FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Thomas, SH Winsor, GR Pang, PS Driscoll, KA Parry, BA AF Thomas, SH Winsor, GR Pang, PS Driscoll, KA Parry, BA TI Use of a radial artery compression device for noninvasive, near-continuous blood pressure monitoring in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston MedFlight, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 109 BP S30 EP S30 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200108 ER PT J AU Wittels, KA Mello, MJ Palmisciano, L AF Wittels, KA Mello, MJ Palmisciano, L TI The effectiveness of a scooter safety video as a teaching method in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. Brown Med Sch, Providence, RI USA. Rhode Isl Hosp, Providence, RI USA. Hasbro Childrens Hosp, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 63 BP S18 EP S18 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200063 ER PT J AU Ness, RB Bondy, ML Branas, C Camargo, CA Rothenberg, R Samet, JM Sandler, DP Swanson, GM Strom, BL AF Ness, RB Bondy, ML Branas, C Camargo, CA Rothenberg, R Samet, JM Sandler, DP Swanson, GM Strom, BL TI Untitled SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material ID DISSENT; ADVICE C1 Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Sch Med, Amer Coll Epidemiol Policy Comm, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Natl Inst Environm Hlth Sci, Chapel Hill, NC USA. RP Ness, RB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2003 VL 13 IS 9 BP 597 EP 598 DI 10.1016/j.annepidem.2003.09.001 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 737PM UT WOS:000186241000001 PM 14732297 ER PT J AU Schupf, N Pang, D Patel, BN Silverman, W Schubert, R Lai, F Kline, JK Stern, Y Ferin, M Tycko, B Mayeux, R AF Schupf, N Pang, D Patel, BN Silverman, W Schubert, R Lai, F Kline, JK Stern, Y Ferin, M Tycko, B Mayeux, R TI Onset of dementia is associated with age at menopause in women with Down's syndrome SO ANNALS OF NEUROLOGY LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; OLDER COMMUNITY WOMEN; ALZHEIMERS-DISEASE; POSTMENOPAUSAL WOMEN; COGNITIVE FUNCTION; BASAL FOREBRAIN; BETA PEPTIDES; SEX-HORMONES; RISK; ESTRADIOL AB Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD. C1 Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Neurol, Belmont, MA USA. McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Dept Neurol & Psychiat, New York, NY 10032 USA. RP Schupf, N (reprint author), Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, POB 16,630 W 168th St, New York, NY 10032 USA. FU NIA NIH HHS [AG14673, P50AG08702]; NICHD NIH HHS [HD37425, HD35897] NR 55 TC 55 Z9 55 U1 2 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2003 VL 54 IS 4 BP 433 EP 438 DI 10.1002/ana.10677 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 727QU UT WOS:000185670600004 PM 14520653 ER PT J AU Shamberger, RC LaQuaglia, MP Gebhardt, MC Neff, JR Tarbell, NJ Marcus, KC Sailer, SL Womer, RB Miser, JS Dickman, PS Perlman, EJ Devidas, M Linda, SB Krailo, MD Grier, HE Granowetter, L AF Shamberger, RC LaQuaglia, MP Gebhardt, MC Neff, JR Tarbell, NJ Marcus, KC Sailer, SL Womer, RB Miser, JS Dickman, PS Perlman, EJ Devidas, M Linda, SB Krailo, MD Grier, HE Granowetter, L TI Ewing sarcoma/primitive neuroectodermal tumor of the chest wall - Impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 123rd Annual Meeting of the American-Surgical-Association CY APR 24-26, 2003 CL WASHINGTON, D.C. SP a, Amer Surg Assoc ID HODGKINS-DISEASE; 2ND MALIGNANCIES; SARCOMA; RIB; CHEMOTHERAPY; CHILDREN; BONE AB Objective: To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. Methods: Patients less than or equal to30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. Results: Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). Conclusion: The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Univ Nebraska, Med Ctr, Dept Orthoped Surg, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. UNC, Sch Med, Dept Radiat Oncol, Chapel Hill, NC USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. City Hope Natl Med Ctr, Div Pediat, Duarte, CA USA. Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. Childrens Mem Med Ctr, Dept Pathol, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Florida, Childrens Oncol Grp Res Data Ctr, Gainesville, FL USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Childrens Hosp, Herbert Irving Child & Adolescent Canc Ctr, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Shamberger, RC (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. OI Granowetter MD, Linda/0000-0002-2399-9107 FU NCI NIH HHS [CA-29233, CA-07306, CA-03888, CA-03161, CA-13809, CA-045587, CA-15989, CA-31566, CA-28439, CA-29691, CA-29314, CA-05436, CA-33603, CA-36015, CA-26126, CA-33625, CA-28851, CA-27678, CA-03526, CA-07431, CA-10198, CA-28383, CA-02649, CA-32053, CA-33587, CA-05587, CA-30969, U10 CA029139, CA-41573, CA-11796, CA-03750, CA-02971, CA-11233, CA-28882, CA-26044, CA-28476, CA-26270, CA-13539, CA-14560, CA-29013, CA-15525, CA-42764, CA-69428, CA-25408, CA-69177, CA-20320, CA-17829, CA-29293, CA-20549, CA-53128] NR 16 TC 40 Z9 45 U1 0 U2 2 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 OCT PY 2003 VL 238 IS 4 BP 563 EP 567 DI 10.1097/01.sla.0000089857.45191.52 PG 5 WC Surgery SC Surgery GA 732DX UT WOS:000185926500022 PM 14530727 ER PT J AU Cusack, JC AF Cusack, JC TI Overcoming antiapoptotic responses to promote chemosensitivity in metastatic colorectal cancer to the liver SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE chemotherapy resistance; apoptosis; NF-kappa B; colon cancer; liver metastases ID NF-KAPPA-B; INDUCED APOPTOSIS; CELL-DEATH; IN-VIVO; INDUCIBLE CHEMORESISTANCE; MULTIDRUG-RESISTANCE; PROTEASOME INHIBITOR; TUMOR-DEVELOPMENT; ANTICANCER DRUGS; P-GLYCOPROTEIN AB Background: Metastatic colon cancer is highly resistant to chemotherapy. A variety of mechanisms by which cancer cells resist chemotherapy have been described including enhanced export of drug from cancer cells and alterations in drug metabolism. In addition, the response of cancer cells to genotoxic therapies may be diminished by acquired defects in either the response mechanisms to DNA damage or cell cycle regulatory pathways. Recently, attention has focused on mechanisms that are activated by treatment exposure and subsequently promote resistance by rescuing cancer cells from apoptosis. The objective of this review is to examine the role of antiapoptotic mechanisms of chemotherapy resistance and to determine the potential utility of therapeutic strategies that target these mechanisms. Methods: To accomplish the objectives, a brief overview of mechanisms of chemotherapy resistance is provided. The concept of inducible chemotherapy resistance is introduced by examination of a specific antiapoptotic mechanism, mediated by the transcription factor, nuclear factor kappa B (NF-kappaB). The ability to use inhibitors of NF-kappaB to promote chemosensitivity is examined in vitro and in vivo. Results: Inhibition of chemotherapy-induced NF-kappaB activation enhances apoptosis and augments chemotherapy sensitivity. Conclusions: NF-kappaB inhibition may overcome cancer cell defense against apoptosis. Molecular therapies that target this resistance mechanism may be useful adjuncts to conventional chemotherapy. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 100 Blossom St,Cox 626, Boston, MA 02114 USA. NR 55 TC 24 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2003 VL 10 IS 8 BP 852 EP 862 DI 10.1245/ASO.2003.07.518 PG 11 WC Oncology; Surgery SC Oncology; Surgery GA 729LZ UT WOS:000185776200009 PM 14527902 ER PT J AU Guccione, JM Salahieh, A Moonly, SM Kortsmit, J Wallace, AW Ratcliffe, MB AF Guccione, JM Salahieh, A Moonly, SM Kortsmit, J Wallace, AW Ratcliffe, MB TI Myosplint decreases wall stress without depressing function in the failing heart: A finite element model study SO ANNALS OF THORACIC SURGERY LA English DT Article ID MYOCARDIAL OXYGEN-CONSUMPTION; PARTIAL LEFT VENTRICULECTOMY; VOLUME REDUCTION SURGERY; LEFT-VENTRICLE; DILATED CARDIOMYOPATHY; RESIDUAL-STRESS; FAILURE; HYPERTROPHY; DYSFUNCTION; EXPRESSION AB Background. The Myocor Myosplint is a transcavitary tensioning device designed to change left ventricular (LV) shape and reduce wall stress. Regional wall stress cannot be measured in the intact heart and LV function after surgical remodeling is often confounded by inotropic agents and mitral repair. We used a realistic mathematical (finite element) model of the dilated human LV to test the hypothesis that Myosplint decreased regional ventricular fiber stress and improved LV function. Methods. A finite element model was used to simulate the effects of Myosplint on the LV stroke volume/enddiastolic pressure (Starling) relationship and regional distributions of stress in the local muscle fiber direction (fiber stress) for a wide range of diastolic and endsystolic material properties. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the globally dilated LV wall. Results. Both diastolic compliance and end-systolic elastance shifted to the left on the pressure-volume diagram. LV end-diastolic volume and end-systolic volumes were reduced by 7.6% and 8.6%, respectively. Mean end-diastolic and end-systolic fiber stress was decreased by 24% and 16%, respectively. Although the effect of Myosplint on the Starling relationship was not significant, there were trends toward an improvement in this relationship at low diastolic stiffness, C, high peak intracellular calcium concentration, Ca-0, and high arterial elastance, E-A. Of note, the effect of C was twice that of Ca-0 and E-A. Diastolic function would, therefore, be expected to be the prime determinant of success with Myosplint. Conclusions. Myosplint reduces fiber stress without a decrement in the Starling relationship. Myosplint should be much more effective than partial ventriculectomy as a surgical therapy for patients with dilated cardiomyopathy and end-stage congestive heart failure. C1 San Francisco Vet Affairs Med Ctr, Div Surg Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Surg, Dept Bioengn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, Div Cardiothorac Surg, San Francisco, CA 94143 USA. Maastricht Univ, Dept Biophys, Maastricht, Netherlands. RP Guccione, JM (reprint author), San Francisco Vet Affairs Med Ctr, Div Surg Serv, 112D,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01-HL-58759, R01-HL-63348] NR 35 TC 29 Z9 29 U1 0 U2 1 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 OCT PY 2003 VL 76 IS 4 BP 1171 EP 1180 AR PII S0003-4975(03)00731-8 DI 10.1016/S0003-4975(03)00731-8 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 728LD UT WOS:000185717900046 PM 14530007 ER PT J AU Liu, C Chambers, HF AF Liu, C Chambers, HF TI Staphylococcus aureus with heterogeneous resistance to vancomycin: Epidemiology, clinical significance, and critical assessment of diagnostic methods SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID REDUCED SUSCEPTIBILITY; METHICILLIN; INTERMEDIATE; GLYCOPEPTIDES; HOSPITALS; ENDOCARDITIS; INFECTIONS; STRAINS; BACTEREMIA; EMERGENCE C1 Univ Calif San Francisco, San Francisco Gen Hosp, Div Infect Dis, San Francisco, CA USA. San Francisco Sch Med, San Francisco, CA USA. RP Liu, C (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 635,Suite F, Boston, MA 02114 USA. FU NIAID NIH HHS [AI43959] NR 41 TC 208 Z9 221 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 OCT PY 2003 VL 47 IS 10 BP 3040 EP 3045 DI 10.1128/AAC.47.10.3040-3045.2003 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 726RH UT WOS:000185612600002 PM 14506006 ER PT J AU Serena, C Ortoneda, M Capilla, J Pastor, FJ Sutton, DA Rinaldi, MG Guarro, J AF Serena, C Ortoneda, M Capilla, J Pastor, FJ Sutton, DA Rinaldi, MG Guarro, J TI In vitro activities of new antifungal agents against Chaetomium spp. and inoculum standardization SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FILAMENTOUS FUNGI; AMPHOTERICIN-B; SUSCEPTIBILITY; ASPERGILLUS; CASPOFUNGIN; ITRACONAZOLE; FUSARIUM; MK-0991; SYNERGY AB Chaetomium is an unusual etiological agent of human infections, but the mortality rate among immunocompromised patients is considerably greater than that among nonimmunocompromised individuals. We investigated the in vitro antifungal susceptibilities to novel antifungal agents of 19 strains belonging to three species of Chaetomium which have been involved in human infections, i.e., Chaetomium globosum, C. atrobrunneum, and C. nigricolor, and one strain of the closely related species Achaetomium strumarium. A modification of the NCCLS reference microdilution method (M38-A) was used to evaluate the in vitro activities of ravuconazole, voriconazole, albaconazole, and micafungin. Micafungin was not active at all, while the geometric mean MICs and minimum effective concentrations of the three triazoles were less than 0.5 and 0.4 mug/ml, respectively. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. Univ Rovira & Virgili, Fac Med & Ciencies Salut, Unitat Microbiol, E-43201 Reus, Spain. RP Guarro, J (reprint author), Univ Rovira & Virgili, Fac Med, Unitat Microbiol, Carrer St Llorenc 21, E-43201 Reus, Spain. RI Capilla, Javier/H-4689-2015; OI Capilla, Javier/0000-0002-0765-6403; Serena, Carolina/0000-0003-2251-0856; Guarro, Josep/0000-0002-7839-7568 NR 18 TC 28 Z9 28 U1 0 U2 9 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 OCT PY 2003 VL 47 IS 10 BP 3161 EP 3164 DI 10.1128/AAC.47.10.3161-3164.2003 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 726RH UT WOS:000185612600021 PM 14506025 ER PT J AU Hartnick, CJ Bissell, C Parsons, SK AF Hartnick, CJ Bissell, C Parsons, SK TI The impact of pediatric tracheotomy on parental caregiver burden and health status SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; TRACHEOSTOMY; CHILDREN; EXPERIENCE; STRESS AB Objective: To explore the effects of the placement of a pediatric tracheotomy tube on the degree of caregiver burden and overall health status of parents using general and disease-specific instruments. Methods: Between January and July 2001, the Medical Outcomes Study Short Form 12 (SF-12) and the Pediatric Tracheotomy Health Status Instrument (PTHSI) were administered to 154 families of children requiring tracheotomy. Summary scores were generated for each of the 2 scales of the SF-12 (the Physical Component Score [PCS] and the Mental Component Score [MCS]) as well as for the 4 previously established domains of the PTHSI: domain 1, physical symptoms of the child (7 items) domain 2, medical visits and cost (7 items); domain 3, parental rating of the child's psychological health status (3 items); and domain 4, parental rating of their own caregiver burden (17 items). Correlations between responses from the individual domains and between domain 4 of the PTHSI (reflecting caregiver burden) and the SF-12 were performed. Results: The mean +/-SD summary scores for the 4 domains of the PTHSI were domain 1, 22.7+/-5.3; domain 2, 24.9+/-6.2; domain 3, 10.5+/-4.4; and domain 4,48.3+/-9.5 (lower scores reflect "poorer" health status). The mean +/-SD summary scores of PCS and MCS were 50.5+/-11.3 and 35.8+/-11.4, respectively. There existed a significant correlation between parental caregiver burden (as expressed by domain 4) and the child's physical health status (domain 1) (0.32; P<.001) as well as between parental caregiver burden and increasing economic costs associated with this care (0.27; P<.001). A strong correlation was found between the domain measuring parental caregiver burden (domain 4) and the MCS-12 (r=0.43; P<.001), while a poor correlation existed with the PCS-12 (r=-0.17; P=.14). Nevertheless, in contrast to caregiver burden, the health status of the caregivers as measured by the SF-12 did not alter according to the severity of illness for the children (P=.17). Conclusions: Parents caring for children with tracheotomy tubes experience significant caregiver burden. These parents appear to experience increased burden with respect to the child's severity of illness and increased costs associated with caring for their children. Overall, the mental health status for an adult caring for a child with a tracheotomy tube is significantly reduced and appears to be more affected than physical health status. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 21 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2003 VL 129 IS 10 BP 1065 EP 1069 DI 10.1001/archotol.129.10.1065 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 732FN UT WOS:000185930300007 PM 14568788 ER PT J AU Hartnich, CJ Volk, M Cunningham, M AF Hartnich, CJ Volk, M Cunningham, M TI Establishing normative voice-related quality of life scores within the pediatric otolaryngology population SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID OUTCOME SURVEY; VALIDATION; INSTRUMENT AB Objective: To establish normative values for voice-related quality of life across a broad pediatric otolaryngology population using the Pediatric Voice Outcome Survey (PVOS). Design: Longitudinal study. Setting: Multiphysician outpatient pediatric otolaryngology practice. Methods: The PVOS was completed by 385 parents of children and adolescents aged 2 to 18 years. Of the 385 parents, 75 were readministered the instrument 2 weeks after no intervention had been provided. Data were collected regarding the patients' age, main diagnosis, and operative intervention. Results: The PVOS demonstrated robust internal consistency with an overall Cronbach a value of .70. Test-retest reliability demonstrated a weighted K value of 0.89 (95% confidence interval, 0.84-0.95) The mean +/-SD converted score (based on a 0-100 scale) for the overall population was 80.5+/-19.9. Converted PVOS scores are provided for each subpopulation according to main diagnosis. The PVOS scores varied significantly according to age (P<.05) and preoperative and postoperative status following adenoidectomy (P<.05). Conclusion: The PVOS represents a valid and reliable instrument to measure voice-related quality of life in a broad pediatric otolaryngology population. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Hartnich, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. OI Volk, Mark/0000-0001-5708-5808 NR 11 TC 22 Z9 26 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2003 VL 129 IS 10 BP 1090 EP 1093 DI 10.1001/archotol.129.10.1090 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 732FN UT WOS:000185930300013 PM 14568793 ER PT J AU Liu, JH Etzioni, DA O'Connell, JB Maggard, MA Hiyama, DT Ko, CY AF Liu, JH Etzioni, DA O'Connell, JB Maggard, MA Hiyama, DT Ko, CY TI Inpatient surgery in California: 1990-2000 SO ARCHIVES OF SURGERY LA English DT Article ID COMORBIDITY INDEX; TRENDS AB Background: The practice environment for surgery is changing. However, little is known regarding the trends or current status of inpatient surgery at a population level. Hypothesis: inpatient surgical care has changed significantly over the last 10 years. Design: Longitudinal analysis of California inpatient discharge data (January 1, 1990, through December 31, 2000). Setting: All 503 nonfederal acute care hospitals in California. Patients: All inpatients undergoing general, vascular, and cardiothoracic surgery in California from January 1, 1990, through December 31, 2000, were obtained. Main Outcome Measures: Volume, mean age, comorbidity profile, length of hospital stay, and inhospital mortality were obtained for inpatient general, vascular, and cardiothoracic surgical procedures performed during the period 1990 to 2000. Rates of change and trends were evaluated for the 10-year period. Results: Between January 1, 1990, and December 31, 2000, 1.64 million surgical procedures were performed. The number of surgical procedures increased 20.4%, from 135 795 in 1990 to 163 468 in 2000. Overall, patients were older and had more comorbid disease in 2000 compared with 1990. Both crude and adjusted (by type of operation) in-hospital mortality decreased from 3.9% in 1990 to 2.75% (P<.001) and 2.58% (P<.001), respectively, in 2000. Length of hospital stay decreased over the period for all operations analyzed. Conclusions: The total number of inpatient general, vascular, and cardiothoracic surgical procedures has increased over the past decade. Furthermore, our findings indicate that the outcomes of care (eg, in-hospital mortality and length of hospital stay) for patients who undergo general, vascular, and cardiothoracic surgical procedures have improved. However, continued evaluations at the population level are needed. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Admin, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Admin, Dept Gen Internal Med, Los Angeles, CA USA. RP Liu, JH (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. NR 11 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD OCT PY 2003 VL 138 IS 10 BP 1106 EP 1111 DI 10.1001/archsurg.138.10.1106 PG 6 WC Surgery SC Surgery GA 734UG UT WOS:000186075900013 PM 14557128 ER PT J AU Friedrich, EB Tager, AM Liu, E Pettersson, A Owman, C Munn, L Luster, AD Gerszten, RE AF Friedrich, EB Tager, AM Liu, E Pettersson, A Owman, C Munn, L Luster, AD Gerszten, RE TI Mechanisms of leukotriene B-4-triggered monocyte adhesion SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article ID T-CELL-ACTIVATION; ENDOTHELIAL-CELLS; SIGNAL-TRANSDUCTION; FLOW CONDITIONS; PHOSPHOINOSITIDE 3-KINASE; P-SELECTIN; IN-VITRO; B-4; ATHEROSCLEROSIS; MICE AB Objective - Leukotriene B-4 (LTB4) has been implicated in the trafficking of monocytes to inflammatory pathologicconditions, such as transplant rejection and atherosclerosis. The aim of this study was to determine the mechanisms by which LTB4 contributes to monocyte capture from the circulation. Methods and Results - In in vitro and in vivo vascular models, the lipid chemoattractant LTB4 was an equipotent agonist of monocyte adhesion compared with the chemokine monocyte chemoattractant protein-1 (MCP-1). Adenoviral gene transfer of specific endothelial adhesion molecules and blocking monoclonal antibody studies demonstrated that LTB4 triggers both beta(1)- and beta(2)-integrin-dependent adhesion. Flow cytometry studies suggested that changes in integrin avidity or affinity, rather than alterations of integrin surface expression, were responsible for the chemoattractant-triggered arrest. Surprisingly, in contrast to the peptide chemokine MCP-1, LTB4 did not activate the phosphoinositide 3-kinase pathway, which is a functionally critical step in chemokine-triggered effector functions. Conclusions - LTB4 is a potent trigger of monocyte adhesion under flow yet mediates its effects via pathways that appear to differ from peptide chemoattractants. A better understanding of the mechanisms of LTB4-induced monocyte trafficking might shed insight into disease pathogenesis and pinpoint critical steps for therapeutic intervention for multiple human inflammatory pathologic conditions. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA USA. Lund Univ, Wallenberg Neurosci Ctr, Lund, Sweden. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp East 8307, Ctr Immunol & Inflammatory Dis, 149 13th St, Charlestown, MA 02129 USA. NR 36 TC 49 Z9 52 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 OCT PY 2003 VL 23 IS 10 BP 1761 EP 1767 DI 10.1161/01.ATV.0000092941.77774.3C PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 730VE UT WOS:000185850200013 PM 12947016 ER PT J AU Michaud, K Messer, J Choi, HK Wolfe, F AF Michaud, K Messer, J Choi, HK Wolfe, F TI Direct medical costs and their predictors in patients with rheumatoid arthritis - A three-year study of 7,527 patients SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DISEASE-ACTIVITY INDEX; HEALTH SURVEY SF-36; SERVICE UTILIZATION; MANAGED CARE; RISK-FACTORS; OSTEOARTHRITIS; RELIABILITY; VALIDITY; QUESTIONNAIRE; CONSEQUENCES AB Objective. To estimate total direct medical costs in persons with rheumatoid arthritis (RA) and to characterize predictors of these costs. Methods. Patients (n = 7,527) participating in a longitudinal study of outcome in RA completed 25,050 semiannual questionnaires from January 1999 through December 2001. From these we determined direct medical care costs converted to 2001 US dollars using the consumer price index. We used generalized estimating equations to examine potential predictors of the costs. Monte Carlo simulations and sensitivity analyses were performed to evaluate the varying prevalence and cost of biologic therapy. Results. The mean total annual direct medical care cost in 2001 for a patient with RA was $9,519. Drug costs were $6,324 (66% of the total), while hospitalization costs were only $1,573 (17%). Approximately 25% of patients received biologic therapy. The mean total annual direct cost for patients receiving biologic agents was $19,016 per year, while the cost for those not receiving biologic therapy was $6,164. RA patients who were in the worst quartile of functional status, as measured by the Health Assessment Questionnaire, experienced direct medical costs for the subsequent year that were $5,022 more than the costs incurred by those in the best quartile. Physical status as determined by the Short Form 36 physical component scale had a similar large effect on RA costs, as did comorbidity. Medical insurance type played a more limited role. However, those without insurance had substantially lower service utilization and costs, and health maintenance organization patients had lower drug costs and total medical costs. Increased years of education, increased income, and majority ethnic status were all associated with increased drug costs but not hospitalization costs. Costs in all categories decreased after age 65 years. Conclusion. Estimates of direct medical costs for patients with. RA are substantially higher than cost estimates before the biologic therapy era, and costs are now driven predominantly by the cost of drugs, primarily biologic agents. RA patients with poor function continue to incur substantially higher costs, as do those with comorbid conditions, and sociodemographic characteristics also play an important role in determination of costs. C1 Natl Data Bank Rheumat Dis, Arthrit Res Ctr Fdn, Wichita, KS 67214 USA. Wichita State Univ, Wichita, KS USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Kansas, Sch Med, Wichita, KS 67214 USA. RP Wolfe, F (reprint author), Natl Data Bank Rheumat Dis, Arthrit Res Ctr Fdn, 1035 N Emporia,Suite 230, Wichita, KS 67214 USA. NR 46 TC 178 Z9 185 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2003 VL 48 IS 10 BP 2750 EP 2762 DI 10.1002/art.11439 PG 13 WC Rheumatology SC Rheumatology GA 734DQ UT WOS:000186040300008 PM 14558079 ER PT J AU Budoff, JE Nirschl, RP Ilahi, OA Rodin, DM AF Budoff, JE Nirschl, RP Ilahi, OA Rodin, DM TI Internal impingement in the etiology of rotator cuff tendinosis revisited SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE internal impingement; rotator cuff; Labrum; impingement syndrome; throwing injuries ID SUPERIOR GLENOID IMPINGEMENT; THROWING ATHLETE; THICKNESS TEARS; EMG ANALYSIS; SHOULDER; ACROMIOPLASTY; INSTABILITY; DEBRIDEMENT; OVERHAND; LABRUM AB Purpose: The theory of internal impingement holds that, in overhead athletes, repeated contact between the undersurface of the rotator cuff and the posterosuperior glenoid rim leads to articular-sided partial-thickness rotator cuff tears and superior labral lesions. However, we have noted this same constellation of lesions in our general patient population. These recreational athletic patients do not routinely assume the position of extreme abduction and external rotation, and thus are unlikely to experience significant internal impingement forces. The goal of this study was to document the prevalence of superior labral lesions in patients being treated for partial-thickness undersurface rotator cuff tears. Type of Study: Retrospective case series. Methods: We retrospectively reviewed the records of 75 shoulders arthroscopically treated for partial-thickness articular-sided rotator cuff tears. With the exception of one professional tennis player, no patients were playing sports at a professional or major college level. No professional or collegiate throwing athletes were included. The prevalence of these lesions and their association with recreational athletics was noted. Results: We found that 55 of 75 (73.3%) shoulders with articular-sided partial-thickness rotator cuff tears also had superior labral lesions. A statistically significant increased prevalence of superior labral lesions in the dominant shoulder was seen (P =.03). In addition, our patients who engaged in overhand throwing had significantly fewer superior labral lesions in the dominant shoulders than did nonthrowers (P =.017). Conclusions: The "kissing lesions" of undersurface rotator cuff tears and posterosuperior labral damage may be explained by mechanisms other than "internal impingement." C1 Baylor Coll Med, Dept Orthopaed Surg, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. Georgetown Univ, Dept Orthopaed Surg, Arlington, VA USA. RP Budoff, JE (reprint author), 6550 Fannin,2525, Houston, TX 77030 USA. NR 30 TC 28 Z9 29 U1 0 U2 12 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2003 VL 19 IS 8 BP 810 EP 814 DI 10.1053/S0749-8063(03)00732-1 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 735WQ UT WOS:000186137900002 PM 14551541 ER PT J AU Blackburn, ML Chansky, HA Zielinska-Kwiatkowska, A Matsui, Y Yang, L AF Blackburn, ML Chansky, HA Zielinska-Kwiatkowska, A Matsui, Y Yang, L TI Genomic structure and expression of the mouse ESET gene encoding an ERG-associated histone methyltransferase with a SET domain SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE historic H3; methyltransferase; chromatin; transcription initiation; splicing ID RNA POLYMERASE-II; SUPPRESSOR GENE; DNA METHYLATION; H3; TRANSCRIPTION; CHROMATIN; PROTEINS; SU(VAR)3-9; INTERACTS; COMPLEXES AB ESET (ERG-associated protein with a SET domain, also called SETDB1) is a novel histone methyltransferase that catalyzes methylation of histone H3-lysine 9 (H3-K9). Here we describe the genomic structure and expression of the mouse ESET gene that gives rise to ESET protein and its alternative splicing product. ESET is a 36-kb single copy gene and full-length ESET transcript consisting of 22 exons. The splicing variant retains only the first 12 exons and thus lacks sequences encoding the methyl CpG-binding domain and the catalytic SET domain. The U2 type conserved GT/AG consensus sequence is present at all of the splicing junctions within the ESET gene. The transcription initiation site of the ESET gene was determined by 5'-RACE experiment and by primer extension. The 5'-flanking sequence of the ESET gene does not contain the consensus TATA box. Instead, this ESET promoter region has features such as SP1-binding sites that are typical of housekeeping genes. The ESET promoter was functionally active when tested in transfection and luciferase assay. Full-length ESET transcript appears to be ubiquitously expressed. While the SET domain-deficient splicing variant is present in immortalized cell lines, it is undetectable by RT-PCR in the majority of normal mouse tissues. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Washington, Sch Med, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Hematol, Seattle, WA 98195 USA. RP Yang, L (reprint author), Univ Washington, Sch Med, Dept Orthoped, 1660 S Columbian Way,GMR 151, Seattle, WA 98108 USA. FU NCI NIH HHS [1R01CA90941] NR 26 TC 19 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 1 PY 2003 VL 1629 IS 1-3 BP 8 EP 14 DI 10.1016/S0167-4781(03)00155-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 731HD UT WOS:000185877500002 PM 14522075 ER PT J AU Levin, M AF Levin, M TI Motor protein control of ion flux is an early step in embryonic left-right asymmetry SO BIOESSAYS LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; RIGHT AXIS FORMATION; CHICK-EMBRYO; SITUS-INVERSUS; MOUSE EMBRYO; NODAL CILIA; EXPRESSION PATTERNS; SODIUM-CHANNELS; HEAVY-CHAINS; KINESIN-II AB The invariant left-right asymmetry of animal body plans raises fascinating questions in cell, developmental, evolutionary, and neuro-biology. While intermediate mechanisms (e.g., asymmetric gene expression) have been well-characterized, very early steps remain elusive. Recent studies suggested a candidate for the origins of asymmetry: rotary movement of extracellular morphogens by cilia during gastrulation. This model is intellectually satisfying, because it bootstraps asymmetry from the intrinsic biochemical chirality of cilia. However, conceptual and practical problems remain with this hypothesis, and the genetic data is consistent with a different mechanism. Based on wide-ranging data on ion fluxes and motor protein action in a number of species, a model is proposed whereby laterality is generated much earlier, by asymmetric transport of ions, which results in pH/voltage gradients across the midline. These asymmetries are in turn generated by a new candidate for "step 1 ": asymmetric localization of electrogenic proteins by cytoplasmic motors. BioEssays 25:1002-1010,2003. (C) 2003 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Dent Med, Cytokine Biol Dept, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Craniofacial & Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Cytokine Biol Dept, Forsyth Inst, 188 Longwood Ave, Boston, MA 02115 USA. NR 89 TC 52 Z9 54 U1 6 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 2003 VL 25 IS 10 BP 1002 EP 1010 DI 10.1002/bies.10339 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 724YW UT WOS:000185516700010 PM 14505367 ER PT J AU Shuster, E AF Shuster, E TI Human cloning: Category, dignity, and the role of bioethics SO BIOETHICS LA English DT Article; Proceedings Paper CT 6th World Congress of the International-Association-of-Bioethics CY 2001 CL BRASILIA, BRAZIL SP Int Assoc Bioeth AB Human cloning has been simultaneously a running joke for. massive worldwide publicity of fringe groups like the Raelians, and the core issue Of an international movement at the United Nations in support of a treaty to ban the use of cloning techniques to produce a child (so called reproductive cloning). Yet, even though debates on human cloning have greatly increased since the birth of Dolly, the clone sheep, in 1997, we, continue to wonder whether cloning is after all any different from other methods of medically assisted reproduction, and what exactly makes cloning an. 'affront. to the dignity of humans.' Categories we adopt matter mightily as they inform but can also misinform and lead to mistaken and unproductive decisions. And thus bioethicists have a responsibility to ensure that the proper categories are used in the cloning debates and denounce those who try to win the ethical debate through well-crafted labels rather than well-reasoned argumentations. But it is as important for bioethicists to take a position on broad issues such as human cloning and species altering interventions. One 'natural question' would be, for example, should there be an international treaty to ban human reproductive cloning? C1 Univ Penn, Vet Affairs Med Ctr, Human Rights & Eth Program, Philadelphia, PA 19104 USA. RP Shuster, E (reprint author), Univ Penn, Vet Affairs Med Ctr, Human Rights & Eth Program, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 10 TC 10 Z9 10 U1 1 U2 6 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0269-9702 J9 BIOETHICS JI Bioethics PD OCT PY 2003 VL 17 IS 5-6 BP 517 EP 525 DI 10.1111/1467-8519.00365 PG 9 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 734PD UT WOS:000186065000012 PM 14959720 ER PT J AU Centorrino, F Albert, MJ Berry, JM Kelleher, JP Fellman, V Line, G Koukopoulos, AE Kidwell, JE Fogarty, KV Baldessarini, RJ AF Centorrino, F Albert, MJ Berry, JM Kelleher, JP Fellman, V Line, G Koukopoulos, AE Kidwell, JE Fogarty, KV Baldessarini, RJ TI Oxcarbazepine: clinical experience with hospitalized psychiatric patients SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; carbamazepine; oxcarbazepine; psychosis ID BIPOLAR DISORDER; CARBAMAZEPINE; EFFICACY; ANTICONVULSANTS; MANIA; CARBAMAZEPINE-10,11-EPOXIDE; TOLERABILITY; MANAGEMENT; EPILEPSY; LITHIUM AB Background: Oxcarbazepine (10-keto-carbamazepine) appears to be better tolerated and simpler to use than carbamazepine. It has antimanic effects but, as its potential clinical usefulness and tolerability in broad samples of psych iatric patients remain to be tested, we reviewed both the pharmacology of oxcarbazepine and our early experience with this new agent among psychiatric inpatients. Methods: We reviewed medical records of all inpatients given oxcarbazepine in the first 15 months of its use at McLean Hospital. Data analyzed included dosing, presenting illnesses, other medications, clinical changes, and adverse effects. Results: Oxcarbazepine was given to 56 inpatients (1.3% of admissions; 31 women, 25 men) presenting with depression (n = 23), mania (n = 19), or psychosis (n = 14). The discharge daily dose for the 43 patients (76%) taking oxcarbazepine was 831 mg/day, 34% higher in men than women, and fell by 9 mg/year-of-age. Oxcarbazepine was the only putative mood-stabilizing agent given at discharge in 19 of 43 cases (44%). It was discontinued in 20% of patients for apparent inefficacy, and 4% for adverse effects. Changes in CGI and GAF scores were similarly high across illnesses, and unrelated to days of use of oxcarbazepine or its dose. Conclusions: Oxcarbazepine was well tolerated and simpler to use clinically than its precursor carbamazepine. This agent should be studied in controlled trials to test its efficacy in specific types of major psychiatric disorders, and particularly for long-term maintenance treatment in bipolar disorder. C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. RP Centorrino, F (reprint author), McLean Hosp, Bipolar & Psychot Disorders Clin, N Belknap 3, Belmont, MA 02478 USA. NR 27 TC 19 Z9 20 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2003 VL 5 IS 5 BP 370 EP 374 DI 10.1034/j.1399-5618.2003.00047.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 728VK UT WOS:000185736900010 PM 14525559 ER PT J AU Hoshiya, M Christian, BP Cromie, WJ Kim, H Zhan, Y MacLaughlin, DT Donahoe, PK AF Hoshiya, M Christian, BP Cromie, WJ Kim, H Zhan, Y MacLaughlin, DT Donahoe, PK TI Persistent Mullerian duct syndrome caused by both a 27-bp deletion and a novel splice mutation in the MIS type II receptor gene SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID INHIBITING SUBSTANCE; EMBEDDED TISSUES; SEQUENCE; HORMONE; EXON; RECOGNITION; EXPRESSION; INTRONS; MALES; CELLS AB BACKGROUND: Persistent Mullerian duct syndrome (PMDS) is a rare form of male pseudohermaphroditism that is characterized by the persistence of Mullerian derivatives in otherwise normally virilized males. Mutations of the Mullerian inhibiting substance (MIS) gene or the MIS type II receptor (MISRII) gene have been identified in PMDS patients with autosomal recessive transmission. We analyzed a compound heterozygote PMDS patient who had a 27-bp deletion in exon 10 in one allele and a novel mutation in intron 5 in the other allele of the MISRII gene. METHODS: Whole blood and tissue samples were obtained from a one-month-old 46,XY male with persistent PMDS and the MISRII gene was sequenced and compared to his mother's genomic DNA and that of 22 normal individuals. Serum MIS and the reproductive hormones were measured by standard immunoassays. RESULTS: The patient's hormone levels were normal but the gene for MISRII contained several mutations, a 27-bp deletion in exon 10 on one allele (one of the most common mutations in PMDS) and a novel mutation in intron 5 in the other allele that altered splicing, resulting in retention of the intron and a frameshift, introducing a stop codon. Other mutations in introns 6 and 9 and in exon 11 might not be functionally significant. CONCLUSIONS: This case reveals a novel mutation in the MISRII gene involving intronic sequences, which when coexisting with the already identified 27-bp deletion in exon 10, leads to PMDS. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Serv,Dept Surg, Boston, MA 02114 USA. Univ Chicago Hosp, Urol Sect, Dept Surg, Chicago, IL 60637 USA. RP Donahoe, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs,Dept Surg, Warren 11, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu FU NCI NIH HHS [CA17393]; NICHD NIH HHS [HD32112] NR 28 TC 20 Z9 21 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD OCT PY 2003 VL 67 IS 10 BP 868 EP 874 DI 10.1002/bdra.10091 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 736AR UT WOS:000186148500006 PM 14745940 ER PT J AU Scadden, DT AF Scadden, DT TI T-cell differentiation: Notch another step SO BLOOD LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT 1 PY 2003 VL 102 IS 7 BP 2316 EP 2316 DI 10.1182/blood-2003-08-2653 PG 1 WC Hematology SC Hematology GA 727PD UT WOS:000185666500006 ER PT J AU Stoll, BR Migliorini, C Kadambi, A Munn, LL Jain, RK AF Stoll, BR Migliorini, C Kadambi, A Munn, LL Jain, RK TI A mathematical model of the contribution of endothelial progenitor cells to angiogenesis in tumors: implications for antiangiogenic therapy SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; GROWTH-FACTOR; TYROSINE KINASE; IN-VITRO; NEOVASCULARIZATION; REGENERATION; MOBILIZATION; INHIBITOR; ADHESION; TISSUE AB The traditional view of angiogenesis emphasizes proliferation and migration of vessel wall-associated endothelial cells. However, circulating endothelial progenitor cells have recently been shown to contribute to tumor angiogenesis. Here we quantify the relative contributions of endothelial and endothelial progenitor cells to angiogenesis using a mathematical model. The model predicts that during the early stages of tumor growth, endothelial progenitors have a significant impact on tumor growth and angiogenesis, mediated primarily by their localization in the tumor, not by their proliferation. The model also shows that, as the tumor grows, endothelial progenitors adhere preferentially near the tumor periphery, coincident with the location of highest vascular density, supporting their potential utility as vectors for targeted delivery of therapeutics. Model simulations of various antiangiogenic strategies show that those therapies that effectively target both endothelial and endothelial progenitor cells, either by restoring the balance between angiogenic stimulators and inhibitors or by targeting both types of cells directly, are most effective at delaying tumor growth. The combination of continuous low-dose chemotherapy and antiangiogenic therapy is predicted to have the most significant effect on therapeutic outcome. The model offers new insight into tumor angiogenesis with implications for the rational design of antiangiogenic therapy. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA USA. RP Jain, RK (reprint author), Harvard Univ, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Massachusetts Gen Hosp,Sch Med, 100 Biossom St,Cox 7, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [R24 CA85140, P01 CA80124] NR 45 TC 79 Z9 86 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 OCT 1 PY 2003 VL 102 IS 7 BP 2555 EP 2561 DI 10.1182/blood-2003-02-0365 PG 7 WC Hematology SC Hematology GA 727PD UT WOS:000185666500041 PM 12775571 ER PT J AU Fonseca, R Debes-Marun, CS Picken, EB Dewald, GW Bryant, SC Winkler, JM Blood, E Oken, MM Santana-Davila, R Gonzalez-Paz, N Kyle, RA Gertz, MA Dispenzieri, A Lacy, MQ Greipp, PR AF Fonseca, R Debes-Marun, CS Picken, EB Dewald, GW Bryant, SC Winkler, JM Blood, E Oken, MM Santana-Davila, R Gonzalez-Paz, N Kyle, RA Gertz, MA Dispenzieri, A Lacy, MQ Greipp, PR TI The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma SO BLOOD LA English DT Article ID PLASMA-CELL LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; COOPERATIVE-ONCOLOGY-GROUP; DNA CONTENT; PROGNOSTIC IMPLICATIONS; TUMOR-CELL; CHROMOSOME-13 ABNORMALITIES; CYTOGENETIC ABNORMALITIES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY AB Aneuploid is ubiquitous in multiple myeloma (MM), and 4 cytogenetic subcategories are recognized: hypodiploid (associated with a shorter survival), pseudodiploid, hyperdiploid, and near-tetraploid MM. The hypodiploid, pseudodiploid, and near-tetraploid karyotypes can be referred to as the nonhyperdiploid MM. Immunoglobulin heavy-chain (IgH) translocations are seen in 60% of patients. We studied the relation between aneuploidy and IgH translocations in MM. Eighty patients with MM and abnormal metaphases were studied by means of interphase fluorescent in situ hybridization (FISH) to detect IgH translocations. We also studied a second cohort of 199 patients (Eastern Cooperative Oncology Group [ECOG]) for IgH translocations, chromosome 13 monosomy/deletions (Delta13), and ploidy by DNA content. Mayo Clinic patients with abnormal karyotypes and FISH-detected IgH translocation were more likely to be nonhyperdiploid (89% versus 39%, P < .0001). Remarkably, 88% of tested patients with hypodiploidy (16 of 18) and 90% of tested patients with tetraploidy (9 of 10) had an IgH translocation. ECOG patients with IgH translocations were more likely to have nonhyperdiploid MM by DNA content (68% versus 21%, P < .001). This association was seen predominantly in patients with recurrent chromosome partners to the IgH translocation (11q13, 4p16, and 16q23). The classification of MM into hyperdiploidy and nonhyperdiploidy is dictated largely by the recurrent (primary) IgH translocations in the latter. (C) 2003 by The American Society of Hematology. C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Biostat, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp, ECOG, Boston, MA 02115 USA. RP Fonseca, R (reprint author), Mayo Clin & Mayo Fdn, Div Hematol, Hematol ST 6-28, Rochester, MN 55905 USA. OI Fonseca, Rafael/0000-0002-5938-3769; Dispenzieri, Angela/0000-0001-8780-9512 FU NCI NIH HHS [CA21115-25C, P01 CA62242, R01 CA83724-01] NR 42 TC 161 Z9 168 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 OCT 1 PY 2003 VL 102 IS 7 BP 2562 EP 2567 DI 10.1182/blood-2003-02-0493 PG 6 WC Hematology SC Hematology GA 727PD UT WOS:000185666500042 PM 12805059 ER PT J AU Gascoyne, RD Lamant, L Martin-Subero, JI Lestou, VS Harris, NL Muller-Hermelink, HK Seymour, JF Campbell, LJ Horsman, DE Auvigne, I Espinos, E Siebert, R Delsol, G AF Gascoyne, RD Lamant, L Martin-Subero, JI Lestou, VS Harris, NL Muller-Hermelink, HK Seymour, JF Campbell, LJ Horsman, DE Auvigne, I Espinos, E Siebert, R Delsol, G TI ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases SO BLOOD LA English DT Article ID INFLAMMATORY MYOFIBROBLASTIC TUMOR; NON-HODGKINS-LYMPHOMA; ANAPLASTIC LYMPHOMA; KINASE ALK; ATIC-ALK; GENE; FUSION; NPM; INV(2)(P23Q35); TRANSLOCATIONS AB Expression of ALK protein by lymphoid cells and the description of variant anaplastic lymphoma kinase (ALK) translocations have typically been restricted to cases of T-cell and null anaplastic large-cell lymphoma (ALCL). All such cases result from a novel fusion created by the ALK gene on chromosome 2p23 and NPM on 5q35 or other variant translocation partners. A rare variant of diffuse large B-cell lymphoma (DLBCL), originally described in 1997, was thought to overexpress full-length ALK in contrast to a chimeric protein characteristic of ALCL. However, full-length ALK protein lacks tyrosine kinase activity and thus the mechanism of oncogenesis has remained elusive. We describe 6 cases of ALK(+) DLBCL characterized by a simple or complex t(2;17)(p23;q23) involving the clathrin gene (CLTC) at chromosome band 17q23 and the ALK gene at chromosome band 2p23. All cases were studied using fluorescence in situ hybridization (FISH), complemented in one case with standard cytogenetic analysis, multicolor karyotyping (M-FISH), and reverse transcriptase-polymerase chain reaction. These results clearly demonstrate that most cases of ALK(+) DLBCL share the same mechanism of deregulated ALK expression. Moreover, these results demonstrate the presence of CLTC-ALK fusions in these tumors and extend the list of diseases associated with this genetic abnormality to include classical T-cell or null ALCL, ALK(+) DLBCL, and inflammatory myofibroblastic tumors. (C) 2003 by The American Society of Hematology. C1 INSERM, U563, Dept Oncogenesis & Signaling Hematopoiet Cells, Ctr Physiopathol Toulouse Purpan, Toulouse, France. British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada. Inst Human Genet, Kiel, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Pathol, Wurzburg, Germany. Peter MacCallum Canc Inst, Dept Med Oncol, Melbourne, Vic 3000, Australia. St Vincents Hosp, Victorian Canc Cytogenet Unit, Fitzroy, Vic, Australia. RP Delsol, G (reprint author), CHU Purpan, Anat Pathol Lab, Pl Docteur Baylac, F-31059 Toulouse, France. RI Siebert, Reiner/A-8049-2010; Espinos, Estelle/A-4661-2015; OI Espinos, Estelle/0000-0002-5693-8941; Martin-Subero, Jose Ignacio/0000-0001-8809-5195 FU NCI NIH HHS [1-U01-CA84967-01] NR 27 TC 157 Z9 166 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 OCT 1 PY 2003 VL 102 IS 7 BP 2568 EP 2573 DI 10.1182/blood-2003-03-0786 PG 6 WC Hematology SC Hematology GA 727PD UT WOS:000185666500043 PM 12763927 ER PT J AU Catley, L Weisberg, E Tai, YT Atadja, P Remiszewski, S Hideshima, T Mitsiades, N Shringarpure, R LeBlanc, R Chauhan, D Munshi, NC Schlossman, R Richardson, P Griffin, J Anderson, KC AF Catley, L Weisberg, E Tai, YT Atadja, P Remiszewski, S Hideshima, T Mitsiades, N Shringarpure, R LeBlanc, R Chauhan, D Munshi, NC Schlossman, R Richardson, P Griffin, J Anderson, KC TI NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma SO BLOOD LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; WAF1/CIP1 GENE PROMOTER; PHASE-I TRIAL; SODIUM-BUTYRATE; RECEPTOR EXPRESSION; HUMAN NEUROBLASTOMA; DOWN-REGULATION; CULTURED-CELLS; TRICHOSTATIN-A; RETINOIC ACID AB Histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in hematologic malignancies. Here we show that NVP-LAQ824, a novel hydroxamic acid derivative, induces apoptosis at physiologically achievable concentrations (median inhibitory concentration [IC50] of 100 nM at 24 hours) in multiple myeloma (MM) cell lines resistant to conventional therapies. MM.1S myeloma cell proliferation was also inhibited when cocultured with bone marrow stromal cells, demonstrating ability to overcome the stimulatory effects of the bone marrow microenvironment. Importantly, NVP-LAQ824 also inhibited patient MM cell growth in a dose- and time-dependent manner. NVP-LA0824-induced apoptotic signaling includes up-regulation of p21, caspase cascade activation, and poly (adenosine diphosphate [ADP]) ribose (PARP) cleavage. Apoptosis was confirmed with cell cycle analysis and annexin-propidium iodide staining. Interestingly, treatment of MM cells with NVP-LAQ824 also led to proteasome inhibition, as determined by reduced proteasome chymotrypsin-like activity and increased levels of cellular polyubiquitin conjugates. Finally, a study using NVP-LAQ824 in a preclinical murine myeloma model provides in vivo relevance to our in vitro studies. Taken together, these findings provide the framework for NVP-LAQ824 as a novel therapeutic in MM. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Novartis Inst Biomed Res, E Hanover, NJ USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Mayer Bldg,Room M557,44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [P0178378, R0150947] NR 53 TC 161 Z9 166 U1 1 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 OCT 1 PY 2003 VL 102 IS 7 BP 2615 EP 2622 DI 10.1182/blood-2003-01-0233 PG 8 WC Hematology SC Hematology GA 727PD UT WOS:000185666500049 PM 12816865 ER PT J AU Hayashi, F Means, TK Luster, AD AF Hayashi, F Means, TK Luster, AD TI Toll-like receptors stimulate human neutrophil function SO BLOOD LA English DT Article ID MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; MYD88-DEPENDENT SIGNALING PATHWAY; RESPIRATORY BURST OXIDASE; GENE-EXPRESSION; BACTERIAL FLAGELLIN; SURFACE EXPRESSION; CELL ACTIVATION; DENDRITIC CELLS; IMMUNE CELLS; CUTTING EDGE AB The first immune cell to arrive at the site of infection is the neutrophil. Upon arrival, neutrophils quickly initiate microbicidal functions, including the production of antimicrobial products and proinflammatory cytokines; that serve to contain infection. This allows the acquired immune system enough time to generate sterilizing immunity and memory. Neutrophils detect the presence of a pathogen through germ line-encoded receptors that recognize microbe-associated molecular patterns. In vertebrates, the best characterized of these receptors are Toll-like receptors (TLRs). We have determined the expression and function of TLRs in freshly isolated human neutrophils. Neutrophils expressed TLR1, 2, 4, 5, 6, 7, 8, 9, and 10-all the TLRs except TILR3. Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increased TLR2 and TLR9 expression levels. The agonists of all TLRs expressed in neutrophils triggered or primed cytokine release, superoxide generation, and L-selectin shedding, while inhibiting chemotaxis to interleukin-8 (IL-8) and increasing phagocytosis of opsonized latex beads. The response to the TLR9 agonist nonmethylated CpG-motif-containing DNA (CpG DNA) required GM-CSF pretreatment, which also enhanced the response to the other TLR agonists. Finally, using quantitative polymerase chain reaction (QPCR), we demonstrate a chemokine expression profile that suggests that TLR-stimulated neutrophils recruit innate, but not acquired, immune cells to sites of infection. (C) 2003 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA69212]; NHLBI NIH HHS [T32-HL07874]; NIAMS NIH HHS [T32-AR07258]; NIDDK NIH HHS [P01-DK50305] NR 46 TC 483 Z9 507 U1 4 U2 28 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 OCT 1 PY 2003 VL 102 IS 7 BP 2660 EP 2669 DI 10.1182/blood-2003-04-1078 PG 10 WC Hematology SC Hematology GA 727PD UT WOS:000185666500056 PM 12829592 ER PT J AU Friedberg, JW Kim, H Li, S Neuberg, D Boyd, K Daley, H Fisher, DC Gribben, JG Spitzer, T Freedman, AS AF Friedberg, JW Kim, H Li, S Neuberg, D Boyd, K Daley, H Fisher, DC Gribben, JG Spitzer, T Freedman, AS TI Ex vivo B cell depletion using the Eligix B Cell SC system and autologous peripheral blood stem cell transplantation in patients with follicular non-Hodgkin's lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Article DE purged ASCT; follicular NHL; immunocytochemistry; PCR; Bcl-2/IgH; T(14;18) ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE THERAPY; PROGRESSION-FREE SURVIVAL; POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODY; FOLLOW-UP; RITUXIMAB; BCL-2; CHEMOTHERAPY; TUMOR AB One limitation of ASCT is the potential reinfusion of tumor cells contaminating PBSC. The Eligix B cell SC system consists of high-density microparticles coated with anti-B cell antibodies. To determine if this system eliminates B cells and lymphoma cells from PBSC, immunocytochemistry and PCR of the bcl-2/IgH rearrangement were performed, and correlated with patient outcome after ASCT. Eligible patients (n = 29) had relapsed or transformed follicular NHL with bone marrow involvement <20%, and all lymph nodes <5 cm. PBSCs were mobilized with cyclophosphamide/G-CSF (n = 21), and patients were conditioned with cyclophosphamide, carmustine and etoposide. Using immunocytochemistry on PBSC, the median number of CD20+ cells pre-purge was 310/10(6) (range 0-16692) and post-purge was 0.75/10(6); the median log B cell depletion was 2.7 (range 1.4-3.9). B cell depletion correlated with PFS after ASCT (P = 0.06). Of 17 available samples for PCR, only four had a detectable t(14; 18) breakpoint. After purging, all four remained PCR+; two had a 1-3 log depletion of lymphoma cells. At median follow-up of 18 months, 10 patients, including five infused with PCR-negative PBSC, have had disease progression. The paucity of PCR-informative patients, possibly related to in vivo rituximab therapy, limited the utility of minimal residual disease as a surrogate marker of clinical outcome. C1 Univ Rochester, James P Wilmot Canc Ctr, Lymphoma Program, Rochester, NY 14642 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Friedberg, JW (reprint author), Univ Rochester, James P Wilmot Canc Ctr, Lymphoma Program, 601 Elmwood Ave, Rochester, NY 14642 USA. FU NCI NIH HHS [CA 66996] NR 40 TC 3 Z9 3 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 OCT PY 2003 VL 32 IS 7 BP 681 EP 686 DI 10.1038/sj.bmt.1704212 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 721UA UT WOS:000185335100007 PM 13130315 ER PT J AU Evert, DL McGlinchey-Berroth, R Verfaellie, M Milberg, WP AF Evert, DL McGlinchey-Berroth, R Verfaellie, M Milberg, WP TI Hemispheric asymmetries for selective attention apparent only with increased task demands in healthy participants SO BRAIN AND COGNITION LA English DT Article DE hemispheric asymmetries; hemispheric specialization; selective attention; task demands ID VISUOSPATIAL ATTENTION; REACTION-TIME; LESIONS; BRAIN; DOMINANCE; NEGLECT; SYSTEM AB This study examined the possibility that lack of behavioral evidence indicating hemispheric specialization for selective attention in healthy individuals is due to the use of tasks that are not sufficiently demanding to require selective attention. In a group of 43 participants (ages 17-23), we compared selective attention on a cued-response time task when the target was presented alone and when a distractor was simultaneously presented. The costs of invalid cueing were minimal when the right hemisphere (RH) processed the target relative to when the left hemisphere (LH) processed the target, but only for the high load condition. These results are interpreted as RH specialization in light of evidence suggesting that the RH can direct attention to a larger portion of the visual field. (C) 2003 Elsevier Inc. All rights reserved. C1 Skidmore Coll, Dept Psychol, Saratoga Springs, NY 12866 USA. Skidmore Coll, Program Neurosci, Saratoga Springs, NY 12866 USA. Boston VA Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Boston Univ, Memory Disorders Res Ctr, Sch Med, Boston, MA USA. Boston VA Healthcare Syst, Boston, MA USA. RP Evert, DL (reprint author), Skidmore Coll, Dept Psychol, Saratoga Springs, NY 12866 USA. RI McGlinchey, Regina/R-1971-2016; OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIDCD NIH HHS [T32 DC00017]; NINDS NIH HHS [NS29342] NR 28 TC 22 Z9 22 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 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD OCT PY 2003 VL 53 IS 1 BP 34 EP 41 DI 10.1016/S0278-2626(03)00207-0 PG 8 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 738BR UT WOS:000186267300005 PM 14572500 ER PT J AU Pashek, GV Bachman, DL AF Pashek, GV Bachman, DL TI Cognitive, linguistic, and motor speech effects of donepezil hydrochloride in a patient with stroke-related aphasia and apraxia of speech SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID NONFLUENT APHASIA; DOUBLE-BLIND; BROMOCRIPTINE C1 Univ Florida, Commun Sci & Disorders Dept, Tampa, FL USA. Ralph H Johnson VAMC, Charleston, SC USA. NR 13 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 2003 VL 87 IS 1 BP 179 EP 180 DI 10.1016/S0093-934X(03)00259-1 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 730ND UT WOS:000185836100091 ER PT J AU Katchanov, J Waeber, C Gertz, K Gietz, A Winter, B Bruck, W Dirnagl, U Veh, RW Endres, M AF Katchanov, J Waeber, C Gertz, K Gietz, A Winter, B Bruck, W Dirnagl, U Veh, RW Endres, M TI Selective neuronal vulnerability following mild focal brain ischemia in the mouse SO BRAIN PATHOLOGY LA English DT Article ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; TRANSIENT FOREBRAIN ISCHEMIA; CEREBRAL-ISCHEMIA; HUNTINGTONS-DISEASE; STRIATAL NEURONS; BINDING-SITES; RAT-BRAIN; ACTIVATED MICROGLIA; HIPPOCAMPAL-NEURONS; MULTIPLE-SCLEROSIS AB The evolution of cellular damage over time and the selective vulnerability of different neuronal sub-types was characterized in the striatum following 30-minute middle cerebral artery occlusion and reperfusion in the mouse. Using autoradiography we found an increase in the density of [H-3]PK11195 binding sites-likely reflecting microglial activation-in the lesion border at 3 days and in the whole striatum from 10 days to 6 weeks. This was accompanied by a distinct loss of [H-3]flumazenil and [H-3]CGP39653 binding sites from 10 days up to 6 weeks reflecting neuronal loss. Brain ischemia resulted in a substantial loss of medium spiny projection neurons as seen at three days by Nissl staining, TUNEL and immunocytochemistry using antibodies against microtubule-associated protein (MAP2), NeuN, mu-opioid receptors, substance P, L-enkephalin, neurokinin B, choline acetyltransferase, parvalbumin, calretinin and somatostatin. Both patch and matrix compartments were involved in ischemic damage. In contrast, the numbers of cholinergic, GABAergic, and somatostatin-containing interneurons in the ischemic striatum were not different from those in the contralateral hemisphere at 3 and 14 days. A low density of glutamate receptors, the ability to sequester calcium by calcium-binding proteins and other hitherto unidentified factors may explain this relative resistance of interneurons to acute ischemia. C1 Humboldt Univ, Neurol Klin & Poliklin, Charite, D-10117 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Humboldt Univ, Inst Neuropathol, D-10117 Berlin, Germany. Humboldt Univ, Inst Anat, D-10117 Berlin, Germany. RP Endres, M (reprint author), Humboldt Univ, Neurol Klin & Poliklin, Charite, Schumannstr 20-21,Charite Campus Mitte, D-10117 Berlin, Germany. RI Waeber, Christian/A-8333-2009; Gertz, Karen/J-1603-2015; OI Waeber, Christian/0000-0001-6078-0027; Dirnagl, Ulrich/0000-0003-0755-6119 FU NINDS NIH HHS [NS 043216] NR 48 TC 50 Z9 51 U1 0 U2 1 PU INT SOC NEUROPATHOLOGY PI LOS ANGELES PA UCLA MEDICAL CENTER, SECTION NEUROPATHOLGY, C H S 18-126, LOS ANGELES, CA 90095-1732 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 2003 VL 13 IS 4 BP 452 EP 464 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 744ED UT WOS:000186614200003 PM 14655751 ER PT J AU Merrell, M Suarez-Cuervo, C Harris, KW Vaananen, HK Selander, KS AF Merrell, M Suarez-Cuervo, C Harris, KW Vaananen, HK Selander, KS TI Bisphosphonate induced growth inhibition of breast cancer cells is augmented by p38 inhibition SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT 3rd North American Symposium on Skeletal Complications of Malignancy CY APR 25-27, 2002 CL BETHESDA, MARYLAND SP Paget Fdn DE bisphosphonates; breast cancer; p38 ID NITROGEN-CONTAINING BISPHOSPHONATES; ADJUVANT CLODRONATE TREATMENT; PLACEBO-CONTROLLED TRIAL; BONE-RESORPTION; IN-VITRO; SKELETAL METASTASES; MAP KINASE; PROTEIN PRENYLATION; MEVALONATE PATHWAY; ZOLEDRONIC ACID AB Bisphosphonates (BPs) inhibit osteoclast-mediated bone resorption. They also protect from cancer-induced osteolysis and inhibit breast cancer growth in vitro. Some breast cancer cell lines, however, are relatively resistant to the growth inhibitory effects of BPs. We studied the mechanism of BP resistance in human MDA-MB-231 breast cancer cells. We show that both pyrophosphate-resembling (p-) and nitrogen-containing (n-) BPs induce activation of p38 mitogen activated protein (MAP) kinase pathway in MDA-MB-231 cells in vitro. MDA-MB-231 cells stably expressing a dominant negative form of the p38 MAP kinase (p38/AF) exhibited a dramatic increase in growth inhibition in response to BPs in vitro, compared to control cells. SB203580, a specific inhibitor of the p38 MAP kinase, also augmented BP-induced growth inhibition of parental MDA-MB-231 cells. Similar results were obtained also in murine macrophage-like J774 cells in vitro. Finally, no BP-induced phosphorylation of p38, or augmentation of BP-induced growth inhibition by SB203580 were detected in MCF-7 or HCC38 breast cancer cells, which are more sensitive than MDA-MB-231 cells especially to n- BP induced growth inhibition. In conclusion, these results suggest that BPs activate the p38 pathway in MDA-MB-231 and J774 cells. This activation may be associated with increased survival or proliferation because inhibition of p38 augments BP-induced growth inhibition. These findings may apply to the development of novel approaches for the treatment of breast cancer. C1 Univ Alabama, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Turku, Inst Biomed, Dept Anat, FIN-20520 Turku, Finland. RP Selander, KS (reprint author), Univ Alabama, Dept Med, Div Hematol Oncol, WTI T558,1824 6th Ave S, Birmingham, AL 35294 USA. NR 46 TC 24 Z9 24 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2003 VL 81 IS 3 BP 231 EP 241 DI 10.1023/A:1026126430905 PG 11 WC Oncology SC Oncology GA 732BG UT WOS:000185920500006 PM 14620918 ER PT J AU Emmons, KM Stoddard, AM Gutheil, C Suarez, EG Lobb, R Fletcher, R AF Emmons, KM Stoddard, AM Gutheil, C Suarez, EG Lobb, R Fletcher, R TI Cancer prevention for working class, multi-ethnic populations through health centers: the healthy directions study SO CANCER CAUSES & CONTROL LA English DT Article ID COLORECTAL-CANCER; PHYSICAL-ACTIVITY; COLON-CANCER; PROSPECTIVE COHORT; SMOKING CESSATION; PROSTATE-CANCER; UNITED-STATES; BREAST-CANCER; RISK; CONSUMPTION AB Background: This paper presents the study design and baseline data from Healthy Directions-Health Centers (HCs), a study designed to address social contextual factors in cancer prevention interventions for working class, multiethnic populations. This study is part of the Harvard Cancer Prevention Program Project. Methods: Ten community HCs were paired and randomly assigned to intervention or control. Patients who resided in low income, multi-ethnic neighborhoods were identified and approached for participation. This study targeted fruit and vegetable consumption, red meat consumption, multi-vitamin intake, and physical activity. The intervention components consisted of: (1) a brief in-person study endorsement from the participant's clinician at a scheduled routine care visit; ( 2) an initial in-person counseling session with a health advisor; ( 3) four follow-up telephone counseling sessions; ( 4) multiple mailings of tailored materials; and ( 5) linkages to relevant activities in the local community. Results: Fifteen percent of the sample smoked, 86% reported eating fewer than five servings of fruits and vegetables per day, 50% reported eating more than the recommended amounts of red meat, 40% did not meet recommended physical activity levels, and 63% did not take a multi-vitamin on a daily basis. Although overall social support was high, participants reported low levels of social norms for the target prevention behaviors. Other social contextual mediators and modifying factors are reported. Conclusions: By examining the relationships between social contextual factors and health behaviors, it may be possible to enhance the effectiveness of interventions aimed at reducing social inequalities in risk behaviors. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. OI Lobb, Rebecca/0000-0003-3503-0675 FU NCI NIH HHS [5 PO1 CA 75308] NR 55 TC 27 Z9 27 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2003 VL 14 IS 8 BP 727 EP 737 DI 10.1023/A:1026375408862 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 738DW UT WOS:000186272300005 PM 14674737 ER PT J AU Hunt, MK Stoddard, AM Barbeau, E Goldman, R Wallace, L Gutheil, C Sorensen, G AF Hunt, MK Stoddard, AM Barbeau, E Goldman, R Wallace, L Gutheil, C Sorensen, G TI Cancer prevention for working class, multiethnic populations through small businesses: the healthy directions study SO CANCER CAUSES & CONTROL LA English DT Article DE cancer prevention; health disparities; process evaluation; social context; worksite health promotion ID SMALL WORKPLACES; TREATWELL 5-A-DAY; COLORECTAL-CANCER; UNITED-STATES; PROMOTION; INTERVENTION; TRIAL; PARTICIPATION; PROGRAMS; WORKERS AB Objective: We report demographic and social contextual characteristics of multiethnic, blue-collar workers from the baseline survey of a study conducted in 24 small businesses. We discuss ways in which we incorporated these characteristics into the design of the intervention. Methods: We used a randomized controled design, with 12 small businesses assigned to a social contextual intervention and 12 to a minimum intervention control condition. The response rates to the survey were 84% at baseline (n = 1717). Primary outcomes included reduction in red meat consumption and increase in physical activity and daily multivitamin intake. Secondary outcomes targeted reduction in smoking and occupational exposures. Results: The majority of the respondents were male (67.6%). This was an ethnically diverse sample with 24.7% representing racial/ethnic groups other than white and 43.6% of participants or their parents born outside of the US. To meet study recommendations, workers needed improvement in all behaviors measured. Participants reported a smoking rate of 25.8, 86.2% ate fewer than 5 servings of fruits and vegetables a day 69.5% ate more than three servings of red meat a week, 46.8% engaged in less than 2.5 h a week and 72.4% reported that they did not consume a daily multivitamin. Conclusions: Interventions that address the contextual environment in which health behaviors occur, may provide a method that researchers and practitioners can use to reduce health disparities. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Brown Univ, Sch Med, Dept Family Med, Providence, RI 02912 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. RP Hunt, MK (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA 75308] NR 55 TC 29 Z9 29 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2003 VL 14 IS 8 BP 749 EP 760 DI 10.1023/A:1026327525701 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 738DW UT WOS:000186272300007 PM 14674739 ER PT J AU Haddad, RI Van Echo, DA AF Haddad, RI Van Echo, DA TI Phase II study of docetaxel and topotecan combination chemotherapy in patients with advanced head and neck cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE head and neck cancer; docetaxel; topotecan ID SQUAMOUS-CELL CARCINOMA; SOLID TUMORS; RECURRENT; CISPLATIN AB Purpose. To evaluate the activity of combination chemotherapy with docetaxel and topotecan in patients with advanced head and neck cancer. Methods. Docetaxel was given at 60 mg/m(2) as a 60-min intravenous infusion on day 1. Topotecan at 0.75 mg/m(2) per day was infused over 30 min on days 1, 2 and 3. Cycles were repeated every 21 days. Results. There were no responses (CR+PR) seen in the ten patients. Only one patient had stable disease and was able to receive six cycles of chemotherapy. Median survival was 81 days (range 67-161 days). Conclusions. The combination of docetaxel and topotecan at these doses and in this schedule is not recommended for patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Other investigational approaches are needed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Haddad, RI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, SW430G,44 Binney St, Boston, MA 02115 USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2003 VL 52 IS 4 BP 303 EP 306 DI 10.1007/s00280-003-0673-1 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 729TK UT WOS:000185790100006 PM 12827298 ER PT J AU Giovannucci, E Chen, J Smith-Warner, SA Rimm, EB Fuchs, CS Palomeque, C Willett, WC Hunter, DJ AF Giovannucci, E Chen, J Smith-Warner, SA Rimm, EB Fuchs, CS Palomeque, C Willett, WC Hunter, DJ TI Methylenetetrahydrofolate reductase, alcohol dehydrogenase, diet, and risk of colorectal adenomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; NEURAL-TUBE DEFECTS; NESTED CASE-CONTROL; BREAST-CANCER RISK; RED-BLOOD-CELLS; COLON-CANCER; COMMON MUTATION; ALCOHOL-DEHYDROGENASE-3 GENOTYPE; FOLATE STATUS AB An increased occurrence of colorectal cancer and its adenoma precursor is observed among individuals with low intakes or circulating levels of folate, especially if alcohol intake is high, although results have not been statistically significant in all studies. We examined folate and alcohol intake and genetic polymorphisms in methylenetetrahydrofolate reductase [MTHFR 667-->T (ala-->val) and MTHFR 1298A-->C (gln-->ala)] (associated with reduced MTHFR activity) and in alcohol dehydrogenase 3 [ADH(3) (2-2) associated with decreased alcohol catabolism] in relation to risk of colorectal adenoma in the Health Professionals Follow-Up Study. Among 379 cases and 726 controls, MTHFR genotypes were not appreciably related to risk of adenoma, but a suggestive interaction (P = 0.09) was observed between MTHFR 677C-->T and alcohol intake; men with TT homozygotes who consumed 30+ g/day of alcohol had an odds ratio (OR) of 3.52 [95% confidence interval (CI), 1.41-8.78] relative to drinkers of less than or equal to5 g/day with the CC/CT genotypes. ADH(3) genotype alone was not appreciably related to risk, but its influence was modified by alcohol intake. Compared with fast alcohol catabolizers [ADH(3)(1-1)] with low intakes of alcohol (less than or equal to5 g/day), high consumers of alcohol (30+ g/day) had a marked increase in risk if they had the genotype associated with slow catabolism [ADH(3)(2-2); OR, 2.94; 95% CI, 1.24-6.92] or intermediate catabolism [ADH(3)(1-2)] of alcohol (OR, 1.83; 95% CI, 1.03-3.26) but not if they were fast catabolizers [ADH(3)(1-1); OR = 1.27; 95% CI = 0.63-2.53]. In addition, an increased risk of colorectal adenoma (OR, 17.1; 95% CI, 2.1-137) was observed for those with the ADH(3)(2-2) genotype and high alcohol-low folate intake compared with those with low alcohol-high folate intake and the ADH(3)(1-1) genotype (P for interaction = 0.006). Our results indicate that high intake of alcohol is associated with an increased risk of colorectal adenoma, particularly among MTHFR 677TT and ADH(3)(2-2) homozygotes. The findings that alcohol interacts with a folate-related gene (MTHFR) and that the interaction between alcohol and ADH(3) is stronger among those with low folate intake support the hypothesis that the carcinogenic influence of alcohol in the large bowel is mediated through folate status. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, 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. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 81750, CA 55075, CA 70817] NR 86 TC 59 Z9 63 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2003 VL 12 IS 10 BP 970 EP 979 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 736CR UT WOS:000186153500004 PM 14578131 ER PT J AU Prindiville, SA Byers, T Hirsch, FR Franklin, WA Miller, YE Vu, KO Wolf, HJ Baron, AE Shroyer, KR Zeng, C Kennedy, TC Bunn, PA AF Prindiville, SA Byers, T Hirsch, FR Franklin, WA Miller, YE Vu, KO Wolf, HJ Baron, AE Shroyer, KR Zeng, C Kennedy, TC Bunn, PA TI Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ASPIRIN USE; FOLLOW-UP; RISK; MORTALITY; DISEASE; CHEMOPREVENTION; INTERVENTION; PROJECT; TRIAL AB Individuals with cytological atypia in sputum may be at increased risk for lung cancer. We conducted a longitudinal analysis of the association between lung cancer incidence and cytological atypia in sputum samples collected prospectively from an ongoing cohort of adults at high risk for lung cancer. Cohort members had a smoking history of 2:30 pack-years and chronic obstructive pulmonary disease documented by pulmonary airflow testing. Sputum samples collected at baseline and periodically thereafter were examined by standard cytological methods. From the cohort of 2006 people, there were 83 incident lung cancers over 4469 person-years of observation. At baseline, the association between personal and behavioral characteristics, and sputum cytological atypia was assessed by multiple logistic regression. The association between sputum cytological atypia and incident lung cancer was then assessed by hazard ratios using proportional hazards regression analysis, adjusting for potential confounding factors. Cytological atypia graded as moderate or worse was associated with continuing cigarette smoking (adjusted odds ratio, 2.5; 95% confidence interval, 1.5-4.1), and with lower levels of intake of fruits and vegetables (P for trend = 0.04). Atypia was not associated with several other factors, including the degree of airflow obstruction, the use of vitamin supplements, nonsteroidal anti-inflammatory drugs, or metered-dose steroid inhalers. Incident lung cancer was increased among those with moderate or worse cytological atypia (adjusted hazards ratio, 2.8; 95% confidence interval, 1.4-5.5). This association was not confounded by other risk factors. We conclude that in this high-risk cohort, cytological atypia is associated with continuing smoking and low intake of fruits and vegetables, but that independent of these and other factors, the risk of incident lung cancer is increased among those with moderate or worse grades of cytological atypia in their sputum. C1 Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Prevent Med & Biostat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Pathol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Lung Canc Inst Colorado, Denver, CO 80218 USA. RP Byers, T (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Med, 4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [P50CA58187, K07CA75159] NR 38 TC 60 Z9 62 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2003 VL 12 IS 10 BP 987 EP 993 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 736CR UT WOS:000186153500006 PM 14578133 ER PT J AU Cooley, ME Sarna, L Brown, JK Williams, RD Chernecky, C Padilla, G Danao, LL AF Cooley, ME Sarna, L Brown, JK Williams, RD Chernecky, C Padilla, G Danao, LL TI Challenges of recruitment and retention in multisite clinical research SO CANCER NURSING LA English DT Article DE multisite research; recruitment and retention; women and clinical trials; women and lung cancer; quality of life; lung cancer and quality of life ID RESEARCH ETHICS COMMITTEES; QUALITY-OF-LIFE; LUNG-CANCER; WOMEN; TRIALS; SEX; NONRESPONSE; PREVENTION; SYSTEM; BOARDS AB This article reviews recruitment and retention issues in a multisite, multistate (California, New York, Connecticut, Georgia, Alabama) 6-month prospective cross-sectional study focused on quality of life among 230 women with lung cancer. Recruitment of women into clinical trials and their retention are important, yet understudied. To date, few articles have described the challenges associated with recruiting women with lung cancer to participate in clinical research. Data from this trial were used to investigate the most effective strategies for recruitment across sites, to identify the most common reasons for refusal and attrition, and to identify challenges and potential solutions to recruitment and retention issues associated with multisite clinical research studies. Strategies for recruitment included letters from physicians, posters, announcements in community support groups, and newspaper and radio advertisements. Three sites allowed the researchers to contact potential participants directly, whereas 2 sites required the potential participants to contact the researchers for further information. Enrollment included 63% of the women eligible for the study (n = 230). The most common reasons for refusal were health limitations (n = 60), lack of interest (n = 46), and inconvenience (n = 16). The most common reasons for attrition (24% of the sample) were death (n = 21) and severity of illness (n = 13). Challenges related to recruitment and retention varied by geographic location. C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Univ Alabama, Birmingham, AL USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Cooley, ME (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, 44 Binney St,G220, Boston, MA 02115 USA. NR 53 TC 46 Z9 46 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD OCT PY 2003 VL 26 IS 5 BP 376 EP 384 DI 10.1097/00002820-200310000-00006 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA 728UB UT WOS:000185733800006 PM 14710799 ER PT J AU Chauhan, D Li, GL Shringarpure, R Podar, K Ohtake, Y Hideshima, T Anderson, KC AF Chauhan, D Li, GL Shringarpure, R Podar, K Ohtake, Y Hideshima, T Anderson, KC TI Blockade of Hsp27 overcomes bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells SO CANCER RESEARCH LA English DT Article ID MULTIPLE-MYELOMA CELLS; OLIGONUCLEOTIDE ARRAYS; PROTEASOME INHIBITION; APOPTOSIS; OVEREXPRESSION; REGULATORS; CANCER AB Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4 versus DHL6 cells, which correlates with Hsp27 protein expression. Blocking Hsp27 using an antisense strategy restores the apoptotic response to PS-341 in DHL4 cells; conversely, ectopic expression of wild-type Hsp27 renders PS-341-sensitive DHL6 cells resistant to PS-341. These findings provide the first evidence that Hsp27 confers PS-341 resistance. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Asahi Brewery Co Ltd, R&D Planning Dept, Tokyo 1308602, Japan. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [P50 CA 100707, CA 50947, CA 78373] NR 20 TC 171 Z9 183 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2003 VL 63 IS 19 BP 6174 EP 6177 PG 4 WC Oncology SC Oncology GA 732WC UT WOS:000185967700015 PM 14559800 ER PT J AU Akiyama, M Hideshima, T Shammas, MA Hayashi, T Hamasaki, M Tai, YT Richardson, P Gryaznov, S Munshi, NC Anderson, KC AF Akiyama, M Hideshima, T Shammas, MA Hayashi, T Hamasaki, M Tai, YT Richardson, P Gryaznov, S Munshi, NC Anderson, KC TI Effects of oligonucleotide N3 '-> P5 ' thio-phosphoramidate (GRN163) targeting telomerase RNA in human multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID CANCER-CELLS; APOPTOSIS; INTERLEUKIN-6; SENESCENCE; INHIBITION; PROTEINS; GROWTH; P53 AB Telomeres are specialized nucleoprotein complexes that protect against fusion and degradation of linear chromosomes. Critical shortening of telomeres leads to irreversible cessation of cell division, whereas telomerase elongates telomere sequences to compensate for losses that occur with each round of DNA replication. Continued proliferation of tumor cells requires this enzyme to maintain chromosomal stability and to counteract the cellular mitotic clock. In this study, we evaluated the effect of oligonucleotide N3' --> P5' thio-phosphoramidate (NP), which targets template RNA component, in human multiple myeloma (MM) cell lines and patient MM cells. Fluorescein staining at 24 h confirmed NP uptake in 84.7 and 86.1% of MMAS cells and MM patient cells, respectively, without any transfection enhancer. High transfection efficiency was observed into both CD138(+) and CD138(-) MM patient cells. Match NP (7S), but not mismatch NP (30S), inhibited telomerase activity in MM.1S cells, U266 cells, and RPMI 8226 cells, as well as in patient MM cells. Moreover, 7S inhibited cytokine-induced telomerase activity in MMAS cells. 7S treatment-induced progressive telomere shortening was associated with growth inhibition and cell death in MMAS cells with short telomeres (2.5 kb), but not in U266 cells with long telomeres (9.0 kb), at 56 days of culture. Progressive telomere shortening leading to growth inhibition and cell death in MM.1S cells was associated with up-regulation of p21 and phosphorylation of p53 (Ser-15). These studies, therefore, identify the molecular sequelae of NP oligonucleotide (GRN163) against human telomerase RNA component as a telomerase inhibitor and provide the rationale for the development of telomerase-targeted therapies to improve patient outcome in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. VA Boston Healthcare Syst W Roxbury, Boston, MA 02132 USA. Geron Corp, Menlo Pk, CA 94025 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [R01 50947, P01 78378] NR 31 TC 66 Z9 69 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2003 VL 63 IS 19 BP 6187 EP 6194 PG 8 WC Oncology SC Oncology GA 732WC UT WOS:000185967700017 PM 14559802 ER PT J AU Ma, PC Kijima, T Maulik, G Fox, EA Sattler, M Griffin, JD Johnson, BE Salgia, R AF Ma, PC Kijima, T Maulik, G Fox, EA Sattler, M Griffin, JD Johnson, BE Salgia, R TI c-MET mutational analysis in small cell lung cancer: Novel juxtamembrane domain mutations regulating cytoskeletal functions SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE RECEPTOR; PAPILLARY RENAL CARCINOMAS; TPR-MET; THERAPEUTIC INHIBITION; SIGNAL-TRANSDUCTION; SOMATIC MUTATIONS; GASTRIC-CARCINOMA; SCATTER-FACTOR; PROTOONCOGENE AB Small cell lung cancer (SCLC) is an aggressive cancer, and most patients present with cancer already spread beyond the lung. The receptor tyrosine kinase (RTK) c-MET has been implicated in various solid tumors, including SCLC, and is involved in mediating tumorigenesis, cell motility, scattering, invasion and metastasis. Mutations of c-Met have been described in renal papillary carcinoma and gastrointestinal cancers including hepatocellular carcinoma. The sequence of c-MET was examined for possible mutations in the 10 SCLC cell lines and 32 paired-SCLC/normal tissues. Novel c-MET alterations were identified among 3 of 10 separate SCLC cell lines and in 4 of 32 SCLC tumor tissue samples. These include two different c-MET missense mutations in the juxtamembrane (JM) domain (R988C found in NCI-H69 and H249 cell lines; and T10101 in SCLC tumor sample T31). Also, there are one Sema domain missense mutation (E168D in SCLC tumor sample T5), two-base-pair insertional mutations (IVS13- (52-53)insCT in both SCLC tumor samples T26 and T27) within the pre-JM intron 13, as well as an alternative transcript involving exon 10 (11128 cell line). c-MET receptors are expressed at various levels among the 10 SCLC cell lines studied (high expression: H69, H345, H510, and H526; medium-expression: H128 and H146; and low/ no-expression: H82, H209, H249, and H446). The level of c-MET expression does not have any apparent correlation with presence or absence of mutations of c-MET in the cell lines. We show that the two identified JM mutations (11988C and T10101), when introduced into the interleukin-3 (IL-3)-dependent BaF3 cell line, regulated cell proliferation resulting in a small but significant growth factor independence. When introduced into a SCLC cell line (11446, with minimal endogenous wild-type c-MET expression), the JM mutations also regulated cell morphology and adhesion, as well as causing enhanced tumorigenicity by both increases in focusformation and soft-agar colony-formation assays. Both of the JM mutations also increased cell motility and migration evident in wound healing assay and time-lapse video-microscopy speed analysis. The JM mutations also altered the c-MET RTK signaling, resulting in preferentially increased constitutive tyrosine phosphorylation of various cellular proteins, including the key focal adhesion protein paxillin on tyrosine residue Y31 (first CRKL-binding site), correlating with increased motility. These results suggest a novel and unique role of the JM domain in c-MET signaling in SCLC with significant implications in cytoskeletal functions and metastatic potential. The novel JM gain-of-function somatic mutations described are the first to be reported in SCLC, and may be associated with a more aggressive phenotype. It would now be useful to study the inhibition of c-MET as a therapeutic target against SCLC. C1 Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Mol Diagnost, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Tufts New England Med Ctr, Dept Hematol Oncol, Boston, MA 02111 USA. RP Salgia, R (reprint author), Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. NR 53 TC 269 Z9 276 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2003 VL 63 IS 19 BP 6272 EP 6281 PG 10 WC Oncology SC Oncology GA 732WC UT WOS:000185967700029 PM 14559814 ER PT J AU Ahmed, M Monsky, WE Girnun, G Lukyanov, A D'Ippolito, G Kruskal, JB Stuart, KE Torchilin, VP Goldberg, SN AF Ahmed, M Monsky, WE Girnun, G Lukyanov, A D'Ippolito, G Kruskal, JB Stuart, KE Torchilin, VP Goldberg, SN TI Radiofrequency thermal ablation sharply increases intratumoral liposomal doxorubicin accumulation and tumor coagulation SO CANCER RESEARCH LA English DT Article ID SMALL HEPATOCELLULAR-CARCINOMA; RADIO-FREQUENCY ABLATION; HEPATIC METASTASES; INCREASED NECROSIS; COLORECTAL-CANCER; LIVER METASTASES; OSTEOID OSTEOMA; XENOGRAFT MODEL; SOLID TUMORS; HYPERTHERMIA AB Combining radiofrequency (RF) ablation with i.v. liposomal doxorubicin (Doxil) increases intratumoral doxorubicin accumulation and tumor destruction. The purpose of this study was to characterize and better define the specific parameters of such treatment in an animal tumor model. Four hundred R3230 mammary adenocarcinoma nodules were implanted in 250 Fischer rats. First, paired tumors received combined standardized RF (70degreesC +/- 2degreesC, 5 min) followed 30 min later with i.v. Doxil (1 mg) or Doxil alone. Intratumoral doxorubicin uptake was evaluated using fluorospectrophotometry 2-120 h after therapy (n = 110). The effects of varying i.v. Doxil doses (0.0625-7.0 mg; n = 100) and the RF tip temperatures (45degreesC-90degreesC; n = 190) on subsequent intratumoral doxorubicin uptake and induced tumor necrosis were evaluated. Intratumoral doxorubicin accumulation increased to a maximum at 72 h with greater uptake in the RF-ablated tumors compared with controls (P < 0.01). Greater dose-dependent intratumoral doxorubicin increases (to 37.3 +/- 7.7 mug/g) were seen with combined RF/Doxil therapy (P < 0.01). RF ablation reduced the i.v. Doxil dose needed to achieve intratumoral doxorubicin uptake of 13 mu g/g from 7 to 2 mg. Increasing tip temperatures from 50'C to 90 degrees C increased the ratio of doxorubicin in RF to nonablated tumors from 1.2 +/- 0.4 to 5.9 +/- 3.8 (P < 0.01). At all temperatures, greater tumor necrosis was identified for RF/Doxil-treated tumors compared with tumors treated with RF alone (P < 0.05). The threshold for inducing necrosis was 5 degrees C lower for tumors receiving combined therapy (P < 0.01). RF tumor ablation sharply increases intratumoral Doxil accumulation over Lv. Doxil alone, enabling a reduction of systemic dose while obtaining higher intratumoral concentrations than otherwise achievable. Combined therapy also increases tumor destruction over either therapy alone. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Goldberg, SN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu FU NCI NIH HHS [R01 CA 87992-01A1] NR 64 TC 57 Z9 59 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2003 VL 63 IS 19 BP 6327 EP 6333 PG 7 WC Oncology SC Oncology GA 732WC UT WOS:000185967700035 PM 14559820 ER PT J AU Kulke, MH AF Kulke, MH TI Neuroendocrine tumours: clinical presentation and management of localized disease SO CANCER TREATMENT REVIEWS LA English DT Review DE neuroendocrine tumour; carcinoid; islet cell tumour; pancreatic endocrine tumour; local disease ID ZOLLINGER-ELLISON-SYNDROME; VASOACTIVE INTESTINAL POLYPEPTIDE; BRONCHIAL CARCINOID-TUMORS; MULTIPLE ENDOCRINE NEOPLASIA; LONG-ACTING SOMATOSTATIN; ISLET CELL TUMORS; GASTRIC CARCINOIDS; GLUCAGONOMA SYNDROME; SURGICAL APPROACH; PATHOLOGICAL FEATURES AB Neuroendocrine tumours often present a diagnostic and therapeutic challenge. They can arise almost anywhere in the body, and are therefore associated with a broad range of local symptoms. The systemic manifestations of neuroendocrine tumours are also diverse, and are related to the secretion of numerous hormones and biogenic amines. In recent years, improved diagnostic techniques, increased recognition of neuroendocrine tumour subtypes, and new therapeutic modalities have enhanced clinicians' ability to detect and appropriately treat these malignancies. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 102 TC 9 Z9 11 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD OCT PY 2003 VL 29 IS 5 BP 363 EP 370 DI 10.1016/S0305-7372(03)00072-0 PG 8 WC Oncology SC Oncology GA 728CW UT WOS:000185698500002 PM 12972355 ER PT J AU Levine, GN Ferguson, JJ AF Levine, GN Ferguson, JJ TI Low-molecular-weight heparin during percutaneous coronary interventions: Rationale, results, and recommendations SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE enoxaparin; angioplasty; anticoagulation ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; UNFRACTIONATED HEPARIN; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; SUBCUTANEOUS ENOXAPARIN; INTRAVENOUS ENOXAPARIN; ACC/AHA GUIDELINES; AMERICAN-COLLEGE; RANDOMIZED TRIAL C1 Houston VAMC, Cardiol Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. Texas Heart Inst, Houston, TX 77025 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Houston, TX USA. RP Levine, GN (reprint author), Houston VAMC, Cardiol Sect, 3C-310,111-B, Houston, TX 77030 USA. NR 48 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2003 VL 60 IS 2 BP 185 EP 193 DI 10.1002/ccd.10640 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 728DD UT WOS:000185699200008 PM 14517923 ER PT J AU Hong, YK Detmar, M AF Hong, YK Detmar, M TI Prox1, master regulator of the lymphatic vasculature phenotype SO CELL AND TISSUE RESEARCH LA English DT Review DE Prox1; master regulator; lymphatic vasculature phenotype; lineage-specific differentiation; lymphatic vessels; homeobox gene ID CENTRAL-NERVOUS-SYSTEM; GANGLION MOTHER CELLS; TRANSCRIPTION FACTOR; ENDOTHELIAL-CELLS; ASYMMETRIC SEGREGATION; DROSOPHILA-PROSPERO; GENE; LYMPHANGIOGENESIS; EXPRESSION; PROTEIN AB In contrast to the extensive molecular and functional characterization of blood vascular endothelium, little is known about the mechanisms that control the formation and lineage-specific differentiation and function of lymphatic vessels. The homeobox gene Prox1, the vertebrate homologue of the Drosophila prospero gene, has been recently identified to be required for the induction of lymphatic vascular development from preexisting embryonic veins, and studies in Prox1-deficient mice have confirmed Florence Sabin's original hypothesis about the origin of the lymphatic vascular system from embryonic veins. The recent establishment of cell culture models for the selective propagation of blood vascular and lymphatic endothelial cells, together with the findings that these cells maintain their lineage-specific differentiation in vitro, has led to the discovery that Prox1 expression is sufficient to induce a lymphatic phenotype in blood vascular endothelium. Ectopic expression of Prox1 downregulated blood vascular-associated genes and also upregulated some of the known lymphatic endothelial cell markers. Together, these studies suggest that the blood vascular phenotype represents the default endothelial differentiation and they identify an essential role of Prox1 in the program specifying lymphatic endothelial cell fate. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hong, YK (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 45 TC 65 Z9 67 U1 2 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD OCT PY 2003 VL 314 IS 1 BP 85 EP 92 DI 10.1007/s00441-003-0747-8 PG 8 WC Cell Biology SC Cell Biology GA 742WV UT WOS:000186541800010 PM 12883994 ER PT J AU Gartner, W Rossbacher, J Zierhut, B Daneva, T Base, W Weissel, M Waldhaus, W Pasternack, MS Wagner, L AF Gartner, W Rossbacher, J Zierhut, B Daneva, T Base, W Weissel, M Waldhaus, W Pasternack, MS Wagner, L TI The ATP-dependent helicase RUVBL1/TIP49a associates with tubulin during mitosis SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE RUVBL1; TIP49a; Pontin52; mitotic spindle; centrosome; tubulin associated protein ID RUVB-LIKE PROTEIN; MICROTUBULE DYNAMICS; CRYSTAL-STRUCTURE; DNA HELICASE; CELL-CYCLE; BINDING PROTEIN; BETA-CATENIN; GENE; COMPLEX; TIP49A AB RUVBL1/TIP49a/Pontin52 is a recently identified multi-functional protein with 2 ATP binding (WALKER) sites, which is essential for cell proliferation. We recovered and identified RUVBL1/TIP49a as a tubulin-binding protein from Triton X-100 lysates of U937 promonocytic cells by protein affinity chromatography and tryptic peptide microsequencing. Performing co-immunoprecipitation using newly generated RUVBL1/TIP49a-specific antibodies (mAb and rabbit polyclonal Ab) and RUVBL1/ TIP49a-GST fusion protein-pull down assays we demonstrate co-precipitation of alpha- and gamma tubulin with RUVBL1/TIP49a. Confocal immunoflourescence microscopy reveals that RUVBL1/TIP49a was present not only in the nucleus, as expected, but was also concentrated at the centrosome and at the mitotic spindle in colocalization with tubulin. The topology of RUVBL1/TIP49a at the mitotic spindle varied, depending on the mitotic stage. The protein was localized at the centrosome and at the polar and astral microtubules in metaphase, and was detectable at the zone of polar tubule interdigitation in anaphase B and telophase. During cytokinesis the protein reappeared at the area of decondensing chromosomes. Whereas preincubation of U937 cells with colcemid resulted in inhibition of mitotic spindle formation with subsequent loss of RUVBL1/TIP49a mitotic spindle staining, no relevant influence of colcemid on RUVBL1/TIP49a-tubulin binding was observed. An agonistic effect of RUVBL1/ TIP49a on in vitro tubulin assembly is demonstrated. Our results reveal a new functional aspect of RUVBL1/TIP49a. (C) 2003 Wiley-Liss, Inc. C1 Univ Vienna, Dept Med 111, Clin Div Endocrinol & Metab, A-1090 Vienna, Austria. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Pediat & Med Serv, Boston, MA 02114 USA. RP Wagner, L (reprint author), Univ Vienna, Dept Med 111, Clin Div Endocrinol & Metab, Waehringer Guertel 18-20, A-1090 Vienna, Austria. NR 43 TC 39 Z9 40 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD OCT PY 2003 VL 56 IS 2 BP 79 EP 93 DI 10.1002/cm.10136 PG 15 WC Cell Biology SC Cell Biology GA 728CX UT WOS:000185698600001 PM 14506706 ER PT J AU MacRae, CA Peterson, RT AF MacRae, CA Peterson, RT TI Zebrafish-based small molecule discovery SO CHEMISTRY & BIOLOGY LA English DT Review ID TRIAZINE LIBRARY; MODEL; VERTEBRATE; BIOLOGY; EMBRYO; GENE; CYCLOPAMINE; MUTATIONS; DISEASE; BINDING AB The earliest examples of small molecule discovery involved serendipitous phenotypic observations in whole organisms, but this organism-based process has given way in recent decades to systematic, high-throughput assays using purified proteins, cells, or cell extracts' In vitro screens have been successful at identifying modifiers of well-understood biological processes, but they are limited in their ability to discover modifiers of processes that are poorly understood or occur only in an integrated physiological context. Small model organisms, especially the zebrafish, make it possible to combine the advantages of organism-based small molecule discovery with the technologies and throughput of modern screening. The combination of model organisms with high-throughput screening is likely to extend small molecule discovery efforts to fields of study such as developmental biology and to broaden the range of diseases for which drug screening can be performed. C1 Massachusetts Gen Hosp, Dev Biol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Dev Biol Lab, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [K08 HL068711]; NIGMS NIH HHS [R21 GM075946] NR 42 TC 103 Z9 113 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD OCT PY 2003 VL 10 IS 10 BP 901 EP 908 DI 10.1016/j.chembiol.2003.10.003 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 736TZ UT WOS:000186190400004 PM 14583256 ER PT J AU Hirshkowitz, M AF Hirshkowitz, M TI Modafinil adjunctive therapy improves excessive sleepiness and functional status in obstructive sleep apnea: A 12-month open-label extension study SO CHEST LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Chest-Physicians CY OCT 25-30, 2003 CL ORLAMDO, FLORIDA SP Amer Coll Chest Physicians C1 VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 SU S BP 75S EP 75S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 734RG UT WOS:000186070400013 ER PT J AU Hess, DR Hardy, WH AF Hess, DR Hardy, WH TI Laboratory evaluation of Bi-Flex mode of the respironics pro bi-level system SO CHEST LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Chest-Physicians CY OCT 25-30, 2003 CL ORLAMDO, FLORIDA SP Amer Coll Chest Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 SU S BP 227S EP 228S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 734RG UT WOS:000186070400507 ER PT J AU Allan, JS Garrity, JM Donahue, DM AF Allan, JS Garrity, JM Donahue, DM TI The utility of high-frequency chest wall oscillation therapy in the post-operative management of thoracic surgical patients SO CHEST LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Chest-Physicians CY OCT 25-30, 2003 CL ORLAMDO, FLORIDA SP Amer Coll Chest Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 SU S BP 235S EP 235S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 734RG UT WOS:000186070400535 ER PT J AU Flemons, WW Littner, MR AF Flemons, WW Littner, MR TI Measuring agreement between diagnostic devices SO CHEST LA English DT Review DE diagnosis; likelihood ratios; methods; polysomnography; research design; sensitivity and specificity; sleep apnea syndromes AB There is growing interest in using portable monitoring for investigating patients with suspected sleep apnea. Research studies typically report portable monitoring results in comparison with the results of sleep laboratory-based polysomnography. A systematic review of this research has recently been completed by a joint working group of the American College of Chest Physicians, the American Thoracic Society, and the American Academy of Sleep Medicine. The methods for comparing the results of portable monitors and polysomnography include product-moment correlation, intraclass correlation, mean differences/limits of agreement, sensitivity, specificity, and likelihood ratios. Each approach has advantages and limitations, which are highlighted in this review. C1 Univ Calgary, Fac Med, Calgary, AB T2N 2T9, Canada. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Flemons, WW (reprint author), Univ Calgary, Fac Med, 1403 29th Sw NW, Calgary, AB T2N 2T9, Canada. NR 5 TC 58 Z9 60 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2003 VL 124 IS 4 BP 1535 EP 1542 DI 10.1378/chest.124.4.1535 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 733LU UT WOS:000186002500051 PM 14555591 ER PT J AU An, JB Sun, YP Adams, J Fisher, M Belldegrun, A Rettig, MB AF An, JB Sun, YP Adams, J Fisher, M Belldegrun, A Rettig, MB TI Drug interactions between the proteasome inhibitor bortezomib and cytotoxic chemotherapy, tumor necrosis factor (TNF) alpha, and TNF-related apoptosis-inducing ligand in prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; APO-2 LIGAND; CONSTITUTIVE ACTIVATION; IN-VIVO; CELLS; RESISTANCE; PS-341; PATHWAY; PROTEIN; MODEL AB Purpose: Proteasome inhibition has been shown to be an effective anticancer therapy in many tumor models, including prostate cancer. We sought to identify drug interactions between the proteasome inhibitor bortezomib and other apoptotic stimuli, including cytotoxic chemotherapy and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In addition, we wanted to gain insight into the role of nuclear factor kappaB inhibition as a mediator of bortezomib cytotoxic effects. Experimental Design: Prostate cancer cell lines (LNCaP, LAPC4, CL1, and DU145) were treated with bortezomib and apoptotic stimuli (TRAIL, chemotherapy, and tumor necrosis factor alpha), alone or in combination. Apoptosis and cell viability were measured, and median effect/combination index analyses were used to quantitate drug interactions. Nuclear factor kappaB activity at baseline and in response to drug treatment was determined by gel shift and reporter gene assays. Results: Bortezomib induced cell death of androgen-dependent (LNCaP and LAPC4) and androgen-independent (CL1 and DU145) prostate cancer cell lines, although androgen-dependent cells were more sensitive to proteasome inhibition. Bortezomib synergized with TRAIL and tumor necrosis factor a to induce death in both androgen-dependent and androgen-independent cells. Conclusions: Bortezomib and TRAIL represent a synergistic drug combination that warrants further evaluation in in vivo models of prostate cancer. C1 Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Rettig, MB (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Bldg 304,Room E1-113,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 57 Z9 59 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2003 VL 9 IS 12 BP 4537 EP 4545 PG 9 WC Oncology SC Oncology GA 730KV UT WOS:000185830700032 PM 14555528 ER PT J AU Rhew, DC Bernal, M Aguilar, D Iloeje, U Goetz, MB AF Rhew, DC Bernal, M Aguilar, D Iloeje, U Goetz, MB TI Association between protease inhibitor use and increased cardiovascular risk in patients infected with human immunodeficiency virus: A systematic review SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1-INFECTED PATIENTS; INSULIN-RESISTANCE; METABOLIC ALTERATIONS; LIPID ABNORMALITIES; AQUITAINE COHORT; HIV-1 INFECTION; LIPODYSTROPHY; DISEASE; HYPERLIPIDEMIA AB Some studies have shown that currently available protease inhibitors (PIs) are associated with an increased risk of cardiovascular disease. We have systematically reviewed the published literature and conference abstracts for studies evaluating cardiovascular risk factors and events in patients receiving highly active antiretroviral therapy, with and without PIs. The majority of studies showed that the use of PIs was associated with increased levels of total cholesterol ( 36 [75%] of 48 studies), triglycerides ( 35 [73%] of 48 studies), and low-density lipoprotein ( 12 [100%] of 12 studies). PI use was often associated with morphological signs of cardiovascular disease, such as increased carotid intima thickness or atherosclerotic lesions ( 7 [88%] of 8 studies). Finally, 2 (67%) of 3 long-term observational studies that met our inclusion criteria demonstrated an association between use of PIs and subsequent myocardial infarction. The benefits of the currently available PIs should be balanced against the long-term risk of cardiovascular disease. C1 Zynx Hlth, Cedars Sinai Dept Med, Beverly Hills, CA 90212 USA. Zynx Hlth, Cedars Sinai Dept Hlth Serv, Beverly Hills, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. David Geffen UCLA Sch Med, Los Angeles, CA USA. Bristol Myers Squibb Co, Outcomes Res, Wallingford, CT 06492 USA. RP Rhew, DC (reprint author), Zynx Hlth, Cedars Sinai Dept Med, 9100 Wilshire Blvd,Ste 655E, Beverly Hills, CA 90212 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 92 TC 41 Z9 42 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 OCT 1 PY 2003 VL 37 IS 7 BP 959 EP 972 DI 10.1086/378064 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 727TR UT WOS:000185677400014 PM 13130409 ER PT J AU Osipova, D Ahveninen, J Kaakkola, S Jaaskelainen, IP Huttunen, J Pekkonen, E AF Osipova, D Ahveninen, J Kaakkola, S Jaaskelainen, IP Huttunen, J Pekkonen, E TI Effects of scopolamine on MEG spectral power and coherence in elderly subjects SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE scopolamine; magnetoencephalogram; spectral power; coherence; aging; acetylcholine ID INTERHEMISPHERIC EEG COHERENCE; EVOKED MAGNETIC-FIELDS; ALZHEIMERS-DISEASE; PHOTIC-STIMULATION; QUANTITATIVE EEG; SENILE DEMENTIA; HUMAN BRAIN; MEMORY; REST; MAGNETOENCEPHALOGRAPHY AB Objective: Scopolamine, a muscarinic receptor antagonist, can produce temporary cognitive impairments as well as electroencephalographic changes that partially resemble those observed in Alzheimer's disease. In order to test the sensitivity of spectral power and hemispheric coherence to changes in cholinergic transmission, we evaluated quantitative magnetoencephalogram (MEG) after intravenous injection of scopolamine. Methods: MEG of 8 elderly healthy subjects (59-80 years) were measured with a whole-head magnetometer after intravenous injection of scopolamine. An injection of glycopyrrolate, a peripheral muscarinic antagonist, was used as the placebo in a double-blind, randomized, cross-over design. Spectral power and coherence were computed over 7 brain regions in 3 frequency bands. Results: Scopolamine administration increased theta activity (4-8 Hz) and resulted in the abnormal pattern of MEG desynchronization in eyes-open vs. eyes-closed conditions in the alpha band (8-13 Hz). These effects were most prominent over the posterior regions. Interhemispheric and left intrahemispheric coherence was significantly decreased in the theta band (4-8 Hz). Conclusions: Spontaneous cortical activity at the theta and alpha range and functional coupling in the theta band are modulated by the cholinergic system. MEG may provide a tool for monitoring brain dynamics in neurological disorders associated with cholinergic abnormalities. (C) 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Ctr Engn, BioMag Lab, FIN-00014 Helsinki, Finland. Helsinki Brain Res Ctr, Helsinki, Finland. Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Helsinki Univ Technol, Lab Computat Engn, FIN-02150 Espoo, Finland. RP Osipova, D (reprint author), Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, POB 9, FIN-00014 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; OI Jaaskelainen, Iiro/0000-0001-6001-6950; Pekkonen, Eero/0000-0003-1621-8752 NR 39 TC 52 Z9 53 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2003 VL 114 IS 10 BP 1902 EP 1907 DI 10.1016/S1388-2457(03)00165-2 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 733CL UT WOS:000185982300015 PM 14499752 ER PT J AU Tingart, MJ Apreleva, M Lehtinen, JT Capell, B Palmer, WE Warner, JJP AF Tingart, MJ Apreleva, M Lehtinen, JT Capell, B Palmer, WE Warner, JJP TI Magnetic resonance imaging in quantitative analysis of rotator cuff muscle volume SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Tears of the rotator cuff are accompanied by muscle atrophy, which has direct implications on patient outcome after rotator cuff surgery. However, no reliable method exists to determine muscle volumes in situ. The current authors evaluated the reliability of magnetic resonance imaging in assessing rotator cuff muscle volumes. Muscle volumes were determined in 10 shoulders from cadavers using two methods: (1) oblique sagittal shoulder scans were obtained, the contours of the supraspinatus, infraspinatus and teres minor, and subscapularis muscles were traced, and muscle volumes were calculated using image analysis software; and (2) rotator cuff muscles were dissected and muscle volumes were measured by water displacement. The average magnetic resonance imaging volume of the supraspinatus, infraspinatus and teres minor, and subscapularis muscles were 36 12,96 41, and 99 33 mL, respectively. There was a significant correlation between magnetic resonance imaging and water displacement measurements. The intraobserver and interobserver variabilities were less than 4%. The results indicate that magnetic resonance imaging is a reliable method to determine rotator cuff muscle volumes with good intraobserver and interobserver variability. This method may prove valuable for preoperative assessment of rotator cuff muscles and prediction of outcome after rotator cuff repair. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Orthoped Biomech Lab, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Apreleva, M (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Orthoped Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. NR 12 TC 38 Z9 40 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2003 IS 415 BP 104 EP 110 DI 10.1097/01/blo.0000092969.12414.cl PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 737ZX UT WOS:000186263200014 PM 14612636 ER PT J AU Randolph, MA Anseth, K Yaremchuk, MJ AF Randolph, MA Anseth, K Yaremchuk, MJ TI Tissue engineering of cartilage SO CLINICS IN PLASTIC SURGERY LA English DT Review ID MESENCHYMAL PROGENITOR CELLS; RABBIT-ARTICULAR-CARTILAGE; EXPANDED POLYTETRAFLUOROETHYLENE MEMBRANE; IN-SITU PHOTOPOLYMERIZATION; HUMAN DERMAL FIBROBLASTS; GROWTH-FACTOR; COLLAGEN SPONGE; ALGINATE BEADS; STEM-CELLS; TRANSDERMAL PHOTOPOLYMERIZATION AB The primary goal of engineering cartilage as a therapeutic approach is to restore the physiological conditions of an affected or defective tissue in the body. Cartilage tissue is distributed widely in the human body and possesses an organization related to the specific demand of a particular anatomical region. In selecting the proper material for engineering cartilage, the functional demands of the replacement tissue must be considered. In summary, there is a multitude of scaffolds, naturally occurring and synthetic, that are suitable for engineering cartilage. Investigators have shown that the characteristics of the neocartilage differ significantly depending upon which scaffold is used. There are also large differences when a single scaffold is tested in vitro as opposed to in vivo. Moreover, the addition of other materials internally or externally to the cartilage composite influences the physical and biomechanical properties of the newly formed tissue. The results achieved so far are extremely encouraging and motivate further investigative efforts in the field. The biochemical composition and, more importantly, the biomechanical properties of the native tissue still represent the ideal replacement tissue. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. Univ Colorado, Dept Chem Engn, Boulder, CO 80309 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WAC 453,15 Parkman St, Boston, MA 02114 USA. NR 120 TC 28 Z9 33 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0094-1298 J9 CLIN PLAST SURG JI Clin. Plast. Surg. PD OCT PY 2003 VL 30 IS 4 BP 519 EP + DI 10.1016/S0094-1298(03)00070-1 PG 21 WC Surgery SC Surgery GA 738XP UT WOS:000186313400005 PM 14621300 ER PT J AU Bierer, LM Yehuda, R Schmeidler, J Mitropoulou, V New, AS Silverman, JM Siever, LJ AF Bierer, LM Yehuda, R Schmeidler, J Mitropoulou, V New, AS Silverman, JM Siever, LJ TI Abuse and neglect in childhood: Relationship to personality disorder diagnoses SO CNS SPECTRUMS LA English DT Article ID SEXUAL ABUSE; SUICIDAL-BEHAVIOR; TRAUMA QUESTIONNAIRE; EARLY ADULTHOOD; PHYSICAL ABUSE; RISK-FACTORS; PSYCHOPATHOLOGY; SELF; INPATIENTS; INTERVIEW AB Background: Childhood history of abuse and neglect has been associated with personality disorders and has been observed in subjects with lifetime histories of suicidality and self-injury. Most of these findings have been generated from inpatient clinical samples. Methods: This study evaluated self-rated indices of sustained childhood abuse and neglect in an outpatient sample of well-characterized personality disorder subjects (n=182) to determine the relative associations of childhood trauma indices to specific personality disorder diagnoses or clusters and to lifetime history of suicide attempts or gestures. Subjects met criteria for similar to2.5 Axis II diagnoses and 24% reported past suicide attempts. The Childhood Trauma Questionnaire was administered to assess five dimensions of childhood trauma exposure (emotional, physical, and sexual abuse, and emotional and physical neglect). Logistic regression was employed to evaluate salient predictors among the trauma measures for each cluster, personality disorder, and history of attempted suicide and self-harm. All analyses controlled for gender distribution. Results: Seventy-eight percent of subjects met dichotomous criteria for some form of childhood trauma; a majority reported emotional abuse and neglect. The dichotomized criterion for global trauma severity was predictive of cluster B, borderline, and antisocial personality disorder diagnoses. Trauma scores were positively associated with cluster A, negatively with cluster C, but were not significantly associated with cluster B diagnoses. Among the specific diagnoses comprising cluster A, paranoid disorder alone was predicted by sexual, physical, and emotional abuse. Within cluster B, only antisocial personality disorder showed significant associations with trauma scores, with specific prediction by sexual and physical abuse. For borderline personality disorder, there were gender interactions for individual predictors, with emotional abuse being the only significant trauma predictor, and only in men. History of suicide gestures was associated with emotional abuse in the entire sample and in women only; self-mutilatory behavior was associated with emotional abuse in men. Conclusion: These results suggest that childhood emotional abuse and neglect are broadly represented among personality disorders, and associated with indices of clinical severity among patients with borderline personality disorder. Childhood sexual and physical abuse are highlighted as predictors of both paranoid and antisocial personality disorders.. These results help qualify prior observations of the association of childhood sexual abuse with borderline personality disorder. C1 Gen Clin Res Ctr, Dept Psychiat, New York, NY USA. Gen Clin Res Ctr, Dept Biomath Sci, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Bierer, LM (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIMH NIH HHS [R01-MH5606] NR 42 TC 98 Z9 105 U1 10 U2 41 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 OCT PY 2003 VL 8 IS 10 BP 737 EP + PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 736EB UT WOS:000186157100006 PM 14712172 ER PT J AU Goodman, M Weiss, DS Koenigsberg, H Kotlyarevsky, V New, AS Mitropoulou, V Silverman, JM O'Flynn, K Siever, LJ AF Goodman, M Weiss, DS Koenigsberg, H Kotlyarevsky, V New, AS Mitropoulou, V Silverman, JM O'Flynn, K Siever, LJ TI The role of childhood trauma in differences in affective instability in those with personality disorders SO CNS SPECTRUMS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; PSYCHOLOGICAL RISK-FACTORS; BORDERLINE PERSONALITY; SEXUAL-ABUSE; DISSOCIATIVE EXPERIENCES; SELF-MUTILATION; FEMALE-PATIENTS; HERITABILITY; AGGRESSION; NEGLECT AB Background: This study examined the relationship of self-reported histories of childhood trauma to measures of affective instability in a sample of unmedicated outpatients with various personality disorders (n=174). Methods: Childhood trauma was measured by the Childhood Trauma Questionnaire. Affective instability comprises at least two dimensions: affective lability, assessed using the Affective Lability Scale, and affective intensity, assessed using the Affective Intensity Measure. Results: A history of emotional abuse was the only trauma variable that significantly correlated with the affect measures in the total sample (r=.21-.30). More fine-grained analyses revealed that the relationship of emotional abuse and affective instability measures varied as a function of both gender and personality disorder type. In subjects with borderline personality disorder, the correlation for emotional abuse was greatly attenuated for both Affective Lability Scale (r=.10) and Affective Intensity Measure (r=.15) total scores. Conclusion: This suggests that nontrauma-related factors may be more predominant in affective dyscontrol in individuals with borderline personality disorder. C1 Gen Clin Res Ctr, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Goodman, M (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIMH NIH HHS [R01-MH606] NR 70 TC 15 Z9 15 U1 1 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 OCT PY 2003 VL 8 IS 10 BP 763 EP 770 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 736EB UT WOS:000186157100008 PM 14712174 ER PT J AU Dien, J Spencer, KM Donchin, E AF Dien, J Spencer, KM Donchin, E TI Localization of the event-related potential novelty response as defined by principal components analysis SO COGNITIVE BRAIN RESEARCH LA English DT Article DE P300; novelty P3; inverse problem; event related potential; electroencephalography ID AUDITORY ODDBALL TASKS; TARGET DETECTION; FUNCTIONAL NEUROANATOMY; PARIETAL CORTEX; VISUAL-STIMULI; BRAIN ACTIVITY; DIPOLE MODEL; FMRI; P300; MISALLOCATION AB Recent research indicates that novel stimuli elicit at least two distinct components, the Novelty P3 and the P300. The P300 is thought to be elicited when a context updating mechanism is activated by a wide class of deviant events. The functional significance of the Novelty P3 is uncertain. Identification of the generator sources of the two components could provide additional information about their functional significance. Previous localization efforts have yielded conflicting results. The present report demonstrates that the use of principal components analysis (PCA) results in better convergence with knowledge about functional neuroanatomy than did previous localization efforts. The results are also more convincing than that obtained by two alternative methods, MUSIC-RAP and the Minimum Norm. Source modeling on 129-channel data with BESA and BrainVoyager suggests the P300 has sources in the temporal-parietal junction whereas the Novelty P3 has sources in the anterior cingulate. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. Tulane Univ, Dept Psychol, New Orleans, LA 70118 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. RP Dien, J (reprint author), Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. OI Spencer, Kevin/0000-0002-5500-7627 NR 76 TC 133 Z9 133 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD OCT PY 2003 VL 17 IS 3 BP 637 EP 650 DI 10.1016/S0926-6410(03)00188-5 PG 14 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 739QY UT WOS:000186359000010 ER PT J AU Swenson, ER AF Swenson, ER TI A comparative approach to carbonic anhydrase: the work of Thomas H. Maren SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Physiological-Society CY AUG 27, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Physiolog Soc DE Thomas H. Maren; carbonic anhydrase; kidney; cerebrospinal fluid; bicarbonate; acid; comparative physiology; marine fish ID CAT CHOROID-PLEXUS; CEREBROSPINAL-FLUID; BICARBONATE SECRETION; MARINE TELEOST; RAT-KIDNEY; CELL PH; ACETAZOLAMIDE; EXCRETION; EXCHANGE; DISSOCIATION AB Thomas H. Maren studied carbonic anhydrase (CA) for half a century, venturing into all aspects of this powerful enzyme from active site chemistry to clinical medicine. He was a keen proponent of comparative physiology to illuminate basic principles of the chemistry and biology of CA and spent 47 Summers at the Mt. Desert Island Biological Laboratory (MDIBL) studying many non-mammalian species. Following the venerable strategy of selecting the right creature to explore a particular question, Maren derived important insights into the role of CA in ion transport, acid-base regulation and gas exchange. Using the fact that tissue CAs are expressed variably in different species, and that these animals differ in temperature, acid-base status and metabolic rate, he defined the contributions of un-catalyzed and catalyzed CO, reactions in many physiological processes. Often this strategy simplified a problem and offered answers not easily obtainable in mammals. As examples, he verified the primary role of HCO3- as lead ion in CSF formation in fish and extended this to mammals. Using marine fish whose kidneys have very little CA, he uncovered mechanisms of acid-base transfer independent of CA that help to explain why CA inhibition does not lead to total bicarbonate depletion. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, S-111-Pulm,1660 S Columbian Way, Seattle, WA 98108 USA. NR 46 TC 7 Z9 7 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD OCT PY 2003 VL 136 IS 2 BP 229 EP 241 DI 10.1016/S1095-6433(03)00174-0 PG 13 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 728AZ UT WOS:000185694200002 PM 14511743 ER PT J AU Strominger, JL Byrne, MC Wilson, SB AF Strominger, JL Byrne, MC Wilson, SB TI Regulation of dendritic cell subsets by NKT cells SO COMPTES RENDUS BIOLOGIES LA English DT Article DE dendritic cell; expression profile; immune response; NKT cell; T cell ID V-ALPHA-24J-ALPHA-Q T-CELLS AB NKT cells expressing both invariant TCRs and NK cell receptors are an important regulatory cell subset active during initiation of innate immune responses. They are involved in a wide variety of immune responses, but the molecular details of their regulatory action are unknown. Transcriptional profiling has been used for analysis of NKT cell activation profiles, revealing that NKT cells differ from conventional T cells and would be expected to regulate immune responses by controlling dendritic cell activation. (C) 2003 Published by Elsevier SAS on behalf of Academie des sciences. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Genet Inst Inc, Cambridge, MA 02140 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Strominger, JL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM jlstrom@fas.harvard.edu; wilson@dfci.harvard.edu NR 7 TC 4 Z9 4 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1631-0691 J9 CR BIOL JI C. R. Biol. PD OCT-NOV PY 2003 VL 326 IS 10-11 BP 1045 EP 1048 DI 10.1016/j.crvi.2003.09.023 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 762TC UT WOS:000187997400021 PM 14744112 ER PT J AU Evgenov, OV Pacher, P Williams, W Evgenov, NV Mabley, JG Cicila, J Siko, ZB Salzman, AL Szabo, C AF Evgenov, OV Pacher, P Williams, W Evgenov, NV Mabley, JG Cicila, J Siko, ZB Salzman, AL Szabo, C TI Parenteral administration of glipizide sodium salt, an inhibitor of adenosine triphosphate-sensitive potassium channels, prolongs short-term survival after severe controlled hemorrhage in rats SO CRITICAL CARE MEDICINE LA English DT Article DE hemorrhage; shock; resuscitation; adenosine triphosphate-sensitive potassium channels; mean arterial pressure; survival ID K+ CHANNELS; SKELETAL-MUSCLE; SMOOTH-MUSCLE; ATP; SHOCK; RESUSCITATION; INSULIN; PHARMACOLOGY; HYPOTENSION; GLUCOSE AB Objective: Recent experimental evidence suggests that activation of adenosine triphosphate (ATP)-sensitive potassium channels contributes to vascular failure and early mortality after hemorrhagic shock. The present investigation evaluated the effects of the water-soluble sodium salt of glipizide, an inhibitor of ATP-sensitive potassium channels, in anesthetized and awake rats subjected to severe controlled hemorrhage. Design: Prospective, randomized, controlled study. Setting. Animal research laboratory. Subjects: Male Wistar rats. Interventions: Anesthetized rats were subjected to bleeding to reduce mean arterial pressure to either 40 or 35 mm Hg, which was maintained constant for 60 mins. In addition, awake rats underwent blood withdrawal of 4.25 mL/100 g over 20 mins. At the end of the hemorrhage period and 30 mins later, the animals received intravenous (5 and 20 mg/kg) or intramuscular (10 and 40 mg/kg) injections of glipizide sodium salt or vehicle. Measurements and Main Results. In anesthetized rats subjected to pressure-controlled hemorrhage, glipizide sodium salt improved mean arterial pressure in a dose-dependent manner. Compared with the vehicle-treated animals, mean arterial pressure increased from 41.6 +/- 4.6 to 63.1 +/- 3.1 mm Hg in the 20 mg/kg intravenous group and from 33.2 4.9 to 54.0 +/- 4.7 mm Hg in the 40 mg/kg intramuscular group 60 mins after a 40-mm Hg shock. Furthermore, the drug did not affect the hemorrhage-induced changes in blood glucose concentrations. However, the higher doses of glipizide sodium salt attenuated the increments in plasma concentrations of lactate, alanine aminotransferase, creatinine, and amylase. Moreover, the higher doses markedly improved short-term survival after pressure- and volume-controlled bleeding. Overall, the intramuscular injections of the drug exerted salutary effects that were comparable to the intravenous administration. Conclusions. In rats, parenteral administration of the water-soluble glipizide sodium salt attenuates vascular and end-organ dysfunction associated with severe hemorrhagic shock and prolongs short-term survival. The intramuscular administration provides comparable benefits as obtained by the intravenous injection. C1 Inotek Corp, Beverly, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Sch Med, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Dept Surg, Newark, NJ USA. Semmelweis Univ, Dept Pharmacol, H-1085 Budapest, Hungary. RP Evgenov, OV (reprint author), Inotek Corp, Beverly, MA USA. RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 NR 32 TC 13 Z9 13 U1 0 U2 5 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 OCT PY 2003 VL 31 IS 10 BP 2429 EP 2436 DI 10.1097/01.CCM.0000089639.84344.A7 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 733LZ UT WOS:000186003100002 PM 14530747 ER PT J AU Carman, CV Springer, TA AF Carman, CV Springer, TA TI Integrin avidity regulation: are changes in affinity and conformation underemphasized? SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID FUNCTION-ASSOCIATED ANTIGEN-1; TRANSIENT UP-REGULATION; INSIDE-OUT ACTIVATION; I-DOMAIN; LIGAND-BINDING; CELL-ADHESION; A-DOMAIN; EXTRACELLULAR SEGMENT; CYTOPLASMIC DOMAINS; LEUKOCYTE ADHESION AB Integrins play critical roles in development, wound healing, immunity and cancer. Central to their function is their unique ability to modulate dynamically their adhesiveness through both affinity- and valency-based mechanisms. Recent advances have shed light on the structural basis for affinity regulation and on the signaling mechanisms responsible for both affinity and valency modes of regulation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Carman, CV (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 NR 86 TC 359 Z9 369 U1 0 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2003 VL 15 IS 5 BP 547 EP 556 DI 10.1016/j.ceb.2003.08.003 PG 10 WC Cell Biology SC Cell Biology GA 730TP UT WOS:000185846500007 PM 14519389 ER PT J AU Lieberman, J AF Lieberman, J TI Mechanisms of granule-mediated cytotoxicity - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material ID GRANZYME-B; CASPASE ACTIVATION; APOPTOSIS; REQUIRES C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 12 TC 9 Z9 10 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2003 VL 15 IS 5 BP 513 EP 515 DI 10.1016/S0952-7915(03)00102-X PG 3 WC Immunology SC Immunology GA 728TE UT WOS:000185731800007 ER PT J AU Lieberman, J Fan, ZS AF Lieberman, J Fan, ZS TI Nuclear war: the granzyme A-bomb SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID PROTEIN PHOSPHATASE 2A; ACTIVATING FACTOR-I; LYMPHOCYTE-MEDIATED APOPTOSIS; DNA-BINDING ACTIVITY; CD8 T-CELLS; SERINE-PROTEASE; EXTRACELLULAR ACTIVITIES; CYTOTOXIC LYMPHOCYTES; HISTONE ACETYLATION; REPLICATION FACTOR AB Granzyme A, a serine protease in the cytotoxic granules of natural killer cells and cytotoxic T lymphocytes, induces caspase-independent cell death when introduced into target cells by perforin. Granzyme A induces single-stranded DNA damage as well as rapid loss of cell membrane integrity and mitochondrial transmembrane potential through unknown mechanisms. Granzyme A destroys the nuclear envelope by targeting lamins and opens up DNA for degradation by targeting histories. A special target of the granzyme A cell death pathway is an endoplasmic reticulum-associated complex, called the SET complex, which contains three granzyme A substrates, the nucleosome assembly protein SET, the DNA bending protein HMG-2, and the base excision repair endonuclease Ape1. The SET complex also contains the tumor suppressor protein pp32 and the granzyme A-activated DNase NM23-H1, which is inhibited by SET. Granzyme A cleavage of SET releases the inhibition and unleashes NM23-H1. Cleavage of Ape1 by granzyme A interferes with the ability of the target cell to repair itself. The novel cell death pathway initiated by granzyme A provides a parallel pathway for apoptosis, important in destroying targets that overexpress bcl-2 or are otherwise invulnerable to the caspases. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-45587] NR 76 TC 132 Z9 137 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2003 VL 15 IS 5 BP 553 EP 559 DI 10.1016/S0952-7915(03)00108-0 PG 7 WC Immunology SC Immunology GA 728TE UT WOS:000185731800013 PM 14499264 ER PT J AU Glorioso, JC Mata, M Fink, DJ AF Glorioso, JC Mata, M Fink, DJ TI Gene therapy for chronic pain SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE enkephalin; GDNF; gene therapy; HSV; pain ID HERPES-SIMPLEX-VIRUS; INITIAL CLINICAL-EXPERIENCE; SPINAL SUBARACHNOID SPACE; CHRONIC NEUROPATHIC PAIN; CHROMAFFIN CELL THERAPY; IMMEDIATE-EARLY GENES; BONE CANCER PAIN; NEUROTROPHIC-FACTOR; NERVE INJURY; LUMBAR TRANSPLANT AB The dorsal horn of the spinal cord represents an attractive site for interventions designed to treat chronic pain, but it has been difficult to identify small molecules that act selectively on pain transmission at the spinal level. One approach is the use of viral vector-mediated gene transfer to achieve focal production and release of short-lived analgesic peptides. Herpes simplex virus-based vectors, expressing proenkephalin delivered by subcutaneous inoculation, transduce neurons of the dorsal root ganglion, leading to release of enkephalin from nerve terminals in dorsal horn to produce an analgesic effect in several models of chronic pain. A clinical trial is set to commence. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. RP Fink, DJ (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, 200 Lothrop St, Pittsburgh, PA 15213 USA. NR 45 TC 16 Z9 20 U1 0 U2 2 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2003 VL 5 IS 5 BP 483 EP 488 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 735GE UT WOS:000186103400005 PM 14601516 ER PT J AU Bunney, TD De Boer, AH Levin, M AF Bunney, TD De Boer, AH Levin, M TI Fusicoccin signaling reveals 14-3-3 protein function as a novel step in left-right patterning during amphibian embryogenesis SO DEVELOPMENT LA English DT Article DE left-right asymmetry; 14-3-3 protein; fusicoccin; Xenopus ID LEFT-RIGHT ASYMMETRY; MEMBRANE H+-ATPASE; 1ST CLEAVAGE PLANE; DEVELOPING XENOPUS-EMBRYOS; JUNCTIONAL COMMUNICATION; SEPARATE MECHANISMS; INTRACELLULAR PH; NODAL EXPRESSION; SITUS-INVERSUS; AXIS FORMATION AB To gain insight into the molecular mechanisms underlying the control of morphogenetic signals by H+ flux during embryogenesis, we tested Fusicoccin-A (FC), a compound produced by the fungus Fusicoccum amygdali Del. In plant cells, FC complexes with 14-3-3 proteins to activate H+ pumping across the plasma membrane. It has long been thought that FC acts on higher plants only; here, we show that exposing frog embryos to FC during early development specifically results in randomization of the asymmetry of the left-right (LR) axis (heterotaxia). Biochemical and molecular-genetic evidence is presented that 14-3-3-famfly proteins are an obligate component of Xenopus FC receptors and that perturbation of 14-3-3 protein function results in heterotaxia. The subcellular localization of 14-3-3 mRNAs and proteins reveals novel cytoplasmic destinations, and a left-right asymmetry at the first cell division. Using gain-of-function and loss-of-function experiments, we show that 14-3-3E protein is likely to be an endogenous and extremely early aspect of LR patterning. These data highlight a striking conservation of signaling pathways across kingdoms, suggest common mechanisms of polarity establishment between C. elegans and vertebrate embryos, and uncover a novel entry point into the pathway of left-right asymmetry determination. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev & Craniofacial Biol, Boston, MA 02115 USA. Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Dev Genet, Sect Mol Plant Physiol & Biophys, NL-1081 HV Amsterdam, Netherlands. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, 140 The Fenway, Boston, MA 02115 USA. NR 90 TC 68 Z9 70 U1 1 U2 11 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 OCT PY 2003 VL 130 IS 20 BP 4847 EP 4858 DI 10.1242/dev.00698 PG 12 WC Developmental Biology SC Developmental Biology GA 755JG UT WOS:000187399300008 PM 12930777 ER PT J AU MacLean, HE Kim, JI Glimcher, MJ Wang, JX Kronenberg, HM Glimcher, LH AF MacLean, HE Kim, JI Glimcher, MJ Wang, JX Kronenberg, HM Glimcher, LH TI Absence of transcription factor c-maf causes abnormal terminal differentiation of hypertrophic chondrocytes during endochondral bone development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE c-maf; chondrocyte; cartilage; differentiation; vascular invasion; ossification; MMP-13 ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; INDIAN HEDGEHOG; COLLAGENASE-3 PROMOTER; CBFA1-DEFICIENT MICE; SKELETAL DEVELOPMENT; GENE-EXPRESSION; GROWTH-PLATE; MOUSE; CBFA1 AB In this study, we report that the transcription factor c-Maf is required for normal chondrocyte differentiation during endochondral bone development. c-maf is expressed in hypertrophic chondrocytes during fetal development (E14.5-E18.5), with maximal expression in the tibia occurring at E15.5 and E16.5, in terminally differentiated chondrocytes. In c-maf-null mice, fetal bone length is decreased similar to 10%, and hypertrophic chondrocyte differentiation is perturbed. There is an initial decrease in the number of mature hypertrophic chondrocytes at E15.5 in c-maf-null tibiae, with decreased expression domains of collagen X and osteopontin, markers of hypertrophic and terminal hypertrophic chondrocytes, respectively. By E16.5, there is an expanded domain of late hypertrophic, osteopontin-positive chondrocytes in the c-maf(-/-). This accumulation of hypertrophic chondrocytes persists and is still observed at 4 weeks of age. These data suggest that c-Maf facilitates the initial chondrocyte terminal differentiation and influences the disappearance of hypertrophic chondrocytes. BrdU and TUNEL analyses show normal proliferation rate and apoptosis in the c-maf-null. There is a specific decrease in MMP-13 expression at El 5.5 in the c-maf-null. MMP-13 is known to be regulated by AP-1 and may also be a target of c-Maf. Thus, cartilage is a novel system in which c-Maf acts during development, where c-Maf is required for normal chondrocyte differentiation. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR46983]; NIDDK NIH HHS [DK-56246] NR 52 TC 54 Z9 59 U1 0 U2 5 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 OCT 1 PY 2003 VL 262 IS 1 BP 51 EP 63 DI 10.1016/S0012-1606(03)00324-5 PG 13 WC Developmental Biology SC Developmental Biology GA 726TR UT WOS:000185616400004 PM 14512017 ER PT J AU Sever, S AF Sever, S TI AP-2 makes room for rivals SO DEVELOPMENTAL CELL LA English DT Editorial Material ID CLATHRIN-MEDIATED ENDOCYTOSIS; YEAST; BINDING; ADAPTER C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Charlestown, MA 02129 USA. RP Sever, S (reprint author), Harvard Univ, Sch Med, Dept Med, 149 13th St, Charlestown, MA 02129 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2003 VL 5 IS 4 BP 530 EP 532 DI 10.1016/S1534-5807(03)00304-6 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 731ED UT WOS:000185870800004 PM 14536052 ER PT J AU Tewari, M Vidal, M AF Tewari, M Vidal, M TI RNAi on the apoptosis TRAIL: The mammalian cell genetic screen comes of age SO DEVELOPMENTAL CELL LA English DT Editorial Material ID FUNCTIONAL GENOMIC ANALYSIS; ELEGANS; INTERFERENCE; IDENTIFICATION C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Tewari, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2003 VL 5 IS 4 BP 534 EP 535 DI 10.1016/S1534-5807(03)00303-4 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 731ED UT WOS:000185870800006 PM 14536054 ER PT J AU Kashyap, S Belfort, R Gastaldelli, A Pratipanawatr, T Berria, R Pratipanawatr, W Bajaj, M Mandarino, L DeFronzo, R Cusi, K AF Kashyap, S Belfort, R Gastaldelli, A Pratipanawatr, T Berria, R Pratipanawatr, W Bajaj, M Mandarino, L DeFronzo, R Cusi, K TI A sustained increase in plasma free fatty acids impairs insulin secretion in nondiabetic subjects genetically predisposed to develop type 2 diabetes SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; POLYCYSTIC OVARIAN SYNDROME; ORAL GLUCOSE-TOLERANCE; ADOLESCENT GIRLS; HEALTHY-SUBJECTS; SKELETAL-MUSCLE; DOSE-RESPONSE; CHAIN-LENGTH; RAT ISLETS; RESISTANCE AB Acute elevations in free fatty acids (FFAs) stimulate insulin secretion, but prolonged lipid exposure impairs beta-cell function in both in vitro studies and in vivo animal studies. In humans data are limited to short-term (less than or equal to48 h) lipid infusion studies and have led to conflicting results. We examined insulin secretion and action during a 4-day lipid infusion in healthy normal glucose tolerant subjects with (FH+ group, n = 13) and without (control subjects, n = 8) a family history of type 2 diabetes. Volunteers were admitted twice to the clinical research center and received, in random order, a lipid or saline infusion. On days 1 and 2, insulin and C-peptide concentration were measured as part of a metabolic profile after standardized mixed meals. Insulin secretion in response to glucose was assessed with a +125 mg/dl hyperglycemic clamp on day 3. On day 4, glucose turnover was measured with a euglycemic insulin clamp with [3-H-3]glucose. Day-long plasma FFA concentrations with lipid infusion were increased within the physiological range, to levels seen in type 2 diabetes (similar to500-800 mumol/l). Lipid infusion had strikingly opposite effects on insulin secretion in the two groups. After mixed meals, day-long plasma C-peptide levels increased with lipid infusion in control subjects but decreased in the FH+ group (+28 vs. -30%, respectively, P < 0.01). During the hyperglycemic clamp, lipid infusion enhanced the insulin secretion rate (ISR) in control subjects but decreased it in the FH+ group (first phase: +75 vs. -60%, P < 0.001; second phase: +25 vs. -35%, P < 0.04). When the ISR was adjusted for insulin resistance (ISRRd = ISR divided by [1/R-d] where R-d is the rate of insulin-stimulated glucose disposal), the inadequate P-cell response in the FH+ group was even more evident. Although ISRRd, was not different between the two groups before lipid infusion, in the FH+ group, lipid infusion reduced first- and second-phase ISRRd to 25 and 42% of that in control subjects, respectively (both P < 0.001 vs. control subjects). Lipid infusion in the FH+ group (but not in control subjects) also caused severe hepatic insulin resistance with an increase in basal endogenous glucose production (EGP), despite an elevation in fasting insulin levels, and impaired suppression of EGP to insulin. In summary, in individuals who are genetically predisposed to type 2 diabetes, a sustained physiological increase in plasma FFA impairs insulin secretion in response to mixed meals and to intravenous glucose, suggesting that in subjects at high risk of developing type 2 diabetes, beta-cell lipotoxicity may play an important role in the progression from normal glucose tolerance to overt hyperglycemia. C1 Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Cusi, K (reprint author), Univ Texas, Hlth Sci Ctr, Diabet Div, Dept Med, Room 3-380S7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Bajaj, Mandeep/B-6060-2009; Gastaldelli, Amalia/H-3319-2014 OI Gastaldelli, Amalia/0000-0003-2594-1651 FU NCRR NIH HHS [M01-RR-01346]; NIDDK NIH HHS [R01 DK-24092] NR 62 TC 258 Z9 288 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2003 VL 52 IS 10 BP 2461 EP 2474 DI 10.2337/diabetes.52.10.2461 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729AL UT WOS:000185748500002 PM 14514628 ER PT J AU Wang, CCL Gurevich, I Draznin, B AF Wang, CCL Gurevich, I Draznin, B TI Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways SO DIABETES LA English DT Article ID CORONARY HEART-DISEASE; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PLASMA-INSULIN; PROTEIN; KINASE; PROLIFERATION; WORTMANNIN AB Insulin maintains vascular smooth muscle cell (VSMC) quiescence yet can also promote VSMC migration. The mechanisms by which insulin exerts these contrasting effects were examined using alpha-smooth muscle actin (alpha-SMA) as a marker of VSMC phenotype because alpha-SMA is highly expressed in quiescent but not migratory VSMC. Insulin alone maintained VSMC quiescence and modestly stimulated VSMC migration. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of a-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration. PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels. Platelet-derived growth factor (PDGF) promoted dedifferentiation of VSMC, and insulin counteracted this effect. Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin. In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. Thus, with impaired PI3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration. C1 Denver VA Med Ctr, Vet Affairs Res Serv, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Endocrinol Metab & Diabet, Denver, CO 80202 USA. RP Draznin, B (reprint author), ACOS Res Serv, 1055 Clemont St 151, Denver, CO 80220 USA. NR 42 TC 91 Z9 107 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2003 VL 52 IS 10 BP 2562 EP 2569 DI 10.2337/diabetes.52.10.2562 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729AL UT WOS:000185748500015 PM 14514641 ER PT J AU Meneilly, GS Greig, N Tildesley, H Habener, JF Egan, JM Elahi, D AF Meneilly, GS Greig, N Tildesley, H Habener, JF Egan, JM Elahi, D TI Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID MEDIATED GLUCOSE-UPTAKE; ENERGY-INTAKE; 7-36 AMIDE; BETA-CELL; INFUSION; DETERMINANTS; MELLITUS; HUMANS; GLP-1 AB OBJECTIVE-Glucagon-like peptide 1 (GLP-1) is an insulinotropic gut hormone that, when given exogenously, may be a useful agent in the treatment of type 2 diabetes. We conducted a 3-month trial to determine the efficacy and safety of GLP-1 in elderly diabetic patients. RESEARCH DESIGN AND METHODS-A total of 16 patients with type 2 diabetes who were being treated with oral hypoglycemic agents were enrolled. Eight patients (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) remained on usual glucose-lowering therapy and eight patients (aged 73 +/- 1 years, BMI 27 +/- 1 kg/m(2)), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol (.) kg(-1) (.) h(-1). Patients recorded their capillary blood glucose (CBG) levels (four times per day, 3 days per week) and whenever they perceived hypoglycemic symptoms. The primary end points were HbA(1c) and CBG determinations. Additionally, changes in beta-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined. RESULTS-HbA(1c) levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of less than or equal to3.6 mmol/l during the study, and only 1 such measurement (3.5 mmol/l) was recorded in the GLP-1 group. Infusion of GLP-1 enhanced glucose-induced insulin secretion (pre: 119 +/- 21; post: 202 +/- 51 pmol/l; P < 0.05) and insulin-mediated glucose disposal (pre: 29.8 +/- 3.3; post: 35.9 +/- 2.3 mumol (.) kg(-1) (.) min(-1) ; P < 0.01). No effect of GLP-1 treatment was seen on the fasting plasma ghrelin levels. Although plasma ghrelin levels decreased during both portions of the clamp, a drug effect was not present. CONCLUSIONS-A GLP-1 compound is a promising therapeutic option for elderly diabetic patients. C1 Harvard Univ, Geriatr Res Lab, Massachusetts Gen Hosp, Dept Med,Med Sch, Boston, MA 02114 USA. Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. NIA, NIH, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Elahi, D (reprint author), Harvard Univ, Geriatr Res Lab, Massachusetts Gen Hosp, Dept Med,Med Sch, GRB SB 0015,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-98-02]; PHS HHS [00599] NR 31 TC 65 Z9 66 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2003 VL 26 IS 10 BP 2835 EP 2841 DI 10.2337/diacare.26.10.2835 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729HD UT WOS:000185766900020 PM 14514588 ER PT J AU Memisoglu, A Hu, FB Hankinson, SE Liu, SM Meigs, JB Altshuler, DM Hunter, DJ Manson, JE AF Memisoglu, A Hu, FB Hankinson, SE Liu, SM Meigs, JB Altshuler, DM Hunter, DJ Manson, JE TI Prospective study of the association between the proline to aline codon 12 polymorphism in the PPAR gamma gene and type 2 diabetes SO DIABETES CARE LA English DT Article ID MELLITUS; WOMEN AB OBJECTIVE-To determine whether the Pro12Ala polymorphism in the PPARgamma gene was associated with risk of type 2 diabetes in the Nurses' Health Study. RESEARCH DESIGN AND METHODS-The study was a nested case-control study of 387 incident cases of type 2 diabetes and 771 matching control subjects nested within the Nurses' Health Study, a prospective cohort study. Association between PPARgamma genotype and incident type 2 diabetes was estimated using logistic regression. RESULTS-Carriers of the PPARgamma variant 12Ala allele had reduced risk of type 2 diabetes compared with noncarriers. Unadjusted and adjusted odds ratios of type 2 diabetes were 0.74 (95% CI 0.55-1.00) and 0.72 (0.52-0.99), respectively. CONCLUSIONS-The results of this study provide further support for an inverse association between the PPARgamma variant 12Ala allele and risk of type 2 diabetes. 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, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Ctr Canc Prevent, Boston, MA 02115 USA. RP Memisoglu, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Bldg 11,Rm 109, Boston, MA 02115 USA. RI Altshuler, David/A-4476-2009; Liu, Simin/I-3689-2014 OI Altshuler, David/0000-0002-7250-4107; Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA09001, CA49449]; NIDDK NIH HHS [DK046519, DK058845] NR 8 TC 44 Z9 45 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2003 VL 26 IS 10 BP 2915 EP 2917 DI 10.2337/diacare.26.10.2915 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729HD UT WOS:000185766900033 PM 14514601 ER PT J AU Huang, Y Tola, VB Fang, PK Soybel, DI Van Hoek, AN AF Huang, Y Tola, VB Fang, PK Soybel, DI Van Hoek, AN TI Partitioning of aquaporin-4 water channel mRNA and protein in gastric glands SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE water channels; stomach; intercalated cells; fundus ID ORTHOGONAL ARRAYS; PARIETAL-CELL; K+-ATPASE; RAT; STOMACH; MUCOSA; LOCALIZATION; PARTICLES; SECRETION; H+ AB Immunolocalization studies in proximal, middle, and distal stomach indicated that aquaporin-4 (AQP4) protein is localized only in parietal cells located in the middle or deep regions of the gastric glands. In studies using in situ hybridization, AQP4 mRNA failed to localize in parietal cells but was identified in neighboring mucosal cells that were triangular in shape and smaller than parietal cells in size, and in columnar cells at the base of the gastric gland. This spatial separation of mRNA and protein was also observed in other species and with other kind of mRNA/protein. In neonatal and adolescent rats, the appearance of morphologically mature parietal cells was preceded by identification of mRNA-bearing triangular cells. Cells harboring both protein and mRNA were observed in postnatal rats and in the pyloric region of the glandular stomach, during induced hypergastrinaemia. The results suggest that such cells represent a transition between those that bear only mRNA and those that are terminally differentiated, expressing proteins that are related to acid secretion. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02132 USA. Boston VA Healthcare Syst, W Roxbury Div, Boston, MA 02132 USA. RP Van Hoek, AN (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R01 DK 55864] NR 22 TC 8 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2003 VL 48 IS 10 BP 2027 EP 2036 DI 10.1023/A:1026266225912 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 732TP UT WOS:000185961900022 PM 14627352 ER PT J AU Leonard, S AF Leonard, S TI Consequences of low levels of nicotinic acetylcholine receptors in schizophrenia for drug development SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE nicotine; nicotinic receptor; smoking; schizophrenia; drug development; addiction ID BIND ALPHA-BUNGAROTOXIN; VENTRAL TEGMENTAL AREA; PURSUIT EYE-MOVEMENTS; INBRED MOUSE STRAINS; CIGARETTE-SMOKING; ALZHEIMERS-DISEASE; TREATMENT STRATEGY; PREFRONTAL CORTEX; POSTMORTEM BRAIN; RAT HIPPOCAMPUS AB The incidence of smoking in the mentally ill is much higher than in the general population and is inordinately high in schizophrenia. It has been suggested that this might be an attempt to self-medicate an underlying biological deficit. The receptors that mediate nicotinic responses are decreased in many regions of postmortem brain in schizophrenic smokers, compared to control smokers. Patients exhibit differential responses to nicotine in a number of behavioral, cognitive, and metabolic measures. As nicotine regulates the release of a large number of neurotransmitters, it is likely that differences in downstream neuroadaptation of other transmitter/receptor systems would result from the reduced level of nicotinic receptors in these patients. The disparate responses to nicotine have consequences for the development of cholinergic drug therapies in schizophrenia. (C) 2003 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Leonard, S (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, 4200 E 9th Ave,C268-71, Denver, CO 80262 USA. NR 103 TC 12 Z9 12 U1 3 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD OCT PY 2003 VL 60 IS 2 BP 127 EP 136 DI 10.1002/ddr.10292 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728BG UT WOS:000185694900007 ER PT J AU Weisberg, E Griffin, JD AF Weisberg, E Griffin, JD TI Resistance to imatinib (Glivec): update on clinical mechanisms SO DRUG RESISTANCE UPDATES LA English DT Review DE drug resistance; STI571; imatinib; chronic myeloid leukemia; gastrointestinal stromal cancer; BCR/ABL ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; ACUTE LYMPHOBLASTIC-LEUKEMIA; ABL-POSITIVE CELLS; GASTROINTESTINAL STROMAL TUMORS; FARNESYL TRANSFERASE INHIBITOR; POLYMERASE-CHAIN-REACTION; BCR-ABL; IN-VITRO AB Imatinib mesylate, an orally administered 2-phenylaminopyrimidine derivative that inhibits BCR/ABL tyrosine kinase activity, has shown great promise in the treatment of chronic myelogenous leukemia (CML). This small molecule, tyrosine kinase inhibitor, has also been shown to be effective against metastatic gastrointestinal stromal tumors (GISTs) expressing the stem cell factor (SCF) receptor kit. However, the threat of resistance in patients has prompted investigators to uncover the mechanisms whereby malignant cells develop resistance to imatinib, and has also led to the establishment of strategies designed to over-ride imatinib resistance. Here, we provide a comprehensive overview of the effectiveness of imatinib in the treatment of chronic, accelerated and blast crisis-phase CML, Philadelphia chromosome-positive (Ph+) acute lymphoid leukemia (ALL) and metastatic GIST. Established mechanisms of resistance to imatinib are discussed, as are novel therapeutic approaches to improving drug responsiveness by reversing development of imatinib resistance in patients. (C) 2003 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 71 TC 66 Z9 69 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD OCT PY 2003 VL 6 IS 5 BP 231 EP 238 DI 10.1016/S1368-7646(03)00062-1 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 752XC UT WOS:000187200600001 PM 14643293 ER PT J AU Lynch, T AF Lynch, T TI Clinical benefit in NSCLC: the evidence for gefitinib ('Iressa', ZD1839) SO EJC SUPPLEMENTS LA English DT Article DE gefitinib; Iressa; ZD1839; clinical benefit; epidermal growth factor receptor; EGFR ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; CHEMOTHERAPY REGIMENS; SOLID TUMORS; PHASE-II; TRIAL; DOCETAXEL; PLATINUM AB In recent years it has become widely recognised that clinical benefit in cancer patients depends on factors such as symptom improvement, symptom-free survival and low toxicity, as well as the more conventional measures of tumour regression and improved overall survival. Advanced non-small-cell lung cancer (NSCLC) is a debilitating disease, the prognosis for which has improved very little over the past few decades. There is therefore a clear need for alternative options for the treatment of advanced NSCLC. The epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) has been in use in clinical trials for several years. The clinical benefit it provides in patients with advanced NSCLC is a product of the notable antitumour activity, high rates of symptom improvement and. favourable tolerability profile. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Lynch, T (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 24 TC 4 Z9 4 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2003 VL 1 IS 8 BP 17 EP 22 DI 10.1016/S1359-6349(03)80016-2 PG 6 WC Oncology SC Oncology GA 837LI UT WOS:000222631500004 ER PT J AU Merriam, GR Schwartz, RS Vitiello, MV AF Merriam, GR Schwartz, RS Vitiello, MV TI Growth hormone-releasing hormone and growth hormone secretagogues in normal aging SO ENDOCRINE LA English DT Article; Proceedings Paper CT 4th International Symposium on Growth Hormone Secretagogues CY NOV 07-10, 2002 CL CLEARWATER BEACH, FLORIDA DE aging; ghrelin; growth hormone (somatotropin); growth hormone-releasing hormone; growth hormone secretagogues; insulin-like growth factor-I ID HEALTHY OLDER MEN; FACTOR-I LEVELS; BODY-COMPOSITION; GH SECRETION; WOMEN; ADULTS; EXERCISE; PEPTIDE; GHRELIN; MK-677 AB Growth hormone (GH) secretion declines with aging, and parallels between normal aging and the signs and symptoms of adult GH deficiency have led to interest in the potential utility of replacing or stimulating GH to promote physical and psychological function and to prolong the capacity for independent living in older adults. The aging pituitary remains responsive to GH-releasing hormone (GHRH) and to ghrelin-mimetic GH secretagogues (GHS), and these agents have both theoretical and practical potential advantages as alternatives to the use of GH itself in this setting. Studies of the long duration and large scale needed to test the efficacy of GHRH or GHS on clinically important endpoints cannot be designed or conducted without first obtaining promising results in studies of smaller size focused on manageable intermediate endpoints, and all studies published to date have been of this latter type. GH RH and GHS both stimulate GH secretion, and, when given repeatedly, elevate IGF-I levels to within younger adult normal ranges. When GHRH treatment is continued for several months, these hormonal changes yield an increase in lean body (muscle) mass. GHRH, like GH, reduces body fat, but similar effects have not yet been shown with GHS. GH RH treatment has not yielded consistent improvements in physical function, although it may have a stabilizing effect. Chronic treatment with a short-acting GHRH did not improve sleep, possibly due to lack of sustained activity throughout the night. Compared to placebo, GHRH treatment improved certain tests of cognitive performance. These results, while encouraging, do not yet support the routine use of G H RH or GHS in normal aging. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Colorado, Hlth Sci Ctr, Div Geriatr Med, Denver, CO 80202 USA. RP Merriam, GR (reprint author), VA Puget Sound Hlth Care Syst, Res A-151, Tacoma, WA 98493 USA. OI Vitiello, Michael/0000-0002-9776-0473 FU NCRR NIH HHS [M01 RR 00037]; NIA NIH HHS [R01 AG 10943]; NIMH NIH HHS [R01 MH 53575, K02 MH 01158] NR 49 TC 16 Z9 16 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD OCT PY 2003 VL 22 IS 1 BP 41 EP 48 DI 10.1385/ENDO:22:1:41 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738YF UT WOS:000186314900006 PM 14610297 ER PT J AU Hsieh, TJ Fustier, P Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Fantus, IG Hamet, P Chan, JSD AF Hsieh, TJ Fustier, P Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Fantus, IG Hamet, P Chan, JSD TI High glucose stimulates angiotensinogen gene expression and cell hypertrophy via activation of the hexosamine biosynthesis pathway in rat kidney proximal tubular cells SO ENDOCRINOLOGY LA English DT Article ID CONVERTING ENZYME-INHIBITION; GLOMERULAR MESANGIAL CELLS; PROTEIN-KINASE PATHWAY; II-INDUCED HYPERTROPHY; GROWTH-FACTOR BETA-1; DIABETIC-NEPHROPATHY; RESPONSIVE ELEMENT; MOLECULAR MECHANISMS; MESSENGER-RNA; TGF-BETA AB The present study investigated whether activation of the hexosamine biosynthesis pathway might mediate at least in part the high glucose effect on angiotensinogen (ANG) gene expression and immortalized renal proximal tubular cell (IRPTC) hypertrophy. IRPTC were cultured in monolayer. ANG, renin, and beta-actin mRNA expression were determined by specific RT-PCR assays. Phosphorylation of p38 MAPK, activating transcription factor-2 (ATF-2), and cAMP-responsive element-binding protein (CREB) was determined by Western blot analysis. Cell hypertrophy was assessed by flow cytometry, intracellular p27(kip1) protein levels, and [H-3] leucine incorporation into proteins. Glucosamine stimulated ANG and renin mRNA expression and enhanced p38 MAPK, ATF-2, and CREB phosphorylation in normal glucose (5 mM) medium. Azaserine and 6-diazo-5-oxo-L-norleucine (inhibitors of glutamine: fructose-6-phosphate amino transferase enzyme) blocked the stimulatory effect of high glucose, but not that of glucosamine, on ANG gene expression in IRPTCs. SB 203580 (a specific p38 MAPK inhibitor) attenuated glucosamine action on ANG gene expression as well as p38 MAPK and ATF-2 phosphorylation, but not that of CREB. GF 109203X and calphostin C (inhibitors of protein kinase C) blocked the effect of glucosamine on ANG gene expression and CREB phosphorylation, but had no impact on p38 MAPK and ATF-2 phosphorylation. Finally, both glucosamine and high glucose induced IRPTC hypertrophy. The hypertrophic effect of glucosamine was blocked in the presence of GF 109203X, but not azaserine and SB 203580. In contrast, the hypertrophic effect of high glucose was blocked in the presence of azaserine and GF 109203X, but not SB203580. Our studies demonstrate that the stimulatory effect of high glucose on ANG gene expression and IRPTC hypertrophy may be mediated at least in part via activation of hexosamine biosynthesis pathway signaling. C1 Univ Montreal, Ctr Hosp Univ Montreal, Hotel Dieu, Ctr Rech Pavillon Masson, Montreal, PQ H2W 1T8, Canada. Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. RP Chan, JSD (reprint author), Univ Montreal, Ctr Hosp Univ Montreal, Hotel Dieu, Ctr Rech Pavillon Masson, Montreal, PQ H2W 1T8, Canada. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 53 TC 61 Z9 67 U1 0 U2 11 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT 1 PY 2003 VL 144 IS 10 BP 4338 EP 4349 DI 10.1210/en.2003-0220 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 723JP UT WOS:000185429500019 PM 12960040 ER PT J AU Farrell, JJ Graeme-Cook, F Kelsey, PB AF Farrell, JJ Graeme-Cook, F Kelsey, PB TI Treatment of bleeding colonic diverticula by endoscopic band ligation: an in-vivo and ex-vivo pilot study SO ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy/Digestive Disease Week CY MAY 16-19, 1999 CL ORLANDO, FLORIDA SP Amer Soc Gastrointestinal Endoscopy ID URGENT COLONOSCOPY; HEMORRHAGE; HEMOSTASIS; MANAGEMENT; DIAGNOSIS; INJECTION; THERAPY AB Background and Study Aims: Angiographic and surgical therapy are standards of care for persistent diverticular bleeding. Colonoscopic intervention using epinephrine injection, multipolar electrocautery, and placement of an Endoclip has not gained widespread acceptance due to concerns about complications, and the widespread management of severe lower gastrointestinal bleeding by surgeons and interventional radiologists. The utility of colonoscopic band ligation for control of diverticular bleeding was evaluated both in vivo and ex vivo. Patients and Methods: Endoscopic band ligation of diverticula was performed on surgical resection specimens and in patients with actively bleeding colonic diverticula. Results: In the in-vivo study, active diverticular bleeding was completely controlled in four patients by endoscopic band ligation. In two cases, a visible vessel was seen on the everted and banded diverticulum. Procedure time ranged from 45 to 140 min. The total lengths of hospital stays for the four patients were 2, 6, 14, and 35 days. The long hospital stays (> 7 days) were associated with non-gastrointestinal co-morbidity. There were no acute complications of band ligation. No rebleeding or need for surgery occurred during a follow-up period of 12 months in any of the patients. In the ex-vivo study, 11 diverticula were successfully everted and banded in five of nine surgical specimens (one right colon and four left colons). Mucosa was identified in all of the "banded" segments. Ten of 11 ligated diverticula revealed evidence of blood vessels or submucosal tissue. The presence of subserosal fat was suggested in three of the 11 "banded" segments, and none of the ex-vivo ligated diverticula contained muscularis propria or serosal involvement. There was no evidence of perforation. Conclusions: Both in-vivo and ex-vivo data suggest that endoscopic band ligation may be a safe and effective therapy for actively bleeding colonic diverticula. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit Med Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Farrell, JJ (reprint author), Univ Calif Los Angeles, Sch Med, Div Digest Dis, 200 UCLA Med Plaza,Suite 365, Los Angeles, CA 90095 USA. NR 23 TC 43 Z9 45 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 2003 VL 35 IS 10 BP 823 EP 829 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 726GX UT WOS:000185591500003 PM 14551859 ER PT J AU Kim, JY Hauser, R Wand, MP Herrick, RF Amarasiriwardena, CJ Christiani, DC AF Kim, JY Hauser, R Wand, MP Herrick, RF Amarasiriwardena, CJ Christiani, DC TI The association of expired nitric oxide with occupational particulate metal exposure SO ENVIRONMENTAL RESEARCH LA English DT Article DE particulate matter; metals; air pollutants; occupational; nitric oxide; epidemiology ID FUEL-OIL ASH; AIR-POLLUTION; FLY-ASH; TRANSITION-METALS; LUNG INJURY; MEDIATE; MATTER; SMOKE; HYPERREACTIVITY; INFLAMMATION AB Toxicologic studies have shown that soluble transition metals in residual oil fly ash (ROFA) can induce pulmonary injury. In this study, we investigated the association between the fractional concentration of expired nitric oxide (FENO) and exposure to metal constituents of particulate matter with an aerodynamic mass median diameter less than or equal to2.5 mum (PM2.5) in boilermakers exposed to ROFA and metal fume. Metals investigated included vanadium, chromium, manganese, nickel, copper, and lead. Subjects were monitored for 5 consecutive days during boiler repair overhauls in 1999 (n = 20) and 2000 (n = 14). In 1999, we found a significant inverse association between log-transformed FENO and PM2.5 metal concentrations. LogF(E)NO changed by -0.03 (95% Cl: -0.04, -0.01), -0.56 (95% CI: -0.88, -0.24), -0.09 (95% CI: -0.16, -0.02), and -0.04 (95% CI: -0.07, -0.02) per mug/m(3) of PM2.5 vanadium, chromium, manganese, and nickel, respectively. In 2000, no significant associations were observed, most likely due to exposure misclassification resulting from the use of respirators. The inverse association between PM2.5 metal exposure and FENO in subjects with limited respirator usage suggests that soluble transition metals might be partially responsible for the adverse pulmonary responses seen in workers exposed to ROFA. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1402,665 Huntington Ave, Boston, MA 02115 USA. RI Wand, Matt /F-9413-2012 OI Wand, Matt /0000-0003-2555-896X FU NIEHS NIH HHS [ES09860, ES00002]; NIOSH CDC HHS [OH00152]; PHS HHS [T42110421] NR 36 TC 15 Z9 16 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 2003 VL 93 IS 2 BP 158 EP 166 DI 10.1016/S0013-9351(03)00017-3 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 724WN UT WOS:000185509800007 PM 12963400 ER PT J AU Takeda, A Homma, S Okamoto, T Kufe, D Ohno, T AF Takeda, A Homma, S Okamoto, T Kufe, D Ohno, T TI Immature dendritic cell/tumor cell fusions induce potent antitumour immunity SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cancer vaccine; cell fusion; dendritic cell; immunotherapy; maturation; tumour-bearing host ID COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; CANCER-IMMUNOTHERAPY; ANTIGEN PRESENTATION; CARCINOMA-CELLS; T-LYMPHOCYTES; MATURATION; RESPONSES; TUMORS; IMMUNIZATION AB Background Maturation of dendritic cells (DCs) is important to induce antigen-specific antitumour immunity in cancer immunotherapy with antigen-loaded DCs. However, DCs from tumour-bearing hosts are immature and functionally defective for antigen presentation. We examined whether DCs from tumour-bearing mice could be an effective part of a DC/ tumour cell fusion vaccine. Materials and methods Dendritic cells from healthy (DC-Hs) or MC38 tumour-bearing mice (DC-TBs) were examined for endocytotic capacity of FITC-labelled dextran, antigen-presenting capacity in allogeneic mixed leucocyte reaction (allo-MLR) and expression of I-A(b), CD80, and CD86. Fusion cells (FCs) of DC-Hs or DC-TBs and MC38 cells (FC-Hs or FC-TBs) were generated by treatment with polyethylene glycol ( PEG). Mice vaccinated with FC-Hs or FC-TBs were studied for cytolytic activity of splenocytes and suppressive activity against established MC38 pulmonary metastases. Results Dendritic cell-TBs showed higher endocytotic capacity and lower antigen-presenting capacity than did DC-Hs, results indicating that DC-TBs are more immature and functionally defective for antigen presentation than are DC-Hs. Expression of surface molecules, however, was almost same between DC-Hs and DC-TBs. Splenocytes from mice immunized with FC-Hs or FC-TBs induced the same high cytolytic activity against MC38 cells. Vaccination of mice with FC-Hs or FC-TBs resulted in the same significant suppressive effect against established pulmonary metastases of MC38. Conclusion Dendritic cells from tumour-bearing mice, despite being functionally defective, are effective vehicles for immunotherapy using DC/ tumour cell fusion vaccines. C1 Jikei Univ, Sch Med, Dept Oncol, Inst DNA Med, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1058461, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Homma, S (reprint author), Jikei Univ, Sch Med, Dept Oncol, Inst DNA Med, 3-25-8 Nishi Shinbashi,Minato Ku, Tokyo 1058461, Japan. NR 35 TC 21 Z9 24 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 2003 VL 33 IS 10 BP 897 EP 904 DI 10.1046/j.1365-2362.2003.01194.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 723RR UT WOS:000185445800010 PM 14511362 ER PT J AU Liang, SC Latchman, YE Buhlmann, JE Tomczak, MF Horwitz, BH Freeman, GJ Sharpe, AH AF Liang, SC Latchman, YE Buhlmann, JE Tomczak, MF Horwitz, BH Freeman, GJ Sharpe, AH TI Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE PD-1; PD-L1; PD-L2; EAE; NOD ID NF-KAPPA-B; NONOBESE DIABETIC MOUSE; T-CELL-ACTIVATION; COSTIMULATORY MOLECULES; TH2 CELLS; ENDOTHELIAL-CELLS; DENDRITIC CELLS; CYTOKINE; B7-H1; MICE AB Newer members of the B7-CD28 superfamily include the receptor PD-1 and its two ligands, PD-L1 and PD-L2. Here, we characterize the expression of PD-1, PD-L1, and PD-L2 in tissues of naive mice and in target organs from two models of autoimmunity, the pancreas from non-obese diabetic (NOD) mice and brain from mice with experimental autoimmune encephalomyelitis (EAE). In naive mice, protein expression of PD-1, PD-L1, and PD-L2 was detected in the thymus, while PD-1 and PD-L1 were detected in the spleen. PD-L1, but not PD-L2, was also detected at low levels on cardiac endothelium, pancreatic islets, and syncyciotrophoblasts in the placenta. In pre-diabetic NOD mice, PD-1 and PD-L1 were expressed on infiltrating cells in the pancreatic islets. Furthermore, PD-L1 was markedly up-regulated on islet cells. In brains from mice with EAE, PD-1, PD-L1, and PD-L2 were expressed on infiltrating inflammatory cells, and PD-L1 was up-regulated on endothelium within EAE brain. The distinct expression patterns of PD-L1 and PD-L2 led us to compare their transcriptional regulation in STAT4(-/-), STAT6(-/-), or NF-kB p50(-/-) p65(+/-) dendritic cells (DC). PD-L2, but not PD-L1, expression was dramatically reduced in p50(-/-) p65(+/-) DC. Thus, PD-L1 and PD-L2 exhibit distinct expression patterns and are differentially regulated on the transcriptional level. C1 Harvard Univ, Sch Med, Div Med Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Eugene Braunwald Res Ctr, 221 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA84500]; NIAID NIH HHS [AI38310, AI39671, AI40614] NR 43 TC 259 Z9 278 U1 6 U2 33 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 OCT PY 2003 VL 33 IS 10 BP 2706 EP 2716 DI 10.1002/eji.200324228 PG 11 WC Immunology SC Immunology GA 733JG UT WOS:000185996200007 PM 14515254 ER PT J AU Straessle, A Loup, F Arabadzisz, D Ohning, GV Fritschy, JM AF Straessle, A Loup, F Arabadzisz, D Ohning, GV Fritschy, JM TI Rapid and long-term alterations of hippocampal GABA(B) receptors in a mouse model of temporal lobe epilepsy SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; kainic acid; metabotropic receptors; neurodegeneration; recurrent seizures; synaptic plasticity ID HUMAN EPILEPTOGENIC HIPPOCAMPUS; DENTATE GYRUS; RAT HIPPOCAMPUS; NEUROPEPTIDE-Y; SYNAPTIC REORGANIZATION; PYRAMIDAL CELLS; CELLULAR-DISTRIBUTION; EPILEPTIFORM ACTIVITY; RECURRENT SEIZURES; ANIMAL-MODELS AB Alterations of gamma-aminobutyric acid (GABA)(B) receptor expression have been reported in human temporal lobe epilepsy (TLE). Here, changes in regional and cellular expression of the GABA(B) receptor subunits R1 (GBR1) and R2 (GBR2) were investigated in a mouse model that replicates major functional and histopathological features of TLE. Adult mice received a single, unilateral injection of kainic acid (KA) into the dorsal hippocampus, and GABA(B) receptor immunoreactivity was analysed between 1 day and 3 months thereafter. In control mice, GBR1 and GBR2 were distributed uniformly across the dendritic layers of CA1-CA3 and dentate gyrus. In addition, some interneurons were labelled selectively for GBR1. At 1 day post-KA, staining for both GBR1 and GBR2 was profoundly reduced in CA1, CA3c and the hilus, and no interneurons were visible anymore. At later stages, the loss of GABA(B) receptors persisted in CA1 and CA3, whereas staining increased gradually in dentate gyrus granule cells, which become dispersed in this model. Most strikingly, a subpopulation of strongly labelled interneurons reappeared, mainly in the hilus and CA3 starting at 1 week post-KA. In double-staining experiments, these cells were selectively labelled for neuropeptide Y. The number of GBR1-positive interneurons also increased contralaterally in the hilus. The rapid KA-induced loss of GABA(B) receptors might contribute to epileptogenesis because of a reduction in both presynaptic control of transmitter release and postsynaptic inhibition. In turn, the long-term increase in GABA(B) receptors in granule cells and specific subtypes of interneurons may represent a compensatory response to recurrent seizures. C1 Univ Zurich, Inst Pharmacol & Toxicol, CH-8006 Zurich, Switzerland. VA GLAHS W Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Fritschy, JM (reprint author), Univ Zurich, Inst Pharmacol & Toxicol, CH-8006 Zurich, Switzerland. FU NIDDK NIH HHS [NIH DK4130] NR 68 TC 48 Z9 52 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2003 VL 18 IS 8 BP 2213 EP 2226 DI 10.1046/j.1460-9568.2003.02964.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 735ML UT WOS:000186119100012 PM 14622182 ER PT J AU Huisman, TAGM AF Huisman, TAGM TI Diffusion-weighted imaging: basic concepts and application in cerebral stroke and head trauma SO EUROPEAN RADIOLOGY LA English DT Article DE diffusion-weighted imaging; apparent diffusion coefficient; fractional anisotropy; cerebral ischemia; traumatic brain injury ID MAGNETIC-RESONANCE; ISCHEMIC PENUMBRA; BRAIN-INJURY; TIME-COURSE; VENOUS THROMBOSIS; ARTERY OCCLUSION; AXONAL INJURY; WHITE-MATTER; MR; PERFUSION AB Diffusion-weighted imaging (DWI) of the brain represents a new imaging technique that extends imaging from depiction of neuroanatomy to the level of function and physiology. DWI measures a fundamentally different physiological parameter compared with conventional MRI. Image contrast is related to differences in the diffusion rate of water molecules rather than to changes in total tissue water. DWI can reveal pathology in cases where conventional MRI remains unremarkable. DWI has proven to be highly sensitive in the early detection of acute cerebral ischemia and seems promising in the evaluation of traumatic brain injury. DWI can differentiate between lesions with decreased and increased diffusion. In addition, full-tensor DWI can evaluate the microscopic architecture of the brain, in particular white matter tracts, by measuring the degree and spatial distribution of anisotropic diffusion within the brain. This article reviews the basic concepts of DWI and its application in cerebral ischemia and traumatic brain injury. C1 Univ Zurich, Childrens Hosp, Dept Radiol, CH-8032 Zurich, Switzerland. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Huisman, TAGM (reprint author), Univ Zurich, Childrens Hosp, Dept Radiol, Steinwiesstr 75, CH-8032 Zurich, Switzerland. NR 55 TC 98 Z9 104 U1 2 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD OCT PY 2003 VL 13 IS 10 BP 2283 EP 2297 DI 10.1007/s00330-003-1843-6 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 729TU UT WOS:000185791000010 PM 14534804 ER PT J AU Royall, DR Palmer, R Chiodo, LK Polk, MJ AF Royall, DR Palmer, R Chiodo, LK Polk, MJ TI Decline in learning ability best predicts future dementia type: The Freedom House Study SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID MILD COGNITIVE IMPAIRMENT; MINI-MENTAL-STATE; PROBABLE ALZHEIMERS-DISEASE; EXECUTIVE INTERVIEW; STRUCTURAL MODELS; DIAGNOSIS; PREVALENCE; FEATURES; RETIREES; CRITERIA AB The authors studied longitudinal change in learning efficiency as a predictor of future dementia type among healthy, well-educated, noninstitutionalized elderly retirees. Serial assessments of memory were obtained using the California Verbal Learning Test (CVLT). Latent growth (LG) models were developed from the slopes of the subjects' performance over the first five CVLT learning trials at each of three serial administrations (e.g., cohort inception [i.e., baseline] [CVLT1], 18 months [CVLT2] and 36 months [CVLT3]). The resulting growth curves were incorporated into a higher order LG model representing the dynamic change in learning efficiency over time (DeltaCVLT). DeltaCVLT was used to predict each subject's "dementia type'' (i.e., clinical state) at 36 months (e.g., no dementia, Type 1 [Alzheimer type] dementia or Type 2 [non-Alzheimer type] dementia), after adjusting for CVLT1, baseline age, and baseline dementia type. Nonlinear (logarithmic) LG models of CVLT1-CVLT3 and DeltaCVLT best fit the data. There was significant variability about both CVLT1 and DeltaCVLT, suggesting subgroups in the sample with significantly different baseline memory function, and different rates of deterioration in learning efficiency. Age, baseline dementia type, and DeltaCVLT made significant independent contributions to final dementia type. CVLT1 did not predict final dementia type independently of the other covariates. These data suggest that baseline memory performance in noninstitutionalized elderly retirees does not predict future dementia type independently of the dynamic rate of change in memory measures. Serial administrations of memory tests may help identify nondemented persons at greater or lesser risk for conversion to frank dementia in the near-term. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Pharmacol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd curl Dr, San Antonio, TX 78284 USA. NR 70 TC 15 Z9 15 U1 4 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD OCT-DEC PY 2003 VL 29 IS 4 BP 385 EP 406 DI 10.1080/03610730390228303 PG 22 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 716FC UT WOS:000185017300001 PM 12959874 ER PT J AU Koenecke, C Shaffer, J Alexander, SI Preffer, F Dombkowski, D Saidman, SL Dey, B McAfee, S Spitzer, TR Sykes, M AF Koenecke, C Shaffer, J Alexander, SI Preffer, F Dombkowski, D Saidman, SL Dey, B McAfee, S Spitzer, TR Sykes, M TI NK cell recovery, chimerism, function, and recognition in recipients of haploidentical hematopoietic cell transplantation following nonmyeloablative conditioning using a humanized anti-CD2 mAb, Medi-507 SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; NATURAL-KILLER-CELLS; COMPLEX CLASS-I; ALLOGENEIC CHIMERAS; PROGENITOR CELLS; GRAFT-REJECTION; DENDRITIC CELLS; LYMPHOCYTES-T; RECEPTORS; EXPRESSION AB Objective. Natural killer (NK) cells kill allogeneic cells that lack a class I MHC ligand for clonally distributed killer inhibitory receptors (KIR). Following HLA-mismatched hematopoietic cell transplantation (HCT), donor NK cells might mediate graft-vs-host (GVH) reactions that promote donor chimerism and mediate anti-tumor effects. Additionally, recipient NK cells might mediate donor marrow rejection. We have developed a nonmyeloablative approach to haploidentical HCT involving recipient treatment with a T cell-depleting mAb, Medi-507, that can achieve donor engraftment and mixed hematopoietic chimerism without graft-vs-host disease (GVHD). Donor lymphocyte infusions (DLI) are later administered in an effort to achieve graft-vs-leukemia/lymphoma (GVL) effects without GVHD. It is unknown whether NK cell "tolerance" develops in human mixed chimeras. Methods. We have addressed these issues in 12 patients receiving Medi-507-based nonmyeloablative haploidentical HCT. Results. NK cells recovered relatively early, despite the presence of circulating anti-CD2 mAb, but the majority of initially recovering cells lacked CD2 expression. These NK cells showed a reduced capacity, compared to those from normal donors, to kill class I-deficient targets. No association was detected between KIR mismatches in the host-vs-graft (HVG) or GVH direction and graft or tumor outcomes in this small series. NK cell chimerism did not correlate with chimerism in other lineages in mixed chimeras. NK cell tolerance to the host was not observed in a patient with full donor chimerism. One patient developed NK cell reactivity against donor-derived lymphoblast targets after loss of chimerism, despite the absence of an HVG KIR mismatch. Conclusion. Our results do not show an impact of NK cells on the outcome of nonmyeloablative, even T cell-depleted, HCT across haplotype barriers using an anti-CD2 mAb. Our data also raise questions about the applicability of observations made with NK cell clones to the bulk NK cell repertoire in humans. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Pediat, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit,Dept Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu RI Koenecke, Christian/C-3138-2009 OI Koenecke, Christian/0000-0001-7025-1735 FU NCI NIH HHS [R01 CA79986]; NHLBI NIH HHS [R01 HL63474] NR 57 TC 22 Z9 24 U1 0 U2 1 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 OCT PY 2003 VL 31 IS 10 BP 911 EP 923 DI 10.1016/S0301-472X(03)00224-8 PG 13 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HB UT WOS:000220964700010 PM 14550807 ER PT J AU Wu, CJ Hochberg, EP Rogers, SA Kutok, JL Biernacki, M Nascimento, AF Marks, P Bridges, K Ritz, J AF Wu, CJ Hochberg, EP Rogers, SA Kutok, JL Biernacki, M Nascimento, AF Marks, P Bridges, K Ritz, J TI Molecular assessment of erythroid lineage chimerism following nonmyeloablative allogeneic stem cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; SINGLE-NUCLEOTIDE POLYMORPHISMS; DONOR LYMPHOCYTE INFUSION; MIXED HEMATOPOIETIC CHIMERISM; MULTIPLE-MYELOMA; HUMAN GENOME; HUMAN GENES; THERAPY; DISEASE AB Objective. Nonmyeloablative conditioning regimens for allogeneic stem cell transplantation are now commonly used in the treatment of patients with hematologic malignancies. Since this treatment often results in the establishment of mixed hematopoietic chimerism, this approach may also prove to be useful in the treatment of nonmalignant disorders, such as sickle cell disease and thalassemia major. To apply this approach to these diseases, it will be necessary to determine the levels of donor erythropoiesis required to correct hemolysis and ameliorate disease symptoms. Current methods for measuring hematopoietic chimerism are based on DNA polymorphisms that distinguish recipient from donor. These methods accurately measure donor leukocyte engraftment but do not quantify the relative contributions of recipient and donor erythropoiesis following transplant. Methods. To specifically measure erythroid-lineage chimerism, we used pyrosequencing of the sickle cell mutation to quantify the relative levels of normal and sickle beta-globin mRNA in patient samples. Results of P-globin RNA chimerism were compared to assessment of beta-globin DNA chimerism as well as analysis of short tandem repeat (STR) polymorphisms, cytogenetics, and hemoglobin electrophoresis. Results. Donor engraftment was measured in two adult patients following nonmyeloablative stem cell transplant for sickle cell disease. In Patient 1, 25 to 30% of peripheral leukocytes were donor derived after day 41. In contrast, more than 55% of peripheral blood P-globin mRNA was of donor origin, and these results correlated with posttransplant clinical improvement. Patient 2 achieved 40 to 50% donor leukocyte engraftment from day 33 onward. This was associated with 70 to 100% peripheral blood donor P-globin mRNA. Conclusions. These studies demonstrate that relatively low levels of donor leukocyte engraftment can be associated with higher levels of donor erythropoiesis and with significant clinical improvement. Pyrosequencing of lineage-specific mRNA directly measures functional reconstitution of donor cells and provides valuable information that can affect clinical decisions in patients with nonmalignant diseases following allogeneic transplant. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wu, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM cwu@partners.org RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [K08 HL04293]; NIAID NIH HHS [AI29530] NR 32 TC 13 Z9 14 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 OCT PY 2003 VL 31 IS 10 BP 924 EP 933 DI 10.1016/S0301-472X(03)00227-3 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HB UT WOS:000220964700011 PM 14550808 ER PT J AU Vaquero, EC Edderkaoui, M Nam, KJ Gukovsky, I Pandol, SJ Gukovskaya, AS AF Vaquero, EC Edderkaoui, M Nam, KJ Gukovsky, I Pandol, SJ Gukovskaya, AS TI Extracellular matrix proteins protect pancreatic cancer cells from death via mitochondrial and nonmitochondrial pathways SO GASTROENTEROLOGY LA English DT Article ID CYTOCHROME-C RELEASE; DEPENDENT CASPASE ACTIVATION; PERMEABILITY TRANSITION PORE; DETACHMENT-INDUCED APOPTOSIS; EPITHELIAL-CELLS; IN-VIVO; NECROSIS; INHIBITION; ANOIKIS; CARCINOMA AB Background & Aims: Pancreatic cancer is a very aggressive malignancy. Normal cells die through apoptosis when detached from extracellular matrix (ECM), but the role of ECM in cancer cell survival is poorly understood. Here, we determined the effects of ECM proteins on death responses and underlying signaling pathways in human pancreatic cancer cells. Methods: We measured apoptosis and necrosis, caspase activation, and mitochondrial dysfunction in MIA PaCa-2 and PANC-1 pancreatic carcinoma cells both detached and attached to ECM proteins. Results: Detachment of pancreatic cancer cells from ECM did not induce classic apoptosis, as it does in normal cells, but induced necrosis and apoptosis associated with secondary necrosis. It caused a pronounced mitochondrial depolarization and release of cytochrome c and Smac/DIABLO. However, as different from normal cells, cytochrome c release did not result in downstream caspase activation. Executioner caspases were activated in detached pancreatic cancer cells independent of cytochrome c. Laminin and fibronectin, but not collagen 1, markedly increased pancreatic cancer cell survival by inhibiting both mitochondrial dysfunction (leading to inhibition of necrosis) and caspase activity (leading to decreased apoptotic DNA fragmentation). Conclusions: ECM proteins greatly protect pancreatic cancer cells from death by mechanisms different from those operating in normal cells. The results suggest ECM proteins and their receptors as potential targets for treatment of pancreatic cancer. C1 W Los Angeles Healthcare Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), W Los Angeles Healthcare Ctr, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 57 TC 41 Z9 42 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2003 VL 125 IS 4 BP 1188 EP 1202 DI 10.1053/S0016-5085(03)01203-4 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 728TB UT WOS:000185731500023 PM 14517801 ER PT J AU Fuhrmann, S Stark, MR Heller, S AF Fuhrmann, S Stark, MR Heller, S TI Expression of Frizzled genes in the developing chick eye SO GENE EXPRESSION PATTERNS LA English DT Article DE development; retina; retinal pigmented epithelium; frizzled; Wnt; in situ hybridization; chick AB Frizzleds are transmembrane receptors that can transduce signals dependent upon binding of Writs, a large family of secreted glycoproteins homologous to the Drosophila wingless (wg) gene product and critical for a wide variety of normal and pathological developmental processes. In the nervous system, Wnts and Frizzleds play an important role in anterior-posterior patterning, cell fate decisions, proliferation, and synaptogenesis. However, little is known about the role of Frizzled signaling in the developing eye. We isolated cDNAs for ten chick Frizzleds and analyzed the spatial and temporal expression patterns during eye development in the chick embryo. Frizzled-1 to -9 are specifically expressed in the eye at various stages of development and show a complex and partially overlapping pattern of expression. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Utah, Dept Ophthalmol & Visual Sci, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Brigham Young Univ, Dept Physiol & Dev Biol, Provo, UT 84602 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Fuhrmann, S (reprint author), Univ Utah, Dept Ophthalmol & Visual Sci, Eccles Inst Human Genet, 15 North 2030 East, Salt Lake City, UT 84112 USA. FU NEI NIH HHS [R01 EY014954, R01 EY014954-01]; NICHD NIH HHS [R03 HD41510]; NIDCD NIH HHS [DC00241] NR 6 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD OCT PY 2003 VL 3 IS 5 BP 659 EP 662 DI 10.1016/S1567-133X(03)00107-8 PG 4 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 726DD UT WOS:000185582300016 PM 12972002 ER PT J AU Tian, W Boggs, DA Uko, G Essiet, A Inyama, M Banjoko, B Adewold, T Ding, WZ Mohseni, M Fritz, R Chen, DF Palmer, LJ Fraser, PA AF Tian, W Boggs, DA Uko, G Essiet, A Inyama, M Banjoko, B Adewold, T Ding, WZ Mohseni, M Fritz, R Chen, DF Palmer, LJ Fraser, PA TI MICA, HLA-B haplotypic variation in five population groups of sub-Saharan African ancestry SO GENES AND IMMUNITY LA English DT Article DE MICA; HLA; SSOP; linkage disequilibrium; sub-Saharan Africans ID MAJOR HISTOCOMPATIBILITY COMPLEX; EWENS SAMPLING DISTRIBUTION; CLASS-I REGION; LINKAGE DISEQUILIBRIUM; T-CELLS; GENE; ALLELES; DISEASE; POLYMORPHISM; NKG2D AB The human major histocompatibility complex (MHC) class I chain-related gene A (MICA), located 46 kb centromeric to HLA-B, encodes a stress-inducible protein, which is a ligand for the NKG2D receptor. In addition to its primary role in immune surveillance, data suggest that MICA is involved in the immune response to transplants and in susceptibility to some diseases. In this study, 152 subjects from the Yoruba (n=74), Efik (n=32), and Igbo (n=46) tribes of southern Nigeria, 39 nationwide African-American stem cell donors, and 60 African-American individuals residing in the metropolitan Boston area were studied for MICA, HLA-B allelic variation, haplotypic diversity, and linkage disequilibrium (LD). MICA and HLA-B exhibited a high degree of genetic diversity among the populations studied. In particular, MICA allele and HLA-B-MICA haplotype frequencies and LD in the Efik and Igbo tribes were significantly different from the other study groups. HLA-B and MICA loci demonstrated significant global LD in all five populations (P-values <0.00001). LD also varied in a haplotype-specific manner. A novel MICA allele was detected in the Boston population. These findings are important from an anthropologic perspective, and will inform future HLA-linked disease association studies in related ethnic groups of African-derived ancestry. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Calabar, Teaching Hosp, Dept Surg, Calabar, Nigeria. Blue Cross Hosp, Lagos, Nigeria. Univ Coll Ibadan Hosp, Dept Pathol, Ibadan, Nigeria. Nigerian Inst Med Res, Yaba, Nigeria. Brigham & Womens Hosp, Natl Marrow Donor Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Tian, W (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Palmer, Lyle/K-3196-2014 OI Palmer, Lyle/0000-0002-1628-3055 NR 53 TC 18 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2003 VL 4 IS 7 BP 500 EP 505 DI 10.1038/sj.gene.6364017 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 732XH UT WOS:000185970500006 PM 14551603 ER PT J AU David, G Turner, GM Yao, Y Protopopov, A DePinho, RA AF David, G Turner, GM Yao, Y Protopopov, A DePinho, RA TI mSin3-associated protein, mSds3, is essential for pericentric heterochromatin formation and chromosome segregation in mammalian cells SO GENES & DEVELOPMENT LA English DT Article DE Sin3 complex; historic modification; pericentric heterochromatin; chromosome segregation ID HISTONE DEACETYLASE COMPLEX; TRANSCRIPTIONAL REPRESSION; CENTROMERE FUNCTION; INTEGRAL COMPONENT; LYSINE 9; SIN3; DNA; METHYLTRANSFERASE; INSTABILITY; METHYLATION AB The histone code guides many aspects of chromosome biology including the equal distribution of chromosomes during cell division. In the chromatin domains surrounding the centromere, known as pericentric heterochromatin, histone modifications, particularly deacetylation and methylation, appear to be essential for proper chromosome segregation. However, the specific factors and their precise roles in this highly orchestrated process remain under active investigation. Here, we report that germ-line or somatic deletion of mSds3, an essential component of the functional mSin3/HDAC corepressor complex, generates a cell-lethal condition associated with rampant aneuploidy, defective karyokinesis, and consequently, a failure of cytokinesis. mSds3-deficient cells fail to deacetylate and methylate pericentric heterochromatin histones and to recruit essential heterochromatin-associated proteins, resulting in aberrant associations among heterologous chromosomes via centromeric regions and consequent failure to properly segregate chromosomes. Mutant mSds3 molecules that are defective in mSin3 binding fail to rescue the mSds3 null phenotypes. On the basis of these findings, we propose that mSds3 and its associated mSin3/HDAC components play a central role in initiating the cascade of pericentric heterochromatin-specific modifications necessary for the proper distribution of chromosomes during cell division in mammalian cells. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. OI , gregory/0000-0002-3371-4558 FU NCI NIH HHS [R01CA86379, R01 CA086379] NR 38 TC 67 Z9 70 U1 0 U2 2 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 OCT 1 PY 2003 VL 17 IS 19 BP 2396 EP 2405 DI 10.1101/gad.1109403 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 729DW UT WOS:000185757800008 PM 14522945 ER PT J AU Peri, S Navarro, JD Amanchy, R Kristiansen, TZ Jonnalagadda, CK Surendranath, V Niranjan, V Muthusamy, B Gandhi, TKB Gronborg, M Ibarrola, N Deshpande, N Shanker, K Shivashankar, HN Rashmi, BP Ramya, MA Zhao, ZX Chandrika, KN Padma, N Harsha, HC Yatish, AJ Kavitha, MP Menezes, M Choudhury, DR Suresh, S Ghosh, N Saravana, R Chandran, S Krishna, S Joy, M Anand, SK Madavan, V Joseph, A Wong, GW Schiemann, WP Constantinescu, SN Huang, LL Khosravi-Far, R Steen, H Tewari, M Ghaffari, S Blobe, GC Dang, CV Garcia, JGN Pevsner, J Jensen, ON Roepstorff, P Deshpande, KS Chinnaiyan, AM Hamosh, A Chakravarti, A Pandey, A AF Peri, S Navarro, JD Amanchy, R Kristiansen, TZ Jonnalagadda, CK Surendranath, V Niranjan, V Muthusamy, B Gandhi, TKB Gronborg, M Ibarrola, N Deshpande, N Shanker, K Shivashankar, HN Rashmi, BP Ramya, MA Zhao, ZX Chandrika, KN Padma, N Harsha, HC Yatish, AJ Kavitha, MP Menezes, M Choudhury, DR Suresh, S Ghosh, N Saravana, R Chandran, S Krishna, S Joy, M Anand, SK Madavan, V Joseph, A Wong, GW Schiemann, WP Constantinescu, SN Huang, LL Khosravi-Far, R Steen, H Tewari, M Ghaffari, S Blobe, GC Dang, CV Garcia, JGN Pevsner, J Jensen, ON Roepstorff, P Deshpande, KS Chinnaiyan, AM Hamosh, A Chakravarti, A Pandey, A TI Development of human protein reference database as an initial platform for approaching systems biology in humans SO GENOME RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CANCER SUSCEPTIBILITY; HUMAN GENOME; YEAST; PHOSPHORYLATION; IDENTIFICATION; KNOWLEDGEBASE; MICROARRAYS; PROTEOMICS; COMPLEXES AB Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, and subcellular localization were extracted from the literature for a nonredundant set of 2750 human proteins. Almost all the information was obtained manually by biologists who read and interpreted >300,000 published articles during the annotation process. This database, which has an intuitive query interface allowing easy access to all the features of proteins, was built by using open source technologies and will be freely available at http://www.hprd.org to the academic community. This unified bioinformatics platform will be useful in cataloging and mining the large number of proteomic interactions and alterations that will be discovered in the postgenomic era. C1 Johns Hopkins Univ, McKursick Nathans Inst Genet Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Kennedy Krieger Res Inst, Baltimore, MD 21287 USA. Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark. Univ Navarra, CIMA, Unidad Proteom, Div Hepatol & Terapia Gen, Pamplona 31008, Spain. Int Technol Pk Ltd, Inst Bioinformat, Bangalore 560066, Karnataka, India. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Natl Jewish Med & Res Ctr, Denver, CO 80202 USA. Ludwig Inst Canc Res, Brussels, Belgium. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Duke Univ, Pharmacol & Canc Biol Program, Durham, NC 27710 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. RP Pandey, A (reprint author), Johns Hopkins Univ, McKursick Nathans Inst Genet Med, Baltimore, MD 21287 USA. EM pandey@jhmi.edu RI Khosravi-Far, Roya/C-3789-2008; Pandey, Akhilesh/B-4127-2009; Garcia, Joe/E-8862-2010; Gowda, Harsha/A-8526-2011; Kalyana-Sundaram, Shanker/F-6860-2012; Constantinescu, Stefan /E-5277-2012; Jensen, Ole/J-1763-2012; Prasad, Rashmi/H-7381-2016; Niranjan, Vidya/O-6464-2016; Prasad, Rashmi/D-7067-2017; OI Pandey, Akhilesh/0000-0001-9943-6127; Jensen, Ole/0000-0003-1862-8528; Prasad, Rashmi/0000-0002-4400-6741; Niranjan, Vidya/0000-0001-9187-7753; Prasad, Rashmi/0000-0002-4400-6741; Amanchy, Ramars/0000-0001-9315-8488; Constantinescu, Stefan/0000-0002-8599-2699 NR 39 TC 657 Z9 690 U1 4 U2 37 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2003 VL 13 IS 10 BP 2363 EP 2371 DI 10.1101/gr.1680803 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 731GR UT WOS:000185876400019 PM 14525934 ER PT J AU Rankin, S Winder, P Hiltunen, E Sethares, K Butzlaff, A Carroll, D AF Rankin, S Winder, P Hiltunen, E Sethares, K Butzlaff, A Carroll, D TI Partnerships in mending hearts: Elder peer advisors and nurse collaboration SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 239 EP 239 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100673 ER PT J AU Mistry, R Gokhman, I Jimenez, E Maxwell, A Rosansky, J Van Stone, W Jarvik, L AF Mistry, R Gokhman, I Jimenez, E Maxwell, A Rosansky, J Van Stone, W Jarvik, L TI Including acute medical conditions may not undermine usefulness of CIRS in measuring medical burden: Results of pilot study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Charles R Drew Univ Med & Sci, Dept Psychiat, Los Angeles, CA 90059 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 246 EP 247 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100690 ER PT J AU Kramer, B Finke, B Wang, M Harker, J AF Kramer, B Finke, B Wang, M Harker, J TI American Indian veterans' federal healthcare utilization: VA and IHS SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA GRECC, Sepulveda, CA USA. Indian Hlth Serv, Zuni, NM USA. VA HSR&D Ctr Excellence, Sepulveda, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 247 EP 247 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100692 ER PT J AU Evans, W Lambert, C Bamman, M Quinn, L AF Evans, W Lambert, C Bamman, M Quinn, L TI Va grecc symposium: Exercise and aging molecular and whole body responses SO GERONTOLOGIST LA English DT Meeting Abstract C1 Cent Arkansas Vet Healhcare Syst, Ctr Geriatr Res Educ & Clin, Little Rock, AR 72205 USA. Birmingham VA Med Ctr, Muscle Res Lab, GRECC, Muscle Res Lab, Birmingham, AL USA. VA Puget Sound Healthcare Syst, Div Gerontol & Geriatr Med, Tacoma, WA 98493 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 274 EP 274 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100773 ER PT J AU Benton, N Brighton, T Crane, M Espe, E Jenkins, K Parkison, T Setka, D AF Benton, N Brighton, T Crane, M Espe, E Jenkins, K Parkison, T Setka, D TI Innovations in home health care: Acute home care and the changing role of home care nurses SO GERONTOLOGIST LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 313 EP 313 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078100860 ER PT J AU Pawlowski, C Lee, M Kier, F Kendjelic, E AF Pawlowski, C Lee, M Kier, F Kendjelic, E TI Neuropsychological functioning and depressive symptoms in older veterans with cognitive impairment SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 410 EP 410 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101116 ER PT J AU Evans, L Rubenstein, L Abrass, I AF Evans, L Rubenstein, L Abrass, I TI Joseph T. Freeman award lecture SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Seattle, WA USA. VA Greater Los Angeles Healthcare Ctr, GRECC 11E, Sepulveda, CA 91343 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 429 EP 429 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101183 ER PT J AU McDermott, S Tennstedt, S Kasten, L Billings, J Portenoy, R AF McDermott, S Tennstedt, S Kasten, L Billings, J Portenoy, R TI The use of advanced directives in patients with end-stage disease SO GERONTOLOGIST LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Med Ctr, New York, NY 10003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 449 EP 450 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101233 ER PT J AU McDermott, S Tennstedt, S Kasten, L Portenoy, R Billings, J AF McDermott, S Tennstedt, S Kasten, L Portenoy, R Billings, J TI The effect of symptom burden on change in function in patients with end-stage disease SO GERONTOLOGIST LA English DT Meeting Abstract C1 Beth Israel Med Ctr, New York, NY 10003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 449 EP 449 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101231 ER PT J AU Tennstedt, S McDermott, S Kasten, L Portenoy, R Billings, A AF Tennstedt, S McDermott, S Kasten, L Portenoy, R Billings, A TI Predictors of change in quality of life at end of life SO GERONTOLOGIST LA English DT Meeting Abstract C1 Beth Israel Med Ctr, New York, NY 10003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 450 EP 450 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101234 ER PT J AU Webber, A Alessi, C Harker, J Martin, J Josephson, K AF Webber, A Alessi, C Harker, J Martin, J Josephson, K TI Association between sedative medication use and actigraphic-scored sleep in long-stay nursing home residents SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, GRECC Sepulveda, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2003 VL 43 SI 1 BP 490 EP 491 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 734VF UT WOS:000186078101352 ER PT J AU Blumenthal, D Thier, SO AF Blumenthal, D Thier, SO TI Improving the generation, dissemination, and use of management research SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Blumenthal, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD OCT-DEC PY 2003 VL 28 IS 4 BP 366 EP 375 PG 10 WC Health Policy & Services SC Health Care Sciences & Services GA 740QD UT WOS:000186412300008 PM 14682677 ER PT J AU Goldman, R Hunt, MK Allen, JD Hauser, S Emmons, K Maeda, M Sorensen, G AF Goldman, R Hunt, MK Allen, JD Hauser, S Emmons, K Maeda, M Sorensen, G TI The life history interview method: Applications to intervention development SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE qualitative research; life history method; multicultural; intervention ID HEALTH-SERVICES RESEARCH; COLORECTAL-CANCER; QUALITATIVE RESEARCH; OCCUPATIONAL-THERAPY; AFRICAN-AMERICANS; SOCIAL-CONTEXT; BREAST-CANCER; WOMEN; CARE; PROMOTION AB There is an urgent need to develop and test health promotion strategies that both address health disparities and elucidate the full impact of social, cultural, economic, institutional, and political elements on people's lives. Qualitative research methods, such as life history interviewing, are well suited to exploring these factors. Qualitative methods are also helpful for preparing field staff to implement a social contextual approach to health promotion. This article reports results and application of findings of life history interviews conducted as part of intervention planning for the Harvard Cancer Prevention Program Project, "Cancer Prevention in Working-Class, Multi-Ethnic Populations". The salient themes that emerged from interviews with a multi-ethnic, purposive sample are centered on six construct domains: immigration and social status, social support, stress, food, physical activity, and occupational health. Insights gained from thematic analysis of the interviews were integrated throughout intervention and materials development processes. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol,Dept Hlth & Social Behav, Boston, MA 02115 USA. Brown Med Sch, Dept Family Med, Providence, RI USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. RP Goldman, R (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol,Dept Hlth & Social Behav, 44 Binney St, Boston, MA 02115 USA. RI Allen, Jennifer/M-2113-2015 FU NCI NIH HHS [1 PO1 CA75308-01] NR 79 TC 24 Z9 24 U1 5 U2 28 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2003 VL 30 IS 5 BP 564 EP 581 DI 10.1177/1090198103254393 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 726UP UT WOS:000185619600003 PM 14582598 ER PT J AU Liu, CF Sales, AE Sharp, ND Fishman, P Sloan, KL Todd-Stenberg, J Nichol, WP Rosen, AK Loveland, S AF Liu, CF Sales, AE Sharp, ND Fishman, P Sloan, KL Todd-Stenberg, J Nichol, WP Rosen, AK Loveland, S TI Case-mix adjusting performance measures in a veteran population: Pharmacy- and diagnosis-based approaches SO HEALTH SERVICES RESEARCH LA English DT Article DE case-mix adjustment; pharmacy data; profiling ID CHRONIC DISEASE SCORE; RISK ADJUSTMENT; AMBULATORY CARE; MODEL; AFFAIRS; HEALTH; COSTS; RECORDS; SYSTEM; RATES AB Objective. To compare the rankings for health care utilization performance measures at the facility level in a Veterans Health Administration (VHA) health care delivery network using pharmacy- and diagnosis-based case-mix adjustment measures. Data Sources/Study Setting. The study included veterans who used inpatient or outpatient services in Veterans Integrated Service Network (VISN) 26 during fiscal year 1998 (October 1997 to September 1998; N = 126,076). Utilization and pharmacy data were extracted from VHA national databases and the VISN 20 data warehouse. Study Design. We estimated concurrent regression models using pharmacy or diagnosis information in the base year (FY1998) to predict health service utilization in the same year. Utilization measures included bed days of care for inpatient care and provider visits for outpatient care. Principal Findings. Rankings of predicted utilization measures across facilities vary by case-mix adjustment measure. There is greater consistency within the diagnosis-based models than between the diagnosis- and pharmacy-based models. The eight facilities were ranked differently by the diagnosis- and pharmacy-based models. Conclusions. Choice of case-mix adjustment measure affects rankings of facilities on performance measures, raising concerns about the validity of profiling practices. Differences in rankings may reflect differences in comparability of data capture across facilities between pharmacy and diagnosis data sources, and unstable estimates due to small numbers of patients in a facility. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,HSR&D 152, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 48 TC 21 Z9 21 U1 1 U2 5 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2003 VL 38 IS 5 BP 1319 EP 1337 DI 10.1111/1475-6773.00179 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 734JF UT WOS:000186051500008 PM 14596393 ER PT J AU Lin, WY Hiasa, Y Kamegaya, Y Blackard, J Zander, C Beck, G Schmidt, EV Chung, RT AF Lin, WY Hiasa, Y Kamegaya, Y Blackard, J Zander, C Beck, G Schmidt, EV Chung, RT TI HCV expression inhibits interferon signaling in a cell-based HCV replication model. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 31 BP 170A EP 170A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700032 ER PT J AU Servoss, JC Kitch, D Andersen, J Robbins , GK Reisler , RB Chung, RT AF Servoss, JC Kitch, D Andersen, J Robbins , GK Reisler , RB Chung, RT TI Predictors of antiretroviral-related hepatotoxicity in the adult aids clinical trials group (AACTG). SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Robbins, Gregory/F-7988-2011 NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 70 BP 189A EP 189A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700071 ER PT J AU Luo, B Tang, LP Zhang, JL Ling, YQ Fallon, MB AF Luo, B Tang, LP Zhang, JL Ling, YQ Fallon, MB TI Endothelin-1 in experimental hepatopulmonary syndrome: Evaluation in prehepatic portal hypertension, biliary and nonbiliary cirrhosis. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 90 BP 199A EP 199A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700091 ER PT J AU Sherman, KE Horn, PS Rouster, SD Peters, MG Koziel, MJ Israel, B Chung, RT AF Sherman, KE Horn, PS Rouster, SD Peters, MG Koziel, MJ Israel, B Chung, RT TI Modeling HCV viral kinetic response to PEG-IFN/ribavirin in HCV/HIV coinfected patients. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Cincinnati, Cincinnati, OH 45221 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 315 BP 308A EP 309A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700316 ER PT J AU Smyk-Pearson, S Tester, I Sasaki, AW Rosen, HR AF Smyk-Pearson, S Tester, I Sasaki, AW Rosen, HR TI Comprehensive HCV genome-wide analysis of CD4+ and CD8+ T cells reveals hierarchy of immunodominance. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 383 BP 344A EP 344A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700384 ER PT J AU Timm, J Lauer, GM Lewis-Ximenez, LL Ouchi, K Kim, AY Walker, BD Allen, TM AF Timm, J Lauer, GM Lewis-Ximenez, LL Ouchi, K Kim, AY Walker, BD Allen, TM TI Longitudinal full genome sequencing to assess the extent of CD8+CTL escape in HCV. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Massachusetts Gen Hosp, Charlestown, MA USA. Inst Oswaldo Cruz, BR-20001 Rio De Janeiro, Brazil. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 400 BP 352A EP 353A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700401 ER PT J AU Lauer, GM Lucas, M Ouchi, K Kim, AY Day, CL Casson, DR Sheridan, I Lavender, B Ghandhi, RT Reiser, M Chung, RT Walker, BD Klenerman, P AF Lauer, GM Lucas, M Ouchi, K Kim, AY Day, CL Casson, DR Sheridan, I Lavender, B Ghandhi, RT Reiser, M Chung, RT Walker, BD Klenerman, P TI T-cell responses during early therapy for HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Oxford, Oxford OX1 2JD, England. Ruhr Univ Bochum, D-4630 Bochum, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 403 BP 354A EP 355A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700404 ER PT J AU Tester, IA Pearson, SS Dean, S Rosen, HR AF Tester, IA Pearson, SS Dean, S Rosen, HR TI Acute hepatitis C infection following patellar tendon transplantation: Immunologic correlates of recovery. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 411 BP 358A EP 358A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700412 ER PT J AU Hiasa, Y Blackard, J Kamegaya, Y Horiike, N Onji, M Schmidt, EV Chung, RT AF Hiasa, Y Blackard, J Kamegaya, Y Horiike, N Onji, M Schmidt, EV Chung, RT TI Sustained, interferon-sensitive HCV replication in a cell-based HCV replication model using replication defective adenoviral vectors or stable cell lines expressing T7 polymerase. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ehime Univ, Sch Med, Matsuyama, Ehime 790, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 415 BP 360A EP 360A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700416 ER PT J AU Song, DS Ku, D Fallon, MB AF Song, DS Ku, D Fallon, MB TI Enhanced ETB receptor mediated vasodilatation in response to ET-1 in pulmonary artery segments from animals with prehepatic portal hypertension and experimental HPS. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 496 BP 398A EP 399A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700500 ER PT J AU Kamegaya, Y Hiasa, Y Zukerberg, L Fowler, N Blackard, J Lin, WY Schmidt, E Chung, RT AF Kamegaya, Y Hiasa, Y Zukerberg, L Fowler, N Blackard, J Lin, WY Schmidt, E Chung, RT TI HCV core-E1-E2 acts as an HCC tumor accelerator through suppression of apoptosis. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 502 BP 401A EP 401A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700506 ER PT J AU Ling, YQ Zhang, JL Tang, LP Luo, B Fallon, MB AF Ling, YQ Zhang, JL Tang, LP Luo, B Fallon, MB TI Effects of selective endothelin receptor antagonists on the molecular and physiologic alterations in experimental HPS in vivo. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 544 BP 421A EP 421A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700548 ER PT J AU Sugimoto, K Kaplan, DE Ikeda, F Stadanlick, J Suh, G Aytaman, A Lucey, M Ray, S Nunes, F Reddy, KR Chang, KM AF Sugimoto, K Kaplan, DE Ikeda, F Stadanlick, J Suh, G Aytaman, A Lucey, M Ray, S Nunes, F Reddy, KR Chang, KM TI Host-virus interactions in acute hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Brooklyn VA Med Ctr, Brooklyn, NY USA. Univ Wisconsin, Madison, WI 53706 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Penn Hosp, Philadelphia, PA 19107 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 547 BP 422A EP 423A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700551 ER PT J AU Di Bisceglie, AM Dienstag, J Bonkovsky, H Sterling, R Chung, R Everhart, J Wright, E AF Di Bisceglie, AM Dienstag, J Bonkovsky, H Sterling, R Chung, R Everhart, J Wright, E TI Serum alpha-fetoprotein (AFP) levels in patients with advanced hepatitis C-associated liver disease without hepatocellular carcinoma: Results from the HALT-C trial. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. NIH, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 567 BP 434A EP 434A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700571 ER PT J AU Lok, AS Everhart, JE Wright, E Chung, R Greenson, JK AF Lok, AS Everhart, JE Wright, E Chung, R Greenson, JK TI Steatosis is common in advanced hepatitis C and related to BMI, hypertriglyceridemia, and genotype 3. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIDDK, Bethesda, MD USA. NERI, Watertown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 574 BP 437A EP 437A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700578 ER PT J AU Hu, KQ Cheung, RC Currie, S Bini, EJ Shen, H Anand, B Jeffers, LJ Ho, SB Brau, N Schmidt, WN McCracken, J Rossi, SJ Wright, TL AF Hu, KQ Cheung, RC Currie, S Bini, EJ Shen, H Anand, B Jeffers, LJ Ho, SB Brau, N Schmidt, WN McCracken, J Rossi, SJ Wright, TL TI Hepatic steatosis in patients with chronic hepatitis C: A multicenter study of US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Loma Linda Univ, Med Ctr, Loma Linda, CA 92350 USA. Loma Linda VA Med Ctr, Loma Linda, CA USA. Palo Alto VA Med Ctr, Palo Alto, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. New York Harbor VAMC, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Houston VA Med Ctr, Houston, TX USA. Miami VA Med Ctr, Miami, FL USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. Bronx VAMC, Bronx, NY USA. Iowa VAMC, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 589 BP 445A EP 445A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700593 ER PT J AU Wurcel, A Bica, I Gandhi, R Bradley, M Galvin, S Kim, A Corcoran, C Timm, J McGovern, B AF Wurcel, A Bica, I Gandhi, R Bradley, M Galvin, S Kim, A Corcoran, C Timm, J McGovern, B TI Acute hepatitis C (HCV) in incarcerated patients with history of intravenous drug use (IDU). SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Lemuel Shattuck Hosp, Jamaica Plain, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 595 BP 448A EP 448A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700599 ER PT J AU Bini, EJ Brau, N Currie, S Shen, H Anand, B Hu, KQ Jeffers, L Ho, SB Johnson, D Schmidt, W King, P Cheung, R Morgan, T Awad, J Pedrosa, M Chang, KM Aytaman, A Simon, F Hagedorn, C Moseley, R Ahmad, J Mendenhall, C Rossi, S Wright, T AF Bini, EJ Brau, N Currie, S Shen, H Anand, B Hu, KQ Jeffers, L Ho, SB Johnson, D Schmidt, W King, P Cheung, R Morgan, T Awad, J Pedrosa, M Chang, KM Aytaman, A Simon, F Hagedorn, C Moseley, R Ahmad, J Mendenhall, C Rossi, S Wright, T TI Epidemiology of hepatitis C infection and eligibility for antiviral therapy among US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 VA Med Ctr, New York, NY USA. VA Med Ctr, Bronx, NY USA. VA Med Ctr, San Francisco, CA USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Loma Linda, CA USA. VA Med Ctr, Miami, FL USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Bay Pines, FL USA. VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Columbia, MO USA. VA Med Ctr, Palo Alto, CA USA. VA Med Ctr, Long Beach, CA USA. VA Med Ctr, Nashville, TN USA. VA Med Ctr, Boston, MA USA. VA Med Ctr, Philadelphia, PA USA. VA Med Ctr, Brooklyn, NY USA. VA Med Ctr, Denver, CO USA. VA Med Ctr, Atlanta, GA USA. VA Med Ctr, Ann Arbor, MI USA. VA Med Ctr, Pittsburgh, PA USA. VA Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 603 BP 452A EP 452A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700607 ER PT J AU Blackard, JT AF Blackard, JT TI Hepatitis C virus (HCV) diversity in HIV-HCV coinfected persons initiating antiretroviral therapy. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 629 BP 464A EP 464A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700633 ER PT J AU Hay, JE Angulo, P McGuire, B Rossaro, L Chung, R Munoz, S Lee, W AF Hay, JE Angulo, P McGuire, B Rossaro, L Chung, R Munoz, S Lee, W TI Lactulose therapy in acute liver failure. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Mayo Clin, Rochester, MN USA. Univ Alabama, Birmingham, AL USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Univ Texas, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 814 BP 554A EP 555A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816700818 ER PT J AU Brau, N Bini, EJ Currie, S Shen, H Anand, BS Hu, KQ Ho, SB Johnson, D Schmidt, WN King, PD Cheung, RC Rossi, SJ Jeffers, LJ Wright, TL AF Brau, N Bini, EJ Currie, S Shen, H Anand, BS Hu, KQ Ho, SB Johnson, D Schmidt, WN King, PD Cheung, RC Rossi, SJ Jeffers, LJ Wright, TL TI Treatment of chronic hepatitis C with interferon alfa-2b and ribavirin in the community-based practice. A prospective study of 813 US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Vet Affairs Med Ctr, Bronx, NY USA. VA Med Ctr, New York, NY USA. VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Loma Linda, CA USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Bay Pines, FL USA. VA Med Ctr, Iowa City, IA USA. VA Med Ctr, Columbia, MO USA. VA Med Ctr, Palo Alto, CA USA. VA Med Ctr, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1009 BP 643A EP 643A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701009 ER PT J AU Zander, C Andersen, J Blackard, J Lin, WY Zdunek, D Hess, G Peters, M Koziel, M Sherman, KE Robbins, GK Chung, RT AF Zander, C Andersen, J Blackard, J Lin, WY Zdunek, D Hess, G Peters, M Koziel, M Sherman, KE Robbins, GK Chung, RT TI GB virus-C clearance is frequent in HIV/HCV co-infected patients receiving interferon and ribavirin treatment but does not adversely affect HIV-1 viremia: The adult ACTG A5071 study group. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Roche Diagnost, Basel, Switzerland. Univ Calif San Francisco, San Francisco, CA 94143 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Robbins, Gregory/F-7988-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1066 BP 669A EP 669A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701066 ER PT J AU Kanwal, F Dulai, GS Gornbein, J Gralnek, IM AF Kanwal, F Dulai, GS Gornbein, J Gralnek, IM TI Recipient characteristics and post-liver tranplantation (LT) outcomes before and after MELD. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1112 BP 691A EP 691A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701111 ER PT J AU Kramer, JR Giordano, TP Souchek, J Richardson, P El-Serag, H AF Kramer, JR Giordano, TP Souchek, J Richardson, P El-Serag, H TI The effect of HIV co-infection on the risk of cirrhosis and hepatocellular carcinoma in HCV-infected patients. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Houston VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1118 BP 694A EP 694A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701117 ER PT J AU Lok, AS Lai, CL Leung, N Yao, GB Cui, ZY Schiff, ER Dienstag, JL Heathcote, J Little, NR Griffiths, DA Gardner, SD Castiglia, M AF Lok, AS Lai, CL Leung, N Yao, GB Cui, ZY Schiff, ER Dienstag, JL Heathcote, J Little, NR Griffiths, DA Gardner, SD Castiglia, M TI 5-year follow-up of 998 chronic hepatitis B patients to determine long-term safety of lamivudine and clinical consequences of lamivudine-resistant mutations. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Hong Kong, Hong Kong, Peoples R China. Prince Wales Hosp, Hong Kong, Peoples R China. Jiangan Qu Cent Hosp, Shanghai, Peoples R China. Ditan Hosp, Beijing, Peoples R China. Univ Miami, Miami, FL 33152 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Toronto, Toronto, ON, Canada. GSK, Res Triangle Pk, NC USA. RI Lok, Anna /B-8292-2009; Lai, Ching Lung/C-4298-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1147 BP 708A EP 708A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701146 ER PT J AU Moriguchi, H Chung, RT Kobayashi, M Sato, C AF Moriguchi, H Chung, RT Kobayashi, M Sato, C TI Tumor ablation plus interferon therapy for HCV-related early hepatocellular carcinoma: A meta-analysis of randomized controlled trials. SO HEPATOLOGY LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Association-for-the-Study-of-Liver-Disease CY OCT 24-28, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Diseases C1 Univ Tokyo, Adv Sci & Technol Res Ctr, Tokyo, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Crecon Res & Consulting Inc, Tokyo, Japan. Tokyo Med & Dent Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2003 VL 38 IS 4 SU 1 MA 1198 BP 736A EP 736A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730ER UT WOS:000185816701197 ER PT J AU Visted, T Furmanek, T Sakariassen, P Foegler, WB Sim, K Westphal, H Bjerkvig, R Lund-Johansen, M AF Visted, T Furmanek, T Sakariassen, P Foegler, WB Sim, K Westphal, H Bjerkvig, R Lund-Johansen, M TI Prospects for delivery of recombinant angiostatin by cell-encapsulation therapy SO HUMAN GENE THERAPY LA English DT Article ID ALGINATE MICROCAPSULES; TUMOR SUPPRESSION; GENE-THERAPY; ENDOSTATIN; GROWTH; ISLETS; MICE; MICROENCAPSULATION; RELEASE; MODEL AB Implantation of encapsulated nonautologous cells that have been genetically modified to secrete proteins with tumor suppressor properties represents an alternative nonviral strategy to cancer gene therapy. We report an approach to raise the yield of recombinant proteins from encapsulated cells substantially. We hypothesized that by optimizing the encapsulation procedure, the production efficacy from the encapsulated cells could be increased. HEK 293 EBNA cells were genetically engineered to produce angiostatin. Encapsulation was performed by varying bead size, cellular density, homogeneity, and ion composition of the gel. The morphology and viability of the cells and the release of angiostatin were studied. Computer software was developed for three-dimensional imaging and quantification of cell viability. Angiostatin production was assessed at 3, 6, and 11 weeks using enzyme-linked immunosorbent assay ( ELISA). Inhomogeneous gels facilitated cell growth and viability. The most efficient inhomogeneous microcapsules were generated by reducing the size and cellular density of the beads. The viability and the production of angiostatin were 3 to 5 times higher than in the homogeneous capsules. Significant amounts of viable cells were present in both homogeneous and inhomogeneous beads after 6 months of culture. The stability of the alginate matrix was greatly enhanced by gelling in the presence of barium. In conclusion, the viability and production efficacy of recombinant angiostatin from alginate-encapsulated cells can be increased considerably by optimizing the encapsulation procedure. The development of such optimized microcapsules brings cell-encapsulation therapy further towards clinical use in cancer therapy. C1 Univ Bergen, Dept Anat & Cell Biol, N-5020 Bergen, Norway. EntreMed Inc, Rockville, MD 20850 USA. Catholic Univ Nijmegen, Dept Pathol, NL-6500 HC Nijmegen, Netherlands. Univ Bergen, Haukeland Hosp, Dept Neurosurg, N-5021 Bergen, Norway. RP Visted, T (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Mol Neurooncol Labs, 149 13th St,POB 57, Charlestown, MA 02129 USA. EM tvisted@partners.org RI Westphal, J.R./L-4754-2015 NR 35 TC 16 Z9 17 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2003 VL 14 IS 15 BP 1429 EP 1440 DI 10.1089/104303403769211646 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 736MV UT WOS:000186175300004 PM 14577923 ER PT J AU Cannon, JW Stoll, JA Selha, SD Dupont, PE Howe, RD Torchiana, DF AF Cannon, JW Stoll, JA Selha, SD Dupont, PE Howe, RD Torchiana, DF TI Port placement planning in robot-assisted coronary artery bypass SO IEEE TRANSACTIONS ON ROBOTICS AND AUTOMATION LA English DT Article; Proceedings Paper CT 8th Conference on Telemanipulator and Telepresence Technologies CY OCT 28, 2001 CL NEWTON, MA SP SPIE DE medical robotics; port placement; teleoperation ID SYSTEM AB Properly selected port sites for robot-assisted coronary artery bypass graft (CABG) improve the efficiency and quality of these procedures. In clinical practice, surgeons select port locations using external anatomic landmarks to estimate a patient's internal anatomy. This paper proposes an automated approach to port selection based on a preoperative image of the patient, thus avoiding the need to estimate internal anatomy. Using this image as input, port sites are chosen from a grid of surgeon-approved options by defining a performance measure for each possible port triad. This measure seeks to minimize the weighted squared deviation of the instrument and endoscope angles from their optimal orientations at each internal surgical site. This performance measure proves insensitive to perturbations in both its weighting factors and moderate intraoperative displacements of the patient's internal anatomy. A validation study of this port site selection algorithm was also performed. Six cardiac surgeons dissected model vessels using the port triad selected by this algorithm with performance compared to dissection using a surgeon-selected port triad and a port triad template described by Tabaie et al., 1999. With the algorithm-selected ports, dissection speed increased by up to 43% (p = 0.046) with less overall vessel trauma. Thus, this algorithmic approach to port site selection has important clinical implications for robot-assisted CABG which warrant further investigation. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Boston Univ, Dept Aerosp & Mech Engn, Boston, MA 02215 USA. Harvard Univ, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jcannon@massmed.org; pierre@bu.edu; howe@deas.harvard.edu; dtorchiana@partners.org OI Dupont, Pierre/0000-0001-7294-640X FU NHLBI NIH HHS [F32 HL068404, F32 HL068404-01] NR 16 TC 36 Z9 37 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1042-296X J9 IEEE T ROBOTIC AUTOM JI IEEE Trans. Robot. Autom. PD OCT PY 2003 VL 19 IS 5 BP 912 EP 917 DI 10.1109/TRA.2003.817502 PG 6 WC Automation & Control Systems; Engineering, Electrical & Electronic; Robotics SC Automation & Control Systems; Engineering; Robotics GA 731VD UT WOS:000185906400016 PM 22287831 ER PT J AU Delgado, JC Leung, JY Baena, A Clavijo, OP Vittinghoff, E Buchbinder, S Wolinsky, S Addo, M Walker, BD Yunis, EJ Goldfeld, AE AF Delgado, JC Leung, JY Baena, A Clavijo, OP Vittinghoff, E Buchbinder, S Wolinsky, S Addo, M Walker, BD Yunis, EJ Goldfeld, AE TI The -1030/-862-linked TNF promoter single-nucleotide polymorphisms are associated with the inability to control HIV-1 viremia SO IMMUNOGENETICS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA GENE PROMOTER; REGION; EXPRESSION; COMPLEX; REPLICATION; CLONING; AIDS AB Control of HIV-1 viremia and progression to AIDS has been associated with specific HLA genes. The tumor necrosis factor (TNF) and the non-classical major histocompatibility (MHC) class I chain-related A (MICA) genes are located in the genomic segment between the HLA class I and II genes and variants of both genes have been identified. We thus analyzed TNF promoter and MICA variants in a well-characterized group of HIV-1 infected individuals with different abilities to control HIV-1 viremia. In our cohort, the -1030/-862-linked TNF promoter single-nucleotide polymorphisms (SNPs), but not MICA variants, are significantly associated with lack of control of HIV-1 viremia (P=0.03). This association is independent of those HLA-B35 alleles associated with HIV-1 disease progression with which the -862 TNF SNP has previously been independently associated. Thus, non-randomly associated genes near the TNF locus are likely involved in control of HIV-1 viremia. C1 Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Stat, San Francisco, CA 94105 USA. San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Immunol & AIDS, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NHLBI NIH HHS [HL-67471, HL-59838]; NIAID NIH HHS [AI-28568] NR 24 TC 8 Z9 8 U1 2 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD OCT PY 2003 VL 55 IS 7 BP 497 EP 501 DI 10.1007/s00251-003-0604-7 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 736YQ UT WOS:000186201200008 PM 14517700 ER PT J AU Wen, Y Marcus, EA Matrubutham, U Gleeson, MA Scott, DR Sachs, G AF Wen, Y Marcus, EA Matrubutham, U Gleeson, MA Scott, DR Sachs, G TI Acid-adaptive genes of Helicobacter pylori SO INFECTION AND IMMUNITY LA English DT Article ID UREASE APOPROTEIN COMPLEXES; ESCHERICHIA-COLI; GASTRIC-MUCOSA; LOW-PH; INTRACELLULAR PH; IN-VIVO; EXPRESSION; IDENTIFICATION; COLONIZATION; RESISTANCE AB Helicobacter pylori is the only neutralophile that has been able to colonize the human stomach by using a variety of acid-adaptive mechanisms. One of the adaptive mechanisms is increased buffering due to expression of an acid-activated inner membrane urea channel, UreI, and a neutral pH-optimum intrabacterial urease. To delineate other possible adaptive mechanisms, changes in gene expression in response to acid exposure were examined using genomic microarrays of H. pylori exposed to different levels of external pH (7.4, 6.2, 5.5, and 4.5) for 30 min in the absence and presence of 5 mM urea. Gene expression was correlated with intrabacterial pH measured using 2',7'-bis-(2-carboxyethyl)-5-carboxyfluorescein and compared to that observed with exposure to 42degreesC for 30 min. Microarrays containing the 1,534 open reading frames of H. pylori strain 26695 were hybridized with cDNAs from control (pH 7.4; labeled with Cy3) and acidic (labeled with Cy5) conditions. The intrabacterial pH was 8.1 at pH 7.4, fell to 5.3 at pH 4.5, and rose to 6.2 with urea. About 200 genes were up-regulated and similar to100 genes were down-regulated at pH 4.5 in the absence of urea, and about half that number changed in the presence of urea. These genes included pH-homeostatic, transcriptional regulatory, motility, cell envelope, and pathogenicity genes. The up-regulation of some pH-homeostatic genes was confirmed by real-time PCR. There was little overlap with the genes induced by temperature stress. These results suggest that H. pylori has evolved multifaceted acid-adaptive mechanisms enabling it to colonize the stomach that may be novel targets for eliminating infection. C1 Univ Calif Los Angeles, Membrane Biol Lab, Dept Physiol & Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Invitrogen Corp, Carlsbad, CA USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Membrane Biol Lab, Dept Physiol & Med, 11301 Wilshire Blvd,Bldg 113,Room 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 17294, DK 41301, DK 46917, DK 534652, R01 DK046917] NR 57 TC 119 Z9 125 U1 2 U2 6 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 OCT PY 2003 VL 71 IS 10 BP 5921 EP 5939 DI 10.1128/IAI.71.10.5921-5939.2003 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 725PH UT WOS:000185551200053 PM 14500513 ER PT J AU Glickstein, L Moore, B Bledsoe, T Damle, N Sikand, V Steere, AC AF Glickstein, L Moore, B Bledsoe, T Damle, N Sikand, V Steere, AC TI Inflammatory cytokine production predominates in early Lyme disease in patients with erythema migrans SO INFECTION AND IMMUNITY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; BORRELIA-BURGDORFERI; MICE; ARTHRITIS AB In a study of cytokine production ex vivo by Borrelia burgdorferi-stimulated peripheral blood mononuclear cells from 27 patients with culture-positive erythema migrans, production of inflammatory cytokines predominated, particularly gamma interferon and, to a lesser degree, tumor necrosis factor alpha. In contrast, with the exception of interleukin-13, anti-inflammatory cytokine production was negligible. Thus, B. burgdorferi antigens in early Lyme disease often induce a strong inflammatory response. C1 Tufts Univ, Sch Med, New England Med Ctr, Div Rheumatol Immunol, Boston, MA 02111 USA. RP Glickstein, L (reprint author), Massachusetts Gen Hosp, 149 13th St,Rm 8301, Charlestown, MA 02129 USA. FU ODCDC CDC HHS [CCU 110291] NR 14 TC 17 Z9 18 U1 1 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 OCT PY 2003 VL 71 IS 10 BP 6051 EP 6053 DI 10.1128/IAI.71.10.6051-6053.2003 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 725PH UT WOS:000185551200068 PM 14500528 ER PT J AU Sands, KE Yokoe, DS Hooper, DC Tully, JL Horan, TC Gaynes, RP Solomon, SL Platt, R AF Sands, KE Yokoe, DS Hooper, DC Tully, JL Horan, TC Gaynes, RP Solomon, SL Platt, R TI Detection of postoperative surgical-site infections: Comparison of health plan-based surveillance with hospital-based programs SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID WOUND INFECTIONS; NOSOCOMIAL-INFECTIONS; DISCHARGE; IMPACT; RATES AB BACKGROUND: Review of health plan administrative data has been shown to be more sensitive than other methods for identifying postdischarge surgical-site infections (SSIs), but there has not been a direct comparison between this method and hospital-based surveillance for all infections, including those diagnosed before discharge. We compared these two methods for identifying SSIs following coronary artery bypass graft (CABG) procedures. METHODS: We studied 1,352 CABG procedures performed among members of one health plan from March 1993 through June 1997. Health plan administrative records were reviewed based on claims containing diagnoses or procedures suggestive of infection or outpatient dispensing of antibiotics appropriate for SSI. Hospital-based surveillance information was also reviewed. SSI rates were calculated based on the total events identified by either mechanism. RESULTS: Postdischarge information was reviewed for 328 (85%) of 388 procedures. SSIs were confirmed in 167 patients (13% overall risk of confirmed SSI; range, 3% to 14% in the 5 hospitals). The overall sensitivity of hospital-based surveillance was 49.7% (83 of 167), and that of health plan data was 71.8% (120 of 167). There was no significant difference among hospitals in the sensitivity of either surveillance mechanism. CONCLUSIONS: Surveillance based on health plan data identified more postoperative infections, including those occurring before discharge, than did hospital-based surveillance. Screening administrative data and pharmacy activity may be an important adjunct to SSI surveillance, allowing efficient comparison of hospital-specific rates. Interpretation of differences among hospitals' infection rates requires case mix adjustment and understanding of variations in hospitals' discharge diagnosis coding practices. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Ctr Dis Control & Prevent, Eastern Massachusetts Prevent Epictr, Boston, MA USA. Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Auburn Hosp, Cambridge, MA USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Cambridge, MA 02138 USA. Harvard Univ, Med Associates, Boston, MA USA. RP Sands, KE (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. FU ODCDC CDC HHS [UR8/CCU115079] NR 18 TC 36 Z9 36 U1 0 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2003 VL 24 IS 10 BP 741 EP 743 DI 10.1086/502123 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 734ZD UT WOS:000186087100007 PM 14587934 ER PT J AU Bigatello, LM Hellman, J AF Bigatello, LM Hellman, J TI Inhaled nitric oxide for ARDS: searching for a more focused use SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; ENDOTOXIN; FAILURE; SHEEP C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Bigatello, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. NR 18 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2003 VL 29 IS 10 BP 1623 EP 1625 DI 10.1007/s00134-003-1851-7 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 732AJ UT WOS:000185918400003 PM 14635625 ER PT J AU Kacmarek, RM AF Kacmarek, RM TI Is high frequency oscillation the best lung protective ventilatory approach for ARDS? SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; CONVENTIONAL MECHANICAL VENTILATION; STRATEGY; VOLUME; ADULTS; INJURY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 16 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2003 VL 29 IS 10 BP 1629 EP 1631 DI 10.1007/s00134-003-1939-0 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 732AJ UT WOS:000185918400005 PM 12923623 ER PT J AU Schmitz, I Clayton, LK Reinherz, EL AF Schmitz, I Clayton, LK Reinherz, EL TI Gene expression analysis of thymocyte selection in vivo SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE apoptosis; DNA microarray; gene profiling; T cell differentiation; thymus ID DOUBLE-POSITIVE THYMOCYTES; T-CELL-ACTIVATION; NEGATIVE SELECTION; DENDRITIC CELLS; PHOSPHOINOSITIDE 3-KINASE; AUTOREACTIVE THYMOCYTES; PERIPHERAL TOLERANCE; MOLECULAR ANALYSIS; THYMIC SELECTION; APOPTOTIC CELLS AB Self versus non-self discrimination is a key feature of immunorecognition. Through TCR-activated apoptotic mechanisms, autoreactive thymocytes are purged at the CD4(+)CD8(+) double-positive (DP) precursor stage prior to maturation to CD4(+) or CD8(+) single-positive (SP) thymocytes. To investigate this selection process in vivo, gene expression analysis by oligonucleotide array was performed in TCR transgenic mice. In total, 244 differentially expressed DP thymocyte genes induced or repressed by TCR triggering in vivo were identified. Genes involved in the biological processes of apoptosis, DNA recombination, antigen processing and adhesion are coordinately engaged. Moreover, analysis of gene expression in thymocyte subsets revealed that TCR ligand-induced expression profiles vary according to their developmental stage, with 48 genes showing DP preference and nine showing SP thymocyte preference. Finally, our data suggest that both the extrinsic and the intrinsic apoptosis pathways are operating in thymic selection. C1 Dana Farber Canc Inst, 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, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. RI Schmitz, Ingo/G-2093-2013 OI Schmitz, Ingo/0000-0002-5360-0419 FU NIAID NIH HHS [AI50900, AI45022] NR 79 TC 35 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 2003 VL 15 IS 10 BP 1237 EP 1248 DI 10.1093/intimm/dxg125 PG 12 WC Immunology SC Immunology GA 728DZ UT WOS:000185701200011 PM 13679393 ER PT J AU Weber, RL Gans, JS AF Weber, RL Gans, JS TI The group therapist's shame: A much undiscussed topic SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID GROUP-PSYCHOTHERAPY; COUNTERTRANSFERENCE; EXPERIENCE AB The topic of shame in group therapy has received limited attention in the group therapy literature. When the topic has been addressed, the focus has been on the shame of the group members. The shame of the group leader and its effect on leadership efficacy and group process has received inadequate attention, given what seems to be its power and prevalence. In this article we examine shame and the group therapist with regard to (1) potentially shameful topics and (2) dynamics that evoke shame. Suggestions for both the mitigation of shame and the enhancement of the leader's self esteem in dispatching the role and functions of group therapist are offered. In discussing this subject, we propose to normalize group therapist shame by emphasizing the challenges and complexity of group leadership. While the examples illustrate an array of emotions, our purpose is to focus on their shameful elements because they are (1) frequently ignored or overlooked; (2) not made explicit; or (3) discussed in other terms, such as narcissism. In doing so, we invite the reader to consider the clinical utility of the hypothesis that shame has a powerful presence and impact on our leadership image and effectiveness. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Ctr Grp Therapy, Boston, MA USA. Grp Solut Network Inc, Boston, MA USA. RP Weber, RL (reprint author), 385 Broadway, Cambridge, MA 02139 USA. NR 27 TC 4 Z9 4 U1 1 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD OCT PY 2003 VL 53 IS 4 BP 395 EP 416 DI 10.1521/ijgp.53.4.395.42833 PG 22 WC Psychology, Clinical SC Psychology GA 727AJ UT WOS:000185633500001 PM 14562519 ER PT J AU Murray, SK Young, RH Scully, RE AF Murray, SK Young, RH Scully, RE TI Unusual epithelial and stromal changes in myoinvasive endometrioid adenocarcinoma: A study of their frequency, associated diagnostic problems, and prognostic significance SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE endometrium; carcinoma; endometrioid carcinoma; fibromyxoid stroma; lymphocytic reaction; prognosis ID STAGE-I; MYOMETRIAL INVASION; RISK-FACTORS; VASCULAR INVASION; UTERINE CORPUS; CARCINOMA; CANCER; PREDICTORS; RECURRENCE; FAILURE AB The authors have noted that when the myoinvasive glands of endometrioid carcinomas evoke a prominent fibromyxoid stromal reaction, they sometimes undergo distinctive changes. These are characterized by outpouchings from typical neoplastic glands that become detached and often lined by flattened epithelium, sometimes appearing as microcysts. The glands may less often become elongated or undergo fragmentation into small solid clusters or single cells. For this constellation of changes, which in aggregate are distinctive, the authors have coined the acronym MELF (microcystic, elongated, fragmented). The authors evaluated the prognostic significance of these stromal and glandular features and their association with each other and with other histopathologic and clinical prognostic factors by studying 115 unselected myoinvasive endometrial endometrioid carcinomas. The histologic slides and clinical records were reviewed to collect data on age, recurrences or metastases, survival, stromal reaction pattern (fibromyxoid, lymphocytic, or absent), presence of MELF, FIGO grade, depth of myometrial invasion, vascular invasion, squamous differentiation, and presence or absence of necrosis. Factors associated with an unfavorable outcome (recurrence or death) included a fibromyxoid stromal reaction, age older than 70 years, advanced stage, vascular invasion, FIGO grade, depth of myoinvasion, and the presence of tumor necrosis. The presence of a host lymphocytic reaction was associated with a favorable outcome. A multivariate logistic regression model identified stage and age older than 70 years as independent prognostic factors. The MELF changes were associated with the presence of a host stromal reaction (most strongly with a fibromyxoid reaction) and vascular invasion. Within the group associated with a fibromyxoid reaction, patients exhibiting MELF had a better survival. In conclusion, a fibromyxoid reaction in cases of endometrioid carcinoma is associated with a higher frequency of death or recurrence and it is frequently accompanied by distinctive morphologic changes (MELF) in myoinvasive glands as well as lymphatic or blood vessel invasion. MELF is associated with a fibromyxoid reaction but is not independently associated with an adverse effect on prognosis. A lymphocytic stromal reaction is associated with a favorable effect on prognosis and is less often accompanied by the distinctive morphologic changes (MELF) highlighted herein. C1 QEII Hlth Sci Ctr, Dept Pathol, Halifax, NS B3H 1V8, Canada. Dalhousie Univ, Dept Pathol, Halifax, NS B3H 3J5, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Murray, SK (reprint author), QEII Hlth Sci Ctr, Dept Pathol, Room 736,7th Floor,Mackenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. NR 29 TC 54 Z9 55 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2003 VL 22 IS 4 BP 324 EP 333 DI 10.1097/01.pgp.0000092161.33490.a9 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 723GD UT WOS:000185423600002 PM 14501811 ER PT J AU Baergen, RN Rutgers, J Young, RH AF Baergen, RN Rutgers, J Young, RH TI Extrauterine lesions of intermediate trophoblast SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE trophoblast; extrauterine; placental site trophoblastic tumor; placental site nodule ID PLACENTAL SITE NODULE; FALLOPIAN-TUBE; ECTOPIC PREGNANCY; TUMOR; CHORIOCARCINOMA; DISEASE AB Lesions of intermediate trophoblast arising in the uterus include exaggerated placental site, placental site nodule, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor. Only 12 examples of extrauterine lesions of intermediate trophoblast (ELIT) have been previously reported; 7 new cases are described herein. Six lesions were located in the fallopian tube or paratubal region and one in the ovary. The patients were 25 to 47 (average 36) years of age. The lesions ranged from 0.6 to 4 cm in diameter; four were cystic. The four placental site nodules (three tubal, one paratubal) were composed of small, sharply circumscribed nodules of intermediate trophoblast with no mitotic activity. The three PSTTs (two tubal, one ovarian) exhibited irregular stromal infiltration by intermediate trophoblast, mitotic activity, and necrosis. Chronic salpingitis was seen in the six tubal/paratubal cases, and endometriosis was seen in four cases. Immunoreactivity for human placental lactogen, human chorionic gonadotropin, and cytokeratin in two cases was consistent with an origin from intermediate trophoblast. ELITs presumably arise from previous ectopic pregnancies, a history of which was present in two of these patients. Follow-up, available on two of the three patients with PSTT, was uneventful at 6 and 12 years, but study of additional cases is necessary to reliably determine the behavior of extrauterine PSTTs. C1 Cornell Univ, New York Presbyterian Hosp, Weill Cornell Ctr, New York, NY 10021 USA. Long Beach Mem Med Ctr, Long Beach, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Baergen, RN (reprint author), Cornell Univ, New York Presbyterian Hosp, Weill Cornell Ctr, Starr-1002,525 E 68th St, New York, NY 10021 USA. NR 22 TC 22 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2003 VL 22 IS 4 BP 362 EP 367 DI 10.1097/01.pgp.0000092132.88121.d1 PG 6 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 723GD UT WOS:000185423600008 PM 14501817 ER PT J AU Pawlik, TM Carter, EA Bode, BP Fischman, AJ Tompkins, RG AF Pawlik, TM Carter, EA Bode, BP Fischman, AJ Tompkins, RG TI Central role of interleukin-6 in burn induced stimulation of hepatic amino acid transport SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article ID HEMORRHAGIC-SHOCK; THERMAL-INJURY; GLUTAMINE TRANSPORT; METABOLISM; RATS; LIPOPOLYSACCHARIDE; INFLAMMATION; HEPATOCYTES; MACROPHAGES; ACTIVATION AB Burn injury produces a marked and prolonged hypermetabolic state, which is characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The effect of burn injury on hepatocyte transport of glutamine, a key substrate in gluconeogenesis and ureagenesis, was examined following the administration of a full thickness 20% total body surface scald injury. The burn injury was induced in wild-type mice, as well as two types of knockout mice: a CD-14 knockout and an interleukin-6 (IL-6) knockout. In both the wild-type and CD-14 knockout mice a latent and profound 2-fold increase in hepatocyte glutamine transport was seen. In contrast, hepatocytes isolated from IL-6 knockout mice failed to show an induction of glutamine transport after burn injury. Hepatocytes isolated from burned wild-type and CD-14 knockout mice produced significantly higher levels of IL-6 as compared to hepatocytes isolated from sham burned mice. Histologic analysis of skin isolated from wild-type mice showed a robust inflammatory response whereas skin from IL-6 deficient mice showed minimal inflammation and decreased granulation tissue. The results of this study suggest that IL-6 may play a key role in the stimulation of hepatic glutamine transport following burn injury. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Childrens Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. Shriners Burn Hosp Children, Boston, MA USA. RP Pawlik, TM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol 444, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 34 TC 8 Z9 9 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD OCT PY 2003 VL 12 IS 4 BP 541 EP 548 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 732RB UT WOS:000185958400021 PM 12964032 ER PT J AU Silva, NH Fournier, MV Pimenta, G Pulcheri, WA Spector, N Carvalho, MD AF Silva, NH Fournier, MV Pimenta, G Pulcheri, WA Spector, N Carvalho, MD TI HLM/OSBP2 is expressed in chronic myeloid leukemia SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE HLM/OSBP2; oxysterol-binding proteins; chronic myeloid leukemia ID OXYSTEROL-BINDING-PROTEIN; CDNA CLONING; FAMILY; GENE; METABOLISM; HOMOLOGS; MOUSE AB Oxysterols are oxygenated derivatives of cholesterol that have been shown to influence a wide variety of cellular processes including sterol metabolism, lipid trafficking, apoptosis and more recently, cell differentiation. The oxysterol binding proteins (OSBPs) comprise a large conserved family of proteins in eukaryotes with high affinity for oxysterols, but their precise function has not been defined yet. One member of this family in humans, HLM/OSBP2 protein, has recently been reported as a potential marker for solid tumor dissemination and worse prognosis in these cases. In this study we focused on the evaluation of HLM/OSBP2 expression in malignant cell lines from different origins (blood and solid tumors) and we also evaluated its expression in chronic myeloid leukemia patients, correlating the molecular findings with clinical outcome. Our results showed that HLM/OSBP2 was expressed in 80% of the analysed CML patients, suggesting that this protein could constitute a helpful tool for disease monitoring and reinforces recent findings that HLM/OSBP2 protein could be involved in the mainteinance of the undifferentiated state necessary for leukemogenesis. C1 Univ Fed Rio de Janeiro, Lab Controle Expressao Genica, Inst Biofis Carlos Chagas Filho, CCS, BR-21949900 Rio De Janeiro, Brazil. Dana Farber Canc Inst, Adult Oncol Div, Boston, MA 02115 USA. Hosp Univ Clementino Fraga Filho, UFRJ, Mol Oncol Lab, Serv Pneumol, BR-21941590 Rio De Janeiro, Brazil. Hosp Univ Clementino Fraga Filho, UFRJ, Dept Hematol, BR-21941590 Rio De Janeiro, Brazil. RP Carvalho, MD (reprint author), Univ Fed Rio de Janeiro, Lab Controle Expressao Genica, Inst Biofis Carlos Chagas Filho, CCS, Bloco G,Ilha Fundao, BR-21949900 Rio De Janeiro, Brazil. OI carvalho, maria da gloria/0000-0001-5890-8095 NR 27 TC 9 Z9 9 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD OCT PY 2003 VL 12 IS 4 BP 663 EP 666 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 732RB UT WOS:000185958400040 ER PT J AU Wang, XR Christiani, DC AF Wang, XR Christiani, DC TI Occupational lung disease in China SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article ID COTTON TEXTILE WORKERS; CANCER MORTALITY; PULMONARY-FUNCTION; SILICOSIS; BYSSINOSIS; PREVENTION; GUANGZHOU; MINERS; DUST AB Occupational lung disease has been a major public health problem in China. The recently transformed industrial structure and expansion of the industrial labor force, accompanying the rapid industrialization and economic growth, pose both tremendous challenges and opportunities for occupational health policy and research. New occupational health problems are emerging, while the traditional occupational lung disease continued to occur. Simultaneously, relevant scientific research and professional activities have accelerated notably. The progress and achievement in occupational health research are creating more powerful forces in eliminating industrial hazards and protecting workers' health in China. Key words: China; occupational lung disease; pneumoconiosis; silicosis. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Lin, Sihao/A-8412-2012 FU NIOSH CDC HHS [R01OH02421] NR 28 TC 26 Z9 27 U1 0 U2 3 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD OCT-DEC PY 2003 VL 9 IS 4 BP 320 EP 325 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 817EY UT WOS:000221162000005 PM 14664484 ER PT J AU Perrott, DH Rahn, B Wahl, D Linke, B Thuruller, P Troulis, M Glowacki, J Kaban, LB AF Perrott, DH Rahn, B Wahl, D Linke, B Thuruller, P Troulis, M Glowacki, J Kaban, LB TI Development of a mechanical testing system for a mandibular distraction wound SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE mandibular distraction; distraction wound stiffness; porcine distraction; distraction mechanical testing ID BONE STIFFNESS; OSTEOGENESIS; STRENGTH; FRACTURES; MODEL; FEMUR AB The purpose of this study was to develop a mechanical testing system to estimate stiffness of an experimental porcine mandibular distraction osteogenesis (DO) wound. The system was designed to function without changing the morphology of the healing mandible. A customized jig was designed to allow cantilever-bending tests of the Yucatan mini-pig hemi-mandible. Experimental and control hemi-mandibles were placed in the jig and the proximal segment was secured. A material testing unit applied progressively increasing downward force on the pre-molar occlusal surface. The maximum force applied was 0.030 kN. The stiffness value for each hemi-mandible was represented by the slope of the plot of force (kN) vs displacement (mm). Radiographs were taken before and after mechanical testing to demonstrate any gross morphologic changes or identifiable fractures across the distraction wound. A total of 24 mini-pigs underwent DO.of the right mandible with 0-day latency and distraction rates of 1, 2, and 4 mm per day resulting in a 12 turn gap. At the completion of 0, 8, 16, and 24 days of neutral fixation, two animals for each of three different distraction rates were sacrificed for mechanical testing. Stiffness of control hemi-mandibles ranged between 0.018 and 0.317 kN/mm (median 0.063; mean 0.099 +/- 0.080). Stiffness of experimental hemi-mandibles ranged between 0 and 0.025 kN/mm (median 0.004; mean 0.005). The subset that was tested at the end of neutral fixation had stiffness between 0.005 and 0.025 (median 0.011; mean 0.012 +/- 0.011). No morphologic changes were evident on the X-rays after testing. The results indicate that the cantilever-bending model is useful for testing stiffness of an experimental mandibular DO wound without destroying its morphology. C1 Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. AO ASIF Inst, Davos, Switzerland. RP Kaban, LB (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Massachusetts Gen Hosp, Fruit St, Boston, MA 02114 USA. NR 24 TC 15 Z9 15 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD OCT PY 2003 VL 32 IS 5 BP 523 EP 527 DI 10.1054/ijom.2003.0424 PG 5 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 745ZC UT WOS:000186720500012 PM 14759112 ER PT J AU Mamon, HJ Dahlberg, W Azzam, EI Nagasawa, H Muto, MG Little, JB AF Mamon, HJ Dahlberg, W Azzam, EI Nagasawa, H Muto, MG Little, JB TI Differing effects of breast cancer 1, early onset (BRCA1) and ataxia-telangiectasia mutated (ATM) mutations on cellular responses to ionizing radiation SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID DNA-DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; DEPENDENT PHOSPHORYLATION; CHECKPOINT PATHWAY; HUMAN-CELLS; CHROMOSOMAL-ABERRATIONS; XERODERMA PIGMENTOSUM; GENETIC INSTABILITY; MISSENSE MUTATIONS; CYCLE PROGRESSION AB Purpose: The ataxia-telangiectasia mutated (ATM ) gene encodes a protein kinase, the activation of which is an early event in the cellular response to ionizing radiation. One of the many substrates of ATM is BRCA1 (breast cancer 1, early onset gene), which has been associated with susceptibility to breast and ovarian cancer, and has been implicated in DNA repair processes. Various cellular responses to radiation were analysed in cells with mutations in ATM or BRCA1 in an attempt to clarify which effects of ATM can be mediated through BRCA1. Materials and methods: The response to radiation of cells with mutations in ATM or BRCA1 was examined, as were BRCA1 -mutant tumour cells transfected with an exogenous wild-type BRCA1 allele. Assays included cell-survival curves, studies of potentially lethal damage repair, measurement of chromosomal aberrations and of G1 arrest, and Western blot analysis of lysates of irradiated cells to determine the phosphorylation of the product of the human Mdm2 gene (HDM2). Results: Both ATM and BRCA1 mutations were associated with sensitivity to ionizing radiation, deficient repair of potentially lethal damage and markedly increased chromosomal aberrations. A BRCA1-mutated tumour cell line HCC1937, like ATM mutant cells, did not exhibit a normal G1 arrest but, unlike ATM mutant cells, did exhibit phosphorylation of HDM2. Expression of wild-type BRCA1 in HCC1937 cells partially restored radioresistance, restored repair of potentially lethal damage and markedly reduced radiation-induced chromosomal aberrations. G1 arrest, however, was not restored by expression of BRCA1 . Conclusions: The results are consistent with a model in which ATM phosphorylation of BRCA1 regulates DNA repair functions, particularly those involved in potentially lethal damage repair and chromosomal integrity, but not other aspects of the cellular response to radiation such as G1 cell cycle arrest. To the authors' knowledge, this is the first demonstration of the ability of exogenously expressed BRCA1 to restore the ability to perform potentially lethal damage repair and maintain chromosomal integrity in irradiated cells. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Radiobiol Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Gynecol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. UMDNJ, Dept Radiol, New Jersey Med Sch, Newark, NJ 07103 USA. RP Mamon, HJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA47542]; NIEHS NIH HHS [ES00002] NR 70 TC 15 Z9 16 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD OCT PY 2003 VL 79 IS 10 BP 817 EP 829 DI 10.1080/09553000310001610952 PG 13 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 745HN UT WOS:000186683400007 PM 14630541 ER PT J AU Wei, XB Runnels, JM Lin, CP AF Wei, XB Runnels, JM Lin, CP TI Selective uptake of indocyanine green by reticulocytes in circulation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SICKLE-CELL-DISEASE; ORANGE-MEDIATED PHOTODAMAGE; TUMOR-NECROSIS-FACTOR; ACRIDINE-ORANGE; FLUORESCENCE MICROSCOPY; MUTAGENIC ACTIVITY; TNF-ALPHA; ADHESION; NEOVASCULARIZATION; MATURATION AB PURPOSE. Hyperfluorescent cells labeled with indocyanine green (ICG) have been observed in retinal and choroidal circulation using scanning laser ophthalmoscopy. It has been suggested that ICG labels leukocytes and that ICG can be used to track leukocyte movement in vivo. The purpose of this study is to identify the cell population that takes up ICG and to study their trafficking pattern in vivo by confocal fluorescence microscopy. METHODS. ICG was injected into the mouse tail vein, and images were taken by in vivo confocal microscopy. The trafficking pattern of ICG-labeled cells was compared with that of rhodamine 6G-labeled leukocytes. in vitro labeling of human blood cells with antibodies against cell lineage markers and with DNA stains was further used to identify the ICG-labeled cells. Antibodies against the following cell surface markers were Used: CD45 (leukocytes), CD3 (T lymphocytes), CD19 (B lymphocytes), CD16 (Fc receptor), glycophorin A (erythroid lineage cells), and CD71 (transferrin receptor). RESULTS. The ICG-labeled cells were made up of two blood cell populations with distinct levels of ICG uptake. The strongly ICG-labeled cells did not roll on dermal vascular endothelium in vivo, in contrast to rhodamine 6G-labeled leukocytes. They were identified as reticulocytes because antibody staining showed that they were CD 45(-), glycophorin A(+) and CD 71(+). The weakly ICG-labeled cells were identified as neutrophils because they were CD45(+), CD16(+), CD3(-), and CD19(-). CONCLUSIONS. ICG strongly labels reticulocytes and weakly labels neutrophils. To the authors' knowledge, this is the first report of selective staining of reticulocytes by ICG. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,BHX 630, Boston, MA 02114 USA. RP Wei, XB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,BHX 630, 50 Blossom St, Boston, MA 02114 USA. FU NCRR NIH HHS [P41 RR011823, P41 RR011823-128210]; NEI NIH HHS [R01 EY014106, EY12970, EY14106] NR 41 TC 18 Z9 18 U1 0 U2 3 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 OCT PY 2003 VL 44 IS 10 BP 4489 EP 4496 DI 10.1167/iovs.03-0041 PG 8 WC Ophthalmology SC Ophthalmology GA 727BT UT WOS:000185636700042 PM 14507897 ER PT J AU Dolan, S Montagno, A Wilkie, S Aliabadi, N Sullivan, M Zahka, N Sherman, JC Grinspoon, S AF Dolan, S Montagno, A Wilkie, S Aliabadi, N Sullivan, M Zahka, N Sherman, JC Grinspoon, S TI Neurocognitive function in HIV-infected patients with low weight and weight loss SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE neurocognitive function; HIV/AIDS; women ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; KARNOFSKY PERFORMANCE STATUS; QUALITY-OF-LIFE; HIV-1-INFECTED WOMEN; ANOREXIA-NERVOSA; TESTOSTERONE; MEN; VALIDITY; MEMORY AB Objective: To determine neurocognitive function in HIV-infected subjects with low weight and weight loss. Design: Cross-sectional cohort. Methods: Baseline data from male and female participants in longitudinal treatment studies of AIDS wasting were analyzed. Fiftyseven HIV-infected women (age: 38 5 years, education level: 12.3 +/- 2.3 years) and 24 HIV-infected men (age: 37 5 years, education level: 13.5 +/- 2.9 years) with weight <90% IBW or loss of >10% of preillness weight maximum underwent standardized neurocognitive testing to measure intellectual functioning, attention, memory, and fine motor dexterity. The z scores were determined using age- and gender-specific normative data. Results: Among women, IQ (87 +/- 13, z score: -0.8 +/- 10.8 SD) and executive functioning scores (-0.7 +/- 1.2 SD) were below average but within normal limits. In contrast, performance (z scores) on measures of verbal learning (-2.5 +/- 1.5 SD), visuospatial abilities (-2.5 +/- 2.0 SD), and motor coordination (-2.3 +/- 3.3 SD) fell significantly below normal limits. Among men, IQ score was 96 +/- 13 SD (z score: -0.3 +/- 1 0.8 SD). Performance was below average on measures of verbal learning (-1.0 +/- 1.7 SD) and visual construction (-1.6 +/- 1.7 SD) but within normal limits on executive functioning (-0.1 +/- 1.0 SD). Conclusions: HIV-infected women at low weight demonstrate significantly reduced verbal learning, memory, and motor function, whereas HIV-infected men at low weight demonstrate more moderate impairment in verbal learning and other measures of neurocognitive function. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuropsychol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Grinspoon, S (reprint author), Neuroendocrine Unit, 55 Fruit St,LON207, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-54167] NR 32 TC 8 Z9 8 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2003 VL 34 IS 2 BP 155 EP 164 DI 10.1097/00126334-200310010-00005 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 732YK UT WOS:000185973000005 PM 14526204 ER PT J AU Lin, HR Bauer-Wu, SM AF Lin, HR Bauer-Wu, SM TI Psycho-spiritual well-being in patients with advanced cancer: an integrative review of the literature SO JOURNAL OF ADVANCED NURSING LA English DT Review DE attitude to death; awareness; cancer; psychology; nursing; religion; spirituality; social support; terminally ill ID METASTATIC BREAST-CANCER; PALLIATIVE HOME CARE; TERMINALLY-ILL; RECURRENT CANCER; SOCIAL SUPPORT; QUALITY; LIFE; ADJUSTMENT; DISEASE; IMPACT AB Purpose. An integrative literature review was undertaken to examine the research on psycho-spiritual well-being in terminally ill people, specifically patients with advanced cancer. Method. A comprehensive search of MEDLINE, CINAHL, CancerLit and PsycINFO using relevant keywords produced 43 primary research studies that investigated psycho-spiritual well-being in patients with advanced cancer. Each report was read, critiqued and systematically assessed for purpose statement or research questions, study design, sample size, characteristics of the subjects, measurement of independent and dependent variables, sample attrition, method of data analysis and results. Major themes and findings were identified for each of the studies. Findings. Psycho-spiritual well-being is an area of interest to researchers all over the world. Retrieved studies had been conducted in 14 countries by researchers in a variety of disciplines, including nursing, medicine, psychology and theology. Six major themes repeatedly emerged as essential components of psycho-spiritual wellbeing: self-awareness, coping and adjusting effectively with stress, relationships and connectedness with others, sense of faith, sense of empowerment and confidence, and living with meaning and hope. Conclusion. Patients with an enhanced sense of psycho-spiritual well-being are able to cope more effectively with the process of terminal illness and find meaning in the experience. Prognostic awareness, family and social support, autonomy, hope and meaning in life all contribute to positive psycho-spiritual well-being. Emotional distress, anxiety, helplessness, hopelessness and fear of death all detract from psycho-spiritual well-being. The research indicated that health professionals can play an important role in enhancing psycho-spiritual well-being, but further research is needed to understand specific interventions that are effective and contribute to positive patient outcomes. C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr, Res Nursing & Patient Care Serv, Boston, MA 02115 USA. Natl Taipei Coll Nursing, Ctr Res & Dev, Planning Div, Taipei, Taiwan. Harvard Univ, Sch Med, Boston, MA USA. RP Bauer-Wu, SM (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr, Res Nursing & Patient Care Serv, 44 Binney St,G220, Boston, MA 02115 USA. NR 49 TC 114 Z9 116 U1 4 U2 46 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD OCT PY 2003 VL 44 IS 1 BP 69 EP 80 DI 10.1046/j.1365-2648.2003.02768.x PG 12 WC Nursing SC Nursing GA 719GT UT WOS:000185195800014 PM 12956671 ER PT J AU Cashman, LS Burns, JT Otieno, IM Fung, T AF Cashman, LS Burns, JT Otieno, IM Fung, T TI Massachusetts registered dietitians' knowledge, attitudes, opinions, personal use, and recommendations to clients about herbal supplements SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ALTERNATIVE MEDICINE AB Objective: To assess the knowledge, personal use and recommendations of herbal supplements among registered dietitians (RDs) in Massachusetts. Design: A descriptive, cross-sectional study conducted by a self-administered survey. Subjects: One hundred and fifty-eight RDs from active members of the Massachusetts Dietetic Association (MDA). Statistical analysis: One-way analysis of variance (ANOVA), Kruskal-Wallis tests, and multivariate regression identified statistical significance and examined the association between the dietitians' test scores from eight herbal knowledge questions with their personal herbal use and recommendations to clients and their age, education, work experience, and work status. Results: We obtained a 53% response rate. The dietitians scored an average of 5.4 of a possible 8 on the herbal knowledge questions. Seventy-three percent (73%) perceived themselves to have little or no knowledge of herbal supplements. Only 37% reported using herbs and 22% recommending herbs to clients in the past year. A significant positive association was observed between herbal supplement knowledge score and frequency of personal use (p = 0.004), and recommendation to clients (p = 0.001). Eighty-nine percent (89%) agreed that herbal supplement education should be incorporated into dietetic curricula. Discussion: The majority of the dietitians may lack herbal supplement familiarity. Therefore, these dietitians may be reluctant to personally use or recommend herbs to clients, even though the majority believe herbs can be effective for specific illness and health maintenance. These results may indicate a need to include more extensive education in the dietetic curricula and to continue education regarding herbal supplements in response to the increasing consumer herbal supplement use. C1 S Shore Hosp, Dept Nutr, S Weymouth, MA 02190 USA. Germain Ctr Extended Care, W Roxbury, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Simmons Coll, Dept Nutr, Boston, MA 02115 USA. RP Cashman, LS (reprint author), S Shore Hosp, Dept Nutr, 55 Fogg Rd, S Weymouth, MA 02190 USA. NR 20 TC 7 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2003 VL 9 IS 5 BP 735 EP 746 DI 10.1089/107555303322524580 PG 12 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 738LE UT WOS:000186288400019 PM 14629851 ER PT J AU Muratoglu, OK Ruberti, J Melotti, S Spiegelberg, SH Greenbaum, ES Harris, WH AF Muratoglu, OK Ruberti, J Melotti, S Spiegelberg, SH Greenbaum, ES Harris, WH TI Optical analysis of surface changes on early retrievals of highly cross-linked and conventional polyethylene tibial inserts SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Hip-and-Knee-Surgeons CY NOV, 2002 CL DALLAS, TEXAS SP Amer Assoc Hip Knee Surg DE polyethylene; cross-linked polyethylene; explant analysis; total knee arthroplasty ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL KNEE ARTHROPLASTY; WEAR; OSTEOLYSIS; PROSTHESES; OXIDATION AB Retrieved tibial liners of highly cross-linked and conventional polyethylene were examined for articular and backside surface damage. Surfaces were graded for pitting, machine-mark loss, scratching, abrasion, delamination, and embedded debris. Whereas no difference existed in the damage score for the 2 groups, the highly crosslinked group showed significantly less elimination of machine marks. Wear, surface plastic deformation, or a combination, could account for the damage on these components. Only 1 of the highly crosslinked polyethylene inserts was available for destructive testing. That insert was melted to activate the shape memory, and thus differentiate, between wear versus plastic deformation. Nearly all changes on the articular and backside surfaces disappeared upon melting, and original machining marks reappeared, Suggesting that the surface changes for that component were primarily the result of plastic deformation and not material removal. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Cambridge Polymer Grp, Somerville, MA USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206, Boston, MA 02114 USA. NR 12 TC 42 Z9 43 U1 1 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2003 VL 18 IS 7 SU 1 BP 42 EP 47 DI 10.1054/S0883-5403(03)00293-6 PG 6 WC Orthopedics SC Orthopedics GA 734QY UT WOS:000186069400009 PM 14560410 ER PT J AU Freund, C Kuhne, R Park, S Thiemke, K Reinherz, EL Wagner, G AF Freund, C Kuhne, R Park, S Thiemke, K Reinherz, EL Wagner, G TI Structural investigations of a GYF domain covalently linked to a proline-rich peptide SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article ID PHOSPHOLIPASE-C; SH3 DOMAINS; WW DOMAIN; BINDING; PROTEIN; SIMILARITY; PROFILIN; COMPLEX; SRC AB Protein structure determination of low affinity complexes of interacting macromolecules is often hampered by a lack of observable NOEs between the binding partners. Covalent linkage offers a way to shift the equilibrium of the interaction partners to the bound state. Here we show that a single-chain protein containing the GYF domain of CD2BP2 and the target peptide SHRPPPPGHRV from CD2 allows for the intramolecular association of the binding partners. We obtained NOEs between the GYF domain and the peptide that could define the principal orientation of the peptide in the complex. In conjunction with general recognition rules for proline-rich sequence recognition these NOEs allowed the accurate modeling of the protein-peptide complex. C1 Forschungsinst Mol Pharmakol, Prot Engn Grp, D-13125 Berlin, Germany. Forschungsinst Mol Pharmakol, Mol Modeling Grp, D-13125 Berlin, Germany. Free Univ Berlin, D-13125 Berlin, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Freund, C (reprint author), Forschungsinst Mol Pharmakol, Prot Engn Grp, Robert Rossle Str 10, D-13125 Berlin, Germany. FU NIAID NIH HHS [AI 37581, AI 21226] NR 19 TC 19 Z9 20 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD OCT PY 2003 VL 27 IS 2 BP 143 EP 149 DI 10.1023/A:1024983029700 PG 7 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 705WM UT WOS:000184419100004 PM 12913410 ER PT J AU Herndon, JH AF Herndon, JH TI One more turn of the wrench SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID HEALTH-CARE; ADVERSE-EVENTS; MEDICAL ERRORS; PATIENT SAFETY; QUALITY; PHYSICIANS; IMPROVEMENT; HAZARDS; SURGERY C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Herndon, JH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, 55 Fruit St,Gray 624, Boston, MA 02114 USA. NR 68 TC 9 Z9 10 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD OCT PY 2003 VL 85A IS 10 BP 2036 EP 2048 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 732YE UT WOS:000185972500026 PM 14563815 ER PT J AU Frame, LH AF Frame, LH TI Responses to pacing depend on electrical and structural properties of the reentrant circuit SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material ID DOUBLE-WAVE REENTRY; VENTRICULAR-TACHYCARDIA; ATRIAL-FLUTTER; TERMINATION; MECHANISMS; ACCELERATION; PROPAGATION; STIMULATION; HEART; CONDUCTION C1 Philadelphia VA Med Ctr, Cardiol Sect 111C, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA. RP Frame, LH (reprint author), Philadelphia VA Med Ctr, Cardiol Sect 111C, 3900 Univ Ave, Philadelphia, PA 19104 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 2003 VL 14 IS 10 BP 1075 EP 1076 DI 10.1046/k/1540-8167.2003.09999.x PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 741ZC UT WOS:000186489400008 PM 14521660 ER PT J AU Solomon, R Donnenfeld, ED Azar, DT Holland, EJ Palmon, FR Pflugfelder, SC Rubenstein, JB AF Solomon, R Donnenfeld, ED Azar, DT Holland, EJ Palmon, FR Pflugfelder, SC Rubenstein, JB TI Infectious keratitis after laser in situ keratomileusis: Results of an ASCRS survey SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT Symposium on Cataract, IOL and Refractive Surgery CY JUN, 2002 CL PHILADELPHIA, PENNSYLVANIA SP ASCRS, IOL ID MYCOBACTERIUM-CHELONAE KERATITIS; PHOTOREFRACTIVE KERATECTOMY; ULCERATIVE KERATITIS; FUNGAL KERATITIS; POLYMICROBIAL KERATITIS; PNEUMOCOCCAL KERATITIS; BACTERIAL KERATITIS; NOCARDIAL KERATITIS; HIGH MYOPIA; LASIK AB To investigate the incidence, culture results, treatment, and visual outcomes of infectious keratitis after laser in situ keratomileusis (LASIK) worldwide, the Cornea Clinical Committee of the American Society of Cataract and Refractive Surgery (ASCRS) contacted 8600 United States and international ASCRS members by e-mail and asked them to respond to a questionnaire about post-LASIK infectious keratitis. One hundred sixteen infections were reported by 56 LASIK surgeons who had performed an estimated 338 550 procedures. Seventy-six cases presented in the first week after surgery, 7 during the second week, 17 between the second and fourth weeks, and 16 after 1 month. Forty-seven cases were not diagnosed on initial presentation. The most common organisms cultured were atypical mycobacteria and staphylococci. Empiric therapy is not recommended as most of the organisms are opportunistic and not responsive to conventional therapy. Flap elevation and culturing should be performed when post-LASIK infectious keratitis is suspected. (C) 2003 ASCRS and ESCRS C1 Nassau Univ, Ctr Med, Dept Ophthalmol, E Meadow, NY USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH USA. Ctr Eye, Ft Myers, FL USA. Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. Rush Univ, Rush Med Coll, Dept Ophthalmol, Chicago, IL 60612 USA. RP Donnenfeld, ED (reprint author), Ryan Med Arts Bldg,Suite 402,2000 N Village Ave, Rockville Ctr, NY 11570 USA. NR 52 TC 64 Z9 71 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD OCT PY 2003 VL 29 IS 10 BP 2001 EP 2006 DI 10.1016/S0886-3350(03)00512-1 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 739LM UT WOS:000186347800033 PM 14604725 ER PT J AU Cao, GD Clark, RSB Pei, W Yin, W Zhang, F Sun, FY Graham, SH Chen, J AF Cao, GD Clark, RSB Pei, W Yin, W Zhang, F Sun, FY Graham, SH Chen, J TI Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis-inducing factor; mitochondria; caspases; DNA fragmentation; Bcl; xL ID HIPPOCAMPAL CA1 NEURONS; CYTOCHROME-C RELEASE; CELL-DEATH; DNA FRAGMENTATION; SUPEROXIDE-DISMUTASE; FACTOR AIF; BCL-X; MITOCHONDRIAL RELEASE; GLOBAL-ISCHEMIA; NERVOUS-SYSTEM AB Loss of mitochondrial membrane integrity and the resulting release of apoptogenic factors may play a critical role in mediating hippocampal neurodegeneration after transient global ischemia. In the present study, the authors have cloned and characterized the rat cDNA encoding apoptosis-inducing factor (AIF), an intramitochondrial protein that promotes cell death in a caspase-independent manner upon release into non-mitochondrial compartments. In contrast to the expression patterns of a number of apoptosis-regulatory gene products during brain development, the expression of AIF protein increases gradually with brain maturation and peaks in adulthood. In a rat model of transient global ischemia, AIF was found to translocate from mitochondria to the nucleus in the hippocampal CA I neurons after ischemia and to manifest a DNA-degrading activity that mimicked the purified AIF protein and was inhibitable by AIF immunodepletion. The temporal profile of AIF translocation after ischemia (24 to 72 hours) coincided with the induction of large-scale DNA fragmentation at the size of 50 kbp, a well-characterized hallmark of AIF-like activity but preceded the formation of internucleosomal DNA fragmentation (72 hours), a DNA degradation associated with the terminal stage of cell death. Further, the nuclear translocation of AIF after ischemia was not blocked by inhibiting caspase-3/-7 activities, but, as shown in neuronal cultures that were challenged with transient oxygen-glucose deprivation, it can be prevented by intracellular delivery of the mitochondria-associated antiapoptotic protein Bcl-xL. The results presented here strongly suggest that mitochondrial release of AIF may be an important factor, in addition to the previously reported cytochrome c and Smac, which could contribute to the selective vulnerability of CA1 neurons to transient global ischemic injury. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15213 USA. Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS38560, NS43802, NS45048] NR 46 TC 124 Z9 132 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2003 VL 23 IS 10 BP 1137 EP 1150 DI 10.1097/01.WCB.0000087090.01171.E7 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 729DD UT WOS:000185755500004 PM 14526224 ER PT J AU Atochin, DN Demchenko, IT Astern, J Boso, AE Piantadosi, CA Huang, PL AF Atochin, DN Demchenko, IT Astern, J Boso, AE Piantadosi, CA Huang, PL TI Contributions of endothelial and neuronal nitric oxide synthases to cerebrovascular responses to hyperoxia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE nitric oxide; superoxide; oxygen vasoconstriction; hyperbaric; hyperoxia ID CEREBRAL-BLOOD-FLOW; HYPERBARIC-OXYGEN EXPOSURE; SUPEROXIDE-DISMUTASE; TRANSCRANIAL DOPPLER; RAT-BRAIN; PEROXYNITRITE; MICE; HYPERTENSION; INHIBITION; PRESSURE AB Hyperoxia causes a transient decrease in CBF, followed by a later rise. The mediators of these effects are not known. We used mice lacking endothelial or neuronal nitric oxide synthase (NOS) isoforms (eNOS(-/-) and nNOS(-/-) mice) to study the roles of the NOS isoforms in mediating changes in cerebral vascular tone in response to hyperoxia. Resting regional cerebral blood flow (rCBF) did not differ between wild type (WT), eNOS(-/-) mice, and nNOS(-/-) mice. eNOS(-/-) mice showed decreased cerebrovascular reactivities to N-G-nitro-L-arginine methyl ester (L-NAME), PAPA NONOate, acetylcholine (Ach), and SOD1. In response to hyperbaric oxygen (HBO2) at 5 ATA, WT and nNOS(-/-) mice showed decreases in rCBF over 30 minutes, but eNOS(-/-) mice did not. After 60 minutes HBO2, rCBF increased more in WT mice than in eNOS(-/-) or nNOS(-/-) mice. Brain NO-metabolites (NOx) decreased in WT and eNOS(-/-) mice within 30 minutes of HBO2, but after 45 minutes, NOx rose above control levels, whereas they did not change in nNOS(-/-) mice. Brain 3NT increased during HBO2 in WT and eNOS(-/-) but did not change in nNOS(-/-) mice. These results suggest that modulation of eNOS-derived NO by HBO2 is responsible for the early vasoconstriction responses, whereas late HBO2-induced vasodilation depends upon both eNOS and nNOS. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Duke Univ, Ctr Hyperbar Med & Environm Physiol, Durham, NC USA. Russian Acad Sci, Inst Evolut Physiol & Biochem, St Petersburg, Russia. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Atochin, Dmitriy/Q-3150-2016 FU NHLBI NIH HHS [HL42444-08]; NINDS NIH HHS [NS33335-09] NR 25 TC 56 Z9 62 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 2003 VL 23 IS 10 BP 1219 EP 1226 DI 10.1097/01.WCB.0000089601.87125.E4 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 729DD UT WOS:000185755500012 PM 14526232 ER PT J AU Nunes, F MacCollin, M AF Nunes, F MacCollin, M TI Neurofibromatosis 2 in the pediatric population SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Child-Neurology-Society CY OCT 09-12, 2002 CL WASHINGTON, D.C. SP Child Neurol Soc ID VESTIBULAR SCHWANNOMAS; NF2 GENE; TYPE-2; MUTATIONS; DISEASE; ABNORMALITIES; MANAGEMENT; SEVERITY AB Neurofibromatosis 2 is a severe autosomal dominant disorder characterized by the occurrence of bilateral vestibular schwannomas and other benign tumors of the nervous system. Excellent natural history studies exist for adults with neurofibromatosis 2, but limited outcome data are available for children with neurofibromatosis 2. In this study, we present clinical data on 12 patients with neurofibromatosis 2 and age at diagnosis before 18 years. Full record review included surgical reports, pathology reports, and imaging studies; all patients were personally examined by a single author. One third of the patients presented with hearing impairment and another third presented with other cranial nerve dysfunction. Tumor load was extensive, including cranial meningiomas in 75%, cranial schwannomas other than vestibular schwannomas in 83%, and spinal cord tumors in 75%. Family history was present in two thirds of the patients. Surgical removal of vestibular schwannomas was performed in 58%; none had full preservation of hearing postsurgery. Functionally, 75% of children had hearing loss, 83% had visual impairment, 25% had abnormal ambulation, and 25% were performing below grade level. In conclusion, increased clinical awareness, better imaging techniques, and molecular diagnostics have made pediatric diagnosis of neurofibromatosis 2 feasible, but outcomes appear to be worse than in adult patients. Further work is needed to determine optimal management of pediatric neurofibromatosis 2. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP MacCollin, M (reprint author), Bldg 149,13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [R01 NS40527] NR 20 TC 33 Z9 33 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD OCT PY 2003 VL 18 IS 10 BP 718 EP 724 DI 10.1177/08830738030180101301 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 740XP UT WOS:000186428300012 PM 14649556 ER PT J AU Seidman, LJ Lanca, M Kremen, WS Faraone, SV Tsuang, MT AF Seidman, LJ Lanca, M Kremen, WS Faraone, SV Tsuang, MT TI Organizational and visual memory deficits in schizophrenia and bipolar-psychoses using the Rey-Osterrieth complex figure: Effects of duration of illness SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID CARD-SORTING-TEST; NEUROPSYCHOLOGICAL DEFICITS; PREFRONTAL DYSFUNCTION; GENETIC TRANSMISSION; COGNITIVE IMPAIRMENT; QUANTITATIVE MODELS; AFFECTIVE-DISORDERS; PERFORMANCE; RECALL; NEUROPATHOLOGY AB Verbal declarative memory deficits in schizophrenia are well documented whereas visual declarative memory is less studied. Moreover, there are limited data on whether organizational and visual memory deficits are specific to schizophrenic psychoses. We compared visual memory and organizational function in patients with chronic schizophrenia (n = 79) and chronic bipolar psychotic disorder (n = 14), and in healthy controls (n = 84) using the Rey-Osterrieth Complex Figure (ROCF), testing whether organizational impairments (i.e., executive dysfunctions) account for the visual memory deficit. Groups were comparable on age, handedness and expected intellectual ability (based on single word reading). Using analyses of covariance with sex, parental SES and ethnicity as co-variates, patients with schizophrenia were significantly more impaired than controls on copy accuracy, on recall accuracy, and on percent accuracy of recall. Patients with schizophrenia used a more detail-oriented style on copy and recall and had significantly worse recognition memory. After co-varying IQ, copy organization was also significantly different between the groups. Results for accuracy of copy and recall were not significantly attenuated when controlling for copy organization. Duration of illness was associated with visual memory. Bipolar patients performed at an intermediate level between controls and patients with schizophrenia. The data suggest that in schizophrenia, patients have a visual memory disorder characterized by both organizational processing impairments and retention difficulties, and that there is a decline in visual memory functions with duration of illness. Further research is required to determine whether similar mechanisms underlie the neurocognitive deficits in these psychotic disorders. C1 Harvard Univ, Sch Med, Dept Psychiat, Neuropsychol Lab,Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA 02401 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Cambridge Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Calif State Univ Sacramento, Sch Med, Dept Psychiat, Sacramento, CA 95819 USA. UC Davis, Napa Psychiat Res Ctr, Napa State Hosp, Napa, CA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Seidman, LJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Neuropsychol Lab,Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH43518, MH46318] NR 83 TC 37 Z9 37 U1 2 U2 7 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 2003 VL 25 IS 7 BP 949 EP 964 DI 10.1076/jcen.25.7.949.16482 PG 16 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 739WM UT WOS:000186369800005 PM 13680442 ER PT J AU Barker, FG Klibanski, A Swearingen, B AF Barker, FG Klibanski, A Swearingen, B TI Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: Mortality, morbidity, and the effects of hospital and surgeon volume SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM MORTALITY; ADMINISTRATIVE DATA; CUSHINGS-DISEASE; STRICT CRITERIA; NATIONAL-SURVEY; COMPLICATIONS; EXPERIENCE; OUTCOMES; ADENOMAS; QUALITY AB Larger surgical caseload is associated with better patient outcome for many complex procedures. We examined the volume-outcome relationship for transsphenoidal pituitary tumor surgery using the Nationwide Inpatient Sample, 1996-2000. Multivariate regression adjusted for patient demographics, acuity measures, medical comorbidities, and endocrine status. A total of 5497 operations were performed at 538 hospitals by 825 surgeons. Outcome measured at hospital discharge was: death (0.6%), discharge to long-term care (0.9%), to short-term rehabilitation (2.1%), or directly home (96.2%). Outcomes were better after surgery at higher-volume hospitals (OR 0.74 for 5-fold-larger caseload, P = 0.007) or by higher-volume surgeons (OR 0.62, P = 0.02). A total of 5.4% of patients were not discharged directly home from lowest-volume-quartile hospitals, compared with 2.6% at highest-volume-quartile hospitals. In-hospital mortality was lower with higher-volume hospitals (P = 0.03) and surgeons (P = 0.09). Mortality rates were 0.9% at lowest-caseload-quartile hospitals and 0.4% at highest-volume-quartile hospitals. Postoperative complications (26.5% of admissions) were less frequent with higher-volume hospitals (P = 0.03) or surgeons (P = 0.005). Length of stay was shorter with high-volume hospitals (P = 0.02) and surgeons (P < 0.001). Hospital charges were lower for high-volume hospitals, but not significantly. This analysis suggests that higher-volume hospitals and surgeons provide superior short-term outcomes after transsphenoidal pituitary tumor surgery with shorter lengths of stay and a trend toward lower charges. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, ACC 331,Fruit St, Boston, MA 02114 USA. EM swearingen@helix.mgh.harvard.edu NR 52 TC 214 Z9 219 U1 2 U2 6 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 OCT 1 PY 2003 VL 88 IS 10 BP 4709 EP 4719 DI 10.1210/jc.2003-030461 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731VC UT WOS:000185906300030 PM 14557445 ER PT J AU Clemmons, DR Chihara, K Freda, PU Ho, KKY Klibanski, A Melmed, S Shalet, SM Strasburger, CJ Trainer, PJ Thorner, MO AF Clemmons, DR Chihara, K Freda, PU Ho, KKY Klibanski, A Melmed, S Shalet, SM Strasburger, CJ Trainer, PJ Thorner, MO TI Optimizing control of acromegaly: Integrating a growth hormone receptor antagonist into the treatment algorithm SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM TREATMENT; SECRETING PITUITARY-ADENOMAS; RELEASE LANREOTIDE TREATMENT; ANALOG SANDOSTATIN-LAR; FACTOR-BINDING-PROTEIN; SOMATOSTATIN ANALOG; TRANSSPHENOIDAL SURGERY; FOLLOW-UP; FACTOR-I; IGF-I AB Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs. C1 Kobe Univ, Grad Sch Med, Dept Clin Mol Med, Div Endocrinol Metab Neurol & Hematol Oncol, Kobe, Hyogo 6500017, Japan. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. St Vincents Hosp, Dept Endocrinol, Darlinghurst, NSW 2010, Australia. Univ N Carolina, Chapel Hill, NC 27599 USA. St Vincents Hosp, Garvan Inst Med Res, Pituitary Res Unit, Darlinghurst, NSW 2010, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Los Angeles, CA 90048 USA. Christie Hosp, Dept Endocrinol, Manchester M20 4BX, Lancs, England. Div Endocrinol, D-80336 Berlin, Germany. Dept Med, D-80336 Berlin, Germany. Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA. RP Clemmons, DR (reprint author), Univ N Carolina, 6111 Thurston Bowles Bldg,CB 7170, Chapel Hill, NC 27599 USA. EM endo@med.unc.edu RI Ho, Ken/E-5832-2011; OI Trainer, Peter/0000-0003-0146-3835 NR 92 TC 48 Z9 52 U1 0 U2 0 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 OCT 1 PY 2003 VL 88 IS 10 BP 4759 EP 4767 DI 10.1210/jc.2003-030518 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731VC UT WOS:000185906300037 PM 14557452 ER PT J AU Sowers, M Derby, C Jannausch, ML Torrens, JI Pasternak, R AF Sowers, M Derby, C Jannausch, ML Torrens, JI Pasternak, R TI Insulin resistance, hemostatic factors, and hormone interactions in pre- and perimenopausal women: SWAN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; POLYCYSTIC-OVARY-SYNDROME; RECURRENT MYOCARDIAL-INFARCTION; TYPE-2 DIABETES-MELLITUS; VON-WILLEBRAND-FACTOR; BINDING GLOBULIN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; BLOOD-COAGULATION; UNSTABLE ANGINA AB We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH, estradiol, testosterone, and SHBG. SHBG was used to calculate the free estradiol index and free androgen index. We studied 3,200 women, aged 42-52 yr, in the Study of Women's Health Across the Nation, a prospective multiethnic study of the menopausal transition. We measured the hemostatic factors, fibrinogen, factor VIIc, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor type 1 (PAI-1), as well as glucose and insulin to calculate insulin resistance. After adjustment for body mass index, site, and ethnicity, SHBG was correlated with PAI-1 (partial r = -0.30) and t-PA (partial r = -0.12). Although testosterone was associated with t-PA (partial r = 0.13) and PAI-1 (partial r = 0.07), free androgen index was strongly correlated with t-PA (partial r = 0.18) and PAI-1 (partial r = 0.26). SHBG modified the association of hemostatic factors with insulin resistance. Women with greater insulin resistance had lower SHBG and higher PAI-1. Estrogen measures were not associated with insulin resistance. The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood. SHBG, which influences the amount of bioavailable hormone, significantly modified the association of PAI-1 and t-PA with insulin resistance. The longitudinal Study of Women's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women. C1 Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurol, New York, NY 10461 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07103 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Sowers, M (reprint author), Univ Michigan, Dept Epidemiol, 109 Observ St,Room 2624, Ann Arbor, MI 48109 USA. EM mfsowers@umich.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 35 TC 38 Z9 42 U1 0 U2 0 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 OCT 1 PY 2003 VL 88 IS 10 BP 4904 EP 4910 DI 10.1210/jc.2003-030350 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731VC UT WOS:000185906300057 PM 14557472 ER PT J AU Xu, JM Moatamed, F Caldwell, JS Walker, JR Kraiem, Z Taki, K Brent, GA Hershman, JM AF Xu, JM Moatamed, F Caldwell, JS Walker, JR Kraiem, Z Taki, K Brent, GA Hershman, JM TI Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARKINSONS-DISEASE; OLIGONUCLEOTIDE ARRAYS; GENE-EXPRESSION; LIVER CYTOSOL; CANCER; ACTIVATION; GROWTH; ESTABLISHMENT; REARRANGEMENT; HYBRIDIZATION AB To gain an understanding of the molecular pathogenesis of thyroid cancer, we used DNA microarray to study the expression profiles of 10 different human thyroid carcinoma cell lines. These included papillary lines BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, NPA 87, and TPC1; anaplastic lines ARO 81-1 and DRO 90-1; follicular line WRO 82-1; and medullary line HRO 85-1. Among the genes with increased expression in the cancer cell lines, a gene coding for nicotinamide N-methyltransferase (NNMT) was identified for being highly expressed only in the papillary cell lines. NNMT catalyzes N-methylation of nicotinamide and other structurally related compounds and is highly expressed in the human liver. The results were further confirmed by semiquantitative RT-PCR and Northern blot analysis. NNMT catalytic activities were determined in all of the cells described above and in additional cell lines. Significantly higher NNMT enzyme activities were detected in eight of 10 of the papillary lines and three of six of the follicular cell lines tested. Normal thyroid tissue, thyroid primary cultures, anaplastic cancer cells, and medullary cancer cells showed no or low enzyme activity. Immunohistochemical staining for NNMT of human thyroid specimens showed strong and abundant cytoplasmic reactions in the sections of papillary carcinomas, and weak or scanty reaction in the normal thyroid tissues. These results indicate that NNMT is a potential biomarker for papillary thyroid carcinoma. C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Vet Affairs Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. Novartis Genom Res Fdn, San Diego, CA 92121 USA. Carmel Hosp, Endocrine Res Unit, Haifa, Israel. RP Hershman, JM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol Div 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 45 TC 52 Z9 54 U1 0 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 OCT 1 PY 2003 VL 88 IS 10 BP 4990 EP 4996 DI 10.1210/jc.2002-021843 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731VC UT WOS:000185906300070 PM 14557485 ER PT J AU Gopal, DV Corless, CL Rabkin, JM Olyaei, AJ Rosen, HR AF Gopal, DV Corless, CL Rabkin, JM Olyaei, AJ Rosen, HR TI Graft failure from severe recurrent primary sclerosing cholangitis following orthotopic liver transplantation SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE sclerosing cholangitis; recurrence of underlying liver disease; autoimmune; rejection ID BILIARY STRICTURES; COMPLICATIONS; ALLOGRAFTS; RECIPIENTS AB Speculation that primary sclerosing cholangitis (PSC) may recur in the transplanted liver is based on the relative increase in frequency of biliary abnormalities and histologic evidence of periportal fibrosis without other causes. A recent study demonstrated almost 9% of patients undergoing liver transplantation (OLT) for primary sclerosing cholangitis (PSC) develop recurrent sclerosing cholangitis although the patient and graft survival is not different from those in whom recurrence does not develop. Most reports of PSC recurrence post-OLT estimate rates of 1% to 14%, but to date, no center has reported rapidly progressive fibro-obliterative cholangitis leading to graft failure. Case Report: DV was a 39-year-old white man with ulcerative colitis, since age 2 1, who developed jaundice and pruritis in 1992. ERCP and liver biopsy were consistent with PSC, and he developed thrombocytopenia and bleeding esophageal varices. He underwent an uneventful OLT in May 1994 with an ABO-compatible organ and normal ischemic times. There was no evidence of postoperative cytomegalovirus infection, hepatic artery thrombosis, or rejection. In October 1994, mild abnormalities of liver function tests (LFTs) led to liver biopsy that revealed inflammatory infiltrate in triad with spill-over into lobules and mild periportal fibrosis. LFTs normalized without any treatment, but in February 1995 repeat liver biopsy for increased LFTs revealed moderate periportal fibrosis with inflammatory cells in triads and lobules. Viral shell and CMV titers were negative. No evidence of infectious etiology or rejection was noted. The patient was started on ursodeoxycholic acid at that time and percutaneous transhepatic cholangiogram (PTC) revealed marked narrowing of the intrahepatic ducts. Esophagogastroduodenoseopy (EGD) revealed esophageal varices. Hepatic arteriogram and Doppler ultrasound were negative. He developed progressive graft failure, and died at home while awaiting re-transplant. Conclusions: Although most series report mild recurrence of PSC following OLT, this case illustrates that early, severe recurrence of PSC may occur, leading to graft failure and need for re-transplantation. C1 Portland Vet Affairs Med Ctr, US Vet Hosp, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Div Clin Pharmacol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg & Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Univ Wisconsin Hosp & Clin, Sect Gastroenterol & Hepatol, Madison, WI 53792 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, US Vet Hosp, Div Gastroenterol Hepatol, 3710 SW,P3-G1, Portland, OR 97207 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 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 OCT PY 2003 VL 37 IS 4 BP 344 EP 347 DI 10.1097/00004836-200310000-00015 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 723YD UT WOS:000185458400015 PM 14506394 ER PT J AU Jain, RK Booth, MF AF Jain, RK Booth, MF TI What brings pericytes to tumor vessels? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID BLOOD-VESSELS; CELLS; INDUCTION; VEGF; ANGIOGENESIS; RECRUITMENT; VASCULATURE; EXPRESSION; PDGF AB Paracrine signaling via platelet-derived growth factor B (PDGFB), expressed by endothelial cells, and its receptor PDGFR-beta, expressed by pericytes, plays a central role in blood vessel maturation. A new study (see the related article beginning on page 1142) reveals that it is not just the presence of PDGFB, but how it is presented to pericytes, that determines the quality of the endothelium-pericyte interaction. C1 Harvard Univ, Sch Med, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Edwin L Steele Lab, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 18 TC 119 Z9 123 U1 2 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2003 VL 112 IS 8 BP 1134 EP 1136 DI 10.1172/JCI200320087 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 733KW UT WOS:000186000300003 PM 14561696 ER PT J AU Kanters, E Pasparakis, M Gijbels, MJJ Vergouwe, MN Partouns-Hendriks, I Fijneman, RJA Clausen, BE Forster, I Kockx, MM Rajewsky, K Kraal, G Hofker, MH de Winther, MPJ AF Kanters, E Pasparakis, M Gijbels, MJJ Vergouwe, MN Partouns-Hendriks, I Fijneman, RJA Clausen, BE Forster, I Kockx, MM Rajewsky, K Kraal, G Hofker, MH de Winther, MPJ TI Inhibition of NF-kappa B activation in macrophages increases atherosclerosis in LDL receptor-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; TRANSGENIC MICE; LIVER DEGENERATION; EMBRYONIC LETHALITY; KNOCKOUT MICE; LACKING; CELLS; GENE; INTERLEUKIN-10; INFLAMMATION AB Atherosclerosis is now generally accepted as a chronic inflammatory condition. The transcription factor NF-kappaB is a key regulator of inflammation, immune responses, cell survival, and cell proliferation. To investigate the role of NF-kappaB activation in macrophages during atherogenesis, we used LDL receptor-deficient mice with a macrophage-restricted deletion of IkappaB kinase 2 (IKK2), which is essential for NF-kappaB activation by proinflammatory signals. These mice showed increased atherosclerosis as quantified by lesion area measurements. In addition, the lesions were more advanced and showed more necrosis and increased cell number in early lesions. Southern blotting revealed that deletion of IKK2 was approximately 65% in macrophages, coinciding with a reduction of 50% in NF-kappaB activation as compared with controls. In both groups, the expression of differentiation markers, uptake of bacteria, and endocytosis of modified LDL was similar. Upon stimulation with LPS, production of TNF was reduced by approximately 50% in IKK2-deleted macrophages. Interestingly, we also found a major reduction in the anti-inflammatory cytokine IL-10. Our data show that inhibition of the NF-kappaB pathway in macrophages leads to more severe atherosclerosis in mice, possibly by affecting the pro-and anti-inflammatory balance that controls the development of atherosclerosis. C1 Cardiovasc Res Inst Maastricht, Dept Mol Genet, NL-6229 ER Maastricht, Netherlands. Vrije Univ Amsterdam, Ctr Med, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands. European Mol Biol Lab, Mouse Biol Programme, Monterotondo, Italy. Maastricht Univ, Cardiovasc Res Inst Maastricht, Dept Pathol, Maastricht, Netherlands. Acad Med Ctr, Dept Cell Biol & Histol, Amsterdam, Netherlands. Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany. Middelheim Hosp, Dept Pathol, Antwerp, Belgium. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. RP de Winther, MPJ (reprint author), Cardiovasc Res Inst Maastricht, Dept Mol Genet, UNS50-11,Universiteitssingel 50, NL-6229 ER Maastricht, Netherlands. RI CLAUSEN, Bjorn/A-8229-2010; de Winther, Menno/E-8721-2012; Forster, Irmgard/P-8545-2016; OI CLAUSEN, Bjorn/0000-0002-2484-7842; de Winther, Menno/0000-0002-4038-6636; Fijneman, Remond/0000-0003-2076-5521; Pasparakis, Manolis/0000-0002-9870-0966 NR 33 TC 190 Z9 202 U1 1 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2003 VL 112 IS 8 BP 1176 EP 1185 DI 10.1172/JCI200318580 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 733KW UT WOS:000186000300009 PM 14561702 ER PT J AU Yoshimura, S Teramoto, T Whalen, MJ Irizarry, MC Takagi, Y Qiu, JH Harada, J Waeber, C Breakefield, XO Moskowitz, MA AF Yoshimura, S Teramoto, T Whalen, MJ Irizarry, MC Takagi, Y Qiu, JH Harada, J Waeber, C Breakefield, XO Moskowitz, MA TI FGF-2 regulates neurogenesis and degeneration in the dentate gyrus after traumatic brain injury in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; CONTROLLED CORTICAL IMPACT; CENTRAL-NERVOUS-SYSTEM; HIPPOCAMPAL-NEURONS; ADULT-RAT; NEURAL PROGENITORS; ENDOTHELIAL-CELLS; TRANSGENIC MICE; PROLIFERATION; ISCHEMIA AB We studied the role of FGF-2 on regulation of neurogenesis and cell loss in the granule cell layer (GCL) of the hippocampal dentate gyrus after experimental traumatic brain injury (TBI). in both FGF-2(-/-) and FGF-2(+/+) mice subjected to controlled cortical impact, the number of dividing cells labeled with BrdU, injected on posttrauma days 6 through 8, increased at 9 days after TBI, and the number of BrdU-positive cells colabeled with neuron-specific nuclear antigen significantly increased at 35 days. However, in injured FGF-2(-/-) mice, BrdU-positive cells and BrdU-positive neurons (days 9, 35) were fewer compared with FGF-2(+/+) mice. The re was also a decrease in the volume of the GCL and the number of GCL neurons after TBI in both FGF-2(-/-) and FGF-2(+/+) mice, but the decrease in both was greater in FGF-2(-/-) mice at 35 days. Overexpression of FGF-2 by intracerebral injection of herpes simplex virus-1 amplicon vectors encoding this factor increased numbers of dividing cells (day 9) and BrdU-positive neurons (day 35) significantly in C57BL/6 mice. Furthermore, the decrease in GCL volume was also attenuated. These results suggest that FGF-2 upregulates neurogenesis and protects neurons against degeneration in the adult hippocampus after TBI, and that FGF-2 supplementation via gene transfer can reduce GCL degeneration after TBI. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Ctr, Radiol Dept, Boston, MA USA. Harvard Univ, Sch Med, Alzheimer Dis Res Unit, Ctr Aging, Boston, MA USA. Harvard Univ, Sch Med, Alzheimer Dis Res Unit, Ctr Genet, Boston, MA USA. Harvard Univ, Sch Med, Alzheimer Dis Res Unit, Ctr Neurodegenerat, Boston, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Bldg 149,13th St Rm 6403, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [P50 NS010828, 5 P50 NS10828, K08 NS041969, KO8 NS41969-02, NS24279, P01 NS024279] NR 52 TC 110 Z9 117 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2003 VL 112 IS 8 BP 1202 EP 1210 DI 10.1172/JCI200316618 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 733KW UT WOS:000186000300012 PM 14561705 ER PT J AU Zhang, HB Cicchetti, G Onda, H Koon, HB Asrican, K Bajraszewski, N Vazquez, F Carpenter, CL Kwiatkowski, DJ AF Zhang, HB Cicchetti, G Onda, H Koon, HB Asrican, K Bajraszewski, N Vazquez, F Carpenter, CL Kwiatkowski, DJ TI Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; P70 S6 KINASE; TUBEROUS SCLEROSIS; CELL-GROWTH; 3-KINASE/AKT PATHWAY; EMBRYONIC LETHALITY; TSC2 MUTATION; COMPLEX; PROTEIN; ACID AB Tuberous sclerosis (TSC) is a familial tumor syndrome due to mutations in TSC1 or TSC2, in which progression to malignancy is rare. Primary Tsc2(-/-) murine embryo fibroblast cultures display early senescence with overexpression of p21(CIP1/WAF1) that is rescued by loss of TP53. Tsc2(-/-)TP53(-/-) cells, as well as tumors from Tsc2(+/-) mice, display an mTOR-activation signature with constitutive activation of S6K, which is reverted by treatment with rapamycin. Rapamycin also reverts a growth advantage of Tsc2(-/-)TP53(-/-) cells. Tsc1/Tsc2 does not bind directly to mTOR, however, nor does it directly influence mTOR kinase activity or cellular phosphatase activity. There is a marked reduction in Akt activation in Tsc2(-/-)TP53(-/-) and Tsc1(-/-) cells in response to serum and PDGF, along with a reduction in cell ruffling. PDGFRalpha and PDGFRbeta expression is markedly reduced in both the cell lines and Tsc mouse renal cystadenomas, and ectopic expression of PDGFRbeta in Tsc2-null cells restores Akt phosphorylation in response to serum, PDGF, EGF, and insulin. This activation of mTOR along with downregulation of PDGFR PI3K-Akt signaling in cells lacking Tsc1 or Tsc2 may explain why these genes are rarely involved in human cancer. This is in contrast to PTEN, which is a negative upstream regulator of this pathway. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Kwiatkowski, DJ (reprint author), Genet Lab, Hematol Div, 221 Longwood Ave,LM-302, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL-07680, T32 HL007680]; NIGMS NIH HHS [GM-54389, R01 GM054389]; NINDS NIH HHS [NS-31535, NS-41498, R01 NS031535, R37 NS031535] NR 35 TC 330 Z9 335 U1 2 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2003 VL 112 IS 8 BP 1223 EP 1233 DI 10.1172/JCI200317222 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 733KW UT WOS:000186000300014 PM 14561707 ER PT J AU Bastepe, M Frohlich, LF Hendy, GN Indridason, OS Josse, RG Koshiyama, H Korkko, J Nakamoto, JM Rosenbloom, AL Slyper, AH Sugimoto, T Tsatsoulis, A Crawford, JD Juppner, H AF Bastepe, M Frohlich, LF Hendy, GN Indridason, OS Josse, RG Koshiyama, H Korkko, J Nakamoto, JM Rosenbloom, AL Slyper, AH Sugimoto, T Tsatsoulis, A Crawford, JD Juppner, H TI Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GS-ALPHA GENE; G-PROTEIN; PRADER-WILLI; ANGELMAN-SYNDROMES; PARATHYROID-HORMONE; MOLECULAR-CLONING; LOCALIZATION; METHYLATION; RECEPTOR; PEPTIDE AB Patients with pseudohypoparathyroidism type Ib (PHP-Ib) have hypocalcemia and hyperphosphatemia due to renal parathyroid hormone (PTH) resistance, but lack physical features of Albright hereditary osteodystrophy. PHP-Ib is thus distinct from PHP-Ia, which is caused by mutations in the GNAS exons encoding the G protein alpha subunit. However, an imprinted autosomal dominant form of PHP-Ib (AD-PHP-Ib) has been mapped to a region of chromosome 20q13.3 containing GNAS. Furthermore, loss of methylation at a differentially methylated region (DMR) of this locus, exon A/B, has been observed thus far in all investigated sporadic PHP-Ib cases and the affected members of multiple AD-PHP-Ib kindreds. We now report that affected members and obligate gene carriers of 12 unrelated AD-PHP-Ib kindreds and four apparently sporadic PHP-Ib patients, but not healthy controls, have a heterozygous approximately 3-kb microdeletion located approximately 220 kb centromeric of GNAS exon A/B. The deleted region, which is flanked by two direct repeats, includes three exons of STX16, the gene encoding syntax-in-16, for which no evidence of imprinting could be found. Affected individuals carrying the microdeletion show loss of exon A/B methylation but no epigenetic abnormalities at other GNAS DMRs. We therefore postulate that this microdeletion disrupts a putative cis-acting element required for methylation at exon A/B, and that this genetic defect underlies the renal PTH resistance in AD-PHP-Ib. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. McGill Univ, Calcium Res Lab, Royal Victoria Hosp, Dept Med, Montreal, PQ, Canada. McGill Univ, Calcium Res Lab, Royal Victoria Hosp, Dept Physiol, Montreal, PQ, Canada. McGill Univ, Calcium Res Lab, Royal Victoria Hosp, Dept Human Genet, Montreal, PQ, Canada. Landspitali Univ Hosp, Renal Unit, Dept Med, Reykjavik, Iceland. Univ Toronto, St Michaels Hosp, Div Endocrinol & Metab, Toronto, ON, Canada. Kitano Hosp, Med Res Inst, Dept Med, Div Diabet & Endocrinol, Kyoto, Japan. Kyoto Univ, Grad Sch Med, Dept Diabet & Clin Nutr, Kyoto, Japan. Oulu Univ Hosp, Dept Clin Genet, Oulu, Finland. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Pediat Endocrinol, Los Angeles, CA USA. Univ Florida, Div Endocrinol, Dept Pediat, Gainesville, FL USA. Med Coll Wisconsin, Coll Med, Dept Pediat, Milwaukee, WI 53226 USA. Kobe Univ, Grad Sch Med, Dept Clin Mol Med, Div Endocrinol Metab & Neurol, Kobe, Hyogo, Japan. Kobe Univ, Grad Sch Med, Dept Clin Mol Med, Dept Hematol Oncol, Kobe, Hyogo, Japan. Univ Ioannina, Dept Med, Div Endocrinol, Ioannina, Greece. Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mass Gen Hosp Children, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Wellman 5, Boston, MA 02114 USA. RI Koshiyama, Hiroyuki/H-3877-2011 FU NIDDK NIH HHS [KO1 DK-062973-01A1, K01 DK062973]; PHS HHS [R01 46718-10] NR 43 TC 139 Z9 147 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2003 VL 112 IS 8 BP 1255 EP 1263 DI 10.1172/JCI200319159 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 733KW UT WOS:000186000300017 PM 14561710 ER PT J AU Taplin, ME Kantoff, PW AF Taplin, ME Kantoff, PW TI The ingredients for prostate cancer nomograms: The addition of biomarkers sets the table for future recipes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID RADICAL PROSTATECTOMY; ANTIGEN RECURRENCE; PLASMA-LEVELS; PROGRESSION; RECEPTOR C1 Dana Farber Canc Ctr, Boston, MA USA. RP Taplin, ME (reprint author), Dana Farber Canc Ctr, Boston, MA USA. NR 13 TC 2 Z9 2 U1 0 U2 0 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 OCT 1 PY 2003 VL 21 IS 19 BP 3552 EP 3553 DI 10.1200/JCO.2003.07.083 PG 2 WC Oncology SC Oncology GA 727KQ UT WOS:000185657600003 PM 12913104 ER PT J AU Goldberg, JM Silverman, LB Levy, DE Dalton, VK Gelber, RD Lehmann, L Cohen, HJ Sallan, SE Asselin, BL AF Goldberg, JM Silverman, LB Levy, DE Dalton, VK Gelber, RD Lehmann, L Cohen, HJ Sallan, SE Asselin, BL TI Childhood T-cell acute lymphoblastic leukemia: The Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; CRANIAL RADIOTHERAPY; DRUG-RESISTANCE; CHILDREN; INDUCTION; THERAPY; IMMUNOPHENOTYPE; METHOTREXATE; PROTOCOLS; RADIATION AB Purpose: T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10% to 15% of newly diagnosed cases of childhood acute lymphoblastic leukemia (ALL). Historically, T-ALL patients have had a worse prognosis than other ALL patients. Patients and Methods: We reviewed the outcomes of 125 patients with T-ALL treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium trials between 1981 and 1995. Therapy included four- or five-agent remission induction; consolidation therapy with doxorubicin, vincristine, corticosteroid, mercaptopurine, and weekly high-dose asparaginase; and cranial radiation. T-ALL patients were treated the same as high-risk B-progenitor ALL patients. Fifteen patients with T-cell lymphoblastic lymphoma were also treated with the same high-risk regimen between 1981 and 2000. Results: The 5-year event-free survival (EFS) rate for T-ALL patients was 75% +/- 4%. Fourteen of 15 patients with T-cell lymphoblastic lymphoma were long-term survivors. There was no significant difference in EFS comparing patients with T-ALL and B-progenitor ALL (P = .56), although T-ALL patients had significantly higher rates of induction failure (P < .0001), and central nervous system (CNS) relapse (P = .02). The median time to relapse in T-ALL patients was 1.2 years versus 2.5 years in B-progenitor ALL patients (P = .001). There were no pretreatment characteristics associated with worse prognosis in patients with T-ALL. Conclusion: T-ALL patients fared as well as B-progenitor patients on DFCI ALL Consortium protocols. Patients with T-ALL remain at increased risk for induction failure, early relapse, and isolated CNS relapse. Future studies should focus on the identification of and treatment for T-ALL patients at high risk for treatment failure. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Univ Rochester, Med Ctr, Dept Pediat, Div Hematol Oncol, Rochester, NY 14627 USA. RP Asselin, BL (reprint author), 601 Elmwood Ave,Box 777, Rochester, NY 14642 USA. FU NCI NIH HHS [CA06516, CA68484] NR 30 TC 150 Z9 164 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 OCT 1 PY 2003 VL 21 IS 19 BP 3616 EP 3622 DI 10.1200/JCO.2003.10.116 PG 7 WC Oncology SC Oncology GA 727KQ UT WOS:000185657600014 PM 14512392 ER PT J AU Tepper, JE O'Connell, M Hollis, D Niedzwiecki, D Cooke, E Mayer, RJ AF Tepper, JE O'Connell, M Hollis, D Niedzwiecki, D Cooke, E Mayer, RJ TI Analysis of surgical salvage after failure of primary therapy in rectal cancer: Results from Intergroup Study 0114 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC SCORING SYSTEM; COLORECTAL-CANCER; HEPATIC RESECTION; LIVER METASTASES; PULMONARY METASTASES; FOLLOW-UP; CARCINOMA; 10-YEAR; ADENOCARCINOMA AB Purpose: Intergroup Study 0114 was designed to study the effect of various chemotherapy-regimens delivered after potentially curative surgical resection of T3, T4, and/or node-positive rectal cancer. A subset analysis was undertaken to investigate the prevalence and influence of salvage therapy among patients with recurrent disease. Patients and Methods: Adjuvant therapy consisted of two cycles of fluorouracil (FU)-based chemotherapy followed by pelvic irradiation with chemotherapy and two more cycles of chemotherapy after radiation therapy. A total of 1,792 patients were entered onto the study and 1,696 were assessable. After a median of 8.9 years of follow-up, 715 patients (42%) had disease recurrence, and an additional 10% died without evidence of disease. Five hundred patients with follow-up information available had a single organ or single site of first recurrence (73.5% of all recurrences). Results: A total of 171 patients (34% of those with a single organ or single site of recurrence) had a potentially curative resection of the metastatic or locally recurrent disease. Single-site first recurrences in the liver, lung, or pelvis occurred in 448 patients (90% of the single-site recurrences), with 159 (35%) of these undergoing surgical resection for attempted cure. Overall survival differed significantly between the resected and nonresected groups (P < .0001), with overall 5-year probabilities of .27 and .06, respectively. Controlling for worst performance status at the time of recurrence does not alter this relationship. Patients who underwent salvage surgery had significantly increased survival (P < .001) for each site. Conclusion: Attempted surgical salvage of rectal cancer recurrence is performed commonly in the United States. The chance of a long-term cure with such intervention is approximately 27%. (C) 2003 by American Society of Clinical Oncology. C1 Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, CALGB Stat Off, Durham, NC 27706 USA. Mayo Clin, Ctr Canc, Rochester, MN USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Tepper, JE (reprint author), Univ N Carolina, Dept Radiat Oncol, Campus Box 7512, Chapel Hill, NC 27599 USA. NR 30 TC 61 Z9 62 U1 0 U2 0 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 OCT 1 PY 2003 VL 21 IS 19 BP 3623 EP 3628 DI 10.1200/JCO.2003.03.018 PG 6 WC Oncology SC Oncology GA 727KQ UT WOS:000185657600015 PM 14512393 ER PT J AU Sekeres, MA Chernoff, M Lynch, TJ Kasendorf, EI Lasser, DH Greenberg, DB AF Sekeres, MA Chernoff, M Lynch, TJ Kasendorf, EI Lasser, DH Greenberg, DB TI The impact of a physician awareness group and the first year of training on hematology-oncology fellows SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PATIENT-GENERATED DYSPHORIA; BREAKING BAD-NEWS; HOUSE OFFICERS; CARE; FAMILY; CANCER; COMMUNICATION; SATISFACTION; ATTITUDES; MEDICINE AB Purpose : To assess the impact of a Balint-like physician awareness group on hematology-oncology fellows' attitudes and measure changes in attitudes during the first fellowship year. Patients and Methods: We used a modified crossover design in which one half of a fellowship class at a time was exposed to the group intervention over a 2-year period, (2000 to 2002). Two 14-fellow classes were followed for 1 year each and were given three "attitudes" questionnaires, at the beginning, middle, and end of the academic year. Results: Forty Balint group sessions were held during the 2-year study period; 82 questionnaires of the 84 administered (98%) were recovered. Instrument content and criterion validity were demonstrated, as was topic domain reliability. Overall, mean attitude scores increased following the group intervention, from 3.6 (95% Cl, 3.5 to 3.7) to 3.7 (95% Cl, 3.6 to 3.8; P = .09). Within domains, scores increased in a "fellow's views of him/herself as a physician," from 3.8 (95% Cl, 3.6 to 3.9) to 4.1 (95% Cl, 3.9 to 4.2; P = .008) and "comfort dealing with emotional patient/ clinical situatioris," from 3.5 (95% Cl, 3.3 to 3.7) to 3.7 (95% Cl, 3.6 to 3.9; P = .11). Changes in responses to individual questions included: an increase in fellows' comfort with the technical aspects of being an oncologist (P < .03); an increase in fellows' comfort with discussing the stress of home at work (P < .023); and an increase among fellows in feeling pressed for time to discuss psychosocial issues with patients (P = .035). Conclusion: A physician awareness group was feasible and enhanced fellows' development as physicians. Further research is needed to determine how to incorporate such groups into oncology fellowships. (C) 2003 by American Society of Clinical Oncology. C1 Cleveland Clin Fdn, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. Clark Univ, Worcester, MA 01610 USA. Univ Massachusetts, Dept Family Med, Worcester, MA 01605 USA. RP Sekeres, MA (reprint author), Cleveland Clin Fdn, Dept Hematol & Med Oncol, 9500 Euclid Ave,Desk R35, Cleveland, OH 44195 USA. NR 36 TC 19 Z9 19 U1 1 U2 4 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 OCT 1 PY 2003 VL 21 IS 19 BP 3676 EP 3682 DI 10.1200/JCO.2003.12.014 PG 7 WC Oncology SC Oncology GA 727KQ UT WOS:000185657600022 PM 14512400 ER PT J AU Roberts, TG Lynch, TJ Chabner, BA AF Roberts, TG Lynch, TJ Chabner, BA TI The phase III trial in the era of targeted therapy: Unraveling the "go or no go" decision SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; CELL LUNG-CANCER; DRUG DEVELOPMENT; END-POINTS; ANTINEOPLASTIC AGENTS; ANTICANCER AGENTS; CYTOSTATIC AGENTS; AWARD-LECTURE; CHEMOTHERAPY; ONCOLOGY AB Purpose : To review characteristics of contemporary phase III oncology trials and create an explicit framework to help clinical researchers prioritize novel therapies for phase III testing. Methods: We searched the MEDLINE and EMBASE databases for all reviews of phase III trials; cataloged all phase III trials in two national clinical trial databases; and reviewed approval criteria of recently approved oncology drugs from public data provided by the US Food and Drug Administration. Industry data not available elsewhere in the medical literature were obtained from a sourcebook published by a large contract research organization. Results: Phase III oncology trials are the most expensive and time-consuming aspect of the drug development process. The results of these trials continue to exert the greatest influence on the treatment decision of oncologists and remain pivotal to the granting of drug approval. Making optimal decisions about which agents to advance to phase III testing may decrease the overall cost of cancer drug development and limit the number of patients exposed to ineffective drugs. A conceptual decision model for prioritizing novel therapies for phase III testing is presented. Conclusion: Cancer drug development has become more complex and expensive, whereas overall clinical progress remains slow. The transition from phase II to phase III requires a strategic decision that is based on new considerations. A greater investment in phase I and II drug trials may be required to provide the information necessary for phase III planning. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. MIT, Program Pharmaceut Ind, Cambridge, MA 02139 USA. RP Roberts, TG (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [R25T CA92203, R25 CA092203] NR 63 TC 69 Z9 70 U1 1 U2 3 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 OCT 1 PY 2003 VL 21 IS 19 BP 3683 EP 3695 DI 10.1200/JCO.2003.01.204 PG 13 WC Oncology SC Oncology GA 727KQ UT WOS:000185657600023 PM 14512401 ER PT J AU Sekino, S Ramberg, P Uzel, NG Socransky, S Lindhe, J AF Sekino, S Ramberg, P Uzel, NG Socransky, S Lindhe, J TI Effect of various chlorhexidine regimens on salivary bacteria and de novo plaque formation SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE chlorhexidine; microorganisms in saliva; plaque formation ID PARTIAL-MOUTH DISINFECTION; STAGE FULL-MOUTH; BACTEROIDES-MELANINOGENICUS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; MICROBIOLOGICAL OBSERVATIONS; PERIODONTAL INFECTIONS; ORAL CAVITY; SURFACES; RECOVERY; SCHOOLCHILDREN AB Aim: The aim of the present experiment was to study the effect of different chlorhexidine regimens on the number of bacteria in saliva, and on de novo plaque fori-nation. Material and Methods: Ten subjects with gingivitis, but no signs of destructive periodontitis. were recruited. Following a screening examination, the volunteers were given oral hygiene instruction, meticulous scaling and professional mechanical tooth cleaning (PTC). The PTC was repeated once every 3 days during a 2-week period to establish healthy gingival conditions. The study was designed as a double-blind crossover clinical trial including three phases. Each experimental phase comprised one preparatory period of 7 days and one plaque accumulation period (no oral hygiene measures) of 4 days. During all preparatory periods, the volunteers (i) performed mechanical tooth cleaning using a toothbrush and dentifrice and (ii) were, in addition, given two sessions of PTC. The final PTC was delivered after bacterial sampling had been made on Day 0. Preparatory period A: the participants continued the self-performed plaque control regimen that employed only mechanical means. Preparatory period B: the participants were in addition instructed to rinse and gargle, twice daily, with a 0.2% chlorhexidine mouthrinse. Preparatory period C: in addition to the above, the participants were instructed to brush the dorsum of the tongue for 60 s, twice daily, with a 1.0% chlorhexidine gel. Following each plaque accumulation period, there was a 10-day washout interval. The presence and amount of dental plaque (QHI) was scored after 1, 2 and 4 days of no oral hygiene. Samples of saliva were obtained on Day 0 and after I and 2 days. The samples were placed on Brucella agar plates and incubated (anaerobically) for 5 days. The total number of colony-forming units was determined and used to estimate the density of bacteria in saliva. Results: In period A, the mean QHI increased from 1.0 (Day 1) to 1.4 (Day 2) and 2.1 (Day 4). The corresponding scores for periods B and C were 0.5, 0.8, 1.6 and 0.3, 0.8, 1.2, respectively. At all re-examination intervals more plaque formed during period A than during periods B and C. Further, during period C, less plaque formed than that during period B. Saliva samples from Day 0 in period A contained a larger number of TVC than the baseline samples in periods B and C. There was no significant difference in TVC among the groups on Day 2. Conclusion: The daily use of chlorhexidine as an adjunct to mechanical tooth cleaning markedly reduced the number of microorganisms that could be detected in saliva. The number of salivary bacteria may have influenced the amount of plaque that formed during an early phase of no oral hygiene. C1 Univ Gothenburg, Dept Periodontol, Inst Odontol, SE-40530 Gothenburg, Sweden. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Univ Gothenburg, Dept Periodontol, Inst Odontol, Box 450, SE-40530 Gothenburg, Sweden. EM ramberg@odontologi.gu.se NR 34 TC 16 Z9 19 U1 2 U2 4 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6979 EI 1600-051X J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2003 VL 30 IS 10 BP 919 EP 925 DI 10.1034/j.1600-051X.2003.00420.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 731RD UT WOS:000185899500010 PM 14710772 ER PT J AU Boas, DA Bouman, CA Webb, KJ AF Boas, DA Bouman, CA Webb, KJ TI Special section on Imaging through scattering media SO JOURNAL OF ELECTRONIC IMAGING LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Boas, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU I S & T - SOC IMAGING SCIENCE TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA SN 1017-9909 J9 J ELECTRON IMAGING JI J. Electron. Imaging PD OCT PY 2003 VL 12 IS 4 BP 581 EP 582 DI 10.1117/1.1601618 PG 2 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA 743NH UT WOS:000186579000001 ER PT J AU Wimbush, T Brown, DFM Nadel, ES AF Wimbush, T Brown, DFM Nadel, ES TI Fever and rash SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID MENINGOCOCCAL DISEASE C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 1 Z9 1 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 OCT PY 2003 VL 25 IS 3 BP 315 EP 318 DI 10.1016/S0736-4679(03)00211-7 PG 4 WC Emergency Medicine SC Emergency Medicine GA 738LX UT WOS:000186290500013 PM 14585461 ER PT J AU Guo, SS Wu, X Shimoide, AT Wong, J Moatamed, F Sawicki, MP AF Guo, SS Wu, X Shimoide, AT Wong, J Moatamed, F Sawicki, MP TI Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SUPPRESSOR GENE; NEUROENDOCRINE TUMORS; PREDICTS PROGNOSIS; BREAST-CANCER; EXPRESSION; GASTRINOMAS; CARCINOMA; DELETION; KINASE AB Pancreatic endocrine tumours (PETS) occur sporadically or are inherited as part of the multiple endocrine neoplasia type-1 syndrome. Little is known about the molecular events leading to these tumours. Cyclin D1, a key regulator of the G1/S transition of the cell cycle, is overexpressed in a variety of human cancers as well as certain endocrine tumours. We hypothesized that similar to other endocrine tumours, cyclin D1 is overexpressed in human sporadic PETS. Cyclin D l protein overexpression was found in 20 of 31 PETS (65%) when compared with normal pancreatic tissue. Furthermore, Northern blot analysis suggests that cyclin D1 up-regulation occurs at the post-transcriptional level in some PETS. Because the key cell growth signalling pathways p42/p44/ERK (extracellular signal-regulated kinase), p38/MAPK (mitogen-activated protein kinase), and Akt/PKB (protein kinase B) can regulate cyclin D1 protein expression in other cell types, pancreatic endocrine tumours were analysed with phospho-specific antibodies against the active forms of these proteins to elucidate a tissue-specific regulatory mechanism of cyclin D1 in PETS. We found frequent activation of the p38/MAPK and Akt pathways, but down-regulation of the ERK pathway, in cyclin D1 overexpressing PETS. This study demonstrates that cyclin D1 overexpression is associated with human sporadic PET tumorigenesis, and suggests that this up-regulation may occur at the post-transcriptional level. These findings will direct future studies of PETS towards cell cycle dysregulation and the identification of key growth factor pathways involved in the formation of these tumours. C1 Univ Calif Los Angeles, Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Pathol, Los Angeles, CA 90073 USA. RP Sawicki, MP (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Surg, Room 72-215,CHS10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 36 TC 34 Z9 35 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2003 VL 179 IS 1 BP 73 EP 79 DI 10.1677/joe.0.1790073 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 737JH UT WOS:000186226300008 PM 14529567 ER PT J AU Wicky, S Doenz, F Meuwly, JY Portier, F Schnyder, P Denys, A AF Wicky, S Doenz, F Meuwly, JY Portier, F Schnyder, P Denys, A TI Clinical experience with retrievable Gunther tulip vena cava filters SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE pulmonary embolism; deep venous thrombosis; inferior vena Cava filter; Gunther Tulip IVC filter; filter retrieval ID PULMONARY-EMBOLISM; FOLLOW-UP; IN-VITRO; PLACEMENT; MULTICENTER; REGISTRY; FLOW AB Purpose: To report clinical experience with retrievable Gunther Tulip filters from implantation to retrieval and their status in nonretrieved situations. Methods: Seventy-five Gunther Tulip filter implantations were performed in 71 patients (43 women; mean age 55 years). Indications for filter placement were pulmonary embolism (PE) or iliofemoral deep vein thrombosis (DVT) in patients with a contraindication to anticoagulation (43, 61%) or perioperative PE prophylaxis (28, 39%) in patients with confirmed iliofemoral DVT. Retrieval procedures were planned for each patient. Patients with nonretrieved filters were followed with plain radiography and duplex sonography. Results: Technical success of filter insertion was 97.3% (73/75). Eighteen (25%) patients died from unrelated causes prior to retrieval attempts, and 6 other patients were too critically ill for a retrieval procedure. Of 49 (67%) planned retrieval attempts, 14 (19%) filters could not be removed owing to large trapped thrombi. The mean implantation period for the 35 (48%) retrieved filters was 8.2 days (range 1-13). Delivery tilt was observed in 12 (16%) filters and during retrieval attempts in 1 more case. For 9 nonretrieved filters, tilt and migration were observed in 22% at a mean follow-up of 30 months, but no venous thrombosis was assessed. Conclusions: Our data confirm the clinical efficacy of the Gunther Tulip filter during implantation and the feasibility of its retrieval. Further long-term follow-up should be conducted on nonretrieved filters to confirm our results. C1 Univ Lausanne Hosp, Dept Radiol, Lausanne, Switzerland. RP Wicky, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, CIMIT Div, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 21 TC 58 Z9 62 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD OCT PY 2003 VL 10 IS 5 BP 994 EP 1000 DI 10.1583/1545-1550(2003)010<0994:CEWRGT>2.0.CO;2 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 756YE UT WOS:000187512700024 PM 14656169 ER PT J AU Homma, S Matai, K Irie, M Ohno, T Kufe, D Toda, G AF Homma, S Matai, K Irie, M Ohno, T Kufe, D Toda, G TI Immunotherapy using fusions of autologous dendritic cells and tumor cells showed effective clinical response in a patient with advanced gastric carcinoma SO JOURNAL OF GASTROENTEROLOGY LA English DT Article DE dendritic cells; gastric carcinoma; immunotherapy; cell fusion; cell therapy ID ANTITUMOR-ACTIVITY; CANCER; VACCINATION; IMMUNIZATION; REGRESSION AB Immunotherapy using, tumor antigen-loaded dendritic cells is a new approach for the treatment of various types of malignant tumors. Here, we describe a patient with advanced gastric carcinoma who received immunotherapy using fused autologous dendritic cells and carcinoma cells (fusions) and showed effective clinical responses to the treatment. A 74-year-old man showed massive ascitic effusion due to peritonitis carcinomatosa after surgical operation for gastric carcinoma. A gastric carcinoma cell line was established from the patient's tumor tissue. Dendritic cells were obtained by cultivation of the adherent cell fraction of the patient's peripheral blood mononuclear cells (PBMCs) with granulocyte macrophage-colony stimulating factor, interleukin-4, and tumor necrosis factor-alpha. The cells were mixed with irradiated tumor cells and treated with 50% polyethyleneglycol (PEG) for the generation of fusions, as described previously. The PEG-treated cells were injected subcutaneously every 2 weeks. Low-grade fever was observed after the first and second treatments. After the third treatment, ascitic effusion and leg edema decreased markedly, without any other treatments. Serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 decreased to levels lower than those at the initiation of treatment. PBMCs collected after the fifth treatment elicited cytotoxic activity against autologous tumor cells. Although treatment was continued in the same way, recurrence of the disease was observed about 5 months after the start of the treatment. This is the first report of immunotherapy utilizing fusions of autologous dendritic cells and tumor cells resulting in effective clinical responses in advanced gastric carcinoma, without severe adverse effects. C1 Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Minato Ku, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Surg, Tokyo, Japan. Jikei Univ, Sch Med, Dept Oncol, Inst DNA Med, Tokyo, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Homma, S (reprint author), Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Minato Ku, 3-25-8 Nishi Shinbashi, Tokyo 1058461, Japan. NR 20 TC 18 Z9 26 U1 0 U2 2 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD OCT PY 2003 VL 38 IS 10 BP 989 EP 994 DI 10.1007/s00535-002-1183-3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 739XF UT WOS:000186371500011 PM 14614608 ER PT J AU Linder, JA Singer, DE AF Linder, JA Singer, DE TI Desire for antibiotics and antibiotic prescribing for adults with upper respiratory tract infections 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 antibiotics; respiratory tract diseases; physician's practice patterns ID PRIMARY-CARE PHYSICIANS; SORE THROAT; EXPECTATIONS; BRONCHITIS; CHILDREN; TRENDS; COUGH; COLDS AB OBJECTIVE: Prior studies have shown that 60% to 75% of adults with upper respiratory tract infections want antibiotics. More recent research indicates declines in antibiotic prescribing for upper respiratory tract infections. To investigate whether there has been a comparable decrease in patients' desire for antibiotics, we measured the proportion of adults with upper respiratory tract infections who wanted antibiotics in the winter of 2001-2002. We also sought to identify factors independently associated with wanting antibiotics and antibiotic prescribing. DESIGN: Prospective survey of adults with upper respiratory tract infections prior to visiting an acute care clinic from November 2001 to February 2002. MEASUREMENTS AND MAIN RESULTS: Thirty-nine percent of 310 patients wanted antibiotics. Many patients wanted relief from symptoms (43%) or pain (24%) and many patients expected to receive a diagnosis (49%) or reassurance during the visit (13%). In multivariable modeling, independent predictors of wanting antibiotics were prior antibiotic use (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.7) and current smoking (OR, 3.1; 95% CI, 1.3 to 7.3). Physicians prescribed antibiotics to 46% of patients who wanted antibiotics and 29% of patients who did not want antibiotics (P= .01). In multivariable modeling, wanting antibiotics was an independent predictor of antibiotic prescribing (OR, 2.1; 95% CI, 1.1 to 4.4). CONCLUSIONS: Only 39% of adults seeking care for upper respiratory tract infections wanted antibiotics, less than in previous studies. In continuing efforts to break the cycle of inappropriate antibiotic use, physicians should not assume that most patients with upper respiratory tract infections want antibiotics. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. FU BHP HRSA HHS [5T32PE11001-12] NR 23 TC 26 Z9 28 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2003 VL 18 IS 10 BP 795 EP 801 DI 10.1046/j.1525-1497.2003.21101.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 730HF UT WOS:000185823300004 PM 14521641 ER PT J AU Linder, JA Singer, DE AF Linder, JA Singer, DE TI Health-related quality of life of adults with upper respiratory tract infections SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality of life; health status; respiratory infections; common cold ID RANDOMIZED CONTROLLED-TRIAL; ACUTE BRONCHITIS; COMMON COLD; INFLUENZA; EFFICACY; OUTCOMES; CHILDREN AB OBJECTIVE: To determine the impact that upper respiratory tract infections have on patients' physical, social, and emotional functioning, we measured the health-related quality of life (HRQL) of adults with upper respiratory tract infections. SETTING: Acute care clinic from November 2001 to February 2002. DESIGN: Prospectively administered survey. To measure HRQL, we used the Acute Form of the Short Form-36, version 2 (SF-36). For all 8 SF-36 subscales, we used norm-based scoring, in which the general U.S. population has a mean of 50. PATIENTS: Adults who had symptoms for fewer than 30 days completed the SF-36; and were diagnosed with nonspecific upper respiratory infection, viral syndrome, otitis media, sinusitis, nonstreptococcal pharyngitis, streptococcal pharyngitis, or acute bronchitis. MEASUREMENTS AND MAIN RESULTS: The sample of 318 patients was 63% female, 81% white, and had a mean age of 35 years. The primary diagnoses were nonspecific upper respiratory infection (42%), acute bronchitis (16%), sinusitis (12%), viral syndrome (9%), nonstreptococcal pharyngitis (8%), otitis media (7%), and streptococcal pharyngitis (6%). Patients had a mean general health subscale score of 50.9, which is not significantly different from the mean population value of 50 (P = .09). However, there were significant decrements in the remaining 7 subscales of the SF-36: physical functioning (45.5), role-physical (38.5), bodily pain (42.6), vitality (40.8), social functioning (37.8), role-emotional (46.8), and mental health (46.8; P < .0001 for all 7 subscales compared with normative values). Results were similar for the subset of patients with no comorbid illnesses (P < .001 for the same 7 subscales) and patients diagnosed with nonspecific upper respiratory infection (P < .001 for the same 7 subscales). These decrements were similar in magnitude, but somewhat different in subscale pattern, to those of adults with chronic lung disease, osteoarthritis, and depression. CONCLUSIONS: Physicians should remember that adults who seek care for upper respiratory tract infections have measurable, significant decrements in HRQL. For researchers, HRQL is an attractive, potential measure of outcome in future trials of established and novel therapies for upper respiratory tract infections. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. NR 21 TC 18 Z9 18 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2003 VL 18 IS 10 BP 802 EP 807 DI 10.1046/j.1525-1497.2003.21246.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 730HF UT WOS:000185823300005 PM 14521642 ER PT J AU Switzer, GE Halm, EA Chang, CCH Mittman, BS Walsh, MB Fine, MJ AF Switzer, GE Halm, EA Chang, CCH Mittman, BS Walsh, MB Fine, MJ TI Physician awareness and self-reported use of local and national guidelines for community-acquired pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE community-acquired pneumonia; medical practice guidelines ID CLINICAL-PRACTICE GUIDELINES; ANTIMICROBIAL THERAPY; MEDICAL OUTCOMES; HOSPITAL STAY; MANAGEMENT; ADULTS; CARE; IMPROVEMENT; DIAGNOSIS; ATTITUDES AB OBJECTIVES: To assess physician awareness and reported use of medical guidelines for community-acquired pneumonia (CAP), and to identify factors associated with variations in awareness and use of these guidelines. DESIGN: A questionnaire was administered during the preintervention phase of a randomized clinical trial of a pneumonia guideline implementation strategy. PARTICIPANTS: Three hundred and fifty-two physicians who managed CAP patients at 7 Pittsburgh, PA hospitals completed the questionnaire. Physician and practice setting characteristics, and physician awareness and reported use of national American Thoracic Society (ATS) and local (hospital-developed) guidelines for CAP were assessed. RESULTS: Overall, 48% reported being influenced by ATS guidelines and 20% reported using these guidelines; 48% were uncertain whether a local pneumonia guideline existed. Only 28% of physicians who knew a local guideline existed reported frequently using the guideline. Use of national ATS guidelines was independently associated with practice as an infectious disease or pulmonary medicine specialist, nonpatient care-related professional activities, and intellect personality score. Use of local guidelines was independently negatively associated with practice as an infectious disease or pulmonary medicine specialist, and positively associated with positive attitudes toward practice guidelines. CONCLUSIONS: Results indicate low levels of awareness and use of guidelines for the management of CAP. Key indicators (e.g., medical specialty, fewer clinical duties, and positive attitudes about guidelines) were associated with greater use of national and local guidelines. If replicated with data on actual physician management practices, more effective guideline implementation strategies will be necessary to encourage compliance with practice guidelines for the management of CAP. C1 Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. CUNY Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. CA RAND, Santa Monica, CA USA. RP Switzer, GE (reprint author), Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Iroquois Bldg 502,3600 Forbes Ave, Pittsburgh, PA 15213 USA. FU AHRQ HHS [R01HS08282] NR 28 TC 30 Z9 31 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2003 VL 18 IS 10 BP 816 EP 823 DI 10.1046/j.1525-1497.2003.20535.