FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Buck, T Jansen, CHP Yoganathan, AP Levine, RA Handschumacher, MD AF Buck, T Jansen, CHP Yoganathan, AP Levine, RA Handschumacher, MD TI Hemisphere versus hemiellipse: When is each most accurate for proximal isovelocity calculation of regurgitant flows SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 385A EP 385A DI 10.1016/S0735-1097(97)85379-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601641 ER PT J AU Wilkerson, PW Yoganathan, AP Levine, RA AF Wilkerson, PW Yoganathan, AP Levine, RA TI Quantifying mitral regurgitation using correlated Doppler measurements SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Georgia Inst Technol, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 385A EP 386A DI 10.1016/S0735-1097(97)85380-6 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601642 ER PT J AU Goldberg, LR Dec, GW DiSalvo, TG Philbin, EF AF Goldberg, LR Dec, GW DiSalvo, TG Philbin, EF TI Coronary revascularization is under-utilized in Medicaid patients with acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 392A EP 392A DI 10.1016/S0735-1097(97)85408-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601670 ER PT J AU Laham, RJ Sellke, FW Edelman, ER Pearlman, JD Simons, M AF Laham, RJ Sellke, FW Edelman, ER Pearlman, JD Simons, M TI Local perivascular basic fibroblast growth factor (bFGF) treatment in patients with ischemic heart disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 394A EP 394A DI 10.1016/S0735-1097(97)85415-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601677 ER PT J AU Schunkert, H Harrell, L Palacios, IF AF Schunkert, H Harrell, L Palacios, IF TI Small coronary vessels: A suitable target for percutaneous revascularization in the new device era? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 416A EP 416A DI 10.1016/S0735-1097(97)85508-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601770 ER PT J AU Khankirawatana, B Lu, P Handschumacher, MD Levine, RA Jiang, L AF Khankirawatana, B Lu, P Handschumacher, MD Levine, RA Jiang, L TI Left atrial volume quantitation using a simplified three-dimensional echocardiographic reconstruction from three apical views SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 436A EP 436A DI 10.1016/S0735-1097(97)85597-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601861 ER PT J AU Khankirawatana, B Lu, P Handschumacher, MD Levine, RA Jiang, L AF Khankirawatana, B Lu, P Handschumacher, MD Levine, RA Jiang, L TI Accuracy of quantitating left ventricular volume by reconstruction of three apical views: Comparison with conventional three-dimensional echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 436A EP 436A DI 10.1016/S0735-1097(97)85597-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601859 ER PT J AU Scherrer-Crosbie, M Steudel, W Hunziker, PR Liel-Cohen, N Zapol, WM Picard, MH AF Scherrer-Crosbie, M Steudel, W Hunziker, PR Liel-Cohen, N Zapol, WM Picard, MH TI Noninvasive assessment of myocardial perfusion in mice: A contrast echocardiography study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 438A EP 439A DI 10.1016/S0735-1097(97)87904-1 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601871 ER PT J AU Zaroff, JG Rordorf, GA Titus, JS Nowak, NJ Torchiana, DF Aretz, TH Picard, MH AF Zaroff, JG Rordorf, GA Titus, JS Nowak, NJ Torchiana, DF Aretz, TH Picard, MH TI Regional myocardial perfusion in experimental subarachnoid hemorrhage SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 439A EP 440A DI 10.1016/S0735-1097(97)87908-9 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920601875 ER PT J AU Padial, LR Oliver, A Levine, RA AF Padial, LR Oliver, A Levine, RA TI Aortic flow reversal: Does its extent distinguish the severity of aortic regurgitation? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Virgen Salud, Toledo, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 475A EP 475A DI 10.1016/S0735-1097(97)88069-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602036 ER PT J AU Hunziker, PR Liel-Cohen, N Scherrer-Crosbie, M Buck, T Levine, RA Picard, MH AF Hunziker, PR Liel-Cohen, N Scherrer-Crosbie, M Buck, T Levine, RA Picard, MH TI Determination of myocardial fiber architecture in man by high-resolution echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 478A EP 478A DI 10.1016/S0735-1097(97)88079-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602046 ER PT J AU Gibson, M Sparano, A Ryan, K Moynihan, J Kelley, M Rizzo, M Marble, S McCabe, C Dodge, T Cannon, CP AF Gibson, M Sparano, A Ryan, K Moynihan, J Kelley, M Rizzo, M Marble, S McCabe, C Dodge, T Cannon, CP TI Flow distal and not proximal to the lesion is a correlate of clinical outcomes after thrombolysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI 10B Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 492A EP 492A DI 10.1016/S0735-1097(97)88141-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602108 ER PT J AU Grimes, RY Yoganathan, AP Levine, RA AF Grimes, RY Yoganathan, AP Levine, RA TI Computer simulations of the change in mitral regurgitant volume after repair of concomitant aortic stenosis: Significance of pressure dependent mitral effective orifice area SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 503A EP 503A DI 10.1016/S0735-1097(97)88190-9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602157 ER PT J AU Otsuji, Y Handschumacher, MD Liel-Cohen, N Tanabe, H Guerrero, JL Nicholls, LA Vlahakes, GJ Levine, RA AF Otsuji, Y Handschumacher, MD Liel-Cohen, N Tanabe, H Guerrero, JL Nicholls, LA Vlahakes, GJ Levine, RA TI Mechanism of ischemic mitral regurgitation with ventricular remodeling after myocardial infarction: Demonstration of leaflet tethering by three-dimensional echocardiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 503A EP 504A DI 10.1016/S0735-1097(97)88193-4 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602160 ER PT J AU Fry, SJ Palacios, IF Akins, CW Levine, RA AF Fry, SJ Palacios, IF Akins, CW Levine, RA TI Respirophasic two-dimensional echocardiographic signs are highly sensitive and specific for pericardial constriction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 SU A BP 515A EP 515A DI 10.1016/S0735-1097(97)88244-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YW305 UT WOS:000071920602211 ER PT J AU Rattner, DW AF Rattner, DW TI Gastrointestinal conditions SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 67 TC 1 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD FEB PY 1998 VL 186 IS 2 BP 150 EP 161 DI 10.1016/S1072-7515(98)00003-9 PG 12 WC Surgery SC Surgery GA YX515 UT WOS:000072048300012 PM 9482618 ER PT J AU Kaufer, DI Cummings, JL Christine, D Bray, T Castellon, S Masterman, D MacMillan, A Ketchel, P DeKosky, ST AF Kaufer, DI Cummings, JL Christine, D Bray, T Castellon, S Masterman, D MacMillan, A Ketchel, P DeKosky, ST TI Assessing the impact of neuropsychiatric symptoms in Alzheimer's disease: The Neuropsychiatric Inventory caregiver distress scale SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the American-Neuropsychiatric-Association CY FEB 02-04, 1997 CL ORLANDO, FLORIDA SP Amer Neuropsychiat Assoc ID NURSING-HOME PLACEMENT; BEHAVIORAL SYMPTOMS; PSYCHIATRIC-SYMPTOMS; RATING-SCALE; DEMENTIA; PSYCHOPATHOLOGY; TROUBLESOME; DIAGNOSIS; DELUSIONS; TACRINE AB OBJECTIVES: To develop an adjunct scale to the Neuropsychiatric Inventory (NPI) for assessing the impact of neuropsy chiatric symptoms in Alzheimer's disease (AD) patients on caregiver distress, DESIGN: Cross-sectional descriptive and correlational study. SETTING: University out-patient memory disorders clinics. PARTICIPANTS: Eighty-five AD subjects and their caregivers (54 spouses, 31 children). MEASUREMENTS: The NPI and NPI Caregiver Distress Scale (NPI-D) were used to assess neuropsychiatric symptoms in AD patients and related caregiver distress, respectively. Criterion validity of the NPI-D tvas examined(N = 69) by comparison with an abridged version of the Relatives' Stress Scale (RSS'), a general measure of sari giver stress, using item clusters that had previously been correlated to behavioral disturbances in demented patients. Test-retest in = 20) and inter-rater reliability (n = 16) of the NPI-D were also assessed. RESULTS: Test-retest and interrater reliability of the NPT-D were both adequate, Overall, caregiver NPI-D distress ratings were correlated significantly with the RSS' (r = .60, P < .001), RSS' ratings correlated strongly with NPI scores (r .64, P < .001), even after controlling for degree of cognitive impairment based on the Mini-Mental State Exam (MMSE) score (r = .61). MMSE scores showed a moderate correlation to RSS' ratings (-.30, P = .02), but this association was markedly attenuated when controlling for the degree of neuropsychiatric disturbance based on the NPI score (r = -.14). NPI-D ratings for 9 of 10 NPI symptom domains correlated most strongly with either NPI symptom severity or total (frequency X severity) scores. Agitation, dysphoria, irritability, delusions, and apathy were the symptoms most often reported to be severely distressing to caregivers. CONCLUSIONS: The NPI-D provides a reliable and valid measure of subjective caregiver distress in relation to neuropsychiatric symptoms measured by the NPI. Neuropsychiatric alterations are more strongly associated than cognitive symptoms to caregiver distress. The NPI-D may be useful in both clinical and research settings for assessing the contribution to caregiver distress of neuropsychiatric symptoms in AD patients. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Behav Neurosci Sect, Psychiat Serv, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Nursing Serv, Los Angeles, CA USA. RP Kaufer, DI (reprint author), 4 West,MUH,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NIA NIH HHS [AG10123, AG10533] NR 42 TC 265 Z9 276 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 1998 VL 46 IS 2 BP 210 EP 215 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA YW198 UT WOS:000071908300015 PM 9475452 ER PT J AU Breton, S Brown, D AF Breton, S Brown, D TI Cold-induced microtubule disruption and relocalization of membrane proteins in kidney epithelial cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NA+-K+-ATPASE; ANTIDIURETIC-HORMONE; HEYMANN NEPHRITIS; WATER CHANNEL; POLARITY; ANTIGEN; TUBULE; GLYCOPROTEIN; VASOPRESSIN; EXPRESSION AB Cold preservation of kidneys is commonly used in human transplantation and in vitro studies. However, although disruption of the cytoskeleton by cold has been demonstrated in cultured cells, the effect of cold treatment on intact kidney is poorly understood. In this study, specific antibodies were used to examine the effect of hypothermia on the cytoskeletal network and the trafficking of some membrane proteins in the urinary tubule. Rat kidneys were cut into thin slices (approximately 0.5 mm) that were divided into several groups: (I) some were immediately fixed in paraformaldehyde, sodium periodate, and lysine (PLP); (2) some were stored at 4 degrees C for 15 min or 4 h before being fixed in cold PLP; or (3) after 4 h cold treatment, some slices were rewarmed to 37 degrees C for 15, 30, and 60 min in a physiologic solution, pH 7.4, and were then fixed in warm PLP. Immunofluorescence staining revealed an almost complete disruption of the microtubule network in proximal tubules after 15 min cold treatment, whereas microtubules in other segments were affected after 4 h. A partial recovery of the microtubule network was observed after 60 min rewarming. In contrast, actin filaments seemed to be resistant to cold treatment. gp330, aquaporin-2, H(+)ATPase, and the AE1 anion exchanger were all relocated into numerous vesicles that were distributed throughout the cytoplasm after hypothermia followed by rewarming, whereas Na-K-ATPase retained its basolateral localization. The vasopressin stimulated insertion of aquaporin-2 water channels into the apical membrane was inhibited during the initial rewarming period after cold exposure. Thus, cold preservation of tissues might impair, at least transiently, the polarized membrane expression and function of some transport proteins in renal epithelial cells. C1 Massachusetts Gen Hosp E, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St,8th Floor, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 42956, DK38452] NR 38 TC 70 Z9 73 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1998 VL 9 IS 2 BP 155 EP 166 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA YU525 UT WOS:000071726600001 PM 9527391 ER PT J AU Himmelfarb, J Rubin, NT Chandran, P Parker, RA Wingard, RL Hakim, R AF Himmelfarb, J Rubin, NT Chandran, P Parker, RA Wingard, RL Hakim, R TI A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CRITICALLY-ILL PATIENTS; ACUTE TUBULAR-NECROSIS; MEDICAL INTENSIVE-CARE; RISK-FACTORS; HEMODIALYSIS; PREDICTION; PROGNOSIS; MORTALITY; RECOVERY; SURVIVAL AB The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis. C1 Maine Med Ctr, Div Nephrol, Portland, ME 04102 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Iowa Methodist Med Ctr, Des Moines, IA USA. Beth Israel Med Ctr, Boston, MA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Himmelfarb, J (reprint author), Maine Med Ctr, Div Nephrol, 22 Bramhall St, Portland, ME 04102 USA. FU NHLBI NIH HHS [R01-HL36015-05] NR 47 TC 110 Z9 113 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1998 VL 9 IS 2 BP 257 EP 266 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA YU525 UT WOS:000071726600012 PM 9527402 ER PT J AU Bromley, B Lieberman, E Shipp, TD Richardson, M Benacerraf, BR AF Bromley, B Lieberman, E Shipp, TD Richardson, M Benacerraf, BR TI Significance of an echogenic intracardiac focus in fetuses at high and low risk for aneuploidy SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE echogenic intracardiac focus; aneuploidy ID FETAL HEART; BENIGN AB Our objective was to evaluate the significance of an echogenic intracardiac focus in a mixed population of fetuses at high and low risk for aneuploidy. Over a 1 year period, we prospectively identified all fetuses with an echogenic intracardiac focus seen during prenatal sonography. A detailed structural evaluation was performed on each fetus as permitted by gestational age. The location and number of foci were tabulated prospectively, as were associated abnormalities. Follow-up was obtained by review of the medical record. Of the 290 fetuses who had an echogenic intracardiac focus, 14 of them were aneuploid (4.8%). Of the 290 mothers, 125 women were aged 35 years or older and 165 women were younger than 35 years old. Among the 125 fetuses born to women 35 years or older, eight were aneuploid fetuses (6.4%), while among the 165 fetuses of younger mothers, six were aneuploid fetuses (3.6%) (rate ratio = 1.8; 95% confidence interval [extremes] = 0.6, 4.9). Only one of the 14 aneuploid fetuses had an echogenic intracardiac focus as the only sonographic finding, and this occurred in a woman aged 41 years. The majority of the echogenic intracardiac foci (87.6%) were located in the left ventricle, while 4.8% of the foci were right-sided and 7.6% were bilateral. Among the 14 aneuploid fetuses, 14% had bilateral echogenic intracardiac foci and 7% had right-sided foci. Among the euploid fetuses, 7.3% had bilateral echogenic intracardiac foci and 4.7% had right-sided foci. In conclusion, we have shown that the presence of an echogenic intracardiac focus does raise the risk that the fetus has a chromosomal abnormality, most commonly Down syndrome, although all but one aneuploid fetus in our study had other sonographic findings. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 11 TC 70 Z9 72 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD FEB PY 1998 VL 17 IS 2 BP 127 EP 131 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA YU773 UT WOS:000071752700009 PM 9527573 ER PT J AU Stampfer, DS Carpinito, GA Rodriguez-Villanueva, J Willsey, LW Dinney, CP Grossman, HB Fritsche, HA McDougal, WS AF Stampfer, DS Carpinito, GA Rodriguez-Villanueva, J Willsey, LW Dinney, CP Grossman, HB Fritsche, HA McDougal, WS TI Evaluation of NMP22 in the detection of transitional cell carcinoma of the bladder SO JOURNAL OF UROLOGY LA English DT Article DE bladder; carcinoma, transitional cell; bladder neoplasms; nuclear matrix; tumor markers, biological ID URINARY-TRACT; CANCER; MARKER; RECURRENCE AB Purpose: Urinary nuclear matrix protein (NMP22) was evaluated for detection of new and recurrent bladder tumors in patients with a history of transitional cell carcinoma. Our objective was to determine sensitivity and specificity of this marker for tumors of various stages and grades, as well as its use as an adjunct to or substitute for urinary cytology. Materials and Methods: A total of 231 patients with a history of transitional cell carcinoma provided 288 voided urine samples before cystoscopic examination at 1 of 3 institutions (53 patients were reevaluated at least once). Urine samples were assayed for NMP22 using the NMP22 Test Kit.dagger Select patients underwent biopsy with appropriate additional therapy. Voided urinary cytology was obtained in 200 cases. End points for determination of the absence and presence of tumor were negative cystoscopy and positive biopsy, respectively. A receiver operating characteristics curve was constructed to determine the optimal NMP22 threshold for detection of transitional cell carcinoma. For positive biopsies NMP22 values were also correlated with tumor stage and grade. Comparison to cytology was limited to patients with complete data. Results: There were 208 negative cystoscopies (158 with cytology) and 66 positive cystoscopies with biopsy (42 with cytology). Of the cases 14 were eliminated from statistical analysis due to incomplete data. Receiver operating characteristics curve interpretation determined that 6.4 units per mi. was an optimal reference value for detection of transitional cell carcinoma in this patient group. Sensitivity and specificity for all pathological groupings was 68 and 80%, respectively. When compared to cytology the sensitivities of NMP22 and cytology were 67 versus 31 or 40% (depending on the definition of positive cytology). Conclusions: NMP22 values represented significant improvement over urinary cytology for detection of transitional cell carcinoma. The sensitivity of NMP22 for detection of transitional cell carcinoma in bladder cancer patients was as much as twice that of cytology when a reference value of 6.4 units per mi. was used. NMP22 analysis was less costly than cytology and operator independent. While NMP22 has previously been shown to be a strong predictor of recurrence after tumor resection, it is an effective and sensitive screening test for detecting tumors in patients with transitional cell carcinoma. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Boston Univ, Med Ctr, Dept Urol, Boston, MA 02215 USA. Univ Texas, Md Anderson Canc Ctr, Dept Lab Sci, Houston, TX USA. Univ Texas, Md Anderson Canc Ctr, Dept Urol, Houston, TX USA. RP Stampfer, DS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 14 TC 123 Z9 130 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1998 VL 159 IS 2 BP 394 EP 398 DI 10.1016/S0022-5347(01)63930-2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA YQ660 UT WOS:000071410500016 PM 9649246 ER PT J AU McDougal, WS AF McDougal, WS TI Burns to the genitalia and the perineum - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1998 VL 159 IS 2 BP 419 EP 419 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA YQ660 UT WOS:000071410500024 ER PT J AU Planz, B Brunner, K Kalem, T Schlick, RW Kind, M AF Planz, B Brunner, K Kalem, T Schlick, RW Kind, M TI Primary leiomyosarcoma of the epididymis and late recurrence on the penis SO JOURNAL OF UROLOGY LA English DT Article DE leiomyosarcoma; epididymis; penis AB The occurrence of leiomyosarcoma is low with an incidence of 0.05 to 0.1%. Testicular leiomyosarcoma is rare and the incidence of paratesticular leiomyosarcoma is even more uncommon. Of the cases of paratesticular leiomyosarcoma 90% are located in the spermatic cord.(1) To our knowledge this is only the fifteenth case of leiomyosarcoma of the epididymis reported in the literature. C1 Teaching Hosp, Dept Urol, Fulda, Germany. Teaching Hosp, Dept Pathol, Fulda, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Planz, B (reprint author), Teaching Hosp, Dept Urol, Fulda, Germany. NR 3 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1998 VL 159 IS 2 BP 508 EP 508 DI 10.1016/S0022-5347(01)63966-1 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA YQ660 UT WOS:000071410500052 PM 9649277 ER PT J AU Tuffereau, C Benejean, J Alfonso, AMR Flamand, A Fishman, MC AF Tuffereau, C Benejean, J Alfonso, AMR Flamand, A Fishman, MC TI Neuronal cell surface molecules mediate specific binding to rabies virus glycoprotein expressed by a recombinant baculovirus on the surfaces of lepidopteran cells SO JOURNAL OF VIROLOGY LA English DT Article ID ACETYLCHOLINE-RECEPTOR; MEASLES-VIRUS; RHINOVIRUS RECEPTOR; SYNAPSE FORMATION; AMINOPEPTIDASE-N; DOWN-REGULATION; ADULT MICE; CVS STRAIN; CER CELLS; MEMBRANE AB The existence of specific rabies virus (RV) glycoprotein (G) binding sites on the surfaces of neuroblastoma cells is demonstrated. Spodoptera frugiperda (Sf2l) cells expressing G of the RV strain CVS (Gcvs-Sf21 cells) bind specifically to neuroblastoma cells of different species but not to any other cell type (fibroblast, myoblast, epithelial, or glioma). Attachment to mouse neuroblastoma NG108-15 cells is abolished by previous treatment of Gcvs-Sf21 cells with anti-G antibody. Substitutions for lysine at position 330 and for arginine at position 333 in RV G greatly reduce interaction between Gcvs-Sf2l cells and NG108-15 cells. These data are consistent with in vivo results: an avirulent RV mutant bearing the same double mutation is not able to infect sensory neurons or motoneurons (P. Coulon, J. P. Ternaux, A. Flamand, and C. Tuffereau, J. Virol. 72:273-278, 1998) after intramuscular inoculation into a mouse. Furthermore, infection of NG108-15 cells by RV but not by vesicular stomatitis virus leads to a reduction of the number of binding sites at the neuronal-cell surface. Our data strongly suggest that these specific attachment sites on neuroblastoma cells represent a neuronal receptor(s) used by RV to infect certain types of neurons in vivo. C1 CNRS, Lab Genet Virus, F-91198 Gif Sur Yvette, France. Massachusetts Gen Hosp, CVRC, Dev Biol Lab, Charlestown, MA 02129 USA. RP Tuffereau, C (reprint author), CNRS, Lab Genet Virus, Bat 14C, F-91198 Gif Sur Yvette, France. NR 63 TC 40 Z9 42 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1085 EP 1091 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200024 PM 9445003 ER PT J AU Farzan, M Choe, H Vaca, L Martin, K Sun, Y Desjardins, E Ruffing, N Wu, LJ Wyatt, R Gerard, N Gerard, C Sodroski, J AF Farzan, M Choe, H Vaca, L Martin, K Sun, Y Desjardins, E Ruffing, N Wu, LJ Wyatt, R Gerard, N Gerard, C Sodroski, J TI A tyrosine-rich region in the N terminus of CCR5 is important for human immunodeficiency virus type 1 entry and mediates an association between gp120 and CCR5 SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOTROPIC RETROVIRUS; ENVELOPE GLYCOPROTEIN; HIV-1 INFECTION; RECEPTOR; AIDS; BINDING; COFACTOR; GENE; COMPLEMENTATION; IDENTIFICATION AB Human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter target cells. The chemokine receptor CCR5 is used by the macrophage-tropic strains of HIV-1 that predominate during the asymptomatic stages of infection. Here we identify a small tyrosine-rich region of CCR5 proximal to the N-terminal cysteine that is critical for entry of macrophage-tropic and dual-tropic variants of HIV-1. HIV-1 infection of cells expressing CCR5 mutants with changes in this region was substantially reduced compared with the infection of cells bearing wild-type CCR5. Simian immunodeficiency virus (SIV(mac)239) entry was also ablated on a subset of these mutants hut enhanced on others. These differences in virus entry were correlated with the relative ability of soluble, monomeric HIV-1 and SIV(mac)239 gp120 glycoproteins to bind the CCR5 mutants. These results identify a region of CCR5 that is necessary for the physical association of the gp120 envelope glycoprotein with CCR5 and for HIV-1 infection. C1 Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Div Human Retrovirol, Boston, MA 02115 USA. Beth Israel Hosp, Dept Med, Boston, MA 02215 USA. Beth Israel Hosp, Dept Pediat, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Leukosite Inc, Cambridge, MA 02142 USA. RP Sodroski, J (reprint author), Childrens Hosp, Ina Sue Perlmutter Lab, 300 Longwood Ave, Boston, MA 02115 USA. OI Vaca, Luis/0000-0003-2266-4847 FU NIAID NIH HHS [AI 41581] NR 41 TC 170 Z9 175 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1160 EP 1164 PG 5 WC Virology SC Virology GA YQ942 UT WOS:000071440200034 PM 9445013 ER PT J AU Desrosiers, RC Lifson, JD Gibbs, JS Czajak, SC Howe, AYM Arthur, LO Johnson, RP AF Desrosiers, RC Lifson, JD Gibbs, JS Czajak, SC Howe, AYM Arthur, LO Johnson, RP TI Identification of highly attenuated mutants of simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID UPSTREAM U3 SEQUENCES; RHESUS MACAQUES; NEF GENE; T-CELL; INFECTION; SIV; CHALLENGE; MONKEYS; VACCINE; ABSENCE AB Deletion mutants of the pathogenic clone of simian immunodeficiency virus isolate 239 (SIVmac239) were derived that are missing nef, vpr, and upstream sequences (US) in the U3 region of the LTR (SIVmac239 Delta 3), nef, vpx, and US (SIVmac239 Delta 3x), and nef, vpr, vpx, and US (SIVmac239 Delta 4). These multiply deleted derivatives replicated well in the continuously growing CEMx174 cell line and were infectious for rhesus monkeys. However, on the basis of virus load measurements, strength of antibody responses, and lack of disease progression, these mutants were highly attenuated. Measurements of cell-associated viral load agreed well with assays of plasma viral RNA load and with the strengths of the antibody responses; thus, these measurements likely reflected the extent of viral replication in vivo. A derivative of SIVmac239 lacking vif sequences (SIVmac239 Delta vif) could be consistently grown only in a vif-complementing cell line. This Delta vif virus appeared to be very weakly infectious for rhesus monkeys on the basis of sensitive antibody tests only. The weak antibody responses elicited by SIVmac239 Delta vif were apparently in response to low levels of replicating virus since they were not elicited by heat-inactivated virus and the anti-SIV antibody responses persisted for greater than 1 year. These results, and the results of previous studies, allow a rank ordering of the relative virulence of nine mutant strains of SIVmac according to the following order: Delta vpr > Delta vpx > Delta vpr Delta vpx congruent to Delta nef > Delta 3 > Delta 3x greater than or equal to Delta 4 > Delta vif > Delta 5. The results also demonstrate that almost any desired level of attenuation can be achieved, ranging from still pathogenic in a significant proportion of animals (Delta vpr and Delta vpx) to not detectably infectious (Delta 5), simply by varying the number and location of deletions in these five loci. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Desrosiers, RC (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, 1 Pine Hill Dr,Box 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR 00168]; NIAID NIH HHS [AI 35365, AI 25328, P01 AI035365, R01 AI025328, R37 AI025328, U01 AI035365] NR 36 TC 194 Z9 195 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1431 EP 1437 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200066 PM 9445045 ER PT J AU Andre, S Seed, B Eberle, J Schraut, W Bultmann, A Haas, J AF Andre, S Seed, B Eberle, J Schraut, W Bultmann, A Haas, J TI Increased immune response elicited by DNA vaccination with a synthetic gp120 sequence with optimized codon usage SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL MESSENGER-RNA; GENE-EXPRESSION; PLASMID DNA; IN-VIVO; ENVELOPE GLYCOPROTEIN; PROTECTIVE IMMUNITY; NONHUMAN-PRIMATES; INFLUENZA-VIRUS; NUCLEAR EXPORT AB DNA vaccination elicits humoral and cellular immune responses and has been shown to confer protection against several viral, bacterial, and parasitic pathogens. Here we report that optimized codon usage of an injected DNA sequence considerably increases both humoral and cellular immune responses, We recently generated a synthetic human immunodeficiency virus type 1 gp120 sequence in which most wild-type codons were replated with codons from highly expressed human genes (syngp120). In vitro expression of syngp120 is considerably increased in comparison to that of the respective wild-type sequence, In BALB/c mice, DNA immunization with syngp120 resulted in significantly increased antibody titers and cytotoxic T-lymphocyte reactivity, suggesting a direct correlation between expression levels and the immune response. Moreover, syngp120 is characterized by rev-independent expression and a low risk of recombination with viral sequences. Thus, synthetic genes with optimized codon usage represent a novel strategy to increase the efficacy and safety of DNA vaccination. C1 Univ Munich, Genzentrum, Max Von Pettenkofer Inst, D-81377 Munich, Germany. Univ Munich, Inst Immunol, D-80336 Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. RP Haas, J (reprint author), Univ Munich, Genzentrum, Max Von Pettenkofer Inst, Feodor Lynen Str 25, D-81377 Munich, Germany. EM haas@lmb.uni-muenchen.de NR 73 TC 240 Z9 253 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1497 EP 1503 PG 7 WC Virology SC Virology GA YQ942 UT WOS:000071440200074 PM 9445053 ER PT J AU Connor, RI Korber, BTM Graham, BS Hahn, BH Ho, DD Walker, BD Neumann, AU Vermund, SH Mestecky, J Jackson, S Fenamore, E Cao, Y Gao, F Kalams, S Kunstman, KJ McDonald, D McWilliams, N Trkola, A Moore, JP Wolinsky, SM AF Connor, RI Korber, BTM Graham, BS Hahn, BH Ho, DD Walker, BD Neumann, AU Vermund, SH Mestecky, J Jackson, S Fenamore, E Cao, Y Gao, F Kalams, S Kunstman, KJ McDonald, D McWilliams, N Trkola, A Moore, JP Wolinsky, SM TI Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN GP120; INCREASED REPLICATIVE CAPACITY; BLOOD MONONUCLEAR-CELLS; CANDIDATE AIDS VACCINES; PRIMARY HIV-1 INFECTION; PERIPHERAL-BLOOD; DISEASE PROGRESSION; IMMUNE-RESPONSES; NEUTRALIZATION SEROTYPES AB We have studied 18 participants in phase I/II clinical trials of recombinant gp120 (rgp120) subunit vaccines (MN and SF-2) who became infected with human immunodeficiency virus type 1 (HIV-1) during the course of the trials. Of the 18 individuals, 2 had received a placebo vaccine, 9 had been immunized with MN rgp120, and seven had been immunized with SF-2 rgp120, Thirteen of the 18 infected vaccinees had received three or four immunizations prior to becoming infected, Of these, two were placebo recipients, six had received MN rgp120, and five had received SF-2 rgp120, Only 1 of the 11 rgp120 recipients who had multiple immunizations failed to develop a strong immunoglobulin G antibody response to the immunogen, However, the antibody response to rgp120 was transient, typically having a half-life of 40 to 60 days, No significant neutralizing activity against the infecting strain was detected in any of the infected individuals at any time prior to infection. Antibody titers in subjects infected despite vaccination and in noninfected subjects were not significantly different, Envelope-specific cytotoxic T-lymphocyte responses measured after infection were infrequent and weak in the nine vaccinees who were tested. HIV-1 was isolated successfully from all 18 individuals. Sixteen of these strains had a non-syncytium-inducing (NSI) phenotype, while two had a syncytium-inducing (SI) phenotype. NSI strains used the CCR5 coreceptor to enter CD4(+) cells, while an SI strain from one of the vaccinees also used CXCR4, Viruses isolated from the blood of rgp120 vaccinees were indistinguishable from viruses isolated front control individuals in terms of their inherent sensitivity to neutralization by specific monoclonal antibodies and their replication rates in vitro. Furthermore, genetic sequencing of the env genes of strains infecting the vaccinees did not reveal any features that clearly distinguished these viruses from contemporary clade B viruses circulating in the United States. Thus. despite rigorous genetic analyses, using various breakdowns of the data sets, we could find no evidence that rgp120 vaccination exerted selection pressure on the infecting HIV-1 strains, The viral burdens in the infected rgp120 vaccine recipients were also determined, and they were found to be not significantly different from those in cohorts of placebo-vaccinated and nonvaccinated individuals. In summary, we conclude that vaccination with rgp120 has had, to date, no obvious beneficial or adverse effects on the individuals we have studied. C1 Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Univ Calif Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wolinsky, SM (reprint author), Northwestern Univ, Sch Med, Dept Med, Tarry Bldg,Room 3-735,303 E Chicago Ave, Chicago, IL 60611 USA. EM s-wolinsky@nwu.edu RI Wolinsky, Steven/B-2893-2012; Trkola, Alexandra/K-2115-2012; OI Wolinsky, Steven/0000-0002-9625-6697; Trkola, Alexandra/0000-0003-1013-876X; Korber, Bette/0000-0002-2026-5757; Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [AI45218] NR 158 TC 188 Z9 192 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1552 EP 1576 PG 25 WC Virology SC Virology GA YQ942 UT WOS:000071440200080 PM 9445059 ER PT J AU Parolin, C Borsetti, A Choe, HY Farzan, M Kolchinsky, P Heesen, M Ma, Q Gerard, C Palu, G Dorf, ME Springer, T Sodroski, J AF Parolin, C Borsetti, A Choe, HY Farzan, M Kolchinsky, P Heesen, M Ma, Q Gerard, C Palu, G Dorf, ME Springer, T Sodroski, J TI Use of murine CXCR-4 as a second receptor by some T-cell-tropic human immunodeficiency viruses SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; MOLECULAR-CLONING; HIV-1 ENTRY; PRODUCTIVE INFECTION; HTLV-III; MONONUCLEAR PHAGOCYTES; MACROPHAGE TROPISM; AIDS PATIENTS; TYPE-1; GENE AB The human CXCR-4 molecule serves as a second receptor for primary, T-cell-tropic, and laboratory-adapted human immunodeficiency virus type 1 (HIV-1) isolates. Here we show that murine CXCR-4 can support the entry of some of these HIV-1 isolates. Differences between mouse and human CXCR-4 in the ability to function as an HIV-1 receptor are determined by sequences in the second extracellular loop of the CXCR-4 protein. C1 Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Beth Israel Hosp, Dept Med, Boston, MA 02215 USA. Beth Israel Hosp, Dept Pediat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Padua, Inst Microbiol, I-35121 Padua, Italy. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, JFB 824,44 Binney St, Boston, MA 02115 USA. RI borsetti, alessandra/K-4103-2016 FU NCI NIH HHS [CA 06516, P30 CA006516]; NHLBI NIH HHS [R01 HL051366]; NIAID NIH HHS [AI 24755, AI 28691, P30 AI028691, R37 AI024755] NR 64 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1998 VL 72 IS 2 BP 1652 EP 1656 PG 5 WC Virology SC Virology GA YQ942 UT WOS:000071440200093 PM 9445072 ER PT J AU Donovan, JM Syngal, S AF Donovan, JM Syngal, S TI Colorectal cancer in women: An underappreciated but preventable risk SO JOURNAL OF WOMENS HEALTH LA English DT Review ID SCREENING FLEXIBLE SIGMOIDOSCOPY; FECAL OCCULT BLOOD; UNITED-STATES; COLON-CANCER; MORTALITY; POLYPECTOMY; ENDOSCOPY; KNOWLEDGE; ATTITUDES; ADHERENCE AB Colorectal cancer is the third most common non-skin malignancy in women, after breast and lung cancer. Although approximately 40% of the 65,000 women diagnosed each year eventually die of the disease, colon cancer is highly curable when diagnosed at an early stage. Moreover, because the majority of colon cancers arise in previously benign colonic polyps, there is a substantial period, up to several years, in which removal of polyps can reduce the risk of colon cancer. Recently, the United States Preventive Task Force recommended universal screening for colon cancer after age 50. Strong evidence from randomized controlled trials and case-control studies supports use of annual testing for occult blood in stool and flexible sigmoidoscopy every 5-7 years. Although the risk of colon cancer is similar in men and women, women frequently have the perception that colorectal cancer is a man's disease. Partially in consequence, women are less likely than men to undergo screening sigmoidoscopy. Further barriers include primary care providers' lack of awareness of updated guidelines and patients' lack of compliance with multiple screening tests and their fear of discomfort. Because the risk of colorectal cancer can be reduced by up to 75% in those who undergo screening and subsequent surveillance