FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jellinek, MS McDermott, JF AF Jellinek, MS McDermott, JF TI Formulation: Putting the diagnosis into a therapeutic context and treatment plan SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Child Psychiat Serv, Newton Wellesley Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Hawaii, Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Newton Wellesley Hosp, Boston, MA 02114 USA. NR 6 TC 10 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2004 VL 43 IS 7 BP 913 EP 916 DI 10.1097/01.chi.0000125090.35109.57 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 832DF UT WOS:000222246700017 PM 15213593 ER PT J AU Pataki, C Bostic, JQ AF Pataki, C Bostic, JQ TI Who killed Kurt Cobain? The mysterious death of an icon. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Pataki, C (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. NR 1 TC 0 Z9 0 U1 2 U2 14 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 JUL PY 2004 VL 43 IS 7 BP 920 EP 921 DI 10.1097/01.chi.0000125088.35109.c8 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 832DF UT WOS:000222246700021 ER PT J AU Chodosh, J Petitti, DB Elliott, M Hays, RD Crooks, VC Reuben, DB Buckwalter, JG Wenger, N AF Chodosh, J Petitti, DB Elliott, M Hays, RD Crooks, VC Reuben, DB Buckwalter, JG Wenger, N TI Physician recognition of cognitive impairment: Evaluating the need for improvement SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE dementia; cognitive impairment; physician behavior; documentation ID PRIMARY-CARE PHYSICIANS; MINI-MENTAL-STATE; PLACEBO-CONTROLLED TRIAL; ALZHEIMERS-DISEASE; DEMENTIA QUESTIONNAIRE; MEMORY IMPAIRMENT; US MULTICENTER; DISORDERS; DONEPEZIL; DIAGNOSIS AB OBJECTIVES: To assess physician recognition of dementia and cognitive impairment, compare recognition with documentation, and identify physician and patient factors associated with recognition. DESIGN: Survey of physicians and review of medical records. SETTING: Health maintenance organization in southern California. PARTICIPANTS: Seven hundred twenty-nine physicians who provided care for women participating in a cohort study of memory (Women's Memory Study). MEASUREMENTS: Percentage of patients with dementia or cognitive impairment (using the Telephone Interview of Cognitive Status supplemented by the Telephone Dementia Questionnaire) recognized by physicians. Relationship between physician recognition and patient characteristics and physician demographics, practice characteristics, training, knowledge, and attitudes about dementia. RESULTS Physicians (n=365) correctly identified 81% of patients with dementia and 44% of patients with cognitive impairment without definite dementia. Medical records documented cognitive impairment in 83% of patients with dementia and 26% of patients with cognitive impairment without definite dementia. In a multivariable model, physicians with geriatric credentials (defined as geriatric fellowship experience and/or the certificate of added qualifications) recognized cognitive impairment more often than did those without (risk ratio (RR)=1.56, 95% confidence interval (CI)=1.04-1.66). Physicians were more likely to recognize cognitive impairment in patients with a history of depression treatment (RR=1.3, 95% CI=1.03-1.45) or stroke (RR=1.37, 95% CI=1.04-1.45) and less likely to recognize impairment in patients with cognitive impairment without definite dementia than in those with dementia (RR=0.46, 95% CI=0.23-0.72) and in patients with a prior hospitalization for myocardial infarction (RR=0.37, 95% CI=0.09-0.88) or cancer (RR=0.49, 95% CI=0.18-0.90). CONCLUSION: Medical record documentation reflects physician recognition of dementia, yet physicians are aware of, but have not documented, many patients with milder cognitive impairment. Physicians are unaware of cognitive impairment in more than 40% of their cognitively impaired patients. Additional geriatrics training may promote recognition, but systems solutions are needed to improve recognition critical to provision of emerging therapies for early dementia. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. So Calif Permanente Med Grp, Dept Res & Evaluat, Pasadena, CA USA. RP Chodosh, J (reprint author), Univ Calif Los Angeles Geriatr, 10945 Le Conte 2339, Los Angeles, CA 90095 USA. EM jchodosh@mednet.ucla.edu RI Hays, Ronald/D-5629-2013; OI Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [AG10415] NR 45 TC 116 Z9 117 U1 1 U2 4 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 JUL PY 2004 VL 52 IS 7 BP 1051 EP 1059 DI 10.1111/j.1532-5415.2004.52301.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 829SV UT WOS:000222070900002 PM 15209641 ER PT J AU Penrod, JD Boockvar, KS Litke, A Magaziner, J Hannan, EL Halm, EA Silberzweig, SB Sean Morrison, R Orosz, GM Koval, KJ Siu, AL AF Penrod, JD Boockvar, KS Litke, A Magaziner, J Hannan, EL Halm, EA Silberzweig, SB Sean Morrison, R Orosz, GM Koval, KJ Siu, AL TI Physical therapy and mobility 2 and 6 months after hip fracture SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hip fractures; physical therapy; mobility; disability ID FUNCTIONAL INDEPENDENCE; MORTALITY; ADMISSION; OUTCOMES; PAIN; COMPLICATIONS; DELIRIUM; RECOVERY; SYSTEM; CARE AB OBJECTIVES: To examine the relationship between early physical therapy (PT), later therapy, and mobility 2 and 6 months after hip fracture. DESIGN: Prospective, multisite observational study. SETTING: Four hospitals in the New York City area. PARTICIPANTS: Four hundred forty-three hospitalized older patients discharged after surgery for hip fracture in 1997-98. MEASUREMENTS: Patient demographics, fracture type, comorbidities, dementia, number of new impairments at discharge, amount of PT between day of surgery and postoperative day (POD) 3, amount of therapy between POD4 and 8 weeks later, and prefracture, 2-, and 6-month mobility measured using the Functional Independence Measure. RESULTS: More PT immediately after hip fracture surgery was associated with significantly better locomotion 2 months later. Each additional session from the day of surgery through POD3 was associated with an increase of 0.4 points (P=.032) on the 14-point locomotion scale, but the positive relationship between early PT and mobility was attenuated by 6 months postfracture. There was no association between later therapy and 2- or 6-month mobility. CONCLUSION: PT immediately after hip fracture surgery is beneficial. The effects of later therapy on mobility were difficult to assess because of limitations of the data. Well-designed randomized, controlled trials of the effect of varying schedules and amounts of therapy on functional status after hip fracture would be informative. C1 Bronx Vet Affairs Med Ctr, Program Res Serious Phys & Mental Illness, New York, NY USA. Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, New York, NY USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. SUNY Albany, Sch Publ Hlth, Dept Hlth Policy Management & Behav, Rensselaer, NY USA. NYU, Sch Med, Dept Orthoped Surg, New York, NY USA. RP Penrod, JD (reprint author), CUNY Mt Sinai Sch Med, Brookdale Dept Geriatr, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA. EM joan.penrod@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU AHRQ HHS [U18 HS009459, U18HS09459]; NIA NIH HHS [K24 AG000918, R01 AG021992] NR 29 TC 33 Z9 33 U1 1 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 JUL PY 2004 VL 52 IS 7 BP 1114 EP 1120 DI 10.1111/j.1532-5415.2004.52309.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 829SV UT WOS:000222070900010 PM 15209649 ER PT J AU Brophy, MT Snyder, KE Gaehde, S Ives, C Gagnon, D Fiore, LD AF Brophy, MT Snyder, KE Gaehde, S Ives, C Gagnon, D Fiore, LD TI Anticoagulant use for atrial fibrillation in the elderly SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE atrial fibrillation; anticoagulation; geriatrics; warfarin ID BLEEDING COMPLICATIONS; RISK-FACTORS; THROMBOEMBOLIC COMPLICATIONS; ANTITHROMBOTIC THERAPY; STROKE PREVENTION; WARFARIN; PHYSICIANS; OUTPATIENTS; VALIDATION; ATTITUDES AB OBJECTIVES: To determine the influence of advanced age on anticoagulant use in subjects with atrial fibrillation and to explore the extent to which risk factors for stroke and contraindications to anticoagulant therapy predict subsequent use. DESIGN: Retrospective cohort study. SETTING: The Veterans Affairs Boston Healthcare System. PARTICIPANTS: A total of 2,217 subjects with nonvalvular atrial fibrillation. MEASUREMENTS: Administrative databases were use to identify subject's age, anticoagulant use, and the presence of a diagnosis of atrial fibrillation, cerebrovascular accident, hypertension, diabetes mellitus, congestive heart failure, or gastrointestinal or cerebral hemorrhage. RESULTS: Unadjusted analysis showed no difference in warfarin use between those aged 75 and older and younger subjects regardless of the presence (33.9% vs 35.7%, P=.37) or absence (33.4% vs 34.7%, P=.58) of contraindications to anticoagulant therapy. Multivariate modeling demonstrated a 14% reduction (95% confidence interval (CI)=4-22%) in anticoagulant use with each advancing decade of life. Intracranial hemorrhage was a significant deterrent (odds ratio (OR)=0.27 95% CI=0.06-0.85). History of hypertension (OR=2.90, 95% CI=2.15-3.89), congestive heart failure (OR=1.70, 95% CI=1.41-2.04), and cerebrovascular accident (OR=1.54, 95% CI=1.25-1.89) were significant independent predictors for anticoagulant use. CONCLUSION: Despite consensus guidelines to treat all atrial fibrillation patients aged 75 and older with anticoagulants, advancing age was found to be a deterrent to warfarin use. Better estimates of the risk:benefit ratio for oral anticoagulant therapy in older patients with atrial fibrillation are needed to optimize decision-making. C1 VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. RP Snyder, KE (reprint author), VA Boston Healthcare Syst, MAVERIC, 150 S Huntington Ave, Boston, MA 02130 USA. EM kerri.snyder@med.va.gov NR 30 TC 44 Z9 45 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 JUL PY 2004 VL 52 IS 7 BP 1151 EP 1156 DI 10.1111/j.1532-5415.2004.52314.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 829SV UT WOS:000222070900015 PM 15209654 ER PT J AU Knight, EL Rimm, EB Pai, JK Rexrode, KM Cannuscio, CC Manson, JE Stampfer, MJ Curhan, GC AF Knight, EL Rimm, EB Pai, JK Rexrode, KM Cannuscio, CC Manson, JE Stampfer, MJ Curhan, GC TI Kidney dysfunction, inflammation, and coronary events: A prospective study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID C-REACTIVE PROTEIN; LOW-DENSITY LIPOPROTEINS; TUMOR-NECROSIS-FACTOR; CHRONIC-RENAL-FAILURE; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR OUTCOMES; CREATININE CLEARANCE; PHYSICAL-ACTIVITY; SERUM CREATININE; DISEASE AB Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl <60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl greater than or equal to90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl <60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl less than or equal to74 ml/min but not in women with an estimated CrCl greater than or equal to75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl less than or equal to74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and greater than or equal to90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Merck & Co Inc, Whitehouse Stn, NJ USA. RP Curhan, GC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM gcurhan@partners.org RI Cannuscio, Carolyn/A-1123-2007; OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [T32DK07791] NR 40 TC 95 Z9 98 U1 0 U2 2 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 JUL PY 2004 VL 15 IS 7 BP 1897 EP 1903 DI 10.1097/01.asn.0000128966.55133.69 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 832OA UT WOS:000222275600026 PM 15213279 ER PT J AU Keller, SM Vangel, MG Wagner, H Schiller, JH Herskovic, A Komaki, R Marks, RS Perry, MC Livingston, RB Johnson, DH AF Keller, SM Vangel, MG Wagner, H Schiller, JH Herskovic, A Komaki, R Marks, RS Perry, MC Livingston, RB Johnson, DH CA Eastern Cooperative Oncology Group TI Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-07, 2003 CL BOSTON, MA SP Amer Assoc Thorac Surg ID LYMPH-NODE METASTASES; MEDIASTINAL LYMPHADENECTOMY; PROGNOSTIC FACTORS; CARCINOMA; DISSECTION AB Objectives: To test the hypothesis that patients with non-small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non-small cell lung cancer) by site of primary tumor and pattern of lymph node metastases. Methods: Accurate staging was ensured by mandating either systematic sampling or complete dissection of the ipsilateral mediastinal lymph nodes. The overall survival of patients with left lung non-small cell lung cancer and metastases in only 1 of lymph node levels 5, 6, or 7 and right lung non-small cell lung cancer with metastases in only I of levels 4 or 7 was compared with that of patients with NI disease originating in the same lobe. Results: The median survival of the 172 patients with single-level N2 disease was 35 months (95% confidence interval: 27-40 months) versus 65 months (95% confidence interval: 45-84 months) for the 150 patients with N1 disease (median follow-up 84 months, P = .01). However, among patients with left upper lobe tumors, survival was not significantly different between patients with N1 disease and patients with single-level N2 disease (49 vs 51 months, P = .63). The median survival of the 71 patients with single-level N2 metastases without concomitant N1 disease (skip metastases) was 59 months (95% confidence interval: 36-107 months) versus 26 months (95% confidence interval: 16-36 months) for the 145 patients with both NI and N2 metastases (P = .001). Conclusions: Survival of patients with left upper lobe non-small cell lung cancer and metastases to single-level N2 lymph nodes is not significantly different from that of patients with N1 disease. The presence of isolate N2 skip metastases is associated with improved survival when compared with patients with both N1 and N2 disease. Survival should be reported by the lobe of primary tumor and metastatic pattern to guide future clinical trial development, treatment strategies, and revisions of the TNM staging system. C1 Montefiore Med Ctr, Dept Cardiothorac Surg, Bronx, NY 10467 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiat Oncol, Tampa, FL 33682 USA. Univ Wisconsin, Dept Med Oncol, Madison, WI USA. Oakwood Hosp, Dept Radiat Oncol, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. Univ Missouri, Dept Med Oncol, Columbia, MO USA. Univ Washington, Dept Med Oncol, Seattle, WA 98195 USA. Vanderbilt Univ, Dept Med Oncol, 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 [CA14958, CA20319, CA21076, CA21115, CA21661, CA23318, CA25224, CA49957, CA66636, CA73590] NR 27 TC 54 Z9 58 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 2004 VL 128 IS 1 BP 130 EP 137 DI 10.1016/j.jtcvs.2003.11.061 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 834IZ UT WOS:000222406100022 PM 15224032 ER PT J AU Wittram, C Meehan, MJ Halpern, EF Shepard, JAO McLoud, TC Thrall, JH AF Wittram, C Meehan, MJ Halpern, EF Shepard, JAO McLoud, TC Thrall, JH TI Trends in thoracic radiology over a decade at a large academic medical center SO JOURNAL OF THORACIC IMAGING LA English DT Article DE radiology; trends; chest; pulmonary embolism ID PULMONARY-EMBOLISM; CT AB Objective: To investigate thoracic radiology usage over and above the secular trends associated with hospital-wide changes in the number of patients over a decade. Materials and Methods: We retrospectively reviewed administrative data from our 905-bed tertiary-care hospital between January 1, 1992, to December 31, 2001. Three points of entry to the radiology department were identified: inpatient (IP), outpatient (OP), and the emergency room (ER). The total numbers of patients, imaging studies, chest radiographs, chest CTs, CTs for pulmonary embolism, pulmonary angiograms, ventilation/perfusion scintigrams (V/Qs), lung biopsies, cardiac and chest MRIs, and FDG-PET scans for lung nodules and masses were collected. The significance of trends using linear regression analysis was evaluated. Results: IP and OP numbers have significantly increased over a decade (P = 0.04 and P = 0.01 respectively); ER patient numbers have not. There has been an increase in the ratio of chest radiographs per patient arising from the ER area (P = 0.0002). All 3 areas demonstrated an increase in the ratio of chest CTs per patient: IP (P = 0.0002), OP (P = <0.0001), and ER (P = <0.0001). IP and ER areas demonstrated an increase in the ratio of CTs for pulmonary embolism per patient (P = 0.006, P = 0.04 respectively). There was a decrease in the ratios of pulmonary angiograms and V/Qs per IP (P = 0.02 & P = 0.0003 respectively). Cardiac MRIs per patient demonstrated an increase (IP P = 0.01, OP P = 0.02). FDG-PET for lung nodules and masses per patient demonstrated an increase in IP (P = 0.03) and OP (P = 0.003) areas. The total number of chest imaging studies divided by the total number of imaging studies demonstrated an increase in IP and ER areas (P = 0.02 and P = 0.02 respectively). Conclusion: There has been an increase in thoracic radiology usage above secular trends, particularly in the regions of chest CT and FDG-PET. CT is replacing more traditional techniques to diagnose pulmonary embolism for inpatients. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM cwittram@partners.org NR 8 TC 38 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD JUL PY 2004 VL 19 IS 3 BP 164 EP 170 DI 10.1097/01.rti.0000117623.02841.e6 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 841SC UT WOS:000222950700004 PM 15273612 ER PT J AU Jensen, DM Machicado, GA Hirabayashi, K AF Jensen, DM Machicado, GA Hirabayashi, K TI Randomized double-blind studies of polysaccharide gel compared with glue and other agents for hemostasis of large veins and bleeding canine esophageal or gastric varices SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical Activity and Mode of Action of the Hemostatic Agent Poly-N-Acetyl Glucosamine CY FEB 25, 2003 CL Harvard, Boston, MA HO Harvard DE abdominal varices; venous collaterals; esophageal varices; gastric varices; hemostatic agents ID ENDOSCOPIC INJECTION; FUNDIC VARICES; SCLEROTHERAPY; N-BUTYL-2-CYANOACRYLATE; CLASSIFICATION; CYANOACRYLATE; BUCRYLATE; MODEL AB Background. The safety and efficacy of poly-N-acetyl glucosamine (p-GlcNAc) gels were compared with standard agents in three different dog studies to assess abdominal venous collaterals, bleeding esophageal varices, and bleeding gastric varices. Methods: Adult dogs with prehepatic portal hypertension and large abdominal venous collaterals, esophageal varices, or gastric varices were studied. Results: Significantly higher sclerosis rates were seen with F2 or F4 p-GlcNAc gels and standard sclerosants. F2 and F4 gels had high rates of permanent hemostasis, low rates of secondary ulceration, and significant reductions in esophageal and gastric variceal size. These results were either equivalent to or significantly better than the most commonly used gastric varix hemostatic agent (glue) or other sclerosing agents. Conclusion. F2 and F4 poly-N-acetyl glucosantine gels are promising therapeutic agents for venous and variceal hemostasis. C1 VA Greater Los Angles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Jensen, DM (reprint author), VA Greater Los Angles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM djensen@mednet.ucla.edu FU NIDDK NIH HHS [K24 DK02650] NR 21 TC 6 Z9 6 U1 0 U2 1 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 JUL PY 2004 VL 57 IS 1 SU S BP S33 EP S37 DI 10.1097/01.TA.0000136748.42934.AB PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 860YP UT WOS:000224380900009 PM 15280749 ER PT J AU Najjar, SF Healey, NA Healey, CM McGarry, B Khan, B Thatte, HS Khuri, SF AF Najjar, SF Healey, NA Healey, CM McGarry, B Khan, B Thatte, HS Khuri, SF TI Evaluation of poly-N-acetyl glucosamine as a hemostatic agent in patients undergoing cardiac catheterization: A double-blind, randomized study SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical Activity and Mode of Action of the Hemostatic Agent Poly-N-Acetyl Glucosamine CY FEB 25, 2003 CL Harvard, Boston, MA HO Harvard DE poly-N-acetyl glucosamine p-GLcNAc) patch; placebo patch; pressure; hemostasis; arterial puncture site ID ARTERY CLOSURE DEVICES; VASCULAR COMPLICATIONS; PUNCTURE; COLLAGEN; ACCESS; SITE AB Background: This is the first blinded, randomized, placebo-controlled clinical trial to evaluate the efficacy of poly-N-acetyl glucosamine (p-GLcNAc) in improving hemostasis in patients undergoing cardiac catheterization. Methods: Patients were randomly assigned to have either a placebo-treated (n = 17) or a p-GlcNAc-treated (n = 16) 3 x 3-cm patch topically placed at the femoral insertion site at the completion of their catheterization procedure with a mechanical pressure clamp applied over it. The amount of pressure was measured. Results: Although the placebo group had slightly higher clamp pressure applied to the femoral arterial puncture site at the end of the catheterization procedure (189 +/- 47 vs. 149 +/- 49 mm Hg, p = 0.042), the time to effective hemostasis (16 +/- 7 vs. 10 +/- 3 minutes, p = 0.01) was decreased in the p-GlcNAc group by 37%. Conclusion: The application of p-GlcNAc patches improved hemostasis at the arterial puncture site in patients undergoing cardiac catheterization. C1 Brigham & Womens Hosp, Dept Surg, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 30 TC 23 Z9 23 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 JUL PY 2004 VL 57 IS 1 SU S BP S38 EP S41 DI 10.1097/01.TA.0000136749.20063.FU PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 860YP UT WOS:000224380900010 PM 15280750 ER PT J AU Thatte, HS Zagarins, SE Amiji, M Khuri, SF AF Thatte, HS Zagarins, SE Amiji, M Khuri, SF TI Poly-N-acetyl glucosamine-mediated red blood cell interactions SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical Activity and Mode of Action of the Hemostatic Agent Poly-N-Acetyl Glucosamine CY FEB 25, 2003 CL Harvard, Boston, MA HO Harvard DE red blood cell surface charge; poly-N-acetyl glucosamine (p-GlcNAc); configuration; red blood cell aggregation ID MODEL; FORMULATION; HEMORRHAGE; HEMOSTASIS AB Background: Investigations were performed to assess the effect of poly-N-acetyl glucosamine (p-GlcNAc) fiber slurry-mediated hemostasis by interactions with red blood cells. Methods: Red blood cell aggregation studies were performed using test material-coated microscope slides and multiphoton microscopic measurements. Enzymatic removal of red blood cell surface proteins was achieved using trypsin and neuraminidase treatment. Zeta-potential measurements (surface charge) were performed. Results: Red blood cells interact directly with poly-N-acetyl glucosamine polymers through ionic interactions and cell-surface proteins. The effective concentration of poly-N-acetyl glucosamine fiber material for 50% red blood cell aggregation was 0.28 mg/mL. The p-GlcNAc beta-configuration fibers and an alpha-configuration structural modification of the fibers both produced maximal responses because of their zeta-potentials, whereas other chemically modified p-GlcNAcs and chitosans were ineffective. Conclusion. Poly-N-acetyl glucosamine-induced red blood cell aggregation is mediated by interactions with red blood cell surface charges. C1 Harvard Univ, VA Boston Healthcare Syst, Dept Surg, Brigham & Womens Hosp,Sch Med, Boston, MA 02115 USA. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Thatte, HS (reprint author), VA Boston Healthcare Syst, Dept Surg 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM hemant_thatte@hms.harvard.edu RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X NR 13 TC 33 Z9 34 U1 0 U2 8 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 JUL PY 2004 VL 57 IS 1 SU S BP S7 EP S12 DI 10.1097/01.TA.0000136742.04816.38 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 860YP UT WOS:000224380900004 PM 15280744 ER PT J AU Thatte, HS Zagarins, S Khuri, SF Fischer, TH AF Thatte, HS Zagarins, S Khuri, SF Fischer, TH TI Mechanisms of poly-N-acetyl glucosamine polymer-mediated hemostasis: Platelet interactions SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT Symposium on Clinical Activity and Mode of Action of the Hemostatic Agent Poly-N-Acetyl Glucosamine CY FEB 25, 2003 CL Harvard, Boston, MA HO Harvard DE platelet phosphatidylserine; platelet calcium; platelet p selectin; alpha(IIb beta 3) integrin ID ENDOTHELIAL-CELLS; BLOOD PLATELETS; ADHESION; GLASS; FORMULATION; FIBRONECTIN; FIBRINOGEN; INTERFACE; SURFACE; BINDING AB Background: Investigations were performed to determine whether poly-N-acetyl glucosamine (p-GlcNAc) induces hemostasis by the activation of platelets. Methods: Platelets were isolated from human blood, fixed in the presence poly-N-acetyl glucosamine fibers, and visualized with scanning electron microscopy. Platelet activation surface markers were measured by fluorescence multiphoton microscopy. Platelet aggregation in the presence of p-GlcNAc fibers and integrin receptor blockers was measured. Results. Scanning electron microscopy indicated that contact of platelets with poly-N-acetyl glucosamine fibers resulted in platelet activation. Fluorescent microscopy showed that contact of platelets with the marine polymer increased intracellular levels of free calcium and resulted in surface exposure of platelet phosphatidylserine, P selectin, and the alpha(IIb)beta(3) integrin. Antibody inhibitors of the platelet alpha(IIb)beta(3) integrin inhibited p-GlcNAc to stimulate fibrin polymerization. Conclusion: Poly-N-acetyl glucosamine fiber material promotes hemostasis by the activation of platelets. C1 Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27516 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg,VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP Fischer, TH (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27516 USA. EM tfischer@med.unc.edu NR 43 TC 38 Z9 39 U1 0 U2 9 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 JUL PY 2004 VL 57 IS 1 SU S BP S13 EP S21 DI 10.1097/01.TA.0000136743.12440.89 PG 9 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 860YP UT WOS:000224380900005 PM 15280745 ER PT J AU Bazan, HA Schanzer, H AF Bazan, HA Schanzer, H TI Transposition of the brachial vein: A new source for autologous arteriovenous fistulas SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID UNITED-STATES; BASILIC VEIN; HEMODIALYSIS; GRAFTS AB Increasing the prevalence of arteriovenous fistula over arteriovenous synthetic graft is critical for decreasing the morbidity and costs of dialysis patients. This is highlighted in the guidelines set forth by The National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI), which encourage the increased use of autogenous vein in fistula creation. In addition to the basilic and cephalic veins, another source of autogenous vein is the brachial vein, a deep vein of the upper arm. Here we describe 2 patients with absence of adequate superficial veins, in whom a transposed brachial vein was used for the creation of an arteriovenous fistula. C1 Mt Sinai Sch Med, Dept Surg, New York, NY 10028 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Bazan, HA (reprint author), Mt Sinai Sch Med, Dept Surg, Box 1259,1 Gustave L Levy Pl, New York, NY 10028 USA. EM hernan.bazan@mssm.edu RI Bazan, Hernan/D-4923-2011 NR 12 TC 28 Z9 30 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2004 VL 40 IS 1 BP 184 EP 186 DI 10.1016/j.jvs.2004.03.044 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 835YT UT WOS:000222522300032 PM 15218484 ER PT J AU Blutt, SE Crawford, SE Warfield, KL Lewis, DE Estes, MK Conner, ME AF Blutt, SE Crawford, SE Warfield, KL Lewis, DE Estes, MK Conner, ME TI The VP7 outer capsid protein of rotavirus induces polyclonal B-cell activation SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; MAMMARY-TUMOR VIRUS; MONOCLONAL-ANTIBODIES; INFLUENZA-VIRUS; IN-VIVO; T-CELLS; 3-DIMENSIONAL STRUCTURE; HETEROLOGOUS ROTAVIRUS; LIPOPOLYSACCHARIDE LPS AB The early response to a homologous rotavirus infection in mice includes a T-cell-independent increase in the number of activated B lymphocytes in the Peyer's patches. The mechanism of this activation has not been previously determined. Since rotavirus has a repetitively arranged triple-layered capsid and repetitively arranged antigens can induce activation of B cells, one or more of the capsid proteins could be responsible for the initial activation of B cells during infection. To address this question, we assessed the ability of rotavirus and virus-like particles to induce B-cell activation in vivo and in vitro. Using infectious rotavirus, inactivated rotavirus, noninfectious but replication-competent virus, and virus-like particles, we determined that neither infectivity nor RNA was necessary for B-cell activation but the presence of the rotavirus outer capsid protein, VP7, was sufficient for murine B-cell activation. Preincubation of the virus with neutralizing VP7 antibodies inhibited B-cell activation. Polymyxin B treatment and boiling of the virus preparation were performed, which ruled out possible lipopolysaccharide contamination as the source of activation and confirmed that the structural conformation of VP7 is important for B-cell activation. These findings indicate that the structure and conformation of the outer capsid protein, VP7, initiate intestinal B-cell activation during rotavirus infection. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Med Res Serv, Houston, TX 77030 USA. RP Conner, ME (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mconner@bcm.tmc.edu FU NIAID NIH HHS [R21 AI024998, R01 AI024998, AI36211, AI10604, AI24998, F32 AI010604, P30 AI036211]; NIDDK NIH HHS [P30 DK056338, DK56338] NR 62 TC 30 Z9 33 U1 0 U2 0 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 JUL PY 2004 VL 78 IS 13 BP 6974 EP 6981 DI 10.1128/JVI.78.13.6974-6981.2004 PG 8 WC Virology SC Virology GA 830WC UT WOS:000222153800030 PM 15194774 ER PT J AU Allen, TM Altfeld, M Yu, XG O'Sullivan, KM Lichterfeld, M Le Gall, S John, M Mothe, BR Lee, PK Kalife, ET Cohen, DE Freedberg, KA Strick, DA Johnston, MN Sette, A Rosenberg, ES Mallal, SA Goulder, PJR Brander, C Walker, BD AF Allen, TM Altfeld, M Yu, XG O'Sullivan, KM Lichterfeld, M Le Gall, S John, M Mothe, BR Lee, PK Kalife, ET Cohen, DE Freedberg, KA Strick, DA Johnston, MN Sette, A Rosenberg, ES Mallal, SA Goulder, PJR Brander, C Walker, BD TI Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID CELLULAR IMMUNE-RESPONSES; HIV-1 NEF PROTEIN; MHC CLASS-I; DISEASE PROGRESSION; CTL ESCAPE; ENDOPLASMIC-RETICULUM; HLA-A; IMMUNODOMINANCE; EPITOPES; VIREMIA AB Numerous studies now support that human immunodeficiency virus type 1 (HIV-1) evolution is influenced by immune selection pressure, with population studies showing an association between specific HLA alleles and mutations within defined cytotoxic T-lymphocyte epitopes. Here we combine sequence data and functional studies of CD8 T-cell responses to demonstrate that allele-specific immune pressures also select for mutations flanking CD8 epitopes that impair antigen processing. In persons expressing HLA-A3, we demonstrate consistent selection for a mutation in a C-terminal flanking residue of the normally immunodominant Gag KK9 epitope that prevents its processing and presentation, resulting in a rapid decline in the CD8 T-cell response. This single amino acid substitution also lies within a second HLA-A3-restricted epitope, with the mutation directly impairing recognition by CD8 T cells. Transmission of the mutation to subjects expressing HLA-A3 was shown to prevent the induction of normally immunodominant acute-phase responses to both epitopes. However, subsequent in vivo reversion of the mutation was coincident with delayed induction of new CD8 T-cell responses to both epitopes. These data demonstrate that mutations within the flanking region of an HIV-1 epitope can impair recognition by an established CD8 T-cell response and that transmission of these mutations alters the acute-phase CD8(+) T-cell response. Moreover, reversion of these mutations in the absence of the original immune pressure reveals the potential plasticity of immunologically selected evolutionary changes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Infect Dis Div, Howard Hughes Med Inst,Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Fenway Community Hlth Ctr, Boston, MA USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia. Epimmune, San Diego, CA 92121 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Univ Oxford, Nuffield Dept Med, Dept Pediat, Oxford OX1 2JD, England. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Bldg 149,13th St,Rm 6003, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 NR 68 TC 192 Z9 196 U1 1 U2 7 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 JUL PY 2004 VL 78 IS 13 BP 7069 EP 7078 DI 10.1128/JVI.78.13.7069-7078.2004 PG 10 WC Virology SC Virology GA 830WC UT WOS:000222153800039 PM 15194783 ER PT J AU Mulky, A Sarafianos, SG Arnold, E Wu, XY Kappes, JC AF Mulky, A Sarafianos, SG Arnold, E Wu, XY Kappes, JC TI Subunit-specific analysis of the human immunodeficiency virus type 1 reverse transcriptase in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-SYNTHESIS; MUTATIONAL ANALYSIS; POLYMERASE-ACTIVITY; PRECURSOR PROTEIN; CRYSTAL-STRUCTURE; HIV-1; MUTAGENESIS; DIMERIZATION; INHIBITOR; COMPLEX AB The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a heterodimer comprised of two structurally distinct subunits (p51 and p66). Since p51 and p66 are derived from the same coding region, subunit-specific structure-function studies of RT have been conducted exclusively by in vitro biochemical approaches. To study RT subunit function in the context of infectious virus, we constructed an LTR-vpr-p51IRES-p66 expression cassette in which the HIV-1 vpr gene was fused in frame with p51, followed by an internal ribosome entry site (IRES) sequence and the p66 coding region. By coexpression with RT-deficient proviral DNA, we demonstrated that the p66 subunit is specifically and selectively packaged into virions as a Vpr-p51/ p66 complex. Our analysis showed that cleavage by the viral protease liberates Vpr and generates functional heterodimeric RT (p51/p66) that supports HIV-1 reverse transcription and virus infection. By exploiting this novel trans-complementation approach, we demonstrated, for the first time with infectious virions, that the YMDD aspartates of p66 are both required and sufficient for RT polymerase function. Mutational analyses of the p51 YMDD aspartates indicated that they play an important structural role in p51 folding and subunit interactions that are required for the formation of an active RT heterodimer within infected cells. Understanding the role of the individual RT subunits in RNA- and DNA-dependent DNA synthesis is integral to our understanding of RT function. Our findings will lead to important new insights into the role of the p51 and p66 subunits in HIV-1 reverse transcription. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL 35233 USA. RP Kappes, JC (reprint author), Univ Alabama, Dept Med, LHRB 613,701 S 19th St, Birmingham, AL 35294 USA. EM kappesjc@uab.edu OI Sarafianos, Stefan G/0000-0002-5840-154X FU NCI NIH HHS [CA73470]; NIAID NIH HHS [P30-AI-27767, AI47714, P30 AI027767, R01 AI047714] NR 51 TC 19 Z9 21 U1 0 U2 0 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 JUL PY 2004 VL 78 IS 13 BP 7089 EP 7096 DI 10.1128/JVI.78.13.7089-7096.2004 PG 8 WC Virology SC Virology GA 830WC UT WOS:000222153800041 PM 15194785 ER PT J AU Letvin, NL Huang, Y Chakrabarti, BK Xu, L Seaman, MS Beaudry, K Korioth-Schmitz, B Yu, F Rohne, D Martin, KL Miura, A Kong, WP Yang, ZY Gelman, RS Golubeva, OG Montefiori, DC Mascola, JR Nabel, GJ AF Letvin, NL Huang, Y Chakrabarti, BK Xu, L Seaman, MS Beaudry, K Korioth-Schmitz, B Yu, F Rohne, D Martin, KL Miura, A Kong, WP Yang, ZY Gelman, RS Golubeva, OG Montefiori, DC Mascola, JR Nabel, GJ TI Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; GAG-POL; GENETIC IMMUNIZATION; MUCOSAL CHALLENGE; IMMUNE-RESPONSES; INFECTION; MACAQUES; ENV; VIREMIA AB Because a strategy to elicit broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies has not yet been found, the role of an Env immunogen in HIV-1 vaccine candidates remains undefined. We sought to determine whether an HIV-1 Env immunogen genetically disparate from the Env of the challenge virus can contribute to protective immunity. We vaccinated Indian-origin rhesus monkeys with Gag-Pol-Nef immunogens, alone or in combination with Env immunogens that were either matched or mismatched with the challenge virus. These animals were then challenged with a pathogenic simian-human immunodeficiency virus. The vaccine regimen included a plasmid DNA prime and replication-defective adenoviral vector boost. Vaccine regimens that included the matched or mismatched Env immunogens conferred better protection against CD4(+) T-lymphocyte loss than that seen with comparable regimens that did not include Env immunogens. This increment in protective immunity was associated with anamnestic Env-specific cellular immunity that developed in the early days following viral challenge. These data suggest that T-lymphocyte immunity to Env can broaden the protective cellular immune response to HIV despite significant sequence diversity of the strains of the Env immunogens and can contribute to immune protection in this AIDS vaccine model. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Letvin, NL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 NR 24 TC 114 Z9 120 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 JUL PY 2004 VL 78 IS 14 BP 7490 EP 7497 DI 10.1128/JVI.78.14.7490-7497.2004 PG 8 WC Virology SC Virology GA 834JK UT WOS:000222407200021 PM 15220422 ER PT J AU Mickley, D Hamburg, P Godfrey, JR AF Mickley, D Hamburg, P Godfrey, JR TI Toward optimal health: The experts discuss eating disorders SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 Journal Womens Hlth, Montclair, NJ 07043 USA. Yale Univ, Sch Med, Greenwich, CT USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Adult Eating Disorders Program, Boston, MA 02114 USA. RP Godfrey, JR (reprint author), Journal Womens Hlth, 31 Macopin Ave, Montclair, NJ 07043 USA. EM jgmeisler@comcast.net NR 3 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL-AUG PY 2004 VL 13 IS 6 BP 662 EP 667 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 849BV UT WOS:000223513700002 PM 15333280 ER PT J AU Pirraglia, PA Sanyal, P Singer, DE Ferris, TG AF Pirraglia, PA Sanyal, P Singer, DE Ferris, TG TI Depressive symptom burden as a barrier to screening for breast and cervical cancers SO JOURNAL OF WOMENS HEALTH LA English DT Article; Proceedings Paper CT Meeting of the Society-for-General-Internal-Medicine CY MAY, 2003 CL Vancouver, CANADA SP Soc Gen Internal Med ID PRIMARY-CARE PATIENTS; HEALTH-INSURANCE; COMPETING DEMANDS; PREVENTIVE CARE; SELF-EFFICACY; MAMMOGRAPHY; WOMEN; PREDICTORS; OUTCOMES; RISK AB Background: Depression has been associated with lower cancer screening rates in some studies. We examined whether a higher depressive symptom burden presented a barrier to subsequent mammography and Papanicolaou (Pap) smear testing. Methods: Study of Women's Health Across the Nation (SWAN) is a cohort study of 3302 community-dwelling women. At baseline, participants were 42-52 years old, had no surgical removal of the uterus or both ovaries, no current use of hormones that affect the ovaries, and at least one menses in the previous 3 months. SWAN data spanned 4 years. Repeated measures logistic models determined odds of mammography and of Pap screening in the year following depressive symptom burden, as determined by Center for Epidemiological Studies Depression score (CES-D). The models controlled for age, race/ethnicity, health insurance, medical history and use, smoking, obesity, and socioeconomic status. Results: At baseline, 75.6% (2493 of 3297) had a low depressive symptom burden (CES-D score <16, referent), 9.5% (312 of 3297) had a moderate burden (CES-D 16-20), and 14.9% (492/3297) had a high burden (CES-D&GE;21). Women with a high depressive symptom burden had, in the subseqent year, significantly lower odds of mammography (OR 0.84, 95% CI 0.73-0.97) but not Pap smear (OR 0.88, 95% CI 0.76-1.03). There was not a significant dose-response relationship between depressive symptom burden and screening. Conclusions: The presence of a high depressive symptom burden is a modest independent risk factor for lack of subsequent mammography. Ensuring that depressed patients receive regular cancer screening services is important. C1 Rhode Isl Hosp, Div Gen Internal Med, Providence, RI 02903 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Pirraglia, PA (reprint author), Rhode Isl Hosp, Div Gen Internal Med, 593 Eddy St,MPB-1, Providence, RI 02903 USA. EM ppirraglia@lifespan.org FU BHP HRSA HHS [5T32 PE 11001-14]; NIA NIH HHS [U01 AG 12546, U01 AG 12505, U01 AG 12531, U01 AG 12535, U01 AG 12539, U01 AG 12554]; NINR NIH HHS [U01 NR 04061] NR 39 TC 49 Z9 49 U1 3 U2 8 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL-AUG PY 2004 VL 13 IS 6 BP 731 EP 738 DI 10.1089/jwh.2004.13.731 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 849BV UT WOS:000223513700010 PM 15333288 ER PT J AU Dember, LM Holmberg, EF Kaufman, JS AF Dember, LM Holmberg, EF Kaufman, JS TI Randomized controlled trial of prophylactic repair of hemodialysis arteriovenous graft stenosis SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Meeting of the American-Society-of-Nephrology CY NOV, 2002 CL Philadelphia, PA SP Amer Soc Nephrol DE hemodialysis; AV graft; thrombosis; stenosis; vascular access; end-stage renal disease; randomized trial ID BLOOD-FLOW; ACCESS MORBIDITY; VENOUS-PRESSURE; THROMBOSIS; SURVEILLANCE; SURVIVAL; PATENCY; FAILS AB Background. Previous nonrandomized studies suggest that prophylactic repair of hemodialyisis arteriovenous (AV) graft stenosis reduces thrombosis rates and increases cumulative graft survival. The present study is a randomized trial comparing prophylactic repair of AV graft stenosis with repair at the time of thrombosis. Methods. Sixty-four patients with elevated static venous pressure measured in an upper extremity AV graft were randomized to Intervention or Observation. Monthly static venous pressure/systolic blood pressure ratios (SVPR) were determined for all patients throughout the duration of study participation. Patients in the Intervention group underwent angiography and repair of identified stenoses if the monthly SVPR was elevated (greater than or equal to0.4). Patients in the Observation group underwent stenosis repair only in the event of access thrombosis or clinical evidence of access dysfunction. The primary end point was access abandonment. Results. Access abandonment occurred in 14 patients in the Intervention group and 14 patients in the Observation group during the 3.5-year study period. Time to access abandonment did not differ significantly between the treatment groups (hazard ratio for randomization to Intervention 1.75, 95% CI 0.80-3.82, P = 0.16). The proportion of patients with a thrombotic event was greater in the Observation group (72%) than in the Intervention group (44%) (P = 0.04), but overall thrombosis rates were similar in the groups. Conclusion. Compared with a strategy of observation and repair of accesses only in the event of thrombosis, prospective static venous pressure monitoring with prophylactic stenosis repair did not prolong graft survival. C1 Boston Univ, Med Ctr, Sch Med, Renal Sect, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Dember, LM (reprint author), Boston Univ, Med Ctr, Sch Med, Renal Sect, EBRC 504,650 Albany St, Boston, MA 02118 USA. EM ldember@bumc.bu.edu NR 19 TC 69 Z9 69 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2004 VL 66 IS 1 BP 390 EP 398 DI 10.1111/j.1523-1755.2004.00743.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 827NO UT WOS:000221906900042 PM 15200448 ER PT J AU Mithofer, K Gill, TJ Vrahas, MS AF Mithofer, K Gill, TJ Vrahas, MS TI Tibial plateau fracture following anterior cruciate ligament reconstruction SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY LA English DT Article DE anterior cruciate ligament; complication; tibia; operative treatment ID REPLACEMENT; HOLE AB A case is presented of a tibial plateau fracture after previous anterior cruciate ligament reconstruction using patellar tendon autograft. The tibial plateau fracture occurred through the transosseous tibial tunnel and followed a torsional injury to the involved extremity. The stress riser effect of the transosseous tibial tunnel and the anatomic location of the cortical defect probably facilitated development of the fracture. Minimally invasive fixation of the fracture was effective in preserving knee stability without need for revision anterior cruciate ligament reconstruction. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Mithofer, K (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Wang Ambulatory Care Ctr 525,15 Parkman St, Boston, MA 02114 USA. EM mithoeferk@aol.com NR 11 TC 14 Z9 17 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0942-2056 J9 KNEE SURG SPORT TR A JI Knee Surg. Sports Traumatol. Arthrosc. PD JUL PY 2004 VL 12 IS 4 BP 325 EP 328 DI 10.1007/s00167-003-0445-9 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 846IY UT WOS:000223310400012 PM 14740154 ER PT J AU Stone, ME AF Stone, ME TI The medical library association encyclopedic guide to searching and finding health information on the web. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell 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 JUL PY 2004 VL 129 IS 12 BP 119 EP 119 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 836RH UT WOS:000222572800357 ER PT J AU Reid, AE Resnick, M Chang, YC Buerstatte, N Weissman, JS AF Reid, AE Resnick, M Chang, YC Buerstatte, N Weissman, JS TI Disparity in use of orthotopic liver transplantation among blacks and whites SO LIVER TRANSPLANTATION LA English DT Article ID CHRONIC HEPATITIS-C; UNITED-STATES; RENAL-TRANSPLANTATION; RACIAL-DIFFERENCES; ETHNIC DISPARITIES; VIRUS-INFECTION; WAITING TIME; RACE; MORTALITY; DISEASE AB Orthotopic liver transplantation (OLT) is the best treatment for end-stage liver disease. Limited data exist access of minorities to OLT. The aim of this study was to determine whether disparities exist among black and white OLT patients. Data were collected from the United Network for Organ Sharing on black and white 18-70 year-old OLT waiting list registrants (n = 29,013) and OLT recipients (n = 15,805) between 1994 and 1998. Standardized transplant ratios were generated by comparing the racial distribution of OLT patients with the US population. Demographic and clinical characteristics of OLT registrants were compared by race. Multivariate analyses were performed to identify predictors of time to OLT and the likelihood of dying or receiving OLT within 4 years, controlling for severity of illness and other factors. The standardized transplant ratio for black OLT recipients (0.65) was significantly lower than the standardized transplant ratio for white OLT recipients (1.05). Blacks were younger and sicker than whites. After adjustment for severity and other factors, time to OLT among recipients did not differ by race (P > .05). Blacks were more likely to die or become too ill for OLT while waiting (P < .001). Blacks were less likely to receive OLT within 4 years (P < .001). In conclusion, adult blacks were underrepresented among OLT patients. Although waiting times were similar once listed, black race affected outcomes while awaiting OLT. The process of referral and evaluation for OLT should be investigated further. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Reid, AE (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, GJ 724,55 Fruit St, Boston, MA 02114 USA. EM areid@partners.org FU NIDDK NIH HHS [5KO8DK02842-02] NR 38 TC 65 Z9 65 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2004 VL 10 IS 7 BP 834 EP 841 DI 10.1002/lt.20174 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 833NR UT WOS:000222345100003 PM 15237365 ER PT J AU Krause, MHJ Kwong, KK Gragoudas, ES Young, LHY AF Krause, MHJ Kwong, KK Gragoudas, ES Young, LHY TI MRI of blood volume with superparamagnetic iron in choroidal melanoma treated with thermotherapy SO MAGNETIC RESONANCE IMAGING LA English DT Article DE nuclear magnetic resonance; melanoma; blood volume; choroid neoplasms; pathology; physiopathology; ferric compounds; diagnostic use; pharmacokinetics ID TRANSPUPILLARY THERMOTHERAPY; PHOTODYNAMIC THERAPY; SIMULATING LESIONS; UVEAL MELANOMA; 5-AMINOLEVULINIC ACID; MALIGNANT-MELANOMA; INTRAOCULAR TUMORS; IMAGING EVALUATION; MURINE TUMOR; RABBIT MODEL AB Functional magnetic resonance imaging (MRI) with a new intravascular contrast agent, monocrystalline iron oxide nanoparticles (MION), was applied to assess the effect of transpupillary thermotherapy in a rabbit model of choroidal melanoma. 3D-spoiled gradient recalled sequences were used for quantitative assessment of blood volume. The MRI-parameters were 5/22/35degrees (time of repetition (TR)/echo delay (TE)/flip angle (FA)) for T-1- and 50/61/10degrees for T-2-weighted sequences. Images were collected before and at different times after MION injection. In all untreated tissues studied, MION reduced the T-2-weighted signal intensity within 0.5 h and at 24 h (all p less than or equal to 0.012), whereas no significant changes were detected in treated tumors. T-1-weighted images also revealed differences of MION-related signal changes between treated tumors and other tissues, yet at lower sensitivity and specificity than T-2. The change of T-2-weighted MRI signal caused by intravascular MION allows early distinction of laser-treated experimental melanomas from untreated tissues. Further study is necessary to determine whether MRI can localize areas of tumor regrowth within tumors treated incompletely. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. Univ Saarland, Dept Ophthalmol, D-6650 Homburg, Germany. Univ Saarland, Hosp Eye, D-6650 Homburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp Nucl Magnet Resonance, Charlestown, MA USA. RP Young, LHY (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. EM lhyoung@meei.harvard.edu NR 48 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JUL PY 2004 VL 22 IS 6 BP 779 EP 787 DI 10.1016/j.mri.2004.01.052 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 835ON UT WOS:000222493200004 PM 15234446 ER PT J AU Richardson, P Schlossman, R Jagannath, S Alsina, M Desikan, R Blood, E Weller, E Mitsiades, C Hideshima, T Davies, F Doss, D Freeman, A Bosch, J Patin, J Knight, R Zeldis, J Dalton, W Anderson, K AF Richardson, P Schlossman, R Jagannath, S Alsina, M Desikan, R Blood, E Weller, E Mitsiades, C Hideshima, T Davies, F Doss, D Freeman, A Bosch, J Patin, J Knight, R Zeldis, J Dalton, W Anderson, K TI Thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation: Results of an open-label Multicenter phase 2 study of efficacy, toxicity, and biological activity SO MAYO CLINIC PROCEEDINGS LA English DT Article ID DRUG-RESISTANCE; THERAPY; ANALOGS; GROWTH; DEXAMETHASONE; ANGIOGENESIS; COMBINATION; SURVIVAL AB OBJECTIVES: To determine the progression-free survival at 12 weeks, to evaluate the toxic effects, and to analyze the biological activity of thalidomide in patients with relapsed multiple myeloma (MM) after high-dose chemotherapy and stem cell transplantation. PATIENTS AND METHODS: From 1999 to 2001, we performed a multicenter prospective phase 2 study in patients with MM that relapsed after high-dose chemotherapy and stem cell transplantation to evaluate the efficacy of oral thalidomide, with dose escalation from 200 to 600 mg/d over 12 weeks and a subsequent maintenance phase of 200 mg/d for up to I year. Outcome was correlated with serum and plasma levels of vascular endothelial growth factor and serum levels of tumor necrosis factor alpha, soluble intercellular adhesion molecule 1, interferon gamma, interleukin (IL) 2, and IL-6 during treatment. RESULTS: Thirty patients were treated (19 men and 11 women; median age, 58 years). The median number of prior therapies was 5, and the median duration from diagnosis of MM to study enrollment was 4.3 years. The 12-week progression-free survival rate was 67% (95% confidence interval [CI], 48%-86%). The observed response rate (partial response plus minor response) was 43% (95% CI, 28%-60%) with a median duration of 6 months. Attributable toxicities included constipation, fatigue, rash, and neuropathy, which was dose limiting in 8 patients (27%). Dose escalation from 200 to 600 mg/d was achieved in 50% of patients. Although responses were observed with lower doses, possibly eliminating the need to escalate the dose, responses were also seen in patients who completed the dose escalation. Some patients had disease progression while receiving the maintenance dose of 200 mg/d. Analysis of biomarker assays did not identify any biomarker associated with greater response, but a significant increase in levels of soluble intercellular adhesion molecule 1, IL-2, and interferon gamma was seen with thalidomide therapy. CONCLUSION: The optimal thalidomide dose varies, and adverse effects can be dose limiting. The dose of thalidomide therapy should be based on the individual patient to ensure that it is well tolerated and that a response is achieved. C1 Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Celgene Corp, Warren, NJ USA. St Vincents Catholic Med Ctr, New York, NY USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. RP Richardson, P (reprint author), Dana Farber Canc Inst, Div Hematol Oncol, D1B02,44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 22 TC 85 Z9 86 U1 0 U2 1 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2004 VL 79 IS 7 BP 875 EP 882 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 833MZ UT WOS:000222342900006 PM 15244383 ER PT J AU Gaglia, JL Wyckoff, J Abrahamson, MJ AF Gaglia, JL Wyckoff, J Abrahamson, MJ TI Acute hyperglycemic crisis in the elderly SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID SEVERE DIABETIC-KETOACIDOSIS; PHOSPHATE THERAPY; HYPEROSMOLAR COMA; VASCULAR COMPLICATIONS; BICARBONATE THERAPY; INSULIN THERAPY; CEREBRAL EDEMA; MELLITUS; ACIDOSIS; CHILDREN AB The geriatric population is at particular risk for developing hyperglycemic crises with the development of diabetes. With increasing age, insulin secretory reserve, insulin sensitivity, and thirst mechanisms decrease. The elderly are particularly vulnerable to hyperglycemia and dehydration, the key components of hyperglycemic emergencies. If recognized early, hyperglycemia can frequently be treated in the outpatient setting even with moderate or large ketonuria, provided patients can take fluids, monitor blood glucose frequently, and follow standard "sick day rules." With increased diabetes surveillance and aggressive early treatment of hyperglycemia and its complications, morbidity and mortality from acute diabetic crises in the geriatric population can be greatly reduced. C1 Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Abrahamson, MJ (reprint author), Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM martin.abrahamson@joslin.harvard.edu OI Gaglia, Jason/0000-0003-2904-312X NR 67 TC 22 Z9 26 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 2004 VL 88 IS 4 BP 1063 EP + DI 10.1016/j.mcna.2004.04.010 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 851HM UT WOS:000223676200012 PM 15308390 ER PT J AU Elstein, AS Fryback, DG Weinstein, MC Pauker, SG Holmes-Rovner, M Young, MJ Barry, MJ Eckman, MH Hunink, MGM Tsevat, J Wong, JB AF Elstein, AS Fryback, DG Weinstein, MC Pauker, SG Holmes-Rovner, M Young, MJ Barry, MJ Eckman, MH Hunink, MGM Tsevat, J Wong, JB TI Presidential reflections on the 25th anniversary of the society for medical decision making SO MEDICAL DECISION MAKING LA English DT Article ID ATRIAL-FIBRILLATION; CLINICAL DECISIONS; CANCER; WOMEN C1 Tufts Univ, New England Med Ctr, Div Clin Desis Making, Boston, MA 02111 USA. Univ Illinois, Dept Med Educ, Chicago, IL USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Michigan State Univ, Div Hlth Serv Res, E Lansing, MI 48824 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. Lehigh Valley Hosp Ctr, Allentown, PA 18102 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Univ Cincinnati, Med Ctr, Dept Internal Med, Cincinnati, OH 45267 USA. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. Univ Cincinnati, Med Ctr, Dept Internal Med, Cincinnati, OH 45267 USA. Cincinnati Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. RP Wong, JB (reprint author), Tufts Univ, New England Med Ctr, Div Clin Desis Making, 750 Washington St 302, Boston, MA 02111 USA. EM jwong@tufts-nemc.org NR 42 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JUL-AUG PY 2004 VL 24 IS 4 BP 408 EP 420 DI 10.1177/027989X04267676 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 839VV UT WOS:000222813900008 PM 15271279 ER PT J AU Papiez, L Bortfeld, T Hendee, WR AF Papiez, L Bortfeld, T Hendee, WR TI Very high energy electromagnetically-scanned electron beams are an attractive alternative to photon IMRT SO MEDICAL PHYSICS LA English DT Editorial Material ID DELIVERY; THERAPY; MOTION; RADIOTHERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Papiez, L (reprint author), Indiana Univ, Dept Radiat Oncol, Indianapolis, IN 46202 USA. EM lpapiez@iupui.edu; tbortfeld@partners.org NR 15 TC 4 Z9 4 U1 1 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2004 VL 31 IS 7 BP 1945 EP 1948 DI 10.1118/1.1760769 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 839NA UT WOS:000222790600001 PM 15305443 ER PT J AU Paganetti, H Jiang, H Lee, SY Kooy, HM AF Paganetti, H Jiang, H Lee, SY Kooy, HM TI Accurate Monte Carlo simulations for nozzle design, commissioning and quality assurance for a proton radiation therapy facility SO MEDICAL PHYSICS LA English DT Article DE proton therapy; Monte Carlo; Bragg peak; quality assurance ID NUCLEAR-INTERACTIONS; BEAM; SCATTERING; RADIOTHERAPY; PARTICLES; DOSIMETRY; NEUTRON; MODELS AB Monte Carlo dosimetry calculations are essential methods in radiation therapy. To take full advantage of this tool, the beam delivery system has to be simulated in detail and the initial beam parameters have to be known accurately. The modeling of the beam delivery system itself opens various areas where Monte Carlo calculations prove extremely helpful, such as for design and commissioning of a therapy facility as well as for quality assurance verification. The gantry treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH) were modeled in detail using the GEANT4.5.2 Monte Carlo code. For this purpose, various novel solutions for simulating irregular shaped objects in the beam path, like contoured scatterers, patient apertures or patient compensators, were found. The four-dimensional, in time and space, simulation of moving parts, such as the modulator wheel, was implemented. Further, the appropriate physics models and cross sections for proton therapy applications were defined. We present comparisons between measured data and simulations. These show that by modeling the treatment nozzle with millimeter accuracy, it is possible to reproduce measured dose distributions with an accuracy in range and modulation width, in the case of a spread-out Bragg peak (SOBP), of better than 1 mm. The excellent agreement demonstrates that the simulations can even be used to generate beam data for commissioning treatment planning systems. The Monte Carlo nozzle model was used to study mechanical optimization in terms of scattered radiation and secondary radiation in the design of the nozzles. We present simulations on the neutron background. Further, the Monte Carlo calculations supported commissioning efforts in understanding the sensitivity of beam characteristics and how these influence the dose delivered. We present the sensitivity of dose distributions in water with respect to various beam parameters and geometrical misalignments. This allows the definition of tolerances for quality assurance and the design of quality assurance procedures. (C) 2004 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. FU NCI NIH HHS [CA 21239] NR 31 TC 135 Z9 136 U1 3 U2 12 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 2004 VL 31 IS 7 BP 2107 EP 2118 DI 10.1118/1.1762792 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 839NA UT WOS:000222790600021 PM 15305464 ER PT J AU Buckley, TC Mozley, SL Bedard, MA Dewulf, AC Greif, J AF Buckley, TC Mozley, SL Bedard, MA Dewulf, AC Greif, J TI Preventive health behaviors, health-risk behaviors, physical morbidity, and health-related role functioning impairment in veterans with post-traumatic stress disorder SO MILITARY MEDICINE LA English DT Article ID ABUSE SCREENING-TEST; POPULATION; SYMPTOMS; MEN AB An examination of the relationships between health behaviors (preventive and risk-related), physician-diagnosed medical problems, role-functioning impairment because of physical morbidity, and post-traumatic stress disorder was conducted on a large cohort of consecutive treatment-seeking cases IN 826) presenting to an outpatient Veterans Affairs post-traumatic stress disorder clinic. Results revealed that the sample rates of several medical conditions were markedly elevated when compared with general population rates for men of a comparable age. The rates of smoking and other behavioral risk variables were greater than rates among men in the general population. Moreover, the majority of the sample did not engage in preventive health behaviors such as exercise and medical screening at levels consistent with health care guidelines. Physical role functioning indices of the SF-36 reveal greater role-functioning impairment because of physical morbidity in this psychiatric sample relative to the age adjusted general population norms. The health care implications of these data are discussed, as are areas for future research. C1 Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Catholique Louvain, B-1200 Brussels, Belgium. RP Buckley, TC (reprint author), Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. NR 27 TC 71 Z9 71 U1 2 U2 7 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 2004 VL 169 IS 7 BP 536 EP 540 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 019IY UT WOS:000235830000012 PM 15291186 ER PT J AU Wang, XZ Andreassen, PR D'Andrea, AD AF Wang, XZ Andreassen, PR D'Andrea, AD TI Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; FANCONI-ANEMIA PROTEINS; ATM-DEPENDENT PHOSPHORYLATION; HOMOLOGY-DIRECTED REPAIR; NUCLEAR-COMPLEX; BRCA PATHWAY; RAD51; RECOMBINATION; BINDING; CANCER AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with at least 11 complementation groups (A, B, C, D1, D2, E, F, G, 1, J, and L), and eight FA genes have been cloned. The FANCD] gene is identical to the breast cancer susceptibility gene, BRCA2. The FA proteins cooperate in a common pathway, but the function of BRCA2/FANCD1 in this pathway remains unknown. Here we show that monoubiquitination of FANCD2, which is activated by DNA damage, is required for targeting of FANCD2 to chromatin, where it interacts with BRCA2. FANCD2-Ub then promotes BRCA2 loading into a chromatin complex. FANCD2(-/-) cells are deficient in the assembly of DNA damage-inducible BRCA2 foci and in chromatin loading of BRCA2. Functional complementation with the FANCD2 cDNA restores BRCA2 foci and its chromatin loading following DNA damage. BRCA2(-/-) cells expressing a carboxy-terminal truncated BRCA2 protein form IR-inducible BRCA2 and FANCD2 foci, but these foci fail to colocalize. Functional complementation of these cells with wild-type BRCA2 restores the interaction of BRCA2 and FANCD2. The C terminus of BRCA2 is therefore required for the functional interaction of BRCA2 and FANCD2 in chromatin. Taken together, our results demonstrate that monoubiquitination of FANCD2, which is regulated by the FA pathway, promotes BRCA2 loading into chromatin complexes. These complexes appear to be required for normal homology-directed DNA repair. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu FU NHLBI NIH HHS [P01HL54785, P50 HL054785, R01 HL052725, R01HL52725]; NIDDK NIH HHS [R01 DK043889, R01DK43889] NR 33 TC 231 Z9 241 U1 2 U2 6 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 JUL PY 2004 VL 24 IS 13 BP 5850 EP 5862 DI 10.1128/MCB.24.13.5850-5862.2004 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 830UL UT WOS:000222149200021 PM 15199141 ER PT J AU Le Cam, L Lacroix, M Ciemerych, MA Sardet, C Sicinski, P AF Le Cam, L Lacroix, M Ciemerych, MA Sardet, C Sicinski, P TI The E4F protein is required for mitotic progression during embryonic cell cycles SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR P120(E4F); DNA-DAMAGE; CHECKPOINT; GENE; IDENTIFICATION; MITOSIS; ARREST; MICE; PHOSPHORYLATION; LOCALIZATION AB The ubiquitously expressed E4F protein was originally identified as an E1A-regulated cellular transcription factor required for adenovirus replication. The function of this protein in normal cell physiology remains largely unknown. To address this issue, we generated E4F knockout mice by gene targeting. Embryos lacking E4F die at the peri-implantation stage, while in vitro-cultured E4F(-/-) blastocysts exhibit defects in mitotic progression, chromosomal missegregation, and increased apoptosis. Consistent with these observations, we found that E4F localizes to the mitotic spindle during the M phase of early embryos. Our results establish a crucial role for E4F during early embryonic cell cycles and reveal an unexpected function for E4F in mitosis. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CNRS, Inst Mol Genet, UMR 5535, IFR122, F-34293 Montpellier, France. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu RI Le Cam, Laurent/O-1408-2016 NR 36 TC 30 Z9 31 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 JUL PY 2004 VL 24 IS 14 BP 6467 EP 6475 DI 10.1128/MCB.24.14.6467-6475.2004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 835NQ UT WOS:000222490900031 PM 15226446 ER PT J AU Duan, ZF Brakora, KA Seiden, MV AF Duan, ZF Brakora, KA Seiden, MV TI Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article; Proceedings Paper CT RNAi 2003 Boston Meeting CY MAY 05-06, 2003 CL Waltham, MA SP RNAi ID P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; MONOCLONAL-ANTIBODIES; PHASE-II; GENE; PHENOTYPE; LEUKEMIA; LINES; CDNA AB Ovarian cancer is currently the most lethal gynecologic malignancy in developed countries, and paclitaxel is a cornerstone in the treatment of this malignancy. Unfortunately, the efficacy of paclitaxel is limited by the development of drug resistance. Clinical paclitaxel resistance is often associated with ABCB1 (MDR1) overexpression, and in vitro paclitaxel resistance typically demonstrates overexpression of the ABCB1 gene. In this study, we demonstrate that paclitaxel-resistant cell lines overexpress both ABCB1 and ABCB4 (MDR3). To evaluate the role of these transporters in paclitaxel-resistant ovarian cancer cells, small interference RNAs (siRNAs) were used to target ABCB1 and ABCB4 RNA in the paclitaxel-resistant SKOV-3(TR) and OVCAR8(TR) ovarian cancer cell lines. Treatment of these lines with either chemically synthesized siRNAs or transfection with specific vectors that express targeted siRNAs demonstrated decreased mRNA and protein levels of ABCB1 or ABCB4. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays of siRNA-treated cells demonstrated 7- to 12.4-fold reduction of paclitaxel resistance in the lines treated with the synthesized siRNA of ABCB1 and 4.7- to 7.3-fold reduction of paclitaxel resistance in the cell lines transfected with siRNA of ABCB1 expressing vectors. ABCS4 siRNA-treated cell lines showed minor reduction in paclitaxel resistance. These results indicate that siRNA targeted to ABCB1 can sensitize paclitaxel-resistant ovarian cancer cells in vitro and suggest that siRNA treatment may represent a new approach for the treatment of ABCB1-mediated drug resistance. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640, Boston, MA 02114 USA. EM mseiden@partners.org FU NCI NIH HHS [CA 89150] NR 28 TC 117 Z9 131 U1 3 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2004 VL 3 IS 7 BP 833 EP 838 PG 6 WC Oncology SC Oncology GA 838SB UT WOS:000222732300008 PM 15252144 ER PT J AU Zhou, YL Scolavino, S Funderburk, SF Ficociello, LF Zhang, X Klibanski, A AF Zhou, YL Scolavino, S Funderburk, SF Ficociello, LF Zhang, X Klibanski, A TI Receptor internalization-independent activation of Smad2 in activin signaling SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SERINE THREONINE KINASE; FYVE DOMAIN PROTEIN; II RECEPTOR; SERINE/THREONINE KINASES; CLATHRIN ADAPTERS; ENDOCYTOSIS; EXPRESSION; CLONING; COMPLEX AB Activin, a member of the TGFbeta family of cytokines, signals through heteromeric transmembrane complexes composed of type I and type II Ser/Thr kinase receptors. Activated by type II receptors, the type I receptor phosphorylates, thereby activating its effectors Smad2 and Smad3. It has been shown that the ligand-bound TGFbeta receptors endocytose to early endosomes, where they phosphorylate Smads. However, whether TGFbeta and activin can signal without receptor internalization is still in question. We report that a mutation changing Trp(477) to Ala in the kinase domain rendered the type I activin receptor Alk4 unable to undergo ligand-dependent internalization. However, the resultant receptor, named Alk4W(477) A, retained the ability to phosphorylate Smad2 and mediate activin-induced transcription activation. Also, a Trp(477) to Ala mutation abolished the endocytosis of Alk4T(206) D, a constitutively active type I activin receptor. The action of the mutant Alk4T(206) D became activin dependent. Finally, blocking endocytosis by depletion of intracellular potassium did not inhibit Smad2 phosphorylation by Alk4W(477) A. Taken together, our data indicate that activin receptors can transduce activin signals without endocytosis and suggest the possibility that an endocytosis-independent activin signaling pathway exists, which may act as an alternative mechanism for signal transduction. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCI NIH HHS [F32 CA88519]; NIDDK NIH HHS [R01-DK-40947] NR 50 TC 19 Z9 19 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2004 VL 18 IS 7 BP 1818 EP 1826 DI 10.1210/me.2004-0079 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 832HV UT WOS:000222259000020 PM 15087470 ER PT J AU Babic, AM Wang, HW Lai, MJ Daniels, TG Felbinger, TW Burger, PC Stricker-Krongrad, A Wagner, DD AF Babic, AM Wang, HW Lai, MJ Daniels, TG Felbinger, TW Burger, PC Stricker-Krongrad, A Wagner, DD TI ICAM-1 and beta 2 integrin deficiency impairs fat oxidation and insulin metabolism during fasting SO MOLECULAR MEDICINE LA English DT Article ID ACTIVATED PROTEIN-KINASE; QUANTITATIVE EXPRESSION; C-PEPTIDE; OBESITY; LIVER; INFLAMMATION; LFA-1; RAT; STARVATION; RESISTANCE AB Intercellular adhesion molecule 1 (ICAM-1) and beta 2 integrins play critical roles in immune responses. ICAM-1 may also participate in regulation of energy balance because ICAM-1-deficient mice become obese on a high-fat diet. We show that mice deficient in these adhesion receptors are unable to respond to fasting by up-regulation of fatty acid oxidation. Normal mice, when fasted, exhibit reduced circulating neutrophil counts and increased ICAM-1 expression and neutrophil recruitment in liver. Mice lacking ICAM-1 or 132 integrins fail to show these responses-instead they become hypoglycemic with steatotic livers. Fasting ICAM-1-deficient mice reduce insulin more slowly than wild-type mice. This produces fasting hyperinsulinemia that prevents activation of adenosine mono-phosphate (AMP)-activated protein kinase in muscles and liver, which results in decreased import of long chain fatty acids into mitochondria. Thus, we show a new role for immune cells and their adhesion receptors in regulating metabolic response to fasting. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Clin Pathol, Boston, MA 02115 USA. Millennium Pharmaceut, Metab Dis Physiol & Pharmacol, Cambridge, MA USA. Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Wagner, DD (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R01 HL053756, R01-HL53756] NR 36 TC 5 Z9 5 U1 0 U2 1 PU NORTH SHORE-LONG ISLAND JEWISH RESEARCH INSTITUTE PI MANHASSET PA 350 COMMUNITY DRIVE, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JUL-DEC PY 2004 VL 10 IS 7-12 BP 72 EP 79 DI 10.2119/2004-00038.Wagner PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 994LM UT WOS:000234033300002 PM 15706402 ER PT J AU Yildiz, FH Liu, XS Heydorn, A Schoolnik, GK AF Yildiz, FH Liu, XS Heydorn, A Schoolnik, GK TI Molecular analysis of rugosity in a Vibrio cholerae O1 El Tor phase variant SO MOLECULAR MICROBIOLOGY LA English DT Article ID VIRULENCE GENE-EXPRESSION; ALTERNATIVE SIGMA-FACTOR; VPS BIOSYNTHESIS GENES; BIOFILM FORMATION; ESCHERICHIA-COLI; EXOPOLYSACCHARIDE PRODUCTION; POLYSACCHARIDE PRODUCTION; COLONY MORPHOLOGY; II SECRETION; SURVIVAL AB Reversible phase variation between the rugose and smooth colony variants is predicted to be important for the survival of Vibrio cholerae in natural aquatic habitats. Microarray expression profiling studies of the rugose and smooth variants of the same strain led to the identification of 124 differentially regulated genes. Further expression profiling experiments showed how these genes are regulated by the VpsR and HapR transcription factors, which, respectively, positively and negatively regulate production of VPSEl Tor, a rugose-associated extracellular polysaccharide. The study of mutants of rpoN and rpoS demonstrated the effects of these alternative sigma factors on phase variation-specific gene expression. Bioinformatics analysis of these expression data shows that 'rugosity' and 'smoothness' are determined by a complex hierarchy of positive and negative regulators, which also affect the biofilm, surface hydrophobicity and motility phenotypes of the organism. C1 Univ Calif Santa Cruz, Dept Environm Toxicol, Santa Cruz, CA 95064 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Copenhagen, Panum Inst, Dept Pharmacol, DK-2200 Copenhagen, Denmark. Stanford Univ, Sch Med, Beckman Ctr, Dept Med,Div Infect Dis & Geog Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Beckman Ctr, Dept Microbiol & Immunol, Stanford, CA 94305 USA. RP Yildiz, FH (reprint author), Univ Calif Santa Cruz, Dept Environm Toxicol, 269 Jack Baskin Engn Bldg, Santa Cruz, CA 95064 USA. EM yildiz@etox.ucsc.edu FU NIAID NIH HHS [R01-AI43422] NR 53 TC 141 Z9 148 U1 1 U2 9 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 JUL PY 2004 VL 53 IS 2 BP 497 EP 515 DI 10.1111/j.1365-2958.2004.04154.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 834PM UT WOS:000222423000014 PM 15228530 ER PT J AU Liu, J Wolfe, D Hao, SL Huang, SH Glorioso, JC Mata, M Fink, DJ AF Liu, J Wolfe, D Hao, SL Huang, SH Glorioso, JC Mata, M Fink, DJ TI Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain SO MOLECULAR THERAPY LA English DT Article DE gene therapy; spinal cord injury; neuropathic pain; HSV; GABA; GAD ID SUPERFICIAL DORSAL HORN; NEUROPATHIC PAIN; INTRATHECAL BACLOFEN; CENTRAL SENSITIZATION; EVOKED ALLODYNIA; NERVE INJURY; RAT; GABA; INHIBITION; MECHANISMS AB Neuropathic pain after spinal cord injury (SCI) represents a difficult problem that is commonly refractory to conventional medical management. To determine if spinal release of gamma-amino butyric acid (GABA) could reduce below-level central neuropathic pain after SCI, we constructed a replication-incompetent herpes simplex virus (HSV)-based vector encoding one isoform of human glutamic acid decarboxylase (GAD67). Dorsal root ganglion (DRG) neurons transduced in vitro or in vivo by subcutaneous inoculation produced GAD and released GABA constitutively. T13 spinal cord hemisection resulted in central neuropathic pain manifested by mechanical allodynia and thermal hyperalgesia. Subcutaneous inoculation of the vector into both feet reduced both manifestations of below-level SCI pain; the vector-mediated effect was partially reversed by intrathecal bicuculline or phaclofen at doses that did not affect thresholds in normal or injured uninoculated animals. Vector-mediated GABA release attenuated the increase in spinal calcitonin gene-related peptide immunoreactivity caused by cord hemisection. These results suggest that HSV-mediated gene transfer to DRG could be used to treat below-level central neuropathic pain after incomplete SCI. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Ann Arbor VA Med Ctr, Ann Arbor, MI 48109 USA. RP Fink, DJ (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. EM djfink@umich.edu NR 43 TC 91 Z9 100 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2004 VL 10 IS 1 BP 57 EP 66 DI 10.1016/j.ymthe.2004.04.017 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843SF UT WOS:000223106100011 PM 15233942 ER PT J AU Puskovic, V Wolfe, D Goss, J Huang, SH Mata, M Glorios, JC Fink, DJ AF Puskovic, V Wolfe, D Goss, J Huang, SH Mata, M Glorios, JC Fink, DJ TI Prolonged biologically active transgene expression driven by HSV LAP2 in brain in vivo SO MOLECULAR THERAPY LA English DT Article DE gene therapy; herpes simplex virus; latency; Parkinson disease; glial cell-derived neurotrophic factor; 6-hydroxydopamine; MPTP; rat; mouse ID HERPES-SIMPLEX-VIRUS; LATENCY-ASSOCIATED TRANSCRIPT; MEDIATED GENE-TRANSFER; CENTRAL-NERVOUS-SYSTEM; TYPE-1 LATENCY; PARKINSONS-DISEASE; FUNCTIONAL RECOVERY; TRIGEMINAL GANGLIA; STAIRCASE TEST; MESSENGER-RNA AB Herpes simplex virus (HSV) naturally establishes a life-long latent state in neurons, characterized by the expression of latency-associated transcripts (LATs) in the absence of viral lytic functions, and the latency-associated promoter (LAP2) has been identified as a moveable element responsible for the expression of LATs from latent HSV genomes. Prolonged transgene expression will be required for the treatment of chronic diseases of the CNS using HSV vectors. We therefore examined the ability of LAP2 to drive prolonged expression of a biologically active transgene from latent HSV vector genomes in brain in vivo using the 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson disease. A replication-incompetent HSV vector containing the glial cell-derived neurotrophic factor (GDNF) under the control of LAP2 was injected into the substantia nigra and 5 and a half months later 6-OHDA was injected into the striatum. GDNF expression from the vector preserved dopaminergic function measured by histology and behavior 6 months after vector inoculation. Mice inoculated with the LAP2-GDNF replication-incompetent HSV vector followed by 3 months of daily low-dose MPTP injections were substantially protected against the consequences of that treatment measured by weekly behavioral testing and histologic measures at the conclusion of the experiment. These studies using subacute and chronic models of neurodegeneration demonstrate that the HSV LAP2 promoter element provides prolonged expression of relevant amounts of a transgene to produce significant biological effects in brain in vivo over the course of many months. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. Ann Arbor VA Healthcare Syst, Ann Arbor, MI 48109 USA. RP Fink, DJ (reprint author), Taubman Ctr, MD1914,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM djfink@umich.edu NR 53 TC 33 Z9 36 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2004 VL 10 IS 1 BP 67 EP 75 DI 10.1016/j.ymthe.2004.04.004 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843SF UT WOS:000223106100012 PM 15233943 ER PT J AU Erdag, G Medalie, DA Rakhorst, H Krueger, GG Morgan, JR AF Erdag, G Medalie, DA Rakhorst, H Krueger, GG Morgan, JR TI FGF-7 expression enhances the performance of bioengineered skin SO MOLECULAR THERAPY LA English DT Article DE fibroblast growth factor; skin; wound healing; vascularization; infection; tissue engineering ID KERATINOCYTE GROWTH-FACTOR; HUMAN EPIDERMAL-CELLS; EQUIVALENT; GENE; HYPERPROLIFERATION; DIFFERENTIATION; TISSUE; MODEL; MICE; KGF AB To improve the performance of bioengineered skin, we used a recombinant retrovirus encoding FGF-7 to modify diploid human keratinocytes genetically. Control or FGF-7-expressing keratinocytes were seeded onto acellular human dermis to form bioengineered skin. Gene-modified skin secreted significant levels of FGF-7 and formed a thicker and hyperproliferative epidermis with about four times the number of cells per square centimeter. Secretion of an endogenous trophic factor, VEGF, was increased similar to5-fold. Migration of FGF-7-expressing keratinocytes was stimulated as was the self-healing of bioengineered skin expressing FGF-7. When tested in a bacterial infection model, the antimicrobial properties of FGF-7-expressing skin were increased >500-fold against both gram-negative and gram-positive bacteria. After transplantation to full-thickness wounds on athymic mice, skin expressing FGF-7 was revascularized more rapidly. These results demonstrate that genetic modification can be used to enhance performance and that expression of FGF-7 augments several properties important to the wound-healing properties of bioengineered skin. C1 Brown Univ, Ctr Biomed Engn, Providence, RI 02912 USA. Brown Univ, Biomed Ctr, Dept Mol Pharmacol Physiol & Biotechol, Providence, RI 02912 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT 84132 USA. RP Morgan, JR (reprint author), Brown Univ, Biomed Ctr, Dept Mol Pharmacol Physiol & Biotechol, G-B 393,171 Meeting St, Providence, RI 02912 USA. EM Jeffrey_Morgan@Brown.edu OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 30 TC 24 Z9 32 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2004 VL 10 IS 1 BP 76 EP 85 DI 10.1016/j.ymthe.2004.04.013 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843SF UT WOS:000223106100013 PM 15233944 ER PT J AU Kamm, C Leung, J Joseph, S Dobyns, WB Brashear, A Breakefield, XO Ozelius, LJ AF Kamm, C Leung, J Joseph, S Dobyns, WB Brashear, A Breakefield, XO Ozelius, LJ TI Refined linkage to the RDP/DYT12 locus on 19q13.2 and evaluation of GRIK5 as a candidate gene SO MOVEMENT DISORDERS LA English DT Article DE DYT12; rapid-onset dystonia-parkinsonism; kainate receptor ID ONSET DYSTONIA-PARKINSONISM; BASAL GANGLIA; EXPRESSION; RECEPTORS; FAMILY AB By examining two previously described families with rapid-onset dystonia parkinsonism, we have identified a key recombination event that places the disease locus (DYT12) into a 5.9 cM interval flanked by markers D19S224 and D19S900. Evaluation of a positional candidate gene, the glutamate receptor subunit GRIK5, revealed no mutations. (C) 2004 Movement Disorder Society. C1 Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ozelius, LJ (reprint author), Albert Einstein Coll Med, Dept Mol Genet, Ullmann 1211,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM ozelius@aecom.vu.edu RI Brashear, Allison/G-3853-2015; OI Dobyns, William/0000-0002-7681-2844 FU NINDS NIH HHS [NS38372] NR 10 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2004 VL 19 IS 7 BP 845 EP 847 DI 10.1002/mds.20095 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 840JQ UT WOS:000222855000021 PM 15254951 ER PT J AU Han, JDJ Bertin, N Hao, T Goldberg, DS Berriz, GF Zhang, LV Dupuy, D Walhout, AJM Cusick, ME Roth, FP Vidal, M AF Han, JDJ Bertin, N Hao, T Goldberg, DS Berriz, GF Zhang, LV Dupuy, D Walhout, AJM Cusick, ME Roth, FP Vidal, M TI Evidence for dynamically organized modularity in the yeast protein-protein interaction network SO NATURE LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; SCALE DATA; IDENTIFICATION; ROBUSTNESS; MUTATIONS; COMPLEXES; DATABASE; SCREENS; GENES; MAP AB In apparently scale-free protein-protein interaction networks, or 'interactome' networks(1,2), most proteins interact with few partners, whereas a small but significant proportion of proteins, the 'hubs', interact with many partners. Both biological and nonbiological scale-free networks are particularly resistant to random node removal but are extremely sensitive to the targeted removal of hubs(1). A link between the potential scale-free topology of interactome networks and genetic robustness(3,4) seems to exist, because knockouts of yeast genes(5,6) encoding hubs are approximately threefold more likely to confer lethality than those of non-hubs(1). Here we investigate how hubs might contribute to robustness and other cellular properties for protein protein interactions dynamically regulated both in time and in space. We uncovered two types of hub: 'party' hubs, which interact with most of their partners simultaneously, and 'date' hubs, which bind their different partners at different times or locations. Both in silico studies of network connectivity and genetic interactions described in vivo support a model of organized modularity in which date hubs organize the proteome, connecting biological processes-or modules(7)-to each other, whereas party hubs function inside modules. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. 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, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Roth, Frederick/H-6308-2011; Dupuy, Denis/M-7299-2014; OI Bertin, Nicolas/0000-0002-9835-9606; Roth, Frederick/0000-0002-6628-649X; Walhout, Marian/0000-0001-5587-3608 NR 28 TC 949 Z9 982 U1 10 U2 82 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 1 PY 2004 VL 430 IS 6995 BP 88 EP 93 DI 10.1038/nature02555 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 833RP UT WOS:000222356800049 PM 15190252 ER PT J AU Hong, YK Foreman, K Shin, JW Hirakawa, S Curry, CL Sage, DR Libermann, T Dezube, BJ Fingeroth, JD Detmar, M AF Hong, YK Foreman, K Shin, JW Hirakawa, S Curry, CL Sage, DR Libermann, T Dezube, BJ Fingeroth, JD Detmar, M TI Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus SO NATURE GENETICS LA English DT Article ID GROWTH-FACTOR RECEPTOR-3; GENE-EXPRESSION; CELLS; IDENTIFICATION; ORIGIN; PROX1; KSHV AB Kaposi sarcoma is considered a neoplasm of lymphatic endothelium infected with Kaposi sarcoma-associated herpesvirus. It is characterized by the expression of lymphatic lineage-specific genes by Kaposi sarcoma tumor cells. Here we show that infection of differentiated blood vascular endothelial cells with Kaposi sarcoma-associated herpesvirus leads to their lymphatic reprogramming; induction of similar to70% of the main lymphatic lineage-specific genes, including PROX1, a master regulator of lymphatic development; and downregulation of blood vascular genes. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Beth Israel Deaconess Med Ctr, Dept Med, BIDMC Genom Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM michael.detmar@cbrc2.mgh.harvard.edu OI Curry, Christine L/0000-0003-4783-9623; Libermann, Towia/0000-0002-4006-8179 NR 15 TC 222 Z9 228 U1 0 U2 0 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 JUL PY 2004 VL 36 IS 7 BP 683 EP 685 DI 10.1038/ng1383 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 833QT UT WOS:000222354100016 PM 15220917 ER PT J AU Scadden, DT AF Scadden, DT TI Cancer stem cells refined SO NATURE IMMUNOLOGY LA English DT Editorial Material ID SCID MICE; LEUKEMIA; IDENTIFICATION AB A hierarchy of stem cells has been identified within leukemias, providing a more complex view of how these self-renewing populations parallel the normal stem cell compartment. As the resemblance between normal and malignant stem cells deepens, new opportunities for understanding and treating malignancy emerge. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St,Room 5212, Boston, MA 02129 USA. EM scadden.david@mgh.harvard.edu NR 10 TC 27 Z9 32 U1 1 U2 1 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 JUL PY 2004 VL 5 IS 7 BP 701 EP 703 DI 10.1038/ni0704-701 PG 4 WC Immunology SC Immunology GA 833IO UT WOS:000222331200014 PM 15224098 ER PT J AU Bender, TP Kremer, CS Kraus, M Buch, T Rajewsky, K AF Bender, TP Kremer, CS Kraus, M Buch, T Rajewsky, K TI Critical functions for c-Myb at three checkpoints during thymocyte development SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; DIFFERENTIAL EXPRESSION; GENE REARRANGEMENT; TRANSGENIC MICE; ALPHA; PHOSPHORYLATION; ACCESSIBILITY; ACTIVATION; SELECTION; ENHANCER AB The transcription factor c-Myb is expressed throughout T cell development in the thymus. However, little is understood about c-Myb function because of the embryonic lethality of traditional Myb-null mutations. Using tissue-specific deletion to abrogate c-Myb expression at distinct stages of T cell development, we identify three points at which c-Myb activity is required for normal T cell differentiation: transition through the double-negative 3 stage, survival of preselection CD4(+)CD8(+) thymocytes, and differentiation of CD4 thymocytes. Thus, c-Myb is essential at several stages during T cell development in the thymus. C1 Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. RP Bender, TP (reprint author), Univ Virginia Hlth Syst, Dept Microbiol, POB 800734, Charlottesville, VA 22908 USA. EM tpb3e@virginia.edu FU FIC NIH HHS [F06 TW002297, TW02297]; NCI NIH HHS [CA85842, R01 CA085842] NR 47 TC 129 Z9 130 U1 1 U2 4 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 JUL PY 2004 VL 5 IS 7 BP 721 EP 729 DI 10.1038/ni1085 PG 9 WC Immunology SC Immunology GA 833IO UT WOS:000222331200025 PM 15195090 ER PT J AU Kolonel, LN Altshuler, D Henderson, BE AF Kolonel, LN Altshuler, D Henderson, BE TI The multiethnic cohort study: Exploring genes, lifestyle and cancer risk SO NATURE REVIEWS CANCER LA English DT Review ID HAWAII UNITED-STATES; BREAST-CANCER; PROSTATE-CANCER; LINKAGE DISEQUILIBRIUM; LOS-ANGELES; JAPANESE-AMERICAN; PHYSICAL-ACTIVITY; ESTROGEN-LEVELS; HUMAN GENOME; BODY-SIZE AB The search for the causes of cancer and means of cancer prevention has entered a new era as recent developments allow correlation of environmental and behavioural exposures, genetic variation and patient outcomes. The Multiethnic Cohort Study was designed to take advantage of these advances to prospectively explore the roles of lifestyle and genetic susceptibility in the occurrence of cancer. The ethnic diversity of the cohort in this study provides a wide range of dietary exposures and genetic variation, thereby providing a unique dimension to this research. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA. RP Henderson, BE (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. EM behender@usc.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 57 TC 153 Z9 157 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JUL PY 2004 VL 4 IS 7 BP 519 EP 527 DI 10.1038/nrc1389 PG 9 WC Oncology SC Oncology GA 834UD UT WOS:000222435500012 PM 15229477 ER PT J AU Chaudhuri, J Alt, FW AF Chaudhuri, J Alt, FW TI Class-switch recombination: Interplay of transcription, DNA deamination and DNA repair SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID DOUBLE-STRAND BREAKS; DEPENDENT PROTEIN-KINASE; RNA EDITING ENZYME; SOMATIC HYPERMUTATION; B-CELLS; MISMATCH REPAIR; HISTONE H2AX; ANTIBODY DIVERSIFICATION; V(D)J RECOMBINATION; MU-REGION AB Class-switch recombination (CSR) of immunoglobulin heavy chains is the genetic process by which a B cell switches from the production of IgM to the production of IgG, IgE or IgA. Although the general characteristics of CSR have been known for some time, the detailed molecular mechanism of this process is only now emerging. CSR is unique, in that it seems to involve transcription-generated, higher-order RNA - DNA structures, specific DNA deamination and several DNA-repair pathways. In this review, we discuss our current knowledge of the mechanism of CSR and highlight the important unanswered questions. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu NR 106 TC 318 Z9 326 U1 0 U2 17 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 JUL PY 2004 VL 4 IS 7 BP 541 EP 552 DI 10.1038/nri1395 PG 12 WC Immunology SC Immunology GA 834UF UT WOS:000222435700016 PM 15229473 ER PT J AU Bacskai, BJ Skoch, J Klunk, WE Nesterov, E Swager, TM Mathis, CA Dunn, A Hyman, BT AF Bacskai, BJ Skoch, J Klunk, WE Nesterov, E Swager, TM Mathis, CA Dunn, A Hyman, BT TI Novel approaches for non-invasive optical detection of amyloid-beta plaques in vivo SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. MIT, Cambridge, MA 02139 USA. EM bbacskai@partners.org RI Mathis, Chester/A-8607-2009; Swager, Timothy/H-7459-2012 OI Swager, Timothy/0000-0002-3577-0510 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S57 EP S58 DI 10.1016/S0197-4580(04)80194-5 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700194 ER PT J AU Barnham, KJ Haeffner, F Ciccotosto, GD Curtain, CC Tew, D Masters, CL Chemy, RA Cappai, R Bush, AI AF Barnham, KJ Haeffner, F Ciccotosto, GD Curtain, CC Tew, D Masters, CL Chemy, RA Cappai, R Bush, AI TI The mechanism by which A beta produces hydrogen peroxide and its role in neurotoxicity SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Melbourne, Parkville, Vic 3052, Australia. Mental Hlth Res Inst, Melbourne, Vic, Australia. Stockholm Univ, Dept Phys, S-10691 Stockholm, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol, Cambridge, MA 02138 USA. EM kbarnham@unimelb.edu.au RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007 OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069 NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S544 EP S544 DI 10.1016/S0197-4580(04)81799-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701795 ER PT J AU Berezovska, O Lleo, A Herl, L Hyman, BT AF Berezovska, O Lleo, A Herl, L Hyman, BT TI Molecular conformation of PS1 is affected by FAD mutations SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM oberezovska@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S62 EP S62 DI 10.1016/S0197-4580(04)80210-0 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700210 ER PT J AU Bertram, L Hiltunen, M Parkinson, M Mullin, K Moscarillo, T Becker, KD Elliott, KJ AF Bertram, L Hiltunen, M Parkinson, M Mullin, K Moscarillo, T Becker, KD Elliott, KJ TI Genetic association of UBQLN1 and Alzheimer's disease in multiple independent study populations SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. Neurogenet Inc, La Jolla, CA USA. Kuopio Univ Hosp, SF-70210 Kuopio, Finland. EM bertram@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S509 EP S509 DI 10.1016/S0197-4580(04)81677-4 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701674 ER PT J AU Blacker, D AF Blacker, D TI Alzheimer's genetics: Where are we now, and where are we going? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM blacker@psych.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S26 EP S26 DI 10.1016/S0197-4580(04)80084-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700085 ER PT J AU Breitner, JCS Zandi, PP Li, G Rea, TD Psaty, BM AF Breitner, JCS Zandi, PP Li, G Rea, TD Psaty, BM TI Can statins prevent AD, or are they just prescribed less often to those with cognitive disorders? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 GRECC, VA Puget Sound HCS, Seattle, WA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. EM jcsb@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S5 EP S5 DI 10.1016/S0197-4580(04)80016-2 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700017 ER PT J AU Brendza, RP Bacskai, BJ Simmons, KA Skoch, JM Klunk, WE Mathis, CA Bales, KR Paul, SM Holtzman, DM AF Brendza, RP Bacskai, BJ Simmons, KA Skoch, JM Klunk, WE Mathis, CA Bales, KR Paul, SM Holtzman, DM TI In vivo dynamics of amyloid associated neuritic dystrophy before and after anti-A beta immunotherapy SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Washington Univ, Sch Med, St Louis, MO USA. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. Eli Lilly Inc, Indianapolis, IN USA. EM brendzab@neuro.wustl.edu RI Mathis, Chester/A-8607-2009 NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S241 EP S242 DI 10.1016/S0197-4580(04)80810-8 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700808 ER PT J AU Bush, AI AF Bush, AI TI Copper and zinc in Alzheimer's disease: From bench to clinic SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. EM bush@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S69 EP S70 DI 10.1016/S0197-4580(04)80236-7 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700236 ER PT J AU Choi, EK Choi, JK Jin, YL Jin, JK Lee, JH Lee, HP Buxbaum, JD Wasco, W Carp, RI Kim, YS AF Choi, EK Choi, JK Jin, YL Jin, JK Lee, JH Lee, HP Buxbaum, JD Wasco, W Carp, RI Kim, YS TI Expression and potential roles of the members of calsenilin family in the brains of scrapie-infected mice SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Hallym Univ, Ilsong Inst Life Sci, Anyang, Kyonggi Do, South Korea. Harvard Univ, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. Mt Sinai Sch Med, Lab Mol Neuropsychiat, New York, NY USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Dept Microbiol, Chunchon, Kangwon Do, South Korea. EM ekchoi@hallym.ac.kr NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S456 EP S456 DI 10.1016/S0197-4580(04)81504-5 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701501 ER PT J AU Cooper, MJ Deng, A Rebeck, GW AF Cooper, MJ Deng, A Rebeck, GW TI Modulation of brain cholesterol metabolism by the liver X receptor: Effects on A beta levels SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Georgetown Univ, Washington, DC 20057 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mjc68@georgetown.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S157 EP S157 DI 10.1016/S0197-4580(04)80528-1 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700526 ER PT J AU Desikan, RS Fischl, B Dale, AM Salat, DH Makris, N Buckner, RL Albert, MS Killiany, R AF Desikan, RS Fischl, B Dale, AM Salat, DH Makris, N Buckner, RL Albert, MS Killiany, R TI Development of automated identification of cortical regions on MRI scans in AD patients SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO USA. Johns Hopkins Univ, Baltimore, MD USA. EM desikan@bu.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S376 EP S376 DI 10.1016/S0197-4580(04)81233-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701231 ER PT J AU Dickerson, BC Salat, DH Bates, JF Atiya, M Killiany, RJ Greve, DN Dale, AM Stern, CE Blacker, D Albert, MS Sperling, RA AF Dickerson, BC Salat, DH Bates, JF Atiya, M Killiany, RJ Greve, DN Dale, AM Stern, CE Blacker, D Albert, MS Sperling, RA TI Functional and structural MRI in questionable AD: Relationships to clinical impairment and future decline SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. Boston Univ, Boston, MA 02215 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. EM bradd@nmr.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S272 EP S273 DI 10.1016/S0197-4580(04)80912-6 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700910 ER PT J AU Duda, JE Moberg, PJ Balderston, C Roalf, DR Doty, RL Stern, MB AF Duda, JE Moberg, PJ Balderston, C Roalf, DR Doty, RL Stern, MB TI Meta-analysis of olfactory dysfunction in Alzheimer's, Parkinson's and Huntington's Diseases SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. EM john.duda@med.va.gov RI Doty, Richard/B-7623-2012; Doty, Richard/G-1602-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S95 EP S95 DI 10.1016/S0197-4580(04)80320-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700318 ER PT J AU Fadeeva, JV Walsh, DM Tang, J Luo, Y Citron, M Wasco, W Selkoe, DJ AF Fadeeva, JV Walsh, DM Tang, J Luo, Y Citron, M Wasco, W Selkoe, DJ TI Generation of the intracellular C-terminal domain of the APP family of proteins does not require beta-secretase SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Ctr Neurol Dis, Boston, MA USA. Univ Coll Dublin, Consway Inst, Dublin 2, Ireland. Univ Oklahoma, Med Ctr, Oklahoma City, OK USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Massachusetts Gen Hosp, Charlestown, MA USA. EM jfadeeva@rics.bwh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S158 EP S158 DI 10.1016/S0197-4580(04)80531-1 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700529 ER PT J AU Go, RC Perry, RT Wiener, H Bassett, SS Blacker, D Devlin, BJ Sweet, RA AF Go, RC Perry, RT Wiener, H Bassett, SS Blacker, D Devlin, BJ Sweet, RA TI Neuregulin-1 polymorphism in load with psychosis in the NIMH AD sibling families SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Alabama, Birmingham, AL USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM rgo@uab.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S488 EP S488 DI 10.1016/S0197-4580(04)81611-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701608 ER PT J AU Goldstein, LE Hartley, DM Moir, RD Blakely, EA Chang, PI Marcus, MA Martin-Rehrmann, M Ko, G Ericsson, MH Huang, XD Tanzi, RE Bush, AI Chylack, LT AF Goldstein, LE Hartley, DM Moir, RD Blakely, EA Chang, PI Marcus, MA Martin-Rehrmann, M Ko, G Ericsson, MH Huang, XD Tanzi, RE Bush, AI Chylack, LT TI (A beta) in human lens & aqueous humor: Further characterization of a novel AD biomarker SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. SRI Int, Menlo Pk, CA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S135 EP S136 DI 10.1016/S0197-4580(04)80454-8 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700452 ER PT J AU Hale, C Baker, LD Reger, M Rhoads, K Cholerton, B Watson, GS Craft, S AF Hale, C Baker, LD Reger, M Rhoads, K Cholerton, B Watson, GS Craft, S TI Agraphic changes in mild cognitive impairment SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Puget Sound, Tacoma, WA 98416 USA. Univ Washington, Seattle, WA 98195 USA. GRECC, VA Puget Sound HCS, Seattle, WA USA. EM hale@ups.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S338 EP S338 DI 10.1016/S0197-4580(04)81112-6 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701110 ER PT J AU Hayden, KM Norton, MC Tschanz, JT Zandi, PP Lyketsos, CG Khachaturian, AS Pieper, CF Welsh-Bohmer, KA Breitner, JC AF Hayden, KM Norton, MC Tschanz, JT Zandi, PP Lyketsos, CG Khachaturian, AS Pieper, CF Welsh-Bohmer, KA Breitner, JC TI The complex role of cardiovascular risk factors, cerebrovascular disease, and gender, with the incidence of Alzheimer's disease: Findings from the Cache County Study SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Duke Univ, Med Ctr, Ctr Study Aging, Durham, NC 27706 USA. Utah State Univ, Dept Family Consumer & Hlth Dev, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD USA. Khachaturian & Associates Inc, Potomac, MD USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27706 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM khayden@duke.edu RI Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S388 EP S388 DI 10.1016/S0197-4580(04)81268-5 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701266 ER PT J AU Hill, WD Perry, RT Wiener, H Harrell, L Gearha, DA Ozcan, O Blacker, D Tanzi, RE McInnis, MG Bassett, SSD Go, RCP AF Hill, WD Perry, RT Wiener, H Harrell, L Gearha, DA Ozcan, O Blacker, D Tanzi, RE McInnis, MG Bassett, SSD Go, RCP TI Protection from AD by the XmnI gamma (G) polymorphism may be mediatedby interactions between vascular Ab1-42 and methemoglobin SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Med Coll Georgia, Augusta, GA 30912 USA. Univ Alabama, Birmingham, AL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. EM whill@mail.mcg.edu RI Hill, William/F-9632-2012; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S507 EP S507 DI 10.1016/S0197-4580(04)81672-5 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701669 ER PT J AU Hiltunen, M Bertram, L Lu, A Xie, ZC Tanzi, RE AF Hiltunen, M Bertram, L Lu, A Xie, ZC Tanzi, RE TI Effects of ubiquilin-1 RNA interference (RNAI) on APP processing SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. EM mhiltunen@partners.org NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S154 EP S154 DI 10.1016/S0197-4580(04)80517-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700515 ER PT J AU Hirschman, KB James, BD Joyce, CM Karlawish, JH Casarett, D AF Hirschman, KB James, BD Joyce, CM Karlawish, JH Casarett, D TI Do Alzheimer's disease patients want to participate in an AD treatment decision and will their family let them? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equit Res & Promot, Philadelphia, PA USA. Ctr Bioeth, Dept Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. EM hirschk@mail.med.upenn.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S21 EP S22 DI 10.1016/S0197-4580(04)80070-8 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700071 ER PT J AU Ingelsson, M Cantuti-Castelvetri, I Ramasamy, K Orne, JD Augustinack, JC Vanderburg, CR Growdon, JH Frosch, MP Irizarry, MC Standaert, DG Hyman, BT AF Ingelsson, M Cantuti-Castelvetri, I Ramasamy, K Orne, JD Augustinack, JC Vanderburg, CR Growdon, JH Frosch, MP Irizarry, MC Standaert, DG Hyman, BT TI Analysis of gene expression in the Alzheimer's disease brain SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM mingelsson@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S420 EP S420 DI 10.1016/S0197-4580(04)81379-4 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701376 ER PT J AU Irizarry, MC Fukumoto, H Daly, E Gunther, J Hyman, BT Albert, MS Blacker, D AF Irizarry, MC Fukumoto, H Daly, E Gunther, J Hyman, BT Albert, MS Blacker, D TI Cross-sectional measures of plasma amyloid-beta protein do not correlate with functional status in prodromal Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Boston, MA USA. EM mirizarry@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S354 EP S354 DI 10.1016/S0197-4580(04)81164-3 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701162 ER PT J AU Johnson, KA Moran, EK Becker, JA Killiany, R Blacker, D Fischman, AJ Albert, M AF Johnson, KA Moran, EK Becker, JA Killiany, R Blacker, D Fischman, AJ Albert, M TI Prediction of clinical stability vs. progression in questionable ad using perfusion SPECT SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Johns Hopkins Univ, Baltimore, MD USA. EM kajohnson@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S300 EP S300 DI 10.1016/S0197-4580(04)80986-2 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700984 ER PT J AU Johnson, KA Rentz, DM Moran, EK Becker, JA Schlossmacher, MG Lewis, RSY Fischman, AJ AF Johnson, KA Rentz, DM Moran, EK Becker, JA Schlossmacher, MG Lewis, RSY Fischman, AJ TI Combined dopamine transporter and FDG PET IN DLB, AD, and PD SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. EM kajohnson@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S86 EP S87 DI 10.1016/S0197-4580(04)80293-8 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700292 ER PT J AU Johnson, SC Schmitz, TW Kawahara-Baccus, TN Jahn, NM Gleason, CE Carlsson, CM Sager, MA Rowley, HA Moritz, CH Meyerand, EM Asthana, S AF Johnson, SC Schmitz, TW Kawahara-Baccus, TN Jahn, NM Gleason, CE Carlsson, CM Sager, MA Rowley, HA Moritz, CH Meyerand, EM Asthana, S TI MCI patients with better RAVLt learning performance have greater FMRI activation in the anterior hippocampus during an encoding task SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Univ Wisconsin, Madison, WI 53706 USA. EM scj@medicine.wisc.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S275 EP S275 DI 10.1016/S0197-4580(04)80918-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700916 ER PT J AU Khachaturian, AS Zandi, PP Hayden, KM Lyketsos, CG Mayer, LS Skoog, I Tschanz, JT Norton, MC Welsh-Bohmer, KA Breitner, JCS AF Khachaturian, AS Zandi, PP Hayden, KM Lyketsos, CG Mayer, LS Skoog, I Tschanz, JT Norton, MC Welsh-Bohmer, KA Breitner, JCS TI Anti-hypertensive medication use may reduce risk of incident Alzheimer's disease. The cache county study SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Khachaturian & Associates Inc, Potomac, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Univ Gothenburg, Inst Clin Neurosci, Unit Neuropsychiat Epidemiol, Gothenburg, Sweden. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RI Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 NR 0 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S53 EP S53 DI 10.1016/S0197-4580(04)80181-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700181 ER PT J AU Kim, DY Ingano, LAM Carey, BW Pettingell, W Kovacs, DM AF Kim, DY Ingano, LAM Carey, BW Pettingell, W Kovacs, DM TI Voltage-gated sodium channel beta2 subunit is processed by alpha-, beta- and gamma-secretases, generating fragments elevated in AD brains SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM dkim@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S557 EP S558 DI 10.1016/S0197-4580(04)81848-7 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701844 ER PT J AU Kim, MJ Bertram, L Lu, A Tanzi, RE AF Kim, MJ Bertram, L Lu, A Tanzi, RE TI Functional analysis of the insulin degrading enzyme in genetically-associated AD families SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM mjkim@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S503 EP S503 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701657 ER PT J AU Koh, YH Ginestroni, A Tanzi, RE Tesco, G AF Koh, YH Ginestroni, A Tanzi, RE Tesco, G TI BACE1 is degraded via the lysosomal pathway SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM ykoh@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S527 EP S527 DI 10.1016/S0197-4580(04)81740-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701737 ER PT J AU Kovacs, DM AF Kovacs, DM TI Novel cholesterol-based regulation of beta- and gamma-secretase activities SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kovacs@helix.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S29 EP S29 DI 10.1016/S0197-4580(04)80095-2 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700096 ER PT J AU Kuller, LH Lopez, OL Jagust, WJ Becker, JT DeKosky, ST Lyketsos, C Kawas, C Breitner, JCS Fitzpatrick, A Dulberg, B AF Kuller, LH Lopez, OL Jagust, WJ Becker, JT DeKosky, ST Lyketsos, C Kawas, C Breitner, JCS Fitzpatrick, A Dulberg, B TI Clinical and MRI factors for vascular dementia in the Cardiovascular Health Study Cognition Study SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. Univ Pittsburgh, Dept Neurol & Psychiat, Pittsburgh, PA 15260 USA. Johns Hopkins Univ, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD 21218 USA. Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. VA Puget Sound Hlth Care Syst, Div Geriatr Psychiat Psychiat & Behav Sci, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM kullerl@edc.pitt.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S483 EP S484 DI 10.1016/S0197-4580(04)81597-5 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701594 ER PT J AU Kulstad, J Green, PS Cook, DG Watson, GS Reger, M Cholerton, B Baker, LD Plymate, SR Asthana, S Fishel, M Kahn, SE Craft, S AF Kulstad, J Green, PS Cook, DG Watson, GS Reger, M Cholerton, B Baker, LD Plymate, SR Asthana, S Fishel, M Kahn, SE Craft, S TI Effects of rosiglitazone treatment on serum amyloid-beta 1-40 and 1-42 in patients with early Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Med Ctr, Seattle, WA USA. Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. EM jkulstad@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S354 EP S355 DI 10.1016/S0197-4580(04)81167-9 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701165 ER PT J AU Li, GG Kukull, WA Peskind, E Moore, KV Higdon, R Tsuang, D van Belle, G McCormick, W Bowen, JD Teri, L Schellenberg, GD Larson, EB AF Li, GG Kukull, WA Peskind, E Moore, KV Higdon, R Tsuang, D van Belle, G McCormick, W Bowen, JD Teri, L Schellenberg, GD Larson, EB TI Statin therapy and risk of dementia in the elderly: A community-based prospective cohort study SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. EM gli@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S388 EP S389 DI 10.1016/S0197-4580(04)81269-7 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701267 ER PT J AU Li, GG Cherrier, M Tsuang, D Petrie, E Colasurdo, EPE Charles, WW Peskind, E Raskind, M AF Li, GG Cherrier, M Tsuang, D Petrie, E Colasurdo, EPE Charles, WW Peskind, E Raskind, M TI Salivary cortisol associated with cognitive decline in normal elderly SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM gli@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S357 EP S357 DI 10.1016/S0197-4580(04)81177-1 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701175 ER PT J AU Lichtenthaler, SF Schobel, S Neumann, S Seed, B Haass, C AF Lichtenthaler, SF Schobel, S Neumann, S Seed, B Haass, C TI Genome-wide screen identifies proteins stimulating the alpha- and beta-secretase cleavage of APP SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Munich, D-80539 Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM stefan.lichtenthaler@med.uni-muenchen.de RI Lichtenthaler, Stefan/B-6587-2016 OI Lichtenthaler, Stefan/0000-0003-2211-2575 NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S531 EP S531 DI 10.1016/S0197-4580(04)81756-1 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701753 ER PT J AU Lleo, A Berezovska, O Herl, L Raju, S Deng, A Irizarry, M Hyman, BT AF Lleo, A Berezovska, O Herl, L Raju, S Deng, A Irizarry, M Hyman, BT TI Nonsteroidal anti-inflammatory drugs (NSAIDs) lower A beta(42) and change presenilin1 confomation SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM alleo@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S567 EP S567 DI 10.1016/S0197-4580(04)81882-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701878 ER PT J AU McLean, PJ Klucken, J Shin, Y Hyman, BT AF McLean, PJ Klucken, J Shin, Y Hyman, BT TI Geldanamycin inhibits but does not reverse alpha-synuclein aggregation SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM pmclean@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S183 EP S183 DI 10.1016/S0197-4580(04)80617-1 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700615 ER PT J AU McMillan, PJ Leverenz, JB Bird, TD Schellenberg, GD Craft, S AF McMillan, PJ Leverenz, JB Bird, TD Schellenberg, GD Craft, S TI Insulin degrading enzyme immunostaining is decreased in the hippocampus of familial Alzheimer's disease subjects with presenilin 1 mutations SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM pammcm@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S556 EP S556 DI 10.1016/S0197-4580(04)81843-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701839 ER PT J AU Moir, RD Tseitlin, KA Soscia, S Hyman, BT Irizarry, MC Tanzi, RE AF Moir, RD Tseitlin, KA Soscia, S Hyman, BT Irizarry, MC Tanzi, RE TI Levels of autoantibodies to redox-modified abeta are attenuated in the plasma of Alzheimer's disease patients SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. EM moir@helix.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S35 EP S36 DI 10.1016/S0197-4580(04)80118-0 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700119 ER PT J AU Opazo, CR Luza, S Volitakis, I Masters, CL Bush, AI Chemy, R AF Opazo, CR Luza, S Volitakis, I Masters, CL Bush, AI Chemy, R TI Clioquinol targets metallated abeta in human Alzheimer's and Tg2576 mouse brains SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Melbourne, Mental Hlth Res Inst, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit,Lab Oxidat Biol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. EM copazo@mhri.edu.au RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S593 EP S593 DI 10.1016/S0197-4580(04)81975-4 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701971 ER PT J AU Rebeck, GW Deng, A Hyman, BT Irizarry, MC AF Rebeck, GW Deng, A Hyman, BT Irizarry, MC TI Apolipoprotein E inhibits gamma-secretase cleavage of the amyloid precursor protein SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Georgetown Univ, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EM gwr2@georgetown.