treatment was reduced in past and recent drinkers. Recent alcohol use was associated with increased treatment discontinuation and lower SVR. However, patients who use alcohol and completed the treatment had a response comparable to that of nondrinkers. Patients with a history of alcohol use should not be excluded from HCV therapy. Instead, additional support should be provided to these patients to ensure their ability to complete treatment. C1 Michael E DeBakey VA Med Ctr, Digest Dis Sect, Dept Med, Houston, TX 77030 USA. San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Minneapolis VA Med Ctr, Dept Med, Minneapolis, MN USA. VA New York Harbor Healthcare Syst, Dept Med, Brooklyn, NY USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Anand, BS (reprint author), Michael E DeBakey VA Med Ctr, Digest Dis Sect, Dept Med, 2002 Holcombe Blvd,111D, Houston, TX 77030 USA. EM anaO@flash.net NR 34 TC 84 Z9 85 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2006 VL 130 IS 6 BP 1607 EP 1616 DI 10.1053/j.gastro.2006.02.023 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 044QG UT WOS:000237686700011 PM 16697724 ER PT J AU Bradesi, S Kokkotou, E Simeonidis, S Patierno, S Ennes, HS Mittal, Y McRoberts, JA Ohning, G McLean, P Marvizon, JC Sternini, C Pothoulakis, C Mayer, EA AF Bradesi, S Kokkotou, E Simeonidis, S Patierno, S Ennes, HS Mittal, Y McRoberts, JA Ohning, G McLean, P Marvizon, JC Sternini, C Pothoulakis, C Mayer, EA TI The role of neurokinin 1 receptors in the maintenance of visceral hyperalgesia induced by repeated stress in rats SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/106th Annual Meeting of the American-Gastroenterological-Association CY MAY 14-19, 2005 CL Chicago, IL SP Amer Gastroenterol Assoc ID SUBSTANCE-P RECEPTOR; CLOSTRIDIUM-DIFFICILE TOXIN; IRRITABLE-BOWEL-SYNDROME; SPINAL-CORD SLICES; NK1 RECEPTOR; TACHYKININ NK1; GASTROINTESTINAL-TRACT; DORSAL-HORN; LAMINA-I; MUCOSAL INFLAMMATION AB Background & Aims: The neurokinin 1 receptors (NK(1)Rs) and substance P (SP) have been implicated in the stress and/or pain pathways involved in chronic pain conditions. Here we examined the participation of NK(1)Rs in sustained visceral hyperalgesia observed in rats exposed to chronic psychological stress. Methods: Male Wistar rats were exposed to daily 1-hour water avoidance stress (WA) or sham WA for 10 consecutive days. We tested intraperitoneal or intrathecal injection of the NK1R antagonist SR140333 on the visceromotor reflex to colorectal distention in both groups at day 11. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were used to assess the expression of NK(1)Rs and/or SP in samples of colon, spinal cord, and dorsal root ganglia. Results: Both intraperitoneal and intrathecal SR140333 injection diminished the enhanced visceromotor reflex to colorectal distention at day 11 in stressed rats but did not affect the response in control animals. Realtime polymerase chain reaction and Western blotting demonstrated stress-induced up-regulation of spinal NK(1)LRs. Immunohistochemistry showed an increased number of NK1R-expressing neurons in the laminae I of the dorsal horn in stressed rats. The expression of NK(1)Rs was decreased in colon from stressed rats compared with control. The expression of SP gene precursor in dorsal root ganglia was unchanged in stressed rats compared with controls. Conclusions: Stress-induced increased NK1R expression on spinal neurons and the inhibitory effect of intrathecal NK1R antagonist on visceral hyperalgesia support the key contribution of spinal NK(1)Rs in the molecular pathways involved in the maintenance of visceral hyperalgesia observed after chronic WA. C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Brain Res, Dept Neurobiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol,Gastrointestinal Neuropeptide C, Boston, MA 02115 USA. GlaxcoSmithKline, Neurol & G1 Ctr Excellence Drug Discovery, Harlow, Essex, England. RP Mayer, EA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth, Room 223,VAGLAHS,11301 Willshire Blvd,CURE Bldg, Los Angeles, CA 90073 USA. EM emayer@ucla.edu FU NCCIH NIH HHS [R24 AT00281]; NIDDK NIH HHS [DK41301, DK47343, DK57037, R21 DK071767, R21 DK071767-01, DK54155, P50 DK64539] NR 69 TC 35 Z9 37 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2006 VL 130 IS 6 BP 1729 EP 1742 DI 10.1053/j.gastro.2006.01.037 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 044QG UT WOS:000237686700024 PM 16697737 ER PT J AU Rattner, D Hawes, RH AF Rattner, D Hawes, RH TI Notes: Gathering momentum SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gastrointestinal & Gen Surg, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Div Gastrointestinal & Gen Surg, Boston, MA 02114 USA. NR 2 TC 21 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2006 VL 63 IS 6 BP 838 EP 839 DI 10.1016/j.gie.2006.03.915 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 039SK UT WOS:000237327000020 PM 16650549 ER PT J AU Muthusamy, V Hobbs, C Nogueira, C Cordon-Cardo, C McKee, PH Chin, L Bosenberg, MW AF Muthusamy, V Hobbs, C Nogueira, C Cordon-Cardo, C McKee, PH Chin, L Bosenberg, MW TI Amplification of CDK4 and MDM2 in malignant melanoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE AMPLIFICATION; CDKN2A P16(INK4A); COPY NUMBER; INACTIVATION; TARGETS; CANCER; P14(ARF); GLIOMAS; MOUSE; PCR AB Amplification of the 12q 13-15 region is a common event in several human tumors including liposarcomas, gliomas, and osteosarcomas. We have demonstrated high-level amplification of 12q 14 in a subset of uncultured malignant melanomas (3 of 53). High-resolution mapping of the amplicon using quantitative PCR revealed a bipartite amplicon consisting of a primary 50-kb amplicon centered on CDK4 and a secondary amplicon centered on MDM2, without amplification of the intervening 11 Mb of genomic DNA. Analysis of mRNA and protein levels in melanomas with 12q 14 amplification demonstrated overexpression of target genes CDK4 and MDM2 without loss of CDKN2A-P16 (P16INK4A) or CDKN2A-P14ARF (P14ARF) expression, important regulators of the RBI and TP53 pathways, which are commonly lost or mutated in melanoma. These results suggest that coamplification of CDK4 and MDM2 may substitute for loss of P16INK4A and P14ARF function in a subset of melanomas. (c) 2006 Wiley-Liss, Inc. C1 Univ Vermont, Dept Pathol, Burlington, VT 05495 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Univ Porto, Fac Med, IPATIMUP, Oporto, Portugal. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Vermont Canc Ctr, Burlington, VT USA. RP Bosenberg, MW (reprint author), Univ Vermont, Dept Pathol, 323 HSRF,149 Beaumont Ave, Burlington, VT 05495 USA. EM Marcus.Bosenberg@uvm.edu RI Nogueira, Cristina/N-4574-2015 OI Nogueira, Cristina/0000-0002-0853-5304 FU NCI NIH HHS [K08 CA89124, P30 CA22435, R01 CA112054] NR 22 TC 85 Z9 88 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2006 VL 45 IS 5 BP 447 EP 454 DI 10.1002/gcc.20310 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 030LJ UT WOS:000236635800003 PM 16419059 ER PT J AU Bosenberg, M Muthusamy, V Curley, DR Wang, ZX Hobbs, C Nelson, B Nogueira, C Horner, JW DePinho, R Chin, L AF Bosenberg, M Muthusamy, V Curley, DR Wang, ZX Hobbs, C Nelson, B Nogueira, C Horner, JW DePinho, R Chin, L TI Characterization of melanocyte-specific inducible Cre recombinase transgenic mice SO GENESIS LA English DT Article DE melanocyte; Cre; mouse; skin; tamoxifen; tyrosinase; melanoma ID EXPRESSION; MUTAGENESIS; RAS AB Conditional Cre-mediated recombination has emerged as a robust method of introducing somatic genetic alterations in an organ-specific manner in the mouse. Here, we generated and characterized mice harboring a 4-hydroxytamoxifen (OHT)-inducible Cre recombinase-estrogen receptor fusion transgene under the control of the melanocyte-specific tyrosinase promoter, designated Tyr::CreER(T2). Cre-mediated recombination was induced in melanocytes in a spatially and temporally controlled manner upon administration of OHT and was documented in embryonic melanoblasts, follicular bulb melanocytes, dermal dendritic melanocytes, epidermal melanocytes of tail skin, and in putative melanocyte stem cells located within the follicular bulge. Functional evidence suggestive of recombination in follicular melanocyte stem cells included the presence of Cre-mediated recombination in follicular bulb melanocytes 1 year after topical OHT administration, by which time several hair cycles have elapsed and the melanocytes residing in this location have undergone multiple rounds of apoptosis and replenishment. These Tyr::CreER(T2) transgenic mice represent a useful resource for the evaluation of melanocyte developmental genetics, the characterization of melanocyte stem cell function and dynamics, and the construction of refined mouse models of malignant melanoma. C1 Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA USA. Univ Porto, Fac Med, Inst Mol Pathol & Immunol, Oporto, Portugal. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. RP Bosenberg, M (reprint author), Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. EM Marcus.Bosenberg@uvm.edu RI Nogueira, Cristina/N-4574-2015 OI Nogueira, Cristina/0000-0002-0853-5304 NR 17 TC 52 Z9 53 U1 0 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD MAY PY 2006 VL 44 IS 5 BP 262 EP 267 DI 10.1002/dvg.20205 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 049RN UT WOS:000238034300006 PM 16676322 ER PT J AU Foster, R Solano, S Mahoney, J Fuller, A Oliva, E Seiden, MV AF Foster, R Solano, S Mahoney, J Fuller, A Oliva, E Seiden, MV TI Reclassification of a tubal leiomyosarcoma as an eGIST by molecular evaluation of c-KIT SO GYNECOLOGIC ONCOLOGY LA English DT Article DE sarcoma; c-KIT mutation; eGIST; imatimb ID GASTROINTESTINAL STROMAL TUMORS; EXPRESSION; MUTATIONS; IMATINIB; BIOLOGY; MASS AB Background. Extragastrointestinal stromal tumors (eGISTs) are rare mesenchymal-derived tumors arising outside of the GI tract. eGISTs are often histologically confused with leiomyosarcoma. Distinction between eGIST and leiomyosarcoma is critical because of the unique responsiveness of eGISTs to the molecularly targeted agent imatinib. Case. A woman presented with a history of tubal spindle cell tumor that was initially diagnosed and treated as a leiomyosarcoma. Because of minimal response to sarcoma directed chemotherapy, the possibility that the tumor was in fact an eGIST was investigated and supported by immunohistochemical and mutational analyses of the c-Kit receptor tyrosine kinase. The patient currently has stable disease control on imatinib for the last 18 months. Conclusions. The possibility of eGIST should be considered in the differential diagnosis of tumors with a spindle cell morphology in the gynecologic tract especially when involving the ovary, fallopian tube, or uterine serosa. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Foster, R (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. EM Rfoster1@partners.org NR 23 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2006 VL 101 IS 2 BP 363 EP 366 DI 10.1016/j.ygyno.2005.12.022 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 046LS UT WOS:000237813700033 PM 16439005 ER PT J AU Fox, RA Neufeld, EJ Bennett, CM AF Fox, RA Neufeld, EJ Bennett, CM TI Rituximab for adolescents with haemophilia and high titre inhibitors SO HAEMOPHILIA LA English DT Article DE haemophilia; immune tolerance; inhibitors; paediatrics; rituximab ID MONOCLONAL-ANTIBODY TREATMENT; AUTOIMMUNE HEMOLYTIC-ANEMIA; IMMUNE TOLERANCE INDUCTION; FACTOR-VIII INHIBITORS; FACTOR-IX ANTIBODIES; THROMBOCYTOPENIC PURPURA; ACQUIRED HEMOPHILIA; THERAPY; AUTOANTIBODY; DEFICIENCY AB Neutralizing alloantibodies (inhibitors) to factor VIII or factor IX develop in approximately 25% of patients with haemophilia A and < 3% of patients with haemophilia B treated with factor concentrate. Patients with high titre inhibitors, in whom immune tolerance therapy fails, have few treatment options. Targeted anti-B-cell therapy with rituximab (chimeric anti-CD20) has been useful in several antibody-mediated autoimmune states. Case reports of rituximab treatment in small numbers of haemophilia patients with inhibitors have been inconclusive. We describe three adolescent patients with severe haemophilia and inhibitors treated with four weekly doses of rituximab, 375 mg m(-2). Treatment with rituximab was effective in reducing the inhibitor titre in two of three patients. Rituximab may be beneficial for patients with severe haemophilia and inhibitors in whom standard therapies have failed, but larger prospective studies are required to determine safety, efficacy and predictors of success. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Bennett, CM (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Fegan 702, Boston, MA 02115 USA. EM carolyn.bennett@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011 NR 26 TC 35 Z9 36 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2006 VL 12 IS 3 BP 218 EP 222 DI 10.1111/j.1365-2516.2006.01215.x PG 5 WC Hematology SC Hematology GA 035PQ UT WOS:000237014200003 PM 16643204 ER PT J AU Cunningham, MG Goldstein, M Katz, D O'Neil, SQ Joseph, A Price, B AF Cunningham, MG Goldstein, M Katz, D O'Neil, SQ Joseph, A Price, B TI Coalescence of psychiatry, neurology, and neuropsychology: From theory to practice SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Neuropsychiatry-Association CY FEB-MAR -, 2005 CL Bal Harbour, FL SP Amer Neuropsychiat Assoc DE collaboration; cross-training; multidisciplinary; neurology; neuropsychiatry; psychiatry ID TRAUMATIC BRAIN-INJURY; BORDERLINE PERSONALITY-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSION; FUNCTIONAL NEUROANATOMY; INTELLECTUAL FRAMEWORK; HIPPOCAMPAL-NEURONS; CINGULATE CORTEX; METABOLIC-RATE; SCHIZOPHRENIA AB In a climate of renewed interest in the synergy between neurology and psychiatry, practitioners are increasingly recognizing the importance of exchange and collaboration between these two disciplines. However, there are few working models of interdisciplinary teams that freely share expertise in real time, while providing clinical and academic training to future physicians who specialize in the central nervous system. Over the past 11 years, the McLean Hospital Neuropsychiatry and Behavioral Neurology service has provided proof-of-principle for such collaboration, demonstrating that a team comprising psychiatrists, neurologists, and neuropsychologists can function effectively as a unit while maintaining the autonomy of these three disciplines and also synthesizing their combined knowledge. In addition to delivering enhanced patient care and promoting medical research, this clinical service has provided enriched cross-specialty training for fellows, residents, and medical students. The practical functioning of the team is described, and case vignettes are presented to illustrate the team's collaborative synergism in practice. C1 McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Med Sch, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Med Sch, Dept Neurol, Cambridge, MA 02138 USA. Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Univ British Columbia, Dept Psychol, Vancouver, BC, Canada. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Cunningham, MG (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM mcunningham@mclean.harvard.edu NR 48 TC 9 Z9 10 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2006 VL 14 IS 3 BP 127 EP 140 DI 10.1080/10673220600748536 PG 14 WC Psychiatry SC Psychiatry GA 058XH UT WOS:000238697400001 PM 16787885 ER PT J AU O'Brien, LM Ziegler, DA Deutsch, CK Kennedy, DN Goldstein, JM Seidman, LJ Hodge, S Makris, N Caviness, V Frazier, JA Herbert, MR AF O'Brien, LM Ziegler, DA Deutsch, CK Kennedy, DN Goldstein, JM Seidman, LJ Hodge, S Makris, N Caviness, V Frazier, JA Herbert, MR TI Adjustment for whole brain and cranial size in volumetric brain studies: A review of common adjustment factors and statistical methods SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE adjustment factors; allometry; autism; brain morphometry; brain size; head size; macrocephaly; MRI; regional brain volumes; statistical methods; volumetrics ID PERVASIVE DEVELOPMENTAL DISORDERS; HEAD CIRCUMFERENCE; INTRACRANIAL VOLUME; CEREBRAL-CORTEX; AUTISM; EVOLUTION; CHILDREN; ADULTS; MRI; AGE AB In this article we address analytic challenges inherent in brain volumetrics (i.e., the study of volumes of brains and brain regions). It has sometimes been assumed in the literature that deviations in regional brain size in clinical samples are directly related to maldevelopment or pathogenesis. However, this assumption may be incorrect; such volume differences may, instead, be wholly or partly attributable to individual differences in overall dimension (e.g., for head, brain, or body size). What quantitative approaches can be used to take these factors into account? Here, we provide a review of volumetric and nonvolumetric adjustment factors. We consider three examples of common statistical methods by which one can adjust for the effects of body, head, or brain size on regional volumetric measures: the analysis of covariance, the proportion, and the residual approaches. While the nature of the adjustment will help dictate which method is most appropriate, the choice is context sensitive, guided by numerous considerations-chiefly the experimental hypotheses, but other factors as well (including characteristic features of the disorder and sample size). These issues come into play in logically framing the assessment of putative abnormalities in regional brain volumes. C1 Colby Coll, Waterville, ME 04901 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. McLean Hosp, Belmont, MA USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Belmont, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Cambridge Hlth Alliance, Cambridge, MA USA. RP Herbert, MR (reprint author), Massachusetts Gen Hosp, Ctr Morphometr Anal, 149 13th St 6th Fl, Charlestown, MA 02129 USA. RI Kennedy, David/H-3627-2012 NR 63 TC 41 Z9 42 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 2006 VL 14 IS 3 BP 141 EP 151 DI 10.1080/10673220600784119 PG 11 WC Psychiatry SC Psychiatry GA 058XH UT WOS:000238697400002 PM 16787886 ER PT J AU Young, MRI AF Young, MRI TI Protective mechanisms of head and neck squamous cell carcinomas from immune assault SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE head and neck cancer; HNSCC; immune; immunosuppression; suppressor cells ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; MACROPHAGE SUPPRESSOR ACTIVITY; COLONY-STIMULATING FACTOR; CD34(+) PROGENITOR CELLS; BLOOD MONONUCLEAR-CELLS; TUMOR-BEARING MICE; HLA CLASS-I; CANCER-PATIENTS; PERIPHERAL-BLOOD AB Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that is the sixth most common neoplasm in the world. Despite advances in treatments involving surgery, radiation, and chemotherapy, the 5-year survival has remained at less than 50% for the past 30 years, primarily because of local recurrences, Thus, the possibility of immunotherapeutic approaches for patients with HNSCC has gained interest. Unfortunately, patients with HNSCC have profound immune defects that are associated with increased recurrence. This review aims to provide an overview of both the defensive and immune subversive mechanisms by which patients with HNSCC can protect themselves from immune antitumor assault. (c) 2005 Wiley Periodicals, Inc. C1 Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. NR 92 TC 40 Z9 42 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAY PY 2006 VL 28 IS 5 BP 462 EP 470 DI 10.1002/hed.20331 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 039HP UT WOS:000237296900011 PM 16284974 ER PT J AU Levine, AJ Hinkin, CH Marion, S Keuning, A Castellon, SA Lam, MN Robinet, M Longshore, D Newton, T Myers, H Durvasula, RS AF Levine, AJ Hinkin, CH Marion, S Keuning, A Castellon, SA Lam, MN Robinet, M Longshore, D Newton, T Myers, H Durvasula, RS TI Adherence to antiretroviral medications in HIV: Differences in data collected via self-report and electronic monitoring SO HEALTH PSYCHOLOGY LA English DT Article DE adherence; electronic monitoring; self-report; HAART; HIV ID PROTEASE INHIBITORS; VIRAL LOAD; THERAPY; PREDICTORS; ADULTS AB Controversy remains regarding the reliability of methods used to determine adherence to antiretroviral medication in HIV. In this study the authors compared adherence rates of 119 HIV-positive participants during a 6-month study, as estimated via electronic monitoring (EM) and self-report (SR). Adherence for both short (4-day) and long (4-week, or intervisit) periods was examined, as well as factors that underlie discrepancies between EM and SR. Results showed that intervisit EM estimates were consistently lower than those of SR. SR estimates based on shorter periods (4 days) were closer to those of EM. Higher discrepancies between EM and SR estimates were associated with lower cognitive functioning and externalized focus of control. These findings lend support for using both EM and SR methods; however, study design (e.g., length) and other factors (e.g., cognitive status, cost) should be considered. C1 Univ Calif Los Angeles, Dept Neurol, Natl Neurol AIDS Bank, Inst Neuropsychiat, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90032 USA. RP Levine, AJ (reprint author), Univ Calif Los Angeles, Dept Neurol, Natl Neurol AIDS Bank, Inst Neuropsychiat, 11645 Wilshire Blvd,Suite 770, Los Angeles, CA 90025 USA. EM ajlevine@mednet.ucla.edu OI newton, thomas/0000-0002-3198-5901 FU NIDA NIH HHS [R01 DA13799, R01 DA013799]; NIMH NIH HHS [T32 MH19535] NR 29 TC 40 Z9 41 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAY PY 2006 VL 25 IS 3 BP 329 EP 335 DI 10.1037/0278-6133.25.3.329 PG 7 WC Psychology, Clinical; Psychology SC Psychology GA 045SB UT WOS:000237761300009 PM 16719604 ER PT J AU Sigalovsky, IS Melcher, JR AF Sigalovsky, IS Melcher, JR TI Effects of sound level on fMRI activation in human brainstem, thalamic and cortical centers SO HEARING RESEARCH LA English DT Article DE BOLD; sound intensity; level coding; cardiac gating; sparse imaging; interleaved sampling ID PRIMARY AUDITORY-CORTEX; DEPENDENT REPRESENTATION; TEMPORAL ENVELOPE; PRESSURE LEVEL; HESCHLS GYRUS; STIMULI; NOISE; CAT; INTENSITY; FREQUENCY AB The dependence of fMRI activation on sound level was examined throughout the auditory pathway of normal human listeners using continuous broadband noise, a stimulus widely used in neuroscientific investigations of auditory processing, but largely neglected in neuro-imaging. Several specialized techniques were combined here for the first time to enhance detection of brainstem activation, mitigate scanner noise, and recover temporal resolution lost by the mitigation technique. The main finding was increased activation with increasing level in cochlear nucleus, superior olive, inferior colliculus, medial geniculate body and auditory cortical areas. We suggest that these increases reflect monotonically increasing activity in a preponderance of individual auditory neurons responsive to broadband noise. While the time-course of activation changed with level, the change was subtle and only significant in a part of the cortex. To our knowledge, these are the first fMRI data showing the effects of sound level in subcortical centers or for a non-tonal, non-speech stimulus at any stage of the pathway. The present results add to the body of parametric data in normal human listeners and are fundamental to the design of any fMRI experiment employing continuous noise. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Sigalovsky, IS (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM plumbum@alum.mit.edu FU NIDCD NIH HHS [P01 DC000119, P01 DC000119-260023, P01 DC00119, P30 DC005209] NR 40 TC 50 Z9 53 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 2006 VL 215 IS 1-2 BP 67 EP 76 DI 10.1016/j.heares.2006.03.002 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 052ZX UT WOS:000238273900008 PM 16644153 ER PT J AU Ioannou, GN Weiss, NS Boyko, EJ Mozaffarian, D Lee, SP AF Ioannou, GN Weiss, NS Boyko, EJ Mozaffarian, D Lee, SP TI Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; INSULIN-RESISTANCE; NONALCOHOLIC STEATOHEPATITIS; METABOLIC SYNDROME; ASSOCIATION; PREVALENCE; POPULATION; PREDICTION; FRAMINGHAM; CIRRHOSIS AB In the United States, elevated serum alanine aminotransferase (ALT) activity in the absence of viral hepatitis of excessive alcohol consumption is most commonly attributed to nonalcoholic fatty liver disease (NAFLD). NAFLD is related to predictors of coronary heart disease (CHD) such as insulin resistance and central obesity. We examined the association between elevated serum ALT activity and the 10-year risk of CHD as estimated using the Framingham risk score (FRS). We performed a cross-sectional analysis comparing participants in the Third National Health and Nutrition Examination Survey with normal and elevated ALT activity (> 43 IU/L), examining the mean levels of FRS. Among participants without viral hepatitis or excessive alcohol consumption, those with elevated ALT activity (n = 267) had a higher FRS than those with normal ALT activity (n = 7,259), both among men (mean difference in FRS 0.25, 95% CI 0.07-0.4; hazard ratio for CHD 1.28, 95% CI 1.07-1.5) and women (mean difference in FRS 0.76, 95% CI 0.4-1.1; hazard ratio for CHD 2.14, 95% CI 1.5-3.0). The ALT threshold for increased risk of CHD was higher in men (> 43 IU/L) than in women (> 30 IU/L). Elevated ALT activity was not associated with higher FRS among nonobese participants with viral hepatitis or excessive alcohol consumption. In conclusion, individuals with elevated serum ALT activity in the absence of viral hepatitis or excessive alcohol consumption, most of whom have NAFLD, have an increased calculated risk of CHD. This association is more prominent in women. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu RI Mozaffarian, Dariush/B-2276-2008; Lee, Sum Ping/C-4333-2009 NR 32 TC 120 Z9 125 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2006 VL 43 IS 5 BP 1145 EP 1151 DI 10.1002/hep.21171 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 039SM UT WOS:000237327200031 PM 16628637 ER PT J AU Rishikof, DC Lucey, EC Kuang, PP Snider, GL Goldstein, RH AF Rishikof, DC Lucey, EC Kuang, PP Snider, GL Goldstein, RH TI Induction of the myofibroblast phenotype following elastolytic injury to mouse lung SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE elastase; emphysema; alpha-smooth muscle actin; elastin; type I collagen ID ELASTASE-INDUCED EMPHYSEMA; RETINOIC ACID; PULMONARY-EMPHYSEMA; REGULATES ELASTIN; GROWTH; FIBROBLASTS; EXPRESSION; COLLAGEN; CELLS; TRANSCRIPTION AB The repair of alveolar structures following endotracheal administration of porcine pancreatic elastase (PPE) to mice involves the coordinated deposition of new matrix elements. We determined the induction of the myofibroblast phenotype following elastolytic injury to mouse lung by examining the expression of alpha-smooth muscle actin (alpha-SMA) by immunohistochemistry. We also examined elastin and alpha 1(I) collagen mRNA expression by in situ hybridization. Changes in airspace dimensions were assessed by determining mean linear intercept. In untreated mice, alpha-SMA was localized to vascular structures and large airways, with no detectable expression in alveolar units. PPE induced alpha-SMA expression in damaged areas surrounding large vessels, in septal remnants, and in the opening ring of alveolar ducts. Elastin and alpha 1(I) collagen mRNA expression were up-regulated in residual alveolar structures and septal walls. PPE dose-response studies indicated that alpha 1(I) collagen and elastin mRNA expression were not induced in areas of normal lung adjacent to damaged lung. The administration of low dose PPE resulted in increased alpha-SMA protein and elastin mRNA expression in the cells comprising the opening ring of alveolar ducts. Our data suggest that repair mechanisms following elastolytic injury are confined to overtly damaged alveolar structures and involve the induction of the myofibroblast phenotype. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Goldstein, RH (reprint author), Boston Univ, Sch Med, Ctr Pulm, 715 Albany St,R-304, Boston, MA 02118 USA. EM rgoldstein@lung.bumc.bu.edu FU NHLBI NIH HHS [HL70182, HL46902, HL04232, HL66547] NR 30 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD MAY PY 2006 VL 125 IS 5 BP 527 EP 534 DI 10.1007/s00418-005-0109-6 PG 8 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 036QN UT WOS:000237090000008 PM 16328432 ER PT J AU Sankale, JL Tong, Q Hadigan, CM Tan, G Grinspoon, SK Kanki, PJ Hotamisligil, GS AF Sankale, JL Tong, Q Hadigan, CM Tan, G Grinspoon, SK Kanki, PJ Hotamisligil, GS TI Regulation of adiponectin in adipocytes upon exposure to HIV-1 SO HIV MEDICINE LA English DT Article DE adipocyte; adiponectin; HAART; HIV; insulin resistance; lipodystrophy ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS-INFECTED PATIENTS; INSULIN-RESISTANCE; PROTEASE INHIBITORS; PREADIPOCYTE DIFFERENTIATION; FAT REDISTRIBUTION; NEGATIVE MEN; LIPODYSTROPHY; ACCUMULATION; INCREASES AB Objectives Adipose dysregulation, dyslipidemia, and insulin resistance are hallmarks of HIV-related lipodystrophy. The precise mechanisms behind these disturbances are unknown. In HIV-infected patients, we previously demonstrated a strong relationship between lipodystrophy and levels of adiponectin, an adipose peptide implicated in regulation of glucose and lipid metabolisms. In this study we investigated the effect of HIV on adipocytes, to determine whether HIV can directly infect adipocytes and/or alter the regulation and secretion of the adipocyte-derived hormone adiponectin. Methods Human subcutaneous preadipocytes and adipocytes were exposed to HIV-1 under various conditions. Adiponectin was measured in supernatants and cell lysates. Results Although adipocytes expressed CD4, the major HIV receptor, they could not be infected in vitro. However, exposure to HIV dramatically increased the secretion of adiponectin from human adipocytes, in the absence of infection. This was exacerbated with sustained exposure to HIV in a transwell assay. Further, human peripheral mononuclear cells also produced adiponectin, but this was largely dependent upon T-cell activation. Conclusions We propose that the stimulation of adiponectin production by HIV can perturb adiponectin regulation, leading to substantially decreased levels upon viral suppression by antiretroviral therapy. These data suggest a potential molecular mechanism of adiponectin regulation in HIV-infected patients. C1 Harvard Univ, Sch Publ Hlth, Div Biol Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard AIDS Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA USA. RP Hotamisligil, GS (reprint author), Harvard Univ, Sch Publ Hlth, Div Biol Sci, 655 Huntington Ave, Boston, MA 02115 USA. EM ghotamis@hsph.harvard.edu FU NIAID NIH HHS [AI43879, AI46724]; NIDDK NIH HHS [R01DK-59535] NR 28 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD MAY PY 2006 VL 7 IS 4 BP 268 EP 274 DI 10.1111/j.1468-1293.2006.00372.x PG 7 WC Infectious Diseases SC Infectious Diseases GA 028BO UT WOS:000236460700010 PM 16630040 ER PT J AU Kraemer, BC Burgess, JK Chen, JH Thomas, JH Schellenberg, GD AF Kraemer, BC Burgess, JK Chen, JH Thomas, JH Schellenberg, GD TI Molecular pathways that influence human tau-induced pathology in Caenorhabditis elegans SO HUMAN MOLECULAR GENETICS LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; PAIRED HELICAL FILAMENTS; AXONAL-TRANSPORT DEFECTS; PROTEIN PHOSPHATASE 2A; TRANSGENIC MICE; FRONTOTEMPORAL DEMENTIA; C-ELEGANS; TRANSCRIPTION FACTORS; ALZHEIMERS-DISEASE; NEURONAL POLARITY AB Mutations in the gene encoding tau cause frontotemporal dementia with parkinsonism-chromosome 17 type (FTDP-17). In FTDP-17, Alzheimer's disease, and other tauopathies, aggregated hyper-phosphorylated tau forms the neurofibrillary tangles characteristic of these disorders. We previously reported a Caenorhabditis elegans model for tauopathies using human normal and FTDP-17 mutant tau as transgenes. Neuronal transgene expression caused insoluble phosphorylated tau accumulation, neurodegeneration and uncoordinated (Unc) movement. Here we describe a genome-wide RNA-mediated interference (RNAi) screen for genes that modify the tau-induced Unc phenotype. We tested RNAi sequences for 16 757 genes and found 75 that enhanced the transgene-induced Unc phenotype. Forty-six of these genes have sequence similarity to known human genes and fall into a number of broad classes including kinases, chaperones, proteases and phosphatases. The remaining 29 modifiers have sequence similarity only with other nematode genes. To determine if the enhancers are specific for the tau-induced Unc behavior, we exposed several non-tau Unc mutants to tau RNAi enhancer clones. Fifteen enhancers modified phenotypes in multiple Unc mutants, whereas 60 modified only the Unc phenotype in the tau transgenic lines. We also introduced the tau transgene into the background of genetic loss-of-function mutations for a subset of the enhancer genes. Tau transgenic animals homozygous for loss of these enhancer genes exhibited increased impaired motility relative to the tau transgene line alone. This work uncovers novel candidate genes that prevent tau toxicity, as well as genes previously implicated in tau-mediated neurodegeneration. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Div Neurogenet, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle Div, 1660 S Columbian Ave, Seattle, WA 98108 USA. EM zachdad@u.washington.edu FU NIA NIH HHS [AG017586] NR 94 TC 71 Z9 90 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2006 VL 15 IS 9 BP 1483 EP 1496 DI 10.1093/hmg/ddl067 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 035LL UT WOS:000237002400010 PM 16600994 ER PT J AU Dhingra, R Pencina, MJ Wang, TJ Nam, BH Benjamin, EJ Levy, D Larson, MG Kannel, WB D'Agostino, RB Vasan, RS AF Dhingra, R Pencina, MJ Wang, TJ Nam, BH Benjamin, EJ Levy, D Larson, MG Kannel, WB D'Agostino, RB Vasan, RS TI Electrocardiographic QRS duration and the risk of congestive heart failure - The Framingham heart study SO HYPERTENSION LA English DT Article DE electrocardiography; epidemiology; heart failure ID BUNDLE-BRANCH BLOCK; LEFT-VENTRICULAR HYPERTROPHY; CARDIAC RESYNCHRONIZATION; DILATED CARDIOMYOPATHY; SYSTOLIC DYSFUNCTION; CRITERIA; POPULATION AB Prolonged electrocardiographic QRS duration is frequently observed in congestive heart failure (CHF) patients. We hypothesized that CHF risk increases with longer QRS interval in individuals free of CHF. We evaluated 1759 Framingham Study participants ( mean age, 69 years; 63% women) without prior myocardial infarction or CHF who attended a routine examination. QRS duration was analyzed as a continuous (log-transformed) and a categorical variable [referent, < 100 ms; incomplete bundle branch block (BBB), 100 to 119 ms; complete BBB, >= 120 ms]. During follow-up ( mean, 12.7 years), 324 participants (205 women) developed CHF. CHF incidence increased across the 3 baseline QRS duration categories in both sexes. Each SD increment in log-QRS duration was associated with a multivariable-adjusted 23% increase in CHF risk [95% confidence interval [CI] 8% to 38%; P < 0.001]. In time-dependent models with QRS category and risk factors updated every 2 years, incomplete BBB was associated with a 1.4-fold (95% CI, 1.05 to 1.96; P = 0.03) and complete BBB with a 1.7-fold (95% CI, 1.28 to 2.35; P < 0.001) risk of CHF. These associations were maintained on adjustment for baseline left ventricular mass. In our community-based sample, longer electrocardiographic QRS was associated with increased CHF risk, consistent with the hypothesis that depolarization delay may increase CHF risk. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288, 2K24HL04334, K23HL74077, N01-HC-25195] NR 30 TC 42 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2006 VL 47 IS 5 BP 861 EP 867 DI 10.1161/01.HYP.0000217141.20163.23 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 034PP UT WOS:000236943400014 PM 16585411 ER PT J AU Moran, A Palmas, W Pickering, TG Schwartz, JE Field, L Weinstock, RS Shea, S AF Moran, A Palmas, W Pickering, TG Schwartz, JE Field, L Weinstock, RS Shea, S TI Office and ambulatory blood pressure are independently associated with albuminuria in older subjects with type 2 diabetes SO HYPERTENSION LA English DT Article DE blood pressure monitoring, ambulatory; diabetes mellitus; elderly ID CARDIOVASCULAR-DISEASE; EXCRETION RATE; METABOLIC-CONTROL; IDDM PATIENTS; FOLLOW-UP; MICROALBUMINURIA; RISK; HYPERTENSION; NEPHROPATHY; MELLITUS AB Blood pressure strongly predicts microalbuminuria and later progression to renal failure in people with diabetes. Ambulatory blood pressure monitoring seems to be superior to office blood pressure in predicting progression to microalbuminuria in type 1 diabetes. The associations of ambulatory blood pressure with office blood pressure and microalbuminuria in type 2 diabetes remain unclear. We studied the association of office blood pressure taken with an automated device and ambulatory blood pressure with spot urine albumin: creatinine ratio in 1180 older people with type 2 diabetes participating in the Informatics for Diabetes Education and Telemedicine Study. Office and awake systolic blood pressure were independently associated with albuminuria ( P < 0.001 for both) in a multivariate linear regression analysis that adjusted for age, gender, duration of diabetes, hemoglobin A1c, number of antihypertensive medications, and use of an angiotensin- converting enzyme inhibitor or angiotensin receptor blocker. Twelve percent of participants had well- controlled office blood pressure but not ambulatory blood pressure, whereas 14% had well- controlled ambulatory but not office blood pressure. The prevalence of microalbuminuria and macroalbuminuria in these subgroups was intermediate between those with well- controlled or uncontrolled blood pressure by both methods. We found, in a multiethnic group of older subjects with type 2 diabetes, that office systolic blood pressure and awake systolic ambulatory blood pressure exhibited independent associations with degree of albuminuria. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Biomed Informat, New York, NY USA. Columbia Univ, Behav Cardiovasc Hlth & Hypertens Program, New York, NY USA. Columbia Univ, Dept Epidemiol, Joseph Mailman Sch Publ Hlth, New York, NY USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. RP Shea, S (reprint author), Div Gen Med, 622 W 168th St,PH 9-E, New York, NY 10032 USA. EM ss35@columbia.edu NR 41 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2006 VL 47 IS 5 BP 955 EP 961 DI 10.1161/01.HYP.0000216634.73504.7d PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 034PP UT WOS:000236943400026 PM 16585416 ER PT J AU Salazar-Gonzalez, RM Niess, JH Zammit, DJ Ravindran, R Srinivasan, A Maxwell, JR Stoklasek, T Yadav, R Williams, IR Gu, XB McCormick, BA Pazos, MA Vella, AT Lefrancois, L Reinecker, HC McSorley, SJ AF Salazar-Gonzalez, RM Niess, JH Zammit, DJ Ravindran, R Srinivasan, A Maxwell, JR Stoklasek, T Yadav, R Williams, IR Gu, XB McCormick, BA Pazos, MA Vella, AT Lefrancois, L Reinecker, HC McSorley, SJ TI CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches SO IMMUNITY LA English DT Article ID EPITHELIAL-CELLS; IN-VIVO; SALMONELLA INFECTION; ANTIGEN; HOMEOSTASIS; RESPONSES; IMMUNITY; MICE; TOLERANCE; MIGRATION AB T cell activation by dendritic cells (DCs) is critical to the initiation of adaptive immune responses and protection against pathogens. Here, we demonstrate that a specialized DC subset in Peyer's patches (PPs) mediates the rapid activation of pathogen specific T cells. This DC subset is characterized by the expression of the chemokine receptor CCR6 and is found only in PPs. CCR6(+) DCs were recruited into the dome regions of PPs upon invasion of the follicle associated epithelium (FAE) by an enteric pathogen and were responsible for the rapid local activation of pathogen-specific T cells. CCR6-deficient DCs were unable to respond to bacterial invasion of PPs and failed to initiate T cell activation, resulting in reduced defense against oral infection. Thus, CCR6-dependent regulation of DCs is responsible for localized T cell dependent defense against entero-invasive pathogens. C1 Univ Minnesota, Sch Med, Mcguire Translat Facil, GI Div,Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Mcguire Translat Facil, Ctr Infect Dis & Microbiol Translat Res Facil, Minneapolis, MN 55455 USA. Univ Connecticut, Ctr Hlth, Div Immunol, Dept Med, Farmington, CT 06030 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. RP McSorley, SJ (reprint author), Univ Minnesota, Sch Med, Mcguire Translat Facil, GI Div,Dept Med, TRF DC 2873,2001 6th St SE, Minneapolis, MN 55455 USA. EM mcsor002@umn.edu RI Williams, Ifor/D-3648-2011; Niess, Jan /E-8361-2017 OI Williams, Ifor/0000-0002-8810-2911; Niess, Jan /0000-0001-6902-5650 FU NIAID NIH HHS [AI055743, AI056172, AI142858, P01 AI056172, P01 AI056172-05, R01 AI055743]; NIDDK NIH HHS [DK43351, DK068181, DK33506, DK64730, P01 DK033506, P30 DK043351, R01 DK064730, R01 DK068181] NR 36 TC 154 Z9 161 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2006 VL 24 IS 5 BP 623 EP 632 DI 10.1016/j.immuni.2006.02.015 PG 10 WC Immunology SC Immunology GA 048TT UT WOS:000237970100018 PM 16713979 ER PT J AU Chlosta, S Fishman, DS Harrington, L Johnson, EE Knutson, MD Wessling-Resnick, M Cherayil, BJ AF Chlosta, S Fishman, DS Harrington, L Johnson, EE Knutson, MD Wessling-Resnick, M Cherayil, BJ TI The iron efflux protein ferroportin regulates the intracellular growth of Salmonella enterica SO INFECTION AND IMMUNITY LA English DT Article ID IN-VITRO; AFRICAN-AMERICANS; HEMOCHROMATOSIS; EXPRESSION; HEPCIDIN; MUTATIONS; OVERLOAD; MACROPHAGES; TUBERCULOSIS; INFECTIONS AB We investigated the influence of the macrophage iron exporter ferroportin and its ligand hepcidin on intracellular Salmonella growth. Elevated ferroportin expression inhibited bacterial multiplication; hepcidin-induced ferroportin down-regulation enhanced it. Expression analysis of iron-responsive Salmonella genes indicated ferroportin-mediated iron deprivation. These results demonstrate a role for ferroportin in antimicrobial resistance. C1 Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Charite Med Sch, Dept Med Microbiol & Immunol & Infect, Berlin, Germany. Childrens Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU NIAID NIH HHS [AI065619, R21 AI065619]; NIDDK NIH HHS [R01 DK056160-01, DK05610, DK064750, P30 DK040561, P30 DK040561-06, P30 DK040561-11, R01 DK056160, R01 DK056160-02, R01 DK056160-03, R01 DK056160-04, R01 DK056160-05, R01 DK064750, R01 DK064750-01A1, R01 DK064750-02, R01 DK064750-03, R01 DK064750-04] NR 29 TC 78 Z9 78 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2006 VL 74 IS 5 BP 3065 EP 3067 DI 10.1128/IAI.74.5.3065-3067.2006 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 039MX UT WOS:000237311200068 PM 16622252 ER PT J AU Stock, W Yu, DH Karrison, T Sher, D Stone, RM Larson, RA Bloomfield, CD AF Stock, W Yu, DH Karrison, T Sher, D Stone, RM Larson, RA Bloomfield, CD TI Quantitative real-time RT-PCR monitoring of BCR-ABL in chronic myelogenous leukemia shows lack of agreement in blood and bone marrow samples SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE molecular monitoring; quantitative real-time RT-PCR; BCR-ABL; chronic myelogenous leukemia; blood and bone marrow analysis ID CHRONIC MYELOID-LEUKEMIA; POLYMERASE-CHAIN-REACTION; STEM-CELL TRANSPLANTATION; CYTOGENETIC RESPONSE; INTERFERON-ALPHA; IMATINIB MESYLATE; REACTION PREDICTS; MESSENGER-RNA; CML; TRANSCRIPTS AB Molecular monitoring of the BCR-ABL transcript in chronic myelogenous leukemia (CML) using quantitative RT-PCR provides clinicians with important diagnostic and prognostic information. To determine whether molecular detection and monitoring of CML is comparable using peripheral blood (PB) and bone marrow (BM) aspirate samples, we performed a prospective study using quantitative real-time RT-PCR (QRT-PCR) of paired PB and BM samples from 41 patients with CML entered onto a single Cancer and Leukemia Group B (CALGB) treatment Study. QRT-PCR analysis of PB and BM samples was performed prior to initiation of, and during, treatment with homoharringtonine and cytarabine on a CALGB study for previously untreated CML. Statistical analyses demonstrated good agreement of PB and BM pretreatment samples. However, using the Bland-Altman statistical method that measures true agreement between PB and BM values, we found that there was only modest agreement of BCR-ABL measurements in PB and BM for samples obtained during treatment. PB values obtained during treatment tended to be lower than the corresponding BM values [average difference = -0.37 (p < 0.001) in 36 paired samples] and the 95% limits of agreement ranged from -1.23 to 0.48. Nevertheless, our study demonstrates that BM and PB QRT-PCR values followed a similar trend during treatment (Spearman correlation coefficient, 0.83; 95% CI, 0.70, 0.96). Our data suggest that, quantitatively, PB and BM measurements of BCR-ABL are frequently disparate. Since BM values tended to be higher than PB values, BM sampling provides the most accurate assessment of minimal residual disease (MRD). Based on these results, we caution against interchanging BM with PB sampling for MRD monitoring during treatment of CML since this may lead to misinterpretation of treatment results. C1 Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. CALGB Stat Ctr, Durham, NC USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc & Leukemia Grp B, Chicago, IL USA. RP Stock, W (reprint author), Univ Chicago, Canc Res Ctr, 5841 S Maryland,M-C 2115, Chicago, IL 60637 USA. EM wstock@medicine.bsd.uchicago.edu OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA77658, CA16058, CA31946, U10-CA101140] NR 20 TC 21 Z9 22 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 2006 VL 28 IS 5 BP 1099 EP 1103 PG 5 WC Oncology SC Oncology GA 034FM UT WOS:000236914400008 PM 16596225 ER PT J AU McDermott, NE Chuang, SK Woo, VV Dodson, TB AF McDermott, Nancy E. Chuang, Sung-Kiang Woo, Valerie V. Dodson, Thomas B. TI Maxillary sinus augmentation as a risk factor for implant failure SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Academy-of-Osseointegration CY FEB 17-21, 2003 CL Boston, MA SP Acad Osseointegrat DE implant failure; retrospective cohort studies; risk factors; sinus augmentation ID LONGITUDINAL DATA-ANALYSIS; FREEZE-DRIED BONE; MINERAL BIO-OSS; AUTOGENOUS BONE; BOVINE BONE; ENDOSSEOUS IMPLANTS; FLOOR AUGMENTATION; DENTAL IMPLANTS; POSTERIOR MAXILLA; CLINICAL REPORT AB Purpose: The investigators sought to determine whether maxillary sinus augmentation (MSA) was an independent risk factor for implant failure. Materials and Methods: Using a retrospective cohort study design, the investigators enrolled a sample composed of subjects having 1 or more implants placed in the posterior maxilla. The primary predictor variable was MSA status at the time of implant placement (MSA present or absent). MSA consisted of a lateral window (external) or an osteotome (internal) procedure. The outcome variable was implant failure defined as implant removal. Demographic, health status, anatomic, implant-specific, abutment-specific, prosthetic, and perioperative variables were also examined. Overall implant survival was estimated using Kaplan-Meier analysis. Risk factors for implant failure were identified using Cox proportional hazard regression models. Results: The sample consisted of 318 patients and 762 posterior maxillary implants. The mean duration of follow-up was 22.50 +/- 19.06 months. The 5-year survival rates for implants in the ungrafted and grafted posterior maxilla were 88.0% and 87.9%, respectively (P =.08). After adjustment for covariates, MSA status was not an independent risk factor for implant failure (P =.9). Tobacco use (P <.001), implants replacing molars (P <.001), and 1-stage implants (P <.001) were statistically associated with an increased risk for implant failure. Discussion: MSA status was not associated with implant failure risk. This finding may be subject to selection bias, as successful MSA was requisite prior to implant placement. Conclusion: MSA status was not associated with an increased risk for implant failure. Of the 3 factors associated with an increased risk for failure, tobacco use and implant staging may be modified by the clinician to enhance outcome. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP McDermott, NE (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM nemcdermott@partners.org FU NIDCR NIH HHS [K16 DE000275] NR 70 TC 17 Z9 20 U1 0 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAY-JUN PY 2006 VL 21 IS 3 BP 366 EP 374 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 057JK UT WOS:000238591900004 PM 16796278 ER PT J AU Katz, A Niemierko, A Gage, I Evans, S Shaffer, M Smith, FP Taghian, A Magnant, C AF Katz, A Niemierko, A Gage, I Evans, S Shaffer, M Smith, FP Taghian, A Magnant, C TI Factors associated with involvement of four or more axillary nodes for sentinel lymph node-positive patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast neoplasms; radiation; lymphatic metastasis; axilla; sentinel lymph node biopsy ID BREAST-CANCER; CONSERVATIVE SURGERY; RADIATION-THERAPY; MASTECTOMY; FAILURE; CHEMOTHERAPY; IRRADIATION; CARCINOMA; PATTERNS; FIELDS AB Purpose: Sentinel lymph node-positive (SLN+) patients who are unlikely to have 4 or more involved axillary nodes might be treated with less extensive regional nodal radiation. The purpose of this study was to define possible predictors of having 4 or more involved axillary nodes. Methods and Materials: The records of 224 patients with breast cancer and 1 to 3 involved SLNs, who underwent completion axillary dissection without neoadjuvant chemotherapy or hormonal therapy were reviewed. Factors associated with the presence of 4 or more involved axillary nodes (SLNs plus non-SLNs) were evaluated by Pearson chi-square test of association and by simple and multiple logistic-regression analysis. Results: Of 224 patients, 42 had involvement of 4 or more axillary nodes. On univariate analysis, the presence of 4 or more involved axillary nodes was positively associated with increased tumor size, lobular histology, lymphovascular space invasion (LVSI), increased number of involved SLNs, decreased number of uninvolved SLNs, and increased size of SLN metastasis. On multivariate analysis, the presence of 4 or more involved axillary nodes was associated with LVSI, increased number of involved SLNs, increased size of SLN metastasis, and lobular histology. Conclusions: Patients with 1 or more involved SLN, LVSI, or SLN macrometastasis should be treated to the supraclavicular fossa/axillary apex if they do not undergo completion axillary dissection. Other SLN+ patients might be adequately treated with less extensive radiation fields. (c) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Sibley Mem Hosp, Breast Canc Treatment Grp, Washington, DC USA. RP Katz, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 301, Boston, MA 02114 USA. EM abkatz@partners.org FU NCI NIH HHS [CA21239, CA50628] NR 11 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2006 VL 65 IS 1 BP 40 EP 44 DI 10.1016/j.ijrobp.2005.11.021 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 051LM UT WOS:000238162600006 PM 16488555 ER PT J AU Galpern, WR Singhal, AB AF Galpern, Wendy R. Singhal, Aneesh B. TI Neuroprotection: lessons from a spectrum of neurological disorders SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material ID ACUTE ISCHEMIC-STROKE; PARKINSON-DISEASE; CLINICAL-TRIAL; MOUSE MODEL; CREATINE; THROMBOLYSIS; MINOCYCLINE; SCLEROSIS; THERAPY C1 NINDS, NIH, Ctr Neurosci, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Galpern, WR (reprint author), NINDS, NIH, Ctr Neurosci, 2225 6001 Execut Blvd, Bethesda, MD 20892 USA. EM galpernw@ninds.nih.gov NR 23 TC 4 Z9 4 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD MAY PY 2006 VL 1 IS 2 BP 97 EP 99 DI 10.1111/j.1747-4949.2006.00023.x PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178DL UT WOS:000247201300009 PM 18706052 ER PT J AU Sterling, TR Zhao, Z Khan, A Chaisson, RE Schluger, N Mangura, B Weiner, M Vernon, A AF Sterling, TR Zhao, Z Khan, A Chaisson, RE Schluger, N Mangura, B Weiner, M Vernon, A CA Tuberculosis Trials Consortium TI Mortality in a large tuberculosis treatment trial: modifiable and non-modifiable risk factors SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; mortality; HIV; malignancy ID HIV-RELATED TUBERCULOSIS; CASE-FATALITY RATE; PULMONARY TUBERCULOSIS; DEATH CERTIFICATE; NETHERLANDS; RIFAPENTINE; DIAGNOSIS; THERAPY; TWICE; CITY AB SETTING: North America. OBJECTIVES: Tuberculosis (TB) patients in North America often have characteristics that may increase overall mortality. Identifying modifiable risk factors would allow for improvements in outcome. DESIGN: We evaluated mortality in a large TB treatment trial conducted in the United States and Canada. Persons with culture-positive pulmonary TB were enrolled after 2 months of treatment, treated for 4 more months under direct observation, and followed for 2 years (total observation: 28 months). Cause of death was determined by death certificate, autopsy, and/or clinical observation. RESULTS: Of 1075 participants, 71 (6.6%) died: 15/71 (21.1%) HIV-infected persons, and 56/1004 (5.6%) non-HIV-infected persons (P < 0.001). Only one death was attributed to TB. Cox multivariate regression analysis identified four independent risk factors for death after controlling for age: malignancy (hazard ratio [HR] 5.28, P < 0.0001), HIV (HR 3.89, P < 0.0001), daily alcohol (HR 2.94, P < 0.0001), and being unemployed (HR 1.99, P = 0.01). The risk of death increased with the number of independent risk factors present (P < 0.0001). Extent of disease and treatment failure/relapse were not associated with an increased risk of death. CONCLUSIONS: Death due to TB was rare. Interventions to treat malignancy, HIV, and alcohol use in TB patients are needed to reduce mortality in this patient population. C1 Vanderbilt Univ, Med Ctr, Div Infect Dis, Nashville, TN 37232 USA. Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD USA. Columbia Univ Coll Phys & Surg, Div Pulm Allergy & Crit Care Med, New York, NY 10032 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Natl TB Ctr, Newark, NJ 07103 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Sterling, TR (reprint author), Vanderbilt Univ, Med Ctr, Div Infect Dis, A2209 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM timothy.sterling@vanderbilt.edu NR 30 TC 53 Z9 53 U1 0 U2 3 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAY PY 2006 VL 10 IS 5 BP 542 EP 549 PG 8 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 038JT UT WOS:000237216500012 PM 16704037 ER PT J AU Makino, CL Wen, XH Michaud, N Peshenko, IV Pawlyk, B Brush, RS Soloviev, M Liu, XQ Woodruff, ML Calvert, PD Savchenko, AB Anderson, RE Fain, GL Li, TS Sandberg, MA Dizhoor, AM AF Makino, CL Wen, XH Michaud, N Peshenko, IV Pawlyk, B Brush, RS Soloviev, M Liu, XQ Woodruff, ML Calvert, PD Savchenko, AB Anderson, RE Fain, GL Li, TS Sandberg, MA Dizhoor, AM TI Effects of low AIPL1 expression on phototransduction in rods SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOTORECEPTOR GUANYLATE-CYCLASE; LEBER CONGENITAL AMAUROSIS; GTPASE ACCELERATING PROTEIN; DOMINANT CONE DYSTROPHY; CGMP PHOSPHODIESTERASE; ACTIVATING PROTEINS; RETINAL RODS; VERTEBRATE PHOTORECEPTORS; TRANSGENIC MICE; KNOCKOUT MICE AB PURPOSE. To investigate the impact of aryl hydrocarbon receptor-interacting protein-like (AIPL)-1 on photoreception in rods. METHODS. Photoresponses of mouse rods expressing lowered amounts of AIPL1 were studied by single-cell and electroretinogram ( ERG) recordings. Phototransduction protein levels and enzymatic activities were determined in biochemical assays. Ca2+ dynamics were probed with a fluorescent dye. Comparisons were made to rods expressing mutant Y99C guanylate cyclase activating protein (GCAP)-1, to understand which effects arose from elevated dark levels of cGMP and Ca2+. RESULTS. Except for PDE, transduction protein levels were normal in low-AIPL1 retinas, as were guanylate cyclase ( GC), rhodopsin kinase (RK), and normalized phosphodiesterase (PDE) activities. Y99C and low-AIPL1 rods were more sensitive to flashes than normal, but flash responses of low-AIPL1 rods showed an abnormal delay, reduced rate of increase, and longer recovery not present in Y99C rod responses. In addition, low-AIPL1 rods but not Y99C rods failed to reach the normal light-induced minimum in Ca2+ concentration. CONCLUSIONS. Reduced AIPL1 delayed the photoresponse, decreased its amplification constant, slowed a rate-limiting step in its recovery, and limited the light-induced decrease in Ca2+. Not all changes were attributable to decreased PDE or to elevated cGMP and Ca2+ in darkness. Therefore, AIPL1 directly or indirectly affects more than one component of phototransduction. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Dept Ophthalmol, Boston, MA 02114 USA. Penn Coll Optometry, Hafter Res Labs, Elkins Pk, PA USA. Univ Oklahoma, Coll Med, Dept Cell Biol, Oklahoma City, OK 73190 USA. Univ Oklahoma, Coll Med, Dept Ophthalmol, Oklahoma City, OK 73190 USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA. RP Makino, CL (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cmakino@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [EY10309, EY12190, EY11522, EY12944, EY11358, EY04149, EY014104, EY00871, EY01844] NR 50 TC 12 Z9 12 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2006 VL 47 IS 5 BP 2185 EP 2194 DI 10.1167/iovs.05-1341 PG 10 WC Ophthalmology SC Ophthalmology GA 041JL UT WOS:000237451100060 PM 16639031 ER PT J AU Kuperberg, GR Sitnikova, T Goff, D Holcomb, PJ AF Kuperberg, GR Sitnikova, T Goff, D Holcomb, PJ TI Making sense of sentences in schizophrenia: Electrophysiological evidence for abnormal interactions between semantic and syntactic processing SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE language; schizophrenia; N400 event-related potential; semantics; syntax ID EVENT-RELATED POTENTIALS; BRAIN POTENTIALS; THOUGHT-DISORDER; SPOKEN SENTENCES; LANGUAGE; ERP; N400; CONTEXT; INFORMATION; MEMORY AB Event-related potentials to critical verbs were measured as patients with schizophrenia and healthy controls read sentences word by word. Relative to their preceding context, critical verbs were (a) congruous, (b) incongruous and semantically unrelated to individual preceding words (pragmatic-semantic violations), (c) incongruous but semantically related to individual preceding words (animacy-semantic violations), or (d) syntactically anomalous. The N400 was modulated normally in patients, suggesting that semantic integration between individual words within sentences was normal in schizophrenia. The amplitude of the P600 to both syntactic and animacy-semantic violations was reduced in patients relative to controls. The authors suggest that, in schizophrenia, an abnormality in combining semantic and syntactic information online to build up propositional meaning leaves sentence processing to be primarily driven by semantic relationships between individual words. C1 Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neurosci Program, Charlestown, MA 02129 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neurosci Program, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kuperber@nmr.mgh.harvard.edu FU NICHD NIH HHS [R01 HD025889, R01 HD025889-15, R01 HD025889-16, R01 HD025889-17] NR 71 TC 30 Z9 30 U1 2 U2 8 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2006 VL 115 IS 2 BP 251 EP 265 DI 10.1037/0021-843X.115.2.251 PG 15 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 048SX UT WOS:000237967900012 PM 16737390 ER PT J AU Miller, MW Vogt, DS Mozley, SL Kaloupek, DG Keane, TM AF Miller, MW Vogt, DS Mozley, SL Kaloupek, DG Keane, TM TI PTSD and substance-related problems: The mediating roles of disconstraint and negative emotionality SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE disconstraint; posttraumatic stress disorder; negative emotionality; substance use; alcohol use ID POSTTRAUMATIC-STRESS-DISORDER; BINGE DRINKING TRAJECTORIES; DSM-IV ANXIETY; MENTAL-DISORDERS; ALCOHOL-ABUSE; INTERNALIZING SUBTYPES; MOOD DISORDERS; BIRTH COHORT; FIT INDEXES; DRUG-USE AB The authors examined competing hypotheses regarding the role of 2 personality dimensions, disconstraint and negative emotionality, in mediating the relationship between posttraumatic stress disorder (PTSD) severity and substance-related problems. Data were drawn from a large sample of male Vietnam veterans. The best-fitting structural model included significant indirect paths from PTSD to both alcohol- and drug-related outcomes through disconstraint, and a significant indirect path from PTSD to alcohol-related problems through negative emotionality. There were no direct effects of PTSD on either substance-related outcome. These findings indicate distinct pathways to different forms of substance-related problems in PTSD and underscore the role of personality in mediating these relationships. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychol, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Kaloupek, Danny/0000-0002-0795-593X NR 86 TC 48 Z9 48 U1 4 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2006 VL 115 IS 2 BP 369 EP 379 DI 10.1037/0021-843X.115.2.369 PG 11 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 048SX UT WOS:000237967900023 PM 16737401 ER PT J AU Kellogg, DL AF Kellogg, DL TI In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans during thermoregulatory challenges SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE thermoregulation; heat stress; cold stress; skin blood flow; cotransmission ID SKIN BLOOD-FLOW; VASOACTIVE INTESTINAL POLYPEPTIDE; NITRIC-OXIDE CONCENTRATION; COLD-INDUCED CONSTRICTION; HEAT-STRESS; ACTIVE VASODILATION; NEUROPEPTIDE-Y; SWEAT GLANDS; LOCAL TEMPERATURE; CARDIOVASCULAR ADJUSTMENTS AB This review focuses on the neural and local mechanisms that have been demonstrated to effect cutaneous vasodilation and vasoconstriction in response to heat and cold stress in vivo in humans. First, our present understanding of the mechanisms by which sympathetic cholinergic nerves mediate cutaneous active vasodilation during reflex responses to whole body heating is discussed. These mechanisms include roles for cotransmission as well as nitric oxide ( NO). Next, the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active vasoconstriction during whole body cooling are reviewed, including cotransmission by neuropeptide Y ( NPY) acting through NPY Y1 receptors. Subsequently, current concepts for the mechanisms that effect local cutaneous vascular responses to direct skin warming are examined. These mechanisms include the roles of temperature-sensitive afferent neurons as well as NO in causing vasodilation during local heating of skin. This section is followed by a review of the mechanisms that cause local cutaneous vasoconstriction in response to direct cooling of the skin, including the dependence of these responses on intact sensory and sympathetic, noradrenergic innervation as well as roles for nonneural mechanisms. Finally, unresolved issues that warrant further research on mechanisms that control cutaneous vascular responses to heating and cooling are discussed. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Geronterol, San Antonio, TX 78229 USA. Audie L Murphys Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Kellogg, DL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Geronterol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu FU NHLBI NIH HHS [HL-65599] NR 96 TC 166 Z9 171 U1 9 U2 40 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 2006 VL 100 IS 5 BP 1709 EP 1718 DI 10.1152/japplphysiol.01071.2005 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 040DE UT WOS:000237358400040 PM 16614368 ER PT J AU Kohane, DS Tse, JY Yeo, Y Padera, R Shubina, M Langer, R AF Kohane, DS Tse, JY Yeo, Y Padera, R Shubina, M Langer, R TI Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE microparticles; nanoparticles; adhesion; peritoneum; biocompatibility ID SUGAR PARTICLES; BIOCOMPATIBILITY; MICROPARTICLES; BUPIVACAINE AB Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 mu m in diameter, into the murine peritoneum, in dosages of 10-100 mg (n = 3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-mu m microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles > 5 mu m in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (1.6.7%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also Caused much fewer adhesions (6.3% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied. (c) 2006 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Boston, MA USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dkohane@partners.org FU NIGMS NIH HHS [GM00684] NR 15 TC 95 Z9 97 U1 4 U2 43 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAY PY 2006 VL 77A IS 2 BP 351 EP 361 DI 10.1002/jbm.a.30654 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 029LB UT WOS:000236562800016 PM 16425240 ER PT J AU Hsiao, JK Law, B Weissleder, R Tung, CH AF Hsiao, Jong-Kai Law, Benedict Weissleder, Ralph Tung, Ching-Hsuan TI In-vivo imaging of tumor associated urokinase-type plasminogen activator activity SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE urokinase-type plasminogen activator; protease; optical imaging; fluorescence; tumor ID BREAST-CANCER PATIENTS; COLON-CARCINOMA CELLS; ENZYME-ACTIVITY; INHIBITOR; RECEPTOR; SYSTEM; INVASIVENESS; FEASIBILITY; METASTASIS; REPORTER AB The ability to image tumor associated protease in vivo has biological and clinical implications. In the present study, we describe the development and validation of a urokinase-type plasminogen activator (uPA) sensitive fluorescence imaging probe. The activation of our probe is highly specific to uPA in both enzymatic and cellular-based assays. In two distinct in-vivo tumor models (human colon adenocarcinoma HT-29 and human fibrosarcoma HT-1080), the observed fluorescence changes correlate well with tumor associated uPA activity. The signal intensities of the tumors are about three-fold higher in animals with probe injections. Our results suggest a direct detection method for uPA activity in vivo and the approach can be used for monitoring tumor growth and development. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Hsiao, JK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01-CA99385] NR 28 TC 23 Z9 23 U1 0 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2006 VL 11 IS 3 AR 034013 DI 10.1117/1.2204029 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 071FJ UT WOS:000239583600017 PM 16822063 ER PT J AU Yasuhara, S Kaneki, M Sugita, H Sugita, M Asai, A Sahani, N Chon, JY Tompkins, RG Martyn, JAJ AF Yasuhara, Shingo Kaneki, Masao Sugita, Hiroki Sugita, Michiko Asai, Akihiro Sahani, Nita Chon, Jin-Young Tompkins, Ronald G. Martyn, J. A. Jeevendra TI Adipocyte apoptosis after burn injury is associated with altered fat metabolism SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; AIRWAY SMOOTH-MUSCLE; INTERFERON-GAMMA; ADIPOSE; OBESITY; CELLS; INSULIN; ACTIVATION; CYTOKINES; RECEPTOR AB Burn injury often is associated with the abnormal lipid metabolism, including hyperlipidemia, desensitization to lipolytic responses to catecholamines, and reduction in the size of the white adipose tissue. Understanding the biological mechanisms for the decrease in fat mass despite desensitization to catecholamines is important both for the study of lipid metabolism and for the study of its relationship to concomitant insulin resistance. Using epididymal adipose tissue from adult male Sprague-Dawley rats after burn injury (n = 102) or sham-burn injury (n = 102), we tested the hypothesis that a whole-body burn injury causes apoptosis in that tissue. At 1, 3, and 7 days after 40% to 50% body burn injury to the rat, epidydimal adipose tissue was harvested and studied for apoptotic changes and lipolytic properties. For apoptosis, paraformaldehyde-fixed tissue sections were analyzed by in situ TdT-mediated dUTP-X nick-end labeling (TUNEL) staining, and tissue homogenates were also analyzed for DNA fragmentation by enzyme-linked immunoassay and ligation-mediated polymerase chain reaction ladder assay. Isolated adipocytes were stimulated with isoprotenerol, and glycerol production was measured as a reflector of effectiveness of lipolysis. Epididymal adipose tissue showed increased apoptosis manifested by the positive TUNEL staining and increased DNA fragmentation by enzyme-linked immunoassay at day 3 and 7 after burn injury. The DNA fragmentation was confirmed further by the ligation-mediated polymerase chain reaction ladder assay. This elevated DNA fragmentation persisted in the burned animals from day 3 until day 7 after burn injury, the end of observation period. Increase in apoptosis was correlated with decrease in DNA content and tissue weight in the epidydimis. At the functional level, a significant decrease in isoproterenol-induced lipolytic activity (glycerol production) was observed to almost 50% of control level at day 3 and 7 but was not decreased at day 1. Apoptosis of adipocytes; may play a role in the altered lipid metabolism, including hyperlipidemia observed in burned subjects. C1 Massachusetts Gen Hosp, Dept Anesthesiol & Surg, Boston, MA 02114 USA. Shriners Burn Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kumamoto Univ, Sch Med, Kumamoto 860, Japan. Catholic Univ Korea, Sch Med, Seoul, South Korea. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. OI Asai, Akihiro/0000-0003-3029-5754 FU NIDDK NIH HHS [DK58127]; NIGMS NIH HHS [GM2500, GM31569, GM55082, GM61411, R01 GM055082] NR 40 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2006 VL 27 IS 3 BP 367 EP 376 DI 10.1097/01.BCR.0000216777.94365.47 PG 10 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 045MX UT WOS:000237747300019 PM 16679908 ER PT J AU Paul, S Leacche, M Unic, D Couper, GS Macgillivray, TE Agnihotri, AK Cohn, LH Byrne, JG AF Paul, S Leacche, M Unic, D Couper, GS Macgillivray, TE Agnihotri, AK Cohn, LH Byrne, JG TI Determinants of outcomes for postcardiotomy VAD placement: An 11-year, two-institution study SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID MECHANICAL VENTRICULAR ASSISTANCE; CARDIOGENIC-SHOCK; SUPPORT; DEVICES; EXPERIENCE; FAILURE AB Objective: Ventricular assist device (VAD) placement after postcardiotomy failure is associated with a high mortality. We sought to determine prognostic factors in order to help better select patients who may benefit from VAD placement. Methods: From January 1992 to January 2003, 63 patients out of approximately 30,000 cardiac surgery patients (0.21%) developed postcardiotomy failure requiring VADs. Planned VAD for bridge to transplant or bridge to recovery were excluded. Multivariate logistic regression analysis, based on pre-VAD placement parameters, was used to determine prognostic factors for in-hospital 30-day mortality. Results: Overall operative mortality was 73% (46 of 63). Multivariate logistic regression analysis identified median age <= 50 (each additional year) (OR = 0.85, 95% CI = 0.77 to 0.95, p = 0.004) and median base deficit >= 0 mEq/L (each additional mEq/L) prior to VAD placement (OR = 0.60, 95% CI = 0.48 to 0.91, p = 0.012) to be independent predictors of improved 30-day survival. Conclusions: Postcardiotomy failure is a rare event but is associated with a very poor prognosis despite salvage therapies utilizing VADs. Age <= 50 years and base deficit >= 0 (mEq/L) prior to VAD placement are associated with improved 30-day survival. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA. RP Byrne, JG (reprint author), Vanderbilt Univ, Med Ctr, Dept Cardiac Surg, Nashville, TN 37232 USA. EM john.byrne@vanderbilt.edu NR 16 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAY-JUN PY 2006 VL 21 IS 3 BP 234 EP 237 DI 10.1111/j.1540-8191.2006.00223.x PG 4 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 036ZS UT WOS:000237117100007 PM 16684048 ER PT J AU Monks, NR Pardee, AB AF Monks, NR Pardee, AB TI Targeting the NF-kappa B pathway in estrogen receptor negative MDA-MB-231 breast cancer cells using small inhibitory RNAs SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE nuclear factor kappa B (NF-kappa B); inhibitor of kappa B Kinase (IKK); siRNA; breast cancer ID ACTIVATION; KINASE; PROTEASOME; DEGRADATION; ALPHA; CYCLE; IKK; PHOSPHORYLATION; PROGRESSION; EXPRESSION AB Cancer cells in order to survive are often mutated to block apoptosis. One chemotherapeutic option is the re-establishment of apoptosis. An example of such a therapy is the PKC inhibitor Go6976, which activates apoptosis and shrinks in vivo tumors in estrogen receptor-negative breast cancers. We proposed as a mechanism blockage of activation of the transcription factor NF-kappa B, which is anti-apoptotic and often elevated in cancers. Over recent years, questions have arisen regarding the specificity of these "small-molecule inhibitors." We have therefore explored the role of NF-kappa B inhibition in MDA-MB-231 breast cancer cells using small inhibitory RNAs (siRNA). siRNAs designed against NF-kappa B protein p65 (RelA) and IKK alpha, IKK beta, and IKK gamma, strongly decreased the target proteins. But, unlike Go6976, they did not decrease basal NF-kappa B or cause apoptosis. In particular, the decrease in p65 protein had no effects on apoptosis or cell proliferation, thus questioning the importance of NF-kappa B alone in the maintenance of these cells. Furthermore, the proteasome inhibitor MG-132 caused loss of I kappa B alpha, and an increase of it is phosphorylated form, but basal NF-kappa B was unchanged, whilst activation of NF-kappa B by TNF alpha was completely inhibited, suggesting that MG-132 activity is independent of constitutive NF-kappa B activation. We ascribe these differences to the specificity of inhibition by siRNAs as compared to the well-known non-specificity of small-molecule inhibitors. We conclude that the mutations in these cancer cells made them resistant to apoptosis, by elevating their NF-kappa B and activating other basal pathways that are blocked by Go6976 but not by IKK and p65 siRNAs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, SM 936,44 Binney St, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu RI Monks, Noel/B-5886-2013 OI Monks, Noel/0000-0001-6587-9827 NR 34 TC 15 Z9 17 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 2006 VL 98 IS 1 BP 221 EP 233 DI 10.1002/jcb.20789 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 034KN UT WOS:000236928000018 PM 16408291 ER PT J AU Bermpohl, D You, ZR Korsmeyer, SJ Moskowitz, MA Whalen, MJ AF Bermpohl, D You, ZR Korsmeyer, SJ Moskowitz, MA Whalen, MJ TI Traumatic brain injury in mice deficient in Bid: effects on histopathology and functional outcome SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; Bid; brain injury; necrosis; trauma ID FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; NEURONAL APOPTOSIS; SIGNALING COMPLEX; ACTIVATION; CASPASE-3; PATHWAY; MITOCHONDRIA; RECEPTORS; CLEAVAGE AB Bid is a proapoptotic member of the Bcl-2 family that mediates cell death by caspase-dependent and -independent pathways. We tested mice genetically deficient in Bid in a controlled cortical impact (CCI) model to examine the hypothesis that Bid contributes to cell death and functional outcome after traumatic brain injury. After CCI, truncated Bid (15 kDa) was robustly detected in cortical brain homogenates of wild-type mice. Bid-/- mice had decreased numbers of cortical cells with acute plasmalemma injury at 6 h (wild type (WT), 1721 +/- 124; Bid-/-, 1173 +/- 129 cells/ x 200 field; P < 0.01), decreased numbers of cells expressing cleaved caspase-3 in the dentate gyrus at 48 h (WT, 113 +/- 15; Bid-/-, 65 +/- 9 cells/ x 200 field; P < 0.05), and reduced lesion volume at 12 days (Bid-/-, 5.9 +/- 0.4 mm(3); WT, 8.4 +/- 0.4 mm(3); P < 0.001), but did not differ from WT mice at later times after injury regarding lesion size (30 days) or brain tissue atrophy (40 days). Compared with naive mice, injured mice in both groups performed significantly worse on motor and Morris water maze (MWM) tests; however, mice deficient in Bid did not differ from WT in postinjury motor and MWM performance. The data show that Bid deficiency decreases early posttraumatic brain cell death and tissue damage, but does not reduce functional outcome deficits after CCI in mice. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Neurosci Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Charlestown, MA 02129 USA. RP Whalen, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Neurosci Ctr, 149 13th St RM 6403, Charlestown, MA 02129 USA. EM mwhalen@partners.org RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [KO8NS41969, R01NS37141, R01NS47447] NR 32 TC 47 Z9 50 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2006 VL 26 IS 5 BP 625 EP 633 DI 10.1038/sj.jcbfm.9600258 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 038RA UT WOS:000237239500004 PM 16395279 ER PT J AU Strong, AJ Bezzina, EL Anderson, PBJ Boutelle, MG Hopwood, SE Dunn, AK AF Strong, Anthony J. Bezzina, Elizabeth Lindsey Anderson, Peter J. B. Boutelle, Martyn G. Hopwood, Sarah E. Dunn, Andrew K. TI Evaluation of laser speckle flowmetry for imaging cortical perfusion in experimental stroke studies: quantitation of perfusion and detection of peri-infarct depolarisations SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral blood flow; cortical spreading depression; focal cerebral ischaemia; laser speckle flowmetry; penumbra; periinfarct depolarisation ID FOCAL CEREBRAL-ISCHEMIA; SPREADING DEPRESSION; BLOOD-FLOW; FUNCTIONAL ACTIVATION; ARTERY OCCLUSION; MOUSE CORTEX; RAT; OXYGENATION; TOPOGRAPHY; GLUCOSE AB Laser speckle imaging of the exposed cerebral cortex allows detailed examination of the time course and topography of perfusion under different experimental conditions. Here we examine the quantitative capacity of the method and its sensitivity for the detection of peri-infarct depolarisations (PIDs). In four cats anaesthetised with chloralose, the right hemisphere was exposed and the right middle cerebral artery was occluded. The brain was illuminated with a laser diode, the speckle pattern was imaged, and images of inverse speckle correlation time (ICT) were derived from the calculated speckle contrast images. We examined the relationship of ICT with perfusion, as imaged quantitively using umbelliferone clearance (CBFumb). Values of ICT and CBFumb were compared and regression parameters were calculated for each experiment. In eight cats, cortical surface direct current (DC) potential was monitored at two locations and detection of PIDs by DC potential and ICT change was compared. ICT- and CBFumb-derived values of perfusion were closely correlated, with a high degree of significance (P < 0.0001). Overall, monitoring of DC potential detected 90% of PIDs, whereas ICT detected 56%. We conclude that (1) laser speckle imaging provides an index of perfusion that has a linear relationship with the clearance rate of umbelliferone within the range of levels of perfusion examined; (2) this relationship is relatively stable between experiments; and (3) the method's ability to detect blood flow changes associated with PIDs likely depends on the noise level of the speckle measurements. C1 Kings Coll London, Dept Clin Neurosci Neurosurg, London, England. Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, London, England. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Strong, AJ (reprint author), Kings Coll Hosp London, Dept Neurosurg, Denmark Hill, London SE5 9RS, England. EM Anthony.strong@kcl.ac.uk RI Dunn, Andrew/I-9527-2014 NR 30 TC 52 Z9 53 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2006 VL 26 IS 5 BP 645 EP 653 DI 10.1038/sj.jcbfm.9600240 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 038RA UT WOS:000237239500006 PM 16251884 ER PT J AU Offner, H Subramanian, S Parker, SM Afentoulis, ME Vandenbark, AA Hurn, PD AF Offner, H Subramanian, S Parker, SM Afentoulis, ME Vandenbark, AA Hurn, PD TI Experimental stroke induces massive, rapid activation of the peripheral immune system SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE chemokines; cytokines; peripheral immunity; receptors; stroke ID MIDDLE CEREBRAL-ARTERY; CENTRAL-NERVOUS-SYSTEM; INTERFERON-INDUCIBLE PROTEIN-10; CHEMOKINE RECEPTOR ANTAGONIST; MESSENGER-RNA EXPRESSION; RAT ISCHEMIC CORTEX; SPINAL-CORD; PERMANENT OCCLUSION; GENE-EXPRESSION; FOCAL STROKE AB Clinical experimental stroke induces injurious local brain inflammation. However, effects on the peripheral immune system have not been well characterized. We quantified mRNA and protein levels for cytokines, chemokines, and chemokine receptors (CCR) in brain, spinal cord, peripheral lymphoid organs (spleen, lymph node, blood, and cultured mononuclear cells from these sources), and blood plasma after reversible middle cerebral artery occlusion (MCAO) or sham treatment in male C57BL/6 mice. Middle cerebral artery occlusion induced a complex, but organ specific, pattern of inflammatory factors in the periphery. At both 6 and 22 h after MCAO, activated spleen cells from stroke-injured mice secreted significantly enhanced levels of TNF-alpha, IFN-gamma, IL-6, MCP-1, and IL-2. Unstimulated splenocytes expressed increased chemokines and CCR, including MIP-2 and CCR2, CCR7 & CCR8 at 6 h; and MIP-2, IP-10, and CCR1 & CCR2 at 22 h. Also at 22 h, T cells from blood and lymph nodes secreted increased levels of inflammatory cytokines after activation. As expected, there were striking proinflammatory changes in postischemic brain. In contrast, spinal cord displayed suppression of all mediators, suggesting a compensatory response to intracranial events. These data show for the first time that focal cerebral ischemia results in dynamic and widespread activation of inflammatory cytokines, chemokines, and CCR in the peripheral immune system. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NINDS NIH HHS [NS33668, NS49210, R01 NS076013]; NINR NIH HHS [NR03521] NR 40 TC 248 Z9 261 U1 3 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2006 VL 26 IS 5 BP 654 EP 665 DI 10.1038/sj.jcbfm.9600217 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 038RA UT WOS:000237239500007 PM 16121126 ER PT J AU Molitch, ME Clemmons, DR Malozowski, S Merriam, GR Shalet, SM Vance, ML AF Molitch, ME Clemmons, DR Malozowski, S Merriam, GR Shalet, SM Vance, ML CA Endocrine Societys Clinical Guidel TI Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society clinical practice guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID GH-REPLACEMENT THERAPY; BONE-MINERAL DENSITY; CARDIOVASCULAR RISK-FACTORS; INTIMA-MEDIA THICKNESS; QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; RECOMBINANT HUMAN GH; BENIGN INTRACRANIAL HYPERTENSION; MIMICKING DIABETIC-RETINOPATHY; RANDOMIZED CONTROLLED TRIAL AB Objective: The objective is to provide guidelines for the evaluation and treatment of adults with GH deficiency (GHD). Participants: The chair of the Task Force was selected by the Clinical Guidelines Subcommittee of The Endocrine Society (TES). The chair selected five other endocrinologists and a medical writer, who were approved by the Council. One closed meeting of the group was held. There was no corporate funding, and members of the group received no remuneration. Evidence: Only fully published, peer-reviewed literature was reviewed. The Grades of Evidence used are outlined in the Appendix. Consensus Process: Consensus was achieved through one group meeting and e-mailing of drafts that were written by the group with grammatical/style help from the medical writer. Drafts were reviewed successively by the Clinical Guidelines Subcommittee, the Clinical Affairs Committee, and TES Council, and a version was placed on the TES web site for comments. At each level, the writing group incorporated needed changes. Conclusions: GHD can persist from childhood or be newly acquired. Confirmation through stimulation testing is usually required unless there is a proven genetic/structural lesion persistent from childhood. GH therapy offers benefits in body composition, exercise capacity, skeletal integrity, and quality of life measures and is most likely to benefit those patients who have more severe GHD. The risks of GH treatment are low. GH dosing regimens should be individualized. The final decision to treat adults with GHD requires thoughtful clinical judgment with a careful evaluation of the benefits and risks specific to the individual. C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98432 USA. Christie Hosp NHS Trust, Manchester M20 4BX, Lancs, England. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. RP Molitch, ME (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. NR 166 TC 218 Z9 228 U1 0 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2006 VL 91 IS 5 BP 1621 EP 1634 DI 10.1210/jc.2005-2227 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000001 PM 16636129 ER PT J AU Lo, J Dolan, SE Kanter, JR Hemphill, LC Connelly, JM Lees, RS Grinspoon, SK AF Lo, J Dolan, SE Kanter, JR Hemphill, LC Connelly, JM Lees, RS Grinspoon, SK TI Effects of obesity, body composition, and adiponectin on carotid intima-media thickness in healthy women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INDEPENDENT RISK-FACTOR; CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; PLASMA-PROTEIN; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; ABDOMINAL OBESITY; WALL THICKNESS AB Context: Increased common carotid intima-media thickness (IMT) is predictive of coronary artery disease and stroke. Objective: In this study, we investigated common carotid IMT by obesity category in a cohort of healthy women without previously known cardiovascular disease. Design, Setting, Participants, and Main Outcome Measures: One hundred healthy women (aged 24-59 yr) from the general community enrolled in an observational study conducted at an academic medical center participated in the study. B-mode ultrasound imaging of the common carotid arteries was used to measure common carotid IMT in 99 subjects. Fat distribution was determined by computed tomography. Hormonal and inflammatory parameters related to cardiovascular disease and obesity were measured. Results: IMT was higher in obese [body mass index (BMI) >= 30 kg/m(2)], compared with overweight women (BMI >= 25 and < 30 kg/m(2)) [0.69 mm, interquartile range (IQR) 0.60 - 0.75 mm] vs. 0.62 mm [IQR 0.56 - 0.68 mm), P = 0.044] and in comparison with lean women ( BMI < 25 kg/m2) [0.69 mm ( IQR 0.60 - 0.75 mm) vs. 0.59 mm ( IQR 0.54 - 0.67 mm), P = 0.016]. In multivariate modeling, age ( beta = 0.0050 mm change in IMT per year of age, P = 0.003), smoking ( beta = 0.0044 mm change in IMT per pack-year, P = 0.046), and sc abdominal adiposity ( beta = 0.00026 mm change in IMT per square centimeter, P = 0.010) were positively associated with IMT, whereas adiponectin ( beta = -0.0042 mm change in IMT per milligram per liter, P = 0.045) was negatively associated with IMT. Visceral adiposity ( beta = 0.00048 mm change in IMT per square centimeter, P = 0.092) was not significantly associated with IMT after adjusting for age, race, smoking, sc abdominal adiposity, and adiponectin. Conclusions: Obesity is associated with increased common carotid IMT in young and middle-aged women. Adiponectin and sc abdominal adiposity are associated with carotid IMT in this population. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston Heart Fdn, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [K30 RR022292, K30 RR022292-07, M01 RR001066, M01 RR01066-25S1]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11, R01 DK 59535, R01 DK059535] NR 37 TC 63 Z9 66 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2006 VL 91 IS 5 BP 1677 EP 1682 DI 10.1210/jc.2005-2775 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000011 PM 16522690 ER PT J AU Miller, KK Biller, BMK Beauregard, C Lipman, JG Jones, J Schoenfeld, D Sherman, JC Swearingen, B Loeffler, J Klibanski, A AF Miller, KK Biller, BMK Beauregard, C Lipman, JG Jones, J Schoenfeld, D Sherman, JC Swearingen, B Loeffler, J Klibanski, A TI Effects of testosterone replacement in androgen-deficient women with hypopituitarism: A randomized, double-blind, placebo-controlled study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; SURGICALLY MENOPAUSAL WOMEN; HYPOACTIVE SEXUAL DESIRE; SUBJECTIVE HEALTH-STATUS; POSTMENOPAUSAL WOMEN; TRANSDERMAL TESTOSTERONE; BODY-COMPOSITION; CONTROLLED-TRIAL; DEHYDROEPIANDROSTERONE REPLACEMENT; ADRENAL INSUFFICIENCY AB Context: Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported. Objective: The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism. Design: This was a 12-month randomized, placebo-controlled study. Setting: The study was conducted at a general clinical research center. Study Participants: Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated. Intervention: Physiologic testosterone administration using a patch that delivers 300 mu g daily or placebo was administered. Main Outcome Measures: Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires. Results: Mean free testosterone increased into the normal range during testosterone administration. Mean hip ( P = 0.023) and radius ( P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass ( P = 0.040) and thigh muscle area ( P = 0.038), but there was no change in fat mass. Mood ( P = 0.029) and sexual function ( P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects. Conclusions: This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU FDA HHS [FD-R-001981]; NCRR NIH HHS [M01 RR01066] NR 46 TC 86 Z9 91 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2006 VL 91 IS 5 BP 1683 EP 1690 DI 10.1210/jc.2005-2596 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000012 PM 16478814 ER PT J AU Redondo, MJ Babu, S Zeidler, A Orban, T Yu, LP Greenbaum, C Palmer, JP Cuthbertson, D Eisenbarth, GS Krischer, JP Schatz, D AF Redondo, MJ Babu, S Zeidler, A Orban, T Yu, LP Greenbaum, C Palmer, JP Cuthbertson, D Eisenbarth, GS Krischer, JP Schatz, D CA DPT 1 Study Grp TI Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 1ST DEGREE RELATIVES; PREVENTION TRIAL; ISLET; INSULIN; DQA1-ASTERISK-0102/DQB1-ASTERISK-0602; DQB1-ASTERISK-0602; SUSCEPTIBILITY; PROTECTION; TOLERANCE; CHILDREN AB Context: Human leukocyte antigen (HLA) DQ haplotypes have the strongest genetic association with type 1 diabetes (T1DM) risk. Objective: The objective of the study was to analyze whether HLA DQ alleles influence the development of antiislet autoantibodies, the progression to T1DM among autoantibody-positive relatives, or both. Design: The Diabetes Prevention Trial-1 screened more than 90,000 nondiabetic relatives of patients for cytoplasmic islet-cell autoantibody (ICA) expression between 1994 and 2002. Setting: The study was conducted in the general community. Participants: The Diabetes Prevention Trial-1 found 2817 ICA-positive relatives who were tested for biochemical autoantibodies (GAD65, ICA512, and insulin) and HLA-DQ haplotypes, and 2796 of them were followed up for progression to diabetes for up to 8 yr (median, 3.6 yr). Main Outcome Measure: Progression to T1DM was measured. Results: High-risk DQ haplotypes and genotypes were associated with a higher percentage of relatives expressing multiple biochemical auto-antibodies and higher T1DM risk (e.g., respectively, 59 and 36% at 5 yr for carriers of the DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 genotype). The number of autoantibodies expressed significantly increased T1DM risk and across different DQ genotypes, autoantibody positivity directly correlated with diabetes risk. However, multivariate analyses indicated that the influence of most genotypes on T1DM risk was not independent from autoantibody expression, with the possible exception of DQA1*0102-DQB1*0602. Specific genotypic combinations conferred 5-yr diabetes risks significantly lower (e.g. 7%-DQA1*0201-DQB1*0201/DQA1*0501-DQB1*0201 and 14%-DQA1*0301-DQB1*0301/DQA1*0501-DQB1*0201) than when those haplotypes were found in other combinations. Conclusion: HLA DQ alleles determine autoantibody expression, which is correlated with diabetes progression. Among autoantibody-positive relatives, most HLA DQ genotypes did not further influence T1DM risk. C1 Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80045 USA. Univ Navarra Clin, Dept Endocrinol, Pamplona 31008, Spain. Los Angeles Cty Univ So Calif Med Ctr, Div Endocrinol & Diabet, Los Angeles, CA 90033 USA. Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Benaroya Res Inst, Diabet Clin Res, Seattle, WA 98101 USA. Univ Washington, Dept Vet Affairs Puget Sound, Seattle, WA 98108 USA. Univ S Florida, Dept Pediat, Tampa, FL 33612 USA. Univ Florida, Ctr Diabet, Gainesville, FL 32611 USA. RP Eisenbarth, GS (reprint author), Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, 1775 N Ursula St,POB 6511, Aurora, CO 80045 USA. EM george.eisenbarth@uchsc.edu FU NCRR NIH HHS [N01RR00037, M01RR00069]; NIDDK NIH HHS [5R37DK32083]; PHS HHS [R01A139213, R01 A1 4431-03] NR 20 TC 16 Z9 17 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2006 VL 91 IS 5 BP 1705 EP 1713 DI 10.1210/jc.2005-1695 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000015 PM 16464953 ER PT J AU Matthews, KA Santoro, N Lasley, B Chang, YF Crawford, S Pasternak, RC Sutton-Tyrrell, K Sowers, M AF Matthews, KA Santoro, N Lasley, B Chang, YF Crawford, S Pasternak, RC Sutton-Tyrrell, K Sowers, M TI Relation of cardiovascular risk factors in women approaching menopause to menstrual cycle characteristics and reproductive hormones in the follicular and luteal phases SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PERIMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; DISEASE RISK; NATION SWAN; BODY-SIZE; TRANSITION; ETHNICITY; HEALTHY; URINE AB Context: Menstrual cycle characteristics may be associated with cardiovascular disease (CVD) risk. Objective: The objective of this study was to describe the relationships between menstrual cycle characteristics and daily reproductive hormone measures with CVD risk factors in middle-aged women. Design and Setting: Cross-sectional associations were examined between CVD risk factors and urinary LH, FSH, estrone conjugates, and pregnanediol glucuronide (Pdg) measured across one menstrual cycle or 50 d. Participants: Menstruating women (n = 500) who were free from diabetes or past stroke or heart attack enrolled in the Daily Hormone Study-Study of Women's Health across the Nation were studied. Main Outcome Measures: Body mass index (BMI), blood pressure, hemostatic, and metabolic factors were measured. Results: Few differences existed in risk factors between women with evidence of luteal activity and those with no evidence of luteal activity. Associations between elevated CVD risk factors and long cycle length were reduced substantially by age and BMI adjustments. Those with lower estrone conjugate and PdG averaged across the follicular phase had higher waist circumference, triglycerides, insulin, plasminogen activator inhibitor type-1, tissue type plasminogen activator-antigen, and factor VIIc levels in age- and BMI-adjusted analyses (P < 0.05). Conclusions: In midlife menstruating women, a longer cycle length was related to CVD risk factors, in large part through their common association with BMI. More favorable levels of metabolic and hemostatic factors were associated with higher levels of follicular-phase estrogen, a pattern consistent with a more competent ovary, and higher levels of follicular-phase PdG, perhaps of adrenal origin. Metabolic and hemostatic factors may be sensitive to hormonal variation during the early perimenopausal transition. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10461 USA. Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. Kaiser Permanente, Davis, CA 95616 USA. Univ Massachusetts, Sch Med, Dept Epidemiol & Biostat, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Matthews, KA (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. EM matthewska@upmc.edu RI 段, 沛沛/C-9902-2010 FU NIA NIH HHS [U01 AG12495, U01 AG12505, U01 AG12531, U01 AG12535, U01 AG12546, U01 AG12553, U01 AG12554]; NINR NIH HHS [U01 NR04061]; PHS HHS [U01 A12539] NR 27 TC 30 Z9 30 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2006 VL 91 IS 5 BP 1789 EP 1795 DI 10.1210/jc.2005-1057 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 039TL UT WOS:000237330000027 PM 16492698 ER PT J AU Sontag, SJ Sonnenberg, A Schnell, TG Leya, J Metz, A AF Sontag, SJ Sonnenberg, A Schnell, TG Leya, J Metz, A TI The long-term natural history of gastroesophageal reflux disease SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE natural history; gastroesophageal reflux diseases ID RISK-FACTORS; FOLLOW-UP; ESOPHAGITIS AB Introduction: Long-term gastric acid suppression has been suggested as a means to prevent complications of reflux esophagitis. We report on the 20-year follow-up of 2,306 patients with at least two endoscopic examinations who were taking no antisecretory medication before baseline endoscopy and whose long-term treatment was determined by reflux symptoms. Methods: From 1979 through 1998, endoscopy and biopsy were performed in the Hines Veterans Affairs Hospital endoscopy clinic by three endoscopists. Antireflux treatment was symptom-driven, and endoscopies were repeated mostly for symptomatic recurrence due to cessation of therapy. Results: Of 4,633 patients undergoing endoscopy for reflux symptoms, 2,306 had at least one follow-up endoscopy and biopsy. Over a mean follow-up period of 7.6 years (range, 1-20 years), the esophageal mucosa of 67% of patients remained unchanged, that of 21% improved, and that of 11% worsened. Esophageal stricture requiring dilation developed from a normal baseline mucosa in one of 1,313 patients (0.08%) and from an erosive baseline mucosa in 18 of 957 patients (1.9%). The overall incidence of stricture in patients with gastroesophageal reflux (GER) disease was < 1/1,000 per year. Nonsteroidal antiinflammatory drug (NSAID) consumption was associated with less mucosal improvement (odds ration [OR] = 0.67; confidence interval [CI] = 0.46-0.98). Use of histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was associated with mucosal improvement (OR for PPIs = 1.49, CI = 1.14-2.17). Cohn's kappa was 42%, confirming the results that demonstrate stability of esophageal mucosal disease in the majority of patients. Conclusions: Symptom-driven treatment of GER disease after a thorough endoscopic examination to exclude premalignant or malignant esophageal mucosal disease is practical and safe for the vast majority of patients with uncomplicated GER symptoms. C1 Hines Vet Affairs Hosp, Hines, IL 60141 USA. Loyola Univ, Sch Med, Maywood, IL 60153 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Sontag, SJ (reprint author), Hines Vet Affairs Hosp, Bldg 1,Room B321 151B3, Hines, IL 60141 USA. EM Stephen.Sontag@med.va.gov NR 16 TC 33 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2006 VL 40 IS 5 BP 398 EP 404 DI 10.1097/00004836-200605000-00007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 045LF UT WOS:000237742900007 PM 16721220 ER PT J AU Vauthey, JN Pawlik, TM Ribero, D Wu, TT Zorzi, D Hoff, PM Xiong, HQ Eng, C Lauwers, GY Mino-Kenudson, M Risio, M Muratore, A Capussotti, L Curley, SA Abdalla, EK AF Vauthey, JN Pawlik, TM Ribero, D Wu, TT Zorzi, D Hoff, PM Xiong, HQ Eng, C Lauwers, GY Mino-Kenudson, M Risio, M Muratore, A Capussotti, L Curley, SA Abdalla, EK TI Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FATTY LIVER-DISEASE; PORTAL-VEIN EMBOLIZATION; LONG-TERM SURVIVAL; NONALCOHOLIC STEATOHEPATITIS; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; EXTENDED HEPATECTOMY; KAPPA-B; RESECTION; CANCER AB Purpose Chemotherapy before resection of hepatic colorectal metastases (CRM) may cause hepatic injury and affect postoperative outcome. Patients and Methods Four hundred six patients underwent hepatic resection of CRM between 1992 and 2005. Pathologic review of the nontumorous liver was performed using established criteria for steatosis, steatohepatitis, and sinusoidal injury. The effect of chemotherapy and liver injury on perioperative outcome was analyzed. Results One hundred fifty-eight patients (38.9%) received no preoperative chemotherapy, whereas 248 patients (61.1%) did. The median duration of chemotherapy was 16 weeks (range, 2 to 70 weeks). Chemotherapy consisted of fluoropyrimidine-based regimens (fluorouracil [FU] alone, 15.5%; irinotecan plus FU, 23.1%; and oxaliplatin plus FU, 19.5%) and other therapy (3.0%). On pathologic analysis, 36 patients (8.9%) had steatosis, 34 (8.4%) had steatohepatitis, and 22 (5.4%) had sinusoidal dilation. Oxaliplatin was associated with sinusoidal dilation compared with no chemotherapy (18.9% v 1.9%, respectively; P<.001; odds ratio [OR]=8.3; 95% CI, 2.9 to 23.6). In contrast, irinotecan was associated with steatohepatitis compared with no chemotherapy (20.2% v 4.4%, respectively; P<.001; OR=5.4; 95% CI, 2.2 to 13.5). Patients with steatohepatitis had an increased 90-day mortality compared with patients who did not have steatohepatitis (14.7% v 1.6%, respectively; P=001; OR=10.5; 95% CI, 2.0 to 36.4). Conclusion Steatohepatitis is associated with an increased 90-day mortality after hepatic surgery. In patients with hepatic CRM, the chemotherapy regimen should be carefully considered because the risk of hepatortoxicity is significant. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ist Ric & Cura Canc, Dept Pathol, Turin, Italy. Ist Ric & Cura Canc, Dept Surg Oncol, Turin, Italy. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jvauthey@mdanderson.org NR 47 TC 659 Z9 677 U1 1 U2 15 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2006 VL 24 IS 13 BP 2065 EP 2072 DI 10.1200/JCO.2005.05.3074 PG 8 WC Oncology SC Oncology GA 040IF UT WOS:000237371500017 PM 16648507 ER PT J AU Wilens, TE Zusman, RM Hammerness, PG Podolski, A Whitley, J Spencer, TJ Gignac, M Biederman, J AF Wilens, TE Zusman, RM Hammerness, PG Podolski, A Whitley, J Spencer, TJ Gignac, M Biederman, J TI An open-label study of the tolerability of mixed amphetamine salts in adults with attention-deficit/hyperactivity disorder and treated primary essential hypertension SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; BLOOD-PRESSURE; DOUBLE-BLIND; CHILDREN; PLACEBO; METHYLPHENIDATE; ADOLESCENTS; COMORBIDITY; PERSPECTIVE AB Objective: To evaluate the short-term tolerability of an extended-release preparation of the stimulant medication mixed amphetamine salts (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) whose hypertension has been successfully treated with anti hypertensive medications. Method. An 8-week, 2-phase, open-label study design was implemented. All adults had ADHD (DSM-IV diagnosis) and essential hypertension and were required to be normotensive (blood pressure < 135/85 mm Hg, treated) for at least 4 weeks at entry into the study. MAS XR was given for a 6-week period, titrated once each week to a target maximum dose of 60 mg/day given once daily in the morning (phase 1), and then discontinued for 2 weeks at the end of the study (phase 2). At baseline, subjects underwent a comprehensive clinical assessment, medical history, vital signs assessment, and electrocardiogram (ECG). Rating scales were used throughout the study to assess response to treatment, and blood pressure was measured manually at each study visit. The primary outcome was the effect of MAS XR on blood pressure and the development of hypertension. Results: Thirteen subjects receiving antihypertensive therapy were entered and placed on MAS XR treatment and completed the trial. There were no serious adverse events. No sustained elevated blood pressure (> 140/90 mm Hg at 2 consecutive visits) was observed in the subjects treated with MAS XR. Similar rates of single episodes of hypertension were observed in phases 1 and 2. Similarly, there was no group mean increase in systolic or diastolic blood pressure or pulse during treatment with MAS XR. No clinically significant changes in the ECG were observed. During the 6-week medication phase, significant improvement was found on rating scales assessing ADHD symptoms and severity that reversed with discontinuation of MAS XR. Conclusion: The results of this open study suggest that adults with ADHD and controlled hypertension can be safely treated with MAS XR. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hypertens Unit, Div Cardiol, Boston, MA 02114 USA. Univ Montreal, Inst Philippe Pinel, Montreal, PQ, Canada. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, YAW 6A,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU NIDA NIH HHS [K24 DA016264] NR 41 TC 15 Z9 15 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2006 VL 67 IS 5 BP 696 EP 702 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 051OZ UT WOS:000238171700002 PM 16841618 ER PT J AU Ernst, CL Bird, SA Goldberg, JF Ghaemi, SN AF Ernst, CL Bird, SA Goldberg, JF Ghaemi, SN TI The prescription of psychotropic medications for patients discharged from a psychiatric emergency service SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID REFERRALS; ROOM; ANTIDEPRESSANTS AB Objective: Considerable debate exists about the value and wisdom of initiating "definitive" pharmacotherapies, particularly antidepressants, in the psychiatric emergency setting. We evaluated the nature and prevalence of medication prescriptions for patients discharged from an urban psychiatric emergency service and the extent to which pharmacotherapy initiation was predictive of follow-through with aftercare. Method: Records were reviewed for 675 consecutive individuals evaluated and discharged from a community-based psychiatric emergency service over a 3-month period (January 2003-March 2003). Information was obtained regarding diagnoses, past and current treatments, and demographic and clinical features, as well as outcomes for the subgroup of patients who received aftercare appointments within the institutional system. Results: Fifty-five percent of psychiatric emergency service visits resulted in discharge, with psychotropic drug prescriptions given to about 30% of this group. Prescriptions most often included antidepressants (64%), benzodiazepines (25%), nonbenzodiazepine sedatives (20%), antipsychotics (18%), and mood stabilizers (10%). After controlling for potential confounders, the decision to prescribe was significantly associated with a clinical diagnosis of major depressive disorder or bipolar disorder and the preexisting use of psychotropic medications. Nonprescribing occurred most often in discharged patients who had suicidal ideation, substance abuse or dependence, and an existing outpatient psychiatrist. Follow-up emergency service and new outpatient appointments were more often given to patients discharged with a prescription, but follow-through with aftercare was not more likely in this group. Conclusions: Psychiatrists in an emergency service prescribe antidepressants or other major psychotropics for about one third of discharged patients, rarely in the presence of suicidality or substance abuse or dependence, and with little evidence that initiating such medications in the emergency setting promotes more successful bridging to outpatient treatment. C1 Silver Hill Hosp, Affect Disorders Program, New Canaan, CT 06840 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. Zucker Hillside Hosp, Dept Psychiat Res, N Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA. Emory Univ, Sch Med, Bipolar Disorder Res Program, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Goldberg, JF (reprint author), Silver Hill Hosp, Affect Disorders Program, 208 Valley Rd, New Canaan, CT 06840 USA. EM JFGoldberg@yahoo.com NR 16 TC 9 Z9 9 U1 1 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2006 VL 67 IS 5 BP 720 EP 726 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 051OZ UT WOS:000238171700005 PM 16841621 ER PT J AU Biederman, J Swanson, JM Wigal, SB Boellner, SW Earl, CQ Lopez, FA AF Biederman, J Swanson, JM Wigal, SB Boellner, SW Earl, CQ Lopez, FA CA Modafinil ADHD Study Grp TI A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: A randomized, double-blind, and placebo-controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; FILM-COATED TABLETS; INDUCED WAKEFULNESS; ADOLESCENTS; AMPHETAMINE; BRAIN AB Objective: This randomized, double-blind, placebo-controlled study assessed the efficacy and tolerability of several modafinil dosing regimens in children with attention-deficit/hyperactivity disorder (ADHD) to determine whether modafinil can be given once daily in pediatric ADHD. Method: Children and adolescents (age range, 6-13 years) (N = 248) with DSM-IV-defined ADHD were enrolled in a 4-week, double-blind, placebo-controlled study, conducted February-May 2002. The group was assigned to receive oral (100-mg tablets) modafinil 300 mg once daily (300 mg in the morning followed by placebo at midday), modafinil 300 mg as a divided dose (100/200 mg or 200/100 mg), or matching placebo. In children weighing ! 30 kg, a higher dose of 400 mg (200/200 mg) was evaluated. Efficacy measures included the teacher-rated School Version and clinician-rated Home Version of the ADHD Rating Scale-IV and the parent-completed Conners' ADHD/DSM-IV Scales. Results: 223 children completed the study. Those who received modafinil 300 mg once daily showed a significantly greater improvement (change from baseline) than those who received placebo in symptoms of ADHD across all rating scales and subscales (all p < .05). Divided 300-mg doses of modafinil provided some significant but inconsistent improvements in ADHD symptoms. In children weighing >= 30 kg, modafinil 400 mg (200/200 mg) was significantly superior to placebo on clinician- and parent-completed scales (all p < .05). Insomnia was the only adverse event to occur with significantly greater frequency in a modafinil group (200/100) than in the placebo group (14% vs. 2%) (p = .03). Conclusion: Modafinil significantly improved ADHD symptoms in children. Once-daily dosing (300 mg) provided the most consistent improvement in symptoms. All dosing regimens of modafinil were well tolerated. C1 Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. Neurol & Clin Study Ctr, Little Rock, AR USA. Cephalon Inc, Frazer, PA USA. Childrens Dev Ctr PA, Matieland, FL USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Yawkey Ctr Outpatient Care, Yaw 6A 6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org NR 24 TC 34 Z9 35 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2006 VL 67 IS 5 BP 727 EP 735 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 051OZ UT WOS:000238171700006 PM 16841622 ER PT J AU Henderson, DC Copeland, PM Borba, CP Daley, TB Nguyen, DD Cagliero, E Evins, AE Zhang, H Hayden, DL Freudenreich, O Cather, C Schoenfeld, DA Goff, DC AF Henderson, DC Copeland, PM Borba, CP Daley, TB Nguyen, DD Cagliero, E Evins, AE Zhang, H Hayden, DL Freudenreich, O Cather, C Schoenfeld, DA Goff, DC TI Glucose metabolism in patients with schizophrenia treated with olanzapine or quetiapine: A frequently sampled intravenous glucose tolerance test and minimal model analysis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DIABETES-MELLITUS; INSULIN SENSITIVITY; ANTIPSYCHOTIC TREATMENT; CLOZAPINE; RISPERIDONE; RESISTANCE; DATABASE; DISEASE; RISK; HYPERLIPIDEMIA AB Objective: Clozapine and olanzapine treatment has been associated with insulin resistance in nonobese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism. Method: A cross-sectional comparison of quetiapine-treated and olanzapine-treated nonobese (body mass index < 30.0 kg/m(2)) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls). Results: There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p =. 1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049). Conclusions: Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mallinckrodt Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henderson, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM dchenderson@partners.org FU NCRR NIH HHS [5M01RR01066-24] NR 56 TC 49 Z9 49 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2006 VL 67 IS 5 BP 789 EP 797 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 051OZ UT WOS:000238171700013 PM 16841629 ER PT J AU Kalva, SP Sahani, DV Hahn, PF Saini, S AF Kalva, SP Sahani, DV Hahn, PF Saini, S TI Using the K-edge to improve contrast conspicuity and to lower radiation dose with a 16-MDCT: a phantom and human study SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT angiography; CT technique ID TUBE CURRENT MODULATION; MULTIDETECTOR-ROW CT; IMAGE QUALITY; COMPUTED-TOMOGRAPHY; 80 KVP; ANGIOGRAPHY; REDUCTION; ENHANCEMENT; IODINE AB Purpose: To study the effect of tube current (milliamperes; mA) and potential (peak kilovolt; kVp) on the attenuation values and contrast-to-noise ratios of iodine- and gadolinium-based contrast media (CM) for computed tomography angiography (CTA). Materials and Methods: Phantom Study: A water-filled phantom with five 20-mL syringes filled with 1:20 dilution of 282, 300, 370, and 400 milligrams of iodine per milliliter concentration CM and gadopentetate dimeglumine (Magnevist, Berlex Laboratories, Wayne, NJ, 0.5 mol/L) was scanned with a 16-multidetector CT using 80, 100, 120, and 140 kVp and 500-millisecond gantry rotation time. The milliampere was either fixed at 100, 200, 300, and 380 or automatically adjusted with noise indices of 15, 20, and 25 or manually adjusted to maintain a constant image noise. The attenuation value (Hounsfield unit; HU) and its standard deviation of CM in each syringe and of the water phantom were obtained. Statistical analysis was performed to determine difference between attenuation values and contrast medium-to-water contrast-to-noise ratios at various kVp and mA selection. Human Study: Three groups of patients had CTA for abdominal aortic aneurysm with similar computed tomography parameters, varying only in kVp selection of either 100 (group A), 120 (group B), or 140 (group Q. Another group (group D) had CTA at 100 kVp but with the CM volume reduced to 60%. The CTA studies were evaluated for the quality of axial and 3D images; attenuation values in the aorta, superior mesenteric artery, and iliac arteries; image noise; and scanner-estimated radiation dose. Statistical analysis was performed to determine the difference in image quality and radiation dose among the groups. Results: Phantom Study: In comparison with 140 kVp, regardless of selected milliampere or noise indices, images acquired at 80, 100, and 120 kVp showed 90.8% to 94.2%, 47% to 49.7%, and 18.9% to 20.7% (P < 0.0001) increase in HU of iodine-based CM, respectively, and 62.9%, 39.6%, and 16.8% (P < 0.0001) increase in HU of gadolinium-based CM, respectively. Human Study: The axial images in all the groups were diagnostically acceptable. There was significantly inferior quality of axial images associated with greater image noise in group A and group D (P < 0.01) in comparison with group C, but there was no difference in the quality of 3D images among the 4 groups. In comparison with group C, there was significantly higher attenuation of the aorta, superior mesenteric artery, and iliac arteries in group A (P< 0.01), group B (P< 0.05), andgroup D (P< 0.01). The radiation dose (CT dose index volume) decreased to 12 +/- 4 in groups A and D compared with 17 +/- 4 in group B and 24 +/- 5 in group C. Conclusions: Lower kVp increases the attenuation of iodinated and gadolinium CM. CTA of the abdominal aorta performed at low kVp results in higher attenuation in aorta with reduced radiation dose and without degrading the diagnostic image quality. The iodinated CM volume can be reduced by reducing kVp during CTA. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM dsahani@partners.org NR 16 TC 87 Z9 91 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2006 VL 30 IS 3 BP 391 EP 397 DI 10.1097/00004728-200605000-00008 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054XH UT WOS:000238411400008 PM 16778612 ER PT J AU Powitzky, ES Hayman, LA Chau, J Bartling, SH Gupta, R Shukla, V AF Powitzky, ES Hayman, LA Chau, J Bartling, SH Gupta, R Shukla, V TI High-resolution computed tomography of temporal bone - Part IV. Coronal postoperative anatomy SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE temporal bone anatomy; temporal bone computed tomography; temporal bone surgical anatomy; prospective temporal bone ID MIDDLE-EAR; OSSICULAR RECONSTRUCTION; COCHLEAR IMPLANTATION; PREOPERATIVE ANATOMY; VOLUME-CT; SURGERY AB The purpose of this 4-part series is to illustrate the nuances of temporal bone anatomy using a high-resolution (200 mu isotropic) prototype volume computed tomography (CT) scanner. The normal anatomy in axial and coronal sections is depicted in the first and second parts. In this, the fourth part, and the third part, the structures that are removed and/or altered in 9 different surgical procedures are color coded and inscribed in the same coronal (article IV) and axial (article III) sections. The text stresses clinically important imaging features, including the normal postoperative appearance, and common complications after these operations. The superior resolution of the volume CT images is vital to the comprehensive and accurate representation of these operations. Minuscule intricate structures that are currently only localized in the mind's eye because of the resolution limit of conventional CT are clearly seen on these scans. This enhanced visualization, together with the information presented in the text, should assist in interpreting temporal bone scans, communicating with surgeons, and teaching this complex anatomy. C1 Ctr ENT, Houston, TX 77030 USA. Baylor Coll Med, Dept Otolaryngol, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX USA. Univ Alberta, Dept Otolaryngol, Edmonton, AB, Canada. Hannover Med Sch, Dept Neuroradiol, D-3000 Hannover, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Powitzky, ES (reprint author), Ctr ENT, 6624 Fannin,Suite 1480, Houston, TX 77030 USA. EM epo@centerforent.com OI Powitzky, Eric/0000-0002-1747-9439 NR 17 TC 0 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2006 VL 30 IS 3 BP 548 EP 554 DI 10.1097/00004728-200605000-00033 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 054XH UT WOS:000238411400033 PM 16778637 ER PT J AU McLachlan, MJ Weissman, K Nadel, ES Brown, DFM AF McLachlan, MJ Weissman, K Nadel, ES Brown, DFM TI Intermittent fevers SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID MALARIA C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Bulfinch 105, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2006 VL 30 IS 4 BP 425 EP 428 DI 10.1016/j.jemermed.2006.02.002 PG 4 WC Emergency Medicine SC Emergency Medicine GA 050QM UT WOS:000238103000012 PM 16740454 ER PT J AU Haidet, P Kelly, PA Bentley, S Blatt, B Chou, CL Fortin, AH Gordon, G Gracey, C Harrell, H Hatem, DS Helmer, D Paterniti, DA Wagner, D Inui, TS AF Haidet, P Kelly, PA Bentley, S Blatt, B Chou, CL Fortin, AH Gordon, G Gracey, C Harrell, H Hatem, DS Helmer, D Paterniti, DA Wagner, D Inui, TS CA Communication Curriculum Culture TI Not the same everywhere - Patient-centered learning environments at nine medical schools SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE physician-patient relations; patient-centered care; schools, medical; students; medical; culture; organizational culture; education, medical, undergraduate; curriculum ID INTERVIEWING SKILLS; STUDENTS; CURRICULUM; EDUCATION; CARE; COMMUNICATION; ACQUISITION; RETENTION; ATTITUDES; CONTEXT AB BACKGROUND: Learning environments overtly or implicitly address patient-centered values and have been the focus of research for more than 40 years, often in studies about the "hidden curriculum." However, many of these studies occurred at single medical schools and used time-intensive ethnographic methods. This field of inquiry lacks survey methods and information about how learning environments differ across medical schools. OBJECTIVE: To examine patient-centered characteristics of learning environments at 9 U.S. medical schools. DESIGN: Cross-sectional internet-based survey. PARTICIPANTS: Eight-hundred and twenty-three third- and fourth-year medical students in the classes of 2002 and 2003. MEASUREMENTS: We measured the patient-centeredness of learning environments with the Communication, Curriculum, and Culture (C-3) Instrument, a 29-item validated measure that characterizes the degree to which a medical school's environment fosters patient-centered care. The C-3 Instrument contains 3 content areas (role modeling, students' experiences, and support for students' patient-centered behaviors), and is designed to measure these areas independent of respondents' attitudes about patient-centered care. We also collected demographic and attitudinal information from respondents. RESULTS: The variability of C-3 scores across schools in each of the 3 content areas of the instrument was striking and statistically significant (P values ranged from .001 to .004). In addition, the patterns of scores on the 3 content areas differed from school to school. CONCLUSIONS: The 9 schools demonstrated unique and different learning environments both in terms of magnitude and patterns of characteristics. Further multiinstitutional study of hidden curricula is needed to further establish the degree of variability that exists, and to assist educators in making informed choices about how to intervene at their own schools. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Yale Univ, Sch Med, New Haven, CT USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Univ Florida, Coll Med, Gainesville, FL USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, E Orange, NJ USA. Univ Calif Davis, Ctr Hlth Serv Res Primary Care, Sacramento, CA 95817 USA. Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. Regenstrief Inst Hlth Care, Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. RP Haidet, P (reprint author), Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM phaidet@bcm.tmc.edu NR 37 TC 31 Z9 31 U1 1 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2006 VL 21 IS 5 BP 405 EP 409 DI 10.1111/j.1525-1497.2006.00417.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 040ZL UT WOS:000237422300001 PM 16704378 ER PT J AU Harrison, R Allen, E AF Harrison, R Allen, E TI Teaching internal medicine residents in the new era - Inpatient attending with duty-hour regulations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE resident education; inpatient teaching; duty hours ID WORK HOURS; SLEEP AB BACKGROUND: Little is known about the impact of resident duty-hour regulations on the inpatient teaching experience. OBJECTIVE: Provide descriptive information on the effect of resident duty-hour regulations on attendings and the educational environment. DESIGN: Qualitative analysis of attending focus groups and e-mail survey of residents in Internal Medicine. PARTICIPANTS: Inpatient attending physicians at 2 academic centers and residents at the affiliated university-based Internal Medicine residency program in Portland, OR. RESULTS: Seventy-two percent of eligible attendings participated in 2 focus groups. Three themes were generated: increased clinical role, altered time management, and altered teaching. Attending physicians report performing more clinical work, teaching less, using more focused teaching methods, and experiencing an increased perception of intensity. Forty percent of eligible residents completed our e-mail survey. We organized residents data using the same 3 themes as attending physician data. Residents observed attending physicians performing increased clinical work, being more time aware, delivering more focused teaching, and having less time to teach. Participants noted changes in autonomy and professionalism. Strategies to enhance teaching effectiveness in the new environment were described. CONCLUSION: Duty-hour regulations have increased attending clinical responsibility and decreased teaching time in 1 residency program, leading to the perception of a more intense attending experience. Duty-hour regulations encourage educators to determine what is critical to preserve in the educational experiences of learners and challenge us to reexamine autonomy and professionalism in training. C1 Oregon Hlth Sci Univ, Div Hospitalist Med, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Harrison, R (reprint author), Oregon Hlth Sci Univ, Div Hospitalist Med, BTE 119,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM harrisor@ohsu.edu NR 21 TC 22 Z9 22 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2006 VL 21 IS 5 BP 447 EP 452 DI 10.1111/j.1525-1497.2006.00425.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 040ZL UT WOS:000237422300009 PM 16704386 ER PT J AU Park, ER Betancourt, JR Miller, E Nathan, M MacDonald, E Ananeh-Firempong, O Stone, VE AF Park, ER Betancourt, JR Miller, E Nathan, M MacDonald, E Ananeh-Firempong, O Stone, VE TI Internal medicine residents' perceptions of cross-cultural training - Barriers, needs, and educational recommendations SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cross-cultural; graduate education; communication; barriers ID CARE; COMPETENCE AB BACKGROUND: Physicians increasingly face the challenge of managing clinical encounters with patients from a range of cultural backgrounds. Despite widespread interest in cross-cultural care, little is known about resident physicians' perceptions of what will best enable them to provide quality care to diverse patient populations. OBJECTIVES: To assess medicine residents' (1) perceptions of cross-cultural care, (2) barriers to care, and (3) training experiences and recommendations. DESIGN, SETTING, AND PATIENTS: Qualitative individual interviews were conducted with 26 third-year medicine residents at Massachusetts General Hospital in Boston (response rate=87%). Interviews were recorded, transcribed, and analyzed. RESULTS: Despite significant interest in cross-cultural care, almost all of the residents reported very little training during residency. Most had gained cross-cultural skills through informal learning. A few were skeptical about formal training, and some expressed concern that it is impossible to understand every culture. Challenges to the delivery of cross-cultural care included managing patients with limited English proficiency, who involve family in critical decision making, and who have beliefs about disease that vary from the biomedical model. Residents cited many implications to these barriers, ranging from negatively impacting the patient-physician relationship to compromised care. Training recommendations included making changes to the educational climate and informal and formal training mechanisms. CONCLUSIONS: If cross-cultural education is to be successful, it must take into account residents' perspectives and be focused on overcoming residents' cited barriers. It is important to convey that cross-cultural education is a set of skills that can be taught and applied, in a time-efficient manner, rather than requiring an insurmountable knowledge base. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Park, ER (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org RI Miller, Elizabeth/E-7939-2012 NR 27 TC 17 Z9 17 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAY PY 2006 VL 21 IS 5 BP 476 EP 480 DI 10.1111/j.1525-1497.2006.00430.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 040ZL UT WOS:000237422300014 PM 16704391 ER PT J AU Doornberg, JN van Duijn, J Ring, D AF Doornberg, JN van Duijn, J Ring, D TI Coronoid fracture height in terrible-triad injuries SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE elbow; fracture; instability; coronoid process ID RADIAL HEAD; ELBOW; DISLOCATIONS; STABILITY AB Purpose: The coronoid fractures that occur in the terrible-triad pattern of traumatic elbow instability (posterior dislocation with fractures of the radial head and coronoid) usually are small transverse fragments. Attempts to classify these fragments according to height as suggested by Regan and Morrey have been inconsistent and contentious. The purpose of this study was to quantify coronoid fracture height in terrible-triad injuries. Methods: The height of the coronoid process of the ulna and the coronoid fracture fragment were measured on computed tomography scans of 13 patients with terrible-triad-pattern elbow injuries. Two observers performed the measurements with excellent intraobserver and interobserver reliability. Results: The total height of the coronoid process of the ulna averaged 19 mm. The average height of the coronoid fracture fragment was 7 mm. This corresponds to an average of 35% of the total height of the coronoid process. Conclusions: The transverse coronoid fractures associated with terrible-triad elbow injuries have a variable height that may not be easy to classify according to the system of Regan and Morrey. Classification of coronoid fractures according to fracture morphology and injury pattern may be preferable. C1 Massachusetts Gen Hosp, Orthopaed Hand & Upper Extremt Serv, Yawkey Ctr, Boston, MA 02114 USA. Univ Amsterdam, Orthotrauma Res Ctr, Amsterdam, Netherlands. Harvard Univ, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extremt Serv, Yawkey Ctr, Ste 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 11 TC 36 Z9 44 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY-JUN PY 2006 VL 31A IS 5 BP 794 EP 797 DI 10.1016/j.jhsa.2006.01.004 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 047LV UT WOS:000237881700017 PM 16713844 ER PT J AU Butt, AA Evans, R Skanderson, M Shakil, AO AF Butt, AA Evans, R Skanderson, M Shakil, AO TI Comorbid medical and psychiatric conditions and substance abuse in HCV infected persons on dialysis SO JOURNAL OF HEPATOLOGY LA English DT Article DE HCV; dialysis; comorbidities; treatment ID CHRONIC HEPATITIS-C; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; HUMAN-IMMUNODEFICIENCY-VIRUS; HEMOLYTIC-ANEMIA; HEPATOCELLULAR-CARCINOMA; INITIAL TREATMENT; RANDOMIZED-TRIAL; VETERANS; HIV; COINFECTION AB Background/Aims: The burden of comorbidity in the Hepatitis C virus (HCV) infected persons on dialysis is unknown. Methods: We identified all HCV infected and uninfected subjects in the United States Renal Data System in the years 1997-1998 using ICD-9 codes. Controls were matched on the date of first dialysis. ICD-9 codes and claims data was used to identify medical and psychiatric comorbidities. Results: We identified 5,737 HCV infected persons and 11,228 HCV uninfected subjects. HCV infected subjects were younger, more likely to be black race and male and more likely to have the following comorbidities: hypertension; hepatitis B; cirrhosis; wasting; anemia; human immunodeficiency virus (HIV) infection; major depression; mild depression; bipolar disorder; schizophrenia; post-traumatic stress disorder; drug use; alcohol use; smoking and less likely to have the following comorbidities: coronary artery disease; stroke; peripheral vascular disease; diabetes; cancer; erythropoietin use. After adjusting for age, gender and race, HCV infected subjects were more likely to have hypertension, hepatitis B, cirrhosis, wasting, anemia and HIV infection and less likely to have coronary artery disease and stroke. Conclusions: HCV infected persons on dialysis are more likely to have psychiatric comorbidities and substance abuse, as well as certain medical comorbidities. These factors should be considered when developing future intervention strategies. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Univ Pittsburgh, Med Ctr, Sch Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, Falk Med Bldg,3601 5th Ave,Suite 3A, Pittsburgh, PA 15213 USA. EM butta@dom.pitt.edu RI Langan Martin, Julie/M-4658-2015 FU NIDA NIH HHS [DA016175-01A1] NR 26 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAY PY 2006 VL 44 IS 5 BP 864 EP 868 DI 10.1016/j.jhep.2006.01.024 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 039SS UT WOS:000237327800006 PM 16516332 ER PT J AU Leykum, L Pugh, J Diuguid, D Papadopoulos, K AF Leykum, Luci Pugh, Jacqueline Diuguid, David Papadopoulos, Kyriakos TI Cost utility of substituting enoxaparin for unfractionated heparin for prophylaxis of venous thrombosis in the hospitalized medical patient SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE heparin-induced thrombocytopenia; VTE prophylaxis; cast-utility ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; TOTAL HIP-REPLACEMENT; LOW-DOSE HEPARIN; INDUCED THROMBOCYTOPENIA; DOUBLE-BLIND; PHARMACOECONOMIC EVALUATION; COLORECTAL SURGERY; RANDOMIZED-TRIAL; RISK-FACTORS AB BACKGROUND: Both heparin and enoxaparin are effective for the prevention of venous thromboembolism (VTE) in medical patients. On the basis of price, heparin appears preferable because it is less expensive. However, choosing enoxaparin may have greater cost utility when the outcomes of heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) are considered. OBJECTIVE: To determine the cost utility of substituting enoxaparin for heparin from payer and institutional perspectives. DESIGN: A decision analysis model was used. Cost data were based on Medicare reimbursement and the medication and laboratory costs for a multi-institutional healthcare system. Quality-adjusted life years (QALYs) saved by preventing HIT/HITT through the use of enoxaparin were based on published data. Costs are expressed on a per-day basis, and the incremental cost of enoxaparin over that of heparin was used in the calculation of cost/QALY. A sensitivity analysis also was performed. SETTING: inpatient medicine. PATIENTS: All medical patients for whom VTE prophylaxis was appropriate. INTERVENTIONS: Substitution of enoxaparin for heparin. MEASUREMENT: Cost/QALY. RESULTS: From a payer perspective, using enoxaparin resulted in a decrease in cost of $28.61 over that of heparin and saved 0.00629 QALYs in the base case, resulting in a savings of $4550.17/QALY. The sensitivity analysis showed this finding of decreased cost and increased effectiveness to be consistent. From an institutional perspective, the use of heparin generally appeared less costly but was dependent on medication price, length of stay required, and bed utilization. CONCLUSIONS: From a payer and, by extrapolation, a societal perspective, cost-utility analysis supports the use of enoxaparin in place of heparin for the prevention of VTE in medical inpatients. From an institutional perspective, the decision is more complicated, but in most cases, the use of enoxaparin also is supported. C1 [Leykum, Luci; Pugh, Jacqueline; Papadopoulos, Kyriakos] S Texas Veterans Hlth Care Syst, San Antonio, TX USA. [Leykum, Luci; Pugh, Jacqueline] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Diuguid, David] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Papadopoulos, Kyriakos] Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. RP Leykum, L (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Ambulatory Care 11C6,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM leykum@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X NR 34 TC 12 Z9 13 U1 3 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD MAY-JUN PY 2006 VL 1 IS 3 BP 168 EP 176 DI 10.1002/jhm.97 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 291PS UT WOS:000255209900006 PM 17219491 ER PT J AU de Pooter, RF Schmitt, TM de la Pompa, JL Fujiwara, Y Orkin, SH Zuniga-Pflucker, JC AF de Pooter, Renee F. Schmitt, Thomas M. de la Pompa, Jose Luis Fujiwara, Yuko Orkin, Stuart H. Zuniga-Pflucker, Juan Carlos TI Notch signaling requires GATA-2 to inhibit myelopoiesis from embryonic stem cells and primary hemopoietic progenitors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-2; T-CELL; IN-VITRO; MYELOID DIFFERENTIATION; LYMPHOID PROGENITORS; CYCLE KINETICS; EXPRESSION; PU.1; LIGAND; RECEPTOR AB The bone marrow and thymus, although both hemopoietic environments, induce very distinct differentiation outcomes. The former supports hemopoietic stem cell self-renewal and multiple hemopoietic lineages, while the latter supports T lymphopoiesis almost exclusively. This distinction suggests that the thymic environment acts to restrict the hemopoietic fates available to thymic immigrants. In this study, we demonstrate that the addition of the Notch ligand Delta-like-1 (DII-1) to an in vitro system that otherwise supports myelopoiesis, greatly reduces the myelopoietic potential of stem cells or uncommitted progenitors. In contrast, committed myeloid progenitors mature regardless of the presence of DII-1. The block in myelopoiesis is the direct result of Notch signaling within the hemopoietic progenitor, and DII-1-induced signals cause a rapid increase in the expression of the zinc finger transcription factor GATA-2. Importantly, in the absence of GATA-2, DII-1-induced signals fail to inhibit commitment to the myeloid fate. Taken together, our results support a role for GATA-2 in allowing DII-1 to restrict non-T cell lineage differentiation outcomes. C1 Univ Toronto, Sunnybrook & Womens Res Inst, Dept Immunol, Toronto, ON M4N 3M5, Canada. Univ Autonoma Madrid, Consejo Super Invest Cientificas, Ctr Nacl Biotecnol, Dept Immunol & Oncol, Madrid, Spain. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Zuniga-Pflucker, JC (reprint author), Univ Toronto, Sunnybrook & Womens Res Inst, Dept Immunol, 2075 Bayview Ave,Room A-331, Toronto, ON M4N 3M5, Canada. EM jczp@swri.ca RI Zuniga-Pflucker, Juan/H-1295-2012; De La Pompa Minguez, Jose Luis/F-9719-2014; OI De La Pompa Minguez, Jose Luis/0000-0001-6761-7265; Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 NR 74 TC 43 Z9 43 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2006 VL 176 IS 9 BP 5267 EP 5275 PG 9 WC Immunology SC Immunology GA 059YS UT WOS:000238768700021 PM 16621992 ER PT J AU Perez, LE Chandrasekar, B Saldarriaga, OA Zhao, WG Arteaga, LT Travi, BL Melby, PC AF Perez, Luis E. Chandrasekar, Bysani Saldarriaga, Omar A. Zhao, Weiguo Arteaga, Lourdes T. Travi, Bruno L. Melby, Peter C. TI Reduced nitric oxide synthase 2 (NOS2) promoter activity in the Syrian hamster renders the animal functionally deficient in NOS2 activity and unable to control an intracellular pathogen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; EXPERIMENTAL VISCERAL LEISHMANIASIS; REGULATORY FACTOR-I; INTERFERON-GAMMA; PROINFLAMMATORY CYTOKINE; MESOCRICETUS-AURATUS; MURINE MACROPHAGES; IMMUNE-RESPONSE; GOLDEN-HAMSTER; MESSENGER-RNA AB Progressive disease in the hamster model of visceral leishmaniasis, caused by Leishmania donovani, in contrast to infection in mice, mimics the progressive disease observed in untreated humans. During progressive infection in hamsters, there was a vigorous type 1 cellular immune response, which is typically associated with control of infection, suggesting that there was ineffective IFN-gamma-mediated macrophage activation. Indeed, at the site of infection, hamsters did not express NO synthase 2 (NOS2), which is the primary mechanism for control of infection in mice. Furthermore, in striking contrast to mouse macrophages, IFN-gamma-activated hamster macrophages did not did not express NOS2 nor generate NO, and were unable to restrict the replication of intracellular L. donovani. The absent hamster NOS2 expression was not the result of NOS2 gene deletion and the NOS2 cDNA had an intact open reading frame. Furthermore, the impaired transcription of NOS2 mRNA was selective and not due to global impairment of IFN-gamma signaling (members of the IFN-gamma-signaling pathway were expressed and functional and IFN-gamma up-regulated several primary and secondary response genes). Strikingly, the proximal hamster NOS2 promoter, like the human ortholog, had > 20-fold less basal and IFN-gamma/LPS-inducible activity than the corresponding mouse promoter. Thus, reduced basal and IFN-gamma-induced activity of the hamster NOS2 transcriptional unit, which is unique to this small animal and similar to the human counterpart, accompanies the inability of the animal to control an intracellular pathogen. C1 Dept Vet Affairs Med Ctr, Res Serv, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Dept Med, Hlth Sci Ctr, San Antonio, TX 78229 USA. Univ Texas, Dept Microbiol & Immunol, Hlth Sci Ctr, San Antonio, TX 78229 USA. Ctr Int Entrenamiento & Invest Med, Cali, Colombia. RP Melby, PC (reprint author), Dept Vet Affairs Med Ctr, Res Serv, S Texas Vet Hlth Care Syst, 7400 Merton Minter Dr,Mailstop 151, San Antonio, TX 78229 USA. EM melby@uthscsa.edu FU NCRR NIH HHS [RR 12469]; NIAID NIH HHS [AI 61624] NR 51 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2006 VL 176 IS 9 BP 5519 EP 5528 PG 10 WC Immunology SC Immunology GA 059YS UT WOS:000238768700050 PM 16622021 ER PT J AU Maynard, CJ Cappai, R Volitakis, I Cherny, RA Masters, CL Li, QX Bush, AI AF Maynard, CJ Cappai, R Volitakis, I Cherny, RA Masters, CL Li, QX Bush, AI TI Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: Implications for Alzheimer beta-amyloid pathology SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Conference on Biological Inorganic Chemistry CY JUL 31-AUG 05, 2005 CL Ann Arbor, MI DE Alzheimer; amyloid-beta; amyloid precursor protein; metals; gender ID DEFICIENT HIPPOCAMPAL-NEURONS; CYTOCHROME-C-OXIDASE; A-BETA; OXIDATIVE STRESS; PRECURSOR PROTEIN; TRACE-ELEMENTS; CEREBROSPINAL-FLUID; DISEASE; COPPER; ZINC AB The incidence of Alzheimer's disease (AD) is greater in women than men at any age, as is the development of amyloid pathology in several transgenic mouse models of AD. Due to the involvement of metals in AD pathogenesis, variations between the sexes in metal metabolism may contribute to the sex difference in AD risk. In this study, we investigated sex differences in brain metal levels across the lifespan in mice of two different background strains, as well as in mice overexpressing the human amyloid precursor protein (APP) and amyloid-beta protein (AP). We demonstrate consistently lower Cu and higher Mn levels in females compared with males at any age studied. The sex differences in Cu and Mn levels are independent of APP/A beta expression. AD brain exhibits decreased Cu and increased Mn levels, as do transgenic mice overexpressing APP or A beta. The age-dependent elevations of Cu, Fe and Co levels were found to be significantly greater in mice of B6/SJL background compared with B6/DBA. If depleting Cu and/or rising Mn levels contribute to AD pathogenesis, natural sex differences in these brain metal levels may contribute to the increased propensity of females to develop AD. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. Mental Hlth Res Inst Victoria, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. Mental Hlth Res Inst Victoria, Alzheimers Dis Div, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Psychiat, Charlestown, MA 02129 USA. RP Bush, AI (reprint author), Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. EM christa.maynard@cmb.ki.se; abush@mhri.edu.au RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007; OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X FU NIA NIH HHS [R01AG12686] NR 65 TC 67 Z9 67 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD MAY PY 2006 VL 100 IS 5-6 BP 952 EP 962 DI 10.1016/j.jinorgbio.2006.02.010 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 049GR UT WOS:000238004700010 PM 16574231 ER PT J AU Campaner, AB Ferreira, LM Gragnani, A Bruder, JM Cusick, JL Morgan, JR AF Campaner, Anelisa B. Ferreira, Lydia M. Gragnani, Alfredo Bruder, Jan M. Cusick, Jennifer L. Morgan, Jeffrey R. TI Upregulation of TGF-beta 1 expression may be necessary but is not sufficient for excessive scarring SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; HYPERTROPHIC SCAR; TRANSFORMING GROWTH-FACTOR-BETA-1; GRANULATION-TISSUE; TGF-BETA; HUMAN FIBROBLASTS; DOWN-REGULATION; MESSENGER-RNA; ATHYMIC MICE; KELOIDS AB Transforming growth factor beta 1 (TGF-beta 1) upregulation has been implicated in hypertrophic scars and keloids, but it is unclear if it is the cause or an effect of excessive scar formation. In this study, we overexpressed TGF-beta 1 in fibroblasts and characterized its role. Normal human dermal fibroblasts were genetically modified to overexpress TGF-beta 1 as the wild-type latent molecule or as a mutant constitutively active molecule. TGF-beta 1 secretion was measured, as were the effects of TGF-beta 1 upregulation on cell proliferation, expression of smooth muscle cell alpha actin (SMC alpha-actin) and ability to contract collagen lattices. Fibroblasts were implanted intradermally into athymic mice and tissue formation was analyzed over time by histology and immunostaining. Gene-modified fibroblasts secreted similar to 20 times the TGF-beta 1 released by control cells, but only cells expressing mutant TGF-beta 1 secreted it in the active form. Fibroblasts expressing the active TGF-beta 1 gene had increased levels of SMC alpha-actin and enhanced ability to contract a collagen lattice. After intradermal injection into athymic mice, only fibroblasts expressing active TGF-beta 1 formed "keloid-like'' nodules containing collagen, which persisted longer than implants of the other cell types. We conclude that upregulation of TGF-beta 1 by fibroblasts may be necessary, but is not sufficient for excessive scarring. Needed are other signals to activate TGF-beta 1 and prolong cell persistence. C1 Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA. Univ Fed Sao Paulo, Div Plast Surg, Sao Paulo, Brazil. Harvard Univ, Sch Med, Ctr Engn Med & Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA USA. RP Morgan, JR (reprint author), Brown Univ, Dept Mol Pharmacol, Biomed Ctr, G-B 393,171 Meeting St, Providence, RI 02912 USA. EM Jeffrey_Morgan@Brown.edu RI GRAGNANI, ALFREDO/C-3576-2012; Ferreira, Lydia/B-7511-2012; OI GRAGNANI, ALFREDO/0000-0001-5913-7114; Morgan, Jeffrey/0000-0002-7546-3443 NR 46 TC 53 Z9 57 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2006 VL 126 IS 5 BP 1168 EP 1176 DI 10.1038/sj.jid.5700200 PG 9 WC Dermatology SC Dermatology GA 062TY UT WOS:000238968700035 PM 16498396 ER PT J AU Elosua, R Ordovas, JM Cupples, LA Lai, CQ Demissie, S Fox, CS Polak, JF Wolf, PA D'Agostino, RB O'Donnell, CJ AF Elosua, R Ordovas, JM Cupples, LA Lai, CQ Demissie, S Fox, CS Polak, JF Wolf, PA D'Agostino, RB O'Donnell, CJ TI Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study SO JOURNAL OF LIPID RESEARCH LA English DT Article DE apolipoproteins; carotid arteries; epidemiology; genetics; apolipoprotein A5 gene ID INTIMA-MEDIA THICKNESS; PLASMA TRIGLYCERIDE LEVELS; CORONARY-ARTERY-DISEASE; APOLIPOPROTEIN A5 GENE; MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIOVASCULAR-DISEASE; LIPOPROTEIN-LIPASE; HAPLOTYPE ANALYSIS; AV GENE AB Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (-1131T > C, -3A > G, 56C > G, IVS3+476G > A, and 1259T > C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C > G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the -1131T > C, -3A > G, IVS3+476G > A, and 1259T > C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Inst Municipal Invest Med, E-08003 Barcelona, Spain. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. EM codonnell@nih.gov OI Cupples, L. Adrienne/0000-0003-0273-7965; ELOSUA, ROBERTO/0000-0001-8235-0095; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL-54776, N01 HC-25195]; NINDS NIH HHS [5R01 NS-17950-22] NR 41 TC 51 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2006 VL 47 IS 5 BP 990 EP 996 DI 10.1194/jlr.M500446-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048GQ UT WOS:000237936000012 PM 16474174 ER PT J AU Houben, E Holleran, WM Yaginuma, T Mao, CG Obeid, LM Rogiers, V Takagi, Y Elias, PM Uchida, Y AF Houben, E Holleran, WM Yaginuma, T Mao, CG Obeid, LM Rogiers, V Takagi, Y Elias, PM Uchida, Y TI Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ceramide; sphingolipid; sphingosine ID HUMAN ACID CERAMIDASE; NEUTRAL CERAMIDASE; STRATUM-CORNEUM; PERMEABILITY BARRIER; MOLECULAR-CLONING; INDUCED APOPTOSIS; ALKALINE CERAMIDASE; ATOPIC-DERMATITIS; GLUCOSYLCERAMIDE; PURIFICATION AB Ceramides (Cers) accumulate within the interstices of the outermost epidermal layers, or stratum corneum (SC), where they represent critical components of the epidermal permeability barrier. Although the SC contains substantial sphingol, indicative of ceramidase (CDase) activity, which CDase isoforms are expressed in epidermis remains unresolved. We hypothesized here that CDase isoforms are expressed within specific epidermal compartments in relation to functions that localize to these layers. Keratinocytes/epidermis express all five known CDase isoforms, of which acidic and alkaline CDase activities increase significantly with differentiation, persisting into the SC. Conversely, neutral and phytoalkaline CDase activities predominate in proliferating keratinocytes. These differentiation-associated changes in isoform activity/protein are attributed to corresponding, differentiation-associated changes in mRNA levels (by quantitative RT-PCR). Although four of the five known CDase isoforms are widely expressed in cutaneous and extracutaneous tissues, alkaline CDase-1 occurs almost exclusively in epidermis. These results demonstrate large, differentiation-associated, and tissue-specific variations in the expression and activities of all five CDase isoforms. Because alkaline CDase-1 and acidic CDase are selectively upregulated in the differentiated epidermal compartment, they could regulate functions that localize to the distal epidermis, such as permeability barrier homeostasis and antimicrobial defense. C1 Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Vrije Univ Brussels, Dept Toxicol DermatoCosmetol & Pharmacognosy, Brussels, Belgium. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Kao Corp, Biol Sci Lab, Haga, Tochigi, Japan. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Uchida, Y (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. EM uchiday@itsa.ucsf.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA-104834]; NIAMS NIH HHS [AR-19098, AR-050629, AR-39448] NR 46 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2006 VL 47 IS 5 BP 1063 EP 1070 DI 10.1194/jlr.M600001-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048GQ UT WOS:000237936000020 PM 16477081 ER PT J AU Roberts, DJ Oliva, E AF Roberts, DJ Oliva, E TI Clinical significance of placental examination in perinatal medicine SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Review DE placental pathology; perinatal pathology; congenital infections; fetal thrombotic vasculopathy ID MATERNAL FLOOR INFARCTION; MASSIVE CHRONIC INTERVILLOSITIS; CONGENITAL NEURO-BLASTOMA; MESENCHYMAL DYSPLASIA; REACTION PATTERNS; CELL LYMPHOMA; HEMORRHAGIC ENDOVASCULITIS; TRANSPLACENTAL TRANSFER; UNKNOWN ETIOLOGY; INFECTION AB Complete pathologic evaluation of the placenta provides valuable information for perinatal care for the obstetrician, neonatologist, pediatrician, and family. The histopathology of the placenta can answer specific questions about in utero insults, give insight into management of subsequent pregnancies, and provide an assessment of the newborn risk. Placental pathology has been a key litigious informant in inferring timing of insults. Despite these well known advantages of placental pathologic examination, it remains an under-utilized part of perinatal medicine. This stems from a historically under-taught part of surgical and autopsy pathology resulting in inadequate reporting. This review will focus on the utility of the placental examination for fetal and maternal well-being. This review will be restricted to singleton births. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM djroberts@partners.org NR 77 TC 17 Z9 17 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAY PY 2006 VL 19 IS 5 BP 255 EP 264 DI 10.1080/14767050600676349 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 054XP UT WOS:000238412200001 PM 16753764 ER PT J AU Colombo, AV Silva, CM Haffajee, A Colombo, APV AF Colombo, AV Silva, CM Haffajee, A Colombo, APV TI fIdentification of oral bacteria associated with crevicular epithelial cells from chronic periodontitis lesions SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID DNA-DNA HYBRIDIZATION; PORPHYROMONAS-GINGIVALIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; SUBGINGIVAL MICROBIOTA; IN-VITRO; INVASION; ATTACHMENT; DISEASES; HEALTH; PLAQUE AB Bacterial invasion of host epithelial cells plays an important role in the pathogenesis of periodontal diseases; however, the interactions between subgingival species and the gingival crevice cells are not fully understood. This study determined the prevalence of a group of oral bacterial species on or in epithelial cells derived from periodontal pockets and the gingival crevice of subjects with periodontitis. Samples of epithelial cells were obtained from 120 sites with periodontal pockets >= 4 mm and 92 periodontally healthy sites from 49 patients (mean age 46.3 +/- 1.4 years; 43% males) with chronic periodontitis. Bacteria in or on epithelial cells were separated from unattached bacteria by Percoll density-gradient centrifugation. The presence and levels of 33 oral species were determined in epithelial cell samples by whole genomic DNA probes and the checkerboard method. The most frequently detected species were Porphyromonas gingivalis (42%), Treponema denticola (38%), Prevotella intermedia (37%), Streptococcus intermedius (36%), Campylobacter rectus (35%), Streptococcus sanguinis (35%) and Streptococcus oralis (34%) Species of Actinomyces were found in low prevalence and levels. The data indicated that there were more micro-organisms on or in epithelial cells obtained from periodontal pockets than from healthy sulci; however, no significant differences regarding the percentage and level of any specific species were found between these sites. Veillonella parvula, S. oralis, Streptococcus gordonii and Streptococcus mitis tended to be more prevalent in sites without disease. These findings demonstrated that a wide range of oral species may be detected on or in crevicular epithelial cells from sites with periodontitis and from periodontally healthy sulci. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Med Microbiol, BR-21941 Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Sch Dent, Dept Periodontol, BR-21941 Rio De Janeiro, Brazil. Forsyth Inst, Boston, MA USA. RP Colombo, APV (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Med Microbiol, BR-21941 Rio De Janeiro, Brazil. EM apcolombo@micro.ufrj.br RI Silva-Boghossian, Carina M./G-9440-2012 OI Silva-Boghossian, Carina M./0000-0002-4500-4350 NR 32 TC 40 Z9 45 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD MAY PY 2006 VL 55 IS 5 BP 609 EP 615 DI 10.1099/jmm.0.46417-0 PG 7 WC Microbiology SC Microbiology GA 037ME UT WOS:000237150200020 PM 16585650 ER PT J AU Gregory, KN Ginsburg, KS Bodi, I Hahn, H Marreez, YMA Song, QJ Padmanabhan, PA Mitton, BA Waggoner, JR Del Monte, F Park, WJ Dorn, GW Bers, DM Kranias, EG AF Gregory, Kimberly N. Ginsburg, Kenneth S. Bodi, Ilona Hahn, Harvey Marreez, Yehia M. A. Song, Qiujing Padmanabhan, Prabhu A. Mitton, Bryan A. Waggoner, Jason R. Del Monte, Fedenica Park, Woo Jin Dorn, Gerald W., II Bers, Donald M. Kranias, Evangelia G. TI Histidine-rich Ca binding protein: a regulator of sarcoplasmic reticulum calcium sequestration and cardiac function SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE sarcoplasmic reticulum; calcium cycling; calcium uptake; heart failure; histidine-rich calcium binding protein ID CA2+-BINDING PROTEIN; MYOCARDIAL-CONTRACTILITY; TRANSGENIC MOUSE; SERCA2 GENE; IN-VIVO; PHOSPHOLAMBAN; OVEREXPRESSION; TRIADIN; MICE; MUSCLE AB Defects in the pathways that regulate cardiac sarcoplasmic reticulum (SR) calcium (Ca) cycling represent prime targets for driving the deterioration of function and progression to heart failure. We hypothesized that the histidine-rich Ca binding protein (HRC) in the SR may be involved in SR Ca cycling and that alterations in HRC levels would result in abnormal cardiac Ca homeostasis. In order to test this hypothesis, we generated transgenic mice with cardiac overexpression (3-fold) of HRC. Increased cardiac HRC levels were associated with impaired SR Ca uptake rates (35%) and attenuated cardiomyocyte Ca transient decay (38%), without alterations in peak Ca transients or SR Ca load. The depressed SR Ca sequestration was associated with attenuated rate of Ca extrusion via Na-Ca exchange. Triadin protein expression levels and L-type Ca channel current density were increased, while the channel inactivation kinetics were not altered. Impaired SR Ca uptake and delayed Ca decline rates triggered hypertrophy and compromised the heart's responses to increased stress by either hemodynamic overload or the aging process. By 18 months of age, cardiac remodeling deteriorated to congestive heart failure in transgenic mice. Collectively, these data suggest that HRC may be an integral regulatory protein involved in cardiac muscle SR Ca uptake and Ca homeostasis. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Loyola Univ, Stritch Sch Med, Dept Physiol, Maywood, IL 60153 USA. Univ Cincinnati, Inst Mol Pharmacol & Biophys, Cincinnati, OH USA. Univ Cincinnati, Dept Med, Cincinnati, OH 45221 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02115 USA. GIST, Dept Life Sci, Kwangju, South Korea. GIST, Natl Res Lab Proteolysis, Kwangju, South Korea. RP Kranias, EG (reprint author), Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM Litsa.Kranias@uc.edu RI Bers, Donald/C-4507-2012 FU NHLBI NIH HHS [HL-64724, HL-77101, HL-30077, HL-26057, HL-64018, HL-52318] NR 33 TC 43 Z9 43 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2006 VL 40 IS 5 BP 653 EP 665 DI 10.1016/j.yjmec.2006.02.003 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 041NS UT WOS:000237463500009 PM 16600288 ER PT J AU Lebeche, D Kaprielian, R Hajjar, R AF Lebeche, Djamel Kaprielian, Roger Hajjar, Roger TI Modulation of action potential duration on myocyte hypertrophic pathways SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE K+ channel; lto; action potential duration; hypertrophy; hypertrophic response; MAPKs; gene transfer; angiotensin II; signaling ID RAT VENTRICULAR MYOCYTES; OUTWARD POTASSIUM CURRENT; NA+-CA2+ EXCHANGER; HEART-FAILURE; MYOCARDIAL-INFARCTION; CARDIAC-HYPERTROPHY; K+ CURRENTS; SIGNALING PATHWAYS; TRANSGENIC MICE; MOLECULAR-BASIS AB Prolongation of the action potential duration (APD) has consistently been observed in experimental models of cardiac hypertrophy and failure as well as in humans and is partially attributed to a reduction of a hyperpolarizing current provided by the calcium-independent transient outward K+ channel (I-to). In the present study, we examined the effects of manipulating ion channel currents (I-to and sodium/calcium exchanger (NCX)) and the associated alterations in action potential duration on cardiomyocyte hypertrophy and signaling induced by angiotensin 11 (Ang11). Our aim was to examined whether distinct patterns of intracellular calcium manipulation could generate distinct patterns of MAPkinase activation and cellular hypertrophy. Cultured neonatal rat ventricular myocytes (NRVMs) were infected with Ad. beta-gal/GFP, Ad.Kv4.3, Ad.Kv4.3 antisense or Ad.NCX adenoviruses and hypertrophy induced by incubation with AngII. Overexpression of Kv4.3 increased It, density, shortened APD, decreased Ca2+ influx and inhibited Ang11-induced H-3-leucine incorporation and ANF and beta-MHC expression. These hypertrophic changes were also paralleled by blockade of ERK MAP kinases activation as well as calcineurin expression. These electrical and hypertrophic changes produced by overexpression of Kv4.3 were completely and significantly reversed by Kv4.3 antisense and NCX gene transfer. Our findings indicate that AngII-mediated hypertrophy response in NRVMs can be abrogated by an enhancement of I-to function through overexpression of Kv4.3 and that modulation of action potential duration can be important in the development of cardiac hypertrophy. (c) 2006 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. AMGEN Canada Med Affairs, Oakville, ON L6L 5J2, Canada. RP Lebeche, D (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. EM dlebeche@partners.org FU NHLBI NIH HHS [HL 57623, HL 076659, HL 71763] NR 40 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2006 VL 40 IS 5 BP 725 EP 735 DI 10.1016/j.yjmcc.2006.01.018 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 041NS UT WOS:000237463500016 PM 16600293 ER PT J AU Ogino, S Kawasaki, T Brahmandam, M Cantor, M Kirkner, GJ Spiegelman, D Makrigiorgos, GM Weisenberger, DJ Laird, PW Loda, M Fuchs, CS AF Ogino, S Kawasaki, T Brahmandam, M Cantor, M Kirkner, GJ Spiegelman, D Makrigiorgos, GM Weisenberger, DJ Laird, PW Loda, M Fuchs, CS TI Precision and performance characteristics of bisulfite conversion and real-time PCR (MethyLight) for quantitative DNA methylation analysis SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; CPG ISLAND HYPERMETHYLATION; PROMOTER METHYLATION; COLORECTAL-CANCER; PRIMER EXTENSION; ASSAY; QUANTIFICATION; PATTERNS; PYROSEQUENCING(TM); ADENOCARCINOMA AB Assays to measure DNA methylation, which are important in epigenetic research and clinical diagnostics, typically rely on conversion of unmethylated. cytosine to uracil by sodium bisulfite. However, no study has comprehensively evaluated the precision and performance characteristics of sodium bisulfite conversion and subsequent quantitative methylation assay. We developed quantitative real-time polymerase chain reaction (MethyLight) to measure percentage of methylated reference (PMR, ie, degree of methylation) for the MGMT, MLH1, and CDKN2A (p16) promoters. To measure the precision of bisulfite conversion, we bisulfite-treated seven different aliquots of DNA from each of four paraffin-embedded colon cancer samples. To assess run-to-run variation, we repeated MethyLight five times. Bisulfite-to-bisulfite coefficient of variation (CV) of PMR ranged from 0.10 to 0.38 (mean, 0.21), and run-to-run CV of PMR ranged from 0.046 to 0.60 (mean, 0.31). Interclass correlation coefficients were 0.74 to 0.84 for the three loci, indicating good reproducibility. DNA mixing study with methylated and unmethylated. DNA showed good linearity of the assay. Of 272 colorectal cancers evaluated, most showed PMR either < 1 or > 10, and promoter methylation (PMR > 4) was tightly associated with loss of respective protein expression (P < 10(-16)). In conclusion, sodium bisulfite conversion and quantitative MethyLight assays have good precision and linearity and can be effectively used for high-throughput DNA methylation analysis on paraffin-embedded tissue. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Surg, Los Angeles, CA USA. Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu RI Laird, Peter/G-8683-2012 FU NCI NIH HHS [P01 CA055075, P01 CA087969, P01 CA55075-13, P01 CA87969-03, R01 CA075090] NR 43 TC 260 Z9 271 U1 1 U2 23 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2006 VL 8 IS 2 BP 209 EP 217 DI 10.2353/jmoldx.2006.050135 PG 9 WC Pathology SC Pathology GA 046CH UT WOS:000237788500009 PM 16645207 ER PT J AU Mohapatra, G Betensky, RA Miller, ER Carey, B Gaumont, LD Engler, DA Louis, DN AF Mohapatra, G Betensky, RA Miller, ER Carey, B Gaumont, LD Engler, DA Louis, DN TI Glioma test array for use with formalin-fixed, paraffin-embedded tissue - Array comparative genomic hybridization correlates with loss of heterozygosity and fluorescence in situ hybridization SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID HIGH-RESOLUTION ANALYSIS; GLIOBLASTOMA-MULTIFORME; EGFR AMPLIFICATION; DNA; OLIGODENDROGLIOMAS; MICROARRAYS; CANCER; TUMORS; CGH; 1P AB Array-based comparative genomic hybridization (aCGH) is a powerful, high-throughput tool for whole genome analysis. Until recently, aCGH could only be reproducibly performed on frozen tissue samples and with significant tissue amounts. For brain tumors however, paraffin-embedded tissue blocks from small stereotactic biopsies may be the only tissue routinely available. The development of methods to analyze formalin-fixed, paraffin-embedded (FFPE) material therefore has the potential to impact molecular diagnosis in a significant way. To this end, we constructed a BAC array representing chromosomes 1, 7, 19, and X because 1p/19q deletion and EGFR gene amplification provide clinically relevant information for glioma diagnosis. We also optimized a two-step labeling procedure using an amine-modified nucleotide for generating aCGH probes. Using this approach, we analyzed a series of 28 FFPE oligodendroglial tumors for alterations of chromosomes 1, 7, and 19. We also independently assayed these tumors for 1p/19q deletion by fluorescence in situ hybridization and by loss of heterozygosity analyses. The concordance between aCGH, standard loss of heterozygosity and fluorescence in situ hybridization was nearly 100% for the chromosomes analyzed. These results suggest that aCGH could offer an improved molecular diagnostic approach for gliomas because of its ability to detect clinically relevant molecular alterations in small FFPE specimens. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurol Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, CNY7,149 13th St, Charlestown, MA 02129 USA. EM dlouis@partners.org FU NCI NIH HHS [CA106695, CA57683, R01 CA057683, R21 CA106695, R33 CA106695]; NINDS NIH HHS [NS048005, T32 NS048005] NR 27 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2006 VL 8 IS 2 BP 268 EP 276 DI 10.2353/jmoldx.2006.050109 PG 9 WC Pathology SC Pathology GA 046CH UT WOS:000237788500017 PM 16645215 ER PT J AU Minzenberg, MJ Poole, JH Vinogradov, S AF Minzenberg, Michael J. Poole, John H. Vinogradov, Sophia TI Adult social attachment disturbance is related to childhood maltreatment and current symptoms in borderline personality disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat DE borderline personality disorder; social attachment; childhood maltreatment; impulsivity; affect ID SUICIDAL-BEHAVIOR; SEXUAL ABUSE; WOMEN; PSYCHOPATHOLOGY; PREDICTORS; SEVERITY; STYLES; SAMPLE AB We characterized borderline personality disorder (BPD) along two fundamental dimensions of adult social attachment and evaluated attachment associations with childhood maltreatment and current symptoms using self-report measures in 40 outpatients with DSM-IV BPD. The BPD group had significantly greater dimensional attachment impairment and rate of fearful attachment type compared with a healthy control group. Among BPD subjects, dimensional attachment-anxiety was specifically associated with sexual abuse, whereas attachment-avoidance was associated with all five maltreatment types. The two attachment dimensions showed divergent associations with current interpersonal problems, impulsivity subtypes and mood symptoms. We conclude that (1) BPD is characterized by adult attachment disturbance; (2) these attachment problems are strongly related to childhood maltreatment, and to current interpersonal problems and clinical symptoms that are considered core features of BPD; and (3) the diverse problems of BPD patients may arise from two basic mechanisms, each tied to a different type of attachment disturbance, developmental history, and clinical outcome. C1 Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Minzenberg, MJ (reprint author), Univ Calif Davis, Imaging Res Ctr, UC Davis Hlth Syst, 4701 10 St, Sacramento, CA 95817 USA. NR 44 TC 24 Z9 27 U1 8 U2 27 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAY PY 2006 VL 194 IS 5 BP 341 EP 348 DI 10.1097/01.nmd.0000218341.54333.4e PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 044RH UT WOS:000237689500006 PM 16699383 ER PT J AU Stern, BV Baehring, JM Kleopa, KA Hochberg, FH AF Stern, BV Baehring, JM Kleopa, KA Hochberg, FH TI Multifocal motor neuropathy with conduction block associated with metastatic lymphoma of the nervous system SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE conduction block; intravenous immunoglobulin; multifocal motor neuropathy; Non-Hodgkin Lymphoma ID DETERIORATION AB Peripheral neuropathies occur in 5% of patients with Non-Hodgkin Lymphoma and represent the effects of therapy, direct compression or nerve infiltration by tumor, or paraneoplastic effects. Multifocal motor neuropathy with conduction block (MMNCB) is a rare demyelinating disorder of unknown etiology characterized by progressive, distal, asymmetric weakness mostly of the upper limbs with minimal or no sensory loss. We report a patient, who developed MMNCB at the time of isolated CNS relapse from a diffuse large B-cell lymphoma. Marked neurological improvement was achieved using intravenous immunoglobulin treatment. To our knowledge, MMNCB has thus far not been described as part of the spectrum of lymphoma-related peripheral neuropathies. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Dept Neurol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Neurosurg, Yale Brain Tumor Ctr, New Haven, CT 06510 USA. Cyprus Inst Neurol & Genet, Dept Clin Neurosci, Nicosia, Cyprus. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9010, Boston, MA 02114 USA. EM fhochberg@partners.org NR 16 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2006 VL 78 IS 1 BP 81 EP 84 DI 10.1007/s11060-005-9060-6 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 046FF UT WOS:000237796100014 PM 16554970 ER PT J AU Matsui, T Ramasamy, K Ingelsson, M Fukunioto, H Conrad, C Frosch, MP Irizarry, MC Yuan, JY Hyman, BT AF Matsui, Toshifumi Ramasamy, Karunya Ingelsson, Martin Fukunioto, Hiroaki Conrad, Cintia Frosch, Matthew P. Irizarry, Michael C. Yuan, Junying Hyman, Bradley T. TI Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: Relationship to formic acid extractable A beta 42 levels SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; amyloid beta protein; apoptosis; caspase ID AMYLOID PRECURSOR PROTEIN; NEURONAL APOPTOSIS; TRANSGENIC MICE; BETA-PROTEIN; BRAIN; CELLS; CLEAVAGE; TAU; ACTIVATION; MECHANISM AB Recent studies support the hypothesis that Alzheimer disease (AD)-associated amyloid-beta protein (AP) may induce apoptosis mediated by a caspase cascade. To assess whether mRNA levels of caspase-3, 7, 8 and 9 change in AD brain, and whether these changes correlate with neurofibrillary tangles, A beta(40) or A beta(42) protein levels or senile plaques, 25 AD and 21 non-demented control brains were examined. Elevated mRNA levels of caspases-7 and 8 measured by a quantitative PCR method were observed in the AD temporal neocortex as compared to the control brains. No significant differences were noticed in levels of caspases-3 or 9 between AD and control brains. Multiple regression analysis demonstrated that, within subjects, the mRNA levels of caspase-8 strongly correlated with both caspse-3 and caspase-7 independently of postmortem interval. Further, there was a strong positive correlation of caspase-8 levels with formic acid extractable A beta(42) levels. Our results suggest that the transcriptional activation of key components of the apoptotic cascade correlates with accumulation of A beta(42). Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain. C1 Massachusetts Gen Hosp, Dept Pathol, Massachusetts Gen Inst Neurodegenerat Dis, Alzheimers Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Pathol, Massachusetts Gen Inst Neurodegenerat Dis, Alzheimers Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIA NIH HHS [AG08487, P50AG 05134] NR 44 TC 41 Z9 43 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2006 VL 65 IS 5 BP 508 EP 515 DI 10.1097/01.jnen.0000229238.05748.12 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 100TO UT WOS:000241692000009 PM 16772874 ER PT J AU Denny, CA Kasperzyk, JL Gorham, KN Bronson, RT Seyfried, TN AF Denny, CA Kasperzyk, JL Gorham, KN Bronson, RT Seyfried, TN TI Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE inflammation; ganglioside; ketone; rotorod; glucose; neurodegeneration ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BONE-MARROW-TRANSPLANTATION; LYSOSOMAL STORAGE DISEASES; THIN-LAYER CHROMATOGRAPHY; TAY-SACHS; KETONE-BODIES; MOUSE MODELS; N-BUTYLDEOXYNOJIRIMYCIN; AUDIOGENIC-SEIZURES; GM1 GANGLIOSIDOSIS AB Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase beta knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo-GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15-18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb-/- and the Hexb+/-mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb-/- mice. In addition, rotorod performance was significantly worse in the Hexb-/- mice than in the Hexb+/- mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb-/- mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR-fed than in the AL-fed Hexb-/- mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms. (c) 2006 Wiley-Liss, Inc. C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seyfried, TN (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. EM thomas.seyfried@bc.edu RI Denny, Christine Ann/I-5235-2015; Biguzzi, Felipe/E-4724-2015; OI Denny, Christine Ann/0000-0002-6926-2020; Seyfried, Thomas/0000-0003-1491-3989 FU NICHD NIH HHS [HD39722] NR 63 TC 27 Z9 28 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 2006 VL 83 IS 6 BP 1028 EP 1038 DI 10.1002/jnr.20798 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 038JZ UT WOS:000237217100010 PM 16521125 ER PT J AU Hoffmann, U Ferencik, M Cury, RC Pena, AJ AF Hoffmann, U Ferencik, M Cury, RC Pena, AJ TI Coronary CT angiography SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE coronary CT angiography; coronary MDCT; coronary artery stenosis; cardiology ID SPIRAL COMPUTED-TOMOGRAPHY; STABLE ANGINA-PECTORIS; ACUTE MYOCARDIAL-INFARCTION; ARTERY STENOSES; HEART-RATE; IMAGE QUALITY; INTRAVASCULAR ULTRASOUND; DIAGNOSTIC-ACCURACY; ATHEROSCLEROTIC PLAQUES; NONINVASIVE DETECTION AB Advances in multiedetector CT (MDCT) technology with submillimeter slice collimation and high temporal resolution permit contrast-enhanced imaging of coronary arteries and coronary plaque during a single breath hold. Appropriate patient preparation, detailed technical and technological knowledge with regard to recognition of typical imaging artifacts (such as beam hardening or motion artifacts), and the adequate choice of postprocessing techniques to detect stenosis and plaque are prerequisites to achieving diagnostic image quality. A growing number of studies have suggested that 64-slice coronary CT angiography is highly accurate for the exclusion of significant coronary artery stenosis (> 50% luminal narrowing), with negative predictive values of 97%-100%, in comparison with invasive selective coronary angiography. In addition, several studies have indicated that MDCT also can detect calcified and noncalcified coronary atherosclerotic plaques, especially in proximal vessel segments, showing a good correlation with intracoronary ultrasound. Studies on clinical utility, cost, and cost-effectiveness are now warranted to demonstrate whether and how this technique can change and improve the current management of patients with suspected or confirmed coronary artery disease. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffman@partners.org NR 59 TC 85 Z9 90 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2006 VL 47 IS 5 BP 797 EP 806 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 040HF UT WOS:000237368900028 PM 16644750 ER PT J AU Bauer-Wu, S Epshtein, A Ponte, PR AF Bauer-Wu, S Epshtein, A Ponte, PR TI Promoting excellence in nursing research and scholarship in the clinical setting SO JOURNAL OF NURSING ADMINISTRATION LA English DT Editorial Material C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr, Nursing Serv, Boston, MA 02115 USA. Phyllis F Cantor Ctr Res, Patient Care Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Nursing Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Clin Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bauer-Wu, S (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr, Nursing Serv, 44 Binney St, Boston, MA 02115 USA. EM susan_bauer_wu@dfci.harvard.edu NR 2 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD MAY PY 2006 VL 36 IS 5 BP 224 EP 227 DI 10.1097/00005110-200605000-00002 PG 4 WC Nursing SC Nursing GA 042LF UT WOS:000237528800002 PM 16705290 ER PT J AU Donoff, RB AF Donoff, RB TI Treatment of the irradiated patient with dental implants: The case against hyperbaric oxygen treatment SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ANGIOGENESIS; BONE; RADIATION; RADIOTHERAPY; REGENERATION; PLACEMENT; PROTOCOL; DEFECTS; THERAPY C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Donoff, RB (reprint author), Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. EM bruce_donoff@hms.harvard.edu NR 25 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2006 VL 64 IS 5 BP 819 EP 822 DI 10.1016/j.joms.2006.01.011 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 040IT UT WOS:000237372900012 PM 16631491 ER PT J AU Yoshimura, M Fueki, K Garrettt, N Ohyama, T AF Yoshimura, M Fueki, K Garrettt, N Ohyama, T TI Influence of food platform width of mandibular removable partial denture on food mixing ability SO JOURNAL OF ORAL REHABILITATION LA English DT Article DE removable partial denture; food platform; tooth width; masticatory function; food mixing ability ID MASTICATORY FUNCTION; CHEWING GUM; PERFORMANCE; TEETH; SIZE AB The aim of this study was to clarify the influence of food platform width on food mixing ability in patients with mandibular removable partial dentures (RPDs). Twelve subjects (six males and six females, mean age 56(.)8 years) with intact dentition except for unilaterally missing mandibular first and second molars participated in the study. The food platforms of their RPDs were made of light polymerized composite and three platform conditions were evaluated. A food platform (Control condition) had 7 mm width with a central focus on the top of the residual ridge. Narrowed platforms (5 mm) were created by trimming a lingual portion (Buccally oriented occlusion, Buccal condition) or a buccal portion (Lingually oriented occlusion, Lingual condition) from the control. Subjects chewed a standardized wax cube which provided an estimate of food mixing ability [Mixing Ability Index (MAI)] for each of the three platforms. A significant effect (P < 0(.)001) on the MAI was found for food platform type (repeated measures one-way analysis of variance). Tukey multiple comparisons found significant differences of MAI between Control condition (1(.)05 +/- 0(.)26) and Buccal condition (0(.)86 +/- 0(.)23) (P = 0(.)032), and between Control and Lingual condition (0(.)54 +/- 0(.)37) (P < 0(.)001). Furthermore, MAI with Lingual condition was significantly smaller than that with Buccal condition (P < 0(.)001). These results suggest that reduction in the width of the food platform may impair masticatory function and the buccal portion of mandibular food platform of RPD is more critical for food mixing than the lingual portion of the platform. C1 Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, Tokyo 1138549, Japan. Univ Calif Los Angeles, Sch Dent, Jane & Jerry Weintraub Ctr Reconstruct Biotechnol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Div Adv Prosthodont Biomat, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Fueki, K (reprint author), Tokyo Med & Dent Univ, Grad Sch, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138549, Japan. EM kunfu.rpro@tmd.ac.jp RI Fueki, Kenji/A-9909-2008 OI Fueki, Kenji/0000-0002-5885-2447 NR 28 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0305-182X J9 J ORAL REHABIL JI J. Oral Rehabil. PD MAY PY 2006 VL 33 IS 5 BP 335 EP 340 DI 10.1111/j.1365-2842.2005.01570.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 045YB UT WOS:000237777500004 PM 16629891 ER PT J AU Hanson, GR Suggs, JF Freiberg, AA Durbhakula, S Li, GA AF Hanson, GR Suggs, JF Freiberg, AA Durbhakula, S Li, GA TI Investigation of in vivo 6DOF total knee arthoplasty kinematics using a dual orthogonal fluoroscopic system SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE in vivo kinematics; biplanar fluoroscopy; total knee arthoplasty (TKA); image analysis; knee ID REPLACEMENT KINEMATICS; ARTHROPLASTY; REGISTRATION; IMAGES; MODELS AB Fluoroscopic techniques have been recently used to detect in vivo knee joint kinematics. This article presents a technique that uses two fluoroscopes to form a dual orthogonal fluoroscopic system for accurately measuring in vivo 6DOF total knee arthoplasty (TKA) kinematics. The system was rigorously validated and used to investigate in vivo kinematics of 12 patients after cruciate-retaining TKA. In a repeatability study, the pose of two different TKA components was reproduced with standard deviations (SD) of 0.17 mm and 0.57 degrees about all three axes. In an accuracy study, the reproduced component positions were compared to the known component positions. Position and rotation mean errors were all within 0.11 mm and 0.24 degrees, with SD within 0.11 mm and 0.48 degrees, respectively. The results of this study show that the matching process of the imaging system is able to accurately reproduce the spatial positions and orientations of both the femoral and tibial components. For CR TKA patients, a consistent anterior femoral translation was observed with flexion through 45 degrees of flexion, and thereafter, the femur translated posteriorly with further flexion. The medial-lateral translation was measured to be less than 2 mm throughout the entire flexion range. Internal tibial rotation steadily increased through maximum flexion by approximately 6 degrees. Varus rotation was also measured with flexion but had a mean magnitude less than 2.0 degrees. In conclusion, the dual orthogonal fluoroscopic system accurately detects TKA kinematics and is applicable towards otherjoints of the musculoskeletal system, including the wrist, elbow, shoulder, ankle, and spine. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:974-981, 2006. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gil1@partners.org NR 17 TC 47 Z9 49 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2006 VL 24 IS 5 BP 974 EP 981 DI 10.1002/jor.20141 PG 8 WC Orthopedics SC Orthopedics GA 039MQ UT WOS:000237310500014 PM 16596640 ER PT J AU de Asla, RJ Wan, L Rubash, HE Li, G AF de Asla, RJ Wan, L Rubash, HE Li, G TI Six DOF in vivo kinematics of the ankle joint complex: Application of a combined dual-orthogonal fluoroscopic and magnetic resonance imaging technique SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE in vivo kinematics; joint biomechanics; ankle joint; fluoroscopy; joint kinematics ID STANCE PHASE; SUBTALAR JOINTS; FOOT COMPLEX; 3-DIMENSIONAL KINEMATICS; TIBIOCALCANEAL MOTION; TALOCALCANEAL JOINT; TRIPLE ARTHRODESIS; KNEE FLEXION; FOLLOW-UP; WALKING AB Accurate knowledge of in vivo ankle joint complex (AJC) biomechanics is critical for understanding AJC disease states and for improvement of surgical treatments. This study investigated 6 degrees-of-freedom (DOF) in vivo kinematics of the human AJC using a combined dual-orthogonal fluoroscopic and magnetic resonance imaging (MRI) technique. Five healthy ankles of living subjects were studied during three in vivo activities of the foot, including maximum plantarflexion and dorsiflexion, maximum supination and pronation, and three weight-bearing positions in simulated stance phases of walking. A three-dimensional (3D) computer model of the AJC (including tibia, fibula, talus, and calcaneus) was constructed using 3D MR images of the foot. The in vivo AJC position at each selected position of the foot was captured using two orthogonally positioned fluoroscopes. In vivo AJC motion could then be reproduced by coupling the orthogonal images with the 3D AJC model in a virtual dual-orthogonal fluoroscopic system. From maximum dorsiflexion to plantarflexion, the arc of motion of the talocrural joint (47.5 +/- 2.2 degrees) was significantly larger than that of the subtalar joint (3.1 +/- 6.8 degrees). Both joints showed similar degrees of internal-external and inversion-eversion rotation. From maximum supination to pronation, all rotations and translations of the subtalar joint were significantly larger than those of the talocrural joint. From heel strike to midstance, the plantarflexion contribution from the talocrural joint (9.1 +/- 5.3 degrees) was significantly larger than that of the subtalar joint (-0.9 +/- 1.2 degrees). From midstance to toe off, internal rotation and inversion of the subtalar joint (12.3 +/- 8.3 degrees and -10.7 +/- 3.8 degrees, respectively) were significantly larger than those of the talocrural joint (-1.6 +/- 5.9 degrees and -1.7 +/- 2.7 degrees). Strong kinematic coupling between the talocrural and subtalar joints was observed during in vivo AJC activities. The contribution of the talocrural joint to active dorsi-plantarflexion was higher than that of the subtalar joint, whereas the contribution of the subtalar joint to active supination-pronation was higher than that of the talocrural joint. In addition, the talocrural joint demonstrated larger motion during the early part of stance phase while the subtalar joint contributes more motion during the later part of stance phase. The results add quantitative data to an in vivo database of normals that can be used in clinical diagnosis, treatment, and evaluation of the AJC after injuries. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. MIT, Dept Phys, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 31 TC 52 Z9 52 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2006 VL 24 IS 5 BP 1019 EP 1027 DI 10.1002/jor.20142 PG 9 WC Orthopedics SC Orthopedics GA 039MQ UT WOS:000237310500019 PM 16609963 ER PT J AU Handelsman, JE Weinberg, J Hersch, JC AF Handelsman, JE Weinberg, J Hersch, JC TI Corrective supracondylar humeral osteotomies using the small AO external fixator SO JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B LA English DT Article DE AO external fixator; cubitus valgus; cubitus varus; supracondylar fracture; supracondylar humeral osteotomy ID CUBITUS VARUS DEFORMITY; POPULATION; CHILDREN AB Traditional methods of correcting malunited distal humeral fractures in children involve complex wedge osteotomies held with pins or internal fixation devices. These require a large exposure and challenging fixation. We elected to perform simple transverse osteotomies, without wedges, using a lateral incision. These were maintained by the small AO external fixator. Between 1987 and 2004, five children with malunited distal humeral fractures were treated. Angular and rotational correction was obtained in each case. Bony union occurred at an average of 8 weeks. A simple osteotomy held by the small AO external fixator provides accurate correction, precise adjustability, and solid stability. C1 Schneider Childrens Hosp, Div Pediat Orthopaed Surg, New Hyde Pk, NY 11042 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Handelsman, JE (reprint author), 915 Hillside Ave, New Hyde Pk, NY 11040 USA. EM jhandelsman@optonline.net NR 18 TC 10 Z9 10 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1060-152X J9 J PEDIATR ORTHOP B JI J. Pediatr. Orthop.-Part B PD MAY PY 2006 VL 15 IS 3 BP 194 EP 197 PG 4 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 047UE UT WOS:000237903400007 PM 16601588 ER PT J AU Hall, E Saxe, G Stoddard, F Kaplow, J Koenen, K Chawla, N Lopez, C King, L King, D AF Hall, E Saxe, G Stoddard, F Kaplow, J Koenen, K Chawla, N Lopez, C King, L King, D TI Posttraumatic stress symptoms in parents of children with acute burns SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE burns; Parents; PTSD ID PEDIATRIC TRAFFIC INJURY; SOCIAL IMPLICATIONS; CHILDHOOD-CANCER; SCARRED CHILDREN; PRESCHOOL-CHILD; THERMAL-INJURY; PSYCHOMETRIC PROPERTIES; PTSD CHECKLIST; MOTHERS; SURVIVORS AB Objective To develop a model of risk factors for posttraumatic stress disorder (PTSD) symptoms in parents of children with burns. Methods Immediately following the burn and 3 months later, parents reported on their children's and their own psychological functioning and traumatic stress responses. Results Approximately 47% of the parents reported experiencing significant posttraumatic stress symptoms 3 months after the burn. Our model indicates three independent pathways to PTSD symptoms (i.e., parent-child conflict, parents' dissociation, and children's PTSD symptoms). Additionally, parents' anxiety predicted increased parent-child conflict, conflict with extended family and size of the burn predicted parents' dissociation, and size of the burn and children's dissociation predicted children's PTSD symptoms. Conclusions This study suggests that many parents of children with burns suffer from posttraumatic stress symptoms. Interventions that target factors such as family conflict, children's symptoms, and parents' acute anxiety and dissociation may diminish the risk for PTSD. C1 Boston Univ, Boston Med Ctr, Boston, MA 02118 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Cambridge, MA 02138 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Boston Univ, VA Boston Healthcare Syst, Boston, MA 02215 USA. RP Hall, E (reprint author), Boston Univ, Boston Med Ctr, Dowling 1 N,1 Boston Med Ctr Pl, Boston, MA 02118 USA. EM erin.hall@bmc.org RI Koenen, Karestan/K-5402-2014; OI Koenen, Karestan/0000-0003-3293-4281; Saxe, Glenn/0000-0002-4756-1169 FU CMHS SAMHSA HHS [U79 SM54305]; NIMH NIH HHS [R01 MH57370] NR 48 TC 59 Z9 62 U1 3 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD MAY PY 2006 VL 31 IS 4 BP 403 EP 412 DI 10.1093/jpepsy/jsj016 PG 10 WC Psychology, Developmental SC Psychology GA 032XI UT WOS:000236809400008 PM 15788717 ER PT J AU Schmidt, DDN Yunes, RA Schaab, EH Malheiros, A Cechinel, V Franchi, GC Nowill, AE Cardoso, AA Yunes, JA AF Navarro Schmidt, Dionezine de F. Yunes, Rosendo A. Schaab, Estela H. Malheiros, Angela Cechinel Filho, Valdir Franchi, Gilberto C., Jr. Nowill, Alexandre E. Cardoso, Angelo A. Yunes, Jose A. TI Evaluation of the anti-proliferative effect the extracts of Allamanda blanchetti and A-schottii on the growth of leukemic and endothelial cells SO JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES LA English DT Article ID TUMOR-GROWTH; ANGIOGENESIS; CATHARTICA; PLUMERIA; METASTASIS; PLUMIERIDE; INHIBITOR; IRIDOIDS AB PURPOSE. To investigate the anti-proliferative effect of A. blanchetti and A. schottii extracts. METHODS. The anti-proliferative effect of A. blanchetti and A. schottii ethanolic extracts on K562 leukemic cells as well as on BMEC and HUVEC were evaluated. Phytochemical analysis to identify the possible active components was carried out. RESULTS. The root extract of A. schottii was the most active of them. At 80 mu g/mL, the root extracts showed a cytostatic effect on K562, whereas at 400 mu g/mL, there was a strong cytotoxic effect. Similar cytostatic and cytotoxic effects were seen in the endothelial cells, but at lower doses. The effect of A. schottii root extract on endothelial cells was seen at concentrations ten times lower (8 mu g/mL) than the effect of the A. blanchetti root extract (80 mu g/mL). Phytochemical investigation of different fractions and parts of the plant led to the isolation of several known compounds, some of which are described for the first time in the genus Allamanda, and with previous evidence of anticancer and antitumoral properties. CONCLUSIONS. Our results suggest that both plants studied exhibit cytostatic and cytotoxic activity, but the most active compounds are located in the roots. C1 UNIVALI, NIQFAR CCS, BR-88302202 Itajai, SC, Brazil. Univ Fed Santa Catarina, Curso Posgrad Quim, BR-88040900 Florianopolis, SC, Brazil. Univ Estadual Campinas, CIPOI, Campinas, SP, Brazil. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA 02138 USA. Ctr Infantil Boldrini, Mol Biol Lab, Campinas, SP, Brazil. RP Malheiros, A (reprint author), UNIVALI, NIQFAR CCS, BR-88302202 Itajai, SC, Brazil. EM angela@univali.br RI Nowill, Alexandre Eduardo/I-9038-2012; Franchi, Gilberto/J-7590-2012 OI Nowill, Alexandre Eduardo/0000-0003-0648-6913; Franchi, Gilberto/0000-0002-8138-7088 NR 25 TC 9 Z9 9 U1 0 U2 2 PU CANADIAN SOC PHARMACEUTICAL SCIENCES PI EDMONTON PA 3118 DENTISTRY-PHARMACY CENTRE UNIV ALBERTA CAMPUS, EDMONTON, ALBERTA T6G2N8, CANADA SN 1482-1826 J9 J PHARM PHARM SCI JI J. Pharm. Pharm. Sci. PD MAY-AUG PY 2006 VL 9 IS 2 BP 200 EP 208 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 087ZF UT WOS:000240780600009 ER PT J AU Apert, JE AF Apert, JE TI Improving depression outcome: new concepts, strategies and technologies SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Editorial Material ID SEROTONIN REUPTAKE INHIBITORS; RESIDUAL SYMPTOMS; REMISSION RATES; DISORDER C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Apert, JE (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM jalpert@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 10 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD MAY PY 2006 VL 20 IS 3 SU S BP 3 EP 4 DI 10.1177/1359786806064304 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 047AK UT WOS:000237852000001 ER PT J AU Petersen, TJ AF Petersen, TJ TI Enhancing the efficacy of antidepressants with psychotherapy SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 158th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 2005 CL Atlanta, GA SP Amer Psychiat Assoc DE depression; antidepressants; psychotherapy; cognitive behavioural therapy ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; RECURRENT MAJOR DEPRESSION; RESIDUAL DEPRESSION; INTERPERSONAL PSYCHOTHERAPY; MAINTENANCE THERAPIES; PHARMACOTHERAPY; PREVENTION; SYMPTOMS; RELAPSE AB Even after optimal treatment with and response to antidepressant medications during acute treatment of major depressive disorder, residual symptoms are common. Patients with residual symptoms are at increased risk of relapse and recurrence. Research suggests that psychotherapy may play an important rote in enhancing the effects of antidepressant drug therapy and improving patients' long-term prognosis. Psychotherapy targets specific symptoms associated with relapse (e.g., guilt, hopelessness, negativity, low self-esteem) that antidepressants may not, reduces residual symptoms (e.g., irritability), improves coping skills for long-term disease management and promotes sustained, healthy cognitive changes. In addition, neuroimaging data suggest that psychotherapy and pharmacotherapy target different primary sites of the cortical-limbic pathway with differential top-down and bottom-up effects, resulting in modulation of critical common targets and facilitation of disease remission. The use of adjunctive psychotherapy in the acute phase of depression treatment appears to provide only a modest increase in response rates, although combined pharmaco-psychotherapy may prevent or delay relapse. Simultaneous application of pharmacotherapy and psychotherapy during the maintenance phase does not consistently provide a clear advantage over maintenance pharmacotherapy. In contrast, sequential use of psychotherapy after induction of remission with acute antidepressant drug therapy may confer a better long-term prognosis in terms of preventing relapse or recurrence and, for some patients, may be a viable alternative to maintenance medication therapy. C1 Massachusetts Gen Hosp, Depres Clin & Res Program, Boston, MA 02114 USA. RP Petersen, TJ (reprint author), Massachusetts Gen Hosp, Depres Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM tpetersen@partners.org NR 34 TC 26 Z9 29 U1 3 U2 12 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD MAY PY 2006 VL 20 IS 3 SU S BP 19 EP 28 DI 10.1177/1359786806064314 PG 10 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 047AK UT WOS:000237852000004 PM 16644768 ER PT J AU Fava, M AF Fava, M TI Pharmacological approaches to the treatment of residual symptoms SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 158th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 2005 CL Atlanta, GA SP Amer Psychiat Assoc DE major depressive disorder; MDD; therapy; administration and dosage; antidepressive agents; recurrence; prevention and control; remission induction; residual symptoms ID MAJOR DEPRESSIVE DISORDER; CLINICAL-SIGNIFICANCE; FLUOXETINE; ANTIDEPRESSANT; REMISSION; INSOMNIA; THERAPY; FATIGUE; ANXIETY; RELAPSE AB Despite the efficacy of currently available antidepressant treatment, residual symptoms are common among individuals treated for major depressive disorder and are associated with an increased risk of relapse and poor psychosocial functioning. However, distinguishing treatment-emergent side effects from residual symptoms can be challenging for clinicians. Anxiety, sleep disturbance, somnolence/fatigue, apathy and cognitive dysfunction are among the more frequent residual symptoms. Approaches to the management of residual symptoms include addressing treatment-emergent side effects and co-morbid conditions, optimizing antidepressant dosing and using augmentation therapy. Clinicians are often guided in their decisions by anecdotal impressions. Studies assessing the evaluation and treatment of residual symptoms and side effects will contribute importantly to the optimal acute and tong-term management of depression. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC-812, Boston, MA 02114 USA. EM MFava@partners.org NR 34 TC 31 Z9 32 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PD MAY PY 2006 VL 20 IS 3 SU S BP 29 EP 34 DI 10.1177/13597806064325 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 047AK UT WOS:000237852000005 PM 16644769 ER PT J AU Rubin, A Migneault, JP Marks, L Goldstein, E Ludena, K Friedman, RH AF Rubin, A Migneault, JP Marks, L Goldstein, E Ludena, K Friedman, RH TI Automated telephone screening for problem drinking SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID VOICE RESPONSE TECHNOLOGY; IDENTIFICATION TEST AUDIT; ALCOHOL-USE; CONSUMPTION; INSTRUMENTS; BEHAVIORS AB Objective: This study assessed test-retest reliability and criterion validity for an automated version of the Alcohol Use Disorders Identification Test (AUDIT), a screening tool for alcohol-related problems. Participants' willingness to use such a system to learn about and change their drinking behavior was also assessed. Method: Participants were 202 callers recruited through newspaper ads and flyers asking for volunteers concerned about their drinking and willing to help test a new method of screening and referral for alcohol problems. Participants were divided into two groups. The first group of subjects recruited received the Telephone-Linked Communications (TLC)-AUDIT twice, administered a week apart. The second group received the TLC-AUDIT once and a human-administered AUDIT once, also a week apart, Results: Test-retest reliability was assessed in 102 participants; the intraclass correlation of AUDIT scores between both administrations was .87; kappa for nonproblem versus problem drinking (AUDIT score of 8 or above) was .89. The validity study compared the TLC-AUDIT scores of the next 100 participants to AUDIT questions administered by a human interviewer. The intraclass correlation was .94; kappa was .75. Seventy-five percent of all participants who screened positive for problem drinking agreed they would "talk to a computer again to learn more about your drinking pattern and how to deal with it." Conclusions: Automated telephone technology can be used to administer the AUDIT instrument with high levels of reliability and validity. This technology Could be used to deliver behavioral change interventions. C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Serv WEH 101, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rubin, A (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Addict Serv WEH 101, 16 Blossom St, Boston, MA 02114 USA. EM arubin1@partners.org NR 20 TC 20 Z9 20 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD MAY PY 2006 VL 67 IS 3 BP 454 EP 457 PG 4 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 031AN UT WOS:000236676600015 PM 16608156 ER PT J AU Avansino, JR Chen, DC Woolman, JD Hoagland, VD Stelzner, M AF Avansino, JR Chen, DC Woolman, JD Hoagland, VD Stelzner, M TI Engraftment of mucosal stem cells into murine jejunum is dependent on optimal dose of cells SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE intestinal stem cell transplantation; GFP; neo-mucosa; mucosal restitution; intestinal stem cell seeding density; jejunal debridment time ID SMALL-BOWEL; TRANSPLANTATION; ENTEROCYTES; MOUSE AB Background. Transplantation of intestinal mucosal stem cells is an important step in the development of intestinal gene therapy and treatment of intestinal mucosal diseases. We hypothesized that engraftment rates increase proportionally with increasing doses of seeded stem cells and increasing jejunal debridment. Materials and methods. Intestinal mucosal organoids were harvested from neonatal mice carrying a green-fluorescent protein (GFP) transgene and transplanted into adult GFP(-) mice (n = 66). In recipients, two jejunal segments (1.5 cm) were isolated with their blood circulation left intact with anastomosis of the distal and proximal segments to restore continuity. Debridement of native enterocytes was performed by perfusing luminally with ethylene diamine tetraacetc acid solutions for 20 min. A total of 5,000, 10,000, or 25,000 organoids were then seeded. Three weeks later, cross sections (n = 398) of the segments were evaluated for the presence of GFP(+) neomucosa using fluorescence microscopy. Additional segments were debrided for 30 and 40 min (n = 83). Other conditions were not tested because of the rate of high mortality in these experiments. Results. The group seeded with 10,000 organoid units at 20 min showed the highest engraftment of GFP(+) epithelium. Engraftment was improved by increasing debridment times at this seeding density. Overall mortality was 70%. Conclusions. These findings suggest that there is an optimal seeding density of stem cell clusters for enhanced engraftment in this model. Mortality prohibited complete testing of all combinations of seeding density and debridement times. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Surg, Seattle, WA 98105 USA. Vet Adm Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Avansino, JR (reprint author), Univ Washington, Dept Surg, Box 356410, Seattle, WA 98105 USA. EM javansin@u.washington.edu NR 12 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY PY 2006 VL 132 IS 1 BP 74 EP 79 DI 10.1016/j.jss.2005.09.009 PG 6 WC Surgery SC Surgery GA 035CH UT WOS:000236977100013 PM 16297408 ER PT J AU Backus, BC Guinan, JJ AF Backus, BC Guinan, JJ TI Time-course of the human medial olivocochlear reflex SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID GUINEA-PIG COCHLEA; OUTER HAIR-CELLS; SPONTANEOUS OTOACOUSTIC EMISSIONS; MATRIX PENCIL METHOD; AUDITORY-NERVE; BUNDLE STIMULATION; EFFERENT STIMULATION; CONTRALATERAL SOUND; RAPID ADAPTATION; ACETYLCHOLINE AB The time-course of the human medial olivocochlear reflex (MOCR) was measured via its suppression of stimulus-frequency otoacoustic emissions (SFOAEs) in nine ears. MOCR effects were elicited by contralateral, ipsilateral or bilateral wideband acoustic stimulation. As a first approximation. MOCR effects increased like a saturating exponential with a time constant of 277 +/- 62 ms, and decayed exponentially with a time constant of 159 +/- 54 ms. However, in ears with the highest signal-to-noise ratios (4/9), onset time constants Could be separated into "fast," tau = similar to 70 ms. "medium," tau = similar to 330 ms, and "slow," tau = similar to 25 s components, and there was an overshoot in the decay like all under-damped sinusoid. Both the buildup and decay Could be modeled as a second order differential equation and the differences between the buildup and decay could be accounted for by decreasing one coefficient by a factor of 2. The reflex onset and offset delays were both similar to 25 ms. Although changing elicitor level over a 20 dB SPL range produced a consistent systematic change in response amplitude, the time course did not show a consistent dependence oil elictor level. nor did the time-courses of ipsilaterally, contralaterally, and bilaterally activated MOCR responses differ significantly. Given the MOCR's time-course, it is best suited to operate oil acoustic changes that persist for 100's of milliseconds. (c) 2006 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Backus, BC (reprint author), UCL, Ear Inst, 332-226 Grays Inn Rd, London WC1X 8EE, England. EM bradford.c.backus.95@alum.dartmouth.org FU NIDCD NIH HHS [P30 DC005209, R01 DC005977] NR 53 TC 83 Z9 84 U1 1 U2 6 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2006 VL 119 IS 5 BP 2889 EP 2904 DI 10.1121/1.2169918 PN 1 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 041ME UT WOS:000237459500035 PM 16708947 ER PT J AU Greenhill, LL Biederman, J Boellner, SW Rugino, TA Sangal, RB Earl, CQ Jiang, JG Swanson, JM AF Greenhill, LL Biederman, J Boellner, SW Rugino, TA Sangal, RB Earl, CQ Jiang, JG Swanson, JM TI A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE modafinil; modafinil film-coated tablets; attention-deficit/hyperactivity disorder; clinical trial ID INDUCED WAKEFULNESS; OPEN-LABEL; ADHD; METHYLPHENIDATE; AMPHETAMINE; ATOMOXETINE; TRIAL; PREVENTION; VERSION; BRAIN AB Objective: To evaluate the efficacy and tolerability of modafinil in children and adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD). Method: In this 9-week, double-blind, flexible-dose study, patients were randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included ADHD Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global Impression of Improvement (CGI-I) scale. Results: Two hundred patients were randomized. Modafinil produced significant reductions in ADHD-RS-IV total scores at school (n = 128; mean change SD: -17.5 +/- 13.1 points) compared with placebo (n = 66; -9.7 +/- 10.3 points; p < .0001). Similarly, modafinil reduced ADHD-RS-IV total scores at home compared with placebo (-17.6 +/- 13.3 versus -7.5 +/- 11.8 points; p < .0001). Fifty-two percent of patients randomized to modafinil and 18% of those randomized to placebo met prestudy criteria for responder on the CGH (p < .0001). Randomization to modafinil was associated with significantly more insomnia, headache, decreased appetite, and weight loss than randomization to placebo, but discontinuation attributed to adverse events did not differ statistically between treatment groups (modafinil, 5%; placebo, 6%). Conclusion: Modafinil was well tolerated and reduced ADHD symptoms at school and home compared with placebo. C1 New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Pediat Psychopharmacol, Boston, MA 02114 USA. Neurol & Clin Study Ctr, Little Rock, AR USA. Childrens Specialized Hosp, Mountainside, NJ USA. Clin Neurophysiol Serv PC, Troy, NY USA. Cephalon Inc, W Chester, PA USA. Univ Calif Irvine, Irvine Child Dev Ctr, Irvine, CA 92717 USA. RP Greenhill, LL (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr, New York, NY 10032 USA. EM larrylgreenhill@cs.com NR 38 TC 54 Z9 55 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2006 VL 45 IS 5 BP 503 EP 511 DI 10.1097/01.chi.0000205709.63571.c9 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 036TM UT WOS:000237098400001 PM 16601402 ER PT J AU Spencer, TJ Faraone, SV Biederman, J Lerner, M Cooper, KM Zimmerman, B AF Spencer, TJ Faraone, SV Biederman, J Lerner, M Cooper, KM Zimmerman, B CA Concerta Study Grp TI Does prolonged therapy with a long-acting stimulant suppress growth in children with ADHD? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE growth; height; weight; attention-deficit/hyperactivity disorder; methylphenidate; OROS methylphenidate; CONCERTA ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; ONCE-A-DAY; HYPERACTIVE-CHILDREN; FOLLOW-UP; OROS METHYLPHENIDATE; PSYCHIATRIC STATUS; DEFICIT DISORDER; BOYS; DRUGS; PREDICTORS AB Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the first year and every 3 months thereafter. Results: At baseline, subjects were approximately the expected height for their age and somewhat heavier than expected. Subjects gained height steadily throughout the study and were on average 0.23 cm less than expected at month 21. Weight did not increase and BMI decreased slightly in the first 4 months. Thereafter, weight Z score and BMI Z score remained relatively constant and children were on average 1.23 kg less than expected at month 21. Previous stimulant therapy tended to be associated with a smaller decrease in Z score during the study compared with no previous stimulant therapy. Drug holidays did not significantly affect growth. Conclusions: The effects of prolonged OROS MPH therapy on growth were clinically insignificant and limited to slight decreases in weight during the first months of therapy. Drug holidays did not reduce any impact on growth and are thus of questionable utility for limiting potential effects of treatment on growth. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. Univ Calif Irvine, Irvine, CA USA. McNeil Consumer & Specialty Pharmaceut, Ft Washington, MD USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 725, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 41 TC 66 Z9 68 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2006 VL 45 IS 5 BP 527 EP 537 DI 10.1097/01.chi.0000205710.01690.d4 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 036TM UT WOS:000237098400004 PM 16670649 ER PT J AU Halpern, LR Dodson, TB AF Halpern, LR Dodson, TB TI A predictive-model to identify women with injuries related to intimate partner violence SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE intimate partner violence; maxillofacial trauma; diagnostic protocol ID DOMESTIC VIOLENCE; EMERGENCY-DEPARTMENT; FACIAL INJURIES; MARKERS; HEALTH; ABUSE; NECK; HEAD; AGE AB Purpose. The diagnosis of intimate partner violence (IPV) is challenging. The authors conducted a cross-sectional study to develop a predictive model to identify IPV-related injuries and validate the model with an independent sample. Materials and Methods. The authors enrolled women older than 18 years seeking treatment for injuries. They randomized the sample into index and validation datasets. They used the index dataset to develop a predictive model; the validation set served as an independent sample for assessing the predictive model's goodness of fit. Study variables included risk of self-report of an IPV-related injury and demographic and socioeconomic variables. The outcome variable was self-reported injury etiology (IPV or other). The authors used multiple logistic regression techniques to develop a predictive model that they then applied to the validation dataset and they measure goodness of fit with the Hosmer-Lemeshow test. Results. The sample was randomized into index (n = 201) and validation (n = 104) sets. For the index set, age, race and risk of IPV were associated with IPV-related injuries (P < .01). The accuracy of the model was 92 percent. Application of the model to the validation dataset resulted in excellent agreement between the observed and actual number of women with IPV-related injuries (accuracy: 93 percent). No statistically significant differences existed between the observed and predicted outcomes (P = .64). Conclusions. A predictive model composed of age, race and risk of experiencing IPV accurately characterizes women likely to report IPV-related injuries. Clinical Implications. Once the clinician diagnoses IPV-related injury, he or she can intervene to prevent future IPV-related injuries. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp,Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Halpern, LR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp,Ctr Appl Clin Invest, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM jhalpern1@partners.org NR 31 TC 13 Z9 13 U1 1 U2 2 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2006 VL 137 IS 5 BP 604 EP 609 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 044RG UT WOS:000237689400021 PM 16739539 ER PT J AU Delahanty, LM Conroy, MB Nathan, DM AF Delahanty, LM Conroy, MB Nathan, DM CA Diabet Prevention Program Res Grp TI Psychological predictors of physical activity in the Diabetes Prevention Program SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; BEHAVIOR-CHANGE; EXERCISE; INTERVENTION; PARTICIPANTS; DEPRESSION; MELLITUS; WEIGHT AB before receiving a Diabetes Prevention Program (DPP) lifestyle intervention that predict physical activity levels (PALs) at baseline, I year, and end of study (2 to 3 years after randomization). Design and subjects Of the final 293 DPP lifestyle participants randomized, 274 (94%) completed validated questionnaires at baseline assessing stage of change for PAL, exercise self-efficacy, perceived stress, depression, and anxiety. Statistical analyses performed Correlations and stepwise multiple regression analyses. Results At baseline, this subset was similar to the entire DPP lifestyle cohort: mean age was 52.5 years, 65% were women, and mean PAL was 15.7 metabolic equivalent hours per week. Higher levels of baseline leisure PAL correlated with greater readiness to change PAL (r=0.44, P < 0.0001), higher exercise self-efficacy (r=0.18, P=0.002), and lower levels of perceived stress (r=-0.16, P=0.009), depression (r=-0.18, P=0.003), and anxiety (r=-0.14, P=0.03), with similar correlations at 1 year and end of study. In multivariate models, being a man, lower levels of depression, and lower body mass index were independent correlates of higher baseline leisure PAL; being a man, greater baseline exercise self-efficacy, and activity level were independent correlates of greater leisure PAL levels at 1 year and end of study. Greater readiness to change PAL at baseline was also an independent correlate of greater PAL at end of study. Conclusions In this representative sample of DPP lifestyle participants, being a man, lower body mass index, greater readiness for change in PAL, higher exercise self-efficacy, and lower perceived stress, depression, and anxiety scores correlated with higher levels of baseline PAL with similar patterns at 1 year and end of study. These findings may help determine which patients are most likely to increase PAL in lifestyle intervention programs. C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Stanford St,Ste 340, Boston, MA 02114 USA. EM ldelahanty@partners.org FU NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 30 TC 67 Z9 67 U1 1 U2 7 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 2006 VL 106 IS 5 BP 698 EP 705 DI 10.1016/j.jada.2006.02.011 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 039TF UT WOS:000237329300016 PM 16647327 ER PT J AU Rosen, S Weintraub, N AF Rosen, Sonja Weintraub, Nancy TI The efficacy of performing screening mammograms in the frail elderly population SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID BREAST-CANCER; OLDER WOMEN; AGE; SURVIVAL; COMORBIDITY; OPPORTUNITY; CARCINOMA; DIAGNOSIS; MORTALITY; BARRIERS C1 VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Sepulveda Vet Affairs Acad Nursing Home, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Multicampus Program Geriatr & Gerontol, Los Angeles, CA USA. RP Weintraub, N (reprint author), VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Sepulveda Vet Affairs Acad Nursing Home, 11E,16111 Plummer St, Sepulveda, CA 91343 USA. EM nancy.weintraub@med.va.gov NR 35 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD MAY PY 2006 VL 7 IS 4 BP 230 EP 233 DI 10.1016/j.jamda.2006.01.026 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 081JW UT WOS:000240314900006 PM 16698509 ER PT J AU Rosenbloom, ST Miller, RA Johnson, KB Elkin, PL Brown, SH AF Rosenbloom, ST Miller, RA Johnson, KB Elkin, PL Brown, SH TI Interface terminologies: Facilitating direct entry of clinical data into electronic health record systems SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review ID CONTROLLED MEDICAL TERMINOLOGY; DECISION-SUPPORT; KNOWLEDGE REPRESENTATION; INFORMATION-TECHNOLOGY; COMPUTER; LANGUAGE; VOCABULARIES; GUIDELINE; CARE; CLASSIFICATIONS AB Previous investigators have defined clinical interface terminology as a systematic collection of health care-related phrases (terms) that supports clinicians' entry of patient-related information into computer programs, such as clinical "note capture" and decision support tools. Interface terminologies also can facilitate display of computer-stored patient information to clinician-users. Interface terminologies "interface" between clinicians' own unfettered, colloquial conceptualizations of patient descriptors and the more structured, coded internal data elements used by specific health care application programs. The intended uses of a terminology determine its conceptual underpinnings, structure, and content. As a result, the desiderata for interface terminologies differ from desiderata for health care-related terminologies used for storage (e.g., SNOMED-CT (R)), information retrieval (e.g., MeSH), and classification (e.g., ICD9-CM (R)). Necessary but not sufficient attributes for an interface terminology include adequate synonym coverage, presence of relevant assertional knowledge, and a balance between pre- and post-coordination. To place interface terminologies in context, this article reviews historical goals and challenges of clinical terminology development in general and then focuses on the unique features of interface terminologies. C1 Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37240 USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Vanderbilt Univ, Sch Nursing, Nashville, TN USA. Mayo Fdn Med Educ & Res, Rochester, MN USA. US Dept Vet Affairs, Nashville, TN USA. RP Rosenbloom, ST (reprint author), Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37240 USA. EM trent.rosenbloom@vanderbilt.edu FU NLM NIH HHS [5R01 LM007995, 1K22 LM008576-01] NR 97 TC 95 Z9 96 U1 1 U2 24 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2006 VL 13 IS 3 BP 277 EP 288 DI 10.1197/jamia.M1957 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 052WI UT WOS:000238264200006 PM 16501181 ER PT J AU Yu, CG Liu, ZQ McKenna, T Reisner, AT Reifman, J AF Yu, CG Liu, ZQ McKenna, T Reisner, AT Reifman, J TI A method for automatic identification of reliable heart rates calculated from ECG and PPG waveforms SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID TRAUMA PATIENTS; HOLTER ECG; RECOGNITION; SYSTEM AB Objective: The development and application of data-driven decision-support systems for medical triage, diagnostics, and prognostics pose special requirements on physiologic data. In particular, that data are reliable in order to produce meaningful results. The authors describe a method that automatically estimates the reliability of reference heart rates (HRr) derived from electrocardiogram (ECG) waveforms and photoplethysmogram (PPG) waveforms recorded by vital-signs monitors. The reliability is quantitatively expressed through a quality index QI) for each HRr. Design: The proposed method estimates the reliability of heart rates from vital-signs monitors by (1) assessing the quality of the ECG and PPG waveforms, (2) separately computing heart rates from these waveforms, and (3) concisely combining this information into a QI that considers the physical redundancy of the signal sources and independence of heart rate calculations. The assessment of the waveforms is performed by a Support Vector Machine classifier and the independent computation of heart rate from the waveforms is performed by an adaptive peak identification technique, termed ADAPIT, which is designed to filter out motion-induced noise. Results: The authors evaluated the method against 158 randomly selected data samples of trauma patients collected during helicopter transport, each sample consisting of 7-second ECG and PPG waveform. segments and their associated HRr. They compared the results of the algorithm against manual analysis performed by human experts and found that in 92% of the cases, the algorithm either matches or is more conservative than the human's QI qualification. In the remaining 8% of the cases, the algorithm infers a less conservative QI, though in most cases this was because of algorithm/human disagreement over ambiguous waveform quality. If these ambiguous waveforms were relabeled, the misclassification rate would drop from 8% to 3%. C1 US Army Med Res & Mat Command MRMC, TATRC, Ft Detrick, MD 21702 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Reifman, J (reprint author), US Army Med Res & Mat Command MRMC, TATRC, 504 Scott St, Ft Detrick, MD 21702 USA. EM jaques.reifman@us.army.mil NR 20 TC 46 Z9 47 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2006 VL 13 IS 3 BP 309 EP 320 DI 10.1197/jamia.M1925 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 052WI UT WOS:000238264200009 PM 16501184 ER PT J AU La Fontaine, J Harkless, LB Davis, CE Allen, MA Shireman, PK AF La Fontaine, J Harkless, LB Davis, CE Allen, MA Shireman, PK TI Current concepts in diabetic microvascular dysfunction SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Review ID ENDOTHELIAL DYSFUNCTION; VASCULAR-DISEASE; NITRIC-OXIDE; CARDIOVASCULAR EVENTS; BASEMENT-MEMBRANE; OXIDATIVE STRESS; FOOT ULCERATION; BLOOD-VISCOSITY; LOWER-EXTREMITY; MELLITUS AB Microvascular dysfunction is an important component of the pathologic processes that occur in diabetic foot disease. The endothelial abnormalities observed in patients with diabetes mellitus are poorly understood, and evidence suggests that endothelial dysfunction could be involved in the pathogenesis of diabetic macroangiopathy and microangiopathy. With the advent of insulin replacement in the early 1900s and increased efforts toward metabolic control of diabetes, long-term complications of this disease have become apparent. These late-term complications are primarily disorders of the vascular system. This article reviews the process of microvascular dysfunction and how it may relate to the pathogenesis of diabetic foot problems. C1 Univ Texas, Hlth Sci Ctr, Dept Orthoped, Podiatry Div, San Antonio, TX 78229 USA. Assoc Podiatrist Connecticut, Manchester, CT USA. Sports Med Assoc San Antonio, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Surg, Div Vasc Surg, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX USA. RP La Fontaine, J (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthoped, Podiatry Div, 7703 Floyd Curl Dr,MSC 7776, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL 074236, HL 070158] NR 73 TC 12 Z9 12 U1 0 U2 2 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAY-JUN PY 2006 VL 96 IS 3 BP 245 EP 252 PG 8 WC Orthopedics SC Orthopedics GA 047PH UT WOS:000237890700010 PM 16707637 ER PT J AU Katavetin, P Miyata, T Inagi, R Tanaka, T Sassa, R Ingelfinger, JR Fujita, T Nangaku, M AF Katavetin, Pisut Miyata, Toshio Inagi, Reiko Tanaka, Tetsuhiro Sassa, Ryoji Ingelfinger, Julie R. Fujita, Toshiro Nangaku, Masaomi TI High glucose blunts vascular endothelial growth factor response to hypoxia via the oxidative stress-regulated hypoxia-inducible factor/hypoxia-responsible element pathway SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID REMNANT KIDNEY MODEL; IMPAIRED ANGIOGENESIS; DIABETIC-NEPHROPATHY; GENE-EXPRESSION; RENAL-DISEASE; ANTIOXIDANT THERAPY; PERITONEAL-DIALYSIS; INFARCT SIZE; AGING KIDNEY; FACTOR VEGF AB Vascular endothelial growth factor (VEGF) is an important survival factor for endothelial cells in hypoxic environments. High glucose regulates certain aspects of VEGF expression in various cell types, including proximal tubular cells. Thus, ambient glucose levels may modulate the progression of chronic kidney disease, especially diabetic nephropathy. Immortalized rat proximal tubular cells (IRPTC) were cultured for 24 h under hypoxic conditions (1% 02), with or without high D-glucose (25 mM), or with or without high L-glucose (25 mM). Controls included culture in normoxic conditions and normal D-glucose (5.5 mM). VEGF mRNA expression was assessed by real-time quantitative PCR, and VEGF protein in the supernatant was assessed by ELISA. Hypoxia increased VEGF expression. This response was significantly blunted by high D-glucose (1.98 +/- 0.11-versus 2.65 +/- 0.27-fold increase for VEGF mRNA expression, 252.8 +/- 14.7 versus 324.0 +/- 11.5 pg/10(5) cells for VEGF protein; P < 0.05 both) but not by high L-glucose. It is interesting that hydrogen peroxide also blunted this response, whereas alpha-tocopherol restored the VEGF response to hypoxia in the presence of high D-glucose. For determination of involvement of the hypoxia-inducible factor (HIF)/hypoxia-responsible element (HRE) pathway, IRPTC that were stably transfected with HRE-luciferase were cultured under the previous conditions. High D-glucose also reduced luciferase activity under hypoxia, whereas alpha-tocopherol restored activity. In vivo experiments using streptozotocin-induced diabetic rats confirmed that hyperglycemia blunted HIF-HRE pathway activation. Insulin treatment restored activation of the HIF-HRE pathway in streptozotocin-induced diabetic rats. In conclusion, high glucose blunts VEGF response to hypoxia in IRPTC. This effect is mediated by the oxidative stress-regulated HIF-HRE pathway. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 1138655, Japan. Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 25911, Japan. Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa 25911, Japan. Okazaki Kita Clin, Aichi, Japan. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1,Hongo, Tokyo 1138655, Japan. EM mnangaku-tky@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 NR 45 TC 75 Z9 79 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2006 VL 17 IS 5 BP 1405 EP 1413 DI 10.1681/ASN.2005090918 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 044WZ UT WOS:000237705500025 PM 16597689 ER PT J AU Agnihotri, AK Desai, SC Lai, YQ Fitzsimons, MG Hilgenberg, AD Vlahakes, GJ AF Agnihotri, AK Desai, SC Lai, YQ Fitzsimons, MG Hilgenberg, AD Vlahakes, GJ TI Two distinct clinical presentations in adult unicuspid aortic valve SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID REPLACEMENT; STENOSIS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Anesthesiol, Boston, MA 02114 USA. Anzhen Hosp, Dept Cardiac Surg, Beijing, Peoples R China. RP Agnihotri, AK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, 119,55 Fruit St, Boston, MA 02114 USA. EM aagnihotri@partners.org NR 4 TC 9 Z9 10 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2006 VL 131 IS 5 BP 1169 EP 1170 DI 10.1016/j.jtcvs.2005.11.040 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 039QW UT WOS:000237322500039 PM 16678607 ER PT J AU Vagefi, PA Bates, NR Ptaszek, LM Adams, MS Walker, JD AF Vagefi, PA Bates, NR Ptaszek, LM Adams, MS Walker, JD TI Valve-sparing excision of aortic valve papillary fibroelastoma SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiothorac Anesthesia, Boston, MA 02114 USA. RP Walker, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,EDR 105, Boston, MA 02114 USA. EM jdwalker@partners.org NR 5 TC 2 Z9 2 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2006 VL 131 IS 5 BP 1177 EP U74 DI 10.1016/j.jtcvs.2005.12.053 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 039QW UT WOS:000237322500044 PM 16678612 ER PT J AU Halpern, LR Perciaccante, VJ Hayes, C Susarla, S Dodson, TB AF Halpern, LR Perciaccante, VJ Hayes, C Susarla, S Dodson, TB TI A protocol to diagnose intimate partner violence in the emergency department SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 10-14, 2003 CL Orlando, FL SP Amer Assoc Oral & Maxillofacial Surg DE intimate partner violence; diagnostic protocol; injuries; questionnaires ID DOMESTIC VIOLENCE; FACIAL INJURIES; TRAUMA SERVICE; WOMEN; PREVALENCE; MARKERS; VICTIMS; ASSAULT; HEAD; NECK AB Background. To better identify women at risk for intimate partner violence (IPV), we developed a diagnostic protocol composed of injury location and response to a verbal questionnaire to identify women at high risk for reporting an IPV-related injury etiology. The purpose of this study was to test the external validity of the protocol when applied at two institutions that differ considerably in terms of geography and socioeconomic measures. Methods: A cross-sectional design was used at two demographically and geographically different hospitals, designated H1 and H2. The sample was composed of adult females age >= 18 years presenting to the emergency department (ED) for evalnation and management of nonveriflable traumatic injuries. The predictor variable was risk for reporting an IPV-related injury. Risk was categorized per the protocol as high or low. High-risk subjects had visible head, neck, or face (HNF) injuries and positive responses to the questionnaires. Low-risk subject had non-HNF injuries or negative responses to the screening questionnaires. The outcome variable was self-reported injury etiology classified as IPV-related or other. Descriptive and bivariate statistics and standard measurements for a diagnostic test were computed. Results. The sample was composed of 400 subjects, with 200 subjects enrolled at each institution. Self-reported IPV was 34% and 9.5% at H1 and 112, respectively. The protocol classified 33% (H1) and 18% (H2) of subjects as high risk. Sensitivities were 90% (H1) and 74% (H2). Specificities were 96% (H1) and 88% (H2). Subjects classified per protocol as high-risk had an 18-fold (p < 0.01, 111) and 13-fold (p < 0.01, H2) increased risk for reporting IPV-related injuries. Conclusions: Despite significant geographic and socioeconomic differences between the two hospitals, the results suggest that our protocol may be applicable in disparate clinical settings. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. Emory Univ, Sch Med, Div Oral & Maxillofacial Surg, Atlanta, GA USA. RP Halpern, LR (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM lhalpern1@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 25 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 2006 VL 60 IS 5 BP 1101 EP 1105 DI 10.1097/01.ta.0000218247.58465.db PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 044NB UT WOS:000237678100037 PM 16688077 ER PT J AU Inagami, S Borrell, LN Wong, MD Fang, J Shapiro, MF Asch, SM AF Inagami, S Borrell, LN Wong, MD Fang, J Shapiro, MF Asch, SM TI Residential segregation and Latino, black and white mortality in New York City SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Hispanic; Latino; morality; New York City; race; segregation ID DISPARITIES GEOCODING PROJECT; LOW-BIRTH-WEIGHT; UNITED-STATES; ETHNIC DENSITY; SOCIOECONOMIC-FACTORS; INFANT-MORTALITY; HEALTH RESEARCH; SMALL-AREA; LONDON; SCHIZOPHRENIA AB Although racial segregation is associated with health status, few studies have examined this relationship among Latinos. We examined the effect of race/ethnic group concentration of Latinos, blacks and whites on all-cause mortality rates within a highly segregated metropolitan area, New York City (NYC). We linked NYC mortality records from 1999 and 2000 with the 2000 U.S. Census data by zip code area. Age-adjusted mortality rates by race/ethnic concentration were calculated. Linear regression was used to determine the association between population characteristics and mortality. Blacks living in predominantly black areas had lower all-cause mortality rates than blacks living in other areas regardless of gender (16161100,000 vs. 20141100,000 for men; 10321100,000 vs. 13621100 000 for women). Amongst whites, those living in predominantly white areas had the lowest mortality rates. Latinos living in predominantly Latino areas had lower mortality rates than those in predominantly black areas (1187/100,000 vs. 1950/100,000 for men; 760/100,000 vs. 7791100,000 for women). After adjustment for socioeconomic conditions, whites, older blacks, and young Latino men experienced decreasing mortality rates when living in areas with increasing similar race/ethnic concentrations. Increasing residential concentration of blacks is independently associated with lower mortality in older blacks; similarly, increasing residential concentration of Latinos and whites is associated with lower mortality in young Latino men and whites, respectively. C1 VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med 111G, Los Angeles, CA 90073 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. RAND Hlth, Div Gen Internal Med 111G, Los Angeles, CA 90073 USA. RP Inagami, S (reprint author), VA Greater Los Angeles Hlth Care Syst, Div Gen Internal Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sinagami@ucla.edu OI Wong, Mitchell/0000-0002-4800-8410 FU NCI NIH HHS [F32 CA090073] NR 54 TC 36 Z9 36 U1 3 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAY PY 2006 VL 83 IS 3 BP 406 EP 420 DI 10.1007/s11524-006-9035-8 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 054CY UT WOS:000238355600008 PM 16739044 ER PT J AU Wolff, RA Malinowski, RL Heaton, NS Hullett, DA Hoch, JR AF Wolff, RA Malinowski, RL Heaton, NS Hullett, DA Hoch, JR TI Transforming growth factor-beta 1 antisense treatment of rat vein grafts reduces the accumulation of collagen and increases the accumulation of h-caldesmon SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID GROWTH-FACTOR-BETA; SMOOTH-MUSCLE-CELLS; INTIMAL HYPERPLASIA; GENE-EXPRESSION; TGF-BETA; MATRIX METALLOPROTEINASES; ALLOGRAFT-REJECTION; TISSUE INHIBITORS; SAPHENOUS-VEIN; BYPASS GRAFTS AB Background: The main cause of occlusion and vein graft failure after peripheral and coronary arterial reconstruction is intimal hyperplasia. Transforming growth factor beta-1 (TGF-beta 1) is a pleiotropic cytokine known to have powerful effects on cell growth, apoptosis, cell differentiation, and extracellular matrix synthesis. Methods: To investigate the role of TGF-beta 1 in intimal hyperplasia, we used adenovirus to deliver to superficial epigastric vein messenger RNA (mRNA) antisense to TGF-beta 1 (Ad-AST) or the sequence encoding the bioactive form of TGF-beta 1 (Ad-BAT). Infection with "empty" virus was used as a control (Ad-CMVpLpA). The treated vein was then used for an interposition graft into rat femoral artery. Grafts were harvested at 1, 2, 4, and 12 weeks and formalin-fixed for histologic studies or placed in liquid nitrogen for mRNA studies. Results. Ad-AST treatment resulted in an overall reduction of TGF-beta 1 expression (P = .001), and Ad-BAT treatment resulted in an overall increase in TGF-beta 1 expression (P = .007). Histologic analysis showed Ad-AST caused reduced collagen build up in the neointima at 12 weeks (P = .0001.). Immunohistochemical staining for h-caldesmon at 12 weeks indicated Ad-AST increased smooth muscle cells throughout the vessel wall compared with Ad-CMVpLpA (P = .0024) or Ad-BAT (P = .04). Ad-AST also resulted in reduced CD68-positive cells in the media/adventitia (P = .005 vs Ad-CMVpLpA, P = .01 vs Ad-BAT). To further understand how Ad-AST was influencing the build up of collagen, we performed quantitative polymerase chain reaction on complimentary DNA (cDNA) from homogenates of the vein grafts. Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) was increased at 1 week by Ad-BAT (P = .048 vs AdCMVpLpA) and decreased by Ad-AST at all time points (P <= .038). The mRNA for collagen-1 alpha-1 was decreased by Ad-AST at 2, 4, and 12 weeks (P <= .05) and increased by Ad-BAT at 1 week (P = .01). Conclusions: TGF-beta 1 antisense treatment of vein grafts prevents the accumulation of collagen in the neointima in part by (1) changing the proportions of the cell types populating the vein graft wall, (2) reducing the mRNA for TIMPs, and (3) reducing the amount of collagen mRNA. With the Ad-AST and Ad-BAT treatments, we have been able to tip the maturation of the vein graft toward positive remodeling (artery-like phenotype) or toward negative remodeling (fibroproliferation and stenosis), respectively. C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. Univ Wisconsin, Sch Med, Madison, WI 53792 USA. RP Wolff, RA (reprint author), William S Middleton Mem Vet Adm Med Ctr, H5-3 CSC,VA G-Wing,600 Highland Ave, Madison, WI 53792 USA. EM wolff@surgery.wisc.edu NR 47 TC 15 Z9 17 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2006 VL 43 IS 5 BP 1028 EP 1036 DI 10.1016/j.jvs.2006.01.016 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 038WY UT WOS:000237261400030 PM 16678700 ER PT J AU Borger, DR DeCaprio, JA AF Borger, DR DeCaprio, JA TI Targeting of p300/CREB binding protein coactivators by simian virus 40 is mediated through p53 SO JOURNAL OF VIROLOGY LA English DT Article ID LARGE-T-ANTIGEN; NIJMEGEN BREAKAGE SYNDROME; HUMAN ADENOVIRUS TYPE-5; DOUBLE-STRAND BREAKS; PRB-RELATED PROTEINS; DNA-DAMAGE RESPONSE; TRANSCRIPTIONAL COACTIVATOR; DEPENDENT PHOSPHORYLATION; HISTONE ACETYLTRANSFERASE; ACTIVATES TRANSCRIPTION AB The primary transforming functions of simian virus 40 large T antigen (SV40 LT) are conferred primarily through the binding and inactivation of p53 and the retinoblastoma family members. Normal p53 function requires an association with the CREB binding protein (CBP)/p300 coactivators, and a ternary complex containing SV40 LT, p53, and CBP/p300 has been identified previously. In this report, we have evaluated a secondary function of p53 bound to the SV40 LT complex in mediating the binding of human CBP/p300. We demonstrate that p53 associated with SV40 LT was posttranslationally modified in a manner consistent with the binding of CBP/p300. Futhermore, expression of SV40 LT induced the proportion of p53 phosphorylated on S15. An essential function for p53 in bridging the interaction between SV40 LT and CBP/p300 was identified through thre reconstitution of the SV40 LT-CBP/p300 complex upon p53 reexpression in p53-null cells. In addition, the SV40 LT-CBP/p300 complex was disrupted through RNA interference-mediated depletion of endogenous p53. We also demonstrate that SV40 LT was acetylated in a p300- and p53-dependent manner, at least in part through the CH3 domain of p300. Therefore, the binding of p53 serves to modify SV40 LT by targeting CBP and p300 binding to direct the acetylation of SV40 LT. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Mayer Bldg 457,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [F32 CA099357, F32CA99357-01A1, R01 CA063113, R01CA063113] NR 93 TC 29 Z9 30 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 9 BP 4292 EP 4303 DI 10.1128/JVI.80.9.4292-4303.2006 PG 12 WC Virology SC Virology GA 035DI UT WOS:000236980000009 PM 16611888 ER PT J AU Yang, XZ Kurteva, S Ren, XP Lee, S Sodroski, J AF Yang, XZ Kurteva, S Ren, XP Lee, S Sodroski, J TI Subunit stoichiometry of human immunodeficiency virus type 1 envelope glycoprotein trimers during virus entry into host cells SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENTRY; HEMAGGLUTININ TRIMERS; GP120 GLYCOPROTEIN; RECEPTOR-BINDING; ATOMIC-STRUCTURE; CD4 RECEPTOR; INFECTION; GP41; FUSION; ANTIBODY AB The envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) function as a homotrimer of gp120/gp41 heterodimers to support virus entry. During the process of virus entry, an individual HIV-1 envelope glycoprotein trimer binds the cellular receptors CD4 and CCR5/CXCR4 and mediates the fusion of the viral and the target cellular membranes. By studying the function of heterotrimers between wild-type and nonfunctional mutant envelope glycoproteins, we found that two wild-type subunits within an envelope glycoprotein trimer are required to support virus entry. Complementation between HIV-1 envelope glycoprotein mutants defective in different functions to allow virus entry was not evident. These results assist our understanding of the mechanisms whereby the HIV-1 envelope glycoproteins mediate virus entry and membrane fusion and guide attempts to inhibit these processes. C1 Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Biostat Sci, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Sch Med, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Yang, XZ (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM xinzhen_yang@dfci.harvard.edu FU NIAID NIH HHS [AI24755, AI31782, R37 AI024755, AI46725, U01 AI046725] NR 50 TC 44 Z9 44 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 9 BP 4388 EP 4395 DI 10.1128/JVI.80.9.4388-4395.2006 PG 8 WC Virology SC Virology GA 035DI UT WOS:000236980000019 PM 16611898 ER PT J AU Crawford, SE Patel, DG Cheng, E Berkova, Z Hyser, JM Ciarlet, M Finegold, MJ Conner, ME Estes, MK AF Crawford, SE Patel, DG Cheng, E Berkova, Z Hyser, JM Ciarlet, M Finegold, MJ Conner, ME Estes, MK TI Rotavirus viremia and extraintestinal viral infection in the neonatal rat model SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY-TRACT; HISTOLOGIC DISTRIBUTION; ACUTE GASTROENTERITIS; BILIARY ATRESIA; YOUNG-CHILDREN; ANIMAL-MODEL; SIALIC-ACID; ASSOCIATION; INFANT; SPREAD AB Rotaviruses infect mature, differentiated enterocytes of the small intestine and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The neonatal rat model of rotavirus infection was used to determine the kinetics of viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day-old rat pups were inoculated intragastrically with an animal (RRV) or human (HALI 166) rotavirus or phosphate-buffered saline. Blood was collected from a subset of rat pups, and following perfusion to remove residual blood, organs were removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed in formalin for histology and immunohistochemistry. Viremia was detected following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose was 1.8 x 10(3) PFU, and the 50% diarrhea dose was 7.7 x 10(5) PFU, indicating that infection and viremia occurred in the absence of diarrhea and that detecting rotavirus antigen in the blood was a more sensitive measure of infection than diarrhea. Rotavirus antigens and infectious virus were detected in multiple organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus. and bladder). Histopathological changes due to rotavirus infection included acute inflammation of the portal tract and bile duct, microsteatosis, necrosis, and inflammatory cell infiltrates in the parenchymas of the liver and lungs. Colocalization of structural and nonstructural proteins with histopathology in the liver and lungs indicated that the histological changes observed were due to rotavirus infection and replication. Replicating rotavirus was also detected in macrophages in the lungs and blood vessels, indicating a possible mechanism of rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea, was observed in the presence of passively or actively acquired rotavirus-specific antibody. These findings alter the previously accepted concept of rotavirus pathogenesis to include not only gastroenteritis but also viremia, and they indicate that rotavirus could cause a broad array of systemic diseases in a number of different organs. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Merck & Co Inc, Clin Res Dept, Blue Bell, PA 19422 USA. RP Estes, MK (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. EM mestes@bcm.tmc.edu FU NIAID NIH HHS [AI 24998, R01 AI024998, R21 AI024998]; NIDDK NIH HHS [P30 DK056338, T32 DK007664, R56 DK030144, DK 30144, DK 56338, R01 DK030144, DK 07664] NR 56 TC 76 Z9 85 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2006 VL 80 IS 10 BP 4820 EP 4832 DI 10.1128/JVI.80.10.4820-4832.2006 PG 13 WC Virology SC Virology GA 041LK UT WOS:000237457500018 PM 16641274 ER PT J AU Jang, IK Baron, SJ Hursting, MJ Anglade, E AF Jang, IK Baron, SJ Hursting, MJ Anglade, E TI Heparin-induced thrombocytopenia and argatroban therapy in women SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Clin Sci Consulting, Austin, TX USA. CTI Clin Trial & Consulting Serv, Blue Ash, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2006 VL 15 IS 4 BP 468 EP 468 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 052BO UT WOS:000238205800062 ER PT J AU Cabelof, DC Raffoul, JJ Ge, YB Van Remmen, H Matherly, LH Heydari, AR AF Cabelof, DC Raffoul, JJ Ge, YB Van Remmen, H Matherly, LH Heydari, AR TI Age-related loss of the DNA repair response following exposure to oxidative stress SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BASE EXCISION-REPAIR; IN-VIVO; APURINIC/APYRIMIDINIC ENDONUCLEASE; CALORIC RESTRICTION; AP ENDONUCLEASE-1; STRAND BREAKS; UP-REGULATION; MOUSE-BRAIN; P53; INDUCTION AB Young (4- to 6-month-old) and aged (24- to 28-month-old) mice were exposed to 2-nitropropane (2-NP), a DNA oxidizing agent, and the ability to induce DNA polymerase beta (beta-pol) and AP endonuclease (APE) was determined. In contrast to the inducibility of these gene products in response to oxidative damage in young mice, aged mice showed a lack of inducibility of beta-pol and APE. APE protein level and endonuclease activity were both reduced 40% (p <.01) in response to 2-NP. Accordingly, the accumulation of DNA repair intermediates in response to 2-NP differed with age. Young animals accumulated 3'OH-containing DNA strand breaks, whereas the aged animals did not. A role for p53 in the difference in DNA damage response with age is suggested by the observation that the accumulation of p53 protein ill response to DNA damage in young animals was absent in the aged animals. Our results are consistent with a reduced ability to process DNA damage with age. C1 Wayne State Univ, Barbara Ann Karmanos Canc Inst, Sch Med, Dev Therapeut Program, Detroit, MI 48201 USA. Wayne State Univ, Dev Therapeut Program, Detroit, MI 48201 USA. Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48201 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Barshop Inst Longev & Aging Studies, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. RP Cabelof, DC (reprint author), Wayne State Univ, Barbara Ann Karmanos Canc Inst, Sch Med, Dev Therapeut Program, 110 E Warren Ave, Detroit, MI 48201 USA. EM d.cabelof@wayne.edu FU NIDDK NIH HHS [1R21-DK62256]; NIEHS NIH HHS [1F32-ES013643, ES06639] NR 40 TC 30 Z9 33 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2006 VL 61 IS 5 BP 427 EP 434 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 046NL UT WOS:000237818200002 PM 16720738 ER PT J AU Young, BA Rudser, K Kestenbaum, B Seliger, SL Andress, D Boyko, EJ AF Young, BA Rudser, K Kestenbaum, B Seliger, SL Andress, D Boyko, EJ TI Racial and ethnic differences in incident myocardial infarction in end-stage renal disease patients: The USRDS SO KIDNEY INTERNATIONAL LA English DT Article DE race; ESRD; transplant; dialysis; mortality; myocardial infarction ID CORONARY-ARTERY CALCIFICATION; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR-DISEASE; REVASCULARIZATION PROCEDURES; DIABETIC-NEPHROPATHY; UNITED-STATES; MORTALITY; RISK; POPULATION; RACE AB African Americans have a greater risk of cardiovascular disease (CVD) than Caucasians in early chronic kidney disease; however, limited data describe racial and ethnic differences in the risk of incident myocardial infarction (MI) among patients with end-stage renal disease ( ESRD). We conducted a prospective, observational cohort study among 271 102 incident dialysis patients receiving renal replacement therapy enrolled in the United States Renal Data System (USRDS) for whom Medicare was the primary insurer between 1995 and 2000. The incidence and risk of any MI (non-fatal or fatal) estimated by Cox proportional hazards models was the primary outcome of interest. Of those with prevalent CVD at baseline ( 118 708), 14 849 had an incident non-fatal MI compared with 9926 events for those without prevalent CVD ( 152 394). Patients with prevalent CVD had higher crude rates of combined fatal and non-fatal MI (99.3/1000 person-years vs 42.9/1000 person-years) compared with those without prevalent CVD. Among those with prevalent CVD, African Americans ( adjusted relative risk (aRR) 0.65, 95% confidence interval (CI): 0.62 - 0.68), Asian Americans (aRR = 0.74, 95% CI: 0.66 - 0.83), and Hispanics (aRR 0.72, 95% CI: 0.68 - 0.77) were 26 - 35% less likely to have an incident MI compared to Caucasians. Similarly, among those without prevalent CVD, racial/ethnic minorities were 26 - 42% less likely to have an incident MI compared to Caucasians. We conclude that in a national setting where comparable access to dialysis and associated medical care, exist, racial/ ethnic minorities were found to have a lower risk of non- fatal and fatal MI than Caucasians. C1 VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Primary & Special Med Care Serv, Seattle, WA USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. NW Kidney Ctr, Seattle, WA USA. Univ Washington, Dept Biostat, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Univ Maryland, Div Nephrol, Baltimore, MD 21201 USA. RP Young, BA (reprint author), VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, 1600 S Columbian Way,152-E, Seattle, WA 98108 USA. EM youngb@u.washington.edu NR 36 TC 34 Z9 34 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2006 VL 69 IS 9 BP 1691 EP 1698 DI 10.1038/sj.ki.5000346 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 038QP UT WOS:000237238400034 PM 16598201 ER PT J AU Friedman, B Berman, JJ Balis, UJ AF Friedman, B Berman, JJ Balis, UJ TI Reinventing pathology: Clinical pathology informatics in the era of the electronic medical record SO LABMEDICINE LA English DT Editorial Material C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan Hlth Syst, Div Pathol Informat, Ann Arbor, MI USA. NCI, Canc Diag Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Shriners Hosp, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Friedman, B (reprint author), Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD MAY PY 2006 VL 37 IS 5 BP 313 EP 314 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 036LR UT WOS:000237073100022 ER PT J AU Montet, X Yuan, HS Weissleder, R Josephson, L AF Montet, X Yuan, HS Weissleder, R Josephson, L TI Enzyme-based visualization of receptor-ligand binding in tissues SO LABORATORY INVESTIGATION LA English DT Article DE receptor activity; binding; tissue microarray; fluorescein; antifluorescein ID EPIDERMAL GROWTH-FACTOR; BREAST-CANCER-CELLS; NEUROPEPTIDE-Y; PEPTIDE RECEPTORS; HUMAN PROSTATE; BIOTIN STATUS; BOMBESIN; ANGIOGENESIS; LOCALIZATION; FLUORESCEIN AB New methods of elucidating the ligand-binding activity of receptors could improve our understanding of receptor function, key events they control, and their presence in normal and pathological states. We describe a method for visualizing receptor-ligand binding in cells and tissues that substitutes fluorescein for radioactive labels, and detects receptor bound, fluoresceinated ligand with an antifluorescein/horseradish peroxidase amplification system. Receptor-bound ligand is then visualized by light microscopy against a standard hemotoxylin-stained background of cell structure. Quantitative versions of the assay provide an apparent dissociation constant and number of receptors per cell at saturation in cell or tissue specimens. Receptors examined include the folate receptor, bombesin peptide-binding receptors, the epidermal growth factor receptor, the neuropeptide Y receptor, the asialoglycoprotein receptor, and RGD peptide-binding integrins. Using fluoresceinated versions of molecules, we show the method can visualize and quantitate receptor-bound ligands in cell culture monolayers and animal tissue specimens. Ligand binding to receptors present in tissues was visualized in normal and pathological samples of human tissue microarrays. The enzyme-amplified detection of receptor-bound fluoresceinated ligand is a simple and nonradioactive-based method that provides information on the receptor activity in tissue specimens. C1 Geneva Hosp, Dept Radiol, Geneva, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02115 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. EM ljosephson@partners.org OI Montet, Xavier/0000-0003-2442-5866 FU NCI NIH HHS [P50 CA86355, P01 CA69246]; NIBIB NIH HHS [R01 EB00662] NR 36 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2006 VL 86 IS 5 BP 517 EP 525 DI 10.1038/labinvest.3700404 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 036FW UT WOS:000237057700008 PM 16568109 ER PT J AU Barker, FG Chang, SM AF Barker, FG Chang, SM TI Improving resection of malignant glioma SO LANCET ONCOLOGY LA English DT Editorial Material ID SURVIVAL; SURGERY C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, Neurooncol Serv, San Francisco, CA 94143 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. EM BARKER@HELIX.MGH.HARVARD.EDU NR 10 TC 10 Z9 10 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2006 VL 7 IS 5 BP 359 EP 360 DI 10.1016/S1470-2045(06)70669-6 PG 2 WC Oncology SC Oncology GA 041XB UT WOS:000237488800004 PM 16648038 ER PT J AU Gross, RD Steinhauer, KM Zajac, DJ Weissler, MC AF Gross, RD Steinhauer, KM Zajac, DJ Weissler, MC TI Direct measurement of subglottic air pressure while swallowing SO LARYNGOSCOPE LA English DT Article DE swallowing; deglutition; subglottic air pressure; tracheostomy tube ID PASSY-MUIR VALVE; NORMAL ADULTS; PHASE-RELATIONSHIPS; BOLUS VOLUME; LUNG-VOLUME; TRACHEOSTOMY; ASPIRATION; COORDINATION; RESPIRATION; PHYSIOLOGY AB Objective: The subglottic pressure theory for swallowing asserts that laryngeal mechanoreceptors have a role in the regulation of swallowing function. The primary purpose of this study was to determine if subglottic air pressure is generated during swallowing in a healthy, nontracheostomized person. Methods. This pilot investigation used a prospective, repeated-measures design in a single subject. Direct measurement of subglottic air pressure was obtained through percutaneous puncture of the cricothyroid membrane. Swallows were timed with four randomly assigned lung volumes: total lung capacity, tidal volume, functional residual capacity (FRC), and residual volume. Results: Lung volumes above FRC generated positive subglottic pressure during the swallow, whereas lung volumes below FRC generated consistently negative subglottic pressures. The degree and polarity of the pressure was directly related to lung volume at the time of the swallow. Conclusion. These findings illustrate that during normal swallowing, positive subglottic air pressure is likely present. Previously, subglottic air pressure during swallowing had been measured in tracheostomy patients only. C1 Univ Pittsburgh, Sch Med, Dept Otolaryngol, Inst Eye & Ear, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Think Voice Int LLC, Pittsburgh, PA USA. Univ N Carolina, Dept Dent Ecol, Craniofacial Ctr, Chapel Hill, NC USA. Univ N Carolina, Dept Otolaryngol, Chapel Hill, NC USA. RP Gross, RD (reprint author), Univ Pittsburgh, Sch Med, Dept Otolaryngol, Inst Eye & Ear, Suite 500,200 Lothrop St, Pittsburgh, PA 15213 USA. EM Grossrd@upmc.edu FU NIDCR NIH HHS [R01-DE10175] NR 24 TC 20 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2006 VL 116 IS 5 BP 753 EP 761 DI 10.1097/01.mlg.0000205168.39446.12 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 040KB UT WOS:000237376300013 PM 16652083 ER PT J AU Timmer, FCA Zhou, GW Guinan, JJ Kujawa, SG Herrmann, BS Rauch, SD AF Timmer, FCA Zhou, GW Guinan, JJ Kujawa, SG Herrmann, BS Rauch, SD TI Vestibular evoked myogenic potential (VEMP) in patients with Meniere's disease with drop attacks SO LARYNGOSCOPE LA English DT Article DE Meniere's disease; VEMP; vestibular evoked myogenic potentials; drop attack ID ANGULAR VESTIBULOOCULAR REFLEX; INTRATYMPANIC GENTAMICIN; MULTIVARIATE-STATISTICS AB Objective. In this retrospective study, we tested the hypothesis that vestibular evoked myogenic potential (VEMP) thresholds are more often elevated or absent in patients with Meniere's disease experiencing Tumarkin drop attacks than in other patients with Meniere's disease. Methods: Subjects included normal subjects (n = 14) and patients with unilateral Meniere's disease by AAO-HNS (1995) diagnostic criteria with (n = 12) and without (n = 82) Tumarkin drop attacks at a large specialty hospital otology service. VEMP threshold testing was conducted using 250, 500, and 1,000 Hz tone burst stimuli. Results. VEMP responses were present in at all frequencies in both ears of all normal subjects. In unaffected ears of patients with unilateral Meniere's disease, VEMPs were undetectable in 13% of measurements attempted. This number rose to 18% in affected ears of patients with unilateral Meniere's disease and to 41% in Meniere ears with Tumarkin drop attacks. Frequency tuning of the VEMP response in normal subjects showed lowest thresholds at 500 Hz. In Meniere ears, the tuning was altered such that the 500-Hz thresholds were higher than the 1,000-Hz thresholds. There was a gradient of threshold elevation and altered tuning that corresponded to the gradient of worsening disease. Conclusion: Our findings support the hypothesis that Tumarkin drop attacks arise from advanced disease involving the saccule and that VEMP may be a clinically valuable metric of disease severity or progression in patients with Meniere's disease. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM steven_rauch@meei.harvard.edu FU NIDCD NIH HHS [R01 DC04425] NR 17 TC 34 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2006 VL 116 IS 5 BP 776 EP 779 DI 10.1097/01.mlg.0000205129.78600.27 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 040KB UT WOS:000237376300016 PM 16652086 ER PT J AU Chng, W Santana-Davila, R Van Wier, S Ahmann, GJ Jalal, SM Bergsagel, PL Chesi, M Trendle, MC Jacobus, S Blood, E Oken, MM Henderson, K Kyle, RA Gertz, MA Lacy, MQ Dispenzieri, A Greipp, PR Fonseca, R AF Chng, W Santana-Davila, R Van Wier, S Ahmann, GJ Jalal, SM Bergsagel, PL Chesi, M Trendle, MC Jacobus, S Blood, E Oken, MM Henderson, K Kyle, RA Gertz, MA Lacy, MQ Dispenzieri, A Greipp, PR Fonseca, R TI Prognostic factors for hyperdiploid-myeloma: effects of chromosome 13 deletions and IgH translocations SO LEUKEMIA LA English DT Article DE hyperdiploid; myeloma; prognosis; IgH translocations; chromosome 13 deletion ID COOPERATIVE-ONCOLOGY-GROUP; IN-SITU HYBRIDIZATION; CELL LABELING INDEX; C-REACTIVE PROTEIN; P53 GENE DELETION; MULTIPLE-MYELOMA; STAGING SYSTEM; CYTOGENETIC ABNORMALITIES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY AB Chromosomal hyperdiploidy is the defining genetic signature in 40 - 50% of myeloma ( MM) patients. We characterize hyperdiploid-MM (H-MM) in terms of its clinical and prognostic features in a cohort of 220 H-MM patients entered into clinical trials. Hyperdiploid-myeloma is associated with male sex, kappa immunoglobulin subtype, symptomatic bone disease and better survival compared to nonhyperdiploid-MM (median overall survival 48 vs 35 months, log-rank P = 0.023), despite similar response to treatment. Among 108 H-MM cases with FISH studies for common genetic abnormalities, survival is negatively affected by the existence of immunoglobulin heavy chain (IgH) translocations, especially those involving unknown partners, while the presence of chromosome 13 deletion by FISH did not significantly affect survival (median overall survival 50 vs 47 months, log-rank P = 0.47). Hyperdiploid-myeloma is therefore a unique genetic subtype of MM associated with improved outcome with distinct clinical features. The existence of IgH translocations but not chromosome 13 deletion by FISH negatively impacts survival and may allow further risk stratification of this population of MM patients. C1 Mayo Clin Scottsdale, Div Hematol Oncol, Scottsdale, AZ 85259 USA. Mayo Clin, Dept Pathol & Lab Med, Rochester, MN USA. Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA 02115 USA. Natl Univ Singapore Hosp, Dept Haematol Oncol, Singapore 117548, Singapore. RP Fonseca, R (reprint author), Mayo Clin Scottsdale, Div Hematol Oncol, Johnson Res Bldg,13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM fonseca.rafael@mayo.edu RI Bergsagel, Peter/A-7842-2011; OI Bergsagel, Peter/0000-0003-1523-7388; Fonseca, Rafael/0000-0002-5938-3769; Dispenzieri, Angela/0000-0001-8780-9512 FU NCI NIH HHS [CA21115-25C, P01 CA62242, P50 CA100707-01, R01 CA83724-01] NR 42 TC 77 Z9 82 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2006 VL 20 IS 5 BP 807 EP 813 DI 10.1038/sj.leu.2404172 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 038QZ UT WOS:000237239400008 PM 16511510 ER PT J AU Tsoulfas, G Hertl, M Elias, N Kawai, T Cosimi, BA Ko, D AF Tsoulfas, G Hertl, M Elias, N Kawai, T Cosimi, BA Ko, D TI Single US institution 20 year review of combined liver-kidney transplantation. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the ILTS, ELITA, AND LICAGE CY MAY 03-06, 2006 CL Milan, ITALY SP ILTS, ELITA, LICAGE C1 Massachusetts Gen Hosp, Dept Transplantat Surg, Boston, MA 02114 USA. RI Tsoulfas, Georgios/K-4801-2012 OI Tsoulfas, Georgios/0000-0001-5043-7962 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD MAY PY 2006 VL 12 IS 5 BP C19 EP C19 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 035YG UT WOS:000237037100111 ER PT J AU Oxnard, GR Armato, SG Kindler, HL AF Oxnard, GR Armato, SG Kindler, HL TI Modeling of mesothelioma growth demonstrates weaknesses of current response criteria SO LUNG CANCER LA English DT Article; Proceedings Paper CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN SP Int Assoc Study Lung Canc DE mesothelioma; response evaluation; criteria in solid; tumors (RECIST); tumor measurement; tumor response; tumor volume ID MALIGNANT PLEURAL MESOTHELIOMA; RECIST CRITERIA; SOLID TUMORS; PHASE-II; CT SCANS; CHEMOTHERAPY; CISPLATIN; VOLUME AB Applicability of the Response Evaluation Criteria in Solid Tumors (RECIST) to the geometry of mesothelioma has been recently investigated. A "modified RECIST" measurement technique developed for mesothelioma proposes measurement of tumor thickness rather than maximum diameter. This study evaluated the volumetric consistency of the RECIST response criteria as applied to the modified RECIST measurement technique. Geometric models were developed to simulate mesothelioma growth, and measurements of these models were calculated. Relationships between change in model measurements and corresponding change in model volume were derived and evaluated. Application of the RECIST response criteria to the typical spherical tumor model results in partial response (PR) classification based on a 66% volume decrease and progressive disease (PD) based on a 73% volume increase; for mesothelioma model thickness measurements, the RECIST criteria result in PR classification based on a 30% volume decrease and PD based on a 20% volume increase. Alternative response criteria for mesothelioma thickness measurement (-66% for PR, +74% for PD) achieve volumetric equivalence with the RECIST criteria for spherical tumor measurement. Application of the RECIST response criteria to mesothelioma thickness measurements yields PR and PD classifications based on smaller volume changes than for spherical tumors. (C) 2006 Eisevier Ireiand Ltd. All rights reserved. C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. RP Armato, SG (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA. EM s-armato@uchicago.edu NR 20 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAY PY 2006 VL 52 IS 2 BP 141 EP 148 DI 10.1016/j.tungcan.2005.12.013 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 037LV UT WOS:000237149300003 PM 16530882 ER PT J AU Schmid, MC Oeltermann, A Juchem, C Logothetis, NK Smirnakis, SM AF Schmid, MC Oeltermann, A Juchem, C Logothetis, NK Smirnakis, SM TI Simultaneous EEG and fMRI in the macaque monkey at 4.7 Tesla SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 23-29, 2005 CL Erice, ITALY DE electroencephalography; fMRI; macaque monkey ID INTERICTAL EPILEPTIFORM ACTIVITY; TRIGGERED FUNCTIONAL MRI; VISUAL-EVOKED POTENTIALS; TARGET DETECTION; BRAIN ACTIVITY; REACTION-TIME; ALPHA-RHYTHM; VEP LATENCY; CORTEX; EPILEPSY AB Simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) acquisition can identify the brain networks involved in generating specific EEG patterns. Yet, the combination of these methodologies is hampered by strong artifacts that arise due to electromagnetic interference during magnetic resonance (MR) image acquisition. Here, we report corrections of the gradient-induced artifact in phantom measurements and in experiments with an awake behaving macaque monkey during fMRI acquisition at a magnetic field strength of 4.7 T. Ninety-one percent of the amplitude of a 10 mu V, 10 Hz phantom signal could successfully be recovered without phase distortions. Using this method, we were able to extract the monkey EEG from scalp recordings obtained during MR image acquisition. Visual evoked potentials could also be reliably identified. In conclusion, simultaneous EEG/fMRl acquisition is feasible in the macaque monkey preparation at 4.7 T and holds promise for investigating the neural processes that give rise to particular EEG patterns. (c) 2006 Elsevier Inc. All rights reserved. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Schmid, MC (reprint author), Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. EM michael.schmid@tuebingen.mpg.de RI Schmid, Michael/G-1867-2010 OI Schmid, Michael/0000-0003-1424-130X FU PHS HHS [KO8] NR 71 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 2006 VL 24 IS 4 SI SI BP 335 EP 342 DI 10.1016/j.mri.2005.12.024 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044YZ UT WOS:000237711000002 PM 16677938 ER PT J AU Clever, SL Ford, DE Rubenstein, LV Rost, KM Meredith, LS Sherbourne, CD Wang, NY Arbelaez, JJ Cooper, LA AF Clever, SL Ford, DE Rubenstein, LV Rost, KM Meredith, LS Sherbourne, CD Wang, NY Arbelaez, JJ Cooper, LA TI Primary care patients' involvement in decision-making is associated with improvement in depression SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med DE depression; primary care; shared decision-making; patient involvement in care; patient-centered care ID QUALITY IMPROVEMENT; OUTCOMES; INTERVENTION; INTERVIEW; PROVIDER; HEALTH; COMMUNICATION; PHYSICIANS; IMPACT; MODEL AB Background: Depression is undertreated in primary care settings. Little research investigates the impact of patient involvement in decisions on guideline-concordant treatment and depression outcomes. Objective: The objective of this study was to determine whether patient involvement in decision-making is associated with guideline-concordant care and improvement in depression symptoms. Design: Prospective cohort study Setting: Multisite, nationwide randomized clinical trial of quality improvement strategies for depression in primary care. Subjects: Primary care patients with current symptoms and probable depressive disorder. Measurements: Patients rated their involvement in decision-making (IDM) about their care on a 5-point scale from poor to excellent 6 months after entry into the study. Depressive symptoms were measured every 6 months for 2 years using a modified version of the Center for Epiderniologic Studies-Depression (CES-D) scale. We examined probabilities (Pr) of receipt of guideline-concordant care and resolution of depression across IDM groups using multi-variate logistic regression models controlling for patient and provider factors. Results: For each 1-point increase in IDM ratings, the probability of patients' report of receiving guideline-concordant care increased 4% to 5% (adjusted Pr 0.31 vs. 0.50 for the lowest and highest IDM ratings, respectively, P < 0.001). Similarly, for each 1-point increase in IDM ratings, the probability of depression resolution increased 2% to 3% (adjusted Pr 0.10 vs. 0.19 for the lowest and highest IDM ratings respectively, P = 0.004). Conclusions: Depressed patients with higher ratings of involvement in medical decisions have a higher probability of receiving guideline-concordant care and improving their symptoms over an 18-month period. Interventions to increase patient involvement in decision-making may be an important means of improving care for and outcomes of depression. C1 Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA. Johns Hopkins Sch Med, Div Gen Internal Med, Dept Med, Baltimore, MD USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RAND Corp, Hlth Program, Santa Monica, CA USA. Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO 80202 USA. RP Cooper, LA (reprint author), Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-500, Baltimore, MD 21287 USA. EM lisa.cooper@jhmi.edu OI Wang, Nae-Yuh/0000-0001-6513-9730 FU NIMH NIH HHS [R01 MH5443, R01 MH5444, R01 MH57992] NR 42 TC 89 Z9 89 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2006 VL 44 IS 5 BP 398 EP 405 DI 10.1097/01.mlr.0000208117.15531.da PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 037MC UT WOS:000237150000003 PM 16641657 ER PT J AU Weinberger, M Mahrshak, I Keller, N Goldscmied-Reuven, A Amariglio, N Kramer, M Tobar, A Samra, Z Pitlik, SD Rinaldi, MG Thompson, E Sutton, D AF Weinberger, M. Mahrshak, I. Keller, N. Goldscmied-Reuven, A. Amariglio, N. Kramer, M. Tobar, A. Samra, Z. Pitlik, S. D. Rinaldi, M. G. Thompson, E. Sutton, D. TI Isolated endogenous endophthalmitis due to a sporodochial-forming Phialemonium curvatum acquired through intracavernous autoinjections SO MEDICAL MYCOLOGY LA English DT Article DE Phialemonium curvatum; endophthalmitis; injections; contamination; outbreak ID DEXTROSE INFUSION FLUID; FUNGAL ENDOPHTHALMITIS; ENDOCARDITIS; INJECTION; INFECTION; OBOVATUM; THERAPY; ASPERGILLUS; IMPOTENCE; OUTBREAK AB We report a case of endogenous endophthalmitis due to a sporodochial-forming species of Phialemonium curvatum. The infection led to the enucleation of the affected eye, but there was no evidence of systemic dissemination. The isolated P. curvatum produced aggregates of phialides, many occurring on coils or in verticils, which eventually develop into sporodochia. The initial and post-enucleation isolates revealed they were identical to strains of P. curvatum from Israel causing disseminated disease in patients practicing intracavernous auto-injections for the treatment of erectile dysfunction. The reported case had unusual clinical and microbiological features. Despite the route of acquisition and the lack of systemic antifungal therapy, the infection did not spread beyond the eye. The morphology of the phialides aggregates was also unique, and the distinction between Volutella and Acremonium is discussed. This case expands the spectrum of infections due to Phialemonium species, and reveals a novel way of developing fungal endophthalmitis. C1 Rabin Med Ctr, Dept Ophthalmol, Petah Tiqwa, Israel. Chaim Sheba Med Ctr, Microbiol Lab, IL-52621 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Hematol Lab, IL-52621 Tel Hashomer, Israel. Rabin Med Ctr, Inst Pathol, Petah Tiqwa, Israel. Rabin Med Ctr, Clin Microbiol Lab, Petah Tiqwa, Israel. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Tel Aviv Univ, Sackler Sch Med, Ramat Aviv, Israel. RP Weinberger, M (reprint author), Assaf Harofeh Med Ctr, Infect Dis Unit, IL-70300 Zerifin, Israel. EM miriw@netvision.net.il NR 30 TC 10 Z9 10 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2006 VL 44 IS 3 BP 253 EP 259 DI 10.1080/13693780500411097 PG 7 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 061NA UT WOS:000238878100008 PM 16702105 ER PT J AU Anstead, GM Martinez, M Graybill, JR AF Anstead, G. M. Martinez, M. Graybill, J. R. TI Control of a Candida glabrata prosthetic endovascular infection with posaconazole SO MEDICAL MYCOLOGY LA English DT Article DE Candida glabrata; infection; posaconazole; transjugular intrahepatic portosystemic shunt ID INTRAHEPATIC PORTOSYSTEMIC SHUNT; IN-VITRO ACTIVITIES; ANTIFUNGAL AGENTS; TORULOPSIS-GLABRATA; FLUCONAZOLE; FUNGEMIA; SUSCEPTIBILITY; ITRACONAZOLE; VORICONAZOLE; BACTEREMIA AB A 63-year-old man with a history of cirrhosis of the liver developed Candida glabrata fungemia after undergoing transjugular intrahepatic portosystemic shunt ( TIPS) placement. Treatment with oral fluconazole was initially effective, but when the patient became neutropenic, subsequent blood cultures grew C. glabrata and a thrombus developed, which partially occluded the stent. Despite treatment with fluconazole, blood cultures remained positive for C. glabrata. Treatment with posaconazole resulted in clinical improvement and the patient had only intermittently positive fungal cultures for 6 weeks. A CT scan showed resolution of the inferior vena cava thrombus. Subsequently, the patient developed hepatocellular carcinoma and hepatic encephalopathy and became noncompliant with posaconazole. Blood cultures again became positive for C. glabrata. The patient died a few weeks after the diagnosis of hepatocellular carcinoma, but the cause of death was believed to be worsening liver dysfunction, not C. glabrata infection. Posaconazole had controlled the infection for about 3 months prior to his death. In conclusion, posaconazole may be a useful option in the management of prosthetic endovascular infections caused by C. glabrata. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Dept Vet Affairs, Med Ctr, Med Serv, San Antonio, TX USA. David Powell Clin, Austin, TX USA. RP Graybill, JR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM graybill@uthscsa.edu NR 30 TC 10 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2006 VL 44 IS 3 BP 273 EP 277 DI 10.1080/13693780500049152 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 061NA UT WOS:000238878100011 PM 16702108 ER PT J AU Lu, HM Kooy, H AF Lu, HM Kooy, H TI Optimization of current modulation function for proton spread-out Bragg peak fields SO MEDICAL PHYSICS LA English DT Article DE proton therapy; SOBP fields AB Proton treatments with spread-out Bragg peak (SOBP) fields often use a rotating modulation wheel of varying thickness to modulate the pristine Bragg peak in depth and intensity. The technique of modulating also the beam current independently over the wheel rotation provides an additional control over the intensities of the pulled-back Bragg peaks. As a result, a single wheel can be used over a large range of energies and SOBP parameters and field-specific wheels are no longer necessary. An essential task in commissioning a particular treatment depth is the determination of this current modulation function. We have developed a method for the optimization of the current modulation function. The basic idea is to treat the entire beam nozzle, housing the various beam scattering and modulating components, as a whole and to characterize its effect as a transformation from a modulating beam current to a depth-dose distribution. While this transformation is difficult to calculate theoretically due to the complex scattering paths in the nozzle and the phantom, it can, however, be determined by time-resolved dose measurements. Using this transformation, we can calculate SOBP depth-dose distributions for any current modulation function and optimize it by a simple numerical optimization. We have applied the new method to a number of proton beams with satisfactory results. (c) 2006 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, NE Proton Therapy Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lu, HM (reprint author), Harvard Univ, Sch Med, NE Proton Therapy Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. FU NCI NIH HHS [5 P01 CA21239-24] NR 4 TC 29 Z9 29 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2006 VL 33 IS 5 BP 1281 EP 1287 DI 10.1118/1.2188072 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044LJ UT WOS:000237673600011 PM 16752563 ER PT J AU Beddar, AS Biggs, PJ Chang, S Ezzell, GA Faddegon, BA Hensley, FW Mills, MD AF Beddar, AS Biggs, PJ Chang, S Ezzell, GA Faddegon, BA Hensley, FW Mills, MD TI Intraoperative radiation therapy using mobile electron linear accelerators: Report of AAPM radiation therapy committee task group no. 72 SO MEDICAL PHYSICS LA English DT Article ID PARALLEL IONIZATION CHAMBERS; INTRA-OPERATIVE IRRADIATION; MONTE-CARLO CALCULATIONS; BEAM APPLICATOR SYSTEM; DOSIMETRY CHARACTERISTICS; RECTAL-CANCER; EXTERNAL BEAM; RADIOTHERAPY; CARCINOMA; DESIGN AB Intraoperative radiation therapy (IORT) has been customarily performed either in a shielded operating suite located in the operating room (OR) or in a shielded treatment room located within the Department of Radiation Oncology. In both cases, this cancer treatment modality uses stationary linear accelerators. With the development of new technology, mobile linear accelerators have recently become available for IORT. Mobility offers flexibility in treatment location and is leading to a renewed interest in IORT. These mobile accelerator units, which can be transported any day of use to almost any location within a hospital setting, are assembled in a nondedicated environment and used to deliver IORT. Numerous aspects of the design of these new units differ from that of conventional linear accelerators. The scope of this Task Group (TG-72) will focus on items that particularly apply to mobile IORT electron systems. More specifically, the charges to this Task Group are to (i) identify the key differences between stationary and mobile electron linear accelerators used for IORT, (ii) describe and recommend the implementation of an IORT program within the OR environment, (iii) present and discuss radiation protection issues and consequences of working within a nondedicated radiotherapy environment, (iv) describe and recommend the acceptance and machine commissioning of items that are specific to mobile electron linear accelerators, and (v) design and recommend an efficient quality assurance program for mobile systems. (c) 2006 American Association of Physicists in Medicine. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Div Radiat Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Mayo Clin, Dept Radiat Oncol, Scottsdale, AZ 85259 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Univ Heidelberg, Dept Radiat Oncol, D-69120 Heidelberg, Germany. James Graham Brown Canc Ctr, Dept Radiat Oncol, Louisville, KY 40202 USA. RP Beddar, AS (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Div Radiat Oncol, Unit 94, Houston, TX 77030 USA. EM abeddar@mdanderson.org NR 60 TC 35 Z9 38 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2006 VL 33 IS 5 BP 1476 EP 1489 DI 10.1118/1.2194447 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 044LJ UT WOS:000237673600030 PM 16752582 ER PT J AU Bammert, CS O'Connell, S Miskevics, S Collins, EG Budiman-Mak, E AF Bammert, Christine S. O'Connell, Susan Miskevics, Scott Collins, Eileen G. Budiman-Mak, Elly TI Increased Mobility in Obese Elderly with Knee Osteoarthritis - A Home-Based Walking and Strength Program SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Bammert, Christine S.; O'Connell, Susan; Miskevics, Scott] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Collins, Eileen G.] Univ Illinois, Chicago, IL USA. [Budiman-Mak, Elly] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. EM christine.maloney@med.va.gov NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S419 EP S420 PG 2 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070803163 ER PT J AU Bennett, GG Wolin, KY Puleo, E Emmons, KM AF Bennett, Gary G. Wolin, Kathleen Y. Puleo, Elaine Emmons, Karen M. TI Perceptions of Neighborhood Safety and Pedometer-Determined Activity Among Low Income Housing Residents SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Bennett, Gary G.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolin, Kathleen Y.] Northwestern Univ, Chicago, IL 60611 USA. [Puleo, Elaine] Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S539 EP S540 PG 2 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070803643 ER PT J AU Conroy, MB Garber, CE Delichatsios, HK O'Hare, NE AF Conroy, Molly B. Garber, Carol Ewing Delichatsios, Helen K. O'Hare, Nancy E. TI Evaluation of an Innovative Physical Activity Collaboration between Medical Students and Master's Exercise Physiology Students SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Conroy, Molly B.] Univ Pittsburgh, Pittsburgh, PA USA. [Garber, Carol Ewing] Northeastern Univ, Boston, MA 02115 USA. [Delichatsios, Helen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [O'Hare, Nancy E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM conroymb@upmc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2006 VL 38 IS 5 SU S BP S368 EP S368 DI 10.1249/00005768-200605001-01561 PG 1 WC Sport Sciences SC Sport Sciences GA V19KH UT WOS:000208070802738 ER PT J AU Grady, D AF Grady, D TI Helping women stop postmenopausal hormone therapy SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; HEALTH INITIATIVE MEMORY; ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; DEMENTIA C1 Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. RP Grady, D (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2006 VL 13 IS 3 BP 323 EP 324 DI 10.1097/01.gme.0000222473.16217.0f PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 050VD UT WOS:000238116100001 PM 16735925 ER PT J AU Ettinger, B Harris, ST Kendler, D Kessel, B McClung, MR Gorodeski, GI Rothert, ML Henderson, VW Richardson, MK Freedman, RR Gallagher, JC Goldstein, SR Kessel, B Pinkerton, JV Reame, NK Speroff, L Stuenkel, CA Schiff, I Utian, WH Graham, ID Lammers, PK Boggs, PP AF Ettinger, B Harris, ST Kendler, D Kessel, B McClung, MR Gorodeski, GI Rothert, ML Henderson, VW Richardson, MK Freedman, RR Gallagher, JC Goldstein, SR Kessel, B Pinkerton, JV Reame, NK Speroff, L Stuenkel, CA Schiff, I Utian, WH Graham, ID Lammers, PK Boggs, PP CA NAMS TI Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Review DE menopause; osteoporosis; fractures; bone mineral density; estrogen therapy; hormone therapy; bisphosphonate; selective estrogen-receptor modulator; calcitonin; parathyroid hormone; calcium; vitamin D; NAMS ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; HORMONE-REPLACEMENT THERAPY; INCIDENT VERTEBRAL FRACTURES; VITAMIN-D SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; CONTINUING OUTCOMES RELEVANT; INTERVENTIONS PEPI TRIAL; X-RAY ABSORPTIOMETRY AB Objective: To update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2002 regarding the management of osteoporosis in postmenopausal women. Design: NAMS followed the general principles established for evidence-based guidelines to create this updated document. A panel of clinicians and researchers expert in the field of metabolic bone diseases and/or women's health was enlisted to review the 2002 NAMS position statement, compile supporting statements, and reach consensus on recommendations. The panel's recommendations were reviewed and approved by the NAMS Board of Trustees. Results: Osteoporosis, whose prevalence is especially high among elderly postmenopausal women, increases the risk of fractures. Hip and spine fractures are associated with particularly high morbidity and mortality in this population. Given the health implications of osteoporotic fractures, the primary goal of osteoporosis therapy is to prevent fractures, which is accomplished by slowing or stopping bone loss, maintaining bone strength, and minimizing or eliminating factors that may contribute to fractures. The evaluation of postmenopausal women for osteoporosis risk requires a medical history, physical examination, and diagnostic tests. Major risk factors for postmenopausal osteoporosis (as defined by bone mineral density) include advanced age, genetics, lifestyle factors (such as low calcium and vitamin D intake, smoking), thinness, and menopause status. The most common risk factors for osteoporotic fracture are advanced age, low,bone mineral density, and previous fracture as an adult. Management focuses first on nonpharmacologic measures, such as a balanced diet, adequate calcium and vitamin D intake, adequate exercise, smoking cessation, avoidance of excessive alcohol intake, and fall prevention. If pharmacologic therapy is indicated, government-approved options are bisphosphonates, a selective estrogen-receptor modulator, parathyroid hormone, estrogens, and calcitonin. Conclusions: Management strategies for postmenopausal women involve identifying those at risk of low bone density and fracture, followed by instituting measures that focus on reducing modifiable risk factors through lifestyle changes and, if indicated, pharmacologic therapy. C1 NAMS, Cleveland, OH 44101 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Hawaii, John A Burns Sch Med, Dept Obstet & Gynecol & Womens Hlth, Honolulu, HI 96822 USA. Oregon Osteoporosis Ctr, Portland, OR USA. Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Harvard Vanguard Med Associates, Boston, MA USA. Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Creighton Univ, Sch Med, St Josephs Hosp, Dept Metab, Omaha, NE USA. NYU, Sch Med, New York, NY USA. Univ Virginia, Hlth Sci Ctr, Dept Obstet & Gynecol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Midlife Hlth Ctr, Womens Pl, Charlottesville, VA USA. Columbia Univ, Sch Nursing, DNSc Program, New York, NY USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Womens Care Div, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Ettinger, B (reprint author), NAMS, POB 94527, Cleveland, OH 44101 USA. NR 234 TC 121 Z9 124 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2006 VL 13 IS 3 BP 340 EP 367 DI 10.1097/01.gme.0000222475.93345.b3 PG 28 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 050VD UT WOS:000238116100006 ER PT J AU Joffe, H Hall, JE Gruber, S Sarmiento, IA Cohen, LS Yurgelun-Todd, D Martin, KA AF Joffe, H Hall, JE Gruber, S Sarmiento, IA Cohen, LS Yurgelun-Todd, D Martin, KA TI Estrogen therapy selectively enhances prefrontal cognitive processes: a randomized, double-blind, placebo-controlled study with functional magnetic resonance imaging in perimenopausal and recently postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE estrogen; cognition; menopause; hot flash; hot flush; sleep; functional neuroimaging ID HORMONE-REPLACEMENT THERAPY; SURGICALLY MENOPAUSAL WOMEN; HEALTH INITIATIVE MEMORY; CEREBRAL-BLOOD-FLOW; WORKING-MEMORY; ALZHEIMER-DISEASE; CONTROLLED-TRIAL; SLEEP QUALITY; VERBAL MEMORY; ELDERLY WOMEN AB Objective: Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ET's influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. The aim of this study was to determine which cognitive domains are influenced by ET and whether hot flushes and sleep play mediating roles in these effects. Design: In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n=26) or placebo transdermal patches (n=26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. Results: Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P=0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P<0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P<0.001). Conclusions: Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Perinatal & Reprod Psychiat Clin Re, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Womens Ctr Behav Endocrinol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Reprod Endocrine Unit, Boston, MA USA. Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr,Cognit Neuroimaging Lab, Boston, MA USA. RP Joffe, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Perinatal & Reprod Psychiat Clin Re, 15 Parkman St,WACC 815, Boston, MA 02114 USA. EM hjoffe@partners.org NR 63 TC 116 Z9 122 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2006 VL 13 IS 3 BP 411 EP 422 DI 10.1097/01.gme.0000189618.48774.7b PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 050VD UT WOS:000238116100012 PM 16735938 ER PT J AU Friedberg, SJ Lam, YWF Blum, JJ Gregerman, RI AF Friedberg, SJ Lam, YWF Blum, JJ Gregerman, RI TI Insulin absorption: a major factor in apparent insulin resistance and the control of type 2 diabetes mellitus SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ISOPHANE NPH INSULIN; TIME-ACTION PROFILES; SUBCUTANEOUS-INSULIN; FEEDBACK INHIBITION; OBESE SUBJECTS; GLUCOSE RESPONSES; REGULAR INSULIN; INJECTION-SITE; SECRETION; PHARMACOKINETICS AB Our experience over many years from 2 diabetes clinics with large patient populations indicated that, apparently, excessive doses of intermediate-acting insulin preparations (150-300 U of NPH insulin), alone or in combination with rapid-acting insulin, generally did not result in acceptable control of fasting blood glucose. We hypothesized that insulin resistance at the tissue level and the known variability of insulin absorption were not satisfactory explanations. To deal with the ambiguities of available data on insulin absorption, we elected to measure insulin bioavailability via a different approach. Thirteen publications provided plasma insulin concentrations after the subcutaneous administration of defined doses of insulin. These data were then analyzed by noncompartmental analysis and by standard pharmacokinetic methods. Analyses required only knowledge of the areas under the plasma insulin curve and the metabolic clearance rate of insulin. Both of these are parameters measurable with considerable accuracy. Quantitative pharmacokinetic analysis of published insulin absorption curves for insulin administered subcutaneously revealed mean absorption levels for regular and lispro insulin of 70 to 80%, 30% or less for NPH insulin, and 30 to 40% for lente insulin. In conclusion, poor absorption of intermediate-acting insulin preparations, or combinations of intermediate and rapid-acting insulin preparations, explains the difficulty in lowering blood glucose in patients with type 2 diabetes mellitus who have had long-standing disease, are insulin resistant, and have a flat insulin response to a glucose load. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27705 USA. RP Friedberg, SJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM sjfriedberg@sbcglobal.net NR 49 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 2006 VL 55 IS 5 BP 614 EP 619 DI 10.1016/j.metabol.2005.12.004 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 040SM UT WOS:000237400700009 PM 16631437 ER PT J AU Bach, S Tribouillard, D Talarek, N Desban, N Gug, F Galons, H Blondel, M AF Bach, Stephane Tribouillard, Deborah Talarek, Nicolas Desban, Nathalie Gug, Fabienne Galons, Herve Blondel, Marc TI A yeast-based assay to isolate drugs active against mammalian prions SO METHODS LA English DT Article DE prion; screening assay; budding yeast; [PSI+]; [URE3]; ERG6 ID GUANIDINE-HYDROCHLORIDE; SACCHAROMYCES-CEREVISIAE; SHEEP SCRAPIE; PROTEIN; PROPAGATION; INHIBITORS; HSP104; CELLS; THERAPEUTICS; ACCUMULATION AB Recently, we have developed a yeast-based (Saccharomyces cerevisiae) assay to isolate drugs active against mammalian prions. The initial assumption was that mechanisms controlling prion appearance and/or propagation could be conserved from yeast to human, as it is the case for most of the major cell biology regulatory mechanisms. Indeed, the vast majority of drugs we isolated as active against both [PSI+] and [URE3] budding yeast prions turned out to be also active against mammalian prion in three different mammalian cell-based assays. These results strongly argue in favor of common prion controlling mechanisms conserved in eukaryotes, thus validating our yeast-based assay and also the use of budding yeast to identify antiprion compounds and to study the prion world. (c) 2006 Elsevier Inc. All rights reserved. C1 CNRS, Biol Stn, UMR7150, F-29680 Roscoff, France. CNRS, Biol Stn, UPS2682, F-29680 Roscoff, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Paris 05, INSERM U648, Lab Chim Organ 2, F-75006 Paris, France. RP Blondel, M (reprint author), CNRS, Biol Stn, UMR7150, Pl G Teissie R, F-29680 Roscoff, France. EM blondel@sb-roscoff.fr NR 31 TC 27 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2006 VL 39 IS 1 BP 72 EP 77 DI 10.1016/j.ymeth.2006.04.005 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 073WN UT WOS:000239773500011 PM 16750390 ER PT J AU Maguen, S Litz, BT AF Maguen, S Litz, BT TI Predictors of barriers to mental health treatment for Kosovo and Bosnia peacekeepers: A preliminary report SO MILITARY MEDICINE LA English DT Article; Proceedings Paper CT National Meeting of the VA-Health-Services-Research-and-Development-Service CY MAR 10, 2004 CL Washington, DC SP VA Hlth Serv Res Dev Serv ID POSTTRAUMATIC-STRESS-DISORDER; SERVICES; REASONS; CARE AB In this study, we assessed basic, physical, and mental health needs of peacekeepers; determined barriers to mental health treatment; and examined predictors of barriers to mental health care. Active duty peacekeepers were surveyed before and after their deployment to Kosovo (n = 203) concerning their stress symptoms and attitudes about seeking mental health care after peacekeeping. Sixty-five peacekeepers were evaluated before and after their peacekeeping deployment to Bosnia. Upon returning from their mission, between 5% and 9% of Kosovo and Bosnia peacekeepers reported needing help for anger or hostility, depression, or deployment-related stress. The most frequently endorsed barrier was concern about the personal cost of mental health care. Among Kosovo peacekeepers, pre- and postdeployment post-traumatic stress disorder symptoms were the most robust predictors of mental health treatment barriers. Peacekeepers report a number of treatment needs and barriers that could prevent them from receiving care. The soldiers most in need of services are also those who report the most barriers to care. C1 VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Maguen, S (reprint author), Vet Affairs Med Ctr, PTSD Program 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov NR 15 TC 12 Z9 12 U1 2 U2 4 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAY PY 2006 VL 171 IS 5 BP 454 EP 458 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 041ZR UT WOS:000237496800023 PM 16761899 ER PT J AU Affar, E Gay, F Shi, YJ Liu, HF Huarte, M Wu, S Collins, T Li, E Shi, Y AF Affar, E Gay, F Shi, YJ Liu, HF Huarte, M Wu, S Collins, T Li, E Shi, Y TI Essential dosage-dependent functions of the transcription factor Yin Yang 1 in late embryonic development and cell cycle progression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RESTRICTIVE SILENCER FACTOR; P53 TARGET GENES; ELEMENT-BINDING PROTEIN; POLYCOMB GROUP GENE; FACTOR YY1; C-MYC; MAMMALIAN-CELLS; ADENOVIRUS E1A; MICE LACKING; TRANSACTIVATION DOMAIN AB Constitutive ablation of the Yin Yang 1 (YY1) transcription factor in mice results in peri-implantation lethality. In this study, we used homologous recombination to generate knockout mice carrying yy1 alleles expressing various amounts of YY1. Phenotypic analysis of yy1 mutant embryos expressing similar to 75%, similar to 50%, and similar to 25% of the normal complement of YY1 identified a dosage-dependent requirement for YY1 during late embryogenesis. Indeed, reduction of YY1 levels impairs embryonic growth and viability in a dose-dependent manner. Analysis of the corresponding mouse embryonic fibroblast cells also revealed a tight correlation between YY1 dosage and cell proliferation, with a complete ablation of YY1 inducing cytokinesis failure and cell cycle arrest. Consistently, RNA interference-mediated inhibition of YY1 in HeLa cells prevents cytokinesis, causes proliferative arrest, and increases cellular sensitivity to various apoptotic agents. Genome-wide expression profiling identified a plethora of YY1 target genes that have been implicated in cell growth, proliferation, cytokinesis, apoptosis, development, and differentiation, suggesting that YY1 coordinates multiple essential biological processes through a complex transcriptional network. These data not only shed new light on the molecular basis for YY1 developmental roles and cellular functions, but also provide insight into the general mechanisms controlling eukaryotic cell proliferation, apoptosis, and differentiation. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM yang_shi@hms.harvard.edu OI Huarte, Maite/0000-0003-3753-6493 NR 83 TC 64 Z9 69 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2006 VL 26 IS 9 BP 3565 EP 3581 DI 10.1128/MCB.26.9.3565-3581.2006 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 035ID UT WOS:000236993300019 ER PT J AU Isaac, CE Francis, SM Martens, AL Julian, LM Seifried, LA Erdmann, N Binne, UK Harrington, L Sicinski, P Berube, NG Dyson, NJ Dick, FA AF Isaac, CE Francis, SM Martens, AL Julian, LM Seifried, LA Erdmann, N Binne, UK Harrington, L Sicinski, P Berube, NG Dyson, NJ Dick, FA TI The retinoblastoma protein regulates pericentric heterochromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE ARREST; HISTONE DEACETYLASE; S-PHASE; CONSTITUTIVE HETEROCHROMATIN; REPRESSES TRANSCRIPTION; DNA-REPLICATION; G(1) CONTROL; PRB-FAMILY; RB; E2F AB The retinoblastoma protein (pRb) has been proposed to regulate cell cycle progression in part through its ability to interact with enzymes that modify histone tails and create a repressed chromatin structure. We created a mutation in the murine Rb1 gene that disrupted pRb's ability to interact with these enzymes to determine if it affected cell cycle control. Here, we show that loss of this interaction slows progression through mitosis and causes aneuploidy. Our experiments reveal that while the LXCXE binding site mutation does not disrupt pRb's interaction with the Suv4-20h histone methyltransferases, it dramatically reduces H4-K20 trimethylation in pericentric heterochromatin. Disruption of heterochromatin structure in this chromosomal region leads to centromere fusions, chromosome missegregation, and genomic instability. These results demonstrate the surprising finding that pRb uses the LXCXE binding cleft to control chromatin structure for the regulation of events beyond the G(1)-to-S-phase transition. C1 Univ Western Ontario, London Reg Canc Program, London, ON, Canada. Univ Western Ontario, Childrens Hlth Res Inst, London, ON, Canada. Univ Western Ontario, Dept Biochem, London, ON, Canada. Campbell Family Inst Breast Canc Res, Toronto, ON, Canada. Gen Hosp Canc Ctr, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dick, FA (reprint author), Canc Res Labs, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. EM fdick@uwo.ca FU NCI NIH HHS [CA64402, R01 CA064402]; NIA NIH HHS [AG024398, R01 AG024398] NR 60 TC 76 Z9 82 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2006 VL 26 IS 9 BP 3659 EP 3671 DI 10.1128/MCB.26.9.3659-3671.2006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 035ID UT WOS:000236993300026 PM 16612004 ER PT J AU Rowntree, RK Lee, JT AF Rowntree, RK Lee, JT TI Mapping of DNA replication origins to noncoding genes of the X-inactivation center SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; EMBRYONIC STEM-CELLS; POLYMERASE-CHAIN-REACTION; XIST GENE; ASYNCHRONOUS REPLICATION; CHROMOSOME INACTIVATION; INITIATION SITES; MAMMALIAN CHROMOSOMES; EUKARYOTIC ORIGINS; ACTIVE-X AB In mammals, few DNA replication origins have been identified. Although there appears to be an association between origins and epigenetic regulation, their underlying link to monoallelic gene expression remains unclear. Here, we identify novel origins of DNA replication (ORIs) within the X-inactivation center (Xic). We analyze 86 kb of the Xic using an unbiased approach and find an unexpectedly large number of functional ORIs. Although there has been a tight correlation between ORIs and CpG islands, we find that ORIs are not restricted to CpG islands and there is no dependence on transcriptional activity. Interestingly, these ORIs colocalize to important genetic elements or genes involved in X-chromosome inactivation. One prominent ORI maps to the imprinting center and to a domain within Tsix known to be required for X-chromosome counting and choice. Location and/or activity of ORIs appear to be modulated by removal of specific Xic elements. These data provide a foundation for testing potential relationships between DNA replication and epigenetic regulation in future studies. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst,Med Sch,Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst,Med Sch,Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM38895] NR 74 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2006 VL 26 IS 10 BP 3707 EP 3717 DI 10.1128/MCB.26.10.3707-3717.2006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041LV UT WOS:000237458600003 PM 16648467 ER PT J AU Anders, L Mertins, P Lammich, S Murgia, M Hartmann, D Saftig, P Haass, C Ullrich, A AF Anders, L Mertins, P Lammich, S Murgia, M Hartmann, D Saftig, P Haass, C Ullrich, A TI Furin-, ADAM 10-, and gamma-secretase-mediated cleavage of a receptor tyrosine phosphatase and regulation of beta-catenin's transcriptional activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; EPIDERMAL-GROWTH-FACTOR; R-PTP-KAPPA; INTRACELLULAR DOMAIN; HOMOPHILIC BINDING; ENDOTHELIAL-CELLS; SIGNALING PATHWAY; N-CADHERIN; FAMILY; MU AB Several receptor protein tyrosine phosphatases (RPTPs) are cell adhesion molecules involved in homophilic interactions, suggesting that RPTP outside-in signaling is coupled to cell contact formation. However, little is known about the mechanisms by which cell density regulates RPTP function. We show that the MAM family prototype RPTP kappa is cleaved by three proteases: furin, ADAM 10, and gamma-secretase. Cell density promotes ADAM 10-mediated cleavage and shedding of RPTP kappa. This is followed by gamma-secretase-dependent intramembrane proteolysis of the remaining transmembrane part to release the phosphatase intracellular portion (PIC) from the membrane, thereby allowing its translocation to the nucleus. When cells were treated with leptomycin B, a nuclear export inhibitor, PIC accumulated in nuclear bodies. PIC is an active protein tyrosine phosphatase that binds to and dephosphorylates beta-catenin, an RPTP kappa substrate. The expression of RPTP kappa suppresses beta-catenin's transcriptional activity, whereas the expression of PIC increases it. Notably, this increase required the phosphatase activity of PIC. Thus, both isoforms have acquired opposing roles in the regulation of beta-catenin signaling. We also found that RPTP mu, another MAM family member, undergoes gamma-secretase-dependent processing. Our results identify intramembrane proteolysis as a regulatory switch in RPTP kappa signaling and implicate PIC in the activation of beta-catenin-mediated transcription. C1 Max Planck Inst Biochem, Dept Mol Biol, D-82152 Martinsried, Germany. Univ Munich, Lab Alzheimers & Parkinsons Dis Res, Dept Biochem, Adolf Butenandt Inst, D-80336 Munich, Germany. Katholieke Univ Leuven, Dept Human Genet, B-3000 Louvain, Belgium. Flanders Interuniv Inst Biotechnol, B-3000 Louvain, Belgium. Univ Kiel, Inst Biochem, D-24118 Kiel, Germany. RP Anders, L (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM lars_anders@dfci.harvard.edu; ullrich@biochem.mpg.de RI Saftig, Paul/A-7966-2010 NR 48 TC 66 Z9 72 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2006 VL 26 IS 10 BP 3917 EP 3934 DI 10.1128/MCB.26.10.3917-3934.2006 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041LV UT WOS:000237458600021 PM 16648485 ER PT J AU Puebla-Osorio, N Lacey, DB Alt, FW Zhu, CM AF Puebla-Osorio, N Lacey, DB Alt, FW Zhu, CM TI Early embryonic lethality due to targeted inactivation of DNA ligase III SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STRAND BREAK REPAIR; BASE-EXCISION-REPAIR; POLYMERASE-BETA; POLY(ADP-RIBOSE) POLYMERASE; V(D)J RECOMBINATION; MOLECULAR-CLONING; MEIOTIC RECOMBINATION; XRCC1 PROTEIN; GENE ENCODES; ZINC-FINGER AB DNA ligases catalyze the joining of strand breaks in the phosphodiester backbone of duplex DNA and play essential roles in DNA replication, recombination, repair, and maintenance of genomic integrity. Three mammalian DNA ligase genes have been identified, and their corresponding ligases play distinct roles in DNA metabolism. DNA ligase III is proposed to be involved in the repairing of DNA single-strand breaks, but its precise role has not yet been demonstrated directly. To determine its role in DNA repair, cellular growth, and embryonic development, we introduced targeted interruption of the DNA ligase III (LIG3) gene into the mouse. Mice homozygous for LIG3 disruption showed early embryonic lethality. We found that the mutant embryonic developmental process stops at 8.5 days postcoitum (dpc), and excessive cell death occurs at 9.5 dpc. LIG3 mutant cells have relatively normal XRCC1 levels but elevated sister chromatid exchange. These findings indicate that DNA ligase III is involved in essential DNA repair activities required for early embryonic development and therefore cannot be replaced by other DNA ligases. C1 Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. Childrens Hosp, Howard Hughes Med Inst, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zhu, CM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Immunol, 1515 Holcombe Blvd,Unit 902, Houston, TX 77030 USA. EM czhu@mdanderson.org FU NIAID NIH HHS [AI35714, P01 AI035714] NR 56 TC 57 Z9 58 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2006 VL 26 IS 10 BP 3935 EP 3941 DI 10.1128/MCB.26.10.3935-3941.2006 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 041LV UT WOS:000237458600022 PM 16648486 ER PT J AU Seijffers, R Allchorne, AJ Woolf, CJ AF Seijffers, R Allchorne, AJ Woolf, CJ TI The transcription factor ATF-3 promotes neurite outgrowth SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID DORSAL-ROOT GANGLION; PRIMARY SENSORY NEURONS; MESSENGER-RNA EXPRESSION; PERIPHERAL-NERVE GRAFTS; INJURED SPINAL-CORD; C-JUN; AXONAL REGENERATION; ADULT-RATS; GAP-43 EXPRESSION; MOLECULAR-BIOLOGY AB Dorsal root ganglion (DRG) neurons regenerate after a peripheral nerve injury but not after injury to their axons in the spinal cord. A key question is which transcription factors drive the changes in gene expression that increase the intrinsic growth state of peripherally injured sensory neurons? A prime candidate is activating transcription factor-3 (ATF-3), a transcription factor that we find is induced in all DRG neurons after peripheral, but not central axonal injury. Moreover, we show in adult DRG neurons that a preconditioning peripheral, but not central axonal injury, increases their growth, correlating closely with the pattern of ATF-3 induction. Using viral vectors, we delivered ATF-3 to cultured adult DRG neurons and find that ATF-3 enhances neurite outgrowth. Furthermore, ATF-3 promotes long sparsely branched neurites. ATF-3 overexpression did not increase c-Jun expression. ATF-3 may contribute, therefore, to neurite outgrowth by orchestrating the gene expression responses in injured neurons. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. EM woolf.clifford@mgh.harvard.edu NR 86 TC 115 Z9 118 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY-JUN PY 2006 VL 32 IS 1-2 BP 143 EP 154 DI 10.1016/j.mcn.2006.03.005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 058TZ UT WOS:000238688800012 PM 16713293 ER PT J AU Kiener, HP Stipp, CS Allen, PG Higgins, JMG Brenner, MB AF Kiener, HP Stipp, CS Allen, PG Higgins, JMG Brenner, MB TI The cadherin-11 cytoplasmic juxtamembrane domain promotes alpha-catenin turnover at adherens junctions and intercellular motility SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-CELL ADHESION; MEMBRANE-PROXIMAL REGION; BETA-CATENIN; PHOSPHATIDYLINOSITOL 3-KINASE; P120 CATENIN; RHO GTPASES; N-CADHERIN; C-CADHERIN; COMPLEX; MORPHOGENESIS AB Cadherins mediate homophilic cell adhesion and contribute to tissue morphogenesis and architecture. Cadherin cell adhesion contacts are actively remodeled and impact cell movement and migration over other cells. We found that expression of a mutant cadherin-11 lacking the cytoplasmic juxtamembrane domain (JMD) diminished the turnover of a-catenin at adherens junctions as measured by fluorescence recovery after photobleaching. This resulted in markedly diminished cell intercalation into monolayers reflecting reduced cadherin-11-dependent cell motility on other cells. Furthermore, the actin cytoskeleton in cadherin-11 Delta JMD cells revealed a more extensive cortical F-actin ring that correlated with significantly higher levels of activated Rac1. Together, these data implicate the cadherin-11 cytoplasmic JMD as a regulator of alpha-catenin turnover at adherens junctions and actin-cytoskeletal organization that is critical for intercellular motility and rearrangement in multicellular clusters. C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Brenner, MB (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. EM mbrenner@rics.bwh.harvard.edu FU NCI NIH HHS [CA-86712, R01 CA086712]; NIAMS NIH HHS [AR48114, R01 AR048114] NR 48 TC 24 Z9 26 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2006 VL 17 IS 5 BP 2366 EP 2376 DI 10.1091/mbc.E05-08-0745 PG 11 WC Cell Biology SC Cell Biology GA 040KZ UT WOS:000237378800025 PM 16525026 ER PT J AU Gerweck, LE Vijayappa, S Kozin, S AF Gerweck, LE Vijayappa, S Kozin, S TI Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID M-IODOBENZYLGUANIDINE; INTRACELLULAR PH; INTERSTITIAL PH; CYTOTOXICITY; ADRIAMYCIN; GRADIENT; CELLS; BINDING; OXYGEN; PHARMACOKINETICS AB The extracellular pH of tumor tissue is significantly lower than the extracellular pH of normal tissue, whereas the intracellular pH of both tissues is similar. In principle, extracellular acidity may be expected to enhance the intracellular uptake and cytotoxicity of weak acid chemotherapeutics that are membrane permeable in their uncharged state and inhibit the efficacy of weak bases. However, procedures for assessing the role of the gradient as a determinant of drug efficacy in vivo by altering the pH gradient may also alter drug availability and thus mask or exaggerate the effect of the gradient change. In the present study, we have altered the extracellular pH of tumors and compared the effect of the resultant pH gradient change on the efficacy of a weak acid versus a weak base. This experimental design gives rise to a change in the ratio of chlorambucil- to doxorubicin-induced tumor growth delay, independent of possible changes in drug availability. The extracellular pH of the 54A human tumor in NCr/Sed/nu/nu mice was altered by administration of 5 mg/g i.v. glucose. The resultant 0.2 pH unit increase in the tumor cell pH gradient gives rise to a predicted 2.3-fold increase in the ratio of chlorambucil to doxorubicin growth delay. The experimentally measured change in the growth delay ratio was 2.1. The results provide compelling evidence that the pH gradient in a determinant of the efficacy of weak electrolytes in the complex in vivo environment and may be exploited for the treatment of cancer. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gerweck, LE (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM lgerweck@partners.org FU NCI NIH HHS [R01 CA092366] NR 38 TC 155 Z9 169 U1 2 U2 28 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2006 VL 5 IS 5 BP 1275 EP 1279 DI 10.1158/1535-7163.MCT-06-0024 PG 5 WC Oncology SC Oncology GA 050FV UT WOS:000238073800021 PM 16731760 ER PT J AU Sakata, S Lebeche, D Sakata, Y Sakata, N Chemaly, ER Liang, LF Padmanabhan, P Konishi, N Takaki, M del Monte, F Hajjar, RJ AF Sakata, S Lebeche, D Sakata, Y Sakata, N Chemaly, ER Liang, LF Padmanabhan, P Konishi, N Takaki, M del Monte, F Hajjar, RJ TI Mechanical and metabolic rescue in a type II diabetes model of cardiomyopathy by targeted gene transfer SO MOLECULAR THERAPY LA English DT Article DE gene therapy; heart failure; SERCA2a; energetic function; diabetes mellitus ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; HEART-FAILURE; RENAL COMPLICATIONS; RYANODINE RECEPTOR; HUMAN MYOCARDIUM; NA/CA EXCHANGE; OXYGEN COST; RAT MODEL; DYSFUNCTION; CONTRACTILITY AB The Otsuka-Long-Evans Tokushima Fatty rat represents a model for spontaneous non-insulin-dependent type 11 diabetes mellitus (DM), characterized by diastolic dysfunction and associated with abnormal calcium handling and decrease in sarcoplasmic reticulum Ca 2(+)-ATPase (SERCA2a) expression. The aim of this study was to examine whether SERCA2a gene transfer can restore the energetic deficiency and left ventricular (LV) function in this model. DM rats were randomized to receive adenovirus carrying either the SERCA2a gene (DM + Ad.SERCA2a) or the beta-galactosidase gene (DM + Acl.beta Gal) or saline (DM + saline). LV mechanoenergetic function was measured in cross-circulated heart preparations 3 days after infection. In DM, end-systolic pressure at 0.1 ml intraballoon water (ESP0.1) was low and end-diastolic pressure at 0.1 ml intraballoon water (EDP0.1) was high (22 mm Hg), compared with non-DM (EDP0.1 12 mm Hg). In DM + Ad.SERCA2a, however, ESP0.1 was increased over 200 mm Hg and EDP0.1 was decreased to 7 mm Hg. LV relaxation rate was fast in DM + Ad.SERCA(2)a, but slow in the other DM groups. There was no difference in relation between cardiac oxygen consumption per beat and systolic pressure-volume area among all groups. Finally, the oxygen cost of LV contractility in DM was about three times as high as that of normal. In DM + Ad.SERCA2a, the oxygen cost decreased to control levels, but in DM + Ad.pGal/DM + saline it remained high. In DM failing hearts, the high oxygen cost indicates energy wasting, which contributes to the contractile dysfunction observed in diabetic cardiomyopathy. SERCA2a gene transfer transforms this inefficient energy utilization into a more efficient state and restores systolic and diastolic function to normal. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Lab Integrat Physiol & Imaging, Charlestown, MA 02129 USA. Nara Med Univ, Dept Pathol, Kashihara, Nara 6348521, Japan. Nara Med Univ, Dept Physiol 2, Kashihara, Nara 6348521, Japan. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Lab Integrat Physiol & Imaging, 149 13th St,CNY-4, Charlestown, MA 02129 USA. EM rhajjar@partners.org FU NHLBI NIH HHS [HL71763, K08 HL069842, R01 HL078691, HL057263, K01 HL076659] NR 34 TC 35 Z9 38 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 IS 5 BP 987 EP 996 DI 10.1016/j.ymthe.2006.01.002 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 042JA UT WOS:000237523000021 PM 16503203 ER PT J AU Badr, CE Zalloua, P Breakefield, XO Tannous, BA AF Badr, Christian E. Zalloua, Pierre Breakefield, Xandra O. Tannous, Bakhos A. TI Imaging of Radiation-Inducible Promoters Using a Naturally Secreted Luciferase from the Marine Copepod Gaussia princeps SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Badr, Christian E.; Breakefield, Xandra O.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Mol Neurogenet Uit, Boston, MA 02114 USA. [Badr, Christian E.; Breakefield, Xandra O.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Breakefield, Xandra O.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Badr, Christian E.; Zalloua, Pierre] Amer Univ Beirut, Cellular & Mol Biol Unit, Beirut, Lebanon. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 956 BP S369 EP S369 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502354 ER PT J AU Broekman, MLD Baek, R Comer, LA Seyfried, TN Sena-Esteves, M AF Broekman, Marike L. D. Baek, Rena Comer, Laryssa A. Seyfried, Thomas N. Sena-Esteves, Miguel TI Complete Correction of Enzymatic Deficiency and Lysosomal Storage throughout the Brain in a Mouse Model of GM1-gangliosidosis after Neonatal Intracerebroventricular Injection of an AAV1 Vector Encoding Lysosomal Acid Betagalactosidase SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Broekman, Marike L. D.; Comer, Laryssa A.; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Broekman, Marike L. D.; Baek, Rena; Comer, Laryssa A.; Seyfried, Thomas N.; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Broekman, Marike L. D.] Univ Med Ctr Utrecht, Rudolph Magnus Inst Neurosci, Dept Pharmacol & Anat, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 409 BP S157 EP S157 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501333 ER PT J AU Chemaly, ER Pomerantseva, I Yoneyama, R Lebeche, D Gianni, D Hoshino, K Kawase, Y del Monte, F Hajjar, RJ AF Chemaly, Elie R. Pomerantseva, Irina Yoneyama, Ryuichi Lebeche, Djamel Gianni, Davide Hoshino, Kozo Kawase, Yoshiaki del Monte, Federica Hajjar, Roger J. TI Tracking and Gene Expression Profile of Bone Marrow Mesenchymal Stem Cells Injected into Pig Myocardium by Magnetic Resonance Imaging and Laser-Capture Microdissection SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Chemaly, Elie R.; Pomerantseva, Irina; Yoneyama, Ryuichi; Lebeche, Djamel; Gianni, Davide; Hoshino, Kozo; Kawase, Yoshiaki; del Monte, Federica; Hajjar, Roger J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chemaly, Elie R.; Pomerantseva, Irina; Yoneyama, Ryuichi; Lebeche, Djamel; Gianni, Davide; Hoshino, Kozo; Kawase, Yoshiaki; del Monte, Federica; Hajjar, Roger J.] Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 1042 BP S399 EP S400 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502439 ER PT J AU Comer, LA Fernandez, JL Camp, SM Tebbets, JC Breakefield, XO Sena-Esteves, M AF Comer, Laryssa A. Fernandez, Juliet L. Camp, Sara M. Tebbets, Jessica C. Breakefield, Xandra O. Sena-Esteves, Miguel TI Tetracycline-Inducible HSV Amplicon Vectors with Expanded Range of Gene Expression Regulation SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Comer, Laryssa A.; Fernandez, Juliet L.; Camp, Sara M.; Breakefield, Xandra O.; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Neurol Dept, Charlestown, MA USA. [Comer, Laryssa A.; Fernandez, Juliet L.; Camp, Sara M.; Breakefield, Xandra O.; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Tebbets, Jessica C.] Childrens Hosp Philadelphia, Surg Dept, Philadelpia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 154 BP S60 EP S60 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501078 ER EF