to remove further polyps, it is crucial that women be targeted to undergo screening tests for colorectal cancer. C1 Brockton W Roxbury Vet Affairs Med Ctr, Dept Med, Boston, MA 02132 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Donovan, JM (reprint author), Brockton W Roxbury Vet Affairs Med Ctr, Dept Med, 1400 VFW Pkwy, Boston, MA 02132 USA. NR 26 TC 24 Z9 24 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD FEB PY 1998 VL 7 IS 1 BP 45 EP 48 DI 10.1089/jwh.1998.7.45 PG 4 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 YZ473 UT WOS:000072257600014 PM 9511131 ER PT J AU Wang, LS Lei, CL Zhang, SL Roberts, KD Tang, SS Ingelfinger, JR Chan, JSD AF Wang, LS Lei, CL Zhang, SL Roberts, KD Tang, SS Ingelfinger, JR Chan, JSD TI Synergistic effect of dexamethasone and isoproterenol on the expression of angiotensinogen in immortalized rat proximal tubular cells SO KIDNEY INTERNATIONAL LA English DT Article DE dexamethasone; isoproterenol; angiotensinogen; immortalized PT cells; proximal tubule cells ID OPOSSUM KIDNEY-CELLS; ADENOSINE-MONOPHOSPHATE; SEQUENCE-ANALYSIS; MESSENGER-RNA; GENE; RECEPTOR; SYSTEM; GLUCOCORTICOIDS; TRANSPORT; STIMULATE AB To investigate whether the expression of angiotensinogen (ANG) in rat kidney proximal tubules is stimulated by dexamethasone and isoproterenol, immortalized rat proximal tubular cells (IRPTC) were cultured in a monolayer. Immunoreactive rat ANG (IR-rANG) in the culture medium was measured by a specific radioimmunoassay (RIA) for rANG. This RIA was developed by employing rabbit antiserum against the purified recombinant rat ANG (rANG). The purified rANG from plasma and the iodinated rANG were used as the hormone standard and tracer, respectively. The RIA is specific for rat ANG and it has no cross-reactivity with other pituitary hormone preparations or other rat plasma proteins. The sensitivity of detection of the RIA is approximately 2 ng of rANG. The levels of IR-rANG in the culture media of IRPTC ranged from 2 to 5 ng/ml/24 hr/10(6) cells. The addition of dexamethasone (10(-13) to 10(-5) M) stimulated the expression and secretion of rANG from IRPTC in a dose-dependent manner, whereas the addition of isoproterenol alone had no effect. However, a combination of both dexamethasone and isoproterenol synergistically stimulated the expression and secretion of rANG by IRPTC. The synergistic effect of dexamethasone and isoproterenol was blocked by the presence of RU 486 (a glucocorticoid receptor antagonist) or propranolol (beta-adrenoceptor blocker). These studies suggest that the addition of dexamethasone and isoproterenol acts synergistically to stimulate the expression and secretion of ANG protein in rat proximal tubules in vivo. C1 Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Chan, JSD (reprint author), Univ Montreal, Hop Maison Neuve Rosemont, Res Ctr, 5415 Boul Assompt, Montreal, PQ H1T 2M4, Canada. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 29 TC 33 Z9 33 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1998 VL 53 IS 2 BP 287 EP 295 DI 10.1046/j.1523-1755.1998.00759.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA YU007 UT WOS:000071670500006 PM 9461088 ER PT J AU Jung, FF Bachinsky, DR Tang, SS Zheng, G Diamant, D Haveran, L McCluskey, RT Ingelfinger, JR AF Jung, FF Bachinsky, DR Tang, SS Zheng, G Diamant, D Haveran, L McCluskey, RT Ingelfinger, JR TI Immortalized rat proximal tubule cells produce membrane bound and soluble megalin SO KIDNEY INTERNATIONAL LA English DT Article DE megalin (gp330); receptor associated protein; immortalized rat proximal tubule cells; glycoprotein receptor ID DENSITY-LIPOPROTEIN-RECEPTOR; NEPHRITIS ANTIGENIC COMPLEX; PASSIVE HEYMANN NEPHRITIS; BRUSH-BORDER ANTIGENS; LDL-RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; MEDIATES ENDOCYTOSIS; IN-VIVO; APOLIPOPROTEIN-J/CLUSTERIN; GLYCOPROTEIN 330/MEGALIN AB Megalin (gp330), a glycoprotein receptor found on renal proximal tubule cells and several other epithelial cells, is deduced to be a type I integral membrane protein, but may also exist as a cell surface form lacking a cytoplasmic domain. Furthermore, soluble megalin products have been detected in urine, and in culture medium of a rat yolk sac carcinoma cell line, combined with receptor associated protein (RAP). Permanent renal cell lines expressing megalin were unavailable until the recent description of two immortalized rat proximal tubule cell lines (IRPTC). The present study demonstrated megalin on IRPTC surface by immunofluorescence, without surface staining for RAP, which was, however, readily detected within cells. Antibodies to ectodomain megalin epitopes immunoprecipitated megalin products both from cell lysates and culture medium, whereas antibodies to cytoplasmic domain epitopes precipitated megalin only from lysates. Western blots showed two major megalin products in medium, a prominent band al similar to 200 kDa, and a fainter band above 400 kDa, slightly below intact megalin in cell lysates. Anti-receptor associated protein antibodies immunoprecipitated megalin from IRPTC lysates, but not from media. We propose that portions of megalin are spontaneously produced by IRPTC, probably either by cleavage in the ectodomain or release of forms lacking a cytoplasmic domain. C1 Massachusetts Gen Hosp, Pediat Renal Res Lab, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, Pediat Renal Res Lab, Bartlett Hall Extens 411, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-40210, HL-48455]; NIDDK NIH HHS [DK-46301] NR 71 TC 23 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1998 VL 53 IS 2 BP 358 EP 366 DI 10.1046/j.1523-1755.1998.00766.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA YU007 UT WOS:000071670500013 PM 9461095 ER PT J AU Meara, JG Shah, S Li, KK Cunningham, MJ AF Meara, JG Shah, S Li, KK Cunningham, MJ TI The odontogenic keratocyst: A 20-year clinicopathologic review SO LARYNGOSCOPE LA English DT Review ID SURGICAL-MANAGEMENT; CYSTS; EXPRESSION; DIAGNOSIS; GROWTH; AID AB The odontogenic keratocyst (OKC) is a jaw cyst with a proclivity for local invasion and recurrence. This 20-year retrospective study was conducted to evaluate methods of treatment and recurrence rates. Forty-nine patients were identified with an average age at presentation of 39.5 years. The molar region of either the mandible or maxilla was the principal primary location; the maxillary antrum was also a common site, The majority of cysts were unilocular and associated with adjacent dentition, Initial therapy was typically enucleation with or without extraction of associated teeth; seven cases of recurrent or second primary odontogenic keratocysts required more extensive surgery, Follow-up ranged from 1 to 15 years with an average duration of 4.3 years. The overall recurrence rate was 35%, and the average time to recurrence 4 years. A recurrence rate of 60% was documented for patients with basal cell nevus syndrome or a family history thereof, Long-term follow-up is necessary following initial OKC treatment, The high rate of recurrence in patients with documented or suspected basal cell nevus syndrome suggests the need for more aggressive initial surgical management in this selected patient population. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Meara, JG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 35 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 1998 VL 108 IS 2 BP 280 EP 283 DI 10.1097/00005537-199802000-00022 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA YV429 UT WOS:000071822700022 PM 9473082 ER PT J AU Berenson, JR Vescio, RA Said, J AF Berenson, JR Vescio, RA Said, J TI Multiple myeloma: the cells of origin - A two-way street SO LEUKEMIA LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Hematology CY DEC 05-09, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Soc Hematol DE multiple myeloma; immunoglobulin genes; Kaposi's sarcoma-associated herpes virus ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN BONE-MARROW; PERIPHERAL-BLOOD; KAPOSIS-SARCOMA; B-CELL; DNA-SEQUENCES; ANTIGENIC SELECTION; MALIGNANT-CELLS; GENE SEGMENT; PLASMA-CELLS AB Multiple myeloma results from an interplay between the manoclonal malignant plasma cells and supporting nonmalignant cells in the bone marrow. Recent studies suggest that the final transforming event in this B cell disorder occurs at a late stage of B cell differentiation based on the characteristics of the immunoglobulin genes expressed by the malignant clone as well as surface markers present on the tumor cells. Recently, an increasing pathogenic role in this malignancy by the nonmalignant cells in the bone marrow has been suggested by several studies. Specific infection of these supporting cells by the recently identified Kaposi's sarcoma-associated herpes virus (KSHV) suggests a novel mechanism by which this nonmalignant population may lead to the development of this B cell malignancy and support its growth. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Berenson, JR (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd 111H, Los Angeles, CA 90073 USA. NR 98 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1998 VL 12 IS 2 BP 121 EP 127 DI 10.1038/sj.leu.2400947 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA ZB085 UT WOS:000072434200004 PM 9519771 ER PT J AU Lee, EJ George, SL Amrein, PC Paciucci, P Allen, SL Schiffer, CA AF Lee, EJ George, SL Amrein, PC Paciucci, P Allen, SL Schiffer, CA TI An evaluation of combinations of diaziquone, etoposide and mitoxantrone in the treatment of adults with relapsed or refractory acute myeloid leukemia: results of 8722, a randomized phase II study conducted by Cancer and Leukemia Group B SO LEUKEMIA LA English DT Article DE acute myeloid leukemia; diaziquone; mitoxantrone; etoposide; chemotherapy ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; CONTINUOUS-INFUSION DIAZIQUONE; ACUTE NONLYMPHOCYTIC LEUKEMIA; CLINICAL-TRIALS; ELDERLY PATIENTS; CHEMOTHERAPY AB A phase II trial was conducted to determine which of the three possible two-drug combinations of diaziquone, etoposide and mitoxantrone was associated with the highest response rate in patients with relapsed or refractory acute myeloid leukemia (AML). Of the 167 patients (median age 55) with AML who entered the trial, 123 were in first relapse, 22 were in second relapse and 22 had failed to achieve complete remission (CR). CR rates were 30% for diaziquone and mitoxantrone, and 23% for the other two combinations (mitoxantrone/etoposide and diaziquone/etoposide), NS. Patients in first relapse had higher CR rates (40%) than other patients. Of the 166 patients who actually received treatment, 43 died before having either a CR or persistent leukemia. Non-hematologic toxicity was primarily mucosal with 24% of patients experiencing grade 3 or greater stomatitis on the two diaziquone arms, and 43% on the mitoxantrone/etoposide arm. The combination of diaziquone and mitoxantrone was selected for further testing in patients with AML. C1 Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. N Shore Univ Hosp, Manhasset, NY USA. Mt Sinai Sch Med, Dept Neoplast Dis, New York, NY USA. CALGB, Chicago, IL USA. RP Schiffer, CA (reprint author), Harper Hosp, Div Hematol & Oncol, 5 Hudson,3990 John R, Detroit, MI 48201 USA. OI Allen, Steven/0000-0002-3482-3182 NR 27 TC 10 Z9 11 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1998 VL 12 IS 2 BP 139 EP 143 DI 10.1038/sj.leu.2400905 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA ZB085 UT WOS:000072434200007 PM 9519774 ER PT J AU Vortkamp, A Pathi, S Peretti, GM Caruso, EM Zaleske, DJ Tabin, CJ AF Vortkamp, A Pathi, S Peretti, GM Caruso, EM Zaleske, DJ Tabin, CJ TI Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Ihh; parathyroid hormone-related protein; fracture repair; bone; endochondral ossification ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; SONIC-HEDGEHOG; INDIAN HEDGEHOG; DEVELOPING LIMB; MOUSE; EXPRESSION; PROTEIN; GENE; RECEPTOR AB A number of proteins have recently been identified which play roles in regulating bone development. One important example is Indian hedgehog (Ihh) which is secreted by the prehyprtrophic chondrocytes. Ihh acts as an activator of a second secreted factor, parathyroid hormone-related protein (PTHrP), which, in turn, negatively regulates the rate of chondrocyte differentiation. Here we examine the expression of these genes and their molecular targets during different stages of bone development. In addition to regulating PTHrP expression in the perichondrium, we find evidence that Ihh may also act on the chondrocytes themselves at particular stages. As bone growth continues postnatally in mammals and the developmental process is reactivated during fracture repair, understanding the molecular basis regulating bone development is of medical relevance. We find that the same molecules that regulate embryonic endochondral ossification are also expressed during postnatal bone growth and fracture healing, suggesting that these processes are controlled by similar mechanisms. (C) 1998 Elsevier Science Ireland Ltd. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Orthoped Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tabin, CJ (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM Tabin@rascal.med.harvard.edu RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 44 TC 236 Z9 241 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD FEB PY 1998 VL 71 IS 1-2 BP 65 EP 76 DI 10.1016/S0925-4773(97)00203-7 PG 12 WC Developmental Biology SC Developmental Biology GA ZE059 UT WOS:000072753500005 PM 9507067 ER PT J AU O'Connell, JX Nanthakumar, SS Nielsen, GP Rosenberg, AE AF O'Connell, JX Nanthakumar, SS Nielsen, GP Rosenberg, AE TI Osteoid osteoma: The uniquely innervated bone tumor SO MODERN PATHOLOGY LA English DT Article DE bone tumors; immunohistochemistry; osteoblastoma; osteoid osteoma; peripheral nerves ID OSTEOBLASTOMA; GROWTH AB Osteoid osteomas are benign bone-forming tumors that despite their small size (<2.0 cm) characteristically produce severe nocturnal bone pain that is relieved by aspirin. This typical clinical presentation is virtually unique among bone tumors, Histologically, osteoid osteomas are circumscribed nodules of woven bone and osteoid with prominent osteoblastic rimming (the nidus), surrounded by thickened cortical and trabecular bone and loose fibrovascular tissue (the reactive zone), Prostaglandins mediate the pain of osteoid osteomas, but there have been few studies of their innervation, We investigated 34 osteoid osteomas using a streptavidin immunohistochemical technique and a panel of antibodies to neural and neural-associated antigens (phosphorylated neurofilament, neurofilament, and S-100 protein), Whenever possible, sections of the nidus and the reactive zone were stained, As controls, we stained other bone tumors that can be painful, including 10 osteoblastomas, 5 osteosarcomas, 6 giant cell tumors, 4 chondroblastomas, 3 aneurysmal bone cysts, and 6 cases of fibrous dysplasia, Twenty-five osteoid osteomas contained phosphorylated neurofilament-, neurofilament-, and/or S-100-positive nerve fibers in the reactive zone around the nidus and/or in the nidus, The nerve fibers were larger and more abundant in the reactive zone than in the nidus, and they were occasionally visible on hematoxylin-and eosin-stained slides on retrospective review, The smaller nerve fibers within the nidi were never identified, even after extensive review of those slides. In the nine cases in which nerve fibers were not identified. C1 Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, James Homer Wright Dept Pathol, Boston, MA 02114 USA. RP O'Connell, JX (reprint author), Vancouver Gen Hosp, Dept Pathol & Lab Med, 855 W 10th Ave, Vancouver, BC V5Z 1M9, Canada. NR 28 TC 46 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD FEB PY 1998 VL 11 IS 2 BP 175 EP 180 PG 6 WC Pathology SC Pathology GA YX661 UT WOS:000072063700008 PM 9504688 ER PT J AU Lonergan, KM Iliopoulos, O Ohh, M Kamura, T Conaway, RC Conaway, JW Kaelin, WG AF Lonergan, KM Iliopoulos, O Ohh, M Kamura, T Conaway, RC Conaway, JW Kaelin, WG TI Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; FACTOR MESSENGER-RNA; GENE-PRODUCT; SOMATIC MUTATIONS; VHL GENE; EXPRESSION; CYCLE; HEMANGIOBLASTOMAS; IDENTIFICATION AB The von Hippel-Lindau tumor suppressor protein(pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O-2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Howard Hughes Med Inst, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Mayer 657, Boston, MA 02115 USA. OI Conaway, Joan/0000-0002-2786-0663 NR 51 TC 273 Z9 277 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1998 VL 18 IS 2 BP 732 EP 741 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000008 PM 9447969 ER PT J AU Lundberg, AS Weinberg, RA AF Lundberg, AS Weinberg, RA TI Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID E2F TRANSCRIPTION FACTOR; CELL-CYCLE; GENE-PRODUCT; DIFFERENTIAL REGULATION; SUSCEPTIBILITY GENE; PHASE-TRANSITION; RB PROTEIN; G1 PHASE; PHOSPHORYLATION; KINASE AB The retinoblastoma protein (pRb) acts to constrain the G(1)-S transition in mammalian cells. Phosphorylation of pRb in G(1) inactivates its growth-inhibitory function, allowing for cell cycle progression. Although several cyclins and associated cyclin-dependent kinases (cdks) have been implicated in pRb phosphorylation, the precise mechanism by which pRb is phosphorylated in vivo remains unclear. By inhibiting selectively either cdk4/6 or cdk2, we show that endogenous D-type cyclins,acting with cdk4/6, are able to phosphorylate pRb only partially, a process that is likely to be completed by cyclin E-cdk2 complexes. Furthermore, cyclin E-cdk2 is unable to phosphorylate pRb in the absence of prior phosphorylation by cyclin D-cdk4/6 complexes. Complete phosphorylation of pRb, inactivation of E2F binding, and activation of E2F transcription occur only after sequential action of at least two distinct G(1) cyclin kinase complexes. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lundberg, AS (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [K11-CA69242] NR 64 TC 697 Z9 710 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1998 VL 18 IS 2 BP 753 EP 761 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU427 UT WOS:000071716000010 PM 9447971 ER PT J AU D'Andrea, AD Serhan, CN AF D'Andrea, AD Serhan, CN TI Relieving the itch SO NATURE GENETICS LA English DT Editorial Material ID UBIQUITIN; PROTEASOME; PATHWAY; ENZYME; GENE C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Anesthesia, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1998 VL 18 IS 2 BP 97 EP 99 DI 10.1038/ng0298-97 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA YV010 UT WOS:000071779500005 PM 9462731 ER PT J AU Hagstrom, SA North, MA Nishina, PM Berson, EL Dryja, TP AF Hagstrom, SA North, MA Nishina, PM Berson, EL Dryja, TP TI Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with Retinitis pigmentosa SO NATURE GENETICS LA English DT Article ID ROD PHOSPHODIESTERASE; OCULAR FINDINGS; ALPHA-SUBUNIT; BETA-SUBUNIT; RHODOPSIN; MOUSE; IDENTIFICATION; FAMILY; DNA AB A recessive mutation in the tub gene causes obesity, deafness and retinal degeneration in tubby mice(1-4). The tub gene is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates and invertebrates(4). The TULP proteins share a conserved carboxy-terminal region of approximately 200 amino-acid residues(5). Here we report the analysis of the human gene TULP?, which is expressed specifically in the retina(5). Upon analysing 162 patients with nonsyndromic recessive retinitis pigmentosa (RP) and 374 simplex cases of RP, we found two who were compound heterozygotes for mutations that cosegregated with disease in the respective families. Three of the mutations are missense changes affecting the conserved C-terminal region; the fourth mutation affects a splice donor site upstream of this region. Our data suggest that mutations in TULP1 are a rare cause of recessive RP and indicate that TULP1 has an essential role in the physiology of photoreceptors. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Sequana Therapeut Inc, La Jolla, CA 92037 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Dryja, TP (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683] NR 24 TC 135 Z9 136 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1998 VL 18 IS 2 BP 174 EP 176 DI 10.1038/ng0298-174 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA YV010 UT WOS:000071779500029 PM 9462750 ER PT J AU Bach, FH Fishman, JA Daniels, N Proimos, J Anderson, B Carpenter, CB Forrow, L Robson, SC Fineberg, HV AF Bach, FH Fishman, JA Daniels, N Proimos, J Anderson, B Carpenter, CB Forrow, L Robson, SC Fineberg, HV TI Uncertainty in xenotransplantation: Individual benefit versus collective risk SO NATURE MEDICINE LA English DT Editorial Material ID REJECTION C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Tufts Univ, Dept Philosophy, Medford, MA 02155 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. RP Bach, FH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 99 Brookline Ave, Boston, MA 02215 USA. NR 21 TC 152 Z9 152 U1 1 U2 16 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 1998 VL 4 IS 2 BP 141 EP 144 DI 10.1038/nm0298-141 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ392 UT WOS:000072249800020 PM 9461178 ER PT J AU Kay, LE Muhandiram, DR Wolf, G Shoelson, SE Forman-Kay, JD AF Kay, LE Muhandiram, DR Wolf, G Shoelson, SE Forman-Kay, JD TI Correlation between binding and dynamics at SH2 domain interfaces SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID HIGH-AFFINITY BINDING; N-15 NMR RELAXATION; MAGNETIC-RESONANCE RELAXATION; SRC HOMOLOGY-2 DOMAIN; MODEL-FREE APPROACH; BACKBONE DYNAMICS; METHYL-GROUPS; STAPHYLOCOCCAL NUCLEASE; PHOSPHOTYROSYL PEPTIDE; SECONDARY STRUCTURE AB Protein recognition is a key determinant in regulating biological processes. Structures of complexes of interacting proteins provide significant insights into the mechanism of specific recognition. However, studies performed by modifying residues within a protein interface demonstrate that binding is not fully explained by these static pictures. Thus, structural data alone was not predictive of affinities in binding studies of phospholipase C gamma 1 and Syp phosphatase SH2 domains with phosphopeptides. NMR relaxation experiments probing dynamics of methyl groups of these complexes indicate a correlation between binding energy and restriction of motion at the interfacial region responsible for specific binding. C1 Univ Toronto, Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Biochem, Toronto, ON M5G 1X8, Canada. Univ Toronto, Prot Engn Network Ctr Excellence, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Biochem & Chem, Toronto, ON M5S 1A8, Canada. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Forman-Kay, JD (reprint author), Univ Toronto, Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. EM forman@sickkids.on.ca NR 48 TC 123 Z9 125 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD FEB PY 1998 VL 5 IS 2 BP 156 EP 163 DI 10.1038/nsb0298-156 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YV007 UT WOS:000071779200018 PM 9461082 ER PT J AU Lev, MH Curtin, HD AF Lev, MH Curtin, HD TI Larynx SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article AB The complex anatomy of the larynx, best conceptualized as a set of mucosal folds draped over a cartilaginous skeleton, has developed as a consequence of its many upper airway functions. Despite its deep location in the neck, much of the mucosal surface of the larynx is amenable to direct laryngoscopic Inspection. The role of the radiologist in laryngeal imaging, therefore, is not primarily to diagnose disease, but to aid in both surgical staging and in the evaluation, of potential clinical "blind spots." In this article, the normal anatomy of the larynx is reviewed, with special attention to important surgical and functional structures. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 27 TC 6 Z9 6 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD FEB PY 1998 VL 8 IS 1 BP 235 EP + PG 23 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZC576 UT WOS:000072594500014 PM 9449763 ER PT J AU Buckner, RL Goodman, J Burock, M Rotte, M Koutstaal, W Schacter, D Rosen, B Dale, AM AF Buckner, RL Goodman, J Burock, M Rotte, M Koutstaal, W Schacter, D Rosen, B Dale, AM TI Functional-anatomic correlates of object priming in humans revealed by rapid presentation event-related fMRI SO NEURON LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; IMPLICIT MEMORY; HUMAN BRAIN; HIPPOCAMPAL-FORMATION; TASKS; AREAS; STIMULATION; ACTIVATION; MECHANISMS AB Human functional-anatomic correlates of object repetition were explored in a cohort of 20 subjects using fMRI. Subjects performed an object classification task where the target objects were either novel or repeated. Objects appeared rapidly, one every 2 s, in a randomly intermixed task design similar to traditional behavioral, event-related potential (ERP), and single-unit physiological studies. Recently developed event-related fMRI methods were used to analyze the data. Clear effects of repetition were observed. Brain areas in mid-levels of the processing hierarchy, including extrastriate visual cortex extending into inferotemporal cortex and left dorsal prefrontal cortex, showed reductions in the amount of activation after repetition. By contrast, early visual areas and output motor areas were activated equally by both novel and repeated objects and did not show effects of repetition, suggesting that the observed correlates of repetition were anatomically selective. We discuss these findings in relation to previous positron emission tomography (PET) and fMRI studies of item repetition and single-unit physiological studies; we also address the broad impact that rapid event-related fMRI is likely to have on functional neuroimaging. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychol,Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ Magdeburg, Dept Neurophysiol, D-39120 Magdeburg, Germany. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Buckner, RL (reprint author), Washington Univ, Dept Psychol, St Louis, MO 63130 USA. RI Dale, Anders/A-5180-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441]; NIDCD NIH HHS [DC03245] NR 67 TC 456 Z9 458 U1 4 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 1998 VL 20 IS 2 BP 285 EP 296 DI 10.1016/S0896-6273(00)80456-0 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YY510 UT WOS:000072154700013 PM 9491989 ER PT J AU Peters, N Wellenreuther, R Rollbrocker, B Hayashi, Y Meyer-Puttlitz, B Duerr, EM Lenartz, D Marsh, DJ Schramm, J Wiestler, OD Parsons, R Eng, C von Deimling, A AF Peters, N Wellenreuther, R Rollbrocker, B Hayashi, Y Meyer-Puttlitz, B Duerr, EM Lenartz, D Marsh, DJ Schramm, J Wiestler, OD Parsons, R Eng, C von Deimling, A TI Analysis of the PTEN gene in human meningiomas SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE meningioma; progression; PTEN; MMAC1; TEP1; mutation ID CHROMOSOME-10; PROGRESSION; ASSOCIATION; REGIONS; LOCI AB Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2) plays an important role in the pathogenesis of the transitional, fibroblastic and malignant variants of human meningiomas. No specific genes have been associated with the pathogenesis of meningothelial meningiomas and with the progression to anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and 14q have been implicated in the process of malignant progression. Recently, PTEN (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF-regulated and epithelial cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3. Initial