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S14 EP S14 DI 10.1016/S0197-4580(04)80044-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700045 ER PT J AU Reger, M Watson, GS Cholerton, B Baker, LD Asthana, S Plymate, S Wilkinson, CW Peskind, ER Enstrom, K Hyde, K Belongia, D Craft, S AF Reger, M Watson, GS Cholerton, B Baker, LD Asthana, S Plymate, S Wilkinson, CW Peskind, ER Enstrom, K Hyde, K Belongia, D Craft, S TI Cortisol infusion attenuates insulin's facilitation of verbal memory in patients with Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. VA Puget Sound Hlth Care Syst, Tacoma, WA USA. EM mreger@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S168 EP S169 DI 10.1016/S0197-4580(04)80568-2 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700566 ER PT J AU Rhoads, K Cholerton, B Baker, LD Reger, M Watson, GS Plymate, S Fishel, MA Asthana, S Enstrom, K Keeling, M AF Rhoads, K Cholerton, B Baker, LD Reger, M Watson, GS Plymate, S Fishel, MA Asthana, S Enstrom, K Keeling, M TI The effect of insulin and octreotide on verbal memory and attention in cognitively impaired older adults SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Tacoma, WA USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. EM kristofferrhoads@med.va.gov NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S169 EP S169 DI 10.1016/S0197-4580(04)80569-4 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700567 ER PT J AU Robbins, EM Domnitz, SB Rebeck, GW Greenberg, SM Frosch, MP Bacskai, BJ AF Robbins, EM Domnitz, SB Rebeck, GW Greenberg, SM Frosch, MP Bacskai, BJ TI Progression of cerebrovascular beta-amyloid deposition in living mice SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgetown Univ, Washington, DC USA. EM erobbins@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S245 EP S245 DI 10.1016/S0197-4580(04)80823-6 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700821 ER PT J AU Rogers, JT Payton, S Greig, NH Jensen, R Cuny, G Lahiri, DK Morse, LJ Tanzi, RE Westaway, D Bush, A Gullans, S Sarang, S Huang, XD AF Rogers, JT Payton, S Greig, NH Jensen, R Cuny, G Lahiri, DK Morse, LJ Tanzi, RE Westaway, D Bush, A Gullans, S Sarang, S Huang, XD TI Alzheimer's disease drug discovery targeted to the APP MRNA 5 ' untranslated region, a validated target SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NIA, Baltimore, MD 21224 USA. Brigham & Womens Hosp, Cambridge, MA USA. Indiana Sch Med, Indianapolis, IN USA. Univ Toronto, Toronto, ON, Canada. EM Rogersj@helix.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S589 EP S589 DI 10.1016/S0197-4580(04)81959-6 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701955 ER PT J AU Rogers, JT Morse, LJ Lombardi, M Devaney, P Jensen, R AF Rogers, JT Morse, LJ Lombardi, M Devaney, P Jensen, R TI Metallothionein 3 gene expression is up-regulated by intracellular iron chelation, the role of a putative iron-responsive element in the 3 ' untranslated region SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Cambridge, MA USA. EM Rogersj@helix.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S545 EP S545 DI 10.1016/S0197-4580(04)81803-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701799 ER PT J AU Sager, MA Hermann, BP Gleason, C Johnson, S Cooper, J AF Sager, MA Hermann, BP Gleason, C Johnson, S Cooper, J TI Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 UW Med Sch, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI USA. Affin Hlth Syst, Oshkosh, WI USA. EM masager@wisc.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S115 EP S115 DI 10.1016/S0197-4580(04)80385-3 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700383 ER PT J AU Shin, Y McLean, PJ Hyman, BT AF Shin, Y McLean, PJ Hyman, BT TI Chip colocalizes with phosphorylated tau in neurofibrillary tangles in AD brain SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. EM yshin2@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S431 EP S431 DI 10.1016/S0197-4580(04)81418-0 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701415 ER PT J AU Sperling, R Dickerson, B Rand-Giovannetti, E Chua, EF Driscoll, AE Rentz, D Blacker, D Albert, MS AF Sperling, R Dickerson, B Rand-Giovannetti, E Chua, EF Driscoll, AE Rentz, D Blacker, D Albert, MS TI Increased medial temporal lobe FMRI activation in questionable AD compared to normal aging SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. EM reisa@rics.bwh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S383 EP S383 DI 10.1016/S0197-4580(04)81252-1 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701250 ER PT J AU Szot, P White, SS Leverenz, JB Greenup, L Peskind, ER Raskind, MA AF Szot, P White, SS Leverenz, JB Greenup, L Peskind, ER Raskind, MA TI Increased H-3-prazosin binding sites in the dentate gyrus of Alzheimer's disease and dementia with Lewy bodies is due to alpha(1A)-adrenoreceptors SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM szot@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S439 EP S440 DI 10.1016/S0197-4580(04)81448-9 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701445 ER PT J AU Tanzi, RE AF Tanzi, RE TI Regulating A-Beta: Clues from AD genetic studies SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. EM tanzi@helix.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S2 EP S2 DI 10.1016/S0197-4580(04)80004-6 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700005 ER PT J AU Tesco, G Koh, YH Dolios, G Trendafilova, VM Wang, R Tanzi, RE AF Tesco, G Koh, YH Dolios, G Trendafilova, VM Wang, R Tanzi, RE TI Increased activity of beta-amyloidogenic secretases via stabilization of BACE and gamma-secretase complex components during apoptosis SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Mt Sinai Sch Med, New York, NY USA. EM tescog@helix.mgh.harvard.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S530 EP S530 DI 10.1016/S0197-4580(04)81751-2 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058701748 ER PT J AU Tomidokoro, Y Rostagno, A Greenberg, SM Frangione, B Rebeck, WG Ghiso, J AF Tomidokoro, Y Rostagno, A Greenberg, SM Frangione, B Rebeck, WG Ghiso, J TI Biochemical analysis of A beta amyloid deposits in the Iowa variant of Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 NYU, Sch Med, Dept Pathol, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgetown Univ, Dept Neurosci, Washington, DC USA. EM tomidy01@popmail.med.nyu.edu RI Rostagno, Agueda/A-5801-2008 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S38 EP S38 DI 10.1016/S0197-4580(04)80125-8 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700126 ER PT J AU Tsuang, D Riekse, R Bird, T Muilenberg, M Steinbart, E McCutcheon, M Purganan, K Leverenz, J AF Tsuang, D Riekse, R Bird, T Muilenberg, M Steinbart, E McCutcheon, M Purganan, K Leverenz, J TI Familial dementia with Lewy bodies SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ N Dakota, Fargo, ND USA. EM dwt1I@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S86 EP S86 DI 10.1016/S0197-4580(04)80291-4 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700290 ER PT J AU Watson, GS Reger, MA Cholerton, BA Asthana, S Baker, LD Rhoads, KW Plymate, SR Fishel, MA Kahn, SE Craft, S AF Watson, GS Reger, MA Cholerton, BA Asthana, S Baker, LD Rhoads, KW Plymate, SR Fishel, MA Kahn, SE Craft, S TI Rosiglitazone preserves cognitive functions in patients with early Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA USA. Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. EM gswatson@u.washington.edu NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S83 EP S83 DI 10.1016/S0197-4580(04)80284-7 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700283 ER PT J AU Zaitchik, D Fitzpatrick, K Albert, M AF Zaitchik, D Fitzpatrick, K Albert, M TI Concepts of living things in patients with Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Conference on Alzheimers Disease and Related Disorders CY JUL 17-22, 2004 CL Philadelphia, PA SP Alzheimers Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. EM dzaitchiksamet@partners.org NR 0 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2004 VL 25 SU 2 BP S111 EP S111 DI 10.1016/S0197-4580(04)80371-3 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 843EK UT WOS:000223058700369 ER PT J AU Hadjikhani, N Joseph, RM Snyder, J Chabris, CF Clark, J Steele, S McGrath, L Vangel, M Aharon, I Feczko, E Harris, GJ Tager-Flusberg, H AF Hadjikhani, N Joseph, RM Snyder, J Chabris, CF Clark, J Steele, S McGrath, L Vangel, M Aharon, I Feczko, E Harris, GJ Tager-Flusberg, H TI Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces SO NEUROIMAGE LA English DT Article DE autism; asperger disorder; face perception; fusiform gyrus; visual processing ID PERVASIVE DEVELOPMENTAL DISORDERS; HUMAN EXTRASTRIATE CORTEX; HUMAN NEURAL SYSTEM; FACIAL EXPRESSIONS; OBJECT RECOGNITION; HUMAN BRAIN; FUNCTIONAL NEUROANATOMY; COORDINATE SYSTEM; CORTICAL SURFACE; HUMAN AMYGDALA AB Prior imaging studies have failed to show activation of the fusiform gyros in response to emotionally neutral faces in individuals with autism spectrum disorder (ASD) [Critchley et al., Brain 124 (2001) 2059; Schultz et al., Arch. Gen. Psychiatry 57 (2000) 331]. However, individuals with ASD do not typically exhibit the striking behavioral deficits that might be expected to result from fusiform gyrus damage, such as those seen in prosopagnosia, and their deficits appear to extend well beyond face identification to include a wide range of impairments in social perceptual processing. In this study, our goal was to further assess the question of whether individuals with ASD have abnormal fusiform gyrus activation to faces. We used high-field (3 T) functional magnetic resonance imaging to study face perception in 11 adult individuals with autism spectrum disorder (ASD) and 10 normal controls. We used face stimuli, object stimuli, and sensory control stimuli (Fourier scrambled versions of the face and object stimuli) containing a fixation point in the center to ensure that participants were looking at and attending to the images as they were presented. We found that individuals with ASD activated the fusiform face area and other brain areas normally involved in face processing when they viewed faces as compared to non-face stimuli. These data indicate that the face-processing deficits encountered in ASD are not due to a simple dysfunction of the fusiform area, but to more complex anomalies in the distributed network of brain areas involved in social perception and cognition. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02108 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02108 USA. RP Hadjikhani, N (reprint author), Harvard Univ, Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp,Martinos Ctr Biomed Imagin, Room 417, Charlestown, MA 02129 USA. EM nouchine@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008; Tager-Flusberg, Helen/D-5265-2009 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NCRR NIH HHS [P41RR14075]; NIDCD NIH HHS [P01/U19 DC 03610]; NINDS NIH HHS [R01 NS44824-01] NR 65 TC 181 Z9 187 U1 7 U2 30 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 JUL PY 2004 VL 22 IS 3 BP 1141 EP 1150 DI 10.1016/j.neuroimage.2004.03.025 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 834PO UT WOS:000222423200012 PM 15219586 ER PT J AU Roman, GC AF Roman, GC TI Brain hypoperfusion: a critical factor in vascular dementia SO NEUROLOGICAL RESEARCH LA English DT Article DE Binswanger disease; cardiac surgery; cognition; congestive heart failure; hypotension; stroke; vascular dementia ID CORONARY-ARTERY-BYPASS; CEREBRAL WHITE-MATTER; LOW BLOOD-PRESSURE; CONGESTIVE-HEART-FAILURE; COGNITIVE IMPAIRMENT; HIPPOCAMPAL SCLEROSIS; KUNGSHOLMEN PROJECT; ATRIAL-FIBRILLATION; PULSE PRESSURE; OFF-PUMP AB Subcortical ischemic vascular dementia is a relatively common form of dementia. Anatomical changes of ageing in the brain arteries predispose the elderly to the effects of hypotension. Depending on their circulatory pattern, particular regions of the brain are susceptible to ischemic hypoperfusive lesions. These regions include the periventricular white matter, basal ganglia, and hippocampus. Interruption of prefrontal-basal ganglia circuits important for cognition and memory may result from these lesions. Hypotension and hypoperfusion explain the high risk for the development of cognitive impairment and vascular dementia in older patients affected by orthostatic hypotension, congestive heart failure, as well as in those undergoing surgical procedures such as hip and knee replacement and coronary artery bypass graft (CABG). Recognition of the susceptibility of elderly subjects to cerebral lesions induced by hypoperfusion should result in appropriate preventive measures and better treatment. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, MSC 883,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM romang@uthscsa.edu NR 64 TC 99 Z9 109 U1 2 U2 4 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD JUL PY 2004 VL 26 IS 5 BP 454 EP 458 DI 10.1179/016164104225017686 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 836GZ UT WOS:000222545100002 PM 15265263 ER PT J AU Erkinjuntti, T Roman, G Gauthier, S AF Erkinjuntti, T Roman, G Gauthier, S TI Treatment of vascular dementia - evidence from clinical trials with cholinesterase inhibitors SO NEUROLOGICAL RESEARCH LA English DT Article DE cerebrovascular disease; dementia; elderly; vascular dementia; cholinesterase inhibitors ID ALZHEIMERS-DISEASE; CEREBROVASCULAR-DISEASE; COGNITIVE DECLINE; EFFICACY; RIVASTIGMINE; GALANTAMINE; DONEPEZIL; TOLERABILITY AB Cerebrovascular disease (CVD), as well as secondary ischemic brain injury from cardiovascular disease, are common causes of dementia and cognitive decline in the elderly. Also, CVD frequently contributes to cognitive loss in patients with Alzheimer's disease (AD). Progress in understanding the pathogenetic mechanism involved in vascular cognitive impairment and vascular dementia (VaD) has resulted in promising treatments of these conditions. Cholinergic deficits in VaD are due to ischemia of basal forebrain nuclei and of cholinergic pathways and can be treated with the use of the cholinesterase inhibitors used in AD. Controlled clinical trials with donepezil, galantamine, and rivastigmine in VaD, as well as in patients with AD plus CVD, have demostrated improvement in cognition, behavior and activites of daily living. C1 Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. A Murphy Vet Adm Hosp, San Antonio, TX USA. McGill Ctr Studies Aging, Alzheimers & Relates Disorders Res Unit, Montreal, PQ, Canada. RP Roman, G (reprint author), Dept Med, Div Neurol, MSC 883,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM romang@uthsca.edu NR 21 TC 7 Z9 8 U1 0 U2 0 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD JUL PY 2004 VL 26 IS 5 BP 603 EP 605 DI 10.1179/01610425017631 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 836GZ UT WOS:000222545100022 PM 15265282 ER PT J AU Chapman, PH Ogilvy, CS Loeffler, JS AF Chapman, PH Ogilvy, CS Loeffler, JS TI The relationship between occlusive hyperemia and complications associated with the radiosurgical treatment of arteriovenous malformations: Report of two cases SO NEUROSURGERY LA English DT Article DE arteriovenous malformation; cerebral veins; complications; radiosurgery ID RISK AB OBJECTIVE AND IMPORTANCE: It has been suggested that impaired venous drainage of normal brain after surgical removal of an arterioveneous malformation (AVM) may cause perinidal edema and hemorrhage. The term occlusive hyperemia has been proposed for this phenomenon. There is evidence that occlusive hyperemia also may occur after radiosurgical treatment of AVMs. The purpose of this article is to lend further support to the concept that venous occlusion may be responsible for some complications observed after AVM radiosurgery. CLINICAL PRESENTATION: We report two patients with unusual radiosurgery-associated complications, and we examine the evidence for venous occlusion as the mechanism underlying the observed clinical sequelae in each patient. INTERVENTION: Patient 1 had a large parietal venous infarct remote from her frontal AVM site 11 months after radiosurgery. At that time, the AVM was confirmed by angiography to have been obliterated. During the next 4 years, the patient experienced persistent posterior hemispheric edema with recurrent focal hemorrhages until the patient's death from massive swelling and uncal herniation. During this period, radiographic studies, including repeat angiography, demonstrated sequential cortical venous occlusions and findings most consistent with venous insufficiency. Postmortem examination revealed no evidence of radionecrosis. Patient 2 exhibited a biphasic pattern of neurological deterioration at 3 and 6 years after radiosurgery. Associated with this unusual phenomenon, there was radiographic evidence of venous outflow obstruction of her thalamic AVM with prominent perinidal edema and progressive occlusion of the nidus. CONCLUSION: We conclude that occlusive hyperemia is responsible for some cases of neurological deterioration after AVM radiosurgery, especially in a setting for which the time course or other clinical features are not as might be expected from a radiobiological perspective. The two patients we describe in this report suggest that manifestations may vary. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Radiat Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Chapman, PH (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, 55 Fruit St,GRB 502, Boston, MA 02114 USA. FU NCI NIH HHS [P01 CA21239] NR 12 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2004 VL 55 IS 1 BP 228 EP 233 DI 10.1227/01.NEU.0000126950.67029.F8 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 885UZ UT WOS:000226183900061 PM 15214994 ER PT J AU Mollica, RF AF Mollica, RF TI Global health: Surviving torture SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Mollica, RF (reprint author), Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Cambridge, MA 02138 USA. NR 6 TC 22 Z9 22 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 JUL 1 PY 2004 VL 351 IS 1 BP 5 EP 7 DI 10.1056/NEJMp048141 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 833QC UT WOS:000222352200002 PM 15229300 ER PT J AU Vasan, RS Evans, JC Larson, MG Wilson, PWF Meigs, JB Rifai, N Benjamin, EJ Levy, D AF Vasan, RS Evans, JC Larson, MG Wilson, PWF Meigs, JB Rifai, N Benjamin, EJ Levy, D TI Serum aldosterone and the incidence of hypertension in nonhypertensive persons SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLASMA-RENIN ACTIVITY; BLOOD-PRESSURE; VASCULAR ALDOSTERONE; ANGIOTENSIN-II; SODIUM-INTAKE; HEART; FRAMINGHAM; SALT; POTASSIUM; SYSTEM AB Background: Primary hyperaldosteronism is a well-recognized cause of secondary hypertension. It is unknown whether serum aldosterone levels within the physiologic range influence the risk of hypertension. Methods: We investigated the relation of baseline serum aldosterone levels to increases in blood pressure and the incidence of hypertension after four years in 1688 nonhypertensive participants in the Framingham Offspring Study (mean age, 55 years), 58 percent of whom were women. We defined an increase in blood pressure as an increment of at least one blood-pressure category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and defined hypertension as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications. Results: At follow-up, the blood-pressure category had increased in 33.6 percent of the participants, and hypertension had developed in 14.8 percent. In multivariable models, a 16 percent increase in the risk of an elevation in blood pressure (P=0.002) and a 17 percent increase in the risk of hypertension (P=0.03) were observed per quartile increment in the serum aldosterone level. The highest serum aldosterone quartile, relative to the lowest, was associated with a 1.60-fold risk of an elevation in blood pressure (95 percent confidence interval, 1.19 to 2.14) and a 1.61-fold risk of hypertension (95 percent confidence interval, 1.05 to 2.46). The associations between the serum aldosterone level and blood-pressure outcomes were not significantly affected by adjustment for urinary sodium excretion or left ventricular thickness or internal dimensions. Conclusions: In our community-based sample, increased aldosterone levels within the physiologic range predisposed persons to the development of hypertension. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K24 HL04334, N01-HC-25195] NR 43 TC 306 Z9 317 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 JUL 1 PY 2004 VL 351 IS 1 BP 33 EP 41 DI 10.1056/NEJMoa033263 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 833QC UT WOS:000222352200007 PM 15229305 ER PT J AU Livni, E Berker, M Hillier, S Waller, SC Ogan, MD Discordia, RP Rienhart, JK Rubin, RH Fischman, AJ AF Livni, E Berker, M Hillier, S Waller, SC Ogan, MD Discordia, RP Rienhart, JK Rubin, RH Fischman, AJ TI Preparation and pharmacokinetics of C-11 labeled stavudine (d4T) SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE stavudine; d4T; pharmacokinetics; radiolabeling; HIV; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; POSITRON EMISSION TOMOGRAPHY; HEALTHY-HUMAN SUBJECTS; ANTI-HIV; DNA-POLYMERASES; NUCLEOSIDE ANALOGS; CONTROLLED-TRIAL; PHASE-I; ZIDOVUDINE; INVITRO AB Stavudine, a potent antiviral agent for treating human immunodeficiency virus (HIV) infections, was radiolabeled with C-11 by methylation of a specifically designed precursor, 5'-O-(2-tetrahydropyranyl)-5-bromo-2',3'-didehydro-3'-deoxythymidine, with C-11 H3I. The radiolabeled drug was isolated by reverse phase HPLC. A total time of approximately 45 minutes was required for synthesis, purification and isolation of C-11 stavudine with chemical and radiochemical purities of greater than 98%. C-11 stavudine was combined with unlabeled drug (2.0 mg/kg) and used to study its pharmacokinetics in rats by measurement of radioactivity in excised tissues. In this species, there was rapid accumulation of drug in all tissue. In all tissues, with the exceptions of testis and brain, highest concentrations of drug were detected at 5 minutes after injection and decreased monotonically thereafter. The peak concentration (mug/g) of stavudine in blood was 1.78 +/- 0.16 and similar levels were achieved in most other tissues; heart 1.66 +/- 0.11, lung 1.60 +/- 0.15, liver 2.13 +/- 0.17, spleen 1.61 +/- 0.15, adrenal 1.47 +/- 0.20, stomach 1.40 +/- 0.11, GI tract 1.44 +/- 0.14, skeletal muscle 1.38 +/- 0.15 and bone 1.30 +/- 0.16. Much higher peak concentrations were achieved in kidney; 7.23 +/- 0.57 mug/g. Concentrations in testis were lower and remained relatively constant over I hour; peak 0.62 +/- 0.14 mug/g at 15 min Brain concentrations were low but increased monotonically over time; peak 0.26 +/- 0.02 mug/g at 60 min. Future PET studies with this radiopharmaceutical will allow in vivo measurements of the pharmacokinetics of stavudine in both animal models and human subjects. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, MIT, Ctr Expt Pharmacol & Therapeut, Div Hlth Sci & Technol, Boston, MA 02115 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 55 Fruit St, Boston, MA 02114 USA. EM fischman@pet.mgh.harvard.edu NR 33 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JUL PY 2004 VL 31 IS 5 BP 613 EP 621 DI 10.1016/j.nucmedbio.2003.11.006 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 834QP UT WOS:000222425900011 PM 15219280 ER PT J AU Liu, YY Wei, LP Batzoglou, S Brutlag, DL Liu, JS Liu, XS AF Liu, YY Wei, LP Batzoglou, S Brutlag, DL Liu, JS Liu, XS TI A suite of web-based programs to search for transcriptional regulatory motifs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA; SEQUENCES; IDENTIFICATION; STRATEGIES; ALIGNMENT AB The identification of regulatory motifs is important for the study of gene expression. Here we present a suite of programs that we have developed to search for regulatory sequence motifs: (i) BioProspector, a Gibbs-sampling-based program for predicting regulatory motifs from co-regulated genes in prokaryotes or lower eukaryotes; (ii) CompareProspector, an extension to BioProspector which incorporates comparative genomics features to be used for higher eukaryotes; (iii) MDscan, a program for finding protein-DNA interaction sites from ChIP-on-chip targets. All three programs examine a group of sequences that may share common regulatory motifs and output a list of putative motifs as position-specific probability matrices, the individual sites used to construct the motifs and the location of each site on the input sequences. The web servers and executables can be accessed at http://seqmotifs.stanford.edu. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Stanford Univ, Stanford Med Informat, Stanford, CA 94305 USA. Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. Peking Univ, Coll Life Sci, Ctr Bioinformat, Beijing 100871, Peoples R China. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. EM xsliu@jimmy.harvard.edu NR 11 TC 23 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2004 VL 32 SU 2 BP W204 EP W207 DI 10.1093/nar/gkh461 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 832NB UT WOS:000222273100043 PM 15215381 ER PT J AU Ponte, PR Connor, M DeMarco, R Price, J AF Ponte, PR Connor, M DeMarco, R Price, J TI Linking patient and family-centered care and patient safety: The next leap SO NURSING ECONOMICS LA English DT Editorial Material AB At the 6th Annual National Patient Safety Foundation (NPSF) Congress held in Boston, a presentation by nursing leaders and a patient from the Dana-Farber Cancer Institute (DFCI) challenged conference participants to think more broadly about how they could incorporate patients and families into their patient safety programs. A project funded by the NPSF and the Commonwealth Fund, in which patients and families are included in safety rounds, was presented as an example of patient and family inclusion in a key initiative to improving patient safety. The patient and family-centered care model and a commitment to interdisciplinary collaboration established at DFCI was described as the foundation of the project. Key elements of the presentation and the work underway in this organization toward creating a culture of safety with the active participation of patient and family involvement are presented. C1 Brigham & Womens Hosp, Patient Care Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Faber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Hematol Oncol MT Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA USA. Boston Coll, William F Connell Sch Nursing, Boston, MA USA. RP Ponte, PR (reprint author), Brigham & Womens Hosp, Patient Care Serv, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JUL-AUG PY 2004 VL 22 IS 4 BP 211 EP + PG 4 WC Nursing SC Nursing GA 046GX UT WOS:000237800600007 ER PT J AU Bates-Jensen, BM Alessi, CA Cadogan, M Levy-Storms, L Jorge, J Yoshii, J Al-Samarrai, NR Schnelle, JF AF Bates-Jensen, BM Alessi, CA Cadogan, M Levy-Storms, L Jorge, J Yoshii, J Al-Samarrai, NR Schnelle, JF TI The minimum data set bedfast quality indicator: Differences among nursing homes SO NURSING RESEARCH LA English DT Article DE bedfast; immobility; nursing home quality indicators quality assessment ID ENVIRONMENTAL INTERVENTION; REFLECT DIFFERENCES; CARE; RESIDENTS; OUTCOMES; SLEEP; PREVALENCE AB Background. Excessive time in bed has negative effects on both physical conditioning and functioning. There are no data or practice guidelines relevant to how nurses should manage the in-bed times of nursing home residents, although all nursing homes receive a bedfast prevalence quality indicator report generated from the Minimum Data Set. Objectives: To compare nursing homes that score in the upper and lower quartiles on the Minimum Data Set bedfast prevalence quality indicator for proportion of bedfast residents, activity and mobility nursing care, and amount of time all residents spend in bed, and to evaluate whether residents who spend more time in bed are different from those who spend less time in bed according to functional measures. Methods: A cohort design used medical records, resident interviews, and direct observation data to compare 15 nursing homes (n = 451 residents) on the proportion of bedfast residents, the amount of time residents spent in bed, the frequency of activity, and the scores on six activity and mobility care process indicators. Results: Significant differences were found between upper (i.e., higher prevalence of bedfast residents) and lower quartile nursing homes in the proportion of time residents were observed in bed (43% vs. 34%, respectively; p = .007), and in the proportion of residents who spent more than 22 hours in bed per day (18% vs. 8%, respectively; p = .002). All nursing homes underestimated the number of bedfast residents. The residents of upper quartile homes showed more activity episodes and reported receiving more walking assistance than the residents of lower quartile homes. Discussion: Minimum Data Set bedfast quality indicator identified nursing homes in which residents spent more time in bed, but did not reflect differences in activity and mobility care. In fact, upper quartile homes provided more activity and mobility care than lower quartile homes. Across all the nursing homes, most of the residents spent at least 17 hours a day in bed. Further study of activity and mobility care and bedfast outcomes in nursing homes is needed, and nurses need to note the amount of time nursing home residents spend in bed. C1 Calif State Univ Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, Reseda, CA 91335 USA. Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr Med, Los Angeles, CA USA. Clin Ctr Septulveda, Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. RP Bates-Jensen, BM (reprint author), Calif State Univ Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. EM batesjen@ucla.edu FU NIA NIH HHS [AG 10415] NR 39 TC 25 Z9 25 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD JUL-AUG PY 2004 VL 53 IS 4 BP 260 EP 272 DI 10.1097/00006199-200407000-00009 PG 13 WC Nursing SC Nursing GA 841SB UT WOS:000222950600009 PM 15266165 ER PT J AU Al Moustafa, AE Foulkes, WD Wong, A Jallal, H Batist, G Yu, QY Herlyn, M Sicinski, P Alaoui-Jamali, MA AF Al Moustafa, AE Foulkes, WD Wong, A Jallal, H Batist, G Yu, QY Herlyn, M Sicinski, P Alaoui-Jamali, MA TI Cyclin D1 is essential for neoplastic transformation induced by both E6/E7 and E6/E7/ErbB-2 cooperation in normal cells SO ONCOGENE LA English DT Article DE cyclin D1; E6/E7 of HPV; ErbB-2; cell transformation ID HUMAN-PAPILLOMAVIRUS INFECTION; GENE AMPLIFICATION; CERVICAL-CANCER; UTERINE CERVIX; GROWTH-FACTOR; IN-VIVO; EXPRESSION; CARCINOMA; P53; OVEREXPRESSION AB More than 25% of head and neck squamous cell carcinomas (HNSCC) and 99% of cervical cancers (CxCa) are positive for high-risk human papillomaviruses (HPVs). Furthermore, the type I tyrosine kinase receptor ErbB-2 is overexpressed in at least 30% of HNSCC and CxCa. Recently, we demonstrated that E6/E7 of HPV type 16 cooperate with ErbB-2 to induce cell transformation of human normal oral epithelial ( NOE) cells. This is accompanied by overexpression of cyclin D1 in NOE cells. To determine the role of cyclin D1 in E6/E7/ErbB-2 cooperation, we examined the independent effects of E6/E7 and ErbB-2, and the combined effect of E6/E7 and ErbB-2 in mouse normal embryonic. broblast (NEF), wild type (wt), and knockout cyclin D1 ( D1(-/-)) cells. We report that NEF-wt cells transduced with E6/E7 alone and E6/E7/ ErbB-2 together form small and large tumors in nude mice, respectively, as well as different sized colonies in soft agar; whereas ErbB-2 alone elicits neither tumor formation in vivo nor colony formation in soft agar. More importantly, E6/E7, ErbB-2 and E6/E7/ ErbB-2 together all fail to induce neoplastic transformation of cyclin D1(-/-) cells in vivo and in vitro. Furthermore, using antisense cyclin D1 we completely inhibited tumor and colony formation of NEF-wt-E6/E7 and wt-E6/E7-ErbB-2 as well as human NOE-E6/E7-ErbB-2-transformed cells. These analyses reveal that cyclin D1 is the downstream target of the neoplastic transformation induced by E6/E7 or E6/E7/ ErbB-2 cooperation in normal cells. Our data suggest that anti-cyclin D1 therapy may be highly specific in the treatment of all human cancers expressing high-risk HPVs or HPVs/ErbB-2. C1 McGill Univ, Program Canc Genet, Montreal, PQ H3T 1E2, Canada. McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Expt Therapeut Canc,Dept Oncol, Montreal, PQ, Canada. McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Expt Therapeut Canc,Dept Med, Montreal, PQ, Canada. McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Expt Therapeut Canc,Dept Pathol, Montreal, PQ, Canada. McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Lady Davis Inst Med Res, Ctr Expt Therapeut Canc,Dept Pharmacol & Therapeu, Montreal, PQ, Canada. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Al Moustafa, AE (reprint author), McGill Univ, Program Canc Genet, 3755 Ch Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada. EM aalmoust@ldi.jgh.mcgill.ca OI foulkes, william/0000-0001-7427-4651 NR 28 TC 21 Z9 22 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 JUL 1 PY 2004 VL 23 IS 30 BP 5252 EP 5256 DI 10.1038/sj.onc.1207679 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 834AE UT WOS:000222382500014 PM 15229656 ER PT J AU Anderson, KC AF Anderson, KC TI Novel immunomodulatory therapies in the treatment of multiple myeloma - From the multiple myeloma research foundation SO ONCOLOGY-NEW YORK LA English DT Article ID THALIDOMIDE; DEXAMETHASONE AB Treatment regimens for multiple myeloma are evolving because of new advances in both pharmacotherapy and transplantation strategies. The Multiple Myeloma Research Foundation (MMRF) has gathered the,top thought leaders in myeloma I research to prepare an engaging; interactive series of case studies in multiple myeloma, which are available online at www.multiplemyeloma.org and will be published on a regular basis in ONCOLOGY For more information about the interactive series, seethe MMRF ad appearing 1 on page 1073. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2004 VL 18 IS 8 BP 988 EP 990 PG 3 WC Oncology SC Oncology GA 052DN UT WOS:000238211500006 PM 15328893 ER PT J AU Greenberg, DB AF Greenberg, DB TI Breast cancer and depression - The Somerset/Stout/Miller et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID RANDOMIZED-TRIAL C1 Massachusetts Gen Hosp, Cox Psychooncol Serv, Div Psychiat & Med, Boston, MA 02114 USA. RP Greenberg, DB (reprint author), Massachusetts Gen Hosp, Cox Psychooncol Serv, Div Psychiat & Med, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2004 VL 18 IS 8 BP 1035 EP 1036 PG 2 WC Oncology SC Oncology GA 052DN UT WOS:000238211500012 ER PT J AU Sami, N Letko, E Androudi, S Daoud, Y Foster, CS Ahmed, AR AF Sami, N Letko, E Androudi, S Daoud, Y Foster, CS Ahmed, AR TI Intravenous immunoglobulin therapy in patients with ocular-ciatricial pemphigoid - A long-term follow-up SO OPHTHALMOLOGY LA English DT Article ID CONSENSUS AB Objective: To report the clinical outcome and long-term follow-up of 10 patients with progressive ocular-cicatricial pemphigoid (OCP), nonresponsive to conventional therapy and treated with IV immunoglobulin (IVIg) therapy, reported earlier as a preliminary study. Design: Noncomparative, prospective, interventional case series according to a defined protocol for IVIg therapy. Participants: Ten patients, with a diagnosis of OCP present bilaterally confirmed by both biopsy and immunofluorescence studies and who had failed conventional therapy and had objectively demonstrated a positive response to IVIg therapy in a preliminary study, published in 1999. Main Outcome Measures: Comparison of objective clinical outcome parameters before and after IVIg therapy, including visual acuity (VA) and prevention of progression of subepithelial conjunctival fibrosis and blindness. Results: All 10 patients initially demonstrated signs of clinical improvement with IVIg therapy. The total number of IVIg cycles ranged from 20 to 42 (mean, 32), and the total duration of IVIg therapy ranged from 25 to 43 months (mean, 35). Eight patients who completed the protocol had an improvement in their VA and did not have further progression of subepithelial conjunctival fibrosis. These 8 patients have been maintained in a sustained remission for a total follow-up period ranging from 24 to 48 months (mean, 35) after the discontinuation of IVIg therapy. Two patients did not complete the protocol. Both had initially demonstrated a positive clinical response. One patient had worsening of the OCP and, after IVIg therapy, was abruptly and involuntarily withdrawn. In the second patient, deterioration occurred after ocular surgery. Intravenous immunoglobulin therapy was not provided postoperatively. These 2 patients who did not complete the protocol lost vision. Conclusions: Intravenous immunoglobulin therapy is an effective treatment in OCP in patients nonresponsive to conventional therapy. In 8 patients who completed the protocol, progression of the disease was not observed. A gradual withdrawal of IVIg therapy, as described in the protocol, may be beneficial in maintaining a sustained clinical remission. Abrupt cessation or discontinuation can result in a severe recurrence that may possibly progress to blindness. (C) 2004 by the American Academy of Ophthalmology. C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. New England Baptist Hosp, Dept Med, Ctr Blistering Dis, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med, 188 Longwood Ave, Boston, MA 02115 USA. EM Razzaque_Ahmed@hsdm.harvard.edu NR 8 TC 50 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 2004 VL 111 IS 7 BP 1380 EP 1382 DI 10.1016/j.ophtha.2003.11.012 PG 3 WC Ophthalmology SC Ophthalmology GA 834NX UT WOS:000222418900021 PM 15234140 ER PT J AU Boas, DA Chen, K Grebert, D Franceschini, MA AF Boas, DA Chen, K Grebert, D Franceschini, MA TI Improving the diffuse optical imaging spatial resolution of the cerebral hemodynamic response to brain activation in humans SO OPTICS LETTERS LA English DT Article ID SCATTERING MEDIA; TOMOGRAPHY; OXYGENATION; RAT AB We compare two geometries of sources and detectors for optimizing the diffuse optical imaging resolution of brain activation in humans. Because of limitations in the instruments' dynamic range, most diffuse optical brain activation images have used only nonoverlapping measurements. We demonstrate theoretically and with a human experiment that a simple geometry of sources and detectors can provide overlapping measurements within the limitation of instrumentation: dynamic range and produce an image resolution and localization-accuracy that is twofold better. (C) 2004 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Anthinoula A Martinos Ctr Biomed Imag, Charlestown, MA 02129 USA. RP Boas, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Anthinoula A Martinos Ctr Biomed Imag, Charlestown, MA 02129 USA. EM dboas@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41-RR14075]; NIBIB NIH HHS [R01-EB002482] NR 17 TC 110 Z9 112 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUL 1 PY 2004 VL 29 IS 13 BP 1506 EP 1508 DI 10.1364/OL.29.001506 PG 3 WC Optics SC Optics GA 830OV UT WOS:000222133100024 PM 15259728 ER PT J AU Smullin, SE Fielding, AF Susarla, SM Pringle, G Eichstaedt, R AF Smullin, SE Fielding, AF Susarla, SM Pringle, G Eichstaedt, R TI Canalicular adenoma of the palate: Case report and literature review SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID MINOR SALIVARY-GLANDS; BASAL-CELL-ADENOMA; TUMORS AB Canalicular adenoma is a rare benign salivary gland tumor of the oral cavity, typically located in the upper lip and buccal mucosa and infrequently found on the palate. The tumor is usually confined to soft tissue and rarely presents with bone erosion. A case of a large and locally-aggressive palatal canalicular adenoma is presented. The lesion presented herein was an asymptomatic ulcerated mass with significant bone erosion. The tumor was managed surgically with excision and reconstruction of the resulting palatal defect with a full temporalis muscle flap. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Temple Univ, Sch Dent, Philadelphia, PA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Smullin, SE (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM steven_smuIlin@student.hms.harvard.edu OI Susarla, Srinivas/0000-0003-0155-8260 NR 15 TC 12 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUL PY 2004 VL 98 IS 1 BP 32 EP 36 DI 10.1016/j.tripleo.2004.02.065 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 838IB UT WOS:000222705800007 PM 15243467 ER PT J AU Schwartz, SR Yueh, B Maynard, C Daley, J Henderson, W Khuri, SF AF Schwartz, SR Yueh, B Maynard, C Daley, J Henderson, W Khuri, SF TI Predictors of wound complications after laryngectomy: A study of over 2000 patients SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 09-14, 2001 CL DENVER, CO SP Amer Acad Otolaryngol Head & Neck Surg ID CLEAN-CONTAMINATED HEAD; NECK-CANCER SURGERY; ONCOLOGIC SURGERY; STAGING SYSTEM; RISK-FACTORS; INFECTION; RADIOTHERAPY; PROPHYLAXIS; FISTULA AB OBJECTIVES: To identify risk factors for and the rate of wound complications after laryngectomy in a large, prospectively collected national dataset, and to generate a predictive model. STUDY DESIGN: We used the National Surgical Quality Improvement Program (NSQIP) registry created by the Department of Veterans Affairs (VA) to identify patients undergoing total laryngectomy from 1989 to 1999 (n = 2063). We linked these data to inpatient and outpatient VA administrative records to capture data for prior radiation. Over 20 preoperative and intraoperative risk factors were analyzed using bivariate techniques. Those significant at the P < 0.01 level were analyzed with logistic regression and conjunctive consolidation to identify independent predictors of wound complications. RESULTS: The overall wound complication rate was 10.0%. In adjusted analyses, prolonged operative time (> 10 hours, odds ratio = 2.10, 95% confidence interval: 1.32-3.36), exposure to prior radiation therapy (OR =1.63, 1.07-2.46), presence of diabetes (OR = 1.78, 1.04-3.04), preoperative hypoalbuminemia (OR = 1.90, 1.32-2.74), anemia (OR = 1.59, 1.072.36), and thrombocytosis (OR =1.48, 1.04-2.10) were independently associated with postoperative wound complications. A prognostic model using three variables-prior radiation therapy, diabetes, and hypoalbuminemia-provided excellent risk stratification into three tiers (6.3%, 13.7%, 21.7%). CONCLUSIONS: Preoperative radiation, prolonged operative time, low albumin, and diabetes were independently associated with postoperative wound infections. These results will help to identify patients at risk for wound complications, thus allowing for heightened surveillance and preventive measures where possible. C1 Univ Washington, Med Ctr,VA Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, Hlth Serv Res & Dev Serv,Sch Med, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Tenet Hlth Syst, Dallas, TX USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Schwartz, SR (reprint author), Univ Washington, Med Ctr,VA Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, Hlth Serv Res & Dev Serv,Sch Med, 1959 NE Pacific St,Box 356515, Seattle, WA 98195 USA. EM schwarsr@u.washington.edu RI Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Yueh, Bevan/0000-0003-1380-1053 NR 28 TC 75 Z9 75 U1 0 U2 1 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 JUL PY 2004 VL 131 IS 1 BP 61 EP 68 DI 10.1016/j.otohns.2003.08.028 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 837MI UT WOS:000222639200011 PM 15243559 ER PT J AU McKenna, TJ Nguyen-Huynh, TT Kristiansen, TG AF McKenna, TJ Nguyen-Huynh, TT Kristiansen, TG TI Association of otosclerosis with Sp1 binding site polymorphism in COL1A1 gene: Evidence for a shared genetic etiology with osteoporosis SO OTOLOGY & NEUROTOLOGY LA English DT Article DE COL1A1; collagen; osteoporosis; otosclerosis; Sp1; transcription ID SENSORINEURAL HEARING-LOSS; MILD OSTEOGENESIS IMPERFECTA; DRINKING-WATER FLUORIDATION; SODIUM-FLUORIDE; NULL ALLELES; POSTMENOPAUSAL OSTEOPOROSIS; BONE-DENSITY; 1ST INTRON; COLLAGEN; OTOSPONGIOSIS AB Hypothesis: There is an association between otosclerosis and osteoporosis. Background: Both osteoporosis and otosclerosis are common bone diseases to which relatively large portions of the population are genetically predisposed. Recently, a strong association has been described between osteoporosis and an Sp1 binding site of putative functional significance in the first intron of the COLIA1 gene. Methods: We applied polymerase chain reaction-based restriction enzyme analysis to determine the polymorphic distribution of the Sp1 site in 100 patients with otosclerosis and 108 control subjects. Results: This study showed a significant association between otosclerosis and the COLIA1 first intron Sp1 site. The allelic frequency of the Sp1 site is very similar between otosclerosis and osteoporosis. Conclusion: Some cases of otosclerosis and osteoporosis could share a functionally significant polymorphism in the Sp1 transcription factor binding site in the first intron of the COLIA1 gene. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP McKenna, TJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 34 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2004 VL 25 IS 4 BP 447 EP 450 PG 4 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 837FO UT WOS:000222614100007 ER PT J AU Barnet, CS Tse, JY Kohane, DS AF Barnet, CS Tse, JY Kohane, DS TI Site 1 sodium channel blockers prolong the duration of sciatic nerve blockade from tricyclic antidepressants SO PAIN LA English DT Article DE sodium channel blockers; nerve blockade; bupivacaine; tricyclic antidepressants; local anesthetics; tetrodotoxin ID LOCAL-ANESTHETIC ACTIVITY; PROTEIN-SUGAR PARTICLES; TETRODOTOXIN; BUPIVACAINE; SAXITOXIN; RAT; AMITRIPTYLINE; PAIN AB Many recent reports in the literature address the local anesthetics efficacy of tricyclic antidepressants (TCAs). Here we investigated whether nerve block from TCAs is prolonged by site 1 sodium channel blockers such as tetrodotoxin and saxitoxin, which are known to prolong block from conventional local anesthetics. Tetrodotoxin and saxitoxin greatly prolonged block from TCAs. For example, the median duration of thermal nociceptive blocks for 10 mM amitriptyline, nortriptyline and doxepin were 0, 0, and 124 min; co-injection with 20 muM TTX (median block duration = 0), yielded blocks lasting 404, 325, and 697 min, respectively. Co-injection of 12 muM saxitoxin (median block duration= 0) with 10 mM amitriptyline resulted in a thermal nociceptive block duration of 373 min. Co-injection of 7.7 mM bupivacaine and 7.7 mM amiptriptyline did not result in block prolongation. Systemic (subcutaneous) delivery of tetrodotoxin or amitriptyline did not result in prolongation of block from the other class of drug injected at the sciatic nerve. In TCA-containing formulations, motor blockade was consistently longer than thermal nociceptive block; motor blockade was also prolonged by tetrodotoxin and saxitoxin. In summary site 1 sodium channel blockers prolong the duration of TCAs via a locally mediated mechanism. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Pediat Intens Care Unit, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, Ellison 317,55 Fruit St, Boston, MA 02114 USA. EM dkohane@partners.org NR 23 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2004 VL 110 IS 1-2 BP 432 EP 438 DI 10.1016/j.pain.2004.04.027 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 845HL UT WOS:000223232800052 PM 15275796 ER PT J AU Raphael, KG Janal, MN Nayak, S Schwartz, JE Gallagher, RM AF Raphael, KG Janal, MN Nayak, S Schwartz, JE Gallagher, RM TI Familial aggregation of depression in fibromyalgia: a community-based test of alternate hypotheses SO PAIN LA English DT Article DE fibromyalgia; major depressive disorder; first-degree relatives ID POSTTRAUMATIC-STRESS-DISORDER; MYOFASCIAL FACE PAIN; STRUCTURED CLINICAL INTERVIEW; DSM-III-R; MAJOR DEPRESSION; HISTORY METHOD; LIFE EVENTS; SEX-DIFFERENCES; PERSONALITY-DISORDERS; RHEUMATOID-ARTHRITIS AB Numerous studies report that fibromyalgia (FM), a syndrome characterized by widespread pain and generalized tender points, is comorbid with major depressive disorder (MDD). The current study tests two alternate explanations for their comorbidity using a family study methodology. The first is that FM is a depression spectrum disorder. The second is that depression is a consequence of living with FM. We recruited potential probands by initially screening by telephone for FM and MDD among women in the NY/NJ metropolitan area, randomly selecting telephone numbers from a list of households with women. Eligible women were invited for second stage physical examinations for FM diagnosis and psychiatric interviews for MDD diagnosis. All available adult, first-degree relatives received psychiatric interviews. Relatives of probands were divided into four groups on the basis of the probands' FM and MDD diagnoses (FM+/MDD+ (n = 156), FM+/MDD- (n = 51), FM-/MDD+ (n = 351) and FM-/MDD- (n = 101)). Results indicated that rates of MDD in the relatives of probands with FM but without personal histories of MDD were virtually identical to rates of MDD in relatives of probands with MDD themselves. This outcome is consistent with the hypothesis that FM is a depression spectrum disorder, in which FM and MDD are characterized by shared, familially mediated risk factors. The implications of these findings for a stress-vulnerability model of FM are discussed. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, Newark, NJ 07103 USA. SUNY Stony Brook, Sch Med, Dept Psychiat & Behav Sci, New York, NY USA. Philadelphia Vet Affairs Med Ctr, Pain Management Serv, Philadelphia, PA USA. Univ Penn, Dept Psychiat & Anesthesiol, Philadelphia, PA 19104 USA. RP Raphael, KG (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Psychiat, BHSB F1512,183 S Orange Ave, Newark, NJ 07103 USA. EM raphaekg@umdnj.edu OI Raphael, Karen/0000-0002-2804-8124 FU NIDCR NIH HHS [R01 DE13486] NR 80 TC 66 Z9 67 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2004 VL 110 IS 1-2 BP 449 EP 460 DI 10.1016/j.pain.2004.04.039 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 845HL UT WOS:000223232800054 PM 15275798 ER PT J AU Grande, LA Loeser, JD Ozuna, J Ashleigh, A Samii, A AF Grande, LA Loeser, JD Ozuna, J Ashleigh, A Samii, A TI Complex regional pain syndrome as a stress response SO PAIN LA English DT Article DE complex regional pain syndrome; reflex sympathetic dystrophy; conversion disorder; post-traumatic stress disorder; encephalomalacia; traumatic brain injury ID REFLEX SYMPATHETIC DYSTROPHY; SYNDROME TYPE-I; DISORDER AB A man in his 50's with a prior traumatic brain injury and multiple psychiatric disorders developed acute pain and swelling in his left leg distal to the mid shin. These symptoms arose during an exacerbation of his post-traumatic stress disorder (PTSD). Among his traumatic memories, he reported having witnessed the combat injury and death of a friend who had lost his left leg distal to the mid shin. A diagnosis of conversion disorder was technically excluded because the findings met criteria for Complex Regional Pain Syndrome (CRPS) type 1. Based on recent research into the neurobiology of CRPS, PTSD and conversion disorder, we propose a supraspinal mechanism which could explain how emotional stress can produce both symptoms and signs. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Psychiat, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. RP Samii, A (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Neurol, Mailstop 127,1660 S Columbian Way, Seattle, WA 98108 USA. EM asamii@u.washington.edu NR 26 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2004 VL 110 IS 1-2 BP 495 EP 498 DI 10.1016/j.pain.2004.03.032 PG 4 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 845HL UT WOS:000223232800059 PM 15275803 ER PT J AU Salusky, IB Juppner, H AF Salusky, IB Juppner, H TI New PTH assays and renal osteodystrophy SO PEDIATRIC NEPHROLOGY LA English DT Editorial Material DE new PTH assays; chronic kidney disease ID INTERMITTENT CALCITRIOL THERAPY; UREMIC BONE-DISEASE; PARATHYROID-HORMONE; SECONDARY HYPERPARATHYROIDISM; IMMUNORADIOMETRIC ASSAY; PEDIATRIC-PATIENTS; PREDICTIVE-VALUE; FAILURE; FRAGMENTS; TURNOVER AB Parathyroid hormone (PTH) levels have been used instead of bone histomorphometric analysis in renal failure, but the assessment of tetracycline-labeled bone biopsy remains the most reliable method to diagnose the different subtypes of renal osteodystrophy. The availability of the first-generation immunometric PTH assay (1(st) PTH-IMA) allowed the distinction between the different types of renal bone diseases. However, 1(st) PTH-IMA not only detects the intact hormone PTH(1-84), but also additional PTH truncated fragments. A second-generation immunometric PTH assay (2(nd) PTH-IMA) recognizes only PTH(1-84) and possible PTH fragments that are truncated at the carboxyl-terminus, but not PTH(7-84). In addition, whether assessment of the ratio PTH(1-84) and amino-terminally truncated PTH(1-84) fragments is a better predictor of bone turnover remains controversial. An initial study using the 2(nd) PTH-IMA suggested that the ratio between PTH(1-84) and amino-terminally truncated PTH(1-84) fragments more accurately predicts bone turnover in adult patients treated with hemodialysis. However, subsequent studies using the Scantibodies assay have failed to better predict the underlying bone disease in adults undergoing maintenance hemodialysis. Furthermore, a different 2(nd) PTH-IMA (Immutopics) with similar, but not identical, in vitro characteristics did not show a superior predictive value of the ratio in pediatric patients treated with peritoneal dialysis. Although the 2(nd) PTH-IMA may provide important new insights into the physiology of parathyroid gland function, at present, measurement of PTH using either 1(st) or 2(nd) PTH-IMAs provides similar accuracy for predicting bone turnover in patients treated with dialysis. Thus, the current data do not yet support the claim that 2(nd) PTH-IMAs provide an advantage over 1(st) PTH-IMAs for the diagnosis of the different subtypes of renal bone diseases. C1 Univ Calif Los Angeles, Med Ctr, Div Pediat Nephrol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Salusky, IB (reprint author), Univ Calif Los Angeles, Med Ctr, Div Pediat Nephrol, Box 951752, Los Angeles, CA 90095 USA. EM isalusky@mednet.ucla.edu FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 38 TC 9 Z9 10 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUL PY 2004 VL 19 IS 7 BP 709 EP 713 DI 10.1007/s00467-004-1433-0 PG 5 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 825JF UT WOS:000221752000002 PM 15173936 ER PT J AU Anselmo, MA Lash, KM Stieb, ES Haver, KE AF Anselmo, MA Lash, KM Stieb, ES Haver, KE TI Cystic fibrosis on the Internet: A survey of site adherence to AMA guidelines SO PEDIATRICS LA English DT Article DE Internet; guidelines; adherence; cystic fibrosis ID HEALTH INFORMATION; WEB SITES; QUALITY AB Objectives. The Internet permits unprecedented and mostly unrestricted access to medical knowledge; however, concerns exist regarding viewer privacy, accountability of authorship, accuracy of information, and patient safety. To address these issues, the American Medical Association (AMA) has developed guidelines concerning web site content and visitor rights. Cystic fibrosis (CF) is the most common genetically inherited lethal disease in North America. Many Internet sites that provide information on CF have been developed, although adherence to validated guidelines for online health information is not required. The purpose of this study was to assess systematically web sites with content pertaining to CF for adherence to the published AMA guidelines. Methods. The search term "cystic fibrosis" was entered into a commonly used search engine (Google), and the first 100 eligible sites were reviewed. Each site was examined for adherence to the AMA Guidelines for Medical and Health Information Sites on the Internet using a series of adapted questions. There were 15 questions divided into the following main categories: 1) site structure and viewer privacy, 2) author accountability, 3) scientific citation, and 4) patient safety. The number of positives for each question was tabulated. Results. With respect to site structure, fewer than half (45%) of the reviewed sites indicated a date of last revision. Only 11 (11%) carried an explicit privacy policy. A responsible author or group was listed in only 43 (43%) of 100 sites. Presented data regarding CF was supported by references, sources, or expert review in only 38 (38%) of 100 sites. A medical disclaimer noting that information provided does not substitute for evaluation by a health care team was evident in only 37 (37%) sites. Conclusions. The majority of easily accessible CF informational web sites do not adhere to guidelines published by the AMA. Patients and families who use the Internet as a CF information resource should examine the web sites carefully and be familiar with the guidelines established by the AMA. Personal information is not protected, and few sites provide explicit privacy guarantees. Finally, CF care teams should inquire about Internet use by patients and families and be prepared to discuss findings from the Internet to heighten patient safety and awareness. C1 Harvard Univ, Sch Med, MassGen Hosp Children, Joey ODonnell Cyst Fibrosis Ctr,ACC 712, Boston, MA 02114 USA. RP Haver, KE (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Joey ODonnell Cyst Fibrosis Ctr,ACC 712, 15 Parkman St, Boston, MA 02114 USA. EM khaver@partners.org NR 16 TC 20 Z9 20 U1 1 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2004 VL 114 IS 1 BP 100 EP 103 DI 10.1542/peds.114.1.100 PG 4 WC Pediatrics SC Pediatrics GA 834VO UT WOS:000222439200036 PM 15231914 ER PT J AU Chehab, EW Patharkar, OR Hegeman, AD Taybi, T Cushman, JC AF Chehab, EW Patharkar, OR Hegeman, AD Taybi, T Cushman, JC TI Autophosphorylation and subcellular localization dynamics of a salt- and water deficit-induced calcium-dependent protein kinase from ice plant SO PLANT PHYSIOLOGY LA English DT Article ID CALMODULIN-LIKE DOMAIN; MESEMBRYANTHEMUM-CRYSTALLINUM L; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; BINDING SITES; H+-ATPASE; BIOCHEMICAL-CHARACTERIZATION; ARABIDOPSIS-THALIANA; SYNTHETIC PEPTIDES; SOLANUM-TUBEROSUM AB A salinity and dehydration stress-responsive calcium-dependent protein kinase (CDPK) was isolated from the common ice plant (Mesembryanthemum crystallinum; McCPK1). McCPK1 undergoes myristoylation, but not palmitoylation in vitro. Removal of the N-terminal myristate acceptor site partially reduced McCPK1 plasma membrane (PM) localization as determined by transient expression of green fluorescent protein fusions in microprojectile-bombarded cells. Removal of the N-terminal domain (amino acids 1-70) completely abolished PM localization, suggesting that myristoylation and possibly the N-terminal domain contribute to membrane association of the kinase. The recombinant, Escherichia coli-expressed, full-length McCPK1 protein was catalytically active in a calcium-dependent manner (K-0.5 = 0.15 mum). Autophosphorylation of recombinant McCPK1 was observed in vitro on at least two different Ser residues, with the location of two sites being mapped to Ser-62 and Ser-420. An Ala substitution at the Ser-62 or Ser-420 autophosphorylation site resulted in a slight increase in kinase activity relative to wild-type McCPK1 against a histone H1 substrate. In contrast, Ala substitutions at both sites resulted in a dramatic decrease in kinase activity relative to wild-type McCPK1 using histone H1 as substrate. McCPK1 undergoes a reversible change in subcellular localization from the PM to the nucleus, endoplasmic reticulum, and actin microfilaments of the cytoskeleton in response to reductions in humidity, as determined by transient expression of McCPK1-green fluorescent protein fusions in microprojectile-bombarded cells and confirmed by subcellular fractionation and western-blot analysis of 6x His-tagged McCPK1. C1 Univ Nevada, Dept Biochem MS200, Reno, NV 89557 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Wisconsin, Ctr Biotechnol, Dept Biochem, Madison, WI 53706 USA. Univ Newcastle Upon Tyne, Sch Biol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Cushman, JC (reprint author), Univ Nevada, Dept Biochem MS200, Reno, NV 89557 USA. EM jcushman@unr.edu RI Hegeman, Adrian/D-5984-2013 OI Hegeman, Adrian/0000-0003-1008-6066 FU NIGMS NIH HHS [F32 GM069315, F32 GM069315-01, F32 GM069315-02] NR 96 TC 56 Z9 61 U1 0 U2 11 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUL PY 2004 VL 135 IS 3 BP 1430 EP 1446 DI 10.1104/pp.103.035238 PG 17 WC Plant Sciences SC Plant Sciences GA 838DD UT WOS:000222692700026 PM 15247393 ER PT J AU Castro, P Xia, C Gomez, L Lamb, DJ Ittmann, M AF Castro, P Xia, C Gomez, L Lamb, DJ Ittmann, M TI Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia SO PROSTATE LA English DT Article DE benign prostatic hyperplasia; cytokines; senescence ID GROWTH-FACTOR; CELLULAR SENESCENCE; HUMAN FIBROBLASTS; PARACRINE INDUCER; CANCER; CULTURE; PATHOGENESIS; GENES; FGF7 AB BACKGROUND. Benign prostatic hyperplasia (BPH) is an extremely common disease of older men characterized by increased growth of prostatic epithelial and stromal cells. Previously we showed that senescent epithelial cells accumulate in the prostate of aging men and secrete interleukin-1alpha (IL-1alpha). IL-8 is also present at increased levels in BPH tissues and induces expression of FGF2, a potent stromal growth factor. Therefore, we sought to determine if IL-8 is also expressed at increased levels by senescent epithelial cells and if this secreted IL-8 plays a robe in the pathogenesis of BPH. METHODS. Expression of IL-8 in human BPH tissue and primary cultures of prostatic epithelial cells was analyzed using an enzyme-linked immunoabsorption assay (ELISA). Tissue senescence was assessed by a quantitative assay for senescence-associated beta galactosidase (SA-beta gal). Proliferation of primary and immortalized prostatic epithelial cells in response to IL-8 was determined by counting of cells at intervals after addition of IL-8. RESULTS. Expression of IL-8 is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence. Quantitative assay of BPH tissue extracts revealed that tissue IL-8 levels are correlated with both SA-beta gal activity and prostate weight. IL-8 promotes proliferation of primary and immortalized prostfatic epithelial cells in culture. CONCLUSIONS. Senescence of prostatic epithelial cells results in increased expression of IL-8, which can promote proliferation of non-senescent epithelial and stromal cells by direct and indirect mechanisms, and in this manner contributes to the increased tissue growth seen in BPH. (C) 2004 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX USA. RP Ittmann, M (reprint author), VAMC, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU NIDDK NIH HHS [R01 DK54170, T32 DK07763] NR 27 TC 59 Z9 59 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUL 1 PY 2004 VL 60 IS 2 BP 153 EP 159 DI 10.1002/pros.20051 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 829UQ UT WOS:000222076100008 PM 15162381 ER PT J AU Ablon, JS Marci, C AF Ablon, JS Marci, C TI Psychotherapy process: The missing link: Comment on Westen, Novotny, and Thompson-Brenner (2004) SO PSYCHOLOGICAL BULLETIN LA English DT Editorial Material ID COLLABORATIVE RESEARCH-PROGRAM; MENTAL-HEALTH TREATMENT; NATIONAL INSTITUTE; COGNITIVE THERAPY; DEPRESSION AB In this comment J. S. Ablon and C. Marci argue that focusing on the empirical validation of manualized treatment packages misses important information about what is efficacious about a given treatment. Psychotherapy process has demonstrated that treatments may promote change in ways other than their underlying theories claim. Manualized therapies may appear distinct despite important similarities in dyadic interaction. These functional similarities in the emergent transactional process between therapist and patient may help explain the difficulty demonstrating differential outcomes across brands of brief therapy. Rather than focus on treatment packages targeting patient symptomatology, the authors recommend a shift in focus to the empirical validation of change processes coconstructed by therapist and patient in naturalistic settings. C1 Massachusetts Gen Hosp, Dept Psychiat, Newton, MA 02458 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ablon, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 313 Washington St,Suite 402, Newton, MA 02458 USA. EM sablon@sprintpcs.com NR 18 TC 24 Z9 26 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD JUL PY 2004 VL 130 IS 4 BP 664 EP 668 DI 10.1037/0033-2909.130.4.664 PG 5 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 833OP UT WOS:000222347700006 PM 15250816 ER PT J AU Deckersbach, T McMurrich, S Ogutha, J Savage, CR Sachs, G Rauch, SL AF Deckersbach, T McMurrich, S Ogutha, J Savage, CR Sachs, G Rauch, SL TI Characteristics of non-verbal memory impairment in bipolar disorder: the role of encoding strategies SO PSYCHOLOGICAL MEDICINE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; DORSOLATERAL PREFRONTAL CORTEX; MAJOR DEPRESSIVE DISORDER; EUTHYMIC PATIENTS; NEUROPSYCHOLOGICAL FUNCTION; COGNITIVE DYSFUNCTIONS; LEARNING-STRATEGIES; EPISODIC MEMORY; EXPLICIT MEMORY; MOOD DISORDERS AB Background. There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during episodes of depression or mania but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in episodic memory. Learning and memory depend on individuals' ability to organize information during learning. A recent study by our group showed that verbal episodic memory impairments in euthymic patients with bipolar I disorder (BP-I) are mediated by difficulties in organizing verbal information appropriately during learning. The purpose of the present study was to determine whether memory impairments in euthymic individuals with BP-I extend to non-verbal memory and whether non-verbal memory impairments are mediated by difficulties in organizing non-verbal information during encoding. Method. Study participants were 25 euthymic, remitted individuals with BP-I and 25 age, gender and education matched control participants. Participants completed the Rey-Osterrieth Complex Figure Test (RCFT), a well-established measure of non-verbal memory that enables assessment of organization during learning. Results. Compared to control participants, BP-I participants showed impaired performance on the RCFT immediate recall. They also relied less on organizational strategies during encoding. Multiple regression modeling indicated that group differences between control and BP-I participants in long-delayed free recall did not remain statistically significant when effects of lower organization were partialled out. Conclusions. Non-verbal memory problems in individuals with bipolar disorder, while euthymic, are mediated by poor use of non-verbal organization strategies during encoding, but do not appear to reflect deficits in retention of information. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neurosci Program,Biopolar Res Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Deckersbach, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neurosci Program,Biopolar Res Program, 149-9102 Bldg,149,13th St, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org FU NIMH NIH HHS [MH60219] NR 57 TC 47 Z9 49 U1 4 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2004 VL 34 IS 5 BP 823 EP 832 DI 10.1017/S0033291703001685 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 844EF UT WOS:000223139500007 PM 15500303 ER PT J AU Franko, DL Keel, PK Dorer, DJ Blais, MA Delinsky, SS Eddy, KT Charat, V Renn, R Herzog, DB AF Franko, DL Keel, PK Dorer, DJ Blais, MA Delinsky, SS Eddy, KT Charat, V Renn, R Herzog, DB TI What predicts suicide attempts in women with eating disorders? SO PSYCHOLOGICAL MEDICINE LA English DT Article; Proceedings Paper CT 9th International Conference on Eating Disorders CY MAY 04-07, 2000 CL NEW YORK, NEW YORK ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; FOLLOW-UP; LONG-TERM; MORTALITY; PERSONALITY; DEPRESSION; BEHAVIOR; RECOVERY; RELAPSE AB Background. Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. Method. In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = I 10) were interviewed and assessed for suicide attempts and suicidal intent every 6-12 months over 8.6 years. Results. Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22.1 %) than bulimic subjects (10.9 %) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. Conclusions. Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial comorbidity. C1 Harvard Univ, Massachusetts Gen Hosp, Eating Disorders Ctr, Boston, MA 02114 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Franko, DL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Eating Disorders Ctr, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM d.franko@neu.edu FU NIMH NIH HHS [5R01 MH38333 05] NR 43 TC 46 Z9 51 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2004 VL 34 IS 5 BP 843 EP 853 DI 10.1017/S0033291703001545 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 844EF UT WOS:000223139500009 PM 15500305 ER PT J AU McNally, RJ Lasko, NB Clancy, SA Macklin, ML Pitman, RK Orr, SP AF McNally, RJ Lasko, NB Clancy, SA Macklin, ML Pitman, RK Orr, SP TI Psychophysiological responding during script-driven imagery in people reporting abduction by space aliens SO PSYCHOLOGICAL SCIENCE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; RECOVERED MEMORIES; FALSE MEMORIES; SCALE; WOMEN; DISTORTION; SCHIZOTYPY; TRAUMA; PTSD AB Is recollection of highly improbable traumatic experiences accompanied by psychophysiological responses indicative of intense emotion? To investigate this issue, we measured heart rate, skin conductance, and left lateral frontalis electromyographic responses in individuals who reported having been abducted by space aliens. Recordings of these participants were made during script-driven imagery of their reported alien encounters and of other stressful, positive, and neutral experiences they reported. We also measured the psychophysiological responses of control participants while they heard the scripts of the abductees. We predicted that if "memories" of alien abduction function like highly stressful memories, then psychophysiological reactivity to the abduction and stressful scripts would be greater than reactivity to the positive and neutral scripts, and this effect would be more pronounced among abductees than among control participants. Contrast analyses confirmed this prediction for all three physiological measures (ps < .05). Therefore, belief that one has been traumatized may generate emotional responses similar to those provoked by recollection of trauma (e.g., combat). C1 Harvard Univ, Dept Psychol, Sch Med, Cambridge, MA 02138 USA. Vet Affairs Med Ctr, Manchester, NH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, Sch Med, 33 Kirkland St, Cambridge, MA 02138 USA. EM rjm@wjh.harvard.edu NR 28 TC 62 Z9 63 U1 5 U2 15 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD JUL PY 2004 VL 15 IS 7 BP 493 EP 497 DI 10.1111/j.0956-7976.2004.00707.x PG 5 WC Psychology, Multidisciplinary SC Psychology GA 829MM UT WOS:000222052700010 PM 15200635 ER PT J AU Sampogna, F Picardi, A Chren, MM Melchi, F Pasquini, P Masini, C Abeni, D AF Sampogna, F Picardi, A Chren, MM Melchi, F Pasquini, P Masini, C Abeni, D TI Association between poorer quality of life and psychiatric morbidity in patients with different Dermatological conditions SO PSYCHOSOMATIC MEDICINE LA English DT Article DE quality of life; psychiatric morbidity; dermatology; Skindex-29; GHQ-12 ID SKIN DISEASES; ATOPIC-DERMATITIS; OUTPATIENTS; RELIABILITY; PSORIASIS; VALIDITY; DEPRESSION; DISORDERS; VITILIGO; VERSION AB Objective: To determine the relationship between skin-related quality of life and psychiatric morbidity in patients with different skin conditions. Methods: We recruited all adults attending the outpatient clinics of the Dermatological Institute IDI-IRCCS, Rome, Italy, during 14 predetermined days. Eligible patients, who gave their informed consent, completed the Skindex-29 and the 12-item General Health Questionnaire (GHQ-12). We used a stringent cut-off threshold (greater than or equal to5 on the GHQ-12) for identification of psychiatric morbidity. Skindex-29 scale scores were computed separately for GHQ noncases and GHQ cases. Results: A total of 2,136 patients were included in the analysis. For all skin conditions, GHQ cases had substantially poorer score in all 3 domains of quality of life, Symptoms, Emotions, and Functioning. Most differences remained significant after adjusting for clinical severity, age, sex, and education in multiple regression models. These differences were not as marked in the Symptoms scale for some conditions known to be nearly asymptomatic (eg, alopecia, vitiligo, nevi), suggesting that, although patients with psychiatric morbidity might be more burdened by their symptoms, nevertheless they do not perceive nonexistent symptoms. Conclusion: In most skin conditions we considered, psychiatric morbidity was strongly associated with poorer quality of life. Although the cross-sectional nature of our study does not allow identification of the direction of this association, care for the psychological condition of patients might have an impact on their quality of life. C1 IRCCS, IDI, Inst Dermatol, I-00167 Rome, Italy. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, HSR&D Res Enhancement Award Program, San Francisco, CA USA. RP Abeni, D (reprint author), IRCCS, IDI, Inst Dermatol, Via Monti Creta 104, I-00167 Rome, Italy. EM d.abeni@idi.it RI Picardi, Angelo/B-2181-2013; OI Picardi, Angelo/0000-0003-2392-3011; Abeni, Damiano/0000-0002-0167-7617 FU NIAMS NIH HHS [K02 AR 02203-01] NR 26 TC 73 Z9 75 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2004 VL 66 IS 4 BP 620 EP 624 DI 10.1097/01.psy.0000132869.96872.b2 PG 5 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 840KX UT WOS:000222858600024 PM 15272112 ER PT J AU Rigalleau, F Caplan, D Baudiffier, V AF Rigalleau, F Caplan, D Baudiffier, V TI New arguments in favour of an automatic gender pronominal process SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY LA English DT Article ID IMPLICIT CAUSALITY; PRONOUN RESOLUTION; DISCOURSE; MEMORY; REPRESENTATION; COMPREHENSION; CONTINUITY; ATTENTION; LANGUAGE AB This paper examines the automatic and strategic use of gender information in pronominal processing. Experiments 1 and 2 used short sentences where a pronoun was preceded by two potential antecedents. Results showed that even when adult readers did not use pronominal gender to strategically accelerate pronominal resolution, they remained sensitive to a gender disagreement between the pronoun and its potential referents. This gender sensitivity was further explored in Experiments 3 and 4. These experiments used longer texts where only one of the two potential referents was highly accessible when the pronoun was encountered. A gender disagreement between the pronoun and this antecedent induced longer reading times. The four experiments confirm the existence of a nonstrategic gender coindexation process between a pronoun and the entity in the focus of a discourse. C1 Univ Poitiers, Poitiers, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rigalleau, F (reprint author), CNRS, UMR 6096, Lab Langage & Cognit, 99 Ave Recteur Pineau, F-86022 Poitiers, France. EM frigalleau@compuserve.com FU NIDCD NIH HHS [DC04608] NR 35 TC 12 Z9 14 U1 0 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0272-4987 J9 Q J EXP PSYCHOL-A JI Q. J. Exp. Psychol. Sect A-Hum. Exp. Psychol. PD JUL PY 2004 VL 57 IS 5 BP 893 EP 933 DI 10.1080/02724980343000549 PG 41 WC Psychology; Psychology, Experimental SC Psychology GA 828UQ UT WOS:000221999200007 PM 15204122 ER PT J AU Sahani, D D'souza, R Kadavigere, R Hertl, M McGowan, J Saini, S Mueller, PR AF Sahani, D D'souza, R Kadavigere, R Hertl, M McGowan, J Saini, S Mueller, PR TI Evaluation of living liver transplant donors: Method for precise anatomic definition by using a dedicated contrast-enhanced MR imaging protocol SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 88th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 2002 CL CHICAGO, IL SP Radiol Soc N Amer DE bile ducts, MR; hepatic arteries, MR; hepatic veins, MR; liver, transplantation; portal vein, MR ID MAGNETIC-RESONANCE VENOGRAPHY; BILE-DUCT; LOBE; ADULT; CT; CHOLANGIOGRAPHY; ANGIOGRAPHY; HEPATECTOMY; CANDIDATES; MODALITY AB Liver transplantation from a living donor involves removal of part of the donor liver in a fashion that does not endanger its vascular supply or metabolic function. The radiologist plays an important role in evaluation of the living donor to define the conditions under which graft donation is Contraindicated and to identify anatomic variations that may alter the surgical approach. In the past, diagnostic work-up of the donor involved costly and invasive tests. Currently, dynamic contrast material-enhanced computed tomography and magnetic resonance (MR) imaging are the imaging tests performed, each of which has advantages and limitations. MR imaging performed with liver-specific and extravascular contrast agents may be used as a single imaging test for comprehensive noninvasive evaluation of living liver transplant donors. MR imaging provides valuable information. gin about variations in the vascular and biliary anatomy and allows evaluation of the hepatic parenchyma for diffuse or focal abnormalities. (C) RSNA, 2004. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 30 TC 22 Z9 24 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL-AUG PY 2004 VL 24 IS 4 BP 957 EP 967 DI 10.1148/rg.244035186 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 834UJ UT WOS:000222436100003 PM 15256620 ER PT J AU Blanchard, JJ Sayers, SL Collins, LM Bellack, AS AF Blanchard, JJ Sayers, SL Collins, LM Bellack, AS TI Affectivity in the problem-solving interactions of schizophrenia patients and their family members SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; emotion; negative symptoms; family ID LOW EXPRESSED EMOTION; NEGATIVE SYMPTOMS; GENDER-DIFFERENCES; DEFICIT SCHIZOPHRENIA; TRANSACTIONAL PROCESS; INTERPERSONAL CONTROL; SOCIAL COMPETENCE; NONDEFICIT FORMS; AFFECTIVE STYLE; RELIABILITY AB This study sought to examine the relationship between symptomatology and the affect expressed between individuals with schizophrenia and their family members. It was hypothesized that, because of their impact on patient social behavior and potential burden on relatives, greater negative symptoms would be associated with less emotional expression in patients but would be related to the greater expression of negative emotions in their relatives within a problem-solving discussion. Informed by research on the structure of emotion, a broad assessment of affect, including Negativity, Positivity, and Disengagement, was utilized to examine affect expressed by patients with schizophrenic disorders (N = 91) and their family members during videotaped problem-solving discussions. Although individuals with schizophrenia were comparable to their family members in displays of Negativity, patients displayed less Positivity and greater Disengagement. Greater negative symptoms (in particular blunted or flat affect) were related to a general diminution of affective expression in the schizophrenia group. However, negative symptoms were unrelated to the emotional expression of family members. Other symptoms such as thought disorder and mood symptoms of anxiety, depression, and hostility were not related to displays of affect by either patients or their family members. The findings indicate the importance of examining domains of affect other than negativity and demonstrate that negative symptoms are related to interpersonal displays of affect in schizophrenia. Additionally, these results suggest that schizophrenic symptoms, by themselves, may contribute little to the conflict between patients and their family members. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Baltimore Vet Affairs Capitol Hlth Care Network, Mental Illness Res Educ & Clin Ctr, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. RP Blanchard, JJ (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM jblanchard@psyc.umd.edu FU NIMH NIH HHS [MH39998, MH41577, MH51240] NR 67 TC 15 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL 1 PY 2004 VL 69 IS 1 BP 105 EP 117 DI 10.1016/j.schres.2003.07.008 PG 13 WC Psychiatry SC Psychiatry GA 826EJ UT WOS:000221811800013 PM 15145476 ER PT J AU Rizouli, V Gribben, JG AF Rizouli, V Gribben, JG TI The role of stem cell transplantation in chronic lymphocytic leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMERASE-CHAIN-REACTION; ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; VERSUS-HOST-DISEASE; HIGH-DOSE THERAPY; TERM-FOLLOW-UP; ZAP-70 EXPRESSION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 65 TC 3 Z9 4 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 JUL PY 2004 VL 41 IS 3 BP 246 EP 253 DI 10.1053/j.seminhematol.2004.05.006 PG 8 WC Hematology SC Hematology GA 841BG UT WOS:000222903700008 PM 15269884 ER PT J AU Hak, AE Ma, J Powell, CB Campos, H Gaziano, JM Willett, WC Stampfer, MJ AF Hak, AE Ma, J Powell, CB Campos, H Gaziano, JM Willett, WC Stampfer, MJ TI Prospective study of plasma carotenoids and tocopherols in relation to risk of ischemic stroke SO STROKE LA English DT Article DE antioxidants; carotenoids; tocopherols; ischemic stroke ID FOOD FREQUENCY QUESTIONNAIRE; HEART-DISEASE; VEGETABLE INTAKE; BETA-CAROTENE; VITAMIN-C; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; ALPHA-TOCOPHEROL; MEN; FRUIT AB Background and Purpose - Intake of fruits and vegetables has been related to lower risk of ischemic stroke, but nutrients responsible for this apparent benefit remain ill-defined. Tocopherols ( vitamin E) have also been proposed to be protective. Methods - We conducted a prospective, nested case-control analysis among male physicians without diagnosed cardiovascular disease followed-up for up to 13 years in the Physicians' Health Study. Samples from 297 physicians with ischemic stroke were analyzed with paired controls, matched for age and smoking, for 5 major carotenoids (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene), retinol, and alpha- and gamma-tocopherol. Results - Baseline plasma levels of alpha- carotene and beta-carotene and lycopene tended to be inversely related to risk of ischemic stroke with an apparent threshold effect. As compared with men whose plasma levels were in the lowest quintile, the multivariate adjusted odds ratios (ORs) of ischemic stroke among men with levels in the second through fifth quintiles were 0.59 (95% CI, 0.36 to 0.98) for alpha-carotene, 0.62 ( 95% CI, 0.38 to 1.01) for beta-carotene, and 0.61 ( 95% CI, 0.37 to 1.00) for lycopene. A tendency toward an inverse association was found for beta-cryptoxanthin, but the result was not statistically significant. No association was found for lutein, retinol, and tocopherols. Conclusion - Our data suggest that higher plasma levels of carotenoids, as markers of fruit and vegetable intake, are inversely related to risk of ischemic stroke and provide support for recommendations to consume fruits and vegetables regularly. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. RP Ma, J (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu FU NCI NIH HHS [CA58684, CA42182, CA78293, CA90598, R01 CA097193] NR 28 TC 56 Z9 61 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2004 VL 35 IS 7 BP 1584 EP 1588 DI 10.1161/01.STR.0000132197.67350.bd PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 832HE UT WOS:000222257300012 PM 15178820 ER PT J AU Rattner, DW AF Rattner, DW TI Invited commentary: "Objective evaluation of the effect of noise on the performance of a complex laparoscopic task" SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WAC337, Boston, MA 02114 USA. NR 1 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 0039-6060 J9 SURGERY JI Surgery PD JUL PY 2004 VL 136 IS 1 BP 31 EP 31 DI 10.1016/j.surg.2004.01.012 PG 1 WC Surgery SC Surgery GA 836WL UT WOS:000222586700006 ER PT J AU Ellsmere, J Stoll, M Wells, W Kikinis, R Vosburgh, K Kane, R Brooks, D Rattner, D AF Ellsmere, J Stoll, M Wells, W Kikinis, R Vosburgh, K Kane, R Brooks, D Rattner, D TI A new visualization technique for laparoscopic ultrasonography SO SURGERY LA English DT Editorial Material ID PANCREATIC-CANCER; LIVER-TUMORS; ULTRASOUND; CARCINOMA; SURGERY; MODEL AB Background. Using laparoscopic ultrasonography (LUS) is challenging for both novice and experienced ultrasonographers. The major difficulty surgeons experience is understanding. the orientation of the ultrasonography image. The purpose of this study was to assess whether providing surgeons with orientation information improves their ability to interpret LUS images. Methods. We performed a L US examination on a 25-kg pig and simultaneously digitized video from the laparoscopic camera, the LUS, and a novel orientation system. From the video recordings, 12 different clips of intra-abdominal anatomy were prepared. Twenty surgeons (18 staff, 2 fellows) volunteered to participate in an experimental crossover study. Test subjects reviewed the LUS clips along with the laparoscopic video images and the orientation display. Controls reviewed the LUS clips with only the loparoscopic video images. Diagnostic accuracy was compared by using the odds ratio. Results. For all vessels, the orientation display improved the odds ratio for correctly identifying structures from 3.7 to 8.9 (P = .02). For arteries, the orientation display improved the odds ratio from 2.4 to 9.6 (P =. 01). For. veins, the orientation display improved the odds ratio from 4.4 to 13.6 (P = .04). Conclusions. Providing orientation information significantly improves a surgeon's ability to interpret LUS images. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA USA. Boston Univ, Dept Mech Engn, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC 337, Boston, MA 02114 USA. NR 23 TC 26 Z9 26 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 JUL PY 2004 VL 136 IS 1 BP 84 EP 92 DI 10.1016/j.surg.2004.03.005 PG 9 WC Surgery SC Surgery GA 836WL UT WOS:000222586700013 PM 15232543 ER PT J AU Perez, VL Chavala, SH Ahmed, M Chu, D Zafirakis, P Baltatzis, S Ocampo, V Foster, CS AF Perez, VL Chavala, SH Ahmed, M Chu, D Zafirakis, P Baltatzis, S Ocampo, V Foster, CS TI Ocular manifestations and concepts of systemic vasculitides SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE Churg-Strauss syndrome; cutaneous leukocytoclastic angiitis; giant cell arteritis; Henoch-Schonlein purpura; Kawasaki disease; microscopic polyangiitis; ocular manifestations; polyarteritis nodosa; primary vasculitis; Takayasu's arteritis; Wegener's granulomatosis ID GIANT-CELL ARTERITIS; CHURG-STRAUSS-SYNDROME; ERYTHROCYTE SEDIMENTATION-RATE; HEPATITIS-C VIRUS; ESSENTIAL MIXED CRYOGLOBULINEMIA; RHEUMATOLOGY 1990 CRITERIA; HENOCH-SCHONLEIN PURPURA; ISCHEMIC OPTIC NEUROPATHY; LYMPH-NODE SYNDROME; WEGENERS-GRANULOMATOSIS AB Vasculitic disorders are relatively rare. Their etiology and pathophysiology remain enigmatic, leading to confusing nomenclature and multiple classification schemes. Untreated vasculitis can be fatal. Early diagnosis is the key to successful treatment and better prognosis. However, early diagnosis can be difficult; vasculitic conditions usually present with non-specific symptoms for a long period before clinically overt manifestations occur. Ophthalmologists should be familiar with the ocular manifestations of the vasculitic disorders because they may not only be sight-threatening, but more importantly could be the presenting manifestations of active, potentially lethal systemic disease. This review summarizes clinical and ocular manifestations of systemic vasculitic disorders. Furthermore, it discusses general concepts in diagnosis and treatment of these diseases in an effort to provide a practical framework for the ophthalmologist evaluating patients with vasculitis. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. Cleveland Clin Fdn, Cole Eye Inst, Cornea & Uveitis Serv, Cleveland, OH 44195 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [K08 EY021171] NR 183 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JUL-AUG PY 2004 VL 49 IS 4 BP 399 EP 418 DI 10.1016/j.survophthal.2004.04.008 PG 20 WC Ophthalmology SC Ophthalmology GA 836VH UT WOS:000222583400002 PM 15231396 ER PT J AU Vickers, SM Johnson, LL Zou, LQ Yannas, IV Gibson, LJ Spector, M AF Vickers, SM Johnson, LL Zou, LQ Yannas, IV Gibson, LJ Spector, M TI Expression of alpha-smooth muscle actin by and contraction of cells derived from synovium SO TISSUE ENGINEERING LA English DT Article ID COLLAGEN-GAG MATRICES; HUMAN ARTICULAR CHONDROCYTES; ANTERIOR CRUCIATE LIGAMENT; PARTIAL-THICKNESS DEFECTS; FIBROBLAST-GROWTH-FACTOR; IN-VITRO; GLYCOSAMINOGLYCAN MATRIX; CARTILAGE; TISSUE; MYOFIBROBLASTS AB Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells-including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells. C1 Harvard Univ, Dept Orthoped Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Spector, M (reprint author), Harvard Univ, Dept Orthoped Surg, Brigham & Womens Hosp, Sch Med, MRB 106,75 Francis St, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu RI Gibson, Lorna/K-4738-2012 NR 40 TC 14 Z9 15 U1 0 U2 3 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUL-AUG PY 2004 VL 10 IS 7-8 BP 1214 EP 1223 DI 10.1089/1076327041887826 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 853TG UT WOS:000223851200024 PM 15363177 ER PT J AU Gordon, TD Schloesser, L Humphries, DE Spector, M AF Gordon, TD Schloesser, L Humphries, DE Spector, M TI Effects of the degradation rate of collagen matrices on articular chondrocyte proliferation and biosynthesis in vitro SO TISSUE ENGINEERING LA English DT Article ID CROSS-LINKING; EXTRACELLULAR-MATRIX; ARTIFICIAL SKIN; CARTILAGE; BEHAVIOR; REGENERATION; CONTRACTION; HYDROGELS; SCAFFOLD; MODEL AB The objective of this study was to evaluate effects of the degradation rate of type 11 collagen scaffolds on the proliferation and biosynthetic activity of adult canine chondrocytes in vitro. The lower number of cells in more rapidly degrading scaffolds appeared to be related to the loss of scaffold material with dissolution. After 14 days in culture, protein and proteoglycan synthesis rates per cell for rapidly degrading scaffolds were comparable to rates for nondegraded matrices. This result suggests that decoupling of the degradation and formation phases of tissue remodeling may occur under certain circumstances. C1 Harvard Univ, Dept Orthoped Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Geistlich Biomat, Wolhusen, Switzerland. RP Spector, M (reprint author), Harvard Univ, Dept Orthoped Surg, Brigham & Womens Hosp, Sch Med, MRB 106,75 Francis St, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu RI Gordon, Timothy/H-9497-2013 OI Gordon, Timothy/0000-0002-5128-9532 NR 28 TC 9 Z9 10 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2152-4947 J9 TISSUE ENG JI Tissue Eng. PD JUL-AUG PY 2004 VL 10 IS 7-8 BP 1287 EP 1295 DI 10.1089/ten.2004.10.1287 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 853TG UT WOS:000223851200030 PM 15363183 ER PT J AU Nieland, TJF Feng, Y Brown, JX Chuang, TD Buckett, PD Wang, J Xie, XS McGraw, TE Kirchhausen, T Wessling-Resnick, M AF Nieland, TJF Feng, Y Brown, JX Chuang, TD Buckett, PD Wang, J Xie, XS McGraw, TE Kirchhausen, T Wessling-Resnick, M TI Chemical genetic screening identifies sulfonamides that raise organellar pH and interfere with membrane traffic SO TRAFFIC LA English DT Article DE chemical genetics; membrane traffic; organelle pH; sulfonamides ID RECEPTOR-MEDIATED ENDOCYTOSIS; H+-TRANSLOCATING ATPASE; HAMSTER OVARY CELLS; TRANSFERRIN RECEPTOR; PLASMA-MEMBRANE; K562 CELLS; INTRACELLULAR DISSOCIATION; HEPATOMA-CELLS; IRON UPTAKE; ACIDIFICATION AB Chemical genetics seeks to identify small molecules that afford functional dissection of cell biological pathways. Previous screens for small molecule inhibitors of exocytic membrane traffic yielded the identification and characterization of several compounds that block traffic from the Golgi to the cell surface as well as transport from the endoplasmic reticulum to the Golgi network [Feng et al. Proc Natl Acad Sci USA 2003;100:6469-6474; Yarrow et al. Comb Chem High Throughput Screen 2003;6:279-286; Feng et al. EMBO Reports 2004: in press]. Here, we screened these inhibitors for potential effects on endocytic membrane traffic. Two structurally related sulfonamides were found to be potent and reversible inhibitors of transferrin-mediated iron uptake. These inhibitors do not block endoplasmic reticulum-to-Golgi transport, but do disrupt Golgi-to-cell surface traffic. The compounds are members of a novel class of sulfonamides that elevate endosomal and lysosomal pH, down-regulate cell surface receptors, and impair recycling of internalized transferrin receptors to the plasma membrane. In vitro experiments revealed that the sulfonamides directly inhibit adenosine triphosphate (ATP) hydrolysis by the V-ATPase and that they also possess a potent proton ionophore activity. While maintenance of organellar pH is known to be a critical factor in both endocytosis and exocytosis, the precise role of acidification, beyond the uncoupling of ligands from their receptors, remains largely unknown. Identification of this novel class of sulfonamide inhibitors provides new chemical tools to better understand the function of organelle pH in membrane traffic and the activity of V-ATPases in particular. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Inst Chem & Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. Univ Texas, SW Med Ctr, Eugene McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu; wessling@hsph.harvard.edu FU NIDDK NIH HHS [DK33627, DK57689, P01 DK055495, R01 DK052852, R01 DK056160, R01 DK064750, R01 DK064750-01A1, R01 DK057689, DK56160, DK55495, DK52852]; NIGMS NIH HHS [GM36548, R01 GM036548, GM62566, P01 GM062566] NR 49 TC 20 Z9 20 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD JUL PY 2004 VL 5 IS 7 BP 478 EP 492 DI 10.1111/j.1600-0854.2004.00193.x PG 15 WC Cell Biology SC Cell Biology GA 826UC UT WOS:000221853800003 PM 15180825 ER PT J AU Rouhani, FJ Dor, FJMF Cooper, DKC AF Rouhani, FJ Dor, FJMF Cooper, DKC TI Investigation of red blood cells from alpha 1,3-galactosyltransferase-knockout pigs for human blood transfusion SO TRANSFUSION LA English DT Article ID PORCINE ERYTHROCYTES; NATURAL ANTIBODIES; TRANSPLANTATION; CHIMERISM; XENOTRANSPLANTATION; EXPRESSION; PRIMATES AB BACKGROUND: Pigs are a potential source of red blood cells (RBCs) for transfusion into humans, but the presence of galactose-alpha1,3-galactose (Gal) epitopes on their surface, against which humans have anti-Gal, has been perceived as a major barrier. alpha1,3-Galactosyltransferase gene-knockout pigs, which do not express Gal epitopes on RBCs (Gal-/-), have recently become available. STUDY DESIGN AND METHODS: In vitro, RBCs from Gal-/- pigs were exposed to sera from naive humans or baboons or from baboons previously sensitized to pig antigens; immunoglobulin binding Was measured by flow cytometry, and cytotoxicity, by a hemolytic assay. In vivo, relatively small numbers of Gal-/- RBCs were transfused into two nonsensitized untreated baboons. The survival of pig RBCs was detected by flow cytometry. RESULTS: In vitro, binding of immunoglobulin (Ig) M from naive human or baboon sera was detected to Gal-/-RBCs but was significantly less than to Gal+/+ RBCs; IgG binding to Gal-/- RBCs was absent or minimal. Sera had minimal cytotoxicity to Gal-/- RBCs compared to Gal+/+ RBCs. Sensitized baboon sera demonstrated much higher IgG binding to Gal-/- RBCs and increased cytotoxicity, but again these were less than to Gal+/+ RBCs. In vivo, the transfusion of relatively small volumes of Gal-/- RBCs was followed by detection of the cells in the baboon's blood for only 5 minutes. CONCLUSION: Pig RBCs are rapidly phagocytosed from the primate circulation by a mechanism not involving anti-Gal. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM David.Cooper@tbrc.mgh.harvard.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 25 TC 14 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2004 VL 44 IS 7 BP 1004 EP 1012 DI 10.1111/j.1537-2995.2004.04002.x PG 9 WC Hematology SC Hematology GA 832YF UT WOS:000222302900010 PM 15225240 ER PT J AU Bernards, A Settleman, J AF Bernards, A Settleman, J TI GAP control: regulating the regulators of small GTPases SO TRENDS IN CELL BIOLOGY LA English DT Review ID LINKED MENTAL-RETARDATION; PLECKSTRIN HOMOLOGY DOMAIN; NF1 TUMOR-SUPPRESSOR; ACTIVATING PROTEIN; NUCLEOTIDE EXCHANGE; TERMINAL DOMAIN; RHOGAP ACTIVITY; RAS; PHOSPHORYLATION; PATHWAY AB The small GTPases of the Ras superfamily mediate numerous biological processes through their ability to cycle between an inactive GDP-bound and an active GTP-bound form. Among the key regulators of GTPase cycling are the GTPase-activating proteins (GAPs), which stimulate the weak intrinsic GTP-hydrolysis activity of the GTPases, thereby inactivating them. Despite the abundance of GAPs and the fact that mutations in GAP-encoding genes underlie several human diseases, these proteins have received relatively little attention. Recent studies have addressed the regulatory mechanisms that influence GAP activity. So far, findings suggest that GAP activity is regulated by several mechanisms, including protein-protein interactions, phospholipid interactions, phosphorylation, subcellular translocation and proteolytic degradation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 62 TC 195 Z9 199 U1 0 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUL PY 2004 VL 14 IS 7 BP 377 EP 385 DI 10.1016/j.tcb.2004.05.003 PG 9 WC Cell Biology SC Cell Biology GA 842ND UT WOS:000223010200009 PM 15246431 ER PT J AU Li, HW Corrales, CE Edge, A Heller, S AF Li, HW Corrales, CE Edge, A Heller, S TI Stem cells as therapy for hearing loss SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID MOUSE INNER-EAR; AUDITORY HAIR-CELLS; IN-VIVO; PARKINSONS-DISEASE; MAMMALIAN COCHLEA; BONE-MARROW; GUINEA-PIGS; MYOSIN VIIA; EXPRESSION; REGENERATION AB One of the greatest challenges in the treatment of inner-ear disorders is to find a cure for the hearing loss that is caused by the loss of cochlear hair cells or spiral ganglion neurons. The recent discovery of stem cells in the adult inner ear that are capable of differentiating into hair cells, as well as the finding that embryonic stem cells can be converted into hair cells, raise hope for the future development of stem-cell-based treatment regimens. Here, we propose different approaches for using stem cells to regenerate the damaged inner ear and we describe the potential obstacles that translational approaches must overcome for the development of stem-cell-based cell-replacement therapies for the damaged inner ear. 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. EM hellers@epl.meei.harvard.edu NR 69 TC 47 Z9 54 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUL PY 2004 VL 10 IS 7 BP 309 EP 315 DI 10.1016/j.molmed.2004.05.008 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 842RC UT WOS:000223020700004 PM 15242678 ER PT J AU Zhao, JJ Roberts, TM Hahn, WC AF Zhao, JJ Roberts, TM Hahn, WC TI Functional genetics and experimental models of human cancer SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID NORMAL HUMAN-CELLS; HUMAN TUMOR-CELLS; HUMAN EPIDERMAL-KERATINOCYTES; MAMMARY EPITHELIAL-CELLS; HUMAN ENDOTHELIAL-CELLS; PROTEIN PHOSPHATASE 2A; TELOMERASE ACTIVITY; HUMAN-FIBROBLASTS; T-ANTIGEN; NEOPLASTIC TRANSFORMATION AB Abundant evidence supports the hypothesis that cancer arises from normal cells through the stepwise accumulation of genetic mutations. The study of cells obtained from patients with cancer has identified numerous molecules and pathways that fundamentally contribute to malignant transformation; however, cancer cell lines are often difficult to isolate or maintain, and the cell lines that are available for experimentation represent only a small subset of late-stage human cancers. Recent work has elucidated the role of telomerase in regulating human cell lifespan and has enabled the development of new experimental systems to study human cancer. This review highlights the recent progress in combining genetic methods and primary human cells to understand the role of specific genes and pathways in cancer pathogenesis. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Broad Inst, Cambridge, MA 02141 USA. RP Hahn, WC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu NR 70 TC 40 Z9 43 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUL PY 2004 VL 10 IS 7 BP 344 EP 350 DI 10.1016/j.molmed.2004.05.005 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 842RC UT WOS:000223020700009 PM 15242683 ER PT J AU van Zundert, B Yoshii, A Constantine-Paton, M AF van Zundert, B Yoshii, A Constantine-Paton, M TI Receptor compartmentalization and trafficking at glutamate synapses: a developmental proposal SO TRENDS IN NEUROSCIENCES LA English DT Review ID EXTRASYNAPTIC NMDA RECEPTORS; NICOTINIC ACETYLCHOLINE-RECEPTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; SPONTANEOUS RETINAL ACTIVITY; CEREBELLAR GRANULE NEURONS; POSTSYNAPTIC DENSITY; SYNAPTIC-TRANSMISSION; VISUAL-CORTEX; MICE LACKING; DIFFERENTIAL REGULATION AB This article focuses on NMDA receptor subunit changes that occur in the forebrain and midbrain during development, namely the switch from predominance of NMDA receptors rich in NR2B subunits to that of NMDA receptors rich in NR2A subunits. We review the potential roles in brain plasticity of two membrane-associated guanylate kinases (MAGUKs), SAP102 and PSD95, which form a scaffold for the ion-passing glutamate receptors at the postsynaptic density, and we consider the known functional significance of these molecules in subunit switching. In addition, based on recent analyses of the synaptic location of glutamate receptors, activity-dependent changes in developing visual neurons, and extensive data on MAGUKs, we propose a model of glutamatergic synaptic differentiation. In this model, different NMDA receptor scaffolding and signaling complexes effect the trafficking and synaptic localization of NR2A-rich and NR2B-rich receptors, leading to tangential compartmentalization of these receptors and their movement between synaptic and extrasynaptic compartments. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Mcgovern Inst Brain Res, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Day Lab Neuromuscular Res, Boston, MA 02115 USA. RP Constantine-Paton, M (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA. EM mcpaton@mit.edu FU NEI NIH HHS [R01 EY 014074, R03 EY 014420]; NINDS NIH HHS [R01 NS 3290] NR 67 TC 145 Z9 149 U1 1 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2004 VL 27 IS 7 BP 428 EP 437 DI 10.1016/j.tins.2004.05.010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 843MU UT WOS:000223088800013 PM 15219743 ER PT J AU Engelfriet, CP Reessink, HW AF Engelfriet, CP Reessink, HW TI Transfusion safety in the hospital SO VOX SANGUINIS LA English DT Article ID SAMPLE COLLECTION; BLOOD-TRANSFUSION; PERFORMANCE C1 Sanquin Diagnost Serv, NL-1066 CX Amsterdam, Netherlands. Sanquin Blood Bank NW Reg, NL-1066 CX Amsterdam, Netherlands. Sanquin Res, NL-1066 CX Amsterdam, Netherlands. Royal Adelaide Hosp, Inst Med & Vet Sci, Transfus Med Unit, Adelaide, SA 5000, Australia. AO Landeskrankenhaus Univ Kliniken Innsbruck, Immunol Abt, A-6020 Innsbruck, Austria. AO Landeskrankenhaus Univ Kliniken Innsbruck, Vorstand Zent Inst Bluttransfus, A-6020 Innsbruck, Austria. Univ Copenhagen Hosp, Rigshosp, Clin Transfus Serv, HS Blodbank KI 2034, DK-2100 Copenhagen, Denmark. Pirkanmaa Hosp Dist, Ctr Lab Med, Haematol Lab, FIN-33521 Tampere, Finland. Univ Greifswald, Sauerbruchstr Diagnost Zentrum, Inst Immunol & Transfus Med, D-17487 Greifswald, Germany. Natl Blood Ctr, Natl Haemovigilance Off, Dublin 8, Ireland. Azienda Osped Verona, Serv Immunoematol & Trasfus, I-37126 Verona, Italy. Univ Tokyo, Dept Transfus Med, Bunkyo Ku, Tokyo 1138655, Japan. TRIP Dutch Natl Hemovigilance Off, NL-2504 LN The Hague, Netherlands. Leyenburg Hosp, Dept Hematol, NL-2504 LN The Hague, Netherlands. Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus Med, NL-2300 RC Leiden, Netherlands. Rikshosp Univ Hosp, Inst Immunol, NO-0027 Oslo, Norway. Univ Zurich Hosp, Div Haematol Transfus Med, CH-8091 Zurich, Switzerland. John Radcliffe Hosp, Natl Blood Serv, Oxford OX3 9BQ, England. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Engelfriet, CP (reprint author), Sanquin Diagnost Serv, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. EM p.engelfriet@sanquin.nl; h.reesink@sanquin.nl NR 14 TC 4 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2004 VL 87 IS 1 BP 48 EP 62 PG 15 WC Hematology SC Hematology GA 838PM UT WOS:000222725300009 ER PT J AU Hastreiter, D Chao, J Wang, QI Ozuna, RM Spector, M AF Hastreiter, D Chao, J Wang, QI Ozuna, RM Spector, M TI Alpha-smooth muscle actin in pathological human disc nucleus pulposus cells in vivo and in vitro SO WOUND REPAIR AND REGENERATION LA English DT Article ID LUMBAR INTERVERTEBRAL DISCS; ANTERIOR CRUCIATE LIGAMENT; GROWTH-FACTOR-BETA; ARTICULAR-CARTILAGE; GRANULATION-TISSUE; EXPRESSION; CONTRACTION; FIBROBLASTS; MYOFIBROBLASTS; COLLAGEN AB That a contractile actin isoform has been found in cells of other cartilage tissues in healing and disease states prompted this investigation of the presence of alpha-smooth muscle actin (alpha-SMA) in pathological human intervertebral disc tissue. The presence of this isoform has been reported in human intervertebral disc specimens obtained at autopsy from subjects for whom there were no reported symptoms. An objective of this study was to evaluate the cell density and percentage of alpha-SMA-containing cells in pathological nucleus pulposus tissue obtained from lumbar disc surgery from 17 patients. Additionally, explants of nucleus pulposus material were cultured to determine how alpha-SMA expression changed with time in vitro. Seventy-six 5-mm diameter explants (approximately 2 mm thick) pooled from six lumbar surgeries were cultured for 1, 2, 4, or 6 weeks. Microtomed sections of paraffin-embedded specimens were stained with hematoxylin and eosin or a monoclonal antibody to alpha-SMA. Histologically, cells were categorized as to alpha-SMA phenotype (positive or negative), and the areal cell density was determined. The evaluation of the cultured nucleus pulposus explants also included documentation of the percentage of cells that were round or elongated and the percentage of the cells that were part of a group (group: greater than or equal to 2 cells). Every nucleus pulposus section exhibited the presence of alpha-SMA-containing cells, which accounted for approximately 24 percent of the cells in vivo. In vivo, the cell density was significantly higher in older individuals (p = 0.02). The average time for cell outgrowth from the explants was 8.6 days. Approximately 10-15 percent of the cells in the explants stained positive for alpha-SMA. The time in culture had no significant effect on any of the outcome measures except the percentage of alpha-SMA-containing cells that were round (p = 0.008), with values decreasing through 4 weeks and then slightly rising at 6 weeks. The role of alpha-SMA in intervertebral disc pathology warrants further investigation. C1 MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA. MIT, Dept Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Orthopaed Res Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Orthopaed Res Lab,Dept Orthopaed Surg, 75 Francis St,MRB106, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu FU NIDCR NIH HHS [5T32 DE 073121] NR 29 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JUL-AUG PY 2004 VL 12 IS 4 BP 430 EP 438 DI 10.1111/j.1067-1927.2004.12408.x PG 9 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 838PR UT WOS:000222725900006 PM 15260808 ER PT J AU Knosalla, C Ryan, DJJ Moran, K Gollackner, B Schuler, W Sachs, DH Awwad, M Schuurman, HJ Cooper, DKC AF Knosalla, C Ryan, DJJ Moran, K Gollackner, B Schuler, W Sachs, DH Awwad, M Schuurman, HJ Cooper, DKC TI Initial experience with the human anti-human CD154 monoclonal antibody, ABI793, in pig-to-baboon xenotransplantation SO XENOTRANSPLANTATION LA English DT Article DE antibodies; anti-CD154 monoclonal antibody; baboon; CD154; costimulatory blockade; pig; xenotransplantation ID RENAL-ALLOGRAFT REJECTION; CELL-MEDIATED-IMMUNITY; CD40 LIGAND; KIDNEY-TRANSPLANTATION; GAL ANTIBODY; BLOCKADE; ACCEPTANCE; PRIMATES; CD28; RECIPIENTS AB Background: ABI793 (ABI) is a human monoclonal antibody (mAb) specific for human CD154. To assess the suitability of ABI for baboon transplantation studies, we carried out in vitro studies to determine ABI's reactivity with baboon cells expressing CD154, performed in vivo pharmacokinetic studies in two baboons, and tested the effect of ABI administration on elicited antibody production in two baboons undergoing either pig hematopoietic progenitor cell (PBPC) or heterotopic heart transplantation. Methods: In vitro: Baboon peripheral blood mononuclear cells were activated in vitro to upregulate CD154, and binding of ABI to CD154 was measured by flow cytometry. In vivo: Serum levels of ABI were measured immediately before and 15 min after the intravenous administration of ABI (20 mg/kg) to two baboons over 28 days. Subsequently, ABI (25 mg/kg on days 0, 1, 4 and 7, and then 20 mg/kg every 5 days) was included in the immunosuppressive regimen in two pig-to-baboon transplants (PBPC or heart transplantation). Results: In vitro: ABI was almost non-reactive to baboon T cells before stimulation, but bound to activated T cells. In vivo: In the pharmacokinetic study, trough levels of ABI (before the next dose) ranged between 190 and 580 mug/ml, and the estimated half-life was 10-15 days. There was no apparent toxicity. Following pig PBPC or heart transplantation, no elicited antibody was detected while ABI was being administered or during several weeks of follow-up. Conclusions: ABI functions in baboons, is well-tolerated, and prevents an elicited antibody response to pig antigens. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Immerge Biotherapeut, Cambridge, MA USA. Novartis Pharma AG, Basel, Switzerland. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM david.cooper@tbrc.mgh.harvard.edu FU PHS HHS [1P01 A145897] NR 31 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2004 VL 11 IS 4 BP 353 EP 360 DI 10.1111/j.1399-3089.2004.00148.x PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 828NI UT WOS:000221979600007 PM 15196130 ER PT J AU Tseng, YL Dor, FJMF Kuwaki, K Ryan, D Wood, J Denaro, M Giovino, M Yamada, K Hawley, R Patience, C Schuurman, HJ Awwad, M Sachs, DH Cooper, DKC AF Tseng, YL Dor, FJMF Kuwaki, K Ryan, D Wood, J Denaro, M Giovino, M Yamada, K Hawley, R Patience, C Schuurman, HJ Awwad, M Sachs, DH Cooper, DKC TI Bone marrow transplantation from alpha 1,3-galactosyltransferase gene-knockout pigs in baboons SO XENOTRANSPLANTATION LA English DT Article DE alpha 1,3-galactosyltransferase; bone marrow transplantation; chimerism; hematopoietic cells; xenotransplantation ID NONLETHAL PREPARATIVE REGIMEN; HEMATOPOIETIC-CELL CHIMERISM; MIXED CHIMERISM; THROMBOTIC MICROANGIOPATHY; TOLERANCE INDUCTION; ALLOGRAFT TOLERANCE; XENOGENEIC BARRIER; PROGENITOR CELLS; LONG-TERM; ENGRAFTMENT AB Background: Successful hematopoietic cell allotransplantation results in donor-specific tolerance, but this approach has been unsuccessful in the wild-type pig-to-baboon xenotransplantation model, as pig cells were lost from the circulation within 5 days. However, after cessation of immunosuppressive therapy on day 28, all baboons demonstrated non-specific unresponsiveness on mixed leukocyte reaction (MLR) for at least 30 days. We have now investigated the transplantation of bone marrow (BM) cells from miniature swine homozygous for alpha1,3-galactosyltransferase gene-knockout (GalT-KO). Methods: Baboons (n = 3) were pre-treated with whole body and thymic irradiation, anti-thymocyte globulin, and splenectomy, and received immunosuppressive and supportive therapy for 28 days. BM was harvested from GalT-KO swine (n = 3). The baboons were monitored for the presence of pig cells by flow cytometry and colony-forming units (CFUs), and for cellular reactivity by MLR. Results: A mean of 11 x 10(8) BM cells/kg was infused into each baboon. The mean absolute numbers and percentages of pig cells detected in the blood at 2 h and on days 1, 2 and 4, respectively, were 641/mul (9.5%), 132/mul (3.4%), 242/mul (3.9%), and 156/mul (2.9%). One baboon died (from accidental hemorrhage) on day 6, at which time chimerism was present in the blood (2.0%) and BM (6.4%); pig cell engraftment in the BM was confirmed by polymerase chain reaction (PCR) of CFUs. In the two other baboons, blood chimerism was lost after day 5 but returned at low levels (<1%) between days 9 to 16 and 7 to 17, respectively, indicating transient BM engraftment. Both surviving baboons showed non-specific unresponsiveness on MLR until they were euthanized on days 85 and 110, respectively. Conclusions: By using BM cells from GalT-KO pigs, chimerism was detected at levels comparable with previous studies when 30-fold more growth factor-mobilized peripheral blood progenitor cells had been transplanted. In addition, cellular hyporesponsiveness was prolonged. However, long-term engraftment and chimerism were not achieved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge Biotherapeut Inc, Cambridge, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. EM cooperdk@upmc.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU PHS HHS [1P01 A145897] NR 33 TC 32 Z9 35 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2004 VL 11 IS 4 BP 361 EP 370 DI 10.1111/j.1399-3089.2004.00151.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 828NI UT WOS:000221979600008 PM 15196131 ER PT J AU Dor, FJMF Cooper, DKC AF Dor, FJMF Cooper, DKC TI Gal alpha 1,3Gal expression on porcine pancreatic islets, testis, spleen, and thymus (vol 11, pg 101, 2004) SO XENOTRANSPLANTATION LA English DT Correction C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Dor, FJMF (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM cooperdk@upmc.