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 730HF UT WOS:000185823300007 PM 14521644 ER PT J AU DePaolo, RW Rollins, BJ Kuziel, W Karpus, WJ AF DePaolo, RW Rollins, BJ Kuziel, W Karpus, WJ TI CC chemokine ligand 2 and its receptor regulate mucosal production of IL-12 and TGF-beta in high dose oral tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; GROWTH-FACTOR-BETA; TCR-TRANSGENIC MICE; SECRETING T-CELLS; IFN-GAMMA; AUTOIMMUNE ENCEPHALOMYELITIS; CHEMOTACTIC PROTEIN-1; CCR2-DEFICIENT MICE; PEYERS-PATCHES AB Oral tolerance is the result of a complex immunoregulatory strategy used by the gut and its associated lymphoid tissues to render the peripheral immune system unresponsive to nonpathogenic proteins, such as food or commensal bacteria. The mechanism of oral tolerance induction and maintenance is not well understood. We have previously shown that the chemokine, CC chemokine ligand 2 (CCL2), is important for the induction and maintenance of oral tolerance. To address the role CCL2 plays in oral tolerance, we used both CCL2(-/-) and CCR2(-/-) mice. Cells from the spleen, mesenteric lymph nodes, and peripheral lymph nodes of CCL2(-/-) and CCR2(-/-) mice fed high doses of OVA showed robust proliferative responses compared with cells from Ag-fed wild-type mice. CCL2(-/-) and CCR2(-/-) mice also produced high amounts of Th1 cytokines such as IL-2 and IFN-gamma and very low amounts of IL-4 and IL-10. The ability of APCs from the gut of CCL2(-/-) and CCR2(-/-) OVA-fed mice to stimulate an indicator T cell line was evaluated. APCs from the Peyer's patch of OVA-fed knockout animals could induce a T cell response measured by an increase in proliferation and generation of IL-12 and IFN-gamma with a concomitant reduction of TGF-beta compared with wild-type controls that did not induce a Th1 response. These data indicate that CCL2 and signaling through its receptor CCR2 is critical for the induction of oral tolerance by regulating Ag presentation leading to a disruption in the balance of inflammatory and regulatory cytokines. C1 Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. RP Karpus, WJ (reprint author), Northwestern Univ, Dept Pathol, Feinberg Sch Med, 303 E Chicago Ave,W127, Chicago, IL 60611 USA. FU NIAID NIH HHS [R01 AI35934] NR 59 TC 19 Z9 21 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 OCT 1 PY 2003 VL 171 IS 7 BP 3560 EP 3567 PG 8 WC Immunology SC Immunology GA 725MY UT WOS:000185548000031 PM 14500652 ER PT J AU Barthel, R Goldfeld, AE AF Barthel, R Goldfeld, AE TI T cell-specific expression of the human TNF-alpha gene involves a functional and highly conserved chromatin signature in intron 3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; ENHANCER; PROMOTER; ELEMENTS; COMPLEX; SEQUENCES; DELETION; REGION; MICE; ETS AB Using a phylogenetic approach, we identified highly conserved sequences within intron 3 of the human TNF-alpha gene. These sequences form cell type-specific DNase I hypersensitivity sites and display cell type-specific DNA-protein contacts in in vivo genomic footprints. Consistent with these results, intron 3 confers specific activity upon a TNF-alpha reporter gene in Jurkat T cells, but not THP-1 monocytic cells. Thus, using a combinatorial approach of phylogenetic analysis, DNase I hypersensitivity analysis, in vivo footprinting, and transfection analysis, we demonstrate that intronic regulatory elements are involved in the cell type-specific regulation of TNF-alpha gene expression. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59838]; NIGMS NIH HHS [GM56492] NR 27 TC 26 Z9 26 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 OCT 1 PY 2003 VL 171 IS 7 BP 3612 EP 3619 PG 8 WC Immunology SC Immunology GA 725MY UT WOS:000185548000037 PM 14500658 ER PT J AU Levy, O Orange, JS Hibberd, P Steinberg, S LaRussa, P Weinberg, A Wilson, SB Shaulov, A Fleisher, G Geha, RS Bonilla, FA Exley, M AF Levy, O Orange, JS Hibberd, P Steinberg, S LaRussa, P Weinberg, A Wilson, SB Shaulov, A Fleisher, G Geha, RS Bonilla, FA Exley, M TI Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NKT CELLS; IMMUNE-RESPONSES; UNITED-STATES; CYTOMEGALOVIRUS; RECOGNITION; ACTIVATION; DISEASE; CD1D; TCR AB An 11-year-old girl presented with a papulovesicular rash and severe respiratory distress 5 weeks after receiving varicella vaccine. Restriction fragment length - polymorphism analysis of virus isolated from an endotracheal-tube aspirate and from bronchoalveolar lavage revealed that this patient's illness was due to the Oka vaccine strain of varicella. An extensive immunologic analysis failed to identify a known diagnostic entity to explain her susceptibility to this attenuated vaccine strain. Analysis of her lymphocytes on separate occasions, months after recovery from her illness, revealed a profound deficiency of natural killer T (NKT) cells and of NKT-cell activity, suggesting that NKT cells contribute to host defense against varicella virus. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. RP Levy, O (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Orange, Jordan/D-5239-2009; OI orange, jordan/0000-0001-7117-7725 FU NCI NIH HHS [CA89567]; NIAID NIH HHS [AI50583, AI55602] NR 23 TC 108 Z9 113 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2003 VL 188 IS 7 BP 948 EP 953 DI 10.1086/378503 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726HV UT WOS:000185593900002 PM 14513412 ER PT J AU Hanna, GJ Balaguera, HU Freedberg, KA Werner, BG Craven, KAS Craven, DE D'Aquila, RT AF Hanna, GJ Balaguera, HU Freedberg, KA Werner, BG Craven, KAS Craven, DE D'Aquila, RT TI Drug-selected resistance mutations and non-B subtypes in antiretroviral-naive adults with established human immunodeficiency virus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 40th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 17-21, 2000 CL TORONTO, CANADA ID SOCIETY-USA PANEL; HIV-1 INFECTION; UNITED-STATES; TYPE-1; RECOMMENDATIONS; SUSCEPTIBILITY AB The prevalence of human immunodeficiency virus (HIV) type 1 antiretroviral resistance is expected to be higher in recently infected antiretroviral-naive individuals than in those who have been infected longer. Antiretroviral-naive HIV-1-infected adults who presented to an outpatient clinic in an urban hospital in Boston for initial evaluation in 1999 were screened for drug-selected resistance mutations and phylogenetic subtype. Drug-selected mutations were identified in 16 (18%) of 88 subjects. Twelve (14%) included mutations associated with nucleoside reverse-transcriptase inhibitors, 4 (5%) included mutations associated with nonnucleoside reverse-transcriptase inhibitors, and 3 (3%) included mutations associated with protease inhibitors. Two (2%) had resistance mutations associated with multiple classes of drugs. Nine (10%) subjects had infection with non-B subtype HIV-1 and did not have drug-selected mutations. Serological results indicated infection for greater than or equal to6 months. Drug-selected mutations or non-B subtypes were detected in a substantial portion of antiretroviral-naive adults who had been infected for at least 6 months. C1 Massachusetts State Lab Inst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hanna, GJ (reprint author), Bristol Myers Squibb Co, Pharmaceut Res Inst, Clin discovery, POB 4000,E12-15, Princeton, NJ 08543 USA. OI Balaguera, Henri/0000-0001-5604-5767 FU NIAID NIH HHS [AI001696, AI029193, AI042006, K08 AI001696, R01 AI029193, R01 AI042006]; NIDDK NIH HHS [DK056410, R01 DK056410] NR 16 TC 26 Z9 29 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2003 VL 188 IS 7 BP 986 EP 991 DI 10.1086/378280 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726HV UT WOS:000185593900008 PM 14513418 ER PT J AU Pabich, WL Fihn, SD Stamm, WE Scholes, D Boyko, EJ Gupta, K AF Pabich, WL Fihn, SD Stamm, WE Scholes, D Boyko, EJ Gupta, K TI Prevalence and determinants of vaginal flora alterations in postmenopausal women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID URINARY-TRACT INFECTIONS; BACTERIAL VAGINOSIS; RISK-FACTORS; H2O2-PRODUCING LACTOBACILLI; COLONIZATION; MICROFLORA; THERAPY AB The vaginal ecology of 463 community-dwelling postmenopausal women was characterized. Vaginal lactobacilli were present in 62% of the women and were significantly more prevalent among women receiving hormone replacement therapy during the previous year. Vaginal Escherichia coli and enterococci were each present in 39% of women and were significantly more frequent in women with a history of urinary tract infection. Heavy growth of lactobacilli was associated with a lower frequency of vaginal colonization with E. coli. Thus, postmenopausal women have a relative depletion of vaginal lactobacilli and an increase in vaginal E. coli compared with premenopausal women. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. VA Puget Sound, Epidemiol Res & Informat Ctr, Seattle, WA USA. VA Puget Sound, NW Hlth Serv, Res & Dev Program, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Gupta, K (reprint author), 1959 NE Pacific St,BB1221,Box 356523, Seattle, WA 98195 USA. FU NIDDK NIH HHS [P01-DK-53369, K23-DK-02660, R01-DK-43134] NR 22 TC 47 Z9 56 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2003 VL 188 IS 7 BP 1054 EP 1058 DI 10.1086/378203 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726HV UT WOS:000185593900017 PM 14513427 ER PT J AU Champliaud, MF Viel, A Baden, HP AF Champliaud, MF Viel, A Baden, HP TI The expression of vitamin D-upregulated protein 1 in skin and its interaction with sciellin in cultured keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE hair ID FREE-RADICAL REDUCTION; CORNIFIED ENVELOPE; THIOREDOXIN FUNCTION; CELL-ENVELOPE; CLONING; BARRIER; DIFFERENTIATION; LOCALIZATION; INVOLUCRIN; EPIDERMIS AB Sciellin, a precursor of the cornified envelope, contains a LIM domain that is known to function as a protein interaction module. In this study we used the yeast two-hybrid system to find proteins interacting with sciellin and identified vitamin D-upregulated protein 1 (VDUP1). This protein had not been reported in skin, but was shown in a number of cells to interact with reduced thioredoxin and regulate its function. Using an affinity VDUP1 column and an extract of cultured keratinocytes it was shown that VDUP1 and sciellin interacted. By immunohistochemistry VDUP1 was localized to the basal layer of normal human epidermis and the inner and outer root sheaths but not the matrix of the hair follicle. In the proliferative epidermis of psoriasis, VDUP1 was most highly expressed in the upper epidermal layers. In cultured keratinocytes, VDUP1 and sciellin were more highly expressed in cells undergoing differentiation. Colocalization of the proteins could be demonstrated by immunohistochemistry in parts of the follicle, psoriatic epidermis, and cultured keratinocytes. Our results suggested that VDUP1 could have a unique role in epidermis regulating the conversion of postmitotic cells to differentiating ones. C1 Univ Strasbourg, Lab Physiopathol Cellulaire & Mol Retine, Strasbourg, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA USA. RP Massachusetts Gen Hosp, Cutaenous Biol Res Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM hbaden@partners.org NR 31 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 2003 VL 121 IS 4 BP 781 EP 785 DI 10.1046/j.1523-1747.2003.12539.x PG 5 WC Dermatology SC Dermatology GA 729UT UT WOS:000185793900024 PM 14632196 ER PT J AU Maxwell, RB Gerhardt, AL Toner, M Gray, ML Schmidt, MA AF Maxwell, RB Gerhardt, AL Toner, M Gray, ML Schmidt, MA TI A microbubble-powered bioparticle actuator SO JOURNAL OF MICROELECTROMECHANICAL SYSTEMS LA English DT Article DE actuators; biological cells; bioparticle; bubbles; bubble chambers; microbubbles; resistance heating; resistors ID THERMAL BUBBLE FORMATION; SYSTEMS; DEVICES; FABRICATION; MICROPUMP AB We present the results of a device that uses controllable microbubble actuation to manipulate bioparticles. In order to create a useful device for controlling the position of bioparticles, predictable microfluidic actuation is crucial. The goal of this project was to develop fundamental technology that can be used to manipulate single bioparticles (e.g., cells). We use a thermal bubble actuation method to accomplish this goal. Microbubbles have the advantages of relatively simple electronics and fabrication but can be difficult to control. In this paper, we describe two specific accomplishments: the use of micromachined nucleation cavities to precisely localize thermal bubbles and to achieve controllable bubble formation temperatures and bubble dissipation and the demonstration of controllable microbubbles in a new device for particle sorting. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Microsyst Technol Labs, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Maxwell, RB (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. NR 38 TC 53 Z9 56 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1057-7157 J9 J MICROELECTROMECH S JI J. Microelectromech. Syst. PD OCT PY 2003 VL 12 IS 5 BP 630 EP 640 DI 10.1109/JMEMS.2003.818457 PG 11 WC Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Instruments & Instrumentation; Physics, Applied SC Engineering; Science & Technology - Other Topics; Instruments & Instrumentation; Physics GA 736BC UT WOS:000186149600011 ER PT J AU He, ZH Bateman, A AF He, ZH Bateman, A TI Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE growth factor; tumorigenesis; wound repair; neovascularization; inflammation ID NEONATAL RAT HYPOTHALAMUS; STEROID-INDUCIBLE GENE; FOCAL ADHESION KINASE; FISH CYPRINUS-CARPIO; GRANULIN/EPITHELIN PRECURSOR; RHEUMATOID-ARTHRITIS; CARASSIUS-AURATUS; RNA EXPRESSION; FACTOR PCDGF; PROTEIN DLK AB Progranulin (Pgrn) is a pluripotent secreted growth factor that mediates cell cycle progression and cell motility. It activates the extracellular regulated kinases and phosphatidyl inositol-3 kinase signal cascades, among others, and increases expression of cyclins D and B. Structurally, it belongs to none of the well-established growth factor families. It regulates developmental events as diverse as the onset of cavitation in the preimplantation embryo and male-specific brain differentiation. During wound repair it promotes granulation and neovascularization. It regulates inflammation through a tripartite loop with secretory leukocyte protease inhibitor (SLPI) which protects pgrn from proteolysis, and elastase, which digests it to smaller peptides. Intact pgrn is anti-inflammatory through the inhibition of some of the actions of tumor necrosis factor, while the proteolytic peptides may stimulate the production of proinflammatory cytokines such as interleukin 8. Pgrn is highly expressed in aggressive cancer cell lines and clinical specimens including breast, ovarian, and renal cancers as well as gliomas. In experimental systems it confers an aggressive phenotype on poorly tumorigenic epithelial cancer cells. The malignancy of highly tumorigenic progranulin-expressing cell lines depends on the expression level of the pgrn gene since attenuating pgrn mRNA levels in pgrn-responsive cells greatly inhibits tumor progression. Given its actions in wound repair and tumorigenesis pgrn may prove a useful clinical target, both for prognosis and for therapy. C1 McGill Univ, Div Expt Med, Montreal, PQ H3A 1A1, Canada. Royal Victoria Hosp, Endocrine Res lab, Montreal, PQ H3A 1A1, Canada. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Bateman, A (reprint author), McGill Univ, Div Expt Med, 687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. NR 106 TC 281 Z9 295 U1 1 U2 14 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD OCT PY 2003 VL 81 IS 10 BP 600 EP 612 DI 10.1007/s00109-003-0474-3 PG 13 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 741MQ UT WOS:000186462200002 PM 12928786 ER PT J AU Zhang, YU Li, MW Drozda, M Chen, MH Ren, SJ Sanchez, ROM Leavitt, BR Cattaneo, E Ferrante, RJ Hayden, MR Friedlander, RM AF Zhang, YU Li, MW Drozda, M Chen, MH Ren, SJ Sanchez, ROM Leavitt, BR Cattaneo, E Ferrante, RJ Hayden, MR Friedlander, RM TI Depletion of wild-type huntingtin in mouse models of neurologic diseases SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BDNF; brain trauma; huntingtin; Huntington's disease; ischemia; spinal cord injury ID TRANSGENIC MICE; EMBRYONIC LETHALITY; MUTANT HUNTINGTIN; GENE; BRAIN; NEURODEGENERATION; EXPRESSION; APOPTOSIS; REPEAT; INJURY AB Huntington's disease (HD) is caused by a mutation in the gene encoding for huntingtin resulting in selective neuronal degeneration. Because HD is an autosomal dominant disorder, affected individuals have one copy of the mutant and one copy of the wild-type allele. Huntingtin has antiapoptotic properties and is critical for cell survival. However, the important role of wild-type huntingtin in both HD and other neurological diseases has not been fully recognized. We demonstrate disease-associated decreased levels of full-length huntingtin in brains of transgenic mouse models of HD, ischemia, trauma, and in spinal cord after injury. In addition, overexpression of wild-type huntingtin confers in vivo protection of neurodegeneration after ischemia. We propose that in HD, in addition to a toxic gain-of-function of mutant huntingtin, a parallel depletion of wild-type huntingtin results in a detrimental loss-of-function, playing an important role in disease progression. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg,Neuroapoptosis Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Univ Milan, Dept Pharmacol Sci, Milan, Italy. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Boston Univ, Sch Med, Bedford, MA USA. Boston Univ, Sch Med, Neurol Pathol & Psychiat Dept, Boston, MA 02118 USA. RP Friedlander, RM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg,Neuroapoptosis Lab, Boston, MA 02115 USA. RI Leavitt, Blair/G-1934-2012; Friedlander, Robert/A-2845-2016; Hayden, Michael/D-8581-2011; OI Friedlander, Robert/0000-0003-4423-9219; Hayden, Michael/0000-0001-5159-1419; CATTANEO, ELENA/0000-0002-0755-4917 FU Telethon [GGP02215] NR 23 TC 64 Z9 66 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2003 VL 87 IS 1 BP 101 EP 106 DI 10.1046/j.1471-4159.2003.01980.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 721KY UT WOS:000185316600012 PM 12969257 ER PT J AU Topcuoglu, MA Palacios, IF Buonanno, FS AF Topcuoglu, MA Palacios, IF Buonanno, FS TI Contrast M-mode power Doppler ultrasound in the detection of right-to-left shunts: Utility of submandibular internal carotid artery recording SO JOURNAL OF NEUROIMAGING LA English DT Article DE transcranial Doppler ultrasound; microembolic signal; patent foramen ovale; cervical internal carotid artery; middle cerebral artery ID PATENT FORAMEN OVALE; TRANSCRANIAL DOPPLER; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CEREBROVASCULAR EVENTS; STROKE; EMBOLI; BLOOD; SIZE; MICROEMBOLI; INJECTION AB \Cardiac right-to-left shunts (RLSs) can be detected by echocardiography and transcranial Doppler ultrasound (TCD). In patients without adequate transtemporal bone windows, results may be obtained by insonating extracranial arteries; however, the sensitivity and practicality of this approach is unknown. In 34 patients evaluated with echocardiography for RLSs, 73 studies were performed with unilateral, simultaneous contrast TCD (cTCD) of the middle cerebral artery (MCA) and anterior cerebral artery (ACA) and submandibular power M-mode Doppler (PMD) ultrasound of the extracranial internal carotid artery (ecICA). The number of microbubble (MB) signals and their times of first appearance were determined. RLS volume was graded on 6 levels (I = trace, 11 = small, III = medium, IVa = large, IVb = shower, IVc = curtain) and compared between MCA and ecICA recordings. In 2 of 24 cTCD studies in 15 patients without evidence of RLSs on single-gated MCA monitoring, low-volume RLSs (grades I and 11) were detected via ecICA insonation; in both, MB signatures were tracked in the ecICA, passing into the ipsilateral ACA. In 40 of 49 studies (26 patients) in which RLSs were demonstrated with single-gated MCA monitoring, more MBs were detected in the ecICA than the MCA, with either single-gated or M-mode images, with increases of 76.9% and 66.1%, respectively (P = .027). Compared to single-gated studies, M-mode technology detected nonsignificant increases in MB number in both the MCA and the ecICA (by 20.2% and 14.0%, respectively). Contrast PMD with cervical ICA recording is at least as sensitive and specific as the traditional MCA method in detecting RLSs; furthermore, this method seems to be more sensitive for low-volume RLSs (grades I-III) because of air MB decay (9.2%) and entry into the ipsilateral ACA (34.2%). This is in concordance with the increase of detected RLS grades observed in 32.7% of patients with echocardiography-documented RLSs. The authors therefore suggest the incorporation of ecICA PMD not only in patients with poor ultrasonic bone windows but also in every patient being evaluated for suspected RLSs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02114 USA. RP Buonanno, FS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM fbuonanno@partners.org NR 34 TC 13 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD OCT PY 2003 VL 13 IS 4 BP 315 EP 323 DI 10.1177/1051228403257616 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 876CX UT WOS:000225474600005 PM 14569823 ER PT J AU Ezure, K Tanaka, I Kondo, M AF Ezure, K Tanaka, I Kondo, M TI Glycine is used as a transmitter by decrementing expiratory neurons of the ventrolateral medulla in the rat SO JOURNAL OF NEUROSCIENCE LA English DT Article DE expiratory neuron; transmitter; glycine; in situ hybridization; GLYT2; GAD67 ID BULBAR RESPIRATORY NEURONS; GLUTAMIC-ACID DECARBOXYLASE; BOTZINGER-COMPLEX; BRAIN-STEM; SPINAL-CORD; INSPIRATORY NEURONS; RHYTHM GENERATION; DECEREBRATE RAT; MESSENGER-RNA; CHOLINE-ACETYLTRANSFERASE AB The medullary respiratory network involves various types of respiratory neurons. The present study focused on possible inhibitory neurons called decrementing expiratory (E-DEC) neurons and aimed to determine whether their transmitter is glycine or GABA. In Nembutal-anesthetized, neuromuscularly blocked, and artificially ventilated rats we labeled E-DEC neurons with Neurobiotin and processed the tissues for detection of mRNA encoding either glycine transporter 2 (GLYT2) as a marker for glycinergic neurons or glutamic acid decarboxylase isoform 67 (GAD67) as a marker for GABAergic neurons, using in situ hybridization. Of 38 E-DEC neurons that were labeled, cranial motoneurons (n = 14), which were labeled as control, were negative for either GLYT2 mRNA ( n = 10) or GAD67 mRNA ( n = 4). The other E-DEC neurons ( n = 24) were non-motoneurons. Sixteen of them were examined for GLYT2 mRNA, and the majority ( 11 of 16) was GLYT2 mRNA-positive. The remaining E-DEC neurons ( n = 8) were examined for GAD67 mRNA, and all of them were GAD67 mRNA-negative. The GLYT2 mRNA-positive E-DEC neurons were located in the ventrolateral medulla spanning the Botzinger complex ( BOT), the rostral ventral respiratory group (VRG), and the caudal VRG. We conclude that not only E-DEC neurons of the BOT but also many E-DEC neurons of the VRG are inhibitory and use glycine as a transmitter. Although the present negative data cannot rule out completely the release of GABA or co-release of glycine and GABA from E-DEC neurons, several lines of evidence suggest that the glycinergic process is primarily responsible for the phasic inhibition of the respiratory network during the expiratory phase. C1 Tokyo Metropolitan Inst Neurosci, Dept Neurobiol, Tokyo 1838526, Japan. Tokyo Metropolitan Inst Neurosci, Dept Mol Physiol, Tokyo 1838526, Japan. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Ezure, K (reprint author), Tokyo Metropolitan Inst Neurosci, Dept Neurobiol, 2-6 Musashidai, Tokyo 1838526, Japan. NR 66 TC 57 Z9 57 U1 1 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 OCT 1 PY 2003 VL 23 IS 26 BP 8941 EP 8948 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 727PE UT WOS:000185666600016 PM 14523096 ER PT J AU Chauhan, NB Siegel, GJ AF Chauhan, NB Siegel, GJ TI Intracerebroventricular passive immunization with anti-A beta antibody in Tg2576 SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; immunotherapy; intracerebroventricular passive immunization; cerebral hemorrhage; inflammation ID AMYLOID PRECURSOR PROTEIN; ENDOSCOPIC 3RD VENTRICULOSTOMY; ALZHEIMERS-DISEASE MODEL; CENTRAL-NERVOUS-SYSTEM; TRANSGENIC MICE; MOUSE MODEL; CEREBRAL-HEMORRHAGE; PEPTIDE; VACCINATION; PATHOLOGY AB Current Alzheimer's disease (AD) research has established the fact that excessive genesis of Abeta derived from amyloidogenic processing of beta-amyloid (Abeta) precursor protein is fundamental to AD pathogenesis. There has been considerable interest in using immunization strategies for clearing excessive Abeta. Studies in animal models of AD have shown that active immunizations or systemic passive immunizations reduced cerebral plaque load and improved behavioral deficits. However, clinical translation of an active immunization strategy was interrupted because of evidence for meningoencephalitis produced in some patients who received Abeta vaccine. Studies in animal models have shown perimicrovascular hemorrhages and inflammation after sustained systemic immunizations in animals with vascular amyloid. In this light, our data showing the effects of a single intracerebroventricular (ICV) injection of anti-Abeta in the Alzheimer's Swedish mutant model Tg2576 are intriguing. We have previously demonstrated that a single ICV injection of anti-Abeta into the third ventricle of 10-month-old Tg2576 mice reduced cerebral plaques, reversed Abeta-induced depletion of presynaptic SNAP-25, and abolished astroglial activation as seen 1 month post-injection (Chauhan and Siegel [2002] J. Neurosci. Res. 69:10-23). The present report demonstrates that a single ICV injection of 10 mug anti-Abeta in 10-month-old Tg2576 mice reduced cerebral plaques, with decreased inflammation at this stage as evidenced by a reduced number of interleukin-1beta-positive microglia surrounding Congophilic plaques. Moreover, at this particular age, no microhemorrhage was discernible, as evidenced by the absence of hemosiderin deposition after a single ICV injection of anti-Abeta. This is the first report demonstrating absence of microhemorrhage and reduced inflammation after the ICV introduction of anti-Abeta in Tg2576 mice at 10 months of age. These facts indicate that, although invasive, ICV injection of anti-Abeta may be a safer method of vaccination in AD, possibly through reducing the vascular exposure to antibody. Further studies are warranted to determine the lasting effects of a single ICV anti-Abeta injection in animals with and without abundant plaque burden and at older ages. (C) 2003 Wiley-Liss, Inc. C1 W Side VA Med Ctr, Res & Dev 151, Chicago, IL 60612 USA. Univ Illinois, Dept Neuroanesthesiol, Chicago, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. RP Chauhan, NB (reprint author), W Side VA Med Ctr, Res & Dev 151, 820 S Damen Ave, Chicago, IL 60612 USA. NR 39 TC 36 Z9 41 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 1 PY 2003 VL 74 IS 1 BP 142 EP 147 DI 10.1002/jnr.10721 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 725BA UT WOS:000185521700016 PM 13130516 ER PT J AU Bermpohl, D AF Bermpohl, D TI Concomitant antagonism of TNF alpha and Fas-ligand reduces cognitive deficits after traumatic brain injury in mice SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P103 BP 1053 EP 1053 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300015 ER PT J AU Wallis, RA Panizzon, KL AF Wallis, RA Panizzon, KL TI Treatment with BCl-2(20-34) protects against sustained injury susceptibility of CA1 and CA3 hippocampal neurons following controlled cortical impact SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 VA Greater Los Angeles Healthcare, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P117 BP 1057 EP 1057 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300030 ER PT J AU Sheibani, N Moskowitz, MA Whalen, MJ AF Sheibani, N Moskowitz, MA Whalen, MJ TI Granulocyte colony stimulating factor promotes cognitive recovery after traumatic brain injury in mice SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P145 BP 1064 EP 1064 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300058 ER PT J AU Whalen, MJ Alce, G McCarthy, D Bermpohl, D Moskowitz, MA AF Whalen, MJ Alce, G McCarthy, D Bermpohl, D Moskowitz, MA TI Effects of inhibition of tumor necrosis factor family members on histopathologic and cognitive outcome after traumatic brain injury in immature versus adult mice. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P146 BP 1064 EP 1064 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300060 ER PT J AU Long, Y Yuan, XQ Lu, H Yang, K AF Long, Y Yuan, XQ Lu, H Yang, K TI Effects of NGF gene transfer on profiles of gene expression in mouse hippocampus after traumatic brain injury. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. VA Med Ctr, PADRECC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P220 BP 1082 EP 1082 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300133 ER PT J AU Hainsworth, AH McCarthy, D Bermpohl, D Qiu, J Moskowitz, MA Whalen, MJ AF Hainsworth, AH McCarthy, D Bermpohl, D Qiu, J Moskowitz, MA Whalen, MJ TI Changes in cellular FLICE-like inhibitory protein abundance following cortical contusion injury SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Charlestown, MA 02129 USA. De Montfort Univ, Pharmacol Grp, Leicester LE1 9BH, Leics, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P232 BP 1085 EP 1085 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300145 ER PT J AU Panizzon, KL Frautschy, SA Wallis, RA AF Panizzon, KL Frautschy, SA Wallis, RA TI Treatment with Bcl-2(20-34) preserves LTP and provides protection against loss of working memory following controlled cortical impact. SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 21st Annual National-Neurotrauma-Society Symposium CY NOV 06-07, 2003 CL BILOXI, MISSISSIPPI SP Natl Neurotrama Soc C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare, Los Angeles, CA USA. RI yu, yan/C-2322-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2003 VL 20 IS 10 MA P309 BP 1105 EP 1105 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 734RX UT WOS:000186072300221 ER PT J AU Troulis, MJ Coppe, C O'Neill, MJ Kaban, LB AF Troulis, MJ Coppe, C O'Neill, MJ Kaban, LB TI Ultrasound: Assessment of the distraction osteogenesis wound in patients undergoing mandibular lengthening SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Cleft-Palate-Craniofacial-Association CY APR 25-28, 2001 CL MINNEAPOLIS, MINNESOTA SP Amer Cleft Palate Crainofacial Assoc ID SKELETAL DISTRACTION; HEALING FRACTURES; OSTEOTOMIES; DEVICE AB Purpose: Common methods of assessment of the clinical distraction osteogenesis (DO) wound consist of serial physical examinations, plain radiographs, and computed tomography (CT). Ultrasound (US) is an inexpensive and efficient method of imaging that provides detailed assessment of bone formation across a defect. It has proved to be useful for the evaluation of long bone DO healing. The purpose of this study was to determine the efficacy of US for evaluation of bone formation in the mandibular distraction wound. Patients and Methods: Ten patients underwent mandibular expansion (18 sides) with semiburied, unidirectional distraction devices. The wounds were assessed with plain radiographs and US immediately before device removal. Estimates of bone formation, using a semiquantitative bone fill score, were made for plain radiographs and US. US beam penetration depth, in millimeters, was also measured. During removal of the distraction device, bone formation and mandibular stability were assessed by the surgeon and graded on a semiquantitative scale. Results: US bone fill scores correlated with intraoperative assessment of bone formation and stability (r = 0.758, P = .0018) at all 18 mandibular sites. Plain radiographic scores also correlated with bone formation (r = 0.592). However, in 14 of 18 sides, plain radiographs underestimated bone formation compared with US and operative findings. Conclusion: The results of this study indicate that US is an accurate noninvasive technique that may prove to be useful in assessing the mandibular DO regenerate in patients. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Div Ultrasonog,Dept Radiol,Ultrasound Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Troulis, MJ (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Div Ultrasonog,Dept Radiol,Ultrasound Unit, Warren Bldg,55 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [K23 DE14070] NR 25 TC 24 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO 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 OCT PY 2003 VL 61 IS 10 BP 1144 EP 1149 DI 10.1016/S0278-2391(03)00672-4 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 726QR UT WOS:000185611000005 PM 14586848 ER PT J AU Smith, SC Lindsley, SK Felgenhauer, J Hawkins, DS Douglas, JG AF Smith, SC Lindsley, SK Felgenhauer, J Hawkins, DS Douglas, JG TI Intensive induction chemotherapy and delayed irradiation in the management of parameningeal rhabdomyosarcoma SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE parameningeal; radiation; rhabdomyosarcoma ID SOFT-TISSUE SARCOMAS; INTERGROUP-RHABDOMYOSARCOMA; PHASE-II; METASTATIC SARCOMAS; RADIATION-THERAPY; CHILDREN; ADOLESCENTS; IFOSFAMIDE; ETOPOSIDE; ADRIAMYCIN AB Purpose: To evaluate local control, event-free survival, and overall survival for patients with parameningeal (PM) rhabdomyosarcoma (RMS) treated with intensive chemotherapy and delayed irradiation. Patients and Methods: Thirteen consecutive patients with PM RMS were treated with an institutional protocol from 1992 to 1998 at the University of Washington/Children's Hospital and Regional Medical Center and Deaconess Medical Center. Patients received intensive chemotherapy consisting of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide prior to radiotherapy. Irradiation was delayed, in contrast to current Intergroup Rhabdomyosarcoma Study Group (IRSG) recommendations. Results: Median follow-up was 39 months. Eleven patients had high-risk features, including five with intracranial extension. All patients responded to the intensive chemotherapy, with 38% exhibiting a complete response and the remaining 62% a partial response. Radiation was administered a median of 21 weeks from initiation of chemotherapy. The Kaplan-Meier estimate of 5-year local control was 92%, with event-free survival and overall survival rates of 83%. Conclusions: With intensive induction chemotherapy, delayed irradiation for PM RMS does not compromise local control. Event-free survival and overall survival rates compare favorably with recently IRSG trials employing early irradiation. Delaying irradiation allows for intensification of chemotherapy and could permit response-based radiation volume and/or dose modifications, which could decrease treatment-related morbidity. C1 Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Dept Pediat, Seattle, WA USA. Deaconess Med Ctr, Spokane, WA USA. RP Douglas, JG (reprint author), Univ Washington, Dept Radiat Oncol, 1959 NE Pacific St,Box 356043, Seattle, WA 98195 USA. NR 29 TC 10 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD OCT PY 2003 VL 25 IS 10 BP 774 EP 779 DI 10.1097/00043426-200310000-00006 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 729TJ UT WOS:000185790000005 PM 14528099 ER PT J AU Kupst, MJ Patenaude, AF Walco, GA Sterling, C AF Kupst, MJ Patenaude, AF Walco, GA Sterling, C TI Clinical trials in pediatric cancer: Parental perspectives on informed consent SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE clinical trials; cancer; informed consent; pediatrics ID CHILDREN AB To better understand parental perceptions of the informed consent process in pediatric oncology clinical trials, 20 parents of newly diagnosed children at two pediatric cancer centers describe their perceptions in a semi-structured interview. They recalled well the diagnosis, the general treatment plan, and the statistics of survival and/or cure, but the research nature of the clinical trials, particularly randomization, was not well understood. However, despite the need to assimilate a great deal of information, time pressure to make decisions, and reportedly high levels of distress during the discussions, parents expressed general satisfaction with the informed consent discussions with their pediatric oncology providers. However, half to two thirds of parents felt there had been inadequate discussion of alternatives to the proposed treatment and of the research nature of the protocol. While further study of the informed consent process should be conducted in larger, representative samples, the findings from this pilot study suggest that a goal of future informed consent interventions should be to improve parents' understanding of the research aspects of treatment. It is critical to parents' ability to provide informed consent that they feel satisfied that they know alternatives to proposed treatment and that they understand the randomization of treatments, which is the gold standard of clinical trials in pediatric oncology. C1 Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. Midwest Childrens Canc Ctr, Milwaukee, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hackensack Univ, Med Ctr, Hackensack, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Hackensack, NJ USA. RP Kupst, MJ (reprint author), Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. NR 9 TC 45 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD OCT PY 2003 VL 25 IS 10 BP 787 EP 790 DI 10.1097/00043426-200310000-00009 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 729TJ UT WOS:000185790000007 PM 14528101 ER PT J AU Lim, LHY Hartnick, CJ Willging, JP AF Lim, LHY Hartnick, CJ Willging, JP TI A rare case of combined type I and II first branchial sinus SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE first branchial sinus ID CLEFT ANOMALIES; CLINICAL UPDATE; CYSTS AB The authors report a rare case of first branchial sinus with combined Work's type I and type II characteristics. Instead of a sinus opening in the neck, this sinus opened above the angle of the jaw in the face. The facial nerve was significantly more superficial to the tympanomastoid suture line than normal. Early diagnosis, ensuring complete resection, and avoidance of facial nerve injury are challenging issues discussed here. C1 Childrens Hosp, Med Ctr, Dept Pediat Otolaryngol, Cincinnati, OH 45229 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. RP Willging, JP (reprint author), Childrens Hosp, Med Ctr, Dept Pediat Otolaryngol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD OCT PY 2003 VL 38 IS 10 AR E48 DI 10.1016/S0022-3468(03)00521-9 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 735WR UT WOS:000186138000033 ER PT J AU Smith, SR AF Smith, SR TI Rethinking the DSM: A psychological perspective. SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Smith, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD OCT PY 2003 VL 81 IS 2 BP 187 EP 188 DI 10.1207/S15327752JPA8102_11 PG 2 WC Psychology, Clinical; Psychology, Social SC Psychology GA 723YB UT WOS:000185458200011 ER PT J AU Bennett, LAT Johnson, JM Stephens, DP Saad, AR Kellogg, DL AF Bennett, LAT Johnson, JM Stephens, DP Saad, AR Kellogg, DL TI Evidence for a role for vasoactive intestinal peptide in active vasodilatation in the cutaneous vasculature of humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GLAND BLOOD-FLOW; LASER-DOPPLER FLOWMETRY; SWEAT GLANDS; COMPLEMENTARY ROLE; POLYPEPTIDE VIP; NITRIC-OXIDE; CYSTIC-FIBROSIS; SMOOTH-MUSCLE; HEAT-STRESS; HUMAN-SKIN AB Active vasodilatation (AVD) in human, non-glabrous skin depends on functional cholinergic fibres but not on acetylcholine (ACh). We tested whether AVD is a redundant system in which ACh and vasoactive intestinal polypeptide (VIP) are co-released from cholinergic nerves. (1) We administered VIP by intradermal microdialysis to four discrete areas of skin in the presence of different levels of the VIP receptor antagonist, VIP(10-28), also delivered by microdialysis. Skin blood flow (SkBF) was continuously monitored by laser Doppler flowmetry (LDF). Mean arterial pressure (MAP) was measured non-invasively and cutaneous vascular conductance (CVC) calculated as LDF/MAP. Subjects were supine and wore water-perfused suits to control whole-body skin temperature (T-sk) at 34degreesC. Concentrations of 54 mum, 107 mum, or 214 mum VIP(10-28) were perfused via intradermal. microdialysis at 2 mul min(-1) for approximately I h. Then 7.5 mum VIP was added to the perfusate containing VIP (10-28) at the three concentrations or Ringer solution and perfusion was continued for 45-60 min. At the control site, this level of VIP caused approximately the vasodilatation typical of heat stress. All VIP(10-28)-treated sites displayed an attenuated dilatation in response to the VIP. The greatest attenuation was observed at the site that received 214 mum VIP(10-28) (P < 0.01). (2) We used 214 mum VIP(10-28) alone and with the iontophoretically administered muscarinic receptor antagonist atropine (400 muA cm(-2), 45s, 10 mm) in heated subjects to test the roles of VIP and ACh in AVD. Ringer solution and 214 mum VIP(10-28) were each perfused at two sites, one of which in each case was pretreated with atropine. After I h of VIP(10-28) treatment, individuals underwent 45-60 min of whole-body heating (T-sk to 38.5degreesC). VIP(10-28), alone or in combination with atropine, attenuated the increase in CVC during heat stress, suggesting an important role for VIP in AVD. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. RP Johnson, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL 65599, HL 59166, R01 HL065599, R01 HL059166] NR 47 TC 69 Z9 72 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 2003 VL 552 IS 1 BP 223 EP 232 DI 10.1113/jphysiol.2003.042135 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 735EA UT WOS:000186098400018 PM 12847205 ER PT J AU Furst, DE Weisman, M Paulus, HE Bulpitt, K Weinblatt, M Polisson, R Zaug, M Kneer, J Van Der Auwera, P Stevens, RM AF Furst, DE Weisman, M Paulus, HE Bulpitt, K Weinblatt, M Polisson, R Zaug, M Kneer, J Van Der Auwera, P Stevens, RM CA Rheumatology Study Grp 825 TI Intravenous human recombinant tumor necrosis factor receptor p55-Fc IgG1 fusion protein, Ro 45-2081 (lenercept): Results of a dose-finding study in rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE tumor necrosis factor-alpha receptor; rheumatoid arthritis; controlled trial; phase II ID ALPHA MONOCLONAL-ANTIBODY; ADALIMUMAB D2E7; METHOTREXATE; ETANERCEPT; THERAPY; TRIAL AB Objective. To determine the optimal dose regimen of intravenous (IV) Ro 45-2081 (lenercept), a tumor necrosis factor receptor p55-Fc IgG1 fusion protein, in patients with active rheumatoid arthritis (RA) Methods. In a double-blind, placebo-controlled, parallel-group, multicenter trial, adult patients with long-standing active RA stabilized on conventional therapy were randomly assigned to receive 3 IV infusions, one every 4 weeks, of one of the following: (a) placebo, (b) lenercept 0.01 mg/kg (maximum 1 mg), (c) lenercept 0.05 mg/kg (maximum 5 mg), (d) lenercept 0.2 mg/kg (maximum 20 mg), or (e) lenercept 0.5 mg/kg (maximum 50 mg). The material utilized in the study had a lower relative bioavailability [lower area under the time-concentration curve (AUC) per mg infused] than that used in a recent similar trial. Efficacy variables included change from baseline in number of swollen joints and tender joints, scores on physician and patient assessments of disease activity, and patient assessment of pain. Results. Patients treated with lenercept exhibited improvement as early as one day after the first IV infusion. The treatment benefit, however, was modest, maximized by 2 weeks and then diminished or vanished as non-neutralizing anti-lenercept antibody concentrations increased. The majority of adverse experiences were mild or moderate and not considered related to study drug. Conclusion. Our results showed that lenercept administered by IV infusion every 4 weeks is well tolerated, but only transiently effective in patients with long-standing RA, likely due to both the low relative bioavailability of the material used in the study and the formation of non-neutralizing antilenercept antibodies. C1 Virginia Mason Res Ctr, Seattle, WA 98101 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. F Hoffmann La Roche & Co Ltd, Nutley, NJ USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. RP Furst, DE (reprint author), Univ Calif Los Angeles, 1000 Vet Ave, Los Angeles, CA 90095 USA. NR 15 TC 8 Z9 8 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD OCT PY 2003 VL 30 IS 10 BP 2123 EP 2126 PG 4 WC Rheumatology SC Rheumatology GA 728HL UT WOS:000185711700008 PM 14528504 ER PT J AU Brodsky, MB McNeil, MR Doyle, PJ Fossett, TRD Timm, NH Park, GH AF Brodsky, MB McNeil, MR Doyle, PJ Fossett, TRD Timm, NH Park, GH TI Auditory serial position effects in story retelling for non-brain-injured participants and persons with aphasia SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE serial position effect; memory; aphasia; story retelling; discourse ID HEARING HANDICAP INVENTORY; SHORT-TERM-MEMORY; ELDERLY SUBJECTS; FREE-RECALL; INFORMATION; RELIABILITY; EXPLICIT; ADULTS; WORDS; SPAN AB Using story retelling as an index of language ability, it is difficult to disambiguate comprehension and memory deficits. Collecting data on the serial position effect (SPE), however, illuminates the memory component. This study examined the SPE of the percentage of information units (%IU) produced in the connected speech samples of adults with aphasia and age-matched, non-brain-injured (NBI) participants. The NBI participants produced significantly more direct and alternate IUs than participants with aphasia. Significant age and gender differences were found in subsamples of the NBI controls, with younger and female participants generating significantly more direct lUs than male and older NBI participants. Alternate IU productions did not generate an SPE from any group. There was a significant linear increase from the initial (primacy) to the final (recency) portion of the recalled alternate lUs for both the NBI group and the group of participants with aphasia. Results provide evidence that individuals with aphasia recall discourse length information using similar memory functions as the nonimpaired population, though at a reduced level of efficiency or quantity. A quadratic model is suggested for the recall of information directly recalled from discourse-length language material. C1 Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15260 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. RP McNeil, MR (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 49 TC 4 Z9 4 U1 1 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD OCT PY 2003 VL 46 IS 5 BP 1124 EP 1137 DI 10.1044/1092-4388(2003/088) PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 728HD UT WOS:000185711000008 PM 14575347 ER PT J AU Dorafshar, AH Angle, N Bryer-Ash, M Huang, DS Farooq, MM Gelabert, HA Freischlag, JA AF Dorafshar, AH Angle, N Bryer-Ash, M Huang, DS Farooq, MM Gelabert, HA Freischlag, JA TI Vascular endothelial growth factor inhibits mitogen-induced vascular smooth muscle cell proliferation SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Association-for-Academic-Surgery CY NOV 07-09, 2002 CL BOSTON, MASSACHUSETTS SP Assoc Acad Surg DE vascular endothelial growth factor; human aortic smooth muscle; neointimal hyperplasia ID FACTOR-LIKE PROTEIN; FACTOR-B-CHAIN; ARTERIAL INJURY; GENE-TRANSFER; IN-VITRO; THERAPEUTIC ANGIOGENESIS; BALLOON ANGIOPLASTY; INTIMAL HYPERPLASIA; EXPRESSION; RECEPTOR AB Introduction. Delivery of vascular endothelial growth factor (VEGF) protein or gene transfer has been shown to accelerate re-endothelialization and attenuate neointimal hyperplasia in various arterial injury models, including balloon injury, stent implantation, and vein grafts. In addition to stimulating re-endothelialization, we hypothesize that VEGF has further vascular protective functions to prevent neointimal hyperplasia by directly inhibiting mitogen-induced proliferation of vascular smooth muscle cells (VSMCs) via the mitogen-activated protein kinase pathway. Materials and methods. Human aortic VSMCs were seeded and serum starved for 24 h. The cells were then stimulated with a mitogen, recombinant human platelet derived growth factor at 20 ng/mL together with 0, 10, 20, 30, 40, 50 ng/mL recombinant human VEGF. A proliferation assay was used to quantitate bromodeoxyuridine uptake into newly synthesized DNA. Western immunoassay was used to quantify extracellular signal-regulated kinase (ERK) 2 protein and phosphorylation of retinoblastoma and ERK 1/2 protein. Results. VEGF inhibited bromodeoxyuridine incorporation into mitogen-induced VSMC in a dose-dependent manner, reaching statistical significance at concentrations of 30 (P < 0.05), 40 (P < 0.05), and 50 ng/mL (P < 0.01). Densitometry of western immunoblots revealed an inhibition of phosphorylation of retinoblastoma at VEGF concentrations of 40 and 50 ng/mL and ERK 1/2 phosphorylation at concentrations of 30, 40 and 50 ng/mL. Conclusion. In addition to stimulating re-endothelialization, VEGF appears to have a vascular protective function by directly inhibiting VSMC proliferation. This effect occurs in the absence of endothelial cells and via the mitogen-activated protein kinase pathway. VEGF may serve as an important modulator of mitogen-induced VSMC proliferation after vascular injury. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, UCLA Gonda Goldschmied Diabet Ctr, Div Vasc Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, UCLA Gonda Goldschmied Diabet Ctr, Div Endocrinol Diabet & Hypertens, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. RP Angle, N (reprint author), Univ Calif San Diego, Vasc Surg Sect, 200 W Arbor Dr, San Diego, CA 92103 USA. NR 41 TC 23 Z9 28 U1 1 U2 4 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 OCT PY 2003 VL 114 IS 2 BP 179 EP 186 DI 10.1016/S0022-4804(03)00254-3 PG 8 WC Surgery SC Surgery GA 730LF UT WOS:000185831700012 PM 14559444 ER PT J AU Konrad-Martin, D Keefe, DH AF Konrad-Martin, D Keefe, DH TI Time-frequency analyses of transient-evoked stimulus-frequency and distortion-product otoacoustic emissions: Testing cochlear model predictions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT 143rd Annual Meeting of the Acoustical-Society-of-America CY JUN 03-07, 2002 CL PITTSBURGH, PA SP Acoust Soc Amer ID FINE-STRUCTURE; NORMAL EARS; SUPPRESSION; MECHANISMS; 2F(1)-F(2); LATENCY; DISTRIBUTIONS; REFLECTANCE; GENERATION; RESPONSES AB Time-frequency representations (TFRs) of otoacoustic emissions (OAEs) provide information simultaneously in time and frequency that may be obscured in waveform or spectral analyses. TFRs were applied to transient-evoked stimulus-frequency (SF) and distortion-product (DP) OAEs to test cochlear model predictions. SFOAEs and DPOAEs were elicited in 18 normal-hearing subjects using gated tones and tone pips. Synchronous spontaneous (SS) OAEs were measured to assess their contributions to SFOAEs and DPOAEs. A common form of TFR of measured OAEs was a collection of frequency-specific components often aligned with SSOAE sites, with each component characterized by one or more brief segments or a single long-duration segment. The spectral envelope of evoked OAEs differed from that of the evoking stimulus. Strong emission regions or cochlear "hot spots" were detected, and sometimes accounted for OAE energy observed outside the stimulus bandwidth. Contributions of hot spots and multiple internal reflections to the OAE, and differences between measured and predicted OAE spectra, increased as stimulus level decreased, consistent with level-dependent changes in the estimated cochlear reflectance. Suppression and frequency-pulling effects between components were observed. A recursive formulation was described for the linear coherent reflection emission theory [Zweig and Shera, J. Acoust. Soc. Am. 98, 2018-2047 (1995)] that is well suited for time-domain calculations. (C) 2003 Acoustical Society of America. C1 Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Autitory Res, Portland, OR 97239 USA. Rush Univ, Chicago, IL 60612 USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. RP Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Autitory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM dawn.martin@med.va.gov FU NIDCD NIH HHS [R01 DC003784, R01 DC003784-07, T32 DC00013] NR 57 TC 24 Z9 24 U1 0 U2 2 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 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2003 VL 114 IS 4 BP 2021 EP 2043 DI 10.1121/1.1596170 PN 1 PG 23 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 733GU UT WOS:000185992200029 PM 14587602 ER PT J AU Litvak, LM Smith, ZM Delgutte, B Eddington, DK AF Litvak, LM Smith, ZM Delgutte, B Eddington, DK TI Desynchronization of electrically evoked auditory-nerve activity by high-frequency pulse trains of long duration SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT CIAP Conference 2001 CY 2001 CL MONTEREY, CALIFORNIA SP CIAP ID TEMPORAL RESPONSE PATTERNS; HIGH STIMULUS RATES; CONSONANT RECOGNITION; COCHLEAR IMPLANTS; ACTION-POTENTIALS; FIBER RECORDINGS; POINT PROCESS; STIMULATION; CAT; DISCHARGES AB Rubinstein et al. [Hear. Res. 127, 108-118 (1999)] suggested that the neural representation of the waveforms of electric stimuli might be improved by introducing an ongoing, high-rate, desynchronizing pulse train (DPT). A DPT may desynchronize neural responses to electric stimulation in a manner similar to spontaneous activity in a healthy ear. To test this hypothesis, responses of auditory-nerve fibers (ANFs) to 10-min-long electric pulse trains (5 kpps) were recorded from acutely deafened, anesthetized cats. Stimuli were delivered via an intracochlear electrode, and their amplitude was chosen to elicit a response in most ANFs. Responses to pulse trains showed pronounced adaptation during the first 1-2 min, followed by either a sustained response or cessation of spike discharges for the remainder of the stimulus. The adapted discharge rates showed a broad distribution across the ANF population like spontaneous activity. However, a higher proportion of fibers (46%) responded to the DPT at rates below 5 spikes/s than for spontaneous activity, and 12% of the fibers responded at higher rates than any spontaneously active fiber. Interspike interval histograms of sustained responses for some fibers had Poisson-like (exponential) shapes, resembling spontaneous activity, while others exhibited preferred intervals and, occasionally, bursting. Simultaneous recordings from pairs of fibers revealed no evidence of correlated activity, suggesting that the DPT does desynchronize the auditory nerve activity. Overall, these results suggest that responses to an ongoing DPT resemble spontaneous activity in a normal ear for a substantial fraction of the ANFs. (C) 2003 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. MIT, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Res Lab Elect & Neural Prosthesis Res Ctr, Cambridge, MA 02139 USA. RP Litvak, LM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. RI Smith, Zachary/B-2879-2009; OI Smith, Zachary/0000-0002-0819-4562; , /0000-0003-1349-9608 FU NIDCD NIH HHS [DC00361, DC02258, N01-DC-6-2100, P01 DC000361, P01 DC000361-100005, R01 DC002258, R01 DC002258-08] NR 54 TC 50 Z9 50 U1 0 U2 3 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 OCT PY 2003 VL 114 IS 4 BP 2066 EP 2078 DI 10.1121/1.1612492 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 733GU UT WOS:000185992200033 PM 14587606 ER PT J AU Litvak, LM Delgutte, B Eddington, DK AF Litvak, LM Delgutte, B Eddington, DK TI Improved temporal coding of sinusoids in electric stimulation of the auditory nerve using desynchronizing pulse trains SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT CIAP Conference 2001 CY 2001 CL MONTEREY, CALIFORNIA SP CIAP ID RETINAL GANGLION CELLS; STOCHASTIC RESONANCE; RESPONSE PATTERNS; FIBER RESPONSES; SQUIRREL MONKEY; CAT; NEURONS; NOISE; INFORMATION; MODULATION AB Rubinstein et al. [Hearing Res. 127, 108-118 (1999)] suggested that the representation of electric stimulus waveforms in the temporal discharge patterns of auditory-nerve fiber (ANF) might be improved by introducing an ongoing, high-rate, desynchronizing pulse train (DPT). To test this hypothesis, activity of ANFs was studied in acutely deafened, anesthetized cats in response to 10-min-long, 5-kpps electric pulse trains that were sinusoidally modulated for 400 ms every second. Two classes of responses to sinusoidal modulations of the DPT were observed. Fibers that only responded transiently to the unmodulated DPT showed hyper synchronization and narrow dynamic ranges to sinusoidal modulators, much as responses to electric sinusoids presented without a DPT. In contrast, fibers that exhibited sustained responses to the DPT were sensitive to modulation depths as low as 0.25% for a modulation frequency of 417 Hz. Over a 20-dB range of modulation depths, responses of these fibers resembled responses to tones in a healthy ear in both discharge rate and synchronization index. This range is much wider than the dynamic range typically found with electrical stimulation without a DPT, and comparable to the dynamic range for acoustic stimulation. These results suggest that a stimulation strategy that uses small signals superimposed upon a large DPT to encode sounds may evoke temporal discharge patterns in some ANFs that resemble responses to sound in a healthy ear. (C) 2003 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. MIT, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Neural Prosthesis Res Ctr, Cambridge, MA 02139 USA. RP Litvak, LM (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [N01-DC-6-2100, DC00361, DC02258, P01 DC000361, P01 DC000361-100005, R01 DC002258, R01 DC002258-08] NR 56 TC 40 Z9 40 U1 0 U2 2 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 OCT PY 2003 VL 114 IS 4 BP 2079 EP 2098 DI 10.1121/1.1612493 PN 1 PG 20 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 733GU UT WOS:000185992200034 PM 14587607 ER PT J AU Litvak, L Delgutte, B Eddington, D AF Litvak, L Delgutte, B Eddington, D TI Improved neural representation of vowels in electric stimulation using desynchronizing pulse trains SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT CIAP Conference 2001 CY 2001 CL MONTEREY, CA SP CIAP ID AUDITORY-NERVE FIBERS; DISCHARGE PATTERNS; DYNAMIC PROPERTIES; COCHLEAR NUCLEUS; COMPLEX TONES; RESPONSES; PITCH; SYNCHRONY; SOUNDS; UNITS AB Current cochlear implant processors poorly represent sound waveforms in the temporal discharge patterns of auditory-nerve fibers (ANFs). A previous study [Litvak et al., J. Acoust. Soc. Am. 114, 2079-2098 (2003)] showed that the temporal representation of sinusoidal stimuli can be improved in a majority of ANFs by encoding the stimuli as small modulations of a sustained, high-rate (5 kpps), desynchronizing pulse train (DPT). Here, these findings are extended to more complex stimuli by recording ANF responses to pulse trains modulated by bandpass filtered vowels. Responses to vowel modulators depended strongly on the discharge pattern evoked by the unmodulated DPT. ANFs that gave sustained responses to the DPT had period histograms that resembled the modulator waveform for low (<5%) modulation depths. Spectra of period histograms contained peaks near the formant frequencies. In contrast, ANFs that gave a transient (<1 min) response to the DPT poorly represented the formant frequencies. A model incorporating a linear modulation filter, a noisy threshold, and neural refractoriness predicts the shapes of period histograms for both types of fibers. These results suggest that a DPT-enhanced strategy may achieve good representation of the stimulus fine structure in the temporal discharge patterns of ANFs for frequencies up to 1000 Hz. It remains to be seen whether these temporal discharge patterns can be utilized by cochlear implant subjects. (C) 2003 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. MIT, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Neural Prosthesis Res Lab, Cambridge, MA 02139 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM leonid.litvak@advancedbionics.com OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [DC02258, DC00361, N01-DC-6-210, P01 DC000361, P01 DC000361-100005, R01 DC002258, R01 DC002258-08] NR 29 TC 24 Z9 25 U1 0 U2 0 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 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2003 VL 114 IS 4 BP 2099 EP 2111 DI 10.1121/1.1612494 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 733GU UT WOS:000185992200035 PM 14587608 ER PT J AU Gonzalez-Heydrich, J Raches, D Wilens, TE Leichtner, A Mezzacappa, E AF Gonzalez-Heydrich, J Raches, D Wilens, TE Leichtner, A Mezzacappa, E TI Retrospective study of hepatic enzyme elevations in children treated with olanzapine, divalproex, and their combination SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE divalproex; olanzapine; polypharmacy; hepatic function; pancreatitis ID VALPROIC ACID; ACUTE-PANCREATITIS; OPEN-LABEL; OBESE CHILDREN; ADOLESCENTS; STEATOHEPATITIS; HEPATOTOXICITY; CHILDHOOD AB Objective: To evaluate hepatic enzyme elevations during treatment with olanzapine, divalproex, and their combination. Method: Fifty-two children, aged 4 to 18 years, with hepatic enzyme levels measured during treatment with olanzapine (n = 17), divalproex (n = 23), or their combination (n = 12), were identified in the computerized records at a pediatric medical center. Clinical characteristics as well as serial alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were collected. Results: Mean and peak hepatic enzyme levels were significantly higher for the combined treatment group compared to the olanzapine or divalproex groups. All 12 patients who received combined treatment had at least one peak enzyme elevation during the treatment. For 42% of these patients, at least one enzyme level remained elevated during the time for which values were available (mean 8 +/- 6 months). For those treated with divalproex either alone or in combination, the findings were not explained by variations in divalproex plasma levels. Two patients receiving combined treatment had the combination treatment discontinued because of medical complications (pancreatitis in one and steatohepatitis in the other). Conclusions: Combined treatment with olanzapine and divalproex was associated with more elevations of hepatic enzymes than treatment with either agent alone. The long-term significance of this is unknown but warrants study. C1 Harvard Univ, Childrens Hosp, Sch Med, Pediat Psychopharmacol Program, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA USA. RP Gonzalez-Heydrich, J (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Pediat Psychopharmacol Program, Fegan 8,300 Longwood Ave, Boston, MA 02115 USA. NR 27 TC 26 Z9 27 U1 1 U2 1 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 OCT PY 2003 VL 42 IS 10 BP 1227 EP 1233 DI 10.1097/01.chi.0000081803.49840.cc PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 723YW UT WOS:000185460000012 PM 14560173 ER PT J AU Geller, AC Emmons, K Brooks, DR Zhang, Z Powers, C Koh, HK Sober, AJ Miller, DR Li, F Haluska, F Gilchrest, BA AF Geller, AC Emmons, K Brooks, DR Zhang, Z Powers, C Koh, HK Sober, AJ Miller, DR Li, F Haluska, F Gilchrest, BA TI Skin cancer prevention and detection practices among siblings of patients with melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; SELF-EXAMINATION; UNITED-STATES; BREAST-CANCER; RISK; BEHAVIORS; FAMILIES; VALIDITY; TRENDS AB Background: Family members of patients with melanoma have an increased risk of the disease, and families with multiple affected members account for about 10% of melanoma cases. These statistics suggest that first-degree relatives of patients with melanoma, who are at particularly high risk, warrant targeted public health action. Objective: We sought to document rates for dermatologist examinations for cutaneous lesions, the practice of skin self-examination, and sunscreen use in this at-risk group. Methods: Before participation in a randomized trial, 404 siblings of recently diagnosed patients with melanoma completed a survey on beliefs and practices regarding skin cancer prevention and detection. Results: Sixty-two percent of participants had carefully examined their skin, 54% routinely used sunscreen, and 27% had received a skin cancer examination by a dermatologist during the past year; 47% had never received a dermatologist examination. Multivariate analysis found modifiable positive predictors for skin self-examination and dermatologist examinations, including having a clinician with whom to talk about melanoma and believing in the importance of regular skin examinations by a physician. Significant modifiable negative predictors included enjoyment of being tanned, not being sure what to look for when examining moles, and feeling uncomfortable having others look at their skin. Conclusions: Skin self-examination rates among these high-risk siblings are markedly higher than in population-based studies. However, many siblings were not screened for skin cancer by a dermatologist despite having strong risk profiles, being nearly fully insured, and being under care of primary care physicians. Improvements in communication between physicians and high-risk families and changes in office systems to assess family history of melanoma could increase screening rates for the estimated 1 million siblings of patients with melanoma. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB 801A, Boston, MA 02118 USA. OI Brooks, Daniel/0000-0001-6220-6889 FU NCI NIH HHS [R01 CA76333] NR 34 TC 32 Z9 32 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2003 VL 49 IS 4 BP 631 EP 638 DI 10.1067/S0190-9622(03)02126-1 PG 8 WC Dermatology SC Dermatology GA 726NV UT WOS:000185606500008 PM 14512908 ER PT J AU Das, C Berezovska, O Diehl, TS Genet, C Buldyrev, I Tsai, JY Hyman, BT Wolfe, MS AF Das, C Berezovska, O Diehl, TS Genet, C Buldyrev, I Tsai, JY Hyman, BT Wolfe, MS TI Designed helical peptides inhibit an intramembrane protease SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE COMPLEX; ALZHEIMERS-DISEASE; NICASTRIN; MECHANISM; CLEAVAGE C1 Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Alzheimers Dis Res Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Wolfe, MS (reprint author), Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. EM mwolfe@rics.bwh.harvard.edu NR 14 TC 78 Z9 82 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 1 PY 2003 VL 125 IS 39 BP 11794 EP 11795 DI 10.1021/ja037131v PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 726BQ UT WOS:000185578500011 PM 14505382 ER PT J AU Gibson, CM AF Gibson, CM TI Confusion in reperfusion SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; RESCUE ANGIOPLASTY; THROMBOLYSIS; OUTCOMES; RETEPLASE; TRIAL; FLOW C1 Harvard Univ, Sch Med, TIMI Study Chairmans Off, Boston, MA 02115 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 15 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 1 PY 2003 VL 42 IS 7 BP 1186 EP 1187 DI 10.1016/S0735-1097(03)00898-2 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 726QU UT WOS:000185611200006 PM 14522477 ER PT J AU Rumsfeld, JS AF Rumsfeld, JS TI Valve surgery in the elderly - A question of quality (of life)? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID BYPASS GRAFT-SURGERY; OF-LIFE; YOUNGER PATIENTS; REPLACEMENT; MORTALITY; OCTOGENARIANS; PREDICTOR; DISEASE; OLDER; AGE C1 Univ Colorado, Ctr Hlth Sci, Vet Affairs Med Ctr, Denver, CO USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 1055 Clemont St, Denver, CO 80220 USA. NR 25 TC 10 Z9 10 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 OCT 1 PY 2003 VL 42 IS 7 BP 1215 EP 1217 DI 10.1016/S0735-1097(03)00950-1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 726QU UT WOS:000185611200012 PM 14522483 ER PT J AU Friedlander, AH Freymiller, EG AF Friedlander, AH Freymiller, EG TI Detection of radiation-accelerated atherosclerosis of the carotid artery by panoramic radiography - A new opportunity for dentists SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID EXTERNAL CERVICAL IRRADIATION; INTIMA-MEDIA THICKNESS; NASOPHARYNGEAL CARCINOMA; NECK IRRADIATION; RISK FACTOR; STENOSIS; DISEASE; RADIOTHERAPY; HEAD; THERAPY AB Background. The authors review the pathophysiology, epidemiology, course of disease, dental findings and dental treatment of patients who developed atherosclerosis of the carotid artery after having received therapeutic radiation to the neck for squamous-cell carcinoma of the oral cavity, pharynx or larynx; salivary gland tumors; and lymphomas involving the cervical lymph nodes. Type of Studies Reviewed. The authors conducted a MEDLINE search for 1997 through 2002 using the key terms "radiation therapy," "carotid artery" atherosclerosis," "cancer" and "dentistry." The articles selected for further review included those published in English in peer-reviewed journals, with preference given to articles reporting randomized, controlled trials. Results. Recent advances in the delivery of radiation therapy to malignancies of the head and neck have resulted in the prolonged survival of increasing numbers of patients. However, the therapy has been implicated as causing atherosclerotic lesions in the cervical component of the carotid artery, which predisposes patients to an increased risk of developing stroke. Panoramic radiography can identify some of these lesions before they can cause a stroke. Radiation-induced atherosclerosis is Common, with approximately 40 percent of patients developing hemodynamically significant carotid artery plaques within 10 years of having received irradiation. Clinical Implications. Dentists treating patients who have received therapeutic radiation to the neck should examine the patients' panoramic radiographs for evidence of atheromalike calcifications, which appear 1.5 to 2.5 centimeters posterior and inferior to the angle of the mandible. Patients with evidence of such lesions should be referred to their physician for an ultrasound examination of their carotid arteries. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dent Serv, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 51 TC 17 Z9 20 U1 1 U2 1 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 OCT PY 2003 VL 134 IS 10 BP 1361 EP 1365 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 732ZJ UT WOS:000185975200023 PM 14620017 ER PT J AU Karlawish, JHT Casarett, DJ James, BD Tenhave, T Clark, CM Asch, DA AF Karlawish, JHT Casarett, DJ James, BD Tenhave, T Clark, CM Asch, DA TI Why would caregivers not want to treat their relative's Alzheimer's disease? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; treatment; decision-making ID DEMENTIA; CARE; SEVERITY; PREFERENCES; DEPRESSION; PATIENT; BURDEN; SCALE; ONSET AB OBJECTIVES: To determine family caregivers' willingness to use Alzheimer's disease (AD)-slowing medicines and to examine the relationships between this willingness, dementia severity, and caregiver characteristics. DESIGN: Cross-sectional survey. SETTING: In-home interviews of patients from the Memory Disorders Clinic of the University of Pennsylvania's Alzheimer's Disease Center. PARTICIPANTS: One hundred two caregivers of patients with mild to severe AD who were registered at an Alzheimer's disease center. MEASUREMENTS: Subjects participated in an in-home interview to assess their willingness to use a risk-free AD-slowing medicine and a medicine with 3% annual risk of gastrointestinal bleeding. RESULTS: Half of the patients had severe dementia (n = 52). Seventeen (17%) of the caregivers did not want their relative to take a risk-free medicine that could slow AD. Half (n = 52) did not want their relative to take an AD-slowing medicine that had a 3% annual risk of gastrointestinal bleeding. Caregivers who were more likely to forgo risk- free treatment of AD were older (odds ratio (OR) = 1.7, P = .04), were depressed (OR = 3.66, P = .03), had relatives living in a nursing home (OR = 3.6, P = .02), had relatives with more-severe dementia according to the Mini-Mental State Examination (MMSE) (OR = 2.29, P = .03) or Dementia Severity Rating Scale (DSRS) (OR = 2.55, P = .002), and rated their relatives' quality of life (QOL) poorly on a single-item global rating (OR = 0.25, P = .001) and the 13-item quality-of-life (QOL)-AD scale (OR = 0.38, P = .002). Caregivers who were more likely to forgo a risky treatment were nonwhite (OR = 6.53, P = .005), had financial burden (OR = 2.93, P = .02), and rated their relative's QOL poorly on a single-item global rating (OR = 0.61, P = .01) and the QOL-AD (OR = 0.56, P = .01). CONCLUSION: These results suggest that caregivers are generally willing to slow the progression of their relative's dementia even into the severe stage of the disease, especially if it can be done without risk to the patient. Clinical trials and practice guidelines should recognize that a caregiver's assessment of patient QOL and the factors that influence it affect a caregiver's willingness to use AD-slowing treatments. C1 Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Alzheimers Dis Ctr, Philadelphia, PA USA. RP Karlawish, JHT (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NIA NIH HHS [K01 AG-00931, P30-AG01024] NR 25 TC 20 Z9 20 U1 3 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2003 VL 51 IS 10 BP 1391 EP 1397 DI 10.1046/j.1532-5415.2003.51456.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 725GR UT WOS:000185535900007 PM 14511158 ER PT J AU Simmons, SF Garcia, ET Cadogan, MP Al-Samarrai, NR Levy-Storms, LF Osterweil, D Schnelle, JF AF Simmons, SF Garcia, ET Cadogan, MP Al-Samarrai, NR Levy-Storms, LF Osterweil, D Schnelle, JF TI The Minimum Data Set weight-loss quality indicator: Does it reflect differences in care processes related to weight loss? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Minimum Data Set; quality indicator; weight loss; nursing homes; nutrition ID NURSING-HOME RESIDENTS; FEEDING ASSISTANCE; VULNERABLE ELDERS; FOOD-INTAKE; STAFF AB OBJECTIVES: To determine whether nursing homes (NHs) that score differently on prevalence of weight loss, according to a Minimum Data Set (MDS) quality indicator, also provide different processes of care related to weight loss. DESIGN: Cross-sectional. SETTING: Sixteen skilled nursing facilities: 11 NHs in the lower (25th percentile-low prevalence) quartile and five NHs in the upper (75th percentile-high prevalence) quartile on the MDS weight-loss quality indicator. PARTICIPANTS: Four hundred long-term residents. MEASUREMENTS: Sixteen care processes related to weight loss were defined and operationalized into clinical indicators. Trained research staff conducted measurement of NH staff implementation of each care process during assessments on three consecutive 12-hour days (7 a.m. to 7 p.m.), which included direct observations during meals, resident interviews, and medical record abstraction using standardized protocols. RESULTS: The prevalence of weight loss was significantly higher in the participants in the upper quartile NHs than in participants in the lower quartile NHs based on MDS and monthly weight data documented in the medical record. NHs with a higher prevalence of weight loss had a significantly larger proportion of residents with risk factors for weight loss, namely low oral food and fluid intake. There were few significant differences on care process measures between low- and high-weight-loss NHs. Staff in low-weight-loss NHs consistently provided verbal prompting and social interaction during meals to a greater proportion of residents, including those most at risk for weight loss. CONCLUSION: The MDS weight-loss quality indicator reflects differences in the prevalence of weight loss between NHs. NHs with a lower prevalence of weight loss have fewer residents at risk for weight loss and staff who provide verbal prompting and social interaction to more residents during meals, but the adequacy and quality of feeding assistance care needs improvement in all NHs. C1 Univ Calif Los Angeles, Sch Med, Dept Geriatr, Borun Ctr Gerontol Res, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, Reseda, CA 91335 USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [AG10415] NR 30 TC 45 Z9 46 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2003 VL 51 IS 10 BP 1410 EP 1418 DI 10.1046/j.1532-5415.2003.51459.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 725GR UT WOS:000185535900010 PM 14511161 ER PT J AU Seliger, SL Gillen, DL Tirschwell, D Wasse, H Kestenbaum, BR Stehman-Breen, CO AF Seliger, SL Gillen, DL Tirschwell, D Wasse, H Kestenbaum, BR Stehman-Breen, CO TI Risk factors for incident stroke among patients with end-stage renal disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BLACK-WHITE DIFFERENCES; C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; CORONARY HEART-DISEASE; HEMODIALYSIS-PATIENTS; BLOOD-PRESSURE; DIALYSIS PATIENTS; CEREBRAL INFARCTION; MAINTENANCE HEMODIALYSIS; ATHEROSCLEROSIS RISK AB Although patients with ESRD experience markedly higher rates of stroke, no studies in the US have identified risk factors associated with stroke in this population. It was hypothesized that black race, malnutrition, and elevated BP would be associated with the risk of stroke among patients with ESRD. Data from the United States Renal Data Systems were used. Adult Medicare-insured hemodialysis and peritoneal dialysis patients without a history of stroke or transient ischemic attack (TIA) were considered for analysis. The primary outcome was hospitalized or fatal stroke. Cox proportional hazards models were used to determine the associations between the primary predictor variables and stroke. The rate of incident stroke was 33/1,000 person-years in the study sample. After adjustment for age and other patient characteristics, three markers of malnutrition were associated with the risk of stroke-serum albumin (per I g/dl decrease, hazard ratio [HR] = 1.43), height-adjusted body weight (per 25% decrease, HR = 1.09), and a subjective assessment of undernourishment (HR = 1.27)-as was higher mean BP (per 10 mmHg, HR = 1.11). The association between black race varied by cardiac disease status, with blacks estimated to be at lower risk than whites among individuals with cardiac disease (HR = 0.74), but at higher risk among individuals without cardiac disease (HR 1.24). This study confirms the extraordinarily high rates of stroke in ESRD patients on dialysis and identifies high mean BP and malnutrition as potentially modifiable risk factors. The association between black race and stroke differs by cardiac disease status; the reasons for this differing effect of race deserve further investigation. C1 Univ Washington, Div Nephrol, Seattle, WA 98102 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98195 USA. RP Seliger, SL (reprint author), Univ Washington, Div Nephrol, Box 356521, Seattle, WA 98102 USA. RI Wasse, Haimanot/A-5726-2013 OI Wasse, Haimanot/0000-0001-5756-0242 FU NIDDK NIH HHS [DK63079-01, DK07721-6] NR 49 TC 94 Z9 100 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2003 VL 14 IS 10 BP 2623 EP 2631 DI 10.1097/01.ASN.0000088722.56342.A8 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 725JR UT WOS:000185540800025 PM 14514741 ER PT J AU Whelan, JS Dvorkin, L AF Whelan, JS Dvorkin, L TI HolisticKids.org - Evolution of information resources in pediatric complementary and alternative medicine projects: from monographs to Web learning SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT 102nd Annual Meeting of the Medical-Library-Association CY MAY 20-22, 2002 CL DALLAS, TEXAS SP Med Library Assoc ID HEALTH-CARE PROFESSIONALS; DIETARY-SUPPLEMENTS; INSTRUCTION; CURRICULUM; RESIDENTS; ATTITUDES; THERAPIES; CHILDREN; HERBS AB Use of complementary and alternative medicine (CAM) is growing in the United States. Children are a part of this trend, with adolescent self-care exceeding adult use. As a result, the necessity of educating pediatricians on CAM practices has become clear. This paper describes the Pediatric Integrative Medicine Education (PIME) project with a focus on the creation of HolisticKids.org, a Website designed to educate pediatric residents. HolisticKids.org also addresses the needs and interests of medical students, fellows, faculty, and community-based care providers who work with children and CAM. An outstanding aspect of this effort is its interdisciplinary nature, involving physicians, pharmacists, dieticians, nurses, medical librarians, and Web specialists. Collaboration is mirrored on an institutional level, where the participating institutions include Children's Hospital Boston, Harvard Medical School, Boston Medical Center, the Massachusetts College of Pharmacy and Health Sciences, and Dana Farber Cancer Institute. Now in the third year of development, this Web-based education project demonstrates how integrative medical education can contribute to pediatric care for diverse families and complement cultural competency efforts. Ongoing efforts focus on adding content, developing evaluation techniques, and disseminating this resource to the health sciences community. C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA. RP Whelan, JS (reprint author), Massachusetts Gen Hosp, Treadwell Lib, BHX-1,55 Fruit St, Boston, MA 02114 USA. FU NCCIH NIH HHS [R25 AT000538, AT 00213-02, AT 00538-02]; NLM NIH HHS [N01 LM 63528]; PHS HHS [72331-02, 71402-01] NR 17 TC 5 Z9 5 U1 0 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD OCT PY 2003 VL 91 IS 4 BP 411 EP 417 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 734RZ UT WOS:000186072600007 PM 14566371 ER PT J AU Johnson, BE AF Johnson, BE TI Adjuvant chemotherapy for non-small-cell lung cancer: The end of the beginning SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RANDOMIZED-TRIAL; ONCOLOGY-GROUP; THERAPY; METAANALYSIS; REGIMENS C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Rm D1234, Boston, MA 02445 USA. NR 12 TC 9 Z9 9 U1 1 U2 1 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 OCT 1 PY 2003 VL 95 IS 19 BP 1422 EP 1424 DI 10.1093/jnci/djg077 PG 3 WC Oncology SC Oncology GA 725YA UT WOS:000185568900001 PM 14519741 ER PT J AU Finkelstein, DM Muzikansky, A Schoenfeld, DA AF Finkelstein, DM Muzikansky, A Schoenfeld, DA TI Comparing survival of a sample to that of a standard population SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID EXTRAMAMMARY PAGETS-DISEASE; PROGNOSIS C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. FU NCI NIH HHS [CA74302, CA78284, P30 CA06516-39] NR 17 TC 52 Z9 52 U1 0 U2 5 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 OCT 1 PY 2003 VL 95 IS 19 BP 1434 EP 1439 DI 10.1093/jnci/djg052 PG 6 WC Oncology SC Oncology GA 725YA UT WOS:000185568900008 PM 14519749 ER PT J AU Carew, JA Basso, F Miller, GJ Hawe, E Jackson, AA Humphries, SE Bauer, KA AF Carew, JA Basso, F Miller, GJ Hawe, E Jackson, AA Humphries, SE Bauer, KA TI A functional haplotype in the 5 ' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE coagulation; coronary heart disease; factor VII; polymorphism ID COAGULATION-FACTOR-VII; MYOCARDIAL-INFARCTION; HEMOSTATIC FACTORS; HEALTHY-MEN; POLYMORPHISM; HYPERGLYCEMIA; POPULATION; ACTIVATION; ANTIGEN; DIETARY AB Aims: The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study. Methods: One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms. -670A-->C, -402G-->A, a 10 base pair insertion at -323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays. Results: The -670A-->C and -402G-->A polymorphisms were in complete allelic association. The haplotype containing -670C and -402A (frequency =0.23) was associated with significantly increased plasma FVII coagulant activity and increased risk of an initial coronary event, particularly acute myocardial infarction, which remained after correction for conventional risk factors. In contrast. the -323 insertion and Q353 alleles (frequency =0.11 and 0.10, respectively) were associated with decreased plasma FVII levels, but hazard ratios for coronary events in carriers of these alleles were not significantly different from unity. In transiently transfected hepatoma cells, increased basal expression of the reporter gene was directed by a promoter fragment with rare haplotype -670C/-630G/-402A rather than by a promoter fragment with common haplotype -670A/-630A/-402G: -402A was not responsible for this effect. Conclusions: The promoter haplotype, -670C/-630G/402A, was associated with significantly increased plasma FVII coagulant activity, risk of an initial coronary event, particularly acute myocardial infarction, and reporter gene expression. C1 VA Boston Healthcare Syst, Dept Med, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. UCL Royal Free & UCL Med Sch, Dept Cardiovasc Genet, British Heart Fdn Labs, Dept Med, London, England. St Bartholomews & Royal London Sch Med & Dent, MRC Epidemiol & Med Care Unit, Wolfson Inst Prevent Med, London, England. RP Carew, JA (reprint author), VA Boston Healthcare Syst, Dept Med, 1400 VFW Pkwy, Boston, MA 02132 USA. EM josephine_carew@hms.harvard.edu RI Humphries, Stephen/C-5075-2008 NR 30 TC 35 Z9 36 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2003 VL 1 IS 10 BP 2179 EP 2185 DI 10.1046/j.1538-7836.2003.00424.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 736AX UT WOS:000186149100020 PM 14521602 ER PT J AU Sheridan, R Peralta, R Rhea, J Ptak, T Novelline, R AF Sheridan, R Peralta, R Rhea, J Ptak, T Novelline, R TI Reformatted visceral protocol helical computed tornographic scanning allows conventional radiographs of the thoracic and lumbar spine to be eliminated in the evaluation of blunt trauma patients SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID CERVICAL-SPINE; CT; FRACTURES; INJURIES AB Background. Patients suffering high-energy injuries are at risk for occult thoracic and lumbar spine fractures, and the standard of care includes radiographic spine screening. Most such patients require computed tomographic (CT) scanning to screen for chest and/or abdominal visceral injury. Helical CT (HCT) scanning represents a major technologic change that allows data to be reformatted after the patient has left the radiology suite. We explored the possibility of using reformatted visceral protocol HCT scanning to replace radiographs of the thoracic and lumbar spine in the evaluation of seriously injured patients. Methods: A prospective evaluation of consecutive patients with thoracic and lumbar spine fractures admitted over a 12-month period to an urban Level I trauma center was completed. The ability of conventional radiography and reformatted HCT scanning to detect spine fractures was compared. Results: Of 1,915 trauma patients admitted, 78 (4.1%), with an average Injury Severity Score of 21.3 +/- 1.2, sustained one or more thoracic (n = 35 patients) or lumbar (n = 43 patients) spine fractures. The sensitivity of reformatted HCT scanning as a screening test for spine fractures was 97% for thoracic and 95% for lumbar spine fractures, compared with a sensitivity of 62% for thoracic and 86% for lumbar conventional radiographs. Conclusion: Data obtained from HCT scanning performed to evaluate seriously injured multiple trauma patients for thoracic and abdominal visceral injury can be reformatted to screen for thoracic and lumbar spine fractures, providing accurate screening while eliminating the time, expense, and radiation exposure associated with conventional film radiography. C1 Massachusetts Gen Hosp, Clin 108, Dept Surg, Div Trauma & Burns, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Radiol, Dept Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sheridan, R (reprint author), Massachusetts Gen Hosp, Clin 108, Dept Surg, Div Trauma & Burns, Boston, MA 02114 USA. NR 10 TC 55 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2003 VL 55 IS 4 BP 665 EP 669 DI 10.1097/01.TA.0000048094.38625.B5 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 733GN UT WOS:000185991700015 PM 14566120 ER PT J AU Koenen, KC Lyons, MJ Goldberg, J Simpson, J Williams, WM Toomey, R Eisen, SA True, W Tsuang, MT AF Koenen, KC Lyons, MJ Goldberg, J Simpson, J Williams, WM Toomey, R Eisen, SA True, W Tsuang, MT TI Co-twin control study of relationships among combat exposure, combat-related PTSD, and other mental disorders SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; combat exposure; twins; comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; ERA TWIN REGISTRY; COMORBIDITY; TRAUMA AB The well-documented association between combat-related PTSD (C-PTSD) and other mental disorders may be an artifact of shared familial vulnerability. This study uses a co-twin control design to examine whether the association between C-PTSD and other mental disorders persists after adjusting for shared familial vulnerability. Data were from male monozygotic twin pairs in the Vietnam Era Twin Registry. Logistic regression analyses demonstrated that combat exposure, adjusted for C-PTSD, was significantly associated with increased risk for alcohol and cannabis dependence and that C-PTSD mediated the association between combat exposure and both major depression and tobacco dependence. We conclude C-PTSD comorbidity persists after controlling for shared vulnerability. Combat exposure is directly and indirectly, through C-PTSD, associated with increased risk for other mental disorders. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston Med Ctr, Dept Child & Adolescent Psychiat, Boston, MA 02118 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Inst Psychiat Epidemiol & Genet, Brockton, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Seattle VA ERIC, Vietnam Era Twin Registry, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA Boston Healthcare Syst, Brockton, MA USA. St Louis Vet Affairs Med Ctr, Res & Med Serv, St Louis, MO USA. Washington Univ, Dept Internal Med, Div Gen Med Sci, St Louis, MO USA. St Louis Univ, Med Ctr, Sch Publ Hlth, St Louis, MO USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Koenen, KC (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, 150 S Huntington Ave, Boston, MA 02114 USA. RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219 FU NIAAA NIH HHS [AA10339, AA10586]; NIDA NIH HHS [DA04604]; NIMH NIH HHS [MH11954-01, F31 MH011954, F31 MH011954-01] NR 19 TC 48 Z9 49 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2003 VL 16 IS 5 BP 433 EP 438 DI 10.1023/A:1025786925483 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 721DJ UT WOS:000185301500001 PM 14584626 ER PT J AU Shipherd, JC Beck, JG Hamblen, JL Lackner, JM Freeman, JB AF Shipherd, JC Beck, JG Hamblen, JL Lackner, JM Freeman, JB TI A preliminary examination of treatment for posttraumatic stress disorder in chronic pain patients: A case study SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder (PTSD); chronic pain; comorbid conditions; treatment ID MOTOR-VEHICLE ACCIDENTS; EVENT SCALE; IMPACT; PTSD AB Manualized treatments have become popular, despite concern about their use when comorbid diagnoses are present. In this report, the efficacy of manualized posttraumatic stress disorder ( PTSD) treatment was examined in the presence of chronic pain. Additionally, the effect of PTSD treatment on chronic pain and additional psychiatric diagnoses was explored. Six female patients with both PTSD and chronic pain following motor vehicle accidents were treated for PTSD using a multiple baseline design. The results indicate that manualized treatment for PTSD was effective in reducing PTSD symptoms in these patients. Although there were no changes in subjective pain, there were pain-related functional improvements and reductions in other psychiatric diagnoses for the majority of patients. C1 SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. SUNY Buffalo, Sch Med, Dept Med, Buffalo, NY 14260 USA. RP Shipherd, JC (reprint author), Boston VA Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. NR 22 TC 30 Z9 31 U1 4 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2003 VL 16 IS 5 BP 451 EP 457 DI 10.1023/A:1025754310462 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 721DJ UT WOS:000185301500004 PM 14584629 ER PT J AU Pole, N Neylan, TC Best, SR Orr, SP Marmar, CR AF Pole, N Neylan, TC Best, SR Orr, SP Marmar, CR TI Fear-potentiated startle and posttraumatic stress symptoms in urban police officers SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; fear-potentiated acoustic startle; police officers; emotion ID GULF-WAR VETERANS; VIETNAM VETERANS; PHYSIOLOGICAL-RESPONSES; ACOUSTIC STARTLE; LOUD TONES; SKIN-CONDUCTANCE; DISORDER; PTSD; EXPLICIT; REFLEX AB We studied the effects of increasing threat conditions on self-reported emotion, eyeblink electromyogram, and skin conductance responses to startling sounds in 55 police officers who endorsed a range of PTSD (posttraumatic stress disorder) symptoms. We found that contextual threat affected both physiologic and self-reported emotional responses. Greater PTSD symptom severity was related to greater physiologic responses under the low and medium but not under the high threat condition. The relationship between PTSD symptoms and physiologic responses was neither explained by self-reported emotional responses nor preexisting reported exaggerated startle symptoms. Our results emphasize the importance of contextual threat and suggest that laboratory measures of startle improve upon self-reported exaggerated startle alone in indexing PTSD symptom severity in urban police officers. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Pole, N (reprint author), Univ Michigan, Dept Psychol, 2260 E Hall,525 E Univ, Ann Arbor, MI 48109 USA. FU NIMH NIH HHS [R01 MH56350-03] NR 34 TC 40 Z9 41 U1 5 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2003 VL 16 IS 5 BP 471 EP 479 DI 10.1023/A:1025758411370 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 721DJ UT WOS:000185301500006 PM 14584631 ER PT J AU Leibowitz, SB Oh, WK AF Leibowitz, SB Oh, WK TI Overtreatment of a patient with presumed recurrent prostate cancer based on false-positive prostate specific antigen results SO JOURNAL OF UROLOGY LA English DT Editorial Material DE prostate-specific antigen; neoplasm recurrence; local; false positive reactions; prostatic neoplasms/diagnosis C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oh, WK (reprint author), Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2003 VL 170 IS 4 BP 1305 EP 1305 DI 10.1097/01.ju.0000084670.47887.a5 PN 1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 722WN UT WOS:000185401200060 PM 14501750 ER PT J AU Labrijn, AF Poignard, P Raja, A Zwick, MB Delgado, K Franti, M Binley, J Vivona, V Grundner, C Huang, CC Venturi, M Petropoulos, CJ Wrin, T Dimitrov, DS Robinson, J Kwong, PD Wyatt, RT Sodroski, J Burton, DR AF Labrijn, AF Poignard, P Raja, A Zwick, MB Delgado, K Franti, M Binley, J Vivona, V Grundner, C Huang, CC Venturi, M Petropoulos, CJ Wrin, T Dimitrov, DS Robinson, J Kwong, PD Wyatt, RT Sodroski, J Burton, DR TI Access of antibody molecules to the conserved coreceptor binding site on glycoprotein gpl120 is sterically restricted on primary human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; INTERMOLECULAR DISULFIDE BOND; HUMAN MONOCLONAL-ANTIBODY; CELL-CELL FUSION; RECEPTOR-BINDING; SOLUBLE CD4; CONFORMATIONAL-CHANGES; VARIABLE LOOPS; GP41 SUBUNITS; HIV-1 AB Anti-human immunodeficiency virus type I (HIV-1) antibodies whose binding to gp120 is enhanced by CD4 binding (CD4i antibodies) are generally considered nonneutralizing for primary HIV-1 isolates. However, a novel CD4i-specific Fab fragment, X5, has recently been found to neutralize a wide range of primary isolates. To investigate the precise nature of the extraordinary neutralizing ability of Fab X5, we evaluated the abilities of different forms (immunoglobulin G [IgG], Fab, and single-chain Fv) of X5 and other CD4i monoclonal antibodies to neutralize a range of primary HIV-1 isolates. Our results show that, for a number of isolates, the size of the neutralizing agent is inversely correlated with its ability to neutralize. Thus, the poor ability of CD4i-specific antibodies to neutralize primary isolates is due, at least in part, to steric factors that limit antibody access to the gp120 epitopes. Studies of temperature-regulated neutralization or fusion-arrested intermediates suggest that the steric effects are important in limiting the binding of IgG to the viral envelope glycoproteins after HIV-1 has engaged CD4 on the target cell membrane. The results identify hurdles in using CD4i epitopes as targets for antibody-mediated neutralization in vaccine design but also indicate that the CD4i regions could be efficiently targeted by small molecule entry inhibitors. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. ViroLog Inc, San Francisco, CA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21701 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol, IMM2,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI poignard, pascal/N-6678-2013 FU NIAID NIH HHS [AI24755, AI31783, AI33292, AI39420, AI41851, AI42848, AI45357, AI49566, P30 AI042848, R01 AI031783, R01 AI033292, R01 AI039420, R01 AI041851, R01 AI045357, R37 AI024755, R37 AI033292] NR 65 TC 267 Z9 272 U1 0 U2 5 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 OCT PY 2003 VL 77 IS 19 BP 10557 EP 10565 DI 10.1128/JVI.77.19.10557-10565.2003 PG 9 WC Virology SC Virology GA 722WE UT WOS:000185400400038 PM 12970440 ER PT J AU Padow, M Lai, LL Deivanayagam, C DeLucas, LJ Weiss, RB Dunn, DM Wu, XY Kappes, JC AF Padow, M Lai, LL Deivanayagam, C DeLucas, LJ Weiss, RB Dunn, DM Wu, XY Kappes, JC TI Replication of chimeric human immunodeficiency virus type 1 (HIV-1) containing HIV-2 integrase (IN): Naturally selected mutations in IN augment DNA synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; REVERSE-TRANSCRIPTASE; CARBOXYL-TERMINUS; GENETIC-ANALYSIS; TY3 INTEGRASE; POL GENE; PROTEIN; INFECTION; MUTANTS; FUSION AB The human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein augments the initiation of reverse transcription. Chimeric HIV-1 containing HIV-2 IN (SG3(IN2)) is severely impaired in virus infectivity and DNA synthesis. To analyze the nature of this defect, we infected T cells with the chimeric SG3(IN2) virus and by continuous passage in cell culture selected for virus with improved replication properties. Viruses from two different time points were chosen for further analysis, an early culture-adapted virus (CF-65) that exhibited an intermediate level of infectivity, and a later-passaged virus (CF-131) that was significantly more infectious. Sequence analysis of multiple clones derived from the CF-65 virus culture demonstrated a diversity of mutations in the reverse transcriptase (RT) and a common V204I IN mutation. Analysis of clones derived from the CF-131 virus indicated the selection of two additional IN mutations, Q96H and K127E, and a fixed V179I RT mutation. By cloning RT and/or IN sequences back into the original SG3IN2 chimeric virus, we demonstrated that mutations in both RT and IN contributed to the improvement in viral fitness. The effect of the HIV-2IN(IN2) mutations on virus DNA synthesis was analyzed by packaging IN2 mutants into HIV-1 as Vpr-IN2 fusion proteins. This analysis revealed that the Q96H, K127E and V204I mutations increased the infectivity of the chimeric virus by augmenting the initiation of viral cDNA synthesis in infected cells. The Q96H and K127E mutations are present in adjacent helical structures on the surface of the IN protein and together account for most of the increase observed in DNA synthesis. Our findings provide evidence that the IN protein augments the initiation of reverse transcription through specific interactions with other viral components comprising the initiation complex. Moreover, they implicate specific regions on the surface of IN that may help to elucidate mechanisms by which the HIV-1 IN protein augments the initiation of HIV-1 reverse transcription in vivo. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Biophys Sci & Engn, Birmingham, AL 35294 USA. Univ Utah, Dept Genet, Salt Lake City, UT 84112 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL 35233 USA. RP Kappes, JC (reprint author), Univ Alabama, Dept Microbiol, 701 19th St S, Birmingham, AL 35294 USA. FU NCI NIH HHS [CA73470]; NIAID NIH HHS [R01 AI047714, P30 AI027767, AI47714, P30-AI-27767] NR 41 TC 15 Z9 15 U1 0 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 OCT PY 2003 VL 77 IS 20 BP 11050 EP 11059 DI 10.1128/JVI.77.20.11050-11059.2003 PG 10 WC Virology SC Virology GA 727XL UT WOS:000185686100031 PM 14512553 ER PT J AU Andreucci, M Michael, A Kramers, C Park, KM Chen, A Matthaeus, T Alessandrini, A Haq, S Force, T Bonventre, JV AF Andreucci, M Michael, A Kramers, C Park, KM Chen, A Matthaeus, T Alessandrini, A Haq, S Force, T Bonventre, JV TI Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK1 cells result in phosphorylation of FKHR and FKHRL1 SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Meeting of the European-Dialysis-and-Transplantation-Association CY JUL, 2002 CL COPENHAGEN, DENMARK SP European Dialysis & Transplantat Assoc DE hormones; growth factors; cell signaling; forkhead proteins; kidney; hypoxia ID PROTEIN-KINASE-B; FORKHEAD TRANSCRIPTION FACTOR; INDUCED FUNCTIONAL INJURY; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; CAENORHABDITIS-ELEGANS; SIGNAL-TRANSDUCTION; CELLULAR-SURVIVAL; INDUCED APOPTOSIS; C-AKT AB Background. Cell death and survival pathways are critical determinants of epithelial cell fate after ischemia. Forkhead proteins have been implicated in the regulation of cellular survival. Methods and Results. We have found that none of the forkhead family of proteins, FKHR, is phosphorylated after ischemia/ reperfusion in the rat kidney. The time course of phosphorylation is similar to the time course of activation of the forkhead protein kinase Akt/protein kinase B (PKB), with maximal phosphorylation at 24 to 48 hours postreperfusion when the process of regeneration peaks. Extracellular signal-regulated kinase (ERK) 1/2 activation has also been implicated as prosurvival in the injured kidney. ERK1/2 were phosphorylated in postischemic kidneys at 5, 30, and 90 minutes of reperfusion, with phosphorylation decreased by 24 and 48 hours. Immunocytochemical analysis revealed increased phospho-ERK1/2 in the thick ascending limb and isolated cells of the S3 segment, which have lost apical actin staining. To understand the relationship between forkhead phosphorylation, Akt, and ERK1/2, an in vitro model of injury was employed. After 40 minutes of chemical anoxia followed by dextrose addition for 20 minutes to replete adenosine triphosphate (ATP) levels, FKHR and FKHRL1 are phosphorylated. The levels of phospho-Akt are increased for at least 120 minutes after dextrose addition with a maximum at 20 minutes. Phosphorylation of Akt, FKHR, and FKHRL1 are phosphatidylinositol 3-kinase ( PI 3-kinase) dependent since phosphorylation is reduced by the PI 3-kinase inhibitors, wortmannin, or LY294002. Inhibition of mitogen-activated protein kinase ( MAPK)/ERK kinase (MEK1/2), the upstreamactivator of ERK1/2, has no effect on forkhead protein phosphorylation after chemical anoxia/dextrose addition. Conclusion. We conclude that PI 3-kinase and Akt are activated after renal ischemia/reperfusion and that Akt phosphorylation leads to phosphorylation of FKHR and FKHRL1, which may affect epithelial cell fate in acute renal failure. C1 Massachusetts Gen Hosp East, Med Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. Tufts Univ, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Bonventre, JV (reprint author), Brigham & Womens Hosp, 75 Shattuck St, Boston, MA 02135 USA. RI Kramers, C./L-4458-2015; OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK 39773, DK 38452, DK 46267] NR 55 TC 55 Z9 56 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2003 VL 64 IS 4 BP 1189 EP 1198 DI 10.1046/j.1523-1755.2003.00204.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 719VR UT WOS:000185226200006 PM 12969136 ER PT J AU Kalra, MK Maher, MM Prasad, SR Hayat, MS Blake, MA Varghese, J Halpern, EF Saini, S AF Kalra, MK Maher, MM Prasad, SR Hayat, MS Blake, MA Varghese, J Halpern, EF Saini, S TI Correlation of patient weight and cross-sectional dimensions with subjective image quality at standard dose abdominal CT SO KOREAN JOURNAL OF RADIOLOGY LA English DT Article DE computed tomography (CT) ID NOISE-REDUCTION FILTERS; COMPUTED-TOMOGRAPHY; HELICAL CT; SYSTEM; PITCH; RISK AB Objective: We evaluated the association between patients' weight and abdominal cross-sectional dimensions and CT image quality. Materials and Methods: We prospectively evaluated 39 cancer patients aged more than 65 years with multislice CT scan of abdomen. All patients underwent equilibrium phase contrast-enhanced abdominal CT with 4 slices (from top of the right kidney) obtained at standard tube current (240-280 mA). All other scanning parameters were held constant. Patients' weight was measured just prior to the study. Cross-sectional abdominal dimensions such as circumference, area, average anterior abdominal wall fat thickness and, anteroposterior and transverse diameters were measured in all patients. Two subspecialty radiologists reviewed randomized images for overall image quality of abdominal structures using 5-point scale. Non-parametric correlation analysis was performed to determine the association of image quality with patients' weight and cross-sectional abdominal dimensions. Results: A statistically significant negative linear correlation of 0.46, 0.47, 0.47, 0.58, 0.56, 0.54, and 0.56 between patient weight, anterior abdominal fat thickness, anteroposterior and transverse diameter, circumference, cross-sectional area and image quality at standard scanning parameters was found (p<0.01). Conclusion: There is a significant association between image quality, patients' weight and cross-sectional abdominal dimensions. Maximum transverse diameter of the abdomen has the strongest association with subjective image quality. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 19 TC 22 Z9 29 U1 0 U2 1 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD OCT-DEC PY 2003 VL 4 IS 4 BP 234 EP 238 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 761ET UT WOS:000187888300005 PM 14726640 ER PT J AU Hickman, DL Wasson, K Ehrhart, EJ AF Hickman, DL Wasson, K Ehrhart, EJ TI What is your diagnosis? Subclinical hypovitaminosis C SO LAB ANIMAL LA English DT Article ID ASCORBIC-ACID DEFICIENCY; GUINEA-PIGS; COLLAGEN-SYNTHESIS; VITAMIN-C; SCURVY C1 Portland VA Med Ctr, Res & Dev Serv, Portland, OR 97239 USA. Colorado State Univ, Ft Collins, CO 80523 USA. RP Hickman, DL (reprint author), Portland VA Med Ctr, Res & Dev Serv, 3710 SW US Vet Hosp Rd,R&D 36, Portland, OR 97239 USA. RI Hickman, Debra/D-3289-2009 NR 16 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 2003 VL 32 IS 9 BP 23 EP 25 DI 10.1038/laban1003-23 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 727NH UT WOS:000185664600007 PM 15235658 ER PT J AU Foran, SE Lewandrowski, KB Kratz, A AF Foran, SE Lewandrowski, KB Kratz, A TI Effects of exercise on laboratory test results SO LABORATORY MEDICINE LA English DT Editorial Material ID PROSTATE-SPECIFIC ANTIGEN; BRAIN NATRIURETIC PEPTIDE; PHYSICAL-ACTIVITY; MARATHON RUNNERS; ELECTROLYTE BALANCE; LIPOPROTEIN PROFILE; ENDURANCE EXERCISE; HERITAGE FAMILY; CARDIAC MARKERS; RISK-FACTORS C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Foran, SE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. NR 66 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD OCT PY 2003 VL 34 IS 10 BP 736 EP 742 DI 10.1309/3PDQ4AH662ATB6HM PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 726CA UT WOS:000185579500025 ER PT J AU Schuchter, L Meropol, NJ Winer, EP Hensley, ML Somerfield, MR AF Schuchter, L Meropol, NJ Winer, EP Hensley, ML Somerfield, MR TI Amifostine and chemoradiation therapy: ASCO responds SO LANCET ONCOLOGY LA English DT Editorial Material ID CLINICAL-PRACTICE GUIDELINES; RADIOTHERAPY PROTECTANTS; CHEMOTHERAPY; ONCOLOGY C1 Univ Penn, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Amer Soc Clin Oncol, Alexandria, VA 22314 USA. RP Schuchter, L (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 3 TC 3 Z9 3 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 OCT PY 2003 VL 4 IS 10 BP 593 EP 593 DI 10.1016/S1470-2045(03)01216-6 PG 1 WC Oncology SC Oncology GA 731EN UT WOS:000185871700013 PM 14554234 ER PT J AU Bunaprasert, T Hadlock, T Marler, J Kobler, J Cowan, D Faquin, W Varvares, M AF Bunaprasert, T Hadlock, T Marler, J Kobler, J Cowan, D Faquin, W Varvares, M TI Tissue engineered muscle implantation for tongue reconstruction: A preliminary report SO LARYNGOSCOPE LA English DT Article DE tissue engineering; muscle; tongue ID MECHANICAL CELL STIMULATOR; HYBRID MUSCULAR TISSUES; SKELETAL MYOTUBES; TOTAL GLOSSECTOMY; TRANSPLANTATION; MYOBLASTS; INVITRO; CULTURE; FLAP AB Objectives/Hypothesis: Because current tongue reconstructive methods introduce adynamic, variably sensate tissue into the mouth, the critical functions of the tongue in articulation and deglutition may he compromised. The objective of this work was to introduce a combination of myoblasts and scaffolding material into rat hemiglossectomy defects and to examine the extent of neomuscle formation in the reconstructed area, under the hypothesis that the presence of myoblasts leads to formation of new muscle. Study Design: Randomized, prospective animal study Methods. Myoblasts were bar vested from neonatal Lewis rats, and a growth factor enriched collagen gel was prepared. Syngeneic adult animal received either hemiglossectomy alone or reconstruction with one of four experimental reconstructive preparations: collagen gel alone, collagen gel with suspended myoblasts, the gel-cell combination in undifferentiated muscle construct form by way of tissue culture for 7 days in a preformed mold, or differentiated constructs, cultured in myoblast fusion medium. After 6 or 16 weeks, animal weight gain was recorded, animals were killed, and the tongues harvested. The tissue was examined histologically, and quality of the muscular regenerate was rated on a scale according to predefined criteria. Results: Animals in all groups gained weight appropriately. In groups receiving hemiglossectomy alone or acellular (gel only) reconstruction, there was significant scarring and lack of neomuscle formation. In groups receiving myoblast transplantation, either by way of gel suspension or in the form of undifferentiated or differentiated constructs, muscle quality was superior to controls. Conclusions: Myoblast transplantation into hemiglossectomy defects appears to lead to new muscle formation and does not inhibit normal weight gain in animals after tongue implantation. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, HP Mosher Laryngol Res Lab, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Dept Surg Res, Boston, MA 02115 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL068915] NR 18 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2003 VL 113 IS 10 BP 1792 EP 1797 DI 10.1097/00005537-200310000-00025 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 731EL UT WOS:000185871500023 PM 14520108 ER PT J AU Stone, ME AF Stone, ME TI American medical association complete medical encyclopedia. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD OCT 1 PY 2003 VL 128 IS 16 BP 62 EP 62 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 724AP UT WOS:000185464300010 ER PT J AU Hasaba, A Cluette-Brown, JE Laposata, M AF Hasaba, A Cluette-Brown, JE Laposata, M TI Stearic acid stimulates FA ethyl ester synthesis in HepG2 cells exposed to ethanol SO LIPIDS LA English DT Article ID NONOXIDATIVE METABOLITES; FATTY-ACIDS; MARKERS; ARACHIDONATE; ALCOHOL; DAMAGE; LIVER; BLOOD; SERUM AB FA ethyl esters (FAEE) are nonoxidative metabolites of ethanol produced by the esterification of FA and ethanol. FAEE have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro, and are markers of ethanol intake. Upon ethanol intake, FAEE are synthesized in the liver and pancreas in significant quantities. There is limited information on the stimulation of FAEE synthesis upon addition of exogenous FA in vitro. HepG2 cells were incubated with ethanol alone, ethanol with 25 muM linoleate, and ethanol with 25 muM stearate. The amount of FAEE in human hepatoblastoma (HepG2) cells was determined 1-3 h after ethanol and FA addition. Stearate increased the FAEE concentration in HepG2 cells when incubated with the cells for I h, whereas linoleate did not increase the cellular FAEE concentration at any time. Ethyl palmitate, ethyl stearate, and ethyl oleate were the predominant FAEE species identified in all cases, independent of the specific supplemental FA added to the medium. C1 Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Dept Pathol, 55 Fruit St,Gray 235, Boston, MA 02114 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD OCT PY 2003 VL 38 IS 10 BP 1051 EP 1055 DI 10.1007/s11745-006-1160-3 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 746GZ UT WOS:000186739800006 PM 14669970 ER PT J AU Keller, SM Vangel, MG Wagner, H Schiller, J Herskovic, A Komaki, R Gray, R Marks, RS Perry, MC Livingston, RB Johnson, DH AF Keller, SM Vangel, MG Wagner, H Schiller, J Herskovic, A Komaki, R Gray, R Marks, RS Perry, MC Livingston, RB Johnson, DH CA Eastern Cooperative Oncology Grp TI Second primary tumors following adjuvant therapy of resected stages II and IIIa non-small cell lung cancer SO LUNG 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 second primary tumors; non-small cell lung cancer; resectable; adjuvant therapy ID RANDOMIZED-TRIAL; RADIATION-THERAPY; ADENOCARCINOMAS; CHEMOTHERAPY; RADIOTHERAPY; EXPRESSION; RECURRENCE; FREQUENCY; CARCINOMA; SURVIVAL AB The occurrence of second primary tumors (SPTs) following adjuvant therapy for resected stages 11 and IIIa non-small cell lung cancer (NSCLC) was investigated. Data regarding SPT; were prospectively collected in all patients accrued to Eastern Cooperative Group Oncology E3590 (a phase III trial of adjuvant therapy in patients with completely resected stages 11 and IIIa NSCLC). Four hundred eighty-eight patients were accrued to the study, 242 to the RT arm and 246 to the CRT arm. Median follow-up was 73 months. Thirty patients (6.1%) developed 33 SPTs, 20 in the RT arm and ten in the CRT arm. Ten SPTs occurred within the upper aerodigestive tract, six in the RT arm and four in the CRT arm. Twenty-three SPTs occurred in other organs, 17 in the RT arm and six in the CRT arm. Median time to detection of a SPT for those patients randomized to RT and CRT was 43 and 36 months, respectively. The incidence of SPTs was 1.8% per patient-year of follow-up. Excluding skin tumors, the relative risk of death following diagnosis of a SPT for patients randomized to the CRT arm as compared with those randomized to RT alone was 2.26 (95% confidence interval, 0.78-5.58, P = 0.12). Patients are at risk for developing a SPT following resection of stages II and IIIa NSCLC. The majority of SPTs occur outside the aerodigestive tract. Following development of a non-skin SPT, the survival difference between patients who had received adjuvant CRT and those treated with adjuvant RT alone was not significant. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Montefiore Med Ctr, Dept Cardiothorac Surg, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Wisconsin, Madison, WI USA. Oakwood Hosp, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Missouri, Columbia, MO USA. Univ Washington, Seattle, WA 98195 USA. Vanderbilt Univ, Nashville, TN USA. RP Montefiore Med Ctr, Dept Cardiothorac Surg, 3400 Bainbridge Ave,Suite 5B, Bronx, NY 10467 USA. EM skeller@montefiore.org RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA66636, CA14958, CA20319, CA21076, CA21115, CA21661, CA23318, CA25224, CA49957, CA73590] NR 37 TC 11 Z9 12 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD OCT PY 2003 VL 42 IS 1 BP 79 EP 86 DI 10.1016/S0169-5002(03)00274-5 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 731EK UT WOS:000185871400010 PM 14512191 ER PT J AU Wu, O Ostergaard, L Koroshetz, WJ Schwamm, LH O'Donnell, J Schaefer, PW Rosen, BR Weisskoff, RM Sorensen, AG AF Wu, O Ostergaard, L Koroshetz, WJ Schwamm, LH O'Donnell, J Schaefer, PW Rosen, BR Weisskoff, RM Sorensen, AG TI Effects of tracer arrival time on flow estimates in MR perfusion-weighted imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow; perfusion-weighted imaging; cerebral ischemia; dynamic susceptibility contrast-enhance magnetic resonance imaging; humans ID CEREBRAL-BLOOD-FLOW; SINGULAR-VALUE DECOMPOSITION; SUSCEPTIBILITY CONTRAST MRI; HYPERACUTE STROKE; BOLUS TRACKING; POTENTIAL IMPLICATIONS; TRANSIT-TIME; CLINICAL USE; DIFFUSION; MISMATCH AB A common technique for calculating cerebral blood flow (CBF) and mean transit time (MTT) is to track a bolus of contrast agent using perfusion-weighted MRI (PWI) and to deconvolve the change in concentration with an arterial input function (AIF) using singular value decomposition (SVD). This method has been shown to often overestimate the volume of tissue that infarcts and in cases of severe vasculopathy to produce CBF maps that are inconsistent with clinical presentation. This study examines the effects of tracer arrival time differences between tissue and a user-selected global AIF on flow estimates. CBF and MTT were calculated in both numerically simulated and clinically acquired PWI data where the AIF and tissue signals were shifted backward and forward in time with respect to one an, other. Results show that when the AIF leads the tissue, CBF is underestimated independent of extent of delay, but dependent on MTT. When the AIF lags the tissue, flow may be over- or underestimated depending on MTT and extent of timing differences. These conditions may occur in practice due to the application of a user-selected AIF that is not the "true AIF" and therefore caution must be taken in interpreting CBF and MTT estimates. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp,MIT, Sch Med,Althinoula A Martinos Ctr Biomed Imaging, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02114 USA. Aarhus Univ Hosp, Dept Neuroradiol, Ctr Functionally Integrat Neurosci, DK-8000 Aarhus, Denmark. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. EPIX Med, Cambridge, MA USA. RP Wu, O (reprint author), Harvard Univ, Massachusetts Gen Hosp,MIT, Sch Med,Althinoula A Martinos Ctr Biomed Imaging, Harvard Mit Div Hlth Sci & Technol, Mailcode CNY149-2301, Boston, MA 02114 USA. RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008; OI Ostergaard, Leif/0000-0003-2930-6997; Schwamm, Lee/0000-0003-0592-9145 FU NCRR NIH HHS [5P41 RR14075]; NHLBI NIH HHS [5 R01 HL39810]; NINDS NIH HHS [5 R01 NS38477] NR 31 TC 70 Z9 72 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD OCT PY 2003 VL 50 IS 4 BP 856 EP 864 DI 10.1002/mrm.10610 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 728CQ UT WOS:000185698000026 PM 14523973 ER PT J AU Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, ML AF Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, ML TI Induction of a hypermetabolic state in cultured hepatocytes by glucagon and H2O2 SO METABOLIC ENGINEERING LA English DT Article DE rat liver; uncoupling protein; oxidative stress ID MITOCHONDRIAL UNCOUPLING PROTEINS; ISOLATED RAT HEPATOCYTES; NF-KAPPA-B; HYDROGEN-PEROXIDE; SANDWICH CONFIGURATION; SKELETAL-MUSCLE; THERMAL-INJURY; PENTOSE CYCLE; HUMAN-DISEASE; HUMAN PLASMA AB Stress hormones and pro-inflammatory cytokines are putative signals triggering increased energy expenditure or "hypermetabolism" commonly observed in inflammatory states. Cytokines also cause the release of reactive oxidants by immune cells resident in tissues in vivo. Therefore, we hypothesized that oxidative stress plays a role in the induction of hypermetabolism. We examined the effect of glucagon (1.0 nM), a catabolic stress hormone, and the oxidant H2O2 (1.0 mM) on the metabolism of stable hepatocyte cultures for 4 days. Combined H2O2 and glucagon treatment, but not H2O2 or glucagon used alone, increased the hepatocyte oxygen uptake rate 25% above control untreated cells after a lag-time of 72h. The same treatment also increased the expression of mitochondrial uncoupling protein-2 (UCP2). These effects were significantly inhibited by the antioxidant N-acetylcysteine (5 mM) and the pentose phosphate pathway (PPP) inhibitor dehydroepianderosterone (200 muM). Glucagon alone induced urea synthesis and H2O2 alone induced the PPP. These findings show, for the first time, that oxidative stress, in combination with glucagon, increases metabolic energy expenditure in cultured cells, and that this effect may be mediated by UCP-2. Furthermore, the results implicate the PPP in the induction of the hypermetabolic response. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Burn Hosp, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, 55 Fruit St GRB-1401, Boston, MA 02114 USA. EM ireis@sbi.org RI Lee, Kyongbum/D-9230-2013 FU NIGMS NIH HHS [GM58125] NR 52 TC 11 Z9 14 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 1096-7176 J9 METAB ENG JI Metab. Eng. PD OCT PY 2003 VL 5 IS 4 BP 221 EP 229 DI 10.1016/S1096-7176(03)00042-9 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 768DT UT WOS:000188513900001 PM 14642350 ER PT J AU Chen, CL Fei, ZW Carter, EA Lu, XM Hu, RH Young, VR Tompkins, RG Yu, YM AF Chen, CL Fei, ZW Carter, EA Lu, XM Hu, RH Young, VR Tompkins, RG Yu, YM TI Metabolic fate of extrahepatic arginine in liver after burn injury SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PERFUSED-RAT-LIVER; NITRIC-OXIDE SYNTHASE; PLASMA ARGININE; UREA SYNTHESIS; LEUCINE KINETICS; NITROGEN; CITRULLINE; TRANSPORT; ENZYMES; CYCLE AB Increased nitrogen loss in the form of urea is a hallmark of the metabolic aberrations that occur after burn injury. As the immediate precursor for urea production is arginine, we have conducted an investigation on the metabolic fate of arginine in the liver to shed light on the metabolic characteristics of this increased nitrogen loss. Livers from 25% total surface burn (n = 8) and sham burn rats (n = 8) were perfused in a recycling fashion with a medium containing amino acids and stable isotope labeled L-[(15) N-2-guanidino, 5,5-H-2(2)]arginine for 120 minutes. The rates of glucose and urea production and oxygen consumption were measured. The rate of unidirectional arginine transport and the intrahepatic metabolic fate of arginine in relation to urea cycle activity were quantified by tracing the disappearance rate of the arginine tracer from and the appearance rate of [N-15(2)]urea in the perfusion medium. Perfused livers from burned rats showed higher rates of total urea production (mean +/- SE, 4.471 +/- 0.274 v 3.235 +/- 0.261 mumol . g dry liver(-1) . min(-1); P < .01). This was accompanied by increased hepatic arginine transport (1.269 +/- 0.263 v 0.365 +/- 0.021 mumol . g dry liver(-1) . min(-1)) and an increased portion of urea production from the transported extrahepatic arginine (12.9% +/- 2.9% v 3.5% +/- 0.4%, P < .05). The disposal of arginine via nonurea pathways was also increased (0.702 +/- 0.185 v 0.257 +/- 0.025 mumol/g dry weight(-1)/min(-1); P < .05). We propose that increased inward transport and utilization of extrahepatic arginine by the liver contributes to the accelerated urea production after burn injury and accounts, in part, for its conditional essentiality in the nutritional support of burn patients. (C) 2003 Elsevier Inc. All rights reserved. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Natl Cheng Kung Univ Hosp, Dept Surg, Tainan, Taiwan. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. MIT, Human Nutr Lab, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. RP Yu, YM (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. OI Young, Vincent/0000-0003-3687-2364 FU NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM 2700] NR 49 TC 8 Z9 8 U1 0 U2 1 PU W B SAUNDERS CO 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 OCT PY 2003 VL 52 IS 10 BP 1232 EP 1239 DI 10.1016/S0026-0495(03)00282-8 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731YH UT WOS:000185913700002 PM 14564672 ER PT J AU Brochmann, EJ Duarte, ME Zaidi, HA Murray, SS AF Brochmann, EJ Duarte, ME Zaidi, HA Murray, SS TI Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res ID INBRED MOUSE STRAINS; SKIN TUMOR PROMOTION; HIGH-FAT DIETS; CALORIE RESTRICTION; EPIDERMAL HYPERPLASIA; ALTERED EXPRESSION; CALCIUM-REPLETE; INDUCED OBESE; B6C3F1 MICE; DNA DAMAGE AB Dietary restriction (DR) increases the life span and retards aging, in part, by limiting free radical generation and oxidative damage. DR also reduces body mass, a major determinant of bone mass across the life span. We tested the hypothesis that DR has its most beneficial effects on bone in mouse strains with high free radical generation (sensitive to carcinogenesis [SENCAR] > C57 > DBA) versus the hypothesis that bone mass at weight-bearing sites is determined by body mass in DR and ad libitum (AL)-fed mice. Male mice of each strain were killed at 10 weeks of age (t(0)) or randomized to an AL-fed or 30% DR feeding regimen for 6 months. Food consumption by AL-fed mice was measured daily, and DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. Body fat (%) and bone mineral density (BMD) and content (BMC) were determined by PIXImus densitometry. There were strain-dependent effects on body mass, crown-to-rump length, percent body fat, and total body, femoral, and vertebral BMD and BMC under all conditions. SENCAR mice were heavier, longer, had larger bones, and generally exhibited higher total body, femoral, and vertebral BMC and BMD than C57 and DBA mice. DR had beneficial effects on BMD and BMC in the vertebrae of the SENCAR mouse model of high free radical generation and in the obese, diabetes-prone C57 mouse model of high end-stage protein glycation. DR DBA and SENCAR mice had lower femoral BMDs and BMCs than their respective AL-fed controls. Regression analysis confirmed linear relationships between total and lean body mass and total body and femoral BMDs and BMCs, suggesting that physiologic adaptation to a lower body mass accounts for the lower femoral bone mineral values observed in DR versus AL-fed mice. Thus, both hypotheses are, at least, partially valid. DR is beneficial in the trabeculae-rich vertebrae of animal models of high oxidant stress, and total/lean body mass determines BMD and BMC in the weight-bearing femur in DR and AL-fed mice. (C) 2003 Elsevier Inc. All rights reserved. C1 Sepulveda Ambulat Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, 11E GRECC, Sepulveda, CA 91343 USA. Fed Univ Rio De Janeiro, Dept Histol & Embryol, Rio De Janeiro, Brazil. Fed Univ Rio De Janeiro, PABCAM, HUCFF, Rio De Janeiro, Brazil. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Murray, SS (reprint author), Sepulveda Ambulat Care Ctr & Nursing Home, VA Greater Los Angeles Healthcare Syst, GRECC 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. RI Biguzzi, Felipe/E-4724-2015 NR 50 TC 30 Z9 30 U1 0 U2 3 PU W B SAUNDERS CO 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 OCT PY 2003 VL 52 IS 10 BP 1265 EP 1273 DI 10.1016/S0026-0495(03)00194-0 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 731YH UT WOS:000185913700007 PM 14564677 ER PT J AU Krueger, NX Reddy, RS Johnson, K Bateman, J Kaufmann, N Scalice, D Van Vactor, D Saito, H AF Krueger, NX Reddy, RS Johnson, K Bateman, J Kaufmann, N Scalice, D Van Vactor, D Saito, H TI Functions of the ectodomain and cytoplasmic tyrosine phosphatase domains of receptor protein tyrosine phosphatase Dlar in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOTOR AXON GUIDANCE; LEUKOCYTE COMMON ANTIGEN; GROWTH CONE GUIDANCE; DROSOPHILA EMBRYO; CATALYTIC DOMAINS; LAR; EXPRESSION; ALPHA; INTERMEDIATE; DIMERIZATION AB The receptor protein tyrosine phosphatase (PTPase) Dlar has an ectodomain consisting of three immunoglobulin (Ig)-like domains and nine fibronectin type III (FnIII) repeats and a cytoplasmic domain consisting of two PTPase domains, membrane-proximal PTP-D1 and C-terminal PTP-D2. A series of mutant Dlar transgenes were introduced into the Drosophila genome via P-element transformation and were then assayed for their capacity to rescue phenotypes caused by homozygous loss-of-function genotypes. The Ig-like domains, but not the FnIII domains, are essential for survival. Conversely, the FnIII domains, but not the Ig-like domains, are required during oogenesis, suggesting that different domains of the Mar ectodomain are involved in distinct functions during Drosophila development. All detectable PTPase activity maps to PTP-D1 in vitro. The catalytically inactive mutants of Dlar were able to rescue Dlar(-/-) lethality nearly as efficiently as wild-type Dlar transgenes, while this ability was impaired in the PTP-D2 deletion mutants DlarDeltaPTP-D2 and Dlar(bypass). DlarC1929S, in which PTP-D2 has been inactivated, increases the frequency of bypass phenotype observed in Dlar(-/-)genotypes, but only if PTP-D1 is catalytically active in the transgene. These results indicate multiple roles for PTP-D2, perhaps by acting as a docking domain for downstream elements and as a regulator of PTP-D1. C1 Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Canc, Boston, MA 02115 USA. RP Saito, H (reprint author), Univ Tokyo, Inst Med Sci, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. OI Johnson, Karl/0000-0003-3931-5985 FU NIGMS NIH HHS [GM53415]; NINDS NIH HHS [P01 NS040043, NS35909, NS40043, R01 NS035909] NR 51 TC 21 Z9 22 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 OCT PY 2003 VL 23 IS 19 BP 6909 EP 6921 DI 10.1128/MCB.23.19.6909.6921.2003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 725CN UT WOS:000185525700018 PM 12972609 ER PT J AU Rosen, ED Kulkarni, RN Sarraf, P Ozcan, U Okada, T Hsu, CH Eisenman, D Magnuson, MA Gonzalez, FJ Kahn, CR Spiegelman, BM AF Rosen, ED Kulkarni, RN Sarraf, P Ozcan, U Okada, T Hsu, CH Eisenman, D Magnuson, MA Gonzalez, FJ Kahn, CR Spiegelman, BM TI Targeted elimination of peroxisome proliferator-activated receptor gamma in beta cells leads to abnormalities in islet mass without compromising glucose homeostasis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PPAR-GAMMA; INSULIN-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; TERMINAL DIFFERENTIATION; GROWTH-FACTOR; COLON-CANCER; EXPRESSION; TROGLITAZONE; SUBSTRATE-1; MICE AB The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is an important regulator of lipid and glucose homeostasis and cellular differentiation. Studies of many cell types in vitro and in vivo have demonstrated that activation of PPARgamma can reduce cellular proliferation. We show here that activation of PPARgamma is sufficient to reduce the proliferation of cultured insulinoma cell lines. We created a model with mice in which the expression of the PPARG gene in beta cells was eliminated (betagammaKO mice), and these mice were found to have significant islet hyperplasia on a chow diet. Interestingly, the normal expansion of beta-cell mass that occurs in control mice in response to high-fat feeding is markedly blunted in these animals. Despite this alteration in beta-cell mass, no effect on glucose homeostasis in betagammaKO mice was noted. Additionally, while thiazolidinediones enhanced insulin secretion from cultured wild-type islets, administration of rosiglitazone to insulin-resistant control and betagammaKO mice revealed that PPARgamma in beta cells is not required for the antidiabetic actions of these compounds. These data demonstrate a critical physiological role for PPARgamma function in beta-cell proliferation and also indicate that the mechanisms controlling beta-cell hyperplasia in obesity are different from those that regulate baseline cell mass in the islet. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Cell Biol, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Dept Physiol & Mol Biophys, Nashville, TN USA. Natl Canc Inst, Lab Metab, Div Basic Sci, Bethesda, MD USA. RP Rosen, ED (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, 99 Brookline Ave, Boston, MA 02215 USA. RI Magnuson, Mark/B-1335-2009 OI Magnuson, Mark/0000-0002-8824-6499 FU NIDDK NIH HHS [KO8 DK02885, K08 DK002885, KO8 DK02535, R01 DK033201, R01 DK33201, R03 DK58850, R37 DK031405, R37DK31405] NR 47 TC 101 Z9 104 U1 0 U2 2 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 OCT PY 2003 VL 23 IS 20 BP 7222 EP 7229 DI 10.1128/MCB.23.20.7222-7229.2003 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 729CT UT WOS:000185754300013 PM 14517292 ER PT J AU Cable, PL Wilson, CA Calzone, FJ Rauscher, FJ Scully, R Livingston, DM Li, LP Blackwell, CB Futreal, PA Afshari, CA AF Cable, PL Wilson, CA Calzone, FJ Rauscher, FJ Scully, R Livingston, DM Li, LP Blackwell, CB Futreal, PA Afshari, CA TI Novel consensus DNA-binding sequence for BRCA1 protein complexes SO MOLECULAR CARCINOGENESIS LA English DT Article DE BRCA1; cyclic amplification and selection of targets (CASTing); USF2 ID CANCER SUSCEPTIBILITY GENE; BREAST-CANCER; DAMAGE RESPONSE; TRANSCRIPTIONAL ACTIVATION; PROMOTER ACTIVITY; MESSENGER-RNA; CELL-CYCLE; C-MYC; EXPRESSION; REPAIR AB Increasing evidence continues to emerge supporting the early hypothesis that BRCA1 might be involved in transcriptional processes. BRCA1 physically associates with more than 15 different proteins involved in transcription and is paradoxically involved in both transcriptional activation and repression. However, the underlying mechanism by which BRCA1 affects the gene expression of various genes remains speculative. In this study, we provide evidence that BRCA1 protein complexes interact with specific DNA sequences. We provide data showing that the upstream stimulatory factor 2 (USF2) physically associates with BRCA1 and is a component of this DNA-binding complex. interestingly, these DNA-binding complexes are downregulated in breast cancer cell lines containing wild-type BRCA1, providing a critical link between modulations of BRCA1 function in sporadic breast cancers that do not involve germline BRCA1 mutations. The functional specificity of BRCA1 tumor suppression for breast and ovarian tissues is supported by our experiments, which demonstrate that BRCA1 DNA-binding complexes are modulated by serum and estrogen. Finally, functional analysis indicates that missense mutations in BRCA1 that lead to subsequent cancer susceptibility may result in improper gene activation. In summary, these findings establish a role for endogenous BRCA1 protein complexes in transcription via a defined DNA-binding sequence and indicate that one function of BRCA1 is to co-regulate the expression of genes involved in various cellular processes. Published 2003 Wiley-Liss, Inc.(dagger). C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Amgen Inc, Amgen Ctr, Thousand Oaks, CA 91320 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Wellcome Trust Sanger Inst, Sanger Ctr, Cambridge, England. RP Cable, PL (reprint author), GlaxoSmithKline, RCII 807, Res Triangle Pk, NC 27709 USA. RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [K01 CA079576] NR 56 TC 22 Z9 22 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 2003 VL 38 IS 2 BP 85 EP 96 DI 10.1002/mc.10148 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 771TY UT WOS:000188803200005 PM 14502648 ER PT J AU Burns, KH Agno, JE Sicinski, P Matzuk, MM AF Burns, KH Agno, JE Sicinski, P Matzuk, MM TI Cyclin D2 and P27 are tissue-specific regulators of tumorigenesis in inhibin alpha knockout mice SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; DEFICIENT MICE; TARGETED DISRUPTION; CELL-PROLIFERATION; TRANSGENIC MODELS; OVARIAN PHENOTYPE; GENE; DIFFERENTIATION; ONCOGENESIS; EXPRESSION AB Inhibins are heterodimeric (alpha:betaA and alpha:betaB) endocrine, paracrine, and autocrine factors of the TGFbeta superfamily that are produced predominantly by ovarian granulosa cells in females and testicular Sertoli cells in males. Control of granulosa and Sertoli cell proliferation is lost in the inhibin alpha (Inhalpha) knockout mouse model, leading to gonadotrop-independent gonadal tumors of the granulosa/Sertoli cell lineage in both females and males. Castrate Inhalpha knockout mice develop sex steroidogenic tumors of the adrenal cortex. Physiological control of granulosa/Sertoli cell cycle progression depends on p27(Kip1) and cyclin D2, which function in the G(1) --> S phase transition. To study the cell cycle-regulatory factors involved in ovarian, testicular, and adrenal tumor development in vivo, we have bred Inhalpha mutant mice to mice with targeted disruptions of the p27 and cyclin D2 genes. Our previous studies demonstrated that inhibins act cooperatively with p27 to negatively regulate granulosa cell proliferation, as double mutant mice lacking inhibins and p27 develop and succumb to ovarian tumors more rapidly than Inhalpha knockout mice. Here, we report that cyclin D2 antagonizes this inhibition and is key in promoting gonadal growth and tumor development, and tumor development is markedly suppressed in double-mutant mice. We found that double-knockout females lacking cyclin D2 and Inhalpha lived longer than mice lacking inhibins alone; the majority of these double-knockout mice lived longer than 17 wk, as opposed to inhibin alpha single-knockout females with 50% survival at between 12 and 13 wk of age. Moreover, 95% of inhibin alpha knockout males succumb to testicular tumor development by 12 wk of age, whereas double knockouts were protected from early signs of tumor development and had a 50% survival of 40 wk. Interestingly, the results of these studies reflect tissue-specific consequences of loss of these cell cycle regulators. In castrate mice, loss of p27 has little effect on adrenal cortical tumor progression in the absence of inhibins, whereas loss of cyclin D2 prolongs the lifespan of cyclin D2, Inhalpha double knockouts. After gonadectomy, 50% of cyclin D2, Inhalpha double-knockout males live to more than 46 wk of age, 10 wk longer than 50% of littermates lacking only inhibins. Similarly, 50% of female cyclin D2, inhibin alpha double knockouts live to 47 wk of age before succumbing to adrenal tumor development, in contrast to the 50% survival of Inhalpha single-knockout females at between 27 and 28 wk. Thus, identification of genetic modifiers of the Inhalpha knockout tumor phenotype has led us to a better appreciation of how specific components of the cell cycle machinery contribute to tumorigenesis in the ovary, testis, and adrenal gland. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Matzuk, MM (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. RI Burns, Kathleen/A-3360-2011 FU NCI NIH HHS [CA60651]; NICHD NIH HHS [U54 HD28934]; NIGMS NIH HHS [T32 GM07330] NR 31 TC 37 Z9 38 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT 1 PY 2003 VL 17 IS 10 BP 2053 EP 2069 DI 10.1210/me.2003-0038 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 727DA UT WOS:000185640100014 PM 12855747 ER PT J AU Brandon, LD Goehring, N Janakiraman, A Yan, AW Wu, T Beckwith, J Goldberg, MB AF Brandon, LD Goehring, N Janakiraman, A Yan, AW Wu, T Beckwith, J Goldberg, MB TI IcsA, a polarly localized autotransporter with an atypical signal peptide, uses the Sec apparatus for secretion, although the Sec apparatus is circumferentially distributed SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI CELL; MEMBRANE-PROTEIN INSERTION; SHIGELLA-FLEXNERI 2A; RECOGNITION PARTICLE; SUBCELLULAR-LOCALIZATION; INTRACELLULAR MOVEMENT; UNIPOLAR LOCALIZATION; INTERCELLULAR SPREAD; YIELDS MUTATIONS; II SECRETION AB Asymmetric localization of proteins is essential to many biological functions of bacteria. Shigella IcsA, an outer membrane protein, is localized to the old pole of the bacillus, where it mediates assembly of a polarized actin tail during infection of mammalian cells. Actin tail assembly provides the propulsive force for intracellular movement and intercellular dissemination. Localization of IcsA to the pole is independent of the amino-terminal signal peptide (Charles, M., Perez, M., Kobil, J. H., and Goldberg, M. B., 2001, Proc Natl Acad Sci USA 98: 9871 - 9876) suggesting that IcsA targeting occurs in the bacterial cytoplasm and that its secretion across the cytoplasmic membrane occurs only at the pole. Here, we characterize the mechanism by which IcsA is secreted across the cytoplasmic membrane. We present evidence that IcsA requires the SecA ATPase and the SecYEG membrane channel ( translocon) for secretion. Our data suggest that YidC is not required for IcsA secretion. Furthermore, we show that polar localization of IcsA is independent of SecA. Finally, we demonstrate that while IcsA requires the SecYEG translocon for secretion, components of this apparatus are uniformly distributed within the membrane. Based on these data, we propose a model for coordinate polar targeting and secretion of IcsA at the bacterial pole. C1 Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. OI Goehring, Nathan/0000-0001-8710-4467 FU NIAID NIH HHS [R01 AI35817, T32 AI07061] NR 69 TC 85 Z9 89 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 2003 VL 50 IS 1 BP 45 EP 60 DI 10.1046/j.1365-2958.2003.03674.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 723RX UT WOS:000185446300004 PM 14507362 ER PT J AU Tyler, KL AF Tyler, KL TI Origins and early descriptions of "Duchenne muscular dystrophy" SO MUSCLE & NERVE LA English DT Article DE Becker muscular dystrophy; Duchenne muscular dystrophy; Gowers' sign; historical aspects; muscular dystrophy; pseudohypertrophic muscular dystrophy ID HISTORY AB One of the seminal events in the history of neurology was the identification of primary diseases of muscle and their separation from diseases in which muscle weakness was secondary to injury involving the anterior horns of the spinal cord ("progressive muscular atrophy"). Not surprisingly, one of the first groups of primary muscle diseases to be satisfactorily characterized belonged to what would today be classified as muscular dystrophies. Pride of place in this group belongs to Duchenne muscular dystrophy (DMD). DMD's primacy as the first well-characterized muscular dystrophy was due both to the fact that it is relatively common, as well as to the clinically striking feature, apparent in many cases, of apparent paradoxical enlargement of severely weakened muscles ("pseudo-hypertrophy"). This review traces the historical roots of DMD in the 19th century, from the early papers by Conte, Bell, Partridge, and Meryon through the classic monographs by Duchenne and Gowers. In addition, the first American contributions to DMID are reviewed, including those by Pepper, Hammond, and S. Weir Mitchell. Many of the original papers describing this disease are now unavailable outside of major medical libraries, and several important contributions, excepting those of Duchenne, which are recognized eponymously, are now virtually forgotten. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Univ Colorado, Neurol Serv, Dept Neurol B 182, Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, Denver Vet Affairs Med Ctr, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 63 TC 31 Z9 32 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2003 VL 28 IS 4 BP 402 EP 422 DI 10.1002/mus.10435 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 726RN UT WOS:000185613200002 PM 14506712 ER PT J AU Ossipova, O Bardeesy, N DePinho, RA Green, JBA AF Ossipova, O Bardeesy, N DePinho, RA Green, JBA TI LKB1 (XEEK1) regulates Wnt signalling in vertebrate development SO NATURE CELL BIOLOGY LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; SERINE-THREONINE KINASE; TUMOR-SUPPRESSOR; CELL POLARITY; GENE; POLYPOSIS; PROTEIN; EMBRYOS; GROWTH; TRANSFORMATION AB Germline LKB1/STK11 mutations are associated with the cancer-prone Peutz-Jeghers syndrome (PJS) in humans(1-3), and nullizygosity provokes a poorly understood constellation of developmental perturbations in the mid-gestational mouse(4). To gain a better understanding of the processes regulated by LKB1, we have exploited the experimental merits of the developing Xenopus embryo. Here, specific inhibition of XEEK1, the Xenopus orthologue of LKB1, engendered developmental anomalies - shortened body axis and defective dorsoanterior patterning - associated previously with aberrant Wnt signalling. In line with this, LKB1/XEEK1 cooperates with the Wnt - - catenin signalling in axis induction and modulates the expression of Wnt-responsive genes in both Xenopus embryos and mammalian cells. We establish that LKB1/XEEK1 acts upstream of - catenin in the Wnt - - catenin pathway in vivo. LKB1/XEEK1 regulates glycogen synthase kinase (GSK) 3beta phosphorylation and it is physically associated in vivo with GSK3beta and protein kinase C ( PKC)-zeta, a known GSK3 kinase. These studies show that LKB1/XEEK1 is required for Wnt-beta-catenin signalling in frogs and mammals and provides novel insights into its role in vertebrate developmental patterning and carcinogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Green, JBA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 FU NICHD NIH HHS [HD 36345] NR 30 TC 97 Z9 104 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2003 VL 5 IS 10 BP 889 EP 894 DI 10.1038/ncb1048 PG 6 WC Cell Biology SC Cell Biology GA 727FM UT WOS:000185647400014 PM 12973359 ER PT J AU Chan, EM Young, EJ Ianzano, L Munteanu, I Zhao, XC Christopoulos, CC Avanzini, G Elia, M Ackerley, CA Jovic, NJ Bohlega, S Andermann, E Rouleau, GA Delgado-Escueta, AV Minassian, BA Scherer, SW AF Chan, EM Young, EJ Ianzano, L Munteanu, I Zhao, XC Christopoulos, CC Avanzini, G Elia, M Ackerley, CA Jovic, NJ Bohlega, S Andermann, E Rouleau, GA Delgado-Escueta, AV Minassian, BA Scherer, SW TI Mutations in NHLRC1 cause progressive myoclonus epilepsy SO NATURE GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LAFORIN; FAMILY; BODIES AB Lafora progressive myoclonus epilepsy is characterized by pathognomonic endoplasmic reticulum (ER)-associated polyglucosan accumulations. We previously discovered that mutations in EPM2A cause Lafora disease. Here, we identify a second gene associated with this disease, NHLRC1 ( also called EPM2B), which encodes malin, a putative E3 ubiquitin ligase with a RING finger domain and six NHL motifs. Laforin and malin colocalize to the ER, suggesting they operate in a related pathway protecting against polyglucosan accumulation and epilepsy. C1 Hosp Sick Children, Res Inst, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X8, Canada. Inst Nazl Neurol, I-20133 Milan, Italy. Oasi Inst Res Mental Retardat & Brain Aging, Dept Neurol, I-94018 Troina, Italy. Hosp Sick Children, Dept Pathol & Lab Med, Toronto, ON M5G 1X8, Canada. Clin Neurol & Psychiat Children & Youth, YU-11000 Belgrade, Serbia Monteneg, Yugoslavia. King Faisal Specialist Hosp & Res Ctr, Dept Neurosci, Riyadh 11211, Saudi Arabia. McGill Univ, Montreal Neurol Inst, Neurogenet Unit, Montreal, PQ H3A 2B4, Canada. McGill Univ, Montreal Gen Hosp, Ctr Hlth, Res Inst Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Dept Neurol,Comprehens Epilepsy Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles DVA Med Ctr, Brain Res Inst, Los Angeles, CA 90073 USA. Hosp Sick Children, Dept Pediat, Div Neurol, Toronto, ON M5G 1X8, Canada. RP Minassian, BA (reprint author), Hosp Sick Children, Res Inst, Program Genet & Genom Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013; OI Scherer, Stephen /0000-0002-8326-1999; Delgado-Escueta, Antonio V./0000-0002-1581-6999; Elia, Maurizio/0000-0002-0414-1359 FU Telethon [GFP01003] NR 15 TC 140 Z9 145 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2003 VL 35 IS 2 BP 125 EP 127 DI 10.1038/ng1238 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 726WV UT WOS:000185625300007 PM 12958597 ER PT J AU Goodarzi, K Goodarzi, M Tager, AM Luster, AD von Andrian, UH AF Goodarzi, K Goodarzi, M Tager, AM Luster, AD von Andrian, UH TI Leukotriene B-4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues SO NATURE IMMUNOLOGY LA English DT Article ID IN-VIVO; MURINE MODEL; L-SELECTIN; MEMORY; RECEPTOR; ADHESION; MICE; INFLAMMATION; NAIVE; DIFFERENTIATION AB Leukotriene B-4 (LTB4) is a potent chemoattractant for myeloid leukocytes, which express BLT1, the high-affinity receptor for LTB4. We report here that BLT1 is induced substantially in CD8(+) effector T cells and at lower amounts in CD8(+) central memory T cells. LTB4 elicited BLT1-dependent chemotaxis in effector cells, but not in naive or central memory cells. Intravital microscopy showed that BLT1 signaling induced rapid integrin-mediated arrest of rolling effector and central memory cells in postcapillary venules. In competitive homing experiments, wild-type effector cells were three times more efficient at migrating to the inflamed peritoneal cavity than were BLT-deficient effector cells. These results identify LTB4-BLT1 as a potent nonchemokine pathway for cytotoxic effector cell traffic. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL04087, HL48675, HL54936, HL56949]; NIAID NIH HHS [AI050892, AI46999]; NIDDK NIH HHS [DK5005] NR 42 TC 205 Z9 215 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2003 VL 4 IS 10 BP 965 EP 973 DI 10.1038/ni972 PG 9 WC Immunology SC Immunology GA 726GG UT WOS:000185590100012 PM 12949533 ER PT J AU Tager, AM Bromley, SK Medoff, BD Islam, SA Bercury, SD Friedrich, EB Carafone, AD Gerszten, RE Luster, AD AF Tager, AM Bromley, SK Medoff, BD Islam, SA Bercury, SD Friedrich, EB Carafone, AD Gerszten, RE Luster, AD TI Leukotriene B-4 receptor BLT1 mediates early effector T cell recruitment SO NATURE IMMUNOLOGY LA English DT Article ID LUNG MAST-CELLS; AIRWAY INFLAMMATION; ARACHIDONIC-ACID; POLYMORPHONUCLEAR LEUKOCYTES; ALVEOLAR MACROPHAGES; POLARIZED T-HELPER-1; CHEMOKINE PRODUCTION; DENDRITIC CELLS; DEFICIENT MICE; MOUSE MODEL AB Leukotriene B-4 (LTB4) was originally described as a potent lipid myeloid cell chemoattractant, rapidly generated from innate immune cells, that activates leukocytes through the G protein-coupled receptor BLT1. We report here that BLT1 is expressed on effector CD4(+) T cells generated in vitro as well as in vivo when effector T cells migrate out of the lymphoid compartment and are recruited into peripheral tissues. BLT1 mediated LTB4-induced T helper type 1 (T(H)1) and T(H)2 cell chemotaxis and firm adhesion to endothelial cells under flow, as well as early CD4(+) and CD8(+) T cell recruitment into the airway in an asthma model. Our findings show that the LTB4-BLT1 pathway is involved in linking early immune system activation and early effector T cell recruitment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. FU NCI NIH HHS [R01-CA69212]; NHLBI NIH HHS [R01-HL65584, K08-HL04087]; NIAID NIH HHS [F32-AI50399, F32-AI54107, R01-AI050892, R01-AI40618, R01-AI46999]; NIDDK NIH HHS [DK5005] NR 53 TC 245 Z9 255 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2003 VL 4 IS 10 BP 982 EP 990 DI 10.1038/ni970 PG 9 WC Immunology SC Immunology GA 726GG UT WOS:000185590100014 PM 12949531 ER PT J AU Li, HW Liu, H Heller, S AF Li, HW Liu, H Heller, S TI Pluripotent stem cells from the adult mouse inner ear SO NATURE MEDICINE LA English DT Article ID HAIR-CELLS; REGENERATIVE PROLIFERATION; NERVOUS-SYSTEM; GROWTH-FACTORS; EXPRESSION; GENE; GENERATION; CULTURE; MATH1; MICE AB In mammals, the permanence of acquired hearing loss is mostly due to the incapacity of the cochlea to replace lost mechanoreceptor cells, or hair cells. In contrast, damaged vestibular organs can generate new hair cells, albeit in limited numbers. Here we show that the adult utricular sensory epithelium contains cells that display the characteristic features of stem cells. These inner ear stem cells have the capacity for self-renewal, and form spheres that express marker genes of the developing inner ear and the nervous system. Inner ear stem cells are pluripotent and can give rise to a variety of cell types in vitro and in vivo, including cells representative of ectodermal, endodermal and mesodermal lineages. Our observation that these stem cells are capable of differentiating into hair cell-like cells implies a possible use of such cells for the replacement of lost inner-ear sensory cells. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Heller, S (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC006167] NR 43 TC 271 Z9 319 U1 0 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2003 VL 9 IS 10 BP 1293 EP 1299 DI 10.1038/nm925 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 727QK UT WOS:000185669700041 PM 12949502 ER PT J AU Wang, XY Lee, SR Arai, K Lee, SR Tsuji, K Rebeck, GW Lo, EH AF Wang, XY Lee, SR Arai, K Lee, SR Tsuji, K Rebeck, GW Lo, EH TI Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator SO NATURE MEDICINE LA English DT Article ID NEURONAL CELL-DEATH; BLOOD-BRAIN-BARRIER; METHYL-D-ASPARTATE; EXTRACELLULAR PROTEOLYSIS; NERVOUS-SYSTEM; PROTEIN; STROKE; THROMBOLYSIS; EXPRESSION; LRP AB Although thrombolysis with tissue plasminogen activator (tPA) is a stroke therapy approved by the US Food and Drug Administration, its efficacy may be limited by neurotoxic side effects(1,2). Recently, proteolytic damage involving matrix metalloproteinases (MMPs) have been implicated. In experimental embolic stroke models, MMP inhibitors decreased cerebral hemorrhage and injury after treatment with tPA(3,4). MMPs comprise a family of zinc endopeptidases that can modify several components of the extracellular matrix(5,6). In particular, the gelatinases MMP-2 and MMP-9 can degrade neurovascular matrix integrity. MMP-9 promotes neuronal death by disrupting cell-matrix interactions(7), and MMP-9 knockout mice have reduced blood-brain barrier leakage and infarction after cerebral ischemia(8). Hence it is possible that tPA upregulates MMPs in the brain, and that subsequent matrix degradation causes brain injury. Here we show that tPA upregulates MMP-9 in cell culture and in vivo. MMP-9 levels were lower in tPA knockouts compared with wild-type mice after focal cerebral ischemia. In human cerebral microvascular endothelial cells, MMP-9 was upregulated when recombinant tPA was added. RNA interference (RNAi) suggested that this response was mediated by the low-density lipoprotein receptor-related protein (LRP), which avidly binds tPA(9) and possesses signaling properties(10). Targeting the tPA-LRP signaling pathway in brain may offer new approaches for decreasing neurotoxicity and improving stroke therapy. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH E 149-2401, Charlestown, MA 02129 USA. FU NIA NIH HHS [R01-AG14473]; NINDS NIH HHS [R01-NS37074, P50-NS10828, R01-NS38731, R01-NS40529] NR 28 TC 286 Z9 302 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2003 VL 9 IS 10 BP 1313 EP 1317 DI 10.1038/nm926 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 727QK UT WOS:000185669700044 PM 12960961 ER PT J AU Engel, P Eck, MJ Terhorst, C AF Engel, P Eck, MJ Terhorst, C TI The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID LYMPHOCYTIC ACTIVATION MOLECULE; NATURAL-KILLER-CELLS; GENE-PRODUCT SAP; FATAL INFECTIOUS-MONONUCLEOSIS; PROTEIN-TYROSINE-PHOSPHATASE; VIRUS-ASSOCIATED ILLNESSES; HUMAN B-LYMPHOCYTES; T-CELLS; CUTTING EDGE; SH2 DOMAIN AB SAP (signalling lymphocytic activation molecule (SLAM)-associated protein) is a T- and natural killer (NK)-cell-specific protein containing a single SH2 domain encoded by a gene that is defective or absent in patients with X-linked lymphoproliferative syndrome (XLP). The SH2 domain of SAP binds with high affinity to the cytoplasmic tail of the haematopoietic cell-surface glycoprotein SLAM and five related receptors. SAP regulates signal transduction of the SLAM-family receptors by recruiting SRC kinases. Similarly, the SAP-related proteins EAT2A and EAT2B are thought to control signal transduction that is initiated by SLAM-related receptors in professional antigen-presenting cells. In this review, we discuss recent findings on the structure and function of proteins of the SAP and SLAM families. C1 Univ Barcelona, Sch Med, Dept Cellular Biol & Pathol, Immunol Unit, E-08036 Barcelona, Spain. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Immunol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Engel, P (reprint author), Univ Barcelona, Sch Med, Dept Cellular Biol & Pathol, Immunol Unit, E-08036 Barcelona, Spain. NR 108 TC 208 Z9 215 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD OCT PY 2003 VL 3 IS 10 BP 813 EP 821 DI 10.1038/nri1202 PG 9 WC Immunology SC Immunology GA 732XK UT WOS:000185970700014 PM 14523387 ER PT J AU Jin, L Sliz, P Chen, L Macian, F Rao, A Hogan, PG Harrison, SC AF Jin, L Sliz, P Chen, L Macian, F Rao, A Hogan, PG Harrison, SC TI An asymmetric NFAT1 dimer on a pseudo-palindromic kappa B-like DNA site SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; PROTEINS; FAMILY; COMPLEX AB The crystal structure of the NFAT1 Rel homology region (RHR) bound to a pseudo-palindromic DNA site reveals an asymmetric dimer interaction between the RHR-C domains, unrelated to the contact seen in Rel dimers such as NFkappaB. Binding studies with a form of the NFAT1 RHR defective in the dimer contact show loss of cooperativity and demonstrate that the same interaction is present in solution. The structure we have determined may correspond to a functional NFAT binding mode at palindromic sites of genes induced during the anergic response to weak TCR signaling. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02215 USA. RP Harrison, SC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RI Chen, Lin/A-3392-2008; OI Macian, Fernando/0000-0003-2666-035X NR 20 TC 42 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD OCT PY 2003 VL 10 IS 10 BP 807 EP 811 DI 10.1038/nsb975 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 726WQ UT WOS:000185624900011 PM 12949491 ER PT J AU Barr, RG Seliger, S Appel, GB Zuniga, R D'Agati, V Salmon, J Radhakrishnan, J AF Barr, RG Seliger, S Appel, GB Zuniga, R D'Agati, V Salmon, J Radhakrishnan, J TI Prognosis in proliferative lupus nephritis: the role of socio-economic status and race/ethnicity SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE poverty; prognosis; proliferative lupus nephritis; race/ethnicity; socio-economic status; systemic lupus erythematosus ID LONG-TERM PROGNOSIS; 3 ETHNIC-GROUPS; CYCLOPHOSPHAMIDE THERAPY; ERYTHEMATOSUS; PREDICTORS; SURVIVAL; OUTCOMES; RACE; HYPERTENSION; AMERICANS AB Background. Studies of proliferative lupus nephritis (PLN) suggest that African-Americans have a poorer prognosis than Whites. However, no study has simultaneously examined socio-economic status. We studied rates of progression of PLN among a tri-ethnic population with respect to socio-economic status and race/ethnicity. Methods. A retrospective cohort study was carried out using individual and census-based neighbourhood data. Consecutive patients in urban tertiary care centres with biopsy-proven PLN were studied. The main outcome was time to doubling of serum creatinine. Results. Among 128 patients with PLN, the percentage of patients who did not double their serum creatinine at 5 years was 67.0% ( 4.8%) and at 10 years was 58.9% (15.7%). In bivariate analyses, residence in a poor neighbourhood was positively associated with progression (P = 0. 03), as was African-American and Hispanic race/ethnicity (P=0.01). Residence in a poor neighbourhood remained associated with progression of disease after adjustment for age, sex, creatinine, hypertension, cyclophosphamide treatment and race/ ethnicity [relative risk (RR) 3.5, 95% confidence interval (CI) 1.2-11, P=0.03]. After adjustment for poverty and insurance, the RR for African-American race/ethnicity was reduced from 3.5 to 2.7 and was not statistically associated with progression of disease in the full model (P = 0. 10). A similar reduction in RR from 5.5 to 3.6 was seen for Hispanic race/ethnicity, but this retained statistical significance (P = 0.03). Conclusions. Poverty is an important risk factor for progression of PLN, independent of race/ethnicity. Hispanics have an elevated risk similar to or greater than African-Americans. Given these findings, some of the poorer prognosis of African-American patients with PLN may result from socio-economic rather than biological or genetic factors. C1 Columbia Univ, Coll Phys & Surg, Div Gen Med, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Med, Div Nephrol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gen Med Div, Boston, MA USA. Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Univ Arkansas, Div Clin Immunol & Rheumatol, Dept Internal Med, Little Rock, AR 72204 USA. Cornell Univ, Wiell Med Coll, Hosp Special Surg, Dept Med,Div Rheumatol, New York, NY USA. RP Radhakrishnan, J (reprint author), Columbia Presbyterian Med Ctr, 622 W 168th St, New York, NY 10032 USA. FU BHP HRSA HHS [PE-11001] NR 26 TC 119 Z9 121 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2003 VL 18 IS 10 BP 2039 EP 2046 DI 10.1093/ndt/gfg345 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 726FZ UT WOS:000185589400016 PM 13679478 ER PT J AU Thongboonkerd, V Klein, JB Arthur, JM AF Thongboonkerd, V Klein, JB Arthur, JM TI Proteomic identification of a large complement of rat urinary proteins SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE proteomics; proteome; kidney; biomarker; L-myc; ezrin; GAP-43; 2-D PAGE; 2-D Western blot; posttranslational modifications ID OXIDATIVELY MODIFIED PROTEINS; ALZHEIMERS-DISEASE BRAIN; 2-DIMENSIONAL ELECTROPHORESIS; MASS-SPECTROMETRY; L-MYC; EXPRESSION; BINDING; KINASE; PRECIPITATION; GROWTH AB The characterization of urinary proteins is an important tool to identify disease-related biomarkers and to better understand renal physiology. Expression of urinary proteins has been previously studied by Western blotting and other immunological methods. The scope of such studies, however, is limited to previously identified proteins for which specific antibodies are existed. We used proteomic analysis to identify proteins and to construct a proteome map for Sprague-Dawley (SD) rat urine isolated by ultracentrifugation. Urinary proteins were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and visualized by silver staining. Proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), followed by peptide mass fingerprinting using the NCBI protein database. A total of 350 protein spots were visualized. From 250 excised spots, 111 protein components were identified including transporters, transport regulators, chaperones, enzymes, signaling proteins, cytoskeletal proteins, pheromone-binding proteins, receptors, and novel gene products. The presence of a number of these identified proteins was unexpected and had not previously been identified in the urine. 2-D Western blot analyses for randomly selected proteins (ezrin, HSP70, beta- and gamma-actin, Rho-GDI, and I-myc) clearly confirmed the proteomic identification. Several potential posttranslational modifications were predicted by bioinformatic analyses. These data indicate that a large complement of expected and unexpected urinary proteins can be simultaneously studied by proteomic analysis. This approach may lead to better understanding of renal physiology and pathophysiology, and to biomarker discovery. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Louisville, Kidney Dis Program, Core Proteom Lab, Dept Med, Louisville, KY 40202 USA. Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40202 USA. Vet Adm, Louisville, KY USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Thongboonkerd, V (reprint author), Univ Louisville, Kidney Dis Program, Core Proteom Lab, Dept Med, 570 S Preston St,Suite 102, Louisville, KY 40202 USA. RI THONGBOONKERD, VISITH /C-6920-2009; Klein, Jon/B-9833-2013 FU NHLBI NIH HHS [R01 HL66358-01]; NIDDK NIH HHS [R21 DK62086-01] NR 28 TC 29 Z9 32 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PD OCT PY 2003 VL 95 IS 2 BP E69 EP E78 DI 10.1159/000073674 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 742VH UT WOS:000186538400004 PM 14610326 ER PT J AU Brownell, AL Canales, K Chen, YI Jenkins, BG Owen, C Livni, E Yu, MX Cicchetti, F Sanchez-Pernaute, R Isacson, O AF Brownell, AL Canales, K Chen, YI Jenkins, BG Owen, C Livni, E Yu, MX Cicchetti, F Sanchez-Pernaute, R Isacson, O TI Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model SO NEUROIMAGE LA English DT Article DE positron emission tomography; volume rendering; MPTP; Parkinson's disease ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; GLUCOSE METABOLIC-RATE; DOPAMINE D2 RECEPTORS; F-18 FLUORODEOXYGLUCOSE; DIFFERENTIAL-DIAGNOSIS; TREATED MONKEYS; BASAL GANGLIA; NORMAL VALUES; C-11 CFT AB Neurophysiological studies of the brain in normal and Parkinson's disease (PD) patients have indicated intricate connections for basal ganglia-induced control of signaling into the motor cortex. To investigate if similar mechanisms are controlling function in the primate brain (Macaca fascicularis) after MPTP-induced neurotoxicity, we conducted PET studies of cerebral blood flow, oxygen and glucose metabolism, dopamine transporter, and D2 receptor function. Our observations after MPTP-induced dopamine terminal degeneration of the caudate and putamen revealed increased blood flow (15%) in the globus pallidus (GP), while blood flow was moderately decreased (15-25%) in the caudate, putamen, and thalamus and 40 % in the primary motor cortex (PMC). Oxygen extraction fraction was moderately increased (10-20%) in other brain areas but the thalamus, where no change was observable. Oxygen metabolism was increased in the GP and SMA (supplementary motor area including premotor cortex, Fig. 3) by a range of 20-40% and decreased in the putamen and caudate and in the PMC. Glucose metabolism was decreased in the caudate, putamen, thalamus, and PMC (range 35-50%) and enhanced in the GP by 15%. No change was observed in the SMA. In the parkinsonian primate, [C-11]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyltropane) dopamine transporter binding was significantly decreased in the putamen and caudate (range 60-65%). [C-11]Raclopride binding of dopamine D-2 receptors did not show any significant changes. These experimental results obtained in primate studies of striato-thalamocortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. McLean Hosp, Neurogenerat Lab, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. RP Brownell, AL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Bartlett Hall 504R, Boston, MA 02114 USA. EM abrownell@partners.org FU NINDS NIH HHS [NS P50-39793] NR 67 TC 38 Z9 43 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2003 VL 20 IS 2 BP 1064 EP 1075 DI 10.1016/S1053-8119(03)00348-3 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 737YV UT WOS:000186260700038 PM 14568476 ER PT J AU Sperling, R Chua, E Cocchiarella, A Rand-Giovannetti, E Poldrack, R Schacter, DL Albert, M AF Sperling, R Chua, E Cocchiarella, A Rand-Giovannetti, E Poldrack, R Schacter, DL Albert, M TI Putting names to faces: Successful encoding of associative memories activates the anterior hippocampal formation SO NEUROIMAGE LA English DT Article ID MEDIAL TEMPORAL-LOBE; MILD ALZHEIMERS-DISEASE; RECOGNITION MEMORY; WORKING-MEMORY; BRAIN ACTIVITY; RHESUS-MONKEY; RETRIEVAL; FMRI; PARAHIPPOCAMPAL; CORTEX AB The ability to form associations between previously unrelated items of information, such as names and faces, is an essential aspect of episodic memory function. The neural substrate that determines success vs. failure in learning these associations remains to be elucidated. Using event-related functional MRI during the encoding of novel face-name associations, we found that successfully remembered face-name pairs showed significantly greater activation in the anterior hippocampal formation bilaterally and left inferior prefrontal cortex, compared to pairs that were forgotten. Functional connectivity analyses revealed significant correlated activity between the right and left hippocampus and neocortical regions during successful, but not attempted, encoding. These findings suggest that anterior regions, of the hippocampal formation, in particular, are crucial for successful associative encoding and that the degree of coordination between hippocampal and neocortical activity may predict the likelihood of subsequent memory. (C) 2003 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Ctr Neurocognit Studies, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Martinas Ctr Biomed Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. RP Sperling, R (reprint author), Brigham & Womens Hosp, Ctr Neurocognit Studies, Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM reisa@rics.bwh.harvard.edu RI Chua, Elizabeth/B-3770-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [P01 AG004953, P01-AG-04953]; NIMH NIH HHS [MH60941, R01 MH060941]; NINDS NIH HHS [K23 NS002189, K23 NS002189-03, K23-NS02189] NR 58 TC 205 Z9 209 U1 2 U2 13 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 OCT PY 2003 VL 20 IS 2 BP 1400 EP 1410 DI 10.1016/S1053-8119(03)00391-4 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 737YV UT WOS:000186260700071 PM 14568509 ER PT J AU Siri, S Kensinger, EA Cappa, SF Hood, KL Corkin, S AF Siri, S Kensinger, EA Cappa, SF Hood, KL Corkin, S TI Questioning the living/nonliving dichotomy: Evidence from a patient with an unusual semantic dissociation SO NEUROPSYCHOLOGY LA English DT Article ID CATEGORY-SPECIFIC IMPAIRMENT; ALZHEIMERS-DISEASE; CONCEPTUAL KNOWLEDGE; DISTRIBUTED ACCOUNT; MULTIPLE SEMANTICS; FACE PERCEPTION; NEURAL BASIS; DEMENTIA; MEMORY; SPECIFICITY AB In this article the authors describe a patient (J.P.) whose category-specific naming deficit eluded the classical dichotomies between living versus nonliving items or visual versus functional attributes. At age 22, he had herpes simplex encephalitis followed by a left temporal lobectomy. J.P. was tested on measures of visual perception, category naming, fluency, and name-picture matching. He showed a severe impairment naming and identifying fruits, vegetables, and musical instruments. His performance with animals and birds was spared inconsistently, meaning that even the preserved categories were, at some point, affected. J.P.'s unusual deficit supports the hypothesis that semantic knowledge is organized in the brain on the basis of object properties, which can cut across the living-nonliving categorical distinction. C1 Vita Salute San Raffaele Univ, Dept Psychol, I-20132 Milan, Italy. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. IRCCS, Ctr San Giovanni Dio, Neuropsychol Lab, Brescia, Italy. Univ Calif San Diego, Grad Program Neurosci, San Diego, CA 92103 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Siri, S (reprint author), Vita Salute San Raffaele Univ, Dept Psychol, Via Olgettina 58, I-20132 Milan, Italy. FU NCRR NIH HHS [P41RR14075, RR00088] NR 73 TC 9 Z9 9 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD OCT PY 2003 VL 17 IS 4 BP 630 EP 645 DI 10.1037/0894-4105.17.4.630 PG 16 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 740AP UT WOS:000186378900010 PM 14599276 ER PT J AU Brisman, JL Cole, AJ Cosgrove, GR Thornton, AF Rabinov, J Bussiere, M Bradley-Moore, M Hedley-Whyte, T Chapman, PH AF Brisman, JL Cole, AJ Cosgrove, GR Thornton, AF Rabinov, J Bussiere, M Bradley-Moore, M Hedley-Whyte, T Chapman, PH TI Radiosurgery of the rat hippocampus: Magnetic resonance imaging, neurophysiological, histological, and behavioral studies SO NEUROSURGERY LA English DT Article DE behavior; immunocytochemistry; magnetic resonance imaging; neurophysiology; radiosurgery; rat ID GAMMA-KNIFE IRRADIATION; BINDING PROTEIN CALBINDIN-D28K; TEMPORAL-LOBE EPILEPSY; STEREOTACTIC RADIOSURGERY; PROTON-BEAM; PARVALBUMIN IMMUNOCYTOCHEMISTRY; ARTERIOVENOUS-MALFORMATIONS; SELECTIVE VULNERABILITY; STATUS EPILEPTICUS; SEIZURE ACTIVITY AB OBJECTIVE: To explore the histological, electrophysiological, radiological, and behavioral effects of radiosurgery using a new model of proton beam radiosurgery (PBR) of the rodent hippocampus. METHODS: Forty-one rats underwent PBR of the right hippocampus with nominal-doses of 5 to 130 cobalt Gray equivalents (CGE): Three control animals were untreated. Three months after PBR, 41 animals were evaluated with the Morris water maze, 23 with T2-weighted magnetic resonance imaging, and 22 with intrahippocampal microelectrode recordings. Animals that were studied physiologically were killed, and their brains were examined with Nissl staining and immunocytochemical staining for glutamic acid decarboxylase, heat shock in 72 (HSP-72), parvalbumin, calmodulin, calretinin, calbindin, and somatostatin. RESULTS: Ninety and 130 CGE resulted in decreased performance in the Morris water maze, increased signal on T2-weighted magnetic, resonance imaging, diminished granule cell field potentials, and tissue necrosis, which was restricted to the irradiated side. These doses also resulted in ipsilateral, up-regualation of calbindin and HSP-72. Parvalbumin was down-regulated at 130 CGE. The 30 and 60 CGE animals displayed a marked increase in HSP-72 staining on the irradiated side but no demonstrable cell loss. No asymmetries were noted in somatostatin, calretinin, and glutamic acid de-carboxylase staining. Normal physiology was found in rats receiving up to 60 CGE. CONCLUSION: This study expands our understanding of the effects of radiosurgery on the mammalian brain. Three months after PBR, the irradiated rat hippocampus demonstrates necrosis at 90 CGE, but not at 60 CGE, with associated abnormalities in magnetic resonance imaging, physiology and memory testing. HSP-72 was up-regulated at nonnecrotic doses. C1 Massachusetts Gen Hosp, Neurosurg Serv, Epilepsy Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, NE Proton Beam Reg Therapy Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. RP Cole, AJ (reprint author), Massachusetts Gen Hosp, Epilepsy Serv, VBK 830,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 036224] NR 49 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2003 VL 53 IS 4 BP 951 EP 961 DI 10.1227/01.NEU.0000083629.92550.A5 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 731QP UT WOS:000185898200050 PM 14519227 ER PT J AU Rigotti, NA Moran, SE AF Rigotti, NA Moran, SE TI US college students' exposure to tobacco promotions at bars, clubs, and campus events: Prevalence and relationship to tobacco SO NICOTINE & TOBACCO RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD OCT PY 2003 VL 5 IS 5 BP 791 EP 791 PG 1 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 734KF UT WOS:000186054200065 ER PT J AU Hughes, CV Malki, G Loo, CY Tanner, ACR Ganeshkumar, N AF Hughes, CV Malki, G Loo, CY Tanner, ACR Ganeshkumar, N TI Cloning and expression of alpha-D-glucosidase and N-acetyl-beta-glucosaminidase from the periodontal pathogen, Tannerella forsythensis (Bacteroides forsythus) SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Tannerella forsythensis; Bacteroides forsythus; glycosidases; glucosidase; glycosaminidase ID PORPHYROMONAS-GINGIVALIS W50; IDENTIFICATION; GENE; PROTEOGLYCANS; NOV; IGG AB Screening a genomic library of Tannerella forsythensis (Bacteroides forsythus), using synthetic substrates conjugated to a fluorogen, 4-methylumbelliferone identified two glycosidase genes, which encode alpha-D-glucosidase and N-acetyl-beta-D-glucosaminidase, respectively. The alpha-D-glucosidase has a M-r of 81,141 and is homologous to an alpha-D-glucosidase from Bacteroides thetaiotaomicron. The N-acetyl-beta-D-glucosaminidase has a M-r of 87,787 and is homologous to an N-acetyl-beta-D-glucosaminidase in Porphyromonas gingivalis W83. C1 Boston Univ, Goldman Sch Dent Med, Dept Pediat Dent, Boston, MA 02118 USA. Forsyth Inst, Boston, MA USA. RP Ganeshkumar, N (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Pediat Dent, 801 Albany St,S-215, Boston, MA 02118 USA. RI Hughes, Christopher/E-1438-2014 FU NIDCR NIH HHS [DE13328, DE09513] NR 21 TC 26 Z9 27 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD OCT PY 2003 VL 18 IS 5 BP 309 EP 312 DI 10.1034/j.1399-302X.2003.00091.x PG 4 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 717KV UT WOS:000185088400007 PM 12930523 ER PT J AU Haddad, R Colevas, AD Krane, JF Cooper, D Glisson, B Amrein, PC Weeks, L Costello, R Posner, M AF Haddad, R Colevas, AD Krane, JF Cooper, D Glisson, B Amrein, PC Weeks, L Costello, R Posner, M TI Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study SO ORAL ONCOLOGY LA English DT Article DE salivary gland tumors; Herceptin; Her2/Neu ID MONOCLONAL-ANTIBODY; BREAST-CANCER; CHEMOTHERAPY; HER-2/NEU; CISPLATIN; CYCLOPHOSPHAMIDE; OVEREXPRESSION; MALIGNANCIES; DOXORUBICIN; NEOPLASMS AB Phase II study of Herceptin(R) (Trastuzumab) in patients with advanced salivary gland tumors overexpressing Her2/neu. Patients with advanced, incurable salivary gland tumors and 2+ or 3+ Her2/neu expression in their tumors were enrolled in the study. After an initial dose of 4 mg/kg, patients received 2 mg/kg weekly. Patients were treated until they experienced progression of disease or unacceptable toxicity. The study was closed early when it has become clear that the majority of tumors screened did not overexpress Her2/neu. Fourteen patients were enrolled in the study. A total of 86 cycles of Herceptin were delivered with a median of three cycles per patient (range 1-40). Median time to progression was 4.2 months. One patient with metastatic mucoepidermoid carcinoma has received 40 cycles of Herceptin to date with a documented partial response. Herceptin given as a single agent has a low activity in salivary gland tumors overexpressing Her2/neu. New agents are still needed. (C) 2003 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Invest Drug Branch, CTEP, Rockville, MD 20892 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Yale Univ, Ctr Canc, New Haven, CT 06519 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Haddad, R (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, SW430G,44 Binney St, Boston, MA 02115 USA. NR 17 TC 110 Z9 112 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD OCT PY 2003 VL 39 IS 7 BP 724 EP 727 DI 10.1016/S1368-8375(03)00097-6 PG 4 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 721BC UT WOS:000185296300012 PM 12907212 ER PT J AU Gordon, BR AF Gordon, BR TI Approaches to testing for food and chemical sensitivities SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID BASOPHIL HISTAMINE-RELEASE; SKIN PRICK TESTS; CONTACT-DERMATITIS; ATOPIC-DERMATITIS; PATCH TESTS; PROVOCATION-NEUTRALIZATION; INHALANT ALLERGENS; TOOTH FILLINGS; MULTI-CENTER; EXPOSURE AB This article is an introduction to the topic of testing for allergy or sensitivity to foods and chemicals. The clinical patterns of food and chemical sensitivity and the diagnostic methods for determining the existence and magnitude of reactions to either foods or chemicals are surveyed. Concepts of fixed, anaphylactic food allergy and cyclic, non-IgE-mediated food allergy are reviewed and contrasted, and the relative benefits of the appropriate tests for each type are discussed. The pathophysiology of acute and chronic chemical toxicity is briefly reviewed and compared with true chemical allergy, and useful screening and definitive tests to identify each type are identified. C1 Harvard Univ, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Cape Cod Hosp, Hyannis, MA USA. RP Gordon, BR (reprint author), Harvard Univ, Dept Otol & Laryngol, Cambridge, MA 02138 USA. NR 105 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2003 VL 36 IS 5 BP 917 EP + DI 10.1016/S0030-6665(03)00059-8 PG 25 WC Otorhinolaryngology SC Otorhinolaryngology GA 736KM UT WOS:000186170000012 PM 14743781 ER PT J AU Kamil, SH Woda, M Bonassar, LJ Novitsky, YW Vacanti, CA Eavey, RD Vacanti, MP AF Kamil, SH Woda, M Bonassar, LJ Novitsky, YW Vacanti, CA Eavey, RD Vacanti, MP TI Normal features of tissue-engineered auricular cartilage by flow cytometry and histology: Patient safety SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID TUMORS; CHONDROCYTES; GROWTH AB BACKGROUND: Cytokinetic abnormalities in DNA content, such as aneuploidy, haploidy, and tetraploidy, have been found to occur in human cartilaginous tumors. The high number of chondrocytes needed for tissue-engineered cartilaginous implants requires the cells to be passaged repeatedly. The theoretical risk of changes in the normal diploid state of these cells during their growth in vitro and after generation of tissue-engineered cartilage in vivo is not known. MATERIALS AND METHODS: Auricular chondrocytes were obtained from 6 patients and cultured in vitro. Chondrocyte number was increased by repeated passaging. The passaged cells were implanted in nude mice for 8 weeks to generate tissue-engineered cartilage. Fresh control chondrocytes along with the passaged cells and cells obtained from the tissue-engineered constructs were collected and compared for DNA content by flow cytometry. RESULTS: Flow cytometry demonstrated 100% diploidy with no evidence of aneuploidy, haploidy, or tetraploidy in all groups of cells. Histology of the tissue-engineered cartilage also showed no evidence of cellular atypia. CONCLUSION: The number of human auricular chondrocytes can be increased by repeated passaging and passaged chondrocytes can be safely used for implantation to generate tissue-engineered constructs without a change in the normal diploid state of the cells. Histology of the cartilage generated showed normal features without atypia. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Anesthesiol, Lab Tissue Engn, Amherst, MA 01003 USA. Univ Massachusetts, Sch Med, Core Flow Cytometry Lab, Amherst, MA 01003 USA. Univ Massachusetts, Sch Med, Dept Pathol, Amherst, MA 01003 USA. RP Eavey, RD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 NR 15 TC 11 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2003 VL 129 IS 4 BP 390 EP 396 DI 10.1016/S0194-5998(03)00710-1 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 733XM UT WOS:000186026000013 PM 14574294 ER PT J AU Hohler, AD Ransom, BR Chun, MR Troster, AI Samii, A AF Hohler, AD Ransom, BR Chun, MR Troster, AI Samii, A TI The youngest reported case of corticobasal degeneration SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE corticobasal ganglionic degeneration; corticobasal degeneration; Parkinson's disease; Parkinson Plus syndrome; young onset ID PROGRESSIVE SUPRANUCLEAR PALSY; BASAL GANGLIONIC DEGENERATION; MULTIPLE SYSTEM ATROPHY; ALZHEIMERS-DISEASE; DIAGNOSIS AB Corticobasal degeneration (CBD) is a movement disorder characterized by early apraxia and asymmetric parkinsonism that responds poorly to anti-Parkinson medications. There are clinical manifestations reflecting dysfunction in both the cerebral cortex and the basal ganglia. Patients typically present between the sixth and seventh decades. Previously, the youngest clinically diagnosed individual was 40 years old. Here we describe a 34-year-old woman who meets the clinical diagnostic criteria for CBD with onset of symptoms at age 28. In this patient, the first symptom was an 'uncooperative' right hand. This was soon followed by right hand dystonia. Symptoms progressed rapidly, and she developed generalized bradykinesia, rigidity, and corticospinal tract signs with preservation of the initial asymmetry. Her symptoms did not respond to a daily dose of 1200 mg of immediate release levodopa. Extensive laboratory workup and brain imaging were normal. Neuropsychological evaluation revealed mild deficits consistent with frontal-subcortical dysfunction. The chronic, progressive course, asymmetric limb rigidity, apraxia, focal dystonia, and lack of response to levodopa suggest CBD. To our knowledge, this is the youngest reported case of clinically probable CBD. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98108 USA. Madigan Army Med Ctr, Dept Neurol, Tacoma, WA 98431 USA. Everett Neurol Ctr, Everett, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Samii, A (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Neurol, 1660 S Columbian Way,Mailstop 127, Seattle, WA 98108 USA. OI Ransom, Bruce R./0000-0002-9658-0294; Hohler, Anna/0000-0003-3134-1708 NR 18 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD OCT PY 2003 VL 10 IS 1 BP 47 EP 50 DI 10.1016/S1353-8020(03)00046-4 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 737UB UT WOS:000186249200009 ER PT J AU MacGinnitie, AJ Walensky, LD Turvey, SE Orange, JS Bonilla, FA Silverman, LB Oettgen, H AF MacGinnitie, AJ Walensky, LD Turvey, SE Orange, JS Bonilla, FA Silverman, LB Oettgen, H TI Management of an anaphylactoid reaction to methotrexate with a stepwise graded challenge SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Article DE methotrexate; leukemia; hypersensitivity; skin tests ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDREN AB We report the management of a 15-year-old boy with an anaphylactic or anaphylactoid response to his first dose of methotrexate during induction therapy for acute lymphoblastic leukemia (ALL). Because weekly methotrexate therapy is an important component of continuation chemotherapy for pediatric ALL, a stepwise graded challenge was employed to achieve drug tolerance. C1 Childrens Hosp, Div Allergy Immunol, Boston, MA 02446 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP MacGinnitie, AJ (reprint author), Childrens Hosp, Div Allergy Immunol, Fegan 6, Boston, MA 02446 USA. RI Orange, Jordan/D-5239-2009; OI orange, jordan/0000-0001-7117-7725 NR 8 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-6157 J9 PEDIATR ALLERGY IMMU JI Pediatr. Allergy Immunol. PD OCT PY 2003 VL 14 IS 5 BP 409 EP 411 DI 10.1034/j.1399-3038.2003.00073.x PG 3 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA 736JR UT WOS:000186168100012 PM 14641613 ER PT J AU Heath, JA Turner, CD Poussaint, TY Scott, RM Goumnerova, L Kieran, MW AF Heath, JA Turner, CD Poussaint, TY Scott, RM Goumnerova, L Kieran, MW TI Chemotherapy for progressive low-grade gliomas in children older than ten years: The Dana-Farber experience SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE astrocytoma; chemotherapy; children; low-grade glioma ID CENTRAL-NERVOUS-SYSTEM; GROUP PHASE-II; YOUNG-CHILDREN; BRAIN-TUMORS; CARBOPLATIN; RADIATION; ASTROCYTOMA; CHILDHOOD; THERAPY AB The Purpose of this retrospective study was to examine the clinical and radiographic response rates to and toxicity of chemotherapy for low-grade gliomas in children older than 10 years of age. Between June 1999 and January 2001, seven consecutive children between the ages of 10 and 18 were treated with vincristine and carboplatin thioguanine, procarbazine, CCNU[lomustine], and vincristine (TPCV) for progressive low-grade gliomas. All 7 children completed a 10-week induction course of vincristine and carboplatin; 3 were switched to TPCV during the maintenance phase of therapy after developing an allergic reaction to carboplatin. Overall, 4 patients had a radiographic response to treatment with chemotherapy (3 partial responses and I minor response: objective response rate of 57%), and 2 more showed stable disease. One patient progressed while on treatment and I patient progressed off treatment, and after 31 months had elapsed. 7 he resulting progression-free survival at the time of this report was 71%. The median duration of follow-up was 32 months (range 25-42 months). Hematologic toxicity was common, but did not result in cessation of therapy. No other significant treatment-related toxicities were observed. The results suggest that the clinical response/disease stabilization rate in children older than 10 years of age does not differ markedly from that observed in younger children. A prospective clinical trial of chemotherapy for progressive low-grade gliomas in children older than 10 years is therefore warranted. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Neurosurg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Heath, JA (reprint author), Royal Childrens Hosp, Dept Clin Haematol & Oncol, Flemington Rd, Parkville, Vic 3052, Australia. OI Kieran, Mark/0000-0003-2184-7692 NR 18 TC 10 Z9 10 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD OCT-NOV PY 2003 VL 20 IS 7 BP 497 EP 504 DI 10.1080/08880010390232709 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 728YB UT WOS:000185743000001 PM 12959854 ER PT J AU Svoren, BM Butler, D Levine, BS Anderson, BJ Laffel, LMB AF Svoren, BM Butler, D Levine, BS Anderson, BJ Laffel, LMB TI Reducing acute adverse outcomes in youths with type 1 diabetes: A randomized, controlled trial SO PEDIATRICS LA English DT Article; Proceedings Paper CT 60th Scientific Sessions of the American-Diabetes-Association CY JUN 09-13, 2000 CL San Antonio, TX SP Amer Diabet Assoc DE type 1 diabetes; pediatrics; case management; HbA1c; adverse outcomes ID POOR GLYCEMIC CONTROL; COMPLICATIONS TRIAL; METABOLIC-CONTROL; CASE-MANAGEMENT; HEART-FAILURE; MELLITUS; ADOLESCENTS; INTERVENTION; ASSOCIATION; CHILDREN AB Objective. Both acute and chronic complications of diabetes account for a disproportionate percentage of US health care expenditures. Despite improvements in diabetes care, the incidence of adverse events in children with type 1 diabetes remains high, particularly for youths with poor glycemic control. Cost-effective intervention programs designed to reduce complications are needed. This study evaluated a low-intensity, nonmedical intervention using a case manager ( called a "Care Ambassador"), with and without the supplementation of psychoeducational modules, designed to monitor and encourage routine diabetes care visits to reduce short-term adverse outcomes and improve glycemic control in youths with type 1 diabetes. Methods. We performed a 2-year prospective, randomized clinical trial in 299 youths with type 1 diabetes, aged 7 to 16 years, comparing 3 treatment programs ( Care Ambassador [ CA], Care Ambassador plus psychoeducational modules [CA+], and standard multidisciplinary diabetes care [SC]). The study was conducted in a large metropolitan US city from April 1997 through April 2000. Number of medical visits, frequency of hypoglycemic events, hospital/emergency department (ED) utilization, and glycosylated hemoglobin A1c were assessed during follow-up. Results. During the 2-year study period, both the CA and CA+ groups had significantly more routine visits ( mean [ standard deviation]: 7.3 [2.06] and 7.5 [2.02], respectively) compared with the SC group (5.4 [2.62]). The CA+ intervention group had significantly reduced rates of short-term adverse outcomes compared with the other 2 groups; 25% fewer total hypoglycemic events, 60% fewer severe hypoglycemic events, and 40% fewer hospitalizations and ED visits. "High-risk" youths in the CA+ group ( baseline glycosylated hemoglobin A1c greater than or equal to8.7%) were 3.4-fold (1.57-7.41) more likely to improve their glycemic control compared with those at high risk in the other 2 groups. Conclusions. For youths with type 1 diabetes, the CA and CA+ interventions increased visit frequency. Youths in the CA+ intervention had reduced rates of hypoglycemia and hospital/ED utilization with estimated annual cost savings of $80 000 to $90 000. The CA+ intervention compared with the other 2 groups improved glycemic control in "high-risk" youths. Nonmedical case management incorporating psychoeducational modules seems to be a cost-effective approach to improving outcomes in youths with diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr,Behav Res & Menatl Hlth Sect, Pediat & Adolescent Unit,Genet & Epidemiol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA USA. RP Laffel, LMB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr,Behav Res & Menatl Hlth Sect, Pediat & Adolescent Unit,Genet & Epidemiol Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [DK-46887] NR 44 TC 65 Z9 67 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD OCT 1 PY 2003 VL 112 IS 4 BP 914 EP 922 DI 10.1542/peds.112.4.914 PG 9 WC Pediatrics SC Pediatrics GA 727NV UT WOS:000185665700037 PM 14523186 ER PT J AU Mendez, MF AF Mendez, MF TI Surveying a blank field with the attentional spotlight SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID VISUAL-SPATIAL ATTENTION; SELECTIVE ATTENTION; FEATURE-INTEGRATION; EXOGENOUS CUE; MOVEMENT; SHIFTS; VISION; TASKS; FOCUS AB Spatial localization is a unique aspect of selective attention that precedes and facilitates other aspects of sensory processing. A common model of spatial attention is an attentional spotlight that enlarges to fit attentional demands. It is unclear if this attentional spotlight expands to survey a blank field or to scan the spatial environment with a smaller attentional spotlight. Two tachistoscopic experiments with young adults investigated how attention is surveyed in a blank field. Exp. 1 consisted of single letters at two concentric regions and under different conditions of attentional demand. Reaction times were proportionally slower for stimuli occurring in a combination of the two regions located at different distances from the fixation point than for stimuli occurring in each region alone. This finding is not consistent with attentional spread to encompass the entire attentional field. The addition of more stimulus locations within each single region yielded significantly slower reaction times. Together these findings suggest that a small attentional spotlight serially monitors different regions of the visual field when there are anticipated locations to be attended. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol,Neurobehav Unit 116AF, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat,Neurobehav Unit 116AF, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol,Neurobehav Unit 116AF, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 USA SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD OCT PY 2003 VL 97 IS 2 BP 560 EP 568 PG 9 WC Psychology, Experimental SC Psychology GA 736GW UT WOS:000186163900030 PM 14620245 ER PT J AU Kohane, DS Anderson, DG Yu, C Langer, R AF Kohane, DS Anderson, DG Yu, C Langer, R TI pH-triggered release of macromolecules from spray-dried polymethacrylate microparticles SO PHARMACEUTICAL RESEARCH LA English DT Article DE drug delivery; intracellular; biocompatibility; controlled release ID PROTEIN-SUGAR PARTICLES; SCIATIC-NERVE BLOCKADE; SENSITIVE LIPOSOMES; DELIVERY SYSTEMS; DRUG-DELIVERY; IN-VIVO; MICROSPHERES; BIOCOMPATIBILITY; BUPIVACAINE; VACCINES AB Purpose. pH-triggered microparticles release their therapeutic payloads at acidic pH ( e. g., in the phagosome), making intracellular drug delivery more efficient. Here we modify lipid-based microparticles that are safe and efficacious in nerve and brain and are potentially inhalable, making them pH-triggerable by incorporating an acid-soluble polymethacrylate, Eudragit E100 ( E100). Methods. Microparticles were produced by spray-drying and characterized by electron microscopy, Coulter counting, density measurement, and release kinetics of fluorescently labeled proteins. In addition, biocompatibility and cellular uptake were observed in rats. Results. Microparticles were spheroids 3 to 5 mum in diameter with densities of 0.12 to 0.25 g/L. Microparticles with 20% (w/w) or more E100 demonstrated slow release of fluorescently labeled proteins at pH 7.4 but rapid release at pH 5. pH-triggerability was maintained for over 2 weeks in solution. Protein loadings of 0.2 - 20% ( w/w) were pH-triggerable. Histologic examination of particles in rat connective tissue near nerve and muscle demonstrated biocompatibility aside from muscle edema in the cell layers adjacent to the particles and a localized inflammatory reaction with macrophages laden with microparticles. Conclusions. Microparticles containing E100 were pH-triggerable for many days and were taken up by macrophages, suggesting that they may be useful for intracellular drug delivery. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. FU NIGMS NIH HHS [GM00684, GM26698] NR 24 TC 14 Z9 14 U1 1 U2 15 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD OCT PY 2003 VL 20 IS 10 BP 1533 EP 1538 DI 10.1023/A:1026162628965 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 733AK UT WOS:000185977600002 PM 14620503 ER PT J AU Pisegna, JR AF Pisegna, JR TI Treating patients with acute gastrointestinal bleeding or rebleeding SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Spring Practice and Research Forum of the American College of Clinical Pharmacy CY APR 02, 2000 CL MONTEREY, CALIFORNIA SP Amer Coll Clin Pharmacy ID ZOLLINGER-ELLISON-SYNDROME; GASTRIC-ACID HYPERSECRETION; PROTON PUMP INHIBITORS; PEPTIC-ULCER; INTRAVENOUS PANTOPRAZOLE; INTRAGASTRIC PH; ECL CELLS; NONVARICEAL; SUPPRESSION; SECRETION AB Despite advances in medical management, gastrointestinal bleeding remains a substantial cause of morbidity and mortality. At risk are patients with history of the event, those taking nonsteroidal antiinflammatory agents, and those with active peptic ulcer disease. Endoscopy may be performed for diagnosis and treatment. Antisecretory therapy may be employed to control gastric acid secretion, treat active peptic ulcer disease, and control symptoms such as diarrhea and abdominal pain. Options for antisecretory therapy include histamine(2)-receptor antagonists (H2RAs) that target the histamine pathway, and proton pump inhibitors (PPIs) that target the final step in acid secretion. The H2RAs generally are ineffective at reaching a target pH of 6 in patients with gastrointestinal bleeding because of tachyphylaxis. The PPIs are more effective and do not lead to tachyphylaxis. With the availability of an intravenous PPI, pantoprazole, options for managing hospitalized patients with gastrointestinal bleeding are expanding. C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 23 TC 2 Z9 3 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 SU S BP 81S EP 86S DI 10.1592/phco.23.13.81S.31930 PN 2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 730JZ UT WOS:000185828800006 PM 14587962 ER PT J AU Haines, ST AF Haines, ST TI The diabetes epidemic: Can we stop the spread? SO PHARMACOTHERAPY LA English DT Editorial Material ID MULTIFACTORIAL INTERVENTION; LIFE-STYLE; MELLITUS; TRIAL; CARE; OBESITY; CHOLESTEROL; PHARMACISTS; PREVENTION; REDUCTION C1 Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. Univ Maryland Med, Joslin Diabet Ctr, Baltimore, MD USA. RP Haines, ST (reprint author), Univ Maryland, Sch Pharm, Dept Pharm Practice & Sci, 100 Penn St,Room 240H, Baltimore, MD 21201 USA. OI Haines, Stuart/0000-0001-8217-1871 NR 31 TC 3 Z9 3 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1227 EP 1231 DI 10.1592/phco.23.12.1227.32708 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200001 PM 14594339 ER PT J AU Worrall, TJ Simpson, KN Jenrette, DE Johnson, RH AF Worrall, TJ Simpson, KN Jenrette, DE Johnson, RH TI Appropriate treatment of systolic heart failure in the primary care clinics. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1332 EP 1332 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200035 ER PT J AU Lumpkin, AR Hamm, JW Herndon, KC AF Lumpkin, AR Hamm, JW Herndon, KC TI Evaluation of lipid management following coronary artery bypass graft surgery. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Pfizer Inc, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1333 EP 1333 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200037 ER PT J AU McMaster, NL Jung, SA Erwin, TC Linn, WD AF McMaster, NL Jung, SA Erwin, TC Linn, WD TI Acute coronary syndromes: quality of care in an academic VA medical center. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1333 EP 1333 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200036 ER PT J AU Marceille, JR Goins, J Soni, R Biery, J Lee, TA AF Marceille, JR Goins, J Soni, R Biery, J Lee, TA TI Incidence of congestive heart failure-related interventions in patients receiving rosiglitazone and insulin. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1337 EP 1337 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200055 ER PT J AU Weisler, RH Biederman, J Chrisman, A Wilens, TP Michaels, MA Nishihara, K Tulloch, SJ AF Weisler, RH Biederman, J Chrisman, A Wilens, TP Michaels, MA Nishihara, K Tulloch, SJ TI Long-term safety and efficacy of once-daily Adderall (R) XR in adults with attention deficit hyperactivity disorder. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 Univ N Carolina, Raleigh, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Shire Pharmaceut Dev Inc, Rockville, MD USA. Shire US Inc, Newport, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1362 EP 1362 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200164 ER PT J AU Benge, CD Greene, RS AF Benge, CD Greene, RS TI Comprehensive diabetes management: a clinical pharmacy practitioner as a means to improve the health care report card. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeeting of the American-College-of-Clinical-Pharmacy CY NOV 02-05, 2003 CL ATLANTA, GEORGIA SP Amer Coll Clin Pharmacy C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Austin, TX 78712 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Texas Tech Hlth Sci Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2003 VL 23 IS 10 BP 1372 EP 1372 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 728ZX UT WOS:000185747200209 ER PT J AU Zhuang, SG Kochevar, IE AF Zhuang, SG Kochevar, IE TI Singlet oxygen-induced activation of Akt/protein kinase B is independent of growth factor receptors SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID FOCAL ADHESION KINASE; NF-KAPPA-B; PROTEIN-COUPLED RECEPTORS; PHOTODYNAMIC CROSS-LINKING; INDUCED APOPTOSIS; HYDROGEN-PEROXIDE; CELL-SURVIVAL; PHOSPHATIDYLINOSITOL 3-KINASE; OXIDATIVE STRESS; CYTOCHROME-C AB Singlet oxygen (O-1(2))-induced cytotoxicity is believed to be responsible for responses to photodynamic therapy and for apoptosis of T helper cells after UV-A treatment. Other cytotoxic oxidants, such as hydrogen peroxide and peroxynitrite have been shown to stimulate cell survival signaling pathways in addition to causing cell death. Both these oxidants stimulate the Akt/protein kinase B survival signaling pathway through activation of membrane tyrosine kinase growth factor receptors. We evaluated the ability of O-1(2) to activate the Akt/ protein kinase B pathway in NIH 3T3 cells and examined potential activation pathways. Exposure of flbroblasts to O-1(2) elicited a strong and sustained phosphorylation of Akt, which occurred concurrently with phosphorylation of p38 kinase, a proapoptotic signal. Inhibition of phosphatidylinositol-3-OH kinase (PI3-K) completely blocked Akt phosphorylation. Significantly, cell death induced by O-1(2) was enhanced by inhibition of PI3-K, suggesting that activation of Akt by O-1(2) may contribute to fibroblast survival under this form of oxidative stress. O-1(2) treatment did not induce phosphorylation of platelet-derived growth factor receptor (PDGFR) or activate SH-PTP2, a substrate of growth factor receptors, suggesting that PDGFR was not activated. In addition, specific inhibition of PDGFR did not affect Akt phosphorylation elicited by O-1(2). Activation of neither focal adhesion kinase (FAK) nor Ras protein, both of which mediate responses to reactive oxygen species, appeared to be pathways for the O-1(2)-induced activation of the PI3-K-Akt survival pathway. Thus, activation of Akt by O-1(2) is mediated by PI3-K and contributes to a survival response that counteracts cell death after O-1(2)-induced injury. However, unlike the response to other oxidants, activation of the PI3-K-Akt by 1O(2) does not involve activation of growth factor receptors, FAK or Ras protein. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, WEL-224,55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM30755] NR 57 TC 34 Z9 35 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 2003 VL 78 IS 4 BP 361 EP 371 DI 10.1562/0031-8655(2003)078<0361:SOAOPK>2.0.CO;2 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 734YQ UT WOS:000186085900008 PM 14626664 ER PT J AU Iftimia, N AF Iftimia, N TI Grating shrinks endoscope SO PHOTONICS SPECTRA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAURIN PUBL CO INC PI PITTSFIELD PA BERKSHIRE COMMON PO BOX 1146, PITTSFIELD, MA 01202 USA SN 0731-1230 J9 PHOTON SPECTRA JI Photon. Spect. PD OCT PY 2003 VL 37 IS 10 BP 37 EP 38 PG 2 WC Optics SC Optics GA 732FX UT WOS:000185931100006 ER PT J AU Kurylo, DD Tanguay, S AF Kurylo, DD Tanguay, S TI Effects of quinpirole on behavioral extinction SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE quinpirole; dopamine; D-2 receptors; extinction; reinforcement; schizophrenia; obsessive-compulsive disorder ID NUCLEUS-ACCUMBENS DOPAMINE; AGONIST QUINPIROLE; RECEPTOR BLOCKADE; OPERANT-BEHAVIOR; LOCOMOTOR-ACTIVITY; SELF-STIMULATION; FOOD-CONSUMPTION; D-AMPHETAMINE; WATER-INTAKE; RATS AB Behavioral effects of quinpirole (QNP), a dopamine D-2 receptor agonist, suggest it impacts neural mechanisms mediating goal-directed behaviors, as well as behavioral extinction following removal of a primary reinforcer. The present study investigated the effect of QNP on behavioral extinction following the omission of contingent reinforcement, and whether this effect is related to acquisition or processes specific to extinction. Rats were trained on a continuous reinforcement schedule to nose-poke for water reward. Using a free-operant procedure, rats completed approximately 70 responses for each of four consecutive days. On the fifth day reward was withheld. Rats were assigned to one of five groups in which they received 0.3 mg/kg QNP ip either during the first day (acquisition phase), the second 2 days (maintenance phase), the last day (extinction phase), or during all days. A fifth group received vehicle injections. Rats receiving QNP during the acquisition and maintenance phase did not differ significantly from the control group during the extinction phase, although they demonstrated reduced response rates on days they received QNR However, rats treated during the extinction phase or during all phases demonstrated a significant reduction in the rate of extinction. This effect cannot be attributed to an increase in general behavioral arousal because response rates for reinforced responses did not differ significantly among groups following acquisition of the behavior. The reduced extinction effect does not appear to be related to abnormalities in the initial behavior-reward association, but instead may result from enhanced engagement of learned behavioral patterns, or from interference of signals associated with removal of predicted reinforcement. (C) 2003 Elsevier Inc. All rights reserved. C1 CUNY Brooklyn Coll, Dept Psychol, Brooklyn, NY 11210 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kurylo, DD (reprint author), CUNY Brooklyn Coll, Dept Psychol, 2900 Bedford Ave, Brooklyn, NY 11210 USA. NR 55 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD OCT PY 2003 VL 80 IS 1 BP 1 EP 7 DI 10.1016/S0031-9384(03)00218-X PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 737ZV UT WOS:000186263000001 PM 14568302 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Improving aesthetic outcomes after alloplastic chin augmentation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID POROUS POLYETHYLENE IMPLANTS; LOWER LIP POSITION; CEPHALOMETRIC ANALYSIS; ESSENTIAL COMPONENT; BONE-RESORPTION; MENTALIS MUSCLE; GENIOPLASTY; SKELETAL; SURGERY; ALLURES AB A novel approach to increase chin projection with alloplastic material is presented. Key aspects of the technique include the consideration of anthropometric normal values in preoperative assessment and planning, a submental approach with wide subperiosteal exposure of the area to he augmented, the rise of two-piece porous polyethylene implants for augmentation, and screw fixation of the implant to the mandible. Screw fixation improves the predictability and precision of reconstruction by preventing implant displacement, by obliterating gaps between the implant and the facial skeleton, and by facilitating final implant contouring. In a series of 46 patients (24 primary and 22 secondary) operated on over a 6-year period, this approach allowed anatomically correct, stable chin contours to be created. Iatrogenic problems with macrogenia, mentalis dysfunction, and soft-tissue distortion resulting from implant. migration and capsular contracture have been avoided. There have been no infections. Two patients who had had multiple previous chill operations requested revisional surgery, to refine contour. C1 Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, 15 Parkman St,WACC Suite 453, Boston, MA 02114 USA. EM myaremchuk@partners.org NR 40 TC 16 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2003 VL 112 IS 5 BP 1422 EP 1432 DI 10.1097/01.PRS.0000081067.90827.C2 PG 11 WC Surgery SC Surgery GA 800YD UT WOS:000220062700031 PM 14504528 ER PT J AU Cooley, ME Short, TH Moriarty, HJ AF Cooley, ME Short, TH Moriarty, HJ TI Symptom prevalence, distress, and change over time in adults receiving treatment for lung cancer SO PSYCHO-ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED TRIAL; CLINICAL-TRIALS; PAIN MANAGEMENT; SURVIVAL; FATIGUE; RADIOTHERAPY; CHEMOTHERAPY; GUIDELINES; INSTRUMENT AB Adequate management of symptoms in adults with lung cancer is an important focus for clinical interventions. Knowledge of symptom prevalence and distress can be used to develop empirically based interventions that can potentially reduce distressing symptoms and improve quality of life. The purposes of this study were to describe which symptoms are most distressing, describe the prevalence of symptoms in adults receiving treatment for lung cancer, identify how symptoms change over time, and identify patient-related and clinical characteristics related to symptom distress. Data were available from 117 patients. Fatigue and pain were the most distressing symptoms for each group and at each time. Significant differences in distressing symptoms among the treatment groups were noted for nausea, fatigue, bowel pattern, and concentration at entry into the study and difficulty with appetite at 6 months. Many of the individual symptoms demonstrated a decrease in distress from 0 to 3 months and then an increase in distress levels from 3 to 6 months. Many of the individual symptoms were associated with demographic covariates and treatment group values but no consistent pattern emerged over time except for baseline symptom distress. Symptom distress at entry to the study was a strong predictor of nine distressing symptoms at 3 months and seven distressing symptoms at 6 months. Questionnaires such as the SDS may be useful as screening instruments to target those who need more intensive interventions. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing, Boston, MA 02115 USA. Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. Indiana Univ Penn, Dept Math, Indiana, PA USA. Vet Affairs Med Ctr, Nursing Serv, Philadelphia, PA USA. RP Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing, Boston, MA 02115 USA. EM cooleymary@aol.com FU NCI NIH HHS [K07 CA095118]; NINR NIH HHS [T32 NR07035] NR 74 TC 115 Z9 115 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD OCT-NOV PY 2003 VL 12 IS 7 BP 694 EP 708 DI 10.1002/pon.694 PG 15 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 727PR UT WOS:000185667800005 PM 14502594 ER PT J AU Young, AJ Ofori-Boateng, T Rodriguez, KL Plowman, JL AF Young, AJ Ofori-Boateng, T Rodriguez, KL Plowman, JL TI Meaning and agency in discussing end-of-life care: A study of elderly veterans' values and interpretations SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE end-of-life care; communication; geriatrics; veterans ID INCORPORATING PALLIATIVE CARE; ADVANCE DIRECTIVES; DYING PATIENTS; TREATMENT PREFERENCES; PATIENT; EDUCATION; PREDICTIONS; EXPERIENCE; KNOWLEDGE; BARRIERS AB The authors of this exploratory study used textual analysis of transcribed interviews to examine the mental constructs that individuals form around advance care terminology and to learn how elderly veterans conceptualize the language used in the Veterans Administration advance directive. They found that respondents often negotiated meaning by drawing on rigid schemas, specific mental constructs already in place: The Lord's Will, Machine Talk, Being a Burden, and Being Productive. The authors also examined the transcripts for agency. In addition to assigning external agency for end-of-life care decisions, respondents often expressed a complex interaction of ''self'' and "other" agency. These results challenge us to develop communication methods that allow patients to claim agency and participate fully in decisions regarding their health care, especially at the end of life. C1 VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. Metrohlth Med Ctr, Cleveland, OH USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Young, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. NR 66 TC 9 Z9 9 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD OCT PY 2003 VL 13 IS 8 BP 1039 EP 1062 DI 10.1177/1049732303256554 PG 24 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 722BY UT WOS:000185356500002 PM 14556418 ER PT J AU Chen, B Pogue, BW Goodwin, IA O'Hara, JA Wilmot, CM Hutchins, JE Hoopes, PJ Hasan, T AF Chen, B Pogue, BW Goodwin, IA O'Hara, JA Wilmot, CM Hutchins, JE Hoopes, PJ Hasan, T TI Blood flow dynamics after photodynamic therapy with verteporfin in the RIF-1 tumor SO RADIATION RESEARCH LA English DT Article ID MACULAR DEGENERATION; MODEL; IRRADIATION; PERFUSION; HYPOXIA; MARKER AB In the present study, the effects of photodynamic therapy (PDT) with verteporfin on tumor blood flow and tumor regrowth were compared as verteporfin distributed in different compartments within the RIF-1 tumor. Tissue distribution of verteporfin was examined by fluorescence microscopy, and blood flow measurements were taken with a laser Doppler system. It was found that, at 15 min after drug administration, when verteporfin was mainly confined within the vasculature, PDT induced a complete arrest of blood flow by 6 h after treatment. PDT treatment at a longer drug-light interval (3 h), which allowed the drug to diffuse to the tumor interstitium, caused significantly less flow decrease, only to 50% of the initial flow in 6 h. A histological study and Hoechst 33342 staining of functional tumor vasculature confirmed the primary vascular damage and the decrease in tumor perfusion. The regrowth rate of tumors treated with 15-min interval PDT was 64% of that of the control group. However, when tumors were treated with 3-h interval PDT, the regrowth rate was not significantly different from that of the control, indicating that only the 15-min interval PDT caused serious damage to the tumor vascular bed. These results support the hypothesis that temporal pharmacokinetic changes in the distribution of the photosensitizer between the tumor parenchyma and blood vessels can significantly alter the tumor target of PDT. (C) 2003 by Radiation Research Society. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Dartmouth Coll Sch Med, Dept Radiol, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Surg, Lebanon, NH 03756 USA. RP Dartmouth Coll, Thayer Sch Engn, HB 800, Hanover, NH 03755 USA. EM Brian.Pogue@dartmouth.edu FU NCI NIH HHS [P01CA84203, R01CA78734]; NCRR NIH HHS [P41 RR11602] NR 28 TC 57 Z9 62 U1 4 U2 14 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD OCT PY 2003 VL 160 IS 4 BP 452 EP 459 DI 10.1667/RR3059 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 723GL UT WOS:000185424300007 PM 12968929 ER PT J AU Rosenthal, DI Hornicek, FJ Torriani, M Gebhardt, MC Mankin, HJ AF Rosenthal, DI Hornicek, FJ Torriani, M Gebhardt, MC Mankin, HJ TI Osteoid osteoma: Percutaneous treatment with radiofrequency energy SO RADIOLOGY LA English DT Article DE bone neoplasms, therapy; osteoma ID INTERSTITIAL LASER PHOTOCOAGULATION; CT GUIDANCE; FOLLOW-UP; OPERATIVE TREATMENT; ABLATION; EXCISION; BONE; THERMOCOAGULATION; OSTEOBLASTOMA; RESECTION AB PURPOSE: To report our experience with technical success, complications, and long-term clinical success of radiofrequency (RF) ablation of osteoid osteoma. MATERIALS AND METHODS: After needle biopsy, computed tomography (CT)-guided percutaneous RF ablation was performed with general or spinal anesthesia. With an RF electrode, the lesion was heated to 90degreesC for 6 minutes. Patient age and biopsy results, and complications were recorded. lesion size and location sex,, Clinical success was assessed at a minimum of 2 years after the procedure. Significance of patient age and sex and lesion location and size as a predictor of biopsy result was tested by means of chi(2) analysis. In addition, effects of patient age and sex, lesion location and size, and biopsy results on clinical success were tested with the Fisher exact test. RESULTS: During an 11-year period, 263 patients who were suspected of having osteoid osteoma underwent 271 ablation procedures. All procedures were technically successful. There were two anesthesia-related complications (aspiration, cardiac arrest) and two minor procedure-related complications (cellulitis, sympathetic dystrophy). Results at biopsy were positive in 73% (197 of 271 biopsies). Two-year follow-up data were available for 126 procedures. The other procedures had been performed more recently or the patients could not be contacted. There was complete relief of symptoms after 112 of the 126 procedures (89%). For procedures performed as the initial treatment, the success rate was 91% (107 of 117 procedures). Procedures for recurrent lesions had a significantly lower success rate (six of 10 procedures [60%], P < .001). Clinical outcome was not dependent on biopsy result, patient age or sex, or lesion size or location. CONCLUSION: CT-guided percutaneous RF ablation of osteoid osteoma is a safe and effective technique. (C) RSNA, 2003. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 199 Cambridge St, Boston, MA 02114 USA. NR 29 TC 252 Z9 262 U1 0 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2003 VL 229 IS 1 BP 171 EP 175 DI 10.1148/radiol.2291021053 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 723GQ UT WOS:000185424900027 PM 12944597 ER PT J AU Brazitikos, PD Androudi, S D'Amico, DJ Papadopoulos, N Dimitrakos, SA Dereklis, DL Alexandridis, A Lake, S Stangos, NT AF Brazitikos, PD Androudi, S D'Amico, DJ Papadopoulos, N Dimitrakos, SA Dereklis, DL Alexandridis, A Lake, S Stangos, NT TI Perfluorocarson liquid utilization in primary vitrectomy repair of retinal detachment with multiple breaks SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT 22nd Club-Jules-Gonin Meeting CY SEP 02-06, 2000 CL TAORMINA, ITALY SP Club Jules Gronin DE multiple breaks; pars plana vitrectomy; perfluorocarbon liquid; retinal detachment ID PARS-PLANA VITRECTOMY; PIGMENT EPITHELIAL-CELLS; PROLIFERATIVE VITREORETINOPATHY; SURGERY; CRYOTHERAPY; TEARS AB Purpose: To evaluate the efficacy of pars plana vitrectomy in conjunction with intraoperative perfluoro-n-octane (PFO) use as initial treatment of retinal detachment (RD) with multiple breaks located at various distances from the ora serrata. Methods: Twenty-two consecutive eyes (15 phakic, 2 aphakic, and 5 pseudophakic) presenting with RD with multiple breaks and tears underwent primary pars plana vitrectomy, PFO retinal reattachment, transcleral cryopexy or endolaser treatment of breaks, PFO/air exchange, and final injection of 18% perfluoropropane (C3F8). Scleral buckles were not used. The mean follow-up period was 29 months. Results: Temporary PFO utilization attached the posterior retina and facilitated the safe removal of vitreous at its base and around the retinal tears. Intraoperative complications included new breaks (3 eyes), enlargement of breaks (2 eyes), and a small bubble of subretinal PFO (1 eye). Postoperatively, the retina remained attached during follow-up in 19 eyes. Cataract developed or progressed in 13 phakic eyes. Conclusions: Pars plana vitrectomy in conjunction with intraoperative PFO utilization is effective as initial treatment of RDs with multiple breaks. The main limitation of this technique is the postoperative progressive cataract formation in phakic eyes. C1 Aristotelian Univ Salonika, Dept Ophthalmol, GR-54006 Salonika, Greece. Interbalkan Med Ctr, Salonika, Greece. Harvard Univ, Sch Med, Retina Serv, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Brazitikos, PD (reprint author), Tsimiski 62, Salonika 54622, Greece. NR 33 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2003 VL 23 IS 5 BP 615 EP 621 DI 10.1097/00006982-200310000-00002 PG 7 WC Ophthalmology SC Ophthalmology GA 736MM UT WOS:000186174600002 PM 14574244 ER PT J AU Sorensen, G AF Sorensen, G TI High field brain imaging the road ahead SO RIVISTA DI NEURORADIOLOGIA LA English DT Article; Proceedings Paper CT 17th Symposium on Neuroradiologicum CY 2002 CL Paris, FRANCE DE MRI; fMR C1 Massachusetts Gen Hosp, Boston, MA 01890 USA. RP Sorensen, G (reprint author), Massachusetts Gen Hosp, 55,Fruit St, Boston, MA 01890 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI CENTAURO PI BOLOGNA PA VIA DEL PRATELLO, 8, 40122 BOLOGNA, ITALY SN 1120-9976 J9 RIV NEURORADIOL JI Riv. Neuroradiol. PD OCT PY 2003 VL 16 IS 5 BP 728 EP 730 PG 3 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 800PY UT WOS:000220041400006 ER PT J AU Anderson, KC AF Anderson, KC TI The role of immunomodulatory drugs in multiple myeloma SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT 9th International Myeloma Workshop CY MAY, 2003 CL SALAMANCA, SPAIN ID MM CELLS; THALIDOMIDE; THERAPY; ANALOGS; DEXAMETHASONE; APOPTOSIS; SURVIVAL; CC-5013; SMAC C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Medford, MA 02155 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Medford, MA 02155 USA. NR 28 TC 22 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2003 VL 40 IS 4 SU 4 BP 23 EP 32 DI 10.1053/j.seminhematol.2003.09.010 PG 10 WC Hematology SC Hematology GA 754RR UT WOS:000187345700005 PM 15015893 ER PT J AU Armstrong, SA Golub, TR Korsmeyer, SJ AF Armstrong, SA Golub, TR Korsmeyer, SJ TI MLL-rearranged leukemias: Insights from gene expression profiling SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; BONE-MARROW; CHROMOSOME-TRANSLOCATION; DROSOPHILA-TRITHORAX; HOMEOBOX GENES; STEM-CELLS; ALL-1 GENE; LINEAGE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Immunol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept AIDS, Boston, MA USA. Whitehead Inst, Genome Ctr, Cambridge, MA 02142 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 1 Jimmy Find Way, Boston, MA 02115 USA. NR 43 TC 48 Z9 49 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2003 VL 40 IS 4 BP 268 EP 273 DI 10.1053/S0037-1963(03)00196-3 PG 6 WC Hematology SC Hematology GA 735UE UT WOS:000186132300002 PM 14582077 ER PT J AU Ferrando, AA Look, AT AF Ferrando, AA Look, AT TI Gene expression profiling in T-cell acute lymphoblastic leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; CHROMOSOMAL TRANSLOCATION; HEMATOPOIETIC LINEAGES; HOMEOBOX GENE; B-PRECURSOR; MLL; PROTEIN; CHILDREN; HOX11 C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 59571, CA 68484] NR 36 TC 84 Z9 85 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2003 VL 40 IS 4 BP 274 EP 280 DI 10.1053/S0037-1963(03)00195-1 PG 7 WC Hematology SC Hematology GA 735UE UT WOS:000186132300003 PM 14582078 ER PT J AU von Andrian, UH AF von Andrian, UH TI Introduction: chemokines - regulation of immune cell trafficking and lymphoid organ architecture SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD OCT PY 2003 VL 15 IS 5 BP 239 EP 241 DI 10.1016/j.smim.2003.08.001 PG 3 WC Immunology SC Immunology GA 756LG UT WOS:000187466100001 ER PT J AU Weninger, W von Andrian, UH AF Weninger, W von Andrian, UH TI Chemokine regulation of naive T cell traffic in health and disease SO SEMINARS IN IMMUNOLOGY LA English DT Review DE lymphocytes; dendritic cells; homing; lymph node; chemokines ID HIGH ENDOTHELIAL VENULES; LYMPHOID-TISSUE CHEMOKINE; SPHINGOSINE 1-PHOSPHATE RECEPTORS; MICE LACKING EXPRESSION; PRIMARY IMMUNE-RESPONSE; CHEMOTACTIC AGENT 4; DENDRITIC CELLS; CUTTING EDGE; L-SELECTIN; IN-VIVO AB A central feature of the immune response is the precise spatio-temporal convergence of T cells and antigen presenting cells (APC) in particular microenvironments within secondary lymphoid organs (SLO). CCR7 and its ligands CCL19 and CCL21 have been identified as the gatekeepers for both naive T lymphocytes and dendritic cells (DC) to these defined anatomical compartments. A new perception on the regulation of lymphocyte traffic in lymph nodes (LN) has come from observations that sphingosine-1-phosphate (SIP) receptor agonists affect T cell entry and exit from these organs. Recent developments in intravital microscopy (IVM) techniques reveal unexpected autonomous random motion of lymphocytes within secondary lymphoid tissues, and provoke questions about the mechanisms that guide their compartmental navigation. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weninger, W (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008; OI Weninger, Wolfgang/0000-0003-3133-8699 NR 117 TC 54 Z9 57 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD OCT PY 2003 VL 15 IS 5 BP 257 EP 270 DI 10.1016/j.smim.2003.08.007 PG 14 WC Immunology SC Immunology GA 756LG UT WOS:000187466100004 PM 15001175 ER PT J AU Leibowitz, SB Kantoff, PW AF Leibowitz, SB Kantoff, PW TI Differentiating agents and the treatment of prostate cancer: Vitamin D-3 and peroxisome proliferator-activated receptor gamma ligands SO SEMINARS IN ONCOLOGY LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; PHASE-I TRIAL; PPAR-GAMMA; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; GROWTH-INHIBITION; CALCITRIOL 1,25-DIHYDROXYCHOLECALCIFEROL; TERMINAL DIFFERENTIATION; SUBSEQUENT DEVELOPMENT C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Dana 1230,44 Binney St, Boston, MA 02115 USA. NR 71 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO 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 OCT PY 2003 VL 30 IS 5 BP 698 EP 708 DI 10.1053/S0093-7754(03)00352-X PG 11 WC Oncology SC Oncology GA 735VE UT WOS:000186134600013 PM 14571417 ER PT J AU Sahani, DV Kalva, SP Hahn, PF AF Sahani, DV Kalva, SP Hahn, PF TI Imaging of rectal cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SUPERPARAMAGNETIC IRON-OXIDE; COLORECTAL-CANCER; LOCAL RECURRENCE; TRANSRECTAL ULTRASONOGRAPHY; ARTERIAL PORTOGRAPHY; COMPUTED-TOMOGRAPHY; HEPATIC METASTASES; LIVER METASTASES; PREOPERATIVE RADIOTHERAPY C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02115 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, 55 Fruit St, Boston, MA 02115 USA. NR 71 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2003 VL 13 IS 4 BP 389 EP 402 DI 10.1053/S1053-4296(03)00049-3 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 742DC UT WOS:000186499600003 PM 14586829 ER PT J AU Zhu, AX Willett, CG AF Zhu, AX Willett, CG TI Chemotherapeutic and biologic agents as radio sensitizers in rectal cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Review ID METASTATIC COLORECTAL-CANCER; ENDOTHELIAL GROWTH-FACTOR; POSTOPERATIVE RADIATION-THERAPY; PHASE-II TRIAL; FLUOROURACIL PLUS LEUCOVORIN; PROTRACTED VENOUS INFUSION; CARCINOMA CELL-LINES; HIGH-DOSE LEUCOVORIN; TERM FOLLOW-UP; LOCAL EXCISION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners Canc Ctr, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners Canc Ctr, 100 Blossom St, Boston, MA 02114 USA. NR 111 TC 22 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2003 VL 13 IS 4 BP 454 EP 468 DI 10.1053/4296(03)00048-1 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 742DC UT WOS:000186499600008 PM 14586834 ER PT J AU Peng, CC Aspinall, SL Good, CB Atwood, CW Chang, CCH AF Peng, CC Aspinall, SL Good, CB Atwood, CW Chang, CCH TI Equal effectiveness of older traditional antibiotics and newer broad-spectrum antibiotics in treating patients with acute exacerbations of chronic bronchitis SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID 30-CENTER NATIONAL SURVEILLANCE; OBSTRUCTIVE PULMONARY-DISEASE; UNITED-STATES; ANTIMICROBIAL RESISTANCE; OUTPATIENTS; UPDATE AB Background: Choice of antibiotic therapy for acute exacerbations of chronic bronchitis (AECB) is important because of cost and concerns about development of resistance. Methods: A retrospective cohort study was conducted in outpatients with chronic obstructive pulmonary disease and documented AECB treated with antibiotics. Results: We compared outcomes and costs of AECB treated with first-line antibiotics having partial coverage against organisms associated with AECB (eg, amoxicillin), first-line antibiotics with full coverage against organisms associated with AECB (eg, sulfamethoxazole-trimethoprim), and newer broad-spectrum antibiotics (eg, azithromycin). There were no significant differences among the three antibiotic groups in failure rate, hospitalization rate, or time until subsequent AECB. Pharmacy costs were significantly less with first-line antibiotics ($3.18 +/- 0.64, $3.00 +/- 0.48, and $36.70 +/- 16.29, respectively; P < 0.0001), but there was no significant difference among all three groups with regard to total costs. Conclusion: We found no difference in outcome between older traditional antibiotics with adequate coverage against organisms associated with AECB and newer broad-spectrum antibiotics. C1 VA Pittsburgh Healthcare Syst, Pharm Serv 132 MU, Pittsburgh, PA 15240 USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Pharm Serv 132 MU, Univ Dr C, Pittsburgh, PA 15240 USA. EM sherrie.aspinall@med.va.gov NR 16 TC 9 Z9 9 U1 0 U2 0 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 OCT PY 2003 VL 96 IS 10 BP 986 EP 991 DI 10.1097/01.SMJ.0000054536.50460.F1 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 831CP UT WOS:000222170800007 PM 14570342 ER PT J AU Black, S Roman, GC Geldmacher, DS Salloway, S Hecker, J Burns, A Perdomo, C Kumar, D Pratt, R AF Black, S Roman, GC Geldmacher, DS Salloway, S Hecker, J Burns, A Perdomo, C Kumar, D Pratt, R CA Donepezil 307 Vascular Dementia St TI Efficacy and tolerability of donepezil in vascular dementia - Positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial SO STROKE LA English DT Article DE dementia; donepezil; randomized controlled trials ID ALZHEIMERS-DISEASE; DOUBLE-BLIND; MODERATE; GALANTAMINE; POPULATIONS; DIAGNOSIS; 1-YEAR AB Background and Purpose - Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. Methods - Patients (n = 603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d ( n = 198), donepezil 10 mg/d ( 5 mg/d for first 28 days; n = 206), or placebo ( n = 199). Analyses were based on the intent-to-treat population. Results - At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale - cognitive subscale ( mean change from baseline score effect size: donepezil 5 mg/ d, - 1.90; P = 0.001; donepezil 10 mg/ d, - 2.33; P < 0.001). Significant improvements in patients' global function were seen versus placebo at week 24 ( observed cases), on the Clinician's Interview- Based Impression of Change - Plus version only for patients on donepezil 5 mg/ d ( P = 0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/ d ( P = 0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale ( mean change from baseline score effect size at week 24: donepezil 5 mg/ d, - 1.31, P = 0.02; donepezil 10 mg/ d, - 1.31, P = 0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low ( placebo, 11.1%; donepezil 5 mg/ d, 11.1%; donepezil 10 mg/ d, 21.8%; P = 0.005 versus placebo). Conclusions - These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition. C1 Eisai Inc, Glenpointe Ctr W, Teaneck, NJ 07666 USA. Univ Toronto, Dept Med, Div Neurol, Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON, Canada. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Vet Adm Hosp, San Antonio, TX USA. Univ Virginia, Dept Neurol, Memory Disorders Program, Charlottesville, VA USA. Butler Hosp, Brown Med Sch, Providence, RI 02906 USA. Repatriat Gen Hosp, Dept Rehabil & Aged Care, Daw Pk, SA, Australia. Univ Manchester, Manchester, Lancs, England. Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. RP Pratt, R (reprint author), Eisai Inc, Glenpointe Ctr W, Teaneck, NJ 07666 USA. OI Black, Sandra/0000-0001-7093-8289; Burns, Alistair/0000-0002-9837-0645 NR 30 TC 167 Z9 192 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2003 VL 34 IS 10 BP 2323 EP 2330 DI 10.1161/01.STR.0000091396.95360.E1 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 727UK UT WOS:000185679100019 PM 12970516 ER PT J AU Rosand, J Altshuler, D AF Rosand, J Altshuler, D TI Human genome sequence variation and the search for genes influencing stroke SO STROKE LA English DT Article DE genetics; human genome project; stroke ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MYOCARDIAL-INFARCTION; ISCHEMIC STROKE; CANDIDATE GENES; COMMON DISEASE; SUSCEPTIBILITY; ASSOCIATION; VARIANTS AB Background-Technological progress spurred by the Human Genome Project is accelerating the pace of genetic studies of common diseases, including stroke. Stroke clinicians will soon need to interpret increasingly complex genetic studies. Summary of Review-Linkage analysis and epidemiological association are 2 fundamental methods of identifying gene variants affecting common diseases such as stroke. Combining these methods with advanced molecular genetic techniques, 3 recently published studies have made important contributions to the genetics of common vascular diseases: identification of the location of a gene for stroke on chromosome 5q12 and identification of gene variants that may increase risk of myocardial infarction. Driven by genomic technology, future studies will be increasingly comprehensive and systematic in their assessment of the contribution of genetics to the clinical course of stroke. The scale and complexity of such studies will require large-scale collaboration among stroke physicians, geneticists, and biostatisticians. Conclusions-Rapid improvements in technology and study design are likely to elucidate the role of inherited genetic variation in complex diseases such as stroke. Understanding the methods of population-based genetic investigation and the patterns of human genome variation will enable stroke physicians to follow these future developments. C1 Massachusetts Gen Hosp, Stroke Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurocrit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Whitehead Inst Massachusetts Inst Technol Ctr Gen, Program Med & Populat Genet, Boston, MA USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Stroke Unit, VBK-811,32 Fruit St, Boston, MA 02114 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NINDS NIH HHS [1 K23 NS42695-01] NR 22 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2003 VL 34 IS 10 BP 2512 EP 2516 DI 10.1161/01.STR.0000091844.02111.07 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 727UK UT WOS:000185679100060 PM 14500931 ER PT J AU Ogilvy, CS AF Ogilvy, CS TI Neurosurgical clipping versus endovascular coiling of patients with ruptured intracranial aneurysms SO STROKE LA English DT Article DE endovascular coiling; intracranial aneurysm; subarachnoid hemorrhage ID IN-HOSPITAL MORTALITY; EMBOLIZATION; OUTCOMES; VOLUME; EXPERIENCE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,VBK710, Boston, MA 02114 USA. NR 11 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2003 VL 34 IS 10 BP 2540 EP 2542 DI 10.1161/01.STR.0000092894.71909.FF PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 727UK UT WOS:000185679100067 PM 14500927 ER PT J AU Eid, GM Prince, JM Mattar, SG Hamad, G Ikrammudin, S Schauer, PR AF Eid, GM Prince, JM Mattar, SG Hamad, G Ikrammudin, S Schauer, PR TI Medium-term follow-up confirms the safety and durability of laparoscopic ventral hernia repair with PTFE SO SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Central-Surgical-Association CY MAR 20-22, 2003 CL TORONTO, CANADA SP Central Surg Assoc ID INCISIONAL HERNIA; MESH; HERNIORRHAPHY; RECURRENCE; GROIN; RISK AB Background. Ventral abdominal wall hernias are common lesions and may be associated with life-threatening complications. The application of laparoscopic principles to the treatment of ventral hernias has reduced recurrence rates from a range of 25 % to 52 % to a range of 3.4 % to 9 %. In this study, we review our experience and assess the clinical outcome of patients who have undergone laparoscopic repair of ventral hernias. Methods. We reviewed the outcome of 79 patients with more than 1 year of follow-up who underwent laparoscopic ventral hernia repair between March 1996 and December 2001. Patient demographics, hernia characteristics, operative parameters, and clinical outcomes were evaluated. Results. Of the 79 patients, 37 were males. Mean age was 55.8 years (range 28-81). Sixty-eight patients had incisional hernias, including 17 with recurrent hernias. Eleven patients had primary ventral hernias. The mean defect size was 103 cm(2) (range 4-510); incarceration was present in 22 patients (27.8 %), and multiple (Swiss-cheese) defects in 20 (25.3 %). Laparoscopic expanded polytetrafluoroethylene mesh repair by the modified Rives-Stoppa technique was completed in 78 (98.7 %). One conversion occurred because of bowel injury. The mean operating time was 110 minutes (range 45-210) and mean hospital stay was 1.7 days (range 0-20), with 46 patients (58.2 %) being discharged within 24 hours of surgery. Complications included seroma formation (3), chronic pain (3), prolonged dens (1), hematoma formation (1), and missed bowel injury (1)for a complication rate of (11.4 %). There were no deaths. After a follow-up of up to 6 years (a mean of 34 months), there were 4 recurrences (5 %). Conclusion. The laparoscopic repair of ventral hernias is safe, effective, and durable with minimal morbidity. It is particularly successful in patients with recurrent lesions. The laparoscopic approach to ventral hernia repair should be considered the standard of care. C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Minnesota, Minneapolis, MN USA. RP Schauer, PR (reprint author), Magee Womens Hosp, Suite 5500,300 Halket St, Pittsburgh, PA 15213 USA. NR 19 TC 66 Z9 66 U1 0 U2 2 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 OCT PY 2003 VL 134 IS 4 BP 599 EP 603 DI 10.1016/S0039-6060(03)00273-6 PG 5 WC Surgery SC Surgery GA 741KT UT WOS:000186457800022 PM 14605620 ER PT J AU Paganetti, H AF Paganetti, H TI Foreword: Hadron therapy - From yesterday's physics laboratory to today's modern clinical routine SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Editorial Material ID PROTON; BEAMS C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD OCT PY 2003 VL 2 IS 5 BP 353 EP 354 PG 2 WC Oncology SC Oncology GA 739YJ UT WOS:000186374100001 PM 14529301 ER PT J AU Bussiere, MR Adams, JA AF Bussiere, MR Adams, JA TI Treatment planning for conformal proton radiation therapy SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID LIGHT-ION BEAMS; PARTICLE RADIOTHERAPY; EYE; PROSTATE; TUMORS; CANCER; RADIOSURGERY; PHOTONS; PATIENT; MOTION AB Clinical results from various trials have demonstrated the viability of protons in radiation therapy and radiosurgery. This has motivated a few large medical centers to design and build expensive hospital based proton facilities based proton facilities (current cost estimates for a proton facility is around $100 million). Until this development proton therapy was done using retrofitted equipment originally designed for nuclear experiments. There are presently only three active proton therapy centers in the United States, 22 worldwide. However, more centers are under construction and being proposed in the US and abroad. The important difference between proton and x-ray therapy is in the dose distribution. Xrays deposit most of their dose at shallow depths of a few centimeters with a gradual decay with depth in the patient. Protons deliver most of their dose in the Bragg peak, which can be delivered at most clinically required depths followed by a sharp fall-off. This sharp falloff makes protons sensitive to variations in treatment depths within patients, Treatment planning incorporates all the knowledge of protons into a process, which allows patients to be treated accurately and reliably. This process includes patient immobilization, imaging, targeting, and modeling of planned dose distributions. Although the principles are similar to x-ray therapy some significant differences exist in the planning process, which described in this paper. Target dose conformality has recently taken on much momentum with the advent of intensity modulated radiation therapy (IMRT) with photon beams. Proton treatments provide a viable alternative to IMRT because they are inherently conformal avoiding normal tissue while irradiating the intended targets. Proton therapy will soon bring conformality to a new high with the development of intensity modulated proton therapy (IMPT). Future challenges include keeping the cost down, increasing access to conventional proton therapy as well as the clinical implementation of IMPT. Computing advances are making Monte Carlo techniques more accessible to treatment planning for all modalities including proton therapy. This technique will allow complex delivery configurations to be properly modeled in a clinical setting. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Bussiere, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 33 Fruit St, Boston, MA 02114 USA. NR 55 TC 29 Z9 29 U1 0 U2 4 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD OCT PY 2003 VL 2 IS 5 BP 389 EP 399 PG 11 WC Oncology SC Oncology GA 739YJ UT WOS:000186374100004 PM 14529304 ER PT J AU Paganetti, H AF Paganetti, H TI Significance and implementation of RBE variations in proton beam therapy SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Review ID RELATIVE BIOLOGICAL EFFECTIVENESS; LOW-ENERGY PROTONS; CHINESE-HAMSTER CELLS; HUMAN-TUMOR-CELLS; HEAVY-ION BEAMS; TRACK STRUCTURE-ANALYSIS; ULTRASOFT X-RAYS; RADIATION-THERAPY; MAMMALIAN-CELLS; V79 CELLS AB Key to radiation therapy is to apply a high tumor-destroying dose while protecting healthy tissue, especially near organs at risk. To optimize treatment for ion therapy not the dose but the dose multiplied by the relative biological effectiveness (RBE) is decisive. Proton therapy has been based on the use of a generic RBE, which is applied to all treatments independent of dose/fraction, position in the spread-out Bragg peak (SOBP), initial beam energy or the particular tissue. Dependencies of the RBE on various physical and biological properties are disregarded. The variability of RBE in clinical situations is believed to be within 10-20%. This is in the same range of effects that receive high attention these days, i.e., patient set-up uncertainties, organ motion effects, and dose calculation accuracy all affecting proton as well as conventional radiation therapy. Elevated RBE values can be expected near the edges of the target, thus probably near critical structures. This is because the edges show lower doses and, depending on the treatment plan, may be identical with the beam's distal edge, where dose is deposited in part by high-LET protons. We assess the rationale for the continued use of a generic RBE and whether the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBE's. Two aspects have to be considered. Firstly, the available information from experimental studies and secondly, our ability to calculate RBE values for a given treatment plan based on parameters extracted from such experiments. We analyzed published RBE values for in vitro and in vivo endpoints. The values for cell survival in vitro indicate a substantial spread between the diverse cell lines. The average value at mid SOBP over all dose levels is approximate to1.2 in vitro and approximate to1.1 in vivo. Both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. The experimental in vivo data indicate that continued employment of a generic RBE value of 1.1 is reasonable. At present, there seems to be too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, etc. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in animal systems, especially as a function of dose in the range of 1-4 Gy. However, there is a measurable increase in RBE over the terminal few mm of the SOBP, which results in an extension of the bio-effective range of the beam of a few mm. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. To assess our ability to calculate RBE values we studied two approaches, which are both based on the track structure theory of radiation action. RBE calculations are difficult since both the physical input parameters, i.e., LET distributions, and, even more so, the biological input parameters, i.e., local cellular response, have to be known with high accuracy. Track structure theory provides a basis for predicting dose-response curves for particle irradiation. However, designed for heavy ion applications the models show weaknesses in the prediction of proton radiation effects. We conclude that, at present, RBE modeling in treatment planning involves significant uncertainties. To incorporate RBE variations in treatment planning there has to be a reliable biological model to calculate RBE values based on the physical characteristics of the radiation field and based on well-known biological input parameters. In order to do detailed model calculations more experimental data, in particular for in vivo endpoints, are needed. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM HPAGANETTI@partners.org FU NCI NIH HHS [CA 21239] NR 122 TC 37 Z9 37 U1 0 U2 6 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD OCT PY 2003 VL 2 IS 5 BP 413 EP 426 PG 14 WC Oncology SC Oncology GA 739YJ UT WOS:000186374100006 PM 14529306 ER PT J AU Trofimov, A Bortfeld, T AF Trofimov, A Bortfeld, T TI Optimization of beam parameters and treatment planning for intensity modulated proton therapy SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article ID RADIOTHERAPY; DELIVERY AB One of the objectives of the ongoing research and development work at the Northeast Proton Therapy Center (NPTC) in Boston is to perform optimized intensity modulated proton therapy (IMPT) treatments. Such treatments may be delivered by magnetically scanning a narrow proton pencil beam across the target volume, while both the scanning speed and the intensity of the beam are modulated. Localization of the proton dose in space allows one to yield dose distributions that are highly conformal to the target volume, thus minimizing the dose delivered to the surrounding healthy tissue. The aim of the current research is to determine technically optimal and clinically relevant specifications for the scanned beam delivery system, which is being developed in collaboration with Ion Beam Applications (IBA); and to create a link between the treatment planning and the beam delivery. IMPT treatment planning is performed for patient cases treated at the NPTC, with KonRad Pro software developed at the German Cancer Research Center (DKFZ). For the IMPT delivery, the proton intensity maps, optimized for discrete pencil beam spots, need to be translated into continuous scanning patterns. At the same time it is necessary to minimize the discrepancy between the planned and delivered doses which may result from such conversion, as well as from the technical limitations of the delivery system. Possibilities have been investigated for improving the proton dose conformity by optimizing the beam and scanning nozzle parameters, and by taking the specifics and limitations of the system into account in the treatment planning stage. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Trofimov, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA21239] NR 12 TC 16 Z9 16 U1 1 U2 2 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD OCT PY 2003 VL 2 IS 5 BP 437 EP 444 PG 8 WC Oncology SC Oncology GA 739YJ UT WOS:000186374100008 PM 14529308 ER PT J AU Zaleske, D Peretti, G Allemann, F Strongin, D MacLean, R Yates, KE Glowacki, J AF Zaleske, D Peretti, G Allemann, F Strongin, D MacLean, R Yates, KE Glowacki, J TI Engineering a joint: A chimeric construct with bovine chondrocytes in a devitalized chick knee SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Orthopedic-Research-Society CY FEB 12, 2002 CL DALLAS, TEXAS SP Orthoped Res Soc ID FEMORAL FOCAL DEFICIENCY; IN-VITRO; ARTICULAR-CARTILAGE; BONE; RECONSTRUCTION; TRANSMISSION; COLLAGEN AB This study assessed the feasibility of a devitalized knee as a scaffold for an engineered chimeric joint. Embryonic chick knees (19 days old), devitalized by lyophilization or multiple freeze-thaw cycles, were tested as scaffolds for repopulation with bovine articular chondrocytes (bACs). bACs were seeded into porous three-dimensional collagen sponges and were cultured for I day before fabrication of chimeric constructs. A pair of cell-seeded sponges was inserted into the joint space to contact preshaved articular surfaces. In some constructs, a sterile membrane of expanded polytetrafluoroethylene (ePTFE) was inserted between the collagen sponges. Histologic analysis showed that at 1 week, sponges with bACs were adherent to the shaved articular surfaces of the joint with accumulation of metachromatic extracellular matrix. Penetration of bACs and neomatrix into the devitalized matrix appeared to begin in preexistent epiphyseal canals and was observed to some extent in all specimens. Membranes of ePTFE maintained a joint space at 2 and 3 weeks, whereas there was fusion across the two sponges in many specimens lacking the membrane. Gene expression analysis demonstrated that lyophilization, but not multiple freeze-thaw cycles, completely devitalized the chick knees. These studies identified several design parameters crucial for successful engineering of a chimeric joint. C1 Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. RP Glowacki, J (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 FU NIAMS NIH HHS [R01 AR45870] NR 24 TC 9 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2003 VL 9 IS 5 BP 949 EP 956 DI 10.1089/107632703322495592 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 735MD UT WOS:000186118400009 PM 14633379 ER PT J AU Dzik, WH AF Dzik, WH TI Apoptosis, TGF beta and transfusion-related immunosuppression: Biologic versus clinical effects SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article ID BLOOD-TRANSFUSIONS; LEUKOCYTES; CELLS AB Whether or not blood transfusion exerts an immunosuppressive effect on the recipient remains an area of controversy. The mechanism to clearly explain the effect has been elusive. We have previously suggested that there may be two categories of immunosuppressive transfusion effect: one which is HLA-dependent and directed against adaptive immunity and a second category which is mild, non-specific, and directed against innate immunity. This non-specific effect might result from the infusion of apoptotic blood cells. There is solid evidence that blood cells undergo apoptotic changes during refrigerated storage. The infusion of apoptotic cells has recently been shown in animal models to be immunosuppressive. Immunosuppression resulting from the infusion of apoptotic cells may be linked to transforming growth factor beta (TGF-beta). (C) 2003 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, J-224,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 17 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD OCT PY 2003 VL 29 IS 2 BP 127 EP 129 DI 10.1016/S1473-0502(03)00115-0 PG 3 WC Hematology SC Hematology GA 719QY UT WOS:000185216800005 PM 12941349 ER PT J AU Ge, H Walhout, AJM Vidal, M AF Ge, H Walhout, AJM Vidal, M TI Integrating 'omic' information: a bridge between genomics and systems biology SO TRENDS IN GENETICS LA English DT Review ID PROTEIN-PROTEIN INTERACTIONS; SACCHAROMYCES-CEREVISIAE GENOME; GENE-EXPRESSION; C-ELEGANS; CAENORHABDITIS-ELEGANS; FUNCTIONAL-ANALYSIS; INTERACTION MAP; DNA MICROARRAY; YEAST PROTEOME; MAPPING DATA AB The availability of genome sequences for several organisms, including humans, and the resulting first-approximation lists of genes, have allowed a transition from molecular biology to 'modular biology'. In modular biology, biological processes of interest, or modules, are studied as complex systems of functionally interacting macromolecules. Functional genomic and proteomic ('omic') approaches can be helpful to accelerate the identification of the genes and gene products involved in particular modules, and to describe the functional relationships between them. However, the data emerging from individual omic approaches should be viewed with caution because of the occurrence of false-negative and false-positive results and because single annotations are not sufficient for an understanding of gene function. To increase the reliability of gene function annotation, multiple independent datasets need to be integrated. Here, we review the recent development of strategies for such integration and we argue that these will be important for a systems approach to modular biology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, SM858,44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu OI Walhout, Marian/0000-0001-5587-3608 NR 64 TC 266 Z9 284 U1 3 U2 33 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 2003 VL 19 IS 10 BP 551 EP 560 DI 10.1016/j.tig.2003.08.009 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 734LV UT WOS:000186058200006 PM 14550629 ER PT J AU Hunskaar, S Burgio, K Diokno, A Herzog, AR Hjalmas, K Lapitan, MC AF Hunskaar, S Burgio, K Diokno, A Herzog, AR Hjalmas, K Lapitan, MC TI Epidemiology and natural history of urinary incontinence in women SO UROLOGY LA English DT Article; Proceedings Paper CT 26th International-Urogynecological-Association Meeting CY AUG, 2002 CL PRAGUE, CZECH REPUBLIC SP Int Urogynecolog Assoc ID OLDER-PEOPLE; RISK-FACTORS; SEVERITY INDEX; FECAL INCONTINENCE; NURSING-HOMES; PREVALENCE; FEMALE; POPULATION; COMMUNITY; SYMPTOMS AB Understanding the epidemiology (distribution and determinants) of urinary incontinence (UI), as well as its natural history is a very important issue. In this article, we discuss prevalence, incidence, natural history, and the variations that may be related to race and ethnicity. We focus on epidemiologic population comprising community-dwelling women who are not institutionalized. Our review clearly shows that there is a lack of advanced epidemiologic analyses. Variables that better characterize UI include frequency measure, quantity of urine loss, duration, type, and severity. These factors should be incorporated into basic study design so that more advanced and informative analyses may be conducted. (C) 2003 Elsevier Inc. C1 Univ Bergen, Sect Gen Practice, Dept Publ Hlth & Primary Hlth Care, N-5009 Bergen, Norway. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA. Univ Gothenburg, Dept Paediat Surg, Gothenburg, Sweden. Philippine Gen Hosp, Div Urol, Manila, Philippines. RP Hunskaar, S (reprint author), Univ Bergen, Sect Gen Practice, Dept Publ Hlth & Primary Hlth Care, Ulriksdal 8C, N-5009 Bergen, Norway. NR 62 TC 134 Z9 139 U1 0 U2 5 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 OCT PY 2003 VL 62 IS 4A SU S BP 16 EP 23 DI 10.1016/S0090-4295(03)00755-6 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 731QZ UT WOS:000185899100004 PM 14550833 ER PT J AU De Groot, AS Jesdale, B Martin, W Saint Aubin, C Sbai, H Bosma, A Lieberman, J Skowron, G Mansourati, F Mayer, KH AF De Groot, AS Jesdale, B Martin, W Saint Aubin, C Sbai, H Bosma, A Lieberman, J Skowron, G Mansourati, F Mayer, KH TI Mapping cross-clade HIV-1 vaccine epitopes using a bioinformatics approach SO VACCINE LA English DT Article DE HIV-1 vaccine; imminoformatics; cytotoxic T cell; epitope ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; MONOCLONAL-ANTIBODY; CELL RESPONSES; IMMUNE CONTROL; CTL EPITOPES; TYPE-1; INFECTION; IDENTIFICATION; SEQUENCES AB The genomic variability of HIV viruses circulating in different regions of the world has impeded the development of a globally relevant HIV vaccine. Broadly conserved HIV-1 cytotoxic T cell (CTL) epitopes were identified by screening protein sequences in the Los Alamos National Laboratory (LANL) HIV sequence database with a sequence parsing and matching algorithm (Conservatrix). Putative HIV-1 CTL epitopes were selected from this list using the epitope prediction tool EpiMatrix. Methods: One hundred peptides representing putative HLA A*0201, HLA A*1101, HLA A*0301, and HLA B*07 ligands conserved in many isolates of HIV-1 were synthesized. Seventy-five HLA A*0201, HLA A*1101 and HLA B*07 peptides were incubated with transport associated protein (TAP)-deficient T2 cells transfected with the gene for the corresponding human HLA molecule (HLA A*0201, HLA A*1101, and HLA B*07). Binding and stabilization of peptide-HLA complexes on the surface of the T2 cells was measured by FACS. T cell responses to the entire set of 100 peptides (HLA A*0201, HLA A*1101, HLA A*0301, and HLA B*07) were measured in ELIspot assays using PBMC from healthy HIV-1 infected subjects who possessed a matching HLA allele. Results: Fifty-seven (76%) of the 75 peptides tested in binding studies, including all (three of three) of the control (published) ligands bound to the T2 cells expressing the corresponding MHC molecule. Forty-three of the 100 peptides (43%) including all (four of four) of the control (published) epitopes tested in ELIspot assays stimulated gamma-interferon release. Thirty-one of these 43 epitopes are novel, highly conserved HIV-1 epitopes. EpiMatrix predicted and assays confirmed MHC-restriction by more than one HLA allele for nine of the 43 novel epitopes; of these epitopes five were recognized in the context of MHC "supertypes" and four were promiscuous epitopes. Conclusion: Epitopes identified using this approach were conserved in a broad range of HIV-1 sequences derived from isolates obtained in Latin America, Africa, Asia, the Pacific Islands, Europe and the US. The successful identification of cross-clade epitopes by this bioinformatics approach may accelerate the development of a globally relevant HIV-1 vaccine. (C) 2003 Elsevier Ltd. All rights reserved. C1 Brown Univ, TB HIV Res Lab, Providence, RI 02912 USA. EpiVax Inc, Providence, RI USA. Ctr Blood Res, Boston, MA 02115 USA. Roger Williams Gen Hosp, Providence, RI 02908 USA. Brown Univ, AIDS Program, Providence, RI 02912 USA. RP De Groot, AS (reprint author), Brown Univ, TB HIV Res Lab, Providence, RI 02912 USA. RI Lieberman, Judy/A-2717-2015; OI De Groot, Annie/0000-0001-5911-1459 FU NIAID NIH HHS [R43 AI 46212, R01 AI 40888, R21 AI 45416] NR 53 TC 54 Z9 55 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 1 PY 2003 VL 21 IS 27-30 BP 4486 EP 4504 DI 10.1016/S0264-410X(03)00390-6 PG 19 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 747XF UT WOS:000186830800048 PM 14505932 ER PT J AU Bush, AI Masters, CL Tanzi, RE AF Bush, AI Masters, CL Tanzi, RE TI Copper, beta-amyloid, and Alzheimer's disease: Tapping a sensitive connection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID A-BETA; TRANSGENIC MICE; DRINKING-WATER; PLAQUE CORES; ZINC; PROTEIN; BINDING; CHOLESTEROL; ANTIOXIDANT; SIMVASTATIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic, Australia. RP Bush, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU PHS HHS [R0112686] NR 26 TC 89 Z9 96 U1 1 U2 7 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 SEP 30 PY 2003 VL 100 IS 20 BP 11193 EP 11194 DI 10.1073/pnas.2135061100 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727XG UT WOS:000185685700004 PM 14506299 ER PT J AU Fossett, N Hyman, K Gajewski, K Orkin, SH Schulz, RA AF Fossett, N Hyman, K Gajewski, K Orkin, SH Schulz, RA TI Combinatorial interactions of Serpent, Lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ZINC-FINGER PROTEIN; ACUTE MYELOGENOUS LEUKEMIA; X-LINKED THROMBOCYTOPENIA; MEGAKARYOCYTIC DIFFERENTIATION; TRANSCRIPTION FACTORS; INHERITED MUTATION; GATA PROTEINS; COFACTOR; FOG; HEART AB The GATA factor Serpent (Srp) is required for hemocyte precursor formation during Drosophila hematopoiesis. These blood cell progenitors give rise to two distinct lineages within the developing embryo. Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte production, respectively. In contrast U-shaped, a Friend of GATA class factor, antagonizes crystal cell formation. Here we show that Srp, Lozenge, and U-shaped interact in different combinations to regulate crystal cell lineage commitment. Coexpression of Srp and Lozenge synergistically activated the crystal cell program in both embryonic and larval stages. Furthermore, expression of Lozenge and SrpNC, a Srp isoform with N- and C-terminal zinc fingers, inhibited u-shaped expression, indicating that crystal cell activation coincided with the down-regulation of this repressor-encoding gene. In contrast, whereas U-shaped and SrpNC together blocked crystal cell production, coexpression of U-shaped with noninteracting Srp proteins failed to prevent overproduction of this hemocyte population. Such results indicated that U-shaped and SrpNC must interact to block crystal cell production. Taken together, these studies show that the specialized SrpNC isoform plays a pivotal role during crystal cell lineage commitment, acting as an activator or repressor depending on the availability of specific transcriptional coregulators. These findings provide definitive proof of the combinatorial regulation of hematopoiesis in Drosophila and an in vivo demonstration of GATA and Runx functional interaction in a blood cell commitment program. C1 Univ Texas, MD Anderson Canc Ctr, Grad Program Genes & Dev, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Childrens Hosp, Dept Pediat 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 Schulz, RA (reprint author), Univ Texas, MD Anderson Canc Ctr, Grad Program Genes & Dev, Dept Biochem & Mol Biol, Box 117,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA16672, P30 CA016672] NR 41 TC 57 Z9 57 U1 0 U2 2 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 SEP 30 PY 2003 VL 100 IS 20 BP 11451 EP 11456 DI 10.1073/pnas.1635050100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727XG UT WOS:000185685700051 PM 14504400 ER PT J AU Zhong, XB Reynolds, R Kidd, JR Kidd, KK Jenison, R Marlar, RA Ward, DC AF Zhong, XB Reynolds, R Kidd, JR Kidd, KK Jenison, R Marlar, RA Ward, DC TI Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROLLING-CIRCLE AMPLIFICATION; DISPLACEMENT AMPLIFICATION; DISCRIMINATION; SEQUENCE; SILICON; PROBES; ASSAY; RISK AB Single-nucleotide polymorphisms (SNPs) constitute the bulk of human genetic variation and provide excellent markers to identify genetic factors contributing to complex disease susceptibility. A rapid, sensitive, and inexpensive assay is important for large-scale SNIP scoring. Here we report the development of a multiplex SNIP detection system using silicon chips coated to create a thin-film optical biosensor. Allele-discriminating, aldehyde-labeled oligonucleotides are arrayed and covalently attached to a hydrazine-derivatized chip surface. Target sequences (e.g., PCR amplicons) then are hybridized in the presence of a mixture of biotinylated detector probes, one for each SNIP, and a thermostable DNA ligase. After a stringent wash (0.01 M NaOH), ligation of biotinylated detector probes to perfectly matched capture oligomers is visualized as a color change on the chip surface (gold to blue/purple) after brief incubations with an anti-biotin IgG-horseradish peroxidase conjugate and a precipitable horseradish peroxidase substrate. Testing of PCIR fragments is completed in 30-40 min. Up to several hundred SNPs can be assayed on a 36-mm(2) chip, and SNIP scoring can be done by eye or with a simple digital-camera system. This assay is extremely robust, exhibits high sensitivity and specificity, and is format-flexible and economical. In studies of mutations associated with risk for venous thrombosis and genotyping/ haplotyping of African-American samples, we document high-fidelity analysis with 0 misassignments in 500 assays performed in duplicate. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. ThermoBioStar Inc, Louisville, CO 80027 USA. Oklahoma City Vet Affairs Med Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Ward, DC (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06510 USA. FU NIGMS NIH HHS [P01 GM057672, P01GM57672] NR 26 TC 75 Z9 82 U1 2 U2 13 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 SEP 30 PY 2003 VL 100 IS 20 BP 11559 EP 11564 DI 10.1073/pnas.1934783100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727XG UT WOS:000185685700070 PM 12975525 ER PT J AU Morshead, KB Ciccone, DN Taverna, SD Allis, CD Oettinger, MA AF Morshead, KB Ciccone, DN Taverna, SD Allis, CD Oettinger, MA TI Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL-RECEPTOR; CHROMATIN REMODELING COMPLEX; ALLELIC EXCLUSION; PROMOTER NUCLEOSOMES; NONLYMPHOID CELLS; IN-VITRO; RECOMBINATION; ACETYLATION; METHYLATION; ACCESSIBILITY AB In the earliest stages of antigen receptor assembly, D and J segments of the Ig heavy chain and T cell receptor beta loci are recombined in B and T cells, respectively, whereas the V segments are not. Distinct distribution patterns of various histone modifications and the nucleosome-remodeling factor BRG1 are found at "active" (DJ) and "inactive" (V) regions. Striking "hotspots" of histone H3 dimethylated at lysine 4 (di-Me H3-K4) are localized at the ends of the active DJ domains of both the Ig heavy chain and T cell receptor beta loci. BRG1 is not localized to specific sequences, as it is with transcriptional initiation, but rather associates with the entire active locus in a pattern that mirrors acetylation of histone H3. Within some inactive loci marked by H3-K9 dimethylation, two distinct levels of methylation are found in a nonrandom gene-segment-specific pattern. We suggest that the hotspots of di-Me H3-K4 are important marks for locus accessibility. The specific patterns of modification imply that the regulation of V(D)J recombination involves recruitment of specific methyltransferases in a localized manner. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Rockefeller Univ, Lab Chromatin Biol, New York, NY 10021 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM063959, GM63959, R01 GM048026, GM48026] NR 52 TC 150 Z9 150 U1 0 U2 6 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 SEP 30 PY 2003 VL 100 IS 20 BP 11577 EP 11582 DI 10.1073/pnas.1932643100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727XG UT WOS:000185685700073 PM 14500909 ER PT J AU Kyba, M Perlingeiro, RCR Hoover, RR Lu, CW Pierce, J Daley, GQ AF Kyba, M Perlingeiro, RCR Hoover, RR Lu, CW Pierce, J Daley, GQ TI Enhanced hematopoietic differentiation of embryonic stem cells conditionally expressing Stat5 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Arthur M Sackler Colloquium of the National-Academy-of-Sciences on Regenerative Medicine CY OCT 18-22, 2002 CL IRVINE, CALIFORNIA SP Natl Acad Sci DE hematopoiesis ID DNA-BINDING ACTIVITY; YOLK-SAC; TRANSCRIPTIONAL ACTIVATION; CONSTITUTIVE ACTIVATION; SIGNAL TRANSDUCERS; MOUSE EMBRYO; PROGENITORS; PROTEINS; BCR/ABL; LEUKEMIA AB The signal transducer Stat5 plays a key role in the regulation of hematopoietic differentiation and hematopoietic stem cell function. To evaluate the effects of Stat5 signaling in the earliest hematopoietic progenitors, we have generated an embryonic stem cell line in which Stat5 signaling can be induced with doxycycline. Ectopic Stat5 activation at the point of origin of the hematopoietic lineage (from day 4 to day 6 of embryoid body differentiation) significantly enhances the number of hematopoietic progenitors with colony-forming potential. It does so without significantly altering total numbers or apoptosis of hematopoietic cells, suggesting a cell-intrinsic effect of Stat5 on either the developmental potential or clonogenicity of this population. From day-6 embryoid bodies, under the influence of Stat5 signaling, a population of semiadherent cells can be expanded on OP9 stromal cells that is comprised of primitive hematopoietic blast cells with ongoing, mainly myeloid, differentiation. When these cells are injected into lethally irradiated mice, they engraft transiently in a doxycycline-dependent manner. These results demonstrate that the hematopoietic commitment of embryonic stem cells may be augmented by a Stat5-mediated signal, and highlight the utility of manipulating individual components of signaling pathways for engineering tissue-specific differentiation of stem cells. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. OI Kyba, Michael/0000-0002-5579-7534 FU NCI NIH HHS [R01 CA086991, CA86991]; NIDDK NIH HHS [DK59279, R01 DK059279] NR 40 TC 49 Z9 55 U1 0 U2 2 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 SEP 30 PY 2003 VL 100 SU 1 BP 11904 EP 11910 DI 10.1073/pnas.1734140100 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 729ZP UT WOS:000185805000015 PM 12930895 ER PT J AU Christopher, K Mueller, TF DeFina, R Liang, YR Zhang, JH Gentleman, R Perkins, DL AF Christopher, K Mueller, TF DeFina, R Liang, YR Zhang, JH Gentleman, R Perkins, DL TI The graft response to transplantation: a gene expression profile analysis SO PHYSIOLOGICAL GENOMICS LA English DT Article DE gene regulation; rodent ID CLUSTER-ANALYSIS; IN-VIVO; PROTEIN; CELL; C1Q; INNATE; MICE; CALRETICULIN; ACTIVATION; PATTERNS AB Little is known regarding the graft response to transplantation injury. This study investigates the posttransplantation response of genes that are constitutively expressed in the heart. Constitutive heart and lymph node tissue-restricted gene expression was first analyzed with DNA microarrays. To demonstrate changes following transplantation in genes constitutively expressed in the heart, we performed vascularized murine heart transplants in allogeneic (BALB/c to B6), syngeneic ( B6 to B6), and alymphoid (BALB/c-RAG2(-/-) to B6-RAG1(-/-)) experimental groups. Temporal induction of genes posttransplant relative to constitutive expression was evaluated with DNA microarrays. Dendrograms and self-organizing maps were generated to determine the dissimilarity between the experimental groups and to identify subsets of differentially expressed genes within the groups, respectively. Expression patterns of selected genes were confirmed by real-time PCR. Biological processes were assigned to genes induced posttransplant using the Ann-Builder package via the Gene Ontology Database. Posttransplant, a shift was noted in genes classified as defense, communication, and metabolism. Our results identify novel components of the graft response to transplantation injury and rejection. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Lab Mol Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci,Biostat Unit, Boston, MA 02115 USA. RP Perkins, DL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Lab Mol Immunol, PBB 170 75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01-AI-44085] NR 27 TC 9 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD SEP 29 PY 2003 VL 15 IS 1 BP 52 EP 64 DI 10.1152/physiolgenomics.00139.2002 PG 13 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 726WY UT WOS:000185625600007 PM 14517350 ER PT J AU Schmucker, D AF Schmucker, D TI Downstream of guidance receptors: Entering the baroque period of axon guidance signaling SO NEURON LA English DT Editorial Material ID ADAPTER PROTEIN; DROSOPHILA; ROUNDABOUT; MIDLINE; DOCK AB The Roundabout ("Robo") family of transmembrane proteins are the receptors and mediators of the repellent axon guidance signal Slit. However, the molecular mechanisms by which Robo signaling leads to growth cone or neuron repulsion are still poorly understood. A study by Fan et al. in this issue of Neuron expands the repertoire of Robo pathway components and stimulates a new look at axon guidance signaling in general. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurobiol,Dept Canc Biol, Boston, MA 02115 USA. RP Schmucker, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurobiol,Dept Canc Biol, Boston, MA 02115 USA. NR 12 TC 7 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 25 PY 2003 VL 40 IS 1 BP 4 EP 6 DI 10.1016/S0896-6273(03)00603-2 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 726TA UT WOS:000185614700003 PM 14527427 ER PT J AU Szebenyi, G Morfini, GA Babcock, A Gould, M Selkoe, K Stenoien, DL Young, M Faber, PW MacDonald, ME McPhaul, MJ Brady, ST AF Szebenyi, G Morfini, GA Babcock, A Gould, M Selkoe, K Stenoien, DL Young, M Faber, PW MacDonald, ME McPhaul, MJ Brady, ST TI Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport SO NEURON LA English DT Article ID BULBAR MUSCULAR-ATROPHY; KINESIN HEAVY; NUCLEAR-LOCALIZATION; POLYGLUTAMINE TRACT; CYTOPLASMIC DYNEIN; LIGHT-CHAINS; WILD-TYPE; DISEASE; PROTEIN; AXOPLASM AB Huntington's and Kennedy's disease are autosomal dominant neurodegenerative diseases caused by pathogenic expansion of polyglutamine tracts. Expansion of glutamine repeats must in some way confer a gain of pathological function that disrupts an essential cellular process and leads to loss of affected neurons. Association of huntingtin with vesicular structures raised the possibility that axonal transport might be altered. Here we show that polypeptides containing expanded polyglutamine tracts, but not normal N-terminal huntingtin or androgen receptor, directly inhibit both fast axonal transport in isolated axoplasm and elongation of neuritic processes in intact cells. Effects were greater with truncated polypeptides and occurred without detectable morphological aggregates. C1 Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Brady, ST (reprint author), Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. FU NIDDK NIH HHS [DK03892]; NINDS NIH HHS [NS23320, NS16367, NS32765, NS41170, NS43408, NS23868] NR 58 TC 215 Z9 224 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 25 PY 2003 VL 40 IS 1 BP 41 EP 52 DI 10.1016/S0896-6273(03)00569-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 726TA UT WOS:000185614700008 PM 14527432 ER PT J AU Finkelstein, JS Hayes, A Hunzelman, JL Wyland, JJ Lee, H Neer, RM AF Finkelstein, JS Hayes, A Hunzelman, JL Wyland, JJ Lee, H Neer, RM TI The effects of parathyroid hormone, alendronate, or both in men with osteoporosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED TRIAL; GROWTH FACTOR-I; POSTMENOPAUSAL WOMEN; OVARIECTOMIZED RATS; ESTROGEN DEFICIENCY; VERTEBRAL FRACTURES; RESORPTION; MARKERS; MASS AB BACKGROUND: Because parathyroid hormone increases both bone formation and bone resorption, it is possible that combining parathyroid hormone with an antiresorptive agent will enhance its effect on bone mineral density. METHODS: We randomly assigned 83 men who were 46 to 85 years of age and had low bone density to receive alendronate (10 mg daily; 28 men), parathyroid hormone (40 microg subcutaneously daily; 27 men), or both (28 men). Alendronate therapy was given for 30 months; parathyroid hormone therapy was begun at month 6. The bone mineral density of the lumbar spine, proximal femur, radial shaft, and total body was measured every six months with the use of dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured at base line and month 30 by means of quantitative computed tomography. Serum alkaline phosphatase levels were measured every six months. The primary end point was the rate of change in the bone mineral density at the posteroanterior spine. RESULTS: The bone mineral density at the lumbar spine increased significantly more in men treated with parathyroid hormone alone than in those in the other groups (P<0.001 for both comparisons). The bone mineral density at the femoral neck increased significantly more in the parathyroid hormone group than in the alendronate group (P<0.001) or the combination-therapy group (P=0.01). The bone mineral density of the lumbar spine increased significantly more in the combination-therapy group than in the alendronate group (P<0.001). At 12 months, changes in the serum alkaline phosphatase level were significantly greater in the parathyroid hormone group than in the alendronate group or the combination-therapy group (P<0.001 for both comparisons). CONCLUSIONS: Alendronate impairs the ability of parathyroid hormone to increase the bone mineral density at the lumbar spine and the femoral neck in men. This effect may be attributable to an attenuation of parathyroid hormone-induced stimulation of bone formation by alendronate. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-1066]; NIAMS NIH HHS [5 P50 AR44855]; NIDDK NIH HHS [K24 DK02759] NR 37 TC 447 Z9 468 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 25 PY 2003 VL 349 IS 13 BP 1216 EP 1226 DI 10.1056/NEJMoa035725 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 724LJ UT WOS:000185488800004 PM 14500805 ER PT J AU Tancredi, DN Shannon, MW Goldstein, JN Kosowsky, J Lai, M Singh, MK AF Tancredi, DN Shannon, MW Goldstein, JN Kosowsky, J Lai, M Singh, MK TI A man with sudden alteration of mental status - Ingestion of 1,4-butanediol, resulting in gamma-hydroxybutyrate intoxication SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MANAGEMENT; WITHDRAWAL; OVERDOSE; DEATH C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Tancredi, DN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 17 TC 9 Z9 9 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 25 PY 2003 VL 349 IS 13 BP 1267 EP 1275 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 724LJ UT WOS:000185488800010 PM 14507952 ER PT J AU Chen, SJ Paul, P Price, BD AF Chen, SJ Paul, P Price, BD TI ATM's leucine-rich domain and adjacent sequences are essential for ATM to regulate the DNA damage response SO ONCOGENE LA English DT Article DE leucine zipper; ATM; kinase; radiosensitivity; ataxia telangiectasia ID ATAXIA-TELANGIECTASIA GENE; S-PHASE CHECKPOINT; FUNCTIONAL-LINK; BREAST-CANCER; DEPENDENT PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVITY; MISSENSE MUTATIONS; ALLELIC VARIANTS; P53; RADIATION AB The ATM protein kinase regulates the DNA damage response by phosphorylating proteins involved in cell cycle checkpoints and DNA repair. We report here on the function of the predicted leucine zipper (LZ) motif, and sequences adjacent to this, in regulating ATM activity. The predicted LZ sequence was deleted from ATM, generating ATMDeltaLZ, and expressed in an ATM-negative AT cell line. ATM increased cell survival following exposure to ionizing radiation, whereas expression of ATMDeltaLZ failed to increase cell survival. ATMDeltaLZ retained in vitro kinase activity, but was unable to phosphorylate p53 in vivo. Leucine zippers mediate homo- and heterodimerization of proteins. However, the predicted LZ of ATM did not mediate the formation of ATM dimers. We examined if the predicted LZ of ATM was a dominant-negative inhibitor of ATM function in SW480 cells. Expression of amino acids 769-1436 of ATM, including the predicted LZ, sensitized SW480 cells to ionizing radiation, but did not inhibit ATM's kinase activity or its ability to phosphorylate Brca1. Further, this dominant-negative activity was not dependent on the predicted LZ domain. The central region of the ATM protein therefore contains multiple sequences which regulate cell survival following DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,JF513, Boston, MA 02115 USA. FU NCI NIH HHS [CA93602, CA64585] NR 39 TC 15 Z9 16 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 SEP 25 PY 2003 VL 22 IS 41 BP 6332 EP 6339 DI 10.1038/sj.onc.1206760 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 725GK UT WOS:000185535300003 PM 14508513 ER PT J AU Hudson, MM Mertens, AC Yasui, Y Hobbie, W Chen, HG Gurney, JG Yeazel, M Recklitis, CJ Marina, N Robison, LR Oeffinger, KC AF Hudson, MM Mertens, AC Yasui, Y Hobbie, W Chen, HG Gurney, JG Yeazel, M Recklitis, CJ Marina, N Robison, LR Oeffinger, KC CA Childhood Canc Survivor Study Inve TI Health status of adult long-term survivors of childhood cancer - A report from the childhood cancer survivor study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SIBLING ADAPTATION; ADOLESCENT CANCER; HODGKINS-DISEASE; LATE MORTALITY; LATE DEATHS; DIAGNOSIS; LEUKEMIA; SYSTEM; CURE AB Context Adult survivors of childhood cancer are at risk for medical and psychosocial sequelae that may adversely affect their health status. Objectives To compare the health status of adult survivors of childhood cancer and siblings and to identify factors associated with adverse outcomes. Design, Setting, and Participants Health status was assessed in 9535 adult participants of the Childhood Cancer Survivor Study, a cohort of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings (n=2916) served as a comparison group. Main Outcome Measures Six health status domains were assessed: general health, mental health, functional status, activity limitations, cancer-related pain, and cancer-related anxiety/fears. The first 4 domains were assessed in the control group. Results Survivors were significantly more likely to report adverse general health (odds ratio [OR], 2.5; 95% confidence interval [Cl], 2.1-3.0; P<.001), mental health (OR, 1.8; 95% Cl, 1.6-2.1; P<.001), activity limitations (OR, 2.7; 95% Cl, 2.3-3.3; P<.001), and functional impairment(OR, 5.2; 95% Cl, 4.1-6.6; P<.001), compared with siblings. Forty-four percent of survivors reported at least 1 adversely affected health status domain. Sociodemographic factors associated with reporting at least 1 adverse health status domain included being female (OR, 1.4; 95% Cl, 1.3-1.6; P<.001), lower level of educational attainment (OR, 2.0; 95% Cl, 1.8-2.2; P<.001), and annual income less than $20000 (OR, 1.8; 95% Cl, 1.6-2.1; P<.001). Relative to those survivors with childhood leukemia, an increased risk was observed for at least 1 adverse health status domain among those with bone tumors (OR, 2.1; 95% CI, 1.8-2.5; P<.001), central nervous system tumors (OR, 1.7; 95% Cl, 1.5-2.0; P<.001), and sarcomas (OR, 1.2; 95% Cl, 1.1-1.5; P=.01). Conclusion Clinicians caring for adult survivors of childhood cancer should be aware of the substantial risk for adverse health status, especially among females, those with low educational attainment, and those with low household incomes. C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. Univ Tennessee, Coll Med, Memphis, TN 38163 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Family Practice, Minneapolis, MN USA. Univ Minnesota, Dept Biostat, Minneapolis, MN USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. Childrens Hosp Philadelphia, Dept Oncol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Dept Pediat, Stanford, CA 94305 USA. Univ Texas, SW Med Ctr, Dept Family Practice & Community Med, Dallas, TX USA. RP St Jude Childrens Res Hosp, Dept Hematol Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM melissa.hudson@stjude.org RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 FU NCI NIH HHS [5U24-CA-55727, CA 21765] NR 38 TC 416 Z9 421 U1 5 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 24 PY 2003 VL 290 IS 12 BP 1583 EP 1592 DI 10.1001/jama.290.12.1583 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 723ZK UT WOS:000185461300023 PM 14506117 ER PT J AU Dong, HX Fazzaro, A Xiang, CX Korsmeyer, SJ Jacquin, MF McDonald, JW AF Dong, HX Fazzaro, A Xiang, CX Korsmeyer, SJ Jacquin, MF McDonald, JW TI Enhanced oligodendrocyte survival after spinal cord injury in Bax-deficient mice and mice with delayed Wallerian degeneration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; spinal cord hemisection; oligodendrocyte death; Wld(s) mutation; Bax deficiency; Bax(-/-); Wallerian degeneration; immunohistochemistry ID CELL-DEATH; C57BL/OLA MICE; MUTATION WLD(S); DOWN-REGULATION; NEURONAL DEATH; UP-REGULATION; OPTIC-NERVE; DNA PLASMID; BCL-2 GENE; APOPTOSIS AB Mechanisms of oligodendrocyte death after spinal cord injury (SCI) were evaluated by T9 cord level hemisection in wild-type mice (C57BL/6J and Bax+/+ mice), Wld(s) mice in which severed axons remain viable for 2 weeks, and mice deficient in the proapoptotic protein Bax (Bax-/-). In the lateral white-matter tracts, substantial oligodendrocyte death was evident in the ipsilateral white matter 3-7 mm rostral and caudal to the hemisection site 8 d after injury. Ultrastructural analysis and expression of anti-activated caspase-3 characterized the ongoing oligodendrocyte death at 8 d as primarily apoptotic. Oligodendrocytes were selectively preserved in Wlds mice compared with C57BL/6J mice at 8 d after injury, when severed axons remained viable as verified by antereograde labeling of the lateral vestibular spinal tract. However, 30 d after injury when the severed axons in Wlds animals were already degenerated, the oligodendrocytes preserved at 8 d were lost, and numbers were then equivalent to control C57BL/6J mice. In contrast, oligodendrocyte death was prevented at both time points in Bax-/- mice. When cultured oligodendrocytes were exposed to staurosporine or cyclosporin A, drugs known to stimulate apoptosis in oligodendrocytes, those from Bax-/- mice but not from Bax+/+ or Bax+/- mice were resistant to the apoptotic death. In contrast, the three groups were equally vulnerable to excitotoxic necrosis death induced by kainate. On the basis of these data, we hypothesize that the Wallerian degeneration of white matter axons that follows SCI removes axonal support and induces apoptotic death in oligodendrocytes by triggering Bax expression. C1 Washington Univ, Sch Med,Dept Neurol, Restorat Treatment & Res Program, Spinal Cord Injury Neurorehabil Sect, St Louis, MO 63108 USA. Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, Dept Neurol Surg, St Louis, MO 63108 USA. Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, Dept Anat, St Louis, MO 63108 USA. Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, Dept Neurobiol, St Louis, MO 63108 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP McDonald, JW (reprint author), Washington Univ, Sch Med,Dept Neurol, Restorat Treatment & Res Program, Spinal Cord Injury Neurorehabil Sect, Campus Box 8518,4444 Forest Pk Ave, St Louis, MO 63108 USA. FU NINDS NIH HHS [NS01931, NS37927] NR 59 TC 60 Z9 67 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 SEP 24 PY 2003 VL 23 IS 25 BP 8682 EP 8691 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 725GB UT WOS:000185534500007 PM 14507967 ER PT J AU Horner, RD Kamins, KG Feussner, JR Grambow, SC Hoff-Lindquist, J Harati, Y Mitsumoto, H Pascuzzi, R Spencer, PS Tim, R Howard, D Smith, TC Ryan, MAK Coffman, CJ Kasarskis, EJ AF Horner, RD Kamins, KG Feussner, JR Grambow, SC Hoff-Lindquist, J Harati, Y Mitsumoto, H Pascuzzi, R Spencer, PS Tim, R Howard, D Smith, TC Ryan, MAK Coffman, CJ Kasarskis, EJ TI Occurrence of amyotrophic lateral sclerosis among Gulf War veterans SO NEUROLOGY LA English DT Article ID US VETERANS; EPIDEMIOLOGY; MORTALITY; TRAUMA AB Background: In response to Gulf War veterans' concerns of high rates of ALS, this investigation sought to determine if Gulf War veterans have an elevated rate of ALS. Methods: A nationwide epidemiologic case ascertainment study design was used to ascertain all occurrences of ALS for the 10-year period since August 1990 among active duty military and mobilized Reserves, including National Guard, who served during the Gulf War (August 2, 1990, through July 31, 1991). The diagnosis of ALS was confirmed by medical record review. Risk was assessed by the age-adjusted, average, annual 10-year cumulative incidence rate. Results: Among approximately 2.5 million eligible military personnel, 107 confirmed cases of ALS were identified for an overall occurrence of 0.43 per 100,000 persons per year. A significant elevated risk of ALS occurred among all deployed personnel (RR = 1.92; 95% CL = 1.29, 2.84), deployed active duty military (RR = 2.15, 95% CL = 1.38, 3.36), deployed Air Force (RR = 2.68, 95% CL = 1.24, 5.78), and deployed Army (RR = 2;04; 95% CL = 1.10, 3.77) personnel. Elevated, but nonsignificant, risks were observed for deployed Reserves and National Guard (RR = 2.50; 95% CL = 0.88, 7.07), deployed Navy (RR = 1.48, 95% CL = 0.62, 3.57), and deployed Marine Corps (RR = 1.13; 95% CL = 0.27, 4.79) personnel. Overall, the attributable risk associated with deployment was 18% (95% CL = 4.9%, 29.4%). Conclusions: Military personnel who were deployed to the Gulf Region during the Gulf War period experienced a greater post-war risk of ALS than those who were deployed to the Gulf. C1 NINDS, Rockville, MD 20852 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. VA Epidemiol Res & Informat Ctr, Durham, NC 27705 USA. VA Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27705 USA. Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Oregon Hlth & Sci Univ, Portland, OR USA. Durham VA Med Ctr, Durham, NC 27705 USA. USN, Hlth Res Ctr, San Diego, CA 92152 USA. Lexington VA Med Ctr, Lexington, KY 40511 USA. Univ Kentucky, Lexington, KY 40536 USA. RP Horner, RD (reprint author), NINDS, NSC Bldg,Room 2149,6001 Execut Blvd, Rockville, MD 20852 USA. RI Grambow, Steven/E-1422-2015 OI Grambow, Steven/0000-0001-6037-3253 NR 23 TC 141 Z9 143 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 23 PY 2003 VL 61 IS 6 BP 742 EP 749 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 723ZC UT WOS:000185460600006 PM 14504315 ER PT J AU Mink, JW Caruso, PA Pomeroy, SL AF Mink, JW Caruso, PA Pomeroy, SL TI Progressive myoclonus in a child with a deep cerebellar mass SO NEUROLOGY LA English DT Article AB Myoclonus is often associated with pathology of the cerebellum. However, the site of neurons responsible for the generation of myoclonus in cerebellar disease is not known. The authors report a young child with myoclonus associated with a ganglioglioma in the region of the deep cerebellar white matter and cerebellar nuclei. They hypothesize that abnormal paroxysmal discharge of neurons in the cerebellar nuclei can generate myoclonus. C1 Univ Rochester, Med Ctr, Sch Med, Rochester, NY 14642 USA. Golisano Childrens Hosp Strong, Rochester, NY USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Mink, JW (reprint author), Univ Rochester, Med Ctr, Sch Med, Box 631,601 Elmwood Ave, Rochester, NY 14642 USA. NR 10 TC 20 Z9 20 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 SEP 23 PY 2003 VL 61 IS 6 BP 829 EP 831 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 723ZC UT WOS:000185460600022 PM 14504331 ER PT J AU Smoller, JW Pollack, MH Wassertheil-Smoller, S Barton, B Hendrix, SL Jackson, RD Dicken, T Oberman, A Sheps, DS AF Smoller, JW Pollack, MH Wassertheil-Smoller, S Barton, B Hendrix, SL Jackson, RD Dicken, T Oberman, A Sheps, DS TI Prevalence and correlates of panic attacks in postmenopausal women - Results from an ancillary study to the women's health initiative SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; NATIONAL-COMORBIDITY-SURVEY; AREA FOLLOW-UP; ANXIETY DISORDERS; MYOCARDIAL-INFARCTION; FUNCTIONAL DISABILITY; PSYCHIATRIC-DISORDERS; RATE-VARIABILITY; PHOBIC ANXIETY; UNITED-STATES AB Background: Panic attacks are known to be more common in women than in men, but the prevalence and correlates of panic in the postmenopausal period have not been well defined. Methods: Cross-sectional survey of 3369 community dwelling postmenopausal women enrolled between December 1, 1997, and November 30, 2000, in the Myocardial Ischemia and Migraine Study, a 10-center ancillary study of the 40-center Women's Health Initiative. Participants, aged 50 to 79 years and predominantly white (73%), completed questionnaires about the occurrence of panic attacks in the previous 6 months and about migraine headaches and underwent 24-hour ambulatory electrocardiographic monitoring. The 6-month prevalences of full-blown and limited-symptom panic attacks were calculated, and their associations with other sociodemographic and clinical variables were examined in multivariate analyses. Results: One of the panic attack types was reported by 17.9% (95% confidence interval, 16.6%-19.2%) of women (full-blown attacks, 9.8%; limited-symptom attacks, 8.1%). Adjusting for age and race or ethnicity, full-blown panic attacks were more common in women with a history of migraine, emphysema, cardiovascular disease, chest pain during ambulatory electrocardiography, and symptoms of depression. Full-blown panic attacks were associated in a dose-response manner with negative life events during the past year. Panic attacks were associated with functional impairment even after adjusting for comorbid medical conditions and depression. There was no significant association with self-reported use of hormone replacement therapy. Conclusions: Panic attacks may be relatively common among postmenopausal women and seem to be associated with stressful life events, medical comorbidity, and functional impairment. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC-812, Boston, MA 02114 USA. OI Barton, Bruce/0000-0001-7878-8895 NR 58 TC 26 Z9 27 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 22 PY 2003 VL 163 IS 17 BP 2041 EP 2050 DI 10.1001/archinte.163.17.2041 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 724MF UT WOS:000185490800007 PM 14504117 ER PT J AU Barr, RG Rowe, BH Camargo, CA AF Barr, RG Rowe, BH Camargo, CA TI Methylxanthines for exacerbations of chronic obstructive pulmonary disease: meta-analysis of randomised trials SO BRITISH MEDICAL JOURNAL LA English DT Article ID REVERSIBLE AIRWAYS OBSTRUCTION; RELEASE THEOPHYLLINE; CHRONIC-BRONCHITIS; AMINOPHYLLINE; SALBUTAMOL; THERAPY; MANAGEMENT; ASTHMA AB Objective To evaluate the addition of methylxanthines to standard treatments in patients presenting with acute exacerbations of chronic obstructive pulmonary disease (COPD). Design Meta-analysis of randomised controlled trials. Data source The Cochrane air-ways review group's COPD register. Two reviewers independently selected articles for inclusion, assessed methodological quality, and extracted data. Selection of studies Four trials met the inclusion criteria, with 169 patients. Main outcome measures Mean change in spirometry, clinical end points, symptom scores, and adverse events. Results Mean change in forced expiratory volume at one second at two hours was similar in methylxanthine and placebo groups but transiently increased with methylxanthines at three days. Non-significant reductions in admissions to hospital and length of stay were offset by a non-significant increase in relapses at one week. Changes in symptom scores did not reach significance. Methylxanthines caused more nausea and vomiting than placebo (odds ratio 4.6,95% confidence interval 1.7 to 12.6), and non-significant increases in tremor, palpitations, and arrhythmias were also observed. Conclusions The available data do not support the use of methylxanthines for the treatment of exacerbations of chronic obstructive pulmonary disease. Potential benefits of methylxanthines for lung function and symptoms were generally not confirmed at standard levels of significance, whereas the potentially important adverse events of nausea and vomiting were significantly increased in patients receiving methylxanthines. C1 Columbia Presbyterian Med Ctr, Div Gen Med, New York, NY 10032 USA. Univ Alberta, Div Emergency Med, Edmonton, AB T6G 2B7, Canada. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Barr, RG (reprint author), Columbia Presbyterian Med Ctr, Div Gen Med, New York, NY 10032 USA. FU BHP HRSA HHS [PE-11001]; NHLBI NIH HHS [HL-07427, HL-63841] NR 38 TC 48 Z9 50 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD SEP 20 PY 2003 VL 327 IS 7416 BP 643 EP 646A DI 10.1136/bmj.327.7416.643 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 724AC UT WOS:000185463100014 PM 14500434 ER PT J AU Grimm, J Potthast, A Wunder, A Moore, A AF Grimm, J Potthast, A Wunder, A Moore, A TI Magnetic resonance imaging of the pancreas and pancreatic tumors in a mouse orthotopic model of human cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE MRI; tumor model; pancreas ID LIVER-LESIONS; NUDE-MICE; SPIRAL CT; IN-VIVO; MRI; BIOLOGY AB Pancreatic adenocarcinoma has a rising incidence and a very poor survival rate. To develop new treatment strategies, extensive research is performed on animal models of pancreatic cancer. Orthotopic pancreatic tumors models, where the tumor is implanted into the pancreas, resemble the human disease more closely than subcutaneous tumor models, yet are difficult to monitor. In our study we report a magnetic resonance imaging (MRI) approach to visualize the pancreas in mice and to monitor orthotopically implanted pancreatic tumors. An MRI scanner was used to image normal murine pancreas and the pancreas of mice implanted with a human pancreatic adenocarcinoma cell line. Gadolinium (Gd)-DTPA-enhanced T1 - and T2-weighted standard sequences were used with the objective to identify the pancreas and to monitor the growth of orthotopic tumors during 30 days. The pancreas as well as the implanted tumors could be easily identified using MRI. On T2-weighted images, the implanted tumors were easily visualized at the implantation side with high signal intensity. After application of a contrast agent, the tumors showed an enhancement. Heterogeneities within the tumor could be delineated, corresponding to histology, and the size of the tumor could be measured precisely. MR serves as a noninvasive high-resolution image modality to monitor murine pancreas as well as size, growth and even areas of heterogeneity in orthotopic pancreatic tumors. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Gen Hosp,Dept Radiol, MGH,MIT,HMS Athinoula A Martinos Ctr Biomed Imag, Boston, MA 02115 USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Univ Klinikum Schleswig Holstein, Radiol Diagnost Klin, Kiel, Germany. RP Moore, A (reprint author), Bldg 149,13th St,Room 5419, Charlestown, MA 02129 USA. RI Grimm, Jan/B-1937-2008 NR 27 TC 36 Z9 39 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 20 PY 2003 VL 106 IS 5 BP 806 EP 811 DI 10.1002/ijc.11281 PG 6 WC Oncology SC Oncology GA 712HM UT WOS:000184792300023 PM 12866043 ER PT J AU Million, M Grigoriadis, DE Sullivan, S Crowe, PD McRoberts, JA Zhou, HP Saunders, PR Maillot, C Mayer, EA Tache, Y AF Million, M Grigoriadis, DE Sullivan, S Crowe, PD McRoberts, JA Zhou, HP Saunders, PR Maillot, C Mayer, EA Tache, Y TI A novel water-soluble selective CRF1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats SO BRAIN RESEARCH LA English DT Article DE non-peptide receptor antagonist; CRF1 receptor; colonic transit; colorectal distention; visceral pain ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; GASTROINTESTINAL-TRACT; AVOIDANCE STRESS; BINDING-PROTEIN; FOS EXPRESSION; UROCORTIN-II; BRAIN; RESPONSES; SUBTYPE-1 AB The stress response involves the activation of two corticotropin-releasing factor (CRF) receptor subtypes. We investigated the role of CRF, in stress-related visceral responses. A novel water-soluble tricyclic CRF, antagonist, NBI 35965 was developed that displayed a high affinity for CRF1 (K(i)similar to4 nM) while having no binding affinity to CRF2. This antagonist also inhibited the stimulation of cAMP induced by sauvagine in CRF1 transfected cells. NBI 35965 administered per orally (p.o.) in rats (1, 3, 10 or 30 mg/kg) inhibited dose-dependently [I-125] sauvagine binding selectively at brain sites of CRF, distribution as shown by ex vivo receptor autoradiography. At the highest doses, NBI 35965 completely prevented [I-125]sauvagine labeling in the cortex. NBI 35965 (10 mg/kg) administered p.o. or subcutaneously (sc) 1 h before intravenous CRF completely blocked the 81% shortening of distal colonic transit time induced by CRF. NBI 35965 (20 mg/kg s.c.) significantly reduced the defecation in response to water avoidance stress but not that induced by s.c. carbachol. In adult male Long-Evans rats that had undergone maternal separation, acute water avoidance stress significantly increased the visceromotor response to colorectal distention (20-80 mmHg) by 42+/-19% compared with the response before stress. Stress-induced visceral hyperalgesia was abolished by NBI 35965 (20 mg/kg, s.c.). The data show that NBI 35965 is a novel water-soluble selective CRF, antagonist with bioavailability to the brain upon peripheral administration and that CRF1 receptor signaling pathways are involved in water avoidance stress-induced hyperalgesia to colorectal distention and stimulation of colonic transit. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Ctr Neurovisceral Sci & Womens Hlth, Div Digest Dis,Dept Med, Los Angeles, CA 90073 USA. Neurocrine Biosci Inc, San Diego, CA 92121 USA. RP Million, M (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [R43 DK61863, DK 57238-01A1S1, DK-57238, R01 DK-33061, R01 DK58173] NR 53 TC 78 Z9 82 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 19 PY 2003 VL 985 IS 1 BP 32 EP 42 DI 10.1016/S0006-8993(03)03027-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 723TB UT WOS:000185446700004 PM 12957366 ER PT J AU Strack, B Calistri, A Craig, S Popova, E Gottlinger, HG AF Strack, B Calistri, A Craig, S Popova, E Gottlinger, HG TI AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding SO CELL LA English DT Article ID LATE ASSEMBLY DOMAIN; ROUS-SARCOMA-VIRUS; GAG PROTEIN; MULTIVESICULAR-BODY; SACCHAROMYCES-CEREVISIAE; PARTICLE-PRODUCTION; TERMINAL DOMAIN; ESCRT-I; UBIQUITIN; TSG101 AB HIV-1 and other retroviruses exit infected cells by budding from the plasma membrane, a process requiring membrane fission. The primary late assembly (L) domain in the p6 region of HIV-1 Gag mediates the detachment of the virion by recruiting host Tsg101, a component of the class E vacuolar protein sorting (Vps) machinery. We now show that HIV Gag p6 contains a second region involved in L domain function that binds AIP1, a homolog of the yeast class E Vps protein Bro1. Further, AIP1 interacts with Tsg101 and homologs of a subunit of the yeast class E Vps protein complex ESCRT-III. AIP1 also binds to the L domain in EIAV p9, and this binding correlates perfectly with L domain function. These observations identify AIP1 as a component of the viral budding machinery, which serves to link a distinct region in the L domain of HIV-1 p6 and EIAV p9 to ESCRT-III. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [AI29873] NR 40 TC 518 Z9 531 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 19 PY 2003 VL 114 IS 6 BP 689 EP 699 DI 10.1016/S0092-8674(03)00653-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 724AL UT WOS:000185464000007 PM 14505569 ER PT J AU Kim, M Carman, CV Springer, TA AF Kim, M Carman, CV Springer, TA TI Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins SO SCIENCE LA English DT Article ID INSIDE-OUT ACTIVATION; ALPHA-SUBUNIT; AFFINITY; TAILS; LFA-1; FLOW; ALPHA-IIB-BETA-3; ADHESIVENESS; CHEMOKINES; REVEALS AB Although critical for development, immunity, wound healing, and metastasis, integrins represent one of the few classes of plasma membrane receptors for which the basic signaling mechanism remains a mystery. We investigated cytoplasmic conformational changes in the integrin LFA-1 (alpha(L)beta(2)) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein - fused and yellow fluorescent protein - fused alpha(L) and beta(2) cytoplasmic domains. In the resting state these domains were close to each other, but underwent significant spatial separation upon either intracellular activation of integrin adhesiveness (inside-out signaling) or ligand binding (outside-in signaling). Thus, bidirectional integrin signaling is accomplished by coupling extracellular conformational changes to an unclasping and separation of the alpha and beta cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NCI NIH HHS [CA31798] NR 31 TC 519 Z9 538 U1 4 U2 34 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 SEP 19 PY 2003 VL 301 IS 5640 BP 1720 EP 1725 DI 10.1126/science.1084174 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 722QN UT WOS:000185387700044 PM 14500982 ER PT J AU Kim, PW Sun, ZYJ Blacklow, SC Wagner, G Eck, MJ AF Kim, PW Sun, ZYJ Blacklow, SC Wagner, G Eck, MJ TI A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8 SO SCIENCE LA English DT Article ID TYROSINE-PROTEIN-KINASE; AMINO-TERMINAL DOMAIN; CYTOPLASMIC TAIL; SERINE PHOSPHORYLATION; DOWN-REGULATION; COATED PITS; P56LCK; P56(LCK); ANTIGEN; COMPLEX AB The T cell coreceptors CD4 and CD8 both associate via their cytoplasmic tails with the N-terminus of the Src-family tyrosine kinase Lck. These interactions require zinc and are critical for T cell development and activation. We examined the folding and solution structures of ternary CD4-Lck-Zn2+ and CD8alpha-LckZn(2+) complexes. The coreceptor tails and the Lck N-terminus are unstructured in isolation but assemble in the presence of zinc to form compactly folded heterodimeric domains. The cofolded complexes have similar "zinc clasp" cores that are augmented by distinct structural elements. A dileucine motif required for clathrin-mediated endocytosis of CD4 is masked by Lck. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu FU NCI NIH HHS [CA080942]; NHLBI NIH HHS [HL61001] NR 26 TC 114 Z9 117 U1 1 U2 10 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 SEP 19 PY 2003 VL 301 IS 5640 BP 1725 EP 1728 DI 10.1126/science.1085643 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 722QN UT WOS:000185387700045 PM 14500983 ER PT J AU Davidson, AJ Ernst, P Wang, Y Dekens, MPS Kingsley, PD Palis, J Korsmeyer, SJ Daley, GQ Zon, LI AF Davidson, AJ Ernst, P Wang, Y Dekens, MPS Kingsley, PD Palis, J Korsmeyer, SJ Daley, GQ Zon, LI TI cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes SO NATURE LA English DT Article ID HOMEOBOX GENE; HEMATOPOIETIC-CELLS; MYELOID-LEUKEMIA; CAUDAL HOMOLOG; TAIL FORMATION; STEM-CELL; EXPRESSION; MICE; DROSOPHILA; EXPANSION AB Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis(1-3). Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis. C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Max Planck Inst Entwicklungsbiol, Genet Abt, D-72076 Tubingen, Germany. Univ Rochester, Dept Pediat, Ctr Human Genet & Mol Pediat Dis, Rochester, NY 14642 USA. RP Zon, LI (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. NR 30 TC 162 Z9 171 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 18 PY 2003 VL 425 IS 6955 BP 300 EP 306 DI 10.1038/nature01973 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 722JA UT WOS:000185370900047 PM 13679919 ER PT J AU Xu, L Wei, Y Reboul, J Vaglio, P Shin, TH Vidal, M Elledge, SJ Harper, JW AF Xu, L Wei, Y Reboul, J Vaglio, P Shin, TH Vidal, M Elledge, SJ Harper, JW TI BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3 SO NATURE LA English DT Article ID CAENORHABDITIS-ELEGANS; CELL-CYCLE; C-ELEGANS; F-BOX; DEGRADATION; COMPLEX; FAMILY; GENE; PROTEOLYSIS; RECOGNITION AB Programmed destruction of regulatory proteins through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways(1,2). Cullins(3) are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex(4-6). The substrate selectivity of these E3 ligases is dictated by a specificity module that binds cullins. In the SCF complex, this module is composed of Skp1, which binds directly to Cul1, and a member of the F-box family of proteins(4-7). F-box proteins bind Skp1 through the F-box motif(7), and substrates by means of carboxy-terminal protein interaction domains(1,2,5). Similarly, Cul2 and Cul5 interact with BC-box-containing specificity factors through the Skp1-like protein elongin C-2. Cul3 is required for embryonic development in mammals and Caenorhabditis elegans(8-10) but its specificity module is unknown. Here we report the identification of a large family of BTB-domain proteins as substrate-specific adaptors for C. elegans CUL-3. Biochemical studies using the BTB protein MEL-26 and its genetic target MEI-1 (refs 12, 13) indicate that BTB proteins merge the functional properties of Skp1 and F-box proteins into a single polypeptide. C1 Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell & Mol Biol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Harper, JW (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Reboul, Jerome/P-9103-2016; OI Reboul, Jerome/0000-0002-5513-4546; Vaglio, Philippe/0000-0003-2900-5596 FU NIA NIH HHS [R01 AG011085] NR 23 TC 287 Z9 304 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 18 PY 2003 VL 425 IS 6955 BP 316 EP 321 DI 10.1038/nature01985 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 722JA UT WOS:000185370900050 PM 13679922 ER PT J AU Paul, K Keith, DJ Johnson, SW AF Paul, K Keith, DJ Johnson, SW TI Modulation of calcium-activated potassium small conductance (SK) current in rat dopamine neurons of the ventral tegmental area SO NEUROSCIENCE LETTERS LA English DT Article DE Ca2+ dependent potassium SK channel; bicuculline methiodide; apamin; brain slice; dopamine; ventral tegmental area ID BEHAVIORAL REACTIONS; FIRING PROPERTIES; MIDBRAIN; RESPONSES; INVITRO; BICUCULLINE; STIMULI; PATTERN AB Block of calcium-sensitive potassium SK current (gKCa([SK])) by apamin or bicuculline methiodide potentiates burst firing in dopamine neurons in the presence of N-methyl-D-aspartate (NMDA). The purpose of this study was to test the hypothesis that calcium entry through NMDA-gated channels can potentiate gKCa([SK]) in dopamine neurons in the ventral tegmental area. We used microelectrodes to record an outward tail current that was evoked by membrane depolarization under single-electrode voltage-clamp. Using bicuculline methiodide (50 muM) as a reversible inhibitor of gKCa([SK]), we found that NMDA (15 muM) reduced the peak amplitude of the outward tail current by 39%. Contrary to expectations, our results suggest that stimulation of NMDA receptors reduces the calcium-activated potassium gKCa([SK]), an effect that could facilitate NMDA-dependent burst firing. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA. Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97207 USA. RP Paul, K (reprint author), SUNY Stony Brook, Dept Neurobiol & Behav, Rm 550,Life Sci Bldg, Stony Brook, NY 11794 USA. FU NIMH NIH HHS [MH40416] NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 18 PY 2003 VL 348 IS 3 BP 180 EP 184 DI 10.1016/S0304-3940(03)00747-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA 715KZ UT WOS:000184972200014 PM 12932823 ER PT J AU Gutman, JD Harris, NL Pingree, RG Kratz, A Kotton, CN AF Gutman, JD Harris, NL Pingree, RG Kratz, A Kotton, CN TI Case 29-2003: A 60-year-old man with fever, rigors, and sweats - Infection with Babesia microti (the agent that causes babesiosis) and Borrelia burgdorferi (the agent that causes Lyme disease) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EHRLICHIOSIS; ZOONOSES C1 Family Med Associates, S Attleboro, MA 02703 USA. Brown Univ, Dept Family Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Gutman, JD (reprint author), Family Med Associates, S Attleboro, MA 02703 USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 18 PY 2003 VL 349 IS 12 BP 1168 EP 1175 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 722HQ UT WOS:000185369700012 PM 13679532 ER PT J AU Winickoff, DE Winickoff, RN AF Winickoff, DE Winickoff, RN TI The charitable trust as a model for genomic biobanks SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INFORMED CONSENT; HUMAN TISSUE; ICELAND C1 Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winickoff, DE (reprint author), Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. NR 33 TC 102 Z9 102 U1 2 U2 8 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 18 PY 2003 VL 349 IS 12 BP 1180 EP 1184 DI 10.1056/NEJMsb030036 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 722HQ UT WOS:000185369700014 PM 13679534 ER PT J AU Chauhan, D Li, GL Sattler, M Podar, K Mitsiades, C Mitsiades, N Munshi, N Hideshima, T Anderson, KC AF Chauhan, D Li, GL Sattler, M Podar, K Mitsiades, C Mitsiades, N Munshi, N Hideshima, T Anderson, KC TI Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells SO ONCOGENE LA English DT Article DE multiple myeloma; apoptosis; superoxide; cytochrome c; Smac (second mitochondrial activator of caspases); 2-methoxyestradiol; dexamethasone ID MEDIATED APOPTOSIS; CANCER-CELLS; CYTOCHROME-C; ACTIVATION; RESISTANCE; INDUCTION; MECHANISM; PROTEIN; SMAC AB Superoxide (O-2(-)) radicals have been linked to apoptosis. Here, we show that 2-methoxyestradiol (2ME2)-induced apoptosis in multiple myeloma ( MM) cells is associated with O-2(-) generation, whereas dexamethasone (Dex)induced apoptosis occurs without concurrent increase in O-2(-). In contrast, both these agents decrease mitochondrial transmembrane potential (Deltapsi(m)). Treatment of MM cells with an antioxidant N-acetyl-L-cysteine blocks 2ME2, but not Dex-induced apoptosis as well as release of mitochondrial proteins cytochrome c (cyto c) and Smac. Taken together, these results demonstrate that there are at least two distinct apoptotic pathways: one dependent on O-2(-), which is induced by 2ME2 and is associated with release of cyto c and Smac; and the other an independent of O-2(-), which is triggered by Dex and associated with Smac release. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA 78373]; PHS HHS [50947] NR 23 TC 43 Z9 44 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 SEP 18 PY 2003 VL 22 IS 40 BP 6296 EP 6300 DI 10.1038/sj.onc.1206734 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 724UZ UT WOS:000185506200019 PM 13679868 ER PT J AU Baldessarini, RJ Tondo, L AF Baldessarini, RJ Tondo, L TI Suicide risk and treatments for patients with bipolar disorder SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID LITHIUM MAINTENANCE TREATMENT; I DISORDER; TRIAL; DIVALPROEX; PREVENTION; MORTALITY; OUTPATIENTS; DEPRESSION; BEHAVIOR; MANIA C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorder Res, Belmont, MA USA. Massachusetts Gen Hosp, Bipolar & Psychot Disorders Program, Belmont, MA USA. Univ Cagliari, Dept Psychol, Cagliari, Italy. Univ Cagliari, Ctr Bini Stanley Med Res Inst, Cagliari, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02478 USA. NR 34 TC 76 Z9 77 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 17 PY 2003 VL 290 IS 11 BP 1517 EP 1519 DI 10.1001/jama.290.11.1517 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 721RE UT WOS:000185329000037 PM 13129995 ER PT J AU Hassink, RJ Aretz, HT Ruskin, J Keane, D AF Hassink, RJ Aretz, HT Ruskin, J Keane, D TI Morphology of atrial myocardium in human pulmonary veins - A postmortem analysis in patients with and without atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RADIOFREQUENCY ABLATION; ELECTROPHYSIOLOGICAL CHARACTERISTICS; CATHETER ABLATION; INITIATION; JUNCTION; FIXATION AB OBJECTIVES We report an in-depth postmortem morphologic analysis of atrial myocardium in human pulmonary veins (PVs) from patients with and without atrial fibrillation (AF). BACKGROUND Electrophysiologic studies established the critical role of PVs in the initiation of AF. To date, a paucity of data exists about PV morphology as an arrhythmogenic substrate. METHODS Longitudinal tissue-strips of PVs were excised and histologically analyzed from the distal part to just beyond the atriovenous junction in the left atrium from 20 patients, obtained at autopsy. Anatomical measurements, including diameters, lengths, and wall-thicknesses of PVs, obtained at autopsy, were made. RESULTS Histological analysis revealed extension of atrial myocardium into 89% of all PVs. Prevalence of myocardial extension was significantly higher in veins of 6 patients with compared with 14 patients without AF. Other significant diffierences in the histology of PVs between the two groups were a higher frequency of discontinuity and hypertrophy and a higher degree of fibrosis of the atrial myocardium in the PVs of patients with AF. A marked variation existed in anatomical dimensions of PVs, although no differences were observed between patients with or without AF. CONCLUSIONS Atrial myocardium was more often present in the PVs of patients with compared with patients without AF. In the first group, the atrial myocardium in the PVs was characterized by more severe discontinuity, hypertrophy, and fibrosis. A marked variation in anatomical dimensions of the PVs existed. (C) 2003 by the American College of Cardiology Foundation. C1 Univ Utrecht, Med Ctr, Dept Cardiothorac Surg, Heart Lung Ctr, NL-3584 CT Utrecht, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Cardiac Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Hassink, RJ (reprint author), Univ Utrecht, Med Ctr, Dept Cardiothorac Surg, Heart Lung Ctr, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. NR 16 TC 82 Z9 87 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 SEP 17 PY 2003 VL 42 IS 6 BP 1108 EP 1114 DI 10.1016/S0735-1097(03)00918-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721YK UT WOS:000185345900026 PM 13678939 ER PT J AU Moliterno, DJ Hermiller, JB Kereiakes, DJ Yow, E Applegate, RJ Braden, GA Dippel, EJ Furman, MI Grines, CL Kleiman, NS Levien, GN Mann, T Nair, RN Stine, RA Yacubov, SJ Tcheng, JE AF Moliterno, DJ Hermiller, JB Kereiakes, DJ Yow, E Applegate, RJ Braden, GA Dippel, EJ Furman, MI Grines, CL Kleiman, NS Levien, GN Mann, T Nair, RN Stine, RA Yacubov, SJ Tcheng, JE CA ELECT Inv TI A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention - Results of the evaluating enoxaparin clotting times (ELECT) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; TRIAL; THERAPY; SAFETY AB OBJECTIVES The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable. METHODS We analyzed data from 445 enrolled patients receiving subcutaneous or intravenous enoxaparin in a prospective, multicenter study. Serial anticoagulation measurements and clinical outcomes were recorded. RESULTS The in-hospital composite occurrence of death, myocardial infarction, and urgent target vessel revascularization was 5.4%, and Thrombolysis In Myocardial Infarction (TIMI) major bleeding, minor bleeding, and any reported bleeding occurred in 0.2%, 1.3%, and 7.9% of patients, respectively. No significant association between procedural ENOX times and ischemic events was observed (p = 0.222), although the event rate was 4.0% among those with ENOX times between 250 to 450 s versus 7.2% for those outside this range (p = 0.134). Increasing ENOX time at sheath removal was correlated with any bleeding (p = 0.010) with a 1% increase for every similar to30-s rise. CONCLUSIONS Ischemic events were infrequent, and the rate appeared lowest in the mid-range of ENOX times. Bleeding events increased with increasing ENOX times. These observations, combined with a suggested procedural anti-Xa level of 0.8 to 1.8 IU/ml, translate into a recommended ENOX time range of 250 to 450 s for PCI and <200 to 250 s for sheath removal. (C) 2003 by the American College of Cardiology Foundation. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. St Vincent Hosp, Indianapolis, IN USA. Linder Ctr, Ohio Heart Hlth Ctr, Cincinnati, OH USA. Duke Clin Res Inst, Durham, NC USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Forsythe Med Ctr, Winston Salem, NC USA. Genesis Med Ctr, Davenport, IA USA. Univ Massachusetts, Worcester, MA 01605 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist DeBakey Heart Ctr, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Wake Med Ctr, Raleigh, NC USA. Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. Sentara Norfolk Gen, Norfolk, VA USA. Riverside Methodist Hosp, Columbus, OH 43214 USA. RP Moliterno, DJ (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,F-25, Cleveland, OH 44195 USA. OI Dippel, Eric/0000-0003-1085-1178 NR 20 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 17 PY 2003 VL 42 IS 6 BP 1132 EP 1139 DI 10.1016/S0735-1097(03)01053-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721YK UT WOS:000185345900030 PM 13678943 ER PT J AU Lamont, EB Hayreh, D Pickett, KE Dignam, JJ List, MA Stenson, KM Haraf, DJ Brockstein, BE Sellergren, SA Vokes, EE AF Lamont, EB Hayreh, D Pickett, KE Dignam, JJ List, MA Stenson, KM Haraf, DJ Brockstein, BE Sellergren, SA Vokes, EE TI Is patient travel distance associated with survival on phase II clinical trials in oncology? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; BREAST-CANCER PATIENTS; NECK-CANCER; ADVANCED HEAD; CONCURRENT CHEMOTHERAPY; REFERRAL BIAS; FLUOROURACIL; HYDROXYUREA; PACLITAXEL; RADIATION AB Background: Prior research has suggested that patients who travel out of their neighborhood for elective care from specialized medical centers may have better outcomes than local patients with the same illnesses who are treated at the same centers. We hypothesized that this phenomenon, often called "referral bias" or "distance bias," may also be evident in curative-intent cancer trials at specialized cancer centers. Methods: We evaluated associations between overall survival and progression-free survival and the distance from the patient residence to the treating institution for 110 patients treated on one of four phase 11 curative-intent chemoradiotherapy protocols for locoregionally advanced squamous cell cancer of the head and neck conducted at the University of Chicago over 7 years. Results: Using Cox regression that adjusted for standard patient-level disease and demographic factors and neighborhood-level economic factors, we found a positive association between the distance patients traveled from their residence to the treatment center and survival. Patients who lived more than 15 miles from the treating institution had only one-third the hazard of death of those living closer (hazard ratio [HR] = 0.32, 95% confidence interval [CI] = 0.12 to 0.84). Moreover, with every 10 miles that a patient traveled for care, the hazard of death decreased by 3.2% (HR = 0.97,95% CI = 0.94 to 0.99). Similar results were obtained for progression-free survival. Conclusion: Results of phase 11 curative-intent clinical trials in oncology that are conducted at specialized cancer centers may be confounded by patient travel distance, which captures prognostic significance beyond cancer stage, performance status, and wealth. More work is needed to determine what unmeasured factors travel distance is mediating. C1 Northwestern Univ, Evanston NW Healthcare, Evanston, IL USA. Univ Illinois, Sch Med, Chicago, IL USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. RP Lamont, EB (reprint author), Massachusetts Gen Hosp, Ctr Canc, 100 Blossom St,Cox 600, Boston, MA 02115 USA. FU NCI NIH HHS [K07 CA093892, K07 CA93892, P30 CA14599-27]; NIDCR NIH HHS [P50 DE/CA11921] NR 37 TC 71 Z9 71 U1 1 U2 4 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 SEP 17 PY 2003 VL 95 IS 18 BP 1370 EP 1375 DI 10.1093/jnci/djg035 PG 6 WC Oncology SC Oncology GA 722AV UT WOS:000185352900008 PM 13130112 ER PT J AU D'Amico, AV Moul, JW Carroll, PR Sun, L Lubeck, D Chen, MH AF D'Amico, AV Moul, JW Carroll, PR Sun, L Lubeck, D Chen, MH TI Surrogate end point for prostate cancer-specific mortality after radical prostatectomy or radiation therapy SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANTIGEN RECURRENCE; DISEASE RECURRENCE; CAPSURE DATABASE; CLINICAL-TRIALS; PROGRESSION; SURVIVAL; FAILURE; VALIDATION; NOMOGRAM; CRITERIA AB Background: The relationship between prostate-specific antigen (PSA)-defined recurrence and prostate cancer-specific mortality remains unclear. Therefore, we evaluated the hypothesis that a short post-treatment PSA doubling time (PSA-DT) after radiation therapy is a surrogate end point for prostate cancer-specific mortality by analyzing two multi-institutional databases. Methods: Baseline, treatment, and follow-up information was compiled on a cohort of 8669 patients with prostate cancer treated with surgery (5918 men) or radiation (2751 men) from January 1, 1988, through January 1, 2002, for localized or locally advanced, nonmetastatic prostate cancer. We used a Cox regression analysis to test whether the post-treatment PSA-DT was a prognostic factor that was independent of treatment received. All statistical tests were two-sided. Results: The post-treatment PSA-DT was statistically significantly associated with time to prostate cancer-specific mortality and with time to all-cause mortality (all P-Cox<001). However, the treatment received was not statistically significantly associated with time to prostate cancer-specific mortality after PSA-defined disease recurrence for patients with a PSA-DT of less than 3 months (P-Cox =.90) and for patients with a PSA-DT of 3 months or more (P-Cox =.28) when controlling for the specific value of the PSA-DT. Furthermore, after a PSA-defined recurrence, a PSA-DT of less than 3 months was statistically significantly associated with time to prostate cancer-specific mortality (median time = 6 years; hazard ratio = 19.6, 95 % confidence interval = 12.5 to 30.9). Conclusion: A post-treatment PSA-DT of less than 3 months and the specific value of the posttreatment PSA-DT when it is 3 months or more appear to be surrogate end points for prostate cancer-specific mortality after surgery or radiation therapy. We recommend that consideration be given to initiating androgen suppression therapy at the time of a PSA-defined recurrence when the PSA-DT is less than 3 months to delay the imminent onset of metastatic bone disease. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Urol Serv, Ctr Prostate Dis Res, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 37 TC 339 Z9 345 U1 0 U2 4 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 SEP 17 PY 2003 VL 95 IS 18 BP 1376 EP 1383 DI 10.1093/jnci/djg043 PG 8 WC Oncology SC Oncology GA 722AV UT WOS:000185352900009 PM 13130113 ER PT J AU Zhang, H Palmer, R Gao, XB Kreidberg, J Gerald, W Hsiao, LL Jensen, RV Gullans, SR Haber, DA AF Zhang, H Palmer, R Gao, XB Kreidberg, J Gerald, W Hsiao, LL Jensen, RV Gullans, SR Haber, DA TI Transcriptional activation of placental growth factor by the forkhead/winged helix transcription factor FoxD1 SO CURRENT BIOLOGY LA English DT Article ID KIDNEY DEVELOPMENT; NEPHROGENESIS; ANGIOGENESIS; EXPRESSION; MOUSE; BF-2 AB Stromal-epithelial interactions play an important role in renal organogenesis [1]. Expression of the forkhead/ winged helix transcription factor FoxD1 (BF-2) is restricted to stromal cells in the embryonic renal cortex, but it mediates its effects on the adjacent ureteric bud and metanephric mesenchyme, which fail to grow and differentiate in BF-2 null mice [2]. BF-2 is therefore likely to regulate transcription of factors secreted by stromal cells that modulate the differentiation of neighboring epithelial cells. Here, we used cells with inducible expression of BF-2, combined with microarray analysis, to identify Placental Growth Factor (PIGF), a Vascular Endothelial Growth Factor (VEGF) family member previously implicated in angiogenesis, as a downstream target of BF-2. BF-2 binds to a conserved HNF3beta site in the PIGF promoter and activates transcription. PIGF is precisely coexpressed with BF-2, both temporally and spatially, within the developing renal stroma, and it is completely absent in BF-2 null kidney stroma. Addition of PIGF to in vitro kidney organ cultures stimulates branching of the ureteric bud. Our observations indicate that PIGF is a direct and physiologically relevant transcriptional target of BF-2. The contribution of PIGF toward stromal signals that regulate epithelial differentiation suggests novel functions for a growth factor previously implicated in reactive angiogenesis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Neurol, Cambridge, MA 02394 USA. Harvard Univ, Sch Med, Cambridge, MA 02394 USA. Wesleyan Univ, Dept Phys, Middletown, CT 06459 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [2T32CA09216, CA58596]; NIDDK NIH HHS [DK 50118, DK 58849] NR 12 TC 30 Z9 31 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 16 PY 2003 VL 13 IS 18 BP 1625 EP 1629 DI 10.1016/j.cub.2003.08.054 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 722YC UT WOS:000185404800023 PM 13678594 ER PT J AU Cheng, HL Mostoslavsky, R Saito, S Manis, JP Gu, YS Patel, P Bronson, R Appella, E Alt, FW Chua, KF AF Cheng, HL Mostoslavsky, R Saito, S Manis, JP Gu, YS Patel, P Bronson, R Appella, E Alt, FW Chua, KF TI Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; DEPENDENT DEACETYLASE; SIR2-LIKE PROTEINS; SIR2-ALPHA PROTEIN; ACETYLATION; NAD; PHOSPHORYLATION; RECOMBINATION; APOPTOSIS AB SIRT1 is a mammalian homolog of the Saccharomyces cerevisiae chromatin silencing factor Sir2. Dominant-negative and overexpression studies have implicated a role for SIRT1 in deacetylating the p53 tumor suppressor protein to dampen apoptotic and cellular senescence pathways. To elucidate SIRT1 function in normal cells, we used gene-targeted mutation to generate mice that express either a mutant SIRT1 protein that lacks part of the catalytic domain or has no detectable SIRT1 protein at all. Both types of SIRT1 mutant mice and cells had essentially the same phenotypes. SIRT1 mutant mice were small, and exhibited notable developmental defects of the retina and heart, and only infrequently survived postnatally. Moreover, SIRT1-deficient cells exhibited p53 hyper-acetylation after DNA damage and increased ionizing radiation-induced thymocyte apoptosis. In SIRT1-deficient embryonic fibroblasts, however, p53 hyper-acetylation after DNA damage was not accompanied by increased p21 protein induction or DNA damage sensitivity. Together, our observations provide direct evidence that endogenous SIRT1 protein regulates p53 acetylation and p53-dependent apoptosis, and show that the function of this enzyme is required for specific developmental processes. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Ctr Blood Res, Boston, MA 02115 USA. NR 52 TC 633 Z9 672 U1 3 U2 29 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 SEP 16 PY 2003 VL 100 IS 19 BP 10794 EP 10799 DI 10.1073/pnas.1934713100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 723CR UT WOS:000185415300041 PM 12960381 ER PT J AU Porter, D Weremowicz, S Chin, K Seth, P Keshaviah, A Lahti-Domenici, J Bae, YK Monitto, CL Merlos-Suarez, A Chan, J Hulette, CM Richardson, A Morton, CC Marks, J Duyao, M Hruban, R Gabrielson, E Gelman, R Polyak, K AF Porter, D Weremowicz, S Chin, K Seth, P Keshaviah, A Lahti-Domenici, J Bae, YK Monitto, CL Merlos-Suarez, A Chan, J Hulette, CM Richardson, A Morton, CC Marks, J Duyao, M Hruban, R Gabrielson, E Gelman, R Polyak, K TI A neural survival factor is a candidate oncogene in breast cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN TUMOR-CELLS; GENE-EXPRESSION; SERIAL ANALYSIS; PEPTIDE; IDENTIFICATION; MICROARRAYS; INDUCTION; CACHEXIA; PRODUCT; CDNA AB Using serial analysis of gene expression (SAGE), we identified a SAGE tag that was present only in invasive breast carcinomas and their lymph node metastases. The transcript corresponding to this SAGE tag, dermcidin (DCD), encodes a secreted protein normally expressed only in the pons of the brain and sweat glands. Array comparative genomic hybridization, fluorescence in situ hybridization, and immunohistochemical analyses determined that DCD is overexpressed in approximate to10% of invasive breast carcinomas; in some cases its overexpression is coupled with a focal copy number gain of its locus at 12q13.1, and its expression is associated with advanced clinical stage and poor prognosis. Expression of DCD in breast cancer cells promotes cell growth and survival and reduces serum dependency. Putative high- and low-affinity receptors for DCD are present on the cell surface of breast carcinomas and neurons of the brain. Based on these data we hypothesize that DCD may play a role in tumorigenesis by means of enhancing cell growth and survival in a subset of breast carcinomas. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21231 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Ardais Corp, Lexington, MA 02421 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. FU NIA NIH HHS [AG05128, P50 AG005128] NR 29 TC 86 Z9 93 U1 2 U2 6 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 SEP 16 PY 2003 VL 100 IS 19 BP 10931 EP 10936 DI 10.1073/pnas.1932980100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 723CR UT WOS:000185415300064 PM 12953101 ER PT J AU Rubin-Bejerano, I Fraser, I Grisafi, P Fink, GR AF Rubin-Bejerano, I Fraser, I Grisafi, P Fink, GR TI Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION; ENVIRONMENTAL-CHANGES; ISOCITRATE LYASE; MASTER REGULATOR; YEAST; STARVATION; MACROPHAGES; LEUKOCYTES; CYCLE; GCN4P AB The transcriptional profiles of yeast cells that have been phagocytosed by either human neutrophils or monocytes were compared by using whole genome arrays. After phagocytosis by neutrophils, both Saccharomyces cerevisiae and Candida albicans respond by inducing genes of the methionine and arginine pathways. Neither of these pathways is induced upon phagocytosis by monocytes. Both fungi show a similar induction of these pathways when transferred from amino acid-rich medium to amino acid-deficient medium. These data suggest that the internal phagosome of the neutrophil is an amino acid-deficient environment. C1 MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fink, GR (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. FU NIGMS NIH HHS [R01 GM35010, GM 40266, R01 GM035010, R01 GM040266] NR 21 TC 148 Z9 153 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 SEP 16 PY 2003 VL 100 IS 19 BP 11007 EP 11012 DI 10.1073/pnas.1834481100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 723CR UT WOS:000185415300077 PM 12958213 ER PT J AU Sorensen, AG AF Sorensen, AG TI Results of MS-325-13: A phase III magnetic resonance angiography trial with MS-325, a blood pool contrast agent, for the detection of aortoiliac occlusive disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 15th Annual Transcatheter Cardiovascular Therapeutics Symposium CY SEP 15-19, 2003 CL WASHINGTON, D.C. SP Cardiovascular Res Fdn, Lenox Hill Heart & Vasculsr Inst New York C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. EPIX Med, Cambridge, MA USA. NR 0 TC 1 Z9 1 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 SEP 15 PY 2003 VL 92 IS 6A SU S BP 81L EP 81L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 722PQ UT WOS:000185385600178 ER PT J AU Thompson, CA Reddy, V Hayase, M Pomerantsev, E Srinivasan, A D'Avila, A Houser, S McGregor, J Makower, J Lamson, T Vacanti, JP Gold, HK AF Thompson, CA Reddy, V Hayase, M Pomerantsev, E Srinivasan, A D'Avila, A Houser, S McGregor, J Makower, J Lamson, T Vacanti, JP Gold, HK TI Infarct size reduction and functional recovery with transcoronary venous, direct myocardial injection of bone marrow-derived cells SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 15th Annual Transcatheter Cardiovascular Therapeutics Symposium CY SEP 15-19, 2003 CL WASHINGTON, D.C. SP Cardiovascular Res Fdn, Lenox Hill Heart & Vasculsr Inst New York C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. MIT, Cambridge, MA 02139 USA. TransVascular Inc, Menlo Pk, CA USA. RI d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 NR 0 TC 0 Z9 0 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 SEP 15 PY 2003 VL 92 IS 6A SU S BP 105L EP 105L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 722PQ UT WOS:000185385600236 ER PT J AU Kashani, A Murphy, SA Guigliano, RP AF Kashani, A Murphy, SA Guigliano, RP TI Angiography and revascularization in patients with heart failure following fibrinolysis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 15th Annual Transcatheter Cardiovascular Therapeutics Symposium CY SEP 15-19, 2003 CL WASHINGTON, D.C. SP Cardiovascular Res Fdn, Lenox Hill Heart & Vasculsr Inst New York C1 Rochester Gen Hosp, Rochester, NY 14621 USA. Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 SEP 15 PY 2003 VL 92 IS 6A SU S BP 110L EP 110L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 722PQ UT WOS:000185385600248 ER PT J AU Jang, IK Lewis, BE Matthai, WH Kleiman, NS AF Jang, IK Lewis, BE Matthai, WH Kleiman, NS TI Argatroban and glycoprotein IIb/IIIa inhibitor are effective and safe in patients undergoing percutaneous coronary intervention: A prospective, open-label, dose-response study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 15th Annual Transcatheter Cardiovascular Therapeutics Symposium CY SEP 15-19, 2003 CL WASHINGTON, D.C. SP Cardiovascular Res Fdn, Lenox Hill Heart & Vasculsr Inst New York C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 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 SEP 15 PY 2003 VL 92 IS 6A SU S BP 128L EP 128L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 722PQ UT WOS:000185385600294 ER PT J AU Chae, CU Albert, CM Glynn, RJ Guralnik, JM Curhan, GC AF Chae, CU Albert, CM Glynn, RJ Guralnik, JM Curhan, GC TI Mild ronal insufficiency and risk of congestive heart failure in men and women >= 70 years of age SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC RENAL-DISEASE; CARDIOVASCULAR-DISEASE; SERUM CREATININE; SYSTOLIC FUNCTION; HYPERTENSION; DYSFUNCTION; PREDICTION; POPULATION; PRESSURE; IMPACT AB Mild renal insufficiency is increasingly recognized as an independent risk factor for cardiovascular disease. However, few data exist regarding its relation to risk of congestive heart failure (CHF), a major public health I problem in the elderly. To determine if mild renal insufficiency is associated with risk of incident CHIF in the elderly, we analyzed data from 3,618 participants in the prospective, community-based Established Populations for Epidemiologic Studies of the Elderly (EPESE), who had no known CHIF and had serum creatinine levels measured from 1987 to 1989. Mean age of the study population was 78.3 +/- 5.4 years; 84% had creatinine values < 1.5 mg/di and 98% had creatinine values less than or equal to2.0 mg/dl. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault equation. During 3.9 years of follow-up, 488 subjects developed incident CHIF as defined by hospital discharge and death certificate data. In a multivariate proportional hazards model, CrCl was inversely associated with CHIF risk (p value for trend <0.001). Those in the lowest quartile of CrCl (less than or equal to36.9 ml/min) had a nearly twofold (hazards ratio [HR] 1.99, 95% confidence intervals [Cl] 1.43 to 2.79) greater risk of incident CHIF compared with those in the highest quartile (>57.4 ml/min). Renal insufficiency, defined as creatinine greater than or equal to1.5 mg/cll in men and greater than or equal to1.3 mg/dl in, women, was also associated with increased CHIF risk (multivariate HR 1.43, 95% Cl 1.17 to 1.74). Thus, mild renal insufficiency was a strong independent predictor of CHIF in this cohort, suggesting that serum creatinine may offer a readily accessible tool to identify elderly patients at risk for CHF. (C) 2003 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Sch Med, Boston, MA 02115 USA. NIA, Bethesda, MD 20892 USA. RP Chae, CU (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NHLBI NIH HHS [K08 HL 04154]; NIA NIH HHS [AG 1027] NR 29 TC 46 Z9 48 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 SEP 15 PY 2003 VL 92 IS 6 BP 682 EP 686 DI 10.1016/S0002-9149(03)00822-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721RR UT WOS:000185330800007 PM 12972106 ER PT J AU Gehi, AK Rumsfeld, JS Liu, HY Schiller, NB Whooley, MA AF Gehi, AK Rumsfeld, JS Liu, HY Schiller, NB Whooley, MA TI Relation of self-reported angina pectoris to inducible myocardial ischemia in patients with known coronary artery disease: The Heart and Soul Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CLINICAL-DIAGNOSIS; PROBABILITY; LIKELIHOOD; RISK AB To determine whether self-reported angina pectoris is associated with objective evidence of myocardial ischemia, we assessed angina symptoms, using the Seattle Angina Questionnaire, and measured ischemia using stress echocardiography in 933 patients with known coronary artery disease. We observed no association between self-reported angina pectoris and objective evidence of inducible ischemia. (C) 2003 by Excerpta Medica, Inc. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Denver VA Med Ctr, Denver, CO USA. Vet Adm Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Whooley, MA (reprint author), Vet Adm Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01 HL079235-01A1, R01 HL079235] NR 10 TC 14 Z9 14 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 SEP 15 PY 2003 VL 92 IS 6 BP 705 EP 707 DI 10.1016/S0002-9149(03)00831-2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 721RR UT WOS:000185330800013 PM 12972112 ER PT J AU Levine, S Nguyen, T Kaiser, LR Rubinstein, NA Maislin, G Gregory, C Rome, LC Dudley, GA Sieck, GC Shrager, JB AF Levine, S Nguyen, T Kaiser, LR Rubinstein, NA Maislin, G Gregory, C Rome, LC Dudley, GA Sieck, GC Shrager, JB TI Human diaphragm remodeling associated with chronic obstructive pulmonary disease - Clinical implications SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; fiber type transformations; single fiber physiology; specific force; within-fiber type adaptations ID VOLUME REDUCTION SURGERY; MUSCLE-FIBERS; FATIGUE RESISTANCE; SDH ACTIVITY; NORMAL MEN; CONTRACTION; FREQUENCY; DEPENDENCE; ADAPTATION; EMPHYSEMA AB Diaphragm remodeling associated with chronic obstructive pulmonary-disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsieson 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPID on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type 11 fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations. C1 Univ Penn, Sch Med, Surg & Res Serv, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Surg & Res Serv, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Surg & Res Serv, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Surg & Res Serv, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Arts & Sci, Dept Biol, Philadelphia, PA 19104 USA. Mayo Med Sch Clin & Fdn, Dept Physiol & Biophys, Rochester, MN USA. Mayo Med Sch Clin & Fdn, Dept Anesthesiol, Rochester, MN USA. Univ Georgia, Dept Exercise Sci, Athens, GA 30602 USA. RP Levine, S (reprint author), 1345 Bobarn Dr, Narberth, PA 19072 USA. NR 33 TC 76 Z9 80 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 15 PY 2003 VL 168 IS 6 BP 706 EP 713 DI 10.1164/rccm.200209-1070OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 721PK UT WOS:000185324600016 PM 12857719 ER PT J AU Glatt, SJ Faraone, SV Tsuang, MT AF Glatt, SJ Faraone, SV Tsuang, MT TI Schizophrenia is not associated with DRD4 48-base-pair-repeat length or individual alleles: Results of a meta-analysis SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; gene; association; meta-analysis; dopamine; D4 receptor ID D4 RECEPTOR GENE; MAJOR PSYCHOSES; NO ASSOCIATION; ETHNIC HETEROGENEITY; REPEAT POLYMORPHISM; PROMOTER REGION; VARIANTS; CLOZAPINE; SYMPTOMATOLOGY; TRANSMISSION AB Background: The gene DRD4, coding for dopamine receptor D4, was considered a candidate for association with schizophrenia based on its upregulation in postmortem schizophrenic brain and affinity for clozapine. Many studies sought allelic association of a 48-base-pair repeat in DRD4 exon 3 with schizophrenia, but found no strong evidence for a relationship. The present work sought to determine if this observation reflected the true absence of association or the low power of individual studies. Methods: We performed four meta-analyses, sequentially considering the two-, four-, and seven-repeat alleles as risk alleles., and then considering repeat length of the 48-base-pair segment as a risk factor. Each meta-analysis included at least 2300 cases and 2100 controls from 14-16 studies. Results: The pooled odds ratio from each analysis approximated 1.0, and none were significant. Heterogeneity was not observed, although gender moderated the effects of repeat length and the seven-repeat allele. Conclusions: Despite over 90% power to detect a significant odds ratio of 1.4 or less, none was observed. This polymorphism seems not to influence risk for most schizophrenia cases; however, a sex-dependent relationship, or a role in some clinical features of the disorder, cannot be excluded and should be pursued experimentally. C1 Massachusetts Mental Hlth Ctr, Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsuang, MT (reprint author), Massachusetts Mental Hlth Ctr, Harvard Med Sch, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH43518, R01 MH59624, R01 MH60485, R25 MH60485] NR 53 TC 16 Z9 18 U1 1 U2 2 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 SEP 15 PY 2003 VL 54 IS 6 BP 629 EP 635 DI 10.1016/S0006-3223(03)00180-X PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 720MN UT WOS:000185264700006 PM 13129658 ER PT J AU Nathan, DG AF Nathan, DG TI Monosomy 7 and the myeloid malignancies SO BLOOD LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 SEP 15 PY 2003 VL 102 IS 6 BP 1938 EP 1938 DI 10.1182/blood-2003-07-2360 PG 1 WC Hematology SC Hematology GA 721NQ UT WOS:000185322800003 ER PT J AU Feng, SJ Resendiz, JC Lu, X Kroll, MH AF Feng, SJ Resendiz, JC Lu, X Kroll, MH TI Filamin A binding to the cytoplasmic tail of glycoprotein Ib alpha regulates von Willebrand factor-induced platelet activation SO BLOOD LA English DT Article ID IX-V COMPLEX; INTEGRIN ALPHA(IIB)BETA(3); SHEAR-STRESS; INSIDE-OUT; PHOSPHOINOSITIDE 3-KINASE; CALCIUM SIGNALS; MEMBRANE; PROTEIN; PHOSPHORYLATION; ADHESION AB We examined the hypothesis that filamin A binding to the cytoplasmic tail of platelet glycoprotein lbalpha (Gplbalpha) is regulated by pathologic shear stress and modulates von Willebrand factor (VWF)-induced platelet activation. To begin, we examined filamin binding to Gplbalpha in Chinese hamster ovary cells coexpressing mutant human Gplb-IX and wild-type human filamin A. We observed that many different deletions and truncations N-terminal to Gplbalpha's cytoplasmic domain residue 594 disrupted filamin A binding, but that binding was unaffected by 14 different point mutations in hydrophilic residues between amino acids 557 and 593. To try to narrow Gplbalpha's filamin A-binding domain, we next measured the effect of several cytoplasmic domain peptides on human filamin A binding to a GST-Gplbalpha cytoplasmic domain fusion protein. One peptide (residues 557-575; designated "A4 peptide") inhibited filamin A binding to the GST-Gplbalpha cytoplasmic domain fusion protein and competed with Gplbalpha for binding to filamin A. When the A4 peptide was delivered to intact human platelets using a carrier peptide, we observed the dose-dependent inhibition of VWF-induced platelet aggregation in response to both ristocetin and shear stress. The effect of the A4 peptide on shear-induced platelet aggregation was accompanied by the attenuation of shear-induced filamin A binding to Gplbalpha and diminished shear-dependent protein tyrosine phosphorylation. These results suggest that shear-dependent VWF-induced platelet activation affects filamin A binding to Gplb-IX-V, and that filamin A binding to the cytoplasmic tail of Gplbalpha regulates proaggregatory tyrosine kinase signaling. (C) 2003 by The American Society of Hematology. C1 VA Med Ctr, Thrombosis Res Sect 151, Houston, TX 77030 USA. Rice Univ, Dept Biomed Engn, Houston, TX 77251 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Wihuri Res Inst, SF-00140 Helsinki, Finland. RP Kroll, MH (reprint author), VA Med Ctr, Thrombosis Res Sect 151, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL 65967] NR 41 TC 51 Z9 54 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 SEP 15 PY 2003 VL 102 IS 6 BP 2122 EP 2129 DI 10.1182/blood-2002-12-3805 PG 8 WC Hematology SC Hematology GA 721NQ UT WOS:000185322800036 PM 12791664 ER PT J AU Rubio, MT Kim, YM Sachs, T Mapara, M Zhao, G Sykes, M AF Rubio, MT Kim, YM Sachs, T Mapara, M Zhao, G Sykes, M TI Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonrnyeloablative conditioning: critical role for recipient-derived IFN-gamma SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; REFRACTORY HEMATOLOGIC MALIGNANCIES; HOST-INDUCED IMMUNOSUPPRESSION; TUMOR-NECROSIS-FACTOR; MURINE RENAL-CANCER; BONE-MARROW; LYMPHOHEMATOPOIETIC CHIMERISM; INTERFERON-GAMMA; MYELOABLATIVE THERAPY; ALLOGRAFT TOLERANCE AB Some patients lose chimerism following nonmyeloablative hematopoietic cell transplantation (HCT), yet, surprisingly, enjoy sustained tumor remissions. We hypothesized that host-versus-graft (HVG) alloresponses; might induce antitumor effects against recipient tumors. We explored this question in mice by administering recipient leukocyte infusions (RLIs) to mixed chimeras established with nonmyeloablative conditioning. Mixed chimeras were prepared in the B10.A (H2(a))-->B6 (H2(b)) strain combination using depleting anti-T-cell monoclonal antibodies (mAbs), cyclophosphamide, and thymic irradiation. B6 myeloid leukemia cells (MMB3.19) were administered 7 days following donor lymphocyte infusion (DLI) or RLI on day 35. Conversion to full donor chimerism occurred without graft-versus-host-disease (GVHD) following DLI, whereas RLI led to loss of chimerism. Both RLI and DLI significantly delayed tumor mortality. in another strain combination (B10.BR [H2(k)]-->BALB/c [H2(d)]), RLI-induced or spontaneous loss of chimerism was associated with antitumor effects against the host-type B-cell lymphoma A20. HCT was essential for the antitumor effect of RLI. RLI induced elevated serum interferon-gamma (IFN-gamma) levels, and recipient-derived IFN-gamma was critical for their antitumor effects. Thus, HVG reactions (spontaneous or induced by RLI) mediate antitumor effects against hematologic malignancies via a recipient-derived IFN-gamma-mediated mechanism. A novel approach to achieving antitumor effects without the risk of GVHD is suggested. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, MGH-E Bldg 149-5102,13th St, Boston, MA 02129 USA. RI mapara, markus/A-2134-2013 FU NCI NIH HHS [R01 CA 79989] NR 43 TC 60 Z9 61 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 SEP 15 PY 2003 VL 102 IS 6 BP 2300 EP 2307 DI 10.1182/blood-2002-12-3949 PG 8 WC Hematology SC Hematology GA 721NQ UT WOS:000185322800060 PM 12791660 ER PT J AU Beer, TM Garzotto, M Henner, WD Eilers, KM Wersinger, EM AF Beer, TM Garzotto, M Henner, WD Eilers, KM Wersinger, EM TI Intermittent chemotherapy in metastatic androgen-independent prostate cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE docetaxel; calcitriol; vitamin D; prostate cancer; chemotherapy ID QUALITY-OF-LIFE; CLINICAL-TRIALS; PHASE-II; MITOXANTRONE; MEN; HYDROCORTISONE; SUPPRESSION; PREDNISONE; DOCETAXEL; QLQ-C30 AB Intermittent use of chemotherapy for androgen-independent prostate cancer ( AIPC) instead of treatment until disease progression may reduce toxicity. We prospectively tested this approach in eight AIPC patients responding to calcitriol plus docetaxel who reached a serum prostate-specific antigen (PSA) <4 ng ml(-1). Chemotherapy was suspended until a rise in PSA &GE;50% and 1 ng ml(-1). The median duration of treatment holiday was 20 weeks (13 - 43+ weeks) and all patients retained sensitivity to re-treatment. Chemotherapy holiday was associated with an improvement of fatigue ( P = 0.05). Intermittent chemotherapy for AIPC is feasible and deserves further study. C1 Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Div Urol, Portland, OR 97207 USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Hematol & Med Oncol, Mail Code L586,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. FU NCRR NIH HHS [3M01RR00334-33S2, M01 RR000334] NR 12 TC 37 Z9 37 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 15 PY 2003 VL 89 IS 6 BP 968 EP 970 DI 10.1038/sj.bjc.6601232 PG 3 WC Oncology SC Oncology GA 721LY UT WOS:000185318900004 PM 12966410 ER PT J AU Patel, SG Singh, B Polluri, A Bridger, PG Cantu, G Cheesman, AD deSa, GM Donald, P Fliss, D Gullane, P Janecka, I Kamata, S Kowalski, LP Kraus, DH Levine, PA dos Santos, LRM Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP AF Patel, SG Singh, B Polluri, A Bridger, PG Cantu, G Cheesman, AD deSa, GM Donald, P Fliss, D Gullane, P Janecka, I Kamata, S Kowalski, LP Kraus, DH Levine, PA dos Santos, LRM Pradhan, S Schramm, V Snyderman, C Wei, WI Shah, JP TI Craniofacial surgery for malignant skull base tumors - Report of an international collaborative study SO CANCER LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the North-American-Skull-Base-Society CY FEB 22-25, 2003 CL MEMPHIS, TENNESSEE SP N Amer Skull Base Soc DE skull base neoplasms/surgery; postoperative complications; skull base neoplasms/mortality; treatment outcome; international cooperation ID FREE TISSUE TRANSFER; PARANASAL SINUSES; SURVIVAL ANALYSIS; RESECTION; ANTERIOR; COMPLICATIONS AB BACKGROUND. Malignant tumors of the skull base are rare. Therefore, no single center treats enough patients to accumulate significant numbers for meaningful analysis of outcomes after craniofacial surgery (CFS). The current report was based on a large cohort that was analyzed retrospectively by an International Collaborative Study Group. METHODS. One thousand three hundred seven patients who underwent CFS in 17 institutions were analyzable for outcome. The median age was 54 years (range, 1-98 years). Definitive treatment prior to CFS had been administered in 59% of patients and included radiotherapy in 367 patients (28%), chemotherapy in 151 patients (12%), and surgery in 523 patients (40%). The majority of tumors (87%) involved the anterior cranial fossa. Squamous cell carcinoma (29%) and adenocarcinoma (16%) were the most common histologic types. The margins of surgical resection were reported close/positive in 412 patients (32%). Adjuvant postoperative radiotherapy was received by 510 patients (39%), and chemotherapy was received by 57 patients (4%). RESULTS. Postoperative complications were reported in 433 patients (33%), with local wound complications the most common (18%). The postoperative mortality rate was 4%. With a median follow-up of 25 months, the 5-year overall, disease-specific, and recurrence-free survival rates were 54%, 60%, and 53%, respectively. The histology of the primary tumor, its intracranial extent, and the status of surgical margins were independent predictors of overall, disease-specific, and recurrence-free survival on multivariate analysis. CONCLUSIONS. CFS is a safe and effective treatment option for patients with malignant tumors of the skull base. The histology of the primary tumor, its intracranial extent, and the status of surgical margins are independent determinants of outcome. (C) 2003 American Cancer Society. C1 Mem Sloan Kettering Canc Ctr, Head & Neck Serv, Dept Surg, New York, NY 10021 USA. Prince Wales Hosp, Dept Surg, Sydney, NSW, Australia. Ist Nazl Tumori, Dept Surg, I-20133 Milan, Italy. Royal Natl Throat Nose & Ear Hosp, Dept Surg, London WC1X 8DA, England. Ist Nazl Tumori, Dept Surg, Rio De Janeiro, Brazil. Royal Natl Throat Nose & Ear Hosp, Dept Surg, London WC1X 8DA, England. Inst Nacl Canc, Dept Surg, Rio De Janeiro, Brazil. Univ Calif Davis, Med Ctr, Dept Surg, Sacramento, CA 95817 USA. Tel Aviv Sourasky Med Ctr, Dept Surg, Tel Aviv, Israel. Toronto Gen Hosp, Dept Surg, Toronto, ON, Canada. Massachusetts Eye & Ear Infirm, Dept Surg, Boston, MA 02114 USA. Canc Inst Hosp, Dept Surg, Tokyo, Japan. Hosp Canc AC Camargo, Dept Surg, Sao Paulo, Brazil. Univ Virginia, Hlth Syst, Dept Surg, Charlottesville, VA USA. Hosp Clin Sao Paulo, Dept Surg, Sao Paulo, Brazil. Tata Mem Hosp, Dept Surg, Bombay 400012, Maharashtra, India. Ctr Head Neck Surg, Dept Surg, Denver, CO USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. RP Shah, JP (reprint author), Mem Sloan Kettering Canc Ctr, Head & Neck Serv, Dept Surg, 1275 York Ave, New York, NY 10021 USA. RI Wei, William/C-4435-2009; Francisco, Suely/D-9065-2014; Kowalski, Luiz/D-1701-2012; OI Kowalski, Luiz/0000-0001-5865-9308; wei, william/0000-0002-6281-7126; Kowalski, Luiz Paulo/0000-0002-0481-156X; Shah, Jatin/0000-0002-6444-6592 NR 22 TC 149 Z9 158 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2003 VL 98 IS 6 BP 1179 EP 1187 DI 10.1002/cncr.11630 PG 9 WC Oncology SC Oncology GA 720TV UT WOS:000185276800009 PM 12973841 ER PT J AU Polnaszek, N Kwabi-Addo, B Peterson, LE Ozen, M Greenberg, NM Ortega, S Basilico, C Ittmann, M AF Polnaszek, N Kwabi-Addo, B Peterson, LE Ozen, M Greenberg, NM Ortega, S Basilico, C Ittmann, M TI Fibroblast growth factor 2 promotes tumor progression in an autochthonous mouse model of prostate cancer SO CANCER RESEARCH LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; INTRAEPITHELIAL NEOPLASIA; FACTOR EXPRESSION; TRANSGENIC MOUSE; EPITHELIAL-CELLS; GENE-EXPRESSION; FGF RECEPTORS; MESSENGER-RNA; ANGIOGENESIS; MICE AB Fibroblast growth factor (FGF) 2 (or basic FGF) is expressed at increased levels in human prostate cancer. FGF2 can promote cell motility and proliferation, increase tumor angiogenesis, and inhibit apoptosis, all of which play an important role in tumor progression. To determine whether FGF2 plays a critical role in prostate cancer progression, we have used the transgenic adenocarcinoma of the mouse prostate (TRAMP) model system. A high percentage of TRAMP mice develop metastatic prostate cancer, and thus the TRAMP model is useful for evaluating cancer progression. TRAMP mice were crossed with FGF2 knockout (FGF2(-/-)) mice, and tumor progression in TRAMP mice that were either hemi- or homozygous for inactivation of the FGF2 allele was compared with progression in wild-type TRAMP mice. Inactivation of even one FGF2 allele resulted in increased survival, a decrease in metastasis, and inhibition of progression to the poorly differentiated phenotype in primary prostatic tumors. When compared with wild-type mice, poorly differentiated tumors arising in FGF(+/-) and FGF(-/-) mice expressed higher levels of vascular endothelial growth factor and, in some cases, increased levels of acidic FGF intracellular binding protein, a nuclear FGF1-binding protein. These findings suggest that both FGF2-mediated angiogenesis and intranuclear FGF2 activities may promote tumor progression and support the hypothesis that FGF2 plays a significant role in prostate cancer progression in vivo. C1 Houston Vet Affairs Med Ctr, Res Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. RP Ittmann, M (reprint author), Houston Vet Affairs Med Ctr, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Kwabi-Addo, Bernard/A-6993-2016; OI Kwabi-Addo, Bernard/0000-0003-3692-6350; Peterson, Leif/0000-0002-1187-0883 FU NCI NIH HHS [CA058204, CA84926] NR 41 TC 89 Z9 95 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5754 EP 5760 PG 7 WC Oncology SC Oncology GA 727RN UT WOS:000185672600018 PM 14522896 ER PT J AU Cruz, F Rubin, BP Wilson, D Town, A Schroeder, A Haley, A Bainbridge, T Heinrich, MC Corless, CL AF Cruz, F Rubin, BP Wilson, D Town, A Schroeder, A Haley, A Bainbridge, T Heinrich, MC Corless, CL TI Absence of BRAF and NRAS mutations in uveal melanoma SO CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; CUTANEOUS MALIGNANT-MELANOMA; N-RAS; FAMILIAL MELANOMA; IMATINIB MESYLATE; S-100 PROTEIN; CELL-LINES; EXPRESSION; P53; GENE AB Uveal melanoma (UM) and cutaneous melanoma (CM) differ significantly in their epidemiological, clinical, immunophenotypical, and cytogenetic features, but the molecular basis for these differences has not been delineated. CMs frequently harbor an activating mutation in either NRAS or the RAS-regulated kinase BRAF, suggesting that either of these oncogenes may increase signaling through the mitogen-activated protein (MAP) kinase pathway and promote melanoma development. The aim of this study was to examine BPAF and NPAS gene mutations in UM. Genomic DNA from CM and UM was screened for mutations in BRAF exons 11 and 15 and NPAS exons I and 2 using a combination of denaturing high-performance liquid chromatography and direct sequencing. Mutations in BRAF exon 15 were detected in 16 (36.4%) of 44 CMs and 0 (0%) of 62 UMs. The most common mutation in CM was V599E, but a novel point mutation (L596Q) was identified in two cases and an in-frame deletion/insertion (VKSRWK599-604D) was discovered in one case. No BRAF exon 11 mutations were observed among seven CMs and nine UMs that were wild-type for exon 15. Mutation of NRAS exon 2 was rare in CM [1 (3.7%) of 27] and absent in UM [0 (0%) of 47]. No NPAS exon I mutations were detected in either type of melanoma. We conclude that UMs arise independent of oncogenic BRAF and NPAS mutations, an observation that may have implications for therapies targeted to the NRAS-BRAF pathway. C1 Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Hematol & Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Univ Washington, Med Ctr, Dept Anat Pathol, Seattle, WA 98195 USA. RP Corless, CL (reprint author), Oregon Hlth Sci Univ, Dept Pathol, L471,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. NR 57 TC 132 Z9 136 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5761 EP 5766 PG 6 WC Oncology SC Oncology GA 727RN UT WOS:000185672600019 PM 14522897 ER PT J AU Cabelof, DC Guo, ZM Raffoul, JJ Sobol, RW Wilson, SH Richardson, A Heydari, AR AF Cabelof, DC Guo, ZM Raffoul, JJ Sobol, RW Wilson, SH Richardson, A Heydari, AR TI Base excision repair deficiency caused by polymerase beta haploinsufficiency: Accelerated DNA damage and increased mutational response to carcinogens SO CANCER RESEARCH LA English DT Article ID HEPATOCARCINOGEN 2-NITROPROPANE; OXIDATIVE STRESS; NUCLEAR-DNA; POLY(ADP-RIBOSE) POLYMERASE; IN-VIVO; LESIONS; CELLS; MICE; XRCC1; METHYLATION AB The base excision repair pathway (BER) is believed to maintain genomic integrity by repairing DNA damage arising spontaneously or induced by oxidizing and alkylating agents. To establish the role of DNA polymerase beta (beta-pol) in BER and beta-pol-dependent BER in maintaining genomic stability, we have measured the impact of a gene-targeted disruption in the beta-pol gene on DNA repair capacity and on in vivo sensitivity to carcinogens. We have extensively phenotyped the DNA beta-pol heterozygous (beta-pol(+/-)) mouse as expressing similar to50% less beta-pol mRNA and protein and as exhibiting an equivalent reduction in the specific activity of beta-pol. We measured BER activity by in vitro G:U mismatch and (8-OH)G:C repair and find that there is a significant reduction in the ability of extracts from beta-pol(+/-) mice to repair these types of DNA damage. In vivo, the beta-pol(+/-) mice sustain higher levels of DNA single-strand breaks as well as increased chromosomal aberrations as compared with beta-pol(+/+) littermates. Additionally, we show that reduction in beta-pol expression and BER activity results in increased mutagenicity of dimethyl sulfate as evidenced by a 2-fold increase in LacI mutation frequency. Importantly, the beta-pol(+/-) mice do not exhibit increased sensitivity to DNA damage induced by N-nitroso-N-ethylurea, ionizing radiation, or UV radiation, which induce damage processed by alternative repair pathways, demonstrating that this model is specifically a BER-deficient model. C1 Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48202 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Heydari, AR (reprint author), Wayne State Univ, Dept Nutr & Food Sci, 3009 Sci Hall, Detroit, MI 48202 USA. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 FU NIA NIH HHS [1P01-AG14674, 1P30-AG13319, P01-AG19316]; NIDDK NIH HHS [1R21-DK62256] NR 50 TC 71 Z9 75 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5799 EP 5807 PG 9 WC Oncology SC Oncology GA 727RN UT WOS:000185672600024 PM 14522902 ER PT J AU Tai, YT Podar, K Catley, L Tseng, YH Akiyama, M Shringarpure, R Burger, R Hideshima, T Chauhan, D Mitsiades, N Richardson, P Munshi, NC Kahn, CR Mitsiades, C Anderson, KC AF Tai, YT Podar, K Catley, L Tseng, YH Akiyama, M Shringarpure, R Burger, R Hideshima, T Chauhan, D Mitsiades, N Richardson, P Munshi, NC Kahn, CR Mitsiades, C Anderson, KC TI Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of beta 1-integrin and phosphatidylinositol 3 '-kinase/AKT signaling SO CANCER RESEARCH LA English DT Article ID MEMBRANE RAFT MICRODOMAINS; MEDIATED DRUG-RESISTANCE; MARROW STROMAL CELLS; LIPID RAFTS; INTERLEUKIN-6 SECRETION; EXTRACELLULAR-MATRIX; ANTIGEN RECEPTOR; INTEGRIN; PROTEIN; APOPTOSIS AB Insulin-like growth factor-1 (IGF-I) is a growth and survival factor in human multiple myeloma (MM) cells. Here we examine the effect of IGF-I on MM cell adhesion and migration, and define the role of beta1 integrin in these processes. IGF-I increases adhesion of MM.1S and OPM6 MM cells to fibronectin (FN) in a time- and dose-dependent manner, as a consequence of IGF-IR activation. Conversely, blocking anti-beta1 integrin monoclonal antibody, RGD peptide, and cytochalasin D inhibit IGF-I-induced cell adhesion to FN. IGF-I rapidly and transiently induces association of IGF-IR and beta1 integrin, with phosphorylation of IGF-IR, IRS-1, and p85(PI3-K). IGF-I also triggers phosphorylation of AKT and ERK significantly. Both IGF-IR and beta1 integrin colocalize to lipid rafts on the plasma membrane after IGF-I stimulation. In addition, IGF-I triggers polymerization of F-actin, induces phosphorylation of p125(FAK) and paxillin, and enhances beta1 integrin interaction with these focal adhesion proteins. Importantly, using pharmacological inhibitors of phosphatidylinositol 3'-kinase (PI3-K) (LY294002 and wortmannin) and extracellular signal-regulated kinase (PD98059), we demonstrate that IGF-I-induced MM cell adhesion to FN is achieved only when PI3-K/AKT is activated. IGF-I induces a 1.7-2.2 (MM.1S) and 2-2.5-fold (OPM6) increase in migration, whereas blocking anti-IGF-I and anti-beta1 integrin monoclonal antibodies, PI3-K inhibitors, as well as cytochalasin D abrogate IGF-I-induced MM cell transmigration. Finally, IGF-I induces adhesion of CD138+ patient MM cells. Therefore, these studies suggest a role for IGF-I in trafficking and localization of MM cells in the bone mar row microenvironment. Moreover, they define the functional association of IGF-IR and beta1 integrin in mediating MM cell homing, providing the preclinical rationale for novel treatment strategies targeting IGF-I/IGF-IR in MM. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, M557,44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [R0-1 50947, P01-78378] NR 40 TC 148 Z9 155 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2003 VL 63 IS 18 BP 5850 EP 5858 PG 9 WC Oncology SC Oncology GA 727RN UT WOS:000185672600031 PM 14522909 ER PT J AU Bockhorn, M Tsuzuki, Y Xu, L Frilling, A Broelsch, CE Fukumura, D AF Bockhorn, M Tsuzuki, Y Xu, L Frilling, A Broelsch, CE Fukumura, D TI Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID ANGIOGENESIS; TUMOR; EXPRESSION; VEGF; PERMEABILITY; MICROENVIRONMENT; HYPOXIA; DISEASE; MICE AB Purpose: The objectives of this study were to investigate the effects of anti-vascular endothelial growth factor (VEGF) treatment on various vascular functions, gene expression, and growth of orthotopic human pancreatic cancer xenografts and thus to provide useful preclinical data for novel cancer treatments. Experimental Design: Small pieces of a human pancreatic carcinoma, PANC-1, were implanted into the pancreas of male severe combined immunodeficient mice. The animals were treated with anti-human VEGF antibody A.4.6.1 (300 mug, every 3 days i.p.) or a nonspecific IgG between 4 and 8 weeks after tumor implantation. Then, vascular density, diameter, permeability, and tumor growth were determined by intravital microscopy. Subsequently, tumors were harvested, and angiogenic gene expression profile was determined by a microarray kit including 96 genes involved in tumor angiogenesis. Results: Anti-VEGF antibody significantly reduced angiogenesis and growth of orthotopic PANC-1 tumors. In the anti-VEGF treatment group, the vessel density was significantly smaller (67.8 +/- 10.6 cm/cm(2)) than that seen in the control group (146.7 +/- 10.0 cm/cm(2)). However, vessel diameter and permeability were not altered significantly by anti-VEGF antibody treatment. The pancreatic tumors in the treated group were significantly smaller than those in the control group. Microarray and subsequent Northern blot and semiquantitative reverse transcription-PCR analyses revealed both a decrease (fibroblast growth factor 1, transforming growth factor beta1, platelet-derived growth factor alpha, erbB2, and c-ets1,) and an increase (placenta growth factor, hypoxia-inducible factor alpha, and endoglin) in expression of angiogenesis-related genes in the PANC-1 tumors by anti-VEGF treatment. Conclusions: Anti-VEGF antibody treatment has differential effects on vessel functions as well as angiogenic gene expression and inhibitory effects on angiogenesis and growth of the orthotopic pancreatic tumor. Anti-VEGF strategy appears promising for pancreatic cancer treatment. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steel Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Hosp Essen, Dept Gen & Transplantat Surg, D-45122 Essen, Germany. RP Fukumura, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steel Lab, 100 Blossom St,COX-736, Boston, MA 02114 USA. FU NCI NIH HHS [P01 CA 90124] NR 25 TC 48 Z9 50 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 15 PY 2003 VL 9 IS 11 BP 4221 EP 4226 PG 6 WC Oncology SC Oncology GA 727RU UT WOS:000185673300027 PM 14519649 ER PT J AU Chaiyakunapruk, N Veenstra, DL Lipsky, BA Sullivan, SD Saint, S AF Chaiyakunapruk, N Veenstra, DL Lipsky, BA Sullivan, SD Saint, S TI Vascular catheter site care: The clinical and economic benefits of chlorhexidine gluconate compared with povidone iodine SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CRITICALLY-ILL PATIENTS; CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; PROSPECTIVE RANDOMIZED TRIAL; ATTRIBUTABLE MORTALITY; NOSOCOMIAL INFECTIONS; PREVENTION; COHORT; SEPSIS; CONSEQUENCES AB The use of chlorhexidine gluconate solution for vascular catheter insertion site care reduces the risk of catheter-related bloodstream infection by one-half, compared with povidone iodine. Our objective was to evaluate the cost-effectiveness of chlorhexidine gluconate versus povidone iodine. We used data from randomized, controlled trials, meta-analyses, and epidemiologic studies to construct a decision analysis model. We estimated that use of chlorhexidine, rather than povidone, for central catheter site care resulted in a 1.6% decrease in the incidence of catheter-related bloodstream infection, a 0.23% decrease in the incidence of death, and savings of $113 per catheter used. For peripheral catheter site care, the results were similar, although the differences were smaller. The results were found to be robust on multivariate sensitivity analyses. Use of chlorhexidine gluconate in place of the current standard solution for vascular catheter site care is a simple and cost-effective method of improving patient safety in the hospital setting. C1 Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI USA. Naresuan Univ, Dept Pharm Practice, Pitsanuloak, Thailand. RP Veenstra, DL (reprint author), Univ Washington, Dept Pharm, Pharmaceut Outcomes Res & Policy Program, Box 357630, Seattle, WA 98195 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 FU AHRQ HHS [P20-HS11540] NR 46 TC 42 Z9 46 U1 0 U2 0 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 SEP 15 PY 2003 VL 37 IS 6 BP 764 EP 771 DI 10.1086/377265 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 718EA UT WOS:000185131100004 PM 12955636 ER PT J AU Chan, SE Rosen, HR AF Chan, SE Rosen, HR TI Outcome and management of hepatitis C in liver transplant recipients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTERFERON-ALPHA; ANTIVIRAL THERAPY; VIRUS-INFECTION; GRAFT CIRRHOSIS; RIBAVIRIN; COMBINATION; RECURRENCE; EFFICACY; SURVIVAL; RETRANSPLANTATION AB Hepatitis C virus (HCV)- related cirrhosis is the leading indication for liver transplantation. Reinfection of the allograft with HCV is universal in all patients with pretransplantation viremia, and leads to histologically proven hepatitis in 50% - 80% of these patients. Recent data have demonstrated significantly higher mortality among HCV-positive liver transplant recipients. For this subgroup of patients, retransplantation remains highly controversial. As current antiviral therapy is limited in efficacy and tolerability, an improved understanding of those patients at greatest risk of developing serious HCV-induced graft injury is necessary to optimize treatment. C1 Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, 371 0 SW US Vet Hosp,P3-GI, Portland, OR 97207 USA. NR 37 TC 13 Z9 14 U1 0 U2 0 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 SEP 15 PY 2003 VL 37 IS 6 BP 807 EP 812 DI 10.1086/377605 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 718EA UT WOS:000185131100011 PM 12955642 ER PT J AU Takagi, J Strokovich, K Springer, TA Walz, T AF Takagi, J Strokovich, K Springer, TA Walz, T TI Structure of integrin alpha(5)beta(1) in complex with fibronectin SO EMBO JOURNAL LA English DT Article DE conformational change; electron microscopy; fibronectin; integrin; single-particle analysis ID SITE-DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; LIGAND-BINDING; ALPHA-SUBUNIT; EXTRACELLULAR SEGMENT; ELECTRON-MICROSCOPY; MESODERMAL DEFECTS; ADHESIVE FUNCTION; DOMAIN AB The membrane-distal headpiece of integrins has evolved to specifically bind large extracellular protein ligands, but the molecular architecture of the resulting complexes has not been determined. We used molecular electron microscopy to determine the three-dimensional structure of the ligand-binding headpiece of integrin alpha(5)beta(1) complexed with fragments of its physiological ligand fibronectin. The density map for the unliganded alpha(5)beta(1) headpiece shows a 'closed' conformation similar to that seen in the alpha(V)beta(3) crystal structure. By contrast, binding to fibronectin induces an 'open' conformation with a dramatic, similar to80degrees change in the angle of the hybrid domain of the beta subunit relative to its I-like domain. The fibronectin fragment binds to the interface between the beta-propeller and I-like domains in the integrin headpiece through the RGD-containing module 10, but direct contact of the synergy-region-containing module 9 to integrin is not evident. This finding is corroborated by kinetic analysis of real-time binding data, which shows that the synergy site greatly enhances k(on) but has little effect on the stability or k(off) of the complex. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Takagi, J (reprint author), Osaka Univ, Inst Prot Res, 3-2 Yamadaoka, Osaka 5650871, Japan. FU NHLBI NIH HHS [HL48675, P01 HL048675]; NIGMS NIH HHS [P01 GM062580, GM62580] NR 44 TC 217 Z9 220 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 2003 VL 22 IS 18 BP 4607 EP 4615 DI 10.1093/emboj/cdg445 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 721GT UT WOS:000185309200004 PM 12970173 ER PT J AU Mora, A Davies, AM Bertrand, L Sharif, I Budas, GR Jovanovic, S Mouton, V Kahn, CR Lucocq, JM Gray, GA Jovanovic, A Alessi, DR AF Mora, A Davies, AM Bertrand, L Sharif, I Budas, GR Jovanovic, S Mouton, V Kahn, CR Lucocq, JM Gray, GA Jovanovic, A Alessi, DR TI Deficiency of PDK1 in cardiac muscle results in heart failure and increased sensitivity to hypoxia SO EMBO JOURNAL LA English DT Article DE cardiac muscle; heart failure; hypoxia; PDK1; PI 3-kinase; PKB; Akt ID PROTEIN-KINASE-B; SIGNALING PATHWAYS; CELL-SIZE; MYOCARDIAL-CONTRACTILITY; DILATED CARDIOMYOPATHY; ARBITRARY PARTICLES; CRYSTAL-STRUCTURE; TRANSGENIC MICE; BINDING POCKET; DOCKING SITE AB We employed Cre/loxP technology to generate mPDK1(-/-) mice, which lack PDK1 in cardiac muscle. Insulin did not activate PKB and S6K, nor did it stimulate 6-phosphofructo-2-kinase and production of fructose 2,6-bisphosphate, in the hearts of mPDK1(-/-) mice, consistent with PDK1 mediating these processes. All mPDK1(-/-) mice died suddenly between 5 and 11 weeks of age. The mPDK1(-/-) animals had thinner ventricular walls, enlarged atria and right ventricles. Moreover, mPDK1(-/-) muscle mass was markedly reduced due to a reduction in cardiomyocyte volume rather than cardiomyocyte cell number, and markers of heart failure were elevated. These results suggested mPDK1(-/-) mice died of heart failure, a conclusion supported by echocardiographic analysis. By employing a single-cell assay we found that cardiomyocytes from mPDK1(-/-) mice are markedly more sensitive to hypoxia. These results establish that the PDK1 signalling network plays an important role in regulating cardiac viability and preventing heart failure. They also suggest that a deficiency of the PDK1 pathway might contribute to development of cardiac disease in humans. C1 Univ Dundee, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. Univ Dundee, Sch Life Sci, Div Cell Biol & Immunol, Dundee DD1 5EH, Scotland. Univ Dundee, Ninewells Hosp & Med Sch, Tayside Inst Child Hlth, Dundee DD1 9SY, Scotland. Univ Edinburgh, Coll Med & Vet Med, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland. Inst Cellular Pathol, Hormone & Metab Res Unit, Louvain, Belgium. Univ Louvain, Sch Med, Louvain, Belgium. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA USA. RP Mora, A (reprint author), Univ Dundee, MRC, Prot Phosphorylat Unit, Dow St, Dundee DD1 5EH, Scotland. RI Jovanovic, Aleksandar/A-4482-2008; Gray, Gillian/B-4058-2014; Mora, Alfonso/D-2759-2017 OI Jovanovic, Aleksandar/0000-0002-1214-9318; Mora, Alfonso/0000-0002-6397-4836 FU Biotechnology and Biological Sciences Research Council [C15048]; British Heart Foundation [PG/02/117/14488]; Wellcome Trust [059528/Z/99/Z/JMW/CP/JF] NR 64 TC 123 Z9 125 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 15 PY 2003 VL 22 IS 18 BP 4666 EP 4676 DI 10.1093/emboj/cdg469 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 721GT UT WOS:000185309200010 PM 12970179 ER PT J AU Hogan, PG Chen, L Nardone, J Rao, A AF Hogan, PG Chen, L Nardone, J Rao, A TI Transcriptional regulation by calcium, calcineurin, and NFAT SO GENES & DEVELOPMENT LA English DT Review ID ACTIVATED T-CELLS; MUSCLE-FIBER-TYPE; GLYCOGEN-SYNTHASE KINASE-3; HEAVY-CHAIN GENE; COLONY-STIMULATING FACTOR; FAST-TWITCH MUSCLE; KAPPA-B P50; OSTEOCLAST DIFFERENTIATION FACTOR; GROWTH-FACTOR-BETA; NUCLEAR FACTOR C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Chen, Lin/A-3392-2008 FU NIAID NIH HHS [R21 AI049905]; NIGMS NIH HHS [R01 GM064642] NR 230 TC 1008 Z9 1062 U1 8 U2 59 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 SEP 15 PY 2003 VL 17 IS 18 BP 2205 EP 2232 DI 10.1101/gad.1102703 PG 28 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 722NG UT WOS:000185381700002 PM 12975316 ER PT J AU Dimova, DK Stevaux, O Frolov, MV Dyson, NJ AF Dimova, DK Stevaux, O Frolov, MV Dyson, NJ TI Cell cycle-dependent and cell cycle-independent control of transcription by Drosophila E2F/RB pathway SO GENES & DEVELOPMENT LA English DT Article DE E2F; retinoblastoma protein; RBF; Drosophila; cell cycle; differentiation ID MICROARRAY ANALYSIS; DNA-REPLICATION; S-PHASE; CHROMATIN IMMUNOPRECIPITATION; C/EBP-ALPHA; IN-VIVO; GENE; PROTEINS; FAMILY; PRB AB To determine which E2F/RB-family members are functionally important at E2F-dependent promoters, we used RNA interference (RNAi) to selectively remove each component of the dE2F/dDP/RBF pathway, and we examined the genome-wide changes in gene expression that occur when each element is missing. The results reveal a remarkable division of labor between family members. Classic E2F targets, encoding functions needed for cell cycle progression, are expressed in cycling cells and are primarily dependent on dE2F1 and RBF1 for regulation. Unexpectedly, there is a second program of dE2F/RBF-dependent transcription, in which dE2F2/RBF1 or dE2F2/RBF2 complexes repress gene expression in actively proliferating cells. These new E2F target genes encode differentiation factors that are transcribed in developmentally regulated and gender-specific patterns and not in a cell cycle-regulated manner. We propose that dE2F/RBF complexes should not be viewed simply as a cell cycle regulator of transcription. Instead, dE2F/RBF-mediated repression is exerted on genes that encode an assortment of cellular functions, and these effects are reversed on sets of functionally related genes in particular developmental contexts. As a result, dE2F/RBF regulation is used to link gene expression with cell cycle progression at some targets while simultaneously providing stable repression at others. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [F32 CA093045, F32 CA93045]; NIGMS NIH HHS [GM53203, R01 GM053203] NR 56 TC 172 Z9 178 U1 0 U2 2 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 SEP 15 PY 2003 VL 17 IS 18 BP 2308 EP 2320 DI 10.1101/gad.1116703 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 722NG UT WOS:000185381700010 PM 12975318 ER PT J AU Sandor, F Latz, E Re, F Mandell, L Repik, G Golenbock, DT Espevik, T Kurt-Jones, EA Finberg, RW AF Sandor, F Latz, E Re, F Mandell, L Repik, G Golenbock, DT Espevik, T Kurt-Jones, EA Finberg, RW TI Importance of extra- and intracellular domains of TLR1 and TLR2 in NF kappa B signaling SO JOURNAL OF CELL BIOLOGY LA English DT Article DE toll-like receptors; innate immunity; mycobacterium tuberculosis; ara-lipoarabinomannan; signal transduction ID TOLL-LIKE RECEPTORS; CELL WALL COMPONENTS; INNATE IMMUNE-SYSTEM; CUTTING EDGE; BACTERIAL LIPOPOLYSACCHARIDE; MICROBIAL LIPOPROTEINS; PATTERN-RECOGNITION; ADAPTER PROTEIN; DROSOPHILA TOLL; HOST-DEFENSE AB Recognition of ligands by toll-like receptor (TLR) 2 requires interactions with other TLRs. TLRs form a combinatorial repertoire to discriminate between the diverse microbial ligands. Diversity results from extracellular and intracellular interactions of different TLRs. This paper demonstrates that TLR1 and TLR2 are required for ara-lipoarabinomannan- and tripalmitoyl cysteinyl lipopeptide-stimulated cytokine secretion from mononuclear cells. Confocal microscopy revealed that TLR1 and TLR2 co-translationally form heterodimeric complexes on the cell surface and in the cytosol. Simultaneous cross-linking of both receptors resulted in ligand-independent signal transduction. Using chimeric TLRs, we found that expression of the extracellular domains along with simultaneous expression of the intracellular domains of both TLRs was necessary to achieve functional signaling. The domains from each receptor did not need to be contained within a single contiguous protein. Chimeric TLR analysis further defined the toll/1L-1R domains as the area of crucial intracellular TLR1-TLR2 interaction. C1 Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01605 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Norwegian Univ Sci & Technol, Unit Canc Res & Mol Biol, NO-7491 Trondheim, Norway. RP Finberg, RW (reprint author), Univ Massachusetts, Med Ctr, Dept Med, 364 Plantat St, Worcester, MA 01605 USA. RI Latz, Eicke/H-3951-2014 OI Latz, Eicke/0000-0003-1488-5666 FU NIAID NIH HHS [R01 AI052455, AI52455, R01 AI039576, R01 AI051405, R01 AI051415, R01 AI39756, R01 AI51415, R56 AI052455]; NIGMS NIH HHS [R01 GM054060, R01 GM54060, R01 GM63244] NR 36 TC 91 Z9 93 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP 15 PY 2003 VL 162 IS 6 BP 1099 EP 1110 DI 10.1083/jcb.200304093 PG 12 WC Cell Biology SC Cell Biology GA 722WR UT WOS:000185401500013 PM 12975352 ER PT J AU Krzyzanowska, MK Weeks, JC Earle, CC AF Krzyzanowska, MK Weeks, JC Earle, CC TI Treatment of locally advanced pancreatic cancer in the real world: Population-based practices and effectiveness SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LUNG-CANCER; COMORBIDITY INDEX; HOSPITAL VOLUME; BREAST-CANCER; COLON-CANCER; CHEMOTHERAPY; CARCINOMA; THERAPY; RADIATION; SURVIVAL AB Purpose : To evaluate the use and effectiveness of cancer-directed therapy in elderly patients with locally advanced pancreatic cancer (LAPC). Methods: We used the linked Surveillance, Epidemiology, and End Results Medicare database to perform a retrospective cohort study in 1,696 patients diagnosed with LAPC between 1991 and 1996. We calculated cancer-directed treatment use rates, then used logistic regression to identify patient and health system factors that were associated with receipt of treatment. Effectiveness of treatment was estimated using Cox proportional hazards models and propensity score methods. Results: In our cohort, 44% of patients received some form of cancer-directed therapy (24% radiation with concurrent chemotherapy, 13% radiation alone, and 7% chemotherapy alone). Older age, lower socioeconomic status, presence of comorbid illness, no care in a teaching hospital, and residence in the western United States were associated with a lower likelihood of receiving treatment (P less than or equal to 0.05). Among those treated, younger age and certain geographic locations were the only predictors of receiving combined-modality therapy. The adjusted hazard ratio for death associated with any treatment in the Cox model was 0.53 (P < .0001). Effectiveness estimates obtained using propensity score methods were similar. Conclusion: This analysis supports the effectiveness of cancer-directed treatment in elderly patients with LAPC, but use is low. Receipt of treatment is strongly correlated with non-disease-related factors, especially sociodemographic characteristics, indicating possible disparities in access to care. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. NR 32 TC 63 Z9 65 U1 1 U2 1 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 SEP 15 PY 2003 VL 21 IS 18 BP 3409 EP 3414 DI 10.1200/JCO.2003.03.007 PG 6 WC Oncology SC Oncology GA 721ZA UT WOS:000185347300007 PM 12972517 ER PT J AU Ganz, PA Moinpour, CM Pauler, DK Kornblith, AB Gaynor, ER Balcerzak, SP Gatti, GS Erba, HP McCoy, S Press, OW Fisher, RI AF Ganz, PA Moinpour, CM Pauler, DK Kornblith, AB Gaynor, ER Balcerzak, SP Gatti, GS Erba, HP McCoy, S Press, OW Fisher, RI TI Health status and quality of life in patients with early-stage Hodgkin's disease treated on Southwest Oncology Group study 9133 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SUBTOTAL LYMPHOID IRRADIATION; BREAST-CANCER SURVIVORS; PSYCHOSOCIAL ADAPTATION; SURVEY SF-36; FATIGUE; TRIAL; RISK; VINBLASTINE; MANAGEMENT; MORBIDITY AB Purpose : We describe the short and intermediate-term quality-of-life (QOL) outcomes in patients treated on a randomized clinical trial in early-stage Hodgkin's disease (Southwest Oncology Group [SWOG] 9133) comparing subtotal lymphoid irradiation (STLI) with combined-modality treatment (CMT). Patients and Methods: Two hundred forty-seven patients participated in the QOL study (SWOG 9208), completing several standardized instruments (Symptom Distress Scale; Cancer Rehabilitation Evaluation System - Short Form; Medical Outcomes Study 36-Item Short-Form Health Survey Vitality Scale; and a health perception item), as well as questions about work, marital status, and concerns about having children. This article reports on results from baseline before random assignment, at 6 months, and at 1 and 2 years after random assignment. Results : Patients receiving CMT experienced significantly greater symptom distress (P < .0001), fatigue (P = .001), and poorer QOL. (P = .015) at 6 months than the STLI patients, reflecting a shorter time since completion of therapy in the CMT arm. Importantly, patients in the two groups did not differ on any outcomes at the 1 -and 2-year assessments. Both patient groups reported significantly more fatigue before treatment than healthy reference populations, and fatigue did not improve in either group after treatment. Conclusion: This study demonstrated that patients with early-stage Hodgkin's disease experience a short-term decrease in QOL and an increase in symptoms and fatigue with treatment, which is more severe with CMT, by I year, however, CMT and STLI patients report similar outcomes. Fatigue scores for both arms were lower at baseline than scores for the general population and did not return to normal levels 2 years after random assignment. The mechanisms responsible for this lingering problem warrant further investigation. (C) 2003 by American Society of Clinical Oncology. C1 Univ Calif Los Angeles, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Ohio State Univ, Ctr Hlth, Columbus, OH 43210 USA. Columbus Community Clin Oncol Program, Columbus, OH USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Puget Sound Oncol Consortium, Seattle, WA USA. Univ Rochester, Sch Med, Rochester, NY USA. RP Ganz, PA (reprint author), SW Oncol Grp, SWOG 9208, Operat Off, 14980 Omicron Dr, San Antonio, TX 78245 USA. FU NCI NIH HHS [CA35262, CA04919, CA04920, CA12213, CA12644, CA13612, CA14028, CA16386, CA20319, CA22433, CA27057, CA28862, CA32102, CA32291, CA35090, CA35119, CA35128, CA35176, CA35192, CA35281, CA35431, CA35996, CA37981, CA38926, CA42777, CA45377, CA45807, CA46133, CA46282, CA46368, CA52654, CA58348, CA58415, CA58416, CA58658, CA58723, CA58861, CA63844, CA63845, CA65261, CA67575, CA76132, CA76429, CA76447, CA76462] NR 39 TC 53 Z9 54 U1 0 U2 1 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 SEP 15 PY 2003 VL 21 IS 18 BP 3512 EP 3519 DI 10.1200/JCO.2003.01.044 PG 8 WC Oncology SC Oncology GA 721ZA UT WOS:000185347300021 PM 12972528 ER PT J AU von Boehmer, H AF von Boehmer, H TI Dynamics of suppressor T cells: In vivo veritas SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID IMMUNOLOGICAL SELF-TOLERANCE; FAMILY MEMBER BIM; DENDRITIC CELLS; TRANSGENIC MICE; REGULATORY CELLS; CLONAL ELIMINATION; ANTIGEN RECEPTOR; THYMIC SELECTION; LYMPHOCYTES-T; STEADY-STATE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. NR 48 TC 41 Z9 42 U1 0 U2 2 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 SEP 15 PY 2003 VL 198 IS 6 BP 845 EP 849 DI 10.1084/jem.20031358 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 723DB UT WOS:000185416200001 PM 12975452 ER PT J AU Gansuvd, B Hubbard, WJ Hutchings, A Thomas, FT Goodwin, J Wilson, SB Exley, MA Thomas, JM AF Gansuvd, B Hubbard, WJ Hutchings, A Thomas, FT Goodwin, J Wilson, SB Exley, MA Thomas, JM TI Phenotypic and functional characterization of long-term cultured rhesus macaque spleen-derived NKT cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KILLER T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; TCR ALPHA-CHAIN; DENDRITIC CELLS; BONE-MARROW; IN-VIVO; ANTIGEN RECEPTOR; ORAL TOLERANCE; CUTTING EDGE AB Natural killer T cells are immunoregulatory cells, which have important roles in tolerance and autoimmunity, as demonstrated primarily in mice and humans. In this study, we define the phenotype and function of Valpha24(+) T cells derived from the spleens of rhesus macaques, a species increasingly used in models of immune tolerance. Valpha24(+) cells were isolated and expanded with monocyte-derived immature dendritic cells in the presence of alpha-galactosylceramide, IL-2, and IL-15. Rhesus NKT cells were stained with mAbs against both Valpha24 and the invariant complementarity-determining region 3 epitope of the human Valpha24/JalphaQ TCR. The cells were CD4, CD8 double negative and expressed CD56. Rhesus NKT cells also exhibited moderate to high expression of CD95, CD45RO, CD11a, and beta(7) integrin, but did not express CD45 RA, CD62L, CCR7, CD28, and other activation, costimulatory molecules (CD69 and CD40L). By intracellular staining, >90% of unstimulated rhesus NKT cells expressed IL-10, but not IFN-gamma. However, the latter was strongly expressed after stimulation. Rhesus NKT secreted large amounts of TGF-beta, IL-13, and IL-6, and modest levels of IFN-gamma, whereas IL-10 secretion was negligible and no detectable IL-4 was observed either intracellularly or in culture supernatants. Functionally, the NKT cells and their supernatants suppressed T cell proliferation in allogeneic MLR. We conclude that long-term cultured rhesus macaque spleen-derived Valpha24(+) T cells are semi-invariant double-negative cells with effector memory phenotype. These cells are semianergic, polarized to a uniquely Th3 > T regulatory-1 regulatory cell phenotype, and have regulatory/suppressive function in vitro. C1 Univ Alabama, Dept Surg, Div Transplantat Immunobiol, Birmingham, AL 35294 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Biol Program,Hematol Oncol Div, Boston, MA 02215 USA. RP Thomas, JM (reprint author), 564 Boshell Diabet Bldg,1808 7th Ave S, Birmingham, AL 35294 USA. FU NIDDK NIH HHS [1U19DK57958] NR 57 TC 16 Z9 17 U1 1 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 SEP 15 PY 2003 VL 171 IS 6 BP 2904 EP 2911 PG 8 WC Immunology SC Immunology GA 720DY UT WOS:000185247300023 PM 12960313 ER PT J AU Counter, SA Zou, J Bjelke, B Klason, T AF Counter, SA Zou, J Bjelke, B Klason, T TI 3D MRI of the in vivo vestibulo-cochlea labyrinth during Gd-DTPA-BMA uptake SO NEUROREPORT LA English DT Article DE cochlea; magnetic resonance imaging; gadolinium; vestibular ID PAROXYSMAL POSITIONAL VERTIGO; SENSORINEURAL HEARING-LOSS; PERILYMPHATIC FISTULA; GUINEA-PIG; MEMBRANOUS LABYRINTH; SEMICIRCULAR CANALS; INNER-EAR; VISUALIZATION; DEHISCENCE; CT AB The morphology, time-course and volume of the in vivo uptake of the Tl contrast agent gadolinium (Gd) in the perilymphatic vestibulo-cochlea labyrinth, including the utricle, saccule, semicircular canals and scalae of the guinea pig inner ear were analyzed as Fourier transform signal intensity enhancement levels by 3D MRI at 4.7 T. The uptake of Gd as a function of time in the perilymphatic space of the vestibular labyrinth was shown by ANOVA and PLSD post hoc tests to be significantly less (p < 0.05) than that of the scala tympani of the cochlea 10, 30, 60 and 90 min after i.v. injection. Experimentally induced fistulae resulted in MRI detected morphological and quantitative alterations in Gd concentration in the perilymphatic labyrinthine space. The findings demonstrate that Gd-enhanced 3D MRI of the perilymphatic space may be used to examine the morphology, kinetics and intravenous substance delivery in the in vivo mammalian vestibulo-cochlea labyrinth. (C) 2003 Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biol Labs,Neurol Dept, Cambridge, MA 02138 USA. Karolinska Hosp, MR Ctr, Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden. Huddinge Hosp, Surg Sci Ctr, Dept Radiol, KTH & KI Nano & Microtechnol Ctr, SE-14186 Stockholm, Sweden. Konsultfirman Tekn Dr Tomas Klason Sturevagen 4B, S-13338 Saltsjobaden, Sweden. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biol Labs,Neurol Dept, 16 Divin Ave, Cambridge, MA 02138 USA. NR 27 TC 12 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 15 PY 2003 VL 14 IS 13 BP 1707 EP 1712 DI 10.1097/01.wnr.0000088599.08608.a5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 736KR UT WOS:000186170400010 PM 14512842 ER PT J AU Habib, S Molina-Paris, C Deisboeck, TS AF Habib, S Molina-Paris, C Deisboeck, TS TI Complex dynamics of tumors: modeling an emerging brain tumor system with coupled reaction-diffusion equations SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; HUMAN GLIOMA-CELLS; HUMAN ASTROCYTOMA MIGRATION; SCATTER FACTOR EXPRESSION; FACTOR RECEPTOR COMMON; MATHEMATICAL-MODEL; RAT-BRAIN; MULTICELLULAR SPHEROIDS; EXTRACELLULAR-MATRIX; MONOLAYER-CULTURES AB One of the hallmarks of malignant brain tumors is their extensive tissue invasion, which represents a major obstacle for effective treatment. In this paper we specifically model the invasive behavior of such tumors viewed as complex dynamic biosystems. Based on the spatio-temporal patterns seen in an experimental setting for multicellular brain tumor spheroids we propose an invasion-guiding, dynamical profile of heterotype and homotype attractor substances. We present a novel theoretical and numerical framework for a mathematical tumor model composed of a set of coupled reaction-diffusion equations describing chemotactic and haptotactic cell behavior. In particular, our continuum model simulates tumor cell motility guided by the principle of least resistance, most permission and highest attraction. Preliminary numerical results indicate that the computational algorithm is capable of reproducing patterns similar to the experimentally observed behavior. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Warwick, Inst Math, Coventry CV4 7AL, W Midlands, England. Los Alamos Natl Lab, Theoret Div T8, Los Alamos, NM 87545 USA. Univ Leeds, Dept Appl Math, Leeds LS2 9JT, W Yorkshire, England. Harvard Univ, Sch Med, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Molina-Paris, C (reprint author), Univ Warwick, Inst Math, Coventry CV4 7AL, W Midlands, England. NR 66 TC 29 Z9 29 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD SEP 15 PY 2003 VL 327 IS 3-4 BP 501 EP 524 DI 10.1016/S0378-4371(03)00391-1 PG 24 WC Physics, Multidisciplinary SC Physics GA 727YJ UT WOS:000185688200019 ER PT J AU Wilhelmi, BJ Mowlavi, A Neumeister, MW Bueno, R Lee, WPA AF Wilhelmi, BJ Mowlavi, A Neumeister, MW Bueno, R Lee, WPA TI Safe treatment of trigger finger with longitudinal and transverse landmarks: An anatomic study of the border fingers for percutaneous release SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the American-Society-of-Plastic and-Reconstructive-Surgeons CY NOV 03-07, 2001 CL ORLANDO, FLORIDA SP Amer Soc Plast & Reconstruct Surgeons ID LOCAL STEROID INJECTION; DIGITAL BLOCKS; SURGICAL-TREATMENT; PLACEBO INJECTION; EPINEPHRINE; EFFICACY; SURGERY; KNIFE AB Transverse landmarks have recently been determined to predict the proximal and distal edges of the Al pulley for trigger finger release. Percutaneous Al pulley release has been discouraged for the border digits because of the risk of injury to the neurovascular structures of the index and small fingers. The purpose of the study was to identify longitudinal surface landmarks to prevent injury to the neurovascular bundles during percutaneous At pulley release of the ulnar and radial border digits. Longitudinal surface landmarks were identified and marked on 29 cadaver hands. Proximal and distal landmarks for the longitudinal vector through which the Al pulley of the small finger was released include the midline of the proximal digital crease and the scaphoid tubercle. Proximal and distal landmarks for the longitudinal line through which the index finger Al pulley was released include the midline of proximal digital crease and radial edge of the pisiform. Longitudinal incisions were performed between these landmarks, straight through the skin and deep enough to score the Al pulley. The distance of the medial edge of the neurovascular structures from the longitudinal incision in the Al pulley was measured for each small finger and index finger. Using these longitudinal landmarks for the index and small fingers, none of the neurovascular structures was injured while performing these longitudinal incisions through the skin, scoring the Al pulley. In fact, the average distance for the neurovascular structures from the longitudinal vector of the small finger was 5.4 +/- 1.4 mm radially and 6.7 +/- 1.9 mm ulnarly. The average distance for the neurovascular structures from the longitudinal line of the index finger was 8.5 :+/- 1.8 mm radially and 6.2 +/- 1.7 mm ulnarly. Based on the findings of this anatomical study, these longitudinal landmarks can be used to avoid injury to neurovascular structures in the management of trigger finger involving the border digits with steroid-injection, open, or percutaneous At pulley release. C1 So Illinois Univ, Sch Med, Inst Plast Surg, Springfield, IL 62794 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Wilhelmi, BJ (reprint author), So Illinois Univ, Sch Med, Inst Plast Surg, 747 N Rutledge,3rd Floor,POB 19653, Springfield, IL 62794 USA. NR 35 TC 20 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP 15 PY 2003 VL 112 IS 4 BP 993 EP 999 DI 10.1097/01.PRS.0000076225.79854.F4 PG 7 WC Surgery SC Surgery GA 718KM UT WOS:000185144400009 PM 12973214 ER PT J AU Littner, M Hirshkowitz, M Kramer, M Kapen, S Anderson, WM Bailey, D Berry, RB Davila, D Johnson, S Kushida, C Loube, DI Wise, M Woodson, T AF Littner, M Hirshkowitz, M Kramer, M Kapen, S Anderson, WM Bailey, D Berry, RB Davila, D Johnson, S Kushida, C Loube, DI Wise, M Woodson, T TI Practice parameters for using polysomnography to evaluate insomnia: An update SO SLEEP LA English DT Article ID ALPHA-DELTA SLEEP; PANIC DISORDER; ELECTROENCEPHALOGRAPHIC SLEEP; DIFFERENTIAL-DIAGNOSIS; NONDEPRESSED PATIENTS; ALZHEIMER-TYPE; EEG; COMPLAINTS; DISTURBANCES; CONTINUITY AB Insomnia is a common and clinically important problem. It may arise directly from a sleep-wake regulatory dysfunction and/or indirectly result from comorbid psychiatric, behavioral, medical, or neurological conditions. As an important public-health problem, insomnia requires accurate diagnosis and effective treatment. Insomnia is primarily diagnosed clinically with a detailed medical, psychiatric, and sleep history. Polysomnography is indicated when a sleep-related breathing disorder or periodic limb movement disorder is suspected, initial diagnosis is uncertain, treatment fails, or precipitous arousals occur with violent or injurious behavior. However, polysomnography is not indicated for the routine evaluation of transient insomnia, chronic insomnia, or insomnia associated with psychiatric disorders. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Sepulveda, CA USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Maimonides Hosp, Dept Psychiat, Brooklyn, NY 11219 USA. NYU, Sch Med, New York, NY USA. VA Med Ctr, Detroit, MI USA. Wayne State Univ, Detroit, MI USA. Univ S Florida, Coll Med, Tampa, FL USA. Englewood, Colorado Springs, CO USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. Baptist Med Ctr, Little Rock, AR USA. St Patricks Hosp, Sleep Ctr, Missoula, MT USA. Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Swedish Med Ctr, Sleep Med Inst, Seattle, WA USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. RP Littner, M (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 61 TC 115 Z9 118 U1 0 U2 7 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD SEP 15 PY 2003 VL 26 IS 6 BP 754 EP 760 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 724DQ UT WOS:000185472200020 PM 14572131 ER PT J AU Goggins, WC Pascual, MA Powelson, JA Magee, C Tolkoff-Rubin, N Farrell, ML Ko, DSC Williams, WW Chandraker, A Delmonico, FL Auchincloss, H Cosimi, AB AF Goggins, WC Pascual, MA Powelson, JA Magee, C Tolkoff-Rubin, N Farrell, ML Ko, DSC Williams, WW Chandraker, A Delmonico, FL Auchincloss, H Cosimi, AB TI A prospective, randomized, clinical trial of intraoperative versus postoperative thymoglobulin in adult cadaveric renal transplant recipients. SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 19th International Congress of the Transplantation-Society CY AUG 25-30, 2002 CL MIAMI, FLORIDA SP Transplantat Soc ID DELAYED GRAFT FUNCTION; CHRONIC ALLOGRAFT FAILURE; ACUTE HUMORAL REJECTION; ANTITHYMOCYTE GLOBULINS; KIDNEY-TRANSPLANTATION; RISK-FACTORS; ADHESION; ANTIBODIES; MOLECULES; THERAPY AB Background. Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. Methods. We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. Results. There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P<0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. Conclusions. The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. CHU Vaudois, Transplantat Ctr, CH-1011 Lausanne, Switzerland. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. RP Goggins, WC (reprint author), 550 Univ Bldg,UH 4258, Indianapolis, IN 46202 USA. NR 26 TC 122 Z9 130 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 2003 VL 76 IS 5 BP 798 EP 802 DI 10.1097/01.TP.0000081042.67285.91 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 722KV UT WOS:000185374700010 PM 14501856 ER PT J AU Tanaka, T Hanafusa, N Ingelfinger, JR Ohse, T Fujita, T Nangaku, M AF Tanaka, T Hanafusa, N Ingelfinger, JR Ohse, T Fujita, T Nangaku, M TI Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIFI-mediated upregulation of Bax SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE IRPTC; bcl2; caspase-9; p53 ID CHRONIC-RENAL-FAILURE; REOXYGENATION INJURY; CARDIAC MYOCYTES; EPITHELIAL-CELLS; BCL-2 FAMILY; P53 STATUS; LOW-OXYGEN; DEATH; PROTEIN; GENE AB Chronic hypoxia is a major contributor to tubulointerstitial injury in various renal diseases and apoptosis is apparently involved. Although many studies report hypoxia-induced apoptosis in cultured tubular cells, information has been limited in proximal tubular cells, those from the most susceptible portion of renal tubules against hypoxia. This study was to confirm a role for apoptosis in hypoxic proximal tubular cells and to investigate its association with HIF-1. Temperature-sensitive SV40-immortalized rat proximal tubular cells (IRPTCs) showed apoptosis in 21.9+/-2.9% by hypoxia (0.2% O-2, 48 h), with alterations in mitochondrial signaling such as Bcl2 and caspase-9. Bax mRNA was unaffected during the process. However, treating IRPTCs at the nonpermissive temperature showed an upregulation of Bax by hypoxia, which was abrogated by overexpressing dominant-negative HIF-1alpha. These findings extend previous reports on hypoxia-mediated tubular cell apoptosis and demonstrate the possible involvement of HIF-1 as an upstream molecule of Bax. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo 113, 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 113, Japan. RI Nangaku, Masaomi/A-5300-2010 NR 41 TC 49 Z9 51 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 12 PY 2003 VL 309 IS 1 BP 222 EP 231 DI 10.1016/S0006-291X(03)01557-2 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 718WA UT WOS:000185168400033 PM 12943686 ER PT J AU Belham, C Roig, J Caldwell, JA Aoyama, Y Kemp, BE Comb, M Avruch, J AF Belham, C Roig, J Caldwell, JA Aoyama, Y Kemp, BE Comb, M Avruch, J TI A mitotic cascade of NIMA family kinases - Nercc1/Nek9 activates the Nek6 and Nek7 kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE REGULATION; PROTEIN-KINASE; ASPERGILLUS-NIDULANS; S6 KINASE; SUBSTRATE-SPECIFICITY; MASS-SPECTROMETRY; KIDNEY-DISEASE; AUTOPHOSPHORYLATION; PHOSPHORYLATION; REGULATOR AB The Nek family of protein kinases in humans is composed of 11 members that share an amino-terminal catalytic domain related to NIMA, an Aspergillus kinase involved in the control of several aspects of mitosis, and divergent carboxyl-terminal tails of varying length. Nek6 (314AA) and Nek7 (303AA), 76% identical, have little noncatalytic sequence but bind to the carboxyl-terminal noncatalytic tail of Nercc1/Nek9, a NIMA family protein kinase that is activated in mitosis. Microinjection of anti-Nercc1 antibodies leads to spindle abnormalities and prometaphase arrest or chromosome missegregation. Herein we show that Nek6 is increased in abundance and activity during mitosis; activation requires the phosphorylation of Ser(206) on the Nek6 activation loop. This phosphorylation and the activity of recombinant Nek6 is stimulated by coexpression with an activated mutant of Nercc1. Moreover, Nercc1 catalyzes the direct phosphorylation of prokaryotic recombinant Nek6 at Ser(206) in vitro concomitant with 20-25-fold activation of Nek6 activity; Nercc1 activates Nek7 in vitro in a similar manner. Nercc1/Nek9 is likely to be responsible for the activation of Nek6 during mitosis and probably participates in the regulation of Nek7 as well. These findings support the conclusion that Nercc1/Nek9 and Nek6 represent a novel cascade of mitotic NIMA family protein kinases whose combined function is important for mitotic progression. C1 Massachusetts Gen Hosp, Dept Mol Biol & Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Pharmacia Italia SpA, Dept Biol, I-20014 Milan, Italy. MDS Proteom, Charlottesville, VA 22911 USA. St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Cell Signaling Technol, Beverly, MA 01915 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol & Med Serv, Boston, MA 02114 USA. RI Kemp, Bruce/L-2633-2014; OI Kemp, Bruce/0000-0001-6735-5082; Roig, Joan/0000-0002-3872-4712 FU NIDDK NIH HHS [DK17776] NR 36 TC 86 Z9 90 U1 1 U2 9 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 SEP 12 PY 2003 VL 278 IS 37 BP 34897 EP 34909 DI 10.1074/jbc.M303663200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 718UG UT WOS:000185164400021 PM 12840024 ER PT J AU Kemp, DM Lin, JC Habener, JF AF Kemp, DM Lin, JC Habener, JF TI Regulation of Pax4 paired homeodomain gene by neuron-restrictive silencer factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-PRODUCING CELLS; PANCREATIC AR42J CELLS; TRANSCRIPTION FACTORS; TARGET GENES; FACTOR NRSF; BETA-CELLS; ACTIVIN-A; IN-VIVO; EXPRESSION; DIFFERENTIATION AB An elucidation of the key regulatory factors in pancreas development is critical for understanding the pathogenesis of diabetes mellitus. This study examined whether a specific regulatory mechanism that exists in neuronal development also plays a role in the pancreas. In non-neuronal cells, neuron-restrictive silencer factor (NSRF) actively represses gene transcription via a sequence-specific DNA motif known as the neuron-restrictive silencer element (NRSE). This DNA motif has been identified in many genes that are specific markers for cells of neuronal and neuroendocrine lineage. We identified several genes involved in pancreas development that also harbor NRSE-like motifs, including pdx-1, Beta2/NeuroD, and pax4. The paired homeodomain transcription factor Pax4 is implicated in the differentiation of the insulin-producing beta-cell lineage because disruption of the pax4 gene results in a severe deficiency of beta-cells and the manifestation of diabetes mellitus in mice. The NRSE-like motif identified in the upstream pax4 promoter is highly conserved throughout evolution, forms a DNA-protein complex with NRSF, and confers NRSF-dependent transcriptional repression in the context of a surrogate gene promoter. This cis-activating NRSE element also confers NRSF-dependent modulation in the context of the native pax4 gene promoter. Together with earlier reports, these new findings suggest an important functional role for NRSF in the expression of the pax4 gene and infer a role for NRSF in pancreatic islet development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL 320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 55365] NR 25 TC 21 Z9 24 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 SEP 12 PY 2003 VL 278 IS 37 BP 35057 EP 35062 DI 10.1074/jbc.M305891200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 718UG UT WOS:000185164400039 PM 12829700 ER PT J AU Yin, L Li, YQ Ren, J Kuwahara, H Kufe, D AF Yin, L Li, YQ Ren, J Kuwahara, H Kufe, D TI Human MUC1 carcinoma antigen regulates intracellular oxidant levels and the apoptotic response to oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-CATENIN; SIGNALING PATHWAY; REDOX REGULATION; C-SRC; CELLS; DNA; GENERATION; ACTIVATION; TUMORS; DF3 AB The DF3/MUC1 transmembrane oncoprotein is aberrantly overexpressed by most human carcinomas. Certain insights are available regarding a role for MUC1 in intracellular signaling; however, no precise function has been ascribed to this molecule. The present results demonstrate that MUC1 expression is up-regulated by oxidative stress and that this response is mediated by activation of MUC1 gene transcription. A role for MUC1 in the oxidative stress response is supported by the demonstration that MUC1 expression is associated with attenuation of endogenous and H2O2-induced intracellular levels of reactive oxygen species (ROS). MUC1-dependent regulation of ROS is mediated at least in part by up-regulation of anti-oxidant enzyme ( superoxide dismutase, catalase, and glutathione peroxidase) expression. In concert with these findings, we show that the apoptotic response to oxidative stress is attenuated by a MUC1-dependent mechanism. These results support a model in which activation of MUC1 by oxidative stress provides a protective function against increased intracellular oxidant levels and ROS-induced apoptosis. 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, Boston, MA 02115 USA. FU NCI NIH HHS [CA98628, CA97098] NR 33 TC 110 Z9 113 U1 1 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 SEP 12 PY 2003 VL 278 IS 37 BP 35458 EP 35464 DI 10.1074/jbc.M301987200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 718UG UT WOS:000185164400087 PM 12826677 ER PT J AU He, HY Soncin, F Grammatikakis, N Li, YL Siganou, A Gong, JL Brown, SA Kingston, RE Calderwood, SK AF He, HY Soncin, F Grammatikakis, N Li, YL Siganou, A Gong, JL Brown, SA Kingston, RE Calderwood, SK TI Elevated expression of heat shock factor (HSF) 2A stimulates HSF1-induced transcription during stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HSP70 GENE-TRANSCRIPTION; DNA-BINDING DOMAIN; ERYTHROLEUKEMIA-CELLS; MOLECULAR-CLONING; LEUCINE-ZIPPER; FACTOR-II; C-FOS; ACTIVATION; PROTEIN; YEAST AB Heat shock factor 2 (HSF2) belongs to a family of structurally related transcription factors, which share the property of binding to heat shock elements in the promoters of hsp molecular chaperone genes. However, unlike HSF1, which is essential for hsp gene transcription, the cellular functions of HSF2 are not well known. Here we show that human HSF2, although an ineffective activator of the hsp70 promoter in vitro and in vivo in the absence of stress, participates in the activation of the hsp70 promoter by heat shock. HSF2 was not, however, activated by heat shock in cells deficient in functional HSF1, suggesting a requirement for HSF1 in HSF2-mediated transcriptional enhancement. In addition, HSF2 regulation involves differential activity of two isoforms, HSF2A and HSF2B, which arise from alternative splicing of a common hsf2 gene. Under basal conditions, both HSF2 isoforms are ineffective in activating the hsp70 transcription. However, heat shock differentially activates HSF2A in vivo. This phenomenon appears to be physiologically significant, as human myeloprogenitor cells differentiating along the erythroid lineage express HSF2A de novo and undergo a large increase in capacity to activate the hsp70 promoter. Our experiments further show that HSF1 is physically associated with HSF2 in the cell and that such binding is enhanced by heat shock. Our data suggest a mechanism involving the formation of heterocomplexes between HSF1 and HSF2 with enhanced activity to activate the hsp70 promoter when compared with HSF1 or HSF2 homotrimers. C1 Boston Univ, Sch Med, Ctr Mol Stress Response, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02116 USA. RP Calderwood, SK (reprint author), Boston Univ, Sch Med, Ctr Mol Stress Response, 650 Albany St,X300, Boston, MA 02118 USA. EM stuart_calderwood@medicine.bu.edu RI SONCIN, Fabrice/A-1475-2009; OI Soncin, Fabrice/0000-0001-6312-0673 FU NCI NIH HHS [CA47407, CA31303, CA50642] NR 52 TC 55 Z9 62 U1 1 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 SEP 12 PY 2003 VL 278 IS 37 BP 35465 EP 35475 DI 10.1074/jbc.M304663200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 718UG UT WOS:000185164400088 PM 12813038 ER PT J AU Bai, XH Cerimele, F Ushio-Fukai, M Waqas, M Campbell, PM Govindarajan, B Der, CJ Battle, T Frank, DA Ye, KQ Murad, E Dubiel, W Soff, G Arbiser, JL AF Bai, XH Cerimele, F Ushio-Fukai, M Waqas, M Campbell, PM Govindarajan, B Der, CJ Battle, T Frank, DA Ye, KQ Murad, E Dubiel, W Soff, G Arbiser, JL TI Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL-CELL PROLIFERATION; RIE-1 EPITHELIAL-CELLS; INDUCED APOPTOSIS; DIETARY CURCUMIN; MELANOMA-CELLS; MAGNOLIA BARK; COLON-CANCER; ACTIVATION; KINASE; TRAIL AB Natural products comprise a major source of small molecular weight angiogenesis inhibitors. We have used the transformed endothelial cell line SVR as an effective screen of natural product extracts to isolate anti-angiogenesis and anti-tumor compounds. Aqueous extracts of Magnolia grandiflora exhibit potent activity in our SVR proliferation assays. We found that the small molecular weight compound honokiol is the active principle of magnolia extract. Honokiol exhibited potent anti-proliferative activity against SVR cells in vitro. In addition, honokiol demonstrated preferential inhibition of primary human endothelial cells compared with fibroblasts and this inhibition was antagonized by antibodies against TNF alpha-related apoptosis-inducing ligand. In vivo, honokiol was highly effective against angiosarcoma in nude mice. Our preclinical data suggests that honokiol is a systemically available and non-toxic inhibitor of angiogenesis and should be further evaluated as a potential chemotherapeutic agent. C1 Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Cardiol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Univ N Carolina, Lineberger Canc Res Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Humboldt Univ, Dept Surg, Berlin, Germany. Humboldt Univ, Fac Med Charite, Div Mol Biol, Berlin, Germany. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. RP Emory Univ, Sch Med, Dept Dermatol, WMB 5309,1639 Pierce Dr, Atlanta, GA 30322 USA. EM jarbise@emory.edu FU NIAMS NIH HHS [AR02030, AR42687, AR44947] NR 42 TC 209 Z9 223 U1 0 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 12 PY 2003 VL 278 IS 37 BP 35501 EP 35507 DI 10.1074/jbc.M302967200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 718UG UT WOS:000185164400092 PM 12816951 ER PT J AU Mori, S Inoshima, K Shima, Y Schmidt, EV Yokota, Y AF Mori, S Inoshima, K Shima, Y Schmidt, EV Yokota, Y TI Forced expression of cyclin D1 does not compensate for Id2 deficiency in the mammary gland SO FEBS LETTERS LA English DT Article DE Id2; cyclin D1; mammary gland ID LOOP-HELIX PROTEINS; CELL-CYCLE; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTORS; G(1) PROGRESSION; TRANSGENIC MICE; INHIBITOR ID2; DIFFERENTIATION; PROLIFERATION; GROWTH AB Id2 and cyclin D1 share several biological activities, including inhibition of differentiation, stimulation of the G1-S transition in the cell cycle and stimulation of tumorigenesis. Mammary glands of Id2(-/-) mice display severely impaired lobulo-alveolar development during pregnancy, similarly to those of cyclin D1 null females. We investigated the functional relationship between Id2 and cyclin D1 in the mammary gland. Id2(-/-) mammary glands expressed a normal level of cyclin D1. No direct interaction of Id2 with cyclin D1 or its binding partner cdk4 was detected in mammalian two-hybrid assays. Ectopic expression of a cyclin D1 transgene did not rescue the mammary phenotype of Id2(-/-) mice. These results suggest that Id2 acts downstream or independently of cyclin D1 in the control of mammary cell proliferation during pregnancy. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Fukui Med Univ, Dept Biochem, Matsuoka, Fukui 9101193, Japan. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Childrens Serv, Charlestown, MA 02129 USA. RP Yokota, Y (reprint author), Fukui Med Univ, Dept Biochem, 23-3 Shimoaizuki, Matsuoka, Fukui 9101193, Japan. NR 33 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 11 PY 2003 VL 551 IS 1-3 BP 123 EP 127 DI 10.1016/S0014-5793(03)00906-2 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 721GL UT WOS:000185308600023 PM 12965216 ER PT J AU Hylek, EM Go, AS Chang, YC Jensvold, NG Henault, LE Selby, JV Singer, DE AF Hylek, EM Go, AS Chang, YC Jensvold, NG Henault, LE Selby, JV Singer, DE TI Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; ANTITHROMBOTIC THERAPY; RISK-FACTORS; BLEEDING COMPLICATIONS; COST-EFFECTIVENESS; CLINICAL-PRACTICE; WARFARIN; ASPIRIN; THROMBOEMBOLISM; COMMUNITY AB Background: The incidence of stroke in patients with atrial fibrillation is greatly reduced by oral anticoagulation, with the full effect seen at international normalized ratio (INR) values of 2.0 or greater. The effect of the intensity of oral anticoagulation on the severity of atrial fibrillation-related stroke is not known but is central to the choice of the target INR. Methods: We studied incident ischemic strokes in a cohort of 13,559 patients with nonvalvular atrial fibrillation. Strokes were identified through hospitalization data bases and validated on the basis of medical records, which also provided information on the use of warfarin or aspirin, the INR at admission, and coexisting illnesses. The severity of stroke was graded according to a modified Rankin scale. Thirty-day mortality was ascertained from hospitalization and mortality files. Results: Of 596 ischemic strokes, 32 percent occurred during warfarin therapy, 27 percent during aspirin therapy, and 42 percent during neither type of therapy. Among patients who were taking warfarin, an INR of less than 2.0 at admission, as compared with an INR of 2.0 or greater, independently increased the odds of a severe stroke in a proportional-odds logistic-regression model (odds ratio, 1.9; 95 percent confidence interval, 1.1 to 3.4) across three severity categories and the risk of death within 30 days (hazard ratio, 3.4; 95 percent confidence interval, 1.1 to 10.1). An INR of 1.5 to 1.9 at admission was associated with a mortality rate similar to that for an INR of less than 1.5 (18 percent and 15 percent, respectively). The 30-day mortality rate among patients who were taking aspirin at the time of the stroke was similar to that among patients who were taking warfarin and who had an INR of less than 2.0. Conclusions: Among patients with nonvalvular atrial fibrillation, anticoagulation that results in an INR of 2.0 or greater reduces not only the frequency of ischemic stroke but also its severity and the risk of death from stroke. Our findings provide further evidence against the use of lower INR target levels in patients with atrial fibrillation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Clin Epidemiol Unit, Boston, MA 02114 USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Hylek, EM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Clin Epidemiol Unit, 50 Staniford St,9th Fl, Boston, MA 02114 USA. FU NIA NIH HHS [5 R01 AG15478] NR 45 TC 679 Z9 709 U1 0 U2 14 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 11 PY 2003 VL 349 IS 11 BP 1019 EP 1026 DI 10.1056/NEJMoa022913 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 719UH UT WOS:000185223100003 PM 12968085 ER PT J AU Fan, MJ Ryan, PD Shannon, KM Haber, DA Smith, BL Harris, NL AF Fan, MJ Ryan, PD Shannon, KM Haber, DA Smith, BL Harris, NL TI Case 28-2003: A 51-year-old premenopausal woman with newly diagnosed breast cancer and a strong family history of breast cancer - Infiltrating lobular carcinoma of the right breast, two separate foci. Ductal carcinoma in situ of the right breast. Lobular carcinoma in situ and atypical ductal hyperplasia in both breasts. Mutation (6174delT) in the BRCA2 gene. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BILATERAL PROPHYLACTIC MASTECTOMY; WOMEN; OOPHORECTOMY; PATHOLOGY; CARRIERS; RISK C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Div Surg Oncol, 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 Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Fan, MJ (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. NR 16 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 11 PY 2003 VL 349 IS 11 BP 1076 EP 1082 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 719UH UT WOS:000185223100011 PM 12968092 ER PT J AU Gordon, VD Valentine, MT Gardel, ML Andor-Ardo, D Dennison, S Bogdanov, AA Weitz, DA Deisboeck, TS AF Gordon, VD Valentine, MT Gardel, ML Andor-Ardo, D Dennison, S Bogdanov, AA Weitz, DA Deisboeck, TS TI Measuring the mechanical stress induced by an expanding multicellular tumor system: a case study SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE brain tumor; multicellular tumor spheroid; growth dynamics; invasion; traction; stress; strain; matrigel; in vitro assay; particle tracking; microrheology ID GLIOMA-CELLS; MATRIX METALLOPROTEINASES; FIBROBLAST TRACTION; GROWTH DYNAMICS; SPHEROID MODEL; IN-VITRO; COLLAGEN; FORCES; REORGANIZATION; BRAIN AB Rapid volumetric growth and extensive invasion into brain parenchyma are hallmarks of malignant neuroepithelial tumors in vivo. Little is known, however, about the mechanical impact of the growing brain tumor on its microenvironment. To better understand the environmental mechanical response, we used multiparticle tracking methods to probe the environment of a dynamically expanding, multicellular brain tumor spheroid that grew for 6 days in a three-dimensional Matrigel-based in vitro assay containing 1.0-mum latex beads. These beads act as reference markers for the gel, allowing us to image the spatial displacement of the tumor environment using high-resolution time-lapse video microscopy. The results show that the volumetrically expanding tumor spheroid pushes the gel outward and that this tumor-generated pressure propagates to a distance greater than the initial radius of the tumor spheroid. Intriguingly, beads near the tips of invasive cells are displaced inward, toward the advancing invasive cells. Furthermore, this localized cell traction correlates with a marked increase in total invasion area over the observation period. This case study presents evidence that an expanding microscopic tumor system exerts both significant mechanical pressure and significant traction on its microenvironment. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Dept Phys, Div Engn & Appl Sci, Cambridge, MA 02138 USA. Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. MIT, Complex Biosyst Modeling Lab, Harvard MIT Athinoula A Martinos Ctr Biomed Imagi, HST,Biomed Engn Ctr, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Weitz, DA (reprint author), Harvard Univ, Dept Phys, Div Engn & Appl Sci, Cambridge, MA 02138 USA. RI Gardel, Margaret/D-1703-2012; OI Valentine, Megan/0000-0003-4781-8478; Gordon, Vernita/0000-0002-5989-9378 FU NCI NIH HHS [CA69246] NR 36 TC 59 Z9 62 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 10 PY 2003 VL 289 IS 1 BP 58 EP 66 DI 10.1016/S0014-4827(03)00256-8 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 718VL UT WOS:000185167100006 PM 12941604 ER PT J AU Messas, E Pouzet, B Touchot, B Guerrero, JL Vlahakes, GJ Desnos, M Menasche, P Hagege, A Levine, RA AF Messas, E Pouzet, B Touchot, B Guerrero, JL Vlahakes, GJ Desnos, M Menasche, P Hagege, A Levine, RA TI Efficacy of chordal cutting to relieve chronic persistent ischemic mitral regurgitation SO CIRCULATION LA English DT Article; Proceedings Paper CT 75th Annual Scientific Session of the American-Heart-Association CY NOV 17-20, 2002 CL CHICAGO, IL SP Amer Heart Assoc DE mitral valve; regurgitation; remodeling; echocardiography ID 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION; PAPILLARY-MUSCLE DYSFUNCTION; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; SUBVALVULAR APPARATUS; MYOCARDIAL-INFARCTION; VALVE-REPLACEMENT; REPAIR; MECHANISM; INSIGHTS; CARDIOMYOPATHY AB Background - Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Leaflet closure is restricted by tethering to displaced papillary muscles, and is, therefore, incompletely treated by annular reduction. In an acute ischemic model, we reduced such MR by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. Whether this is effective without prolapse, recurrent MR, or left ventricular (LV) failure in chronic persistent ischemic MR, despite greater LV remodeling, remains to be established. Therefore, we studied 7 sheep with chronic inferobasal infarcts known to produce progressive MR over 2 months. In all of those sheep, after a mean of 4.1 months, the 2 central basal ( intermediate) chordae were cut at the chronic ischemic MR stage. 3-Dimensional echo quantified MR, LV function, and valve geometry. Five other sheep were followed for a mean of 7.8 +/- 1.2 months after inferobasal infarction with chordal cutting. Results - All 7 of the sheep with chronic ischemic MR ( increased from 1.4 +/- 0.4 to 11.1 +/- 0.5 mL/beat, regurgitant fraction = 39.0 +/- 4.2%, P < 0.0001) showed anterior leaflet angulation at the basal chord insertion. Although end-systolic volume had doubled, cutting the 2 central basal chordae significantly decreased the MR to baseline (P < 0.0001) without prolapse or decline in EF (41.1 +/- 1.5% to 42.6 +/- 1.6%, P = not significant [NS]). The five sheep with long-term follow-up showed no prolapse or MR, and no significant post-infarct decrease in LV ejection fraction ( EF; 38.9 +/- 2.4% to 41.4 +/- 1.2%, P = NS). Conclusion - Cutting a minimum number of basal ( intermediate) chordae can improve coaptation and reduce chronic persistent ischemic MR without impairing LVEF. No adverse effects were noted long-term after chordal cutting at the time of infarction. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Cardiovasc Lab, Boston, MA 02114 USA. Hop Europeen Georges Pompidou, Fac Med Necker Enfants Malad, INSERM,EMI 0016,Ecole Chirurg, Assistance Publ Hop Paris,Serv Cardiol & Chirurg, Paris, France. RP Levine, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, VBK508, Boston, MA 02114 USA. EM rlevine@partners.org NR 40 TC 88 Z9 89 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 SEP 9 PY 2003 VL 108 IS 10 SU S BP 111 EP 115 DI 10.1161/01.cir.0000087658.47544.7f PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 720MR UT WOS:000185265000020 ER PT J AU Reusch, JEB Klemm, DJ AF Reusch, JEB Klemm, DJ TI Cyclic AMP response element-binding protein in the vessel wall - Good or bad? SO CIRCULATION LA English DT Article DE editorials; protein, DNA-binding, cyclic AMP-responsive; atherosclerosis; restenosis; cells, smooth muscle, vascular ID MUSCLE CELL-PROLIFERATION; EXPRESSION; MIGRATION/; INJURY C1 Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr, Endo 111-H,1055 Clermont St, Denver, CO 80220 USA. FU NHLBI NIH HHS [P01 HL 14985]; NIDDK NIH HHS [R01DK53969] NR 15 TC 17 Z9 17 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 SEP 9 PY 2003 VL 108 IS 10 BP 1164 EP 1166 DI 10.1161/01.CIR.0000084296.45158.50 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 719DF UT WOS:000185187800001 PM 12963681 ER PT J AU Kurth, T Glynn, RJ Walker, AM Chan, KA Buring, JE Hennekens, CH Gaziano, JM AF Kurth, T Glynn, RJ Walker, AM Chan, KA Buring, JE Hennekens, CH Gaziano, JM TI Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs SO CIRCULATION LA English DT Article DE myocardial infarction; aspirin; prevention; epidemiology ID PROSTAGLANDIN H-2 SYNTHASE; PHYSICIANS HEALTH; PLATELET-FUNCTION; CYCLOOXYGENASE; PREVENTION; RISK; IBUPROFEN; NAPROXEN; THERAPY; DISEASE AB Background - There is clear evidence from numerous randomized trials and their meta-analyses that aspirin reduces risks of first myocardial infarction (MI). Recent data also suggest that other nonsteroidal anti-inflammatory drugs ( NSAIDs) may interfere with this benefit of aspirin. Methods and Results - We performed subgroup analysis from a 5-year randomized, double-blind, placebo-controlled trial of 325 mg aspirin on alternate days among 22 071 apparently healthy US male physicians with prospective observational data on use of NSAIDs. A total of 378 MIs were confirmed, 139 in the aspirin group and 239 in the placebo group. Aspirin conferred a statistical extreme ( P < 0.00001) 44% reduction in risk of first MI. Among participants randomized to aspirin, use of NSAIDs on 1 to 59 d/y was not associated with MI ( multivariable adjusted relative risk [RR], 1.21; 95% confidence interval [CI], 0.78 to 1.87), whereas the use of NSAIDs on &GE; 60 d/y was associated with MI ( RR, 2.86; 95% CI, 1.25 to 6.56) compared with no use of NSAIDs. In the placebo group, the RRs for MI across the same categories of NSAID use were 1.14 ( 95% CI, 0.81 to 1.60) and 0.21 ( 95% CI, 0.03 to 1.48). Conclusions - These data suggest that regular but not intermittent use of NSAIDs inhibits the clinical benefits of aspirin. Chance, bias, and confounding remain plausible alternative explanations, despite the prospective design and adjustment for covariates. Nonetheless, we believe the most plausible interpretation of the data to be that regular but not intermittent use of NSAIDs inhibits the clinical benefit of aspirin on first MI. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Ingenix Pharmaceut Serv, Div Epidemiol, Auburndale, MA USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. Univ Miami, Sch Med, Dept Epidemiol, Miami, FL USA. Univ Miami, Sch Med, Dept Publ Hlth, Miami, FL USA. Mt Sinai Med Ctr, Miami Heart Inst, Miami Beach, FL 33140 USA. RP Kurth, T (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Chan, Kinwei/0000-0001-8161-1986 FU NCI NIH HHS [CA-34944, CA-40360, R01 CA097193]; NHLBI NIH HHS [HL-26490, HL-34595] NR 26 TC 163 Z9 169 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 SEP 9 PY 2003 VL 108 IS 10 BP 1191 EP 1195 DI 10.1161/01.CIR.0000087593.07533.9B PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 719DF UT WOS:000185187800006 PM 12939216 ER PT J AU Baehring, JM Betensky, RA Batchelor, TT AF Baehring, JM Betensky, RA Batchelor, TT TI Malignant peripheral nerve sheath tumor - The clinical spectrum and outcome of treatment SO NEUROLOGY LA English DT Article AB Malignant peripheral nerve sheath tumors (MPNST) are derived from Schwann cells or pluripotent cells of the neural crest. Delay of diagnosis is common, especially in lesions affecting proximal parts of the peripheral nervous system. Presented is a series of 54 patients with MPNST seen at a single institution over a 10-year period. In this series, tumor diameter of <5 cm, gross total resection of the tumor, and younger age were favorable prognostic variables. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Batchelor, TT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr,Dept Neurol, Cox 315,100 Blossom St, Boston, MA 02114 USA. NR 10 TC 70 Z9 73 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 SEP 9 PY 2003 VL 61 IS 5 BP 696 EP 698 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 719CX UT WOS:000185187000023 PM 12963767 ER PT J AU Lloyd-Lones, DM Wilson, PWF Larson, MG Leip, E Beiser, A D'Agostino, RB Cleeman, JI Levy, D AF Lloyd-Lones, DM Wilson, PWF Larson, MG Leip, E Beiser, A D'Agostino, RB Cleeman, JI Levy, D TI Lifetime risk of coronary heart disease by cholesterol levels at selected ages SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; HEALTH-CARE PROFESSIONALS; SERUM-CHOLESTEROL; CLINICAL-PRACTICE; TASK-FORCE; FRAMINGHAM; MEN; PREVENTION; MORTALITY; ADULTS AB Background: We sought to assess how cholesterol levels at different ages modify the remaining lifetime risk of coronary heart disease (CHD). Methods: We included all Framingham Heart Study participants examined from 1971 through 1996 who did not have CHD and were not receiving lipid-lowering therapy. At index ages of 40, 50, 60, 70, and 80 years, participants were stratified by total cholesterol level and by cholesterol subfractions. Lifetime risk of CHD was calculated with death free of CHD as a competing event. Results: Among 3269 men and 4019 women, 1120 developed CHD and 1365 died free of CHD during followup. At each index age, lifetime risk of CHD increased with higher cholesterol levels, and time to event decreased. At age 40 years, the lifetime risks of CHD through age 80 years for men with total cholesterol levels less than 200 mg/dL (<5.20 mmol/L), 200 to 239 mg/dL (5.20-6.19 mmol/L), and 240 mg/dL or greater (greater than or equal to6.20 mmol/L), respectively, were 31%, 43%, and 57%; for women, the lifetime risks were 15%, 26%, and 33%, respectively. Lifetime risks contrasted sharply with shorter-term risks: at age 40 years, the 10-year cumulative risks of CHD were 3%, 5%, and 12% for men, and 1%, 2%, and 5% for women, respectively. Conclusions: Lifetime risk of CHD increases sharply with higher total cholesterol levels for men and women at all ages. These data support an important role for cholesterol screening in younger patients, and they may help target high-risk patients for lifestyle modification or drug therapy. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Univ, Stat & Consulting Unit, Boston, MA 02215 USA. NHLBI, Bethesda, MD USA. RP Lloyd-Lones, DM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [K23 HL04253, N01-HC-25195] NR 30 TC 61 Z9 62 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 8 PY 2003 VL 163 IS 16 BP 1966 EP 1972 DI 10.1001/archinte.163.16.1966 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 720ZB UT WOS:000185291600015 PM 12963571 ER PT J AU Hanslik, T Boelle, PY Schwarzinger, M Carrat, F Freedberg, KA Valleron, AJ Flahault, A AF Hanslik, T Boelle, PY Schwarzinger, M Carrat, F Freedberg, KA Valleron, AJ Flahault, A TI Varicella in French adolescents and adults: individual risk assessment and cost-effectiveness of routine vaccination SO VACCINE LA English DT Article DE varicella; vaccination; adult ID UNITED-STATES; BENEFIT-ANALYSIS; ARMY RECRUITS; CHICKENPOX; CHILDREN; AGE; EPIDEMIOLOGY; SEROSURVEY; STRATEGIES; MORTALITY AB Age-specific force of varicella infection, hospitalisation and death rates in non-immune persons were calculated using an age-based mathematical model and national data for France. A cost-effectiveness model was then applied to hypothetical cohorts of persons aged 15-45 years with a negative or uncertain history of varicella. Vaccination strategies with and without prior serotesting, and healthcare payer perspective and societal perspective were considered. A sensitivity analysis was performed. Vaccination prevented more than one third of all varicella-related deaths. With serotesting, compared with no intervention, the cost per case avoided and per year of life saved for subjects aged 15 years were E 335 and 55,100, respectively. When work-loss costs were also included, savings were associated with screening and vaccination of subjects less than 30 years old. Without serotesting, the costs raised markedly, with an almost identical effectiveness, resulting in an unfavourable incremental cost-effectiveness. Based on medical costs, routine serotesting and varicella vaccination for French adolescents and young adults with a negative or uncertain history of varicella affords health benefits at a cost comparable to those of other very expensive therapies considered worthwhile. From the societal perspective, such screening and vaccination might save costs. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Paris 06, Dept Publ Hlth, Hop St Antoine, INSERM,U444,Assistance Publ Hop Paris, Paris, France. Univ Versailles, Hop Ambroise Pare, Dept Internal Med, Assistance Publ Hop Paris, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sect Gen Med, Boston, MA USA. RP Hanslik, T (reprint author), CHU Ambroise Pare, Federat Med Interne, 9 Ave Charles de Gaulle, F-92104 Boulogne, France. RI Schwarzinger, Michael/F-7367-2011; OI CARRAT, fabrice/0000-0002-8672-7918 NR 40 TC 21 Z9 22 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 8 PY 2003 VL 21 IS 25-26 BP 3614 EP 3622 DI 10.1016/S0264-410X(03)00405-5 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 719YY UT WOS:000185233700016 PM 12922090 ER PT J AU Kooy, HM Schaefer, M Rosenthal, S Bortfeld, T AF Kooy, HM Schaefer, M Rosenthal, S Bortfeld, T TI Monitor unit calculations for range-modulated spread-out Bragg peak fields SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article AB We derive, from first principles, a model to predict the output factors for spread-out Bragg peak proton fields (SOBP). The model is based on the simple observation that the output factor is the ratio of SOBP plateau dose to the dose measured in the ionization reference chamber. The latter, in turn, equates to the entrance dose of the SOBP corrected for inverse square. We use a theoretical derivation of this ratio to establish the relationship between the output factor and the distal range and modulation width of the SOBP. In addition, the theoretical derivation reduces the dependence on the distal range and modulation width into a single factor r = (R - M)/M. We compare the theoretical derivation against measurements obtained at the Northeast Proton Therapy Facility for output factors for clinical fields. The agreement between measurements and prediction is 2.9%. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, Boston, MA 02461 USA. Harvard Univ, Sch Med, Boston, MA 02461 USA. RP Kooy, HM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, Boston, MA 02461 USA. FU NCI NIH HHS [5 P01 CA21239-24] NR 8 TC 35 Z9 36 U1 3 U2 6 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 SEP 7 PY 2003 VL 48 IS 17 BP 2797 EP 2808 AR PII S0031-9155(03)60487-2 DI 10.1088/0031-9155/48/17/305 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 725ZT UT WOS:000185573300005 PM 14516102 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, RP Braunwald, E TI Improving antithrombotic treatment in patients after myocardial infarction SO LANCET LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; ASPIRIN; THERAPY; CLOPIDOGREL; WARFARIN; TRIAL; RISK C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 1 Z9 1 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 SEP 6 PY 2003 VL 362 IS 9386 BP 757 EP 757 DI 10.1016/S0140-6736(03)14296-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 719DN UT WOS:000185188500005 PM 13678866 ER PT J AU Mezey, E Parmalee, A Szalayova, I Gill, SP Cuajungco, MP Leyne, M Slaugenhaupt, SA Brownstein, MJ AF Mezey, E Parmalee, A Szalayova, I Gill, SP Cuajungco, MP Leyne, M Slaugenhaupt, SA Brownstein, MJ TI Of splice and men: what does the distribution of IKAP mRNA in the rat tell us about the pathogenesis of familial dysautonomia? SO BRAIN RESEARCH LA English DT Article DE IKAP; mRNA; rat; pathogenesis; familial dysautonomia ID SPINAL MUSCULAR-ATROPHY; ELONGATOR COMPLEX; EXPRESSION; GENE; MUTATIONS; GANGLIA; PROTEIN; HOLOENZYME; COMPONENT AB Familial dysautonomia (FD) is the best-known and most common member of a group of congenital sensory/autonomic neuropathies characterized by widespread sensory and variable autonomic dysfunction. As opposed to the sensory/motor neuropathies, little is known about the causes of neuronal dysfunction and loss in the sensory/autonomic neuropathies. FD involves progressive neuronal degeneration, has a broad impact on the operation of many of the body's systems, and leads to a markedly reduced quality of life and premature death. In 2001, we identified two mutations in the IKBKAP gene that result in FD. IKBKAP encodes IKAP, a member of the putative human holo-Elongator complex, which may facilitate transcription by RNA polymerase II. Whether or not the Elongator plays this role is moot. The FD mutation found on >99.5% of FD chromosomes does not cause complete loss of function. Instead, it results in a tissue-specific decrease in splicing efficiency of the IKBKAP transcript; cells from patients retain some capacity to produce normal mRNA and protein. To better understand the relationship between the genotype of FD patients and their phenotype, we have used in situ hybridization histochemistry to map the IKAP mRNA in sections of whole rat embryos. The mRNA is widely distributed. Highest levels are in the nervous system, but substantial amounts are also present in peripheral organs. Published by Elsevier B.V. C1 NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, Basic Neurosci Program, NIH, Bldg 36,Rm 3D-06, Bethesda, MD 20892 USA. RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 34 TC 14 Z9 14 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 SEP 5 PY 2003 VL 983 IS 1-2 BP 209 EP 214 DI 10.1016/S0006-8993(03)03090-7 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 721KT UT WOS:000185316100022 PM 12914982 ER PT J AU Tung, CH Ho, NH Tang, Q Jaffer, FA Reed, GL Weissleder, R AF Tung, CH Ho, NH Tang, Q Jaffer, FA Reed, GL Weissleder, R TI Novel factor XIII probes for blood coagulation imaging SO CHEMBIOCHEM LA English DT Article DE blood coagulation; factor 13; fluorescent probes; imaging agents; transglutaminase ID FIBRIN; ACTIVATION; THROMBI C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Boston, MA 02115 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. OI Jaffer, Farouc/0000-0001-7980-384X; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01 CA 99385, P50 CA 86355, R33 CA 88365] NR 18 TC 41 Z9 43 U1 6 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD SEP 5 PY 2003 VL 4 IS 9 BP 897 EP 899 DI 10.1002/cbic.200300602 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 723WY UT WOS:000185455600017 PM 12964167 ER PT J AU Minokoshi, Y Kahn, CR Kahn, BB AF Minokoshi, Y Kahn, CR Kahn, BB TI Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ADIPOSE-TISSUE; SKELETAL-MUSCLE; KNOCKOUT MICE; RESISTANCE; GENE; OBESITY; INACTIVATION; INTOLERANCE; METABOLISM; DISPOSAL C1 Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, BB (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrine, Res N 325E,99 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK33201, R01 DK43051] NR 37 TC 124 Z9 126 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 SEP 5 PY 2003 VL 278 IS 36 BP 33609 EP 33612 DI 10.1074/jbc.R300019200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 716UK UT WOS:000185047500001 PM 12788932 ER PT J AU Johnson, KR Johnson, KY Becker, KP Bielawski, J Mao, CG Obeid, LM AF Johnson, KR Johnson, KY Becker, KP Bielawski, J Mao, CG Obeid, LM TI Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1-phosphate levels and cell viability SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SPHINGOSINE KINASE; SPHINGOLIPID METABOLISM; STRESS-RESPONSE; HEAT-STRESS; PHOSPHOHYDROLASE; 1-PHOSPHATE; IDENTIFICATION; DEATH; ACTIVATION AB Sphingosine-1-phosphate (S1P) is a highly bioactive lipid that exerts numerous biological effects both intracellularly as a second messenger and extracellularly by binding to its G-protein-coupled receptors of the endothelial differentiation gene family (S1P receptors-(1-5)). Intracellularly, at least two enzymes, sphingosine kinase and S1P phosphatase, regulate the activity of S1P by governing the phosphorylation status of S1P. To study the regulation of S1P levels, we cloned the human isoform of S1P phosphatase 1 (hSPPase1). The hSPPase1 has 78% homology to the mouse SPPase at the amino acid level with 6-8 possible transmembrane domains. Confocal microscopy revealed green fluorescent protein-tagged hSPPase1, expressed in either MCF7 or HEK293 cells, co-localized to endoplasmic reticulum with calreticulin. According to Northern blot analysis, hSPPase1 is expressed in most tissues, with the strongest levels found in the highly vascular tissues of placenta and kidney. Transient overexpression of hSPPase1 exhibited a 2-fold increase in phosphatase activity against S1P and dihydro-S1P, indicating that the expressed protein was functional. Small interfering RNA (siRNA) knockdown of endogenous hSPPase1 drastically reduced hSPPase1 mRNA levels, as confirmed by reverse transcription PCR, and resulted in an overall 25% reduction of in vitro phosphatase activity in the membrane fractions. Sphingolipid mass measurements in hSPPase1 siRNA knockdown cells revealed a 2-fold increase of S1P levels and concomitant decrease in sphingosine. In vivo labeling of hSPPase1 siRNA-treated cells showed accumulation of S1P within cells, as well as significantly increased secretion of S1P into the media, indicating that hSPPase1 regulates secreted S1P. In addition, siRNA-induced knockdown of hSPPase1 endowed resistance to tumor necrosis factor-alpha and the chemotherapeutic agent daunorubicin. Collectively, these data suggest that regulation of hSPPase1 with the resultant changes in cellular and secreted S1P could have important implications to cell proliferation, angiogenesis, and apoptosis. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Citadel, Dept Biol, Charleston, SC 29409 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCRR NIH HHS [1P20RR17677]; NHLBI NIH HHS [HL 07260]; NIGMS NIH HHS [GM62287] NR 25 TC 100 Z9 102 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 SEP 5 PY 2003 VL 278 IS 36 BP 34541 EP 34547 DI 10.1074/jbc.M301741200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 716UK UT WOS:000185047500115 PM 12815058 ER PT J AU Cristillo, AD Nie, LH Macri, MJ Bierer, BE AF Cristillo, AD Nie, LH Macri, MJ Bierer, BE TI Cloning and characterization of N4WBP5A, an inducible, cyclosporine-sensitive, Nedd4-binding protein in human T lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL NA+ CHANNEL; WW DOMAIN; LIDDLES-SYNDROME; IMMUNE-SYSTEM; LIGASE NEDD4; UBIQUITINATION; FAMILY; IDENTIFICATION; MICE; ITCH AB We have cloned and characterized a human cDNA, designated N4WBP5A, that belongs to the family of Nedd4-binding proteins. We originally identified N4WBP5A as an unknown expressed sequence tag (AA770150) represented in a cDNA microarray analysis that was up-regulated upon activation of T cells and inhibited by cell treatment with the calcineurin phosphatase inhibitors, cyclosporine (CsA) and tacrolimus (FK506). The predicted N4WBP5A amino acid sequence of 242 amino acid residues reveals an open reading frame of 729 nucleotides with a corresponding molecular mass of 27.1 kDa. Detection of N4WBP5A mRNA by reverse transcription-PCR was consistent with the induction of N4WBP5A following mitogenic stimulation of T lymphocytes and inhibition by CsA. Immunoblot analysis revealed endogenous N4WBP5A protein to be up-regulated following T cell activation and inhibited by CsA. This regulation of N4WBP5A mRNA expression differed from that of its homologue (51% identical; 65% similar) N4WBP5. Like N4WBP5, however, expression of epitope-tagged N4WBP5A indicated that the protein is localized predominantly to the Golgi network. Here we show by co-precipitation experiments that N4WBP5A interacts with the WW domains of Nedd4, an E3 ubiquitin ligase. Taken together, our data suggest that N4WBP5A may play a regulatory role in modulating Nedd4 activity at the level of the Golgi apparatus in T lymphocytes. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Bierer, BE (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 17 Z9 18 U1 0 U2 0 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 SEP 5 PY 2003 VL 278 IS 36 BP 34587 EP 34597 DI 10.1074/jbc.M304723200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 716UK UT WOS:000185047500120 PM 12796489 ER PT J AU Ripoll, J Schulz, RB Ntziachristos, V AF Ripoll, J Schulz, RB Ntziachristos, V TI Free-space propagation of diffuse light: Theory and experiments SO PHYSICAL REVIEW LETTERS LA English DT Article ID BOUNDARY-CONDITIONS; OPTICAL TOMOGRAPHY; REGIONS; BREAST; MEDIA AB In this Letter we present a simple and novel theoretical approach for modeling the intensity distribution from an arbitrarily shaped turbid volume in a noncontact geometry by considering diffuse light propagation in free space. This theory is validated with experiments for a diffusive volume of known geometry in a noncontact situation, both with and without the presence of an embedded absorber. The implications of this new formulation in the context of optical tomography in turbid media are discussed. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion, Greece. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 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 FU NCI NIH HHS [CA91807]; NIBIB NIH HHS [R01 EB000750-1] NR 15 TC 76 Z9 78 U1 1 U2 11 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 SEP 5 PY 2003 VL 91 IS 10 AR 103901 DI 10.1103/PhysRevLett.91.103901 PG 4 WC Physics, Multidisciplinary SC Physics GA 724KA UT WOS:000185485700013 PM 14525478 ER PT J AU Fudala, PJ Bridge, TP Herbert, S Williford, WO Chiang, CN Jones, K Collins, J Raisch, D Casadonte, P Goldsmith, RJ Ling, W Malkerneker, U McNicholas, L Renner, J Stine, S Tusel, D AF Fudala, PJ Bridge, TP Herbert, S Williford, WO Chiang, CN Jones, K Collins, J Raisch, D Casadonte, P Goldsmith, RJ Ling, W Malkerneker, U McNicholas, L Renner, J Stine, S Tusel, D CA Buprenorphine Naloxone Collaborati TI Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTROLLED CLINICAL-TRIAL; DRUG-ABUSE TREATMENT; OPIOID DEPENDENCE; INTRAVENOUS BUPRENORPHINE; CRIMINAL ACTIVITY; VOLUNTEERS; COMBINATIONS; PREVALENCE; METHADONE AB Background: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. Methods: We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. Results: The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. Conclusions: Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIDA, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. VA Cooperat Studies Program, Coordinating Ctr, Perry Point, MD USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ New Mexico, VA Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM 87131 USA. NYU, Sch Med, New York Harbor Hlth Care Syst, VA Med Ctr, New York, NY USA. VA Med Ctr, Cincinnati, OH USA. VA Med Ctr, Los Angeles, CA USA. VA Med Ctr, Hines, IL USA. Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. VA Med Ctr, West Haven, CT USA. Univ Calif San Francisco, VA Med Ctr, San Francisco, CA 94143 USA. RP Fudala, PJ (reprint author), VA Med Ctr, Psychiat Serv, Ward 7E 116-7E,Univ & Woodland Aves, Philadelphia, PA 19104 USA. OI Stine, Susan/0000-0001-5426-4448 FU NIDA NIH HHS [3Y01-DA-30011-04] NR 32 TC 258 Z9 261 U1 4 U2 15 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 SEP 4 PY 2003 VL 349 IS 10 BP 949 EP 958 DI 10.1056/NEJMoa022164 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 717HJ UT WOS:000185081400006 PM 12954743 ER PT J AU Li, YQ Liu, D Chen, DS Kharbanda, S Kufe, D AF Li, YQ Liu, D Chen, DS Kharbanda, S Kufe, D TI Human DF3/MUC1 carcinoma-associated protein functions as an oncogene SO ONCOGENE LA English DT Article DE DF3/MUC1; 3Y1 cells; anchorage-independent growth; cellular transformation ID BETA-CATENIN; CELL-ADHESION; C-SRC; ANTIGEN; CANCER; DF3 AB The human DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed by most carcinomas of the breast and other epithelia. The contribution of MUC1 overexpression to the malignant phenotype is, however, not known. In the present studies, we have stably expressed MUC1 in rat 3Y1 fibroblasts. MUC1-positive cells were selected from independent transfections. The results demonstrate that, as found in human carcinomas, MUC1 is expressed on the cell surface and as a complex with P-catenin in the nucleus of the transfectants. Colony formation in soft agar demonstrates that cells expressing MUC1, but not the empty vector, exhibit anchorage-independent growth. The results also show that MUC1 expression confers tumor formation in nude mice. These findings provide the first evidence that MUC1 induces cellular transformation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. ILEX Prod Inc, Boston, MA 02215 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA97098, R01 CA097098] NR 17 TC 143 Z9 145 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 4 PY 2003 VL 22 IS 38 BP 6107 EP 6110 DI 10.1038/sj.onc.1206732 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 718GY UT WOS:000185137800020 PM 12955090 ER PT J AU Landon, BE Normand, SLT Blumenthal, D Daley, J AF Landon, BE Normand, SLT Blumenthal, D Daley, J TI Physician clinical performance assessment - Prospects and barriers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; REPORT CARDS; EXAMINATION SCORES; QUALITY; ASSOCIATION; COMPETENCE; MEDICARE; SURGERY; RATINGS AB The performance of physicians in their day-to-day clinical practices has become an area of intense public interest. Both patients and health care purchasers want more effective means of identifying excellent clinicians, and a variety of organizations are discussing and implementing plans for assessing the performance of individual clinicians. In this article, we review the current state of physician clinical performance assessment with a focus on its usefulness for competency assessment. We describe recommendations for a physician clinical performance assessment system for these purposes, and identify ways in which current methods of performance assessment fall short of these. We conclude that important technical barriers stand in the way of using physician clinical performance assessment for evaluating the competency of individual physicians. Overcoming these barriers will require considerable additional research and development. Even then, for some uses, physician clinical performance assessment at the individual physician level may be technically impossible to accomplish in a valid and fair way. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Care, Boston, MA 02114 USA. RP Landon, BE (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. NR 34 TC 153 Z9 154 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 3 PY 2003 VL 290 IS 9 BP 1183 EP 1189 DI 10.1001/jama.290.9.1183 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 717LK UT WOS:000185090400014 PM 12953001 ER PT J AU Wolfe, JL Wang, BH Kawate, T Stanton, VP AF Wolfe, JL Wang, BH Kawate, T Stanton, VP TI Sequence-specific dinucleotide cleavage promoted by synergistic interactions between neighboring modified nucleotides in DNA SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESTRICTION ENZYMES C1 Nuvelo Inc, Cambridge, MA 02139 USA. RP Wolfe, JL (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. EM wolfe@molbio.mgh.harvard.edu NR 13 TC 13 Z9 13 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 3 PY 2003 VL 125 IS 35 BP 10500 EP 10501 DI 10.1021/ja035646g PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 716DD UT WOS:000185012800009 PM 12940715 ER PT J AU Mann, DL Reid, MB AF Mann, DL Reid, MB TI Exercise training and skeletal muscle inflammation in chronic heart failure: Feeling better about fatigue SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; FACTOR-ALPHA; REACTIVE OXYGEN; DIAPHRAGM CONTRACTILITY; OXIDATIVE STRESS; PROTEIN LOSS; CACHEXIA; APOPTOSIS; DYSFUNCTION C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Cardiol Sect, Houston, TX 77030 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Sect Pulm Med, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Cardiol Sect, MS 524,6565 Fannin, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 38 TC 26 Z9 26 U1 0 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 SEP 3 PY 2003 VL 42 IS 5 BP 869 EP 872 DI 10.1016/S0735-1097(03)00847-7 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 716RH UT WOS:000185029200016 PM 12957434 ER PT J AU Landefeld, CS AF Landefeld, CS TI Improving health care for older persons SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 8th Regenstrief Conference CY SEP 30-OCT 02, 2002 CL MARSHALL, INDIANA ID COMPREHENSIVE GERIATRIC ASSESSMENT; FUNCTIONAL DECLINE; RANDOMIZED-TRIAL; MULTICOMPONENT INTERVENTION; HOSPITALIZED-PATIENTS; PROSTATE-CANCER; OUTCOMES; HOME; ADMISSION; PROGRAM AB Health care of the highest quality promotes successful aging. This paper examines the efforts that have been taken to improve the quality of health care, especially hospital care. Most of these efforts have evaluated conventional treatments of specific diseases; they are critical but underfunded and underused, and many practices persist without much evidence of efficacy. Fewer efforts have attempted to improve care for groups of persons in specific settings, such as the hospital. Three complementary approaches to improving comprehensive outcomes for hospitalized older persons-Geriatric Evaluation and Management, Acute Care for Elders, and the Elder Life Program-demonstrate what has been learned about improving care for older persons by redesigning microsystems of care. A research agenda for advancing successful aging should include specific actions to improve the quality of health care. C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Div Geriatr, Box 1265, San Francisco, CA 94143 USA. FU NIA NIH HHS [K07 AG00912] NR 19 TC 31 Z9 31 U1 0 U2 3 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 SEP 2 PY 2003 VL 139 IS 5 SU S BP 421 EP 424 PN 2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 718FE UT WOS:000185133800008 PM 12965969 ER PT J AU Varo, N de Lemos, JA Libby, P Morrow, DA Murphy, SA Nuzzo, R Gibson, CM Cannon, CP Braunwald, E Schonbeck, U AF Varo, N de Lemos, JA Libby, P Morrow, DA Murphy, SA Nuzzo, R Gibson, CM Cannon, CP Braunwald, E Schonbeck, U TI Soluble CD40L - Risk prediction after acute coronary syndromes SO CIRCULATION LA English DT Article DE coronary disease; myocardial infarction; risk factors ID C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; MORTALITY; TROPONIN; LIGAND; EVENTS AB Background-Elevated plasma concentrations of soluble CD40 ligand (sCD40L) indicate increased risk for future cardiovascular events in apparently healthy women. This study tested the hypothesis that plasma sCD40L, alone or in combination with troponin (cTnI) or C-reactive protein (CRP), may identify patients with acute coronary syndromes at heightened risk for recurrent cardiac events. Methods and Results-In a nested case-control study (cases, n=195; controls, n=195) within the OPUS-TIMI16 trial, patients with the prespecified study end points death, myocardial infarction (MI), or congestive heart failure (CHF) within 10 months had significantly higher median (25th, 75th percentiles) sCD40L plasma levels than did controls (0.78 [0.34, 1.73] ng/mL versus 0.52 [0.16, 1.42] ng/mL, P<0.002). After adjustment for other risk predictors and levels of cTnI and CRP, sCD40L levels above median were associated with higher risk for death, MI, and the composite death/MI or death/MI/CHF (adjusted hazard ratios, 1.9 [P<0.05], 1.9 [P<0.001], 1.9 [P<0.001], and 1.8 [P<0.01], respectively). Interestingly, patients with elevated plasma levels of sCD40L and cTnI showed a markedly increased risk of death, MI, or death/MI/CHF compared with patients with the lowest levels of both markers (adjusted hazard ratios, 12.1, 7.2, and 4.3, respectively; all P<0.01). Conclusions-Elevated plasma levels of sCD40L identify patients with acute coronary syndromes at heightened risk of death and recurrent MI independent of other predictive variables, including cTnI and CRP. Notably, combined assessment of sCD40L with cTnI complements prognostic information for death and MI. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX USA. RP Libby, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, 221 Londwood Ave, Boston, MA 02115 USA. NR 11 TC 236 Z9 258 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 SEP 2 PY 2003 VL 108 IS 9 BP 1049 EP 1052 DI 10.1161/01.CIR.0000088521.04017.13 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 717KN UT WOS:000185087800006 PM 12912804 ER PT J AU Jha, AK Varosy, PD Kanaya, AM Hunninghake, DB Hlatky, MA Waters, DD Furberg, CD Shlipak, MG AF Jha, AK Varosy, PD Kanaya, AM Hunninghake, DB Hlatky, MA Waters, DD Furberg, CD Shlipak, MG TI Differences in medical care and disease outcomes among black and white women with heart disease SO CIRCULATION LA English DT Article DE women; epidemiology; prevention ID ACUTE MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; RACIAL VARIATION; RISK-FACTORS; RACE; SEX; MORTALITY; MEN AB Background-The risk of cardiovascular mortality is higher among black women than white women, and the reasons for this disparity are largely unexplored. We sought to evaluate differences in medical care and clinical outcomes among black and white women with established coronary artery disease. Methods and Results-Among the 2699 women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS), we used Cox proportional hazards models to determine the association of race with risk of coronary heart disease (CHD) events independent of major cardiovascular risk factors or medical therapies. During an average of 4.1 years of follow-up, CHD events were twice as likely in black compared with white women (6.4 versus 3.1 per 100 person-years, hazard ratio, 2.1; 95% confidence interval, 1.5 to 2.8; P<0.001). Black women had higher rates of hypertension, diabetes, and hypercholesterolemia, yet were less likely to receive aspirin or statins. Black women less often had optimal blood pressure (56% versus 63%; P=0.01) and LDL cholesterol (30% versus 38%; P=0.04) control at baseline and during follow-up. After adjusting for these and other differences, black women still had >50% higher CHD event risk (hazard ratio, 1.52; 95% confidence interval, 1.1 to 2.1; P=0.03). Conclusions-In a large cohort of women with heart disease, black women less often received appropriate preventive therapy and adequate risk factor control despite a greater CHD event risk. Interventions to improve appropriate therapy and risk factor control in all women, and especially black women, are needed. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Div Gen Med, San Francisco, CA 94143 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Wake Forest Sch Med, Winston Salem, NC USA. RP Jha, AK (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 85 Z9 85 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 2 PY 2003 VL 108 IS 9 BP 1089 EP 1094 DI 10.1161/01.CIR.0000085994.38132.E5 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 717KN UT WOS:000185087800013 PM 12939228 ER PT J AU Brown, M AF Brown, M TI Role of coregulators in androgen receptor function. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 003-MEDI BP U1 EP U1 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JG UT WOS:000187062500004 ER PT J AU Bush, AI AF Bush, AI TI Medicinal metallochemistry of Alzheimer's disease. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NY SP Amer Chem Soc C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. EM bush@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 576-INOR BP U762 EP U762 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JF UT WOS:000187062403684 ER PT J AU Papisov, M Yurkovetskiy, A Yin, M Leone, P Fischman, AJ Hiller, A Sayed, S AF Papisov, M Yurkovetskiy, A Yin, M Leone, P Fischman, AJ Hiller, A Sayed, S TI Hydrophilic polyals: Biomimetic biodegradable stealth materials for pharmacology and bioengineering. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM papisov@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 126-PMSE BP U477 EP U477 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JG UT WOS:000187062502462 ER PT J AU Sethu, P Mastrangelo, CH AF Sethu, P Mastrangelo, CH TI Epoxy casting for microfluidic systems. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 Univ Michigan, Massachusetts Gen Hosp, Dept Biomed Engn, Cambridge, MA 02138 USA. Univ Michigan, Dept Elect Engn & Comp Sci, Ann Arbor, MI 48109 USA. EM spalania@sbi.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 188-POLY BP U383 EP U383 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 751JG UT WOS:000187062501956 ER PT J AU Wolfe, MS Das, C Berezovska, O Hyman, BT AF Wolfe, MS Das, C Berezovska, O Hyman, BT TI Designed helical peptides inhibit an intramembrane protease. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 226th National Meeting of the American-Chemical-Society CY SEP 07-11, 2003 CL NEW YORK, NEW YORK SP Amer Chem Soc C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Alzheimers Dis Res Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD SEP PY 2003 VL 226 MA 360-MEDI BP U67 EP U68 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 751JG UT WOS:000187062500358 ER PT J AU Bonner, LT AF Bonner, LT TI Merging academic medicine with community activism: An academic psychiatrist chronicles her day SO ACADEMIC PSYCHIATRY LA English DT Editorial Material C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Bonner, LT (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 2003 VL 27 IS 3 BP 209 EP 210 DI 10.1176/appi.ap.27.3.209 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 723ND UT WOS:000185437700026 PM 12969857 ER PT J AU Johnson, R Stockfleth, E AF Johnson, R Stockfleth, E TI Imiquimod 5% cream for the treatment of cutaneous lesions in immunocompromised patients SO ACTA DERMATO-VENEREOLOGICA LA English DT Article; Proceedings Paper CT 20th World Congress of Dermatology CY JUL 03-05, 2002 CL PARIS, FRANCE ID IMMUNE-RESPONSE MODIFIER; CARCINOMA IN-SITU; RENAL-TRANSPLANT RECIPIENTS; EXTERNAL ANOGENITAL WARTS; HIV-INFECTED PATIENTS; CELL-CARCINOMA; MOLLUSCUM CONTAGIOSUM; TOPICAL IMIQUIMOD; LANGERHANS CELLS; GENITAL WARTS C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Universitatshauklin Charite, DE-10117 Berlin, Germany. RP Johnson, R (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall, Boston, MA 02114 USA. NR 43 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PD SEP PY 2003 SU 214 BP 23 EP 27 DI 10.1080/03658340310011915 PG 5 WC Dermatology SC Dermatology GA 732WN UT WOS:000185968700006 PM 14606279 ER PT J AU Blais, MA Matthews, J Lipkis-Orlando, R Lechner, E Jacobo, M Lincoln, R Gulliver, C Herman, JB Goodman, AF AF Blais, MA Matthews, J Lipkis-Orlando, R Lechner, E Jacobo, M Lincoln, R Gulliver, C Herman, JB Goodman, AF TI Predicting length of stay on an acute care medical psychiatric inpatient service SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article DE admission variables; length of stay; LOS; management; prediction AB The goal of this study was to identify variables associated with length of stay (LOS) and to incorporate into the authors' routine preadmission assessment the measurement of these variables. A retrospective study of 80 discharged patients explored the association of 25 variables reflecting a mixture of patient/demographic variables, illness variables, and treatment variables with LOS. Multivariate analysis revealed that 10 variables independently accounted for 62% of the variance in LOS. The information used was obtained primarily in the preadmission screening. The predictive power of the variables shrank in the prospective study. However, fewer individual variables were significantly associated with LOS; the summed score of the variables predicted 17% of the LOS variance. Results indicated that factors important for estimating LOS are available at the time of admission, and these variables can be systematically assessed and incorporated into clinical decision making. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Blais, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 21 Z9 21 U1 0 U2 0 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 SEP PY 2003 VL 31 IS 1 BP 15 EP 29 DI 10.1023/A:1026044106172 PG 15 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 737BC UT WOS:000186207700002 PM 14650646 ER PT J AU Yochim, BP Bank, AL Mast, BT MacNeill, SE Lichtenberg, PA AF Yochim, BP Bank, AL Mast, BT MacNeill, SE Lichtenberg, PA TI Clinical utility of the mattis dementia rating scale in older, urban medical patients: An expanded study SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article ID NORMATIVE DATA; DEPRESSION; PERFORMANCE; ALZHEIMERS; VALIDATION; EDUCATION; VALIDITY AB This study investigated the clinical utility of the Mattis Dementia Rating Scale (DRS), using a sample of 138 cognitively intact and 151 cognitively impaired patients at an urban medical center. The 172 young-old patients (ages 60-79) and the 117 older-old patients (ages 80 and above) were predominantly African American elders who had completed significantly less education than had Mattis's normative samples. Results show that, despite lower mean scores in our sample versus Mattis's normative samples, the best cutoff score is nearly identical to Mattis's in the young-old patients, while a lower cut score provided optimal classification for the older-old patients. C1 Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA. Henry Ford Hlth Syst, Div Neuropsychol, Detroit, MI USA. RP Yochim, BP (reprint author), Wayne State Univ, Inst Gerontol, 87 E Ferry St, Detroit, MI 48202 USA. NR 26 TC 7 Z9 7 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1382-5585 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PD SEP PY 2003 VL 10 IS 3 BP 230 EP 237 DI 10.1076/anec.10.3.230.16448 PG 8 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 737KZ UT WOS:000186230700005 ER PT J AU Cavacini, LA Kuhrt, D Duval, M Mayer, K Posner, MR AF Cavacini, LA Kuhrt, D Duval, M Mayer, K Posner, MR TI Binding and neutralization activity of human IgG1 and IgG3 from serum of HIV-infected individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; GP120 ENVELOPE GLYCOPROTEIN; 1-INFECTED INDIVIDUALS; SEGMENTAL FLEXIBILITY; COMPLEMENT ACTIVATION; TYPE-1 INFECTION; IMMUNOGLOBULIN-G; ANTIGEN-BINDING; CHIMERIC HUMAN AB The IgG1 and IgG3 subclasses represent the predominant antibody response to viral infections, including HIV. IgG subclasses differ in their interaction with antigen and functional effects due to specific physiochemical features. With an elongated hinge, IgG3 antibodies tend to have more segmental flexibility, which can render the antibody more effective at interacting with antigen. We have previously shown that the change of the human anti-CD4-binding site monoclonal antibody F105 from IgG1 to IgG3 results in neutralization of a T cell line-adapted isolate (TCLA) resistant to neutralization by the parental IgG1. In the studies presented here, we have purified IgG1 and IgG3 subclasses from the sera of HIV-infected individuals and tested for immunoreactivity with and neutralization of HIV. Purified total IgG3 tended to have less relative reactivity and mediated relatively poorer neutralization of either laboratory or primary isolates. IgG3 also tended to react relatively less well with gp160 and gp120 and more robustly with gp41 and p24. The contrasting results with serum, as opposed to F105, may result from the polyclonal nature of serum antibodies. There is also a failure to make a robust IgG3 response to neutralizing epitopes on envelope glycoproteins during natural infection. These studies suggest that the investigation of isotype effects on neutralization will require isotype-switched human monoclonal antibodies. Understanding isotype and neutralization will provide important data necessary for designing the most effective possible vaccines. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02215 USA. Fenway Community Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Cavacini, LA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, 330 Brookline Ave,BURL 556, Boston, MA 02215 USA. FU NIAID NIH HHS [AI26926] NR 65 TC 14 Z9 19 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2003 VL 19 IS 9 BP 785 EP 792 DI 10.1089/088922203769232584 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 727TF UT WOS:000185675200008 PM 14585209 ER PT J AU Joffe, S AF Joffe, S TI Rethink "affirmative agreement, if but abandon "assent"" SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID INFORMED CONSENT; CHILDREN; ADOLESCENTS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 8 TC 21 Z9 21 U1 1 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD FAL PY 2003 VL 3 IS 4 BP 9 EP 11 DI 10.1162/152651603322614409 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 816QA UT WOS:000221123200004 PM 14744308 ER PT J AU Gibson, CM Gibson, WJ Murphy, SA Marble, SJ McCabe, CH Turakhia, MP Kirtane, AJ Karha, J Aroesty, JM Giugliano, RP Antman, EM AF Gibson, CM Gibson, WJ Murphy, SA Marble, SJ McCabe, CH Turakhia, MP Kirtane, AJ Karha, J Aroesty, JM Giugliano, RP Antman, EM CA TIMI Study Grp TI Association of the Fibonacci Cascade with the distribution of coronary artery lesions responsible for ST-segment elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PHYLLOTAXIS; THROMBOLYSIS; ABCIXIMAB; THERAPY; TRIAL AB This is the first study to demonstrate the appearance of the Fibonacci Cascade within the distribution of coronary artery lesions in the human heart. The propensity for this ratio to appear in nature may also be because this ratio optimizes the efficiency of packing structures in a limited space in such a way that wasted space is minimized and the supply of energy or nutrients is optimized. (C) 2003 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Dept Med, TIMI Study Chairmans Off, Boston, MA 02115 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 14 TC 12 Z9 12 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 SEP 1 PY 2003 VL 92 IS 5 BP 595 EP 597 DI 10.1016/S0002-9149(03)00731-8 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 716ZP UT WOS:000185060700020 PM 12943884 ER PT J AU Grossman, SA Brown, DFM Chang, Y Chung, WG Cranmer, H Dan, L Fisher, J Tedrow, U Lewandrowski, K Jang, IK Nagurney, JT AF Grossman, SA Brown, DFM Chang, Y Chung, WG Cranmer, H Dan, L Fisher, J Tedrow, U Lewandrowski, K Jang, IK Nagurney, JT TI Predictors of delay in presentation to the ED in patients with suspected acute coronary syndromes SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 23-25, 2000 CL SAN FRANCISCO, CALIFORNIA SP Soc Acad Emergency Med DE predictors; delay; emergency; coronary; chest pain ID ACUTE MYOCARDIAL-INFARCTION; CHEST-PAIN; HEART-DISEASE; PREHOSPITAL DELAY; THROMBOLYTIC THERAPY; SYMPTOM ONSET; MEDICAL-CARE; MORTALITY; TIMES; EMERGENCY AB Delays in seeking medical attention for patients with acute coronary syndromes (ACS) preclude early application of life-saving treatment and diminish efficacy. Previous studies suggest 3-hour delays between onset of symptoms and ED arrival in patients with typical presentations of acute myocardial infarction (AMI). A prospective observational study was conducted in an urban ED measuring lag time (LT) among adults presenting within 48 hours of onset of symptoms suggestive of ACS. Univariate and multiple regression analyses were performed on 5 predictors: age, sex, symptoms at presentation, and 2 different outcomes (AMI and ACS). Three hundred seventy-four patients were enrolled. Mean age was 63 years with 38% 70 years or older. Seventy-three percent of all patients with suspected ACS presented with chest pain, 27% with atypical symptoms. Overall mean LT was 8.7 hours (standard deviation 11). In subgroup analysis, patients aged greater than or equal to70 years were more likely to have LTs > 12 hours (29% vs. 19% P = .043) and patients without chest pain had longer mean LTs (11.6 vs. 7.6 hours, P = .01). Delay in ED presentation is group specific. Advanced age and patients with atypical symptoms are predictive of longer LTs. Contrary to previously published data, patients with symptoms suspicious for ACS can delay an average of 9 hours, which might alter current thinking in the prevention and care of these patients. ((C) 2003 Elsevier Inc. All rights reserved.) C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiol, Boston, MA USA. RP Grossman, SA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Emergency Med, 1 Deaconess Rd,WCC2, Boston, MA 02215 USA. NR 28 TC 26 Z9 26 U1 0 U2 1 PU W B SAUNDERS CO 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 SEP PY 2003 VL 21 IS 5 BP 425 EP 428 DI 10.1016/S0735-6757(03)000106-2 PG 4 WC Emergency Medicine SC Emergency Medicine GA 729LW UT WOS:000185775900003 PM 14523883 ER PT J AU Kearney, DJ Liu, CF Crump, C Brousal, A AF Kearney, DJ Liu, CF Crump, C Brousal, A TI The effect of a Helicobacter pylori treatment strategy on health care expenditures in patients with peptic ulcer disease and dyspepsia SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; DUODENAL-ULCER; DOUBLE-BLIND; FOLLOW-UP; MAINTENANCE ORGANIZATION; CAMPYLOBACTER-PYLORI; NONULCER DYSPEPSIA; GENERAL-PRACTICE AB OBJECTIVE: The aim of this study was to determine whether treatment for Helicobacter pylori (H. pylori) for patients with dyspepsia or a history of peptic ulcer decreases hospital expenditures. METHODS: Patients receiving acid suppressive medications were interviewed. Those with a documented ulcer, a self-reported ulcer, or dyspepsia were tested for H. pylori and treated with antibiotics if seropositive. Acid suppressive medications were stopped on completion of H. pylori therapy unless there was a history of gastroesophageal reflux disease (GERD) or Barrett's esophagus, and were started again at the discretion of primary care providers. Total hospital costs and GI medication costs in the 12 months before H. pylori treatment were compared to costs 12 months after H. pylori treatment. RESULTS: A total of 432 consecutive patients were treated for H. pylori. Of the patients, 125 (29%) had dyspepsia, 45 (10%) documented peptic ulcer, and 262 (61%) self-reported peptic ulcer. Total costs (mean $327 +/- 349 vs $291 +/- 362, p = 0.06) and medication costs (mean $207 +/- 237 vs $224 +/- 277, p = 0.38) were not significantly different after treatment versus before treatment. A significant decrease in expenditures was limited to patients chronically on acid suppressive medications who had documented peptic ulcers and no history of GERD or Barrett's esophagus (mean $482 +/- 274 vs $282 +/- 218, p = 0.03). CONCLUSIONS: Treatment of H. pylori for patients with chronic dyspepsia or self-reported peptic ulcer does not reduce expenditures over 1 yr of follow up. H. pylori treatment for patients chronically receiving acid suppressive treatment with a prior documented ulcer significantly reduces expenditures if GERD and Barrett's esophagus are absent. (C) 2003 by Am. Coll. of Gastroenterology. C1 VA Puget Sound Health Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Serv Pharm, Seattle, WA USA. RP Kearney, DJ (reprint author), VAMC, 111G1,1660 S Columbian Way, Seattle, WA 98108 USA. NR 40 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2003 VL 98 IS 9 BP 1952 EP 1962 DI 10.1016/S0002-9270(03)00433-7 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 726CR UT WOS:000185581000009 PM 14499771 ER PT J AU Ioannou, GN Chapko, MK Dominitz, JA AF Ioannou, GN Chapko, MK Dominitz, JA TI Predictors of colorectal cancer screening participation in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FECAL OCCULT-BLOOD; SERVICES TASK-FORCE; COST-EFFECTIVENESS; ASYMPTOMATIC ADULTS; SOCIETY GUIDELINES; PROSTATE-CANCER; AVERAGE-RISK; SURVEILLANCE; MORTALITY; CARE AB OBJECTIVE: Our aim was to identify predictors of colorectal cancer screening in the United States and subgroups with particularly low rates of screening. METHODS: The responses to a telephone-administered questionnaire of a nationally representative sample of 61,068 persons aged greater than or equal to50 yr were analyzed. Current screening was defined as either sigmoidoscopy/colonoscopy in the preceding 5 years or fecal occult blood testing (FOBT) in the preceding year, or both. RESULTS: Overall, current colorectal cancer screening was reported by 43.4% (sigmoidoscopy/colonoscopy by 22.8%, FOBT by 9.9%, and both by 10.7%). The lowest rates of screening were reported by the following subgroups: those aged 50-54 yr (31.2%), Hispanics (31.2%), Asian/Pacific Islanders (34.8%), those with education less than the ninth grade (34.4%), no health care coverage (20.4%), or coverage by Medicaid (29.2%), those who had no routine doctor's visit in the last year (20.3%), and every-day smokers (32.1%). The most important modifiable predictors of current colorectal cancer screening were health care coverage (OR = 1.7, 95% Cl = 1.5-1.9) and a routine doctor's visit in the last year (OR = 3.5, 95% Cl = 3.2-3.8). FOBT was more common in women than in men (OR = 1.8, 95% Cl = 1.6-2.0); sigmoidoscopy/colonoscopy was more common in Hispanics (OR = 1.4, 95% CI 1.1-1.7) and Asian/Pacific Islanders (OR = 2.4, 95% Cl 1.5-3.9) relative to whites, in persons without routine doctor's visits in the preceding year (OR = 3.3, 95% CI = 2.8-4), and in persons with poor self-reported health (OR = 1.3, 95% CI = 1.2-1.5). CONCLUSIONS: Interventions should be developed to improve screening for the subgroups who reported the lowest screening rates. Such interventions may incorporate individual screening strategy preferences. (C) 2003 by Am. Coll. of Gastroenterology. C1 Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA 98108 USA. Univ Washington, Div Gastroenterol, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, MS 152,Room 422,1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 49 TC 177 Z9 178 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2003 VL 98 IS 9 BP 2082 EP 2091 DI 10.1016/S0002-9270(03)00423-4 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 726CR UT WOS:000185581000030 PM 14499792 ER PT J AU Li, JL Hayden, MR Almqvist, EW Brinkman, RR Durr, A Dode, C Morrison, PJ Suchowersky, O Ross, CA Margolis, RL Rosenblatt, A Gomez-Tortosa, E Cabrero, DM Novelletto, A Frontali, M Nance, M Trent, RJA McCusker, E Jones, R Paulsen, JS Harrison, M Zanko, A Abramson, RK Russ, AL Knowlton, B Djousse, L Mysore, JS Tariot, S Gusella, MF Wheeler, VC Atwood, LD Cupples, LA Saint-Hilaire, M Cha, JHJ Hersch, SM Koroshetz, WJ Gusella, JF MacDonald, ME Myers, RH AF Li, JL Hayden, MR Almqvist, EW Brinkman, RR Durr, A Dode, C Morrison, PJ Suchowersky, O Ross, CA Margolis, RL Rosenblatt, A Gomez-Tortosa, E Cabrero, DM Novelletto, A Frontali, M Nance, M Trent, RJA McCusker, E Jones, R Paulsen, JS Harrison, M Zanko, A Abramson, RK Russ, AL Knowlton, B Djousse, L Mysore, JS Tariot, S Gusella, MF Wheeler, VC Atwood, LD Cupples, LA Saint-Hilaire, M Cha, JHJ Hersch, SM Koroshetz, WJ Gusella, JF MacDonald, ME Myers, RH TI A genome scan for modifiers of age at onset in Huntington disease: The HD MAPS study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRINUCLEOTIDE REPEAT; LINKAGE ANALYSIS; OF-ONSET; GENE; INSTABILITY; NUCLEUS; LENGTH AB Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h(2) = 0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs ( 295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD = 1.93), 6p21 - 23 (LOD = 2.29), and 6q24 - 26(LOD = 2.28),which may be useful for investigation of genes that modify age at onset of HD. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Bioinformat Program, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Wyeth Res, Dept Genom, Cambridge, MA USA. Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. Hop Cochin, Serv Biochim & Genet Mol, F-75674 Paris, France. Belfast City Hosp, Dept Med Genet, Belfast BT9 7AD, Antrim, North Ireland. Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. Johns Hopkins Univ, Program Cellular & Mol Med, Baltimore, MD USA. Fdn Jimenez Diaz, Serv Neurol & Genet, E-28040 Madrid, Spain. Univ Calabria, Dept Cell Biol, I-87036 Arcavacata Di Rende, Italy. CNR, Inst Neurobiol & Mol Med, Rome, Italy. Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Westmead Hosp, Dept Neurol, Sydney, NSW, Australia. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Univ Calif San Francisco, Div Med Genet, San Francisco, CA 94143 USA. William S Hall Psychiat Inst, Columbia, SC USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,E-304, Boston, MA 02118 USA. RI Ross, Christopher/H-8395-2013; Brinkman, Ryan/B-1108-2008; Hayden, Michael/D-8581-2011; Djousse, Luc/F-5033-2017; OI Brinkman, Ryan/0000-0002-9765-2990; Hayden, Michael/0000-0001-5159-1419; Djousse, Luc/0000-0002-9902-3047; Li, Jian-Liang/0000-0002-6487-081X; Novelletto, Andrea/0000-0002-1146-7680 FU NINDS NIH HHS [P50 NS016367, P50NS016367] NR 21 TC 86 Z9 90 U1 0 U2 4 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 SEP PY 2003 VL 73 IS 3 BP 682 EP 687 DI 10.1086/378133 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 718FG UT WOS:000185134000023 PM 12900792 ER PT J AU Basile, AN AF Basile, AN TI Optimizing antihypertensive treatment in clinical practice SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT 18th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 14-17, 2003 CL NEW YORK, NY SP Amer Soc Hypertens DE hypertension; diabetes; ischemic heart disease; antihypertensive therapy; beta-blockers ID HIGH BLOOD-PRESSURE; ACUTE MYOCARDIAL-INFARCTION; CHRONIC HEART-FAILURE; RANDOMIZED-TRIAL; HYPERTENSIVE PATIENTS; PRIMARY PREVENTION; METOPROLOL; MORTALITY; MAPHY; PREVALENCE AB Hypertension affects approximately 50 million individuals in the United States (US) and approximately I billion individuals worldwide. Blood pressure (BP) reduction significantly lowers the risk of cardiovascular (CV) disease the most common cause of death in the US-yet only approximately one third of Americans with hypertension have their disease controlled to the minimum recommended level of <140/90 mm. Hg. Clinical trials such as the Hypertension Optimal Treatment (HOT) study, and Treatment of Mild Hypertension Study (TOMHS) have shown that control of BP to targets of less than or equal to140/90 mm Hg reduces the likelihood of CV disease and improves quality of life. This appears to be true even in patients at high risk, such as those with diabetes. Furthermore, it has become increasingly recognized that multiple BP-lowering agents are usually necessary to achieve BP control (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease). In fact, current hypertension guidelines clearly state that most hypertensive patients will require two or more agents, and recommend initiating treatment with two antihypertensive medications if the BP is >20/10 mm Hg above goal BP. A valuable class of drug in the management of hypertension, beta-blockers (betaB) play an important role-whether as initial agents or as add-on therapy. They are especially useful in hypertensive patients with certain comorbidities such as diabetes or heart failure, in patients post-myocardial infarction, or in those generally at high risk for coronary disease. This article explores the cardioprotective role of how OB may be used to optimize antihypertensive treatment. (C) 2003 American Journal of Hypertension, Ltd. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Div Gen Internal Med Geriatr, Charleston, SC 29401 USA. RP Basile, AN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Dept Med, Div Gen Internal Med Geriatr, 109 Bee St, Charleston, SC 29401 USA. EM Jan.Basile@med.va.gov NR 25 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD SEP PY 2003 VL 16 IS 9 SU S BP 13S EP 17S DI 10.1016/S0895-7061(03)00967-1 PN 2 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 726MN UT WOS:000185603000004 ER PT J AU Kusano, Y Endo, S Mukai, S Yamaguchi, T AF Kusano, Y Endo, S Mukai, S Yamaguchi, T TI Retinopathy after percutaneous transluminal coronary angioplasty and stent insertion for acute myocardial infarction SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report microvascular retinopathy after per, cutaneous transluminal coronary angioplasty and stent insertion for acute myocardial infarction. DESIGN: Observational case series. METHODS: Retrospective review of seven patients with a retinal microangiopathy following coronary catheterization, angioplasty, and stent placement. RESULTS: All patients had bilateral cotton-wool spots in peripapillary distribution; four also had retinal hemorrhages in both eyes. None complained of visual symptoms. Lesions resolved spontaneously within several months in six patients. CONCLUSION: Although angioplasty and stent placement are less invasive than cardiac surgery, they appear to cause a retinopathy similar to postpump retinopathy. (C) 2003 by Elsevier Inc. All rights reserved. C1 St Lukes Int Hosp, Dept Ophthalmol, Chuo Ku, Tokyo 1040044, Japan. Ishida Eye Hosp, Joetsu, Japan. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kusano, Y (reprint author), St Lukes Int Hosp, Dept Ophthalmol, Chuo Ku, 9-1 Akashi Cho, Tokyo 1040044, Japan. NR 5 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2003 VL 136 IS 3 BP 557 EP 560 DI 10.1016/S0002-9394(03)00267-8 PG 4 WC Ophthalmology SC Ophthalmology GA 714XT UT WOS:000184940100029 PM 12967820 ER PT J AU Broberg, CS Giraud, GD Schultz, JM Thornburg, KL Hohimer, AR Davis, LE AF Broberg, CS Giraud, GD Schultz, JM Thornburg, KL Hohimer, AR Davis, LE TI Fetal anemia leads to augmented contractile response to hypoxic stress in adulthood SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE phlebotomy; end-systolic elastance ID PRESSURE-OVERLOAD HYPERTROPHY; CANINE LEFT-VENTRICLE; CARDIOVASCULAR-DISEASE; SHEEP; FLOW; DYSFUNCTION; RESERVE; GROWTH; RATIO; LIFE AB In response to chronic fetal anemia, coronary blood flow, maximal coronary conductance, and coronary reserve increase. We sought to determine whether chronic fetal anemia alters left ventricular (LV) function in adulthood. We studied adult sheep that had been made anemic for 20 days in utero by phlebotomy. They were transfused just before birth. At 7 mo of age, LV function was measured by pressure-volume loops at rest and during hypoxic stress. The in utero anemia group (n = 8) did not differ from controls (n = 5) with respect to hematocrit, heart and body weight, or baseline hemodynamic parameters. However, the effect of hypoxia ( relative to baseline) on multiple indexes of systolic function was different between the two groups. End-systolic elastance increased in the in utero anemia group ( baseline to hypoxia) by 4.15 +/- 3.47 mmHg/ml (mean +/- SD) but changed little in controls (0.24 +/- 0.45), which shows that the response to hypoxia was significantly different (P < 0.01) between groups. Similarly, the maximum derivative of LV pressure with respect to time increased in the in utero anemia group (486 &PLUSMN; 340 mmHg/s,) but on average fell in the controls (-503 &PLUSMN; 211 mmHg/s) with the response again being significantly different ( P < 0.03). We conclude that in sheep, perinatal anemia can alter cardiac responses to hypoxic stress in the adult long after restoration of normocythemia. C1 Oregon Hlth Sci Univ, Dept Med, Div Cardiol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Cardiol, Portland, OR 97201 USA. RP Davis, LE (reprint author), Div Maternal Fetal Med, Med Res Bldg,L-458,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Thornburg, Kent/0000-0002-5561-4785 FU NICHD NIH HHS [P02 HD-34430]; PHS HHS [LH-45043] NR 23 TC 22 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 2003 VL 285 IS 3 BP R649 EP R655 DI 10.1152/ajpregu.00656.2002 PG 7 WC Physiology SC Physiology GA 710KV UT WOS:000184680100022 PM 12775557 ER PT J AU Hazlett, EA Levine, J Buchsbaum, MS Silverman, JM New, A Sevin, EM Maldari, LA Siever, LJ AF Hazlett, EA Levine, J Buchsbaum, MS Silverman, JM New, A Sevin, EM Maldari, LA Siever, LJ TI Deficient attentional modulation of the startle response in patients with schizotypal personality disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID EYEBLINK MODIFICATION; SCHIZOPHRENIA; REFLEX; SYMPTOMS AB Objective: Attentional deficits have been identified as an abnormality that individuals with schizotypal personality disorder share with schizophrenia patients. The purpose of this study was to examine automatic sensorimotor gating and controlled attentional modulation of the startle eye blink response in unmedicated subjects with schizotypal personality disorder. Method: Eighteen unmedicated patients with schizotypal personality disorder and 16 healthy individuals were assessed in an acoustic attention-to-prepulse paradigm. The participants performed a selective attention task involving the presentation of attended, ignored, and novel tones that served as prepulse tones. Acoustic startle probes were presented at short and long lead intervals after the onset of tones and occasionally during the intertone interval. Results: The comparison subjects showed greater prepulse inhibition and prepulse facilitation during the attended than the ignored prepulses, demonstrating early and later attentional modulation of startle eye blink response. In contrast, the subjects with schizotypal personality disorder failed to show this pattern. Conclusions: Subjects with schizotypal personality disorder have deficits in controlled attentional processing, as indexed by modification of the startle eye blink response, that are similar to those observed in patients with schizophrenia. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. FU NCRR NIH HHS [RR 0071]; NIMH NIH HHS [MH 58673] NR 23 TC 20 Z9 21 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, 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 SEP PY 2003 VL 160 IS 9 BP 1621 EP 1626 DI 10.1176/appi.ajp.160.9.1621 PG 6 WC Psychiatry SC Psychiatry GA 718PV UT WOS:000185156400012 PM 12944337 ER PT J AU Murphy, JM Horton, NJ Monson, RR Laird, NM Sobol, AM Leighton, AH AF Murphy, JM Horton, NJ Monson, RR Laird, NM Sobol, AM Leighton, AH TI Cigarette smoking in relation to depression: Historical trends from the Stirling County Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GENERAL-POPULATION; MAJOR DEPRESSION; UNITED-STATES; NATURAL-HISTORY; SUBSTANCE USE; DRUG-USE; PREVALENCE; DISORDERS; ANXIETY; HEALTH AB Objective: Building on findings about the prevalence and incidence of depression over a 40-year period, the authors provide data on trends in cigarette smoking and associations with depression. Method: Data come from interviews with adult population samples (1952, 1970, and 1992) and followed cohorts (1952-1970 and 1970-1992). Logistic regression models and survival regressions were used to analyze the data. Results: The associations between smoking and depression were small and non-significant in 1952 and 1970. In 1992, however, the odds that a smoker would be depressed were three times the odds that a nonsmoker would be depressed. The interaction between smoking and study year was significant, indicating that the association was limited to the most recent sample. in the cohort analysis, smoking at baseline did not predict the onset of depression, but subjects who became depressed were more likely to start or continue smoking and less likely to quit than those who never had a depression. Conclusions: In terms of population trends, the association between depression and cigarette smoking became prominent as the use of tobacco declined because of awareness of the risks involved. The findings about individuals followed over time suggest that those who became depressed were more involved with nicotine than those who never had a depression. The authors discuss hypotheses involving "self-medication," risk-taking, and changes in the social climate but conclude that the relationships between smoking and depression are probably multiple and complex. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Smith Coll, Dept Math, Northampton, MA 01063 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Murphy, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Rm 10028,149 13th St, Charlestown, MA 02129 USA. RI Horton, Nicholas/A-2493-2008; Reis, Aline/G-9573-2012; OI Horton, Nicholas/0000-0003-3332-4311 FU NIMH NIH HHS [MH 39576] NR 40 TC 120 Z9 124 U1 2 U2 6 PU AMER PSYCHIATRIC PRESS, 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 SEP PY 2003 VL 160 IS 9 BP 1663 EP 1669 DI 10.1176/appi.ajp.160.9.1663 PG 7 WC Psychiatry SC Psychiatry GA 718PV UT WOS:000185156400018 PM 12944343 ER PT J AU Wicky, S Fan, CM Geller, SC Greenfield, A Santilli, J Waltman, AC AF Wicky, S Fan, CM Geller, SC Greenfield, A Santilli, J Waltman, AC TI MR angiography of endoleak with inconclusive concomitant CT angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ENDOVASCULAR ANEURYSM REPAIR; ABDOMINAL AORTIC-ANEURYSM; ENDOTENSION; MANAGEMENT; DIAGNOSIS; GROWTH C1 Massachusetts Gen Hosp, CIMIT Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wicky, S (reprint author), Massachusetts Gen Hosp, CIMIT Div, Ste 400,100 Charles River Plaza, Boston, MA 02114 USA. NR 8 TC 16 Z9 16 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2003 VL 181 IS 3 BP 736 EP 738 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 713MH UT WOS:000184861600034 PM 12933471 ER PT J AU Harisinghani, MG Wittenberg, J Lee, W Chen, S Gutierrez, AL Mueller, PR AF Harisinghani, MG Wittenberg, J Lee, W Chen, S Gutierrez, AL Mueller, PR TI Bowel wall fat halo sign in patients without intestinal disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CT; DIAGNOSIS; COLITIS AB OBJECTIVE. Stratification with a fat layer in the intestinal wall is thought to be a reliable marker for inflammatory bowel disease. We evaluated the presence and frequency of the bowel wall fat halo sign in patients undergoing abdominal CT for clinical indications unrelated to the gastrointestinal tract. MATERIALS AND METHODS. We performed a retrospective review of 100 consecutive abdominal and pelvic CT examinations in 61 men and 39 women (mean age, 56 years). with clinical suspicion of renal stone disease. Two radiologists experienced in abdominal imaging performed qualitative and quantifiable assessment of the images. Five segments of the colon (ascending colon, transverse colon, descending colon, sigmoid colon, and rectum) and the terminal ileum (for approximate to I It [30 cm]) were evaluated for the presence of the fat halo sign. If the fat halo sign was present, fat density and total wall-thickness assessments were made. Presence or absence of clinical and radiologic signs of inflammatory bowel disease was determined. The Student's t test was used to evaluate the statistical significance, correlating body weight and presence of the halo sign. RESULTS. The fat halo sign was seen in 21 (21%) of 100 patients. Of the 21 patients with the fat halo sign, six (29%) had renal stone disease and 15 (71%) had no stone disease. The density value of the halo sign ranged from -18 to -64 H (mean, -41 H). The distribution of the fat halo sign was as follows: the terminal ileum, 4%; the ascending colon, 28%; the transverse colon, 34%; the descending colon, 36%; the sigmoid colon, 14%; and rectum, 10%. No patient with this sign had any remote, recent, or subsequently recorded history of inflammatory bowel disease. A statistically significant relationship (p < 0.001) was seen between the presence of the fat halo sign and body weight distribution, with 16 of 21 patients weighing over 200 lb (90 kg). CONCLUSION. In the absence of clinical or radiologic evidence of inflammatory bowel disease, the presence of the fat halo sign may represent a normal finding that is possibly related to obesity. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 23 Z9 24 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2003 VL 181 IS 3 BP 781 EP 784 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 713MH UT WOS:000184861600044 PM 12933481 ER PT J AU Singh, AK Shirkhoda, A Lal, N Sagar, P AF Singh, AK Shirkhoda, A Lal, N Sagar, P TI Bouveret's syndrome: Appearance on CT and upper gastrointestinal radiography before and after stone obturation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GALLSTONE ILEUS C1 William Beaumont Hosp, Dept Diagnost Radiol, Royal Oak, MI 48073 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 10 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2003 VL 181 IS 3 BP 828 EP 830 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 713MH UT WOS:000184861600051 PM 12933489 ER PT J AU Ulbright, TM Young, RH AF Ulbright, TM Young, RH TI Primary mucinous tumors of the testis and paratestis - A report of nine cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testicular neoplasms; paratesticular neoplasms; mucinous cystadenoma; mucinous borderline tumor; mucinous carcinoma ID PRIMARY PURE TERATOMA; IMMUNOHISTOCHEMICAL ANALYSIS; TESTICULAR TERATOMA; OVARIAN METASTASES; CARCINOMA; NEOPLASMS; CYSTADENOCARCINOMA; APPENDIX; ADENOCARCINOMAS; DIFFERENTIATION AB Ovarian-type surface epithelial tumors are rare in the testis and paratestis, with most reported examples being serous. There is little information on mucinous tumors, nine of which are described in this report, applying criteria and terminology used in the ovary. The patients were 44-69 years of age (median 64 years) and presented with masses in the testis (four) or paratestis (five). Eight tumors were cystic (median size, 3.5 cm) and contained gelatinous material; one (a paratesticular carcinoma) appeared as thickening of the tunica vaginalis. Two were classified as mucinous cystadenomas (both paratesticular), six as purely or predominantly borderline tumors (four, testis; two, paratestis; one had intraepithelial carcinoma and one microinvasive carcinoma) and one (paratestis) as mucinous carcinoma. The cystadenomas were composed of endocervical-like cells, but intestinal-like cells typified the borderline tumors and carcinomas. Cyst rupture with mucin dissection into the stroma, inflammation, and dystrophic calcification with ossification were common. No tumor was associated with intratubular germ cell neoplasia, unclassified type or with teratomatous elements. One patient with carcinoma died shortly after presentation with peritoneal spread; autopsy disclosed no other potential primary site. The follow-up (1.8-12 years) in all other cases was uneventful. Mucinous tumors of the testis and paratestis resemble their ovarian counterparts, exhibiting the same morphologic spectrum, from benign to borderline to malignant, and having both endocervical-like and intestinal features. These tumors may derive from mesothelium by the process of mullerian neometaplasia, from mullerian remnants or from the mucinous epithelium of a teratoma. The older age of the patients, lack of nonmucinous elements, and absence of intratubular germ cell neoplasia, unclassified type suggest that, if of teratomatous origin, the teratoma is different from the usual type. Clinical features are important to exclude metastasis, particularly in cases of carcinoma and, to a lesser extent, in tumors of borderline type. C1 Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Ulbright, TM (reprint author), Indiana Univ Hosp, Dept Pathol, 550 N Univ Blvd,Room 3465, Indianapolis, IN 46202 USA. NR 33 TC 32 Z9 33 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 SEP PY 2003 VL 27 IS 9 BP 1221 EP 1228 DI 10.1097/00000478-200309000-00005 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 716AC UT WOS:000185005800005 PM 12960806 ER PT J AU Mino, M Lauwers, GY AF Mino, M Lauwers, GY TI Role of lymphocytic immunophenotyping in the diagnosis of gluten-sensitive enteropathy with preserved villous architecture SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE CD3; CD8; gluten-sensitive enteropathy; immunophenotype; intraepithelial lymphocytes ID CELIAC-DISEASE; INTRAEPITHELIAL LYMPHOCYTES; ENDOMYSIUM ANTIBODIES; NATURAL-HISTORY; SMALL-INTESTINE; EPITHELIUM; DISORDERS; SPECTRUM; SPRUE; LESION AB Clinically significant gluten-sensitive enteropathy (GSE) can be associated with architecturally normal small bowel villi and evenly distributed increased intraepithelial T lymphocytes (IELs). This distribution pattern of IELs has been shown to be a sensitive feature of GSE but to be of relatively low specificity, thus limiting its usage as a diagnostic marker. We demonstrate herein the potential diagnostic role of IEL immunophenotyping. We show that a top-heavy distribution pattern of CD3+ IELs is a sensitive diagnostic feature of GSE. Despite overlap between GSE and non-GSE patients, the difference is underscored when using a tip-to-base ratio. Of the GSE patients, 87.5% showed a tip-to-base ratio >1.7 compared with only 12.5% of non-GSE patients and none in controls. This pattern was retained in 50% of treated GSE patients, although the CD3+ tip-IEL scores were significantly smaller. Conversely, CD8 immunostaining appears of limited diagnostic value. The discrepancy in distribution of CD3+ and CD8+ IELs between GSE and non-GSE patients can be explained by the presence of CD4- CD8- TCR-gammadelta+ IELs which, have been reported in GSE. Since the immunophenotyping of T-IELs is feasible with readily available antibodies, and given the clinical benefits for patients with 'latent' GSE, we advocate using CD3 immunostaining to triage patients with normal villi and increased IELs. C1 Massachusetts Gen Hosp, Dept Pathol WRN 2, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol WRN 2, 55 Fruit St, Boston, MA 02114 USA. NR 38 TC 44 Z9 46 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 SEP PY 2003 VL 27 IS 9 BP 1237 EP 1242 DI 10.1097/00000478-200309000-00007 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 716AC UT WOS:000185005800007 PM 12960808 ER PT J AU de Leval, L Braaten, KM Ancukiewicz, M Kiggundu, E Delaney, T Mankin, HJ Harris, NL AF de Leval, L Braaten, KM Ancukiewicz, M Kiggundu, E Delaney, T Mankin, HJ Harris, NL TI Diffuse large B-cell lymphoma of bone - An analysis of differentiation-associated antigens with clinical correlation SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE diffuse large B-cell lymphoma; bone; germinal center; immunohistochemistry; bcl-6; CD10; CD44; VS38c; CD138; molecular genetics; bcl-2; survival ID NON-HODGKINS-LYMPHOMA; BCL-2 PROTEIN EXPRESSION; MONOCLONAL-ANTIBODY; PROGNOSTIC-SIGNIFICANCE; FOLLICULAR LYMPHOMA; MALIGNANT-LYMPHOMA; GENE REARRANGEMENT; DETECTS EXPRESSION; SOMATIC MUTATION; HUMAN TONSIL AB Twenty-nine patients with diffuse large B-cell lymphomas presenting with bone involvement, including 18 localized primary bone lymphomas (group 1), 2 multifocal primary bone lymphomas (group 2), and 9 patients with extraskeletal disease at diagnosis (group 3), were studied. The tumors were subclassified according to the criteria of the WHO classification and evaluated by immunohistochemistry for expression of antigens associated with germinal center (GC) and non-GC stages of B-cell differentiation (bcl-6, CD10, MUM-1, VS38c, CD138, bcl-2, and CD44). The presence of a BCL2/IgH gene rearrangement was investigated by polymerase chain reaction. All cases were characterized by similar clinicopathologic and morphologic features and had similarly good overall outcome. The patients (23 males, 6 females, median age 44 years) had tumors in long bones (14), axial skeleton (8), limb girdles (3), and multiple sites (4). Most tumors (24) were centroblastic, with multilobated cells in 12 cases. Almost half of the tumors (14 of 29, 48%) were bcl-6+CD10+ (GC-like), 9 of 29 cases (31%) were bcl-6+CD10- (indeterminate phenotype), and 6 of 29 cases (21%) were CD10-bcl-6- (post-GC like). The indeterminate phenotype was seen only in primary bone lymphoma. MUM-1 was frequently expressed in GC-like and non-GC-like categories. We found no evidence of plasmacytic differentiation by CD138, and VS38c immunoreactivity was distinctly rare (2 of 29 cases). CD44 was detected in 6 tumors, all CD10-. Bcl-2 was expressed by 70% of the tumors, but only 1 of 23 cases tested had a Bcl-2/JH rearrangement by polymerase chain reaction. A survival analysis showed that GC-like tumors had a longer overall survival duration compared with non-GC-like tumors (P = 0.0046). In conclusion, a GC-like immunophenotype characterizes roughly half of large B-cell lymphomas of bone and is associated with an improved survival. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 55 TC 33 Z9 34 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 SEP PY 2003 VL 27 IS 9 BP 1269 EP 1277 DI 10.1097/00000478-200309000-00011 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 716AC UT WOS:000185005800011 PM 12960812 ER PT J AU Mueller, NJ Sulling, K Gollackner, B Yamamoto, S Knosalla, C Wilkinson, RA Kaur, A Sachs, DH Yamada, K Cooper, DKC Patience, C Fishman, JA AF Mueller, NJ Sulling, K Gollackner, B Yamamoto, S Knosalla, C Wilkinson, RA Kaur, A Sachs, DH Yamada, K Cooper, DKC Patience, C Fishman, JA TI Reduced efficacy of ganciclovir against porcine and baboon cytomegalovirus in pig-to-baboon xenotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE baboon; breeding; cidofovir; cytomegalovirus; foscarnet; ganciclovir; infection; leflunomide; pig; prophylaxis; resistance; transplantation; virus; xenotransplantation ID ORGAN-TRANSPLANT RECIPIENTS; IMMUNOSUPPRESSIVE AGENT LEFLUNOMIDE; MINIATURE SWINE; IN-VITRO; INFECTION; LYMPHOCYTES; INHIBITION; ACTIVATION; VIRUS; THERAPY AB In pig-to-baboon xenotransplantation, porcine cytomegalovirus (PCMV) causes viremia, consumptive coagulopathy, and tissue-invasive disease. Baboon cytomegalovirus (BCMV) is associated with invasive disease in xenograft recipients. The efficacy of prophylaxis with intravenous ganciclovir (GCV) was studied for prevention of PCMV and BCMV infections in pig-to baboon xenotransplantation. GCV prophylaxis did not alter the incidence of BCMV activation in recipients, but reduced the amount of virus in tissues (mean 8.38 x 10(2) vs. 3.24 x 10(5) copies/mug DNA without treatment) and prevented tissue-invasive infections. PCMV viral loads were unaltered by GCV prophylaxis (8.36 x 10(8) copies/mug DNA without prophylaxis vs. 1.20 x 10(9) copies/mug DNA with prophylaxis). In vitro, PCMV was relatively resistant to GCV [90% inhibitory concentration (IC90) of 10mum, IC50-3mum], acyclovir (100mum), and leflunomide (not achievable). Only cidofovir (IC90 1 mum) and foscarnet (IC90 100mum) might have therapeutic efficacy for PCMV in vivo in achievable concentrations, although these agents often carry significant toxicity in transplant recipients. GCV has limited activity against BCMV and no therapeutic efficacy against PCMV at standard doses in vivo. GCV and other antiviral agents have limited activities against PCMV in vitro. Breeding of PCMV-free xenograft donors may be necessary to prevent PCMV infections in clinical trials. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02114 USA. Immerge BioTherapeut Inc, Cambridge, MA USA. MGH, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. RP Fishman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02114 USA. RI Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 FU NIAID NIH HHS [5T32-AI07529-04, P01-AI45897, R01-AI43890] NR 32 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2003 VL 3 IS 9 BP 1057 EP 1064 DI 10.1034/j.1600-6143.2003.00192.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 719KU UT WOS:000185202900005 PM 12919084 ER PT J AU Mezrich, JD Kesselheim, JA Johnston, DR Yamada, K Sachs, DH Madsen, JC AF Mezrich, JD Kesselheim, JA Johnston, DR Yamada, K Sachs, DH Madsen, JC TI The role of regulatory cells in miniature swine rendered tolerant to cardiac allografts by donor kidney cotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE CD25; heart transplantation; regulatory cells; swine; tolerance ID MAJOR HISTOCOMPATIBILITY COMPLEX; RENAL-ALLOGRAFTS; T-CELLS; TRANSPLANTATION TOLERANCE; COMBINED HEART; VASCULOPATHY; INDUCTION; LYMPHOCYTES; PORCINE; LIVER AB To determine the mechanism by which cotransplantation of a kidney allograft induces tolerance to a donor heart in miniature swine, we examined the role of CD25(+) cells in heart/kidney recipients. Tolerance was induced to class-1 MHC mismatched hearts by cotransplanting a donor-specific kidney with a 12-day course of cyclosporine. Peripheral blood leukocytes (PBL) were isolated from tolerant heart/kidney recipients and used in cell-mediated lympholysis (CML) coculture assays as either unmodified PBL, PBL enriched for CD25(+) cells or PBL depleted of CD25(+) cells to assess their ability to suppress CML responses of naive recipient-matched leukocytes against mismatched target cells. Primed PBL from tolerant heart/kidney recipients completely suppressed lysis by naive cells. Complete suppression of the response of naive recipient-matched leukocytes against donor-matched target cells was lost following the depletion of CD25(+) cells from tolerant heart/kidney animal PBL, but it was reestablished by incubation of naive cells with small populations of CD25(+) cells from tolerant heart/kidney animals. These data suggest that peripheral blood from tolerant heart/kidney recipients contains regulatory cells that, upon priming, can suppress the response of naive-matched PBL in coculture CML assays, and that suppression appears to be dependent on cells expressing CD25. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplatat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Cardiac Surg, Boston, MA USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplatat Biol Res Ctr, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01 HL18646, R01 HL54211]; NIAID NIH HHS [P01 AI50157] NR 26 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2003 VL 3 IS 9 BP 1107 EP 1115 DI 10.1046/j.1600-6143.2003.00202.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 719KU UT WOS:000185202900011 PM 12919090 ER PT J AU Swanton, BJ Keane, D Vlahakes, GJ Streckenbach, SC AF Swanton, BJ Keane, D Vlahakes, GJ Streckenbach, SC TI Intraoperative transesophageal echocardiography in the early detection of acute tamponade after laser extraction of a defibrillator lead SO ANESTHESIA AND ANALGESIA LA English DT Article ID EXPERIENCE; PACEMAKER AB Laser-assisted intracardiac lead extraction is associated with a 1%-2% incidence of pericardial tamponade. Because of this risk, many of these procedures are being performed in an operating room with a cardiac surgeon immediately available. Transesophageal echocardiography is a useful intraoperative monitor during these procedures. C1 Massachusetts Gen Hosp, Dept Anesthesia & Intens Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Streckenbach, SC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Intens Care, 55 Fruit St, Boston, MA 02114 USA. NR 5 TC 11 Z9 11 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 SEP PY 2003 VL 97 IS 3 BP 654 EP 656 DI 10.1213/01.ANE.0000074234.13373.E7 PG 3 WC Anesthesiology SC Anesthesiology GA 714AN UT WOS:000184890300010 PM 12933378 ER PT J AU Bernecker, OY Bocker, W Zhu, XS Sawa, T del Monte, F Grazette, L Rosenzweig, A Hajjar, RJ Schmidt, U AF Bernecker, OY Bocker, W Zhu, XS Sawa, T del Monte, F Grazette, L Rosenzweig, A Hajjar, RJ Schmidt, U TI Cardiac specific promoter for myocardial gene transfer SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Criticae-Care-Anesthesiologists CY OCT 10, 2003 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Crirical Care Anesthesiologists C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA. Teikyo Univ, Sch Med, Dept Anesthesia, Tokyo 173, Japan. 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2003 VL 99 IS 3 BP B15 EP B15 PG 1 WC Anesthesiology SC Anesthesiology GA 715TB UT WOS:000184987400059 ER PT J AU Hellman, J AF Hellman, J TI Modulation of endothelial cell activation by gram-negative bacterial peptidoglycan-associated lipoprotein (PAL) SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Criticae-Care-Anesthesiologists CY OCT 10, 2003 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Crirical Care Anesthesiologists ID OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI J5; ANTISERUM; BLOOD C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2003 VL 99 IS 3 BP B30 EP B30 PG 1 WC Anesthesiology SC Anesthesiology GA 715TB UT WOS:000184987400072 ER PT J AU Pino, RM Dew, RB Spargo, JD Ferraro, MJ AF Pino, RM Dew, RB Spargo, JD Ferraro, MJ TI Comparison of gram negative isolates and susceptibility from surgical and medical intensive care units SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Criticae-Care-Anesthesiologists CY OCT 10, 2003 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Crirical Care Anesthesiologists C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2003 VL 99 IS 3 BP B47 EP B47 PG 1 WC Anesthesiology SC Anesthesiology GA 715TB UT WOS:000184987400084 ER PT J AU Richtsfeld, M Yasuhara, S Blobner, M Martyn, J AF Richtsfeld, M Yasuhara, S Blobner, M Martyn, J TI Chronic administration of pyridostigmine leads to a myasthenia-like state with down-regulation of acetylcholine receptors SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Criticae-Care-Anesthesiologists CY OCT 10, 2003 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Crirical Care Anesthesiologists C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2003 VL 99 IS 3 BP B10 EP B11 PG 2 WC Anesthesiology SC Anesthesiology GA 715TB UT WOS:000184987400055 ER PT J AU Zhu, XS Manohar, NS Bernecker, OY Hajjar, RJ Hellman, J Ichinose, F Valdivia, HH Schmidt, U AF Zhu, XS Manohar, NS Bernecker, OY Hajjar, RJ Hellman, J Ichinose, F Valdivia, HH Schmidt, U TI Altered Ca2+ cycling in rat heart during spesis SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Criticae-Care-Anesthesiologists CY OCT 10, 2003 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Crirical Care Anesthesiologists C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. Univ Wisconsin, Sch Med, Dept Physiol, Madison, WI 53706 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2003 VL 99 IS 3 BP B57 EP B57 PG 1 WC Anesthesiology SC Anesthesiology GA 715TB UT WOS:000184987400091 ER PT J AU Franco, RA Zeitels, SM Farinelli, WA Faquin, W Anderson, RR AF Franco, RA Zeitels, SM Farinelli, WA Faquin, W Anderson, RR TI 585-NM pulsed dye laser treatment of glottal dysplasia SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Laryngological-Association CY MAY 10-11, 2002 CL BOCA RATON, FLORIDA SP Amer Laryngol Assoc DE cancer; glottal dysplasia; glottis; microlaryngoscopy; pulsed dye laser; vocal cord; vocal fold ID SCARS AB Management of glottal dysplasia can be difficult and often results in a suboptimal treatment outcome. The surgeon and patient must cooperatively balance decisions regarding the effects of possible malignancy, vocal dysfunction, and recurrences leading to multiple use of general anesthetics. A pilot study was done in 57 cases (36 patients and 97 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 450-mus pulse width, 19 to 76-J/cm(2) fluence, 1- to 2-mm spot size) in the treatment of vocal fold keratosis. Forty of the 57 cases had bilateral treatment. Phonomicrosurgical resection was done in 35 of the 57 cases after PDL treatment. Of this group, 10 cases were found to have hyperplasia, 21 dysplasia, 4 carcinoma in situ, and 1 carcinoma. One patient had phonomicrosurgical resection before PDL treatment. In 21 of the 57 cases, the disease was irradiated without resection (4 unilateral lesions and 17 bilateral lesions). Approximately 80% of the patients in this series had a greater than 70% reduction in the size of the lesion with the use of the PDL irrespective of whether they underwent resection. Clinical observation revealed no new anterior commissure web formation despite bilateral anterior commissure treatment in 28 of the 57 cases. The PDL enhanced the epithelial excision by improving hemostasis and by creating an optimal dissection plane between the basement membrane and the underlying superficial lamina propria. In this initial trial, the PDL provided relatively safe and effective treatment for glottal dysplasia. Analysis of patterns of recurrence will require longer follow-up. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Franco, RA (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 42 Z9 43 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2003 VL 112 IS 9 BP 751 EP 758 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 722JV UT WOS:000185372700002 PM 14535557 ER PT J AU Grillo, HC Mathisen, DJ Ashiku, SK Wright, CD Wain, JC AF Grillo, HC Mathisen, DJ Ashiku, SK Wright, CD Wain, JC TI Successful treatment of idiopathic laryngotracheal stenosis by resection and primary anastomosis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE idiopathic subglottic stenosis ID SUBGLOTTIC STENOSIS; RECONSTRUCTION AB We studied the early and long-term response of idiopathic laryngotracheal stenosis (ILTS) to treatment by 1-stage laryngotracheal or tracheal resection and reconstruction in 73 patients. Nineteen of the 72 (26%) noted no difference in their voices or any difficulty in breathing after reconstruction. Forty-seven (64%) described loss of ability to project their voices as loudly as before or noted some difficulty in singing as well as they did before. Five (7%) had various degrees of dyspnea or stridor on effort. One needed continued dilation. The median follow-up was 8 years. Surgical treatment gave good or excellent results in 90% of these patients with ILTS. Recurrence or progression of stenosis was not evident. C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570,32 Fruit St, Boston, MA 02114 USA. NR 8 TC 24 Z9 29 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2003 VL 112 IS 9 BP 798 EP 800 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 722JV UT WOS:000185372700009 PM 14535564 ER PT J AU Li, A Miller, EL Kilmer, ME Brukilacchio, TJ Chaves, T Stott, J Zhang, Q Wu, T Chorlton, M Moore, RH Kopans, DB Boas, DA AF Li, A Miller, EL Kilmer, ME Brukilacchio, TJ Chaves, T Stott, J Zhang, Q Wu, T Chorlton, M Moore, RH Kopans, DB Boas, DA TI Tomographic optical breast imaging guided by three-dimensional mammography SO APPLIED OPTICS LA English DT Article ID BRAIN; LIGHT; SPECTROSCOPY; ACTIVATION AB We introduce a modified Tikhonov regularization method to include three-dimensional x-ray mammography as a prior in the diffuse optical tomography reconstruction. With simulations we show that the optical image reconstruction resolution and contrast are improved by implementing this x-ray-guided spatial constraint. We suggest an approach to find the optimal regularization parameters. The presented preliminary clinical result indicates the utility of the method. (C) 2003 Optical Society of America. C1 Tufts Univ, Dept Phys, Medford, MA 02155 USA. Harvard Univ, Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Tufts Univ, Dept Math, Medford, MA 02155 USA. Tufts Univ, Dept Elect Engn, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Breast Imaging Unit, Boston, MA 02114 USA. RP Li, A (reprint author), Tufts Univ, Dept Phys, Medford, MA 02155 USA. EM angli@nmr.mgh.harvard.edu RI Miller, Eric/B-2546-2008 OI Miller, Eric/0000-0002-3156-6002 FU NCI NIH HHS [R01-CA97305]; NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R29-NS38842] NR 26 TC 147 Z9 150 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD SEP 1 PY 2003 VL 42 IS 25 BP 5181 EP 5190 DI 10.1364/AO.42.005181 PG 10 WC Optics SC Optics GA 715GQ UT WOS:000184963200026 PM 12962399 ER PT J AU Chen, Z Isaacson, KB Toth, TL Godfrey-Bailey, L Schiff, I Hauser, R AF Chen, Z Isaacson, KB Toth, TL Godfrey-Bailey, L Schiff, I Hauser, R TI Temporal trends in human semen parameters in New England in the United States, 1989-2000 SO ARCHIVES OF ANDROLOGY LA English DT Article DE human; semen parameters; sperm count; sperm morphology; sperm motility; temporal trends ID FERTILE MEN; QUALITY; BIRTH; INFERTILITY; DECLINE; PERIOD; AREA; PH AB The current study explores trends in semen parameters in New England in the United States. A retrospective review was performed of 551 semen analysis records from 1989 to 2000 at Vincent Memorial Andrology Laboratory of Massachusetts General Hospital. After age adjustment, semen pH and motility significantly increased 0.05 units/year and 2.33%/year, respectively, while sperm with normal morphology decreased 0.33%/year. Sperm concentration showed a small upward trend. The year of birth in the present study ranged from 1932 to 1981; 2% were born between 1932 and 1941, 13% between 1942 and 1951, 48% between 1952 and 1961, 36% between 1962 and 1971, and 1% were born between 1972 and 1981. There were significant positive relationships between year of birth and semen volume (0.04 mL/1-year interval increase in year of birth) and motility (0.61 percent/1-year interval increase in year of birth), as well as with sperm concentration and morphology. Overall, there were temporal and year of birth trends in several human semen parameters. C1 Massachusetts Gen Hosp, Vincent Burham Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. RP Chen, Z (reprint author), Massachusetts Gen Hosp, Vincent Burham Androl Lab, Vincent Mem Obstet & Gynecol Serv, 55 Fruit St,VB Room 130, Boston, MA 02114 USA. FU NIEHS NIH HHS [ES09718, ES00002] NR 22 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0148-5016 J9 ARCH ANDROLOGY JI Arch. Androl. PD SEP-OCT PY 2003 VL 49 IS 5 BP 369 EP 374 DI 10.1080/0145010390219700 PG 6 WC Andrology SC Endocrinology & Metabolism GA 707BJ UT WOS:000184489300008 PM 12893515 ER PT J AU Kuperberg, GR Broome, MR McGuire, PK David, AS Eddy, M Ozawa, F Goff, D West, WC Williams, SCR van der Kouwe, AJW Salat, DH Dale, AM Fischl, B AF Kuperberg, GR Broome, MR McGuire, PK David, AS Eddy, M Ozawa, F Goff, D West, WC Williams, SCR van der Kouwe, AJW Salat, DH Dale, AM Fischl, B TI Regionally localized thinning of the cerebral cortex in schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; BRAIN VOLUME CHANGES; GRAY-MATTER; CORTICAL SURFACE; COORDINATE SYSTEM; NEURONAL DENSITY; BASAL GANGLIA; ABNORMALITIES AB Background: Schizophrenia is characterized by small reductions in cortical gray matter volume, particularly in the temporal and prefrontal cortices. The question of whether cortical thickness is reduced in schizophrenia has not been addressed using magnetic resonance imaging (MRI) techniques. Our objectives were to test the hypothesis that cortical thinning in patients with schizophrenia (relative to control subjects) is greater in temporal and prefrontal regions of interest (ROIs) than in control ROIs (superior parietal, calcarine, postcentral, central, and precentral cortices), and to obtain an unbiased estimate of the distribution of cortical thinning in patients (relative to controls) by constructing mean and statistical cortical thickness difference maps. Methods: Participants included 33 right-handed outpatients receiving medication and meeting DSM-IV criteria for schizophrenia and 32 healthy volunteers, matched on age and parental socioeconomic status. After high-resolution MRI scans, models of the gray-white and pial surfaces were generated for each individual's cortex, and the distance between these 2 surfaces was used to compute cortical thickness. A surface-based averaging technique that aligned the main cortical folds across individuals allowed between-group comparisons of thickness within ROIs, and at multiple, uniformly sampled loci across the cortical ribbon. Results: Relative to controls, patients showed greater cortical thinning in temporal-prefrontal ROIs than in control ROIs, as revealed by a significant (P<.009) interaction between group and region type. Cortical thickness difference maps revealed significant (at P<.05, corrected) thinning within the orbitofrontal cortices bilaterally; the inferior frontal, inferior temporal, and occipitotemporal cortices on the left; and within the medial temporal and medial frontal cortices on the right. Superior parietal and primary somatosensory and motor cortices were relatively spared, even at subthreshold significance levels. Conclusions: Patients with chronic schizophrenia showed widespread cortical thinning that particularly affected the prefrontal and temporal cortices. This thinning might reflect underlying neuropathological abnormalities in cortical structure. C1 Massachusetts Gen Hosp E, Dept Psychiat, Charlestown, MA 02129 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Inst Psychiat, Sect Neuroimaging, Div Psychol Med, London, England. Inst Psychiat, Dept Neurol, London SE5 8AF, England. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kuperberg, GR (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY-9,Bldg 149, Charlestown, MA 02129 USA. RI Williams, Steve/D-6979-2011; Dale, Anders/A-5180-2010 OI Williams, Steve/0000-0003-4299-1941; FU PHS HHS [K23 PA-00-004] NR 58 TC 527 Z9 531 U1 1 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2003 VL 60 IS 9 BP 878 EP 888 DI 10.1001/archpsyc.60.9.878 PG 11 WC Psychiatry SC Psychiatry GA 718PN UT WOS:000185155800003 PM 12963669 ER PT J AU Kao, WHL Kammerer, CM Schneider, JL Bauer, RL Mitchell, BD AF Kao, WHL Kammerer, CM Schneider, JL Bauer, RL Mitchell, BD TI Type 2 diabetes is associated with increased bone mineral density in Mexican-American women SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article DE osteoporosis; diabetes; Mexican-Americans; insulin ID GROWTH FACTOR-I; HORMONE-BINDING GLOBULIN; X-RAY ABSORPTIOMETRY; SARCOMA CELL-LINE; HIP FRACTURE; POSTMENOPAUSAL WOMEN; RISK-FACTORS; ESTROGEN REPLACEMENT; PREMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY AB Background. Our purpose was to determine whether type 2 diabetes is associated with altered bone mineral density (BMD) and whether fasting serum insulin levels are correlated with BMD. Methods. In a population-based family study of Mexican-Americans, we obtained measurements of BMD, diabetes status (by 2-h oral glucose tolerance test), obesity, and serum insulin concentrations in 600 subjects from 34 families. Analyses were stratified by sex and conditioned on the pedigree structure to account for residual correlations among related individuals. Results. Women with diabetes had significantly higher BMD at hip than women without diabetes (p = 0.03) even after adjustment for age, body mass index (BMI), and menopause status. BMD at spine was also higher in diabetic women than in nondiabetic women, although the association was no longer statistically significant after adjustment for BMI. Diabetes was not associated with BMD in men. In nondiabetic men and women, insulin levels were significantly correlated with BMD after adjustment for age and other lifestyle covariates, but correlations were diminished and were no longer statistically significant after further adjustment for body mass index. Conclusions. These results suggest that Mexican-American women with type 2 diabetes have hi-her BMD compared to their nondiabetic counterparts, with the association independent of obesity at hip, although not at spine or forearm. Increased BMD was also correlated with serum insulin levels, although this association was not independent of obesity. Longitudinal studies may be required to better define the mechanisms underlying the observed association between BMD and diabetes. (C) 2003 IMSS. Published by Elsevier Inc. C1 Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. Univ Pittsburgh, Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RP Mitchell, BD (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Room 492, Baltimore, MD 21201 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [P01-HL45522]; NIAMS NIH HHS [R01-AR43351] NR 58 TC 30 Z9 35 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD SEP-OCT PY 2003 VL 34 IS 5 BP 399 EP 406 DI 10.1016/j.rcmed.2002.07.001 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743YT UT WOS:000186601700009 PM 14602507 ER PT J AU Kaufman, DL Heinrich, BS Willett, C Perry, A Finseth, F Sobel, RA MacCollin, M AF Kaufman, DL Heinrich, BS Willett, C Perry, A Finseth, F Sobel, RA MacCollin, M TI Somatic instability of the NF2 gene in Schwannomatosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID NEUROFIBROMATOSIS TYPE-2 GENE; MUTATIONS; DELETIONS; CELLS; MENINGIOMAS; MERLIN; TUMORS AB Context: Schwannomatosis is a newly described form of neurofibromatosis of unclear pathogenesis. Patient and Methods: We studied the NF2 locus on chromosome 22 in 7 tumor specimens resected from a 36-year-old man with schwannomatosis of the right ulnar nerve. Results: Unrelated truncating NF2 gene mutations were detected in 4 tumor specimens. None of the NF2 mutations were present in the blood specimen. Loss of heterozygosity at the NF2 locus was seen in all tumors, and in every case the same allele was lost. Loss of distal chromosome 22 markers was variable. Fluorescence in situ hybridization results were consistent with monosomy 22 in 4 tumors and mitotic recombination or nondisjunction in 1. Conclusions: Molecular analysis of tumor specimens distinguishes schwannomatosis from other forms of neurofibromatosis. Further work is needed to understand the natural history and molecular biology of this condition. C1 Stanford Univ, Dept Plast Surg, Stanford, CA 94305 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Washington Univ, Sch Med, Div Neuropathol, St Louis, MO USA. El Camino Hosp, Dept Plast Surg, Mountain View, CA USA. RP MacCollin, M (reprint author), Massachusetts Gen Hosp E, Ctr Neurosci, Bldg 149,13th St, Hillsborough 02129, North Ireland. OI Perry, Arie/0000-0002-8300-7261 FU NINDS NIH HHS [NS35878-04] NR 19 TC 35 Z9 38 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2003 VL 60 IS 9 BP 1317 EP 1320 DI 10.1001/archneur.60.9.1317 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 720QN UT WOS:000185271600023 PM 12975302 ER PT J AU Atri, A Sheen, V AF Atri, A Sheen, V TI Cavernous sinus syndrome and headache due to bilateral carotid artery aneurysms SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Mem Disorders Univ, Boston, MA 02114 USA. RP Atri, A (reprint author), Massachusetts Gen Hosp, Mem Disorders Univ, WACC 830,15 Parkman St, Boston, MA 02114 USA. OI Atri, Alireza/0000-0003-4405-6973 FU NIMH NIH HHS [1K08MH/NS63886-01, K08 MH063886, R21MH66213-01]; NINDS NIH HHS [R01NS41636-02] NR 6 TC 2 Z9 2 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2003 VL 60 IS 9 BP 1327 EP 1328 DI 10.1001/archneur.60.9.1327 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 720QN UT WOS:000185271600025 PM 12975304 ER PT J AU Sharon, D Sandberg, MA Caruso, RC Berson, EL Dryja, TP AF Sharon, D Sandberg, MA Caruso, RC Berson, EL Dryja, TP TI Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NUCLEAR RECEPTOR GENE; RETINITIS-PIGMENTOSA; CLINICAL FINDINGS; NIGHT BLINDNESS; EPITHELIUM; ELECTRORETINOGRAM; IDENTIFICATION; MACULOPATHY; NRL AB Objectives: To determine if enhanced s-cone syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD) are caused by mutations in the NR2E3 gene and to characterize the clinical findings in patients with NR2E3 mutations. Patients: One patient with ESCS, one with GFS, and 20 with CPRD. Methods: The coding regions of the NR2E3 and NRL genes and part of the THRB1 coding region were scanned for mutations using single-strand conformation and direct sequencing methods. We evaluated visual acuity, refractive error, visual fields, fundi, final dark-adaptation thresholds, and electroretinograms (ERGs). Results: The patients with ESCS and GFS and 9 of the 20 unrelated patients with CPRD had mutations in the NR2E3 gene. Six mutations were found in these 11 patients, including 2 novel mutations: the missense mutation Ala256Glu and the frameshift mutation Pro276del17 (the first obviously null allele reported). Three patients were mutant homozygotes, and 8 had 2 mutations. All but one of the mutations in the patients with ESCS and GFS were also found in patients with CPRD. All NR2E3 cases were hyperopes and had retinal vascular attenuation and reduced and delayed full-field ERGS. Clumped pigment deposits were recognized in the patients with ESCS and GFS. The CPRD patients without NR2E3 mutations had no detected mutations in NRL or THRB1. Conclusions: We found that ESCS, GFS, and CPRD can all have the same genetic basis. Clinical Relevance: The combination of night blindness, hyperopia, and clumped retinal pigment deposits should raise the suspicion that a patient has NR2E3 disease. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ocular Mol Genet Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Cambridge, MA 02138 USA. NEI, Bethesda, MD 20892 USA. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RI Research Datalink, Clinical Practice/H-2477-2013; Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 FU NEI NIH HHS [EY00169, EY08683] NR 33 TC 89 Z9 94 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2003 VL 121 IS 9 BP 1316 EP 1323 DI 10.1001/archopht.121.9.1316 PG 8 WC Ophthalmology SC Ophthalmology GA 721QT UT WOS:000185327600013 PM 12963616 ER PT J AU Debas, HT Frcischlag, JA Schecter, WP Warshaw, AL AF Debas, HT Frcischlag, JA Schecter, WP Warshaw, AL TI Panel on surgical practice SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 16-18, 2003 CL MONTEREY, CALIFORNIA SP Pacific Coast Surg Assoc ID MEDICINE; SURGERY; CAREER C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. San Francisco Gen Hosp, Dept Surg, San Francisco, CA 94110 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Debas, HT (reprint author), Univ Calif San Francisco, 513 Parnassus Ave,S-224, San Francisco, CA 94143 USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 2003 VL 138 IS 9 BP 977 EP 986 DI 10.1001/archsurg.138.9.977 PG 10 WC Surgery SC Surgery GA 721NX UT WOS:000185323400011 PM 12963655 ER PT J AU Cartwright, VW Michaud, K Choi, HK Wolfe, F AF Cartwright, VW Michaud, K Choi, HK Wolfe, F TI Low rates of visual loss in hydroxychloroquine treated patients: Evidence to revise monitoring guidelines. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Washington, Childrens Hosp, Seattle, WA 98195 USA. Natl Databank Rheumat Dis, Wichita, KS USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1741 BP S666 EP S666 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801782 ER PT J AU Cartwright, VW Michaud, K Choi, HK Wolfe, F AF Cartwright, VW Michaud, K Choi, HK Wolfe, F TI Methotrexate, laboratory testing and risk of serious illness: Analyses in 20,000 patients SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Childrens Hosp, Seattle, WA USA. Natl Databank Rheumat Dis, Wichita, KS USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1068 BP S428 EP S429 PG 2 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801112 ER PT J AU Choi, HK Atkinson, K Karlson, E Willett, W Curhan, G AF Choi, HK Atkinson, K Karlson, E Willett, W Curhan, G TI Risk factors for incident gout in a large, long-term, prospective cohort study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1781 BP S680 EP S680 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801822 ER PT J AU Karlson, EW McAlindon, TE Costenbader, KH Massarotti, EM Fitzgerald, LM Jajoo, R Husni, E Watts, J Fossel, AH Pankey, H Fraser, PA AF Karlson, EW McAlindon, TE Costenbader, KH Massarotti, EM Fitzgerald, LM Jajoo, R Husni, E Watts, J Fossel, AH Pankey, H Fraser, PA TI High sensitivity, specificity and predictive value of the Connective Tissue Disease Questionnaire (CSQ) among urban African-American women. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Brigham & Womens Hosp, Boston, MA 02115 USA. New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 390 BP S186 EP S186 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800434 ER PT J AU Kelly, JA Sestak, AL Kilpatrick, J Frank, S Hutchings, D Garriott, CP Weese, J Cooney, C Aberle, TJ Namjou, B Gray-McGuire, C Bruner, GR Kaufman, KM Guthridge, JM James, JA Harley, JB AF Kelly, JA Sestak, AL Kilpatrick, J Frank, S Hutchings, D Garriott, CP Weese, J Cooney, C Aberle, TJ Namjou, B Gray-McGuire, C Bruner, GR Kaufman, KM Guthridge, JM James, JA Harley, JB TI Confirmation of susceptibility loci at 1q22-23, 4p16-15 and 11p13 in pedigrees multiplex for systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Oklahoma, US Dept Vet Affairs, Med Ctr, OMRF,Hlth Sci Ctr, Oklahoma City, OK USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 496 BP S225 EP S225 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800540 ER PT J AU Kline-Schoder, RJ Kane, MA Hogan, N Finger, WH Peterson, JN Breen, K Fishbein, R AF Kline-Schoder, RJ Kane, MA Hogan, N Finger, WH Peterson, JN Breen, K Fishbein, R TI Virtual reality-enhanced range of motion system for treating adhesive capsulitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Creare Res & Dev Inc, Hanover, NH 03755 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1802 BP S689 EP S689 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801842 ER PT J AU Kovac, SH Patino, F Saag, KG Mikuls, TR AF Kovac, SH Patino, F Saag, KG Mikuls, TR TI The association of race and residence on HRQoL for self-reported arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. Univ Nebraska, Ctr Med, Omaha VA Med Ctr, Omaha, NE 68198 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 561 BP S249 EP S249 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800605 ER PT J AU Morehead, K Chan, OTM Daikh, DI AF Morehead, K Chan, OTM Daikh, DI TI Magnetic resonance imaging of central nervous system disease in a murine model of systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Hawaii, Sch Med, Honolulu, HI 96822 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 422 BP S198 EP S198 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800466 ER PT J AU Park, YW Kang, YM Takemura, S Butterfield, J Detmar, M Kurtin, P Vallejo, AN Beckenbaugh, RD Goronzy, JJ Weyand, CM AF Park, YW Kang, YM Takemura, S Butterfield, J Detmar, M Kurtin, P Vallejo, AN Beckenbaugh, RD Goronzy, JJ Weyand, CM TI The matrix protein thrombospondin-2 inhibits angiogenesis in rheumatoid synovitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Mayo Clin, Dept Med, Rochester, MN USA. Mayo Clin, Dept Immunol, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1106 BP S443 EP S443 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801150 ER PT J AU Shadick, NA Maher, NE Huang, JJ Ding, WZ Dong, LS Chen, DF Phillips, CB Fraser, P AF Shadick, NA Maher, NE Huang, JJ Ding, WZ Dong, LS Chen, DF Phillips, CB Fraser, P TI HLA DRB1 alleles in a homogeneous population with persistent Lyme arthropathy and fibromyalgia symptoms: Data from the Nantucket Lyme Disease Cohort Study SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Brigham & Womens Hosp, RB Brigham Arthrit & Musculoskeletal Dis Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Maine Med Ctr, Portland, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 1011 BP S409 EP S409 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432801055 ER PT J AU Wolfe, F Michaud, K Choi, HK Williams, R AF Wolfe, F Michaud, K Choi, HK Williams, R TI Annual and lifetime productivity costs and income losses in persons with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Natl Data Bank Rheumat Dis, Wichita, KS USA. Arthrit Res Ctr, Wichita, KS USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2003 VL 48 IS 9 SU S MA 545 BP S243 EP S243 PG 1 WC Rheumatology SC Rheumatology GA 723LA UT WOS:000185432800589 ER PT J AU King, GL AF King, GL TI The role of protein kinase C activation in cardiovascular dysfunction in diabetes and insulin resistance SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 13th International Symposium on Atherosclerosis CY SEP 28-OCT 02, 2003 CL KYOTO, JAPAN C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD SEP PY 2003 VL 4 IS 2 BP 5 EP 5 DI 10.1016/S1567-5688(03)90023-7 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 749NH UT WOS:000186926500020 ER PT J AU Suzuma, I Suzuma, K Takagi, H Kaneto, H Aiello, L Honda, Y AF Suzuma, I Suzuma, K Takagi, H Kaneto, H Aiello, L Honda, Y TI Cyclic stretch induced reactive oxygen species (ROS) enhances apoptosis in porcine retinal pericytes (PRPC) through JNK/SAPK activation SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 13th International Symposium on Atherosclerosis CY SEP 28-OCT 02, 2003 CL KYOTO, JAPAN C1 Kyoto Univ, Sch Med, Dept Ophthalmol, Kyoto, Japan. Dept Internal Med & Therapeut, Suita, Osaka, Japan. Joslin Diabet Ctr, Dept Vasc Cell Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD SEP PY 2003 VL 4 IS 2 BP 53 EP 53 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 749NH UT WOS:000186926500222 ER PT J AU Aikawa, K Retzlaff, B Fish, B Walden, C Kahn, S Knopp, R AF Aikawa, K Retzlaff, B Fish, B Walden, C Kahn, S Knopp, R TI Dyslipidemia of insulin resistance and obesity: Gender differences SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 13th International Symposium on Atherosclerosis CY SEP 28-OCT 02, 2003 CL KYOTO, JAPAN C1 Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, NW Lipid Res Clin, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD SEP PY 2003 VL 4 IS 2 BP 260 EP 260 DI 10.1016/S1567-5688(03)91120-2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 749NH UT WOS:000186926501117 ER PT J AU Gershuny, BS Baer, L Radomsky, AS Wilson, KA Jenike, MA AF Gershuny, BS Baer, L Radomsky, AS Wilson, KA Jenike, MA TI Connections among symptoms of obsessive-compulsive disorder and posttraumatic stress disorder: a case series SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE obsessive-compulsive disorder; posttraumatic stress disorder; comorbid; symptom connection ID TRAUMATIC EXPERIENCES; BEHAVIOR-THERAPY; EXPOSURE; COMORBIDITY; SCALE; WORRY AB Theoretical, clinical, and empirical implications of the functional connections between symptoms of obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) are abundant. As such, four cases are presented here of men and women who met criteria for comorbid OCD and PTSD. All had been diagnosed with treatment-resistant OCD and were seeking treatment from an OCD specialty clinic or institute, all reported a history of traumatic experiences prior to the onset of OCD, and all appeared to demonstrate negative treatment outcomes. Upon examination, it appeared that symptoms of OCD and PTSD were connected such that decreases in OCD-specific symptoms related to increases in PTSD-specific symptoms, and increases in OCD-specific symptoms related to decreases in PTSD-specific symptoms. Speculations about the function of OCD symptoms in relation to post-traumatic psychopathology are put forth; and theoretical, research, and treatment implications are discussed. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Concordia Univ, Dept Psychol, Montreal, PQ H3G 1M8, Canada. RP Gershuny, BS (reprint author), Harvard Univ, Sch Med, Charlestown, MA 02129 USA. OI Radomsky, Adam/0000-0003-2807-184X NR 23 TC 55 Z9 55 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD SEP PY 2003 VL 41 IS 9 BP 1029 EP 1041 DI 10.1016/S0005-7967(02)00178-X PG 13 WC Psychology, Clinical SC Psychology GA 726HD UT WOS:000185592100003 PM 12914805 ER PT J AU Lu, S Chen, GL Ren, CX Kwabi-Addo, B Epner, DE AF Lu, S Chen, GL Ren, CX Kwabi-Addo, B Epner, DE TI Methionine restriction selectively targets thymidylate synthase in prostate cancer cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE methionine; folate; thymidylate synthase; prostate neoplasms ID LEUKEMIC HEMATOPOIETIC-CELLS; TOTAL PARENTERAL-NUTRITION; BRAIN-TUMOR XENOGRAFTS; HUMAN GASTRIC-CANCER; IN-VIVO; RECOMBINANT METHIONINASE; URACIL MISINCORPORATION; ANTICANCER EFFICACY; METABOLIC DEFECT; CLINICAL-TRIAL AB Tumor cells are more sensitive to methionine restriction than normal tissues, a phenomenon known as methionine auxotrophy. Previous studies showed that 5-fluorouracil and methionine restriction act synergistically against a variety of tumors. The purpose of the current studies was to determine the molecular mechanism(s) underlying this synergy. 5-Fluorouracil is known to inhibit thymidylate synthase (TS), a key enzyme that transfers a methyl group from 5,10-methylene-tetrahydrofolate to dUMP during nucleotide biosynthesis. We found that methionine restriction reduced 5, 10-methylene-tetrahydrofolate levels by 75% and selectively inhibited TS activity in PC-3 human prostate cancer cells within 24 hr, whereas it did not in normal prostate epithelial cells. The observed fall in TS activity was accompanied by a commensurate reduction in TS protein levels as determined by western blot analysis. In contrast, 5-fluorouracil inhibited TS activity by >90% but increased TS protein levels. This increase was abrogated by methionine restriction. Surprisingly, methionine restriction increased H-3-leucine incorporation in PC-3 cells over the first 24 hr, suggesting that reduction of TS levels was not simply due to global protein synthesis inhibition. Methionine restriction also significantly reduced the ratio of dUMP to dTTP in PC-3 cells, creating an imbalanced nucleotide pool. These results suggest that synergy between methionine restriction and 5-fluorouracil is attributable to multiple factors, including depletion of reduced folates, selective inhibition of TS, and creation of an imbalanced nucleotide pool. Dietary and/or enzymatic methionine restriction combined with 5-fluoruracil has great promise as a novel treatment for advanced cancer. (C) 2003 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, VA Med Ctr, Dept Med, Med Serv 111H, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. RP Epner, DE (reprint author), Baylor Coll Med, VA Med Ctr, Dept Med, Med Serv 111H, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Kwabi-Addo, Bernard/A-6993-2016 OI Kwabi-Addo, Bernard/0000-0003-3692-6350 NR 48 TC 6 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 1 PY 2003 VL 66 IS 5 BP 791 EP 800 DI 10.1016/S0006-2952(03)00406-4 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 721NT UT WOS:000185323000012 PM 12948860 ER PT J AU Pham, W Lai, WF Weissleder, R Tung, CH AF Pham, W Lai, WF Weissleder, R Tung, CH TI High efficiency synthesis of a bioconjugatable near-infrared fluorochrome SO BIOCONJUGATE CHEMISTRY LA English DT Article ID TRANSFERRIN RECEPTORS; TRICARBOCYANINE DYES; GENE-EXPRESSION; PROBES; ESTERS AB Near-infrared (NIR) fluorochromes have become important reporter molecules for many biomedical applications, including FACS sorting, confocal microscopy, and more recently in vivo imaging. While the structures of several stable 800 nm fluorochromes have been published, their synthesis is often complex and there are difficulties in rapidly purifying these compounds in large quantities. Here we report on the synthesis of NIR820, ex/em = 790/820, with excellent physicochemical properties. Importantly, NIR820 is conveniently synthesized in a three-step reaction and can be purified by flash column chromatography rather than by HPLC. NIR820 is chemically stable and can be directly coupled to peptides during the solid-phase synthesis. In addition, NIR820 is also suitable for conjugation to proteins and other affinity molecules in aqueous buffer. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. RI leu, borwen/K-8547-2012; OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355, R01-CA99385]; PHS HHS [N01-C017016] NR 18 TC 59 Z9 60 U1 1 U2 9 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 SEP-OCT PY 2003 VL 14 IS 5 BP 1048 EP 1051 DI 10.1021/bc034070h PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 723XP UT WOS:000185457100026 PM 13129411 ER PT J AU Phillips, ML Drevets, WC Rauch, SL Lane, R AF Phillips, ML Drevets, WC Rauch, SL Lane, R TI Neurobiology of emotion perception I: The neural basis of normal emotion perception SO BIOLOGICAL PSYCHIATRY LA English DT Review DE emotion; limbic; amygdala; ventral; dorsal; prefrontal ID ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; FEARFUL FACIAL EXPRESSIONS; HUMAN ORBITOFRONTAL CORTEX; SCRIPT-DRIVEN IMAGERY; HUMAN AMYGDALA; HUMAN BRAIN; BASOLATERAL AMYGDALA; CONDITIONED FEAR AB There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems. C1 Inst Psychiat, Div Psychol Med, London SE5 8AF, England. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA. RP Phillips, ML (reprint author), Inst Psychiat, Div Psychol Med, De Crespigny Pk, Denmark Hill, London SE5 8AF, England. NR 144 TC 1107 Z9 1136 U1 19 U2 162 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 SEP 1 PY 2003 VL 54 IS 5 BP 504 EP 514 DI 10.1016/S0006-3223(03)00168-9 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 714GZ UT WOS:000184906100002 PM 12946879 ER PT J AU Phillips, ML Drevets, WC Rauch, SL Lane, R AF Phillips, ML Drevets, WC Rauch, SL Lane, R TI Neurobiology of emotion perception II: Implications for major psychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Review DE emotion; neuroanatomy; schizophrenia; bipolar disorder; depression ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; SUBGENUAL PREFRONTAL CORTEX; BIPOLAR AFFECTIVE-DISORDER; HIPPOCAMPAL VOLUME REDUCTION; WORKING-MEMORY DYSFUNCTION; BRAIN METABOLIC CHANGES; MOOD DISORDERS; GLUCOSE-METABOLISM; DEPRESSED-PATIENTS AB To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and Junctional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder. C1 Inst Psychiat, Div Psychol Med, London SE5 8AF, England. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA. RP Phillips, ML (reprint author), Inst Psychiat, Div Psychol Med, De Crespigny Pk, Denmark Hill, London SE5 8AF, England. NR 147 TC 951 Z9 975 U1 29 U2 145 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 SEP 1 PY 2003 VL 54 IS 5 BP 515 EP 528 DI 10.1016/S0006-3223(03)00171-9 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 714GZ UT WOS:000184906100003 PM 12946880 ER PT J AU Lima, B Gleit, ZL Cameron, AM Germana, S Murphy, MC Consorti, R Chang, Q Dow, JD LeGuern, C Sachs, DH Huang, CA AF Lima, B Gleit, ZL Cameron, AM Germana, S Murphy, MC Consorti, R Chang, Q Dow, JD LeGuern, C Sachs, DH Huang, CA TI Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; mixed chimerism; miniature swine; cytokine-mobilized peripheral blood ID MAJOR HISTOCOMPATIBILITY COMPLEX; BONE-MARROW TRANSPLANTATION; STEM-CELLS; BODY IRRADIATION; MIXED CHIMERISM; CYCLE KINETICS; TOLERANCE; MOUSE; LYMPHOCYTES; ACTIVATION AB Our laboratory has previously reported a nonmyelosuppressive preparative regimen for hematopoietic cell transplantation that leads to mixed chimerism and allograft tolerance in miniature swine across minor and major histocompatibility disparities. Stable chimerism persisted in most of these animals but was restricted to T cells and confined to peripheral blood. Because of the importance of myeloid and erythroid progenitors for the treatment of hematologic disorders, the objective of this study was to assess whether such cells existed in the bone marrow of these lymphoid chimeras as an indication of functional engraftment. Colony-formation assays were performed on donor inocula before infusion and on bone marrow cells harvested from the transplant recipients. Donor-origin myeloid/erythroid progenitor colonies were detected in bone marrow from 6 of 7 lymphoid chimeric recipients. A delayed donor leukocyte infusion successfully converted a stable lymphoid chimera to full multilineage chimerism within 2 weeks. Donor-origin myeloid/erythroid progenitors could be detected in the bone marrow of a host-matched recipient after myeloablation and adoptive transfer of mobilized cells from one of the engrafted lymphoid chimeras. These data suggest that even when only lymphoid chimerism is readily detected by flow cytometry, dormant myeloid/erythroid progenitors can exist and subsequent conversion to full donor chimerism can be achieved. The ability to establish multilineage engraftment and chimerism without significant toxicity may have important clinical implications for the management of nonmalignant hematopoietic disorders and hematologic malignancies. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Biotransplant Inc, Boston, MA USA. RP Huang, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02114 USA. FU NCI NIH HHS [1R01 CA79989-01A1]; NHLBI NIH HHS [1R01 HL63430-01]; NIAID NIH HHS [1F32AI-10306] NR 40 TC 14 Z9 14 U1 0 U2 2 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 SEP PY 2003 VL 9 IS 9 BP 571 EP 582 DI 10.1016/S1083-8791(03)00227-1 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 741XK UT WOS:000186485500003 PM 14506659 ER PT J AU Irimia, D Karlsson, JOM AF Irimia, D Karlsson, JOM TI Development of a cell patterning technique using poly(ethylene glycol) disilane SO BIOMEDICAL MICRODEVICES LA English DT Article DE micropatterning; poly(ethylene glycol); silane; hepatoma; fibroblast ID POLYETHYLENE-GLYCOL; PROTEIN ADSORPTION; SURFACE-CHEMISTRY; MODEL SURFACES; IN-VITRO; ADHESION; HEPATOCYTES; FIBRONECTIN; GLASS; VITRONECTIN AB A simple technique for controlling cell adhesion on glass substrates by surface modification using a commercially available poly(ethylene glycol) (PEG) disilane, which can bind directly to glass in a single step, in combination with photolithographic micropatterning, was developed, characterized, and evaluated for patterning of HepG2 hepatoma cells and 3T3 fibroblasts. The optimal concentration of PEG-disilane for surface modification was 5 mM, and patterning of strongly adherent cells such as HepG2 required the chelation of divalent metal cations in order to inhibit nonspecific binding and cell aggregation. Whereas the average thickness of the PEG-disilane layer was 18 +/- 3.5 nm, the perimeters of patterned areas of exposed glass exhibited ridges of average height 857 +/- 50 nm, which may have aided in constraining cell spreading and migration. Although unpatterned PEG-treated substrates were hydrophilic (contact angle 46 +/- 1degrees), micropatterned surfaces behaved as if they were somewhat hydrophobic (contact angle similar to90degrees), necessitating special protocols for preventing deleterious dewetting of cells. For optimized protocols, the probability of adhesion of HepG2 cells to a patterned area of exposed glass was almost 15 times higher than the probability of adhesion to a PEG-treated background region of equal area. Our technique is useful for short- to intermediate-term patterning of cell or tissue morphology, e.g., for investigation of the effects of cell-cell interactions or cell geometry. C1 Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Ctr Engn Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Karlsson, JOM (reprint author), Georgia Inst Technol, George W Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. OI Irimia, Daniel/0000-0001-7347-2082 NR 41 TC 19 Z9 19 U1 1 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD SEP PY 2003 VL 5 IS 3 BP 185 EP 194 DI 10.1023/A:1025752007665 PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 722CR UT WOS:000185358300002 ER PT J AU Wadleigh, M Richardson, PG Zahrieh, D Lee, SJ Cutler, C Ho, V Alyea, EP Antin, JH Stone, RM Soiffer, RJ DeAngelo, DJ AF Wadleigh, M Richardson, PG Zahrieh, D Lee, SJ Cutler, C Ho, V Alyea, EP Antin, JH Stone, RM Soiffer, RJ DeAngelo, DJ TI Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; SINUSOIDAL OBSTRUCTION SYNDROME; SIGNIFICANT TOXICITY; COMPASSIONATE-USE; LIVER; DEFIBROTIDE; MYLOTARG(TM); GLUTATHIONE; EXPRESSION AB Gemtuzumab ozogamicin (GO), a monoclonal antibody used in the treatment of acute myelogenous leukemia (AML) has been linked to the development of veno-occlusive disease (VOD). We conducted a retrospective study of 62 patients with previously treated AML/MDS (myelodysplastic syndrome) who underwent allogeneic stem cell (SC) transplantation at our institution from December 2000 to October 2002 to determine whether GO exposure prior to allogeneic SC transplantation increases the risk of developing VOD. Fourteen patients received GO prior to SC transplantation. Of 62 patients, 13 (21%) developed VOD; 9 (64%) of 14 with prior GO exposure developed VOD compared with 4 (8%) of 48 without prior GO exposure (P <.0001). Logistic regression controlling for sex, disease status, donor type, and graft-versus-host disease prophylaxis identified prior treatment with GO as a significant risk factor for VOD (odds ratio [OR], 21.6; 95% confidence interval [CI], 4.2-112.2]. Nine of 10 patients who underwent SC transplantation 3.5 months or less following GO developed VOD compared with none of 4 patients who underwent SC transplantation more than 3.5 months from GO administration. Three of 14 patients who received GO prior to SC transplantation died of VOD. We conclude that patients undergoing SC transplantation within a short interval from GO administration are at increased risk of developing VOD. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP DeAngelo, DJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL07049-01] NR 34 TC 161 Z9 161 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 SEP 1 PY 2003 VL 102 IS 5 BP 1578 EP 1582 DI 10.1182/blood-2003-01-0255 PG 5 WC Hematology SC Hematology GA 714ZH UT WOS:000184945200013 PM 12738663 ER PT J AU Antin, JH Kim, HT Cutler, C Ho, VT Lee, SJ Miklos, DB Hochberg, EP Wu, CJ Alyea, EP Soiffer, RJ AF Antin, JH Kim, HT Cutler, C Ho, VT Lee, SJ Miklos, DB Hochberg, EP Wu, CJ Alyea, EP Soiffer, RJ TI Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; KIDNEY ALLOGRAFT-REJECTION; CHRONIC MYELOID-LEUKEMIA; HUMAN DENDRITIC CELLS; CD8(+) T-CELLS; COMPARING METHOTREXATE; CYCLOSPORINE-A; IN-VITRO; RAPAMYCIN AB We studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), from a 5 of 6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/muL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ 1,L were attained on day +29 (range, 14-98 days). Grades 0-1 acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% Cl 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation. C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Med Oncol & Biostat Sci, Boston, MA 02115 USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL070149] NR 40 TC 113 Z9 119 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 SEP 1 PY 2003 VL 102 IS 5 BP 1601 EP 1605 DI 10.1182/blood-2003-02-0489 PG 5 WC Hematology SC Hematology GA 714ZH UT WOS:000184945200017 PM 12730113 ER PT J AU Crawford, K Stark, A Kitchens, B Sternheim, K Pantazopoulos, V Triantafellow, E Wang, ZG Vasir, B Larsen, CE Gabuzda, D Reinherz, E Alper, CA AF Crawford, K Stark, A Kitchens, B Sternheim, K Pantazopoulos, V Triantafellow, E Wang, ZG Vasir, B Larsen, CE Gabuzda, D Reinherz, E Alper, CA TI CD2 engagement induces dendritic cell activation: implications for immune surveillance and T-cell activation SO BLOOD LA English DT Article ID ALTERNATIVE PATHWAY; CD40 LIGAND; RECEPTOR; SURFACE; LFA-3; INTERLEUKIN-12; SIGNALS; BINDING; ANTIGEN; SYSTEM AB We have shown previously that primary dendritic cells and monocytes express equal levels of CD14 but are distinguishable by the pretence of CD2 on dendritic cells. CD2 is known to mediate the activation of T and natural killer (NK) cells through its interaction with CD58. CD2 epitopes, recognized by anti-T11(1), -T11(2), and -T11(3) monoclonal antibodies (mAbs) are present on dendritic cells. Here we show that CD2 engagement significantly increases class II, costimulatory (CD40, CD80, CD86), adhesion (CD54, CD58), and CCR7 molecule expression on primary dendritic cells. Conversely, minimal or no change in the expression of the above antigens occurs on monocyte-derived dendritic cells, because these molecules are already maximally expressed. However, both kinds of dendritic cells release interleukin-1beta (IL-1beta) and IL-12 after CD2 engagement. Lastly, interference with dendritic cell CD2-T-cell CD58 engagement decreases naive CD4(+)CD45RA(+) T-cell proliferation. Collectively, our results suggest another role of the CD2-CD58 pathway that allows nonimmune and immune cells to interact directly with dendritic cells and initiate innate and adaptive immune responses. C1 Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept AIDS & Adult Oncol, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. Harvard Med Sch, Dept Pediat, Boston, MA USA. Harvard Med Sch, Dept Neurol, Boston, MA USA. RP Alper, CA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA09141]; NHLBI NIH HHS [HL 29583]; NIAID NIH HHS [P30 AI 28691, AI 07382, AI 35630] NR 42 TC 24 Z9 27 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 SEP 1 PY 2003 VL 102 IS 5 BP 1745 EP 1752 DI 10.1182/blood-2002-07-2206 PG 8 WC Hematology SC Hematology GA 714ZH UT WOS:000184945200039 PM 12714509 ER PT J AU Colditz, GA Feskanich, D Chen, WY Hunter, DJ Willett, WC AF Colditz, GA Feskanich, D Chen, WY Hunter, DJ Willett, WC TI Physical activity and risk of breast cancer in premenopausal women SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; physical activity; prospective cohort study ID BODY-MASS INDEX; POSTMENOPAUSAL WOMEN; OVULATORY DISORDER; UNITED-STATES; YOUNG-WOMEN; US WOMEN; COHORT; WEIGHT; INFERTILITY; EXERCISE AB Physical activity appears to be inversely related to risk of breast cancer, yet the results remain inconsistent. To evaluate this relation among premenopausal women and examine variation in risk according to level of obesity and use of oral contraceptives (OCs), the authors examined data from the Nurses' Health Study II. During 10 years of follow-up, 849 cases of invasive premenopausal breast cancer were confirmed. Physical activity was assessed by self-report at baseline and during follow-up using a validated questionnaire. Total physical activity was unrelated to risk of breast cancer. Women engaging in greater than or equal to27 metabolic equivalent (MET)-h week(-1) had a multivariate-adjusted relative risk (RR) of 1.04 (95% confidence interval (CI) 0.82 - 1.33) compared to those in the <3 MET-h week(-1) category. Among women with a BMI &GE;30 kg m(-2), we observed a significant positive dose - response relation (P = 0.04). Activity was unrelated to breast cancer risk at lower levels of BMI. A test for interaction between activity and BMI (<30, greater than or equal to30 kg m(-2)) was statistically significant (P = 0.02). Among current OC users, higher activity was associated with a non-significantly lower risk of breast cancer ( RR = 0.59, 95% CI 0.30 - 1.16 for greater than or equal to27 vs <9 MET-h week(-1\), P for linear trend = 0.14). These results show no overall association between physical activity and risk of breast cancer among premenopausal women, but suggest that the effect of physical activity could be substantially modified by the underlying degree of adiposity. The potential interactions between physical activity, adiposity, and current use of OCs require further study. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, 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 Nutr, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Canc Epidemiol Program, Boston, MA USA. RP Colditz, GA (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50838] NR 30 TC 58 Z9 58 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 1 PY 2003 VL 89 IS 5 BP 847 EP 851 DI 10.1038/sj.bjc.6601175 PG 5 WC Oncology SC Oncology GA 717FC UT WOS:000185074900013 PM 12942116 ER PT J AU Hamblin, MR Miller, JL Rizvi, I Loew, HG Hasan, T AF Hamblin, MR Miller, JL Rizvi, I Loew, HG Hasan, T TI Pegylation of charged polymer-photosensitiser conjugates: effects on photodynamic efficacy SO BRITISH JOURNAL OF CANCER LA English DT Article DE photodynamic therapy; photosensitiser; aggregation state; polyethylene glycol; polylysine conjugate; oxygen consumption ID OVARIAN-CANCER; THERAPY; TUMOR; CELLS; PHOTOIMMUNOTHERAPY; HEMATOPORPHYRIN; BIODISTRIBUTION; ACCUMULATION; LIPOPROTEIN; FIBROBLASTS AB Conjugates between photosensitisers ( PS) and charged polymeric carriers are under investigation for photodynamic therapy of cancer and may allow targeting to certain cell types or compartments in tumours. Covalent attachment of polyethylene glycol to macromolecules (pegylation) may alter their pharmacokinetics, cell type targeting, and photophysical properties. Macrophages may take up large amounts of aggregated PS, thus lessening the selectivity for cancer cells in tumours. We investigated the effect of pegylation on the uptake and phototoxicity of poly-L-lysine chlorin(e6) conjugates with either cationic or anionic charges in two cell lines, human ovarian cancer cells and mouse macrophages. The cationic conjugate after pegylation became less aggregated, consumed less oxygen and had reduced cellular uptake. However, the phototoxicity corrected for cellular uptake increased three- to five-fold. In contrast, the anionic succinylated conjugate on pegylation became more aggregated, consumed similar amounts of oxygen, and had higher cellular uptake. The anionic conjugate showed the highest relative phototoxicity towards both the cell lines ( compared to the other three conjugates) and it decreased most towards the macrophages after pegylation. Pegylation reduced the amount of oxygen consumed per chlorin(e6) molecule when photosensitised cells were illuminated. These in vitro studies suggest that pegylation alters the phototoxicity of PS conjugates depending on the effect produced on the aggregation state. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ Vienna, Dept Therapeut Biol, A-1010 Vienna, Austria. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, BAR314B,55 Fruit St, Boston, MA 02114 USA. RI Loew, Hans Gunter/L-2548-2013; OI Rizvi, Imran/0000-0001-9673-4700; Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, R01 CA83882]; NIAMS NIH HHS [R01 AR040352, R01 AR40352] NR 27 TC 48 Z9 50 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP 1 PY 2003 VL 89 IS 5 BP 937 EP 943 DI 10.1038/sj.bjc.6601210 PG 7 WC Oncology SC Oncology GA 717FC UT WOS:000185074900026 PM 12942129 ER PT J AU Lestou, VS Gascoyne, RD Sehn, L Ludkovski, O Chhanabhai, M Klasa, RJ Husson, H Freedman, AS Connors, JM Horsman, DE AF Lestou, VS Gascoyne, RD Sehn, L Ludkovski, O Chhanabhai, M Klasa, RJ Husson, H Freedman, AS Connors, JM Horsman, DE TI Multicolour fluorescence in situ hybridization analysis of t(14;18)-positive follicular lymphoma and correlation with gene expression data and clinical outcome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE follicular lymphoma; chromosomal alterations; gene expression; clinical outcome ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; COMPARATIVE GENOMIC HYBRIDIZATION; REQUIRING PROLONGED OBSERVATION; CENTER B-CELLS; TRANSLOCATION T(14-18); CYTOGENETIC ANALYSIS; PROGRESSION; PATTERNS; MODEL AB In order fully to identify secondary chromosomal alterations, such as duplications, additions and marker chromosomes that remained unresolved by G banding, 60 cases of t(14;18)-positive follicular lymphoma (FL) were analysed by multicolour karyotyping techniques [multicolour fluorescence in situ hybridization (MFISH)/multicolour banding for chromosome 1 (MBAND1)]. A total of 165 additional structural chromosomal aberrations were delineated. An increased frequency of chromosomal gains involving X, 1q, 2, 3q27-q29, 5, 6p11-p21, 7, 8, 11, 12, 14q32, 17q, 18 and 21 and deletions of 1p36, 3q28-q29, 6q, 10q22-q24 and 17p11-p13 was revealed by the MFISH/MBAND1 analysis. Balanced translocations other than t(14;18) were uncommon, whereas unbalanced translocations were numerous. Deletion of 1p36 and duplication of 1p33-p35, 1p12-p21 and 1q21-q41 were regularly involved in chromosome 1 alterations, seen in 53% of the cases. A strong correlation was demonstrated between gains of individual chromosomal bands and increased gene expression, including 1q22/MNDA, 6p21/CDKN1A, 12q13q14/SAS, 17q23/ZNF161, 18q21/BCL2 and Xq13/IL2RG. Unfavourable overall survival was associated with del(1)(p36) and dup(18q). These data support the notion that translocation events are primarily responsible for FL disease initiation, whereas the unbalanced chromosomal gains and losses that mirror the gene expression patterns characterize clonal evolution and disease progression, and thus provide further insights into the biology of FL. C1 British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Lestou, VS (reprint author), British Columbia Canc Agcy, Dept Pathol & Lab Med, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. FU NCI NIH HHS [1-U01-CA84967-01] NR 51 TC 23 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2003 VL 122 IS 5 BP 745 EP 759 DI 10.1046/j.1365-2141.2003.04502.x PG 15 WC Hematology SC Hematology GA 717TG UT WOS:000185106000004 PM 12930384 ER PT J AU Dallalio, G Fleury, T Means, RT AF Dallalio, G Fleury, T Means, RT TI Serum hepcidin in clinical specimens SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE anaemia; anaemia of chronic disease; hepcidin; iron absorption; iron deficiency ID CHRONIC DISEASE; RHEUMATOID-ARTHRITIS; IRON OVERLOAD; ANEMIA; INFLAMMATION; PEPTIDE; LIVER; PATHOGENESIS; EXPRESSION; MECHANISM AB The hepatic antimicrobial protein, hepcidin, is implicated in duodenal iron absorption and mobilization. Overexpression of the hepcidin gene is associated with a hypoferraemic, microcytic, iron-refractory anaemia. On the basis of these observations, it has been proposed that hepcidin is a mediator of the common clinical syndrome, anaemia of chronic disease (ACD), and recent findings evaluating urinary hepcidin production in patients support this hypothesis. In the present report, serum hepcidin concentrations were measured in 55 specimens submitted for ferritin determination, and in 37 specimens collected from anaemic patients undergoing diagnostic bone marrow examination. The serum hepcidin concentration exhibited a statistically significant correlation with serum ferritin concentrations in both patient subsets. No statistically significant correlations were observed between serum hepcidin and other laboratory markers of iron status or anaemia diagnosis. Serum hepcidin does not appear to correlate as well with clinical diagnosis as urinary hepcidin, suggesting that a better understanding of the clearance and metabolism of this protein is required to understand fully its potential contribution to the pathogenesis of ACD. C1 Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Div Hematol Oncol, Dept Med, Charleston, SC USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL69418-01] NR 19 TC 73 Z9 77 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2003 VL 122 IS 6 BP 996 EP 1000 DI 10.1046/j.1365-2141.2003.04516.x PG 5 WC Hematology SC Hematology GA 719HC UT WOS:000185196700015 PM 12956771 ER PT J AU Albert, M Tempany, CM Schultz, D Chen, MH Cormack, RA Kumar, S Hurwitz, MD Beard, C Tuncali, K O'Leary, M Topulos, GP Valentine, K Lopes, L Kanan, A Kacher, D Rosato, J Kooy, H Jolesz, F Carr-Locke, DL Richie, JP D'Amico, AV AF Albert, M Tempany, CM Schultz, D Chen, MH Cormack, RA Kumar, S Hurwitz, MD Beard, C Tuncali, K O'Leary, M Topulos, GP Valentine, K Lopes, L Kanan, A Kacher, D Rosato, J Kooy, H Jolesz, F Carr-Locke, DL Richie, JP D'Amico, AV TI Late genitourinary and gastrointestinal toxicity after magnetic resonance image-guided prostate brachytherapy with or without neoadjuvant external beam radiation therapy SO CANCER LA English DT Article DE prostate carcinoma; brachytherapy; magnetic resonance imaging (MRI); late toxicity ID INTERSTITIAL BRACHYTHERAPY; CANCER AB BACKGROUND. This study was designed to estimate the rates of late genitourinary (GU) and rectal toxicity after magnetic resonance image (MRI)-guided prostate brachytherapy exclusively or in conjunction with external beam radiation therapy (EBRT). METHODS. Between November 1997 and April 2002, 201 patients with category TIC prostate carcinoma (according to the 2002 American joint Committee on Cancer staging criteria), prostate specific antigen levels < 10 ng/mL, and biopsy Gleason score 3 + 4 disease were treated with MRI-guided brachytherapy exclusively or in conjunction with EBRT. The MRI-guided technique was designed to spare the urethra based on delivery of the prescription dose to the peripheral zone exclusively. The Kaplan-Meier method was used to estimate rates of freedom from late GU and rectal toxicity. Comparisons were made using a log-rank test. RESULTS. At a median follow-up of 2.8 years (range, 0.5-5.0 years), the 4-year estimates of rectal bleeding requiring coagulation for patients who underwent implantation therapy, compared with patients who received combined-modality therapy, were 8% versus 30%, respectively (log-rank P value = 0.0001). Although erectile dysfunction was common (range, 82-93%), with the use of sildenafil citrate (Viagra(R)), it was estimated that at least two-thirds of patients had erectile function comparable to or superior to baseline function, independent of whether they received monotherapy or combined-modality therapy (P = 0.46). The 4-year estimate of freedom from radiation cystitis was 100% verSUS 95% (P = 0.01) for patients who received monotherapy and patients who received combined-modality therapy, respectively. No urethral strictures were observed, and no patients underwent postimplantation transurethral resection of the prostate. CONCLUSIONS. In the current study, rectal bleeding after MRI-guided prostate brachymonotherapy was infrequent, and urethral and bladder toxicity is reported to be rare and may be attributed to the urethral-sparing technique of the MRI-guided approach. (C) 2003 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA USA. Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Albert, M (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2 Level, Boston, MA 02115 USA. OI Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [5R25 CA 89017-03, R25 CA089017]; NIA NIH HHS [R01 AG 19513, R01 AG019513] NR 12 TC 58 Z9 58 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 SEP 1 PY 2003 VL 98 IS 5 BP 949 EP 954 DI 10.1002/cncr.11595 PG 6 WC Oncology SC Oncology GA 714RV UT WOS:000184928000010 PM 12942561 ER EF