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2004 VL 11 IS 4 BP 382 EP 382 DI 10.1111/j.1399-3089.2004.00143.x PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 828NI UT WOS:000221979600013 PM 15196136 ER PT J AU Pannu, R Won, JS Khan, M Singh, AK Singh, I AF Pannu, R Won, JS Khan, M Singh, AK Singh, I TI A novel role of lactosylceramide in the regulation of lipopolysaccharide/interferon-gamma-mediated inducible nitric oxide synthase gene expression: Implications for neuroinflammatory diseases SO JOURNAL OF NEUROSCIENCE LA English DT Article DE iNOS; astrocytes; lactosylceramide; lipopolysaccharide; interferon-gamma; spinal cord injury ID TUMOR-NECROSIS-FACTOR; SPINAL-CORD-INJURY; ACTIVATED PROTEIN-KINASE; CENTRAL-NERVOUS-SYSTEM; SMOOTH-MUSCLE-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CREUTZFELDT-JAKOB-DISEASE; TRAUMATIC BRAIN-INJURY; C-FOS EXPRESSION; MULTIPLE-SCLEROSIS AB In the present study a possible role of glycosphingolipids (GSLs) in inducible nitric oxide synthase ( iNOS) gene expression and nitric oxide ( NO) production after spinal cord injury (SCI) in rats has been established. In primary rat astrocytes lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) treatment increased the intracellular levels of lactosylceramide ( LacCer) and induced iNOS gene expression. D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol . HCI ( PDMP), a glucosylceramide synthase and LacCer synthase ( galactosyltransferase, GalT-2) inhibitor, inhibited LPS/IFN-gamma induced iNOS expression, which was reversed by exogenously supplied LacCer, but not by other glycosphingolipids. LPS/IFN-gamma caused a rapid increase in the activity of GalT-2 and synthesis of LacCer. Silencing of GalT-2 gene with the use of antisense oligonucleotides resulted in decreased LPS/IFN-gamma-induced iNOS, TNF-alpha, and IL-1beta gene expression. The PDMP-mediated reduction in LacCer production and inhibition of iNOS expression correlated with decreased Ras and ERK1/2 activation along with decreased IkappaB phosphorylation, NF-kappaB DNA binding activity, and NF-kappaB-luciferase reporter activity. LacCer-mediated Ras activation was redox-mediated and was attenuated by antioxidants N-acetyl cysteine (NAC) and pyrrolidine dithiocarbamate ( PDTC). In vivo administration of PDMP after SCI resulted in improved functional outcome ( Basso, Beattie, Bresnahan score); inhibition of iNOS, TNF-alpha, and IL-1beta expression; decreased neuronal apoptosis; and decreased tissue necrosis and demyelination. The in vivo studies supported the conclusions drawn from cell culture studies and provided evidence for the possible role of GalT-2 and LacCer in SCI-induced inflammation and pathology. To our knowledge this is the first report of a role of LacCer in iNOS expression and the advantage of GSL depletion in attenuating post-SCI inflammation to improve the outcome of SCI. C1 Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph h Johnson Vet Affairs Med Ctr, Dept Pathol, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, 316 CSB, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810] NR 70 TC 39 Z9 39 U1 0 U2 2 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 JUN 30 PY 2004 VL 24 IS 26 BP 5942 EP 5954 DI 10.1523/JNEUROSCI.1271-04.2004 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 833PZ UT WOS:000222351900011 PM 15229242 ER PT J AU Shin, JM Cho, YM Sachs, G AF Shin, JM Cho, YM Sachs, G TI Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID OMEPRAZOLE ANALOGS; CHEMICAL-REACTIONS; SUBSTITUTED BENZIMIDAZOLES; ACID SECRETION; H+/K+-ATPASE; PANTOPRAZOLE; 2-<(2-PYRIDYLMETHYL)SULFINYL>BENZIMIDAZOLES; 2-MERCAPTOETHANOL; H,K-ATPASE; SYSTEM AB Proton pump inhibitors (PPIs), drugs that are widely used for treatment of acid related diseases, are either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives. They are all prodrugs that inhibit the acid-secreting gastric (H+, K+)-ATPase by acid activation to reactive thiophiles that form disulfide bonds with one or more cysteines accessible from the exoplasmic surface of the enzyme. This unique acid-catalysis mechanism had been ascribed to the nucleophilicity of the pyridine ring. However, the data obtained here show that their conversion to the reactive cationic thiophilic sulfenic acid or sulfenamide depends mainly not on pyridine protonation but on a second protonation of the imidazole component that increases the electrophilicity of the C-2 position on the imidazole. This protonation results in reaction of the C-2 with the unprotonated fraction of the pyridine ring to form the reactive derivatives. The relevant PPI pK(a)'s were determined by UV spectroscopy of the benzimidazole or imidazopyridine sulfinylmethyl moieties at different medium pH. Synthesis of a relatively acid stable analogue, M-methyl lansoprazole, (6b), allowed direct determination of both pK(a) values of this intact PPI allowing calculation of the two pK(a) values for all the PPIs. These values predict their relative acid stability and thus the rate of reaction with cysteines of the active proton pump at the pH of the secreting parietal cell. The PPI accumulates in the secretory canaliculus of the parietal cell due to pyridine protonation then binds to the pump and is activated by the second protonation on the surface of the protein to allow disulfide formation. C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Shin, JM (reprint author), Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. EM jaishin@ucla.edu FU NIDDK NIH HHS [DK46917]; PHS HHS [17294, 41301, 53462] NR 20 TC 150 Z9 152 U1 6 U2 29 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 JUN 30 PY 2004 VL 126 IS 25 BP 7800 EP 7811 DI 10.1021/ja049607w PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 831SY UT WOS:000222217600035 PM 15212527 ER PT J AU Wiviott, SD Antmann, EM AF Wiviott, SD Antmann, EM TI Clopidogrel resistance - A new chapter in a fast-moving story SO CIRCULATION LA English DT Editorial Material DE Focused Perspectives; clopidogrel; aspirin; platelets; drug resistance ID PERCUTANEOUS CORONARY INTERVENTION; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ST-SEGMENT ELEVATION; CARDIOVASCULAR-DISEASE; ANTIPLATELET THERAPY; MYOCARDIAL-INFARCTION; PLATELET-AGGREGATION; AMERICAN-COLLEGE; UNSTABLE ANGINA C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 32 TC 123 Z9 146 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 29 PY 2004 VL 109 IS 25 BP 3064 EP 3067 DI 10.1161/01.CIR.0000134701.40946.30 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300002 PM 15226220 ER PT J AU Kaplan, AV Baim, DS Smith, JJ Feigal, DA Simons, M Jefferys, D Fogarty, TJ Kuntz, RE Leon, MB AF Kaplan, AV Baim, DS Smith, JJ Feigal, DA Simons, M Jefferys, D Fogarty, TJ Kuntz, RE Leon, MB TI Medical device development - From prototype to regulatory approval SO CIRCULATION LA English DT Article; Proceedings Paper CT Dartmouth Drug and Device Development Symposium CY OCT 30-31, 2003 CL Woodstock, VT ID INTERVENTION C1 Dartmouth Hitchcock Med Ctr, Cardiol Sect, Dartmouth Med Sch, Lebanon, NH 03756 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Stanford Univ, Dept Surg, Stanford, CA 94305 USA. Lenox Hill Heart & Vasc Inst, New York, NY USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kaplan, AV (reprint author), Dartmouth Hitchcock Med Ctr, Cardiol Sect, Dartmouth Med Sch, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM aaron.v.kaplan@hitchcock.org RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 5 TC 64 Z9 67 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 29 PY 2004 VL 109 IS 25 BP 3068 EP 3072 DI 10.1161/01.CIR.0000134695.65733.64 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300003 PM 15226221 ER PT J AU Gibson, CM Schomig, A AF Gibson, CM Schomig, A TI Coronary and myocardial angiography - Angiographic assessment of both epicardial and myocardial perfusion SO CIRCULATION LA English DT Review ID TIMI FRAME COUNT; LEFT-VENTRICULAR FUNCTION; TISSUE-PLASMINOGEN ACTIVATOR; TERM CLINICAL-OUTCOMES; ST-SEGMENT RESOLUTION; BLOOD-FLOW; PRIMARY ANGIOPLASTY; QUANTITATIVE ASSESSMENT; CORRECTED THROMBOLYSIS; NONCULPRIT ARTERIES C1 Harvard Univ, TIMI Study Grp, Cambridge, MA 02138 USA. Deutsch Herzzentrum, Munich, Germany. RP Gibson, CM (reprint author), 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 85 TC 96 Z9 110 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 29 PY 2004 VL 109 IS 25 BP 3096 EP 3105 DI 10.1161/01.CIR.0000134278.50359.CB PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300008 PM 15226226 ER PT J AU Ichinose, F Roberts, JD Zapol, WM AF Ichinose, F Roberts, JD Zapol, WM TI Inhaled nitric oxide - A selective pulmonary vasodilator - Current uses and therapeutic potential SO CIRCULATION LA English DT Review ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; CALCIUM-CHANNEL BLOCKERS; CONGENITAL HEART-DISEASE; SICKLE-CELL-DISEASE; IMPROVES OXYGENATION; MECONIUM ASPIRATION; COST-EFFECTIVENESS; DELIVERY-SYSTEM C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM ichinose@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [K08 HL004237, K08 HL004237-04] NR 92 TC 115 Z9 124 U1 1 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 JUN 29 PY 2004 VL 109 IS 25 BP 3106 EP 3111 DI 10.1161/01.CIR.0000134595.80170.62 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300009 PM 15226227 ER PT J AU Ropers, D Kuhlmann, A Weyand, M Faller, G Flachskampf, FA Daniel, WG Baum, U Anders, K Achenbach, S Ludwig, J Garlichs, CD AF Ropers, D Kuhlmann, A Weyand, M Faller, G Flachskampf, FA Daniel, WG Baum, U Anders, K Achenbach, S Ludwig, J Garlichs, CD TI Giant true aneurysms of saphenous vein bypass grafts - A rare cause of tumor-like mediastinal masses SO CIRCULATION LA English DT Editorial Material C1 Univ Erlangen Nurnberg, Med Klin Poliklin 2, Dept Internal Med 2, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Anat & Pathol, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Cardiac Surg, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Diagnost Radiol, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ropers, D (reprint author), Univ Erlangen Nurnberg, Med Klin Poliklin 2, Dept Internal Med 2, Ulmenweg 18, D-91054 Erlangen, Germany. EM dieter.ropers@rzmail.uni-erlangen.de 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 0009-7322 J9 CIRCULATION JI Circulation PD JUN 29 PY 2004 VL 109 IS 25 BP E322 EP E323 DI 10.1161/01.CIR.0000131821.06019.27 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 833GY UT WOS:000222326300038 PM 15226234 ER PT J AU Johnson, BR Nitta, RT Frock, RL Mounkes, L Barbie, DA Stewart, CL Harlow, E Kennedy, BK AF Johnson, BR Nitta, RT Frock, RL Mounkes, L Barbie, DA Stewart, CL Harlow, E Kennedy, BK TI A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUSCULAR-DYSTROPHY; NUCLEAR-ENVELOPE; GENE-PRODUCT; COMPLEX-FORMATION; MAMMALIAN-CELLS; IN-VITRO; PRB; RB; TRANSCRIPTION; EXPRESSION AB The retinoblastoma protein (pRB) is a critical regulator of cell proliferation and differentiation and an important tumor suppressor. In the G(1) phase of the cell cycle, pRB localizes to perinucleolar sites associated with lamin A/C intranuclear foci. Here, we examine pRB function in cells lacking lamin A/C, finding that pRB levels are dramatically decreased and that the remaining pRB is mislocalized. We demonstrate that A-type lamins protect pRB from proteasomal degradation. Both pRB levels and localization are restored upon reintroduction of lamin A. Lmna(-/-) cells resemble Rb-/- cells, exhibiting altered cell-cycle properties and reduced capacity to undergo cell-cycle arrest in response to DNA damage. These findings establish a functional link between a core nuclear structural component and an important cell-cycle regulator. They further raise the possibility that altered pRB function may be a contributing factor in dystrophic syndromes arising from LMNA mutation. C1 Univ Washington, Dept Biochem, Sch Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Canc & Dev Biol, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Kennedy, BK (reprint author), Univ Washington, Dept Biochem, Sch Med, Box 357350, Seattle, WA 98195 USA. EM bkenn@u.washington.edu OI Frock, Richard/0000-0001-6963-4931 NR 39 TC 184 Z9 187 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 JUN 29 PY 2004 VL 101 IS 26 BP 9677 EP 9682 DI 10.1073/pnas.0403250101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 834IU UT WOS:000222405600030 PM 15210943 ER PT J AU Yun, SH Tearney, GJ de Boer, JF Bouma, BE AF Yun, SH Tearney, GJ de Boer, JF Bouma, BE TI Motion artifacts in optical coherence tomography with frequency-domain ranging SO OPTICS EXPRESS LA English DT Article ID SPECTRAL INTERFEROMETRY; INTRAOCULAR DISTANCES; REFLECTOMETRY; WAVELENGTH; RESOLUTION; TISSUE; LASER AB We describe results of theoretical and experimental investigations of artifacts that can arise in spectral-domain optical coherence tomography (SD-OCT) and optical frequency domain imaging (OFDI) as a result of sample or probe beam motion. While SD-OCT and OFDI are based on similar spectral interferometric principles, the specifics of motion effects are quite different because of distinct signal acquisition methods. These results provide an understanding of motion artifacts such as signal fading, spatial distortion and blurring, and emphasize the need for fast image acquisition in biomedical applications. (C) 2004 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR-718, Boston, MA 02114 USA. EM syun@hms.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769, R01 CA103769-02]; NCRR NIH HHS [R01 RR019768, R01 RR019768-02]; NHLBI NIH HHS [R01 HL070039, R01 HL070039-03] NR 32 TC 206 Z9 210 U1 2 U2 24 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUN 28 PY 2004 VL 12 IS 13 BP 2977 EP 2998 DI 10.1364/OPEX.12.002977 PG 22 WC Optics SC Optics GA 833FF UT WOS:000222321200023 PM 19483816 ER PT J AU Ogawa, K Ochoa, ER Borenstein, J Tanaka, K Vacanti, JP AF Ogawa, K Ochoa, ER Borenstein, J Tanaka, K Vacanti, JP TI The generation of functionally differentiated, three-dimensional hepatic tissue from two-dimensional sheets of progenitor small hepatocytes and nonparenchymal cells SO TRANSPLANTATION LA English DT Article ID ADULT-RAT HEPATOCYTES; EPITHELIAL-CELLS; PRIMARY CULTURES; LIVER-CELLS; LONG-TERM; GROWTH; TRANSPLANTATION; LASIOCARPINE; MATURATION; PHENOTYPES AB Background. The authors' laboratory has investigated tissue engineering of the liver as a novel approach for treating end-stage liver disease. Fabrication of thick, viable, three-dimensional liver tissue is limited by the lack of vascularity in the tissue-engineered constructs. To overcome this limitation, the authors fabricated three-dimensional, vascularized liver tissue in vivo from two-dimensional cell sheets created from small hepatocytes (SHC) and nonparenchymal cells (NPC) implanted into rat omentum. Methods. SHC and NPC were cultured on a silicon wafer and lifted as monolayer cell sheets. After maximal hepatotrophic stimulation was induced in the host by injecting retrorsine, creating a portacaval shunt, and performing a partial hepatectomy, these sheets were placed onto the omentum and then rolled into a three-dimensional cylinder. Results. New tissue consisting of both hepatocytes and bile duct-like structures formed by 2 weeks, and the mass of hepatocytes increased in size up to 2 months. The hepatocytes in these constructs were immunohistochemically positive for albumin and transferrin, and bile duct-like structures were positive for gamma-glutamyl transpeptidase, which suggests that they possess liver-specific function. Electron microscopy also revealed structures resembling bile canaliculi. Conclusions. Functional, morphologically complex new tissue was generated from morphologically simple monolayer cell sheets of SHC and NPC. These results represent an essential step toward the design of tissue-engineered complex vascularized thick tissue. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. Ctr Integrat Med & Innovat Technol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Kyoto Univ, Dept Transplantat & Immunol, Kyoto, Japan. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WRN 1157, Boston, MA 02114 USA. EM jvacanti@partners.org NR 29 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2004 VL 77 IS 12 BP 1783 EP 1789 DI 10.1097/01.tp.0000131153.78169.24 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 832XC UT WOS:000222300000002 PM 15223892 ER PT J AU Greenberg, D Rosen, AB Olchanski, NV Stone, PW Nadai, J Neumann, PJ AF Greenberg, D Rosen, AB Olchanski, NV Stone, PW Nadai, J Neumann, PJ TI Delays in publication of cost utility analyses conducted alongside clinical trials: registry analysis SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article C1 Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Columbia Univ, New York, NY 10032 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greenberg, D (reprint author), Harvard Clin Res Inst, 930 Commonwealth Ave, Boston, MA 02215 USA. EM dan.greenberg@hcri.harvard.edu FU AHRQ HHS [R01 HS10919] NR 4 TC 14 Z9 14 U1 1 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JUN 26 PY 2004 VL 328 IS 7455 BP 1536 EP 1537 DI 10.1136/bmj.38079.502326.AE PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 834DV UT WOS:000222392700020 PM 15100148 ER PT J AU Ahuja, SK Catano, G AF Ahuja, SK Catano, G TI Sharing is caring, except when it comes to HLA-class-I alleles in HIV-1 transmission SO LANCET LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; TYPE-1 TRANSMISSION; PROTECT MACAQUES; INFECTION; CONCORDANCE; ANTIBODY; ALLOIMMUNIZATION; ALLOANTIBODY; IMMUNIZATION C1 S Texas Vet Hlth Care Syst, Vet Adm Ctr AIDS & HIV 1 Infect, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Ahuja, SK (reprint author), S Texas Vet Hlth Care Syst, Vet Adm Ctr AIDS & HIV 1 Infect, San Antonio, TX USA. EM ahujas@uthscsa.edu NR 19 TC 4 Z9 4 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 26 PY 2004 VL 363 IS 9427 BP 2103 EP 2104 DI 10.1016/S0140-6736(04)16536-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 832LF UT WOS:000222268300005 PM 15220030 ER PT J AU Sakamoto, K Arnolds, DEW Ekberg, I Thorell, A Goodyear, LJ AF Sakamoto, K Arnolds, DEW Ekberg, I Thorell, A Goodyear, LJ TI Exercise regulates Akt and glycogen synthase kinase-3 activities in human skeletal muscle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE signaling; protein kinase glycogen synthase; contraction; adaptation; exercise; Akt glycogen synthase kinase-3; human; skeletal muscle ID MICE LACKING; BICYCLE EXERCISE; IN-VIVO; INSULIN; PHOSPHORYLATION; ACTIVATION; ISOFORM; CONTRACTION; SPECIFICITY; MECHANISM AB Activation of Akt and deactivation of GSK3 are critical signals regulating a number of cellular processes in multiple systems. Whether physical exercise alters Akt and GSK3 activity in human skeletal muscle is controversial. beta-Catenin, a GSK3 substrate and important Wnt signaling protein that alters gene transcription, has not been investigated in human skeletal muscle. In the present study, eight healthy human subjects performed 30 min of cycling exercise at 75% of maximum workload (submaximal) followed by 6 bouts of 60 s at 125% maximum workload (maximal). Biopsies of vastus lateralis muscle were taken at rest (basal), and within 15 s following cessation of the submaximal and maximal exercise bouts. Exercise at both submaximal and maximal intensities significantly increased Akt activity (40% and 110%, respectively). Increases in Akt activity were accompanied by increases in Akt Thr(308) and Ser(473) phosphorylation, decreased GSK3alpha activity (similar to30% at both intensities), and increased phosphorylation of GSK3alpha Ser(21), Exercise at both intensities also decreased beta-catenin Ser(33/37) Thr(41) phosphorylation (50-60% at both intensities). These results demonstrate that Akt, GSK3, and beta-catenin signaling are regulated by exercise in human skeletal muscle, and as such identify them as possible molecular mediators of exercise's effect on metabolic and transcriptional processes in skeletal muscle. (C) 2004 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ersta Hosp, Karolinska Inst, Surg Sci Ctr, Stockholm, Sweden. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, 75 Francis St, Boston, MA 02115 USA. EM laurie.goodyear@joslin.harvard.edu FU NIAMS NIH HHS [AR42238, AR45670] NR 36 TC 61 Z9 66 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 25 PY 2004 VL 319 IS 2 BP 419 EP 425 DI 10.1016/j.bbrc.2004.05.020 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 829PS UT WOS:000222062700018 PM 15178423 ER PT J AU Dedeoglu, A Choi, JK Cormier, K Kowall, NW Jenkins, BG AF Dedeoglu, A Choi, JK Cormier, K Kowall, NW Jenkins, BG TI Magnetic resonance spectroscopic analysis of Alzheimer's disease mouse brain that express mutant human APP shows altered neurochemical profile SO BRAIN RESEARCH LA English DT Article DE Alzheimer's disease; beta-amyloid; magnetic resonance imaging; magnetic resonance spectroscopy; immunohistochemistry ID PROTON MR-SPECTROSCOPY; N-ACETYL-ASPARTATE; TRANSGENIC MICE; AMYLOID PLAQUES; NEURONAL LOSS; BETA-PROTEIN; ACETYLASPARTATE; GLUTATHIONE; IMPAIRMENT; PRECURSOR AB Transgenic mice that express mutant human amyloid precursor protein (APP(Tg2576)) develop beta-amyloid (Abeta) plaques throughout the cortex starting at 10-12 months of age. We examined the neurochemical profile of APP(Tg2576) mice using in vitro and in vivo magnetic resonance spectroscopy (MRS); gross abnormalities using magnetic resonance imaging (MRI) and plaque distribution; size and number using immunohistochemistry. Transgenic mice were anesthetized with halothane and scanned at 4.7 T using T2-weighted imaging and in vivo MRS of frontal cortex. In vitro MRS was run from brain extracts of frontal cortex in both APP and wild-type mice. Mice were also perfused and brains were collected and cut for immunohistochemistry. We found that N-acetylaspartate (NAA), glutamate and glutathione were decreased by 17%, 22% and 36%, respectively, in the cerebral cortex of APP transgenic mice at 19 months of age when A deposits are widespread. Taurine was increased 21% compared to wild-type. Decreased levels of NAA and increased levels of taurine are consistent with decreased neuronal viability and increased glial volume, and are similar to findings of decreased NAA and increased myoinositol in human Alzheimer's disease (AD) brains. Correlation between the severity of Abeta deposition and altered neurochemical profile remains to be studied. Nevertheless, the altered neurochemical profile may be a valuable marker to test therapeutics in this mouse model. (C) 2004 Elsevier B.V. All rights reserved. C1 Ctr Geriatr Res Educ & Clin, Bedford Vet, Affairs Med Ctr, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dedeoglu, A (reprint author), Ctr Geriatr Res Educ & Clin, Bedford Vet, Affairs Med Ctr, Unit 182B,200 Springs Rd, Bedford, MA 01730 USA. EM dedeoglu@bu.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Dedeoglu, Alpaslan/0000-0003-1156-0874 FU NIA NIH HHS [AG13846] NR 34 TC 86 Z9 89 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 25 PY 2004 VL 1012 IS 1-2 BP 60 EP 65 DI 10.1016/j.brainres.2004.02.079 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 829QA UT WOS:000222063500007 PM 15158161 ER PT J AU Choudhury, GG AF Choudhury, GG TI A linear signal transduction pathway involving phosphatidylinositol 3-kinase, protein kinase C epsilon, and MAPK in mesangial cells regulates interferon-gamma-induced STAT1 alpha transcriptional activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STAT1 SERINE PHOSPHORYLATION; FOS GENE-TRANSCRIPTION; IFN-GAMMA; PKC-EPSILON; TYROSINE PHOSPHORYLATION; DNA-SYNTHESIS; DIFFERENTIAL REGULATION; INDEPENDENT PATHWAYS; TARGETED DISRUPTION; ENDOTHELIAL-CELLS AB Interferon-gamma (IFN-gamma) exerts an pleiotropic effect in mesangial cells in inflammatory glomerular diseases. The biologic effect of IFN-gamma is mediated by STAT1alpha. The precise mechanism by which IFN-gamma stimulates the transcriptional activity of STAT1alpha is poorly understood. I investigated the role of protein kinase C (PKC) epsilon in regulating the transcriptional activation of STAT1alpha in mesangial cells. IFN-gamma increased PKCepsilon activity in a time-dependent manner with a concomitant increase in STAT1alpha transcriptional activity. Expression of constitutively active PKCepsilon mimicked the effect of IFN-gamma on STAT1alpha-dependent transcription. Expression of dominant negative PKCepsilon inhibited IFN-gamma-induced STAT1alpha-dependent transcription. Ly294002, a pharmacological inhibitor of phosphatidylinositol ( PI) 3-kinase, blocked IFN-gamma-induced PKCepsilon activity and resulted in inhibition of STAT1alpha transcriptional activity but had no effect on STAT1alpha tyrosine phosphorylation and STAT1alpha-DNA complex formation. A PKC inhibitor, H7, also had no effect on STAT1alpha tyrosine phosphorylation and DNA binding. However, Ly294002 and H7 blocked IFN-gamma-induced serine phosphorylation of STAT1alpha. These data indicate that PI 3 kinase-dependent PKCepsilon regulates STAT1alpha transcriptional activity in the absence of any effect on its DNA binding capability. In addition to activating PKCepsilon, IFN-gamma increased MAPK activity, resulting in transcriptional activation of Elk-1, a nuclear target of MAPK. Ly294002 or a dominant negative PI 3-kinase significantly blocked IFN-gamma-induced MAPK activity. On the other hand, ectopic expression of constitutively active PKCepsilon significantly increased MAPK activity. IFN-gamma-stimulated MAPK phosphorylated STAT1alpha in vitro. Inhibition of MAPK activity blocked IFN-gamma-induced serine phosphorylation of STAT1alpha; but its tyrosine phosphorylation and DNA binding were partially inhibited. Finally, expression of dominant negative MAPK significantly inhibited IFN-gamma-induced STAT1alpha-dependent transcription. These data provide the first evidence that IFN-gamma stimulates PKCepsilon in a PI 3-kinase-sensitive manner to activate MAPK, which regulates STAT1alpha transcriptional activity. C1 Univ Texas, Dept Med, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Choudhury, GG (reprint author), Univ Texas, Dept Med, Hlth Sci Ctr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIDDK NIH HHS [P50 DK061597, R01 DK55815] NR 78 TC 54 Z9 55 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 JUN 25 PY 2004 VL 279 IS 26 BP 27399 EP 27409 DI 10.1074/jbc.M403530200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 830KH UT WOS:000222120400071 PM 15082710 ER PT J AU Luo, BH Strokovich, K Walz, T Springer, TA Takagi, J AF Luo, BH Strokovich, K Walz, T Springer, TA Takagi, J TI Allosteric beta(1) integrin antibodies that stabilize the low affinity state by preventing the swing-out of the hybrid domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTEGRIN MONOCLONAL-ANTIBODY; I-LIKE DOMAIN; CONFORMATIONAL-CHANGES; FIBRONECTIN RECEPTOR; REGULATORY REGION; BINDING SITES; CELL-ADHESION; SUBUNIT; LIGAND; ACTIVATION AB The ligand binding function of integrins can be modulated by various monoclonal antibodies by both direct and indirect mechanisms. We have characterized an anti-beta(1) antibody, SG/19, that had been reported to inhibit the function of the beta(1) integrin on the cell surface. SG/19 recognized the wild type beta(1) subunit that exists in a conformational equilibrium between the high and low affinity states but bound poorly to a mutant beta(1) integrin that had been locked in a high affinity state. Epitope mapping of SG/19 revealed that Thr(82) in the beta(1) subunit, located at the outer face of the boundary between the I-like and hybrid domains, was the key binding determinant for this antibody. Direct visualization of the alpha(5)beta(1) headpiece fragment in complex with SG/19 Fab with electron microscopy confirmed the location of the binding surface and showed that the ligand binding site is not occluded by the bound Fab. Surface plasmon resonance showed that alpha(5)beta(1) integrin bound by SG/19 maintained a low affinity toward its physiological ligand fibronectin (Fn) whereas binding by function-blocking anti-alpha(5) antibodies resulted in a complete loss of fibronectin binding. Thus a class of the anti-beta antibodies represented by SG/19 attenuate the ligand binding function by restricting the conformational shift to the high affinity state involving the swing-out of the hybrid domain without directly interfering with ligand docking. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Osaka Univ, Inst Prot Res, Lab Prot Synth & Express, Osaka 5650871, Japan. RP Takagi, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM takagi@protein.osaka-u.ac.jp FU NHLBI NIH HHS [HL48675]; NIGMS NIH HHS [GM62580] NR 37 TC 53 Z9 53 U1 0 U2 1 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 JUN 25 PY 2004 VL 279 IS 26 BP 27466 EP 27471 DI 10.1074/jbc.M404354200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 830KH UT WOS:000222120400078 PM 15123676 ER PT J AU Hirche, TO Crouch, EC Espinola, M Brokelman, TJ Mecham, RP DeSilva, N Cooley, J Remold-O'Donnell, E Belaaouaj, A AF Hirche, TO Crouch, EC Espinola, M Brokelman, TJ Mecham, RP DeSilva, N Cooley, J Remold-O'Donnell, E Belaaouaj, A TI Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PULMONARY HOST-DEFENSE; ACUTE LUNG INJURY; PSEUDOMONAS-AERUGINOSA; ENHANCES PHAGOCYTOSIS; ALVEOLAR MACROPHAGES; LEUKOCYTE ELASTASE; CYSTIC-FIBROSIS; SP-A; PROTEASES; BINDING AB Surfactant protein D (SP-D) plays important roles in innate immunity including the defense against bacteria, fungi, and respiratory viruses. Because SP-D specifically interacts with neutrophils that infiltrate the lung in response to acute inflammation and infection, we examined the hypothesis that the neutrophil-derived serine proteinases (NSPs): neutrophil elastase, proteinase-3, and cathepsin G degrade SP-D. All three human NSPs specifically cleaved recombinant rat and natural human SP-D dodecamers in a time- and dose-dependent manner, which was reciprocally dependent on calcium concentration. The NSPs generated similar, relatively stable, disulfide cross-linked immunoreactive fragments of similar to35 kDa ( reduced), and sequencing of a major catheptic fragment definitively localized the major sites of cleavage to a highly conserved subregion of the carbohydrate recognition domain. Cleavage markedly reduced the ability of SP-D to promote bacterial aggregation and to bind to yeast mannan in vitro. Incubation of SP-D with isolated murine neutrophils led to the generation of similar fragments, and cleavage was inhibited with synthetic and natural serine proteinase inhibitors. In addition, neutrophils genetically deficient in neutrophil elastase and/or cathepsin G were impaired in their ability to degrade SP-D. Using a mouse model of acute bacterial pneumonia, we observed the accumulation of SP-D at sites of neutrophil infiltration coinciding with the appearance of similar to35-kDa SP-D fragments in bronchoalveolar lavage fluids. Together, our data suggest that neutrophil-derived serine proteinases cleave SP-D at sites of inflammation with potential deleterious effects on its biological functions. C1 Washington Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. RP Belaaouaj, A (reprint author), Washington Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA. EM azzaq@im.wustl.edu FU NHLBI NIH HHS [R01 HL066548, HL-66548, HL-29594, HL-44015, HL-66415] NR 69 TC 68 Z9 68 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 25 PY 2004 VL 279 IS 26 BP 27688 EP 27698 DI 10.1074/jbc.M402936200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 830KH UT WOS:000222120400103 PM 15078883 ER PT J AU Kaneda, M Okano, M Hata, K Sado, T Tsujimoto, N Li, E Sasaki, H AF Kaneda, M Okano, M Hata, K Sado, T Tsujimoto, N Li, E Sasaki, H TI Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting SO NATURE LA English DT Article ID COMPLETE HYDATIDIFORM MOLES; OOCYTE GROWTH; METHYLATION; GENE; MOUSE; ESTABLISHMENT; LOCUS; MICE AB Imprinted genes are epigenetically marked during gametogenesis so that they are exclusively expressed from either the paternal or the maternal allele in offspring(1). Imprinting prevents parthenogenesis in mammals and is often disrupted in congenital malformation syndromes, tumours and cloned animals(1). Although de novo DNA methyltransferases of the Dnmt3 family are implicated in maternal imprinting(2), the lethality of Dnmt3a and Dnmt3b knockout mice(3) has precluded further studies. We here report the disruption of Dnmt3a and Dnmt3b in germ cells, with their preservation in somatic cells, by conditional knockout technology(4). Offspring from Dnmt3a conditional mutant females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined. Dnmt3a conditional mutant males show impaired spermatogenesis and lack methylation at two of three paternally imprinted loci examined in spermatogonia. By contrast, Dnmt3b conditional mutants and their offspring show no apparent phenotype. The phenotype of Dnmt3a conditional mutants is indistinguishable from that of Dnmt3L knockout mice2,5, except for the discrepancy in methylation at one locus. These results indicate that both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Grad Univ Adv Studies Sokendai, Sch Adv Sci, Dept Biosyst Sci, Hayama 2400193, Japan. JST, PRESTO, Kawaguchi 3320012, Japan. Natl Inst Genet, Res Org Informat & Syst, Dept Integrat Genet, Div Human Genet, Mishima, Shizuoka 4118540, Japan. Grad Univ Adv Studies Sokendai, Sch Life Sci, Dept Genet, Mishima, Shizuoka 4118540, Japan. RIKEN, Ctr Dev Biol, Lab Mammalian Epigenet Studies, Kobe, Hyogo 6500047, Japan. RP Sasaki, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM hisasaki@lab.nig.ac.jp RI Kaneda, Masahiro/E-3117-2010 OI Kaneda, Masahiro/0000-0003-0660-7156 NR 24 TC 647 Z9 683 U1 3 U2 56 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 24 PY 2004 VL 429 IS 6994 BP 900 EP 903 DI 10.1038/nature02633 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 831RE UT WOS:000222213000047 PM 15215868 ER PT J AU Lee, H Engel, U Rusch, J Scherrer, S Sheard, K Van Vactor, D AF Lee, H Engel, U Rusch, J Scherrer, S Sheard, K Van Vactor, D TI The microtubule plus end tracking protein orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance SO NEURON LA English DT Article ID GROWTH CONE GUIDANCE; CELL-ADHESION; F-ACTIN; CYTOSKELETAL DYNAMICS; ROUNDABOUT RECEPTOR; DROSOPHILA CNS; SHORT-STOP; IN-VIVO; ABELSON; MIDLINE AB Axon guidance requires coordinated remodeling of actin and microtubule polymers. Using a genetic screen, we identified the microtubule-associated protein Orbit/MAST as a partner of the Abelson (Abl) tyrosine kinase. We find identical axon guidance phenotypes in orbit/MAST and Ab/ mutants at the midline, where the repellent Slit restricts axon crossing. Genetic interaction and epistasis assays indicate that Orbit/MAST mediates the action of Slit and its receptors, acting downstream of Abl. We find that Orbit/MAST protein localizes to Drosophila growth cones. Higher-resolution imaging of the Orbit/MAST ortholog CLASP in Xenopus growth cones suggests that this family of microtubule plus end tracking proteins identifies a subset of microtubules that probe the actin-rich peripheral growth cone domain, where guidance signals exert their initial influence on cytoskeletal organization. These and other data suggest a model where Abl acts as a central signaling node to coordinate actin and microtubule dynamics downstream of guidance receptors. C1 Harvard Univ, Sch Med, Dept Cell Biol,Harvard Canc Ctr, Program Neurosci,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med,Harvard Ctr Neurodegenerat & Repair, Dept Cell Biol, Program Neurosci, Boston, MA 02115 USA. RP Van Vactor, D (reprint author), Harvard Univ, Sch Med, Dept Cell Biol,Harvard Canc Ctr, Program Neurosci,Dana Farber Canc Inst, 240 Longwood Ave, Boston, MA 02115 USA. EM davie@hms.harvard.edu RI Engel, Ulrike/E-5456-2014 FU NINDS NIH HHS [NS35909, NS40043] NR 81 TC 103 Z9 105 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 24 PY 2004 VL 42 IS 6 BP 913 EP 926 DI 10.1016/j.neuron.2004.05.020 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 833HZ UT WOS:000222329300007 PM 15207236 ER PT J AU Berkowitz, LR AF Berkowitz, LR TI A 46-year-old woman with pelvic-floor relaxation after a second vaginal delivery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID URINARY-INCONTINENCE; STRESS-INCONTINENCE; ORGAN PROLAPSE; CESAREAN-SECTION; VAGINAL DELIVERY; FOLLOW-UP; WOMEN; PREVALENCE; PREGNANCY; CHILDBIRTH C1 Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Berkowitz, LR (reprint author), Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. NR 43 TC 1 Z9 1 U1 0 U2 0 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 JUN 24 PY 2004 VL 350 IS 26 BP 2699 EP 2706 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 831MR UT WOS:000222199000013 PM 15215487 ER PT J AU Newton-Cheh, C O'Donnell, CJ AF Newton-Cheh, C O'Donnell, CJ TI Sex differences and genetic associations with myocardial infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORONARY-ARTERY-DISEASE; RECEPTOR-ALPHA GENE; RANDOMIZED CONTROLLED-TRIAL; HEART-DISEASE; POPULATION STRATIFICATION; LINKAGE DISEQUILIBRIUM; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; COMMON DISEASE; BLOOD-PRESSURE C1 NHLBI Framingham Heart Study, Framingham, MA USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), 73 Mt Wayte Ave 2, Framingham, MA 01702 USA. EM codonnell@nih.gov NR 30 TC 13 Z9 13 U1 0 U2 0 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 JUN 23 PY 2004 VL 291 IS 24 BP 3008 EP 3010 DI 10.1001/jama.291.24.3008 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 831HD UT WOS:000222184600033 PM 15213215 ER PT J AU Nienaber, CA Fattori, R Mehta, RH Richartz, BM Evangelista, A Petzsch, M Cooper, JV Januzzi, JL Ince, H Sechtem, U Bossone, E Fang, JM Smith, DE Isselbacher, EM Pape, LA Eagle, KA AF Nienaber, CA Fattori, R Mehta, RH Richartz, BM Evangelista, A Petzsch, M Cooper, JV Januzzi, JL Ince, H Sechtem, U Bossone, E Fang, JM Smith, DE Isselbacher, EM Pape, LA Eagle, KA CA Int Registry Acute Aortic Dissect TI Gender-related differences in acute aortic dissection SO CIRCULATION LA English DT Article DE aneurysm; aorta; registries; sex; imaging ID STENT-GRAFT PLACEMENT; MYOCARDIAL-INFARCTION; MARFAN-SYNDROME; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; INTERNATIONAL REGISTRY; WOMEN; DIAGNOSIS; PREGNANCY; DISEASE; MEN AB Background - Few data exist on gender-related differences in clinical presentation, diagnostic findings, management, and outcomes in acute aortic dissection (AAD). Methods and Results - Accordingly, we evaluated 1078 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) to assess differences in clinical features, management, and in-hospital outcomes between men and women. Of the patients enrolled in IRAD (32.1%) with AAD, 346 were women. Although less frequently affected by AAD ( 32.1% of AAD), women were significantly older and had more often presented later than men ( P = 0.008); symptoms of coma/altered mental status were more common, whereas pulse deficit was less common. Diagnostic imaging suggestive of rupture, ie, periaortic hematoma, and pleural or pericardial effusion were more commonly observed in women. In-hospital complications of hypotension and tamponade occurred with greater frequency in women, resulting in higher in-hospital mortality compared with men. After adjustment for age and hypertension, women with aortic dissection die more frequently than men ( OR, 1.4, P = 0.04), predominantly in the 66- to 75-year age group. Moreover, surgical outcome was worse in women than men ( P = 0.013); type A dissection in women was associated with a higher surgical mortality of 32% versus 22% in men despite similar delay, surgical technique, and hemodynamics. Conclusions - Our analysis provides insights into gender-related differences in AAD with regard to clinical characteristics, management, and outcomes; important diagnostic and therapeutic implications may help shed light on aortic dissection in women to improve their outcomes. C1 Univ Hosp Rostock, Div Cardiol, Rostock Sch Med, D-18057 Rostock, Germany. Rostock Sch Med, Rostock, Germany. Univ Hosp S Orsola, Bologna, Italy. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Vall Hebron, Gen Hosp, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts Hosp, Worcester, MA USA. Robert Bosch Krankenhaus, Stuttgart, Germany. CNR, Brindisi, Italy. RP Nienaber, CA (reprint author), Univ Hosp Rostock, Div Cardiol, Rostock Sch Med, Ernst Heydemann Str 6, D-18057 Rostock, Germany. EM christoph.nienaber@med.uni-rostock.de NR 37 TC 135 Z9 151 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 22 PY 2004 VL 109 IS 24 BP 3014 EP 3021 DI 10.1161/01.CIR.0000130644.78677.2C PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 831FH UT WOS:000222178800018 PM 15197151 ER PT J AU Aksan, A Toner, M AF Aksan, A Toner, M TI Isothermal desiccation and vitrification kinetics of trehalose-dextran solutions SO LANGMUIR LA English DT Article ID INTRACELLULAR TREHALOSE; MAMMALIAN-CELLS; WATER; SUCROSE; TRANSITION; STABILITY; ALPHA,ALPHA-TREHALOSE; CRYSTALLIZATION; DEHYDRATION; DIFFUSION AB The promise of dried state preservation is based on the hypothesis that lowering molecular mobility to halt chemical reaction and deterioration rates is the primary factor for the long-term stability of the dried specimen. In this research, the feasibility of utilizing isothermal, isobaric vitrification as an economical alternative to the preservation technologies currently in use (mainly, cryopreservation and lyophilization) is explored. Desiccation and vitrification kinetics of model trehalose and trehalose-dextran systems were examined using gravimetric analysis, modulated differential scanning calorimetry, and X-ray crystallography. It was shown that vitrification can be achieved isothermally without crystallization and that vitrification of trehalose solutions can be significantly accelerated by incorporating high-molecular-weight dextrans. Additionally, it was shown that, for the same water content, the glass transition temperature of the trehalose -dextran solution is significantly higher than that of the binary trehalose solution, making the glassy state achievable and storage feasible. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Surg Serv, Boston, MA 02114 USA. RP Aksan, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. RI Aksan, Alptekin/A-7187-2008; Aksan, Alptekin/C-1579-2014 OI Aksan, Alptekin/0000-0001-9891-1715 FU NIDDK NIH HHS [DK46270] NR 39 TC 28 Z9 29 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD JUN 22 PY 2004 VL 20 IS 13 BP 5521 EP 5529 DI 10.1021/la0355186 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 831DZ UT WOS:000222174800055 PM 15986695 ER PT J AU Friedman, DI Gordon, LK Egan, RA Jacobson, DM Pomeranz, H Harrison, AR Goldhammer, Y AF Friedman, DI Gordon, LK Egan, RA Jacobson, DM Pomeranz, H Harrison, AR Goldhammer, Y TI Doxycycline and intracranial hypertension SO NEUROLOGY LA English DT Article ID PSEUDOTUMOR CEREBRI; MINOCYCLINE AB The authors report seven patients from six neuro-ophthalmology referral centers who developed pseudo-tumor cerebri during treatment with doxycycline. All four female patients and one of three male patients were obese. Vision was minimally affected in most patients, but two had substantial visual acuity or visual field loss at presentation. Discontinuation of doxycycline, with or without additional intracranial pressure-lowering agents, yielded improvement, but permanent visual acuity or visual field loss occurred in five patients. C1 Univ Rochester, Sch Med & Dent, Dept Ophthalmol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Adm Healthcare Syst, Casey Eye Inst, Los Angeles, CA USA. Oregon Hlth Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Marshfield Clin Fdn Med Res & Educ, Dept Neurol, Marshfield, WI 54449 USA. Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. Chaim Sheba Med Ctr, Dept Neurol, IL-52621 Tel Hashomer, Israel. RP Friedman, DI (reprint author), Univ Rochester, Sch Med & Dent, Dept Ophthalmol, 601 Elmwood Ave,Box 659, Rochester, NY 14642 USA. EM Deborah_Friedman@urmc.rochester.edu NR 10 TC 25 Z9 27 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 JUN 22 PY 2004 VL 62 IS 12 BP 2297 EP 2299 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 831FF UT WOS:000222178600029 PM 15210900 ER PT J AU McCarty, N Shinohara, ML Lu, LR Cantor, H AF McCarty, N Shinohara, ML Lu, LR Cantor, H TI Detailed analysis of gene expression during development of T cell lineages in the thymus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE serial analysis of gene expression; genetic profiling; CD4/CD8; lineage commitment ID POSITIVE SELECTION; TRANSGENIC MICE; THYMOCYTE DEVELOPMENT; ANTIGEN RECEPTOR; CD8 LINEAGE; INTRAEPITHELIAL LYMPHOCYTES; NEGATIVE SELECTION; INSTRUCTIVE MODEL; MOUSE THYMOCYTES; SERIAL ANALYSIS AB The genetic mechanisms that promote lineage commitment and eliminate autoreactive cells in the thymus are not well understood. To better understand this process, we have identified and quantitated transcripts in the two major thymocyte lineages by using serial analysis of gene expression. Approximately 25 genes displayed almost complete segregation to one or the other T cell lineage. Commitment to the CD4 lineage was marked by upregulation of genes associated with increased survival and chaperone function followed by expression of genes that regulate nucleosome remodeling and T cell receptor signaling. Differentiation within the CD8 lineage, on the other hand, was marked by up-regulation of genes that regulate lymphocyte homing, followed by quenching of genes that inhibit apoptosis. Definition of differential gene expression during development of the two major thymocyte lineages will allow insight into mechanisms of T cell development after positive and negative selection. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu RI Lu, Linrong/A-1429-2013; OI Lu, Linrong/0000-0002-0171-4115 FU NIAID NIH HHS [AI12184, AI13600, AI37562, AI48125, R01 AI013600, R01 AI037562, R01 AI048125, R37 AI012184, T32 AI007386, T32 AI07386] NR 54 TC 11 Z9 12 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 22 PY 2004 VL 101 IS 25 BP 9339 EP 9344 DI 10.1073/pnas.0402654101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 832PE UT WOS:000222278600033 PM 15190182 ER PT J AU Jones, GB Xie, LF El-Shafey, A Crasto, CF Bubley, GJ D'Amico, AV AF Jones, GB Xie, LF El-Shafey, A Crasto, CF Bubley, GJ D'Amico, AV TI Image contrast agents activated by prostate specific antigen (PSA) SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ANGIOGRAPHY; PRODRUG; CANCER AB A family of image contrast agent conjugates designed to undergo enzymatic activation has been synthesized. The agents underwent activation both with enzymatically active prostate specific antigen and alpha-chymotrypsin, releasing free fluorophore via cleavage of a three-component system. (C) 2004 Elsevier Ltd. All rights reserved. C1 Northeastern Univ, Dept Chem & Chem Biol, Bioorgan & Med Chem Labs, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. RP Jones, GB (reprint author), Northeastern Univ, Dept Chem & Chem Biol, Bioorgan & Med Chem Labs, Boston, MA 02115 USA. EM gr.jones@neu.edu NR 16 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 21 PY 2004 VL 14 IS 12 BP 3081 EP 3084 DI 10.1016/j.bmcl.2004.04.041 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 825RU UT WOS:000221776800014 PM 15149649 ER PT J AU Pavel-Mititean, LM Rowbottom, CG Hector, CL Partridge, M Bortfeld, T Schlegel, W AF Pavel-Mititean, LM Rowbottom, CG Hector, CL Partridge, M Bortfeld, T Schlegel, W TI A geometric model for evaluating the effects of inter-fraction rectal motion during prostate radiotherapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DOSE-SURFACE HISTOGRAMS; CONFORMAL RADIOTHERAPY; NORMAL TISSUE; ORGAN MOTION; COMPLICATION PROBABILITIES; RADIATION-THERAPY; VOLUME HISTOGRAMS; SEMINAL-VESICLES; CANCER; BLADDER AB A geometric model is presented which allows calculation of the dosimetric consequences of rectal motion in prostate radiotherapy. Variations in the position of the rectum are measured by repeat CT scanning during the courses of treatment of five patients. Dose distributions are calculated by applying the same conformal treatment plan to each imaged fraction and rectal dose-surface histograms produced. The 2D model allows isotropic expansion and contraction in the plane of each CT slice. By summing the dose to specific volume elements tracked by the model, composite dose distributions are produced that explicitly include measured inter-fraction motion for each patient. These are then used to estimate effective dose-surface histograms (DSHs) for the entire treatment. Results are presented showing the magnitudes of the measured target and rectal motion and showing the effects of this motion on the integral dose to the rectum. The possibility of using such information to calculate normal tissue complication probabilities (NTCP) is demonstrated and discussed. C1 German Canc Res Ctr, Dept Med Phys, Heidelberg, Germany. Christie Hosp, Manchester, Lancs, England. Royal Marsden NHS Fdn Trust, Inst Canc Res, Joint Dept Phys, Sutton, Surrey, England. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Pavel-Mititean, LM (reprint author), German Canc Res Ctr, Dept Med Phys, Heidelberg, Germany. EM m.partridge@physics.org OI Partridge, Mike/0000-0002-8876-8190 NR 26 TC 5 Z9 5 U1 0 U2 0 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 JUN 21 PY 2004 VL 49 IS 12 BP 2613 EP 2629 AR PII s0031-9155(04)71057-x DI 10.1088/0031-9155/49/12/010 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 837NR UT WOS:000222642700010 PM 15272677 ER PT J AU Wang, JB Babcock, GJ Choe, H Farzan, M Sodroski, J Gabuzda, D AF Wang, JB Babcock, GJ Choe, H Farzan, M Sodroski, J Gabuzda, D TI N-linked glycosylation in the CXCR4 N-tenninus inhibits binding to HIV-1 envelope glycoproteins SO VIROLOGY LA English DT Article DE human immunodeficiency virus (HIV-1); envelope glycoprotein (gp120); CXCR4; paramagnetic proteoliposomes (PMPLs); N-linked glycosylation; stromal cell-derived factor (SDF)-1 alpha ID IMMUNODEFICIENCY-VIRUS TYPE-1; TERMINAL EXTRACELLULAR DOMAIN; CHEMOKINE RECEPTORS; AMINO-TERMINUS; LIGAND-BINDING; CORECEPTOR; ENTRY; CELLS; CCR5; INFECTION AB CXCR4 is a co-receptor along with CD4 for human immunodeficiency virus type 1 (HIV-1). We investigated the role of N-linked glycosylation in the N-terminus of CXCR4 in binding to HIV-1 gp120 envelope glycoproteins. Gp120s from CXCR4 (X4) and CCR5 (R5) using HIV-1 strains bound more efficiently to non-N-glycosylated than to N-glycosylated CXCR4 proteoliposomes in a CD4-dependent manner. Similar results were observed in binding studies using non-N-glycosylated or N-glycosylated CXCR4 expressed on cells. Mutation of the N-glycosylation site N11 in CXCR4 (N11Q-CXCR4) enhanced CD4-dependent binding of X4 and R5 gp120s and allowed more efficient entry of viruses pseudotyped with X4 or R5 HIV-1 envelope glycoproteins. However, the binding of R5 gp120 to N11Q-CXCR4 and entry of R5 HIV-1 viruses into cells expressing N11Q-CXCR4 were 20- and 100- to 1000- fold less efficient, respectively, than the levels achieved using X4 gp120 or X4 HIV-1 viruses. Binding of stromal cell-derived factor (SDF)-1alpha, the natural ligand of CXCR4, and SDF-1alpha-induced signaling were reduced by the N11Q mutation. These findings demonstrate that N-glycosylation at N11 inhibits the binding of CXCR4 to X4 and R5 HIV-1 gp120, and provide a better understanding of the structural elements of CXCR4 involved in HIV-1 Env-co-receptor interactions. (C) 2004 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI41851, AI28691, R01 AI043891]; NINDS NIH HHS [NS35734, NS37277] NR 30 TC 30 Z9 30 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 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 2004 VL 324 IS 1 BP 140 EP 150 DI 10.1016/j.virol.2004.03.005 PG 11 WC Virology SC Virology GA 830RO UT WOS:000222140800014 PM 15183061 ER PT J AU Joffe, S Harrington, DP George, SL Emanuel, EJ Budzinski, LA Weeks, JC AF Joffe, S Harrington, DP George, SL Emanuel, EJ Budzinski, LA Weeks, JC TI Satisfaction of the uncertainty principle in cancer clinical trials: retrospective cohort analysis SO BRITISH MEDICAL JOURNAL LA English DT Article ID BREAST-CANCER; EQUIPOISE; ETHICS; PERSPECTIVE; ONCOLOGY; THERAPY; REASONS; SURGERY AB Objective To assess whether publicly funded adult cancer trials satisfy the uncertainty principle, which states that physicians should enrol a patient in a trial only if they are substantially uncertain which of the treatments in the trial is most appropriate for the patient. This principle is violated if trials systematically favour either the experimental or the standard treatment. Design Retrospective cohort study of completed cancer trials, with randomisation as the unit of analysis. Setting Two cooperative research groups in the United States. Studies included 93 phase III randomised trials (103 randomisations) that completed recruitment of patients between 1981 and 1995. Main outcome measures Whether the randomisation favoured the experimental treatment, the standard treatment, or neither treatment; effect size (outcome of the experimental treatment compared with outcome of the standard treatment) for each randomisation. Results Three randomisations (3%) favoured the standard treatment, 70 (68%) found no significant difference between treatments, and 30 (29%) favoured the experimental treatment. The average effect size was 1.20 (95% confidence interval 1.13 to 1.28), reflecting a slight advantage for the experimental treatment. Conclusions In cooperative group trials in adults with cancer, there is a measurable average improvement in disease control associated with assignment to the experimental rather than the standard arm. However, the heterogeneity of outcomes and the small magnitude of the advantage suggest that, as a group, these trials satisfy the uncertainty principle. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Durham, NC 27710 USA. Lesley Coll, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC 27710 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM steven_joffe@dfci.harvard.edu OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [CA23318, CA33601, CA96872] NR 24 TC 14 Z9 14 U1 0 U2 0 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 JUN 19 PY 2004 VL 328 IS 7454 BP 1463 EP 1466 DI 10.1136/bmj.38118.685289.55 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 832CK UT WOS:000222244600014 PM 15163611 ER PT J AU Zhu, XS Zamudio, FZ Olbinski, BA Possani, LD Valdivia, CH AF Zhu, XS Zamudio, FZ Olbinski, BA Possani, LD Valdivia, CH TI Activation of skeletal ryanodine receptors by two novel scorpion toxins from Buthotus judaicus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID II-III-LOOP; MUSCLE DIHYDROPYRIDINE RECEPTOR; CA2+ RELEASE CHANNEL; SARCOPLASMIC-RETICULUM; CARDIAC-MUSCLE; CA2+-RELEASE CHANNEL; PANDINUS-IMPERATOR; POTASSIUM CHANNEL; PEPTIDE; VENOM AB Buthotus judaicus toxin 1 (BjTx-1) and toxin 2 (BjTx-2), two novel peptide activators of ryanodine receptors (RyR), were purified from the venom of the scorpion B. judaicus. Their amino acid sequences differ only in 1 residue out of 28 ( residue 16 corresponds to Lys in BjTx-1 and Ile in BjTx-2). Despite a slight difference in EC50, both toxins increased binding of [H-3] ryanodine to skeletal sarcoplasmic reticulum at micromolar concentrations but had no effect on cardiac or liver microsomes. Their activating effect was Ca2+-dependent and was synergized by caffeine. B. judaicus toxins also increased binding of [ 3H] ryanodine to the purified RyR1, suggesting that a direct protein-protein interaction mediates the effect of the peptides. BjTx-1 and BjTx-2 induced Ca2+ release from Ca2+-loaded sarcoplasmic reticulum vesicles in a dose-dependent manner and induced the appearance of long lived subconductance states in skeletal RyRs reconstituted into lipid bilayers. Three-dimensional structural modeling reveals that a cluster of positively charged residues (Lys(11) to Lys(16)) is a prominent structural motif of both toxins. A similar structural motif is believed to be important for activation of RyRs by imperatoxin A (IpTx(a)), another RyR-activating peptide (Gurrola, G. B., Arevalo, C., Sreekumar, R., Lokuta, A. J., Walker, J. W., and Valdivia, H. H. (1999) J. Biol. Chem. 274, 7879 - 7886). Thus, it is likely that B. judaicus toxins and imperatoxin A bind to RyRs by means of electrostatic interactions that lead to massive conformational changes in the channel protein. The different affinity and structural diversity of this family of scorpion peptides makes them excellent peptide probes to identify RyR domains that trigger the channel to open. C1 Univ Wisconsin, Sch Med, Dept Physiol, Madison, WI 53706 USA. Natl Autonomous Univ Mexico, Inst Biotechnol, Dept Mol Med & Bioproc, Cuernavaca 62271, Morelos, Mexico. RP Zhu, XS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,CYN-4,CVRC 4201, Charlestown, MA 02129 USA. EM xzhu2@bics.bwh.harvard.edu RI Possani, Lourival/J-2397-2013 FU NHLBI NIH HHS [R01HL55438] NR 33 TC 12 Z9 14 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 JUN 18 PY 2004 VL 279 IS 25 BP 26588 EP 26596 DI 10.1074/jbc.M403284200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 828VY UT WOS:000222003000084 PM 15067003 ER PT J AU Zhang, H Christoforou, A Aravind, L Emmons, SW van den Heuvel, S Haber, DA AF Zhang, H Christoforou, A Aravind, L Emmons, SW van den Heuvel, S Haber, DA TI The C-elegans Polycomb gene sop-2 encodes an RNA binding protein SO MOLECULAR CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; HETEROCHROMATIN; METHYLATION; EXPRESSION; MECHANISMS; COMPLEXES; DOMAIN; ESTABLISHMENT; LOCALIZATION; INTERFERENCE AB Epigenetic silencing of Hox cluster genes by Polycomb group (PcG) proteins is thought to involve the formation of a stably inherited repressive chromatin structure. Here we show that the C. elegans-specific PcG protein SOP-2 directly binds to RNA through three nonoverlapping regions, each of which is essential for its localization to characteristic nuclear bodies and for its in vivo function in the repression of Hox genes. Functional studies indicate that the RNA involved in SOP-2 binding is distinct from either siRNA or microRNA. Remarkably, the vertebrate PcG protein Rae28, which is functionally and structurally related to SOP-2, also binds to RNA through an FCS finger domain. Substitution of the Rae28 FCS finger for the essential RNA binding region of SOP-2 partially restores localization to nuclear bodies. These observations suggest that direct binding to RNA is an evolutionarily conserved and potentially important property of PcG proteins. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02139 USA. EM haber@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011 FU NCI NIH HHS [2T32CA09216, CA58596]; NIGMS NIH HHS [GM63081] NR 27 TC 45 Z9 59 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 18 PY 2004 VL 14 IS 6 BP 841 EP 847 DI 10.1016/j.molcel.2004.06.001 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 831DQ UT WOS:000222173800016 PM 15200961 ER PT J AU Huang, MS Harris, NL D'Angelo, HA Hasserjian, RP Weinstein, H AF Huang, MS Harris, NL D'Angelo, HA Hasserjian, RP Weinstein, H TI A 12-year-old boy with fatigue and eosinophilia - Precursor B-cell acute lymphoblastic leukemia with eosinophilia and the t(5;14)(q31;q32) translocation. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; ACUTE LYMPHOCYTIC-LEUKEMIA; LOFFLERS ENDOCARDITIS; ADRENAL INSUFFICIENCY; INTERLEUKIN-3 GENE; MECHANISMS; CHILDREN; DISEASE C1 Massachusetts Gen Hosp, Div Pediat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Huang, MS (reprint author), Massachusetts Gen Hosp, Div Pediat Oncol, Boston, MA 02114 USA. NR 33 TC 6 Z9 7 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 JUN 17 PY 2004 VL 350 IS 25 BP 2604 EP 2612 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 829NE UT WOS:000222054700013 PM 15201418 ER PT J AU Finzer, P Krueger, A Stohr, M Brenner, D Soto, U Kuntzen, C Krammer, PH Rosl, F AF Finzer, P Krueger, A Stohr, M Brenner, D Soto, U Kuntzen, C Krammer, PH Rosl, F TI HDAC inhibitors trigger apoptosis in HPV-positive cells by inducing the E2F-p73 pathway SO ONCOGENE LA English DT Article DE human papillomavirus; cervical carcinoma cells; HDAC inhibitors ID CERVICAL-CARCINOMA CELLS; RETINOBLASTOMA GENE-PRODUCT; HISTONE DEACETYLASE; CD95 APO-1/FAS; ONCOGENE EXPRESSION; SIGNALING PATHWAYS; MAMMALIAN-CELLS; E2F FAMILY; PROTEIN; P53 AB Histone deacetylase (HDAC) inhibitors induce an intrinsic type of apoptosis in human papillomavirus (HPV)-positive cells by disrupting the mitochondrial transmembrane potential (DeltaPsi(m)). Loss of DeltaPsi(m) was only detected in E7, but not in E6 oncogene-expressing cells. HDAC inhibition led to a time-dependent degradation of the pocket proteins pRb, p107 and p130, releasing 'free' E2F-1 following initial G1 arrest. Inhibition of proteasomal proteolysis, but not of caspase activity rescued pRb from degradation and functionally restored its inhibitory effect on the cyclin E gene, known to be suppressedby pRb-E2F-1 in conjunction with HDAC1. Using siRNA targeted against p53, E2F-1 still triggered apoptosis by inducing the E2F-responsive proapoptotic alpha- and beta-isoforms of p73. These data may determine future therapeutic strategies in which HDAC inhibitors can effectively eliminate HPV-positive cells by an apoptotic route that does not rely on the reactivation of the 'classical' p53 pathway through a preceding shut-off of viral gene expression. C1 Deutsch Krebsforschungszentrum, Forschungsschewerpunkt Angew Tumorvirol, Abt Virale Transformat Mech, D-69120 Heidelberg, Germany. Abt Immungenet, D-69120 Heidelberg, Germany. Forschungsschwerpunkt Zytometrie, D-69120 Heidelberg, Germany. Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Finzer, P (reprint author), Deutsch Krebsforschungszentrum, Forschungsschewerpunkt Angew Tumorvirol, Abt Virale Transformat Mech, Neuenheimer Feld 242, D-69120 Heidelberg, Germany. EM p.finzer@dkfz.de RI Krueger, Andreas/B-9427-2009 OI Krueger, Andreas/0000-0001-7873-7334 NR 73 TC 24 Z9 24 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 17 PY 2004 VL 23 IS 28 BP 4807 EP 4817 DI 10.1038/sj.onc.1207620 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 830EK UT WOS:000222104200001 PM 15077164 ER PT J AU Vemula, M Berthiaume, F Jayaraman, A Yarmush, ML AF Vemula, M Berthiaume, F Jayaraman, A Yarmush, ML TI Expression profiling analysis of the metabolic and inflammatory changes following burn injury in rats SO PHYSIOLOGICAL GENOMICS LA English DT Article DE liver; burn mRNA; fatty acids; cholesterol; microarrays ID DENSITY-LIPOPROTEIN RECEPTOR; ACUTE-PHASE RESPONSE; AMINO-ACID; SKELETAL-MUSCLE; SCAVENGER RECEPTOR; GENE-EXPRESSION; THERMAL-INJURY; FLUX ANALYSIS; LIVER; PROTEIN AB Burn injury initiates an inflammatory response as part of the healing process that is associated with extensive metabolic adjustments. While most studies have focused on understanding these changes from a biochemical perspective, not much work has been done to characterize these processes at the gene expression level. As a first step, we have comprehensively analyzed changes in gene expression in rat livers during the first 24 h after burn injury using Affymetrix GeneChips, which showed 339 genes to be differentially expressed at a statistical significance of P < 0.05 and changed at least twofold. Functional classification based on gene ontology terms indicated that two categories, metabolism (28%) and inflammation (14%), accounted for nearly 42%. Detailed analysis of the metabolism group of genes indicated that fatty acid ( FA) and triglyceride (TG) biosynthesis in the liver were unchanged, whereas TG utilization, FA import, and β-oxidation increased after burn injury. The increased FA pools after burn injury appear to serve as substrates for ATP production. Following burn injury, the cholesterol biosynthetic pathway was suppressed while cholesterol was increasingly imported and converted into bile acids. The inflammatory genes that were altered included several classic acute phase response markers, as well as genes involved in the complement, kinin, clotting, and fibrinolytic protein systems. These temporally coordinated changes in gene expression were also corroborated by biochemical measurements for FA, TG, cholesterol, and ATP. Together, these data indicate that FA are increasingly imported and oxidized in the liver to meet the enhanced energy demands arising from an inflammatory response during the first 24 h after burn injury. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIGMS NIH HHS [R01-GM-65474] NR 48 TC 45 Z9 46 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 JUN 17 PY 2004 VL 18 IS 1 BP 87 EP 98 DI 10.1152/physiolgenomics.00189.2003 PG 12 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 829YT UT WOS:000222089100011 PM 15114001 ER PT J AU Call, ME Pyrdol, J Wucherpfennig, KW AF Call, ME Pyrdol, J Wucherpfennig, KW TI Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum SO EMBO JOURNAL LA English DT Article DE assembly; endoplasmic reticulum; membrane; biochemistry; stoichiometry; T-cell receptor ID ANTIGEN RECEPTOR; TCR/CD3 COMPLEX; CD3 COMPLEX; ERYTHROPOIETIN RECEPTOR; MULTIVALENT STRUCTURE; CD3-ZETA CHAIN; BETA-SUBUNIT; TCR CHAINS; IN-VITRO; ALPHA AB The T-cell receptor (TCR)-CD3 complex is critical for T-cell development and function, and represents one of the most complex transmembrane receptors. Models of different stoichiometry and valency have been proposed based on cellular experiments and these have important implications for the mechanisms of receptor triggering. Since determination of receptor stoichiometry in T-cells is not possible due to the presence of previously synthesized, unlabeled receptor components with different half-lives, we examined the stoichiometry of the receptor assembled in endoplasmic reticulum (ER) microsomes of B-cell origin. The stoichiometric relationship among all subunits was directly determined using intact radiolabeled TCRCD3 complexes that were isolated with a sequential, nondenaturing immunoprecipitation method, and identical results were obtained with two detergents belonging to different structural classes. The results firmly establish that the alphabeta Tr-R-CD3 complex assembled in the ER is monovalent and composed of one copy of the TCRap, CD38epsilon, CD3yepsilon and zeta-zeta dimers. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room Dana 1410,44 Binney St, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469 NR 43 TC 72 Z9 77 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 16 PY 2004 VL 23 IS 12 BP 2348 EP 2357 DI 10.1038/sj.emboj.7600245 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 842WT UT WOS:000223035900003 PM 15152191 ER PT J AU Fox, CS Parise, H D'Agostino, RB Lloyd-Jones, DM Vasan, RS Wang, TJ Levy, D Wolf, PA Benjamin, EJ AF Fox, CS Parise, H D'Agostino, RB Lloyd-Jones, DM Vasan, RS Wang, TJ Levy, D Wolf, PA Benjamin, EJ TI Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FOLLOW-UP; FRAMINGHAM; ARRHYTHMIAS; PREVALENCE; IMPACT; ADULTS; STROKE; LOCUS AB Context Atrial fibrillation (AF) is the most common cardiac dysrhythmia in the United States. Whereas rare cases of familial AF have been reported, it is unknown if AF among unselected individuals is a heritable condition. Objective To determine whether parental AF increases the risk for the development of offspring AF. Design, Setting, and Participants Prospective cohort study (1983-2002) within the Framingham Heart Study, a population-based epidemiologic study. Participants were 2243 offspring (1165 women, 1078 men) at least 30 years of age and free of AF whose parents had both been evaluated in the original cohort. Main Outcome Measures Development of new-onset AF in the offspring was prospectively examined in association with previously documented parental AF. Results Among 2243 offspring participants, 681 (30%) had at least 1 parent with documented AF; 70 offspring participants (23 women; mean age, 62 [range, 40-81] years) developed AF in follow-up. Compared with no parental AF, AF in at least 1 parent increased the risk of offspring AF (multivariable-adjusted odds ratio [OR], 1.85; 95% confidence interval [Cl], 1.12-3.06; P=.02). These results were stronger when age was limited to younger than 75 years in both parents and offspring (multivariable-adjusted OR, 3.23; 95% Cl, 1.87-5.58; P<.001) and when the sample was further limited to those without antecedent myocardial infarction, heart failure, or valve disease (multivariable-adjusted OR, 3.17; 95% Cl, 1.71-5.86; P<.001). Conclusions Parental AF increases the future risk for offspring AF, an observation supporting a genetic susceptibility to developing this dysrhythmia. Further research into the genetic factors predisposing to AF is warranted. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [K23-HL-04253, K23-HL-074077-01, K24-HL-04334, N01-HC-25195]; NINDS NIH HHS [5R01-NS-17950] NR 28 TC 316 Z9 319 U1 0 U2 2 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 JUN 16 PY 2004 VL 291 IS 23 BP 2851 EP 2855 DI 10.1001/jama.291.23.2851 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 828GT UT WOS:000221962500031 PM 15199036 ER PT J AU El-Serag, HB Aguirre, T Kuebeler, M Sampliner, RE AF El-Serag, HB Aguirre, T Kuebeler, M Sampliner, RE TI The length of newly diagnosed Barrett's oesophagus and prior use of acid suppressive therapy SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROSPECTIVE MULTIVARIATE-ANALYSIS; GASTROESOPHAGEAL REFLUX DISEASE; HIATAL-HERNIA; OMEPRAZOLE; REGRESSION; ADENOCARCINOMA; EXPOSURE; EXTENT; SIZE AB Background: The length of Barrett's oesophagus seems to correlate well with indicators of severe gastro-oesophageal reflux disease. However, it remains unknown whether prior acid suppressive therapy affects the length of newly diagnosed Barrett's oesophagus. Methods: A retrospective analysis of a well-characterized large cohort of patients with Barrett's oesophagus diagnosed between 1981 and 2000. Aim: To compare the length of Barrett's oesophagus between patients who received acid suppressive therapy prior to their diagnosis to those who did not receive such therapy. Pharmacy records were obtained from Department of the Veterans Affairs computerized records and prospectively collected research records. We further examined the association between prior use of acid suppressive therapy and the length of Barrett's oesophagus in correlation analyses, as well as multivariate linear regression analyses while adjusting for differences in year of diagnosis, age, gender, ethnicity, and the presence of intestinal metaplasia of the gastric cardia. Results: There were 340 patients with Barrett's oesophagus first diagnosed between 1981 and 2000. The average length of Barrett's oesophagus at the time of first diagnosis was 4.4 cm (range: 0.5-16). Of all patients, 139 (41%) had prior use of histamine-2 receptor antagonists, or proton-pump inhibitors (41 used both), and 201 (59%) used neither prior to the diagnosis of Barrett's oesophagus. The mean length of Barrett's oesophagus was significantly shorter in patients with prior use of proton-pump inhibitors (3.4 cm) or proton-pump inhibitors and histamine-2 receptor antagonists (3.1 cm) when compared to those with none of these medications (4.8 cm). In the multivariate linear regression model, the prior use of proton-pump inhibitors or either proton-pump inhibitors or histamine-2 receptor antagonists was an independent predictor of shorter length of Barrett's oesophagus (P = 0.0396). Conclusions: The use of acid suppressive therapy among patients is associated with a reduction in the eventual length of newly diagnosed Barrett's oesophagus with gastro-oesophageal reflux disease. This finding is independent of the year of diagnosis or demographic features of patients. Further studies are required to confirm this finding. C1 Houston Vet Affairs Med Ctr, Sect Gastroenterol, Houston, TX USA. Houston Vet Affairs Med Ctr, Hlth Serv Res, Houston, TX USA. Univ Arizona, Hlth Sci Ctr, Tucson, AZ 85721 USA. RP El-Serag, HB (reprint author), 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bon.unc.edu NR 20 TC 17 Z9 18 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUN 15 PY 2004 VL 19 IS 12 BP 1255 EP 1260 DI 10.1111/j.1365-2036.2004.02006.x PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 834QZ UT WOS:000222426900004 PM 15191506 ER PT J AU Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY AF Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY TI Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BODY-FAT DISTRIBUTION; IMPAIRED GLUCOSE-TOLERANCE; FASTING PLASMA-INSULIN; BLOOD-PRESSURE; ABDOMINAL OBESITY; DIABETES-MELLITUS; VASCULAR-DISEASE; HEART-DISEASE; RISK-FACTORS; OLDER WOMEN AB Background: Visceral adiposity is generally considered to play a key role in the metabolic syndrome. Objective: To examine the relationship between directly measured visceral adiposity and the risk for incident hypertension, independent of other adipose depots and fasting plasma insulin levels. Design: Community-based prospective cohort study with 10- to 11-year follow-up. Setting: King County, Washington. Participants: 300 Japanese Americans with a systolic blood pressure less than 140 mm Hg and a diastolic blood pressure less than 90 mm Hg who were not taking anti hypertensive medications, oral hypoglycemic medications, or insulin at study entry. Measurements: Abdominal, thoracic, and thigh fat areas were measured by using computed tomography. Total subcutaneous fat area was calculated as the sum of these fat areas excluding the intra-abdominal fat area. Hypertension during follow-up was defined as having a systolic blood pressure of 140 mm Hg or greater, having a diastolic blood pressure of 90 mm Hg or greater, or taking anti hypertensive medications. Results: There were 92 incident cases of hypertension during the follow-up period. The intra-abdominal fat area was associated with an increased risk for hypertension. Multiple-adjusted odds ratios of hypertension for quartiles of intra-abdominal fat area (1 = lowest; 4 = highest) were 5.07 (95% CI, 1.75 to 14.73) for quartile 3 and 3.48 (CI, 1.01 to 11.99) for quartile 4 compared with quartile 1 after adjustment for age, sex, fasting plasma insulin level, 2-hour plasma glucose level, body mass index, systolic blood pressure, alcohol consumption, smoking status, and energy expenditure through exercise (P = 0.003 for quadratic trend). The intra-abdominal fat area remained a significant risk factor for hypertension, even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, or waist circumference; however, no measure of these fat areas was associated with risk for hypertension in models that contained the intra-abdominal fat area. Limitations: It is not known whether these results pertain to other ethnic groups. Conclusions: Greater visceral adiposity increases the risk for hypertension in Japanese Americans. C1 Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, S-152E,1660 S Columbian Way, Seattle, WA 98108 USA. EM eboyko@u.washington.edu RI Hayashi, Tomoshige/N-8508-2015 FU NCRR NIH HHS [RR-00037]; NHLBI NIH HHS [HL-49293]; NIDDK NIH HHS [DK-02654, DK-17047, DK-31170, DK-35816] NR 44 TC 148 Z9 157 U1 1 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 2004 VL 140 IS 12 BP 992 EP 1000 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 829NK UT WOS:000222055500002 PM 15197016 ER PT J AU Williams, JW Katon, W Lin, EHB Noel, PH Worchel, J Cornell, J Harpole, L Fultz, BA Hunkeler, E Mika, VS Unutzer, J AF Williams, JW Katon, W Lin, EHB Noel, PH Worchel, J Cornell, J Harpole, L Fultz, BA Hunkeler, E Mika, VS Unutzer, J CA IMPACT Investigators TI The effectiveness of depression care management on diabetes-related outcomes in older patients SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; OF-THE-LITERATURE; MAJOR DEPRESSION; LATE-LIFE; COLLABORATIVE MANAGEMENT; TREATMENT GUIDELINES; IMPROVE TREATMENT; MENTAL-DISORDERS AB Background: Depression frequently occurs in combination with diabetes mellitus, adversely affecting the course of illness. Objective: To determine whether enhancing care for depression improves affective and diabetic outcomes in older adults with diabetes and depression. Design: Preplanned subgroup analysis of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) randomized, controlled trial. Setting: 18 primary care clinics from 8 health care organizations in 5 states. Patients: 1801 patients 60 years of age or older with depression; 417 had coexisting diabetes mellitus. Intervention: A care manager offered education, problem-solving treatment, or support for antidepressant management by the patient's primary care physician; diabetes care was not specifically enhanced. Measurements: Assessments at baseline and at 3, 6, and 12 months for depression, functional impairment, and diabetes self-care behaviors. Hemoglobin A(1c) levels were obtained for 293 patients at baseline and at 6 and 12 months. Results: At 12 months, diabetic patients who were assigned to intervention had less severe depression (range, 0 to 4 on a checklist of 20 depression items; between-group difference, -0.43 [95% CI, -0.57 to -0.29]; P < 0.001) and greater improvement in overall functioning (range, 0 [none] to 10 [unable to perform activities]; between-group difference, -0.89 [CI, -1.46 to -0.32]) than did participants who received usual care. In the intervention group, weekly exercise days increased (between-group difference, 0.50 day [CI, 0.12 to 0.89 day]; P= 0.001); other self-care behaviors were not affected. At baseline, mean (+/-SD) hemoglobin A(1c) levels were 7.28% 1.43%; follow-up values were unaffected by the intervention (P > 0.2). Limitations: Because patients had good glycemic control at baseline, power to detect small but clinically important improvements in glycemic control was limited. Conclusions: Collaborative care improves affective and functional status in older patients with depression and diabetes; however, among patients with good glycemic control, such care minimally affects diabetes-specific outcomes. C1 Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. Duke Univ, Sch Med, Durham, NC USA. Univ Washington, Sch Med, Seattle, WA USA. Grp Hlth Cooperat Puget Sound, Seattle, WA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Cent Texas Vet Hlth Care Syst, Austin, TX USA. Indiana Univ, Ctr Aging Res, Regenstrief Inst, Indianapolis, IN USA. Univ Calif Los Angeles, Los Angeles, CA USA. Kaiser Permanente No Calif, Oakland, CA USA. RP Williams, JW (reprint author), Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, 508 Fulton St, Durham, NC 27705 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 66 TC 168 Z9 173 U1 3 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 2004 VL 140 IS 12 BP 1015 EP 1024 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 829NK UT WOS:000222055500005 PM 15197019 ER PT J AU Wong, AL Harker, JO Lau, VP Shatzel, S Port, LH AF Wong, AL Harker, JO Lau, VP Shatzel, S Port, LH TI Spanish arthritis empowerment program: A dissemination and effectiveness study SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE empowerment; Spanish language; arthritis; selfmanagement ID RHEUMATOID-ARTHRITIS; SELF-MANAGEMENT; RANDOMIZED-TRIAL; EDUCATION; OUTCOMES AB Objective. To evaluate the effectiveness of the Spanish Arthritis Empowerment Program as presented by the Arthritis Foundation, Southern California Chapter, in Orange County, California. Methods. Participants with arthritis (n = 141) enrolled in the program between October 1999 and May 2001. All materials were in Spanish. Written pretest, 6-week posttest, and 6-month followup tests measured pain rating, self-report joint counts, function (modified Health Assessment Questionnaire [mHAQ]), self efficacy, self-care behavior, and arthritis knowledge. Results. Mean age was 51 years, 92% were female, 84% were born in Mexico, 55% had sixth grade education or less, and 60% had no medical insurance. Of the 141 participants, 118 completed 6-month followup testing. Repeated-measures analysis of variance showed significant improvement from pretest to 6-month followup in pain (6.0 versus 3.4); self efficacy (5.5 versus 8.4), self-care behavior (1.7 versus 4.9), arthritis knowledge (1.6 versus 4.5), and general health (2.1 versus 2.5), all at P < 0.001. Small improvement was reported in mHAQ (0.56 versus 0.50; P = 0.024). Conclusion. The Spanish Arthritis Empowerment Program was successfully disseminated. Significant improvements in self efficacy and in arthritis symptoms were maintained at the, 6-month followup. C1 Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. Calif State Univ Los Angeles, Sch Med, Los Angeles, CA 90032 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Arthritis Fdn, No Calif Chapter, San Francisco, CA USA. Arthritis Fdn, So Calif Chapter, Los Angeles, CA USA. RP Wong, AL (reprint author), Olive View UCLA Med Ctr, 14445 Olive View Dr,2B182, Sylmar, CA 91342 USA. EM alunwong@ucia.edu NR 15 TC 16 Z9 16 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2004 VL 51 IS 3 BP 332 EP 336 DI 10.1002/art.20395 PG 5 WC Rheumatology SC Rheumatology GA 827SF UT WOS:000221920200008 PM 15188316 ER PT J AU Amin, S Luepongsak, N McGibbon, CA LaValley, MP Krebs, DE Felson, DT AF Amin, S Luepongsak, N McGibbon, CA LaValley, MP Krebs, DE Felson, DT TI Knee adduction moment and development of chronic knee pain in elders SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE adduction moment; biomechanics; knee pain ID FRAMINGHAM OSTEOARTHRITIS; MUSCLE FORCES; JOINT; GAIT; HIP; OPTIMIZATION; PREDICTION; BIOMECHANICS; PROGRESSION; PREVALENCE AB Objective. To determine whether the adduction moment at the knee during locomotor activity contributes to the development of future chronic knee pain. Methods. We studied 132 community-dwelling elders who had undergone a full kinetic and kinematic motion analysis while performing 4 different activities: standing, walking, rising from a chair, and descending stairs. We contacted the participants 3-4 years after their baseline locomotion analysis and identified those who reported no knee pain at the time of motion analysis but who subsequently developed new chronic knee pain at followup. We examined whether the development of new chronic knee pain was associated with higher peak adduction moment at the knee during activities, measured at baseline. Results. Of the 132 elders evaluated in 1995-1996, 118 (89%) were contacted in 1999. Of the 118 contacted, 80 (mean age 75 years; 781% women) had no lower extremity prosthetic joints at baseline, no known underlying inflammatory arthritis at baseline nor followup, and no baseline knee pain. At followup, 7 had developed new chronic knee pain defined as pain or stiffness on most days of the month and with walking 2 blocks or using stairs. Compared with those who did not develop knee pain, those who did develop new chronic knee pain had higher baseline adduction moments for all activities (P = 0.01), ranging from 8% higher during chair rise to 39% higher during stair descent. Conclusion. We found that greater adduction moment at the knee during activities contributes to the development of future chronic knee pain. Our results suggest that biomechanical factors may play an important role in the pathogenesis of knee pain and should be studied further. C1 Mayo Clin & Mayo Fdn, Div Rheumatol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Amin, S (reprint author), Mayo Clin & Mayo Fdn, Div Rheumatol, 200 1st St SW, Rochester, MN 55905 USA. EM amin.shreyasee@mayo.edu OI Felson, David/0000-0002-2668-2447; LaValley, Michael/0000-0002-8488-5170 FU NIA NIH HHS [R01-AG-12561]; NIAMS NIH HHS [AR-47785] NR 44 TC 117 Z9 118 U1 1 U2 15 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2004 VL 51 IS 3 BP 371 EP 376 DI 10.1002/art.20396 PG 6 WC Rheumatology SC Rheumatology GA 827SF UT WOS:000221920200013 PM 15188321 ER PT J AU Escalante, A Del Rincon, I Cornell, JE AF Escalante, A Del Rincon, I Cornell, JE TI Latent variable approach to the measurement of physical disability in rheumatoid arthritis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE physical disability; rheumatoid arthritis; disease-specific health measures; generic health measures; outcome assessment; factor analysis ID QUALITY-OF-LIFE; HEALTH ASSESSMENT QUESTIONNAIRE; DISABLEMENT PROCESS; MODEL SELECTION; INSTRUMENTS; RESPONSIVENESS; IMPROVEMENT; TRIALS; SCALES AB Objective. To measure physical disability in rheumatoid arthritis (RA) using a latent variable derived from a generic and a disease-specific self-reported disability instrument and an observer-assessed functional status scale. Methods. Consecutive patients with RA completed the modified Health Assessment Questionnaire (M-HAQ) and the Short Form 36 (SF-36) physical function scale. An observer assigned a Steinbrocker functional classification. We used principal component factor analysis to extract a latent variable from the 3 scales. We used the "Bayesian Information Criterion to compare how well the new latent variable and the 3 primary scales fit the criterion standards of current work status; vital status at 6 years; grip strength; walking velocity; the timed-button test; pain; and joint tenderness, swelling, and deformity. Results. Complete data were available for 776 RA patients. The extracted latent variable explained 75% of the variance in the 3 primary scales. On a scale of 0-100, higher scores representing less disability, its mean +/- SD was 56.4 +/- 22.5. Correlation between the latent variable and the M-HAQ was -0.87; between the latent variable and SF-36 physical function scale was 0.89, and between the latent variable and Steinbrocker class was -0.85. Mulltivariate models that included the latent variable had superior fit than did models containing the primary scales for the criteria of current working; death by 6 years; pain; joint tenderness, swelling, or deformity; grip strength; walking velocity; and timed button test. Conclusion. A latent variable derived from the M-HAQ, the SF-36 physical function scale, and the Steinbrocker functional class provides a parsimonious scale to measure physical disability in RA. The fit of the latent variable to comparison standards is equivalent or superior to that of the primary scales. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Adm Hlth Syst, San Antonio, TX USA. RP Escalante, A (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCRR NIH HHS [M01-RR01346]; NHLBI NIH HHS [K23-HL004481]; NIAMS NIH HHS [K24-AR47530]; NICHD NIH HHS [R01-HD37151] NR 42 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2004 VL 51 IS 3 BP 399 EP 407 DI 10.1002/art.20404 PG 9 WC Rheumatology SC Rheumatology GA 827SF UT WOS:000221920200017 PM 15188325 ER PT J AU Li, AH Rue, M Zhou, JB Wang, HJ Goldwasser, MA Neuberg, D Dalton, V Zuckerman, D Lyons, C Silverman, LB Sallan, SE Gribben, JG AF Li, AH Rue, M Zhou, JB Wang, HJ Goldwasser, MA Neuberg, D Dalton, V Zuckerman, D Lyons, C Silverman, LB Sallan, SE Gribben, JG CA Dana-Farber Cancer Ist TI Utilization of Ig heavy chain variable, diversity, and joining gene segments in children with B-lineage acute lymphoblastic leukemia: implications for the mechanisms of VDJ recombination and for pathogenesis SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COMPLEMENTARITY-DETERMINING REGIONS; V-H GENES; V(D)J RECOMBINATION; JUNCTIONAL DIVERSITY; CELL ORIGIN; PREFERENTIAL UTILIZATION; ORDERED REARRANGEMENT; CLONAL DIVERSITY; SIGNAL SEQUENCES AB Sequence analysis of the immunoglobulin heavy chain genes (IgH) has demonstrated preferential usage of specific variable (V), diversity (D), and joining (J) genes at different stages of B-cell development and in B-cell malignancies, and this has provided insight into B-cell maturation and selection. Knowledge of the association between rearrangement patterns based on updated databases and clinical characteristics of pediatric acute lymphoblastic leukemia (ALL) is limited. We analyzed 381 IgH sequences identified at presentation in 317 children with B-lineage ALL and assessed the V(H)D(H)J(H) gene utilization profiles. The D(H)J(H)-proximal V-H segments and the D(H)2 gene family were significantly overrepresented. Only 21% of V-H-J(H) joinings were potentially productive, a finding associated with a trend toward an increased risk of relapse. These results suggest that physical location at the V-H locus is involved in preferential usage of D(H)J(H)-proximal V-H segments whereas D-H and J(H) segment usage is governed by position-independent molecular mechanisms. Molecular pathophysiology appears relevant to clinical outcome in patients who have only productive rearrangements, and specific rearrangement patterns are associated with differences in the tumor biology of childhood ALL. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Med Oncol Biostat Sci & Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Med Oncol Biostat Sci & Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM john_gribben@dfci.harvard.edu RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [P01 CA 68484] NR 69 TC 21 Z9 21 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 JUN 15 PY 2004 VL 103 IS 12 BP 4602 EP 4609 DI 10.1182/blood-2003-11-3857 PG 8 WC Hematology SC Hematology GA 828VL UT WOS:000222001700042 PM 15010366 ER PT J AU Gu, TL Tothova, Z Scheijen, B Griffin, JD Gilliland, DG Sternberg, DW AF Gu, TL Tothova, Z Scheijen, B Griffin, JD Gilliland, DG Sternberg, DW TI NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and proliferative signaling through modulation of FOXO3a SO BLOOD LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; RECEPTOR TYROSINE KINASE; CHRONIC MYELOID-LEUKEMIA; NON-HODGKINS-LYMPHOMA; FACTOR FKHR-L1; FACTOR AFX; PROTEIN; DEATH; NUCLEOPHOSMIN; PHOSPHORYLATION AB Between 30% and 50% of patients with advanced-stage anaplastic large-cell lymphoma (ALCL) harbor the balanced chromosomal rearrangement t(2;5)(p23;q35), which results in the generation of the fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). To further study survival signaling by NPM-ALK, we generated Ba/F3 cell lines with either inducible or constitutive expression of NPM-ALK and examined the regulation of the AKT target FOXO3a. We hypothesized that NPM-ALK signaling through phosphoinositol 3-kinase (Pl 3-kinase) and AKT would regulate FOXO3a, a member of the forkhead family of transcription factors, thereby stimulating proliferation and blocking programmed cell death in NPM-ALK-transformed cells. In Ba/F3 cells with induced or constitutive expression of NPM-ALK, concomitant AKT activation and phosphorylation of its substrate, FOXO3a, was observed. In addition, transient expression of NPM-ALK in U-20S cells inhibited FOXO3a-mediated transactivation of reporter gene expression. Furthermore, NPM-ALK-induced FOXO3a phosphorylation in Ba/F3 cells resulted in nuclear exclusion of this transcriptional regulator, up-regulation of cyclin D2 expression, and down-regulation of P27(kip1) and Bim-1 expression. NPM-ALK reversal of proliferation arrest and of P27(kip1) induction was dependent on the phosphorylation of FOXO3a. Thus, FOXO3a is a barrier to hematopoietic transformation that is overcome by phosphorylation and cytoplasmic relocalization induced by the expression of NPM-ALK. (C) 2004 by The American Society of Hematology. C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sternberg, DW (reprint author), Mt Sinai Sch Med, Div Hematol Oncol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM david.sternberg@mssm.edu RI Scheijen, Blanca/E-3523-2016 OI Scheijen, Blanca/0000-0001-8029-9230 FU NCI NIH HHS [CA 66996, CA 82261]; NIDDK NIH HHS [DK 50604] NR 45 TC 53 Z9 59 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 JUN 15 PY 2004 VL 103 IS 12 BP 4622 EP 4629 DI 10.1182/blood-2003-03-0820 PG 8 WC Hematology SC Hematology GA 828VL UT WOS:000222001700047 PM 14962911 ER PT J AU Gondi, CS Lakka, SS Yanamandra, N Olivero, WC Dinh, DH Gujrati, M Tung, CH Weissleder, R Rao, JS AF Gondi, CS Lakka, SS Yanamandra, N Olivero, WC Dinh, DH Gujrati, M Tung, CH Weissleder, R Rao, JS TI Adenovirus-mediated expression of antisense urokinase plasminogen activator receptor and antisense cathepsin B inhibits tumor growth, invasion, and angiogenesis in gliomas SO CANCER RESEARCH LA English DT Article ID HUMAN GLIOBLASTOMA CELLS; IN-VITRO; CANCER; LOCALIZATION; CARCINOMA; PROGRESSION; MODULATION; METASTASIS; BINDING; TISSUE AB We have shown previously that urokinase plasminogen activator receptor (uPAR) and cathepsin B are overexpressed during glioma progression, particularly at the leading edge of the tumor. In the present study, we simultaneously down-regulated uPAR and cathepsin B in SNB19 glioma cell monolayer or SNB19 spheroids using an adenoviral vector carrying antisense uPAR and antisense cathepsin B and a combination of these genes as determined by Western blot analysis. The Ad-uPAR-Cath B-infected cells revealed a marked reduction in tumor growth and invasiveness as compared with the parental and vector controls. In vitro and in vivo angiogenic assays demonstrated inhibition of capillary-like structure formation and microvessel formation after Ad-uPAR-Cath B infection of SNB19 cells when compared with Ad-cytomegalovirus (CMV)-infected or mock-infected controls. Furthermore, using a near infrared fluorescence probe, in vivo imaging for cathepsin B indicated low/undetectable levels of fluorescence after injection of the Ad-uPAR-Cath B construct into preestablished s.c. tumors as compared with Ad-CMV-treated and untreated tumors. The effect with bicistronic construct (Ad-uPAR-Cath B) was much higher than with single (Ad-uPAR/Ad-Cath B) constructs. These results indicate that the down-regulation of cathepsin B and uPAR plays a significant role in inhibiting tumor growth, invasion, and angiogenesis. Hence, the targeting of these two proteases may be a potential therapy for brain tumors and other cancers. C1 Univ Illinois, Coll Med, Program Canc Biol, Peoria, IL 61656 USA. Univ Illinois, Coll Med, Dept Biomed & Therapeut Sci, Peoria, IL 61656 USA. Univ Illinois, Coll Med, Dept Pathol, Peoria, IL 61656 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Rao, JS (reprint author), Univ Illinois, Coll Med, Program Canc Biol, Box 1649, Peoria, IL 61656 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [CA 76350, CA 75557, CA 85216, CA 92393] NR 56 TC 54 Z9 63 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2004 VL 64 IS 12 BP 4069 EP 4077 DI 10.1158/0008-5472.CAN-04-1243 PG 9 WC Oncology SC Oncology GA 829VH UT WOS:000222077900003 PM 15205313 ER PT J AU Blackwell, KL Dewhirst, MW Liotcheva, V Snyder, S Broadwater, G Bentley, R Lal, A Riggins, G Anderson, S Vredenburgh, J Proia, A Harris, LN AF Blackwell, KL Dewhirst, MW Liotcheva, V Snyder, S Broadwater, G Bentley, R Lal, A Riggins, G Anderson, S Vredenburgh, J Proia, A Harris, LN TI HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; HIGH-DOSE CHEMOTHERAPY; CARBONIC-ANHYDRASE-IX; CELLS IN-VITRO; PROGNOSTIC-SIGNIFICANCE; MICROVESSEL DENSITY; ONCOPROTEIN EXPRESSION; ADJUVANT BREAST; DRUG-RESISTANCE AB Purpose: This study investigated the connection among HER-2 gene amplification, HER-2 protein expression, and markers of tumor angiogenesis and oxygenation in patients with operable, invasive breast tumors. Experimental Design: From 1988 to 1995, 425 patients with metastatic breast cancer were enrolled in a study of high-dose chemotherapy with autologous transplant. Primary tumor blocks were obtained and evaluated using immunohistochemistry (IHC) staining of vessels with von Willebrand factor antibody. Mean microvessel densities (MVD) were determined by counting von Willebrand factor stained cells in three separate "vascular hot spots" using image analysis. Tumor samples were also stained for HER-2 by IHC, HER-2 gene amplification by fluorescence in situ hybridization, carbonic anhydrase 9 by IHC, and vascular endothelial growth factor (VEGF) by IHC. Plasma from 36 patients with primary tumor samples had VEGF (R&D Systems, MN) and D-dimer (American Diagnostica, Greenwich, CT) levels determined. Results: There was a significant positive correlation between HER-2 gene amplification and both maximum and average MVD (Spearman coefficient = 0.51 and 0.50; P = 0.03 and 0.05, respectively). There was an inverse correlation with HER-2 gene amplification and expression of the tumor hypoxia marker CA-9 (chi(2) P = 0.02). The level of HER-2 gene amplification correlated with plasma D-dimer levels (Spearman coefficient = 0.43; P = 0.021). Interestingly, tumors with HER-2 by IHC had decreased amounts of VEGF staining (chi(2) = 5.81; P = 0.01). There was no correlation between HER-2 by IHC and MVD or D-dimer. Of all of the variables examined, only average (P = 0.0016) and maximum MVD (P = 0.0128) predicted disease-free survival (Cox univariate model). Conclusions: HER-2-amplified breast cancers have increased amounts of angiogenesis, decreased amounts of hypoxia, and increased markers of fibrin degradation. These findings have prognostic, predictive, and therapeutic implications in breast cancer treatment. C1 Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA. Labcorp Inc, Res Triangle Pk, NC USA. Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blackwell, KL (reprint author), Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA. EM black034@mc.duke.edu FU NCI NIH HHS [1P50 CA-68438] NR 45 TC 41 Z9 51 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2004 VL 10 IS 12 BP 4083 EP 4088 DI 10.1158/1078-0432.CCR-03-0695 PN 1 PG 6 WC Oncology SC Oncology GA 832ED UT WOS:000222249100022 PM 15217943 ER PT J AU Li, RL Heydon, K Hammond, ME Grignon, DJ Roach, M Wolkov, HB Sandler, HM Shipley, WU Pollack, A AF Li, RL Heydon, K Hammond, ME Grignon, DJ Roach, M Wolkov, HB Sandler, HM Shipley, WU Pollack, A TI Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: An analysis of patients in radiation therapy oncology group protocol 86-10 SO CLINICAL CANCER RESEARCH LA English DT Article ID RADICAL PROSTATECTOMY; CELL-PROLIFERATION; ANDROGEN DEPRIVATION; LABELING INDEX; DNA-PLOIDY; RECURRENCE; EXPRESSION; CARCINOMA; MARKERS; BROMODEOXYURIDINE AB Purpose: Proliferative activity defined by Ki-67 staining index (SI) has been correlated with progression and prognosis in a number of malignant tumors including prostate cancer. However, few studies have examined Ki-67 SI in pretreatment diagnostic material from patients treated with definitive radiotherapy. In a prior study, we found that a Ki-67 SI of >3.5% was associated with poorer patient outcome. The goals of this analysis were to validate the prognostic value of Ki-67 SI and this cut point. Experimental Design: Of 456 assessable patients in Radiation Therapy Oncology Group Protocol 86-10, diagnostic material from 108 patients was available for Ki-67 analysis using MIB-1 antibody. Sixty patients were treated with external beam radiotherapy (EBRT) alone, and 48 patients were treated with short-term androgen deprivation + EBRT. Median follow-up was 9 years for those living. The relationship of Ki-67 with distant metastasis (DM), disease-specific survival (DSS), and overall survival (OS) was examined. Results: The median Ki-67 SI was 7.1% (range, 0.2-45.5%). The 7.1% cut point was associated with DM and DSS; however, the 3.5% cut point was as strong a determinant and was the focus of this analysis. In Cox proportional hazards regression, Ki-67 SI was independently associated with DM and DSS. When the Ki-67 SI was less than or equal to3.5 % and >3.5%, the 5-year risk of DM was 13.5% and 50.8% (P = 0.0005), respectively, and the 5-year risk of DSS was 97.3% and 67.7% (P = 0.0039), respectively. No association of Ki-67 SI with OS was observed. Conclusions: Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Sutter Canc Ctr, Radiat Oncol Ctr, Sacramento, CA USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Wayne State Univ, Detroit, MI USA. Karmanos Canc Inst, Detroit, MI USA. Latter Day St Hosp, Dept Pathol, Salt Lake City, UT 84143 USA. Amer Coll Radiol Headquarters, Philadelphia, PA USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Fox Chase Canc Ctr, Dept Radiat Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM A_Pollack@FCCC.edu NR 20 TC 61 Z9 61 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2004 VL 10 IS 12 BP 4118 EP 4124 DI 10.1158/1078-0432.CCR-1052-03 PN 1 PG 7 WC Oncology SC Oncology GA 832ED UT WOS:000222249100027 PM 15217948 ER PT J AU Lynch, TJ Adjei, AA Bunn, PA DuBois, RN Gandara, DR Giaccone, G Govindan, R Herbst, RS Johnson, BE Khuri, FR Perez-Soler, R Rosell, R Rowinsky, EK Sandler, AB Scagliotti, GV Schiller, JH Shapiro, GI Socinski, MA Hart, CS AF Lynch, TJ Adjei, AA Bunn, PA DuBois, RN Gandara, DR Giaccone, G Govindan, R Herbst, RS Johnson, BE Khuri, FR Perez-Soler, R Rosell, R Rowinsky, EK Sandler, AB Scagliotti, GV Schiller, JH Shapiro, GI Socinski, MA Hart, CS TI Novel agents in the treatment of lung cancer: Conference summary statement SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Vanderbilt Univ, Med Ctr, Div Gastroenterol, Nashville, TN USA. Univ Calif Sacramento, Davis Canc Ctr, Sacramento, CA USA. Vrije Univ Amsterdam, Ctr Med, Dept Med Oncol, Amsterdam, Netherlands. Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Lowe Ctr Thorac Oncol, Dana Farber Canc Inst, Boston, MA USA. Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Hosp Germans Trias & Pujol, Inst Catala Oncol, Barcelona, Spain. Canc Therapy & Res Ctr S Texas, Int Drug Dev, San Antonio, TX 78229 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Turin, Dept Clin & Biol Sci, S Luigi Gonzaga Hosp, Turin, Italy. Univ Wisconsin, Sch Med, Madison, WI USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. InforMED, Narberth, PA USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 210, Boston, MA 02114 USA. EM tlynch@partners.org RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 0 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2004 VL 10 IS 12 BP 4199S EP 4204S DI 10.1158/1078-0432.CCR-040021 PN 2 PG 6 WC Oncology SC Oncology GA 834XW UT WOS:000222445200001 PM 15217958 ER PT J AU Johnson, BE Heymach, JV AF Johnson, BE Heymach, JV TI Farnesyl transferase inhibitors for patients with lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Novel Agents in the Treatment of Lung Cancer CY OCT 17-18, 2003 CL Cambridge, MA ID PROTEIN TRANSFERASE; FARNESYLTRANSFERASE INHIBITORS; PHASE-II; EUROPEAN-ORGANIZATION; RANDOMIZED TRIAL; R115777; GROWTH; CHEMOTHERAPY; MALIGNANCIES; REGIMENS AB The ras family of genes have been identified as potential targets for therapeutic intervention because of somatic mutations in different human cancers. They are mutated in non-small cell lung cancer (NSCLC) similar to20% of the time. The enzyme farnesyl transferase is involved in posttranslational modification of the ras proteins by covalently linking a farnesyl group to the ras protein. This permits the ras protein to be translocated to the surface membrane, allowing the protein to be involved in signaling for increased proliferation and inhibition of apoptosis. The class of farnesyl transferase inhibitors is designed to block farnesylation and prevent the mature ras signaling and thus inhibit cell proliferation and facilitate apoptosis. Multiple agents that inhibit farnesylation have been developed, and two farnesyl transferase inhibitors have been tested in patients with lung cancer in three Phase 11 trials. R115777 has been studied in patients with NSCLC and in patients with relapsed small cell lung cancer (SCLC) after chemotherapy. There has been a single trial of L-778,123 in patients with untreated NSCLC. No objective tumor responses in patients with stage IIIB/IV NSCLC were seen in these studies. There were also no objective responses among the 22 patients with relapsed SCLC treated with R115777. The median survival for the 44 patients with NSCLC treated with R115777 was similar to8 months, whereas it was 11 months for the 23 patients treated with L-778,123. R115777 and L-778,123 were well tolerated in these studies but showed no significant activity as single-agent therapy in relapsed SCLC or untreated NSLC. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bejohnson@partners.org NR 27 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2004 VL 10 IS 12 BP 4254S EP 4257S DI 10.1158/1078-0432.CCR-040016 PN 2 PG 4 WC Oncology SC Oncology GA 834XW UT WOS:000222445200012 PM 15217969 ER PT J AU Shapiro, GI AF Shapiro, GI TI Preclinical and clinical development of the cyclin-dependent kinase inhibitor flavopiridol SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Novel Agents in the Treatment of Lung Cancer CY OCT 17-18, 2003 CL Cambridge, MA ID BREAST-CARCINOMA CELLS; S-PHASE; INDUCED APOPTOSIS; CANCER-CELLS; IN-VIVO; REFRACTORY NEOPLASMS; TRANSFORMED-CELLS; DOWN-REGULATION; E2F-1; PHOSPHORYLATION AB Flavopiridol is the first potent inhibitor of cyclin-dependent kinases (cdks) to reach clinical trial. In the majority of solid tumor cell lines and xenografts, flavopiridol induces cell cycle arrest and tumor growth inhibition. This is reflected in clinical outcomes: across multiple Phase 11 trials there are subsets of patients with prolonged stable disease, although few responses have been observed. Flavopiridol displays sequence-dependent cytotoxic synergy with chemotherapy agents. These effects are most marked when chemotherapy precedes flavopiridol. In the case of DNA-damaging agents that impose S-phase delay, flavopiridol-mediated cdk inhibition disrupts the phosphorylation of E2F-1, leading to inappropriate persistence of its activity, inducing apoptotic pathways. This mechanism has been exploited in a Phase I trial of sequential gemcitabine and flavopiridol that has produced promising results. Flavopiridol is also synergistic with taxanes. Inhibition of cyclin B-cdk1 by flavopiridol accelerates exit from an abnormal mitosis associated with taxane-induced cell death and reduces the phosphorylation of survivin, preventing its stabilization and the cellular protection it affords after taxane exposure. The sequential combination of docetaxel and flavopiridol has been investigated in a Phase I trial in patients with advanced non-small cell lung cancer, and a randomized Phase 11 study is under way. Initial schedules of flavopiridol used prolonged continuous infusions that produced nanomolar levels of drug thought to be capable of achieving cdk inhibition based on results in tumor cell lines. Recently, it has been discovered that micromolar concentrations are likely to be more effective, and shorter infusions that achieve a higher C-a have now been adopted. Loading followed by maintenance infusions are also under development, designed to achieve sustained micromolar drug levels. Clinical trials remain complicated by the absence of pharmacodynamic end points to confirm target inhibition. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu FU NCI NIH HHS [P20 CA90578, R01 CA90687, R01 CA090687] NR 58 TC 47 Z9 48 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2004 VL 10 IS 12 BP 4270S EP 4275S DI 10.1158/1078-0432.CCR-040020 PN 2 PG 6 WC Oncology SC Oncology GA 834XW UT WOS:000222445200016 PM 15217973 ER PT J AU Van Remmen, H Qi, WB Sabia, M Freeman, G Estlack, L Yang, H Guo, ZM Huang, TT Strong, R Lee, S Epstein, CJ Richardson, A AF Van Remmen, H Qi, WB Sabia, M Freeman, G Estlack, L Yang, H Guo, ZM Huang, TT Strong, R Lee, S Epstein, CJ Richardson, A TI Multiple deficiencies in antioxidant enzymes in mice result in a compound increase in sensitivity to oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; CELLULAR GLUTATHIONE-PEROXIDASE; MITOCHONDRIAL-FUNCTION; KNOCKOUT MICE; REPERFUSION INJURY; FREE-RADICALS; DILATED CARDIOMYOPATHY; ISCHEMIA REPERFUSION; NEONATAL LETHALITY; INDUCED APOPTOSIS AB To examine the effect of compound deficiencies in antioxidant defense, we have generated mice (Sod2(+/-)/ Gpx1(-/-)) that are deficient in Mn superoxide dismutase (MnSOD) and glutathione peroxidase 1 (Gpx1) by breeding Sod2(+/-) and Gpx1(-/-) mice together. Although Sod2(+/-)/Gpx(-/-) mice showed a 50% reduction in MnSOD and no detectable Gpx1 activity in either mitochondria or cytosol in all tissues, they were viable and appeared normal. Fibroblasts isolated from Sod2(+/-)/GPx1(-/-) mice were more sensitive (4- to 6-fold) to oxidative stress (t-butyl hydroperoxide or gamma irradiation) than fibroblasts from wild-type mice, and were twice as sensitive as cells from Sod2(+/-) or Gpx1(-/-) mice. Whole-animal studies demonstrated that survival of the Sod2(+/-)/Gpx1(-/-) mice in response to wholebody gamma irradiation or paraquat administration was also reduced compared with that of wild-type, Sod2(+/-), or Gpx1(-/-) mice. Similarly, endogenous oxidative stress induced by cardiac ischemia/reperfusion injury led to greater apoptosis in heart tissue from the Sod2(+/-)/Gpx1(-/-) mice than in that from mice deficient in either MnSOD or Gpx1 alone. These data show that Sod2(+/-)/Gpx1(-/-) mice, deficient in two mitochondrial antioxidant enzymes, have significantly enhanced sensitivity to oxidative stress induced by exogenous insults and to endogenous oxidative stress compared with either wild-type mice or mice deficient in either MnSOD or Gpx1 alone. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Bishop Ctr Longev Studies, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Meharry Med Coll, Dept Anat & Physiol, Nashville, TN 37208 USA. Meharry Med Coll, Dept Pathol, Nashville, TN 37208 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Van Remmen, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM vanremmen@uthscsa.edu FU NIA NIH HHS [R01 AG16998, P30 AG013319, P03 AG13319, P01 AG020591] NR 41 TC 83 Z9 87 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN 15 PY 2004 VL 36 IS 12 BP 1625 EP 1634 DI 10.1016/j.freeradbiomed.2004.03.016 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 831YO UT WOS:000222233000013 PM 15182862 ER PT J AU Reddy, PH McWeeney, S Park, BS Manczak, M Gutala, RV Partovi, D Jung, Y Yau, V Searles, R Mori, M Quinn, J AF Reddy, PH McWeeney, S Park, BS Manczak, M Gutala, RV Partovi, D Jung, Y Yau, V Searles, R Mori, M Quinn, J TI Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID A-BETA; MOUSE MODEL; OXIDATIVE STRESS; MEMORY DEFICITS; CDNA MICROARRAY; MUTANT PRESENILIN-1; PLAQUE-FORMATION; MESSENGER-RNA; ONTOLOGY GO; BRAIN AB Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the impairment of cognitive functions and by beta amyloid (Abeta) plaques in the cerebral cortex and the hippocampus. Our objective was to determine genes that are critical for cellular changes in AD progression, with particular emphasis on changes early in disease progression. We investigated an established amyloid precursor protein (APP) transgenic mouse model (the Tg2576 mouse model) for gene expression profiles at three stages of disease progression: long before (2 months of age), immediately before (5 months) and after (18 months) the appearance of Abeta plaques. Using cDNA microarray techniques, we measured mRNA levels in 11 283 cDNA clones from the cerebral cortex of Tg2576 mice and age-matched wild-type (WT) mice at each of the three time points. This gene expression analysis revealed that the genes related to mitochondrial energy metabolism and apoptosis were up-regulated in 2-month-old Tg2576 mice and that the same genes were up-regulated at 5 and 18 months of age. These microarray results were confirmed using northern blot analysis. Results from in situ hybridization of mitochondrial genes-ATPase-6, heat-shock protein 86 and programmed cell death gene 8-suggest that the granule cells of the hippocampal dentate gyrus and the pyramidal neurons in the hippocampus and the cerebral cortex are up-regulated in Tg2576 mice compared with WT mice. Results from double-labeling in situ hybridization suggest that in Tg2576 mice only selective, over-expressed neurons with the mitochondrial gene ATPase-6 undergo oxidative damage. These results, therefore, suggest that mitochondrial energy metabolism is impaired by the expression of mutant APP and/or Abeta, and that the up-regulation of mitochondrial genes is a compensatory response. These findings have important implications for understanding the mechanism of Abeta toxicity in AD and for developing therapeutic strategies for AD. C1 Oregon Hlth & Sci Univ, Inst Neurol Sci, Neurogenet Lab, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Gene Microarray Shared Resource, Spotted Microarray Core, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Div Biostat, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Reddy, PH (reprint author), Oregon Hlth & Sci Univ, Inst Neurol Sci, Neurogenet Lab, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM reddyh@ohsu.edu OI /0000-0003-3516-7516 FU NCCIH NIH HHS [AT0006]; NIA NIH HHS [P30 AG08017, AG22643] NR 65 TC 183 Z9 193 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2004 VL 13 IS 12 BP 1225 EP 1240 DI 10.1093/hmg/ddh140 PG 16 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 825HZ UT WOS:000221748400004 PM 15115763 ER PT J AU James, MF Beauchamp, RL Manchanda, N Kazlauskas, A Ramesh, V AF James, MF Beauchamp, RL Manchanda, N Kazlauskas, A Ramesh, V TI A NHERF binding site links the beta PDGFR to the cytoskeleton and regulates cell spreading and migration SO JOURNAL OF CELL SCIENCE LA English DT Article DE beta PDGFR; NHERF; cell spreading; migration; merlin; ERM ID FOCAL ADHESION KINASE; TRANSMEMBRANE CONDUCTANCE REGULATOR; TYROSINE-PHOSPHATASE SHP-2; CARBOXYL-TERMINAL REGION; ACTIN STRESS FIBERS; NA+-H+ EXCHANGER; GROWTH-FACTOR; ERM PROTEINS; PHOSPHOINOSITIDE 3-KINASE; BETA(2)-ADRENERGIC RECEPTOR AB The Na+/H+ exchanger regulatory factor, NHERF, is a multifunctional adapter protein involved in a wide range of physiological activities. NHERF associates with merlin and the ezrin/radixin/moesin (MERM) family of membrane-actin cytoskeletal linker proteins through its C-terminus and is capable of interacting via its PDZ1 domain to the betaPDGF receptor (betaPDGFR). Thus, NHERF, potentially links the betaPDGFR to the actin cytoskeleton through its interaction with MERM proteins. In the present study, we have examined whether abolishing the interaction of betaPDGFR with NHERF results in actin cytoskeletal rearrangements. We have stably expressed a wild-type betaPDGFR, a mutant betaPDGFR (L1106A) that is incapable of interacting with NHERF, as well as a kinase defective mutant receptor (K634R), in PDGFR-deficient mouse embryonic fibroblasts. Our observations indicate that cells expressing betaPDGFR (L1106A) were impaired in their ability to spread and migrate on fibronectin compared with wild-type and K634R cells. L1106A mutant cells also revealed an increased number of focal adhesions, a condensed F-actin ring at the cell periphery and a decrease in total focal adhesion kinase (FAK) tyrosine phosphorylation. Further, we show that NHERF and MERM proteins could act as intermediary bridging proteins between betaPDGFR and FAK. Thus, the interaction of betaPDGFR with NHERF may provide an essential link between the cell membrane and the cortical actin cytoskeleton independent of receptor activity. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ramesh@helix.mgh.harvard.edu FU NINDS NIH HHS [NS24279] NR 52 TC 50 Z9 55 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN 15 PY 2004 VL 117 IS 14 BP 2951 EP 2961 DI 10.1242/jcs.01156 PG 11 WC Cell Biology SC Cell Biology GA 840TT UT WOS:000222883500011 PM 15161943 ER PT J AU Brooks, SR Kirkham, PM Freeberg, L Carter, RH AF Brooks, SR Kirkham, PM Freeberg, L Carter, RH TI Binding of cytoplasmic proteins to the CD19 intracellular domain is high affinity, competitive, and multimeric SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; TANDEM SH2 DOMAINS; TYROSINE KINASE; B-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; LYMPHOCYTES-B; ACTIVATION; VAV; SYK; LYN AB CD19 is required for the development of B1 and marginal zone B cells, for Ab responses, and for B cell memory. CD19 immunoprecipitates contain a complex of cytoplasmic proteins, including Lyn, Vav, phospholipase Cgamma2 (PLCgamma2), Grb2, and the p85 subunit of phosphatidylinositol 3-kinase. Which of these bind directly to CD19 and the strengths of the interactions are unknown. These issues are important in understanding the signaling functions of CD19, which are crucial for normal B cell physiology. Using purified, recombinant proteins, we now show that each of these signaling proteins contains at least one Src homology 2 (SH2) domain that interacts directly with the phosphorylated CD19 cytoplasmic domain. The affinities of binding of the SH2 domains of Vav, p85, and Grb2 to CD19 are each in the nanomolar range by surface plasmon resonance (Biacore) analysis. Binding of Lyn and PLCgamma2 do not fit 1:1 modeling. However, analyses of binding data (Lyn) and competition experiments (PLCgamma2) suggest that these bind with comparable affinity. Competition experiments demonstrate that SH2 domains whose binding is dependent on the same CD19 tyrosine(s) compete for binding, but these SH2 domains do not impede binding of different SH2 domains to other CD19 tyrosines. We conclude that binding to the CD19 cytoplasmic domain is multimeric, high affinity, and competitive. The high affinity of the interactions also suggests that tyrosines that were nonessential in vivo are nevertheless functional. A preliminary structural model suggests that CD19 forms a signaling complex containing multiple cytoplasmic proteins in close proximity to each other and to the plasma membrane. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pharmacol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Carter, RH (reprint author), 409 LHRB,701 South 19th St, Birmingham, AL 35294 USA. EM rcarter@uab.edu FU NIAID NIH HHS [AI 07051, AI 42265, T32 AI007051] NR 30 TC 17 Z9 17 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2004 VL 172 IS 12 BP 7556 EP 7564 PG 9 WC Immunology SC Immunology GA 828KV UT WOS:000221973100040 PM 15187135 ER PT J AU Tanaka, Y Koido, S Xia, JC Ohana, M Liu, CL Cote, GM Sawyer, DB Calderwood, S Gong, JL AF Tanaka, Y Koido, S Xia, JC Ohana, M Liu, CL Cote, GM Sawyer, DB Calderwood, S Gong, JL TI Development of antigen-specific CD8+ CTL in MHC class I-deficient mice through CD4 to CD8 conversion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; POLYMERASE CHAIN-REACTION; COMPLEX CLASS-I; BETA(2)-MICROGLOBULIN-DEFICIENT MICE; BREAST-CARCINOMA; TUMOR REJECTION; SINGLE-CELL; ANTITUMOR IMMUNITY; GRAFT-REJECTION; DENDRITIC CELLS AB CD8(+) CTL are the predominant tumoricidal effector cells. We find, however, that MHC class I-deficient mice depleted of CD8(+) T cells are able to mount an effective antitumor immunity after immunization with fused dendritic/tumor cells. Such immunity appears to be mediated by the generation of phenotypic and functional CD8(+) CTL through CD4(+) to CD8(+) conversion, which we have demonstrated at the single cell level. CD4(+) to CD8(+) conversion depends on effective in vivo activation and is promoted by CD4(+) T cell proliferation. The effectiveness of this process is shown by the generation of antitumor immunity through adoptive transfer of primed CD4 T cells to provide protection against tumor cell challenge and to eliminate established pulmonary metastases. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Gong, JL (reprint author), Boston Univ, Sch Med, Dept Med, 650 Albany St,Room 309, Boston, MA 02118 USA. EM jgong@bumc.bu.edu FU NCI NIH HHS [R01 CA 87057] NR 51 TC 16 Z9 17 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 JUN 15 PY 2004 VL 172 IS 12 BP 7848 EP 7858 PG 11 WC Immunology SC Immunology GA 828KV UT WOS:000221973100074 PM 15187169 ER PT J AU Ferrantelli, F Rasmussen, RA Buckley, KA Li, PL Wang, T Montefiori, DC Katinger, H Stiegler, G Anderson, DC McClure, HM Ruprecht, RM AF Ferrantelli, F Rasmussen, RA Buckley, KA Li, PL Wang, T Montefiori, DC Katinger, H Stiegler, G Anderson, DC McClure, HM Ruprecht, RM TI Complete protection of neonatal rhesus macaques against oral exposure to pathogenic simian-human immunodeficiency virus by human anti-HIV monoclonal antibodies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MOTHER-TO-CHILD; BROADLY NEUTRALIZING ANTIBODIES; FOLLICULAR DENDRITIC CELLS; CROSS-CLADE NEUTRALIZATION; PASSIVE-IMMUNIZATION; CONTROLLED-TRIAL; PHASE-I; TYPE-1; TRANSMISSION; INFECTION AB Because milk-borne transmission of human immunodeficiency virus (HIV) diminishes the benefits of perinatal antiviral drug therapy in developing countries, we have developed a new strategy to prevent postnatal and, possibly, intrapartum virus transmission in a primate model. Eight neonatal rhesus macaques were exposed orally to pathogenic simian-human immunodeficiency virus (SHIV); 4 neonates were then given intramuscular postexposure prophylaxis with 3 anti-HIV human neutralizing monoclonal antibodies (nMAbs) with potent cross-clade and cross-group neutralization activity. Untreated infants experienced high viral RNA levels and CD4(+) T-cell losses and died (median survival time, 5.5 weeks). In contrast, all 4 nMAb-treated neonates were protected from infection (P = .028); their plasma, peripheral blood mononuclear cells, and lymph nodes remained virus negative for >1 year. These data are important for designing clinical trials in human neonates and have general implications for AIDS vaccine development, as the epitopes recognized by the 3 nMAbs are conserved among diverse primary isolates. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Univ Nat Resources & Appl Life Sci, Inst Appl Microbiol, Vienna, Austria. Polymun Sci Immunobiol Forsch GmbH, Vienna, Austria. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 FU NCIRD CDC HHS [IP30 28691]; NCRR NIH HHS [RR-00165]; NIAID NIH HHS [P01 AI48240, R01 AI34266]; NIDCR NIH HHS [R01 DE12937] NR 46 TC 112 Z9 115 U1 0 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 JUN 15 PY 2004 VL 189 IS 12 BP 2167 EP 2173 DI 10.1086/420833 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 824PW UT WOS:000221699500003 PM 15181562 ER PT J AU Pappas, PG Bustamante, B Ticona, E Hamill, RJ Johnson, PC Reboli, A Aberg, J Hasbun, R Hsu, HH AF Pappas, PG Bustamante, B Ticona, E Hamill, RJ Johnson, PC Reboli, A Aberg, J Hasbun, R Hsu, HH TI Recombinant interferon-gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 41st Interscience Conference on Antimicrobial Agents and Chemotherapy CY DEC 16-19, 2001 CL CHICAGO, IL ID CHRONIC GRANULOMATOUS-DISEASE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AMPHOTERICIN-B; CUTANEOUS LEISHMANIASIS; ANTIFUNGAL CHEMOTHERAPY; DISSEMINATED INFECTION; GAMMA-INTERFERON; NEOFORMANS; COMBINATION; FLUCYTOSINE AB We conducted a phase 2, double-blind, placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)-gamma1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis. Patients received 100 or 200 mug of rIFN-gamma1b or placebo, thrice weekly for 10 weeks, plus standard therapy with intravenous amphotericin B, with or without flucytosine, followed by therapy with fluconazole. End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks, resolution of symptoms, and survival. Among 75 patients, 2-week culture conversion occurred in 13% of placebo recipients, 36% of rIFN-gamma1b (100 mug) recipients, and 32% of rIFN-gamma1b (200 mug) recipients. There was a trend toward improved combined mycologic and clinical success in rIFN-gamma1b recipients (26% vs. 8%; P = .078). Therapy with rIFN-gamma1b was well tolerated, and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements. Adjunctive therapy with rIFN-gamma1b holds promise for patients with acute cryptococcal meningitis and warrants further study. C1 Univ Alabama, Sch Med, Birmingham, AL 35294 USA. Baylor Univ, Sch Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. Univ Texas, Houston Med Ctr, Houston, TX USA. Univ Med & Dent New Jersey, Cooper Hosp, Camden, NJ 08103 USA. Washington Univ, Sch Med, St Louis, MO USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. InterMune Pharmaceut, Brisbane, CA USA. Univ Peruana Cayetano Heredia, Lima, Peru. Hosp Mayo, Lima, Peru. RP Pappas, PG (reprint author), Univ Alabama, Sch Med, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM pappas@uab.edu NR 25 TC 103 Z9 109 U1 0 U2 4 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 JUN 15 PY 2004 VL 189 IS 12 BP 2185 EP 2191 DI 10.1086/420829 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 824PW UT WOS:000221699500006 PM 15181565 ER PT J AU Saha, D LaRocque, RC Khan, AI Harris, JB Begum, YA Akramuzzaman, SM Faruque, ASG Ryan, ET Qadri, F Calderwood, SB AF Saha, D LaRocque, RC Khan, AI Harris, JB Begum, YA Akramuzzaman, SM Faruque, ASG Ryan, ET Qadri, F Calderwood, SB TI Incomplete correlation of serum vibriocidal antibody titer with protection from Vibrio cholerae infection in urban Bangladesh SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RURAL EAST PAKISTAN; VACCINE FIELD-TRIAL; VIBRIO-CHOLERAE-O139 BENGAL; IMMUNITY; COMPLEMENT; POPULATION; ANTIGENS; STRAIN; TITRE; O139 AB The serum vibriocidal antibody is the only recognized predictor of protection from cholera, but no seroepidemiological data have been gathered since the emergence of Vibrio cholerae O139. We assessed the association between the vibriocidal antibody titer and protection from cholera in an endemic setting. Although a higher baseline vibriocidal titer correlated with protection from V. cholerae O1, infection still developed in some contacts with very high titers. No association between baseline vibriocidal titer and protection from V. cholerae O139 infection was found. Our findings suggest that the vibriocidal antibody is an incomplete predictor of protection from V. cholerae infection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Bangladesh Ctr Hlth & Populat Res, Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Gray Jackson 504, Boston, MA 02114 USA. EM scalderwood@partners.org FU FIC NIH HHS [D43 TW05572, D43 TW005572]; NIAID NIH HHS [T32 AI007061, U01 AI58935, U01 AI058935, AI40725]; NICHD NIH HHS [K12-HD00850] NR 18 TC 60 Z9 61 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 JUN 15 PY 2004 VL 189 IS 12 BP 2318 EP 2322 DI 10.1086/421275 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 824PW UT WOS:000221699500022 PM 15181581 ER PT J AU Aguirre, AJ Brennan, C Bailey, G Sinha, R Feng, B Leo, C Zhang, YY Zhang, J Gans, JD Bardeesy, N Cauwels, C Cordon-Cardo, C Redston, MS DePinho, RA Chin, L AF Aguirre, AJ Brennan, C Bailey, G Sinha, R Feng, B Leo, C Zhang, YY Zhang, J Gans, JD Bardeesy, N Cauwels, C Cordon-Cardo, C Redston, MS DePinho, RA Chin, L TI High-resolution characterization of the pancreatic adenocarcinoma genome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE array comparative genomic hybridization expression profile ID COPY NUMBER; CHROMOSOME-ABNORMALITIES; INTRATUMOR HETEROGENEITY; MICROARRAY ANALYSIS; CANCER; GENE; AMPLIFICATION; CARCINOMAS; TUMORS; ARM AB The pancreatic adenocarcinoma genome harbors multiple amplifications and deletions, pointing to the existence of numerous oncogenes and tumor suppressor genes driving the genesis and progression of this lethal cancer. Here, array comparative genomic hybridization on a cDNA microarray platform and informatics tools have been used to define the copy number alterations in a panel of 24 pancreatic adenocarcinoma cell lines and 13 primary tumor specimens. This high-resolution genomic analysis has identified all known regional gains and losses as well as many previously uncharacterized highly recurrent copy number alterations. A systematic prioritization scheme has selected 64 focal minimal common regions (MCRs) of recurrent copy number change. These MCRs possess a median size of 2.7 megabases (Mb), with 21 (33%) MCRs spanning 1 Mb or less (median of 0.33 Mb) and possessing an average of 15 annotated genes. Furthermore, complementary expression profile analysis of a significant fraction of the genes residing within these 64 prioritized MCRs has enabled the identification of a subset of candidates with statistically significant association between gene dosage and mRNA expression. Thus, the integration of DNA and RNA profiles provides a highly productive entry point for the discovery of genes involved in the pathogenesis of pancreatic adenocarcinoma. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [R01CA86379, R01 CA084628, R01 CA086379, R01 CA099041, R01 CA99041, R01CA84628, T32 CA009382, T32 CA09382] NR 35 TC 173 Z9 181 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 JUN 15 PY 2004 VL 101 IS 24 BP 9067 EP 9072 DI 10.1073/pnas.0402932101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 830EQ UT WOS:000222104900044 PM 15199222 ER PT J AU Polnaszek, N Kwabi-Addo, B Wang, JH Ittmann, M AF Polnaszek, N Kwabi-Addo, B Wang, JH Ittmann, M TI FGFI7 is an autocrine prostatic epithelial growth factor and is upregulated in benign prostatic hyperplasia SO PROSTATE LA English DT Article DE FGF17; fibroblast growth factor; benign prostatic hyperplasia; fibroblast growth factor receptors ID OVER-EXPRESSION; FACTOR FAMILY; CANCER; RECEPTORS; CELLS AB BACKGROUND. Fibroblast growth factors (FGFs) are known to play all important role in the growth of prostatic epithelial cells. Benign prostatic hyperplasia (BPH) is characterized by increased epithelial and stromal proliferation within the transition zone of the prostate. FGF2, FGF7, and FGF9 are expressed in BPH tissue but expression of FGF17 has not been previously characterized in human prostate tissue. METHODS. Expression of FGF17 in human prostate tissue and primary cultures of prostatic epithelial and stromal cells was determined by reverse-transcriptase polymerase chain reaction (RT-PCR). Growth response to FGF17 was assessed by addition of recombinant FGF17 to immortalized normal and neoplastic epithelial. cell lines and primary cultures of prostatic stromal cells in the presence of insulin. Quantitative analysis of expression of FGF17 relative to keratin 18 and/or beta-actin in normal and hyperplastic prostate and prostate carcinoma was carried out by real-time quantitative RT-PCR. RESULTS. FGF17 is expressed by prostatic epithelial cells and can act as an autocrine growth factor for immortalized and neoplastic prostatic epithelial cells. It can also promote stromal proliferation, although only at higher concentrations. Expression of FGH17 per epithelial cell was increased 2-fold in BPH. CONCLUSIONS. FGF17 is expressed by normal, hyperplastic, and neoplastic prostatic epithelial cells and can promote epithelial proliferation in an autocrine manner. FGF17 expression is increased 2-fold in BPH and may contribute to the increased epithelial proliferation seen in this disease. (C) 2003 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Ittmann, M (reprint author), VAMC, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu RI Kwabi-Addo, Bernard/A-6993-2016 OI Kwabi-Addo, Bernard/0000-0003-3692-6350 FU NIDDK NIH HHS [R01 DK54170] NR 20 TC 15 Z9 17 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUN 15 PY 2004 VL 60 IS 1 BP 18 EP 24 DI 10.1002/pros.20026 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 824UE UT WOS:000221711600002 PM 15129425 ER PT J AU Patel, SR Redline, S AF Patel, SR Redline, S TI Two epidemics: Are we getting fatter as we sleep less? Comment on Hasler G et al. The association between short sleep duration and obesity in young adults: a 13-year prospective study. SLEEP 2004;27(4): 661-6. SO SLEEP LA English DT Editorial Material ID POPULATION; WOMEN; RISK; DEBT C1 Brigham & Womens Hosp, BIDMC, BWH Sleep Disorders Lab, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Rainbow Babies & Childrens Hosp, Dept Pediat Med & Epidemiol & Biostat, Cleveland, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Patel, SR (reprint author), Brigham & Womens Hosp, BIDMC, BWH Sleep Disorders Lab, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. EM spatel@partners.org NR 19 TC 17 Z9 17 U1 0 U2 4 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 JUN 15 PY 2004 VL 27 IS 4 BP 602 EP 603 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OW UT WOS:000223169300003 PM 15282992 ER PT J AU Gollackner, B Goh, SK Qawi, I Buhler, L Knosalla, C Daniel, S Kaczmarek, E Awwad, M Cooper, DKC Robson, SC AF Gollackner, B Goh, SK Qawi, I Buhler, L Knosalla, C Daniel, S Kaczmarek, E Awwad, M Cooper, DKC Robson, SC TI Acute vascular rejection of xenografts: Roles of natural and elicited xenoreactive antibodies in activation of vascular endothelial cells and induction of procoagulant activity SO TRANSPLANTATION LA English DT Article ID EPITOPE-MEDIATED ACTIVATION; BABOON CARDIAC TRANSPLANTS; PIG-KIDNEY TRANSPLANTATION; TISSUE FACTOR ACTIVITY; PORCINE; XENOTRANSPLANTATION; COAGULATION; COAGULOPATHY; DISORDERS; PRIMATES AB Background. Hyperacute rejection of vascularized discordant xenografts can now be effectively managed. However, acute vascular rejection (AVR) then ensues, resulting in graft destruction, coagulopathy, or both within weeks. The aim of this study was to determine associations between humoral responses to the xenograft and the induction of AVR, coagulopathy, or both. Methods. In vitro, heat-inactivated, naive or sensitized baboon sera containing xenoreactive natural or elicited antibodies were used to activate porcine aortic endothelial cells (PAEC) in vitro. Tissue factor expression on PAEC was determined as an index of heightened procoagulant activity. In vivo, porcine renal xenografts were transplanted into immunosuppressed baboons, and at the time of rejection or the development of a consumptive coagulopathy, biopsy specimens were obtained for studies of xenoreactive antibody binding and tissue factor expression. Results. In vitro, incubation of PAEC with naive baboon sera containing natural anti-Galalpha1,3Gal (Gal) antibodies resulted in minimal tissue factor induction; the addition of complement boosted procoagulant responses. Elicited xenoreactive antibodies, and to non-Gal epitopes alone, induced high amounts of procoagulant activity on PAEC; the addition of complement resulted in overt cytotoxicity. In vivo, AVR was associated with xenoreactive antibody deposition in the graft. When vascular endothelial binding of xenoreactive antibody was combined with the expression of tissue factor, consumptive coagulopathy developed irrespective of histopathologic features of AVR. Conclusions. Our in vitro results indicate that elicited antibodies, potentially to non-Gal epitopes, induce endothelial cell activation and tissue factor expression; in vivo, a consumptive coagulopathy occurred when there was xenoreactive antibody deposition and increase of tissue factor. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Liver Ctr,Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Biol Res Ctr, Boston, MA 02115 USA. Immerge BioTherapeut Inc, Cambridge, MA USA. RP Robson, SC (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Liver Ctr,Dept Med, Res North,99 Brookline Ave,Room 301, Boston, MA 02215 USA. EM srobson@caregroup.harvard.edu FU NIAID NIH HHS [AI45897] NR 27 TC 64 Z9 68 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 JUN 15 PY 2004 VL 77 IS 11 BP 1735 EP 1741 DI 10.1097/01.TP.0000131167.21930.B8 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 830AP UT WOS:000222094300019 PM 15201675 ER PT J AU Faraone, SV Spencer, TJ Montano, B Biederman, J AF Faraone, SV Spencer, TJ Montano, B Biederman, J TI Attention-deficit/hyperactivity disorder in adults - A survey of current practice in psychiatry and primary care SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; OPEN-LABEL TRIAL; DOUBLE-BLIND; CHILDHOOD-ONSET; CHILDREN; PLACEBO; ATOMOXETINE; METHYLPHENIDATE; SYMPTOMS; ADHD AB Background: Recognition and treatment of attention-deficit/hyperactivity disorder (ADHD) in adults in psychiatry and primary care have faced many obstacles. Methods: Review by 50 psychiatrists and 50 primary care practitioners (PCPs) of 537 and 317 medical records, respectively, of adults diagnosed as having ADHD. Information on other psychiatric disorders, time of onset of ADHD, source of referral, use of referrals for diagnosis, ADHD treatment, and use of drug holidays was recorded. Results: Forty-five percent of the patient records reviewed by psychiatrists and 65% reviewed by PCPs indicated previous diagnoses of ADHD. Only 25% of the adults with ADHD had been first diagnosed as having the disorder in childhood or adolescence. A diagnosis of ADHD was the initial cause for referral in 80% of psychiatric patients and 60% of PCP patients. Most patients with previously diagnosed and undiagnosed ADHD were self-referred. Among patients who had not received a prior diagnosis, 56% complained about ADHD symptoms to other health professionals without being diagnosed; PCPs were the least aggressive in diagnosing ADHD. In psychiatric and PCP settings, there was a statistical difference in the use of pharmacotherapy (91% vs 78%, respectively) and the proportion of patients taking drug holidays (24% vs 17%, respectively); most drug holidays were initiated by the patient (57%). Stimulants were the treatment of choice for adult ADHD (84% treated with stimulants). Conclusion: Data contained within this medical record review suggest that adult ADHD is a substantial source of morbidity in both psychiatric and PCP settings. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Univ Connecticut, Dept Family Practice, Farmington, CT USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WRN 705,55 Fruit St, Boston, MA 02114 USA. EM sfaraone@hms.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 33 TC 71 Z9 71 U1 2 U2 5 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 JUN 14 PY 2004 VL 164 IS 11 BP 1221 EP 1226 DI 10.1001/archinte.164.11.1221 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 830ZN UT WOS:000222162800009 PM 15197048 ER PT J AU Calhoun, EA Collins, MM Pontari, MA O'Leary, MP Leiby, BE Landis, JR Kusek, JW Litwin, MS AF Calhoun, EA Collins, MM Pontari, MA O'Leary, MP Leiby, BE Landis, JR Kusek, JW Litwin, MS CA Members of the Chronic Prostatitis TI The economic impact of chronic prostatitis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Urological-Association CY JUN 02-07, 2001 CL ANAHEIM, CA SP Amer Urol Assoc ID CHRONIC ABACTERIAL PROSTATITIS; RHEUMATOID-ARTHRITIS; SYMPTOM INDEX; COSTS; PREVALENCE; PAIN; DIAGNOSIS; ACCURACY; MEN AB Background: Little information exists on the economic impact of chronic prostatitis. The objective of this study was to determine the direct and indirect costs associated with chronic prostatitis. Methods: Outcomes were assessed using a questionnaire designed to capture health care resource utilization. Resource estimates were converted into unit costs with direct medical cost estimates based on hospital cost accounting data and indirect costs based on modified labor force, employment, and earnings data from the US Census Bureau. Results: The total direct costs for the 3 months prior to entry into the cohort, excluding hospitalization, were $126915 for the 167 study participants for an average of $954 per person among the 133 consumers. Of the men, 26% reported work loss valued at an average of $551. The average total costs (direct and indirect) for the 3 months was $1099 per person for those 137 men who had re-source consumption with an expected annual total cost per person of $4397. For those study participants with any incurred costs, tests for association revealed that the National Institutes of Health Chronic Prostatitis Symptom Index (P < .001) and each of the 3 subcategories of pain (P = .003), urinary function (P = .03), and quality-of-life (P = .002) were significantly associated with resource use, although the quality-of-life subscale score from the National Institutes of Health Chronic Prostatitis Symptom Index was the only predictor of resource consumption. Conclusions: Chronic prostatitis is associated with substantial costs and lower quality-of-life scores, which predicted resource consumption. The economic impact of chronic prostatitis warrants increased medical attention and resources to identify and test effective treatment strategies. C1 Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Med Serv, Gen Med Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. Univ Penn, Med Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. RP Calhoun, EA (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 339 E Chicago Ave,Room 802, Chicago, IL 60611 USA. EM e-calhoun@northwestern.edu RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01 DK53752, T32 DK060455, U01 DK53730, U01 DK53732, U01 DK53734, U01 DK53736] NR 23 TC 57 Z9 67 U1 0 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 JUN 14 PY 2004 VL 164 IS 11 BP 1231 EP 1236 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 830ZN UT WOS:000222162800011 PM 15197050 ER PT J AU Humphreys, BD Sharman, JP Henderson, JM Clark, JW Marks, PW Rennke, HG Zhu, AX Magee, CC AF Humphreys, BD Sharman, JP Henderson, JM Clark, JW Marks, PW Rennke, HG Zhu, AX Magee, CC TI Gemcitabine-associated thrombotic microangiopathy SO CANCER LA English DT Article DE thrombotic microangiopathy; hemolytic uremic syndrome; thrombotic thrombocytopenic purpura; gemcitabine; pancreatic carcinoma; bladder carcinoma; nonsmall cell carcinoma; acute renal failure ID HEMOLYTIC-UREMIC SYNDROME; THROMBOCYTOPENIC PURPURA; VASCULAR-LESIONS; RENAL-FAILURE; THERAPY; HYPERTENSION; DISEASE AB BACKGROUND. Gemcitabine-associated thrombotic microangiopathy (TMA) is believed to be very rare, with an estimated incidence rate of 0.015%. Indications for gemcitabine are expanding, and comprehensive characterization of this complication cation is therefore important. METHODS. The authors performed a retrospective chart review of all cases with gemcitabine-associated TMA diagnosed at Partners Healthcare System (Boston, MA) between January 1997 and February 2002. RESULTS. Nine patients with gemcitabine-associated TMA were identified. Diagnosis was aided by clinical and laboratory features. Renal biopsy confirmed the diagnosis in two patients. The cumulative incidence of gemcitabine-associated TMA was 0.31% (8 cases among 2586 patients) when only the 8 patients with TMA who were treated at clinics associated with the current study were considered (1 patient with a TMA syndrome was transferred from another institution). The 3 median patient age was 53 years, and the median time to development of a TMA syndrome after the initiation of gemcitabine was 8 months (range, 3-18 months), with a cumulative dose ranging from 9 to 56 g/m(2). New or exacerbated hypertension was a prominent feature in 7 of 9 patients and preceded the clinical diagnosis by 0.5-10 weeks. Treatment of TMA included discontinuation of gemcitabine, antihypertensive therapy, plasma exchange, and dialysis. Outcomes are known for all nine patients. Six patients remain alive, whereas three have died of disease progression. No patient died as a direct result of TMA, but two developed kidney failure requiring dialysis, and one developed chronic renal insufficiency. CONCLUSIONS. in the current series, the largest single-institution study to date, the incidence of gemcitabine-associated TMA was higher than previously reported (0.31% vs. 0.015%). Seven of nine patients developed new or exacerbated hypertension, which could be a useful early identifier of patients with gemcitabine-associated TMA syndromes. (C) 2004 American Cancer Society. C1 Brigham & Womens Hosp, Renal Div, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. RP Magee, CC (reprint author), Brigham & Womens Hosp, Renal Div, Dept Med, 75 Francis St,MRB-4, Boston, MA 02115 USA. EM cmagee@partners.org OI Henderson, Joel/0000-0002-9178-1708 FU NIDDK NIH HHS [2 T32 DK007527-18] NR 25 TC 84 Z9 86 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 JUN 12 PY 2004 VL 100 IS 12 BP 2664 EP 2670 DI 10.1002/cncr.20290 PG 7 WC Oncology SC Oncology GA 826UL UT WOS:000221854700021 PM 15197810 ER PT J AU Francis, JW Bastia, E Matthews, CC Parks, DA Schwarzschild, MA Brown, RH Fishman, PS AF Francis, JW Bastia, E Matthews, CC Parks, DA Schwarzschild, MA Brown, RH Fishman, PS TI Tetanus toxin fragment C as a vector to enhance delivery of proteins to the CNS SO BRAIN RESEARCH LA English DT Article DE tetanus toxin fragment C; protein; CNS ID RETROGRADE AXONAL-TRANSPORT; SUPEROXIDE-DISMUTASE; RAT-BRAIN; TRANSSYNAPTIC TRANSFER; NEUROTROPHIC FACTOR; BINDING; MOTONEURONS; NEURONS AB Tire non-toxic neuronal binding domain of tetanus toxin (tetanus toxin fragment C, TTC) has been used as a vector to enhance delivery of potentially therapeutic proteins to motor neurons from the periphery following an intramuscular injection. The unique binding and transport properties of this 50-kDa polypeptide suggest that it might also enhance delivery of proteins to neurons after direct injection into the CNS. Using quantitative fluorimetry, we found that labeled TTC showed vastly superior retention within brain tissue after intracerebral injection compared to a control protein (bovine serum album). Fluorescence microscopy revealed that injected TTC was not retained solely in a restricted deposit along the needle track, but was distributed through gray matter in a pattern not previously described. The distribution of injected protein within the extracellular space of the gray matter and neuropil was also seen after injection of a recombinant fusion protein comprised of TTC linked to the enzyme Superoxide dismutase (TTC-SOD-1). Injections of native SOD-I in contrast showed only minimal retention of protein along the injection track. Immunohistochemistry demonstrated that both TTC and TTC-SOD-1 were distributed in a punctate perineuronal and intraneuronal pattern similar to that seen after their retrograde transport, suggesting localization primarily in synaptic boutons. This synaptic distribution was confirmed using HRP-labeled TTC with electron microscopy along with localization within neuronal endosomes. We conclude that TTC may be a useful vector to enhance neuronal delivery of potentially therapeutic enzymes or trophic factors following direct injection into the brain. (C) 2004 Published by Elsevier B.V. C1 Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. Vet Affairs Med Ctr, Res Serv, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurobiol Lab, Charlestown, MA 02129 USA. RP Fishman, PS (reprint author), Univ Maryland, Sch Med, Dept Neurol, 22 S Greene St, Baltimore, MD 21201 USA. EM pfishman@umaryland.edu FU NIEHS NIH HHS [R01ES10804]; NINDS NIH HHS [P01NS37912, P01NS31248, R01NS38679] NR 21 TC 19 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 11 PY 2004 VL 1011 IS 1 BP 7 EP 13 DI 10.1016/j.braines.2004.03.007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 827YI UT WOS:000221939200002 PM 15140640 ER PT J AU Krahl, SE Martin, FC Handforth, A AF Krahl, SE Martin, FC Handforth, A TI Vagus nerve stimulation inhibits harmaline-induced tremor SO BRAIN RESEARCH LA English DT Article DE tremor; hannaline; essential tremor; vagus nerve stimulation; electrical stimulation ID POSITRON EMISSION TOMOGRAPHY; INFERIOR OLIVE; BRAIN-STEM; SOLITARY TRACT; CAT; PROJECTIONS; SYSTEM; NUCLEUS; VAGAL; RATS AB Excessive olivo-cerebellar burst-firing occurs during harmaline-induced tremor. This system receives rich sensory inputs, including visceral. We hypothesized that electrical vagus nerve stimulation (VNS) Would suppress harmaline tremor, as measured with digitized motion power in the rat. Cervical vagus nerve stimulation suppressed power in the 8-12-Hz tremor range by 40%, whereas sham stimulation was ineffective. This study raises the possibility that activation of various sensory modalities, as well as visceral, may reduce tremor. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Res & Dev Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA 90025 USA. VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. RP Krahl, SE (reprint author), VA Greater Los Angeles Healthcare Syst, Res & Dev Serv, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM scott.krahl@med.va.gov NR 26 TC 9 Z9 9 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 JUN 11 PY 2004 VL 1011 IS 1 BP 135 EP 138 DI 10.1016/j.brainres.2004.03.021 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 827YI UT WOS:000221939200015 PM 15140653 ER PT J AU Kraus, M Alimzhanov, MB Rajewsky, N Rajewsky, K AF Kraus, M Alimzhanov, MB Rajewsky, N Rajewsky, K TI Survival of resting mature B lymphocytes depends on BCR signaling via the Ig alpha/beta heterodimer SO CELL LA English DT Article ID CELL ANTIGEN RECEPTOR; NF-KAPPA-B; CLONAL SELECTION; ACTIVATION MOTIF; IN-VIVO; MICE; BETA; IMMUNOGLOBULIN; IMMATURE; MATURATION AB We previously showed that type I interferon-induced, Cre-mediated ablation of surface BCR expression in mature B cells through Ig-heavy chain deletion results in apoptosis of these cells. This led to the hypothesis that survival signals from the BCR are vital for mature B cells. Here, we test two critical assumptions of this model. First, we demonstrate loss of mature B cells upon induced mutation of a signaling module of the BCR, not precluding BCR surface expression. Second, we show that the cells are also lost upon BCR inactivation in the absence of an exogenous inducer like interferon, excluding that cell death depends on previous cellular activation by the latter. Kinetic data demonstrate that BCR-less mature B cells have a severely reduced lifespan, with a half-life of 3-6 days. Together these results establish that BCR signaling is required to keep resting mature B cells alive in vivo. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. NYU, Dept Biol, New York, NY 10003 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu FU PHS HHS [R01-A1054636-01] NR 52 TC 308 Z9 315 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 JUN 11 PY 2004 VL 117 IS 6 BP 787 EP 800 DI 10.1016/j.cell.2004.05.014 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 829KY UT WOS:000222048400011 PM 15186779 ER PT J AU Sazonova, IY Robinson, BR Gladysheva, IP Castellino, FJ Reed, GL AF Sazonova, IY Robinson, BR Gladysheva, IP Castellino, FJ Reed, GL TI alpha domain deletion converts streptokinase into a fibrin-dependent plasminogen activator through mechanisms akin to staphylokinase and tissue plasminogen activator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; SINGLE-CHAIN UROKINASE; OMEGA-AMINO ACIDS; RECOMBINANT STAPHYLOKINASE; CONFORMATIONAL CHANGE; CIRCULAR-DICHROISM; BINDING SITES; FACTOR-XIII; COMPLEX; PLASMA AB The mechanism of action of plasminogen (Pg) activators may affect their therapeutic properties in humans. Streptokinase (SK) is a robust Pg activator in physiologic fluids in the absence of fibrin. Deletion of a "catalytic switch" (SK residues 1-59), alters the conformation of the SK alpha domain and converts SKDelta59 into a fibrin-dependent Pg activator through unknown mechanisms. We show that the SK alpha domain binds avidly to the Pg kringle domains that maintain Glu-Pg in a tightly folded conformation. By virtue of deletion of SK residues 1-59, SKDelta59 loses the ability to unfold Glu-Pg during complex formation and becomes incapable of nonproteolytic active site formation. In this manner, SKDelta59 behaves more like staphylokinase than like SK; it requires plasmin to form a functional activator complex, and in this complex SKDelta59 does not protect plasmin from inhibition by alpha(2)-antiplasmin. At the same time, SKDelta59 is unlike staphylokinase or SK and is more like tissue Pg activator, because it is a poor activator of the tightly folded form of Glu-Pg in physiologic solutions. SKDelta59 can only activate Glu-Pg when it was unfolded by fibrin interactions or by Cl--deficient buffers. Taken together, these studies indicate that an intact alpha domain confers on SK the ability to nonproteolytically activate Glu-Pg, to unfold and process Glu-Pg substrate in physiologic solutions, and to alter the substrate-inhibitor interactions of plasmin in the activator complex. The loss of an intact alpha domain makes SKDelta59 activate Pg through classical "fibrin-dependent mechanisms" (akin to both staphylokinase and tissue Pg activator) that include: 1) a marked preference for a fibrin-bound or unfolded Glu-Pg substrate, 2) a requirement for plasmin in the activator complex, and 3) the creation of an activator complex with plasmin that is readily inhibited by alpha(2)-antiplasmin. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 665 Huntington Ave, Boston, MA 02115 USA. EM guyreed@hsph.harvard.edu FU NHLBI NIH HHS [HL58496, HL13423] NR 55 TC 13 Z9 14 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 JUN 11 PY 2004 VL 279 IS 24 BP 24994 EP 25001 DI 10.1074/jbc.M400253200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826KL UT WOS:000221827900013 PM 15069059 ER PT J AU Marchesini, N Osta, W Bielawski, J Luberto, C Obeid, LM Hannun, YA AF Marchesini, N Osta, W Bielawski, J Luberto, C Obeid, LM Hannun, YA TI Role for mammalian neutral sphingomyelinase 2 in confluence-induced growth arrest of MCF7 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; CYCLIN-DEPENDENT KINASES; E-CADHERIN; SACCHAROMYCES-CEREVISIAE; CYTOPLASMIC DOMAIN; INDUCED APOPTOSIS; CONTACT INHIBITION; PHOSPHATIDIC-ACID; CERAMIDE PATHWAY; LEUKEMIC-CELLS AB Recently, we reported that neutral sphingomyelinase 2 (nSMase2) functions as a bona fide neutral sphingomyelinase and that overexpression of nSMase2 in MCF7 breast cancer cells caused a decrease in cell growth (Marchesini, N., Luberto, C., and Hannun, Y. A. (2003) J. Biol. Chem. 278, 13775-13783). In this study, the role of endogenous nSMase2 in regulating growth arrest was investigated. The results show that endogenous nSMase2 mRNA was up-regulated similar to5-fold when MCF7 cells became growth-arrested at confluence, and total neutral SMase activity was increased by 119 +/- 41% with respect to control. Cell cycle analysis showed that up-regulation of endogenous nSMase2 correlated with G(0)/G(1) cell cycle arrest and an increase in total ceramide levels (2.4-fold). Analysis of ceramide species showed that confluence caused selective increases in very long chain ceramide C-24:1 (370 +/- 54%) and C-24:0 (266 +/- 81%) during arrest. The role of endogenous nSMase2 in growth regulation and ceramide metabolism was investigated using short interfering RNA (siRNA)-mediated loss-of-function analysis. Down-regulation of nSMase2 with specific siRNA increased the cell population of cells in S phase of the cell cycle by 59 +/- 14% and selectively reverted the effects of growth arrest on the increase in levels of very long chain ceramides. Mechanistically, confluence arrest also induced hypophosphorylation of the retinoblastoma protein (6-fold) and induction of p21(WAF1) (3-fold). Downregulation of nSMase2 with siRNA largely prevented the dephosphorylation of the retinoblastoma protein and the induction of p21(WAF1), providing a link between the action of nSMase2 and key regulators of cell cycle progression. Moreover, studies on nSMase2 localization in MCF7 cells showed that nSMase2 distributed throughout the cells in subconfluent, proliferating cultures. In contrast, nSMase2 became nearly exclusively located at the plasma membrane in confluent, contact-inhibited cells. Hence, we demonstrate for the first time that nSMase2 functions as a growth suppressor in MCF7 cells, linking confluence to the G(0)/G(1) cell cycle check point. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave, Charleston, SC 29425 USA. EM hannun@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG16583]; NIGMS NIH HHS [GM 43825] NR 69 TC 93 Z9 98 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 JUN 11 PY 2004 VL 279 IS 24 BP 25101 EP 25111 DI 10.1074/jbc.M313662200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826KL UT WOS:000221827900025 PM 15051724 ER PT J AU Ajroud, K Sugimori, T Goldmann, WH Fathallah, DM Xiong, JP Arnaout, MA AF Ajroud, K Sugimori, T Goldmann, WH Fathallah, DM Xiong, JP Arnaout, MA TI Binding affinity of metal ions to the CD11b A-domain is regulated by integrin activation and ligands SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIVALENT-CATION REGULATION; I-DOMAIN; CRYSTAL-STRUCTURE; EXTRACELLULAR SEGMENT; STRUCTURAL BASIS; CR3 CD11B/CD18; CA2+; ADHESION; COLLAGEN; SITE AB The divalent cations Mg2+ and Ca2+ regulate the interaction of integrins with their cognate ligands, with Mg2+ uniformly facilitating and Ca2+ generally inhibiting such interactions in vitro. Because both cations are present in mM concentrations in vivo, the physiologic relevance of the in vitro observations is unclear. We measured the affinity of both cations to the inactive and active states of the ligand- and cation-binding A-domain (CD11bA) from integrin CD11b/CD18 in the absence and presence of the single-chain 107 antibody (scFv107), an activation-insensitive ligand- mimetic antibody. Using titration calorimetry, we found that Mg2+ and Ca2+ display equivalent (mM) affinities to inactive CD11bA. Activation induced a similar to10-fold increase in the binding affinity of Mg2+ to CD11bA with no change in that of Ca2+ (106 muM +/- 16 and 2.1 mM +/- 0.19, respectively, n = 4). This increase is largely driven by favorable enthalpy. scFv107 induced a 50-80-fold increase in the binding affinity of Ca2+ (but not Mg2+ or Mn2+) to either form of CD11bA. Thus the affinity of metal ions to integrins is itself regulated by the activation state of these receptors and by certain ligands. These findings, which we expect will be applicable in vivo, elucidate a new level of regulation of the integrin-metal-ligand ternary complex and help explain some of the discrepant effects of Ca2+ on integrin-ligand interactions. C1 Massachusetts Gen Hosp, Renal Unit, Leukocyte Biol & Inflammat Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Inst Pasteur, Immunol Lab, Mol Biotechnol Grp, Tunis 1002, Tunisia. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, Leukocyte Biol & Inflammat Program, 149 13th St, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu RI Goldmann, Wolfgang/H-5572-2013 NR 41 TC 42 Z9 42 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 2004 VL 279 IS 24 BP 25483 EP 25488 DI 10.1074/jbc.M402901200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826KL UT WOS:000221827900072 PM 15070893 ER PT J AU Klucken, J Shin, Y Masliah, E Hyman, BT McLean, PJ AF Klucken, J Shin, Y Masliah, E Hyman, BT McLean, PJ TI Hsp70 reduces alpha-synuclein aggregation and toxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANDROGEN RECEPTOR PROTEIN; BULBAR MUSCULAR-ATROPHY; LEWY BODY FORMATION; PARKINSONS-DISEASE; HEAT-SHOCK; MOLECULAR CHAPERONES; HUNTINGTONS-DISEASE; OXIDATIVE STRESS; IN-VITRO; NEURODEGENERATIVE SYNUCLEINOPATHIES AB Aggregation and cytotoxicity of misfolded alpha-synuclein is postulated to be crucial in the disease process of neurodegenerative disorders such as Parkinson's disease and DLB (dementia with Lewy bodies). In this study, we detected misfolded and aggregated alpha-synuclein in a Triton X-100 insoluble fraction as well as a high molecular weight product by gel electrophoresis of temporal neocortex from DLB patients but not from controls. We also found similar Triton X-100 insoluble forms of alpha-synuclein in an alpha-synuclein transgenic mouse model and in an in vitro model of alpha-synuclein aggregation. Introducing the molecular chaperone Hsp70 into the in vivo model by breeding alpha-synuclein transgenic mice with Hsp70-overexpressing mice led to a significant reduction in both the high molecular weight and detergent-insoluble alpha-synuclein species. Concomitantly, we found that Hsp70 overexpression in vitro similarly reduced detergent-insoluble alpha-synuclein species and protected cells from alpha-synuclein-induced cellular toxicity. Taken together, these data demonstrate that the molecular chaperone Hsp70 can reduce the amount of misfolded, aggregated alpha-synuclein species in vivo and in vitro and protect it from alpha-synuclein-dependent toxicity. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. RP McLean, PJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. EM pmclean@partners.org FU NIA NIH HHS [AG18440]; NIMH NIH HHS [1R24MH68855]; NINDS NIH HHS [NS38372A-06] NR 69 TC 255 Z9 276 U1 3 U2 20 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 JUN 11 PY 2004 VL 279 IS 24 BP 25497 EP 25502 DI 10.1074/jbc.M400255200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826KL UT WOS:000221827900074 PM 15044495 ER PT J AU Kim, M Yang, HL Kim, SK Reche, PA Tirabassi, RS Hussey, RE Chishti, Y Rheinwald, JG Morehead, TJ Zech, T Damon, IK Welsh, RM Reinherz, EL AF Kim, M Yang, HL Kim, SK Reche, PA Tirabassi, RS Hussey, RE Chishti, Y Rheinwald, JG Morehead, TJ Zech, T Damon, IK Welsh, RM Reinherz, EL TI Biochemical and functional analysis of smallpox growth factor (SPGF) and anti-SPGF monoclonal antibodies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HETEROLOGOUS ANTIVIRAL IMMUNITY; ERBB SIGNALING NETWORK; GENOME DNA-SEQUENCES; VACCINIA VIRUS; FACTOR-ALPHA; CRYSTAL-STRUCTURE; FACTOR RECEPTOR; CELLS; EPIREGULIN; SPECIFICITY AB Variola, the causative agent of smallpox, is a highly infectious double-stranded DNA virus of the orthopox genus that replicates within the cytoplasm of infected cells. For unknown reasons prominent skin manifestations, including "pox," mark the course of this systemic human disease. Here we characterized smallpox growth factor (SPGF), a protein containing an epidermal growth factor (EGF)-like domain that is conserved among orthopox viral genomes, and investigated its possible mechanistic link. We show that after recombinant expression, refolding, and purification, the EGF domain of SPGF binds exclusively to the broadly expressed cellular receptor, erb-B1 (EGF receptor), with subnanomolar affinity, stimulating the growth of primary human keratinocytes and fibroblasts. High affinity monoclonal antibodies specific for SPGF reveal in vivo immunoprotection in a murine vaccinia pneumonia model by a mechanism distinct from viral neutralization. These findings suggest that blockade of pathogenic factor actions, in general, may be advantageous to the infected host. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lab Immunobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01655 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Poxvirus Sect, Atlanta, GA 30333 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lab Immunobiol, 44 Binney St, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900, AI19807]; NIAMS NIH HHS [AR35506, P30 AR042689] NR 53 TC 26 Z9 27 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 2004 VL 279 IS 24 BP 25838 EP 25848 DI 10.1074/jbc.M400343200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 826KL UT WOS:000221827900115 PM 15070899 ER PT J AU Mal, TK Masutomi, Y Zheng, L Nakata, Y Ohta, H Nakatani, Y Kokubo, T Ikura, M AF Mal, TK Masutomi, Y Zheng, L Nakata, Y Ohta, H Nakatani, Y Kokubo, T Ikura, M TI Structural and functional characterization on the interaction of yeast TFIID subunit TAF1 with TATA-binding protein SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE general transcription factor; transcriptional regulation; TAF; TBP; TFIID ID RNA-POLYMERASE-II; VP16 ACTIVATION DOMAIN; BOX-BINDING; TRANSCRIPTIONAL ACTIVATOR; SACCHAROMYCES-CEREVISIAE; DNA-BINDING; IN-VIVO; TRANSACTIVATION DOMAIN; GENE-TRANSCRIPTION; CRYSTAL-STRUCTURE AB General transcription factor TRID, consisting of TATA-binding protein (TBP) and TBP-associated factors (TAFs), plays a central role in both positive and negative regulation of transcription. The TAF N-terminal domain (TAND) of TAF1 has been shown to interact with TBP and to modulate the interaction of TBP with the TATA box, which is required for transcriptional initiation and activation of TATA-promoter operated genes. We have previously demonstrated that the Drosophila TAND region of TAF1 (residues 11-77) undergoes an induced folding from a largely unstructured state to a globular structure that occupies the DNA-binding surface of TBP thereby inhibiting the DNA-binding activity of TBP. In Saccharomyces cerevisiae, the TAND region of TAF1 displays marked differences in the primary structure relative to Drosophila TAF1 (11% identity) yet possesses transcriptional activity both in vivo and in vitro. Here we present structural and functional studies of yeast TAND1 and TAND2 regions (residues 10-37, and 46-71, respectively). Our NMR data show that, in yeast, TAND1 contains two alpha-helices (residues 16-23, 30-36) and TAND2 forms a mini beta-sheet structure (residues 53-56, 61-64). These TAND1 and TAND2 structured regions interact with the concave and convex sides of the saddle-like structure of TBP, respectively. Present NMR, mutagenesis and genetic data together elucidate that the minimal region (TAND1 core) required for GAL4-dependent transcriptional activation corresponds to the first helix region of TAND1, while the functional core region of TAND2, involved in direct interaction with TBP convex alpha-helix 2, overlaps with the mini beta-sheet region. (C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Toronto, Ontario Canc Inst, Div Mol & Struct Biol, Toronto, ON M5G 2M9, Canada. Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. Nara Inst Sci & Technol, Div Gene Funct Anim, Ikoma 6300101, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yokohama City Univ, Grad Sch Integrated Sci, Div Mol & Cellular Biol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Ikura, M (reprint author), Univ Toronto, Ontario Canc Inst, Div Mol & Struct Biol, Toronto, ON M5G 2M9, Canada. EM mikura@uhnres.utoronto.ca NR 55 TC 18 Z9 19 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 11 PY 2004 VL 339 IS 4 BP 681 EP 693 DI 10.1016/j.jmb.2004.04.020 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 827RV UT WOS:000221919100001 PM 15165843 ER PT J AU Butterwick, JA Loria, JP Astrof, NS Kroenke, CD Cole, R Rance, M Palmer, AG AF Butterwick, JA Loria, JP Astrof, NS Kroenke, CD Cole, R Rance, M Palmer, AG TI Multiple time scale backbone dynamics of homologous thermophilic and mesophilic ribonuclease HI enzymes SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ribonuclease HI; nuclear magnetic resonance; N-15 relaxation; protein dynamics; thermal stability ID CHEMICAL-SHIFT ANISOTROPY; MODEL-FREE APPROACH; MAGNETIC-RESONANCE RELAXATION; ESCHERICHIA-COLI; THERMUS-THERMOPHILUS; MOLECULAR-DYNAMICS; PROTEIN DYNAMICS; CONFORMATIONAL FLEXIBILITY; BIOLOGICAL MACROMOLECULES; TEMPERATURE-DEPENDENCE AB Backbone conformational fluctuations on multiple time scales in a cysteine-free Thermus thermophilus ribonuclease HI mutant (ttRNH*) are quantified using N-15 nuclear magnetic spin relaxation. Laboratory-frame relaxation data acquired at 310 K and at static magnetic field strengths of 11.7, 14.1 and 18.8 T are analysed using reduced spectral density mapping and model-free approaches. Chemical exchange line broadening is characterized using Hahn-echo transverse and multiple quantum relaxation data acquired over a temperature range of 290-320 K and at a static magnetic field strength of 14.1 T. Results for ttRNH* are compared to previously published data for a mesophilic homologue, Escherichia coli ribonuclease HI (ecRNH). Intramolecular conformational fluctuations on the pico-second-to-nanosecond time scale generally are similar for ttRNH* and ecRNH. beta-Strands 3 and 5 and the glycine-rich region are more rigid while the substrate-binding handle region and C-terminal tail are more flexible in ttRNH* than in ecRNH. Rigidity in the two beta-strands and the glycine-rich region, located along the periphery of the central beta-sheet, may be associated with the increased thermodynamic stability of the thermophilic enzyme. Chemical exchange line broadening, reflecting microsecond-to-millisecond time scale conformational changes, is more pronounced in ttRNH* than in ecRNH, particularly for residues in the handle and surrounding the catalytic site. The temperature dependence of chemical exchange show an increase of similar to15 kJ/mol in the apparent activation energies for ttRNH* residues in the handle compared to ecRNH. Increased activation barriers, coupled with motion between alpha-helices B and C not present in ecRNH, may be associated with the reduced catalytic activity of the thermophilic enzyme at 310 K. (C) 2004 Elsevier Ltd. All rights reserved. C1 Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Yale Univ, Dept Chem, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. RP Palmer, AG (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St,Box 36, New York, NY 10032 USA. EM agp6@columbia.edu FU NIGMS NIH HHS [GM66354, GM08281, GM40089, GM50291] NR 90 TC 56 Z9 56 U1 1 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 11 PY 2004 VL 339 IS 4 BP 855 EP 871 DI 10.1016/j.jmb.2004.03.055 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 827RV UT WOS:000221919100013 PM 15165855 ER PT J AU Fairfield, KM Hunter, DJ Colditz, GA Fuchs, CS Cramer, DW Speizer, FE Willett, WC Hankinson, SE AF Fairfield, KM Hunter, DJ Colditz, GA Fuchs, CS Cramer, DW Speizer, FE Willett, WC Hankinson, SE TI A prospective study of dietary lactose and ovarian cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lactose; ovarian cancer; milk ID GALACTOSE-1-PHOSPHATE URIDYL TRANSFERASE; GROWTH-FACTOR-I; TOTAL-ENERGY-INTAKE; RISK-FACTORS; GALACTOSE CONSUMPTION; UNITED-STATES; CIRCULATING LEVELS; PROSPECTIVE COHORT; FOOD-CONSUMPTION; MILK CONSUMPTION AB The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80,326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each II-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study. (C) 2004 Wiley-Liss, Inc. C1 Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04102 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. 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, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Fairfield, KM (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, 22 Bramhall St, Portland, ME 04102 USA. EM fairfk@mmc.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA5771-08, CA87969] NR 66 TC 37 Z9 38 U1 1 U2 9 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 JUN 10 PY 2004 VL 110 IS 2 BP 271 EP 277 DI 10.1002/ijc.20086 PG 7 WC Oncology SC Oncology GA 817ML UT WOS:000221181500018 PM 15069693 ER PT J AU Zhang, Y McGuire, M White, DP Ling, LM AF Zhang, Y McGuire, M White, DP Ling, LM TI Serotonin receptor subtypes involved in vagus nerve stimulation-induced phrenic long-term facilitation in rats SO NEUROSCIENCE LETTERS LA English DT Article DE vagus nerve stimulation; phrenic; long-term facilitation; serotonin receptors; respiratory control plasticity ID CHRONIC INTERMITTENT HYPOXIA; AWAKE RATS; MOTOR OUTPUT; ACTIVATION; PLASTICITY; MECHANISM AB Episodic vagus nerve stimulation (VNS) induces phrenic long-term facilitation (LTF, a persistent augmentation of phrenic nerve activity after the stimulation ends), sensitive to the serotonin 5-HT1,2.5,6,7 receptor antagonist methysergide and similar to that elicited by episodic hypoxia or carotid sinus nerve stimulation. This study examined the effect of ketanserin (5-HT2 antagonist) or clozapine (5-HT2,6,7 antagonist) on VNS-induced LTF in anesthetized, vagotomized, paralyzed and ventilated rats to determine which receptor subtype(s) is involved. Three episodes of 5 min VNS (50 Hz, 0.1 ms, similar to 500 muA) with 5 min intervals elicited phrenic LTF in control (amplitude: 38% above baseline at 60 min post-VNS) and ketanserin (2 mg(.)kg(-1), i.p.) pre-treated rats (45%), but not clozapine (3 mg(.)kg(-1)) rats (8%). These data suggest that unlike hypoxia-induced LTF (5-HT2 receptor-dependent), VNS-induced LTF requires non-5-HT2 serotonin receptors, perhaps 5-HT6 and/or 5-HT7 subtype(s). (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep Med,BIDMC, Boston, MA 02115 USA. RP Ling, LM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Sleep Med,BIDMC, 75 Francis St, Boston, MA 02115 USA. EM lling@partners.org FU NHLBI NIH HHS [HL64912] NR 20 TC 12 Z9 12 U1 0 U2 1 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 JUN 10 PY 2004 VL 363 IS 2 BP 108 EP 111 DI 10.1016/j.neulet.2004.03.067 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 827ZN UT WOS:000221942300003 PM 15172095 ER PT J AU Shellito, PC Clark, JW Willett, CG Caplan, AP Brugge, W Russell, P Warshaw, AL Cusack, JC AF Shellito, PC Clark, JW Willett, CG Caplan, AP Brugge, W Russell, P Warshaw, AL Cusack, JC TI Case 18-2004: A 61-year-old man with rectal bleeding and a 2-cm mass in the rectum - Adenocarcinoma of the rectum, stage T3N2M0 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TOTAL MESORECTAL EXCISION; METASTATIC COLORECTAL-CANCER; LYMPH-NODE METASTASES; SPHINCTER PRESERVATION; COLOANAL ANASTOMOSIS; RADIATION-THERAPY; RANDOMIZED-TRIAL; ADJUVANT THERAPY; LOCAL EXCISION; FLUOROURACIL C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Hematol Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Shellito, PC (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 29 TC 3 Z9 3 U1 0 U2 0 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 JUN 10 PY 2004 VL 350 IS 24 BP 2500 EP 2509 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 827GH UT WOS:000221887200011 PM 15190143 ER PT J AU Mathur, SK Grodinsky, D AF Mathur, SK Grodinsky, D TI Dislocation of the lenses SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Loyola Univ, Med Ctr, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Mathur, SK (reprint author), Loyola Univ, Med Ctr, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 JUN 10 PY 2004 VL 350 IS 24 BP E22 EP E22 DI 10.1056/NEJMicm030131 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 827GH UT WOS:000221887200010 PM 15190155 ER PT J AU Grunfeld, E Coyle, D Whelan, T Clinch, J Reyno, L Earle, CC Willan, A Viola, R Coristine, M Janz, T Glossop, R AF Grunfeld, E Coyle, D Whelan, T Clinch, J Reyno, L Earle, CC Willan, A Viola, R Coristine, M Janz, T Glossop, R TI Family caregiver burden: results of a longitudinal study of breast cancer patients and their principal caregivers SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID QUALITY-OF-LIFE; PALLIATIVE CARE; DEPRESSION SCALE; HOSPITAL ANXIETY; ELDERLY PEOPLE; HOME CARE; HEALTH; DEATH; RELIABILITY; VALIDITY AB Background: The vital role played by family caregivers in supporting dying cancer patients is well recognized, but the burden and economic impact on caregivers is poorly understood. We prospectively examined the psychosocial, occupational and economic impact of caring for a person with a terminal illness. Methods: We studied 89 caregivers of women with advanced breast cancer receiving care at either the Ottawa or Hamilton regional cancer centres in Ontario. Patients were followed until their death or study completion at 3 years. Patients identified a principal caregiver to participate in the study. The Karnofsky Performance Status (KPS) index, the Medical Outcomes Study 36-item Short Form (SF-36), the Hospital Anxiety and Depression Scale, the Zarit Burden Inventory, FAMCARE and the Medical Outcomes Study Social Support Survey were administered during follow-up. Economic data were collected by means of a questionnaire administered by an interviewer. Assessments were conducted every 3 months during the palliative period (KPS score > 50) and every 2 weeks during the terminal period (KPS score less than or equal to 50). Results: Over half of the caregivers were male (55%) and the patient's spouse or partner (52%), with a mean age of 53 years. At the start of the palliative period, the caregivers' mean physical functioning score was better than the patients' (51.3 v. 35.1, 95% confidence interval [CI] 13.3-20.0); there were similar mean mental functioning scores (46.6 and 47.1 respectively); similar proportions were depressed (11 % and 12%); and significantly more caregivers than patients were anxious (35% v. 19%, p = 0.009). More caregivers were depressed (30% v. 9%, p = 0.02) and had a higher level of perceived burden (26.2 v. 19.4, p = 0.02) at the start of the terminal period than at the start of the palliative period. Burden was the most important predictor of both anxiety and depression. Of employed caregivers, 69% reported some form of adverse impact on work. In the terminal period 77% reported missing work because of caregiving responsibilities. Prescription drugs were the most important component of financial burden. Interpretation: Caregivers' depression and perceived burden increase as patients' functional status declines. Strategies are needed to help reduce the psychosocial, occupational and economic burden associated with caregiving. C1 Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. Univ Ottawa, Div Med Oncol, Ottawa, ON, Canada. Ottawa Hosp, Ottawa Hlth Res Inst, Clin epidemiol Program, Ottawa, ON, Canada. Elizabeth Bruyere Hlth Ctr, Inst Palliat Care, Ottawa, ON, Canada. Vanier Int Family, Ottawa, ON, Canada. McMaster Univ, Reg Canc Ctr, Hamilton, ON L8S 4L8, Canada. McMaster Univ, Div Radiat Oncol, Hamilton, ON L8S 4L8, Canada. St Josephs Hosp, Ctr Evaluat Med, Hamilton, ON, Canada. Dalhousie Univ, Div Med Oncol, Halifax, NS B3H 3J5, Canada. Harvard Univ, Sch Med, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Grunfeld, E (reprint author), Canc Care Nova Scotia, 1278 Tower Rd,Bethune Bldg, Halifax, NS B3H 2Y9, Canada. EM Eva.Grunfeld@ccns.nshealth.ca RI Whelan, Timothy/D-3185-2017 NR 49 TC 343 Z9 357 U1 6 U2 60 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 8 PY 2004 VL 170 IS 12 BP 1795 EP 1801 DI 10.1503/cmaj.1031205 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 829AL UT WOS:000222015100032 PM 15184333 ER PT J AU Huq, F Lebeche, D Iyer, V Liao, RL Hajjar, RJ AF Huq, F Lebeche, D Iyer, V Liao, RL Hajjar, RJ TI Gene transfer of parvalbumin improves diastolic dysfunction in senescent myocytes SO CIRCULATION LA English DT Article DE parvalbumin; aging; gene therapy; myocytes; diastole ID RELAXATION SPEED; HEART-FAILURE; CARDIOMYOCYTES; RESTORATION; MECHANISMS; AGE AB Background - Impaired relaxation is a cardinal feature of senescent myocardial dysfunction. Recently, adenoviral gene transfer of parvalbumin, a small calcium-buffering protein found exclusively in skeletal muscle and neurons, has been shown to improve cardiomyocyte relaxation in disease models of diastolic dysfunction. The goal of this study was to investigate whether parvalbumin gene transfer could reverse diastolic dysfunction in senescent cardiomyocytes. Methods and Results - Myocytes were isolated from senescent ( 26 months) and adult ( 6 months) F344/BN hybrid rats and were infected with Ad. Parv. GFP (where GFP is green fluorescent protein) or Ad.betagal. GFP at a multiplicity of infection of 250 for 48 hours. Uninfected senescent and adult myocytes served as controls. After stimulation at a frequency of 0.5 Hz, intracellular calcium transients and myocyte contractility were measured using dual excitation spectrofluorometry and video-edge detection system (Ionoptix). Parvalbumin significantly improved relaxation parameters in senescent myocytes: Both the rate of calcium transient decay and the rate of myocyte relengthening were dramatically increased in senescent cardiac myocytes transduced with parvalbumin compared with nontransduced and GFP-expressing controls, with no effect on myocyte shortening. Conclusions - Parvalbumin expression corrects impaired relaxation in aging myocytes. Given that abnormalities of myocyte relaxation underlie diastolic dysfunction in a large proportion of elderly patients with heart failure, gene transfer of parvalbumin may thus be a novel approach to target diastolic dysfunction in senescent myocardium. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiac Muscle Res Lab, Boston, MA 02118 USA. RP Hajjar, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Charlestown, MA 02129 USA. EM rhajjar@partners.org FU NHLBI NIH HHS [HL067297, HL073756, HLK0176659, HL057623, HL071763] NR 23 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 8 PY 2004 VL 109 IS 22 BP 2780 EP 2785 DI 10.1161/01.CIR.0000131764.62242.96 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 827FF UT WOS:000221883900019 PM 15173024 ER PT J AU Gibson, FC Hong, C Chou, HH Yumoto, H Chen, JQ Lien, E Wong, J Genco, CA AF Gibson, FC Hong, C Chou, HH Yumoto, H Chen, JQ Lien, E Wong, J Genco, CA TI Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice SO CIRCULATION LA English DT Article DE infection; inflammation; atherosclerosis; receptors; endothelium ID INFECTED ENDOTHELIAL-CELLS; TOLL-LIKE RECEPTOR-4; PORPHYROMONAS-GINGIVALIS; PERIODONTAL-DISEASE; CHLAMYDIA-PNEUMONIAE; EXPRESSION; LESIONS; MURINE; PATHOGENESIS; PROGRESSION AB Background - Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD. Methods and Results - To directly test the connection between periodontal disease and atherosclerosis, apoE(-/-) mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA-). Both wild-type P gingivalis and the FimA- mutant were detected in blood and aortic arch tissue of apoE(-/-) mice by PCR after challenge. ApoE(-/-) mice challenged with wild-type P gingivalis presented with increased atherosclerotic plaque and expressed the innate immune response markers Toll- like receptor (TLR)-2 and TLR-4 in aortic tissue. Despite detection of the FimA- mutant in the blood and in aortic arch tissue, apoE(-/-) mice challenged with the FimA(-) mutant did not present with periodontal disease, upregulation of TLRs, or accelerated atherosclerosis. Furthermore, we demonstrate that immunization to control P gingivalis - elicited periodontal disease concomitantly prevents P gingivalis - accelerated atherosclerosis. Conclusions - We conclude that invasive P gingivalis accelerates atherosclerosis. C1 Boston Univ, Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA. Goldman Sch Dent Med, Dept Endodont, Boston, MA USA. Taipei Med Univ, Coll Oral Med, Sch Dent, Taipei, Taiwan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Norwegian Univ Sci & Technol, Inst Canc Res & Mol Biol, N-7034 Trondheim, Norway. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA. Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA USA. Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. RP Genco, CA (reprint author), EBRC, Room 637,650 Albany St, Boston, MA 02118 USA. EM caroline.genco@bmc.org OI Gibson, Frank/0000-0003-1988-1170 FU NIDCR NIH HHS [F32-DE-05739, P01-DE-13191, R01-DE-12517] NR 49 TC 213 Z9 218 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 8 PY 2004 VL 109 IS 22 BP 2801 EP 2806 DI 10.1161/01.CIR.0000129769.17895.F0 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 827FF UT WOS:000221883900022 PM 15123526 ER PT J AU Moberg, KH Mukherjee, A Veraksa, A Artavanis-Tsakonas, S Hariharan, IK AF Moberg, KH Mukherjee, A Veraksa, A Artavanis-Tsakonas, S Hariharan, IK TI The Drosophila F box protein archipelago regulates dMyc protein levels in vivo SO CURRENT BIOLOGY LA English DT Article ID UBIQUITIN-PROTEASOME PATHWAY; C-MYC PROTEOLYSIS; CYCLIN-E; MULTISITE PHOSPHORYLATION; CELL-PROLIFERATION; TRANSGENIC MICE; CANCER; GROWTH; NOTCH; GENE AB Background: The Myc oncoprotein is an important regulator of cellular growth in metazoan organisms. Its levels and activity are tightly controlled in vivo by a variety of mechanisms. In normal cells, Myc protein is rapidly degraded, but the mechanism of its degradation is not well understood. Results: Here we present genetic and biochemical evidence that Archipelago (Ago), the F box component of an SCF-ubiquitin ligase and the Drosophila ortholog of a human tumor suppressor, negatively regulates the levels and activity of Drosophila Myc (dMyc) protein in vivo. Mutations in archipelago (ago) result in strongly elevated dMyc protein levels and increased tissue growth. Genetic interactions indicate that ago antagonizes dMyc function during development. Archipelago binds dMyc and regulates its stability, and the ability of Ago to bind dMyc in vitro correlates with its ability to inhibit dMyc accumulation in vivo. Conclusions: Our data indicate that archipelago is an important inhibitor of dMyc in developing tissues. Because archipelago can also regulate Cyclin E levels and Notch activity, these results indicate how a single F box protein can be responsible for the degradation of key components of multiple pathways that control growth and cell cycle progression. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Moberg, KH (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kmoberg@cellbio.emory.edu FU NCI NIH HHS [CA95281, CA098402]; NIGMS NIH HHS [R01GM62931, GM61672]; NINDS NIH HHS [R01NS26084] NR 47 TC 90 Z9 93 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 JUN 8 PY 2004 VL 14 IS 11 BP 965 EP 974 DI 10.1016/j.cub.2004.02.040 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 828AB UT WOS:000221943700023 PM 15182669 ER PT J AU Tenor, JL McCormick, BA Ausubel, FM Aballay, A AF Tenor, JL McCormick, BA Ausubel, FM Aballay, A TI Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions SO CURRENT BIOLOGY LA English DT Article ID TYROSINE-PHOSPHATASE; SECRETED PROTEIN; TYPHIMURIUM LT2; KINASE PATHWAY; EXPRESSION; ACTIVATION; SEQUENCE; YERSINIA; ENTERICA; CELLS AB A Caenorhabditis elegans-Salmonella enterica host-pathogen model was used to identify both novel and previously known S. enterica virulence factors (HilA, HilD, InvH, SptP, RhuM, Spi4-F, PipA, VsdA, RepC, Sb25, RfaL, GmhA, LeuO, CstA, and RecC), including several related to the type III secretion system (TTSS) encoded in Salmonella pathogenicity island 1 (SPI-1). Mutants corresponding to presumptive novel virulence-related genes exhibited diminished ability to invade epithelial cells and/or to induce polymorphonuclear leukocyte migration in a tissue culture model of mammalian enteropathogenesis. When expressed in C. elegans intestinal cells, the S. enterica TTSS-exported effector protein SptP inhibited a conserved p38 MAPK signaling pathway and suppressed the diminished pathogenicity phenotype of an S. enterica sptP mutant. These results show that C. elegans is an attractive model to study the interaction between Salmonella effector proteins and components of the innate immune response, in part because there is a remarkable overlap between Salmonella virulence factors required for human and nematode pathogenesis. C1 Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Aballay, A (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. EM a.aballay@duke.edu FU NIDDK NIH HHS [DK56754]; NIGMS NIH HHS [GM48707] NR 35 TC 96 Z9 103 U1 4 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 8 PY 2004 VL 14 IS 11 BP 1018 EP 1024 DI 10.1016/j.cub.2004.05.050 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 828AB UT WOS:000221943700031 PM 15182677 ER PT J AU Herman, AE Freeman, GJ Mathis, D Benoist, C AF Herman, AE Freeman, GJ Mathis, D Benoist, C TI CD4(+)CD25(+) T regulatory cells dependent on ICOS promote regulation of effector cells in the prediabetic lesion SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmunity; diabetes; costimulation; tolerance; microarray ID NONOBESE DIABETIC MICE; IMMUNOLOGICAL SELF-TOLERANCE; PANCREATIC-ISLET ANTIGEN; INTESTINAL INFLAMMATION; DENDRITIC CELLS; IN-VIVO; AUTOIMMUNE-DISEASE; TRANSGENIC MICE; CUTTING EDGE; TGF-BETA AB CD4(+) CD25(+) T regulatory cells (Tregs) prevent autoimmune disease, yet little is known about precisely where they exert their influence naturally in a spontaneous autoimmune disorder. Here, we report that Tregs and T effector cells (Teffs) coexist within the pancreatic lesion before type 1 diabetes onset. We find that BDC2.5 T cell receptor transgenic animals contain a small subset of FoxP3 positive CD4(+) CD25(+) CD69(-) cells in the pancreas, actively turning over, expressing the clonotypic receptor, and containing functional regulatory activity. Gene expression profiling confirms that the CD4(+) CD25(+) CD69(-) cells in pancreatic tissue express transcripts diagnostic of regulatory cells, but with significantly higher levels of interleukin 10 and inducible costimulator (ICOS) than their lymph node counterparts. Blockade of ICOS rapidly converts early insulitis to diabetes, which disrupts the balance of Teffs and Tregs and promotes a very broad shift in the expression of the T regulatory-specific profile. Thus, CD4(+) CD25(+) 69(-) Tregs operate directly in the autoimmune lesion and are dependent on ICOS to keep it in a nondestructive state. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl,Res 4th Fl, Boston, MA 02215 USA. EM dm@joslin.harvard.edu; cb@joslin.harvard.edu RI e-, a/F-9947-2012 FU NCI NIH HHS [CA 84500, R01 CA084500, T32 CA 70083-07, T32 CA070083]; NIAID NIH HHS [AI 39671, P01 AI039671]; NIDDK NIH HHS [2 T32 DK07260-25, T32 DK007260, Z P30 DK36836-17] NR 58 TC 285 Z9 290 U1 3 U2 8 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 JUN 7 PY 2004 VL 199 IS 11 BP 1479 EP 1489 DI 10.1084/jem.20040179 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 829KS UT WOS:000222047800004 PM 15184501 ER PT J AU Samaha, FF Rubenstein, RC Yan, WS Ramkumar, M Levy, DI Ahn, YJ Sheng, SH Kleyman, TR AF Samaha, FF Rubenstein, RC Yan, WS Ramkumar, M Levy, DI Ahn, YJ Sheng, SH Kleyman, TR TI Functional polymorphism in the carboxyl terminus of the alpha-subunit of the human epithelial sodium channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-SURFACE EXPRESSION; SENSITIVE NA+ CHANNEL; LIDDLE-SYNDROME; BETA-SUBUNIT; MEMBRANE TOPOLOGY; GAMMA-SUBUNIT; ESSENTIAL-HYPERTENSION; BLACK-PEOPLE; MUTATIONS; AMILORIDE AB A common human epithelial sodium channel ( ENaC) polymorphism, alphaT663A, is present in the cytoplasmic C terminus of the alpha-subunit, although it is unclear whether this polymorphism segregates with blood pressure. We examined whether this polymorphism was associated with differences in functional Na+ channel expression. Whole cell amiloride-sensitive currents in Xenopus oocytes expressing wild type channels (alphaT663betagamma) were significantly similar to1.3-2.0-fold higher than currents measured in oocytes expressing channels with an Ala, Gly or Leu, or Lys at position alpha663. In contrast, differences in functional human ENaC expression were not observed with oocytes expressing channels having Thr (wild type), Ser, or Asp at this position. The surface expression of channels, measured using an epitope-tagged beta-subunit, was significantly reduced in oocytes expressing alphaT663Abetagamma when compared with oocytes expressing alphaT663betagamma. The corresponding polymorphism was generated in the mouse alpha-subunit (malphaA692T) and was not associated with differences in functional alphabetagamma-mouse ENaC expression. The polymorphism is present in a region that is not well conserved between human and mouse. We generated a mouse/human chimera by replacement of the distal C terminus of the mouse alpha-subunit with the distal C terminus of the human alpha-subunit. Co-expression of this m(1-678)/h(650-669)T663A chimera with mouse betagamma led to a significant reduction in whole cell Na+ currents and surface expression when compared with m(1-678)/h( 650-669) T663-mbetagamma. Our results suggest that h alphaT663A is a functional polymorphism that affects human ENaC surface expression. C1 Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. RP Rubenstein, RC (reprint author), Childrens Hosp Philadelphia, Div Pulm Med, 34th St & Civ Ctr Blvd,Abramson 410C, Philadelphia, PA 19104 USA. EM rrubenst@mail.med.upenn.edu OI Sheng, Shaohu/0000-0002-7198-1702 FU NIDDK NIH HHS [DK58046, DK51391, DK54354] NR 37 TC 31 Z9 34 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 JUN 4 PY 2004 VL 279 IS 23 BP 23900 EP 23907 DI 10.1074/jbc.M401941200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 824RA UT WOS:000221702500010 PM 15069064 ER PT J AU Devroe, E Erdjument-Bromage, H Tempst, P Silver, PA AF Devroe, E Erdjument-Bromage, H Tempst, P Silver, PA TI Human mob proteins regulate the NDR1 and NDR2 serine-threonine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE; TRANSCRIPTION FACTOR; PHOSPHORYLATION; LOCALIZATION; CYTOKINESIS; INTERACTS; INTEGRASE; COMPLEXES; YEAST AB Human NDR1 (nuclear Dbf2-related) is a widely expressed nuclear serine-threonine kinase that has been implicated in cell proliferation and/or tumor progression. Here we present molecular characterization of the human NDR2 serine-threonine kinase, which shares similar to87% sequence identity with NDR1. NDR2 is expressed in most human tissues with the highest expression in the thymus. In contrast to NDR1, NDR2 is excluded from the nucleus and exhibits a punctate cytoplasmic distribution. The differential localization of NDR1 and NDR2 suggests that each kinase may serve distinct functions. Thus, to identify proteins that interact with NDR1 or NDR2, epitope-tagged kinases were immunoprecipitated from Jurkat T-cells. Two uncharacterized proteins that are homologous to the Saccharomyces cerevisiae kinase regulators Mob1 and Mob2 were identified. We demonstrate that NDR1 and NDR2 partially colocalize with human Mob2 in HeLa cells and confirm the NDR-Mob interactions in cell extracts. Interestingly, NDR1 and NDR2 form stable complexes with Mob2, and this association dramatically stimulates NDR1 and NDR2 catalytic activity. In summary, this work identifies a unique class of human kinase-activating subunits that may be functionally analagous to cyclins. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Cell Biol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10021 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu OI Tempst, Paul/0000-0002-6680-3987 NR 23 TC 60 Z9 66 U1 0 U2 1 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 JUN 4 PY 2004 VL 279 IS 23 BP 24444 EP 24451 DI 10.1074/jbc.M401999200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 824RA UT WOS:000221702500071 PM 15067004 ER PT J AU Baron, MJ Bolduc, GR Goldberg, MB Auperin, TC Madoff, LC AF Baron, MJ Bolduc, GR Goldberg, MB Auperin, TC Madoff, LC TI Alpha C protein of group B Streptococcus binds host cell surface glycosaminoglycan and enters cells by an actin-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; EPIDERMAL GROWTH-FACTOR; EPITHELIAL-CELLS; ENDOTHELIAL-CELLS; INTEGRIN ALPHA(IIB)BETA(3); NEISSERIA-GONORRHOEAE; PROTECTIVE EPITOPES; PLASMA-MEMBRANE; VIRUS TYPE-1; ANTIGEN GENE AB Group B Streptococcus (GBS) colonizes mucosal surfaces of the human gastrointestinal and gynecological tracts and causes disease in a wide range of patients. Invasive illness occurs after organisms traverse an epithelial boundary and enter deeper tissues. Previously we have reported that the alpha C protein (ACP) on the surface of GBS mediates GBS entry into ME180 cervical epithelial cells and GBS translocation across layers of these cells. We now demonstrate that ACP interacts with host cell glycosaminoglycan (GAG); the interaction of ACP with ME180 cells is inhibited if cells are pretreated with sodium chlorate, an inhibitor of sulfate incorporation, or with heparitinases. The interaction is also inhibited in the presence of soluble heparin or heparan sulfate or host cell-derived GAG. In addition, ACP binds soluble heparin specifically in inhibition and dot blot assays. After interaction with host GAG, soluble ACP enters ME180 cells and fractionates to the eukaryotic cell cytosol. These events are inhibited in cells pretreated with cytochalasin D or with Clostridium difficile toxin B. These data indicate that full-length ACP interacts with ME180 cell GAG and enters the eukaryotic cell cytosol by a mechanism that involves Rho GTPase-dependent actin rearrangements. We suggest that these molecular interactions drive ACP-mediated translocation of GBS across epithelial barriers, thereby facilitating invasive GBS infection. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Baron, MJ (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM mbaron@partners.org FU NIAID NIH HHS [AI38424, AI51114] NR 70 TC 53 Z9 54 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 JUN 4 PY 2004 VL 279 IS 23 BP 24714 EP 24723 DI 10.1074/jbc.M402164200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 824RA UT WOS:000221702500102 PM 15044471 ER PT J AU Garnovskaya, MN Mukhin, YV Vlasova, TM Grewal, JS Ullian, ME Tholanikunnel, BG Raymond, JR AF Garnovskaya, MN Mukhin, YV Vlasova, TM Grewal, JS Ullian, ME Tholanikunnel, BG Raymond, JR TI Mitogen-induced rapid phosphorylation of serine 795 of the retinoblastoma gene product in vascular smooth muscle cells involves ERK activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID E2F TRANSCRIPTION FACTORS; TUMOR-SUPPRESSOR PROTEIN; CYCLIN-DEPENDENT KINASES; ABL TYROSINE KINASE; BREAST-CANCER CELLS; ANGIOTENSIN-II; PHOSPHATIDYLINOSITOL 3-KINASE; MAP KINASE; DIFFERENTIAL REGULATION; NUCLEAR-LOCALIZATION AB We examined the relationship between mitogen-activated MEK (mitogen and extracellular signal-regulated protein kinase kinase) and phosphorylation of the gene product encoded by retinoblastoma ( hereafter referred to as Rb) in vascular smooth muscle cells. Brief treatment of the cells with 100 nM angiotensin II or 1 muM serotonin resulted in serine phosphorylation of Rb that was equal in magnitude to that induced by treating cells for 20 h with 10% fetal bovine serum (approximate to3 x basal). There was no detectable rapid phosphorylation of two close cousins of Rb, p107 and p130. Phosphorylation state-specific antisera demonstrated that the rapid phosphorylation occurred on Ser(795), but not on Ser(249), Thr(252), Thr(373), Ser(780), Ser(807), or Ser(811). Phosphorylation of Rb Ser(795) peaked at 10 min, lagging behind phosphorylation of MEK and ERK (extracellular signal-regulated protein kinase). Rb Ser(795) phosphorylation could be blocked by PD98059, a MEK inhibitor, and greatly attenuated by apigenin, an inhibitor of the Ras --> Raf --> MEK --> ERK pathway. The effect also appears to be mediated by CDK4. Immunoprecipitation/immunoblot studies revealed that serotonin and angiotensin II induced complex formation between CDK4, cyclin D1, and phosphorylated ERK. These studies show a rapid, novel, and selective phosphorylation of Rb Ser(795) by mitogens and demonstrate an unexpected rapid linkage between the actions of the Ras --> Raf --> MEK --> ERK pathway and the phosphorylation state of Rb. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,Rm 829 CSB,POB 250623, Charleston, SC 29425 USA. EM garnovsk@musc.edu FU NIDDK NIH HHS [R01-DK52448, K01-DK02694]; NIGMS NIH HHS [R01-GM63909] NR 66 TC 28 Z9 28 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 JUN 4 PY 2004 VL 279 IS 23 BP 24899 EP 24905 DI 10.1074/jbc.M311622200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 824RA UT WOS:000221702500122 PM 15069084 ER PT J AU Paez, JG Janne, PA Lee, JC Tracy, S Greulich, H Gabriel, S Herman, P Kaye, FJ Lindeman, N Boggon, TJ Naoki, K Sasaki, H Fujii, Y Eck, MJ Sellers, WR Johnson, BE Meyerson, M AF Paez, JG Janne, PA Lee, JC Tracy, S Greulich, H Gabriel, S Herman, P Kaye, FJ Lindeman, N Boggon, TJ Naoki, K Sasaki, H Fujii, Y Eck, MJ Sellers, WR Johnson, BE Meyerson, M TI EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy SO SCIENCE LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; BRAF GENE; INHIBITOR; SENSITIVITY; TRIAL; AMPLIFICATION; COMBINATION; PACLITAXEL; EFFICACY AB Receptor tyrosine kinase genes were sequenced in non - small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15 of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U. S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA. Natl Naval Med Res Inst, Genet Branch, NCI, Bethesda, MD 20889 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Nagoya City Univ, Sch Med, Dept Surg 2, Nagoya, Aichi 4678601, Japan. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM William_Sellers@dfci.harvard.edu; Bruce_Johnson@dfci.harvard.edu; Matthew_Meyerson@dfci.harvard.edu RI kaye, frederic/E-2437-2011; Meyerson, Matthew/E-7123-2012; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 26 TC 5475 Z9 5795 U1 95 U2 525 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 JUN 4 PY 2004 VL 304 IS 5676 BP 1497 EP 1500 DI 10.1126/science.1099314 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 825YR UT WOS:000221795800043 PM 15118125 ER PT J AU Goldberg, RT Hillberg, R Reinecker, L Goldstein, R AF Goldberg, RT Hillberg, R Reinecker, L Goldstein, R TI Evaluation of patients with severe pulmonary disease before and after pulmonary rehabilitation SO DISABILITY AND REHABILITATION LA English DT Article ID QUALITY-OF-LIFE; HEALTH-STATUS; CHRONIC PAIN; DYSPNEA; COPD; DEPRESSION; CHILDHOOD; ADULTS; SCALE AB Purpose: The purpose was to evaluate the impact of inpatient pulmonary rehabilitation program upon changes in anxiety, depression, psychological outlook, and dyspnea. A secondary purpose was to predict changes in psychological outlook, depression, anxiety, and dyspnea by using three pulmonary function tests and age. Methods: The design consisted of an observational study with pre - post comparisons. Forty-five patients with severe pulmonary disease, mean age 67.4 years (SD 9.2), mean FEV1= 31.44% predicted, 13 men, 32 women were compared on four measures before and after 3 weeks of rehabilitation. Measures were Beck Depression Inventory, Hamilton Anxiety Scale, Goldberg Scale, and Modified Borg Scale. In addition, a linear multiple regression model using age, gender, % predicted FEV1, FEV1/ FVC, % predicted DLCO as independent variables were used to predict changes. Results: Patients who completed the pulmonary program showed significant changes in favour of post scores on all four scales at p<0.001. The program significantly reduced anxiety and depression, and increased positive psychological outlook in severe pulmonary disease. Perceived breathlessness on the Borg Scale was significantly reduced ( p<0.0001). The multiple regression model was not statistically significant for prediction of any of the changes. Conclusions: Patients with severe pulmonary disease can significantly improve their psychological outlook and decrease anxiety and depression when they complete an inpatient pulmonary rehabilitation program. Psychological gains and perception of breathlessness improve with rehabilitation, even though FEV1 and other pulmonary function tests may not predict these changes. A second implication is that rehabilitation improves psychological outlook with both severely ill patients and a group with mixed pulmonary and cardiac disease. C1 Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Dept Psychiat, Div Behav & Mental Hlth, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Spaulding Rehabil Hosp, Dept Med, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Dept Nursing, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RP Goldberg, RT (reprint author), Spaulding Rehabil Hosp, Dept Med, 125 Nashua St, Boston, MA 02114 USA. NR 36 TC 10 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1464-5165 J9 DISABIL REHABIL JI Disabil. Rehabil. PD JUN 3 PY 2004 VL 26 IS 11 BP 641 EP 648 DI 10.1080/09638280410001663120 PG 8 WC Rehabilitation SC Rehabilitation GA 824BL UT WOS:000221658900003 PM 15204502 ER PT J AU Chen, HH Nicoletti, MA Hatch, JP Sassi, RB Axelson, D Brambilla, P Monkul, ES Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Chen, HH Nicoletti, MA Hatch, JP Sassi, RB Axelson, D Brambilla, P Monkul, ES Keshavan, MS Ryan, ND Birmaher, B Soares, JC TI Abnormal left superior temporal gyrus volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study SO NEUROSCIENCE LETTERS LA English DT Article DE magnetic resonance imaging; bipolar disorder; superior temporal gyrus; adolescents ID GRAY-MATTER VOLUME; 1ST-EPISODE SCHIZOPHRENIA; AGE AB Abnormalities in left superior temporal gyrus (STG) have been reported in adult bipolar patients. However, it is not known whether such abnormalities are already present early in the course of this illness. Magnetic resonance imaging (MRI) morphometric analysis of STG was performed in 16 DSM-IV children and adolescents with bipolar disorder (mean age +/- SD 15.5 +/- 3.4 years) and 21 healthy controls (mean age +/- SD 16.9 +/- 3.8 years). Subjects underwent a 3D spoiled gradient recalled acquisition MRI examination. Using analysis of covariance with age, gender and intra-cranial brain volume as covariates, we found significantly smaller left total STG volumes in bipolar patients (12.5 +/- 1.5 cm(3)) compared with healthy controls (13.6 +/- 2.5 cm(3)) (F = 4.45, d.f. = 1, 32, P = 0.04). This difference was accounted for by significantly smaller left and right STG white matter volumes in bipolar patients. Decreased white matter connections may be the core of abnormalities in STG, which is an important region for speech, language and communication, and could possibly underlie neurocognitive deficits present in bipolar patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Ctr Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Verona, Sch Med, Dept Med & Publ Hlth, I-37100 Verona, Italy. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, MC7792,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 59929, MH 01736, MH 30915, MH 55123] NR 20 TC 48 Z9 50 U1 0 U2 4 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 JUN 3 PY 2004 VL 363 IS 1 BP 65 EP 68 DI 10.1016/j.neulet.2004.03.042 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 824SR UT WOS:000221707400016 PM 15157998 ER PT J AU Levy, BD O'Connell, JJ AF Levy, BD O'Connell, JJ TI Health care for homeless persons SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. RP Levy, BD (reprint author), Brigham & Womens Hosp, Dept Internal Med, 75 Francis St, Boston, MA 02115 USA. NR 4 TC 38 Z9 38 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 JUN 3 PY 2004 VL 350 IS 23 BP 2329 EP 2332 DI 10.1056/NEJMp038222 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 825JY UT WOS:000221754200002 PM 15175433 ER PT J AU Mayer, RJ AF Mayer, RJ TI Two steps forward in the treatment of colorectal cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID 1ST-LINE TREATMENT; PLUS FLUOROURACIL; RANDOMIZED-TRIAL; LEUCOVORIN; OXALIPLATIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 18 TC 65 Z9 67 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 JUN 3 PY 2004 VL 350 IS 23 BP 2406 EP 2408 DI 10.1056/NEJMe048098 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 825JY UT WOS:000221754200013 PM 15175443 ER PT J AU Lee, TH Meyer, GS Brennan, TA AF Lee, TH Meyer, GS Brennan, TA TI A middle ground on public accountability SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEALTH-CARE; MORTALITY C1 Partners Healthcare Syst, Boston, MA 02199 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Lee, TH (reprint author), Partners Healthcare Syst, Prudential tower,11th Fl,800 Boylston St, Boston, MA 02199 USA. EM thlee@partners.org NR 8 TC 53 Z9 53 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 JUN 3 PY 2004 VL 350 IS 23 BP 2409 EP 2412 DI 10.1056/NEJMsb041193 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 825JY UT WOS:000221754200014 PM 15175444 ER PT J AU Drivdahl, R Haugk, KH Sprenger, CC Nelson, PS Tennant, MK Plymate, SR AF Drivdahl, R Haugk, KH Sprenger, CC Nelson, PS Tennant, MK Plymate, SR TI Suppression of growth and tumorigenicity in the prostate tumor cell line M12 by overexpression of the transcription factor SOX9 SO ONCOGENE LA English DT Article DE SOX9; prostate; androgens; IGF; cancer ID PROTEIN-RELATED PROTEIN-1; MANGANESE SUPEROXIDE-DISMUTASE; CANCER CELLS; ANDROGEN RECEPTOR; EPITHELIAL-CELLS; TESTIS DEVELOPMENT; SEX DETERMINATION; BINDING; EXPRESSION; GENE AB Overexpression of mac25 in the prostate cancer cell line M12 effects a dramatic reversal of the transformed phenotype. cDNA array analysis of RNA from cells overproducing the mac25 protein (M12/mac25) indicated upregulation of the sex determining transcription factor SOX9. In this study, we have confirmed increased expression of SOX9 in M12/mac25 cells and have further investigated the physiological effects of increased SOX9 production. Greatly increased levels of SOX9 RNA and mature protein were demonstrated in cells transfected with a SOX9 cDNA (M12/SOX9), and gel mobility shift assays confirmed binding of nuclear protein from these cells to an oligonucleotide containing the SOX9 consensus binding sequence. M12/SOX9 cells assumed the spindle-shaped morphology characteristic of M12/mac25 cells, suggesting that SOX9 mediates some effects of mac25. Elevated expression of SOX9 resulted in a decreased rate of cellular proliferation, cell cycle arrest in G0/G1, and increased sensitivity to apoptosis. Tumor development in athymic nude mice was inhibited by 80%. Finally, prostate-specific antigen and the androgen receptor, two genes whose expression is characteristic of differentiated cells, were both upregulated in M12/SOX9 cells. These data indicate that SOX9 contributes to growth regulation by mac25 via inhibition of cell growth and promotion of differentiation. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98105 USA. Univ Washington, Sch Med, Mol & Cell Biol Program, Seattle, WA 98105 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98107 USA. RP Plymate, SR (reprint author), Univ Washington, Harborview Med Ctr, Box 359755,325 9th Ave, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU NCI NIH HHS [P01-CA85859, R01-CA56283] NR 55 TC 40 Z9 45 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 JUN 3 PY 2004 VL 23 IS 26 BP 4584 EP 4593 DI 10.1038/sj.onc.1207603 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 825ZV UT WOS:000221799000008 PM 15077158 ER PT J AU Mizuno, T Hisamoto, N Terada, T Kondo, T Adachi, M Nishida, E Kim, DH Ausubel, FM Matsumoto, K AF Mizuno, T Hisamoto, N Terada, T Kondo, T Adachi, M Nishida, E Kim, DH Ausubel, FM Matsumoto, K TI The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response SO EMBO JOURNAL LA English DT Article DE C. elegans; heavy metal stress; MAP kinase; MAPK phosphatase ID PROTEIN-KINASE PHOSPHATASE; MIXED-LINEAGE KINASE; TRANSDUCTION PATHWAY; DEPENDENT APOPTOSIS; TNF SUPERFAMILY; DORSAL CLOSURE; DROSOPHILA; MOVEMENT; MKP-7; EIGER AB Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and to a wide variety of environmental stresses. MAPK cascades can be inactivated at the MAPK activation step by members of the MAPK phosphatase (MKP) family. However, the components that act in MKP-regulated pathways have not been well characterized in the context of whole organisms. Here we characterize the Caenorhabditis elegans vhp-1 gene, encoding an MKP that acts preferentially on the c-Jun N-terminal kinase (JNK) and p38 MAPKs. We found that animals defective in vhp-1 are arrested during larval development. This vhp-1 defect is suppressed by loss-of-function mutations in the kgb-1, mek-1, and mlk-1 genes encoding a JNK-like MAPK, an MKK7-type MAPKK, and an MLK-type MAPKKK, respectively. The genetic and biochemical data presented here demonstrate a critical role for VHP-1 in the KGB-1 pathway. Loss-of-function mutations in each component in the KGB-1 pathway result in hypersensitivity to heavy metals. These results suggest that VHP-1 plays a pivotal role in the integration and fine-tuning of the stress response regulated by the KGB-1 MAPK pathway. C1 Nagoya Univ, Inst Adv Res, Grad Sch Sci, Dept Mol Biol,Chikusa Ku, Nagoya, Aichi 4648602, Japan. Japan Sci & Technol Corp, CREST, Chikusa Ku, Nagoya, Aichi, Japan. Kyoto Univ, Grad Sch Biostudies, Dept Cell & Dev Biol, Sakyo Ku, Kyoto, Japan. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Matsumoto, K (reprint author), Nagoya Univ, Inst Adv Res, Grad Sch Sci, Dept Mol Biol,Chikusa Ku, Nagoya, Aichi 4648602, Japan. EM g44177a@nucc.cc.nagoya-u.ac.jp FU NIGMS NIH HHS [GM48707, R01 GM048707, R37 GM048707] NR 31 TC 79 Z9 98 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 2 PY 2004 VL 23 IS 11 BP 2226 EP 2234 DI 10.1038/sj.emboj.7600226 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 833JK UT WOS:000222333400005 PM 15116070 ER PT J AU Benza, RL Zoghbi, GJ Tallaj, J Brown, R Kirklin, JK Hubbard, M Rayburn, B Foley, B McGiffin, DC Pinderski, LJ Misra, V Bourge, RC AF Benza, RL Zoghbi, GJ Tallaj, J Brown, R Kirklin, JK Hubbard, M Rayburn, B Foley, B McGiffin, DC Pinderski, LJ Misra, V Bourge, RC TI Palliation of allograft vasculopathy with transluminal angioplasty - A decade of experience SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HEART-TRANSPLANT RECIPIENTS; CORONARY-ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; MYCOPHENOLATE-MOFETIL; BALLOON ANGIOPLASTY; CARDIAC-ANGIOGRAPHY; FOLLOW-UP; IN-VITRO; INTERVENTION; PRAVASTATIN AB OBJECTIVES The goal of this study was to examine the outcomes of percutaneous coronary interventions (PCI) and the predictors for restenosis after cardiac transplantation. BACKGROUND The role of PCI as definitive therapy for allograft coronary disease (ACD) remains contentious. METHODS Between January 1, 1990 and December 31, 2000, 62 patients (1.5 to 15.5 years after transplant) underwent 151 procedures resulting in PCIs of 219 lesions. Follow-up after PCI angiography was usually obtained at three and six months, then yearly. Repeat PCI was routinely done to lesions with >60% restenosis. RESULTS The primary procedural success was 97%. Repeat PCI occurred in 74 of 219 lesions (34%); PCI-related mortality was 2.6% (4 of 151). The freedom from re-PCI (of same vessel site) was 75% at six months, 65% at one year, and 57% at four years. The freedom from restenosis was 95% at one month, 81% at three months, and 57% at six months. Multivariate predictors of freedom from restenosis were the use of stents, higher anti-proliferative immunosuppressant dose, and an era effect. In the setting of one-vessel disease at first PCI, the two-year freedom for ACD death or graft loss was 74%, compared. with 75% for two-vessel and 27% for three-vessel disease (p = 0.009). CONCLUSIONS Despite the increasing effectiveness of PCI for localized ACD, the survival after development of advanced ACD remains poor. Stents appear to increase effectiveness of PCI for ACD, but other factors in the current era contribute to improved outcomes. (C) 2004 by the American College of Cardiology Foundation. C1 Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. Univ Alabama, Dept Surg, Div Cardiovasc Surg, Birmingham, AL 35294 USA. RP Benza, RL (reprint author), Univ Alabama, Dept Med, Div Cardiovasc Dis, 328A THT,1900 Univ Blvd, Birmingham, AL 35294 USA. EM rbenza@uab.edu NR 39 TC 57 Z9 58 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 JUN 2 PY 2004 VL 43 IS 11 BP 1973 EP 1981 DI 10.1016/j.jacc.2004.02.045 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 824VR UT WOS:000221715800008 PM 15172400 ER PT J AU Aguilar, D Skali, H Moye, LA Lewis, EF Gaziano, JM Rutherford, JD Hartley, LH Randall, OS Geltman, EM Lamas, GA Rouleau, JL Pfeffer, MA Solomon, SD AF Aguilar, D Skali, H Moye, LA Lewis, EF Gaziano, JM Rutherford, JD Hartley, LH Randall, OS Geltman, EM Lamas, GA Rouleau, JL Pfeffer, MA Solomon, SD TI Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; AMERICAN-HEART-ASSOCIATION; MORTALITY; RISK; FAILURE; LIGHT; WINE; GUIDELINES; COMMITTEE; DRINKING AB OBJECTIVES We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS The Survival And Ventricular Enlargement (SAVE) trial randomized 2,231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor. (C) 2004 by the American College of Cardiology Foundation. C1 Harvard Univ, Sch Med, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. MAVERIC, Boston VA Healthcare Syst, Boston, MA USA. Howard Univ Hosp, Washington, DC USA. Washington Univ, Sch Med, St Louis, MO USA. Mt Sinai Med Ctr, Miami, FL USA. Univ Montreal, Montreal, PQ, Canada. RP Aguilar, D (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, 6431 Fannin,MSB 1-246, Houston, TX 77030 USA. EM david.aguilar@uth.tmc.edu RI Solomon, Scott/I-5789-2013; OI Skali, Hicham/0000-0002-5629-4138 NR 37 TC 34 Z9 36 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 JUN 2 PY 2004 VL 43 IS 11 BP 2015 EP 2021 DI 10.1016/j.jacc.2004.01.042 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 824VR UT WOS:000221715800014 PM 15172406 ER PT J AU Wong, ML Staszewsky, L Latini, R Barlera, S Glazer, R Aknay, N Hester, A Anand, I Cohn, JN AF Wong, ML Staszewsky, L Latini, R Barlera, S Glazer, R Aknay, N Hester, A Anand, I Cohn, JN TI Severity of left ventricular remodeling defines outcomes and response to therapy in heart failure valsartan - Heart failure trial (Val-HeFT) echocardiographic data SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SURROGATE END-POINTS; ANGIOTENSIN-RECEPTOR BLOCKER; TERM ENALAPRIL THERAPY; INDUCED HYPERTROPHY; EJECTION FRACTION; CARDIAC MYOCYTES; CLINICAL-TRIALS; DYSFUNCTION; PREDICTORS; MORBIDITY AB OBJECTIVES The objective of this study was to test the hypothesis that the severity of left ventricular remodeling predicts the response to treatment and outcomes in chronic heart failure. BACKGROUND Reversal of remodeling should produce the most favorable outcome in patients with the most severe remodeling. METHODS In 5,010 heart failure patients on background therapy and randomized to valsartan and placebo, serial recordings of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were read at sites that had to meet qualifying standards before participating. Baseline LVIDd and EF were pooled across treatments and retrospectively grouped by quartiles Q1 to Q4, representing best to worst. Kaplan-Meier survival curves were obtained by the log-rank test. Q1 was compared with Q4 for mortality and combined mortality and morbidity (M + M) from Cox regression risk ratios (RRs). Valsartan versus placebo changes from baseline in LVIDd and EF were analyzed by quartiles from analysis of covariance. Valsartan and placebo were compared by RRs for M + M. RESULTS Survival rates were greater in the better quartiles for LVIDd and EF (p < 0.00001). The RR for Q1 versus Q4 in events approached 0.5 for both LVIDd and EF (p < 0.0001). An LVIDd decrease and EF increase were quartile-dependent and greater with valsartan than placebo at virtually all time points. The RR for M + M outcomes favored valsartan in the worse quartiles. CONCLUSIONS Stratification by baseline severity of remodeling showed that patients with worse LVIDd and EF are at highest risk for an event, yet appear to gain the most anti-remodeling effect and clinical benefit with valsartan treatment. (C) 2004 by the American College of Cardiology Foundation. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. Ist Rec Farmacol Mario Negri, Milan, Italy. Nova Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Minneapolis, MN USA. RP Wong, ML (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,500-6641, Los Angeles, CA 90073 USA. EM maylene.wong@med.va.gov NR 24 TC 96 Z9 97 U1 1 U2 2 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 JUN 2 PY 2004 VL 43 IS 11 BP 2022 EP 2027 DI 10.1016/j.jacc.2003.12.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 824VR UT WOS:000221715800015 PM 15172407 ER PT J AU Brasch, J Glick, RL Cobb, TG Richmond, J AF Brasch, J Glick, RL Cobb, TG Richmond, J TI Residency training in emergency psychiatry: A model curriculum developed by the education committee of the American association for emergency psychiatry SO ACADEMIC PSYCHIATRY LA English DT Article ID ROOM AB Objective: Describe training goals, objectives and requirements in emergency psychiatry to assist residency programs in developing comprehensive training programs to ensure psychiatric residents acquire the necessary skills and knowledge to competently assess and manage patients with psychiatric emergencies. Methods: The American Association for Emergency Psychiatry (AAEP) Education Committee developed these guidelines using a consensus-building process. Conclusion: These guidelines address all aspects of training including objectives, recommended training sites, rotation length, clinical supervision, curriculum content and evaluation. The objectives emphasize acute assessment and intervention skills. The AAEP Education Committee hopes that by implementing these guidelines, training programs will enable residents to become competent and comfortable working in a psychiatric emergency service. C1 Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA. St Josephs Healthcare, Emergency Serv, Hamilton, ON, Canada. McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. Med Univ S Carolina, Charleston, SC 29425 USA. VA Boston Healthcare Syst, Emergency Psychiat Serv, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Glick, RL (reprint author), Univ Michigan, Sch Med, Dept Psychiat, C5124 Med Sci I-0611,1301 Catherine St, Ann Arbor, MI 48109 USA. EM rglick@umich.edu NR 17 TC 4 Z9 4 U1 0 U2 3 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 SUM PY 2004 VL 28 IS 2 BP 95 EP 103 DI 10.1176/appi.ap.28.2.95 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 843XJ UT WOS:000223120100003 PM 15298860 ER PT J AU Olson, CK AF Olson, CK TI Media violence research and youth violence data: Why do they conflict? SO ACADEMIC PSYCHIATRY LA English DT Article ID VIDEO GAMES; AGGRESSION; PREVALENCE; BEHAVIOR; EXPOSURE; CRIME; LIFE; FEAR; RISK AB Objective: Contrary to media headlines and public perceptions, there is little evidence of a substantial link between exposure to violent interactive games and serious real-life violence or crime. Conclusion: Further research is needed on whether violent games may affect less dramatic but real concerns such as bullying, fighting, or attitudes and beliefs that support aggression, as well as how effects may vary by child characteristics and types of games. There is also a need for research on the potential benefits of violent games for some children and adults. C1 Harvard Univ, Sch Med, Ctr Mental Hlth & Media, Boston, MA USA. RP Olson, CK (reprint author), Harvard Univ, Sch Med, Ctr Mental Hlth & Media, Massachusetts Gen Hosp,Dept Psychiat, 271 Waverley Oaks Rd, Waltham, MA 02452 USA. EM Cheryl_olson@hms.harvard.edu NR 41 TC 41 Z9 41 U1 9 U2 23 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 SUM PY 2004 VL 28 IS 2 BP 144 EP 150 DI 10.1176/appi.ap.28.2.144 PG 7 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 843XJ UT WOS:000223120100011 PM 15298868 ER PT J AU Kiehl, TR Kalkanis, SN Louis, DN AF Kiehl, TR Kalkanis, SN Louis, DN TI Pigmented central neurocytoma SO ACTA NEUROPATHOLOGICA LA English DT Article DE central neurocytoma; hemosiderin iron ID INTRAVENTRICULAR HEMORRHAGE; INTRATUMORAL HEMORRHAGE; EPENDYMOMA AB Central neurocytoma is a low-grade neuronal neoplasm that occurs most often within the lateral ventricles. We report the case of a 60-year-old woman who presented with gait problems, headache and memory loss. Preoperative evaluation demonstrated a heterogeneous, hypervascular and partially cystic mass in the left lateral ventricle. Histopathological examination revealed characteristic features of central neurocytoma, including immunoreactivity for synaptophysin, as well as the unusual feature of abundant pigment in the cytoplasm of tumor cells. Special stains revealed iron, consistent with hemosiderin, but found no evidence of melanin or melanosomes. Previous reports of pigmented central neurocytoma have described the presence of lipofuscin or neuromelanin. To our knowledge, the present case represents the first example of pigmented central neurocytoma secondary to hemosiderin deposition. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. EM dlouis@partners.org NR 20 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUN PY 2004 VL 107 IS 6 BP 571 EP 574 DI 10.1007/s00401-004-0835-1 PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 820DK UT WOS:000221366900014 PM 14991386 ER PT J AU Masson, CL Barnett, PG Sees, KL Delucchi, KL Rosen, A Wong, W Hall, SM AF Masson, CL Barnett, PG Sees, KL Delucchi, KL Rosen, A Wong, W Hall, SM TI Cost and cost-effectiveness of standard methadone maintenance treatment compared to enriched 180-day methadone detoxification SO ADDICTION LA English DT Article DE cost-effectiveness; health care; injection drug use; methadone detoxification; methadone maintenance; opiate use ID EFFECTIVENESS LEAGUE TABLES; HEALTH-CARE; MULTIPLE IMPUTATION; ADDICTION; SERVICES; MODELS; TRIAL; HIV AB Aims To compare the cost and cost-effectiveness of methadone maintenance treatment and 180-day methadone detoxification enriched with psychosocial services. Design Randomized controlled study conducted from May 1995 to April 1999. Setting Research clinic in an established drug treatment program. Participants One hundred and seventy-nine adults with diagnosed opioid dependence. Intervention Patients were randomized to methadone maintenance (n=91), which required monthly 1 hour/week of psychosocial therapy during the first 6 months or 180-day detoxification (n = 88), which required 3 hours/week of psychosocial therapy and 14 education sessions during the first 6 months. Measurements Total health-care costs and self-reported injection drug use. A two-state Markov model was used to estimate quality-adjusted years of survival. Findings Methadone maintenance produced significantly greater reductions in illicit opioid use than 180-day detoxification during the last 6 months of treatment. Total health-care costs were greater for maintenance than detoxification treatment ($7564 versus $668 7; P < 0.001). Although study costs were significantly higher for methadone maintenance than detoxification patients ($4739 versus $2855, P < 0.001), detoxification patients incurred significantly higher costs for substance abuse and mental health care received outside the study. Methadone maintenance may provide a modest survival advantage compared with detoxification. The cost per life-year gained is $16967. Sensitivity analysis revealed a cost-effectiveness ratio of less than $20000 per quality-adjusted life-year over a wide range of modeling assumptions. Conclusions Compared with enriched detoxification services, methadone maintenance is more effective than enriched detoxification services with a cost-effectiveness ratio within the range of many accepted medical interventions and may provide a survival advantage. Results provide additional support for the use of sustained methadone therapy as opposed to detoxification for treating opioid addiction. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Stanford, CA 94305 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Masson, CL (reprint author), San Francisco Gen Hosp, Dept Psychiat, 1001 Potrero Ave,Bldg 20,Suite 2100, San Francisco, CA 94110 USA. EM masson@itsa.ucsf.edu NR 32 TC 30 Z9 33 U1 2 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 2004 VL 99 IS 6 BP 718 EP 726 DI 10.1111/j.1360-0443.2004.00728.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 825NN UT WOS:000221765300008 PM 15139870 ER PT J AU Reynolds, NR Testa, MA Marc, LG Chesney, MA Neidig, JL Smith, SR Vella, S Robbins, GK AF Reynolds, NR Testa, MA Marc, LG Chesney, MA Neidig, JL Smith, SR Vella, S Robbins, GK CA Protocol Team ACTG 384 Protocol Team ACTG 731 Protocol Team A5031s TI Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: A multicenter, cross-sectional study SO AIDS AND BEHAVIOR LA English DT Article DE AIDS; HIV; adherence; beliefs; self-efficacy ID CLINICAL-TRIALS; HIV-INFECTION; PATIENT ADHERENCE; OUTCOMES; AIDS; DISEASE; VALIDATION; MORBIDITY; MORTALITY; BARRIERS AB It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy. As part of a multicenter AIDS Clinical Trial Group (ACTG 384) study, 980 antiretroviral-naive subjects (82% male, 47% White, median age 36 years, and median CD4 cell count 278 cells/mm(3)) completed a self-administered questionnaire prior to random treatment assignment of initial antiretroviral medications. Measures of symptom distress, general health and well-being, and personal and situational factors including demographic characteristics, social support, self-efficacy, depression, stress, and current adherence to (nonantiretroviral) medications were recorded. Associations among variables were explored using correlation and regression analyses. Beliefs about the importance of antiretroviral adherence and ability to take antiretroviral medications as directed ( adherence self-efficacy) were generally positive. Fifty-six percent of the participants were "extremely sure" of their ability to take all medications as directed and 48% were "extremely sure" that antiretroviral nonadherence would cause resistance, but only 37% were as sure that antiretroviral therapy would benefit their health. Less-positive beliefs about antiretroviral therapy adherence were associated with greater stress, depression, and symptom distress. More-positive beliefs about antiretroviral therapy adherence were associated with better scores on health perception, functional health, social-emotional-cognitive function, social support, role function, younger age, and higher education (r values = 0.09-0.24, all p < .001). Among the subset of 325 participants reporting current use of medications (nonantiretrovirals) during the prior month, depression was the strongest correlate of nonadherence (r = 0.33, p < .001). The most common reasons for nonadherence to the medications were "simply forgot" (33%), "away from home" (27%), and "busy" (26%). In conclusion, in a large, multicenter survey, personal and situational factors, such as depression, stress, and lower education, were associated with less certainty about the potential for antiretroviral therapy effectiveness and one's perceived ability to adhere to therapy. Findings from these analyses suggest a role for baseline screening for adherence predictors and focused interventions to address modifiable factors placing persons at high risk for poor adherence prior to antiretroviral treatment initiation. C1 Ohio State Univ, Columbus, OH 43210 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC USA. Ist Super Sanita, I-00161 Rome, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reynolds, NR (reprint author), Ohio State Univ, 1585 Neil Ave, Columbus, OH 43210 USA. EM reynolds.1@osu.edu RI Robbins, Gregory/F-7988-2011; Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 FU NIAID NIH HHS [AI27659, AI25868, AI25924, AI38858] NR 36 TC 111 Z9 116 U1 0 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD JUN PY 2004 VL 8 IS 2 BP 141 EP 150 DI 10.1023/B:AIBE.0000030245.52406.bb PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 827ET UT WOS:000221882600004 PM 15187476 ER PT J AU Mukamal, KJ Maclure, M Muller, JE Sherwood, JB Mittleman, MA AF Mukamal, KJ Maclure, M Muller, JE Sherwood, JB Mittleman, MA TI Caffeinated coffee consumption and mortality after acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; FOLLOW-UP; RISK; DEATH; METAANALYSIS; HEALTH AB Background Previous studies have generally suggested no effect of coffee consumption on the risk of acute myocardial infarction. The effect of coffee consumption on prognosis after acute myocardial infarction is uncertain. Methods In an inception cohort study, we observed 1935 patients who were hospitalized with a confirmed acute myocardial infarction between 1989 and 1994 at 45 community hospitals and tertiary care centers in the United States, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers assessed self-reported caffeinated coffee consumption before infarction with a standardized questionnaire. We analyzed survival censored at December 31, 1995, using Cox proportional hazards regression. Results Of the 1902 patients for whom we had information on coffee intake, 315 (17%) died during a median follow-up period of 3.8 years. Coffee drinkers tended to be men, younger, and free of comorbidity, and they were more likely to be current smokers. Coffee consumption was not associated,with an overall change in long-term post-infarction mortality rate. However, we did observe an unexpected and unexplained variation in the association between coffee consumption and mortality with time, with an apparent inverse association in the first 90 days after infarction. Conclusions Self-reported coffee consumption has no overall association with post-infarction mortality. The unexpected time variation in the effect of coffee intake requires evaluation in other studies. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,RO-114, Boston, MA 02215 USA. EM kmukamal@bidmc.harvard.edu FU NHLBI NIH HHS [R01HL41016]; NIAAA NIH HHS [K23AA00299] NR 18 TC 29 Z9 30 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2004 VL 147 IS 6 BP 999 EP 1004 DI 10.1016/j.ahj.2003.12.038 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832JE UT WOS:000222263000013 PM 15199347 ER PT J AU Scranton, R Sesso, HD Stampfer, MJ Levenson, JW Buring, JE Gaziano, JM AF Scranton, R Sesso, HD Stampfer, MJ Levenson, JW Buring, JE Gaziano, JM TI Predictors of 14-year changes in the total cholesterol to high-density lipoprotein cholesterol ratio in men SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD CHOLESTEROL; RISK-FACTORS; CARDIOVASCULAR-DISEASE; RANDOMIZED TRIAL; SMOKING; PREVENTION; ADULTS; LIPIDS; TRENDS AB Background Although the ratio of total to high-density lipoprotein cholesterol (TC/HDL) is a powerful predictor of cardiovascular disease (CVD), few studies have investigated which factors are associated with changes in this ratio over time. We examined predictors of a change in TC/HDL ratio over a period of 14 years among 4451 men-free of CVD from the Physicians' Health Study. Methods Baseline and updated physician characteristics and CVD risk factors were included in multivariate linear and logistic regression models to determine factors associated with a change in the TC/HDL ratio or of having a ratio of greater than or equal to5 on follow-up. Results After a mean follow-up of 14 years, mean total cholesterol decreased by 7 mg/dL, HDL increased by 1 mg/ dL, and the ratio decreased by 0.37. In multivariate logistic analyses, physicians were more likely to have a TC/HDL ratio of greater than or equal to5 at follow-up if they maintained a weight of greater than or equal to25 kg/m(2) (OR, 1.69 [1.35 - 2.12]), gained weight (OR, 2.01 [1.55 - 2.62]), or became inactive (OR, 1.43 [1.11 - 1.83]). However, older physicians and those who consumed alcohol or received treatment for hyperlipidemia were more likely to have a ratio of <5. Conclusions Although pharmacologic treatment for hyperlipidemia had the greatest favorable impact on the ratio over time, our data also show that maintaining an ideal weight and exercise have beneficial effects. We therefore advocate a renewed fervor for raising public awareness of the benefits of healthy lifestyle behaviors and pharmacologic treatments that are associated with long-term maintenance of favorable cholesterol levels. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Boston, MA USA. RP Scranton, R (reprint author), Massachusetts Vet Affairs Epidemiol, Res & Informat Ctr, 150 S Huntington St,Mail Stop MAV 151, Boston, MA 02130 USA. EM richardscrantonmd@rcn.com FU NCI NIH HHS [CA40360, R01 CA097193] NR 35 TC 5 Z9 6 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2004 VL 147 IS 6 BP 1033 EP 1038 DI 10.1016/j.ahj.2003.11.018 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 832JE UT WOS:000222263000019 PM 15199352 ER PT J AU Sanborn, TA Jacobs, AK Frederick, PD Every, NR French, WJ AF Sanborn, TA Jacobs, AK Frederick, PD Every, NR French, WJ CA Natl Registry Mycardial Infraction TI Comparability of quality-of-care indicators for emergency coronary angioplasty in patients with acute myocardial infarction regardless of on-site cardiac surgery (report from the national registry of myocardial infarction) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID THROMBOLYTIC THERAPY; SURGICAL BACKUP; HOSPITALS; INTERVENTION; ASSOCIATION; EXPERIENCE; TRIAL AB Initial reports have suggested that primary percutaneous coronary intervention (PCI) can be performed safely in selected hospitals without on-site cardiac surgery, however, quality-of-care indicators for primary PCI in these institutions is unknown., Therefore, symptom onset-to-door intervals, door-to-balloon times, compliance with American College of Cardiology/American Heart Association (ACC/AHA) management guidelines, and in-hospital mortality were evaluated in 108,132 patients in 3 hospital settings in the National Registry of Myocardial Infarction: (1) diagnostic laboratories only (n = 47), (2) elective PCI only (n 50), and (3) elective PCI and cardiac surgery (n 562). Mean symptom onset-to-door intervals (127 minutes, 95% confidence interval 118 to 135; 134 minutes, 95% confidence interval 125 to 142; and 140 minutes, 95% confidence intervals 138 to 141; p = 0.01) and door-to-balloon intervals (104 minutes, 95% confidence interval 10 1 to 108; 116 minutes, 95% confidence interval 112 to 119; and 119 minutes, 95% confidence interval 118 to 120; p < 0.0001) were shorter in hospitals without cardiac surgery. Adherence to ACC/AHA guidelines for medications within the first 24 hours'(aspirin, beta blockers, angiotensin-converting enzyme inhibitors) was greater in hospitals without cardiac surgery. There were comparable in-hospital mortality rates (3.2%, 4.2%, and 4.8%, respectively, p 0.07) for patients with similar Thrombolysis In Myocardial Infarction risk scores; however, 4.7% of patients treated with primary PCI,in hospitals without cardiac surgery were transferred to another institution. Thus, hospitals performing primary PCI without on-site cardiac surgery that participated in this registry have quality-of-care indicators and adherence to ACC/AHA management guidelines that are comparable to hospitals with on-site cardiac surgery. The lack of on-site cardiac surgery does not appear to adversely affect quality-of-care indicators in primary PCI. (C)2004 by Excerpta Medica, Inc. C1 Northwestern Univ, Evanston Northwestern Healthcare, Feinberg Sch Med, Evanston, IL 60201 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Univ Washington, Ovat Res Grp, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA. RP Sanborn, TA (reprint author), Northwestern Univ, Evanston Northwestern Healthcare, Feinberg Sch Med, Burch 300,2650 Ridge Ave, Evanston, IL 60201 USA. EM tsanborn@enh.org OI Frederick, Paul/0000-0002-7936-5488 NR 13 TC 21 Z9 21 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 JUN 1 PY 2004 VL 93 IS 11 BP 1335 EP 1339 DI 10.1016/j.amjcard.2004.02.026 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 826FQ UT WOS:000221815100001 PM 15165910 ER PT J AU Giugliano, RP Sabatine, MS Gibson, CM Roe, MT Harrington, RA Murphy, SA Morrow, DA Antman, EM Braunwald, E AF Giugliano, RP Sabatine, MS Gibson, CM Roe, MT Harrington, RA Murphy, SA Morrow, DA Antman, EM Braunwald, E TI Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and st-segment resolution to evaluate epicardial and myocardial reperfusion SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLYCOPROTEIN IIB/IIIA INHIBITION; LEFT-VENTRICULAR FUNCTION; PRIMARY ANGIOPLASTY; RANDOMIZED-TRIAL; FRAME COUNT; TIMI TRIAL; FOLLOW-UP; PHASE-I; THERAPY; ELEVATION AB The restoration of epicardial and myocardial flow re mains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase 11 clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the "trifecta," defined as the presence of TFG 3, MPG 3, and complete (greater than or equal to70%) STRes, occurred: in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs,7.1 %, p = 0.01), and the combination of death or CHIF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3 MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography. (C)2004 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Duke Clin Res Inst, Durham, NC USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM rgiugliano@partners.org NR 30 TC 24 Z9 32 U1 0 U2 5 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 JUN 1 PY 2004 VL 93 IS 11 BP 1362 EP 1367 DI 10.1016/j.amjcard.2004.02.031 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 826FQ UT WOS:000221815100006 PM 15165915 ER PT J AU Koutkia, P Canavan, B Breu, J Johnson, ML Depaoli, A Grinspoon, SK AF Koutkia, P Canavan, B Breu, J Johnson, ML Depaoli, A Grinspoon, SK TI Relation of leptin pulse dynamics to fat distribution in HIV-infected patients SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE leptin; pulsatility; subcutaneous fat; HIV ID ADIPOSE-TISSUE; METABOLIC ABNORMALITIES; ANTIRETROVIRAL THERAPY; INSULIN-RESISTANCE; DIABETES-MELLITUS; GROWTH-HORMONE; PLASMA LEPTIN; OBESE GENE; LIPODYSTROPHY; LIPOATROPHY AB Background: HIV-infected patients are affected by changes in fat distribution, ie, significant losses of subcutaneous fat in association with metabolic abnormalities. Objective: The objective was to investigate the relation between leptin secretion and subcutaneous fat loss in HIV-infected patients. Design: We investigated leptin pulse dynamics, measured every 20 min overnight from 2000 to 0800 in 41 HIV-infected patients with a mean (+/-SEM) age of 42.7 +/- 1.1 y and body mass index (in kg /m(2)) of 24.7 +/- 0.4 and in 20 healthy control subjects (age: 42.8 +/- 1.8 y; body mass index: 24.6 +/- 0.5). Leptin pulse variables were compared with total body fat, abdominal subcutaneous fat, and abdominal visceral fat in univariate and multivariate regression analyses. Results: The number of leptin pulses was not significantly different between the HIV-infected and control subjects. Subcutaneous fat correlated significantly with mean leptin secretion (r = 0.72, P <0.0001), leptin pulse amplitude (r = 0.62, P <0.0001), and leptin nadir (r = 0.62, P <0.0001) in the HIV-infected patients. In stepwise regression modeling, subcutaneous fat (P <0.0001), but not visceral fat, was significantly associated with leptin secretion (overall R 2 for the model = 0.57, P <0.0001) in the HIV-infected patients. For each 1-cm(2) decrease in abdominal subcutaneous fat area, leptin decreased by 0.044 ng/mL when visceral fat was controlled for. Subcutaneous fat was also significantly related to leptin in the control subjects. Conclusions: This is the first study to investigate the relation between fat distribution and leptin pulse dynamics in HIV-infected patients. There was a significant reduction in leptin secretion with subcutaneous fat loss in this population. C1 Massachusetts Gen Hosp, Program Nutr Metab, LON 207, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neuroendocrine Unit, Boston, MA USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. Univ Virginia, Hlth Sci Ctr, Dept Pharmacol, Charlottesville, VA 22908 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON 207, 55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR300088, M01-RR01066] NR 31 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2004 VL 79 IS 6 BP 1103 EP 1109 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 822QA UT WOS:000221553500023 PM 15159242 ER PT J AU Melanson, SF Lewandrowski, EL Januzzi, JL Lewandrowski, KB AF Melanson, SF Lewandrowski, EL Januzzi, JL Lewandrowski, KB TI Reevaluation of myoglobin for acute chest pain evaluation - Would false-positive results on "first-draw" specimens lead to increased hospital admissions? SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE myoglobin; acute myocardial infarction; acute coronary syndrome; CK-MB; creatine kinase isoenzyme; troponin; hospital admission ID ACUTE MYOCARDIAL-INFARCTION; CREATINE-KINASE-MB; ACUTE CORONARY SYNDROMES; TROPONIN-I; EMERGENCY-DEPARTMENT; TRIAGE; RISK AB Myoglobin is an early marker of cardiac injury, although positive results occur in the absence of cardiac myonecrosis. We studied data for 537 patients admitted to the emergency department with symptoms suggestive of myocardial injury who underwent testing for troponin I (ThI), creatine kinase isoenzyme (CK-MB), and myoglobin at the point of care. Physicians were blinded to the myoglobin results. Myoglobin had a sensitivity of 69.7% and a negative predictive value of 97.4% for the diagnosis of acute coronary syndrome (ACS) on "first-draw" specimens. Receiver operating characteristic curve analysis suggested that myoglobin demonstrated optimal sensitivity for ACS, while TnI had optimal specificity. CK-MB was neither the most specific nor the most sensitive marker More than 80% of the patients with false-positive myoglobin results were admitted to the hospital. These data invalidate concerns regarding the putative overtreatment effect of false-positive cases owing to myoglobin results. Furthermore, our data suggest that myoglobin is superior to CK-MB as an adjunct to TnI. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUN PY 2004 VL 121 IS 6 BP 804 EP 808 DI 10.1309/80MCYMBL4DLNJDC3 PG 5 WC Pathology SC Pathology GA 823YV UT WOS:000221651300005 PM 15198351 ER PT J AU Soldani, F Sullivan, PF Pedersen, NL AF Soldani, F Sullivan, PF Pedersen, NL TI Mania in the Swedish Twin Registry: Predictors of validity. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 15-18, 2004 CL Salt Lake City, UT SP Soc Epidemiol Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div, Belmont, MA 02478 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2004 VL 159 IS 11 SU S BP S88 EP S88 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 826GH UT WOS:000221816800351 ER PT J AU Wiggs, JL Lynch, S Ynagi, G Maselli, M Auguste, J Del Bono, EA Olson, LM Haines, JL AF Wiggs, JL Lynch, S Ynagi, G Maselli, M Auguste, J Del Bono, EA Olson, LM Haines, JL TI A genomewide scan identifies novel early-onset primary open-angle glaucoma loci on 9q22 and 20p12 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TRABECULAR MESHWORK CELLS; MYOCILIN GENE; GLN368STOP MUTATION; JUVENILE; FAMILIES; ADULT; RECOMBINATION; PREVALENCE; PHENOTYPE; PEDIGREES AB Glaucoma is a leading cause of blindness worldwide. The disease is characterized by a degeneration of the optic nerve, which is usually associated with elevated intraocular pressure. The common form of adult-onset primary open-angle glaucoma is inherited as a complex trait, whereas the rarer early-onset juvenile open-angle glaucoma (JOAG) exhibits autosomal dominant inheritance. Of all cases of JOAG, similar to10%-20% are caused by mutations in the myocilin gene. We have identified 25 pedigrees that are affected with typical JOAG and that demonstrate autosomal dominant inheritance. We sequenced the myocilin gene in probands from each family and found mutations in 8% of this population. To identify novel genes responsible for JOAG, we used families that did not have myocilin mutations for a genomewide screen. Markers located on chromosomes 9q22 and 20p12 showed evidence for linkage, identifying two novel loci for early-onset open-angle glaucoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012 FU PHS HHS [R01 09847] NR 29 TC 70 Z9 76 U1 0 U2 1 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 JUN PY 2004 VL 74 IS 6 BP 1314 EP 1320 DI 10.1086/421533 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 823ZB UT WOS:000221651900027 PM 15108121 ER PT J AU Weilburg, JB Stafford, RS O'Leary, KM Meigs, JB Finkelstein, SN AF Weilburg, JB Stafford, RS O'Leary, KM Meigs, JB Finkelstein, SN TI Costs of antidepressant medications associated with inadequate treatment SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; PRIMARY-CARE PRACTICE; TREATING MAJOR DEPRESSION; MULTIVARIATE-ANALYSIS; TREATMENT GUIDELINES; QUALITY IMPROVEMENT; MENTAL-DISORDERS; UNITED-STATES; MANAGED CARE; PATTERNS AB Objective: To determine the costs of antidepressant medications used during inadequate treatment. Study Design: Retrospective database analysis of pharmacy claims made by patients who were treated under routine clinical conditions from July 1, 1999, through September 30, 2002. Patients and Methods: Our participants included 21 632 patients enrolled in a commercial HMO who had a primary care physician associated with our healthcare system. Patients never receiving at least a minimum likely effective antidepressant dose for at least 90 days were defined as having inadequate treatment. This study calculated the costs of antidepressants involved with inadequate treatment at the level of the patient and the medication trial. Results: A majority of patients (51%) received inadequate treatment. Of overall antidepressant costs, 16% were incurred during trials for patients never adequately treated. The majority of inadequate trials were short and unlikely to have been effective. Most patients (64%) had only a single trial of antidepressants. Venlafaxine, fluoxetine, and sertraline had significantly lower first-trial inadequacy rates compared with the most commonly prescribed agent, citalopram. Conclusions: improved patient care quality and lower antidepressant costs could result if clinicians and healthcare systems focus on reducing short trial rates. Initiating treatment with agents least likely to be discontinued prematurely may be helpful. C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA USA. MIT, Sloan Sch Management, Cambridge, MA USA. RP Weilburg, JB (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Psychiat, Room 815,55 Fruit St, Boston, MA 02114 USA. EM jweilburg@partners.org NR 51 TC 15 Z9 15 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JUN PY 2004 VL 10 IS 6 BP 357 EP 365 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 827ZC UT WOS:000221941200002 PM 15209479 ER PT J AU Schaefer, PW Hassankhani, A Putman, C Sorensen, AG Schwamm, L Koroshetz, W Gonzalez, RG AF Schaefer, PW Hassankhani, A Putman, C Sorensen, AG Schwamm, L Koroshetz, W Gonzalez, RG TI Characterization and evolution of diffusion MR imaging abnormalities in stroke patients undergoing intra-arterial thrombolysis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Neuroradiology CY APR 21-27, 2001 CL BOSTON, MA SP Amer Soc Neuroradiol ID ACUTE ISCHEMIC-STROKE; FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR; ARTERY OCCLUSION; WEIGHTED MRI; PERFUSION; COEFFICIENT; INJURY; RATS; REGISTRATION AB BACKGROUND AND PURPOSE: Lesions revealed by pretreatment diffusion-weighted imaging (DWI) may not progress to infarction, and apparent diffusion coefficient (ADC) or DWI thresholds for tissue viability may exist. We evaluated the evolution of abnormal DWI findings in patients with acute stroke who underwent thrombolysis. METHODS: Sixteen patients with acute occlusion of the anterior circulation underwent DWI followed by intra-arterial thrombolysis; follow-up CT or MR imaging was performed after reperfusion therapy. Lesion volumes were measured on all images. In three patients with abnormal DWI findings that appeared normal at follow-up, ADC values, ADC ratios, and DWI ratios were obtained on a section-by-section basis in the DWI-hyperintense regions that were either abnormal or normal at follow-up. RESULTS: In three patients, part of the DWI-hyperintense tissue appeared normal and part appeared abnormal at follow-up imaging. In one of these patients, the lesion decreased by -35.6%. In the other two, lesion growth appeared in regions that appeared normal at initial DWI: in one, the overall change in size was -2.4%, and in the other, the lesion increased by 89.8%. Respective mean changes at follow-up in normal-appearing and abnormal-appearing regions were: ADC, 731.7 x 10(-6) mm(2)/s and 650.4 x 10(-6) mm(2)/s; ADC ratio, 0.92 and 0.78; and DWI ratio, 1.16 and 1.32 (P < .001 for all measures). CONCLUSION: In patients with acute stroke who undergo intra-arterial thrombolysis, most abnormal, pretreatment DWI findings indicate eventual infarction. In 19% of the patients described herein, DWI-hyperintense regions appeared normal at follow-up. ADC values, ADC ratios, and DWI ratios may be useful in identifying the portion of abnormal tissue that is potentially salvageable after reperfusion therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, 55 Fruit St,Gray B285, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [NS38477] NR 34 TC 30 Z9 33 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2004 VL 25 IS 6 BP 951 EP 957 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 829RP UT WOS:000222067600010 PM 15205129 ER PT J AU Henson, JW Nogueira, RG Covarrubias, DJ Gonzalez, RG Lev, MH AF Henson, JW Nogueira, RG Covarrubias, DJ Gonzalez, RG Lev, MH TI Gadolinium-enhanced CT angiography of the circle of wllis and neck SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIGITAL SUBTRACTION ANGIOGRAPHY; RENAL-INSUFFICIENCY; CONTRAST-MEDIA; ACCURACY; AGENT AB CT angiography (CTA) of the cervical and intracranial vessels is a rapid, noninvasive, and relatively inexpensive technique for the evaluation of vascular abnormalities. Contraindications to the use of contrast media, however, can preclude use of iodinated agents for CTA. We report the use of gadolinium as contrast agent for CTA of the head and neck in three patients with contraindications to iodinated contrast agents. C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Gray 285,Fruit St, Boston, MA 02114 USA. NR 13 TC 18 Z9 18 U1 1 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUN-JUL PY 2004 VL 25 IS 6 BP 969 EP 972 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 829RP UT WOS:000222067600013 PM 15205132 ER PT J AU Cook, AF Hoas, H Guttmannova, K Joyner, JC AF Cook, AF Hoas, H Guttmannova, K Joyner, JC TI An error by any other name SO AMERICAN JOURNAL OF NURSING LA English DT Article ID MEDICAL LITERATURE; USERS GUIDES; JOB-SATISFACTION; PATIENT; HOSPITALS; NURSES; CARE; SERVICES; BURNOUT; ARTICLE C1 Univ Montana, Dept Psychol, Missoula, MT 59812 USA. Univ Montana, Natl Rural Bioeth Project, Missoula, MT 59812 USA. US Dept Vet Affairs, Off Gen Counsel, Washington, DC USA. RP Cook, AF (reprint author), Univ Montana, Dept Psychol, Missoula, MT 59812 USA. FU AHRQ HHS [R01 HS11930] NR 33 TC 38 Z9 39 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JUN PY 2004 VL 104 IS 6 BP 32 EP 43 PG 12 WC Nursing SC Nursing GA 828KB UT WOS:000221971100026 PM 15187607 ER PT J AU Nakamura, M Matute-Bello, G Liles, WC Hayashi, S Kajikawa, O Lin, SM Frevert, CW Martin, TR AF Nakamura, M Matute-Bello, G Liles, WC Hayashi, S Kajikawa, O Lin, SM Frevert, CW Martin, TR TI Differential response of human lung epithelial cells to Fas-induced apoptosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; TUMOR-NECROSIS-FACTOR; HYDROSTATIC PULMONARY-EDEMA; INFLAMMATORY CYTOKINES; LIGAND EXPRESSION; INTERFERON-GAMMA; IFN-GAMMA; RABBIT LUNGS; FACTOR-ALPHA; TNF-ALPHA AB The Fas (CD95)/Fas ligand (CD178) system plays an important role in epithelial damage during the acute respiratory distress syndrome. The goal of this study was to determine whether proximal and distal human lung epithelial cells differ in their sensitivity to Fas ligand (rh-sFasL), and whether the response of lung epithelium to Fas ligation is modulated by proinflammatory cytokines. Although the expression of both Fas message and protein was similar in proximal and distal lung epithelial cells, only distal cells became apoptotic when exposed to serial dilutions of rh-sFasL. Stimulation with tumor necrosis factor-alpha, interleukin-1beta, or interferon-gamma significantly increased the sensitivity of proximal cells to rh-sFasL, and exposure to either tumor necrosis factor-alpha or interferon-gamma enhanced the sensitivity of distal cells to Fas ligation. These findings suggest that in normal human lungs, the responses of the epithelium to Fas ligation become more pronounced from proximal to distal locations. Furthermore, proinflammatory cytokines sensitize lung epithelium to Fas-induced death. These findings are relevant for understanding the role of the Fas/FasL system in acute lung injury, in which epithelial damage occurs primarily in distal airway and alveolar epithelium, whereas sFasL is present throughout the airspaces. C1 Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. RP Martin, TR (reprint author), Seattle Vet Affairs Med Ctr, 151L,1660 S Columbian Way, Seattle, WA 98108 USA. EM trmartin@u.washington.edu FU NHLBI NIH HHS [HL30542, HL62995, HL 70840-01, K08 HL070840, R01 HL062995] NR 39 TC 44 Z9 52 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2004 VL 164 IS 6 BP 1949 EP 1958 DI 10.1016/S0002-9440(10)63755-8 PG 10 WC Pathology SC Pathology GA 823HK UT WOS:000221601000009 PM 15161631 ER PT J AU Schneeberger, EE Lynch, RD AF Schneeberger, EE Lynch, RD TI The tight junction: a multifunctional complex SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE tight junction structure; function; regulation ID CANINE KIDNEY-CELLS; PROTEIN-KINASE-C; INTEGRAL MEMBRANE-PROTEIN; TUMOR-SUPPRESSOR PROTEIN; E-CADHERIN EXPRESSION; TRANSEPITHELIAL ELECTRICAL-RESISTANCE; EPITHELIAL-MESENCHYMAL TRANSITIONS; HELICOBACTER-PYLORI CAGA; ADHESION MOLECULE JAM; PDZ DOMAIN AB Multicellular organisms are separated from the external environment by a layer of epithelial cells whose integrity is maintained by intercellular junctional complexes composed of tight junctions, adherens junctions, and desmosomes, whereas gap junctions provide for intercellular communication. The aim of this review is to present an updated overview of recent developments in the area of tight junction biology. In a relatively short time, our knowledge of the tight junction has evolved from a relatively simple view of it being a permeability barrier in the paracellular space and a fence in the plane of the plasma membrane to one of it acting as a multicomponent, multifunctional complex that is involved in regulating numerous and diverse cell functions. A group of integral membrane proteins-occludin, claudins, and junction adhesion molecules-interact with an increasingly complex array of tight junction plaque proteins not only to regulate paracellular solute and water flux but also to integrate such diverse processes as gene transcription, tumor suppression, cell proliferation, and cell polarity. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp E, Mol Pathol Unit, 149-7151,149 13th St, Charlestown, MA 02129 USA. EM eschneeberger@partners.org FU NHLBI NIH HHS [HL-25822, HL-36781] NR 167 TC 572 Z9 602 U1 6 U2 51 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2004 VL 286 IS 6 BP C1213 EP C1228 DI 10.1152/ajpcell.00558.2003 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 822EW UT WOS:000221520700001 PM 15151915 ER PT J AU Figlewicz, DP Zavosh, A Sexton, T Neumaier, JF AF Figlewicz, DP Zavosh, A Sexton, T Neumaier, JF TI Catabolic action of insulin in rat arcuate nucleus is not enhanced by exogenous "tub" expression SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE food intake; body weight; hypothalamus ID HERPES-SIMPLEX-VIRUS; MOLECULAR-CLONING; ADIPOSITY SIGNALS; MESSENGER-RNA; FOOD-INTAKE; GENE; MOUSE; OBESITY; PROTEINS; MUTATION AB The central nervous system (CNS) protein "tub" has been identified from the genetically obese "tubby" mouse. Although the native function of tub in situ is not understood, cell-based studies suggest that one of its roles may be as an intracellular signaling target for insulin. In normal animals, insulin acts at the hypothalamic arcuate nucleus (ARC) to regulate energy balance. Here we used a Herpes Simplex viral expression system to evaluate whether tub overexpression in the ARC of normal rats enhances this action of insulin. In chow-fed rats, tub overexpression had no effect on insulin action. In rats fed a high-fat diet snack in addition to chow, simulating the diet of Westernized societies, the body weight regulatory action of insulin was impaired, and tub overexpression further impaired insulin action. Thus an excess of tub at the ARC does not enhance the in vivo effectiveness of insulin and is not able to compensate for the "downstream" consequences of a high-fat diet to impair CNS body weight regulatory mechanisms. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Metab Endocrinol, 151,1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu OI Sexton, Timothy/0000-0002-8821-880X FU NIDDK NIH HHS [DK-R01-40963]; NIMH NIH HHS [MH-63303] NR 32 TC 8 Z9 8 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2004 VL 286 IS 6 BP E1004 EP E1010 DI 10.1152/ajpendo.00427.2003 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 823ZU UT WOS:000221653900020 PM 14749205 ER PT J AU List, JF Habener, JF AF List, JF Habener, JF TI Glucagon-like peptide 1 agonists and the development and growth of pancreatic beta-cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE stem cells; diabetes ID INSULIN-PRODUCING CELLS; EMBRYONIC STEM-CELLS; DIABETES-MELLITUS; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; REPLACEMENT THERAPY; INHIBITS APOPTOSIS; SECRETING CELLS; GENE-EXPRESSION; AR42J CELLS AB Glucagon-like peptide 1 (GLP-1) is an intestine-derived insulinotropic hormone that stimulates glucose-dependent insulin production and secretion from pancreatic beta-cells. Other recognized actions of GLP- 1 are to suppress glucagon secretion and hepatic glucose output, delay gastric emptying, reduce food intake, and promote glucose disposal in peripheral tissues. All of these actions are potentially beneficial for the treatment of type 2 diabetes mellitus. Several GLP-1 agonists are in clinical trials for the treatment of diabetes. More recently, GLP- 1 agonists have been shown to stimulate the growth and differentiation of pancreatic beta-cells, as well as to exert cytoprotective, antiapoptotic effects on beta-cells. Recent evidence indicates that GLP- 1 agonists act on receptors on pancreas-derived stem/progenitor cells to prompt their differentiation into beta-cells. These new findings suggest an approach to create beta-cells in vitro by expanding stem/progenitor cells and then to convert them into beta-cells by treatment with GLP-1. Thus GLP- 1 may be a means by which to create beta-cells ex vivo for transplantation into patients with insulinopenic type 1 diabetes and severe forms of type 2 diabetes. C1 Harvard Univ, Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab,Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab,Sch Med, 55 Fruit St,WEL 320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [R01 DK-30834, T32 DK-07028] NR 77 TC 62 Z9 64 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2004 VL 286 IS 6 BP E875 EP E881 DI 10.1152/ajpendo.00007.2004 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 823ZU UT WOS:000221653900002 PM 15140754 ER PT J AU Hirokawa, M Furukawa, O Guth, PH Engel, E Kaunitz, JD AF Hirokawa, M Furukawa, O Guth, PH Engel, E Kaunitz, JD TI Low-dose PGE(2) mimics the duodenal secretory response to luminal acid in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE luminal acid exposure; in vivo simulation; intestinal ion transport ID STIMULATED ALKALINE SECRETION; BICARBONATE SECRETION; RABBIT DUODENUM; HCO3-SECRETION; RAT; MUCOSA; PROSTAGLANDIN; TRANSPORT; INJURY; INVIVO AB Luminal exposure to concentrated acid, the most accepted physiological stimulus for duodenal bicarbonate secretion (DBS), cannot be used with in vitro preparations due to potential tissue damage. We thus examined whether exposure to PGE(2), a well-characterized physiological duodenal secretagogue, could mimic the effects of acid perfusion. DBS was measured in C57/BL mice by pH-stat/back-titration and measurement of total dissolved CO2 concentration ([CO2](t)). Anion transport inhibitor DIDS, anion channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), carbonic anhydrase inhibitor methazolamide, and nonselective cyclooxygenase inhibitor indomethacin were used to inhibit separate components of HCO3- secretory pathway. Baseline DBS was not altered by exposure to methazolamide (0.1 mM) but was slightly reduced by DIDS (0.5 mM). DBS and [CO2](t) increased after acid and PGE(2) exposure. DIDS ( 0.5 mM) and NPPB (0.2 mM) abolished acid-induced DBS increase. Methazolamide ( 0.1 mM) and DIDS inhibited acid-induced [CO2](t) increase. DIDS, NPPB, or methazolamide had little effect on DBS in response to high concentration PGE(2) (100 mug/ml). Low concentration PGE(2) (1 mug/ml) increased DBS that was inhibited by DIDS, NPPB, and methazolamide. Pretreatment with indomethacin (5 mg/kg) inhibited DBS induced by acid exposure but not by PGE(2). High-dose PGE(2) substantially increases DBS by a mechanism that appears to be different than secretory response to luminal acid perfusion. Secretory response to low-dose PGE(2), at least in terms of inhibitor profile, closely resembles secretion in response to perfusion of physiological acid concentrations and may be a useful stimulus for in vitro study of DBS in isolated mouse duodenum. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90024 USA. Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 114,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK-54221] NR 22 TC 12 Z9 12 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2004 VL 286 IS 6 BP G891 EP G898 DI 10.1152/ajpgi.00458.2003 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 818UE UT WOS:000221269200003 PM 14764447 ER PT J AU Silva, M Song, C Nadeau, WJ Matthews, JB McCormick, BA AF Silva, M Song, C Nadeau, WJ Matthews, JB McCormick, BA TI Salmonella typhimurium SipA-induced neutrophil transepithelial migration: involvement of a PKC-alpha-dependent signal transduction pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE inflammation; intestine; bacterial pathogenesis ID PROTEIN-KINASE-C; INTESTINAL EPITHELIA; PROINFLAMMATORY RESPONSE; BACTERIAL FLAGELLIN; COLONIC MUCOSA; EAR EDEMA; COLITIS; CELLS; ATTACHMENT; SECRETION AB Salmonella typhimurium elicits an intense proinflammatory response characterized by movement of polymorphonuclear neutrophils (PMN) across the epithelial barrier to the intestinal lumen. We previously showed that S. typhimurium, via the type III secretion system effector protein SipA, initiates an ADP-ribosylation factor-6- and phospholipase D-dependent lipid-signaling cascade that directs activation of protein kinase C (PKC) and subsequent transepithelial movement of PMN. Here we sought to determine the specific PKC isoforms that are induced by the S. typhimurium effector SipA in model intestinal epithelia and to link the functional consequences of these isoforms in the promotion of PMN transepithelial migration. In vitro kinase PKC activation assays performed on polarized monolayers of T84 cells revealed that S. typhimurium and recombinant SipA induced activation of PKC-alpha, -delta, and -epsilon. To elucidate which of these isoforms play a key role in mediating epithelial cell responses that lead to the observed PMN transepithelial migration, we used a variety of PKC inhibitors with different isoform selectivity profiles. Inhibitors selective for PKC-alpha (Go-6976 and 2,2', 3,3', 4,4'-hexahydroxyl-1,1'-biphenyl-6,6'-dimethanoldimethyl ether) markedly reduced S. typhimurium- and recombinant SipA-induced PMN transepithelial migration, whereas inhibitors to PKC-delta ( rottlerin) or PKC-epsilon (V1-2) failed to exhibit a significant decrease in transepithelial movement of PMN. These results were confirmed biochemically and by immunofluorescence coupled to confocal microscopy. Our results are the first to show that the S. typhimurium effector protein SipA can activate multiple PKC isoforms, but only PKC-alpha is involved in the signal transduction cascade leading to PMN transepithelial migration. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Dept Surg, Cincinnati, OH 45367 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Div Mucosal Immunol, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-48010, DK-56754, DK-33506, DK-51630] NR 43 TC 28 Z9 29 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2004 VL 286 IS 6 BP G1024 EP G1031 DI 10.1152/ajpgi.00299.2003 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 818UE UT WOS:000221269200019 PM 14739142 ER PT J AU Sinclair, NF Ai, WD Raychowdhury, R Bi, MX Wang, TC Koh, TJ McLaughlin, JT AF Sinclair, NF Ai, WD Raychowdhury, R Bi, MX Wang, TC Koh, TJ McLaughlin, JT TI Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE peptide hormone; gastrointestinal mucosa ID DECARBOXYLASE GENE PROMOTER; FACTOR EXPRESSION; EPITHELIAL-CELLS; TRANSGENIC MICE; PARIETAL-CELLS; EGF RECEPTOR; ACTIVATION; INDUCTION; PROTEIN; LOCALIZATION AB Gastrin is a known growth/differentiation factor for the gastric mucosa. Its effects are likely mediated by the induction of heparin-binding epidermal-like growth factor (HB-EGF), a member of the EGF family of growth factors that is expressed by gastric parietal cells. In this study, we investigated the regulation of the HB-EGF promoter by gastrin in a human gastric cancer cell line. Serial human HB-EGF promoter-luciferase reporter deletion constructs and heterologous promoter constructs were transfected into AGS-E cells and stimulated with gastrin (10(-7) M) with or without various signal transduction inhibitors. EMSA were also performed. Gastrin stimulation resulted in a fivefold increase in HB-EGF-luciferase activity. The cis-acting element mediating gastrin responsiveness was mapped to the - 69 to - 58 region of the HB-EGF promoter. Gastrin stimulation was PKC dependent and at least partially mediated by activation of the EGF receptor. C1 Univ Massachusetts Memorial Med Ctr, Div Digest Dis & Nutr, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Manchester, Salford M6 8HD, Lancs, England. RP Wang, TC (reprint author), Univ Massachusetts Memorial Med Ctr, Div Digest Dis & Nutr, 55 Lake Ave N, Worcester, MA 01655 USA. EM timothy.wang@umassmed.edu OI McLaughlin, John/0000-0001-6158-5135 FU NCI NIH HHS [1 R01-CA-87958]; NIDDK NIH HHS [K08-DK-02545, 5 R01-DK-48077, R01-DK-60225-01] NR 28 TC 28 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUN PY 2004 VL 286 IS 6 BP G992 EP G999 DI 10.1152/ajpgi.00206.2002 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 818UE UT WOS:000221269200015 PM 14764442 ER PT J AU Li, W Knowlton, D Van Winkle, DM Habecker, BA AF Li, W Knowlton, D Van Winkle, DM Habecker, BA TI Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE tyrosine hydroxylase; norepinephrine transporter; myocardial infarction ID TRANSMURAL MYOCARDIAL-INFARCTION; GANGLIONIC TYROSINE-HYDROXYLASE; PREGANGLIONIC NERVE-STIMULATION; VASOACTIVE-INTESTINAL-PEPTIDE; LEUKEMIA INHIBITORY FACTOR; NOREPINEPHRINE TRANSPORTER; RAT-HEART; NEUROPEPTIDE EXPRESSION; CATECHOLAMINE RELEASE; DOWN-REGULATION AB Regional changes occur in the sympathetic innervation of the heart after myocardial infarction (MI), including loss of norepinephrine ( NE) uptake and depletion of neuronal NE. This apparent denervation is accompanied by increased cardiac NE spillover. One potential explanation for these apparently contradictory findings is that the sympathetic neurons innervating the heart are exposed to environmental stimuli that alter neuronal function. To understand the changes that occur in the innervation of the heart after MI, immunohistochemical, biochemical, and molecular analyses were carried out in the heart and stellate ganglia of control and MI rats. Immunohistochemistry with panneuronal markers revealed extensive denervation in the left ventricle (LV) below the infarct, but sympathetic nerve fibers were retained in the base of the heart. Western blot analysis revealed that tyrosine hydroxylase (TH) expression ( normalized to a panneuronal marker) was increased significantly in the base of the heart and in the stellate ganglia but decreased in the LV below the MI. NE transporter ( NET) binding sites, normalized to total protein, were unchanged, except in the LV, where [H-3]nisoxetine binding was decreased. TH mRNA was increased significantly in the left and right stellate ganglia after MI, while NET mRNA was not. In the base of the heart, increased TH coupled with no change in NET may explain the increase in extracellular NE observed after MI. Coupled with substantial denervation in the LV, these changes likely contribute to the onset of cardiac arrhythmias. C1 Portland Vet Affairs Med Ctr, Anesthesiol Serv, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Anesthesiol, Portland, OR 97239 USA. RP Habecker, BA (reprint author), Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, L334,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM habecker@ohsu.edu FU NHLBI NIH HHS [HL 68231, R01 HL068231] NR 43 TC 52 Z9 56 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2004 VL 286 IS 6 BP H2229 EP H2236 DI 10.1152/ajpheart.00768.2003 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 821QQ UT WOS:000221477600024 PM 14726300 ER PT J AU Rao, VU Shiraishi, H McDermott, PJ AF Rao, VU Shiraishi, H McDermott, PJ TI PKC-epsilon regulation of extracellular signal-regulated kinase: a potential role in phenylephrine-induced cardiocyte growth SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart; hypertrophy; cell signaling; mitogen-activated protein kinase ID RAT VENTRICULAR MYOCYTES; ACTIVATED PROTEIN-KINASES; INDUCED CARDIOMYOCYTE HYPERTROPHY; C-EPSILON; CARDIAC-HYPERTROPHY; DIFFERENTIAL ACTIVATION; PRESSURE-OVERLOAD; HEART; TRANSLOCATION; ENDOTHELIN-1 AB Hypertrophic growth of cardiac muscle is dependent on activation of the PKC-epsilon isoform. To define the effectors of PKC-epsilon involved in growth regulation, recombinant adenoviruses were used to overexpress either wild-type PKC-epsilon (PKC-epsilon/WT) or dominant negative PKC-epsilon (PKC-epsilon/DN) in neonatal rat cardiocytes. PKC-epsilon/DN inhibited acute activation of PKC-epsilon produced in response to phorbol ester and reduced ERK1/2 activity as measured by the phosphorylation of p42 and p44 isoforms. The inhibitory effects were specific to PKC-epsilon because PKC-epsilon/DN did not prevent translocation of either PKC-epsilon or PKC-epsilon. Overexpression of PKC-epsilon/DN blunted the acute increase in ERK1/2 phorphorylation induced by the alpha(1)-adrenergic agonist phenylephrine (PE). Inhibition of PKC-delta with rottlerin potentiated the effects of PE on ERK1/2 phosphorylation. PKC-epsilon/DN adenovirus also blocked cardiocyte growth as measured after 48 h of PE treatment, although the multiplicity of infection was lower than that required to block acute ERK1/2 activation. PE activated p38 mitogen-activated protein kinase as measured by its phosphorylation, but the response was not blocked by PKC inhibitors or by overexpression of PKC-epsilon/DN. Taken together, these studies show that the hypertrophic agonist PE regulates ERK1/2 activity in cardiocytes by a pathway dependent on PKC-epsilon and that PE-induced growth is mediated by PKC-epsilon. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP McDermott, PJ (reprint author), 303 Thurmond Bldg,114 Doughty St, Charleston, SC 29403 USA. EM mcdermp@musc.edu FU NHLBI NIH HHS [P01 HL 48788] NR 43 TC 11 Z9 11 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2004 VL 286 IS 6 BP H2195 EP H2203 DI 10.1152/ajpheart.00475.2003 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 821QQ UT WOS:000221477600020 PM 14975926 ER PT J AU Moriyama, K Ishizaka, A Nakamura, M Kubo, H Kotani, T Yamamoto, S Ogawa, EN Kajikawa, O Frevert, CW Kotake, Y Morisaki, H Koh, H Tasaka, S Martin, TR Takeda, J AF Moriyama, K Ishizaka, A Nakamura, M Kubo, H Kotani, T Yamamoto, S Ogawa, EN Kajikawa, O Frevert, CW Kotake, Y Morisaki, H Koh, H Tasaka, S Martin, TR Takeda, J TI Enhancement of the endotoxin recognition pathway by ventilation with a large tidal volume in rabbits SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE acute lung injury; ventilator-induced lung injury ID INDUCED LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; NECROSIS-FACTOR-ALPHA; MECHANICAL VENTILATION; ALVEOLAR; CYTOKINES; CD14; MICE; GENE AB Ventilation with a small tidal volume (V-t) is associated with better clinical outcomes than with a large V-t, particularly in critical settings, including acute lung injury. To determine whether Vt influences the lipopolysaccaharide (LPS) recognition pathway, we studied CD14 expression in rabbit lungs and the release of TNF-alpha by cultured alveolar macrophages after 240 min of ventilation with a large ( 20 ml/kg) vs. a small ( 5 ml/kg) V-t. We also applied small or large Vt to lungs instilled with 50 mug/kg of LPS. The alveolar macrophages collected after large V-t ventilation revealed a 20-fold increase in LPS-induced TNF-alpha release compared with those collected after small V-t ventilation, whereas TNF-alpha was undetectable without LPS stimulation. In animals ventilated with a large V-t, the expression of CD14 mRNA in whole lung homogenates and the expression of CD14 protein on alveolar macrophages, assessed by immunohistochemistry, were both significantly increased in the absence of LPS stimulation. A large V-t applied to LPS-instilled lungs increased the pulmonary albumin permeability and TNF-alpha release into the plasma. These results suggest that mechanical stress caused by a large Vt sensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14. C1 Tokyo Elect Power Co Hosp, Dept Med, Shinjuku Ku, Tokyo 1600016, Japan. Keio Univ, Sch Med, Dept Anesthesiol, Tokyo 1608582, Japan. Keio Univ, Sch Med, Dept Med, Tokyo 1608582, Japan. Va Puget Sound Med Ctr, US Dept Vet Affairs, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98108 USA. Tohoku Univ, Sch Med, Dept Geriatr & Resp Med, Sendai, Miyagi 9808574, Japan. RP Ishizaka, A (reprint author), Tokyo Elect Power Co Hosp, Dept Med, Shinjuku Ku, 9-2 Shinanomachi, Tokyo 1600016, Japan. EM ishiz@attglobal.net RI Morisaki, Hiroshi/J-5960-2013; Kubo, Hiroshi/B-2760-2009 OI Kubo, Hiroshi/0000-0001-6097-4542 FU NHLBI NIH HHS [HL-30542] NR 27 TC 32 Z9 32 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 2004 VL 286 IS 6 BP L1114 EP L1121 DI 10.1152/ajplung.00296.2003 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 819NM UT WOS:000221321700005 PM 14633514 ER PT J AU Mojica, WA Suttorp, MJ Sherman, SE Morton, SC Roth, EA Maglione, MA Rhodes, SL Shekelle, PG AF Mojica, WA Suttorp, MJ Sherman, SE Morton, SC Roth, EA Maglione, MA Rhodes, SL Shekelle, PG TI Smoking-cessation interventions by type of provider - A meta-analysis SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NICOTINE CHEWING-GUM; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED TRIAL; SELF-HELP MATERIALS; GENERAL-PRACTICE; STOP SMOKING; FINANCIAL INCENTIVES; CIGARETTE-SMOKING; HOSPITAL PATIENTS; ADVICE AB Objective: To synthesize the evidence on the effectiveness of smoking-cessation interventions by type of provider. Methods: A random effects meta-regression was estimated to examine the effect of provider and whether the intervention contained nicotine replacement therapy (NRT), on the intervention's relative risk of quitting as compared to placebo or usual care from studies published in databases from inception to 2000. Thirty additional studies not included in the previous 1996 and 2000 U.S. Public Health Service clinical practice guidelines were used to provide the most comprehensive analysis to date of the comparative effectiveness of different types of providers in interventions for smoking cessation that have been published. Results: The effectiveness without NRT follows: psychologist (1.94, 95% confidence interval [Cl]: 1.04-3.62); physician (1.87, CI=1.42-2.45); counselor (1.82, CI=0.84-3.96); nurse (1.76, CI=1.21-2.57); unknown (1.27, CI=0.57-2.82); other (1.18, CI=0.67-2.10); and self-help (1.28, CI=0.89-1.82). Effectiveness of most providers increased by almost twofold with the use of NRT. Conclusions: Smoking-cessation interventions without NRT delivered by psychologists, physicians, or nurses are all effective. NRT increases the effectiveness of most providers. C1 RAND Corp, So Calif Evidence Based Practice Ctr, Hlth Div, Santa Monica, CA 90407 USA. Greater Los Angeles Vet Adam Helathcare Syst, So Calif Avidence Baseed Practice Ctr, Dept Med, Los Angeles, CA USA. RP Mojica, WA (reprint author), RAND Corp, So Calif Evidence Based Practice Ctr, Hlth Div, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. EM Walter_Mojica@rand.org NR 68 TC 37 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2004 VL 26 IS 5 BP 391 EP 401 DI 10.1016/j.ampere.2004.02.014 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 824IU UT WOS:000221680800003 PM 15165655 ER PT J AU Weiner, M Bock, N Peloquin, CA Burman, WJ Khan, A Vernon, A Zhao, Z Weis, S Sterling, TR Hayden, K Goldberg, S AF Weiner, M Bock, N Peloquin, CA Burman, WJ Khan, A Vernon, A Zhao, Z Weis, S Sterling, TR Hayden, K Goldberg, S CA Tuberculosis Trials Consortium TI Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pharmacokinetics; rifapentine; treatment; tuberculosis ID MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; CONTINUATION PHASE; RIFAMPICIN; REGIMENS; TRIAL AB The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean area under the plasma concentration-time curve (AUC(0-infinity)) increased significantly with dose (rifapentine AUC(0-infinity): 296, 410, and 477 mug (.) hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear regression). In multivariate stepwise regression analyses, AUC(0-infinity) values for rifapentine and the active 25-desacetyl metabolite were associated with drug dose and plasma albumin concentration, and were lower among men and among white individuals. Fifty-four percent of patients had total (free and protein-bound) plasma concentrations of rifapentine and of desacetyl rifapentine detected for more than 36 hours after clearance of concurrently administered isoniazid. Serious adverse effects of therapy in these study patients were infrequent (11 of 35 cases; 3%) and not linked with higher rifapentine AUC(0-infinity) or peak concentration. The present pharmacokinetic study supports further trials to determine the optimal rifapentine dose for treatment of tuberculosis. C1 S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78229 USA. Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA. Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Denver Publ Hlth Dept, Denver, CO USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Arkansas Dept Hlth, Little Rock, AR 72205 USA. Seattle King Cty Dept Publ Hlth, Seattle, WA USA. RP Weiner, M (reprint author), S Texas Vet Hlth Care Syst, Dept Med, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu FU NCRR NIH HHS [M01-RR-01346] NR 23 TC 54 Z9 58 U1 0 U2 4 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 JUN 1 PY 2004 VL 169 IS 11 BP 1191 EP 1197 DI 10.1164/rccm.200311-1612OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 824HN UT WOS:000221677400007 PM 14962821 ER PT J AU Ichiyasu, H McCormack, JM McCarthy, KM Dombkowski, D Preffer, FI Schneeberger, EE AF Ichiyasu, H McCormack, JM McCarthy, KM Dombkowski, D Preffer, FI Schneeberger, EE TI Matrix metalloproteinase-9-deficient dendritic cells have impaired migration through tracheal epithelial tight junctions SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TRANSENDOTHELIAL MIGRATION; NEUTROPHIL EMIGRATION; TUMOR INVASION; GELATINASE B; LUNG; RECRUITMENT; MATRIX-METALLOPROTEINASE-9; EXPRESSION; LIGAND; INFLAMMATION AB When sampling inhaled antigens, dendritic cells (DC) must penetrate the tight junction (TJ) barrier while maintaining the TJ seal. In matrix metalloproteinase (MMP)-9-deficient mice, in vivo experiments suggest that migration of DC into air spaces is impaired. To examine the underlying mechanisms, we established a well-defined in vitro model using mouse tracheal epithelial cells and mouse bone marrow DC (BMDC). Transmigration was elicited with either macrophage inflammatory protein (MIP)-1alpha or MIP-3beta in a time-dependent manner. Control MMP-9(+/+) BMDC cultured with granulocyte macrophage-colony-stimulating factor for 7 d showed a 30-fold greater transepithelial migration toward MIP-3beta than MIP-1alpha, indicating a more mature DC phenotype. IVIMP-9(-/-) BMDC as well as MMP9(+/+) BMDC in the presence of the MMP inhibitor GM6001, although showing a similar preference for MIP-3beta, were markedly impaired in their ability to traverse the epithelium. Expression levels of CCR5 and CCR7, however, were similar in both MMP-9(-/-) and MMP9(+/+) BMDC. Expression of the integral TJ proteins, occludin and claudin-1, were examined in BMDC before and after transepithelial migration. Interestingly, occludin but not claudin-1 was degraded following transepithelial migration in both MMP-9(-/-) and control BMDC. In addition, there was a > 2-fold increase in claudin-1 expression in MMP-9(-/-) as compared with control BMDC. These observations indicate that occludin and claudin-1 are differentially regulated and suggest that the lack of MMP-9 may affect claudin-1 turnover. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02139 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Room 7147,149 13th St, Charlestown, MA 02139 USA. EM eschneeberger@partners.org FU NHLBI NIH HHS [HL36781, HL25822] NR 47 TC 62 Z9 70 U1 1 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 2004 VL 30 IS 6 BP 761 EP 770 DI 10.1165/rcmb.2003-0370OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 826NF UT WOS:000221835100001 PM 14656746 ER PT J AU Hassoun, PM Filippov, G Fogel, M Donaldson, C Kayyali, US Shimoda, LA Bloch, KD AF Hassoun, PM Filippov, G Fogel, M Donaldson, C Kayyali, US Shimoda, LA Bloch, KD TI Hypoxia decreases expression of soluble guanylate cyclase in cultured rat pulmonary artery smooth muscle cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; ATRIAL-NATRIURETIC-PEPTIDE; GENE-EXPRESSION; UP-REGULATION; MOLECULAR-CLONING; MESSENGER-RNA; CGMP; LUNG; INHIBITION; MECHANISMS AB Nitric oxide (NO) has an important role in modulating the pulmonary vascular tone. NO acts, in part, by stimulating soluble guanylate cyclase (sGC) to synthesize the intracellular second messenger cyclic GMP. In vascular smooth muscle cells, sGC is a heterodimer composed of alpha1 and beta1 subunits. The objective of this study was to test whether oxygen concentration regulates sGC expression in cultured rat pulmonary artery smooth muscle cells (rPaSMC). rPaSMC were exposed to 0, 3, and 20% oxygen for 1-48 h, and sGC subunit mRNA levels were measured. Compared with rPaSMC exposed to 20% oxygen, sGC alpha1 and beta1 subunit mRNA levels were markedly decreased in rPaSMC exposed to 0% and 3% oxygen. The decrease in sGC subunit mRNA levels in hypoxic rPaSMC was detected as early as 6 h of exposure. Compared with rPaSMC exposed to 20% oxygen, exposure of rPaSMC to 3% oxygen progressively decreased sGC subunit protein levels at 24 and 48 h. There was also a 30% and 50% decrease in sGC enzyme activity in cells exposed to hypoxia for 24 and 48 h (P < 0.05 and P < 0.001, respectively, as compared with cells maintained in normoxia). These results demonstrate that hypoxia decreases sGC expression in cultured pulmonary artery smooth muscle cells and Suggest that, in hypoxic vascular smooth muscle, decreased cyclic GMP synthesis may limit the vasodilator response to NO. C1 Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Pulm & Crit Care Div, Boston, MA 02111 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Hassoun, PM (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM phassoun@jhmi.edu FU NHLBI NIH HHS [HL55377, HL07208, HL49441] NR 39 TC 22 Z9 23 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 2004 VL 30 IS 6 BP 908 EP 913 DI 10.1165/rcmb..2003-0287OC PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 826NF UT WOS:000221835100020 PM 14754757 ER PT J AU Chapman, VM Rhea, JT Sacknoff, R Novelline, RA AF Chapman, VM Rhea, JT Sacknoff, R Novelline, RA TI CT of nontraumatic abdominal fluid collections after initial fluid resuscitation of patients with major burns SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. The purpose of this study was to describe the presence and CT distribution of nontraumatic fluid collections and edema in the abdomen and pelvis after initial fluid resuscitation of patients with major (greater than or equal to 25% total body surface area) thermal burns. CONCLUSION. Awareness of the presence and expected CT distribution of nontraumatic fluid after initial fluid resuscitation in patients with major burns can assist the radiologist in differentiating such collections from those caused by mechanical trauma. C1 Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, Boston, MA 02114 USA. RP Chapman, VM (reprint author), Massachusetts Gen Hosp, Div Emergency Radiol, Dept Radiol, POB 9657,55 Fruit St, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 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 JUN PY 2004 VL 182 IS 6 BP 1493 EP 1496 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 822QW UT WOS:000221555900030 PM 15149995 ER PT J AU DeFrate, LE van der Ven, A Gill, TJ Li, GA AF DeFrate, LE van der Ven, A Gill, TJ Li, GA TI The effect of length on the structural properties of an achilles tendon graft as used in posterior cruciate ligament reconstruction SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE posterior cruciate ligament (PCL) reconstruction; Achilles tendon graft; soft tissue biomechanics ID MEDIAL COLLATERAL LIGAMENT; IN-VITRO; MECHANICAL-PROPERTIES; TIBIAL TUNNEL; KNEE; PLACEMENT; BEHAVIOR; FIXATION; TENSILE; LAXITY AB Background: The clinical outcomes of posterior cruciate ligament reconstruction are varied. No previous studies have investigated the effect of graft length on the structural properties of the graft. Hypothesis: Graft length significantly affects the structural properties of posterior cruciate ligament grafts. Study Design: Controlled laboratory study. Methods: Eight Achilles tendon grafts were tested under tensile loads up to 400 N at 3 different lengths: long (75 mm), medium (48 mm), and short (34 mm). These 3 lengths represent midtunnel fixation, inlay fixation, and fixation near the ligament insertions. Results: Shortening the graft from both long to medium and from medium to short increased the stiffness by approximately 25%. Long and medium grafts displaced significantly more than medium and short grafts, respectively. Conclusion: The effective length of a graft, which is determined by where it is fixed, should be considered an important variable in posterior cruciate ligament reconstruction. C1 Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Li, GA (reprint author), Massachusetts Gen Hosp, Bioengn Lab, GRJ 1215,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 8 Z9 9 U1 1 U2 1 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUN PY 2004 VL 32 IS 4 BP 993 EP 997 DI 10.1177/0363546503261739 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 824SH UT WOS:000221706200019 PM 15150048 ER PT J AU Skinnider, BF Oliva, E Young, RH Amin, MB AF Skinnider, BF Oliva, E Young, RH Amin, MB TI Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma - A significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 11th European Symposium on Radiopharmacy and Radiopharmaceuticals CY MAR 15-18, 2003 CL Innsbruck, AUSTRIA DE nephrogenic adenoma; prostatic adenocarcinoma; AMACR; basal cells; PSA ID URINARY-TRACT; PRECURSOR LESIONS; MOLECULAR MARKER; NEEDLE-BIOPSY; CANCER; URETHRA; CARCINOMA; HYPERPLASIA; 34-BETA-E12; BIOMARKER AB alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a useful marker for the diagnosis of prostatic adenocarcirioma and a potential aid in its distinction from its many mimics. one of which is the benign lesion, nephrogenic adenoma (NA). The goal of this study was to assess the expression of AMACR in NA by immunohistochemistry. as well as other potentially useful markers. high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases showed circumferential granular cytoplasmic AMACR expression of at least moderate intensity. in >75% of tubules in 3 cases and in <10% of tubules in the remaining case. The AMACR-positive cases in the bladder typically showed focal weak noncircumferential staining of the tubules and stronger staining of the cells lining the papillae. 34PE 12 staining was observed in 1/4 prostatic NAs and 4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63 and PSA were negative in all cases. Our data indicate that NA of the prostatiC Urethra commonly expresses AMACR and lacks basal cell-specific markers, making it not only a potential morphologic mimic of prostatic adenocarcinoma but also a significant immunohistochemical mimic as well. Awareness of NA as a significant pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of hematoxylin and eosin-stained sections remains the key to the correct diagnosis, which can be supported by a negative PSA stain. C1 Emory Univ Hosp, Dept Pathol, Atlanta, GA 30322 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Amin, MB (reprint author), Emory Univ Hosp, Dept Pathol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM mahul.amin@emory.org NR 25 TC 54 Z9 61 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 JUN PY 2004 VL 28 IS 6 BP 701 EP 705 DI 10.1097/01.pas.0000126759.43227.d9 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 823XM UT WOS:000221647600001 PM 15166661 ER PT J AU Song, YL Liu, CX McTeague, M Summanen, P Finegold, SM AF Song, YL Liu, CX McTeague, M Summanen, P Finegold, SM TI Clostridium bartlettii sp nov., isolated from human faeces SO ANAEROBE LA English DT Article DE Clostridium bartlettii sp nov.; faeces; 16S rRNA; phylogery; taxonomy ID 16S RIBOSOMAL-RNA; SEQUENCE-ANALYSIS; COMMUNITIES; BACTERIUM; REVEALS; ACID; GUT AB Seven obligately anaerobic, Gram-positive, rod-shaped, spore-forming organisms isolated from human faecal specimens were characterized using phenotypic and molecular taxonomic methods. Strains of the unidentified bacterium used carbohydrates as fermentable substrates, producing acetic acid, isovaleric acid and phenylacetic acid (PAA) as the major products of glucose metabolism, and possessed a G + C content of approximately 29.8 mol%. Comparative 16S rRNA gene sequencing showed that the 7 strains were genetically highly related to each other (displaying > 99.5% sequence similarity) and represent a previously unknown sub-line within the Clostridium Cluster XL The closest described species to the novel bacterium is Clostridium glycolicum, although a 16S rRNA sequence divergence of 4% demonstrates that they represent different species. Genomic DNA-DNA pairing studies confirmed the separateness of the unknown species and C. glycolicum (30.6% similarity between the proposed type strain of the novel species, WAL 16138, and C. glycolicum ATCC 14880(T)). Based on morphologic, phenotypic and phylogenetic evidence, it is therefore proposed that the unknown bacterium be classified as C bartlettii sp. nov. The type strain of C bartlettii is WAL 16138 T (= ATCCBAA-827(T) = CCUG48940(T)). (C) 2004 Elsevier Ltd. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Clin Microbiol Lab, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA. RP Song, YL (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, 11301 Wilshire Blvd,Bldg 304,Room E3-227, Los Angeles, CA 90073 USA. EM yulis1@yahoo.com NR 23 TC 16 Z9 16 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD JUN PY 2004 VL 10 IS 3 BP 179 EP 184 DI 10.1016/j.anaerobe.2004.04.004 PG 6 WC Microbiology SC Microbiology GA 837HP UT WOS:000222619900005 PM 16701516 ER PT J AU Yasukawa, T Kaneki, M Yasuhara, S Lee, SL Martyn, JAJ AF Yasukawa, T Kaneki, M Yasuhara, S Lee, SL Martyn, JAJ TI Steroidal nondepolarizing muscle relaxants do not simulate the effects of glucocorticoids on glucocorticoid receptor-mediated transcription in cultured skeletal muscle cells SO ANESTHESIOLOGY LA English DT Article ID INTENSIVE-CARE UNIT; ACETYLCHOLINE-RECEPTORS; PROLONGED WEAKNESS; D-TUBOCURARINE; UP-REGULATION; INFUSION; IMMOBILIZATION; EXPRESSION; LUCIFERASE; ATROPHY C1 Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Med Ctr, Dept Med, Boston, MA USA. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM jmartyn@etherdome.mgh.harvard.edu FU NIDDK NIH HHS [R01-DK058127-03]; NIGMS NIH HHS [R01-GM61411-06, R01-GM055082-07, R01-GM31569-21] NR 31 TC 2 Z9 2 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 JUN PY 2004 VL 100 IS 6 BP 1615 EP 1619 DI 10.1097/00000542-200406000-00041 PG 5 WC Anesthesiology SC Anesthesiology GA 822PE UT WOS:000221551300040 PM 15166588 ER PT J AU Takayseu, JK Hutson, HR AF Takayseu, JK Hutson, HR TI Communicating life-threatening diagnoses to patients in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID BREAKING BAD-NEWS; CORONARY-ARTERY DISEASE; ANTICIPATORY GRIEF; DEATH NOTIFICATION; CARE; CANCER; SATISFACTION; PHYSICIANS; BEREAVEMENT; PERCEPTIONS AB Disclosing a new, life-threatening diagnosis to a patient is difficult for the physician, the patient, and the family. The disclosure provokes a wide range of reactions from to which the emergency physician must respond. This both the patient and family, interaction is further complicated by the limited time the emergency physician can spend with the patient, the strained resources of a busy emergency department (ED), and, oftentimes, the inability to make a definitive diagnosis based on the ED workup and evaluation. We present a case seen recently in the ED in which a new, life-threatening illness requires disclosure. We offer guidelines for the emergency physician that emphasize patient- and family-centered disclosure of the worrisome diagnostic findings. Additionally, we discuss the essential roles of other allied health professionals in addressing the patient's nonmedical concerns (eg, health insurance, social issues) and in creating a smooth transition for the patient from the ED to further inpatient or outpatient care. C1 Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. RP Takayseu, JK (reprint author), Massachusetts Gen Hosp, Emergency Serv, 55 Fruit St Clin 115, Boston, MA 02114 USA. EM jtakayesu@partners.org NR 52 TC 6 Z9 6 U1 0 U2 4 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 JUN PY 2004 VL 43 IS 6 BP 749 EP 755 DI 10.1016/j.annemergmed.2003.12.013 PG 7 WC Emergency Medicine SC Emergency Medicine GA 825JT UT WOS:000221753700011 PM 15159709 ER PT J AU Mittman, BS AF Mittman, BS TI Creating the evidence base for quality improvement collaboratives SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE; UNITED-STATES; FRAMEWORK; LESSONS AB Intensive efforts are under way to improve health care quality and safety throughout the United States and abroad. Many of these efforts use the quality improvement collaborative method, an approach emphasizing collaborative learning and exchange of insights and support among a set of health care organizations. Unfortunately, the widespread acceptance and reliance on this approach are based not on solid evidence but on shared beliefs and anecdotal affirmations that may overstate the actual effectiveness of the method. More effective use of the collaborative method will require a commitment by users, researchers, and other stakeholders to rigorous, objective evaluation and the creation of a valid, useful knowledge and evidence base. Development of this evidence base will require improved conceptions of the nature of quality problems, quality improvement processes, and the types of research needed to elucidate these processes. Researchers, journal editors, and funding agencies must also cooperate to ensure that published evaluations are relevant, comprehensive, and cumulative. C1 Vet Affairs Greater Los Angeles Healthcare Syst 1, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. Vet Affairs Qual Enchancement Res Initiat, Washington, DC USA. RP Mittman, BS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst 1, Ctr Study Healthcare Provider Behav, 16111 Plummer St, Sepulveda, CA 91343 USA. EM Brian.Mittman@med.va.gov NR 16 TC 153 Z9 154 U1 2 U2 8 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 2004 VL 140 IS 11 BP 897 EP 901 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 824IS UT WOS:000221680600006 PM 15172904 ER PT J AU Goroll, AH Sirio, C Duffy, FD LeBlond, RF Alguire, P Blackwell, TA Rodak, WE Nasca, T AF Goroll, AH Sirio, C Duffy, FD LeBlond, RF Alguire, P Blackwell, TA Rodak, WE Nasca, T CA Residency Review Comm Internal Med TI A new model for accreditation of residency programs in internal medicine SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OUTCOME-BASED EDUCATION; GUIDE NO. 14; QUALITY; COMPETENCE AB A renewed emphasis on clinical competence and its assessment has grown out of public concerns about the safety, efficacy, and accountability of health care in the United States. Medical schools and residency training programs are paying increased attention to teaching and evaluating basic clinical skills, stimulated in part by these concerns and the responding initiatives of accrediting, certifying, and licensing bodies. This paper, from the Residency Review Committee for Internal Medicine of the Accreditation Council for Graduate Medical Education, proposes a new outcomes-based accreditation strategy for residency training programs in internal medicine. It shifts residency program accreditation from external audit of educational process to continuous assessment and improvement of trainee clinical competence. C1 Massachusetts Gen Hosp, Ctr Ambulatory Care, Boston, MA 02114 USA. Accreditat Council Grad Med Educ, Chicago, IL USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Iowa, Sch Med, Iowa City, IA 52242 USA. Thomas Jefferson Univ, Sch Med, Philadelphia, PA 19107 USA. Amer Coll Physicians, Amer Board Internal Med, Philadelphia, PA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goroll, AH (reprint author), Massachusetts Gen Hosp, Ctr Ambulatory Care, Suite 645,15 Parkman St, Boston, MA 02114 USA. EM ahgoroll@partners.org NR 24 TC 62 Z9 64 U1 1 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 JUN 1 PY 2004 VL 140 IS 11 BP 902 EP 909 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 824IS UT WOS:000221680600007 PM 15172905 ER PT J AU von Bergwelt-Baildon, M Maecker, B Schultze, J Gribben, JG AF von Bergwelt-Baildon, M Maecker, B Schultze, J Gribben, JG TI CD40 activation: potential for specific immunotherapy in B-CLL SO ANNALS OF ONCOLOGY LA English DT Review DE antigen presentation; CD40; CD 154; CLL; immunotherapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; T-CELL RESPONSES; FOLLICULAR LYMPHOMA-CELLS; ANTIGEN-PRESENTING CELLS; IMMUNE-RESPONSE; IN-VIVO; INDUCED APOPTOSIS; GENE-TRANSFER; LIGAND; IMMUNOGLOBULIN AB Despite encouraging scientific and therapeutic advances, chronic lymphocytic leukemia (CLL) principally remains an incurable disease. Allogeneic transplantation represents the only curative approach, but is marked by high mortality. Novel and less toxic treatment modalities are needed. Immunotherapeutic approaches have clearly demonstrated potential effectiveness in CLL and other B-cell malignancies. To successfully direct immunity against CLL, highly immunogenic tumor cells or tumor-antigen-loaded antigen-presenting cells are necessary. The CD40-CD40L interaction has been shown to significantly increase antigen presentation in normal and malignant B-cells. Here we discuss biology and potential therapeutic applications of the CD40-system in CLL. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dis Ctr Hematol Neoplasia, Boston, MA 02115 USA. Univ Cologne, Dept Hematol Oncol, Cologne, Germany. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dis Ctr Hematol Neoplasia, 44 Binney St,D540C, Boston, MA 02115 USA. EM john_gribben@dfci.harvard.edu RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 51 TC 19 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2004 VL 15 IS 6 BP 853 EP 857 DI 10.1093/annonc/mdh213 PG 5 WC Oncology SC Oncology GA 833VX UT WOS:000222369700003 PM 15151939 ER PT J AU Berclaz, G Li, S Price, KN Coates, AS Castiglione-Gertsch, M Rudenstam, CM Holmberg, SB Lindtner, J Erzen, D Collins, J Snyder, R Thurlimann, B Fey, MF Mendiola, C Werner, ID Simoncini, E Crivellari, D Gelber, RD Goldhirsch, A International Breast Cancer Study Grp AF Berclaz, G Li, S Price, KN Coates, AS Castiglione-Gertsch, M Rudenstam, CM Holmberg, SB Lindtner, J Erzen, D Collins, J Snyder, R Thurlimann, B Fey, MF Mendiola, C Werner, ID Simoncini, E Crivellari, D Gelber, RD Goldhirsch, A International Breast Cancer Study Grp TI Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience SO ANNALS OF ONCOLOGY LA English DT Article DE body mass index; breast cancer; obesity; prognostic factor; survival ID DISEASE-FREE SURVIVAL; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; RANDOMIZED TRIAL; YOUNG-WOMEN; OBESITY; COMBINATION; DURATION; MASTECTOMY; RECURRENCE AB Background: Current information on the prognostic importance of body mass index (BNH) for patients with early breast cancer is based on a variety of equivocal reports. Few have data on BMI in relationship to systemic treatment. Patients and methods: Patients (6792) were randomized to International Breast Cancer Study Group trials from 1978 to 1993, studying chemotherapy and endocrine therapy. BMI was evaluated with eight other factors: menopausal status, nodal status, estrogen receptor status, progesterone receptor status, tumor size, vessel invasion, tumor grade and treatment. BMI was categorized as normal (less than or equal to24.9), intermediate (25.0-29.9) or obese (greater than or equal to30.0). Results: Patients with normal BMI had significantly longer overall survival (OS) and disease-free survival (DFS) than patients with intermediate or obese BMI in pairwise comparisons adjusted for other factors. Subset analyses showed the same effect in pre- and perimenopausal patients and in those receiving chemotherapy alone. When assessed globally and adjusted for other factors, BMI significantly influenced OS (P = 0.03) but not DFS (P = 0. 12). \ Conclusions: BMI is an independent prognostic factor for OS in patients with breast cancer, especially among pre-/perimenopausal patients treated with chemotherapy without endocrine therapy. C1 Inselspital Bern, Dept Obstet & Gynecol, CH-3010 Bern, Switzerland. Inselspital Bern, Inst Med Oncol, CH-3010 Bern, Switzerland. IBCSG Coordinating Ctr, Bern, Switzerland. Kantonsspital, St Gallen, Switzerland. Oncol Inst So Switzerland, Lugano, Switzerland. Dana Farber Canc Inst, IBCSG, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Canc Council Australia, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW, Australia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. St Vincents Hosp, Dept Oncol, Melbourne, Vic, Australia. Sahlgrens Univ Hosp, W Swedish Breast Canc Study Grp, S-41345 Gothenburg, Sweden. SU Moelndals Hosp, Dept Surg, Molndal, Sweden. Inst Oncol, Ljubljana, Slovenia. Madrid Breast Canc Grp, Madrid, Spain. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Univ Cape Town, ZA-7925 Cape Town, South Africa. Oncol Med Spedali Civili, Brescia, Italy. Ctr Riferimento Oncol, I-33081 Aviano, Italy. European Inst Oncol, Milan, Italy. RP Inselspital Bern, Dept Obstet & Gynecol, Effingerstr 102, CH-3010 Bern, Switzerland. EM gilles.berclaz@insel.ch FU NCI NIH HHS [CA-75362] NR 30 TC 149 Z9 155 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2004 VL 15 IS 6 BP 875 EP 884 DI 10.1093/annonc/mdh222 PG 10 WC Oncology SC Oncology GA 833VX UT WOS:000222369700007 PM 15151943 ER PT J AU Tay, MH Kaufman, DS Regan, MM Leibowitz, SB George, DJ Febbo, PG Manola, J Smith, MR Kaplan, ID Kantoff, PW Oh, WK AF Tay, MH Kaufman, DS Regan, MM Leibowitz, SB George, DJ Febbo, PG Manola, J Smith, MR Kaplan, ID Kantoff, PW Oh, WK TI Finasteride and bicalutamide as primary hormonal therapy in patients with advanced adenocarcinoma of the prostate SO ANNALS OF ONCOLOGY LA English DT Article DE bicalutamide; finasteride; prostate; potency ID ANDROGEN DEPRIVATION THERAPY; ENDOCRINE TREATMENT; CANCER; MONOTHERAPY; ANTIGEN; FLUTAMIDE; NADIR AB Background: Medical or surgical castration is effective in advanced prostate cancer but with profound side-effects, particularly on sexual function. Effective, less toxic therapies are needed. This study examined whether the addition of finasteride to high-dose bicalutamide enhanced disease control, as measured by additional decreases in serum prostate-specific antigen (PSA). Patients and methods: Forty-one patients with advanced prostate cancer received bicalutamide (150 mg/day). Finasteride (5 mg/day) was added at first PSA nadir. Serum PSA was measured every 2 weeks until disease progression. Questionnaires were administered to assess sexual function. Results: Median follow-up is 3.9 years. At the first PSA nadir, median decrease in PSA from baseline was 96.5%. Thirty of 41 patients (73%) achieved a second PSA nadir and median decrease of 98.5% from baseline. Median time to each nadir was 3.7 and 5.8 weeks, respectively. Median time to treatment failure was 21.3 months. Toxicities were minor, including gynecomastia. Seventeen of 29 (59%) and 12 of 24 (50%) men had normal sex drive at baseline and at second PSA nadir, respectively. One-third of men had spontaneous erection at both time points. Conclusion: Finasteride provides additional intracellular androgen blockade when added to bicalutamide. Duration of control is comparable to castration, with preserved sexual function in some patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Solid Tumor Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Solid Tumor Oncol, Lank Ctr Genitourinary Oncol, 1230 Dana Bldg,44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 18 TC 21 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2004 VL 15 IS 6 BP 974 EP 978 DI 10.1093/annonc/mdh221 PG 5 WC Oncology SC Oncology GA 833VX UT WOS:000222369700021 PM 15151957 ER PT J AU Kieff, DA Busaba, NY AF Kieff, DA Busaba, NY TI Isolated chronic maxillary sinusitis of non-dental origin does not correlate per se with ipsilateral intranasal structural abnormalities SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE concha bullosa; correlation; deviated septum; Haller cell; maxillary sinus mucocele; maxillary sinusitis; paradoxical middle turbinate ID ENDOSCOPIC ENDONASAL SURGERY; CONCHA-BULLOSA; CT EVALUATION; RECURRING RHINOSINUSITIS; NASAL POLYPOSIS; DISEASE AB A case series of 35 patients with isolated chronic maxillary sinusitis of inflammatory non-dental origin was retrospectively reviewed to determine the correlation of ipsilateral intranasal structural abnormalities. The records were examined for computed tomographic, nasal endoscopic, and intraoperative findings. The incidence of ipsilateral and contralateral intranasal structural abnormalities at the ostiomeatal complex region, including conchae bullosae, Haller cells, paradoxical middle turbinates, and septal deviations, was determined. Nineteen of 35 patients (54%) had ipsilateral abnormalities and 16 (46%) did not. Of the 19 patients with ipsilateral abnormalities, 4 had Haller cells, 4 had conchae bullosae, 2 had paradoxical middle turbinates, and 12 had septal deviations. (Two patients had multiple ipsilateral factors.) Of the 16 patients with contralateral abnormalities, 4 had Haller cells, 3 had conchae bullosae, 2 had paradoxical middle turbinates, and 9 had septal deviations. Ten patients had only contralateral abnormalities, and 6 had no identifiable anatomic abnormality. The difference between the incidences of ipsilateral and contralateral abnormalities in this series of 35 patients with isolated chronic maxillary sinusitis was not statistically significant when the factors were analyzed as a group or by individual factor (range in odds ratios for the various factors, 1 to 1.54; range in p values for the various factors, .25 to 1). Thus, the data show that ipsilateral structural abnormalities at the ostiomeatal complex region, including conchae bullosae, Haller cells, paradoxical middle turbinates, and septal deviations, did not correlate per se with isolated chronic maxillary sinusitis that was not attributable to dental disease. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 4 Z9 4 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 JUN PY 2004 VL 113 IS 6 BP 474 EP 476 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 828IK UT WOS:000221966800011 PM 15224832 ER PT J AU O'Herrin, JK Fost, N Kudsk, KA AF O'Herrin, JK Fost, N Kudsk, KA TI Health insurance portability accountability act (HIPAA) regulations - Effect on medical record research SO ANNALS OF SURGERY LA English DT Article ID CLINICAL-RESEARCH; PRIVACY RULE; CARE AB Objective: To evaluate the effect of impending HIPAA regulations on Applications for Exemptions from Institutional Review Board (IRB) approval. Summary Background Data: HIPAA was implemented to reduce potential for misuse of personal information and restricts access to medical records by insurers, employers, and clinical researchers. We hypothesized that HIPAA regulations adversely impact medical records research. Methods: The UW-Madison Human Subjects Committee database was accessed to evaluate success and delays in processing Applications for Exemption between September 1999 and March 2003. The number of protocols submitted, number of required revisions, and number considered nonexempt (requiring full IRB review) were determined. Results: Prior to 2000, applications for medical records research were rare (11 applications in 1999-2000). In anticipation of the implementation of HIPAA regulations, a new application process was instituted in 2001. During that year, 92 of 103 were approved by an expedited process with few requiring full IRB approval. In 2002 to 2003, submissions increased to 199 and approval without revision dropped to 59% (P < 0.0001) as the number requiring revision (25%) and full IRB approval (16%) increased significantly (P < 0.0001 and P < 0.05, respectively). Of the 31 requiring full IRB approval, 7 were pursued while 24 (77%) were abandoned. Conclusion: HIPAA appears to inhibit medical record and database research. Ethical considerations in healthcare research are paramount, but current HIPAA implementation strategies increase workload for HSC and researchers, and increase the dropout rate for proposed studies when investigators are unable or unwilling to meet the regulatory requirements. It is unclear whether or to what degree the new requirements add to protection of privacy. Studies designed to investigate the costs and effects on quantity and/or quality of research should be prospectively implemented. C1 Univ Wisconsin, Dept Surg, Madison, WI USA. Univ Wisconsin, Dept Pediat, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI 53705 USA. RP Kudsk, KA (reprint author), Univ Wisconsin Hosp & Clin, Dept Surg, Clin Sci Ctr H4 736, 600 Highland Ave, Madison, WI 53792 USA. EM Kudsk@surgery.wisc.edu NR 8 TC 34 Z9 35 U1 3 U2 7 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 JUN PY 2004 VL 239 IS 6 BP 772 EP 776 DI 10.1097/01.sla.0000128307.98274.dc PG 5 WC Surgery SC Surgery GA 823OM UT WOS:000221622600007 PM 15166956 ER PT J AU Reavis, KM Morris, CD Gopal, DV Hunter, JG Jobe, BA AF Reavis, KM Morris, CD Gopal, DV Hunter, JG Jobe, BA TI Laryngopharyngeal reflux symptoms better predict the presence of esophageal adenocarcinoma than typical gastroesophageal reflux symptoms SO ANNALS OF SURGERY LA English DT Article ID PHARYNGEAL ACID REFLUX; BARRETTS-ESOPHAGUS; POSTERIOR LARYNGITIS; RISK-FACTORS; HIATAL-HERNIA; UNITED-STATES; SURVEILLANCE; PREVALENCE; DYSPLASIA; DISEASE AB Objective: To determine whether the presence of laryngopharyngeal reflux symptoms is associated with the presence of esophageal adenocarcinoma (EAC). Background: Most patients diagnosed with EAC have incurable disease at the time of detection. The majority of these patients are unaware of the presence of Barrett's esophagus prior to cancer diagnosis and many do not report typical symptoms of gastroesophageal reflux disease (GERD). This suggests that the current GERD symptom-based screening paradigm may be inadequate. Data support a causal relation between complicated GERD and laryngopharyngeal reflux symptoms. We theorize that laryngopharyngeal reflux symptoms are not recognized expeditiously, resulting in chronic esophageal injury and an unrecognized progression of Barrett's esophagus to EAC. Methods: This is a case-comparison (control) study. Cases were patients diagnosed with EAC (n = 63) between 1997 and 2002. Three comparison groups were selected: 1) Barrett's esophagus patients without dysplasia (n = 50), 2) GERD patients without Barrett's esophagus (n = 50), and 3) patients with no history of GERD symptoms or antisecretory medication use (n = 56). The risk factors evaluated included demographics, medical history, lifestyle variables, and laryngopharyngeal reflux symptoms. Typical GERD symptoms and antisecretory medication use were recorded. Multivariate analysis of demographics, comorbid risk factors, and symptoms was performed with logistic regression to provide odds ratios for the probability of EAC diagnosis. Results: The prevalence of patients with laryngopharyngeal reflux symptoms was significantly greater in the cases than comparison groups (P = 0.0005). The prevalence of laryngopharyngeal reflux symptoms increased as disease severity progressed from the non-GERD comparison group (19.6%) to GERD (26%), Barrett's esophagus (40%), and EAC patients (54%). Symptoms of GERD were less prevalent in cases (43%) when compared with Barrett's esophagus (66%) and GERD (86%) control groups (P < 0.001). Twenty-seven percent (17 of 63) of EAC patients never had GERD or laryngopharyngeal reflux symptoms. Fifty-seven percent of EAC patients presented without ever having typical GERD symptoms. Chronic cough, diabetes, and age emerged as independent risk factors for the development of EAC. Conclusions: Symptoms of laryngopharyngeal reflux are more prevalent in patients with EAC than typical GERD symptoms and may represent the only sign of disease. Chronic cough is an independent risk factor associated with the presence of EAC. Addition of laryngopharyngeal reflux symptoms to the current Barrett's screening guidelines is warranted. C1 Portland VA Med Ctr, Surg Serv, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. Univ Wisconsin, Sect Gastroenterol & Hepatol, Madison, WI 53706 USA. RP Jobe, BA (reprint author), Portland VA Med Ctr, Surg Serv, P3GS,POB 1034, Portland, OR 97207 USA. EM Blair.Jobe@med.va.gov FU NCI NIH HHS [R03 CA105959, R03 CA105959-01]; NIDDK NIH HHS [K23 DK066165, K23 DK066165-01] NR 36 TC 51 Z9 53 U1 1 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 JUN PY 2004 VL 239 IS 6 BP 849 EP 856 DI 10.1097/01.sla.0000128303.05898.ee PG 8 WC Surgery SC Surgery GA 823OM UT WOS:000221622600022 PM 15166964 ER PT J AU Minneci, PC Deans, KJ Kim, P Mathisen, DJ AF Minneci, PC Deans, KJ Kim, P Mathisen, DJ TI Foramen of Morgagni hernia: Changes in diagnosis and treatment SO ANNALS OF THORACIC SURGERY LA English DT Article ID LAPAROSCOPIC REPAIR; DIAPHRAGMATIC-HERNIA AB Background. Foramen of Morgagni hernias are uncommon diaphragmatic hernias for which there are limited reported data. The purpose of this study is to report a recent case series of foramen of Morgagni hernias in the context of new diagnostic and treatment modalities. Methods. A retrospective chart review was performed over a 15-year period, from 1987 to 2001. Twelve patients who had a foramen of Morgagni hernia repaired at our hospital were identified, and data from these patients were collected. Results. The average age at treatment was 45 years, with 50% of patients being asymptomatic. Radiographic evaluation included computed tomography, scans in two thirds of the patients with a 100% sensitivity for diagnosis. All hernias were right-sided, and the most common contents of the hernias were omentum and colon. The transabdominal route was the preferred surgical approach. Thoracoscopy was used in 2 patients to further characterize a mediastinal mass. Two patients underwent laparoscopic repair. Postoperative complications were infrequent, and there were no recurrences during a 6-month to 10-year follow-up. Conclusions. The emergence of highly accurate diagnostic computed tomography scans combined with less invasive surgical techniques utilizing laparoscopy and thoracoscopy has aided in the treatment of foramen of Morgagni hernias over the last 15 years. (C) 2004 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. RP Minneci, PC (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, Dept Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM dmathisen@partners.org NR 15 TC 50 Z9 52 U1 0 U2 2 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 JUN PY 2004 VL 77 IS 6 BP 1956 EP 1959 DI 10.1016/j.athoracsur.2003.12.028 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 824WF UT WOS:000221717200013 PM 15172245 ER PT J AU Gad, F Zahra, T Hasan, T Hamblin, MR AF Gad, F Zahra, T Hasan, T Hamblin, MR TI Effects of growth phase and extracellular slime on photodynamic inactivation of gram-positive pathogenic bacteria SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; LETHAL PHOTOSENSITIZATION; EFFICIENT PHOTOSENSITIZERS; WOUND INFECTIONS; ICA LOCUS; IN-VITRO; EPIDERMIDIS; AUREUS; PORPHYRINS; ADHERENCE AB The emergence of antibiotic resistance among pathogenic bacteria has led to efforts to find alternative antimicrobial therapeutics to which bacteria will not be easily able to develop resistance. One of these may be the combination of nontoxic dyes (photo sensitizers [PS]) and visible light, known as photodynamic therapy, and we have reported its use to treat localized infections in animal models. While it is known that gram-positive species are generally susceptible to photodynamic inactivation (PDI), the factors that govern variation in degrees of killing are unknown. We used isogenic pairs of wild-type and transposon mutants deficient in capsular polysaccharide and slime production generated from Staphylococcus epidermidis and Staphylococcus aureus to examine the effects of extracellular slime on susceptibility to PDI mediated by two cationic PS (a polylysine-chlorin(e6), conjugate, pL-c(e6), and methylene blue [MB]) and an anionic molecule, free c(e6), and subsequent exposure to 665-nm light at 0 to 40 J/cm(2). Free c(e6) gave more killing of mutant strains than wild type, despite the latter taking up more PS. Log-phase cultures were killed more than stationary-phase cultures, and this correlated with increased uptake. The cationic pL-c(e6) and MB gave similar uptakes and killing despite a 50-fold difference in incubation concentration. Differences in susceptibility between strains and between growth phases observed with free c(e6) largely disappeared with the cationic compounds despite significant differences in uptake. These data suggest that slime production and stationary phase can be obstacles against PDI for gram-positive bacteria but that these obstacles can be overcome by using cationic PS. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, BAR314B,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2, R01AI050875] NR 45 TC 110 Z9 114 U1 1 U2 15 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 JUN PY 2004 VL 48 IS 6 BP 2173 EP 2178 DI 10.1128/AAC.48.6.2173-2178.2004 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 826FE UT WOS:000221813900039 PM 15155218 ER PT J AU Oberley, TD AF Oberley, TD TI Mitochondria, manganese superoxide dismutase, and cancer SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material ID HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; MUTANT MICE; OVEREXPRESSION; PROLIFERATION; ANTIOXIDANT; MODULATION; ENZYMES; MODEL C1 William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@facstaff.wisc.edu NR 33 TC 23 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2004 VL 6 IS 3 BP 483 EP 487 DI 10.1089/152308604773934242 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 825QQ UT WOS:000221773500002 PM 15130275 ER PT J AU Kim, A Zhong, WX Oberley, TD AF Kim, A Zhong, WX Oberley, TD TI Reversible modulation of cell cycle kinetics in NIH/3T3 mouse fibroblasts by inducible overexpression of mitochondrial manganese superoxide dismutase SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID ANTIOXIDANT ENZYME LEVELS; PROSTATE CARCINOMA-CELLS; PARAQUAT RESISTANCE; HYDROGEN-PEROXIDE; GROWTH; INHIBITION; STATE; TUMOR; DNA; REPRESSOR AB To study the mechanism(s) by which manganese-containing superoxide dismutase (MnSOD) mediates cellular growth inhibition, an inducible retroviral vector system regulated by the lac repressor was used to overexpress MnSOD protein in NIH/3T3 cells. Increased MnSOD activity led to decreased cell growth due to prolonged cell cycle transition times in G(1) and S phases without significant changes in G(2)/M phase. Changes in cell cycle transition time were reversible and tightly correlated with MnSOD levels. A transient increase of reactive oxygen species and concomitant decrease in mitochondrial membrane potential were documented following MnSOD induction. N-Acetyl-L-cysteine prevented growth inhibition by MnSOD. Our data suggest that MnSOD may serve a physiological function of regulating cell cycle progression through its prooxidant activity of generating hydrogen peroxide, resulting in coordination of mitochondrial redox state and cellular proliferation. C1 William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Mol & Environm Toxicol Ctr, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@facstaff.wisc.edu FU NCI NIH HHS [CA14520-29] NR 32 TC 23 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2004 VL 6 IS 3 BP 489 EP 500 DI 10.1089/152308604773934251 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 825QQ UT WOS:000221773500003 PM 15130276 ER PT J AU Ridnour, LA Oberley, TD Oberley, LW AF Ridnour, LA Oberley, TD Oberley, LW TI Tumor suppressive effects of MnSOD overexpression may involve imbalance in peroxide generation versus peroxide removal SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; PROSTATE CARCINOMA-CELLS; SYRIAN-HAMSTER TISSUES; GLUTATHIONE-PEROXIDASE; GLIOMA-CELLS; IMMUNOHISTOCHEMICAL LOCALIZATION; DISC ELECTROPHORESIS; MALIGNANT PHENOTYPE; POLYACRYLAMIDE GELS; KIDNEY DEVELOPMENT AB Manganese superoxide dismutase (MnSOD) activity is generally lower in cancer cells when compared with their normal cell counterparts. Many studies have shown that replacing the diminished MnSOD activity leads to inhibition of the malignant phenotype. We sought to overexpress MnSOD in a chemically transformed, malignant rat cell line with low endogenous MnSOD activity to determine the effect on the malignant phenotype. After MnSOD cDNA transfection, clonal populations were characterized at the molecular level for protein, RNA, and DNA, as well as for in vitro and in vivo growth and in vivo lung metastasis. MnSOD transfectants, which both under- and overexpressed MnSOD protein, were identified. These transfectants demonstrated variations in glutathione peroxidase and catalase activity levels, indicating differences in peroxide-generating versus peroxide-metabolizing enzymes (antioxidant imbalance); these differences were suggestive of alterations in their abilities to metabolize peroxide when compared with the parental cell line. In addition, these transfectants demonstrated reductions in both in vitro and in vivo growth, as well as a reduction in metastatic potential, which correlated with antioxidant imbalance. These results suggest that the tumor suppressive effect of MnSOD overexpression is in part mediated by an antioxidant imbalance resulting in the reduced capacity to metabolize increased levels of intracellular peroxides. C1 Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. FU NCI NIH HHS [CA66081] NR 51 TC 49 Z9 53 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2004 VL 6 IS 3 BP 501 EP 512 DI 10.1089/152308604773934260 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 825QQ UT WOS:000221773500004 PM 15130277 ER PT J AU Zhong, WX Yan, T Webber, MM Oberley, TD AF Zhong, WX Yan, T Webber, MM Oberley, TD TI Alteration of cellular phenotype and responses to oxidative stress by manganese superoxide dismutase and a superoxide dismutase mimic in RWPE-2 human prostate adenocarcinoma cells SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID REACTIVE OXYGEN; VITAMIN-C; IN-VITRO; ANTIOXIDANT ENZYMES; HYDROGEN-PEROXIDE; GLUTATHIONE-PEROXIDASE; MALIGNANT PHENOTYPE; CANCER PREVENTION; BINDING-ACTIVITY; REDOX REGULATION AB To study biologic effects of increased manganese superoxide dismutase (MnSOD) on cell behavior, we overexpressed MnSOD in a human prostate cancer cell line RWPE-2 by cDNA transfection. Stable transfectants of MnSOD showed a two- to threefold increase in MnSOD protein and enzymatic activity and a decrease in growth rate with prolonged cell population doubling times. Western blot analysis showed a 1.5- to twofold increase in the cyclin-dependent kinase inhibitor p21(Waf1) in MnSOD transfectants. Overexpression of MnSOD resulted in a seven- to eightfold increase in reduced glutathione (GSH), 18- to 26-fold increase in oxidized glutathione (GSSG), and a two- to threefold decrease in the ratio of GSH to GSSG. MnSOD-overexpressing cells showed an increase in sensitivity to the cytotoxicity of buthionine sulfoximine, a glutathione-depleting agent, and vitamin C, but a decrease in sensitivity to sodium selenite. Treatment with a superoxide dismutase (SOD) mimic MnTMPyP resulted in similar effects of MnSOD overexpression on cell responses to vitamin C and selenium. These data demonstrate that overexpression of MnSOD or treatment with SOD mimics can result in antioxidant or prooxidant effects in cells, depending on the presence of other antioxidants and prooxidants. MnSOD also has redox regulatory effects on cell growth and gene expression. These findings suggest that MnSOD and SOD mimics have the potential for cancer prevention or treatment. C1 Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Ctr Clin Sci, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Hosp Cleveland, Ireland Comprehens Canc Ctr, Dept Radiat Oncol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. RP Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Ctr Clin Sci, K4-868,Box 8550,600 Highland Ave, Madison, WI 53792 USA. EM wzhong3@wisc.edu NR 50 TC 29 Z9 30 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2004 VL 6 IS 3 BP 513 EP 522 DI 10.1089/152308604773934279 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 825QQ UT WOS:000221773500005 PM 15130278 ER PT J AU Oberley, TD Xue, Y Zhao, YF Kiningham, K Szweda, LI Clair, DKS AF Oberley, TD Xue, Y Zhao, YF Kiningham, K Szweda, LI Clair, DKS TI In situ reduction of oxidative damage, increased cell turnover, and delay of mitochondrial injury by overexpression of manganese superoxide dismutase in a multistage skin carcinogenesis model SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID EPSILON TRANSGENIC MICE; ANTIOXIDANT ENZYMES; NIH/3T3 FIBROBLASTS; PROTEIN; TUMOR; LOCALIZATION; INHIBITION; CARCINOMA; GROWTH; KIDNEY AB To study early subcellular pathologic changes of tumorigenesis in mouse skin and possible modulation by overexpression of the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD), skin keratinocytes from nontransgenic (Ntg) and transgenic (TgH) mice overexpressing MnSOD topically treated with one dose of 7,12-dimethylbenz(a)anthracene (DMBA) and a subsequent dose of 12-O-tetradecanoylphorbol 13-acetate (TPA) were analyzed in situ for levels of MnSOD and the oxidative damage product 4-hydroxy2-nonenal (4HNE)-modified proteins using specific antibodies and immunogold electron microscopy. At all selected time points analyzed after TPA treatment, there was more MnSOD immunoreactive protein in mitochondria of keratinocytes of TgH mice than Ntg mice. Compared with untreated groups, there was a large increase in 4HNE-modified proteins at 6-24 h after TPA treatment, and this increase was larger in Ntg than TgH mice. Indices of mitosis and apoptosis of keratinocytes were greater in DMBA/TPA-treated TgH than Ntg mouse skin. Mitochondrial injury detected by transmission electron microscopy was delayed in keratinocytes of TgH compared with Ntg mice. The present study demonstrated that overexpression of MnSOD not only protected cells from oxidative damage, but also affected cell turnover kinetics. Thus, previously identified reduction in papilloma formation observed in TgH mice is correlated with mitochondrial events. C1 William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@facstaff.wisc.edu; dstc100@pop.uky.edu FU NCI NIH HHS [CA73599-S2, CA73599] NR 41 TC 14 Z9 15 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2004 VL 6 IS 3 BP 537 EP 548 DI 10.1089/152308604773934297 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 825QQ UT WOS:000221773500007 PM 15130280 ER PT J AU Liverant, GI Hofmann, SG Litz, BT AF Liverant, GI Hofmann, SG Litz, BT TI Coping and anxiety in college students after the September 11(th) terrorist attacks SO ANXIETY STRESS AND COPING LA English DT Article DE terrorism; September 11th; anxiety & coping ID POSTTRAUMATIC-STRESS-DISORDER; WORLD-TRADE-CENTER; PSYCHOMETRIC PROPERTIES; MENTAL-HEALTH; CITY; STRATEGIES; INVENTORY; SYMPTOMS; DISASTER; SYMPTOMATOLOGY AB This study investigated the presence of a stress response after the September 11(th) terrorist attacks in a sample of indirectly affected college students living in Boston, Massachusetts. Anxiety was examined at two time intervals, approximately 2 and 4 months after the attacks. Methods of coping with the stress of the attacks (assessed using the COPE Inventory) and their impact on initial and longer-term anxiety were also examined. Results demonstrated that the majority of college students in the study were severely psychologically impacted initially by the terrorist attacks. However, this initial impact appears to decay over time for most people. Several potentially maladaptive coping strategies were found to be predictive of initial anxiety, including denial, behavioral disengagement, mental disengagement, and focus on and venting of emotions. However, only focus on and venting of emotions was found to be uniquely predictive of longer-term anxiety. C1 Boston Univ, Sch Med, Boston Vet Affairs Hlth Care Syst, Natl Ctr PTSD, Boston, MA 02118 USA. RP Liverant, GI (reprint author), Boston Univ, Sch Med, Boston Vet Affairs Hlth Care Syst, Natl Ctr PTSD, Boston, MA 02118 USA. EM gliveran@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 NR 39 TC 27 Z9 27 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PD JUN PY 2004 VL 17 IS 2 BP 127 EP 139 DI 10.1080/0003379042000221412 PG 13 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 828UJ UT WOS:000221998500001 ER PT J AU Bowen, JT AF Bowen, JT TI Acute infectious pemphigus in a butcher, during an epizootic of foot and mouth disease, with a consideration of the possible relationship of the two affections. SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Bowen, JT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2004 VL 140 IS 6 BP 656 EP 656 PG 1 WC Dermatology SC Dermatology GA 827XI UT WOS:000221936600001 ER PT J AU Smith, CO Lipe, HP Bird, TD AF Smith, CO Lipe, HP Bird, TD TI Impact of presymptomatic genetic testing for hereditary ataxia and neuromuscular disorders SO ARCHIVES OF NEUROLOGY LA English DT Article ID LATE-ONSET DISORDERS; DISEASE; DISTRESS; SCALE AB Background: With the exception of Huntington disease, the psychological and psychosocial impact of DNA testing for neurogenetic disorders has not been well studied. Objective: To evaluate the psychosocial impact of genetic testing for autosomal dominant forms of hereditary ataxia and neuromuscular disorders. Patients: Fifty subjects at risk for autosomal dominant forms of spinocerebellar ataxia (n=11), muscular dystrophy (n=28), and hereditary neuropathy (n=12). Design and Setting: A prospective, descriptive, observational study in a university setting of individuals who underwent genetic counseling and DNA testing. Participants completed 3 questionnaires before testing and at regular intervals after testing. The questionnaire set included the Revised Impact of Event Scale, the Hospital Anxiety and Depression Scale, demographic information, and an assessment of attitudes and feelings about genetic testing. Results: Thirty-nine subjects (78%) completed 6 months to 5 years of posttest follow-up. Common reasons for pur-suing genetic testing were to provide an explanation for symptoms, emotional relief, and information for future planning. Thirty-four (68%) had positive and 16 (32%) had negative genetic results. In those with a positive result, 26 (76%) had nonspecific signs or symptoms of the relevant disorder. Forty-two participants (84%) felt genetic testing was beneficial. Groups with positive and negative test results coped well with results. However, 13 subjects (10 with positive and 3 with negative results) reported elevated anxiety levels, and 3 (1 with positive and 2 with negative results) expressed feelings of depression during the follow-up period. The test result was not predictive of anxiety or depression. Conclusions: Most individuals find neurogenetic testing to be beneficial, regardless of the result. Anxiety or depression may persist in some persons with positive or negative test results. Testing can have a demonstrable impact on family planning and interpersonal relationships. Further studies are needed to assess the long-term impact of such testing. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Geriatr 182, Seattle, WA 98108 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Geriatr 182, 1660 S Columbian Way, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu NR 14 TC 30 Z9 30 U1 0 U2 0 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 JUN PY 2004 VL 61 IS 6 BP 875 EP 880 DI 10.1001/archneur.61.6.875 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 827XL UT WOS:000221936900007 PM 15210524 ER PT J AU Kesari, S Bundock, EA AF Kesari, S Bundock, EA TI Punched-out skull SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kesari, S (reprint author), Dana Farber Canc Inst, Shields Warren 430,44 Binney St, Boston, MA 02115 USA. EM skesari@partners.org RI Kesari, Santosh/E-8461-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2004 VL 61 IS 6 BP 958 EP 959 DI 10.1001/archneur.61.6.958 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 827XL UT WOS:000221936900023 PM 15210540 ER PT J AU Ho, CL Wong, EYM Walton, DS AF Ho, CL Wong, EYM Walton, DS TI Goniosurgery for glaucoma complicating chronic childhood uveitis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID JUVENILE RHEUMATOID-ARTHRITIS; MITOMYCIN-C; MOLTENO IMPLANTATION; PEDIATRIC GLAUCOMA; YOUNG-PATIENTS; INFLAMMATORY GLAUCOMA; SECONDARY GLAUCOMA; FILTERING SURGERY; AHMED VALVE; TRABECULECTOMY AB Objectives: To describe the safety and efficacy of goniotomy in medically uncontrolled glaucoma complicating chronic uveitis and the factors affecting its outcome. Methods: All goniotomies performed by a single surgeon for refractory childhood uveitic glaucoma were retrospectively reviewed. Success was defined as final intraocular pressure (IOP) of no greater than 21 mm Hg without medications and qualified success as IOP of no greater than 21 mm Hg with medications. Unless otherwise indicated, data are expressed as mean+/-SD. Results: Fifty-four goniotomies were performed. in 40 eyes of 31 patients. juvenile rheumatoid arthritis-associated uveitis was the diagnosis in 30 eyes (75%). Eleven eyes (28%) were aphakic. Mean follow-up was 98.9 months (range, 2-324 months). Mean age at surgery was 10.3 +/- 4.7 years (range, 4-22 years), Mean preoperative IOP was 36.7 +/- 6.4 mm Hg while receiving a mean of 2.9 +/- 1.1 medications. Overall surgical success was achieved in 29 eyes (72%), including success in 22 (55%) and qualified success in 7 (18%) while receiving a mean of 1.6 +/- 1.1 medications. Mean postoperative IOP in the success and. qualified-success groups were 14.3 +/- 2.8 and 15.7 +/- 3.1 mm Hg, respectively. Kaplan-Meier survival probabilities (95% confidence interval) at 1, 5, and 10 years were 0.92 (0.82-1.00), 0.81 (0.65-0.97), and 0.71 (0.49-0.92), respectively. Phakic eyes, eyes with fewer peripheral anterior synechiae, patients younger than 10 years, and eyes with no prior surgery had significantly better outcomes. Hyphema, typically mild and transient, occurred in 43 procedures (80%). Conclusions: Goniosurgery is low risk and effective for refractory glaucoma complicating chronic childhood uveitis. it should be considered the surgical procedure of choice for this condition. Surgical outcome is adversely affected by increased. age, peripheral anterior synechiae, prior surgeries, and aphakia. C1 Singapore Natl Eye Ctr, Singapore, Singapore. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Ho, CL (reprint author), FRCSEd, 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA. EM hocl8@yahoo.com.sg NR 43 TC 24 Z9 25 U1 0 U2 1 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 JUN PY 2004 VL 122 IS 6 BP 838 EP 844 DI 10.1001/archopht.122.6.838 PG 7 WC Ophthalmology SC Ophthalmology GA 828IS UT WOS:000221967600004 PM 15197058 ER PT J AU Cho, EY Seddon, JM Rosner, B Willett, WC Hankinson, SE AF Cho, EY Seddon, JM Rosner, B Willett, WC Hankinson, SE TI Prospective study of intake of fruits, vegetables, vitamins, and carotenoids and risk of age-related maculopathy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; BLUE-MOUNTAINS-EYE; CORONARY-HEART-DISEASE; 1ST NATIONAL-HEALTH; MACULAR DEGENERATION; DIETARY-FAT; CARDIOVASCULAR-DISEASE; BETA-CAROTENE; PROSPECTIVE COHORT AB Objective: To examine the intake of antioxidant vitamins and carotenoids as well as fruits and vegetables in relation to the development of age-related maculopathy (ARM). Methods: We conducted a prospective follow-up study of women in the Nurses' Health Study and men in the Health Professionals Follow-up Study. We followed 77 562 women and 40 866 men who were at least 50 years of age and had no diagnosis of ARM or cancer at baseline for up to 18 years for women and up to 12 years for men. Fruit and vegetable intakes were assessed with a validated semi-quantitative food-frequency questionnaire up to 5 times for women and up to 3 times for men during follow-up. Results: A total of 464 (329 women and 135 men) incident cases of early ARM and 316 (217 women and 99 men) cases of neovascular ARM, all with visual loss of 20/30 or worse due primarily to ARM, were diagnosed during follow-up. Fruit intake was inversely associated with the risk of neovascular ARM. Participants who consumed 3 or more servings per day of fruits had a pooled multivariate relative risk of 0.64 (95% confidence interval, 0.44-0.93; P value for trend = .004) compared with those who consumed less than 1.5 servings per day. The results were similar in women and men. However, intakes of vegetables, antioxidant vitamins, or carotenoids were not strongly related to either early or neovascular ARM. Conclusion: These data suggest a protective role for fruit intake on the risk of neovascular ARM. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Epidemiol Unit, Boston, MA USA. RP Cho, EY (reprint author), Harvard Univ, Sch Med, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu FU NCI NIH HHS [CA55075, CA87969]; NEI NIH HHS [EY09611]; NHLBI NIH HHS [HL35464] NR 59 TC 125 Z9 132 U1 3 U2 12 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 JUN PY 2004 VL 122 IS 6 BP 883 EP 892 DI 10.1001/archopht.122.6.883 PG 10 WC Ophthalmology SC Ophthalmology GA 828IS UT WOS:000221967600010 PM 15197064 ER PT J AU Ray, S Friberg, TA Beatty, RR Loewenstein, J AF Ray, S Friberg, TA Beatty, RR Loewenstein, J TI Late posterior migration of glass intraocular foreign bodies SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Dept Ophthalmol, Retina Serv,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Loewenstein, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Retina Serv,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM john_loewenstein@meei.harvard.edu NR 3 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2004 VL 122 IS 6 BP 923 EP 926 DI 10.1001/archopht.122.6.923 PG 4 WC Ophthalmology SC Ophthalmology GA 828IS UT WOS:000221967600019 PM 15197073 ER PT J AU Mehta, RP Faquin, WC Deschler, DG AF Mehta, RP Faquin, WC Deschler, DG TI Pathology quiz case 1 - Acinic cell carcinoma of the parotid gland with ductal extension SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Mehta, RP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 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 JUN PY 2004 VL 130 IS 6 BP 790 EP + DI 10.1001/archotol.130.6.790 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 828ZQ UT WOS:000222012900017 PM 15210565 ER PT J AU Fay, BT Boninger, ML Fitzgerald, SG Souza, AL Cooper, RA Koontz, AM AF Fay, BT Boninger, ML Fitzgerald, SG Souza, AL Cooper, RA Koontz, AM TI Manual wheelchair pushrim dynamics in people with multiple sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE kinematics; kinetics; multiple sclerosis; rehabilitation; wheelchairs ID PROPULSION; FORCES; BIOMECHANICS; INDIVIDUALS; STRENGTH; KINETICS AB Objectives: To define differences in pushrim dynamics during manual wheelchair propulsion by users with multiple sclerosis (MS) relative to 2 control groups of subjects with spinal cord injury (SCI) and no disability (ND) and to investigate changes in propulsion biomechanics at different speeds and with fatigue. Design: Case-control. Setting: Biomechanics laboratory. Participants: A convenience sample of 42 people, 8 women and 6 men per group. Interventions: Not applicable. Main Outcome Measures: The propulsion pattern, mean maximum speed, percentage of time in push and recovery phases, push angle, push frequency, mean maximum resultant pushrim force, mean work and push cycle, and hand-to-pushrim coupling and decoupling effects. Results: The MS groups tended to use an arcing propulsion pattern more than did the control groups (Pmax=.003). The MS group pushed at a lower mean maximum velocity (v) when allowed to choose the speed of propulsion (nu(MS), .67+/-.20m/s; nu(SCI), 1.10+/-0.23m/s: P=.001), when asked to push at 1m/s (nu(MS), .91+/-.26m/s; nu(SCI), 1.12+/-0.11m/s; nu(ND), 1.05+/-0.13m/s; P=.010). and were unable to maintain a self-selected speed during a 5-minute trial (Deltanu(MS), .15+/-.02m/s; Deltanu(ND), .03+/-.06m/s; P<.001). The MS group spent a higher proportion of time in the push phase of propulsion (Pmax=.001). In general, the MS group had smaller push angles, but push frequencies similar to the controls. Statistically adjusted MS group pushrim forces and work per push measures varied depending on context, but in all trials the MS group displayed a braking effect when grasping and releasing the pushrim. The MS group had declines in most measures when pushing at a self-selected speed for 5 minutes. In all trials, the MS group was more likely to display asymmetry between right and left sides in biomechanic parameters. Conclusions: Manual wheelchair users with MS have difficulty grasping and releasing the pushrim and maintaining speed during a fatigue trial. This likely leads to a slow self-selected speed of propulsion that may not be functional. Clinicians should remember these results when prescribing manual wheelchairs for people with MS. C1 A VA Ctr Excellence, Human Engn Res Labs, Highland Dr Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Alberta, Fac Rehabil Med, Edmonton, AB, Canada. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, 151R-1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM boninger@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 21 TC 12 Z9 12 U1 3 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2004 VL 85 IS 6 BP 935 EP 942 DI 10.1016/j.apmr.2003.08.093 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 826NK UT WOS:000221835600011 PM 15179647 ER PT J AU Shen, WT Kebebew, E Duh, QY Clark, OH AF Shen, WT Kebebew, E Duh, QY Clark, OH TI Predictors of airway complications after thyroidectomy for substernal goiter 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, CA SP Pacific Coast Surg Assoc ID OPERATIVE MANAGEMENT; RETROSTERNAL GOITER; SURGICAL-TREATMENT AB Hypothesis: Airway complications after thyroidectomy for substernal goiter can be predicted by preoperative symptom profiles, radiologic findings, or other factors. Design: Retrospective review. Settings: A university tertiary care center and a veterans' hospital. Patients: Sixty patients with. substernal goiter who underwent thyroidectomy between 1993 and 2002. Main Outcome Measures: Symptoms, preoperative radiologic findings, extent of thyroid resection, tumor size, and postoperative complications. Results: Dysphagia was the most common preoperative symptom (n = 26), followed by dyspnea (n = 21), orthopnea (n = 13), and hoarseness (n = 6); 18 patients (30%) had superior vena caval obstruction. Thirteen patients (22%) were asymptomatic. Preoperative imaging identified tracheal deviation or compression in 45 patients (75%). Substernal goiter was resected via a cervical approach in 59 patients (98%). Of 47 patients with preoperative symptoms, 41 (87%) reported improvement postoperatively. Seven patients (12%) had postoperative airway complications: I developed a neck hematoma requiring reoperation, and 6 could not be immediately extubated; all 6 were successfully extubated after 1 to 10 days. Patients with airway complications were older (mean +/-SEM, 70.3 +/- 3.6 years vs 61.5 +/- 2.2 years), had larger goiters (mean +/- SEM, 210.7 +/- 37.0 g vs 112.2 +/- 7.7 g), and were more likely to have tracheal compression on preoperative imaging than those who did not have complications (P<.05). Conclusions: Most patients with substernal goiters under-went thyroid resection via a cervical approach with an improvement in symptoms. The few patients who developed postoperative airway complications were older, had larger goiters, and were more likely to have tracheal compression on preoperative imaging than those without airway complications. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Duh, QY (reprint author), San Francisco Vet Affairs Med Ctr, Surg Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM quan-yang.duh@med.va.gov NR 15 TC 43 Z9 48 U1 1 U2 2 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 JUN PY 2004 VL 139 IS 6 BP 656 EP 659 DI 10.1001/archsurg.139.6.656 PG 4 WC Surgery SC Surgery GA 828IG UT WOS:000221966400025 PM 15197094 ER PT J AU Liu, WM Szalai, A Zhao, LM Liu, D Martin, F Kimberly, RP Zhou, T Carter, RH AF Liu, WM Szalai, A Zhao, LM Liu, D Martin, F Kimberly, RP Zhou, T Carter, RH TI Control of spontaneous B lymphocyte autoimmunity with adenovirus-encoded soluble TACI SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NECROSIS-FACTOR FAMILY; MRL-LPR MICE; CELL MATURATION; TNF RECEPTOR; T-CELLS; BAFF; SURVIVAL; DISEASE; LIGAND; MEMBER AB Objective. Serum B lymphocyte stimulator (BLyS) is increased in autoimmune diseases, both in animal models and in humans. This study examined the effect of BLyS blockade in 3 animal models of lupus. Methods. Antibodies and lupus-like disease manifestations were examined in mice after administration of a single injection of an adenoviral construct for the transmembrane activator and CAML interactor receptor (AdTACI) that produces high serum levels of TACI-Fc fusion protein. Results. In C57BL/6 (B6) lpr/lpr mice (B6.lpr/lpr), which were used to model autoimmunity in the absence of severe disease, treatment of younger mice with AdTACI prevented the development of hypergammaglobulinemia. In contrast, use of AdTACI for BLyS blockade had only transient effects on the levels of IgG in normal B6 mice. AdTACI blocked the development of autoantibodies in younger B6.lpr/lpr mice and reversed the production of autoantibodies in older B6.lpr/lpr mice, and also reduced the numbers of splenic plasma cells. In MRL.lpr/lpr mice, which were used to examine disease manifestations, AdTACI reduced the extent of glomerulonephritis and proteinuria and improved survival, but had little effect on T cell infiltration and interstitial nephritis. However, in (NZB X NZW)F-1 mice, AdTACI induced neutralizing anti-TACI antibodies and failed to reduce the numbers of B cells. Conclusion. BLyS blockade has little effect on IgG levels in normal mice, but reverses the production of spontaneously produced IgM and IgG autoantibodies in the setting of established autoimmunity. Blockade of BLyS ameliorates B cell-dependent disease manifestations even in the MRL.lpr/lpr model, but its effectiveness on autonomous T cell aspects of the disease is limited. Moreover, its effectiveness is neutralized by anti-TACI antibodies when present. These results provide a basis for understanding the potential effects of BLyS blockade in human disease. C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Carter, RH (reprint author), Univ Alabama, 409 LHRB,701 S 10th St, Birmingham, AL 35294 USA. EM rcarter@uab.edu OI Kimberly, Robert/0000-0002-5330-3086 NR 35 TC 42 Z9 43 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2004 VL 50 IS 6 BP 1884 EP 1896 DI 10.1002/art.2090 PG 13 WC Rheumatology SC Rheumatology GA 827CL UT WOS:000221876000023 PM 15188365 ER PT J AU Trefler, E Fitzgerald, SG Hobson, DA Bursick, T Joseph, R AF Trefler, E Fitzgerald, SG Hobson, DA Bursick, T Joseph, R TI Outcomes of wheelchair systems intervention with residents of long-term care facilities SO ASSISTIVE TECHNOLOGY LA English DT Article DE elderly; outcomes; wheelchair ID NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; MOBILITY AB This pilot study was designed to measure the effects of individually prescribed wheelchair systems on posture and reach, mobility, quality of life, and satisfaction with technology for residents of long-term care facilities. Thirty persons 60 years of age or older who resided permanently in a long-term care facility and who used seating and mobility systems for 6 hours or more each day were recruited for this project. Outcomes included timed independent mobility, forward and lateral reach, quality of life, and satisfaction with assistive technology. The study used semicrossover design with participants measured three times. Measurements were first made in the existing seating and mobility system and a second time immediately after participants were provided with individually prescribed seating and mobility systems. The final measurement was 3 months after the delivery of the individually prescribed system. Results indicated that individually fitted wheelchair systems for elderly residents of long-term care facilities are beneficial. Participants had less difficulty independently propelling their systems and increased forward reach, quality of life for social function and physical role, and satisfaction with the new wheelchair technology. Persons residing in extended care facilities benefit from receiving individually prescribed wheelchair systems. The individual systems enhance elderly persons' independent mobility, functional reach, feeling of well-being, and satisfaction with their assistive technology. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Apria Healthcare, Pittsburgh, PA USA. Invacare Corp, Chicago, IL USA. Univ Pittsburgh, SHRS, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R-1, Pittsburgh, PA 15206 USA. NR 20 TC 29 Z9 29 U1 1 U2 6 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SUM PY 2004 VL 16 IS 1 BP 18 EP 27 PG 10 WC Rehabilitation SC Rehabilitation GA 883OP UT WOS:000226022900003 PM 15357146 ER PT J AU Merfeld, DM AF Merfeld, DM TI Internal models and spatial orientation SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID GRAVITO-INERTIAL CUES; MOTION SICKNESS; HUMANS; TILT; PERCEPTION; ROTATION; MONKEY AB Aspects of "emulation theory" have been seminal to our understanding of spatial orientation for more than 50 years. Sometimes called internal models, existing implementations include both traditional observers and optimal observers (Kalman filters). This theoretical approach has been quite successful in helping understand and explain spatial orientation-successful enough that experiments have been guided by model predictions. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu NR 27 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD JUN PY 2004 VL 27 IS 3 BP 410 EP + PG 8 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 883NY UT WOS:000226021100052 ER PT J AU Figlewicz, DP Bennett, J Evans, SB Kaiyala, K Sipols, AJ Benoit, SC AF Figlewicz, DP Bennett, J Evans, SB Kaiyala, K Sipols, AJ Benoit, SC TI Intraventricular insulin and leptin reverse place preference conditioned with high-fat diet in rats SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID BRAIN REWARD CIRCUITRY; NUCLEUS-ACCUMBENS; FOOD-INTAKE; BODY-WEIGHT; INSTRUMENTAL PERFORMANCE; INDUCED ANOREXIA; ENERGY-BALANCE; DRUG REWARD; SHORT-TERM; SUCROSE AB The authors hypothesized that insulin and leptin, hormones that convey metabolic and energy balance status to the central nervous system (CNS), decrease the reward value of food, as assessed by conditioned place preference (CPP). CPP to high-fat diet was blocked in ad-lib fed rats given intraventricular insulin or leptin throughout training and test or acutely before the test. Insulin or leptin given only during the training period did not block CPP. Thus, elevated insulin and leptin do not prevent learning a food's reward value, but instead block its retrieval. Food-restricted rats receiving cerebrospinal fluid, insulin, or leptin had comparable CPPs. Results indicate that the CNS roles of insulin and leptin may include processes involving memory and reward. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pediat Dent, Seattle, WA 98195 USA. Latvian State Univ, Dept Med, LV-1063 Riga, Latvia. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. RP Figlewicz, DP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Metab Endocrinol 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU NIDA NIH HHS [R21 DA 14545]; NIDDK NIH HHS [R01 DK 40963]; NIMH NIH HHS [R03 MH 65353] NR 65 TC 111 Z9 112 U1 4 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 EI 1939-0084 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 2004 VL 118 IS 3 BP 479 EP 487 DI 10.1037/0735-7044.118.3.479 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 825IO UT WOS:000221750200005 PM 15174925 ER PT J AU Hershman, JM AF Hershman, JM TI Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE human chorionic gonaclotropin; thyrotropin; pregnancy; hyperemesis gravidarum; hydaticliform mole; choriocarcinoma; mutant thyroid-stimulating hormone receptor ID INTRINSIC THYROTROPIC ACTIVITY; COMPLETE HYDATIDIFORM MOLE; NORMAL PREGNANT-WOMEN; HUMAN TSH RECEPTORS; HYPEREMESIS GRAVIDARUM; GESTATIONAL THYROTOXICOSIS; STIMULATING ACTIVITY; IODIDE UPTAKE; HYPERTHYROIDISM; HCG AB Human chorionic gonadotropin (hCG) is a glycoprotein hormone that has structural similarity to TSH. At the time of the peak hCG levels in normal pregnancy, serum TSH levels fall and bear a mirror image to the hCG peak. This reduction in TSH suggests that hCG causes an increased secretion of T4 and T3. Women with hyperemisis gravidarum often have high hCG levels that cause transient hyperthyroidsm. In the vast majority of such patients, there will be spontaneous remission of the increased thyroid function when the vomiting stops in several weeks. When there are clinical features of hyperthyroidism, it is be reasonable to treat with antithyroid drugs or a beta-adrenergic blocker, but treatment is rarely required beyond 22 weeks of gestation. Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors, either hydatiditform mole or choriocarcinoma. The diagnosis of hydatidiform mole is made by ultrasonography that shows a 'snowstorm' appearance without a fetus. Hydatidiform moles secrete large amounts of hCG proportional to the mass of the tumor. The development of hyperthyroidism requires hCG levels of > 200 U/ml that are sustained for several weeks. Removal of the mole cures the hyperthyroidism. There have been many case reports of hyperthyroidism in women with choriocarcinoma and high hCG levels. The principal therapy is chemotherapy, usually given at a specialized center. With effective chemotherapy, long-term survival exceeds 95%. A unique family with recurrent gestational hyperthyroidism associated with hyperemesis gravidarum was found to have a mutation in the extracellular domain of the TSH receptor that made it responsive to normal levels of hCG. C1 VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Hershman, JM (reprint author), VA Greater Los Angeles Healthcare Ctr, IIID,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 71 TC 72 Z9 74 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2004 VL 18 IS 2 BP 249 EP 265 DI 10.1016/j.beem.2004.03.010 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 830XT UT WOS:000222158200010 PM 15157839 ER PT J AU Taha, TA Argraves, KM Obeid, LM AF Taha, TA Argraves, KM Obeid, LM TI Sphingosine-1-phosphate receptors: receptor specificity versus functional redundancy SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE sphingolipid; lysophospholipid; sphingosine-1-phosphate; S1P; edg; GPCR ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR; SMOOTH-MUSCLE-CELLS; MULTIPLE SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; TRANSPLANTATION DRUG; VASCULAR MATURATION; BARRIER INTEGRITY; FTY720; MIGRATION AB Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that has recently been shown to bind cell surface SIP receptors (previously called endothelial differentiation gene (Edg) receptors), which are members of the G-protein-coupled family of receptors. Signaling via S1P is a complex process, as cells usually express a number of these receptors on their surfaces. Many of the SIP receptors share common G-proteins, invoking the question of how these receptors are specific in their actions. This review describes the coupling pathways of SIP receptors, and highlights the in vitro and in vivo evidence for the "uniqueness" of each receptor in activating downstream signaling pathways, taking the effect of SIP on migration as an example. (C) 2004 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Vet Affairs, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA097132-01A1]; NCRR NIH HHS [P20 RR17677-01]; NIA NIH HHS [AG16583]; NIGMS NIH HHS [GM62887] NR 59 TC 132 Z9 136 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD JUN 1 PY 2004 VL 1682 IS 1-3 BP 48 EP 55 DI 10.1016/S1388-1981(04)00023-X PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 831LN UT WOS:000222196000006 PM 15158755 ER PT J AU Boudreau, EA Pelczer, I Borer, PN Heffron, GJ LaPlante, SR AF Boudreau, EA Pelczer, I Borer, PN Heffron, GJ LaPlante, SR TI Changes in drug C-13 NMR chemical shifts as a tool for monitoring interactions with DNA SO BIOPHYSICAL CHEMISTRY LA English DT Article DE netropsin; ligand; nuclear magnetic resonance (NMR); deoxyribo nucleic acid (DNA); drug; chemical shift; carbon; inhibitor ID SEQUENCE-DEPENDENT RECOGNITION; MINOR-GROOVE LIGANDS; G-C-G; OLIGONUCLEOTIDE DUPLEXES; NETROPSIN COMPLEXATION; STRUCTURAL FEATURES; MAGNETIC-RESONANCE; PROTON DETECTION; AQUEOUS-SOLUTION; ASSIGNMENT AB The antibiotic drug, netropsin, was complexed with the DNA oligonucleotide duplex [d(GGTATACC)](2) to monitor drug C-13 NMR chemical shifts changes. The binding mode of netropsin to the minor groove of DNA is well-known, and served as a good model for evaluating the relative sensitivity of 13C chemical shifts to hydrogen bonding. Large downfield shifts were observed for four resonances of carbons that neighbor sites which are known to form hydrogen bond interactions with the DNA minor groove. Many of the remaining resonances of netropsin exhibit shielding or relatively smaller deshielding changes. Based on the model system presented here, large deshielding NMR shift changes of a ligand upon macromolecule binding can likely be attributed to hydrogen bond formation at nearby sites. (C) 2003 Elsevier B.V. All rights reserved. C1 Boehringer Ingelheim Canada Ltd, Res & Dev, Laval, PQ H7S 2G5, Canada. Portland VA Med Ctr, Hlth Sci Res & Dev Program, Portland, OR 97239 USA. Princeton Univ, Dept Chem, Princeton, NJ 08540 USA. Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP LaPlante, SR (reprint author), Boehringer Ingelheim Canada Ltd, Res & Dev, 2100 Cunard St, Laval, PQ H7S 2G5, Canada. EM slaplante@lav.boehringer-ingelheim.com NR 36 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD JUN 1 PY 2004 VL 109 IS 3 BP 333 EP 344 DI 10.1016/j.bpc.2003.12.005 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 820EC UT WOS:000221368900001 PM 15110931 ER PT J AU Cavalli, A Prota, AE Stehle, T Dermody, TS Recanatini, M Folkers, G Scapozza, L AF Cavalli, A Prota, AE Stehle, T Dermody, TS Recanatini, M Folkers, G Scapozza, L TI A molecular dynamics study of reovirus attachment protein sigma 1 reveals conformational changes in sigma 1 structure SO BIOPHYSICAL JOURNAL LA English DT Article ID INFLUENZA HEMAGGLUTININ; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ADENOVIRUS FIBER; NUCLEIC-ACIDS; LOW PH; PARTICLES; SIMULATIONS; RECEPTOR; DOMAINS AB Molecular dynamics simulations were performed using the recently determined crystal structure of the reovirus attachment protein, sigma1. These studies were conducted to improve an understanding of two unique features of sigma1 structure: the protonation state of Asp(345), which is buried in the sigma1 trimer interface, and the flexibility of the protein at a defined region below the receptor-binding head domain. Three copies of aspartic acids Asp(345) and Asp(346) cluster in a solvent-inaccessible and hydrophobic region at the sigma1 trimer interface. These residues are hypothesized to mediate conformational changes in sigma1 during viral attachment or cell entry. Our results indicate that protonation of Asp(345) is essential to the integrity of the trimeric structure seen by x-ray crystallography, whereas deprotonation induces structural changes that destabilize the trimer interface. This finding was confirmed by electrostatic calculations using the finite difference Poisson-Boltzmann method. Earlier studies show that sigma1 can exist in retracted and extended conformations on the viral surface. Since protonated Asp(345) is necessary to form a stable, extended trimer, our results suggest that protonation of Asp(345) may allow for a structural transition from a partially detrimerized molecule to the fully formed trimer seen in the crystal structure. Additional studies were conducted to quantify the previously observed flexibility of sigma1 at a defined region below the receptor-binding head domain. Increased mobility was observed for three polar residues (Ser(291), Thr(292), and Ser(293)) located within an insertion between the second and third beta-spiral repeats of the crystallized portion of the sigma1 tail. These amino acids interact with water molecules of the solvent bulk and are responsible for oscillating movement of the head of similar to50degrees during 5 ns of simulations. This flexibility may facilitate viral attachment and also function in cell entry and disassembly. These findings provide new insights about the conformational dynamics of sigma1 that likely underlie the initiation of the reovirus infectious cycle. C1 Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy. ETH, Dept Chem & Appl Biosci, Zurich, Switzerland. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37212 USA. RP Cavalli, A (reprint author), Univ Bologna, Dept Pharmaceut Sci, Via Belmeloro 6, I-40126 Bologna, Italy. EM andrea.cavalli@unibo.it; leonardo.scapozza@pharma.ethz.ch FU NIAID NIH HHS [AI38296, R01 AI045716, AI45716, R01 AI038296, R37 AI038296]; NIGMS NIH HHS [GM67853, R01 GM067853] NR 41 TC 5 Z9 9 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2004 VL 86 IS 6 BP 3423 EP 3431 DI 10.1529/biophysj.103.030825 PG 9 WC Biophysics SC Biophysics GA 829GK UT WOS:000222035200007 PM 15189844 ER PT J AU Sachs, G Chengappa, KNR Suppes, T Mullen, JA Brecher, M Devine, NA Sweitzer, DE AF Sachs, G Chengappa, KNR Suppes, T Mullen, JA Brecher, M Devine, NA Sweitzer, DE TI Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; combination therapy; divalproex; lithium; mania; quetiapine ID NEGATIVE SYNDROME SCALE; MOOD STABILIZER; RATING-SCALE; SCHIZOPHRENIA; DISORDER; HALOPERIDOL; EFFICACY; OLANZAPINE; SEROQUEL AB Objective: Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania. Methods: Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg to 0.7-1.0 mEq/L; or DVP to 50-100 mug/mL. Results: Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (greater than or equal to50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension. Conclusions: Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy. C1 Harvard Bipolar Res Program, Boston, MA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. AstraZeneca, Wilmington, DE USA. RP Sachs, G (reprint author), Massachusetts Gen Hosp, Harvard Bipolar Res Program, 50 Staniford St,5th Floor, Boston, MA 02114 USA. EM sachsg@aol.com NR 33 TC 170 Z9 175 U1 2 U2 3 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 JUN PY 2004 VL 6 IS 3 BP 213 EP 223 DI 10.1111/j.1399-5618.2004.00115.x PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 822FW UT WOS:000221525200005 PM 15117400 ER PT J AU Deckersbach, T Savage, CR Reilly-Harrington, N Clark, L Sachs, G Rauch, SL AF Deckersbach, T Savage, CR Reilly-Harrington, N Clark, L Sachs, G Rauch, SL TI Episodic memory impairment in bipolar disorder and obsessive-compulsive disorder: the role of memory strategies SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; cognitive dysfunction; episodic memory; euthymic; executive functioning ID DORSOLATERAL PREFRONTAL CORTEX; MAGNETIC-RESONANCE; TEMPORAL-LOBE; EUTHYMIC PATIENTS; MOOD DISORDERS; NEUROPSYCHOLOGICAL FUNCTION; COGNITIVE DYSFUNCTIONS; LEARNING-STRATEGIES; EXPLICIT MEMORY; RATING-SCALE AB Background: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during mood episodes but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is an impairment in verbal episodic memory. Verbal learning and memory depend on individuals' ability to organize verbal information appropriately during learning. The purpose of the present Study was (i) to determine whether episodic memory impairment in euthymic individuals with bipolar disorder is mediated by impairments in organization of verbal information during learning and (ii) to compare the characteristics of memory impairment in bipolar disorder with that previously found in obsessive-compulsive disorder (OCD). Methods: Study participants were 30 individuals with DSM-IV bipolar I disorder (BP-I), 30 individuals with DSM-IV OCD and 30 normal control participants matched for age, gender and education. Participants completed the California Verbal Learning Test (CVLT), a well-established measure of verbal learning and memory that enables assessment of verbal organization strategies during learning. Results: Compared with control subjects, both BP-I and OCD participants showed impaired performance in long-delayed free recall and verbal organization strategies during learning. BP-I participants showed greater long-delay free recall difficulties but not greater verbal organization difficulties during learning than OCD participants. For OCD participants, the long-delay recall impairment was mediated by difficulties using verbal organizational strategies during learning. In contrast, the group difference in long-delayed free recall between BP-I and control participants remained significant even when semantic clustering was introduced as a mediator. This indicated that BP-I participants' long-delayed free recall difficulties were mediated to a lesser extent by difficulties using verbal organizational strategies than for OCD participants. Conclusions: Verbal episodic memory problems in individuals with bipolar I disorder and OCD are mediated to different degrees by difficulties using semantic clustering encoding strategies compared with control participants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat,Harvard Bipolar Res Program, Psychiat Neurosci Program, Charlestown, MA 02129 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Dept Psychiat & Behav Sci, Kansas City, KS 66103 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. RP Deckersbach, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat,Harvard Bipolar Res Program, Psychiat Neurosci Program, 149-2611,Bldg 149,13th St, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org FU NIMH NIH HHS [MH60219] NR 76 TC 85 Z9 86 U1 4 U2 10 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 JUN PY 2004 VL 6 IS 3 BP 233 EP 244 DI 10.1111/j.1399-5618.2004.00118.x PG 12 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 822FW UT WOS:000221525200007 PM 15117402 ER PT J AU Sekeres, MA Peterson, B Dodge, RK Mayer, RJ Moore, JO Lee, EJ Kolitz, J Baer, MR Schiffer, CA Carroll, AJ Vardiman, JW Davey, FR Bloomfield, CD Larson, RA Stone, RM AF Sekeres, MA Peterson, B Dodge, RK Mayer, RJ Moore, JO Lee, EJ Kolitz, J Baer, MR Schiffer, CA Carroll, AJ Vardiman, JW Davey, FR Bloomfield, CD Larson, RA Stone, RM CA Canc Leukemia Grp B TI Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia SO BLOOD LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PA SP Amer Soc Hematol ID ACUTE LYMPHOBLASTIC-LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; RESISTANCE MODULATOR PSC-833; ACUTE PROMYELOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; GROUP-B; SOCIOECONOMIC-STATUS; ETHNIC-DIFFERENCES; COLORECTAL-CANCER; ELDERLY PATIENTS AB Whites have a more favorable prognosis than African Americans for a number of cancers. The relationship between race and outcome is less clear in acute myelold leukemia (AML). Using data from 7 Cancer and Leukemia Group B studies initiated from 1985 to 1997, we conducted a retrospective cross-sectional analysis of 2570 patients (270 African American and 2300 white) with de novo AML who received induction chemotherapy. African Americans were younger than whites (48 versus 54 years, P < .001). African Americans also had different cytogenetic risk group distributions than whites (P < .001): they were more commonly classified in the favorable (23% versus 14%) and unfavorable (31% versus 23%) groups, and less commonly classified in the intermediate group (47% versus 63%). African American men had a lower complete remission (CR) rate (54%, compared with 64% for white men, 65% for white women, and 70% for African American women, P = .001) and a worse overall survival compared with all other patients (P = .004), when known risk factors are taken into account. African Americans and whites with AML differ with respect to important prognostic factors. African American men have worse CR rates and overall survival than whites and African American women, and should be considered a poor-risk group. (C) 2004 by The American Society of Hematology C1 Case Western Reserve Univ, Cleveland Clin Fdn, Lerner Coll Med, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Sinai Hosp, Baltimore, MD 21215 USA. NYU, Sch Med, N Shore Univ Hosp, Manhasset, NY USA. Roswell Pk Canc Inst, Buffalo, NY USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Chicago, Chicago, IL 60637 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Ohio State Univ, Columbus, OH 43210 USA. RP Sekeres, MA (reprint author), Case Western Reserve Univ, Cleveland Clin Fdn, Lerner Coll Med, Dept Hematol & Med Oncol, Desk R35,9500 Euclid Ave, Cleveland, OH 44195 USA. EM sekerem@ccf.org OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA101140, CA33601, CA3946, CA77658, CA31946, CA16058] NR 45 TC 52 Z9 56 U1 1 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 JUN 1 PY 2004 VL 103 IS 11 BP 4036 EP 4042 DI 10.1182/blood-2003-09-3118 PG 7 WC Hematology SC Hematology GA 824BB UT WOS:000221657600016 PM 14976037 ER PT J AU Kurtz, J Shaffer, J Lie, A Anosova, N Benichou, G Sykes, M AF Kurtz, J Shaffer, J Lie, A Anosova, N Benichou, G Sykes, M TI Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells SO BLOOD LA English DT Article ID DONOR-SPECIFIC TOLERANCE; VERSUS-HOST-DISEASE; IN-VIVO; COSTIMULATORY BLOCKADE; ANTIGEN RECEPTOR; HEMATOPOIETIC CHIMERISM; ALLOGRAFT TOLERANCE; CLONAL DELETION; SKIN ALLOGRAFTS; CUTTING EDGE AB Anti-CD154 (CD40L) monoclonal antibody (mAb) plus bone marrow transplantation (BMT) in mice receiving CD8 cell-depleting mAb leads to long-term mixed hematopoietic chimerism and systemic donor-specific tolerance through peripheral and central deletional mechanisms. However, CD4(+) T-cell tolerance is demonstrable in vitro and in vivo rapidly following BMT, before deletion of donor,reactive CD4 cells is complete, suggesting the involvement of other mechanisms. We examined these mechanisms in more detail. Spot enzyme-linked immunosorbent (ELISPOT) analysis revealed specific tolerization (within 4 to 15 days) of both T helper 1 (Th1) and Th2 cytokine responses to the donor, with no evidence for cytokine deviation. Tolerant lymphocytes did not significantly down-regulate rejection by naive donor-reactive T cells in adoptive transfer experiments. No evidence for linked suppression was obtained. when skin expressing donor alloantigens in association with third-party alloantigens was grafted. T-cell receptor (TCR) transgenic mixing studies revealed that specific peripheral deletion of alloreactive CD4 T cells occurs over the first 4 weeks following BMT with anti-CD154. In contrast to models involving anti-CD154 without BMT, BMT with anti-CD154 leads to the rapid induction of anergy followed by deletion of Ore-existing donor-reactive peripheral CD4(+) T cells; the rapid deletion of these cells obviates the need for a regulatory cell population to suppress CD4 cell-mediated alloreactivity. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cellular & Mol Immunol CMI Lab, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. EM m.egan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [HL49915]; NIAID NIH HHS [1T32 AI-07529] NR 49 TC 79 Z9 80 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 JUN 1 PY 2004 VL 103 IS 11 BP 4336 EP 4343 DI 10.1182/blood-2003-08-2642 PG 8 WC Hematology SC Hematology GA 824BB UT WOS:000221657600057 PM 14962909 ER PT J AU Schmahmann, JD Ko, R MacMore, J AF Schmahmann, JD Ko, R MacMore, J TI The human basis pontis: motor syndromes and topographic organization SO BRAIN LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Academy-of-Neurology CY APR 02-03, 2003 CL HONOLULU, HI SP Amer Acad Neurol DE pons; lacune; dysmetria; dysarthria; topography ID CLUMSY HAND SYNDROME; FOU RIRE PRODROMIQUE; ATAXIC-HEMIPARESIS; RHESUS-MONKEY; BRAIN-STEM; CEREBELLAR CONTRIBUTION; DISCONNEXION SYNDROMES; PATHOLOGICAL LAUGHTER; LACUNAR STROKE; INFARCTION AB Clinical-anatomic correlations were performed in 25 patients with focal infarcts in the basilar pons to determine whether pontine lacunar syndromes conform to discrete clinical entities, and whether there is topographic organization of the motor system within the human basis pontis. Twelve clinical signs were scored on a 6-point scale, neuroimaging lesions were mapped and defined with statistical certainty, and structure-function correlation was performed to develop a topographic map of motor function. Clinical findings ranged from major devastation following extensive lesions (pure motor hemiplegia) to incomplete basilar pontine syndrome and restricted deficits after small focal lesions (ataxic hemiparesis, dysarthria-clumsy hand syndrome, dysarthria-dysmetria and dysarthria-facial paresis). The syndromes are not absolutely discrete, and are distinguished from each other by the relative degree of involvement of each clinical feature. Structure-function correlations indicate that strength is conveyed by the corticofugal fibres destined for the spinal cord, whereas dysmetria results from lesions involving the neurons of the basilar pons that link the ipsilateral cerebral cortex with the contralateral cerebellar hemisphere. Facial movement and articulation are localized to rostral and medial basilar pons; hand coordination is medial and ventral in rostral and mid-pons; and arm function is represented ventral and lateral to the hand. Leg coordination is in the caudal half of the pons, with lateral predominance. Swallowing is dependent upon the integrity of a number of regions in the rostral pons. Gait is in medial and lateral locations throughout the rostral- caudal extent of the pons. Dysmetria ipsilateral to the lesion constitutes a disconnection syndrome, as it occurs when the hemipontine lesion is extensive and interrupts pontocerebellar fibres traversing from the opposite, intact side of the pons. The heterogeneity of manifestations reflects the well-organized topography of motor function in the human basis pontis, in agreement with the anatomic organization of the motor corticopontine projections in the monkey. Higher order impairments including motor neglect, paraphasic errors and pathological laughter result from rostral and medial pontine lesions, and may result from disruption of the pontine component of associative corticopontocerebellar circuits. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol VBK 915, Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org NR 74 TC 58 Z9 60 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2004 VL 127 BP 1269 EP 1291 DI 10.1093/brain/awh138 PN 6 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 825IY UT WOS:000221751200006 PM 15128614 ER PT J AU Zhao, JC Zacks, DN Gragoudas, ES Pasquale, LR AF Zhao, JC Zacks, DN Gragoudas, ES Pasquale, LR TI Pupil sparing excision of an atypical iris melanocytoma induces remission of secondary glaucoma SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-PRESSURE ELEVATION; EYES C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Louis_Pasquale@meei.harvard.edu RI Zacks, David/I-4394-2013 NR 7 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 2004 VL 88 IS 6 BP 842 EP 843 DI 10.1136/bjo.2003.037150 PG 2 WC Ophthalmology SC Ophthalmology GA 821QS UT WOS:000221478000034 PM 15148231 ER PT J AU Wu-Chen, WY Bernardino, CR Rubin, PAD Wu-Chen, WY Bernardino, CR AF Wu-Chen, WY Bernardino, CR Rubin, PAD Wu-Chen, WY Bernardino, CR TI The clinical evolution of a kissing naevus after incomplete excision SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article C1 Emory Univ, Sch Med, Emory Eye Ctr, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Thomas Jefferson Univ, Lankanau Hosp, Wynnewood, PA 19096 USA. RP Bernardino, CR (reprint author), Emory Univ, Sch Med, Emory Eye Ctr, 1365B Clifton Rd NE, Atlanta, GA 30322 USA. EM crbernardino@mac.com NR 5 TC 3 Z9 4 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 2004 VL 88 IS 6 BP 848 EP 849 DI 10.1136/bjo.2003.035634 PG 2 WC Ophthalmology SC Ophthalmology GA 821QS UT WOS:000221478000039 PM 15148237 ER PT J AU Erdag, G Sheridan, RL AF Erdag, G Sheridan, RL TI Fibroblasts improve performance of cultured composite skin substitutes on athymic mice SO BURNS LA English DT Article DE fibroblast; skin substitute; wound healing ID BURN WOUND CLOSURE; KERATINOCYTE GROWTH; DERMAL FIBROBLASTS; DIFFERENTIATION; GRAFTS; CELLS; REGENERATION; EXPRESSION; BIOPOLYMERS; CONTRACTION AB Background: This study investigated the impact of adding human fibroblasts to a cultured composite skin substitute model of cultured human keratinocytes and acellular human dermis. Methods: Skin substitutes were prepared by seeding human keratinocytes on the papillary side of acellular dermis with or without seeding fibroblasts on the reticular side. Performance of the grafts was compared both in vitro by histology and in vivo on surgically created full-thickness wounds on athymic mice. Graft size and contraction were measured and immunohistochemical stains were done to reveal vascularization. Results: Skin substitutes with fibroblasts formed thicker epidermis than skin substitutes without fibroblasts. When transplanted onto athymic mice, skin substitutes with fibroblasts maintained their original size with only 2% contraction. In contrast, skin substitutes without fibroblasts showed 29% contraction. Vascular basement membrane specific mouse CD31 staining and endothelial cell specific mouse collagen type IV staining revealed vascularization as early as 1 week posttransplant in grafts with fibroblasts, and was significantly higher than grafts without fibroblasts at 2 weeks. Conclusions: Addition of fibroblasts to keratinocyte based composite skin substitutes improves epidermis formation, enhances vascularization and reduces contraction. (C) 2003 Elsevier Ltd and ISBI. All rights reserved. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Boston, MA 02114 USA. RP Erdag, G (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM erdag@helix.mgh.harvard.edu NR 25 TC 43 Z9 48 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD JUN PY 2004 VL 30 IS 4 BP 322 EP 328 DI 10.1016/j.burns.2003.12.007 PG 7 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 824GH UT WOS:000221673800005 PM 15145189 ER PT J AU Pardee, AB AF Pardee, AB TI Rambling thoughts about doing and thinking research SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 936A, Boston, MA USA. EM arthur_pardee@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2004 VL 3 IS 6 BP 573 EP 577 PG 5 WC Oncology SC Oncology GA 898RP UT WOS:000227094200023 PM 15118417 ER PT J AU Baik, I Becker, PS DeVito, WJ Lagiou, P Ballen, K Quesenberry, PJ Hsieh, CC AF Baik, I Becker, PS DeVito, WJ Lagiou, P Ballen, K Quesenberry, PJ Hsieh, CC TI Stem cells and prenatal origin of breast cancer SO CANCER CAUSES & CONTROL LA English DT Review DE breast cancer; estrogens; growth factors; in utero exposure; perinatal factors; stem cells ID GROWTH-FACTOR-I; UMBILICAL-CORD BLOOD; BONE-MARROW-CELLS; CORONARY-HEART-DISEASE; FACTOR BINDING PROTEIN-1; ESTROGEN-RECEPTOR-ALPHA; STEROID-HORMONE LEVELS; FULL TERM PREGNANCY; MAMMARY-GLAND MASS; ADULT HUMAN BREAST AB The hypothesis that in utero exposure to pregnancy hormones, notably estrogens, is related to the occurrence of breast cancer in the offspring has been examined in a number of epidemiological and experimental studies. Many studies have provided direct or indirect evidence that supports the hypothesis of an intrauterine component in the origin of breast cancer. Human studies to examine the underlying biological mechanisms, however, have been limited. We review the likely role of stem cells in hormone-mediated carcinogenic process, particularly as intermediate steps between in utero exposure to hormones and breast cancer. We summarize also studies related to the assumptions of the hypothesis concerning in utero exposure. We propose the use of stem cell potential as a measurable variable of the 'fertile soil', a term that has been used to characterize the consequences of fetal exposure to intrauterine environment. We conclude by outlining a feasible population-based study that measures stem cell potential to explore mechanisms mediating the relation between in utero exposure to pregnancy hormones and breast cancer risk in the offspring. C1 Univ Massachusetts, Sch Med, Dept Canc Biol, Div Biostat & Epidemiol, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Canc Res Ctr, Worcester, MA 01605 USA. Univ Massachusetts, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Univ Washington, Div Hematol, Seattle, WA 98195 USA. Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Roger Williams Med Ctr, Dept Res, Providence, RI USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. RP Hsieh, CC (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, Div Biostat & Epidemiol, 364 Plantat St,LRB 427, Worcester, MA 01605 USA. EM chung.hsieh@umassmed.edu OI Baik, Inkyung/0000-0002-9524-4344 FU NCI NIH HHS [R01CA90902] NR 216 TC 33 Z9 34 U1 0 U2 3 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 JUN PY 2004 VL 15 IS 5 BP 517 EP 530 DI 10.1023/B:CACO.0000036450.06092.ce PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 850VE UT WOS:000223641700010 PM 15286472 ER PT J AU Ma, XJ Wang, ZC Ryan, PD Isakoff, SJ Barmettler, A Fuller, A Muir, B Mohapatra, G Salunga, R Tuggle, JT Tran, Y Tran, D Tassin, A Amon, P Wang, W Wang, W Enright, E Stecker, K Estepa-Sabal, E Smith, B Younger, J Balis, U Michaelson, J Bhan, A Habin, K Baer, TM Brugge, J Haber, DA Erlander, MG Sgroi, DC AF Ma, XJ Wang, ZC Ryan, PD Isakoff, SJ Barmettler, A Fuller, A Muir, B Mohapatra, G Salunga, R Tuggle, JT Tran, Y Tran, D Tassin, A Amon, P Wang, W Wang, W Enright, E Stecker, K Estepa-Sabal, E Smith, B Younger, J Balis, U Michaelson, J Bhan, A Habin, K Baer, TM Brugge, J Haber, DA Erlander, MG Sgroi, DC TI A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen SO CANCER CELL LA English DT Article ID LASER CAPTURE MICRODISSECTION; ADJUVANT ENDOCRINE THERAPY; ESTROGEN-RECEPTOR STATUS; PACKAGING CELL-LINE; GENE-EXPRESSION; HORMONAL-THERAPY; HOX GENE; ASSAY; RESISTANCE; PROFILES AB Tamoxifen significantly reduces tumor recurrence in certain patients with early-stage estrogen receptor-positive breast cancer, but markers predictive of treatment failure have not been identified. Here, we generated gene expression profiles of hormone receptor-positive primary breast cancers in a set of 60 patients treated with adjuvant tamoxifen monotherapy. An expression signature predictive of disease-free survival was reduced to a two-gene ratio, HOXB13 versus IL17BR, which outperformed existing biomarkers. Ectopic expression of HOXB13 in MCF10A breast epithelial cells enhances motility and invasion in vitro, and its expression is increased in both preinvasive and invasive primary breastcancer. The HOXB13:IL17BR expression ratio may be useful for identifying patients appropriate for alternative therapeutic regimens in early-stage breast cancer. C1 Arcturus Biosci Inc, Carlsbad, CA 92008 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Sgroi, DC (reprint author), Arcturus Biosci Inc, 2715 Loker Ave W, Carlsbad, CA 92008 USA. EM merlander@arctur.com; dsgroi@parnters.org FU NCI NIH HHS [T32 CA009172] NR 55 TC 573 Z9 595 U1 0 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2004 VL 5 IS 6 BP 607 EP 616 DI 10.1016/j.ccr.2004.05.015 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 836HI UT WOS:000222546100012 PM 15193263 ER PT J AU Vernon, SW Meissner, H Klabunde, C Rimer, BK Ahnen, DJ Bastani, R Mandelson, MT Nadel, MR Sheinfeld-Gorin, S Zapka, J AF Vernon, SW Meissner, H Klabunde, C Rimer, BK Ahnen, DJ Bastani, R Mandelson, MT Nadel, MR Sheinfeld-Gorin, S Zapka, J TI Measures for ascertaining use of colorectal cancer screening in behavioral, health services, and epidemiologic research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID FECAL-OCCULT-BLOOD; INCREASE MAMMOGRAPHY USE; SOCIETY GUIDELINES; AVERAGE-RISK; INTERVENTIONS; PREVENTION; SIGMOIDOSCOPY; MORTALITY; UPDATE; QUESTIONNAIRES C1 Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. Univ Texas, Ctr Hlth Promot & Prevent Res, Houston, TX 77030 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. Grp Hlth Cooperat Ctr Hlth Studies, Seattle, WA USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Vernon, SW (reprint author), Univ Texas, Sch Publ Hlth, 7000 Fannin,Suite 2650, Houston, TX 77030 USA. EM svernon@sph.uth.tmc.edu FU NCI NIH HHS [U01 CA086322-01] NR 58 TC 76 Z9 76 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2004 VL 13 IS 6 BP 898 EP 905 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 826ZL UT WOS:000221867900002 PM 15184243 ER PT J AU Tong, RT Boucher, Y Kozin, SV Winkler, F Hicklin, DJ Jain, RK AF Tong, RT Boucher, Y Kozin, SV Winkler, F Hicklin, DJ Jain, RK TI Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors SO CANCER RESEARCH LA English DT Article ID INTERSTITIAL HYPERTENSION; BLOOD-VESSELS; SOLID TUMORS; CANCER; ANTIBODY; THERAPY; ANGIOGENESIS; REGRESSION; LYMPHATICS; XENOGRAFTS AB Elevated interstitial fluid pressure, a hallmark of solid tumors, can compromise the delivery of therapeutics to tumors. Here we show that blocking vascular endothelial growth factor (VEGF) signaling by DC101 (a VEGF-receptor-2 antibody) decreases interstitial fluid pressure, not by restoring lymphatic function, but by producing a morphologically and functionally "normalized" vascular network. We demonstrate that the normalization process prunes immature vessels and improves the integrity and function of the remaining vasculature by enhancing the perivascular cell and basement membrane coverage. We also show that DC101 induces a hydrostatic pressure gradient across the vascular wall, which leads to a deeper penetration of molecules into tumors. Thus, vascular normalization may contribute to the improved survival rates in tumor-bearing animals and in colorectal carcinoma patients treated with an anti-VEGF antibody in combination with cytotoxic therapies. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. ImClone Syst Inc, New York, NY USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, COX 734,100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [P01-CA-80124] NR 31 TC 625 Z9 663 U1 4 U2 48 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2004 VL 64 IS 11 BP 3731 EP 3736 DI 10.1158/0008-5472.CAN-04-0074 PG 6 WC Oncology SC Oncology GA 825AB UT WOS:000221727300002 PM 15172975 ER PT J AU Crandall, JE Hackett, HE Tobet, SA Kosofsky, BE Bhide, PG AF Crandall, JE Hackett, HE Tobet, SA Kosofsky, BE Bhide, PG TI Cocaine exposure decreases GABA neuron migration from the ganglionic eminence to the cerebral cortex in embryonic mice SO CEREBRAL CORTEX LA English DT Article DE cerebral cortex; cocaine; GABA; ganglionic eminence; neurogenesis; neuronal migration ID ANTERIOR CINGULATE CORTEX; PRENATAL COCAINE; IN-UTERO; CORTICAL-NEURONS; RAT-BRAIN; SOMATOSENSORY CORTEX; MONOAMINE-OXIDASE; BINDING-SITES; CELL-CYCLE; DLX GENES AB Recurrent exposure of the developing fetus to cocaine produces persistent alterations in structure and function of the cerebral cortex. Neurons of the cerebral cortex are derived from two sources: projection neurons from the neuroepithelium of the dorsal pallium and interneurons from the ganglionic eminence of the basal telencephalon. The interneurons are GABAergic and reach the cerebral cortex via a tangential migratory pathway. We found that recurrent, transplacental exposure of mouse embryos to cocaine from embryonic day 8 to 15 decreases tangential neuronal migration and results in deficits in GABAergic neuronal populations in the embryonic cerebral wall. GABAergic neurons of the olfactory bulb, which are derived from the ganglionic eminence via the rostral migratory pathway, are not affected by the cocaine exposure suggesting a degree of specificity in the effects of cocaine on neuronal migration. Thus, one mechanism by which prenatal cocaine exposure exerts deleterious effects on cerebral cortical development may be by decreasing GABAergic neuronal migration from the ganglionic eminence to the cerebral wall. The decreased GABA neuron migration may contribute to persistent structural and functional deficits observed in the exposed offspring. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Colorado State Univ, Coll Vet Med, Dept Biomed Sci, Ft Collins, CO 80523 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM Bhide@helix.mgh.harvard.edu OI Tobet, Stuart/0000-0002-1615-7331 FU NICHD NIH HHS [HD 05515, P01 HD005515]; NIDA NIH HHS [DA 00354, DA 08648, K02 DA000354, R01 DA008648, R29 DA008648]; NIMH NIH HHS [MH57748, R01 MH057748]; NINDS NIH HHS [NS 43426, R01 NS043426] NR 65 TC 50 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 2004 VL 14 IS 6 BP 665 EP 675 DI 10.1093/cercor/bhh027 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 822QP UT WOS:000221555200007 PM 15054047 ER PT J AU Chaput, JC Szostak, JW AF Chaput, JC Szostak, JW TI Evolutionary optimization of a nonbiological ATP binding protein for improved folding stability SO CHEMISTRY & BIOLOGY LA English DT Article ID MESSENGER-RNA DISPLAY; IN-VITRO SELECTION; DE-NOVO PROTEIN; FOLDED PROTEINS; LIBRARIES; DESIGN; PEPTIDE; SUPERFAMILIES; RIBONUCLEASE; SEQUENCES AB Structural comparison of in vitro evolved proteins with biological proteins will help determine the extent to which biological proteins sample the structural diversity available in protein sequence space. We have previously isolated a family of nonbiological ATP binding proteins from an unconstrained random sequence library. One of those proteins was further optimized for high-affinity binding to ATP, but biophysical characterization proved impossible due to poor solubility. To determine if such nonbiological proteins can be optimized for improved folding stability, we performed multiple rounds of mRNA-display selection under increasingly denaturing conditions. Starting from a pool of protein variants, we evolved a population of proteins capable of binding ATP in 3 M guanidine hydrochloride. One protein was chosen for further characterization. Circular dichroism, tryptophan fluorescence, and H-1-N-15 correlation NMR studies show that this protein has a unique folded structure. C1 Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu NR 45 TC 21 Z9 22 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD JUN PY 2004 VL 11 IS 6 BP 865 EP 874 DI 10.1016/j.chembiol.2004.04.006 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 834KI UT WOS:000222409600018 PM 15217619 ER PT J AU Olson, AL Gutman, JA Welsh, CH AF Olson, AL Gutman, JA Welsh, CH TI A 50-year-old man with skin lesions and multiple pulmonary nodules SO CHEST LA English DT Article ID SECONDARY SYPHILIS C1 Denver VA Med Ctr, Med Serv, Denver, CO 80220 USA. Eastern Colorado Hlth Care Syst, Denver, CO USA. Univ Colorado, Ctr Hlth Sci, Dept Med, Denver, CO 80202 USA. RP Olson, AL (reprint author), Denver VA Med Ctr, Med Serv, 1055 Clermont St, Denver, CO 80220 USA. EM amy.olson@uchsc.edu NR 10 TC 6 Z9 8 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 JUN PY 2004 VL 125 IS 6 BP 2322 EP 2327 DI 10.1378/chest.125.6.2322 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 832FQ UT WOS:000222253100054 PM 15189957 ER PT J AU Kwek, BH Aquino, SL Fischman, AJ AF Kwek, BH Aquino, SL Fischman, AJ TI Fluorodeoxyglucose positron emission tomography and CT after talc pleurodesis SO CHEST LA English DT Article DE CT pleural cavity; pleurodesis; positron emission tomography; talc ID MALIGNANT PLEURAL EFFUSION; LUNG-CANCER; FDG-PET AB Background: Talc pleurodesis is widely performed for the management of persistent pneumothorax or pleural effusion, particularly malignant effusions. However, there are very few data characterizing fluorodeoxyglucose (FDG)-positron emission tomography (PET) and CT findings after treatment. Methods: We retrospectively evaluated the FDG-PET and CT studies of nine patients who underwent talc pleurodesis for the treatment of malignant pleural effusions or persistent air leak. Results: FDG-PET studies were performed on average 22 months after talc pleurodesis, and the mean CT follow-up period was 25 months. There was moderate-to-intense plaque-like or focal nodular-increased FDG uptake in the pleura on PET with mean standardized uptake value of 5.4 (SEM, 1.2; range, 2.0 to 16.3). The FDG uptake was either diffuse (two patients) or focal (seven patients), and most commonly occurred in the posterior costophrenic angles (five patients), followed by the apical regions (three patients), anterior costophrenic angle (one patient), and the anterior chest wall (one patient). On CT, high-density areas of pleural thickening or nodularity (mean, 230 Hounsfield units [HU]; SEM, 23 HU; range, 140 to 380 HU) corresponded to regions of increased FDG uptake. These pleural foci had an average thickness of 1.2 cm and measured up to 8.2 cm (mean, 7.1 cm) in length. Rounded pleural nodules were as large as 3.1 cm (mean, 1.5 cm). Conclusions: Talc pleurodesis produces increased FDG uptake on PET and high-density areas of pleural thickening on CT that remain unchanged on serial imaging. When PET detects increased uptake in the pleural space, correlation with CT is recommended to detect the presence of pleural thickening of increased attenuation that suggests talc deposits rather than tumor. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM saquino@partners.org NR 15 TC 58 Z9 58 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUN PY 2004 VL 125 IS 6 BP 2356 EP 2360 DI 10.1378/chest.125.6.2356 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 832FQ UT WOS:000222253100060 PM 15189963 ER PT J AU Pulsifer, MB Radonovich, K Belcher, HME Butz, AM AF Pulsifer, MB Radonovich, K Belcher, HME Butz, AM TI Intelligence and school readiness in preschool children with prenatal drug exposure SO CHILD NEUROPSYCHOLOGY LA English DT Article ID UTERO COCAINE EXPOSURE; AGE; ABUSERS; GROWTH AB This prospective, longitudinal study examined factors affecting intelligence and school readiness in children 4-5 years of age with prenatal cocaine/opiate exposure. Intelligence and school readiness scores were not significantly different for the drug-exposed group (N = 104) than for unexposed, demographically matched controls (N = 35), although both groups scored slightly below average. Caregivers of drug-exposed children scored significantly lower in intelligence and reading achievement than caregivers of controls; both were below average. Caregiver reading scores accounted for the largest variance in both child intelligence and school readiness; for school readiness, birth weight also contributed but was less important in the model. Neither prenatal drug exposure nor continuing caregiver drug use was significant in the regression analyses. The relationship between child scores and caregiver reading achievement is consistent with studies showing the importance of a stimulating, supportive home environment, and suggests interventions to foster caregiver literacy skills and facilitate caregiver-child cognitive interactions such as reading to the child. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21218 USA. Kennedy Krieger Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Sch Nursing, Baltimore, MD 21218 USA. RP Pulsifer, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 5 Emerson Pl,Suite 105, Boston, MA 02114 USA. EM mpulsifer@partners.org FU NCRR NIH HHS [M01 RR000052]; NINR NIH HHS [NR03442] NR 37 TC 18 Z9 18 U1 2 U2 5 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD JUN PY 2004 VL 10 IS 2 BP 89 EP 101 DI 10.1080/09297040490911104 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 863TN UT WOS:000224586100004 PM 15590488 ER PT J AU Recklitis, CJ Noam, GG AF Recklitis, CJ Noam, GG TI Aggressive behavior in the adolescent psychiatric patient: A clinical-developmental perspective SO CHILD PSYCHIATRY & HUMAN DEVELOPMENT LA English DT Article DE ego development; adolescents; aggression; defense mechanisms ID DEFENSE-MECHANISM INVENTORY; EGO DEVELOPMENT; ANTISOCIAL-BEHAVIOR; YOUTH VIOLENCE; YOUNG-CHILDREN; MENTAL-HEALTH; RISK-FACTORS; PSYCHOPATHOLOGY; CHILDHOOD; INTERVENTION AB Objective. This study examined the relationship between ego development and psychological defenses to aggressive behavior in a group of psychiatrically hospitalized adolescents. Method: Subjects were 245 adolescents ages 12-16, who were assessed for aggressive behaviors, assaultive incidents, ego development and defenses. Results: Aggressive behavior was found to be negatively associated with ego development, regardless of age, gender or IQ. Defense styles which located the source of conflict outside of the self were associated with higher levels of self-reported aggressive behaviors. Hospital incidents of assault were associated with a lack of cognitively based defenses. Conclusion: Aggressive behavior is tied to the development of critical psychological processes which shape the adolescent's ability to understand themselves and their environment. The results are discussed in the context of a clinical-developmental approach to adolescent aggressive behavior. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Qual Life Clin, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. RP Recklitis, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Qual Life Clin, 44 Binney St, Boston, MA 02115 USA. EM christopher-recklitis@dfci.harvard.edu NR 83 TC 4 Z9 4 U1 0 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0009-398X J9 CHILD PSYCHIAT HUM D JI Child Psychiat. Hum. Dev. PD SUM PY 2004 VL 34 IS 4 BP 341 EP 361 PG 21 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 815EG UT WOS:000221025000006 PM 15039606 ER PT J AU Fifer, MA Pietsch, GE AF Fifer, MA Pietsch, GE TI Household clustering of hypertrophic cardiomyopathy SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Anchor Anim Hosp Inc, N Dartmouth, MA USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, WACC 478,15 Parkman St, Boston, MA 02114 USA. EM mfifer@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 1 PY 2004 VL 109 IS 21 BP 2594 EP 2594 DI 10.1161/01.CIR.0000131494.56361.91 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 825LE UT WOS:000221759000021 PM 15173040 ER PT J AU Park, JW Kerbel, RS Kelloff, GJ Barrett, JC Chabner, BA Parkinson, DR Peck, J Ruddon, RW Sigman, CC Slamon, DJ AF Park, JW Kerbel, RS Kelloff, GJ Barrett, JC Chabner, BA Parkinson, DR Peck, J Ruddon, RW Sigman, CC Slamon, DJ TI Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development SO CLINICAL CANCER RESEARCH LA English DT Review ID METASTATIC BREAST-CANCER; CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR RECEPTOR; CHRONIC MYELOGENOUS LEUKEMIA; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; TYROSINE-KINASE INHIBITORS; GREEN FLUORESCENT PROTEIN; SOFT-TISSUE SARCOMAS; IMATINIB MESYLATE C1 Univ Calif San Francisco, San Francisco Canc Ctr, San Francisco, CA 94115 USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Inst Alternat Futures, Alexandria, VA USA. Johnson & Johnson Corp, New Brunswick, NJ USA. CCS Associates, Mountain View, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Park, JW (reprint author), Univ Calif San Francisco, San Francisco Canc Ctr, 1600 Divisadero St,2nd Floor, San Francisco, CA 94115 USA. EM jpark@cc.ucsf.edu NR 107 TC 107 Z9 114 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2004 VL 10 IS 11 BP 3885 EP 3896 DI 10.1158/1078-0432.CCR-03-0785 PG 12 WC Oncology SC Oncology GA 825UU UT WOS:000221784700036 PM 15173098 ER PT J AU Kelloff, GJ Coffey, DS Chabner, BA Dicker, AP Guyton, KZ Nisen, PD Soule, HR D'Amico, AV AF Kelloff, GJ Coffey, DS Chabner, BA Dicker, AP Guyton, KZ Nisen, PD Soule, HR D'Amico, AV TI Prostate-specific antigen doubling time as a surrogate marker for evaluation of oncologic drugs to treat prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Review ID METASTATIC BREAST-CANCER; CHRONIC MYELOID-LEUKEMIA; RADICAL PROSTATECTOMY; MONOCLONAL-ANTIBODY; RADIATION-THERAPY; PREOPERATIVE NOMOGRAM; REFERENCE RANGES; END-POINT; PHASE-II; PROGRESSION C1 NCI, Div Canc Treatment & Diag, Canc Imaging Program, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. CCS Associates, Mountain View, CA USA. Abbott Labs, Global Oncol Dev, Abbott Pk, IL 60064 USA. CaP CURE, Santa Monica, CA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kelloff, GJ (reprint author), NCI, Div Canc Treatment & Diag, Canc Imaging Program, Execut Plaza S,Room 6058, Bethesda, MD 20892 USA. EM kelloffg@mail.nih.gov OI Dicker, Adam/0000-0003-0733-3337 NR 44 TC 36 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2004 VL 10 IS 11 BP 3927 EP 3933 DI 10.1158/1078-0432.CCR-03-0788 PG 7 WC Oncology SC Oncology GA 825UU UT WOS:000221784700040 PM 15173102 ER PT J AU Jin, M Tuller, P Wener, MH Black, DA Bankson, DD AF Jin, M Tuller, P Wener, MH Black, DA Bankson, DD TI The evaluation of a sex hormone binding globulin assay and its use in the calculation of free testosterone. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 25-29, 2004 CL Los Angeles, CA SP Amer Assoc Clin Chem C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2004 VL 50 IS 6 SU S BP A90 EP A91 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 828EC UT WOS:000221955200299 ER PT J AU Steele, BW Palmer-Toy, DE Elin, RJ Klee, GG Wang, E AF Steele, BW Palmer-Toy, DE Elin, RJ Klee, GG Wang, E TI Long term within laboratory precision of cortisol, thyroxine, free thyroxine and TSH assays based on a CAP fresh frozen serum study SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 25-29, 2004 CL Los Angeles, CA SP Amer Assoc Clin Chem C1 Univ Miami, Sch Med, Miami, FL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40292 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Coll Amer Pathologists, Northfield, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2004 VL 50 IS 6 SU S BP A108 EP A109 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 828EC UT WOS:000221955200361 ER PT J AU Wigren, C Bankson, DD Eng, W Tuller, P Wener, MH AF Wigren, C Bankson, DD Eng, W Tuller, P Wener, MH TI Measurement of monomeric prolactin following polyethylene glycol precipitation. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-Clinical-Chemistry CY JUL 25-29, 2004 CL Los Angeles, CA SP Amer Assoc Clin Chem C1 Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2004 VL 50 IS 6 SU S BP A104 EP A105 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 828EC UT WOS:000221955200348 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Exploring How to Tell the Truth and Preserve Hope: Can a Balance Between Communication and Empathy Be Calculated? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: When told the harsh truth about severe disease, a patient might despair and lose all hope. Without knowing the truth, however, the patient cannot participate in decision making and adjust life according to his illness. The present study aims to analyze the relationships between hope and truth in the decision on how much information to disclose to a patient with severe gastrointestinal disease. Methods: The decision analysis is based on the economic concepts of indifference curves and utility function. An inverse linear relationship exists between hope and truth; as more truth becomes revealed, the amount of hope declines. The utility function and the corresponding indifference curve of hope plotted versus truth describe the patient's personal choices among different combinations of hope and truth. The optimal choice among various combinations of hope and truth corresponds with the point at which the inverse hope-truth line meets the indifference curve. Results: In situations in which hope drops steeply as more medical facts are being revealed, the utility to the patient is maximized with less truth being told. With a less pronounced truth-related decline in hope, utility is maximized at higher levels of truth, and, occasionally, utility is maximized only after all medical facts have been disclosed. The lesser the impact of truth on hope, the more truth is being tolerated. Conclusions: A caring gastroenterologist trying to optimize his/her patient's well-being should try to assess the potential influence of truth on the patient's psyche and dispense it accordingly. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr P3 GI, Gastroenterol Sect, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu RI Girault, Johann/B-2430-2012 NR 26 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2004 VL 2 IS 6 BP 518 EP 522 DI 10.1016/S1542-3565(04)00172-7 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KR UT WOS:000208071800014 PM 15181622 ER PT J AU Gordon, LK Goldman, M Sandusky, H Ziv, N Hoffman, GS Goodglick, T Goodglick, L AF Gordon, LK Goldman, M Sandusky, H Ziv, N Hoffman, GS Goodglick, T Goodglick, L TI Identification of candidate microbial sequences from inflammatory lesion of giant cell arteritis SO CLINICAL IMMUNOLOGY LA English DT Article DE giant cell arteritis; temporal arteritis; vasculitis; laser capture microdissection; representational difference analysis; granulomatous inflammation; aging ID VARICELLA-ZOSTER-VIRUS; POLYMERASE-CHAIN-REACTION; LARGE-VESSEL ARTERITIS; TEMPORAL ARTERITIS; CHLAMYDIA-PNEUMONIAE; OCULAR MANIFESTATIONS; ULCERATIVE-COLITIS; AORTIC-ANEURYSMS; PANCA ANTIBODIES; PARVOVIRUS B19 AB Giant cell arteritis (GCA) is a granulomatous inflammatory disease of medium and large arteries which is prevalent in the elderly population. The etiology of GCA is unknown, although the immunologic features suggest the possible presence of a microorganism. Our group has examined whether microbial DNA fragments were present at GCA lesions and whether such microbial fragments could be associated with disease pathogenesis. Initial identification of microbial sequences was performed using genomic representational difference analysis (RDA). Laser dissecting microscopy was used to isolate cells from GCA lesions and adjacent uninvolved temporal artery. Using genomic RDA, we isolated 10 gene fragments; three of these sequences had high homology with prokaryotic genes and were considered high-priority candidates for further study. An examination of serum from GCA(+) individuals (in contrast to healthy age-matched controls) showed the presence of IgG which recognized in vitro translated proteins from these clones. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Georgetown Univ, Washington Hosp Ctr, Dept Ophthalmol, Washington, DC 20007 USA. RP Goodglick, L (reprint author), Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. EM lgoodglick@mednet.ucla.edu NR 61 TC 11 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2004 VL 111 IS 3 BP 286 EP 296 DI 10.1016/j.clim.2003.12.016 PG 11 WC Immunology SC Immunology GA 830WS UT WOS:000222155500007 PM 15183149 ER PT J AU Letko, E Miserocchi, E Daoud, YJ Christen, W Foster, CS Ahmed, AR AF Letko, E Miserocchi, E Daoud, YJ Christen, W Foster, CS Ahmed, AR TI A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies SO CLINICAL IMMUNOLOGY LA English DT Article DE intravenous immunoglobulin therapy; ocular cicatricial pemphigoid; mucous membrane pemphigoid; cicatricial pemphigoid; immunosuppressive therapy ID NECROSIS-FACTOR-ALPHA; SERUM LEVELS; INTERLEUKIN-6; GAMMA AB The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (NIMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1) presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2) entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3) presence of conventional immunosuppressive therapy at the time of ocular involvement; (4) a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. NE Baptist Hosp, Ctr Blistering Dis, Boston, MA 02120 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. EM razzaque_ahmed@hms.harvard.edu NR 20 TC 51 Z9 54 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 2004 VL 111 IS 3 BP 303 EP 310 DI 10.1016/j.clim.2003.11.002 PG 8 WC Immunology SC Immunology GA 830WS UT WOS:000222155500009 PM 15183151 ER PT J AU Losina, E Islam, R Pollock, AC Sax, PE Freedberg, KA Walensky, RP AF Losina, E Islam, R Pollock, AC Sax, PE Freedberg, KA Walensky, RP TI Effectiveness of Antiretroviral therapy after protease inhibitor failure: An analytic overview SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE INHIBITOR; TREATMENT-EXPERIENCED PATIENTS; PHENOTYPIC DRUG SUSCEPTIBILITY; GENOTYPE-GUIDED TREATMENT; EFAVIRENZ PLUS INDINAVIR; LONG-TERM BENEFIT; SALVAGE THERAPY; VIROLOGICAL RESPONSE; CLINICAL-TRIALS AB To examine effectiveness of subsequent antiretroviral therapy (ART), studies published during the period of 1 January 1997 through 31 May 2003 involving patients who had failed a protease inhibitor (PI)-containing regimen and were switched to another regimen were reviewed. Twelve studies describing 1197 patients were analyzed. A total of 38% of patients had human immunodeficiency virus (HIV) RNA levels of <500 copies/mL at 24 weeks. After adjustment for baseline HIV RNA level, the rate of virologic suppression ranged from 16% for patients switching drugs within previously failed classes to 54% for nonnucleoside reverse-transcriptase inhibitor (NNRTI)-naive patients switched to boosted PI- and NNRTI-containing regimens. ART regimens in patients who failed a PI- containing regimen provided virologic suppression only in a few patients. The best response was seen in NNRTI-naive patients receiving NNRTI- and boosted PI-containing regimens. New approaches are needed to achieve better suppression in pretreated HIV-infected patients. C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Losina, E (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 715 Albany St,Talbot 4-E, Boston, MA 02118 USA. EM lenal@bu.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [R01-AI42006, K25AI50436, R01 AI042006, K23AI01794, K25 AI050436, P30-AI42851, P30 AI042851, K23 AI001794]; ODCDC CDC HHS [U64/CCU 114927] NR 85 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2004 VL 38 IS 11 BP 1613 EP 1622 DI 10.1086/420930 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 821QO UT WOS:000221477400018 PM 15156451 ER PT J AU Ivers, LC Kim, AY Sax, PE AF Ivers, LC Kim, AY Sax, PE TI Predictive value of polymerase chain reaction of cerebrospinal fluid for detection of Epstein-Barr virus to establish the diagnosis of HIV-related primary central nervous system lymphoma SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID EMISSION COMPUTED-TOMOGRAPHY; FOCAL BRAIN-LESIONS; DIFFERENTIAL-DIAGNOSIS; INFECTED PATIENTS; MR SPECTROSCOPY; AIDS PATIENTS; TOXOPLASMOSIS; CSF; DNA AB Polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) for detection of Epstein-Barr virus (EBV) DNA has been proposed as a minimally invasive method for establishing the diagnosis of human immunodeficiency virus-related primary central nervous system lymphoma (PCNSL). In a review of the operational characteristics of this test in our clinical practice, the positive predictive value of CSF PCR for EBV for establishing the diagnosis of PCNSL was only 29%. Of 7 patients with CSF PCR positive for EBV, 2 had PCNSL, and 5 received alternative diagnoses (specificity, 79.1%). C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ivers, LC (reprint author), Brigham & Womens Hosp, Div Infect Dis, 15 Francis St,PBB-A4, Boston, MA 02115 USA. EM livers@partners.org FU NIAID NIH HHS [T32 AI-07433] NR 19 TC 39 Z9 41 U1 0 U2 1 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 JUN 1 PY 2004 VL 38 IS 11 BP 1629 EP 1632 DI 10.1086/420934 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 821QO UT WOS:000221477400020 PM 15156453 ER PT J AU Ecker, JL AF Ecker, JL TI Cesarean delivery for suspected macrosomia: Inefficient at best SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID BRACHIAL-PLEXUS INJURY; FETAL MACROSOMIA; BIRTH-WEIGHT; UNITED-STATES; INFANTS; PREGNANCIES; PALSY; PREDICTION; ACCURACY; NEWBORN C1 Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet Serv, Boston, MA USA. RP Ecker, JL (reprint author), Founders 431,55 Fruit St, Boston, MA 02114 USA. EM jecker@partners.org NR 27 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2004 VL 47 IS 2 BP 352 EP 364 DI 10.1097/00003081-200406000-00009 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 959PQ UT WOS:000231530600007 PM 15166859 ER PT J AU Vrahas, MS Mithoefer, K Joseph, D AF Vrahas, MS Mithoefer, K Joseph, D TI The long-term effects of articular impaction SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TIBIAL PLATEAU FRACTURES; INTRAARTICULAR FRACTURE; DEGENERATIVE ARTHRITIS; HUMAN OSTEOARTHRITIS; CHONDROCYTE DEATH; ANIMAL-MODEL; CELL-DEATH; CARTILAGE; APOPTOSIS; PATHOGENESIS AB Ultimately, the long-term effects of articular impact injury remain unknown. Impact injury has long been considered an explanation for posttramnatic arthritis. It is an attractive hypothesis because often it is the only explanation we can put forth for why arthritis develops in an injured joint. There has been recent interest in the role of chondrocyte apoptosis in the pathogenesis of osteoarthritis. Chondrocyte apoptosis has also been observed with cartilage impact injury and may provide an explanation for how impact injury leads to osteoarthrosis. This paper reviews impact injury and its association with apoptosis as a potential etiology for posttramnatic arthritis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. Cornell Univ, Hosp Special Surg, Dept Orthopaed Surg, New York, NY 10021 USA. Elmhurst Hosp, Elmhurst, NY USA. RP Vrahas, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 55 Fruit St,WACC 5-525, Boston, MA 02114 USA. EM Mvrahas@partners.org NR 33 TC 22 Z9 22 U1 1 U2 2 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 JUN PY 2004 IS 423 BP 40 EP 43 DI 10.1097/01.blo.0000133567.28491.7d PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 830AX UT WOS:000222095100007 PM 15232424 ER PT J AU Lehtinen, JT Macy, JC Cassinelli, E Warner, JJP AF Lehtinen, JT Macy, JC Cassinelli, E Warner, JJP TI The painful scapulothoracic articulation - Surgical management SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SNAPPING SCAPULA SYNDROME; ANATOMY; RESECTION AB To clarify the indications and effectiveness of surgical decompression for scapulothoracic bursitis, 16 patients were evaluated, who during a 5-year period, had surgical treatment of refractory pain and snapping in the scapulothoracic region. Twelve women and four men with a mean age of 41 years had one of five methods of surgical decompression of the scapulothoracic articulation. Six patients had an open resection of the scapulothoracic bursa with excision of the superomedial portion of the scapula, two had this procedure using an arthroscopic method, and six had a combined approach with arthroscopic scapulothoracic bursectomy and open resection of the superomedial scapula through a small incision. One patient had an arthroscopic and one an open scapulothoracic bursectomy only. At final followup of an average of 36 months (range, 24-69 months), 81% of patients reported satisfaction with the procedure and indicated they would have it again based on the relief they obtained from pain. The Simple Shoulder Test was 9.8 (range, 2-12). Although there was no statistical difference in the success using any given technique, we thought that the combined open and arthroscopic approach was the most effective, and surgical treatment is an acceptable method for treatment of refractory painful scapulothoracic bursitis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Shoulder Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Shoulder Serv, Dept Orthopaed Surg, 275 Cambridge St,Suite 403A, Boston, MA 02114 USA. EM jwarner@partners.org OI Macy, John /0000-0002-0517-8022 NR 28 TC 17 Z9 18 U1 0 U2 0 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 JUN PY 2004 IS 423 BP 99 EP 105 DI 10.1097/01.blo.0000128647.38363.8e PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 830AX UT WOS:000222095100016 PM 15232433 ER PT J AU Lee, FYI Hornicek, FJ Dick, HM Mankin, HJ AF Lee, FYI Hornicek, FJ Dick, HM Mankin, HJ TI Synovial chondromatosis of the foot SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SOFT-TISSUE TUMORS; ANKLE TUMORS; BONE; JOINT AB Synovial chondromatosis rarely occurs in the foot. Five patients with synovial chondromatosis in the foot were treated with excision. There were four men and one woman with a mean age of 37 years (range, 19-58 years). Mineral densities adjacent to the joint were seen on radiographs of all patients. Synovial chondromatosis occurred in the calcaneocuboid, tibiotalar, naviculocuneiform, and metatarsophalangeal joints. A painful mass was the common initial presentation in all patients. The patients were followed up for an average of 5 years (range, 3-16 years) after arthrotomy and excision. All patients were relieved of symptoms and retained normal function. There was no clinical or radiographic evidence of recurrence. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Unit, Boston, MA 02114 USA. Columbia Univ, Coll Phys & Surg, Dept Orthopaed Surg, New York, NY USA. RP Hornicek, FJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Unit, 55 Fruit St GRB 606, Boston, MA 02114 USA. EM fhornicek@partners.org NR 20 TC 11 Z9 11 U1 0 U2 1 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 JUN PY 2004 IS 423 BP 186 EP 190 DI 10.1097/01.blo.0000127133.89704.86 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 830AX UT WOS:000222095100030 ER PT J AU Memili, E Behboodi, E Overton, SA Kenney, AM O'Coin, M Zahedi, A Rowitch, DH Echelard, Y AF Memili, E Behboodi, E Overton, SA Kenney, AM O'Coin, M Zahedi, A Rowitch, DH Echelard, Y TI Synchronization of goat fibroblast cells at quiescent stage and determination of their transition from G(0) to G(1) by detection of cyclin D-1 mRNA SO CLONING AND STEM CELLS LA English DT Article ID NUCLEAR TRANSFER EMBRYOS; SOMATIC-CELLS; IN-VITRO; FETAL FIBROBLASTS; DEPENDENT KINASE; MAMMALIAN-CELLS; CALVES; ADULT; IDENTIFICATION; PROLIFERATION AB A number of studies have reported that donor cells consisting of serum starved cells, which are assumed to be at quiescence (GO), or non-starved confluent cells or mitotic cells obtained by shake-off, both of which are assumed to be at G, phase, give better results in nuclear transfer (NT) than cells at other phases of the cell cycle. Whether Go or G, cells function better as donor cells is yet to be determined by detailed studies. The aims of this study were to analyze the cell cycle of goat transfected fibroblasts and determine the timing of transition from Go to G, by detecting G(1)-specific marker, cyclin D, mRNA. Fluorescent-activated cell sorting (FACS) analyses of cells after 4 days of serum starvation showed that more that 90% of cells were in G(0)/G(1). Additionally, detection of cyclin D, mRNA by northern blot analysis showed that 4-day serum starved quiescent cells started entering G, a few hours after addition of 10% serum to the medium. Taken together, the data indicated that serum starved transfected primary fibroblasts of adult goats experienced the Go to G, transition within 5 h of serum stimulation and were at the mid-G(1) stage within 10 h of serum stimulation. C1 GTC Biotherapeut Inc, Framingham, MA 01701 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Echelard, Y (reprint author), GTC Biotherapeut Inc, 5 Mt Rd, Framingham, MA 01701 USA. EM yann.echelard@gtc-bio.com NR 31 TC 10 Z9 11 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1536-2302 J9 CLONING STEM CELLS JI Cloning Stem Cells PD SUM PY 2004 VL 6 IS 2 BP 58 EP 66 DI 10.1089/1536230041372409 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 836CG UT WOS:000222532200002 PM 15268778 ER PT J AU Gulliver, SB Wolfsdorf, BA Morissette, SB AF Gulliver, SB Wolfsdorf, BA Morissette, SB TI Treating tobacco dependence: Development of a smoking cessation treatment program for outpatient mental health clinics SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID DOSE TRANSDERMAL NICOTINE; CIGARETTE-SMOKING; SELF-QUITTERS; PARTNER SUPPORT; PREGNANT-WOMEN; SMOKERS; RELAPSE; SCHIZOPHRENIA; DEPRESSION; METAANALYSIS AB Response to smoking cessation treatment programs sharply decreases when applied to smokers with psychiatric comorbidities. Consequently, the development of smoking cessation treatments that address the needs of psychiatric patients is greatly needed. The primary purpose of this article is to detail the process of development of an empirically informed, theoretically driven treatment program designed to aid multiply diagnosed smokers in their attempts to become tobacco free. Issues related to treating tobacco dependence in the persistently mentally ill are described. Our initial experience providing manualized, cognitive-behavioral smoking cessation treatment with adjunctive nicotine replacement therapy is detailed, along with the iterative process of manual development. Our current treatment program is illustrated with examples of clinical interactions, (is well as a description of our ongoing evaluation of the utility and success of the clinic. C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Gulliver, SB (reprint author), Boston VA Outpatient Clin, Psychol Serv 116B, 251 Causeway St, Boston, MA 02114 USA. EM suzy.gulliver@med.va.gov NR 73 TC 2 Z9 2 U1 0 U2 3 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD SUM PY 2004 VL 11 IS 3 BP 315 EP 330 DI 10.1016/S1077-7229(04)80046-4 PG 16 WC Psychology, Clinical SC Psychology GA 916WS UT WOS:000228417900006 ER PT J AU Aldape, KD Borowsky, AD Louis, DN AF Aldape, KD Borowsky, AD Louis, DN TI Mouse models of nervous system tumors SO COMPARATIVE MEDICINE LA English DT Editorial Material C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Calif Davis, Dept Comparat Med, Dept Med Pathol, Davis, CA 95615 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Mol Pathol & Res, Boston, MA 02114 USA. RP Aldape, KD (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2004 VL 54 IS 3 BP 264 EP 267 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 832WY UT WOS:000222299600006 ER PT J AU Rubenfeld, GD Cooper, C Carter, G Thompson, BT Hudson, LD AF Rubenfeld, GD Cooper, C Carter, G Thompson, BT Hudson, LD TI Barriers to providing lung-protective ventilation to patients with acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article DE lung-protective ventilation; acute lung injury; acute respiratory distress syndrome ID RESPIRATORY-DISTRESS-SYNDROME; INTERNAL-MEDICINE RESIDENTS; CRITICALLY-ILL PATIENTS; MECHANICAL VENTILATION; INTEROBSERVER VARIABILITY; HUMANISTIC BEHAVIOR; CARE PHYSICIANS; CHART AUDIT; SELF-REPORT; NURSES AB Objective. No studies have explored the barriers to implementing lung-protective ventilation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Our objective was to identify barriers to using lung-protective ventilation in patients with ALI/ARDS. Design: Survey with content analysis of open-ended responses. Setting: Medical center. Participants: Experienced intensive care unit nurses and respiratory therapists network identified through purposive sampling at hospitals from the ARDS Network, a National Institutes of Health-sponsored research consortium. Interventions: Survey. Results: Fifty-five surveys representing all ten ARDS Network sites were received. Twenty-seven (49%) of the respondents were intensive care unit nurses, 24 (44%) were respiratory therapists, and four did not indicate their profession. Clinicians had used lung-protective ventilation in a median of 20 (interquartile range, 10-50) patients with ALI/ARDS. Respondents identified physician willingness to relinquish control of ventilator, physician recognition of ALI/ARDS, and physician perceptions of patient contraindications to low tidal volumes as important barriers to initiating lung-protective ventilation. Important barriers to continuing patients on lungprotective ventilation were concerns over patient discomfort and tachypnea and concerns over hypercapnia, acidosis, and hypoxemia. Techniques for overcoming barriers were identified including specific ventilator setup recommendations, clinician education, and tools to assess patient discomfort. Conclusions: Experienced bedside clinicians perceive important barriers to implementing lung-protective ventilation. Successful strategies to increase use of lung-protective ventilation should target these barriers. C1 Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. Harvard Univ, Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. RP Rubenfeld, GD (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. FU NHLBI NIH HHS [HL30542, HR46055, R01HL67939] NR 31 TC 172 Z9 177 U1 1 U2 6 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 JUN PY 2004 VL 32 IS 6 BP 1289 EP 1293 DI 10.1097/01.CCM.0000127266.39560.96 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 831NQ UT WOS:000222201600008 PM 15187508 ER PT J AU Nishida, T Suchodolski, K Schettino, GPP Sedeek, K Takeuch, M Kacmarek, RM AF Nishida, T Suchodolski, K Schettino, GPP Sedeek, K Takeuch, M Kacmarek, RM TI Peak volume history and peak pressure-volume curve pressures independently affect the shape of the pressure-volume curve of the respiratory system SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Thoracic-Society CY MAY, 2002 CL Atlanta, GA SP Amer Thorac Soc DE acute respiratory distress syndrome; pulmonary function tests; pressure-volume curves; inflection point; compliance ID END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; DISTRESS-SYNDROME; RECRUITMENT MANEUVERS; MATHEMATICAL-MODEL; TIDAL VOLUME; VENTILATION; FAILURE; DERECRUITMENT AB Objective: To determine the specific effect of peak volume history pressure on the inflation limb of the pressure-volume curve and peak pressure-volume curve pressure on the deflation limb of the pressure-volume curve. Design: Prospective assessment of pressure-volume curves in saline, lung lavage injured sheep. Setting: Large animal laboratory of a university-affiliated hospital. Subjects: Eight female Dorset sheep. Interventions: The effect of two volume history pressures (40 and 60 cm H2O) and three pressure-volume curve peak pressures (40, 50, and 60 cm H2O) were randomly compared. Measurements and Main Results: Peak volume history pressure affected the inflation curve beyond the lower inflection point but did not affect the inflection point (Pflex). Peak pressure-volume curve pressure affected the deflation curve. Increased peak volume history pressure increased inflation compliance (P < .05). Increased peak pressure-volume curve pressure increased the point of maximum compliance change on the deflation limb and deflation compliance and decreased compliance between peak pressure and the point of maximum curvature on the deflation limb (p < .05). Conclusion: Peak volume history pressure must be considered when interpreting the inflation limb of the pressure-volume curve of the respiratory system beyond the inflection point. The peak pressure achieved during the pressure-volume curve is important during interpretation of deflation compliance and the point of maximum compliance change on the deflation limb. C1 Massachusetts Gen Hosp, Dept Anesthesia Resp Care, Boston, MA 02114 USA. Natl Cardiovasc Ctr, Surg Intens Care Unit, Suita, Osaka 565, Japan. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Resp Care, Ellison 401, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 24 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2004 VL 32 IS 6 BP 1358 EP 1364 DI 10.1097/01.CCM.0000128573.28173.2E PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 831NQ UT WOS:000222201600020 PM 15187520 ER PT J AU Horton, ES Foley, JE Shen, SG Baron, MA AF Horton, ES Foley, JE Shen, SG Baron, MA TI Efficacy and tolerability of initial combination therapy with nateglinide and metformin in treatment-naive patients with type 2 diabetes SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE combination therapy; metformin; nateglinide; oral antidiabetic agents; target HbA(kappa); treatment naive; type 2 diabetes mellitus ID GLYCEMIC CONTROL; INSULIN; MELLITUS; HYPERGLYCEMIA; COMPLICATIONS; HYPOGLYCEMIA; PROGRESSION; GLYBURIDE; RISK; DIET AB Objective: To assess the efficacy and tolerability of the combination of nateglinide (120 mg, ac) and metformin (500 mg, tid) as initial treatment in drug-naive patients with type 2 diabetes mellitus (T2DM). Research design and methods: This study reports data from the treatment-naive (TN) subgroup of patients in a previously published, randomized, multicenter, placebo-controlled, 24-week trial that compared nateglinide, metformin, and the combination therapy (CT) in 701 patients with T2DM with baseline HbA(1c) between 6.8% and 11.0%. Of the 401 TN patients, 104, 104, 89, and 104 patients received nateglinide (120 mg, ac), metformin (500 mg, tid), CT, and placebo, respectively. The baseline characteristics of each group were similar, with mean age, BMI, duration of diabetes, HbA(1c), and fasting plasma glucose (FPG) levels of approximately 58 years, 30 kg/m(2), 4 years, 8.2%, and 10.2 mmol/L, respectively. Results: In patients receiving initial CT, HbA(1c) decreased substantially (Delta = -1.6 +/- 0.1%, p < 0.0001 vs. baseline or placebo) from a mean baseline of 8.2 +/- 0.1%, an effect significantly greater than the 0.8% reduction observed with both monotherapies (p < 0.001); whereas, in placebo-treated patients, HbA(1c) increased modestly (Delta = +0.3 +/- 0.1%, p < 0.05) from an identical baseline value. Seventy percent of CT-treated patients achieved a target HbA(1c) of < 7.0%. Both fasting plasma glucose (FPG) and the 2-hour postprandial glucose excursion (PPGE) after a liquid meal challenge decreased by 2.3 mmol/L in patients receiving CT, while the changes from baseline values in FPG and PPGE were +0.2 +/- 0.3 mmol/L and -0.5 +/- 0.2 mmol/L, respectively, in placebo-treated patients. The incremental 30-minute post-load insulin levels increased by 88 +/- 32 pmol/L (p = 0.006) in patients receiving CT and did not change significantly in placebo-treated patients. Gastrointestinal side effects occurred in 27% of patients receiving CT (vs. 27.9% in the metformin monotherapy, and 14.4% in the placebo groups). Confirmed hypoglycemia (glucose less than or equal to 2.8 mmol/L) occurred in 3.4% of patients receiving CT. Conclusions: Initial CT with the rapid-acting insulinotropic agent, nateglinide, and metformin, an agent with insulin-sensitizing effects in the liver and periphery, is a safe and effective means of achieving glycemic targets in TN patients with T2DM. C1 Nova Pharmaceut Corp, E Hanover, NJ 07936 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Baron, MA (reprint author), Nova Pharmaceut Corp, 1 Hlth Plaza 501-336, E Hanover, NJ 07936 USA. EM michelle.baron@pharma.novartis.com NR 21 TC 23 Z9 26 U1 0 U2 2 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, 26-32 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD JUN PY 2004 VL 20 IS 6 BP 883 EP 889 DI 10.1185/030079903125003881 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 833DY UT WOS:000222317800014 PM 15200747 ER PT J AU Graves, EE Weissleder, R Ntziachristos, V AF Graves, EE Weissleder, R Ntziachristos, V TI Fluorescence molecular imaging of small animal tumor models SO CURRENT MOLECULAR MEDICINE LA English DT Review DE fluorescence; molecular imaging; fluorescence reflectance imaging; fluorescence molecular tomography ID DIFFUSE OPTICAL TOMOGRAPHY; CONTRAST AGENTS; TURBID MEDIA; HUMAN SKIN; MICROSCOPY; PROBES; RECONSTRUCTION; SPECTROSCOPY; BEACONS; CELLS AB In vivo imaging of molecular events in small animals has great potential to impact basic science and drug development. For this reason, several imaging technologies have been adapted to small animal research, including X-ray, magnetic resonance, and radioisotope imaging. Despite this plethora of visualization techniques, fluorescence imaging is emerging as an important alternative because of its operational simplicity, safety, and cost-effectiveness. Fluorescence imaging has recently become particularly interesting because of advances in fluorescent probe technology, including targeted fluorochromes as well as fluorescent "switches" sensitive to specific biochemical events. While past biological investigations using fluorescence have focused on microscopic examination of ex vivo, in vitro, or intravital specimens, techniques for macroscopic fluorescence imaging are now emerging for in vivo molecular imaging applications. This review illuminates fluorescence imaging technologies that hold promise for small animal imaging. In particular we focus on planar illumination techniques, also known as Fluorescence Reflectance Imaging (FRI), and discuss its performance and current use. We then discuss fluorescence molecular tomography (FMT), an evolving technique for quantitative three-dimensional imaging of fluorescence in vivo. This technique offers the promise of non-invasively quantifying and visualizing specific molecular activity in living subjects in three dimensions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Graves, EE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, 149 13th St,Rm 5404, Charlestown, MA 02129 USA. EM graves@helix.mgh.harvard.edu NR 47 TC 139 Z9 146 U1 0 U2 52 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD JUN PY 2004 VL 4 IS 4 BP 419 EP 430 DI 10.2174/1566524043360555 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 824BK UT WOS:000221658700008 PM 15354872 ER PT J AU Nahm, WK Su, TT Rotunda, AM Moy, RL AF Nahm, WK Su, TT Rotunda, AM Moy, RL TI Objective changes in brow position, superior palpebral crease, peak angle of the eyebrow, and jowl surface area after volumetric radiofrequency treatments to half of the face SO DERMATOLOGIC SURGERY LA English DT Article ID NONABLATIVE RADIOFREQUENCY; FOREHEAD LIFT; ABLATION; CATHETER; TISSUE AB Background. Radiofrequency application through a proprietary device has recently been used for facial tissue tightening. Uniform volumetric heating of the dermis is created by passage of electrical current, while protection of the epidermis is maintained by concurrent cryogen cooling. Objective. To objectively quantify the effectiveness of volumetric radiofrequency application on the face, we treated 10 patients on the left side of the face with radiofrequency and evaluated the changes in brow position, superior palpebral crease, angle of the eyebrow, and jowl surface area. Methods. Uniform treatments were applied at 134 J/cm(2) to the left side of the forehead and 1 cm past midline, at 115 J/cm(2) to the left side of temple and cheeks, and at 97 J/cm(2) to the left side of the jaw line and inferior postauricular surface. Patients were evaluated at monthly intervals up to 3 months with digital photography. Morphologic changes were evaluated with the "measuring tool" and "angle tool" of the Mirror Suite imaging system for aligned frontal-view photographs (for eyebrow position, superior palpebral crease elevation, and eyebrow angle changes) and the "outline tool" for aligned oblique-view photographs (for jowl surface area changes). Results. At the end of 3 months on the side that was treated, patients exhibited on average 4.3 mm of brow elevation and 1.9 mm of superior palpebral crease elevation along the midpupillary line and an average of 2.4 mm of brow elevation along the lateral canthal line. There was no significant improvement of brow elevation along the lateral canthal line on the contralateral side. The peak angle of the ipsilateral eyebrow became slightly more acute by an average of 4.5degrees after treatments. Moreover, the jowls on the lower part of the face, displayed a mean decrease of 22.6% in surface area after treatments. The nontreated side displayed a lack of eyebrow angle and jowl surface area changes. Conclusions. The application of radiofrequency to the face provides quantifiable changes. The brow along the midpupillary line is elevated to a greater degree than the lateral brow. This is consistent with acute angle changes seen in the eyebrow. Improvements in the lower part of the face with radiofrequency application can be quantified by demonstrating a decrease jowl surface. Moreover, these measurement techniques can be useful tools for evaluating other treatment parameters with radiofrequency application. . C1 Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Vet Affairs Med Ctr, San Diego, CA 92161 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Moy, RL (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. EM rmoy@ucla.edu NR 25 TC 39 Z9 41 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JUN PY 2004 VL 30 IS 6 BP 922 EP 928 DI 10.1111/j.1524-4725.2004.30263.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 824EE UT WOS:000221667200014 PM 15171772 ER PT J AU Dalvin, S Komatsuzaki, K Anselmo, MA Kling, DE Schnitzer, JJ Kinane, TB AF Dalvin, S Komatsuzaki, K Anselmo, MA Kling, DE Schnitzer, JJ Kinane, TB TI Retinoic acid decreases fetal lung mesenchymal cell proliferation in vivo and in vitro SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE Erk-1/2; G-protein; lung; proliferation; retinoic acid; introduction ID ACTIVATED PROTEIN-KINASE; EMBRYONAL CARCINOMA-CELLS; LYSOPHOSPHATIDIC ACID; PRIMITIVE ENDODERM; TERMINAL KINASE; BETA ISOFORMS; GROWTH; DIFFERENTIATION; RECEPTORS; PATHWAY AB Retinoic acid (RA) is an important coordinator of mammalian organogenesis. RA is implicated in critical lung developmental events. Cell proliferation is precisely regulated during development. We investigated the effect of RA on proliferating mesenchymal cells in both whole organ lung cultures and cell cultures. The potential pathways required for the response were studied in cultures of lung mesenchymal cells from embryonic day (e) 12. We observed an RA-dependent reduction in proliferation of mesenchymal cells in both whole organ and in cell culture. In mesenchymal cell cultures, RA decreased proliferation in lung mesenchymal cells by 72%. This was associated with a decrease of erk-1/2 activity by 68%. Mesenchymal cell proliferation is erk-1/2 dependent. Erk-1/2 can be activated by G-protein coupled receptors (GPCR) or tyrosine kinase receptors (RTK). RA treatment altered both the RTK and the GPCR pathways in primary lung mesenchymal cells. The Epidermal Growth Factor (EGF) dependent erk-1/2 activation was increased by 35% whereas the G(i)-protein cascade was inhibited by 44% in cells treated with RA. Our results suggest that RA decreases proliferation of lung mesenchyme via a G(i)-protein and the erk-1/2 signaling cascade. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Pulm Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Serv,Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Kinane, TB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Pulm Unit, Boston, MA 02114 USA. EM tkinane@partners.org OI Dalvin, Sussie/0000-0002-6092-4710 NR 39 TC 7 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD JUN PY 2004 VL 46 IS 3 BP 275 EP 282 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 830BV UT WOS:000222097500007 PM 15206958 ER PT J AU Aberg, T Wang, XP Kim, JH Yamashiro, T Bei, M Rice, R Ryoo, HM Thesleff, I AF Aberg, T Wang, XP Kim, JH Yamashiro, T Bei, M Rice, R Ryoo, HM Thesleff, I TI Runx2 mediates FGF signaling from epithelium to mesenchyme during tooth morphogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Runx genes; tooth morphogenesis; epithelial-mesenchymal interaction; FGF; SHH; enamel knot ID DEVELOPING MOUSE TOOTH; GROWTH-FACTOR-BETA; MAMMALIAN TOOTH; CLEIDOCRANIAL DYSPLASIA; ENAMEL KNOT; TARGETED DISRUPTION; CELL-PROLIFERATION; MURINE DENTITION; GENE-EXPRESSION; BONE AB Runx2 (Cbfa1) is a runt domain transcription factor that is essential for bone development and tooth morphogenesis. Teeth form as ectodermal appendages and their development is regulated by interactions between the epithelium and mesenchyme. We have shown previously that Runx2 is expressed in the dental mesenchyme and regulated by FGF signals from the epithelium, and that tooth development arrests at late bud stage in Runx2 knockout mice [Development 126 (1999) 2911]. In the present study, we have continued to clarify the role of Runx2 in tooth development and searched for downstream targets of Runx2 by extensive in situ hybridization analysis. The expression of Fgf3 was downregulated in the mesenchyme of Runx2 mutant teeth. FGF-soaked beads failed to induce Fgt3 expression in Runx2 mutant dental mesenchyme whereas in wild-type mesenchyme they induced Fgf3 in all explants indicating a requirement of Runx2 for transduction of FGF signals. Fgt3 was absent also in Cultured Runx2-/- calvarial cells and it was induced by overexpression of Runx2. Furthermore, Runx2 was downregulated in Msx1 mutant tooth germs, indicating that it functions in the dental mesenchyrne between Msx1 and Fgf3. Shh expression was absent from the epithelial enamel knot in lower molars of Runx2 mutant and reduced in upper molars. However, other enamel knot marker genes were expressed normally in mutant upper molars, while reduced or missing in lower molars. These differences between mutant upper and lower molars may be explained by the substitution of Runx2 function by Runx3, another member of the runt gene family that was upregulated in upper but not lower molars of Runx2 mutants. Shh expression in mutant enamel knots was not rescued by FGFs in vitro, indicating that in addition to Fgf3, Runx2 regulates other mesenchymal genes required for early tooth morphogenesis. Also, exogenous FGF and SHH did not rescue the morphogenesis of Runx2 mutant molars. We conclude that Runx2 mediates the functions of epithelial FGF signals regulating Fgt3 expression in the dental mesenchyme and that Fgf3 may be a direct target gene of Runx2. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Helsinki, Inst Biotechnol, Dev Biol Program, Viikki Bioctr 1, FIN-00014 Helsinki, Finland. Kyungpook Natl Univ, Sch Dent, Dept Biochem, Taejon, South Korea. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Thesleff, I (reprint author), Univ Helsinki, Inst Biotechnol, Dev Biol Program, Viikki Bioctr 1, POB 56, FIN-00014 Helsinki, Finland. EM Irma.Thesleff@helsinki.fi RI Ryoo, Hyun-Mo/D-5839-2012; YAMASHIRO, Takashi/B-2026-2011 FU NIDCR NIH HHS [DE 013368] NR 67 TC 103 Z9 109 U1 0 U2 12 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 JUN 1 PY 2004 VL 270 IS 1 BP 76 EP 93 DI 10.1016/j.ydbio.2004.02.012 PG 18 WC Developmental Biology SC Developmental Biology GA 822IK UT WOS:000221532300006 PM 15136142 ER PT J AU McKee, AE Silver, PA AF McKee, AE Silver, PA TI REF-ereeing the cytoplasmic fate of mRNA via nuclear export SO DEVELOPMENTAL CELL LA English DT Editorial Material ID C.-ELEGANS; TRA-2 AB The C. elegans sex-determining gene tra-2 is subject to multiple forms of regulation. A report in the June 4 issue of Molecular Cell now shows that proteins associated with the tra-2 mRNA determine its pathway of nuclear export and influence its cytoplasmic fate. These findings demonstrate an additional level of control and link nuclear export to the regulation of sexual development. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP McKee, AE (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. NR 10 TC 1 Z9 8 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2004 VL 6 IS 6 BP 740 EP 742 DI 10.1016/j.devcel.2004.05.014 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834XC UT WOS:000222443200003 PM 15177019 ER PT J AU Carvalho, P Gupta, ML Hoyt, MA Pellman, D AF Carvalho, P Gupta, ML Hoyt, MA Pellman, D TI Cell cycle control of kinesin-mediated transport of Bik1 (CLIP-170) regulates microtubule stability and dynein activation SO DEVELOPMENTAL CELL LA English DT Article ID METAPHASE CHROMOSOME ALIGNMENT; SPINDLE POLE BODY; SACCHAROMYCES-CEREVISIAE; MITOTIC SPINDLE; NUCLEAR MIGRATION; BUDDING YEAST; FISSION YEAST; PLUS ENDS; POLYMERIZATION DYNAMICS; CYTOPLASMIC DYNEIN AB CLIPs are microtubule plus end-associated proteins that mediate interactions required for cell polarity and cell division. Here vie demonstrate that budding yeast Bik1, unlike its human ortholog CLIP-170, is targeted to the microtubule plus end by a kinesin-dependent transport mechanism. Bik1 forms a complex with the kinesin Kip2. Fluorescently labeled Bik1 and Kip2 co-migrate along individual microtubules. Bik1 exists in distinct intracellular pools: a stable pool at the spindle pole body that is depleted during cell cycle progression, a soluble pool from which Bik1 can be recruited during microtubule initiation, and a dynamic plus end pool maintained by Kip2. Kip2 stabilizes microtubules by targeting Bik1 to the plus end and Kip2 levels are controlled during the cell cycle. As with Bik1, the targeting of dynein to the microtubule plus end requires Kip2. These findings reveal a central role for Kip2-dependent transport in the cell cycle control of microtubule dynamics and dynein-dependent motility. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Biomed Sci Abel Salazar, P-4099003 Oporto, Portugal. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu OI Carvalho, Pedro/0000-0002-9691-5277 FU NIGMS NIH HHS [R01 GM61345-04] NR 67 TC 130 Z9 132 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2004 VL 6 IS 6 BP 815 EP 829 DI 10.1016/j.devcel.2004.05.001 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834XC UT WOS:000222443200014 PM 15177030 ER PT J AU Saotome, I Curto, M McClatchey, AI AF Saotome, I Curto, M McClatchey, AI TI Ezrin is essential for epithelial organization and villus morphogenesis in the developing intestine SO DEVELOPMENTAL CELL LA English DT Article ID ERM PROTEINS; FETAL-RAT; CELL-ADHESION; MOESIN; MOUSE; MERLIN; CYTOSKELETON; ASSOCIATION; MICROVILLI; RADIXIN AB Ezrin, Radixin, and Moesin (the ERM proteins) supply regulated linkage between membrane proteins and the actin cytoskeleton. The study of mammalian ERM proteins has been hampered by presumed functional overlap. We have found that Ezrin, the only ERM detected in epithelial cells of the developing intestine provides an essential role in configuring the mouse intestinal epithelium. Surprisingly, Ezrin is not absolutely required for the formation of brush border microvilli or for the establishment or maintenance of epithelial polarity. Instead, Ezrin organizes the apical terminal web region, which is critical for the poorly understood process of de novo lumen formation and expansion during villus morphogenesis. Our data also suggest that Ezrin controls the localization and/or function of certain apical membrane proteins that support normal intestinal function. These in vivo studies highlight the critical function of Ezrin in the formation of a multicellular epithelium rather than an individual epithelial cell. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM mcclatch@helix.mgh.harvard.edu NR 47 TC 252 Z9 258 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2004 VL 6 IS 6 BP 855 EP 864 DI 10.1016/j.devcel.2004.05.007 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834XC UT WOS:000222443200017 PM 15177033 ER PT J AU Gobel, V Barrett, PL Hall, DH Fleming, JT AF Gobel, V Barrett, PL Hall, DH Fleming, JT TI Lumen morphogenesis in C-elegans requires the membrane-cytoskeleton linker erm-1 SO DEVELOPMENTAL CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; DROSOPHILA; CELL; PROTEIN; INTEGRITY; HOMOLOG; MOESIN AB Epithelial tubes are basic building blocks of complex organs, but their architectural requirements are not well understood. Here we show that erm-1 is a unique C. elegans ortholog of the ERM family of cytoskeleton-membrane linkers, with an essential role in lumen morphogenesis. ERM-1 localizes to the luminal membranes of those tubular organ epithelia which lack stabilization by cuticle. RNA interference (RNAi), a germline deletion, and overexpression of erm-1 cause cystic luminal phenotypes in these epithelia. Confocal and ultrastructural analyses indicate that erm-1 functions directly in apical membrane morphogenesis, rather than in epithelial polarity and junction assembly as has been previously proposed for ERMs. We also show that act-5/cytoplasmic actin and sma-1/ P-H-spectrin are required for lumen formation and functionally interact with erm-1. Our findings suggest that there are common structural constraints on the architecture of diverse organ lumina. C1 Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Ctr C Elegans Anat, Bronx, NY 10461 USA. RP Gobel, V (reprint author), Massachusetts Gen Hosp, Lab Dev Immunol, 55 Fruit St, Boston, MA 02114 USA. EM gobel@helix.mgh.harvard.edu FU NCI NIH HHS [CA 68475, CA 74243]; NCRR NIH HHS [R24 RR012596]; NIH HHS [R24 OD010943] NR 22 TC 90 Z9 95 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2004 VL 6 IS 6 BP 865 EP 873 DI 10.1016/j.devcel.2004.05.018 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834XC UT WOS:000222443200018 PM 15177034 ER PT J AU Rubin, LP Kovacs, CS De Paepe, ME Tsai, SW Torday, JS Kronenberg, HM AF Rubin, LP Kovacs, CS De Paepe, ME Tsai, SW Torday, JS Kronenberg, HM TI Arrested pulmonary alveolar cytodifferentiation and defective surfactant synthesis in mice missing the gene for parathyroid hormone-related protein SO DEVELOPMENTAL DYNAMICS LA English DT Article DE PTHrP; alveolarization; surfactant; lung development; gene ablation ID EMBRYONIC MOUSE LUNG; ENDOCHONDRAL BONE-FORMATION; LIPID INTERSTITIAL CELL; DEVELOPING RAT LUNG; PTH/PTHRP RECEPTOR; FETAL LUNG; EPITHELIAL-CELLS; II CELLS; PEPTIDE; EXPRESSION AB Parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor expression are developmentally regulated in lung epithelium and adepithelial mesenchyme, respectively. To test the hypothesis that PTHrP is a developmental regulator of terminal airway development, we investigated in vivo and in vitro models of alveolar cytodifferentiation using mice in which the gene encoding PTHrP was ablated by homologous recombination. We have determined that fetal and newborn PTHrP(-/-) lungs showed delayed mesenchymal-epithelial interactions, arrested type II cell differentiation, and reduced surfactant lamellar body formation and pulmonary surfactant production. Embryonic PTHrP(-/-) lung buds cultured in the absence of skeletal constriction or systemic compensating factors also exhibited delayed alveolar epithelial (type II cell) and mesenchymal cytodifferentiation, as well as a >40% inhibition of surfactant phospholipid production (n = 3-5). Addition of exogenous PTHrP to embryonic PTHrP(-/-) lung cultures normalized interstitial cell morphology and surfactant phospholipid production. The importance of PTHrP as an endogenous regulatory molecule in mammalian lung development is supported by the findings that ablation of PTHrP expression in isolated developing lung is sufficient to disrupt normal development of the alveolar ducts and the centriacinar regions. (C) 2004 Wiley-Liss, Inc. C1 Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02905 USA. Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA. Brown Univ, Sch Med, Program Fetal Med, Providence, RI 02912 USA. Women & Infants Hosp Rhode Isl, Program Fetal Med, Providence, RI 02905 USA. Mem Univ Newfoundland, Fac Med Endocrinol, Hlth Sci Ctr, St Johns, NF, Canada. Brown Univ, Sch Med, Dept Pathol & Lab Med, Providence, RI USA. Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Providence, RI 02905 USA. Harbor UCLA, Res & Educ Inst, Dept Pediat, Torrance, CA 90509 USA. Harbor UCLA, Res & Educ Inst, Dept Obstet & Gynecol, Torrance, CA 90509 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit,Dept Med, Boston, MA 02115 USA. RP Rubin, LP (reprint author), Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02905 USA. EM lewis_rubin@brown.edu OI Kovacs, Christopher/0000-0002-5219-9993; Torday, John/0000-0001-9071-3052 FU NHLBI NIH HHS [HL55268]; NIDDK NIH HHS [DK47038] NR 58 TC 44 Z9 52 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2004 VL 230 IS 2 BP 278 EP 289 DI 10.1002/dvdy.20058 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 824NX UT WOS:000221694400008 PM 15162506 ER PT J AU Moore, A Grimm, J Han, BY Santamaria, P AF Moore, A Grimm, J Han, BY Santamaria, P TI Tracking the recruitment of diabetogenic CD8(+) T-cells to the pancreas in real time SO DIABETES LA English DT Article ID NONOBESE DIABETIC MICE; POSITRON-EMISSION-TOMOGRAPHY; TRAFFICKING IN-VIVO; TUMOR-CELLS; RECEPTOR; COMPLEX; VISUALIZATION; EXPRESSION; POPULATION; MRI AB Development of autoimmune diabetes in both humans and mice is preceded by a prolonged period of inflammation of pancreatic islets by autoreactive T-cells. Noninvasive imaging techniques, including positron-emission tomography and optical or magnetic resonance imaging, have been used to track the recruitment of lymphocytes to sites of inflammation. These techniques, however, rely on labeling strategies that are non-antigen specific and do not allow specific tracking of the recruitment of autoreactive lymphocytes. Here we describe an antigen-specific magnetic label to selectively target a prevalent population of diabetogenic CD8(+) T-cells that contribute to the progression of insulitis to overt diabetes in NOD mice. Superparamagnetic nanoparticles coated with multiple copies of a high-avidity peptide/major histocompatibility complex ligand of these T-cells (NRP-V7/K-d) are endocytosed by CD8(+) T-cells in an antigen-specific manner. Using these T-cells as probes, we show that inflammation of pancreatic islets by autoreactive T-cells can be detected in real time by magnetic resonance imaging. This study demonstrates the feasibility of visualizing the presence of ongoing autoimmune responses noninvasively. C1 Massachusetts Gen Hosp, Dept Radiol, MIT, HMS,Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calgary, Julia McFarlane Diabet Res Ctr, Calgary, AB T2N 1N4, Canada. Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 1N4, Canada. RP Moore, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, MIT, HMS,Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Boston, MA 02129 USA. EM amoore@helix.mgh.harvard.edu RI Grimm, Jan/B-1937-2008 FU NIDDK NIH HHS [R01 DK63572, R01 DK064850] NR 37 TC 78 Z9 80 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2004 VL 53 IS 6 BP 1459 EP 1466 DI 10.2337/diabetes.53.6.1459 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824MH UT WOS:000221690200009 PM 15161749 ER PT J AU Kulkarni, RN Roper, MG Dahlgren, G Shih, DQ Kauri, LM Peters, JL Stoffel, M Kennedy, RT AF Kulkarni, RN Roper, MG Dahlgren, G Shih, DQ Kauri, LM Peters, JL Stoffel, M Kennedy, RT TI Islet secretory defect in insulin receptor substrate 1 null mice is linked with reduced calcium signaling and expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3 SO DIABETES LA English DT Article ID PANCREATIC BETA-CELLS; DEPENDENT DIABETES-MELLITUS; MOUSE ISLETS; CA2+ OSCILLATIONS; PHOSPHATIDYLINOSITOL 3-KINASE; OXYGEN-CONSUMPTION; GLUCOSE; RELEASE; LANGERHANS; GLUCAGON AB Mice with deletion of insulin receptor substrate (IRS)-1 (IRS-1 knockout [KO] mice) show mild insulin resistance and defective glucose-stimulated insulin secretion and reduced insulin synthesis. To further define the role of IRS-1 in islet function, we examined the insulin secretory defect in the knockouts using freshly isolated islets and primary beta-cells. IRS-1 KO beta-cells exhibited a significantly shorter increase in intracellular free Ca2+ concentration ([Ca2+](i)) than controls when briefly stimulated with glucose or glyceraldehyde and when L-arginine was used to potentiate the stimulatory effect of glucose. These changes were paralleled by a lower number of exocytotic events in the KO beta-cells in response to the same secretagogues, indicating reduced insulin secretion. Furthermore, the normal oscillations in intracellular Ca2+ and O-2 consumption after glucose stimulation were dampened in freshly isolated KO islets. Semiquantitative RT-PCR showed a dramatically reduced islet expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)-2b and -3 in the mutants. These data provide evidence that IRS-1 modulation of insulin secretion is associated with Ca2+ signaling and expression of SERCA-2b and -3 genes in pancreatic islets and provides a direct link between insulin resistance and defective insulin secretion. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Univ Florida, Dept Chem, Gainesville, FL 32611 USA. Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Rm 602, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu RI Roper, Michael/D-2386-2010; Kennedy, Robert/G-9095-2016 OI Kennedy, Robert/0000-0003-2447-7471 FU NIDDK NIH HHS [DK 09225, R01 DK 46960, R01 DK 55033, R01 DK 67536, R03 DK 66207] NR 68 TC 58 Z9 61 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2004 VL 53 IS 6 BP 1517 EP 1525 DI 10.2337/diabetes.53.6.1517 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824MH UT WOS:000221690200016 PM 15161756 ER PT J AU Meigs, JB Williams, K Sullivan, LM Hunt, KJ Haffner, SM Stern, MP Villalpando, CG Perhanidis, JS Nathan, DM D'Agostino, RB D'Agostino, RB Wilson, PWF AF Meigs, JB Williams, K Sullivan, LM Hunt, KJ Haffner, SM Stern, MP Villalpando, CG Perhanidis, JS Nathan, DM D'Agostino, RB D'Agostino, RB Wilson, PWF TI Using metabolic syndrome traits for efficient detection of impaired glucose tolerance SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; CORONARY HEART-DISEASE; SAN-ANTONIO HEART; CARDIOVASCULAR RISK-FACTORS; DIAGNOSTIC-CRITERIA; INSULIN-RESISTANCE; FASTING GLUCOSE; MEXICO-CITY; LIFE-STYLE; POPULATION AB OBJECTIVE - Efficient detection of impaired glucose tolerance (IGT) is needed to implement type 2 diabetes prevention interventions. RESEARCH DESIGN AND METHODS - We assessed the capacity of the metabolic syndrome (MetS) to identify IGT in a cross-sectional analysis of 3,326 Caucasian Framingham Offspring Study (FOS), 1,1.68 Caucasian and 1,812 Mexican-American San Antonio Heart Study (SAHS), 1,983 Mexico City Diabetes Study (MCDS), and 452 Caucasian, 407 MexicanAmerican, and 290 African-American Insulin Resistance Atherosclerosis Study (IRAS) men and women aged 30-79 years who had a clinical examination and an oral glucose tolerance test (OGTT) during 1987-1996. Those with diabetes treatment or fasting plasma glucose greater than or equal to7.0 mmol/l were excluded (MetS was defined by Third Report of the National Cholesterol Education Program's Adult Treatment Panel criteria and IGT as 2-h postchallenge glucose [2hPG] greater than or equal to7.8 mmol/l). We calculated positive (PPV) and negative predictive values (NPV), population attributable risk percentages (PAR%), age- and sex-adjusted odds ratios (ORs), and areas under the receiver operating characteristic curve (AROCs) associated with MetS traits. RESULTS - Among FOS, SAHS, and MCDS subjects, 24-43% had MetS and 15-23% had IGT (including 2-5% with 2hPG greater than or equal to 11.1 mmolA). Among those with MetS, OR for IGT were 3-4, PPV were 0.24-0.41, NPV were 0.84-0.91, and PAR% were 30-40%. Among subjects with MetS defined by impaired fasting glucose (IFG) and any two other traits, OR for IGT were 9-24, PPV were 0.62-0.89, NPV were 0.78-0.87, and PAR% were 3-12%. Among IRAS subjects, 24-34% had MetS and 37-41% had IGT. Among those with MetS, ORs for IGT were 3-6, PPVs were 0.57-0.73, and NPVs were 0.67-0.72. In logistic regression models, IFG, large waist, and high triglycerides were independently associated with IGT (AROC 0.71-0.83) in all study populations. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Div Med Genet, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Diabet, Dept Med, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, Dept Med, San Antonio, TX 78285 USA. Boston Univ, Dept Math & Stat, Stat & Consulting Unit, Boston, MA 02215 USA. Amer British Coudray Hosp, Ctr Estudios Diabet, Mexico City, DF, Mexico. Inst Mexicano Seguro Social, Hosp Gabriel Mancera, Unidades Invest Med Enfermedades Metab & Epidemio, Mexico City, DF, Mexico. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Boston Univ, Sch Med, Framingham, MA USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, Div Med Genet, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NHLBI NIH HHS [N01 HC 25195, R01 HL 24799, R01 HL 36820, R01 HL 58329, U01 HL 47887, U01 HL 47889, U01 HL 47892, U01 HL 47902]; NIDDK NIH HHS [R01 DK 29867] NR 45 TC 44 Z9 48 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 JUN PY 2004 VL 27 IS 6 BP 1417 EP 1426 DI 10.2337/diacare.27.6.1417 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824MM UT WOS:000221690700027 PM 15161798 ER PT J AU Gornstein, B Jacobs, T Bedard, Y Biscotti, C Ducatman, B Layfield, L McKee, G Sneige, N Wang, H AF Gornstein, B Jacobs, T Bedard, Y Biscotti, C Ducatman, B Layfield, L McKee, G Sneige, N Wang, H TI Interobserver agreement of a probabilistic approach to reporting breast fine-needle aspirations on ThinPrep (R) SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, IL SP US & Canadian Acad Pathol DE breast; fine-needle aspiration; interobserver agreement ID CARCINOMA IN-SITU; DIAGNOSTIC PITFALLS; INVASIVE-CARCINOMA; LOBULAR CARCINOMA; GRAY-ZONE; CYTOLOGY; SMEARS; MASSES; CLASSIFICATION; HYPERPLASIA AB We have previously demonstrated the accuracy and reproducibility of a probabilistic/categorical approach for reporting breast fine-needle aspiration (FNA). However, the interobserver agreement in the application of this approach has not been assessed. Twenty breast FNA cases (each on one ThinPrep(R) slide) were pulled from the cytology files of Beth Israel Deaconess Medical Center. The cases included benign epithelial proliferative lesions (6), DCIS (4), and infiltrating carcinoma (10), as shown by subsequent histology. Six pathologists with 14-25 yr of experience in interpreting breast FNA and 0-8 yr of experience with ThinPrep preparations rendered diagnoses according to the probabilistic approach. The kappa statistic for the unremarkable/proliferative, atypical, suspicious, and positive categories were 0.64, 0.08, 0.43, and 0.75, respectively (P < 0.001 for all except for the atypical category [P = 0.09]). Spearman's rho correlating the individual pathologist's diagnosis and the histologic diagnosis ranged from 0.51 (P = 0.02) to 0.78 (P < 0.0001). This was not correlated with the pathologists' years of experience interpreting breast FNA (P = 1.0) or with their years using ThinPrep preparations for breast FNA (P = 0.96). In conclusion, the interobserver agreement was excellent for the positive category in the probabilistic approach, poor for the atypical category, and fair to good for the other categories. The specific level of experience interpreting breast FNA or using ThinPrep among experienced pathologists did not seem to influence their accuracy in reporting the cases in our study. (C) 2004 Wiley-Liss, Inc. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada. Univ Toronto, Toronto, ON, Canada. Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. W Virginia Univ, Robert C Byrd Hlth Sci Ctr, Dept Pathol, Morgantown, WV 26506 USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Wang, H (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM hwang@bidmc.harvard.edu NR 27 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JUN PY 2004 VL 30 IS 6 BP 389 EP 395 DI 10.1002/dc.20041 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 826OP UT WOS:000221838700005 PM 15176025 ER PT J AU Spirt, MJ Guth, PH Randall, G Leung, FW AF Spirt, MJ Guth, PH Randall, G Leung, FW TI Gastroduodenal perfusion and mortality in mechanical ventilation-dependent patients with systemic inflammatory response syndrome SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE gastroduodenal perfusion; mechanical ventilation-dependent patients; systemic inflammatory response syndrome; reflectance spectrophotometry; mortality ID INTENSIVE-CARE-UNIT; MUCOSAL BLOOD-FLOW; ENDOSCOPIC REFLECTANCE SPECTROPHOTOMETRY; CRITICALLY-ILL PATIENTS; SEVERE ACUTE-PANCREATITIS; IN-HOSPITAL MORTALITY; APACHE-II; OXYGEN-SATURATION; SEPTIC SHOCK; HEMORRHAGIC-SHOCK AB The role of gastrointestinal blood flow determination in predicting mortality is not known. We tested the hypothesis that when mechanical ventilation-dependent (MVD) patients with systemic inflammatory response syndrome (SIRS) develop a significant reduction in gastroduodenal blood flow, high mortality will ensue. The design was a prospective, observational study at the intensive care unit (study patients) and outpatient endoscopy suite (controls) of a tertiary care Veterans Affairs Hospital. There were 6 study patients and 10 control subjects. Interventions were endoscopic reflectance spectrophotometry recorded indexes of gastroduodenal mucosal oxygen saturation (ISO2) and hemoglobin concentration (IHB). Data for Acute Physiologic and Chronic Health Evaluation (APACHE) II scores were gathered. All study patients had septic SIRS at enrollment. Gastroduodenal blood flow measurements ranged from 32 to 55% (ISO2) and from 42 to 51% (IHB) of those in control subjects. The significant hypoperfusion upgraded diagnosis to severe sepsis. The APACHE II score of 16.8+/-2.8 (mean+/-SE) predicted similar to25% mortality. Observed in-hospital mortality was 83%. Our study confirmed that MVD patients with severe sepsis have a significant impairment of gastroduodenal blood flow. Such a dramatic reduction is associated with a grave prognosis. The impact of these measurements on physicians' predictions of the likelihood of survival in patients receiving intensive care deserves to be assessed. C1 Vet Adm Med Ctr, Sepulveda VA Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ,Div Gastroenterol,Med Serv, Sepulveda, CA 91343 USA. Vet Adm Med Ctr, Sepulveda VA Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ,Res Serv, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Leung, FW (reprint author), Vet Adm Med Ctr, Sepulveda VA Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ,Div Gastroenterol,Med Serv, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@med.va.gov NR 49 TC 8 Z9 8 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 JUN PY 2004 VL 49 IS 6 BP 906 EP 913 DI 10.1023/B:DDAS.0000034547.87812.74 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 837EB UT WOS:000222610100003 PM 15309876 ER PT J AU Riedl, K Krysan, K Pold, M Dalwadi, H Heuze-Vourc'h, N Dohadwala, M Liu, M Cui, XY Figlin, R Mao, JT Strieter, R Sharma, S Dubinett, SM AF Riedl, K Krysan, K Pold, M Dalwadi, H Heuze-Vourc'h, N Dohadwala, M Liu, M Cui, XY Figlin, R Mao, JT Strieter, R Sharma, S Dubinett, SM TI Multifaceted roles of cyclooxygenase-2 in lung cancer SO DRUG RESISTANCE UPDATES LA English DT Review DE cyclooxygenase; lung cancer; celecoxib; clinical trials ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMA; PROSTAGLANDIN H SYNTHASE-2; ACTIVATED PROTEIN-KINASE; MESSENGER-RNA EXPRESSION; LAMININ-5 GAMMA-2 CHAIN; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; TUMOR ANGIOGENESIS AB Lung cancer is the leading cause of cancer death in the United States. Although the low 5-year survival rate (under 15%) has changed minimally in the last 25 years, new agents and combinations of agents that target tumor proliferation, invasion, and survival may lead to improvement in patient outcomes. There is evidence that cyclooxygenase-2 (COX-2) is overexpressed in lung cancer and promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. COX-2 inhibitors have been found to inhibit tumor growth in animal models and have demonstrated responses when combined with conventional therapy in phase II clinical trials. Further understanding of the mechanisms involved in COX-2-mediated tumorigenesis and its interaction with other molecules in lung cancer may lead to improved therapeutic strategies for this disease. In addition, delineation of how COX-2-dependent genes modulate the malignant phenotype will provide novel insights in lung cancer pathogenesis. (C) 2004 Elsevier Ltd. All fights reserved. C1 Univ Calif Los Angeles, Lung Canc Res Program, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Lung Canc Res Program, Dept Med, David Geffen Sch Med, 10833 LeConte Ave,37-131 CHS, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI HEUZE-VOURC'H, Nathalie/P-8081-2016 FU NCI NIH HHS [P50 CA90388]; NHLBI NIH HHS [1T32HL6699201] NR 206 TC 70 Z9 77 U1 0 U2 0 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 JUN PY 2004 VL 7 IS 3 BP 169 EP 184 DI 10.1016/j.drup.2004.04.003 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 850OU UT WOS:000223623100002 PM 15296859 ER PT J AU Anderson, KC AF Anderson, KC TI The clinical potential of proteasome inhibition SO EJC SUPPLEMENTS LA English DT Article; Proceedings Paper CT Symposium on Proteasome Inhibition as A Major Advance in Oncology CY SEP 21, 2003 CL Copenhagen, DENMARK DE proteasome; bortezomib; multiple myeloma; NF-kappa B; boronic acids ID MULTIPLE-MYELOMA CELLS; MARROW STROMAL CELLS; NF-KAPPA-B; THERAPEUTIC APPLICATIONS; MOLECULAR-MECHANISMS; DRUG-RESISTANCE; PS-341; APOPTOSIS; ADHESION; GROWTH AB The development of the proteasome inhibitor bortezomib is a prime example of successful bench-to-bedside research. NF-kappaB is implicated in the pathogenesis of multiple myeloma (MM), and bortezomib blocks NF-kappaB activation and its sequelae. Additional bortezomib mechanisms include interactions at the MM cell surface and mitochondrial level and in downstream apoptotic signaling. In the pivotal bortezomib study, the response rate was 35%; time to progression (TTP), 7 months; and median duration of response, 14.3 months. Responses were associated with improvements in quality of life, increases in laboratory parameters, and decreased transfusions. Bortezomib is thus indicated in the US for patients with relapsed, progressive MM and recommended for approval in Europe. The confirmatory phase III trial has been stopped early due to a significant improvement in TTP with bortezomib. The success of bortezotrtib in MM demonstrates the utility of targeting the tumour:host interaction and BM milieu, in addition to the tumour itself. (C) 2004 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 22 TC 11 Z9 11 U1 0 U2 0 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 JUN PY 2004 VL 2 IS 6 BP 3 EP 6 DI 10.1016/j.ejcsup.2004.04.002 PG 4 WC Oncology SC Oncology GA 837LO UT WOS:000222632400002 ER PT J AU Feng, Y Jadhav, AP Rodighiero, C Fujinaga, Y Kirchhausen, T Lencer, WI AF Feng, Y Jadhav, AP Rodighiero, C Fujinaga, Y Kirchhausen, T Lencer, WI TI Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic reticulum requires the trans-Golgi network but not the Golgi apparatus in Exo2-treated cells SO EMBO REPORTS LA English DT Article DE chemical genetics; membrane traffic; phenotypic screen; toxin ID PROTEIN DISULFIDE-ISOMERASE; SHIGA TOXIN; BREFELDIN-A; ER; PATHWAY; KDEL; GANGLIOSIDES; RECRUITMENT; MECHANISM; SEQUENCE AB Cholera toxin (CT) follows a glycolipid-dependent entry pathway from the plasma membrane through the trans-Golgi network (TGN) to the endoplasmic reticulum (ER) where it is retro-translocated into the cytosol to induce toxicity. Whether access to the Golgi apparatus is necessary for transport to the ER is not known. Exo2 is a small chemical that rapidly blocks anterograde traffic from the ER to the Golgi and selectively disrupts the Golgi apparatus but not the TGN. Here we use Exo2 to determine the role of the Golgi apparatus in CT trafficking. We find that under the condition of complete Golgi ablation by Exo2, CT reaches the TGN and moves efficiently into the ER without loss in toxicity. We propose that even in the absence of Exo2 the glycolipid pathway that carries the toxin from plasma membrane into the ER bypasses the Golgi apparatus entirely. C1 Harvard Univ, Sch Med, Dept Cell Biol, Inst Chem & Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Dept Gastrointestinal Cell Biol, Childrens Hosp, Harvard Digest Dis Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Inst Chem & Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.med.harvard.edu; wayne.lencer@tch.harvard.edu FU NIDDK NIH HHS [DK34854, P30 DK034854, R01 DK057827, DK48106, R37 DK048106, DK57827, R01 DK048106]; NIGMS NIH HHS [P01 GM62566, P01 GM062566] NR 35 TC 64 Z9 67 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUN PY 2004 VL 5 IS 6 BP 596 EP 601 DI 10.1038/sj.embor.7400152 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 836MT UT WOS:000222560600012 PM 15153932 ER PT J AU Stanojevic, V Habener, JF Thomas, MK AF Stanojevic, V Habener, JF Thomas, MK TI Pancreas duodenum homeobox-1 transcriptional activation requires interactions with p300 SO ENDOCRINOLOGY LA English DT Article ID TYPE-2 DIABETES-MELLITUS; FACTOR-I GENE; HEDGEHOG SIGNALING REGULATION; INSULIN GENE; ISLET CELLS; MISSENSE MUTATIONS; BETA-CELLS; HOMEODOMAIN; EXPRESSION; PROMOTER AB The homeodomain transcription factor, pancreas duodenum homeobox (PDX)-1, is essential for pancreas development, insulin production, and glucose homeostasis. Mutations in pdx-1(ipf-1) are associated both with maturity-onset diabetes of the young and type 2 diabetes. PDX-1 interacts with multiple transcription factors and coregulators, including the coactivator p300, to activate the transcription of the insulin gene and other target genes within pancreatic beta-cells. In characterizing the protein-protein interactions of PDX-1 and p300, we identified mutations in PDX-1 that disrupt its function and are associated with increased or decreased interactions with p300. Several mutant PDX-1 proteins that are associated with heritable forms of diabetes in humans, in particular the mutant P63fsdelC, exhibited increased binding to a carboxy-terminal segment of p300 in the setting of decreased DNA-binding activities, suggesting that sequestration of p300 by mutant PDX-1 proteins may be an additional mechanism by which insulin gene expression is reduced in heterozygous carriers of pdx-1(ipf-1) mutations. The introduction of the point mutations S66A/Y68A in the highly conserved amino-terminal PDX-1 transactivation domain reduced the ability of PDX-1 to interact with p300, substantially diminished the transcriptional activation of PDX-1, and reduced the synergistic activation of glucose-responsive insulin promoter enhancer sequences by PDX-1, E12, and E47. We propose that interactions of PDX-1 with p300 are required for the transcriptional activation of PDX-1 target genes. Impairment of interactions between PDX-1 and p300 in pancreatic beta-cells may limit insulin production and lead to the development of diabetes. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thomas, MK (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Wellman 340,50 Blossom St, Boston, MA 02114 USA. EM mthomas1@partners.org FU NIDDK NIH HHS [DK58783, DK55365, DK02476] NR 39 TC 44 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2004 VL 145 IS 6 BP 2918 EP 2928 DI 10.1021/en.2003.1188 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 823UR UT WOS:000221639300044 PM 15001545 ER PT J AU Ubeda, M Kemp, DM Habener, JF AF Ubeda, M Kemp, DM Habener, JF TI Glucose-induced expression of the cyclin-dependent protein kinase 5 activator p35 involved in Alzheimer's disease regulates insulin gene transcription in pancreatic beta-cells SO ENDOCRINOLOGY LA English DT Article ID DIABETES-MELLITUS; ENDOCRINE-CELLS; CDK5 ACTIVATOR; HYPOTHALAMIC NEURONS; KINASE-5 CDK5; K+ CHANNELS; RISK; RAT; DEMENTIA; COMPLEX AB The deposition of amyloid within the insulin-producing islets of Langerhans in the pancreas is a common pathological finding in patients with type 2 diabetes. Its relationship with age and the progression of the disease resembles the pathological deposition of beta-amyloid in the brains of Alzheimer's patients. Endocrine cells of pancreatic islets and cells of neuronal lineages express a shared subset of specialized genes. The hyperactivity of the cyclin-dependent protein kinase CDK5, involved in the development and differentiation of the nervous system, is associated with Alzheimer's disease. Overactivity of CDK5 occurs by proteolytic cleavage and cellular mislocalization of its activator, p35. These alterations in p35/CDK5 signaling pathway may mediate, at least in part, the functional abnormalities characteristic of Alzheimer's disease. In this study we report that both the p35 and CDK5 genes are expressed in insulin-producing beta-cells of the pancreas. We detect in beta-cells the formation of an active p35/CDK5 complex with specific kinase activity. Notably, elevations of the extracellular concentration of glucose result in increases in p35 mRNA and protein levels that parallel elevations of p35/CDK5 activity. Functional studies show that p35 stimulates the activity of the insulin promoter and that the stimulation requires CDK5 because stimulation is blocked by roscovitine, an inhibitor of CDK5 activity, a dominant negative form of CDK5, and small interfering RNAs against p35. Our findings indicate that the expression of p35 and CDK5 in insulin-producing beta-cells ensembles a new signaling pathway, the activity of which is controlled by glucose, and its functional role may comprise the regulation of various biological processes in beta-cells, such as is the case for expression of the insulin gene. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Howard Hughes Med Inst, 55 Fruit St,Wellman 306, Boston, MA 02114 USA. EM jhabener@partners.org NR 32 TC 50 Z9 56 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2004 VL 145 IS 6 BP 3023 EP 3031 DI 10.1210/en.2003-1522 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 823UR UT WOS:000221639300055 PM 14976144 ER PT J AU Mathew, A Sinha, R Burt, R Caan, B Paskett, E Iber, F Kikendall, W Lance, P Shike, M Weissfeld, J Schatzkin, A Lanza, E AF Mathew, A Sinha, R Burt, R Caan, B Paskett, E Iber, F Kikendall, W Lance, P Shike, M Weissfeld, J Schatzkin, A Lanza, E CA Polyp Prevention Study Grp TI Meat intake and the recurrence of colorectal adenomas SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE recurrent colorectal adenomas; red meat; white meat ID COLON-CANCER; PROSPECTIVE COHORT; UNITED-STATES; RISK; CONSUMPTION; WOMEN; FIBER; FAT; DIET; MEN AB A large multicenter randomized controlled trial was reassessed to check whether meat intake and a reduction in its consumption are associated with recurrence of adenomatous polyps of the large bowel, which are precursors of most colorectal malignancies. All subjects (n = 1905; 958 interventions and 947 controls) had one or more histologically confirmed colorectal adenomas removed during a colonoscopy within 6 months before randomization. The subjects were followed-up for approximately 4 years after randomization and a colonoscopy for detecting adenomas was conducted at the 1st and 4th year after randomization. Dietary variables were assessed at baseline (TO) and in conjunction with annual visits at the end of the 1st (T1), 2nd (T2), 3rd (T3) and 4th (T4) years. Odds ratios using logistic regression models for meat variables were estimated based on the average intake at TO, T1, T2, T3 and T4 (prior to the T4 colonoscopy) as well as change (T0-T4) in intake. In the intervention group, the total reduction in median intake of red meat from TO to T4 was observed by the end of 1st year itself (30 and 31% for men and women, respectively). The analysis provide no evidence to suggest that lower intake or reduction in total and in red meat consumption during a period of 4 years reduces the risk of adenoma recurrence (including multiple or advanced adenoma), whereas the data suggest that high intake of fish is associated with lower risk of adenoma recurrence. (C) 2004 Lippincott Williams Wilkins. C1 Reg Canc Ctr, Div Epidemiol & Clin Res, Nutrit Epidemiol Branch, Trivandrum 695011, Kerala, India. Univ Utah, Salt Lake City, UT 84112 USA. Kaiser Fdn Res Inst, Oakland, CA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL 60141 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. RP Mathew, A (reprint author), Reg Canc Ctr, Div Epidemiol & Clin Res, Nutrit Epidemiol Branch, Trivandrum 695011, Kerala, India. EM amathew@rcctvm.org RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 22 TC 15 Z9 16 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUN PY 2004 VL 13 IS 3 BP 159 EP 164 DI 10.1097/cej.0000130022.23806.7b PG 6 WC Oncology SC Oncology GA 830EA UT WOS:000222103200002 PM 15167213 ER PT J AU Haider, AW Roubenoff, R Wilson, PWF Levy, D D'Agostino, R Silbershatz, H O'Donnell, CI AF Haider, AW Roubenoff, R Wilson, PWF Levy, D D'Agostino, R Silbershatz, H O'Donnell, CI TI Monocyte cytokine production, systemic inflammation and cardiovascular disease in very elderly men and women: The Framingham Heart Study SO EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION & REHABILITATION LA English DT Article DE monocyte cytokine; systemic inflammation; cardiovascular disease ID RISK; MECHANISMS AB In very elderly participants of the Framingham Heart Study (mean age 79 years, 276 men and 462 women), interleukin-6 correlated with C-reactive protein (CRP) levels. Interleukin-6, tumour necrosis factor alpha and interieukin-1 production, and CRP were not associated with prevalent cardiovascular disease, and nonsteroidal anti-inflammatory drug use did not influence cytokine or CRP levels. Further studies are warranted to examine the prognostic implications of CRP and related cytokines for CVD in the elderly. (C) 2004 The European Society of Cardiology. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. Drexel Univ, Coll Med, Div Cardiol, Dept Med, Philadelphia, PA 19104 USA. Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02115 USA. RP O'Donnell, CI (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM Chris@fram.nhlbi.nih.gov NR 7 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1741-8267 J9 EUR J CARDIOV PREV R JI Eur. J. Cardiovasc. Prev. Rehabil. PD JUN PY 2004 VL 11 IS 3 BP 214 EP 215 DI 10.1097/01.hjr.0000124212.21584.3c PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 834DP UT WOS:000222392100006 PM 15179102 ER PT J AU Chiba, N Gralnek, IM AF Chiba, N Gralnek, IM TI Health economics as related to gastroenterology SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material C1 McMaster Univ, Hamilton, ON, Canada. Surrey GI Res Inc, Guelph, ON, Canada. Univ Calif Los Angeles, VA Greater Los Angeles Hlth Care Syst, Daviid Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Ctr Study Digest Hlth Care Qual & Outcomes, Los Angeles, CA 90024 USA. Ctr neurovisceral Sci & Womens Hlth, Los Angeles, CA 90024 USA. RP Chiba, N (reprint author), McMaster Univ, Hamilton, ON, Canada. EM chiban@on.aibn.com 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 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD JUN PY 2004 VL 16 IS 6 BP 511 EP 512 DI 10.1097/01.meg.0000108329.52416.6e PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 827BW UT WOS:000221874300001 ER PT J AU Mazarati, A Lu, XY Kilk, K Langel, U Wasterlain, C Bartfai, T AF Mazarati, A Lu, XY Kilk, K Langel, U Wasterlain, C Bartfai, T TI Galanin type 2 receptors regulate neuronal survival, susceptibility to seizures and seizure-induced neurogenesis in the dentate gyrus SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; peptide nucleic acid antisense; plasticity; rat; status epilepticus ID ELECTROCONVULSIVE SHOCK EXPOSURE; CENTRAL-NERVOUS-SYSTEM; STATUS EPILEPTICUS; MESSENGER-RNA; RAT HIPPOCAMPUS; BASAL FOREBRAIN; CHOLINERGIC NEURONS; PERFORANT PATH; KNOCKOUT MICE; GROWTH-FACTOR AB The neuropeptide galanin has been implicated in inhibiting seizures and protecting hippocampal neurons from excitotoxic injury. In the hippocampus galanin acts through two receptor subtypes, GalR1, expressed in CA1, and GalR2, abundant in dentate gyrus. We developed an approach to induce and to study selective semichronic knockdown of GalR2 in the rat hippocampus. A 50% reduction of GalR2 binding was achieved by continuous infusion of complementary peptide nucleic acid antisense oligonucleotide into the dentate gyrus. This resulted in an increase in the severity of self-sustaining status epilepticus induced by electrical stimulation of the perforant path, induced mild neuronal injury in the dentate hilus, augmented seizure-induced hilar injury and inhibited seizure-induced neurogenesis in the subgranular zone of the dentate gyrus. Our data suggest that in the dentate gyrus, galanin, acting through GalR2, inhibits seizures, promotes viability of hilar interneurons and stimulates seizure-induced neurogenesis. These results are important for understanding the role of galanin and galanin receptor subtypes in the hippocampus both under normal conditions and in excitotoxic injury. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, D Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Scripps Res Inst, Dept Neuropharmacol, Harold L Dorris Neurol Res Ctr, La Jolla, CA 92037 USA. Stockholm Univ, Dept Neurochem & Neurotoxicol, SE-10691 Stockholm, Sweden. RP Mazarati, A (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mazarati@ucla.edu FU NINDS NIH HHS [NS 43409] NR 53 TC 85 Z9 90 U1 1 U2 3 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 JUN PY 2004 VL 19 IS 12 BP 3235 EP 3244 DI 10.1111/j.1460-9568.2004.03449.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 832TE UT WOS:000222289300012 PM 15217380 ER PT J AU Petersen, T Papakostas, GI Mahal, Y Guyker, WM Beaumont, EC Alpert, JE Fava, M Nierenberg, AA AF Petersen, T Papakostas, GI Mahal, Y Guyker, WM Beaumont, EC Alpert, JE Fava, M Nierenberg, AA TI Psychosocial functioning in patients with treatment resistant depression SO EUROPEAN PSYCHIATRY LA English DT Article DE treatment resistant depression; psychosocial functioning ID PRIMARY-CARE PATIENTS; MAJOR DEPRESSION; FOLLOW-UP; GLOBAL BURDEN; DISABILITY; RECOVERY; PREDICTORS; PREVALENCE; CHRONICITY; DISORDERS AB Background. - Depression is a disorder that causes disability, with a profound adverse impact on all areas of psychosocial functioning. This is particularly true for those with treatment resistant depression (TRD). However, to date, no systematic assessments of psychosocial functioning for patients with TRD have been conducted. Methods. - In the present study, we used the Longitudinal Interval Follow-up Evaluation (LIFE) scale to measure psychosocial functioning in 92 patients with TRD. These patients met formal criteria for TRD and were part of a clinical trial examining the efficacy of lithium augmentation of nortriptyline. Results. - Clinicians rated this sample of patients as experiencing mild to moderate impairment in work-related activities, good to fair interpersonal relations, poor level of involvement in recreational activities, and mild impairment of ability to enjoy sexual activity. Patients and clinicians rated global social adjustment as poor. Conclusions. - Patients with formally defined TRD experience significant impairment in psychosocial functioning. In this sample a tendency existed for both clinicians and patients to assign more severely impaired global ratings when compared with ratings for specific functional areas. (C) 2004 Published by Elsevier SAS. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WAC, Boston, MA 02114 USA. EM tpetersen@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH 46952] NR 43 TC 17 Z9 17 U1 2 U2 3 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD JUN PY 2004 VL 19 IS 4 BP 196 EP 201 DI 10.1016/j.eurpsy.2003.11.006 PG 6 WC Psychiatry SC Psychiatry GA 835CJ UT WOS:000222457200003 PM 15196600 ER PT J AU Kradin, RL Sakamoto, H Jain, F Zhao, LH Hymowitz, G Preffer, F AF Kradin, RL Sakamoto, H Jain, F Zhao, LH Hymowitz, G Preffer, F TI IL-10 inhibits inflammation but does not affect fibrosis in the pulmonary response to bleomycin SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE interleukin-10; bleomycin; fibrosis; inflammation ID DENDRITIC CELLS; ALVEOLAR MACROPHAGES; LUNG INJURY; INTERLEUKIN-10; CHEMOKINE; EOSINOPHIL; EXPRESSION; MONOCYTES; EOTAXIN; MICE AB Bleomycin yields pulmonary injury characterized by inflammation that proceeds to fibrosis. The production of IL-10 by pulmonary macrophages is increased in the inflammation that accompanies bleomycin lung injury. In the present study, IL-10 deficient and wildtype mice received 0.075 units of bleomycin intratracheally at day 0 and were sacrificed at day 7 or day 14. At day 7, pulmonary inflammation was increased in IL-10-deficient mice as reflected by increased representation of CD3+ and CD4+ lymphocytes and GR-1+ pulmonary granulocytes in the bronchoalveolar lavage (BAL) fluid. Pulmonary interstitial CD80+ and CD86+ mononuclear cells were increased in situ. At day 14, mononuclear cell inflammation was comparable between groups but pulmonary eosinophils were increased in the wildtype. There was no difference in the degree of pulmonary fibrosis, as judged by histology or lung hydroxyproline content. Lung chemokine expression of MIP-1alpha/1beta, MIP-2, and eotaxin was increased at days 7 and 14 with a trend towards increased MCP-1 expression at day 14. The findings suggest an immumomodulatory role for IL-10 in the inflammatory response but not in the pulmonary fibrosis yielded by bleomycin. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Immunopathol & Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Immunopathol & Pulm & Crit Care Unit, Warren 5, Boston, MA 02114 USA. EM rkradin@partners.org FU PHS HHS [R0139054] NR 36 TC 25 Z9 29 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 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD JUN PY 2004 VL 76 IS 3 BP 205 EP 211 DI 10.1016/j.yexmp.2003.12.010 PG 7 WC Pathology SC Pathology GA 822CX UT WOS:000221513500003 PM 15126102 ER PT J AU Finch, CE Weindruch, R AF Finch, CE Weindruch, R TI In praise of Roy - Honouring Roy L. Walford - June 29, 1924-April 27, 2004 - Preface SO EXPERIMENTAL GERONTOLOGY LA English DT Editorial Material C1 Univ So Calif, Dept Sci Biol, Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Univ Wisconsin, Sch Med, Dept Med,William S Middleton Mem Vet Hosp, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. RP Finch, CE (reprint author), Univ So Calif, Dept Sci Biol, Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. EM cefinch@usc.edu; rhweindr@wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUN PY 2004 VL 39 IS 6 BP 869 EP 869 DI 10.1016/j.exger.2004.03.027 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 825TU UT WOS:000221782000002 ER PT J AU Paglia, DE AF Paglia, DE TI Biosphere 2, black swans, and the essence of serendipity SO EXPERIMENTAL GERONTOLOGY LA English DT Article C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Hematol Res Lab, Los Angeles, CA 90073 USA. Space Biospheres Ventures, Biosphere Project 2, Oracle, AZ USA. RP Paglia, DE (reprint author), Univ Calif Los Angeles, Sch Med, 10833 LeConte Ave, Los Angeles, CA 90095 USA. EM dpaglia@mcn.org NR 2 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUN PY 2004 VL 39 IS 6 BP 919 EP 922 DI 10.1016/j.exger.2004.03.012 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 825TU UT WOS:000221782000018 ER PT J AU Weindruch, R AF Weindruch, R TI Fond memories of my years at UCLA with Roy Walford SO EXPERIMENTAL GERONTOLOGY LA English DT Biographical-Item C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. RP Weindruch, R (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. EM rhweindr@wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUN PY 2004 VL 39 IS 6 BP 943 EP 945 DI 10.1016/j.exger.2004.03.032 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 825TU UT WOS:000221782000024 ER PT J AU Ulbert, I Magloczky, Z Eross, L Czirjak, S Vajda, J Bognar, L Toth, S Szabo, Z Halasz, P Fabo, D Halgren, E Freund, TF Karmos, G AF Ulbert, I Magloczky, Z Eross, L Czirjak, S Vajda, J Bognar, L Toth, S Szabo, Z Halasz, P Fabo, D Halgren, E Freund, TF Karmos, G TI In vivo laminar electrophysiology co-registered with histology in the hippocampus of patients with temporal lobe epilepsy SO EXPERIMENTAL NEUROLOGY LA English DT Article DE temporal lobe epilepsy; hippocampus; human; laminar electrophysiology; histology; CA1; DG; interictal spike; bursting unit ID CURRENT SOURCE-DENSITY; DENTATE GRANULE CELLS; INTERMODAL SELECTIVE ATTENTION; EPILEPTOGENIC FOCUS; ANURAN CEREBELLUM; ENTORHINAL CORTEX; AMYGDALA NEURONS; FIRING PATTERNS; FIBER PATHWAY; BEHAVING RAT AB Laminar multiple microelectrodes have been developed to sample cortical and hippocampal activity in animals. If these measurements are adequately co-registered with the anatomy of the region, they can yield important information about its function and structure. In vivo laminar electrophysiological recordings from the human epileptic hippocampus are rare. However, histological and immunohistochemical analyses are widely used to determine the structural changes associated with temporal lobe epilepsy (TLE). Here we present data obtained by a combined approach: intraoperative recording of laminar field potentials, single and multiple unit activity under anesthesia, accompanied by histology and immunohistochemistry from the same hippocampal region of epileptic patients undergoing temporal lobectomy for drug-resistant TLE. The stability of the electrophysiology and the accuracy of its co-registration with histology were tested successfully. We have found large field potential spikes associated with bursting single units in CA1. Intracortical and subdural strip recordings from the lateral temporal cortex showed similar field potential activation patterns. A prominent oscillatory activity was present in the dentate gyrus with highly localized field potential gradient and multiple unit activity. This pattern could be used as a landmark defining the position of the electrode in the hippocampus. Our findings indicate that some aspects of the local and network epileptiform activity in the hippocampal formation are likely preserved under anesthesia. Electrophysiological identification of the functional state of the hippocampus together with its local structural correlates could further enhance our understanding of this disease. (C) 2004 Elsevier Inc. All rights reserved. C1 Hungarian Acad Sci, Inst Psychol, Dept Psychophysiol, H-1068 Budapest, Hungary. Harvard Univ, MIT, Massachusetts Gen Hosp, Sch Med,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MAV Hosp, Dept Neurosurg, H-1062 Budapest, Hungary. Hungarian Acad Sci, Inst Expt Med, H-1450 Budapest, Hungary. Natl Inst Neurosurg, H-1577 Budapest, Hungary. Natl Inst Psychiat & Neurol, Epilepsy Ctr, H-1021 Budapest, Hungary. INSERM, F-13258 Marseille, France. RP Ulbert, I (reprint author), Hungarian Acad Sci, Inst Psychol, Dept Psychophysiol, Szondi U 83-85, H-1068 Budapest, Hungary. EM ulbert@cogpsyphy.hu RI Ulbert, Istvan/F-2213-2010; OI Czirjak, Sandor/0000-0002-8224-3561; Eross, Lorand/0000-0002-5796-5546 FU NIMH NIH HHS [MH54671]; NINDS NIH HHS [NS18741, NS44623, R01 NS018741, R01 NS044623] NR 55 TC 18 Z9 20 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2004 VL 187 IS 2 BP 310 EP 318 DI 10.1016/j.expneurol.2003.12.003 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 823HU UT WOS:000221602200010 PM 15144857 ER PT J AU Avellino, AM Dailey, AT Harlan, JM Sharar, SR Winn, RK McNutt, LD Kliot, M AF Avellino, AM Dailey, AT Harlan, JM Sharar, SR Winn, RK McNutt, LD Kliot, M TI Blocking of up-regulated ICAM-1 does not prevent macrophage infiltration during Wallerian degeneration of peripheral nerve SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Wallerian degeneration; macrophage; ICAM-1; Mac-1; LFA-1; knockout mouse; rat ID INTERCELLULAR-ADHESION MOLECULE-1; IMMUNE-MEDIATED DEMYELINATION; MONOCYTE MIGRATION; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; SYSTEM; MICE; REGENERATION; RESPONSES; INTEGRIN AB Circulating blood monocytes infiltrate into distal degenerating nerve and differentiate into activated macrophages that remove degenerating axonal and myelin debris and promote axonal regeneration. The cellular and molecular mechanisms responsible for this monocyte-macrophage recruitment remain largely unknown. Cell adhesion molecules which mediate monocyte and endothelial cell interactions, such as the endothelial cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) interaction with the monocyte adhesion molecules Mac-1 (complement receptor type 3) and LFA-1 (lymphocyte function-associated antigen-1), have been shown to play a critical role in mediating the transendothelial migration of circulating monocytes into nonneural tissues following various types of injury. This study investigated whether these cell adhesion molecules also play a critical role in mediating monocyte-macrophage infiltration during Wallerian degeneration of peripheral nerve. Following sciatic nerve transection, Mac-1- and LFA-1-positive macrophages in distal degenerating nerve increased in number at 2 days and peaked at 14 days before declining. The number of ICAM-1-immunostained blood vessels increased maximally at 1 day before declining to baseline levels by 14 days. Three days following nerve transection, the intensity of ICAM-1 immunostaining on intraneural blood vessels was maximal and then decreased to baseline levels by 14 days. To test the role of ICAM-1 in mediating monocyte-macrophage recruitment, we used two complementary experimental strategies following a sciatic nerve transection: (1) intravenous administration of a rat ICAM-1-blocking monoclonal antibody and (2) ICAM-I knockout mice. In both cases, the number of infiltrating monocytes-macrophages was above controls, which is opposite to what has been shown to occur in other tissues following injury. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Div Hematol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. RP Avellino, AM (reprint author), Childrens Hosp & Med Ctr, Dept Neurol Surg, 4800 Sand Point Way NE,POB 5371-6E-1, Seattle, WA 98105 USA. EM anthony.avellino@seattlechildrens.org FU NHLBI NIH HHS [HL18645]; NINDS NIH HHS [1-F32-NS-10480-01A1, 1-K08-NS01790-01, T32NS-07144-15] NR 44 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2004 VL 187 IS 2 BP 430 EP 444 DI 10.1016/j.expneurol.2004.02.004 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 823HU UT WOS:000221602200022 PM 15144869 ER PT J AU Richardson, PG AF Richardson, PG TI A review of the proteasome inhibitor bortezomib in multiple myeloma SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE apoptosis; bortezomib; cell adhesion-mediated drug resistance; dexamethasone; multiple myeloma; NF-kappa B; proteasome inhibitor; ubiquitin-proteasome pathway ID NF-KAPPA-B; MEDIATED DRUG-RESISTANCE; ACTIVATED PROTEIN-KINASE; MARROW STROMAL CELLS; IN-VIVO; THERAPEUTIC APPLICATIONS; PROTEOLYTIC PATHWAY; PROGNOSTIC-FACTORS; INDUCED APOPTOSIS; BETA-CATENIN AB Multiple myeloma (MM) represented 14% of new haematological malignancies in the US in 2003 and almost 19% of anticipated deaths. Treatment with standard chemotherapy has resulted in a median survival of about 3 years and despite the improvements in survival seen with the use of intensive therapy supported by autologous stem cell transplantation, MM remains incurable; hence, new therapeutic strategies are urgently needed. One novel approach to the treatment of MM is the use of proteasome inhibitors. Proteasomes are ubiquitous protease complexes involved in diverse aspects of cell biology, such as protein homeostasis, cell cycle progression, apoptosis and inflammation, as well as resistance to antineoplastic therapy. The first-in-class proteasome inhibitor, bortezomib was recently approved in the US for the treatment of patients with MM who have received at least two prior therapies and are progressing on their last therapy. Its use in earlier-stage MM, other haematological malignancies and in solid tumours as monotherapy and in combination therapy is currently under investigation. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Oncol, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Oncol, 1B02,44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 92 TC 30 Z9 30 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JUN PY 2004 VL 5 IS 6 BP 1321 EP 1331 DI 10.1517/14656566.5.6.1321 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 830UA UT WOS:000222147900009 PM 15163277 ER PT J AU Banerji, L Sattler, M AF Banerji, L Sattler, M TI Targeting mutated tyrosine kinases in the therapy of myeloid leukaemias SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE BCR-ABL; Flt3; myeloid leukaemia; platelet-derived growth factor receptor (PDGFR); tyrosine kinase oncogene ID GROWTH-FACTOR RECEPTOR; CHRONIC MYELOGENOUS LEUKEMIA; STEM-CELL FACTOR; INTERNAL TANDEM DUPLICATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROTOONCOGENE C-KIT; GASTROINTESTINAL STROMAL TUMORS; FACTOR-BETA-RECEPTOR; SRC FAMILY KINASE; CHRONIC MYELOMONOCYTIC LEUKEMIA AB Myeloid leukaemias are frequently associated with translocations and mutations of tyrosine kinase genes. The products of these oncogenes, including BCR-ABL, TEL-PDGFR, Flt3 and c-Kit, have elevated tyrosine kinase activity and transform haematopoietic cells, mainly by augmentation of proliferation and enhanced viability. Activated ABL kinases are associated with chronic myeloid leukaemia. Mutations in platelet-derived growth factor receptor beta are associated with chronic myelomonocytic leukaemia. Flt3 or c-Kit cooperate with other types of oncogenes to create fully transformed acute leukaemias. Elevated activity of these tyrosine kinases is crucial for transformation, thus making the kinase domain an ideal target for therapeutic intervention. Tyrosine kinase inhibitors for various kinases are currently being evaluated in clinical trials and are potentially useful therapeutic agents in myeloid leukaemias. Here, the authors review the signalling activities, mechanism of transformation and therapeutic targeting of several tyrosine kinase oncogenes important in myeloid leukaemias. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu NR 251 TC 12 Z9 12 U1 2 U2 11 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JUN PY 2004 VL 8 IS 3 BP 221 EP 239 DI 10.1517/14728222.8.3.221 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 830TO UT WOS:000222146500005 PM 15161429 ER PT J AU Wen, LK Parchman, ML Shepherd, MD AF Wen, LK Parchman, ML Shepherd, MD TI Family support and diet barriers among older hispanic adults with type 2 diabetes SO FAMILY MEDICINE LA English DT Article ID MEXICAN-AMERICANS; SOCIAL-ENVIRONMENT; SELF-MANAGEMENT; HEALTH BELIEFS; MELLITUS; APGAR; ADHERENCE; VALIDITY; ACCULTURATION; VALIDATION AB Background and Objectives: Diet plays an important role in the management of diabetes, and a suboptimal diet is a commonly identified problem. Family support may be important in overcoming barriers to good diet. We conducted this study to examine the role of the family in overcoming barriers to diet self-care among older Hispanic patients with diabetes. Methods: We performed a cross-sectional survey of 138 older Hispanic adults seeking care at an outpatient university clinic. Patients reported on their perception of family functioning, family support for diet, and barriers to diet self-care. Results: Level of family functioning was related to family support for diet self-care, and family support for diet was related to perceived barriers to diet self-care. Scores for family support were higher for those who perceived their family as functional compared to those who perceived their family as mildly dysfunctional or dysfunctional. As family support for diet increased, perceived barriers to diet self-care decreased. Conclusions: To fully understand difficulties encountered by older Hispanic adults with adherence to a diabetic diet, primary care physicians should explore the role of family support and family functioning. For those with poorly functioning families or low levels of family support, family-level interventions may need to be considered. C1 VERDICT, S Texas Vet Hlth Care Syst, Ambulatory Care 11C6, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. RP Parchman, ML (reprint author), VERDICT, S Texas Vet Hlth Care Syst, Ambulatory Care 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu NR 42 TC 45 Z9 46 U1 0 U2 5 PU SOC TEACHERS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, STE 540, LEAWOOD, KS 66207 USA SN 0742-3225 J9 FAM MED JI Fam. Med. PD JUN PY 2004 VL 36 IS 6 BP 423 EP 430 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 827GW UT WOS:000221888700013 PM 15181555 ER PT J AU Weiner, JB Nagurney, JT Brown, DFM Sane, S Wang, AC AF Weiner, JB Nagurney, JT Brown, DFM Sane, S Wang, AC TI Duration of symptoms and follow-up patterns of patients discharged from the emergency department after presenting with abdominal or flank pain SO FAMILY PRACTICE LA English DT Article DE abdominal pain; follow-up; natural history; telephone ID ACUTE APPENDICITIS AB Background. Little is known about the duration of symptoms and follow-up patterns of patients seen in emergency departments for abdominal or flank pain. Objective. We aimed to measure the duration of symptoms and follow-up rate of patients discharged home from the emergency department after presenting with non-traumatic abdominal or flank pain. Methods. We conducted a single-centre, prospective descriptive study of adult patients who presented to our emergency department with non-traumatic abdominal or flank pain and were discharged from the emergency department. We gathered clinical data during the index emergency department visit and conducted telephone interviews of subjects 2-5 weeks later. Results. We reached 63 of 90 subjects (70%). The median duration of pain was 3 days after the emergency department visit. During the follow-up period, only 41% had followed-up with their family physician or primary care provider, although an additional 21% had planned to. Persistence of symptoms was common in the 37% of subjects who did not follow-up. Conclusion. Of subjects discharged from the emergency department after visits for non-traumatic abdominal or flank pain, most improve within several days. Fewer than half follow-up with a family practitioner or a primary care provider. Emergency department revisits are uncommon and often for unrelated problems. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02115 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Princeton Univ, Princeton, NJ 08544 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, 55 Fruit St, Boston, MA 02115 USA. EM nagurney.john@mgh.harvard.edu NR 7 TC 3 Z9 3 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 J9 FAM PRACT JI Fam. Pr. PD JUN PY 2004 VL 21 IS 3 BP 314 EP 316 DI 10.1093/fampra/cmh318 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 819DW UT WOS:000221294900018 PM 15128696 ER PT J AU Cullen, PA Haake, DA Adler, B AF Cullen, PA Haake, DA Adler, B TI Outer membrane proteins of pathogenic spirochetes SO FEMS MICROBIOLOGY REVIEWS LA English DT Review DE pathogenic spirochetes; outer membrane proteins; lipoproteins; immunity; pathogenesis; surface exposure ID LYME-DISEASE SPIROCHETE; BORRELIA-BURGDORFERI LIPOPROTEINS; DECORIN-BINDING-PROTEIN; MAJOR SURFACE PROTEIN; INACTIVATED TREPONEMA-HYODYSENTERIAE; PEPTIDOGLYCAN-ASSOCIATED LIPOPROTEIN; INTERROGANS SEROVAR HARDJO; RELAPSING FEVER BACTERIUM; VARIABLE ANTIGEN GENES; ESCHERICHIA-COLI AB Pathogenic spirochetes are the causative agents of several important diseases including syphilis, Lyme disease, leptospirosis, swine dysentery, periodontal disease and some forms of relapsing fever. Spirochetal bacteria possess two membranes and the proteins present in the outer membrane are at the site of interaction with host tissue and the immune system. This review describes the current knowledge in the field of spirochetal outer membrane protein (OMP) biology. What is known concerning biogenesis and structure of OMPs, with particular regard to the atypical signal peptide cleavage sites observed amongst the spirochetes, is discussed. We examine the functions that have been determined for several spirochetal OMPs including those that have been demonstrated to function as adhesins, porins or to have roles in complement resistance. A detailed description of the role of spirochetal OMPs in immunity, including those that stimulate protective immunity or that are involved in antigenic variation, is given. A final section is included which covers experimental considerations in spirochetal outer membrane biology. This section covers contentious issues concerning cellular localization of putative OMPs, including determination of surface exposure. A more detailed knowledge of spirochetal OMP biology will hopefully lead to the design of new vaccines and a better understanding of spirochetal pathogenesis. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Monash Univ, Dept Microbiol, Australian Bacterial Pathogenesis Program, Melbourne, Vic 3800, Australia. Monash Univ, Victorian Bioinformat Consortium, Melbourne, Vic 3800, Australia. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. RP Adler, B (reprint author), Monash Univ, Dept Microbiol, Australian Bacterial Pathogenesis Program, Melbourne, Vic 3800, Australia. EM Ben.Adler@med.monash.edu.au FU NIAID NIH HHS [AI-34331, R01 AI034431, R01 AI034431-07, R21 AI034431, R29 AI034431] NR 307 TC 97 Z9 103 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD JUN PY 2004 VL 28 IS 3 BP 291 EP 318 DI 10.1016/j.femsre.2003.10.004 PG 28 WC Microbiology SC Microbiology GA 830RU UT WOS:000222141400002 PM 15449605 ER PT J AU El-Serag, HB Petersen, NJ Carter, J Graham, DY Richardson, P Genta, RM Rabeneck, L AF El-Serag, HB Petersen, NJ Carter, J Graham, DY Richardson, P Genta, RM Rabeneck, L TI Gastroesophageal reflux among different racial groups in the United States SO GASTROENTEROLOGY LA English DT Article ID HELICOBACTER-PYLORI; BARRETTS-ESOPHAGUS; GASTRIC CARDIA; DISEASE; ADENOCARCINOMA; EPIDEMIOLOGY; POPULATION; PREVALENCE; SYMPTOMS AB Background & Aims: White people in the United States are several-fold more affected by esophageal adenocarcinoma than black people. It remains unknown whether this racial discrepancy reflects a higher prevalence of gastroesophageal reflux disease (GERD) symptoms or a higher degree of esophageal damage. Methods: A cross-sectional survey followed by endoscopy was performed among employees at a VA medical center. The association between race and GERD symptoms and erosive esophagitis was analyzed in logistic regression analyses controlling for demographic, clinical, and histologic variables. Results: A total of 496 of 915 people (54%) returned interpretable questionnaires, and endoscopy was performed in 215 participants. The mean age was 45 years, and 336 (68%) were women. Racial distribution was 43% black, 34% white, and 23% other races. Heartburn occurring at least weekly was reported in 27%, 23%, and 24% of these racial groups, respectively. The age-adjusted prevalence of heartburn or regurgitation was not significantly different among the groups. Erosive esophagitis was found in 50 of 2:15 participants (23%); 31 of these cases were mild. Only one person had Barrett's esophagus (0.4%). For weekly heartburn or regurgitation, black participants had significantly less frequent erosive esophagitis than white participants (24% vs. 50%; P = 0.03). With multiple adjustments, black participants had a persistently lower risk of esophagitis (adjusted odds ratio, 0.22-0.46; P < 0.001). Conclusions: White and black people in the United States have a similarly high prevalence of GERD symptoms. However, black people have a lower prevalence of esophagitis for the same frequency of GERD symptoms. Barrett's esophagus was rare in this study, even among those with frequent symptoms. C1 US Dept Vet Affairs, Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. US Dept Vet Affairs, Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP US Dept Vet Affairs, Med Ctr, Gastroenterol Sect, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 24 TC 131 Z9 139 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2004 VL 126 IS 7 BP 1692 EP 1699 DI 10.1053/j.gastro.2004.03.077 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 827GS UT WOS:000221888300013 PM 15188164 ER PT J AU Spiegel, BMR DeRosa, VP Gralnek, IM Wang, V Dulai, GS AF Spiegel, BMR DeRosa, VP Gralnek, IM Wang, V Dulai, GS TI Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: A cost-effectiveness analysis SO GASTROENTEROLOGY LA English DT Article ID ROME CRITERIA; PRIMARY-CARE; DISEASE; PREVALENCE; PROGNOSIS; SYMPTOMS AB Background & Aims: Some patients with diarrhea-predominant irritable bowel syndrome (IBS-D) may have undiagnosed celiac sprue (CS). Because the symptoms of CS respond to a gluten-free diet, testing for CS in IBS may prevent years of morbidity and attendant expense. We sought to determine whether this might be a cost-effective diagnostic strategy in IBS-D. Methods: We used decision analysis to calculate the cost-effectiveness of 2 competing strategies in IBS-D: (1) start empirical IBS treatment and (2) perform serologic test for CS followed by endoscopic biopsy for positive tests. The base-case cohort had a CS prevalence of 3.4%, which was varied between 0% and 100% in sensitivity analysis. The outcome measure was cost per symptomatic improvement. Results: Under base-case conditions, testing for CS instead of starting empiric IBS therapy cost an incremental $11,000 to achieve one additional symptomatic improvement. Testing for CS became the dominant strategy when the prevalence of CS exceeded 8%, the specificity of CS testing exceeded 98%, or the cost of IBS therapy exceeded $130/month. The incremental cost-effectiveness of testing for CS exceeded $50,000 when the prevalence fell below 1%. Conclusions: Testing for CS in patients with IBS-D has an acceptable cost when the prevalence of CS is above 1% and is the dominant strategy when the prevalence exceeds 8%. The decision to test should be based on a consideration of the population prevalence of underlying CS, the operating characteristics of the screening test employed, and the cost of proposed therapy for IBS. C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215B, Los Angeles, CA 90073 USA. EM bspiegel@ucla.edu FU NCRR NIH HHS [K23 RR 16188]; NIDDK NIH HHS [DK 07180] NR 38 TC 85 Z9 90 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2004 VL 126 IS 7 BP 1721 EP 1732 DI 10.1053/j.gastro.2004.03.012 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 827GS UT WOS:000221888300016 PM 15188167 ER PT J AU Faubion, WA De Jong, YP Molina, AA Ji, HB Clarke, K Wang, BP Mizoguchi, E Simpson, SJ Bhan, AK Terhorst, C AF Faubion, WA De Jong, YP Molina, AA Ji, HB Clarke, K Wang, BP Mizoguchi, E Simpson, SJ Bhan, AK Terhorst, C TI Colitis is associated with thymic destruction attenuating CD(4+)25(+) regulatory T cells in the periphery SO GASTROENTEROLOGY LA English DT Article ID NEGATIVE SELECTION; TRANSGENIC MICE; IN-VIVO; TRANSCRIPTION; HOMEOSTASIS; DIFFERENTIATION; AUTOIMMUNITY; THYMECTOMY; EXPRESSION; IMMUNITY AB Background & Aims: Syngeneic bone marrow transplantation into the adult tgepsilon26 mouse results in severe wasting disease and colitis. On transplantation, the rudimentary thymus of the adult tgepsilon26 mouse repopulates briefly but quickly regresses in temporal association with the onset of colitis. The aim of this study is to test the hypothesis that treatment of colitis restores thymic capability to generate regulatory T cells (CD4(+)25(+) T-R cells). Methods: Colitis was induced by bone marrow transplantation into adult irradiated tgepsilon26 mice. Colitis was prevented by 3 distinct modalities. CD4(+)25(+) T cells were collected from both the thymus and spleen and studied for regulatory function by an in vitro suppression assay. Results: CD4(+)25(+) TR cells do not develop efficiently in the thymus of bone marrow transplanted adult tgepsilon26 mice, which have a developmental arrest affecting thymic epithelium. By contrast, the thymic epithelium of neonatal tgepsilon26 mice supports development of TR cells. Consequently, colitis develops only in adult transplanted mice but not in the neonatally transplanted mice. Treatment of colitis prevents destruction of the thymus of adult transplanted tgepsilon26 mice and TR cells are produced. Conclusions: The negative impact of colitis on TR development in the thymus, which was confirmed in a second model of colitis, has profound implications for the pathogenesis and treatment of human inflammatory bowel disease. C1 Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. Novo Nordisk AS, R&D Ctr, Beijing, Peoples R China. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Faubion, WA (reprint author), 330 Brookline Ave,RE-204, Boston, MA 02215 USA. EM faubion.william@mayo.edu FU NIDDK NIH HHS [DK 43351, DK 47677, DK 52510] NR 37 TC 35 Z9 35 U1 0 U2 4 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 JUN PY 2004 VL 126 IS 7 BP 1759 EP 1770 DI 10.1053/j.gastro.2004.03.015 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 827GS UT WOS:000221888300020 PM 15188171 ER PT J AU Korzenik, JR AF Korzenik, JR TI Crohn's disease: future anti-tumor necrosis factor therapies beyond infliximab SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; ENGINEERED HUMAN-ANTIBODY; PLACEBO-CONTROLLED TRIAL; FACTOR-ALPHA LEVELS; DOUBLE-BLIND; ULCERATIVE-COLITIS; OPEN-LABEL; INTESTINAL INFLAMMATION; MONOCLONAL-ANTIBODY AB The dramatic benefit experienced by many Crohn's patients treated with the anti-tumor necrosis factor-alpha (TNF-alpha) antibody infliximab underscores the centrality of this cytokine in the pathogenesis of Crohn's disease and the potential use of the therapeutic strategy of blocking TNF-alpha in this disease. In the hopes of emulating and improving on the success of infliximab, numerous strategies are being devised and studied to inhibit the actions of TNF-alpha. This article focuses on those agents, other than infliximab, which target TNF-alpha to treat inflammatory bowel disease as their central mechanism of action. C1 Massachusetts Gen Hosp, Dept Internal Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Korzenik, JR (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM jkorzeni@partners.org NR 59 TC 10 Z9 11 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2004 VL 33 IS 2 BP 285 EP + DI 10.1016/j.gtc.2004.02.009 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 833EL UT WOS:000222319100009 PM 15177539 ER PT J AU Mills, KD Ferguson, DO Essers, J Eckersdorff, M Kanaar, R Alt, FW AF Mills, KD Ferguson, DO Essers, J Eckersdorff, M Kanaar, R Alt, FW TI Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability SO GENES & DEVELOPMENT LA English DT Article DE DNA break repair; nonhomologous end joining; homologous recombination; Lig4; Rad54 ID STRAND BREAK REPAIR; LEAKY SCID PHENOTYPE; END-JOINING PATHWAY; HOMOLOGOUS RECOMBINATION; V(D)J RECOMBINATION; HISTONE H2AX; GENOMIC INSTABILITY; DEFECTIVE NEUROGENESIS; EMBRYONIC LETHALITY; TARGETED DISRUPTION AB Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous template. Although both NHEJ and HR have been clearly implicated in the maintenance of genome stability, how these apparently independent and mechanistically distinct pathways are coordinated remains largely unexplored. To investigate the relationship between HR and NHEJ modes of DSB repair, we generated cells doubly deficient for the NHEJ factor DNA Ligase IV (Lig4) and the HR factor Rad54. We show that Lig4 and Rad54 cooperate to support cellular proliferation, repair spontaneous DSBs, and prevent chromosome and single chromatid aberrations. These findings demonstrate a role for NHEJ in the repair of DSBs that occur spontaneously during or after DNA replication, and reveal overlapping functions for NHEJ and Rad54-dependent HR in the repair of such DSBs. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. Erasmus MC, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NIAID NIH HHS [U19 AI031541, AI20047, AI31541, AI35714, P01 AI031541, P01 AI035714, R01 AI020047, R37 AI020047] NR 57 TC 86 Z9 90 U1 0 U2 3 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 JUN 1 PY 2004 VL 18 IS 11 BP 1283 EP 1292 DI 10.1101/gad.1204304 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 826SP UT WOS:000221849200007 PM 15175260 ER PT J AU Couedel, C Mills, KD Barchi, M Shen, L Olshen, A Johnson, RD Nussenzweig, A Essers, J Kanaar, R Li, GC Alt, FW Jasin, M AF Couedel, C Mills, KD Barchi, M Shen, L Olshen, A Johnson, RD Nussenzweig, A Essers, J Kanaar, R Li, GC Alt, FW Jasin, M TI Collaboration of homologous recombination and nonhomologous end-joining factors for the survival and integrity of mice and cells SO GENES & DEVELOPMENT LA English DT Article DE DNA double-strand break; homologous recombination; nonhomologous end-joining; Ku80, Rad54 ID DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS; DNA-DAMAGE; IONIZING-RADIATION; EMBRYONIC NEUROGENESIS; GENOMIC INSTABILITY; REPAIR PATHWAY; HISTONE H2AX; KINASE; GENE AB Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are mechanistically distinct DNA repair pathways that contribute substantially to double-strand break (DSB) repair in mammalian cells. We have combined mutations in factors from both repair pathways, the HR protein Rad54 and the DNA-end-binding factor Ku80, which has a role in NHEJ. Rad54(-/-)Ku80(-/-) mice were severely compromised in their survival, such that fewer double mutants were born than expected, and only a small proportion of those born reached adulthood. However, double-mutant mice died at lower frequency from tumors than Ku80 single mutant mice, likely as a result of rapid demise at a young age from other causes. When challenged with an exogenous DNA damaging agent, ionizing radiation, double-mutant mice were exquisitely sensitive to low doses. Tissues and cells from double-mutant mice also showed indications of spontaneous DNA damage. Testes from some Rad54(-/-)Ku80(-/-) mice displayed enhanced apoptosis and reduced sperm production, and embryonic fibroblasts from Rad54(-/-)Ku80(-/-) animals accumulated foci of gamma-H2AX, a marker for DSB s. The substantially increased DNA damage response in the double mutants implies a cooperation of the two DSB repair pathways for survival and genomic integrity in the animal. C1 Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01605 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Erasmus MC, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. Erasmus MC, Dept Radiat Oncol, NL-3000 DR Rotterdam, Netherlands. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Jasin, M (reprint author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, 1275 York Ave, New York, NY 10021 USA. EM m-jasin@ski.mskcc.org OI Barchi, Marco/0000-0003-1104-6234 FU NCI NIH HHS [R01 CA056909, CA56909, CA78497]; NICHD NIH HHS [HD40916, R01 HD040916]; NIGMS NIH HHS [GM54668, R01 GM054668] NR 41 TC 103 Z9 106 U1 3 U2 6 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 JUN 1 PY 2004 VL 18 IS 11 BP 1293 EP 1304 DI 10.1101/gad.1209204 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 826SP UT WOS:000221849200008 PM 15175261 ER PT J AU Wu, XH Avni, D Chiba, T Yan, F Zhao, QP Lin, YF Heng, H Livingston, D AF Wu, XH Avni, D Chiba, T Yan, F Zhao, QP Lin, YF Heng, H Livingston, D TI SV40 T antigen interacts with Nbs1 to disrupt DNA replication control SO GENES & DEVELOPMENT LA English DT Article DE Nbs1; SV40 T; SV40 origin; DNA replication; endoreduplication; mammalian cells ID NIJMEGEN BREAKAGE SYNDROME; DOUBLE-STRAND BREAKS; IN-SITU HYBRIDIZATION; SACCHAROMYCES-CEREVISIAE; SYNDROME PROTEIN; SIMIAN VIRUS-40; CELL-CYCLE; S-PHASE; ATAXIA-TELANGIECTASIA; DAMAGE RESPONSE AB Nijmegen breakage syndrome (NBS) is characterized by radiation hypersensitivity, chromosomal instability, and predisposition to cancer. Nbs1, the NBS protein, forms a tight complex with Mrell and Rad50, and these interactions contribute to proper double-strand break repair. The simian virus 40 (SV40) oncoprotein, large T antigen (T), also interacts with Nbs1, and T-containing cells experience chromosomal hyperreplication in a manner dependent on T/Nbs1 complex formation. A substantial fraction of NBS-deficient fibroblasts reinitiate DNA replication in discrete regions, and wild-type Nbs1 corrects this defect. Similarly, synthesis of an N-terminal Nbs1 fragment induced DNA rereplication and tetraploidy, in NBS-deficient but not NBS-proficient cells. Moreover, SV40 origin-containing DNA hyperreplicated in T-containing NBS-deficient cells by comparison with T-containing, Nbs1-reconstituted derivatives. Thus, Nbs1 suppresses rereplication of cellular DNA and SV40 origin-containing replicons, and T targets Nbs1, thereby enhancing the yield of new SV40 genomes during viral DNA replication. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48202 USA. RP Wu, XH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM xiaohwu@scripps.edu; david_livingston@dfcl.harvard.edu NR 61 TC 65 Z9 68 U1 0 U2 1 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 JUN 1 PY 2004 VL 18 IS 11 BP 1305 EP 1316 DI 10.1101/gad.1182804 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 826SP UT WOS:000221849200009 PM 15175262 ER PT J AU Branda, KJ Tomczak, J Natowicz, MR AF Branda, KJ Tomczak, J Natowicz, MR TI Heterozygosity for Tay-Sachs and Sandhoff diseases in non-Jewish Americans with ancestry from Ireland, Great Britain, or Italy SO GENETIC TESTING LA English DT Article ID BETA-HEXOSAMINIDASE-A; SPLICE-SITE MUTATION; ASHKENAZI JEWISH; FRENCH-CANADIANS; PSEUDODEFICIENCY ALLELE; BRITISH-ISLES; CARRIERS; FREQUENCY; GENE; COMMON AB Previous reports have found that non-Jewish Americans with ancestry from Ireland have an increased frequency of heterozygosity for Tay-Sachs disease (TSD), although frequency estimates are substantially different. Our goal in this study was to determine the frequency of heterozygosity for TSD and Sandhoff diseases (SD) among Irish Americans, as well as in persons of English, Scottish, and/or Welsh ancestry and in individuals with Italian heritage, who were referred for determination of their heterozygosity status and who had no known family history of TSD or SD or of heterozygosity for these conditions. Of 610 nonpregnant subjects with Irish background, 24 TSD heterozygotes were identified by biochemical testing, corresponding to a heterozygote frequency of 1 in 25 (4%; 95% CI, 1/39-1/17). In comparison, of 322 nonpregnant individuals with ancestry from England, Scotland, or Wales, two TSD heterozygotes were identified (I in 161 or 0.62%; 95% CI, 1/328-1/45), and three TSD heterozygotes were ascertained from 436 nonpregnant individuals with Italian heritage (1 in 145 or 0.69%; 95% CI, 1/714-1/50). Samples from 21 Irish heterozygotes were analyzed for HEXA gene mutations. Two (9.5%) Irish heterozygotes had the lethal +1 IVS-9 G --> A mutation, whereas 9 (42.8%) had a benign pseudodeficiency mutation. No mutation was found in 10 (47.6%) heterozygotes. These data allow for a frequency estimate of deleterious alleles for TSD among Irish Americans of 1 in 305 (95% CI, 1/2517-1/85) to 1 in 41 (95% CI, 1/72-1/35), depending on whether one, respectively, excludes or includes enzyme-defined heterozygotes lacking a defined deleterious mutation. Pseudodeficiency mutations were identified in both of the heterozygotes with ancestry from other countries in the British Isles, suggesting that individuals with ancestry from these countries do not have an increased rate of TSD heterozygosity. Four SD heterozygotes were found among individuals of Italian descent, a frequency of 1 in 109 (0.92%; 95% CI, 1/400-1/43). This frequency was higher than those for other populations, including those with Irish (I in 305 or 0.33%; 95% CI, 1/252-1/85), English, Scottish, or Welsh (1 in 161 or 0.62%; 95% CI, 1/1328-1/45), or Ashkenazi Jewish (I in 281 or 0.36%; 95% CI, 1/1361-1/96) ancestry. Individuals of Irish or Italian heritage might benefit from genetic counseling for TSD and SD, respectively. C1 Brandeis Univ, Dept Biol Genet Counseling, Waltham, MA 02454 USA. Thomas Jefferson Univ, Jefferson Med Coll, Div Med Genet, Philadelphia, PA 19107 USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Natowicz, MR (reprint author), Cleveland Clin Fdn, Dept Neurol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM natowim@ccf.org NR 43 TC 7 Z9 7 U1 3 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD SUM PY 2004 VL 8 IS 2 BP 174 EP 180 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 849BW UT WOS:000223513900017 PM 15345116 ER PT J AU Yu, HY Luscombe, NM Lu, HX Zhu, XW Xia, Y Han, JDJ Bertin, N Chung, S Vidal, M Gerstein, M AF Yu, HY Luscombe, NM Lu, HX Zhu, XW Xia, Y Han, JDJ Bertin, N Chung, S Vidal, M Gerstein, M TI Annotation transfer between genomes: Protein-protein interologs and protein-DNA regulogs SO GENOME RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; INTERACTION MAP; C-ELEGANS; SYSTEMATIC DEFINITION; YEAST PROTEOME; BUDDING YEAST; SEQUENCE; DATABASE; COMPLEXES; NETWORKS AB Proteins function mainly through interactions, especially with DNA and other proteins. While some large-scale interaction networks are now available for a number of model organisms, their experimental generation remains difficult. Consequently, interolog mapping-the transfer of interaction annotation from one organism to another using comparative genomics-is of significant value. Here we quantitatively assess the degree to which interologs can be reliably transferred between species as a function of the sequence similarity of the corresponding interacting proteins. Using interaction information from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Helicobacter pylori, we find that protein-protein interactions can be transferred when a pair of proteins has a joint sequence identity >80% or a joint E-value <10(-70). (These "joint" quantities are the geometric means of the identities or E-values for the two pairs of interacting proteins.) We generalize Our interolog analysis to protein-DNA binding, finding such interactions are conserved at specific thresholds between 30% and 60% Sequence identity depending oil the protein family. Furthermore, we introduce the concept of a "regulog"-a conserved regulatory relationship between proteins across different species. We map interologs and regulogs from yeast to a number of genomes with limited experimental annotation (e.g., Arabidopsis thaliana) and make these available through ail online database at http://interolog.gersteinlab.org. Specifically, we are able to transfer -90,000 potential protein-protein interactions to the worm. We test a number of these in two-hybrid experiments and are able to verify 45 overlaps, which we show to be statistically significant. C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gerstein, M (reprint author), Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. EM Mark.Gerstein@yale.edu RI Bertin, Nicolas/C-3025-2008; OI Bertin, Nicolas/0000-0002-9835-9606; Xia, Yu/0000-0002-5596-5518 FU NIGMS NIH HHS [5P50GM062413, P50 GM062413] NR 54 TC 304 Z9 321 U1 0 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 2004 VL 14 IS 6 BP 1107 EP 1118 DI 10.1101/gr.1774904 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 826TR UT WOS:000221852400013 PM 15173116 ER PT J AU Penson, RT Seiden, MV Goodman, A Fuller, AF Berkowitz, RS Matulonis, UA Krasner, C Lee, H Atkinson, T Campos, SM AF Penson, RT Seiden, MV Goodman, A Fuller, AF Berkowitz, RS Matulonis, UA Krasner, C Lee, H Atkinson, T Campos, SM CA Gynecologic Oncology Res Program F TI Phase I trial of escalating doses of topotecan in combination with a fixed dose of pegylated liposomal doxorabicin in women with mullerian malignancies SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; chemotherapy; clinical trials; combination; topoisomerase; palliative ID CELL LUNG-CANCER; COLONY-STIMULATING FACTOR; RECURRENT OVARIAN-CANCER; REFRACTORY SOLID TUMORS; CONTINUOUS-INFUSION; RANDOMIZED TRIAL; TOPOISOMERASE-I; ORAL ETOPOSIDE; DOXORUBICIN; IRINOTECAN AB Background. Topotecan and pegylated liposomal doxorubicin (Doxil) interact with topoisomerase I and II (topo I and II), respectively, with schedule dependent, and potentially synergistic cytotoxicity. Objectives. Define dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) of topotecan delivered by 72-h infusion administered immediately after Doxil delivered at a fixed dose (30 mg/m(2)) in a cohort of women with recurrent mullerian malignancies. Methods. Topotecan dose was escalated from 0.5 mg/m(2)/day for 3 days in 0.2 mg/m(2)/day increments with treatment repeated every 21 days. Eligibility criteria required ECOG less than or equal to 2 and no more than four prior lines of chemotherapy. No dose reductions were allowed in the first two cycles to allow evaluation of cutaneous toxicity. Results. Between November 2000 and August 2002, 18 patients were enrolled. Median age 59 (40-71) years. Patients received a median 1 (1-6) cycles of chemotherapy, with 39 cycles of treatment delivered at DL 1. All patients were evaluable for toxicity and 12 for response. At dose level 2, dose-limiting toxicity consisted of nausea and vomiting, mucositis, cutaneous toxicity, and neutropenia. There was no clinically significant cardiac toxicity. There were no radiologically confirmed partial responses. Conclusions. Doxil 30 mg/m(2) and topotecan 0.5 mg/m(2)/day by 72-h infusion (total dose 1.5 mg/m), although a rational combination of cytotoxic therapies, have limited clinical activity. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02114 USA. Dept Med, Div Adult Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Cox 548,100 Blossom St, Boston, MA 02114 USA. EM rpenson@partners.org NR 31 TC 7 Z9 7 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 2004 VL 93 IS 3 BP 702 EP 707 DI 10.1016/j.ygyno.2004.02.028 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 831OS UT WOS:000222204700022 PM 15196868 ER PT J AU Kazis, LE Lee, A Spiro, A Rogers, W Ren, XHS Miller, DR Selim, A Hamed, A Haffer, SC AF Kazis, LE Lee, A Spiro, A Rogers, W Ren, XHS Miller, DR Selim, A Hamed, A Haffer, SC TI Measurement comparisons of the medical outcomes study and Veterans SF-36 (R) health survey SO HEALTH CARE FINANCING REVIEW LA English DT Article ID QUALITY-OF-LIFE; FEE-FOR-SERVICE; SYSTEMS; CARE AB The Medicare Health Outcomes Survey (HOS) uses the Medical Outcomes Study (MOS) SF-36 (R) among beneficiaries enrolled in Medicare managed care programs, whereas the Department of Veterans Affairs (VA), Veterans Health Administration (VHA) has administered the Veterans version of the SF 360 for quality management purposes. The Veterans version is comparable to the MOS version for 6 of the 8 scales, but distinctly different in role physical (RP) and role emotional (RE) scales. The gains in precision for the Veterans SF-36 (R) provide evidence for the use of this version in future applications for assessing patient outcomes across health care systems. C1 Boston Univ, Sch Publ Hlth, Hlth Serv Dept, Boston, MA 02118 USA. Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA. Boston VA Healthcare Syst, Boston, MA USA. Boston VA Healthcare Syst, Boston, MA 02111 USA. Univ Maryland Baltimore Cty, Ctr Med, Baltimore, MD 21228 USA. Univ Maryland Baltimore Cty, Medicaid Serv, Baltimore, MD 21228 USA. RP Kazis, LE (reprint author), Boston Univ, Sch Publ Hlth, Hlth Serv Dept, T-3W,80 E Concord St, Boston, MA 02118 USA. EM LEK@bu.edu NR 32 TC 36 Z9 36 U1 1 U2 4 PU CENTERS FOR MEDICARE & MEDICAID SERVICES PI BALTIMORE PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD SUM PY 2004 VL 25 IS 4 BP 43 EP 58 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 954VP UT WOS:000231183600005 PM 15493443 ER PT J AU Sorensen, G Fagan, P Hunt, MK Stoddard, AM Girod, K Eisenberg, M Frazier, L AF Sorensen, G Fagan, P Hunt, MK Stoddard, AM Girod, K Eisenberg, M Frazier, L TI Changing channels for tobacco control with youth: developing an intervention for working teens SO HEALTH EDUCATION RESEARCH LA English DT Article ID CONSEQUENCES; HEALTH AB Worksites represent an untapped resource for reaching teens with tobacco control messages, given that 80% of teens have held at least one job by the time they graduate from high school. This paper presents formative research findings from a methods development study aimed at designing and testing a tobacco control intervention targeting working teens. Formative research included qualitative methods as well as quantitative data from a cross-sectional survey of teens employed in 10 participating grocery stores. Contrary to our a priori hypothesis, smoking rates among employed youth in this study were not higher than statewide averages and most of the teen workers were still in school, indicating that worksite interventions, at least in this setting, represent an alternative or adjunct to school-based programs, but do not necessarily capture a unique population. Employed teen tobacco use patterns and work characteristics that emerged from our formative research are presented in this paper, and may be useful in planning future worksite interventions for employed teens. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. NCI, Tobacco Control Res Branch, Rockville, MD 20852 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Harvard Univ, Brigham & Womens Hosp, Med Sch & Pediat Oncol, Channing Lab, Boston, MA 02115 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM Glorian_Sorensen@dfci.harvard.edu FU NINR NIH HHS [R01 NR04748] NR 16 TC 6 Z9 6 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD JUN PY 2004 VL 19 IS 3 BP 250 EP 260 DI 10.1093/her/cyg019 PG 11 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 822QJ UT WOS:000221554400004 PM 15140845 ER PT J AU Elstein, AS Chapman, GB Chmiel, JS Knight, SJ Chan, C Nadler, RB Kuzel, TM Siston, AK Bennett, CL AF Elstein, AS Chapman, GB Chmiel, JS Knight, SJ Chan, C Nadler, RB Kuzel, TM Siston, AK Bennett, CL TI Agreement between prostate cancer patients and their clinicians about utilities and attribute importance SO HEALTH EXPECTATIONS LA English DT Article DE preferences; substituted judgement; utility assessment; values ID QUALITY-OF-LIFE; SUSTAINING TREATMENT INFLUENCE; PHYSICIANS OWN PREFERENCES; DECISION-ANALYSIS; ADVANCE DIRECTIVES; SUBSTITUTED JUDGMENTS; RADICAL PROSTATECTOMY; HEALTH STATES; PERCEPTIONS; PREDICTIONS AB Purpose To examine the agreement between prostate cancer patients' utilities for selected health states and their rankings of the importance of six attributes of the health states and the clinicians' judgements of what would be in the patients' best interests. Method Patients with newly diagnosed localized prostate cancer individually completed a time trade-off utility assessment shortly after being diagnosed. The health states evaluated were constructed from a multi-attribute utility model that incorporated six aspects of living with the disease and outcomes of treatment. Each patient assessed his current health state and three hypothetical states that might occur in the future, and provided rankings of the importance of the six attributes. The clinicians caring for each patient independently provided their views of what utilities and importance rankings would be in the patient's best interest. Results The across-participant correlations between patients' and clinicians' utilities were very low and not statistically significant. Across-participant correlations between patient and clinician importance rankings for the six attributes were also low. Across-health state and across-attribute correlations between utilities or importance rankings were highly variable across patient-clinician pairs. Conclusion In the clinical settings studied, there is not a strong relationship between valuations of current and possible future health states by patients with newly diagnosed prostate cancer and their clinicians. Implications of these results for substituted judgement, when clinicians advise their patients or recommend a treatment strategy, are discussed. C1 Univ Illinois, Dept Med Educ, Chicago, IL 60680 USA. Rutgers State Univ, Dept Psychol, Piscataway, NJ 08855 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. Northwestern Univ, Feinberg Sch Med, Head Sect Endourol Laparoscopy & Stone Dis, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. VA Chicago Healthcare Syst, Midwest Ctr Hlth Serv Res & Policy Studies, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Canc Control Program, Chicago, IL 60611 USA. RP Elstein, AS (reprint author), 338 Brookside Dr, Wilmette, IL 60091 USA. EM aelstein@uic.edu RI Bennett, Charles/C-2050-2008; OI Chapman, Gretchen/0000-0002-1146-480X NR 49 TC 18 Z9 18 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD JUN PY 2004 VL 7 IS 2 BP 115 EP 125 DI 10.1111/j.1369-7625.2004.00267.x PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 879JY UT WOS:000225715300004 PM 15117386 ER PT J AU Wood, MJ Picard, MH AF Wood, MJ Picard, MH TI Utility of echocardiography in the evaluation of individuals with cardiomyopathy SO HEART LA English DT Article ID VENTRICULAR SYSTOLIC DYSFUNCTION; IDIOPATHIC DILATED CARDIOMYOPATHY; CONGESTIVE-HEART-FAILURE; HYPERTROPHIC CARDIOMYOPATHY; DOPPLER ECHOCARDIOGRAPHY; PROGNOSTIC-SIGNIFICANCE; CARDIAC AMYLOIDOSIS; DIASTOLIC FUNCTION; FILLING PATTERN; CLASSIFICATION C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wood, MJ (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab VBK 508, 55 Fruit St, Boston, MA 02114 USA. EM mjwood@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 27 TC 15 Z9 18 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JUN PY 2004 VL 90 IS 6 BP 707 EP 712 DI 10.1136/hrt.2003.024778 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821DI UT WOS:000221439800030 PM 15145892 ER PT J AU Ling, YQ Zhang, JL Luo, B Song, DS Liu, LC Tang, LP Stockard, CR Grizzle, WE Ku, DD Fallon, MB AF Ling, YQ Zhang, JL Luo, B Song, DS Liu, LC Tang, LP Stockard, CR Grizzle, WE Ku, DD Fallon, MB TI The role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat SO HEPATOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; PORTAL HYPERTENSIVE-RATS; CIRRHOTIC RATS; PULMONARY DYSFUNCTION; ENHANCED EXPRESSION; BIG ENDOTHELIN-1; HEME OXYGENASE-1; STELLATE CELLS; LIVER-DISEASE; TNF-ALPHA AB Endothelin-1 (ET-1) stimulation of endothelial nitric oxide synthase (eNOS) via pulmonary endothelial endothelin B (ETB) receptors and pulmonary intravascular macrophage accumulation with expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are implicated in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Our aim was to evaluate the role of ET-1 in the development of experimental HPS. The time course of molecular and physiological changes of HPS and the effects of selective endothelin receptor antagonists in vivo were assessed after CBDL. Effects of ET-1 on intralobar pulmonary vascular segment reactivity and on eNOS expression and activity in rat pulmonary microvascular endothelial cells (RPMVECs) were also evaluated. Hepatic and plasma ET-1 levels increased 1 week after CBDL in association with a subsequent increase in pulmonary microvascular eNOS and ETB receptor levels and the onset of HPS. Selective ETB receptor inhibition in vivo significantly decreased pulmonary eNOS and ETB receptor levels and ameliorated HPS. CBDL pulmonary artery segments had markedly increased ETB receptor mediated, nitric oxide dependent vasodilatory responses to ET-1 compared with controls and ET-1 triggered an ETB receptor dependent stimulation of eNOS in RPMVECs. Pulmonary intravascular macrophages also accumulated after CBDL and expressed HO-1 and iNOS at 3 weeks. Selective ETB receptor blockade also decreased macrophage accumulation and iNOS production. In conclusion, ET-1 plays a central role in modulating pulmonary micovascular tone in experimental HPS. C1 Univ Alabama, Dept Internal Med, Ctr Liver, Birmingham, AL 35294 USA. Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pharmacol, Birmingham, AL 35294 USA. RP Fallon, MB (reprint author), Univ Alabama, Dept Internal Med, Ctr Liver, MCLM 290,1918 Univ Blvd, Birmingham, AL 35294 USA. EM mfallon@uabmc.edu FU NIDDK NIH HHS [DK0203] NR 46 TC 64 Z9 65 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2004 VL 39 IS 6 BP 1593 EP 1602 DI 10.1002/hep.20244 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 826SN UT WOS:000221849000016 PM 15185300 ER PT J AU Murrell, JR Morse, LJ Haupert, GT AF Murrell, JR Morse, LJ Haupert, GT TI Gene silencing of the steroid biosynthetic pathway decreases production of hypothalamic ouabain-like factor SO HYPERTENSION LA English DT Meeting Abstract CT 57th Annual Fall Conference of the Council-for-High-Blood-Pressure-Research CY SEP 23-26, 2003 CL WASHINGTON, DC SP Council High Blood Pressure Res, Amer Heart Assoc, Council Nutrit, Phys Activ & Metabolism C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 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 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2004 VL 43 IS 6 BP 1352 EP 1352 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 824HC UT WOS:000221676300069 ER PT J AU Hokama, A Mizoguchi, E Sugimoto, K Shimomura, Y Tanaka, Y Yoshida, M Rietdijk, ST de Jong, YP Snapper, SB Terhorst, C Blumberg, RS Mizoguchi, A AF Hokama, A Mizoguchi, E Sugimoto, K Shimomura, Y Tanaka, Y Yoshida, M Rietdijk, ST de Jong, YP Snapper, SB Terhorst, C Blumberg, RS Mizoguchi, A TI Induced reactivity of intestinal CD4(+) T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation SO IMMUNITY LA English DT Article ID ALPHA-MUTANT MICE; TUMOR-NECROSIS-FACTOR; KINASE-C-THETA; BOWEL-DISEASE; EXPERIMENTAL COLITIS; IMMUNOLOGICAL SYNAPSE; INTERFERON-GAMMA; IN-VIVO; ACTIVATION; RECEPTOR AB Inflammatory bowel disease is an immune-mediated intestinal inflammatory condition that is associated with an increase in autoantibodies that bind to epithelial cells. However, it is unknown whether the epithelial cell-derived products that are recognized by such autoantibodies are involved in the pathogenic process. Through a combined antigen-screening approach utilizing humoral and cellular immune responses, we identify herein an epithelial lectin, galectin-4, that specifically stimulates IL-6 production by CD4(+) T cells. Interestingly, the reactivity of CD4(+) T cells to galectin-4 is precisely elicited under intestinal inflammatory conditions. The galectin-4-mediated production of IL-6 is MHC class II independent and induced by PKCtheta-associated pathway through the immunological synapse. The galectin-4-mediated stimulation of CD4(+) T cells is shown to exacerbate chronic colitis and delay the recovery from acute intestinal injury. These studies identify the presence of an immunogenic, endogenous lectin in the intestine and dissect the biological role of lectin/CD4(+) T cell interactions under inflammatory conditions. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammat Bowel Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol & Med, Boston, MA USA. RP Mizoguchi, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM amizoguchi@partners.org FU NIDDK NIH HHS [R01 DK44319, R01 DK064351, DK43351C11, R01 DK53056, K08DK64289, R01 DK57362] NR 63 TC 76 Z9 80 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2004 VL 20 IS 6 BP 681 EP 693 DI 10.1016/j.immuni.2004.05.009 PG 13 WC Immunology SC Immunology GA 831OY UT WOS:000222205300005 PM 15189734 ER PT J AU Williams, CJ Naito, T Arco, PGD Seavitt, JR Cashman, SM De Souza, B Qi, XQ Keables, P Von Andrian, UH Georgopoulos, K AF Williams, CJ Naito, T Arco, PGD Seavitt, JR Cashman, SM De Souza, B Qi, XQ Keables, P Von Andrian, UH Georgopoulos, K TI The chromatin remodeler Mi-2 beta is required for CD4 expression and T cell development SO IMMUNITY LA English DT Article ID RNA-POLYMERASE-II; POSITIVE SELECTION; GENE-EXPRESSION; LYMPHOCYTE DEVELOPMENT; THYMOCYTE DEVELOPMENT; HISTONE DEACETYLASE; IKAROS GENE; ALPHA-BETA; PROTEINS; COMPLEX AB Changes in chromatin structure underlie the activation or silencing of genes during development. The chromatin remodeler Mi-2beta is highly expressed in thymocytes and is presumed to be a transcriptional repressor because of its presence in the nucleosome remodeling deacetylase (NuRD) complex. Using conditional inactivation, we show that Mi-2beta is required at several steps during T cell development: for differentiation of P selected immature thymocytes, for developmental expression of CD4, and for cell divisions in mature T cells. We further show that Mi-2beta plays a direct role in promoting CD4 gene expression. Mi-2beta associates with the CD4 enhancer as well as the E box binding protein HEB and the histone acetyltransferase (HAT) p300, enabling their recruitment to the CD4 enhancer and causing histone H3-hyperacetylation to this regulatory region. These findings provide important insights into the regulation of CD4 expression during T cell development and define a role for Mi-2beta in gene activation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Gomez-del Arco, Pablo/L-2728-2013 OI Gomez-del Arco, Pablo/0000-0001-6748-7157 FU NIAID NIH HHS [R01-AI1380342-09] NR 39 TC 139 Z9 142 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2004 VL 20 IS 6 BP 719 EP 733 DI 10.1016/j.immuni.2004.05.005 PG 15 WC Immunology SC Immunology GA 831OY UT WOS:000222205300008 PM 15189737 ER PT J AU Yoshida, M Claypool, SM Wagner, JS Mizoguchi, E Mizoguchi, A Roopenian, DC Lencer, WI Blumberg, RS AF Yoshida, M Claypool, SM Wagner, JS Mizoguchi, E Mizoguchi, A Roopenian, DC Lencer, WI Blumberg, RS TI Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells SO IMMUNITY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; ALPHA-MUTANT MICE; CLASS-I ANTIGENS; IMMUNOGLOBULIN-G; CHRONIC COLITIS; RAT; EXPRESSION; CATABOLISM; IMMUNITY; GAMMA AB Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The mechanism by which IgG reaches luminal secretions and the function of IgG in these locations are unknown. Here, we find that the human neonatal Fc receptor (FcRn) is the vehicle that transports IgG across the intestinal epithelial barrier into the lumen where the IgG can bind cognate antigen. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. These results explain how IgG is secreted onto mucosal surfaces and scavenges luminal antigens for recognition by the immune system. C1 Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Ctr Digest Dis, Boston, MA 02115 USA. RP Blumberg, RS (reprint author), Brigham & Womens Hosp, Dept Med, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM rblumberg@partners.org FU NIDDK NIH HHS [DK44319, DK51362, DK53056, DK56597] NR 49 TC 240 Z9 250 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2004 VL 20 IS 6 BP 769 EP 783 DI 10.1016/j.immuni.2004.05.007 PG 15 WC Immunology SC Immunology GA 831OY UT WOS:000222205300012 PM 15189741 ER PT J AU Gillmore, JD Hutchinson, WL Herbert, J Bybee, A Mitchell, DA Hasserjian, RP Yamamura, KI Suzuki, M Sabin, CA Pepys, MB AF Gillmore, JD Hutchinson, WL Herbert, J Bybee, A Mitchell, DA Hasserjian, RP Yamamura, KI Suzuki, M Sabin, CA Pepys, MB TI Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination? SO IMMUNOLOGY LA English DT Article DE autoimmunity; glomerulonephritis; transgenics : knockouts ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; C-REACTIVE PROTEIN; IN-VIVO; APOPTOTIC CELLS; C1Q DEFICIENCY; CHROMATIN; DISSECTION; PATHOGENESIS; BINDING; DEGRADATION AB Human serum amyloid P component (SAP) binds avidly to DNA, chromatin and apoptotic cells in vitro and in vivo. 129\Sv x C57BL\6 mice with targeted deletion of the SAP gene spontaneously develop antinuclear autoantibodies and immune complex glomerulonephritis. SAP-deficient animals, created by backcrossing the 129\Sv SAP gene deletion into pure line C57BL\6 mice and studied here for the first time, also spontaneously developed broad spectrum antinuclear autoimmunity and proliferative immune complex glomerulonephritis but without proteinuria, renal failure, or increased morbidity or mortality. Mice hemizygous for the SAP gene deletion had an intermediate autoimmune phenotype. Injected apoptotic cells and isolated chromatin were more immunogenic in SAP(-\-) mice than in wild-type mice. In contrast, SAP-deficient pure line 129\Sv mice did not produce significant autoantibodies either spontaneously or when immunized with extrinsic chromatin or apoptotic cells, indicating that loss of tolerance is markedly strain dependent. However, SAP deficiency in C57BL\6 mice only marginally affected plasma clearance of exogenous chromatin and had no effect on distribution of exogenous nucleosomes between the liver and kidneys, which were the only tissue sites of catabolism. Furthermore, transgenic expression of human SAP in the C57BL\6 SAP knockout mice did not abrogate the autoimmune phenotype. This may reflect the different binding affinities of mouse and human SAP for nuclear autoantigens and\or the heterologous nature of transgenic human SAP in the mouse. Alternatively, the autoimmunity may be independent of SAP deficiency and caused by expression of 129\Sv chromosome 1 genes in the C57BL\6 background. C1 UCL Royal Free & Univ Coll Med Sch, Dept Med, Ctr Amyloidosis & Acute Phase Prot, London NW3 2PF, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, Rheumatol Sect, London, England. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kumamoto Univ, Inst Mol Embryol & Genet, Kumamoto 860, Japan. Kumamoto Univ, Ctr Anim Resources & Dev, Kumamoto 860, Japan. UCL Royal Free & Univ Coll Med Sch, Dept Primary Care & Populat Sci, London, England. RP Pepys, MB (reprint author), UCL Royal Free & Univ Coll Med Sch, Dept Med, Ctr Amyloidosis & Acute Phase Prot, Rowland Hill St, London NW3 2PF, England. EM m.pepys@rfc.ucl.ac.uk RI Sabin, Caroline/C-2464-2008; Mitchell, Daniel/A-6580-2009 OI Mitchell, Daniel/0000-0003-0936-6212 NR 31 TC 43 Z9 44 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUN PY 2004 VL 112 IS 2 BP 255 EP 264 DI 10.1111/j.1365-2567.2004.01860.x PG 10 WC Immunology SC Immunology GA 820XM UT WOS:000221423200011 PM 15147569 ER PT J AU Bollyky, PL Wilson, SB AF Bollyky, PL Wilson, SB TI CD1d-restricted T-cell subsets and dendritic cell function in autoimmunity SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Review DE autoimmunity; dendritic cell; diabetes; immunoregulation; iNKT cell ID NONOBESE DIABETIC MICE; ANTIGEN-PRESENTING CELLS; NECROSIS-FACTOR-ALPHA; V(ALPHA)14 NKT CELLS; GENE-EXPRESSION; IN-VIVO; NOD MICE; TUMOR IMMUNOSURVEILLANCE; PROVIDES PROTECTION; INTERLEUKIN (IL)-12 AB CD1-restricted T cells have been shown to play a critical role in host defence, tumour surveillance, and maintenance of tolerance. However, immunologic outcomes resulting from activation of CD1d-restricted T cells can be either beneficial or deleterious. A major mechanism by which CD1d-restricted T cells are thought to exert immunoregulatory control is via effects on dendritic cell (DC) differentiation and migration. Important functional subsets of CD1d-restricted T cells are also known to exist and the potential implications for preferential subset activations are discussed. C1 Massachusetts Gen Hosp, Diabet Res Labs, Cambridge, MA 02139 USA. RP Wilson, SB (reprint author), Massachusetts Gen Hosp, Diabet Res Labs, 65 Landsdowne St, Cambridge, MA 02139 USA. EM bwilson@rics.bwh.harvard.edu NR 115 TC 14 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUN PY 2004 VL 82 IS 3 BP 307 EP 314 DI 10.1111/j.1440-1711.2004.01253.x PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 826YY UT WOS:000221866600011 PM 15186262 ER PT J AU Zhang, JM Zhu, JP Imrich, A Cushion, M Kinane, TB Koziel, H AF Zhang, JM Zhu, JP Imrich, A Cushion, M Kinane, TB Koziel, H TI Pneumocystis activates human alveolar macrophage NF-KB signaling through mannose receptors SO INFECTION AND IMMUNITY LA English DT Article ID KAPPA-B ACTIVATION; CARINII-PNEUMONIA; IL-12 PRODUCTION; DENDRITIC CELLS; GENE-EXPRESSION; IN-VITRO; MICE; INFECTION; PHAGOCYTOSIS; RATS AB Alveolar macrophages (AM) represent important effector cells in the innate immune response to the AIDS-related pathogen Pneumoeystis, but the early AM host defense signaling events are poorly defined. Using AM from healthy individuals, we showed in the present study that Pneumocystis organisms stimulate AM NF-kappaB p50 and p65 nuclear translocation in a time-dependent and multiplicity-of-infection-dependent manner as determined by electrophoretic mobility shift assay and immunofluorescence microscopy and that NF-kappaB nuclear translocation is associated with. I-kappaB phosphorylation. Importantly, competitive inhibition of mannose receptor and targeted short interfering RNA-mediated gene suppression of mannose receptor mRNA and protein is associated with complete elimination of NF-kappaB nuclear translocation in response to Pneumoeystis. Furthermore, human immunodeficiency virus (HIV) infection of AM (as a model human disease state of reduced AM mannose receptor expression and function) inhibits Pneumocystis-mediated NF-kappaB nuclear translocation and is associated with reduced I-kappaB phosphorylation and reduced interleukin-8 (IL-8) release. In contrast, NF-kappaB nuclear translocation and IL-8 release in response to lipopolysaccharide are intact in AM from both healthy and HIV-infected individuals, indicating that the observed impairment is not a global disturbance of the NF-kappaB pathway. Thus, in addition to phagocytic and endocytic effector functions, the present study identifies mannose receptors as pattern recognition receptors capable of NF-kappaB activation in response to infectious non-self challenge. AM mannose receptor-mediated NF-kappaB activation may represent an important mechanism of the host cell response to Pneumocystis, and altered NF-kappaB activation in the context of HIV infection may impair a critical innate immune signaling response and may contribute to pathogenesis of opportunistic lung infections. C1 Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat Med, Lab Dev Immunol, Boston, MA 02114 USA. Univ Cincinnati, Vet Adm Med Ctr, Cincinnati, OH USA. RP Koziel, H (reprint author), Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Med, Kirstein Hall,Room E-KSB-23,330 Brookline Ave, Boston, MA 02215 USA. EM hkoziel@bidmc.harvard.edu FU NHLBI NIH HHS [F32 HL071372, F32 HL71372, R01 HL063655, R01 HL63655] NR 54 TC 58 Z9 63 U1 0 U2 3 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 JUN PY 2004 VL 72 IS 6 BP 3147 EP 3160 DI 10.1128/IAI.72.6.3147-3160.2004 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 824CT UT WOS:000221662400008 PM 15155616 ER PT J AU Engelbert, M Mylonakis, E Ausubel, FM Calderwood, SB Gilmore, MS AF Engelbert, M Mylonakis, E Ausubel, FM Calderwood, SB Gilmore, MS TI Contribution of gelatinase, serine protease, and fsr to the pathogenesis of Enterococcus faecalis endophthalmitis SO INFECTION AND IMMUNITY LA English DT Article ID VIRULENCE; HEMOLYSIN; REGULATOR; MODEL; ENDOCARDITIS; GENERATION; CYTOLYSIN; GENES; MICE AB Gelatinase and serine protease were found to contribute in concert to pathogenesis in a rabbit model of endophthalmitis. However, a mutant defective in the fsr regulator was observed to be more attenuated than a mutant rendered defective in the expression of gelatinase and serine protease as the result of a polar transposon insertion into the former. This increased attenuation suggests that there are possible additional pleiotropic effects of the defect in fsr on expression of traits contributing to the pathogenesis of enterococcal infection. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Gilmore, MS (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, 975 NE 10th St, Oklahoma City, OK 73104 USA. EM Michael-Gilmore@ouhsc.edu FU NEI NIH HHS [EY12190, EY08289, P30 EY012190, R01 EY008289]; NIAID NIH HHS [AI41108, R01 AI041108] NR 19 TC 47 Z9 49 U1 0 U2 3 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 JUN PY 2004 VL 72 IS 6 BP 3628 EP 3633 DI 10.1128/IAI.72.6.3628-3633.2004 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 824CT UT WOS:000221662400065 PM 15155673 ER PT J AU Shafqat, S Kelly, PJ Furie, KL AF Shafqat, S Kelly, PJ Furie, KL TI Holter monitoring in the diagnosis of stroke mechanism SO INTERNAL MEDICINE JOURNAL LA English DT Article DE atrial fibrillation; cerebral embolism; diagnosis; Holter monitoring; cardioembolic stroke ID PAROXYSMAL ATRIAL-FIBRILLATION; RHYTHM CONTROL AB Background: Atrial fibrillation (AF), an important and treatable cause of ischaemic stroke, can occur as a sustained or a paroxysmal arrhythmia. Continuous cardiac rhythm monitoring (Holter monitoring) is often performed in stroke patients to identify paroxysmal AF, which is an indication for warfarin anti-coagulation in this patient population. Aim: The aim of this study was to assess the clinical utility of Holter monitoring in detecting occult AF in patients with possible cardioembolic stroke. Methods: The medical records of ischaemic stroke patients consecutively hospitalized at a single academic centre during a one-year period were reviewed. Data regarding patient demographics, stroke characteristics, electrocardiography and echocardiography results and duration and findings of Holter monitoring were abstracted. The primary outcome was yield of newly diagnosed AF on Holter monitoring. Results: Of 465 consecutive patients admitted with a diagnosis of new ischaemic stroke, 210 underwent Holter monitoring. The mean duration of monitoring was 22.8 +/- 4.0 h. Previously undiscovered AF was -identified in five cases (2.4%), all of which represented non-rheumatic AF. In three cases, the Holter test was negative despite AF documented on an admission electro-cardiogram. Conclusions: Holter monitoring can identify occult -paroxysmal AF, assisting targeted secondary prevention in patients with new ischaemic stroke. However, the standard 24-h duration of monitoring probably under-estimates the prevalence of paroxysmal AF in this population. Prospective studies are indicated to evaluate the value of longer monitoring periods in stroke populations. C1 Aga Khan Univ, Dept Med Neurol, Coll Med, Karachi 74800, Pakistan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Shafqat, S (reprint author), Aga Khan Univ, Dept Med Neurol, Coll Med, Stadium Rd, Karachi 74800, Pakistan. EM saad.shafqat@aku.edu NR 17 TC 36 Z9 38 U1 0 U2 1 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1444-0903 J9 INTERN MED J JI Intern. Med. J. PD JUN PY 2004 VL 34 IS 6 BP 305 EP 309 DI 10.1111/j.1444-0903.2004.00589.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 830OT UT WOS:000222132900002 PM 15228390 ER PT J AU Lawler, J Detmar, M AF Lawler, J Detmar, M TI Tumor progression: the effects of thrombospondin-1 and-2 SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE thrombospondin; cancer; tumor; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; TYPE-1 REPEATS; IN-VIVO; ANGIOGENESIS; GENE; INHIBITION; EXPRESSION; CARCINOGENESIS; CHEMOTHERAPY; METASTASIS AB The thrombospondins (TSPs) are a family of proteins that regulate tissue genesis and remodeling. In many tumors, down-regulation of TSPs accompanies activation of oncogenes or inactivation of tumor suppresser genes and appears to be a prerequisite for the aquisition of a pro-angiogenic phenotype. The normal suppression of angiogenesis by TSP-1 and -2 involves multiple mechanisms including direct interaction with vascular endothelial cell growth factor (VEGF), inhibition of matrix metalloproteinase 9 (MMP9) activation, inhibition of endothelial cell migration and induction of endothelial cell apoptosis. The importance of down-regulation of TSPs for tumor progression is further established by the fact that several different approaches that are designed to increase the levels of TSP-1 or -2 in tumor tissue inhibit tumor growth. These approaches include cell-based gene therapy, low dose chemotherapeutics and systemic delivery of recombinant proteins or synthetic peptides that include type 1 repeat (TSR) sequences. Initial studies indicate that these reagents, in combination with established approaches for the treatment of cancer, will offer more efficacious therapies. (C) 2004 Elsevier Ltd. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lawler, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 99 Brookline Ave, Boston, MA 02215 USA. EM jlawler@bidmc.harvard.edu; michael_detmar@cbrc.mgh.harvard.edu RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA 45461, CA86410, CA92644, CA69184]; NHLBI NIH HHS [HL68003] NR 42 TC 141 Z9 147 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD JUN PY 2004 VL 36 IS 6 BP 1038 EP 1045 DI 10.1016/j.biocel.2004.01.008 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 818YZ UT WOS:000221281700013 PM 15094119 ER PT J AU Mele, D Teoli, R Cittanti, C Pasanisi, G Guardigli, G Levine, RA Ferrari, R AF Mele, D Teoli, R Cittanti, C Pasanisi, G Guardigli, G Levine, RA Ferrari, R TI Assessment of left ventricular volume and function by integration of simplified 3D echocardiography, tissue harmonic imaging and automated extraction of endocardial borders SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE computer; 2DEcho; 3DEcho; ultrasound ID CONTOUR TRACKING METHOD; DIGITAL ECHO QUANTIFICATION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; EJECTION FRACTION; 2-DIMENSIONAL ECHOCARDIOGRAPHY; DIMENSIONAL ECHOCARDIOGRAPHY; SYSTOLIC FUNCTION; CAVITY AREA; REPRODUCIBILITY; SEGMENTATION AB Background: Quantitative three-dimensional echocardiography (3DEcho) of left ventricle (LV) is still limited because of the need for manually tracing endocardial borders: this can increase observer variability depending on the quality of fundamental (FUND) 2D images. We tested the combination of a simplified 3DEcho technique for LV reconstruction with automated endocardial border detection (Digital Echo Quanti. cation, DEQ) and tissue harmonic imaging (THI) for enhancement of endocardium-cavity interface. Methods: Twenty-five consecutive patients with ischaemic heart disease and dilated or distorted LV underwent 3DEcho and gated-SPECT nuclear examinations evaluating: (a)end-diastolic and end-systolic volumes (EDV, ESV); (b) ejection fraction (EF); (c) volume/time curve (VTC). Thereafter, 3DEcho was applied to 47 patients with acute myocardial infarction (AMI) at pre-discharge and 6 months to evaluate remodelling. Results: Integrated 3DEcho values in THI modality were obtained in 84% of patients and correlated well with nuclear data for EDV (r=0.95, mean difference=-2.2+/-15.8 ml), ESV (r=0.98, mean difference=-3.5+/-10.2 ml), and EF (r=0.82, mean difference=0.6+/-6.4%; all mean differences NS vs. 0), with an interobserver variability of 4.9, 5.7 and 8.2% for EDV, ESV and EF respectively. Automated VTC by 3DEcho in THI modality reproduced well that obtained by nuclear technique (r=0.96) and allowed recognition of LV remodelling in 36% of patients at 6 months. Integrated 3DEcho values in FUND modality were obtained only in 52% of patients and showed much higher errors and interobserver variability. Conclusions: THI permits accurate 3D reconstruction of LV borders detected by DEQ, allowing automated VTC throughout the cardiac cycle as well as study of LV remodelling. C1 Univ Ferrara, Azienda Osped, Inst Cardiol, Div Cardiol, I-44100 Ferrara, Italy. Univ Ferrara, Azienda Osped, Inst Nucl Med, I-44100 Ferrara, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Noninvas Cardiac Lab, Boston, MA USA. RP Mele, D (reprint author), Univ Ferrara, Azienda Osped, Inst Cardiol, Div Cardiol, Corso Giovecca No 203, I-44100 Ferrara, Italy. EM donatomele@libero.it NR 35 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-9899 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JUN PY 2004 VL 20 IS 3 BP 191 EP 202 DI 10.1023/B:CAIM.0000021948.96454.3a PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 806SX UT WOS:000220454700005 PM 15139533 ER PT J AU Taneja, A Racette, A Gourgouliatos, Z Taylor, CR AF Taneja, A Racette, A Gourgouliatos, Z Taylor, CR TI Broad-band UVB fiber-optic comb for the treatment of scalp psoriasis: a pilot study SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID PHOTOTHERAPY; MANAGEMENT; LIGHT AB Background Scalp psoriasis is a frustrating condition with limited treatment options. Our objective was to test a new fiber-optic broad-band UVB comb device for the treatment of this condition. Methods Scalp psoriasis on adult subjects was treated three times a week for up to 12 weeks with a fiber-optic UVB comb. A minimum 50-cm(2) scalp area served as the control. Starting doses were based on the standard minimal erythema dose (MED) with increments up to 20% for subsequent treatments. Results Fourteen subjects completed the study without sunburn reactions or blisters. Treated sites showed a mean improvement in the modified PASI score of 3.6. The difference in the mean modified PASI scores between the control and treated sites was 3.9 (<0.0001). Conclusions This fiber-optic broad-band UVB comb can safely and effectively treat scalp psoriasis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Lerner Med Devices Inc, Los Angeles, CA USA. RP Taylor, CR (reprint author), Bartlett 622,32 Fruit St, Boston, MA 02114 USA. EM crtaylor@partners.org NR 11 TC 16 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD JUN PY 2004 VL 43 IS 6 BP 462 EP 467 DI 10.1111/j.1365-4632.2004.01993.x PG 6 WC Dermatology SC Dermatology GA 830GH UT WOS:000222109600017 PM 15186234 ER PT J AU Goff, DC Freudenreich, O AF Goff, DC Freudenreich, O TI Polypharmacy in schizophrenia: does anyone truly benefit? SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID CLOZAPINE; ANTIPSYCHOTICS; RISPERIDONE; EFFICACY; THERAPY C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [MH02025] NR 11 TC 12 Z9 12 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 IS 2 BP 109 EP 111 DI 10.1017/S1461145704004183 PG 3 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 828OM UT WOS:000221982600001 PM 15137932 ER PT J AU Morilak, DA Frazer, A AF Morilak, DA Frazer, A TI Antidepressants and brain monoaminergic systems: a dimensional approach to understanding their behavioural effects in depression and anxiety disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE antidepressants; anxiety disorders; anxiolytics; depression; norepinephrine; serotonin ID POSTTRAUMATIC-STRESS-DISORDER; SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; VENTRAL TEGMENTAL AREA; COERULEUS NORADRENERGIC NEURONS; CORTICOTROPIN-RELEASING-FACTOR; EXTRACELLULAR DOPAMINE LEVELS; LOCUS-CERULEUS NEURONS; FORCED SWIMMING TEST; PANIC DISORDER AB There is extensive comorbidity between depression and anxiety disorders. Dimensional psychiatric and psychometric approaches have suggested that dysregulation of a limited number of behavioural dimensions that cut across diagnostic categories can account for both the shared and unique symptoms of depression and anxiety disorders. Such an approach recognizes that anxiety, the emotional response to stress, is a key element of depression as well as the defining feature of anxiety disorders, and many antidepressants appear to be effective in the treatment of anxiety disorders as well as depression. Therefore, the pharmacological actions of these drugs must account for their efficacy in both. Brain noradrenergic and serotonergic systems, and perhaps to a more limited extent the dopaminergic system, regulate or modulate many of the same behavioural dimensions (e.g. negative or positive affect) that are affected in depression and anxiety disorders, and that are ameliorated by drug treatment. Whereas much recent research has focused on the regulatory effects of antidepressants on synaptic function and cellular proteins, less emphasis has been placed on monoaminergic regulation at a more global systemic level, or how such systemic alterations in monoaminergic function might alleviate the behavioural, cognitive, emotional and physiological manifestations of depression and anxiety disorders. In this review, we discuss how chronic antidepressant treatment might regulate the tonic activity and/or phasic reactivity of brain monoaminergic systems to account for their ability to effectively modify the behavioural dimensions underlying improvement in both depression and anxiety disorders. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Ctr Biomed Neurosci, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Morilak, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr,MC 7764, San Antonio, TX 78229 USA. EM morilak@uthscsa.edu FU NIMH NIH HHS [MH57001, MH58351, MH60118] NR 200 TC 139 Z9 141 U1 1 U2 19 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 IS 2 BP 193 EP 218 DI 10.1017/S1461145704004080 PG 26 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 828OM UT WOS:000221982600013 PM 15003145 ER PT J AU Bangs, ME Allen, AJ Kurlan, R Linder, SL Lewis, DW Winner, PK Gilbert, DL Dunn, D Sallee, F Milton, D Mintz, M Ricardi, RK Erenberg, G Layton, L Feldman, P Kelsey, D Spencer, TJ AF Bangs, ME Allen, AJ Kurlan, R Linder, SL Lewis, DW Winner, PK Gilbert, DL Dunn, D Sallee, F Milton, D Mintz, M Ricardi, RK Erenberg, G Layton, L Feldman, P Kelsey, D Spencer, TJ TI Atomoxetine treatment in children with attention-deficit/hyperactivity disorder and comorbid TIC disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Eli Lilly & Co, Indianapolis, IN USA. Univ Rochester, Sch Med, Rochester, NY 14627 USA. Dallas Pediat Neurol Associates, Dallas, TX USA. Cincinnati Childrens Hosp, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Phoenix Childrens Hosp, Phoenix, AZ USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S441 EP S441 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002452 ER PT J AU Buitelaar, J Michelson, D Danckaerts, M Gillberg, C Spencer, T Zuddas, A Faries, D Zhang, S Biederman, J AF Buitelaar, J Michelson, D Danckaerts, M Gillberg, C Spencer, T Zuddas, A Faries, D Zhang, S Biederman, J TI Continued atomoxetine in pediatric patients with attention-deficit/hyperactivity disorder after 1 year of treatment SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Eli Lilly & Co, Indianapolis, IN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S440 EP S440 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002450 ER PT J AU Carson, W Sachs, G Sanchez, R Marcus, R Kujawa, M Archibald, D Iwamoto, T AF Carson, W Sachs, G Sanchez, R Marcus, R Kujawa, M Archibald, D Iwamoto, T TI Aripiprazole vs placebo for the treatment of acute mania in patients with bipolar I disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Bristol Myers Squibb Co, New York, NY 10154 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S332 EP S332 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002038 ER PT J AU Demopulos, C Sassower, K Siegel, R AF Demopulos, C Sassower, K Siegel, R TI Prevalence of formal sleep disorders and use of modafinil in bipolar patients with and without rapid cycling SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S149 EP S149 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000557 ER PT J AU Goff, DC AF Goff, DC TI Treatment adherence: Motivating patients through a productive therapeutic alliance SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S113 EP S113 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000426 ER PT J AU Goff, DC AF Goff, DC TI Therapeutic experience with glutamatergic agents in schizophrenia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Schizophrenia Program, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S37 EP S37 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000138 ER PT J AU Jakary, A Davis, K Yucel, K Deicken, R AF Jakary, A Davis, K Yucel, K Deicken, R TI Putamen alterations in familial major depression SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S340 EP S340 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002070 ER PT J AU Kinrys, G Worthington, J Melo, MJ Pardo, T Simon, N Reese, H Doyle, A Pollack, M AF Kinrys, G Worthington, J Melo, MJ Pardo, T Simon, N Reese, H Doyle, A Pollack, M TI Adjunctive levetiracetam for treatment refractory anxiety disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Harvard Univ, Sch Med, CHA, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S195 EP S196 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663001141 ER PT J AU Marder, S Archibald, D Manos, G Stock, E Jody, D Tourkodimitris, S Marcus, R Iwamoto, T Yamamoto, Y Carson, W AF Marder, S Archibald, D Manos, G Stock, E Jody, D Tourkodimitris, S Marcus, R Iwamoto, T Yamamoto, Y Carson, W TI Long-term effects of aripiprazole therapy on the negative symptoms of schizophrenia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Bristol Myers Squibb Co, New York, NY 10154 USA. Otsuka Amer Pharmaceut Inc, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S243 EP S243 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663001325 ER PT J AU Moskowitz, MA AF Moskowitz, MA TI Migraine mechanisms from genes to drugs SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S32 EP S33 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000122 ER PT J AU Nierenberg, AA AF Nierenberg, AA TI Critical decision points in antidepressant treatment SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Bipolar Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S18 EP S18 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000067 ER PT J AU Papakostas, GI Iosifescu, DV Renshaw, PF Fava, M AF Papakostas, GI Iosifescu, DV Renshaw, PF Fava, M TI Brain MRI white matter hyperintensities, cardiovascular risk factors, one-carbon cycle metabolism and outcome in major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Mclean, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S340 EP S340 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002071 ER PT J AU Pollack, MH Van Ameringen, M Roy-Byrne, P AF Pollack, MH Van Ameringen, M Roy-Byrne, P TI A randomized, double-blind, placebo-controlled trial of tiagabine in the treatment of generalized anxiety disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McMaster Univ, Ctr Med, Hamilton, ON L8S 4L8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S366 EP S366 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002171 ER PT J AU Powers, PS Sachs, GS Kushner, S Wang, D Olson, WH Capece, JA Fazzio, L Rosenthal, N AF Powers, PS Sachs, GS Kushner, S Wang, D Olson, WH Capece, JA Fazzio, L Rosenthal, N TI Topiramate for the treatment of adults with acute bipolar I mania: Pooled results SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Univ S Florida, Tampa, FL 33620 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S325 EP S325 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002013 ER PT J AU Rauch, SL Wright, CI Cannistraro, P Dougherty, DD Greenberg, BD AF Rauch, SL Wright, CI Cannistraro, P Dougherty, DD Greenberg, BD TI Brain imaging of obsessive compulsive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S39 EP S40 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000150 ER PT J AU Rauch, SL AF Rauch, SL TI The pathophysiology of anxiety SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S17 EP S17 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000062 ER PT J AU Shenton, ME Gerig, G Kwon, JS Park, HJ Deutsch, C Kubicki, M McCarley, RW AF Shenton, ME Gerig, G Kwon, JS Park, HJ Deutsch, C Kubicki, M McCarley, RW TI Midline cavum septi pellucidi abnormalities, hippocampal shape abnormalities, and diffusion tensor corpus callosum asymmetry abormalities in schizophrenia SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Harvard Univ, Sch Med, Boston VA Healthcare Syst, Dept Psychiat, Boston, MA 02115 USA. Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27515 USA. Seoul Natl Univ, Dept Psychiat, Seoul 151, South Korea. Yonsei Univ, Dept Radiol, Seoul 120749, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S59 EP S59 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000220 ER PT J AU Shin, LM Pitman, RK Orr, SP Rauch, SL AF Shin, LM Pitman, RK Orr, SP Rauch, SL TI Brain imaging and posttraumatic stress disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S40 EP S40 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000152 ER PT J AU Siever, LJ Goodman, M Buchsbaum, M Frankle, WG Laruelle, M Gelernter, J Goldman, D AF Siever, LJ Goodman, M Buchsbaum, M Frankle, WG Laruelle, M Gelernter, J Goldman, D TI Genes of susceptibility and intermediate phenotypes in the impulsive personality disorders SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Mt Sinai Sch Med, Dept Psychiat 1, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S57 EP S57 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000213 ER PT J AU Simpson, A Kratochvil, CJ Newcorn, JH Allen, AJ Faries, D Milton, D Feldman, P Michelson, D Biederman, J AF Simpson, A Kratochvil, CJ Newcorn, JH Allen, AJ Faries, D Milton, D Feldman, P Michelson, D Biederman, J TI Efficacy of atomoxetine in placebo-controlled studies in children, adolescents, and adults with attention-deficit/hyperactivity disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Univ Nebraska, Coll Med, Lincoln, NE 68583 USA. Mt Sinai Sch Med, Bronx, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S441 EP S441 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002453 ER PT J AU Spencer, TJ Zhang, S Ruff, D Feldman, P Michelson, D AF Spencer, TJ Zhang, S Ruff, D Feldman, P Michelson, D TI Developmental outcomes of long-term atomoxetine treatment in ADHD SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S273 EP S273 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663001433 ER PT J AU Spencer, TJ AF Spencer, TJ TI Pharmacological treatment options across the lifespan SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S93 EP S93 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000351 ER PT J AU Swindle, RW Mallinckrodt, CH Rosenbaum, JF Lu, Y Watkin, JG Detke, MJ AF Swindle, RW Mallinckrodt, CH Rosenbaum, JF Lu, Y Watkin, JG Detke, MJ TI Efficacy of duloxetine treatment: Analysis of pooled data from six placebo- and SSRI-controlled clinical trials SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, IU Med Sch,Eli & Lilly Co, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S351 EP S351 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002114 ER PT J AU Tohen, M Bowden, C Calabrese, J Sachs, G Risser, R Detke, H Shen, H AF Tohen, M Bowden, C Calabrese, J Sachs, G Risser, R Detke, H Shen, H TI Predictors of time to relapse in bipolar I disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Lilly Res Labs, Indianapolis, IN USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S152 EP S152 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663000570 ER PT J AU Wohlreich, MM Wilson, MG Mallinckrodt, CH Greist, J Delgado, PL Watkin, JG Fava, M AF Wohlreich, MM Wilson, MG Mallinckrodt, CH Greist, J Delgado, PL Watkin, JG Fava, M TI Immediate switching of antidepressant therapy: Results from a clinical trial of duloxetine SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Butler Univ, Indianapolis, IN 46208 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S351 EP S352 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002115 ER PT J AU Zimbroff, DL Pollack, MH Zornberg, GL Tobias, K AF Zimbroff, DL Pollack, MH Zornberg, GL Tobias, K TI Influence of depressive symptoms on anxiolytic efficacy of pregabalin in generalized anxiety disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th CINP Congress CY JUN 20-24, 2004 CL Paris, FRANCE SP CINP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2004 VL 7 SU 1 BP S365 EP S366 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 864WF UT WOS:000224663002168 ER PT J AU Nguyen, PL Whittington, R Koo, S Schultz, D Cote, KB Loffredo, M Tempany, CM Titelbaum, DS Schnall, MD Renshaw, AA Tomaszewski, JE D'Amico, AV AF Nguyen, PL Whittington, R Koo, S Schultz, D Cote, KB Loffredo, M Tempany, CM Titelbaum, DS Schnall, MD Renshaw, AA Tomaszewski, JE D'Amico, AV TI Quantifying the impact of seminal vesicle invasion identified using endorectal magnetic resonance imaging on PSA outcome after radiation therapy for patients with clinically localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; magnetic resonance imaging; seminal vesicle invasion; radiation therapy; hormonal therapy ID PREDICT PATHOLOGICAL STAGE; RADICAL PROSTATECTOMY; GLEASON SCORE; CARCINOMA; ANTIGEN; COIL; RADIOTHERAPY; SURVIVAL; MEN AB Purpose: This study examined the impact that seminal vesicle invasion (SVI), observed on endorectal magnetic resonance imaging (erMRI), had on prostate-specific antigen (PSA) outcome after external beam radiation therapy (EBRT) for patients with clinically localized prostate cancer. Methods and Materials: The study cohort was comprised of 250 patients who received 3D conformal radiation therapy without hormones for clinically localized prostate cancer between 1992 and 2001. The primary end point was PSA failure, defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Cox regression multivariable analysis was used to determine the ability of the pretreatment risk group and erMRI SVI to predict for time to PSA failure after EBRT. Results: Both risk group (p(Cox) = 0.001) and erMRI SVI (p(Cox) = 0.003) were independent and significant predictors of time to PSA failure. For patients beyond low risk, 4-year estimates of PSA failure-free survival for erMRI SVI-negative vs. erMRI SVI-positive patients were 68% vs. 33% (Plog-rank = 0.0014), respectively. Conclusion: Patients with clinically localized disease and PSA >10 or biopsy Gleason score greater than or equal to7 or clinical T category T2b or T2c who also have erMRI evidence of SVI have PSA outcomes similar to patients with locally advanced prostate cancer after EBRT monotherapy. Consideration should be given to combining EBRT with hormonal therapy in these patients. (C) 2004 Elsevier Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Shields Hlth Care, Dept Radiol, Boston, MA USA. Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM adamico@lroc.harvard.edu NR 24 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2004 VL 59 IS 2 BP 400 EP 405 DI 10.1016/j.ijrobp.2003.10.035 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 821DS UT WOS:000221440800011 PM 15145155 ER PT J AU Marucci, L Niemierko, A Liebsch, NJ Aboubaker, F Liu, MCC Munzenrider, JE AF Marucci, L Niemierko, A Liebsch, NJ Aboubaker, F Liu, MCC Munzenrider, JE TI Spinal cord tolerance to high-dose fractionated 3D conformal proton-photon irradiation as evaluated by equivalent uniform dose and dose volume histogram analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE spinal cord tolerance; proton irradiation; equivalent uniform dose; 3D conformal radiotherapy; spinal cord; chordoma; spinal cord chondrosarcoma ID RADIATION TOLERANCE; THERAPY; TIME AB Purpose: To evaluate cervical spinal cord tolerance using equivalent uniform dose (EUD) and dose volume histogram (DVH) analysis after proton-photon radiotherapy. Methods and Material: The 3D dose distributions were analyzed in 85 patients with cervical vertebral tumors. Mean follow-up was 41.3 months. The mean prescribed dose was 76.3 Cobalt Gray Equivalent (CGE = proton dose X RBE 1.1). Dose constraints to the center and the surface of the cervical cord were 55-58 CGE and 67-70 CGE, respectively. Dose parameters, DVH and EUD, were calculated for each patient. The spinal cord toxicity was graded using the European Organization for Research and Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) late effects scoring system. Results: Thirteen patients experienced Grade 1-2 toxicity. Four patients had Grade 3 toxicity. For the dose range used in this study, none of the dosimetric parameters was found to be associated with the observed distribution of cord toxicities. The only factor significantly associated with cord toxicity was the number of surgeries before irradiation. Conclusion: The data and our analysis suggest that the integrity of the normal musculoskeletal supportive tissues and vascular supply may be important confounding factors of toxicity at these dose levels. The results also indicate that the cervical spinal cord dose constraints used in treating these patients are appropriate for conformal proton-photon radiotherapy. (C) 2004 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Marucci, L (reprint author), Res Inst Regina Elena, Dept Radiat Oncol, Via Chianesi 53, I-00144 Rome, Italy. EM marucci_laura@yahoo.com FU NCI NIH HHS [CA21239, CA50628] NR 16 TC 30 Z9 30 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2004 VL 59 IS 2 BP 551 EP 555 DI 10.1016/j.ijrobp.2003.10.058 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 821DS UT WOS:000221440800031 PM 15145175 ER PT J AU Barabino, S Dana, MR AF Barabino, S Dana, MR TI Animal models of dry eye: A critical assessment of opportunities and limitations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LACRIMAL GLAND DISEASE; PRIMARY SJOGRENS-SYNDROME; AUTOIMMUNE DACRYOADENITIS; OCULAR SURFACE; TEAR FILM; KERATOCONJUNCTIVITIS SICCA; MOUSE MODELS; MURINE MODEL; NOD MICE; RABBIT C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Univ Genoa, Dept Neurol Ophthalmol & Genet, Genoa, Italy. RP Dana, MR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu NR 34 TC 65 Z9 67 U1 0 U2 9 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 JUN PY 2004 VL 45 IS 6 BP 1641 EP 1646 DI 10.1167/iovs.03-1055 PG 6 WC Ophthalmology SC Ophthalmology GA 824EO UT WOS:000221668900001 PM 15161821 ER PT J AU Tsilimbaris, MK Lit, ES D'Amico, DJ AF Tsilimbaris, MK Lit, ES D'Amico, DJ TI Retinal microvascular surgery: A feasibility study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CHORIORETINAL VENOUS ANASTOMOSIS; VEIN OCCLUSION; VESSELS; BREAKS; CYANOACRYLATE; SHEATHOTOMY; GLUE AB PURPOSE. To evaluate the feasibility of microvascular surgery at the level of the retinal vasculature. METHOD. Porcine eyes were used, and eyecups were prepared under an operating microscope. Several classic microvascular maneuvers were explored, such as vascular puncturing, catheterization, mobilization, intravascular injections, and various combinations of the same. Instruments used ranged from disposable 30-gauge needles to an Er:YAG laser. Commercially available 10-0 nylon sutures, fine polyimide tubes, and custom-made fine glass tubes were used for vascular catheterization. RESULTS. Puncturing, mobilization, catheterization, and intravascular injection of retinal arteries and veins were possible. The connection of two remote retinal vessels with a fine tube was also achieved with the combination of these maneuvers. CONCLUSIONS. The feasibility of performing several microvascular maneuvers on retinal arteries and veins was demonstrated in porcine eyes. Further experimentation and development of these findings in a living animal model could lead to the development of such microvascular maneuvers in humans. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM didamico@meei.harvard.edu NR 20 TC 15 Z9 15 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2004 VL 45 IS 6 BP 1963 EP 1968 DI 10.1167/iovs.03-0874 PG 6 WC Ophthalmology SC Ophthalmology GA 824EO UT WOS:000221668900044 PM 15161864 ER PT J AU Benson, TE Brown, MC AF Benson, TE Brown, MC TI Postsynaptic targets of type II auditory nerve fibers in the cochlear nucleus SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE outer hair cell; olivocochlear; small cell; multipolar cell; granule cell ID SPIRAL GANGLION-CELLS; GUINEA-PIG COCHLEA; OLIVOCOCHLEAR NEURONS; CENTRAL PROJECTIONS; AFFERENT-FIBERS; FINE-STRUCTURE; CENTRAL TRAJECTORIES; EFFERENT NEURONS; GRANULE CELLS; SINGLE UNITS AB Type II auditory nerve fibers, which provide the primary afferent innervation of outer hair cells of the cochlea, project thin fibers centrally and form synapses in the cochlear nucleus. We investigated the postsynaptic targets of these synapses, which are unknown. Using serial-section electron Microscopy Of fibers labeled with horseradish peroxidase, we examined the border of the granule-cell lamina in mice, an area of type II termination that receives branches having swellings with complex shapes. About 70% of the swellings examined with the electron microscope formed morphological synapses, which is a much higher value than found in previous studies of type II swellings in other parts of the cochlear nucleus. The high percentage of synapses enabled a number of postsynaptic targets to be identified. Most of the tare gets were small dendrites. Two of these dendrites were traced to their somata of origin, which were cochlear-nucleus "small cells" situated at the border of the granule-cell lamina. These cells did not appear to receive any terminals containing synaptic vesicles that were large and round, indicating a lack of input from type I auditory nerve fibers. Nor did type II swellings or targets participate in the synaptic glomeruli formed by mossy terminals and the dendrites of granule cells. Other type II synapses were axosomatic and their targets were large cells, which were presumed multipolar cells and one cell with characteristics of a globular bushy cell. These large cells almost certainly receive additional input from type I auditory nerve fibers, which provide the afferent innervation of the cochlear inner hair cells. A few type II postsynaptic targets-the two small cells as well as a large dendrite-received synapses that had accompanying postsynaptic bodies, a likely marker for synapses of medial olivocochlear branches. These targets thus probably receive convergent input from type II fibers and medial olivocochlear branches. The diverse nature of the type II targets and the examples of segregated convergence of other inputs illustrates the synaptic complexity of type II input to the cochlear nucleus. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mcb@ep1.meei.harvard.edu FU NIDCD NIH HHS [R01 DC001089, DC 01089] NR 66 TC 25 Z9 27 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD JUN PY 2004 VL 5 IS 2 BP 111 EP 125 DI 10.1007/s10162-003-4012-3 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 832JA UT WOS:000222262600002 PM 15357415 ER PT J AU Resendes, BL Kuo, SF Robertson, NG Giersch, ABS Honrubia, D Ohara, O Adams, JC Morton, CC AF Resendes, BL Kuo, SF Robertson, NG Giersch, ABS Honrubia, D Ohara, O Adams, JC Morton, CC TI Isolation from cochlea of a novel human intronless gene with predominant fetal expression SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE novel gene; intronless; GC-rich; cochlea; predominant fetal expression; tetramerization domain; unusually long 3' UTR; hair cells ID ACUTE PROMYELOCYTIC LEUKEMIA; HUMAN INNER-EAR; HISTONE DEACETYLASE; POTASSIUM CHANNEL; CDNA LIBRARY; K+ CHANNELS; TETRAMERIZATION DOMAIN; CANDIDATE GENES; GERBIL COCHLEA; PROTEINS AB We have cloned a novel human gene, designated PFET1 (predominantly fetal expressed T1 domain) (HUGO-approved symbol KCTD12 or C13orf2), by subtractive hybridization and differential screening of human fetal cochlear cDNA clones. Also, we have identified the mouse homolog, designated Pfet1. PTET1/Pfet1 encode a single transcript of approximately 6 kb in human, and three transcripts of approximately 4, 4.5, and 6 kb in mouse with a 70% GC-rich open reading frame (ORF) consisting of 978 bp in human and 984 bp in Mouse. Both genes have unusually long 3' Untranslated (3' UTR) regions (4996 bp in human PFET1, 3700 bp in mouse Pfet1) containing 12 and 5 putative polyadenlation consensus sequences, respectively. Pfetin, the protein encoded by PFET1/Pfet1, is predicted to have 325 amino acids in human and 327 amino acids in Mouse and to contain a voltage-gated potassium (K) channel tetramerization (T1) domain. Otherwise, to date these genes have no significant homology to any known gene. PFET1 maps to the long arm of human chromosome 13, in band q21 as shown by FISH analysis and STS mapping. Pfet1 maps to mouse chromosome 14 near the markers D14Mit8, D14Mit93, and D14Mit145.1. The human 6 kb transcriptis present in a variety of fetal organs, with highest expression levels in the cochlea and brain and, in stark contrast, is detected only at extremely low levels in adult organs, such as brain and lung. Immunohistochemistry with a polyclonal antibody raised against a synthetic peptide to PTET1 sequence (pfetin) reveals immunostaining in a variety of cell types in human, monkey, mouse, and guinea pig cochleas and the vestibular system, including type I vestibular hair cells. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Neonatal Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Kazusa DNA Res Inst, Chiba 2920812, Japan. RIKEN Res Ctr Allergy & Immunol, Lab Immunogenom, Yokohama, Kanagawa 2300045, Japan. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 77 Ave Louise Pasteur, Boston, MA 02115 USA. EM emorton@partners.org RI Ohara, Osamu/A-9119-2012; Ohara, Osamu/G-5448-2015 OI Ohara, Osamu/0000-0002-3328-9571 FU NIDCD NIH HHS [DC03402, DC03929, F32 DC000019, F32 DC000405, F32DC00405, R01 DC003929, T32DC0019] NR 47 TC 30 Z9 32 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD JUN PY 2004 VL 5 IS 2 BP 185 EP 202 DI 10.1007/s10162-003-4042-x PG 18 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 832JA UT WOS:000222262600007 PM 15357420 ER PT J AU Schumacher, HR AF Schumacher, HR TI Management strategies for osteoarthritis, ankylosing spondylitis, and gouty arthritis SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article; Proceedings Paper 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, FL SP Amer Coll Rheumatolog DE osteoarthritis; ankylosing spondylitis; gouty arthritis; management; NSAIDs; coxibs ID NECROSIS-FACTOR-ALPHA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PLACEBO-CONTROLLED TRIAL; CHIMERIC MONOCLONAL-ANTIBODY; SERUM URIC-ACID; DOUBLE-BLIND; RHEUMATOID-ARTHRITIS; MEDICAL-MANAGEMENT; KNEE OSTEOARTHRITIS; CLINICAL-TRIAL AB Rheumatic diseases are among the most frequent causes of pain and disability. Effective management of rheumatic diseases including osteoarthritis (OA), ankylosing spondylitis (AS), and gouty arthritis requires an understanding of the underlying disease mechanisms. Symptoms of OA result from both mechanical factors and elements of inflammation. Current management strategies target both of these factors and generally consist of nonpharmacologic and pharmacologic interventions, including use of nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2-specific inhibitors (coxibs), which have analgesic and antiinflammatory properties. Other approaches include intraarticular hyaluronate and the use of alternative therapies under investigation such as acupuncture or glucosamine. Disease mechanisms in AS involve enthesitis, an inflammation at the site of insertion of ligaments, tendons, or joint capsules to bone. Posture and exercise are important nonpharmacologic strategies that may be made easier with the use of NSAIDs or coxibs. Recently developed therapies, including tumor necrosis factor inhibitors, target the underlying disease mechanisms and have demonstrated dramatic symptomatic effects. Disease-modifying effects still need to be established. In gout, hyperuricemia leads to crystal-induced inflammation in some patients. Etoricoxib, one of the newer coxibs, has shown promise in treating acute gout, with efficacy similar to indomethacin, the current standard NSAID often used in these patients. Oral or intraarticular steroids can also be considered. For chronic care uricosurics can be beneficial if renal function is normal and excretion is not excessive, but allopurinol is used most often. Nonpharmacologic modalities, such as rest and cold applications, are useful for acute episodes, and lifestyle modification in the form of diet can also play a role in chronic disease management. C1 Univ Penn, Sch Med, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Univ Penn, Sch Med, Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu NR 85 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD JUN PY 2004 VL 10 IS 3 SU S BP S18 EP S25 DI 10.1097/01.rhu.0000131745.37852.bb PG 8 WC Rheumatology SC Rheumatology GA 833QE UT WOS:000222352500004 PM 17043496 ER PT J AU Misra, S Ganzini, L AF Misra, S Ganzini, L TI Capacity to consent to research among patients with bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE research; decision-making capacity; bipolar disorder ID DIFFERENT LEGAL STANDARDS; INFORMED-CONSENT; ALZHEIMERS-DISEASE; PSYCHIATRIC RESEARCH; DEPRESSED-PATIENTS; ELDERLY PATIENTS; MENTAL-ILLNESS; COMPETENCE; SCHIZOPHRENIA; PARTICIPATION AB Experts have debated the influence of mental illness on decision-making capacity. This paper reviews concepts of decision-making capacity and existing research on the influence of mental illness on capacity to consent to research. We propose how bipolar disorder, especially mania, may have an effect on consent capacity. The current conceptualization of capacity utilizes legal standards of 'choice', 'understanding', 'appreciation' and 'rational reasoning', as well as voluntarism, or the assurance that the patient is free to agree or to decline to participate in research. Studies of patients with schizophrenia suggest impaired cognition influences 'understanding' and is more important than severity of psychosis in affecting decision-making abilities. There are no studies of sources and extent of impairment to consent to research among manic patients. Mania may influence a patient's understanding of the research protocol, but also alter the patient's views, values and level of insight, thus impairing decision-making abilities at the 'appreciation' standard even when the patient understands the relevant information. Mania may impact freedom to decide, yet paradoxically, manic patients may be less influenced by others and less vulnerable to coercion, undue influence and undue incentives compared to patients without mental illness. We suggest that in patients with mood disorders, the legal standard of appreciation be thoroughly probed during the consent procedure. Studies of the effect of mania and depression on consent capacity and voluntarism are needed in order to develop processes that increase safeguards in the informed consent process. Published by Elsevier B.V. C1 Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Div Mental Hlth, Portland, OR 97239 USA. RP Misra, S (reprint author), Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. EM misras@ohsu.edu NR 29 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN PY 2004 VL 80 IS 2-3 BP 115 EP 123 DI 10.1016/S0165-0327(03)00109-5 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 824UB UT WOS:000221711200002 PM 15207924 ER PT J AU Snow, AL Hovanec, L Brandt, J AF Snow, AL Hovanec, L Brandt, J TI A controlled trial of aromatherapy for agitation in nursing home patients with dementia SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ALZHEIMERS-DISEASE; ALTERNATIVE MEDICINE; ODOR IDENTIFICATION; OLFACTORY DEFICITS; DISTURBANCES; INHALATION; BEHAVIOR; SLEEP; OILS AB Objectives: Two controlled trials of aromatherapy to decrease agitation in persons with dementia have recently produced promising results. However, both studies combined the use of essential oils with massage. Thus, it is unclear if the effect of the aromatherapy intervention was the result of smelling or the cutaneous absorption of the oils. The purpose of this study was to determine whether smelling lavender oil decreases the frequency of agitated behaviors in patients with dementia. Design: The study design was within-subjects ABCBA (A = lavender oil, B = thyme oil, C = unscented grapeseed oil): 4 weeks of baseline measurement, 2 weeks for each of the five treatment conditions (10-week total intervention time), and 2 weeks of postintervention measurement. Oil was placed every 3 hours on an absorbent fabric sachet pinned near the collarbone of each participant's shirt. Setting: A long-term care facility specifically for persons with dementia. Participants: Seven agitated nursing home residents with advanced dementia. Measurements: Agitation was assessed every 2 days using a modified Cohen-Mansfield Agitation Inventory. Olfactory functioning was assessed with structured olfactory identification and discrimination tasks, and with qualitative behavioral observation during those tasks. Results: Split-middle analyses conducted separately for each patient revealed no treatment effects specific to lavender, no treatment effects nonspecific to pleasant smelling substances, and no treatment effects dependent on order of treatment administration. There were no differences between participants with more and less intact olfactory abilities. Conclusion: There is significant evidence in the neurologic and neuropsychologic literature that persons with dementia have impaired olfactory abilities. Concordant with this literature, this study found no support for the use of a purely olfactory form of aromatherapy to decrease agitation in severely demented patients. Cutaneous application of the essential oil may be necessary to achieve the effects reported in previous controlled studies. C1 Michael E Debakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Copper Ridge Inst, Sykesville, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Snow, AL (reprint author), Michael E Debakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Serv, Houston Ctr Qual Care & Utilizat Studies, 2002 Itolcombe Blvd,Mail Code 152, Houston, TX 77030 USA. EM asnow@bcm.tmc.edu OI Brandt, Jason/0000-0001-7381-6244 NR 41 TC 31 Z9 32 U1 4 U2 18 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 JUN PY 2004 VL 10 IS 3 BP 431 EP 437 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 835ID UT WOS:000222475200005 PM 15253846 ER PT J AU Napadow, V Kaptchuk, TJ AF Napadow, V Kaptchuk, TJ TI Patient characteristics for outpatient acupuncture in Beijing, China SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID UNITED-STATES; MEDICINE; PLURALISM AB Objectives: This study quantifies and compares patient characteristics in outpatient acupuncture. Setting/design: Prospective primary source evidence was gathered at two prominent outpatient acupuncture clinics in Beijing, China (n = 563, n = 233). Results: The most common condition was Bell's palsy, which represented 20.6% and 25.3% of total cases at the two clinics, respectively. The second most common condition was cerebrovascular accident (CVA) rehabilitation. These treatments represented 11.9% and 12.0% of treatments at the two clinics, respectively. Other trends at the clinics included the following: (1) neurologic complaints predominated; (2) doctors see a large number of patients per day; (3) the majority of patients overall were female; while (4) the majority of patients treated for CVAs rehabilitation were male. As cultural and socioeconomic differences in perceptions of acupuncture exist between peoples of different countries, this study also compared patient main complaints in China to available data on acupuncture patients seen in other parts of China, Germany, the United Kingdom, Australia, and the United States. Except for the German clinic data, Western clinic acupuncturists saw more musculoskeletal complaints compared to China, where neurologic complaints predominated. Another significant difference between Asian and Western clinics was the number of patients seen per hour. While acupuncturists were reported to see 1.2 patients per hour in U.S. clinics, acupuncturists at the two Beijing, China, clinics saw 7.0 and 10.4 patients per hour, respectively. Conclusion: The main complaints seen in acupuncture outpatient clinics throughout the world likely result from a combination of inherent disease prevalence as well as patients' attitudes toward what acupuncture can treat successfully. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. Harvard Univ, Osher Inst, Boston, MA 02115 USA. RP Napadow, V (reprint author), Martinos Ctr Biomed Imaging, CNY-2301 13th St, Cambridge, MA 02139 USA. EM vitaly@nmr.mgh.harvard.edu FU NCCIH NIH HHS [P01 AT002048-A01, K01 AT02166-01] NR 40 TC 37 Z9 38 U1 0 U2 4 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 JUN PY 2004 VL 10 IS 3 BP 565 EP 572 DI 10.1089/1075553041323849 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 835ID UT WOS:000222475200023 PM 15253864 ER PT J AU Burkhardt, MS Foster, JK Laws, SM Baker, LD Craft, S Gandy, SE Stuckey, BGA Clarnette, R Nolan, D Hewson-Bower, B Martins, RN AF Burkhardt, MS Foster, JK Laws, SM Baker, LD Craft, S Gandy, SE Stuckey, BGA Clarnette, R Nolan, D Hewson-Bower, B Martins, RN TI Oestrogen replacement therapy may improve memory functioning in the absence of APOE epsilon 4 SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE oestrogen supplementation; post-menopausal women; cognition; apolipoprotein E genotype; Alzheimer's disease ID RANDOMIZED CONTROLLED-TRIAL; HEALTHY POSTMENOPAUSAL WOMEN; FAMILIAL ALZHEIMER-DISEASE; APOLIPOPROTEIN-E; PLUS PROGESTIN; TYPE-4 ALLELE; RISK; GENE; ONSET; POLYMORPHISMS AB There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an epsilon4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 +/- 6.34); ERT non-users (n = 80, mean age 67.03 +/- 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2-5; P < 0.05) and memory (e.g. total number of items recalled; P < 0.05) performance was observed in women taking ERT who were not carriers of the APOE epsilon4 allele. APOE epsilon4 carriers receiving ERT performed no better on episodic memory testing than APOE epsilon4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE epsilon4 allele. C1 Univ Western Australia, Sir James McCusker Alzheimers Dis Res Unit, Sch Psychiat & Clin Neurosci, Hollywood Private Hosp, Nedlands, WA 6009, Australia. Murdoch Univ, Sch Psychol, Perth, WA, Australia. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA USA. Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Keogh Inst Med Res, Nedlands, WA, Australia. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. Murdoch Univ, Perth, WA, Australia. RP Martins, RN (reprint author), Univ Western Australia, Sir James McCusker Alzheimers Dis Res Unit, Sch Psychiat & Clin Neurosci, Hollywood Private Hosp, 115 Monash Ave, Nedlands, WA 6009, Australia. EM rmartins@cyllene.uwa.edu.au RI Laws, Simon/C-2858-2014 OI Laws, Simon/0000-0002-4355-7082 NR 28 TC 42 Z9 46 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD JUN PY 2004 VL 6 IS 3 BP 221 EP 228 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 862NR UT WOS:000224498200002 PM 15201477 ER PT J AU Hashim, S Kwon, DH Abdelal, A Lu, CD AF Hashim, S Kwon, DH Abdelal, A Lu, CD TI The arginine regulatory protein mediates repression by arginine of the operons encoding glutamate synthase and anabolic glutamate dehydrogenase in Pseudomonas aeruginosa SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; BACILLUS-SUBTILIS; NUCLEOTIDE-SEQUENCE; GLTBDF OPERON; GENE; ARGR; CLONING; EXPRESSION; PURIFICATION; BIOSYNTHESIS AB The arginine regulatory protein of Pseudomonas aeruginosa, ArgR, is essential for induction of operons that encode enzymes of the arginine succinyltransferase (AST) pathway, which is the primary route for arginine utilization by this organism under aerobic conditions. ArgR also induces the operon that encodes a catabolic NAD+-dependent glutamate dehydrogenase (GDH), which converts L-glutamate, the product of the AST pathway, in alpha-ketoglutarate. The studies reported here show that ArgR also participates in the regulation of other enzymes of glutamate metabolism. Exogenous arginine repressed the specific activities of glutamate synthase (GltBD) and anabolic NADP-dependent GDH (GdhA) in cell extracts of strain PAO1, and this repression was abolished in an argR mutant. The promoter regions of the gltBD operon, which encodes GltBD, and the gdhA gene, which encodes GdhA, were identified by primer extension experiments. Measurements of beta-galactosidase expression from gltB::lacZ and gdhA::lacZ translational fusions confirmed the role of ArgR in mediating arginine repression. Gel retardation assays demonstrated the binding of homogeneous ArgR to DNA fragments carrying the regulatory regions for the gltBD and gdhA genes. DNase I footprinting experiments showed that ArgR protects DNA sequences in the control regions for these genes that are homologous to the consensus sequence of the ArgR binding site. In silica analysis of genomic information for P. fluorescens, P. putida, and P. stutzeri suggests that the findings reported here regarding ArgR regulation of operons that encode enzymes of glutamate biosynthesis in P. aeruginosa likely apply to other pseudomonads. C1 Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RP Lu, CD (reprint author), Georgia State Univ, Dept Biol, 24 Peachtree Ctr Ave, Atlanta, GA 30303 USA. EM biocdl@panther.gsu.edu NR 35 TC 15 Z9 15 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2004 VL 186 IS 12 BP 3848 EP 3854 DI 10.1128/JB.186.12.3848-3854.2004 PG 7 WC Microbiology SC Microbiology GA 826ZX UT WOS:000221869100021 PM 15175298 ER PT J AU Parker, HA McNally, RJ Nakayama, K Wilhelm, S AF Parker, HA McNally, RJ Nakayama, K Wilhelm, S TI No disgust recognition deficit in obsessive-compulsive disorder SO JOURNAL OF BEHAVIOR THERAPY AND EXPERIMENTAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV, 2002 CL Reno, NV SP Assoc Adv Behavior Therapy DE obsessive-compulsive disorder; emotion recognition; basal ganglia dysfunction ID GLUCOSE METABOLIC-RATE; HUNTINGTONS-DISEASE; EMOTIONS; SCALE AB Background: Patients with basal ganglia abnormalities misclassify facial expressions of disgust as expressions of anger when asked to identify the emotion depicted in photographs of individuals displaying different emotions. Sprengelmeyer, Young, Pundt et at. (1997) reported a similar disgust recognition deficit in patients with obsessive-compulsive disorder (OCD)-an anxiety disorder associated with basal ganglia abnormality. Methods: In the present experiment, we attempted to replicate Sprengelmeyer, Young, Pundt et al.'s (1997) findings. Results: We failed to replicate Sprengelmeyer, Young, Pundt et al.'s finding of disgust recognition deficits in OCD patients relative to healthy control subjects. One patient with especially severe OCD did, however, exhibit impairment by misclassifying disgust expressions as anger expressions. Discussion: These data do not confirm the presence of disgust recognition deficits in individuals with OCD. In light of the deficits exhibited by one subject with severe OCD, disgust recognition deficits may be confined to an unidentified subset of people with OCD. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM rjm@wjh.harvard.edu NR 13 TC 21 Z9 22 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7916 J9 J BEHAV THER EXP PSY JI J. Behav. Ther. Exp. Psychiatry PD JUN PY 2004 VL 35 IS 2 BP 183 EP 192 DI 10.1016/j.jbtep.2004.04.008 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 836JP UT WOS:000222552100008 PM 15210378 ER PT J AU Forthman, CL Ponce, BA Mankin, HJ AF Forthman, CL Ponce, BA Mankin, HJ TI Multiple myeloma with a pathologic fracture during pregnancy - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID THERAPY C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Forthman, CL (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, GRB Suite 622,55 Fruit St, Boston, MA 02114 USA. EM cforthman@partners.org NR 19 TC 11 Z9 12 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 JUN PY 2004 VL 86A IS 6 BP 1284 EP 1288 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 826KH UT WOS:000221827500024 PM 15173303 ER PT J AU Hampson, G Bastepe, M Champion, MP Nasar, MA Jueppner, H AF Hampson, G Bastepe, M Champion, MP Nasar, MA Jueppner, H TI Molecular defect in pseudohypoparathyroidism type 1B: 2 illustrative cases SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Bone-and-Tooth-Society CY JUN 29-30, 2004 CL Oxford, ENGLAND SP Bone & Tooth Soc C1 St Thomas Hosp, Dept Chem Pathol, London, England. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Guys Hosp, Dept Paediat, London SE1 9RT, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2004 VL 19 IS 6 BP 1034 EP 1034 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 822XG UT WOS:000221573400049 ER PT J AU Fairfield, KM Chen, WY Colditz, GA Emmons, KM Fletcher, SW AF Fairfield, KM Chen, WY Colditz, GA Emmons, KM Fletcher, SW TI Colon cancer risk counseling by health-care providers: Perceived barriers and response to an Internet-based cancer risk appraisal instrument SO JOURNAL OF CANCER EDUCATION LA English DT Article ID RECOMMENDATIONS; SIGMOIDOSCOPY; INDEX AB Background. Risk appraisal instruments may be helpful in reinforcing prevention messages, although little is known about physician acceptance of such instruments. Objective. We explored perceived barriers to colon cancer risk counseling and responses to the colon cancer component of an Internet-based risk appraisal instrument. Methods. We qualitatively assessed provider perceptions of barriers to colon cancer prevention and screening, and their responses to the Harvard Cancer Risk Index using focus groups of primary care providers. Results. Many providers commented that the risk appraisal instrument may be most helpful to reinforce messages by a health-care provider. The tool may increase awareness about modifiable risk factors for cancer and help patients prioritize changes as well as improve screening acceptance. With regard to barriers to counseling patients about colon cancer prevention and screening, providers expressed concerns that behaviors are too difficult to change. In addition, they were frustrated by limited time for prevention counseling and poor reimbursement. Conclusions. The Internet-based risk index was well accepted, although providers thought it would be most effective when used to complement provider messages about prevention. Use of an Internet-based risk index along with physician counseling could help improve cancer prevention practices and cancer screening acceptance. C1 Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04102 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Med Sch, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Med Sch, Div Community Based Res, Boston, MA USA. RP Fairfield, KM (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, 22 Bramhall St, Portland, ME 04102 USA. EM fairfk@mmc.org RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA57711-08] NR 18 TC 12 Z9 12 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SUM PY 2004 VL 19 IS 2 BP 95 EP 97 DI 10.1207/s15430154jce1902_9 PG 3 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 852CT UT WOS:000223733500009 PM 15456665 ER PT J AU Zile, M Gaasch, W Little, W Francis, G Tavazzi, L Cleland, J Davies, M AF Zile, M Gaasch, W Little, W Francis, G Tavazzi, L Cleland, J Davies, M CA MCC-135 GO1 Investigators TI A phase II, double-blind, randomized, placebo-controlled, dose comparative study of the efficacy, tolerability, and safety of MCC-135 in subjects with chronic heart failure, NYHA class II/III (MCC-135-GO1 study): Rationale and design SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE chronic heart failure; systole; diastole; calcium ID VENTRICULAR EJECTION FRACTION; PRESERVED SYSTOLIC FUNCTION; MYOCARDIAL-INFARCTION; DIASTOLIC DYSFUNCTION; THERAPEUTIC OPTIONS; PART II; OUTCOMES; LEVOSIMENDAN; COMMUNITY; MORTALITY AB Background: Chronic heart failure (CHF) can be caused either by a predominant abnormality in systolic function (systolic heart failure) or a predominant abnormality in diastolic function (diastolic heart failure). Randomized clinical trials have identified a number of pharmaceutical agents that can reduce morbidity and mortality in patients with systolic heart failure. Despite significant therapeutic advances, systolic heart failure continues to result in high rates of morbidity and mortality. In contrast to systolic heart failure, no randomized clinical trials have been performed in patients with diastolic heart failure. Common to the mechanisms causing both systolic and diastolic heart failure are abnormalities in calcium homeostasis. Mitsubishi Pharma Corporation has developed a compound (MCC-135, INN; caldaret) whose mechanism of action is proposed to be modulation of calcium homeostasis at the sarcoplasmic reticulum and cellular membrane. The purpose of this study was to test the safety, tolerability, and efficacy of MCC-135 in patients with mild to moderate heart failure. Methods: This was a phase II, multicenter, randomized, double-blind study of parallel group design comparing 3 oral dose regimens of MCC-135 (5 mg, 25 mg, 50 mg, twice daily) with a placebo control. The treatment period was 24 weeks. A total of 511 patients were recruited from 69 centers in the United States and Europe. One hundred and twenty-five patients were recruited in each of the 4 treatment groups. Patients in each treatment group were divided into 2 cohorts: those with an ejection fraction less than or equal to 40%, and those with an ejection fraction >40% as determined by core laboratory analysis of echocardiographic studies. Conclusion: Patient recruitment was completed in September 2002. Patient follow-up was completed by February 2003; the results will be available for release in 2004. C1 Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs, Med Ctr, Charleston, SC USA. Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA 01805 USA. Wake Forest Univ, Sch Med, Cardiol Sect, Winston Salem, NC 27109 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Osped Gen, Div Cardiol, Pavia, Italy. Univ Hull, Castle Hill Hosp, Kingston Upon Hull, Yorks, England. Mitsubishi Pharma Europe Ltd, London, England. RP Zile, M (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, Gazes Cardiac Res Inst, 135 Rutledge Ave,Suite 1201,POB 250592, Charleston, SC 29425 USA. OI Cleland, John/0000-0002-1471-7016 NR 40 TC 14 Z9 16 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2004 VL 10 IS 3 BP 193 EP 199 DI 10.1016/j.cardfail.2003.10.004 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 831JQ UT WOS:000222191100002 PM 15190528 ER PT J AU Vora, A Karnad, D Goyal, V Naik, A Gupta, A Lokhandwala, Y Kulkarni, H Singh, BN Phil, D AF Vora, A Karnad, D Goyal, V Naik, A Gupta, A Lokhandwala, Y Kulkarni, H Singh, BN Phil, D TI Control of heart rate versus rhythm in rheumatic atrial fibrillation: A randomized study SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE amiodarone; direct current cardioversion; ventricular rate; sinus rhythm; rheumatic heart disease ID MAZE-III PROCEDURE; SINUS RHYTHM; EXERCISE CAPACITY; VALVE DISEASE; AMIODARONE; CARDIOVERSION; MAINTENANCE; PREVENTION; WARFARIN; STROKE AB Background: Patients with rheumatic heart disease with atrial fibrillation incur significant morbidity and mortality. Which approach, ventricular rate control or maintenance of sinus rhythm, in this setting might be superior is not known. The role of amiodarone in this patient population for maintaining sinus rhythm has not been evaluated. Methods and Results: We prospectively studied 144 Patients with chronic rheumatic atrial fibrillation in a double-blind protocol in which rhythm control (group I). comprising 48 patients each with amiodarone (group Ia) and placebo (group Ib), were compared with each other and with patients in a ventricular rate control group (group II) in which the effects by diltiazem were determined (n = 48, open-label). Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6 +/- 10.3 years. left atrial size. 4.7 +/- 0.6 cm; atrial fibrillation duration. 6.1 +/- 5.4 years: and 72.9% had valvular interventions performed. At 1 year, 45 patients with sinus rhythm in group I compared with 48 in group II demonstrated an increase in exercise time (2.6 +/- 1.9 vs. 0.6 +/- 2.5 min. P = .001). improvement in New York Heart Association class of 1 or more (P = .002). and improvement in the quality-of-life score of one or greater (P = 0.01) with no difference in hospitalizations. Systemic bleeds. or thromboembolism. Five patients died in group II: none died in group I (P = .02). In group I, 73 of 87 (83.9%) patients converted to sinus rhythm and 45 of 86 (52.3%) patients maintained the rhythm at 1 year. Conversion rates were 38 of 43 (88.4%) with amiodarone versus 34 of 44 (77.3%) with placebo (P = .49): the corresponding rate for maintaining sinus rhythm was 29 of 42 (69.1%) versus 16 of 44 (36.4%) (P = .008). A larger number of electrical cardioversions were required in the placebo group (2.1 vs. 1.4, P = .011). Conclusions: Maintenance Of Sinus rhythm is superior to ventricular rate control in patients with rheumatic atrial fibrillation with respect to effects on exercise capacity, quality of life. morbidity, and possibly mortality. Sinus rhythm could be restored in most patients. and amiodarone was Superior to placebo in the restoration and maintenance of sinus rhythm. C1 VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. King Edward VII Mem Hosp, Dept Cardiol, Bombay, Maharashtra, India. King Edward VII Mem Hosp, Dept Med, Bombay, Maharashtra, India. RP Singh, BN (reprint author), VA Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu NR 26 TC 15 Z9 18 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD JUN PY 2004 VL 9 IS 2 BP 65 EP 73 DI 10.1177/107424840400900201 PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 885MQ UT WOS:000226161800001 PM 15309242 ER PT J AU Shah, AP Lopez, A Wachsner, RY Meymandi, SK Ei-Bialy, AK Ichiuji, AM AF Shah, AP Lopez, A Wachsner, RY Meymandi, SK Ei-Bialy, AK Ichiuji, AM TI Sinus node dysfunction secondary to hyperparathyroidism SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE sinus node dysfunction; hyperparathyroidism; hypercalcemia ID CARDIAC CONDUCTION; HYPERCALCEMIA AB We present two patients who were diagnosed with symptomatic Sinus node dysfunction in the setting of hypercalcemia secondary to hyperparathyroidism. An extensive review Of the literature has not revealed previous reports of this pathologic process. C1 Univ Calif Los Angeles, Sch Med, Dept Cardiol, W Los Angeles VA, Los Angeles, CA 90073 USA. Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. RP Shah, AP (reprint author), Univ Calif Los Angeles, Sch Med, Dept Cardiol, W Los Angeles VA, 11301 Wilshire Blvd 111E, Los Angeles, CA 90073 USA. EM apshah73@ucla.edu NR 12 TC 2 Z9 2 U1 0 U2 5 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD JUN PY 2004 VL 9 IS 2 BP 145 EP 147 DI 10.1177/107424840400900209 PG 3 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 885MQ UT WOS:000226161800009 PM 15309250 ER PT J AU Watkins, MT Al-Badawi, H Russo, AL Soler, H Peterson, B Patton, GM AF Watkins, MT Al-Badawi, H Russo, AL Soler, H Peterson, B Patton, GM TI Human microvascular endothelial cell prostaglandin E1 synthesis during in vitro ischemia-reperfusion SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ischemia; reperfusion; endothelium; prostaglandin H synthase ID SKELETAL-MUSCLE ISCHEMIA; PROSTACYCLIN PRODUCTION; CHRONIC HYPOXIA; SHEAR-STRESS; EXPRESSION; CYCLOOXYGENASE-2; REOXYGENATION; METABOLISM; GROWTH; COX-2 AB Ischemia-reperfusion injury is a microvascular event documented in numerous in vivo animal models. In animal models, prostaglandin and prostaglandin analogues have been found to ameliorate reperfusion injury. These studies were undertaken to evaluate human microvascular endothelial PGE(1) synthesis during in vitro ischemia followed by reperfusion. Human (neonatal) microvascular endothelial cell (MEC) cultures (n = 6) were subjected to sequential 2 h periods of normoxia (20% O-2), ischemia (1.5% O-2), and reperfusion (20% O-2). Prostaglandin E-2 synthesis in conditioned media was determined by ELISA. Steady state levels of MEC prostaglandin H synthase (PGHS)-1 and -2 mRNA were assessed at the end of each 2-h period using RT-PCR and a quantitative mRNA ELISA. MEC PGHS protein levels were analyzed using an ELISA. PGE(1) release increased significantly during the initial 30 min of ischemia, but rapidly fell below normoxic levels by 90 and 120 min. During reperfusion, PGE(1) release returned to normoxic levels at 30, 60, and 90 min, and exceeded normoxic levels at 120 min. PGHS-1 mRNA levels were undetectable during all experimental conditions. PGHS-2 mRNA levels were unchanged by ischemia, but were decreased by reperfusion. In contrast, PGHS-2 protein levels increased 3-fold during ischemia, and remained elevated during reperfusion. Human MEC do not express PGHS-1 mRNA in vitro. Prolonged ischemia decreases MEC PGE, synthesis, and stimulates increased PGHS-2 protein levels without altering the steady state levels of COX-2 mRNA. During reperfusion, increased PGHS-2 protein levels persist and are associated with stimulated PGE(2) secretion, despite relative decreases in PGHS-2 mRNA. (C) Published 2004 Wiley-Liss, Inc.dagger. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Div Vasc Surg, Boston, MA 02131 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02131 USA. VA Boston Healthcare Syst, Boston, MA 02131 USA. RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 39 TC 5 Z9 7 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 1 PY 2004 VL 92 IS 3 BP 472 EP 480 DI 10.1002/jcb.20077 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 826NM UT WOS:000221835800005 PM 15156559 ER PT J AU Jang, MS Miao, HX Carlesso, N Shelly, L Zlobin, A Darack, N Qin, JZ Nickoloff, BJ Miele, L AF Jang, MS Miao, HX Carlesso, N Shelly, L Zlobin, A Darack, N Qin, JZ Nickoloff, BJ Miele, L TI Notch-1 regulates cell death independently of differentiation in murine erythroleukemia cells through multiple apoptosis and cell cycle pathways SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; HYBRID POLAR COMPOUNDS; C-JUN; RETINOBLASTOMA PROTEIN; NEOPLASTIC TRANSFORMATION; HEMATOPOIETIC PROGENITORS; SIGNALING PROMOTES; LIGAND JAGGED-1; TRANSGENIC MICE AB Notch signaling is a potential therapeutic target for various solid and hematopoietic malignancies. We have recently shown that downregulation of Notch-1 expression has significant anti-neoplastic activity in pre-clinical models. However, the mechanisms through which Notch modulation may affect cell fate in cancer remain poorly understood. We had previously shown that Notch-1 prevents apoptosis and is necessary for pharmacologically induced differentiation in murine erythroleukemia (MEL) cells. We investigated the mechanisms of these effects using three experimental strategies: (1) MEL cells stably transfected with antisense Notch-1 or constitutively active Notch-1, (2) activation of Notch-1 by a cell-associated ligand, and (d3) activation of Notch-1 by a soluble peptide ligand. We show that: (1) downregulation of Notch-1 sensitizes MEL cells to apoptosis induced by a Ca2+ influx or anti-neoplastic drugs; (2) Notch-1 downregulation induces phosphorylation of c-Jun N-terminal kinase (JNK) while constitutive activation of Notch-1 or prolonged exposure to a soluble Notch ligand abolishes it; (3) Notch-1 has dose-and time-dependent effects on the levels of apoptotic inhibitor Bcl-x(L) and cell cycle regulators p21(cip1)/(waf1), p27(kip1), and Rb; and (4) Notch-1 activation by a cell-associated ligand is accompanied by rapid and transient induction of NF-kappaB DNA-binding activity. The relative effects of Notch-1 signaling on these pathways depend on the levels of Notch-1 expression, the mechanism of activation, and the timing of activation. The relevance of these findings to the role of Notch signaling in differentiation and cancer are discussed. J. Cell. Physiol. 199: 418-433, 2004. (C) 2003 Wiley-Liss, Inc. C1 Univ Illinois, Dept Biopharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Ctr Canc, Chicago, IL 60612 USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL USA. Massachusetts Gen Hosp, AIDS Res Ctr Expt Hematol, Boston, MA 02114 USA. Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. Loyola Univ, Dept Pathol, Maywood, IL USA. RP Miele, L (reprint author), Univ Illinois, Dept Biopharmaceut Sci, 833 S Wood St,M-C 865, Chicago, IL 60612 USA. EM lmiele@uic.edu FU NCI NIH HHS [1R01 CA84065-01] NR 101 TC 54 Z9 55 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2004 VL 199 IS 3 BP 418 EP 433 DI 10.1002/jcp.10467 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 817LY UT WOS:000221180200010 PM 15095289 ER PT J AU Deng, YP Albin, RL Penney, JB Young, AB Anderson, KD Reiner, A AF Deng, YP Albin, RL Penney, JB Young, AB Anderson, KD Reiner, A TI Differential loss of striatal projection systems in Huntington's disease: a quantitative immunohistochemical study SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Review DE neurodegeneration; Huntington's disease; striatum; pallidum; substantia nigra; substance P; enkephalin; glutamic acid decarboxylase; immunohistochemistry ID POSTMORTEM BRAIN-TISSUE; CENTRAL-NERVOUS-SYSTEM; PARVALBUMIN-IMMUNOREACTIVE NEURONS; RECEPTOR-MEDIATED EXCITOTOXICITY; GLUTAMIC-ACID DECARBOXYLASE; BASAL GANGLIA VOLUME; SUBSTANCE-P; GLOBUS-PALLIDUS; QUINOLINIC ACID; CANNABINOID RECEPTORS AB Prior studies suggest differences exist among striatal projection neuron types in their vulnerability to Huntington's disease (HD). In the present study, we immunolabeled the fibers and terminals of the four main types of striatal projection neuron in their target areas for substance P, enkephalin, or glutamic acid decarboxylase (GAD), and used computer-assisted image analysis to quantify the abundance of immumolabeled terminals in a large sample of HD cases ranging from grade 0 to grade 4 [J. Neuropathol. Exp. Neurol. 44 (1985) 559], normalized to labeling in control human brains. Our goal was to characterize the relative rates of loss of the two striatopallidal projection systems (to the internal versus the external pallidal segments) and the two striatonigral projections systems (to pars compacta versus pars reticulata). The findings for GAD and the two neuropeptides were similar-the striatal projection to the external pallidal segment was the most vulnerable, showing substantial loss by grade 1. Loss of fibers in both subdivisions of the substantia nigra was also already great by grade 1. By contrast, the loss in the striatal projection system to the internal segment of globus pallidus proceeded more gradually. By grade 4 of HD, however, profound loss in all projection systems was apparent. These findings support the notion that the striatal neurons preferentially projecting to the internal pallidal segment are, in fact, less vulnerable in HD than are the other striatal projection neuron types. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Vet Adm Med Ctr, GRECC, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. RP Reiner, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. EM areiner@utmem.edu FU NINDS NIH HHS [NS01300, NS19613, NS19620, NS28721, NS38166, R01 NS028721] NR 118 TC 89 Z9 91 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JUN PY 2004 VL 27 IS 3 BP 143 EP 164 DI 10.1016/j.jchemneu.2004.02.005 PG 22 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 832SR UT WOS:000222287900001 PM 15183201 ER PT J AU Palumbo, D Spencer, T Lynch, J Co-Chien, H Faraone, SV AF Palumbo, D Spencer, T Lynch, J Co-Chien, H Faraone, SV TI Emergence of tics in children with ADHD: Impact of once-daily OROS (R) methylphenidate therapy SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SINGLE SCHOOL-DISTRICT; TOURETTES-SYNDROME; A-DAY; STIMULANT TREATMENT; CONTROLLED TRIAL; POPULATION AB Objectives: While stimulants are the recognized first-line choice of pharmacotherapy for ADHD, reports that they may induce or exacerbate tics have tended to limit their use in ADHD children who have a history of tics or a family history of Tourette's syndrome. This study analyzes the incidence of tics reported across five studies of children with ADHD who received methylphenidate (MPH)-based therapy as part of the clinical development program for once-daily OROS(R) MPH (CONCERTA(R) McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA). Methods: Data were analyzed from three placebo-controlled, active-controlled studies (studies 1-3) lasting 1-4 weeks, and two open-label studies lasting 2 years (study 4) and 9 months (study 5), respectively. During the course of the studies, parents were asked at the end of each week of treatment (studies 1 and 2), biweekly (study 3), or monthly (for the first year of study 4, then at 3-month intervals thereafter) whether their child had experienced tics. Tics could also be reported as adverse events in the two open-label studies. Results: Pooled data from the three placebo-controlled studies showed that the incidence of tics was not significantly different across all three treatment groups (OROS(R) MPH, 4.0%; MPH tid, 2.3%; placebo, 3.7%, p = 0.5249). During the first year of the 2-year open-label study, the monthly incidence of tics remained constant, at approximately 5%. Analysis of tic episodes per patient in this study found no correlation between an OROS(R) MPH dose and the frequency of tic episodes. The risk of tic episodes was higher in patients with a history of tics than in those with no history of tics (33% versus 7%, p < 0.0001). However, only 2 children with a history of tics (4%) withdrew from therapy because of their tics. Conclusions: These data suggest that MPH-based therapy does not significantly induce or exacerbate tics in children with ADHD. C1 Univ Rochester, Med Ctr, Strong Neurol ADHD Clin, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. McNeil Consumer & Specialty Pharmaceut, Ft Washington, MD USA. Alza Corp, Mountain View, CA USA. RP Palumbo, D (reprint author), Univ Rochester, Med Ctr, Strong Neurol ADHD Clin, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA. EM Donna_Palumbo@URMC.Rochester.edu NR 31 TC 27 Z9 30 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SUM PY 2004 VL 14 IS 2 BP 185 EP 194 DI 10.1089/1044546041649138 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 843MK UT WOS:000223087800005 PM 15319016 ER PT J AU Gonzalez-Heydrich, J Pandina, GJ Fleisher, CA Hsin, O Raches, D Bourgeois, BF Biederman, J AF Gonzalez-Heydrich, J Pandina, GJ Fleisher, CA Hsin, O Raches, D Bourgeois, BF Biederman, J TI No seizure exacerbation from risperidone in youth with comorbid epilepsy and psychiatric disorders: A case series SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DISRUPTIVE BEHAVIOR DISORDERS; EPISODIC-DYSCONTROL SYNDROME; AGGRESSIVE-BEHAVIOR; PEDIATRIC EPILEPSY; SUBAVERAGE IQS; DOUBLE-BLIND; CHILDREN; ADOLESCENTS; PANCREATITIS; SEVERITY AB Objective: The aim of this study was to study risperidone use in pediatric patients with comorbid epilepsy and psychiatric disorders. Method: We retrospectively reviewed the outpatient psychopharmacology medical records of patients with epilepsy, aged 19 and younger, who received risperidone for psychiatric disorders. Results: Twenty-one (21) youths (mean age, 12.0 +/- 4.2 years) met our criteria for review. Mean risperidone dosage was 2.4 +/- 3.5 mg/day. Target symptoms included severe aggression, severe agitation, psychosis, and self-injurious behavior. Diagnoses included attention-deficit hyperactivity disorder (ADHD), learning disorder, and impulse control disorder. Seizure type was partial complex in 12 patients, generalized in 6 patients, neonatal in 1 patient, myoclonic in 1 patient, and unclassified in 1 patient. The average number of previous psychotropic trials was 3.5 +/- 3.0. Using a definition of response of a Clinical Global Impressions (CGI) improvement score of 2 or less, 15 patients (71%) were considered responders. Adverse effects were none to slight in 16 patients, moderate in 4 patients, and severe in 1 patient. Seizures did not worsen in any patient. Conclusions: Risperidone was associated with a clinically significant global improvement, without seizure exacerbation in youths with epilepsy and psychiatric disorders. Despite the limitations of the study design, the 71% responder rate is noteworthy in this treatment-refractory group. C1 Childrens Hosp, Boston, MA 02115 USA. Janssen Pharmaceut, Titusville, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gonzalez-Heydrich, J (reprint author), Childrens Hosp, Fegan 8,300 Longwood Ave, Boston, MA 02115 USA. EM joseph.gonzalezheydrich@tch.harvard.edu NR 40 TC 11 Z9 12 U1 2 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SUM PY 2004 VL 14 IS 2 BP 295 EP 310 DI 10.1089/1044546041649075 PG 16 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 843MK UT WOS:000223087800015 PM 15319026 ER PT J AU Jiang, YD Acquadro, MA AF Jiang, YD Acquadro, MA TI Upper airway obstruction caused by a double-cuffed nasal balloon after extubation SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE airway obstruction; balloon tamponade; epistaxis; general anesthesia; nasal packing ID EPISTAXIS; CATHETERS AB This case report highlights a situation in which a double-cuffed nasal balloon tamponade device can cause an upper airway obstruction. An 89-year-old female required general anesthesia for an emergent embolization for right-sided epistaxis. The patient had no signs of upper airway obstruction when a double-cuffed nasal tamponade balloon was in place prior to general anesthesia. However, upper airway obstruction occurred immediately after extubation and was corrected by cuff deflation. The mechanisms of upper airway obstruction as a result of cuff dysfunction and management are discussed. (C) 2004 by Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN 3, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUN PY 2004 VL 16 IS 4 BP 301 EP 304 DI 10.1016/j.jclinane.2003.09.010 PG 4 WC Anesthesiology SC Anesthesiology GA 842NI UT WOS:000223010700015 PM 15261326 ER PT J AU Cummings, DE Overduin, J Foster-Schubert, KE AF Cummings, DE Overduin, J Foster-Schubert, KE TI Gastric bypass for obesity: Mechanisms of weight loss and diabetes resolution SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the Endocrine-Society CY JUN 12-15, 2004 CL New Orleans, LA SP Endocrine Soc ID VERTICAL BANDED GASTROPLASTY; ROUX-EN-Y; PLASMA GHRELIN LEVELS; GLUCAGON-LIKE PEPTIDE-1; MORBID-OBESITY; JEJUNOILEAL BYPASS; FOOD-INTAKE; CIRCULATING GHRELIN; BARIATRIC SURGERY; SHORT-TERM C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Cummings, DE (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. EM davidec@u.washington.edu FU NIDDK NIH HHS [R01 DK61516] NR 102 TC 280 Z9 316 U1 1 U2 17 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 JUN PY 2004 VL 89 IS 6 BP 2608 EP 2615 DI 10.1210/jc.2004-0433 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826PB UT WOS:000221839900014 PM 15181031 ER PT J AU Santoro, N Lasley, B McConnell, D Allsworth, J Crawford, S Gold, EB Finkelstein, JS Greendale, GA Kelsey, J Korenman, S Luborsky, JL Matthews, K Midgley, R Powell, L Sabatine, J Schocken, M Sowers, MF Weiss, G AF Santoro, N Lasley, B McConnell, D Allsworth, J Crawford, S Gold, EB Finkelstein, JS Greendale, GA Kelsey, J Korenman, S Luborsky, JL Matthews, K Midgley, R Powell, L Sabatine, J Schocken, M Sowers, MF Weiss, G TI Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of Women's Health across the Nation (SWAN) Daily Hormone Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PREMENOPAUSAL WOMEN; GONADOTROPIN-SECRETION; LUTEINIZING-HORMONE; REPRODUCTIVE LIFE; OVARIAN-FUNCTION; DIMERIC INHIBIN; LUTEAL FUNCTION; UNITED-STATES; ACTIVIN-A AB The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women. The Study of Women's Health across the Nation ( SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42 - 52 yr at baseline. All participants are seen annually to assess a variety of endpoints. A subcohort of 848 women undergoes further investigation of their daily patterns of reproductive hormones in the Daily Hormone Study (DHS). DHS enrollees annually complete a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 d ( whichever comes first). Chemiluminescent assays measured urinary LH and FSH, as well as metabolites of estradiol [ estrone conjugates (E1c)] and progesterone [ pregnanediol glucuronide (Pdg)]. Cycles were assessed for evidence of luteal activity and day of luteal transition using previously developed algorithms. Midreproductive-aged women who underwent similar daily urinary analyses served as historical controls. Correlates of cycle features were identified. Eight hundred thirty-three cycles were evaluable and had complete data on covariates. Six hundred seventy-four (80.9%) cycles had evidence of luteal activity, and 159 (19.1%) did not. Women who were at least 49 yr old were less likely to have cycles with luteal activity and had more variable cycle length, higher total-cycle FSH, and lower total-cycle Pdg. Compared with heavier women, those with body mass index less than 25 kg/m(2) had shorter cycles and higher total-cycle LH, FSH, and Pdg but not E1c. Chinese- and Japanese-American women had overall lower adjusted total-cycle E1c excretion. Smoking was not significantly associated with cycle length or hormones. When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition. In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve. C1 Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Div Reprod Endocrinol, Bronx, NY 10461 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Calif Davis, Dept Populat Hlth & Reprod Med Sci, Davis, CA 95616 USA. Univ Calif Davis, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA. Kaiser Permanente, Davis, CA 95616 USA. Univ Michigan, Cent Ligand Assay Satellite Serv, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. New England Res Inst, Watertown, MA 02472 USA. Univ Massachusetts, Med Ctr, Dept Med, Div Prevent & Behav Med, Worcester, MA 02155 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Epidemiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90095 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA. Rush Presbyterian St Lukes Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Dept Epidemiol, Chicago, IL 60612 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Epidemiol & Data Coordinating Ctr, Pittsburgh, PA 15213 USA. RP Santoro, N (reprint author), Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Div Reprod Endocrinol, 1300 Morris Pk Ave,Mazer 316, Bronx, NY 10461 USA. EM glicktoro@aol.com OI Allsworth, Jenifer/0000-0001-6559-8638 FU NCRR NIH HHS [RR-1066]; NICHD NIH HHS [HD 12553]; NINR NIH HHS [U01 NR04061]; PHS HHS [12554, 02759, 12495, 12505, 12535, 12539, 12546, 41978] NR 46 TC 109 Z9 112 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2004 VL 89 IS 6 BP 2622 EP 2631 DI 10.1210/jc.2003-031578 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826PB UT WOS:000221839900016 PM 15181033 ER PT J AU Klein, NA Houmard, BS Hansen, KR Woodruff, TK Sluss, PM Bremner, WJ Soules, MR AF Klein, NA Houmard, BS Hansen, KR Woodruff, TK Sluss, PM Bremner, WJ Soules, MR TI Age-related analysis of inhibin A, inhibin B, and activin a relative to the intercycle monotropic follicle-stimulating hormone rise in normal ovulatory women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; ADVANCED REPRODUCTIVE AGE; DIMERIC INHIBIN; IMMUNOREACTIVE INHIBIN; MENOPAUSAL TRANSITION; SERUM CONCENTRATIONS; LUTEINIZING-HORMONE; OLDER WOMEN; ESTRADIOL; SECRETION AB Previous studies have reported that the monotropic rise in FSH in older women is associated with decreased inhibin B and/or A levels and increased levels of activin A. Whereas most investigators have found decreased follicular-phase inhibin B, the roles of inhibin A and activin A as modulators of the FSH rise are unclear. The objectives of this study were to determine whether deficiencies in circulating levels of inhibin A, inhibin B, and/or activin A exist during the intercycle interval in ovulatory older ( age, 40 - 45 yr; n = 16), compared with younger women ( age, 20 - 25 yr; n = 13). Blood samples were obtained daily throughout one menstrual cycle and the follicular phase of the subsequent cycle and were analyzed for LH, FSH, estradiol, inhibin A and B, and activin A. Despite significant FSH elevation, no deficiencies in inhibin A, activin A, or estradiol were detected in older subjects. In fact, inhibin A was significantly higher in older participants during the intercycle phase ( P = 0.01), whereas inhibin B was significantly lower. Thus, the monotropic rise in FSH does not appear to result from changes in inhibin A or activin A, supporting the concept that inhibin B plays a critical role in mediating the FSH rise in older women. C1 Univ Washington, Dept Obstet & Gynecol, Div Reprod Endocrinol, Seattle, WA 98105 USA. Univ Washington, Dept Med, Seattle, WA 98105 USA. Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA. Northwestern Univ, Dept Physiol, Evanston, IL 60208 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Klein, NA (reprint author), Univ Washington, Dept Obstet & Gynecol, Div Reprod Endocrinol, 4225 Roosevelt Way NE,Suite 305, Seattle, WA 98105 USA. EM nklein@u.washington.edu FU NIA NIH HHS [R01-AG14579]; NICHD NIH HHS [U54-HD29164] NR 31 TC 62 Z9 63 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2004 VL 89 IS 6 BP 2977 EP 2981 DI 10.1210/jc.2003-031515 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 826PB UT WOS:000221839900071 PM 15181087 ER PT J AU Chen, J Wall, NR Kocher, K Duclos, N Fabbro, D Neuberg, D Griffin, JD Shi, Y Gilliland, DG AF Chen, J Wall, NR Kocher, K Duclos, N Fabbro, D Neuberg, D Griffin, JD Shi, Y Gilliland, DG TI Stable expression of small interfering RNA sensitizes TEL-PDGF beta R to inhibition with imatinib or rapamycin SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; ABL GENE-EXPRESSION; BCR-ABL; MAMMALIAN-CELLS; CANCER-THERAPY; RECEPTOR-BETA; BLAST CRISIS; FUSION; STAUROSPORINE AB Small molecule inhibitors, such as imatinib, are effective therapies for tyrosine kinase fusions BCR-ABL-TEL-PDGFbetaR-mediated human leukemias, but resistance may develop. The unique fusion junctions of these molecules are attractive candidates for molecularly targeted therapeutic intervention using RNA interference (RNAi), which is mediated by small interfering RNA (siRNA). We developed a retroviral system for stable expression of siRNA directed to the unique fusion junction sequence of TEL-PDGFbetaR in transformed hematopoietic cells. Stable expression of the siRNA resulted in approximately 90% inhibition of TEL-PDGFbetaR expression and its downstream effectors, including PI3K and mammalian target of rapamycin (mTOR). Expression of TEL-PDGFbetaR-specific siRNA (TPsiRNA) significantly attenuated the proliferation of TEL-PDGFbetaR-transformed Ba/F3 cells or disease latency and penetrance in mice induced by intravenous injection of these Ba/F3 cells. Although a 90% reduction in TEL-PDGFbetaR expression was insufficient to induce cell death, stable siRNA expression sensitized transformed cells to the PDGFbetaR inhibitor imatinib or to the mTOR inhibitor rapamycin. TPsiRNA also inhibited an imatinib-resistant TEL-PDGFbetaR mutant, and the inhibition was enhanced by siRNA in combination with PKC412, another PDGFbetaR inhibitor. Although siRNA delivery in vivo is a challenging problem, stable expression of siRNA, which targets oncogenic fusion genes, may potentiate the effects of conventional therapy for hematologic malignancies. C1 Brigham & Womens Hosp, Div Hematol, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol, Howard Hughes Med Inst, 75 Francis St, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Wall, Nathan/H-7368-2015 OI Wall, Nathan/0000-0002-3235-4386 FU NCI NIH HHS [F32 CA097802, CA67996]; NIDDK NIH HHS [P01 DK050654, DK50654]; NIGMS NIH HHS [R01 GM053874, R01GM53874] NR 39 TC 53 Z9 58 U1 0 U2 4 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 JUN PY 2004 VL 113 IS 12 BP 1784 EP 1791 DI 10.1172/JCI200420673 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 829JV UT WOS:000222045300016 PM 15199413 ER PT J AU Kudva, IT Griffin, RW Murray, M John, M Perna, NT Barrett, TJ Calderwood, SB AF Kudva, IT Griffin, RW Murray, M John, M Perna, NT Barrett, TJ Calderwood, SB TI Insertions, deletions, and single-nucleotide polymorphisms at rare restriction enzyme sites enhance discriminatory power of polymorphic amplified typing sequences, a novel strain typing system for Escherichia coli O157 : H7 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; FOOD-BORNE OUTBREAK; O157-H7; DNA; GENOME; PATHOGENS; PATTERNS; PCR; INFECTIONS; DIVERSITY AB Polymorphic amplified typing sequences (PATS) for Escherichia coli O157:H7 (O157) was previously based on indels containing Xbal restriction enzyme sites occurring in O-island sequences of the O157 genome. This strain-typing system, referred to as XbaI-based PATS, typed every O157 isolate tested in a reproducible, rapid, straightforward, and easy-to-interpret manner and had technical advantages over pulsed-field gel electrophoresis (PFGE). However, the system was less discriminatory than PFGE and was unable to differentiate fully between unrelated isolates. To overcome this drawback, we enhanced PATS by using another infrequently cutting restriction enzyme, AvrII (also known as BlnI), to identify additional polymorphic regions that could increase the discriminatory ability of PATS typing. Referred to as AvrII-based PATS, the system identified seven new polymorphic regions in the O157 genome. Unlike Xbal, polymorphisms involving AvrII sites were caused by both indels and single-nucleotide polymorphisms occurring in O-island and backbone sequences of the O157 genome. AvrII-based PATS by itself provided poor discrimination of the O157 isolates tested. However, when primer pairs amplifying the seven polymorphic AvrII sites were combined with those amplifying the eight polymorphic Xbal sites (combined PATS), the discriminatory power of PATS was enhanced. Combined PATS matched related O157 isolates better than PFGE while differentiating between unrelated isolates. PATS typed every O157 isolate tested and directly targeted polymorphic sequences responsible for differences in the restriction digest patterns of O157 genomic DNA, utilizing PCR rather than relying on gel electrophoresis. This enabled PATS to resolve the ambiguity in PFGE typing, including that arising from the "more distantly related" and "untypeable" profiles. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Wisconsin, Dept Anim Hlth & Biomed Sci, Madison, WI 53706 USA. Ctr Dis Control, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. RP Kudva, IT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM ikudva@partners.org NR 40 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2004 VL 42 IS 6 BP 2388 EP 2397 DI 10.1128/JCM.42.6.2388-2397.2004 PG 10 WC Microbiology SC Microbiology GA 829AS UT WOS:000222015800005 PM 15184409 ER PT J AU Sutton, DA Rinaldi, MG Kielhofner, M AF Sutton, DA Rinaldi, MG Kielhofner, M TI First US report of subcutaneous phaeohyphomycosis caused by Veronaea botryosa in a heart transplant recipient and review of the literature SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Review ID EXOPHIALA-SPINIFERA; BOTHRYOSA; FUNGI AB Veronaea botryosa is a rare agent of human phaeohyphomycosis. We describe the first case of subcutaneous disease occurring in the United States, alert clinicians to the second report of a transplant-associated mycosis in a heart transplant recipient, extend the previously defined area of endemicity, and review the literature. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. St Lukes Episcopal Hosp, Houston, TX 77030 USA. RP Sutton, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM suttond@uthscsa.edu NR 16 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2004 VL 42 IS 6 BP 2843 EP 2846 DI 10.1128/JCM.42.6.2843-2846.2004 PG 4 WC Microbiology SC Microbiology GA 829AS UT WOS:000222015800084 PM 15184488 ER PT J AU Winer, EP Berry, DA Woolf, S Duggan, W Kornblith, A Harris, LN Michaelson, RA Kirshner, JA Fleming, GF Perry, MC Graham, ML Sharp, SA Keresztes, R Henderson, CI Hudis, C Muss, H Norton, L AF Winer, EP Berry, DA Woolf, S Duggan, W Kornblith, A Harris, LN Michaelson, RA Kirshner, JA Fleming, GF Perry, MC Graham, ML Sharp, SA Keresztes, R Henderson, CI Hudis, C Muss, H Norton, L TI Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: Cancer and Leukemia Group B Trial 9342 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; PHASE-II TRIAL; CHEMOTHERAPY; SURVIVAL; CYCLOPHOSPHAMIDE; MULTICENTER; CARCINOMA; THERAPY; SCORES AB Purpose Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer. Patients and Methods Four hundred seventy-four women with metastatic breast cancer who had received one or no prior chemotherapy regimens were randomly assigned to one of three paclitaxel dosing regimens-175 mg/m(2), 210 mg/m(2), or 250 mg/m(2)-each administered as a 3-hour infusion every 3 weeks. Women completed self-administered quality of life and symptom assessment questionnaires at baseline and after three cycles of treatment. Results No evidence of a significant dose-response relationship was demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21% for the three regimens, respectively. A marginally significant association (P = .04) was seen between dose and time to progression; however, in a multivariate analysis, the difference was even less apparent. No statistically significant difference was seen in survival. Neurotoxicity and hematologic toxicity were more severe on the higher dose arms. There was no significant difference in quality of life on the three arms. Conclusion Higher doses of paclitaxel administered as a 3-hour infusion to women with metastatic breast cancer did not improve response rate, survival, or quality of life. There was a slight improvement in time to progression with higher dose therapy, which was offset by greater toxicity. When a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m(2) should be considered the optimal dose. (C) 2004 by American Society of Clinical Oncology. C1 Dana Farber Partners Canc Care, Boston, MA USA. SUNY Upstate Med Univ, Syracuse, NY USA. Mt Sinai Sch Med, New York, NY 10029 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA USA. Vermont Canc Ctr, Burlington, VT USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, 44 Binney St,D1210, Boston, MA 02115 USA. EM ewiner@partners.org OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA33601, CA03927, CA04457, CA07968, CA12046, CA21060, CA32291, CA41287, CA47559, CA47577, CA60138, CA77406, CA77651] NR 27 TC 166 Z9 171 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2004 VL 22 IS 11 BP 2061 EP 2068 DI 10.1200/JCO.2004.08.048 PG 8 WC Oncology SC Oncology GA 826DG UT WOS:000221808800006 PM 15169793 ER PT J AU Kaufman, HL Wang, W Manola, J DiPaola, RS Ko, YJ Sweeney, C Whiteside, TL Schlom, J Wilding, G Weiner, LM AF Kaufman, HL Wang, W Manola, J DiPaola, RS Ko, YJ Sweeney, C Whiteside, TL Schlom, J Wilding, G Weiner, LM TI Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): A trial of the Eastern Cooperative Oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL RETROPUBIC PROSTATECTOMY; RADIATION-THERAPY; DIVERSIFIED PRIME; ANTIGEN PSA; POX VIRUS; T-CELLS; GENERATION; PROGRESSION; SURVIVAL; PEPTIDE AB Purpose. A phase II clinical trial was conducted to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using vaccinia virus and fowlpox virus expressing human prostate-specific antigen (PSA) in patients with biochemical progression after local therapy for prostate cancer. The induction of PSA-specific immunity was also evaluated. Patients and Methods. A randomized clinical trial was conducted by the Eastern Cooperative Oncology group and 64 eligible patients were randomly assigned to receive four vaccinations with fowlpox-PSA (rF-PSA), three rF-PSA vaccines followed by one vaccinia-PSA (rV-PSA) vaccine, or one rV-PSA vaccine followed by three rF-PSA vaccines. The major end point was PSA response at 6 months, and immune monitoring included measurements of anti-PSA and anti-vaccinia antibody titers and PSA-specific T-cell responses. Results. The prime/boost schedule was well tolerated with few adverse events. Of the eligible patients, 45.3% of men remained free of PSA progression at 19.1 months and 78.1 % demonstrated clinical progression-free survival. There was a trend favoring the treatment group that received a priming dose of rV-PSA. Although no significant increases in anti-PSA antibody titers were detected, 46% of patients demonstrated an increase in PSA-reactive T-cells. Conclusion. Therapy with poxviruses expressing PSA and delivered in a prime/boost regimen was feasible and associated with minimal toxicity in the cooperative group setting. A significant proportion of men remained free of PSA and clinical progression after 19 months follow-up, and nearly half demonstrated an increase in PSA-specific T-cell responses. Phase III studies are needed to define the role of vaccination in men with prostate cancer or those who are at risk for the disease. C1 Columbia Univ, Med Ctr, New York, NY 10032 USA. Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA USA. Canc Inst New Jersey, New Brunswick, NJ USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Univ Pittsburgh, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Kaufman, HL (reprint author), Columbia Univ, Med Ctr, 177 Ft Washington Ave, New York, NY 10032 USA. EM hlk2003@columbia.edu FU NCI NIH HHS [CA23318, CA14958, CA39229, CA66636, CA80775, CA21115, CA21076, CA49883, CA49957] NR 34 TC 174 Z9 180 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 JUN 1 PY 2004 VL 22 IS 11 BP 2122 EP 2132 DI 10.1200/JCO.2004.08.083 PG 11 WC Oncology SC Oncology GA 826DG UT WOS:000221808800013 PM 15169798 ER PT J AU Pollack, A DeSilvio, M Khor, LY Li, R Al-Saleem, TI Hammond, ME Venkatesan, V Lawton, CA Roach, M Shipley, WU Hanks, GE Sandler, HM AF Pollack, A DeSilvio, M Khor, LY Li, R Al-Saleem, TI Hammond, ME Venkatesan, V Lawton, CA Roach, M Shipley, WU Hanks, GE Sandler, HM TI Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group trial 92-02 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; CELL-PROLIFERATION; LABELING INDEX; CARCINOMA; MARKERS; EXPRESSION; RECURRENCE; BCL-2; BROMODEOXYURIDINE; IMMUNOREACTIVITY AB Purpose. The Ki-67 staining index (Ki67-Sl) has been associated with prostate cancer patient outcome, however, few studies have involved radiotherapy (RT) -treated patients, The association of Ki67-Sl to local failure (LF), biochemical failure (BF), distant metastasis (DM), cause-specific death (CSD) and overall death (OD) was determined in men randomly assigned to short term androgen deprivation (STAID) + RT or long-term androgen deprivation (LTAD) + RT. Patients and Methods. There were 537 patients (35.5%) on Radiation Therapy Oncology Group (RTOG) 92-02 who had sufficient tissue for Ki67-Sl analysis. Median follow-up was 96.3 months. Ki67-Sl cut points of 3.5% and 7.1 % were previously found to be related to patient outcome and were examined here in a Cox proportional hazards multivariate analysis (MVA). Ki67-Sl was also tested as a continuous variable. Covariates were dichotomized in accordance with stratification and randomization criteria. Results. Median Ki67-SI was 6.5% (range, 0% to 58.2%). There was no difference in the distribution of patients in the Ki-67 analysis cohort (n = 537) and the other patients in RTOG 92-02 (n = 977) by any of the covariates or end points tested. In MVAs, Ki67-SI (continuous) was associated with LF (P = .08), BF (P = .0445), DIM (P < .0001), CSD (P < .0001), and CD (P = .0094). When categoric variables were used in MVAs, the 3.5% Ki67-Sl cut point was not significant. The 7.1 % cut point was related to BF (P = .09), DM (P = .0008), and CSD (P = .017). Ki67-Sl was the most significant correlate of DIM and CSD. A detailed analysis of the hazard rates for DM in all possible covariate combinations revealed subgroups of patients treated with STAID + RT that did not require LTAD. Conclusion. Ki67-Sl was the most significant determinant of DM and CSD and was also associated with CID. The Ki67-SI should be considered for the stratification of patients in future trials. (C) 2004 by American Society of Clinical Oncology. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. RTOG, Amer Coll Radiol, Dept Biostat, Philadelphia, PA USA. Baylor Sch Med, Dept Pathol, Houston, TX USA. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. Univ Western Ontario, Dept Radiat Oncol, London, ON, Canada. Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Fox Chase Canc Ctr, Dept Radiat Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM A_Pollack@fccc.edu FU NCI NIH HHS [CA-06927] NR 25 TC 87 Z9 89 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2004 VL 22 IS 11 BP 2133 EP 2140 DI 10.1200/JCO.2004.09.150 PG 8 WC Oncology SC Oncology GA 826DG UT WOS:000221808800014 PM 15169799 ER PT J AU Jagsi, R DeLaney, TF Donelan, K Tarbell, NJ AF Jagsi, R DeLaney, TF Donelan, K Tarbell, NJ TI Real-time rationing of scarce resources: The Northeast Proton Therapy Center experience SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DONOR LIVER GRAFTS; HEALTH-CARE; MEDICAL RESOURCES; COST-EFFECTIVENESS; ALLOCATION; TRANSPLANTATION; VIEWS; AGE; PREFERENCES; OREGON AB The telephone line is silent. I have just delivered the news to an anxious mother whom I will never meet. We will not be able to offer her 3- year-old son, who recently underwent resection of a posterior fossa ependymoma, a treatment slot at the Northeast Proton Therapy Center in Boston, MA. Postoperative radiation is the standard of care for her son's disease, and radiating with protons might reduce the late effects of treatment to her young son's brain. Yet in light of the other patients competing for the scarce proton treatment slots, we must recommend that she pursue treatment for her son elsewhere, as we will not have an open slot in time. Because proton therapy is only available at our center and one in California, her son will most likely end up receiving conformal photon therapy, with a higher integral dose to the normal brain. "How can this be?" she asks. "Why can't my son get the treatment we feel would be best? We're in America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jagsi, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM rjagsi@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 59 TC 15 Z9 15 U1 1 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 JUN 1 PY 2004 VL 22 IS 11 BP 2246 EP 2250 DI 10.1200/JCO.2004.10.083 PG 5 WC Oncology SC Oncology GA 826DG UT WOS:000221808800031 PM 15169816 ER PT J AU Mueser, KT Clark, RE Haines, M Drake, RE McHugo, GJ Bond, GR Essock, SM Becker, DR Wolfe, R Swain, K AF Mueser, KT Clark, RE Haines, M Drake, RE McHugo, GJ Bond, GR Essock, SM Becker, DR Wolfe, R Swain, K TI The Hartford study of supported employment for persons with severe mental illness SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID TRANSITIONAL EMPLOYMENT; PSYCHIATRIC DISABILITY; HEALTH-SERVICES; WORK; SCHIZOPHRENIA; PEOPLE; REHABILITATION; OUTCOMES; SCALE; PROGRAMS AB The authors compared 3 approaches to vocational rehabilitation for severe mental illness (SMI): the individual placement and support (IPS) model of supported employment, a psychosocial rehabilitation (PSR) program. and standard services. Two hundred four unemployed clients (46% African American, 30% Latino) with SMI were randomly assigned to IPS, PSR, or standard services and followed for 2 years. Clients in IPS had significantly better employment outcomes than clients in PSR and standard Services, including more competitive work (73.9% vs. 18.2% vs. 27.5%, respectively) and any paid work (73.9% vs. 34.8% vs. 53.6%, respectively). There were few differences in nonvocational outcomes between programs. IPS is a more effective model than PSR or standard brokered vocational services for improving employment outcomes in clients with SMI. C1 New Hampshire Dartmouth Psychiat Res Ctr, Dept Psychiat, Concord, NH 03301 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46205 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Mental Hlth Intervent Res & Clin Ctr, New York, NY USA. RP Mueser, KT (reprint author), New Hampshire Dartmouth Psychiat Res Ctr, Dept Psychiat, Main Bldg,105 Pleasant St, Concord, NH 03301 USA. EM kim.t.mueser@dartmouth.edu FU NIMH NIH HHS [MH00842, MH56147] NR 87 TC 110 Z9 112 U1 12 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2004 VL 72 IS 3 BP 479 EP 490 DI 10.1037/0022-006X.72.3.479 PG 12 WC Psychology, Clinical SC Psychology GA 823PH UT WOS:000221624800011 PM 15279531 ER PT J AU DePaola, DP AF DePaola, DP TI Nurturing a culture of innovation SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material C1 Forsyth Inst, Boston, MA 02115 USA. RP DePaola, DP (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM ddepaola@forsyth.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD JUN PY 2004 VL 83 IS 6 BP 446 EP 447 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 891RJ UT WOS:000226597900002 PM 15153449 ER PT J AU Hirakawa, S Detmar, M AF Hirakawa, S Detmar, M TI New insights into the biology and pathology of the cutaneous lymphatic system SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Review ID GROWTH-FACTOR RECEPTOR-3; TUMOR LYMPHANGIOGENESIS; HEREDITARY LYMPHEDEMA; TRANSCRIPTION FACTOR; ENDOTHELIAL-CELLS; VEGF-C; METASTATIC SPREAD; BREAST-CANCER; GENE-THERAPY; PROMOTES AB The cutaneous lymphatic system plays an important role in the maintenance of tissue fluid homeostasis, in the afferent phase of the immune response, and in the metastatic spread of skin cancers. The recent identification of genes that specifically control, lymphatic development and the growth of lymphatic vessels (lymphangiogenesis), together with the discovery of new lymphatic endothelium-specific markers have now provided new insights into the molecular mechanisms that control lymphatic development and function. These scientific advances have also led to a new understanding of the genetic basis of several hereditary diseases that are associated with Lymphedema, and they have provided surprising evidence that malignant tumors can directly promote lymphangiogenesis and lymphatic metastasis. (C) 2003 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM michael.detmar@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA86410, CA92644, CA69184] NR 47 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD JUN PY 2004 VL 35 IS 1 BP 1 EP 8 DI 10.1016/j.jdermsci.2003.10.006 PG 8 WC Dermatology SC Dermatology GA 834NF UT WOS:000222417100001 PM 15194141 ER PT J AU Lee, DC Lim, HK McKay, WB Priebe, MM Holmes, SA Sherwood, AM AF Lee, DC Lim, HK McKay, WB Priebe, MM Holmes, SA Sherwood, AM TI Toward an objective interpretation of surface EMG patterns: a voluntary response index (VRI) SO JOURNAL OF ELECTROMYOGRAPHY AND KINESIOLOGY LA English DT Article DE voluntary motor control; surface electromyography; spinal cord injury; index ID SPINAL-CORD INJURY; MOTOR CONTROL; HUMAN LOCOMOTION; GAIT ANALYSIS; SPASTICITY; PROFILES; WALKING; NORMALIZATION; STIMULATION; AMBULATION AB Individuals with incomplete spinal cord injuries (SCI) retain varying degrees of voluntary motor control. The complexity of the motor control system and the nature of the recording biophysics have inhibited efforts to develop objective measures of voluntary motor control. This paper proposes the definition and use of a voluntary response index (VRI) calculated from quantitative analysis of surface electromyographic (sEMG) data recorded during defined voluntary movement as a sensitive measure of voluntary motor control in such individuals. The VRI is comprised of two numeric values, one derived from the total muscle activity recorded for the voluntary motor task (magnitude), and the other from the sEMG distribution across the recorded muscles (similarity index (SI)). Calculated as a vector, the distribution of sEMG from the test subject is compared to the average vector calculated from sEMG recordings of the same motor task from 10 neurologically intact subjects in a protocol called brain motor control assessment (BMCA). To evaluate the stability of the VRI, a group of five healthy subjects were individually compared to the prototype, average healthy-subject vectors for all of the maneuvers. To evaluate the sensitivity of this method, the VRI was obtained from two SCI subjects participating in other research studies. One was undergoing supported treadmill ambulation training, and the other a controlled withdrawal of anti-spasticity medications. The supported treadmill training patient's VRI, calculated from pre- and post-training BMCA recordings, reflected the qualitative changes in sEMG patterns and functional improvement of motor control. The VRI of the patient followed by serial BMCA during medication withdrawal also reflected changes in the motor control as a result of changes in anti-spasticity medication. To validate this index for clinical use, serial studies using larger numbers of subjects with compromised motor control should be performed. (C) 2003 Elsevier Ltd. All rights reserved. C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Sherwood, AM (reprint author), Baylor Coll Med, VA Med Ctr, 2002 Holcombe 153, Houston, TX 77030 USA. EM ams@bem.tme.edu OI Sherwood, Arthur/0000-0002-0110-4317 NR 39 TC 29 Z9 29 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1050-6411 J9 J ELECTROMYOGR KINES JI J. Electromyogr. Kinesiol. PD JUN PY 2004 VL 14 IS 3 BP 379 EP 388 DI 10.1016/j.jelekin.2003.10.006 PG 10 WC Neurosciences; Physiology; Rehabilitation; Sport Sciences SC Neurosciences & Neurology; Physiology; Rehabilitation; Sport Sciences GA 818ON UT WOS:000221254500010 PM 15094151 ER PT J AU Beyer, F Doebis, C Busch, A Ritter, T Mhashilkar, A Marasco, WM Laube, H Volk, HD Seifert, M AF Beyer, F Doebis, C Busch, A Ritter, T Mhashilkar, A Marasco, WM Laube, H Volk, HD Seifert, M TI Decline of surface MHC I by adenoviral gene transfer of anti-MHC I intrabodies in human endothelial cells - new perspectives for the generation of universal donor cells for tissue transplantation SO JOURNAL OF GENE MEDICINE LA English DT Article DE intrabodies; MHC I; HUVEC; tissue engineering; adenoviral transduction; immunomodulation ID NATURAL-KILLER-CELL; TUMOR-NECROSIS-FACTOR; CD8(+) T-CELLS; BYPASS GRAFTS; INTRACELLULAR ANTIBODIES; VITRO ENDOTHELIALIZATION; ALLOGRAFT-REJECTION; CLONAL EXPANSION; VASCULAR GRAFTS; MEDIATED LYSIS AB Background The seeding of small-calibre vascular polytetrafluoroethylene (PTFE) grafts with endothelial cells provides an increase in biocompatibility of the graft surface. The harvest and ex vivo culture of autologous endothelial cells is highly delicate. Allogeneic human umbilical vein endothelial cells (HUVEC) could be a potential cell source - however, rejection might occur due to major histocompatibility complex (MHC) I mismatches. Lowering cell surface MHC I expression on endothelial cells by gene transfer of an anti-MHC I intrabody might reduce graft failure. The intrabody consists of a single-chain variable fragment (sFv) of an anti-MHC I antibody, carrying a terminal KDEL sequence to retain the molecule together with the MHC I inside the endoplasmic reticulum. Methods Adenoviral gene transfer was used to express the intrabody in HUVEC. The MHC 1 surface expression was measured 48 h after transduction by flow cytometry. Functional effects of the intrabody expression were analyzed in a calcein release cytotoxicity assay. Results A transduction efficiency of more than 95% with EGFP-adenovirus indicates a sufficient gene transfer into HUVEC. Intrabody-adenovirus-transduced HUVEC show a massive reduction in MHC I surface expression creating almost a complete 'knockout' phenotype. Stimulation with inflammatory cytokines could not overcome this effect. The cell lysis of anti-MHC I intrabody-expressing HUVEC in a cytotoxicity assay is reduced when compared with the level of the MHC mismatched control. Conclusions Our data indicate that HUVEC with reduced levels of MHC I might be used as universal donor cells for the seeding of vascular grafts. Copyright (C) 2004 John Wiley Sorts, Ltd. C1 Humboldt Univ, Inst Med Immunol, D-10117 Berlin, Germany. German Heart Inst, D-13353 Berlin, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Seifert, M (reprint author), Humboldt Univ, Inst Med Immunol, Schumannstr 20-21,Campus Charite Mitte, D-10117 Berlin, Germany. EM martina.seifert@charite.de RI Ritter, Thomas/C-1695-2009; OI Ritter, Thomas/0000-0001-7709-8489 NR 46 TC 19 Z9 21 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JUN PY 2004 VL 6 IS 6 BP 616 EP 623 DI 10.1002/jgm.548 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 832OK UT WOS:000222276600003 PM 15170732 ER PT J AU Burrus, JK Matheson, WD Hong, JS Sorscher, EJ Balkovetz, DF AF Burrus, JK Matheson, WD Hong, JS Sorscher, EJ Balkovetz, DF TI Hepatocyte growth factor stimulates adenoviral-mediated gene transfer across the apical membrane of epithelial cells SO JOURNAL OF GENE MEDICINE LA English DT Article DE cell polarity; tight junction; gene therapy ID ACUTE-RENAL-FAILURE; AIRWAY EPITHELIA; TIGHT JUNCTION; FACTOR ALTERS; POLARITY; RECEPTOR; INFECTION; COXSACKIEVIRUS; EFFICIENCY; VECTORS AB Background The apical surface of polarized epithelial cells is relatively resistant to gene delivery by various agents including adenoviral vectors. Hepatocyte growth factor (HGF) dedifferentiates previously well-polarized Madin-Darby canine kidney (MDCK) cell monolayers by altering cell-surface polarity and inhibiting tight junction function. Methods We used an in vitro model of polarized MDCK cells grown on permeable supports to examine the effects of HGF pretreatment on adenoviral (Ad)-mediated gene delivery through the apical surface of epithelial cell monolayers. Results HGF pretreatment of MDCK cell monolayers for 72 h increased Ad-mediated gene transfer and expression of enhanced green fluorescent protein (EGFP) and luciferase in a dose-dependent fashion. Time-course analysis of HGF-induced stimulation of Ad-mediated gene transfer was seen after 24 h and increased further with pretreatment periods extending to 72 h. HGF pretreatment increased Ad-mediated gene transfer at varying multiplicity of infection (MOI; ranging from 0.2-2000). PCR analysis for adenoviral DNA in control and HGF-pretreated MDCK cells suggested increased entry of viral constructs into HGF-pretreated MDCK cell monolayers. HGF-induced alterations in cell polarity are reversible upon removal of HGF. Conclusions These data demonstrate that HGF pretreatment of MDCK cells increases the sensitivity of the cells to Ad-mediated gene delivery. The mechanism by which this occurs appears to be through increased entry of adenovirus into epithelial cells. These data provide evidence that biological agents that transiently alter epithelial cell polarity and tight junction function can be used to augment Ad-mediated gene delivery into epithelial cells from the apical surface. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Balkovetz, DF (reprint author), Univ Alabama, Dept Med, 1530 3rd Ave S,LHRB 642, Birmingham, AL 35294 USA. EM balkovet@uab.edu FU NIDDK NIH HHS [P30 DK54781] NR 29 TC 5 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JUN PY 2004 VL 6 IS 6 BP 624 EP 630 DI 10.1002/jgm.552 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 832OK UT WOS:000222276600004 PM 15170733 ER PT J AU Swarztrauber, K Vickrey, BG AF Swarztrauber, K Vickrey, BG TI Do neurologists and primary care physicians agree on the extent of specialty involvement of patients referred to neurologists? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE referral and consultation; physician's practice patterns ID FINANCIAL INCENTIVES; PARKINSONS-DISEASE; ISCHEMIC-STROKE; MANAGED-CARE; CONSULTATION; PATTERNS; RATES; OUTCOMES; SUBSPECIALISTS; COORDINATION AB OBJECTIVE: Understanding the roles and responsibilities of physicians who manage mutual patients is important for assuring good patient care. Among physicians expressing a preference to involve a neurologist in the care of a patient, we evaluated agreement between neurologists and primary care physicians for the extent of specialty involvement in the evaluation and management of the patient, and the factors influencing those preferences. DESIGN AND SETTING: A self-administered survey containing 3 clinical scenarios was developed with the assistance of a multispecialty advisory board and mailed to a stratified probability sample of physicians. PARTICIPANTS: Six hundred and eight family physicians, 624 general internists, and 492 neurologists in 9 U.S. states. INTERVENTIONS: For each scenario, those respondents who preferred involvement of a specialist were asked about the preferred extent of that involvement: one-time consultation with and without test/medication ordering, consultation and limited follow-up, or taking over ongoing care of the specialty problem as long as it persists. MAIN RESULTS: Survey response rate was 60%. For all 3 scenarios, neurologists preferred a greater extent of specialty involvement compared to primary care physicians (all P < .05). Other physician and practice characteristic factors, including financial incentives, had lesser or no influence on the extent of specialty involvement preferred. CONCLUSIONS: The disagreement between primary care physicians and specialists regarding the preferred extent of specialist involvement in the care of patients with neurological conditions should raise serious concerns among health care providers, policy makers, and educators about whether mutual patient care is coordinated and appropriate. C1 Portland VA Med Ctr, Dept Neurol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Alzheimers Dis Ctr, Los Angeles, CA 90024 USA. Greater Los Angeles VA HealthCare Syst, Parkinsons Dis Res Educ & Clin Ctr, Los Angeles, CA USA. RP Swarztrauber, K (reprint author), Portland VA Med Ctr, Dept Neurol, P-3-PADRECC,POB 1034, Portland, OR 97207 USA. EM swarztra@ohsu.edu NR 47 TC 18 Z9 18 U1 2 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 JUN PY 2004 VL 19 IS 6 BP 654 EP U34 DI 10.1111/j.1525-1497.2004.30535.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 826TN UT WOS:000221852000006 PM 15209604 ER PT J AU Makino, CL Dodd, RL Chen, J Burns, ME Roca, A Simon, MI Baylor, DA AF Makino, CL Dodd, RL Chen, J Burns, ME Roca, A Simon, MI Baylor, DA TI Recoverin regulates light-dependent phosphodiesterasc activity in retinal rods SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE calcium-binding proteins; knockout mice; light adaptation; photoreceptors; phototransduction ID CYCLIC-GMP PHOSPHODIESTERASE; CALCIUM-BINDING PROTEINS; RHODOPSIN KINASE; OUTER SEGMENTS; S-MODULIN; CGMP-PHOSPHODIESTERASE; SENSITIVITY REGULATION; CYTOPLASMIC CALCIUM; GUANYLATE-CYCLASE; SALAMANDER RODS AB The Ca2+-binding protein recoverin may regulate visual transduction in retinal rods and cones, but its functional role and mechanism of action remain controversial. We compared the photoresponses of rods from control mice and from mice in which the recoverin gene was knocked out. Our analysis indicates that Ca2+-recoverin prolongs the dark-adapted flash response and increases the rod's sensitivity to dim steady light. Knockout rods had faster Ca2+ dynamics, indicating that recoverin is a significant Ca2+ buffer in the outer segment, but incorporation of exogenous buffer did not restore wild-type behavior. We infer that Ca2+-recoverin potentiates light-triggered phosphodiesterase activity, probably by effectively prolonging the catalytic activity of photoexcited rhodopsin. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA. Univ So Calif, Doheny Eye Inst, Beckman Macular Res Ctr, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Makino, CL (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cmakino@meei.harward.edu FU NEI NIH HHS [EY14047, EY05750, EY12703, EY12944, R01 EY012155, R01 EY012703, R01 EY012944, R01 EY014047, R01 EY014047-04]; NIA NIH HHS [AG12288] NR 57 TC 98 Z9 100 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUN PY 2004 VL 123 IS 6 BP 729 EP 741 DI 10.1085/jgp.200308994 PG 13 WC Physiology SC Physiology GA 828QO UT WOS:000221988000009 PM 15173221 ER PT J AU Bartlett, NW Dumoutier, L Renauld, JC Kotenko, SV McVey, CE Lee, HJ Smith, GL AF Bartlett, NW Dumoutier, L Renauld, JC Kotenko, SV McVey, CE Lee, HJ Smith, GL TI A new member of the interleukin 10-related cytokine family encoded by a poxvirus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID DIFFERENTIATION-ASSOCIATED GENE; RECOMBINANT VACCINIA VIRUS; HUMAN-MELANOMA DIFFERENTIATION; INTERFERON-GAMMA; CUTTING EDGE; IMMUNODEFICIENT MICE; SPECIES-SPECIFICITY; ECTROMELIA VIRUS; BINDING-PROTEIN; SUPPRESSOR GENE AB Poxviruses express numerous proteins involved in manipulating the host immune response. Analysis of the primary sequence and predicted structure of the 134R protein of Yaba-like disease virus (Y134R) indicated that it is similar to cellular proteins of the IL-10 family, specifically IL-19, IL-20 and IL-24. A flag-tagged Y134R was expressed from mammalian cells and identified as a secreted, monomeric glycoprotein that stimulated signal transduction from class II cytokine receptors IL-20Ralpha/IL-20Rbeta (IL-20R type1) and IL-22R/IL-20Rbeta (IL-20R type 2). Y134R induced phosphorylation of signal transducers and activators of transcription, their translocation to the nucleus and the induction of reporter gene expression. In contrast, Y134R was unable to induce similar responses from either the IL-22 or IFN-lambda (IL-28A, IL-2813, IL-29) class II cytokine receptors. To examine the role Y134R plays during a poxvirus infection, a vaccinia virus recombinant expressing Y134R was constructed and tested in a murine intranasal infection model. Compared with control viruses, the virus expressing Y134R had a reduced virulence, manifested by reduced weight loss, signs of illness and virus titres in infected organs. These results demonstrate that Y134R is a new viral member of the IL-10-related cytokine family and that its activity in vivo affects virus virulence. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Virol, London W2 1PG, England. Univ Catholique Louvain, Expt Med Unit, LICR, B-1200 Brussels, Belgium. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Smith, GL (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Virol, St Marys Campus,Norfolk Pl, London W2 1PG, England. EM glsmith@imperial.ac.uk RI McVey, Colin/C-2110-2008; OI McVey, Colin/0000-0001-7457-2130; Bartlett, Nathan/0000-0002-2715-5163 NR 75 TC 17 Z9 21 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 2004 VL 85 BP 1401 EP 1412 DI 10.1099/vir.0.79980-0 PN 6 PG 12 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 830IW UT WOS:000222116600007 PM 15166422 ER PT J AU Oslin, DW Thompson, R Kallan, MJ TenHave, T Blow, FC Bastani, R Gould, RL Maxwell, AE Rosansky, J Van Stone, W Jarvik, L AF Oslin, DW Thompson, R Kallan, MJ TenHave, T Blow, FC Bastani, R Gould, RL Maxwell, AE Rosansky, J Van Stone, W Jarvik, L TI Treatment effects from UPBEAT: A randomized trial of care management for behavioral health problems in hospitalized elderly patients SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE depression; hospital; alcohol use; collaborative care ID DEPRESSIVE SYMPTOMS; MEDICAL INPATIENTS; ANXIETY DISORDERS; UNITED-STATES; LATE-LIFE; IDENTIFICATION; INTERVENTION; POPULATIONS; PHYSICIANS; COMMUNITY AB The purpose of this study was to examine the impact of the Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT) Program, an interdisciplinary mental health care management program, on the behavioral health symptoms of elderly veterans. Participants, 60 years and older, included 2637 veterans recruited from medical/surgical units who screened positively for significant depressive or anxiety symptoms and/or at-risk alcohol drinking. Participants were randomized to UPBEAT or to usual care. Primary outcomes were measured at baseline and at 6, 12, and 24 months. Participant nonadherence to the protocol was common and is a major limitation. There were no differences between UPBEAT and usual care patients on symptom or functional outcomes at any follow-up point. Exploratory analyses suggested that among participants with more physical health problems, there were greater improvements in depressive symptoms in those assigned to UPBEAT care. Despite a theoretical and practically sound intervention, participation was low and treatment outcomes, while generally good, appeared unaffected by the addition of the program. C1 Univ Penn, Sect Geriatr Psychiat, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Study Addict, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Ann Arbor VA Healthcare Syst, Ann Arbor, MI USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Cent Off, Washington, DC USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Neuropsychiat Inst, Los Angeles, CA 90024 USA. Univ Hosp Calif Los Angeles, Los Angeles, CA USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriatr Psychiat, Dept Psychiat, 3434 Market St,Room 3002, Philadelphia, PA 19104 USA. EM oslin@mail.med.upenn.edu RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X FU NIMH NIH HHS [1K08 MH 01599-01] NR 30 TC 12 Z9 12 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUN PY 2004 VL 17 IS 2 BP 99 EP 106 DI 10.1177/0891988703262539 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 848NT UT WOS:000223475100008 PM 15157351 ER PT J AU Bardeesy, N Lopez, L Depinho, RA AF Bardeesy, N Lopez, L Depinho, RA TI The role of Lkb1 in pancreatic development and cancer SO JOURNAL OF INTERNAL MEDICINE LA English DT Meeting Abstract CT 9th Workshop on Multiple Endocrine Neoplasia CY JUN 20-22, 2004 CL Bethesda, MD SP NIH C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUN PY 2004 VL 255 IS 6 MA O25 BP 704 EP 705 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 821CH UT WOS:000221436800039 ER EF