studies revealed mutations of PTEN in limited series of glioblastomas, breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I), 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of the anaplastic meningiomas carried a somatic mutation. In addition, all tumours were examined for the presence of homozygous deletions of PTEN but these were not detected in any of the meningiomas, Our data suggest that mutations in PTEN are not involved in the formation of low grade meningiomas, but may contribute to malignant progression in a fraction of anaplastic meningiomas. C1 Univ Bonn, Med Ctr, Dept Neuropathol, D-5300 Bonn, Germany. Univ Bonn, Med Ctr, Dept Neurosurg, D-5300 Bonn, Germany. Hosp Koln Merheim, Dept Neurosurg, Cologne, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Human Canc Genet Unit, Boston, MA 02115 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. RP von Deimling, A (reprint author), Univ Kliniken Bonn, Inst Neuropathol, Sigmund Freud Str 25, D-53105 Bonn, Germany. RI Marsh, Deborah/I-1491-2014; von Deimling, Andreas/F-7774-2013; OI Marsh, Deborah/0000-0001-5899-4931; von Deimling, Andreas/0000-0002-5863-540X; Eng, Charis/0000-0002-3693-5145 NR 22 TC 58 Z9 59 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD FEB PY 1998 VL 24 IS 1 BP 3 EP 8 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZB838 UT WOS:000072513100003 PM 9549723 ER PT J AU Di Rocco, F Carroll, RS Zhang, JP Black, PM AF Di Rocco, F Carroll, RS Zhang, JP Black, PM TI Platelet-derived growth factor and its receptor expression in human oligodendrogliomas SO NEUROSURGERY LA English DT Article DE immunohistochemistry; neoplasms; northern analysis; oligodendrogliomas; platelet-derived growth factor ID HUMAN BRAIN-TUMORS; GLIOMA CELL-LINES; FACTOR PDGF; MESSENGER-RNAS; RIBONUCLEIC-ACID; FACTOR-ALPHA; STIMULATION; AUTOCRINE; CANCER; CARCINOMAS AB OBJECTIVE: Platelet-derived growth factor (PDGF) induces cellular proliferation and differentiation by activating intracellular signaling mechanisms via their cognate receptors. In previous studies, we demonstrated that human brain tumors such as meningiomas, astrocytomas, medulloblastomas, and ependymomas expressed the messenger ribonucleic acid for the PDGF subunits and their receptors. In the present study, we investigated the expression of the messenger ribonucleic acid PDGF A and B chains and the PDGF alpha and beta receptors in 17 cases of oligodendrogliomas. METHODS: Measurements of messenger ribonucleic acid levels were obtained using radioactive complementary deoxyribonucleic acid probes. Protein expression was analyzed with specific antibodies. RESULTS: Sixteen of 17 tumors expressed the PDGF A subunit and all the PDGF alpha receptors. Furthermore, all the tumors expressed PDGF B and PDGE beta receptor subunits. CONCLUSION: The results of this study suggest that oligodendrogliomas may have an autocrine loop stimulated by the interaction of PDGF and its receptor simultaneously produced by these tumors. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Neurosurg Labs, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Brain Tumor Ctr, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Carroll, RS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Neurosurg Labs, 221 Longwood Ave,Room 121, Boston, MA 02115 USA. RI DI ROCCO, Federico/C-6343-2015 NR 34 TC 85 Z9 85 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 1998 VL 42 IS 2 BP 341 EP 346 DI 10.1097/00006123-199802000-00080 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YV348 UT WOS:000071814200029 PM 9482185 ER PT J AU Clinton, SK AF Clinton, SK TI Lycopene: Chemistry, biology, and implications for human health and disease SO NUTRITION REVIEWS LA English DT Review ID CERVICAL INTRAEPITHELIAL NEOPLASIA; PLASMA CAROTENOID CONCENTRATIONS; BETA-CAROTENE; VITAMIN-A; ALPHA-TOCOPHEROL; ANTIOXIDANT VITAMINS; SERUM CAROTENOIDS; CANCER PREVENTION; COLORECTAL-CANCER; PROSTATE-CANCER AB A diet rich in carotenoid-containing foods is associated with a number of health benefits. Lycopene provides the familiar red color to tomato products and is one of the major carotenoids in the diet of North Americans and Europeans. interest in lycopene is growing rapidly following the recent publication of epidemiologic studies implicating lycopene in the prevention of cardiovascular disease and cancers of the prostate or gastrointestinal tract. Lycopene has unique structural and chemical features that may contribute to specific biological properties. Data concerning lycopene bioavailability, tissue distribution, metabolism, excretion, and biological actions in experimental animals and humans are beginning to accumulate although much additional research is necessary. This review will summarize our knowledge in these areas as well as the associations between lycopene consumption and human health. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Clinton, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 166 TC 508 Z9 559 U1 9 U2 72 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 1998 VL 56 IS 2 BP 35 EP 51 PN 1 PG 17 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZA683 UT WOS:000072390600001 PM 9529899 ER PT J AU Myers, ER Thompson, JW Simpson, K AF Myers, ER Thompson, JW Simpson, K TI Cost-effectiveness of mandatory compared with voluntary screening for human immunodeficiency virus in pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID HIV-INFECTION; UNITED-STATES; PERINATAL TRANSMISSION; ZIDOVUDINE TREATMENT; PRENATAL-CARE; WOMEN; PREVALENCE; KNOWLEDGE; TYPE-1; IMPACT AB Objective: To determine the cost-effectiveness of mandatory screening for human immunodeficiency virus (HIV) in pregnancy compared with that of voluntary screening under varying assumptions about patient behavior. Methods: Using a health care system perspective, a decision-analysis model was constructed to estimate the outcomes and costs of the two strategies. Average and incremental cost-effectiveness ratios were calculated for each strategy. Sensitivity analyses were performed to test the effects of different values on the results of the simulation. In particular, we examined the potential effects of changes in patient behavior resulting from mandatory screening on our estimates of cost-effectiveness. Results: At a prevalence of 170 per 100,000, average costs per case prevented were $255,158 and $367,998 for mandatory and voluntary screening, respectively. The incremental cost-effectiveness of mandatory compared with voluntary screening was $29,478. These values decreased as prevalence of HIV increased, or as the estimated lifetime cost of pediatric HIV infection increased: above an estimated cost for pediatric HIV of $129,250, mandatory screening was less expensive and more effective than voluntary screening. Assumptions about patient behavior affected these results: a 40% reduction in zidovudine acceptance in women identified only through mandatory screening increased the incremental cost-effectiveness to $112,434. The impact of behavior increased as the prevalence of HIV increased. Conclusion: Mandatory screening will prevent more cases of pediatric AIDS, but at a somewhat higher cost than voluntary screening under baseline assumptions. The cost-effectiveness of mandatory screening will be influenced by patient behavior, especially acceptance of zidovudine treatment among women who would have refused voluntary screening. (C) 1998 by The American College of Obstetricians and Gynecologists. C1 Beth Israel Deaconnes Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. US PHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA. Univ N Carolina, Sch Publ Hlth, Dept Hlth Policy & Adm, Chapel Hill, NC USA. RP Myers, ER (reprint author), Duke Univ, Med Ctr, Dept Obstet & Gynecol, DUMC-3279, Durham, NC 27710 USA. EM myers008@mc.duke.edu NR 45 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1998 VL 91 IS 2 BP 174 EP 181 DI 10.1016/S0029-7844(97)00629-7 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YU010 UT WOS:000071670800004 PM 9469271 ER PT J AU Duska, LR Flynn, CF Chen, A Whall-Strojwas, D Goodman, A AF Duska, LR Flynn, CF Chen, A Whall-Strojwas, D Goodman, A TI Clinical evaluation of atypical glandular cells of undetermined significance on cervical cytology SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ADENOCARCINOMA AB Objective: To determine the incidence of and identify risk factors for clinically significant diagnoses associated with the diagnosis on Papanicolaou test of atypical glandular cells of undetermined significance. Methods: A computer search was initiated of diagnoses of atypical glandular cells of undetermined significance at the Massachusetts General Hospital from January 1993 through December 1996. Seventy-three patients with 81 smears were identified that were seen in the Colposcopy Clinic. All cytology was reviewed. A clinically significant lesion was defined as high-grade squamous intraepithelial lesion (SIL) or worse, endocervical glandular atypia or worse, or carcinoma. Results: The rate of diagnoses of atypical glandular cells of undetermined significance was 0.167%. All patients underwent colposcopy, and 88% underwent endocervical curettage. A clinically significant diagnosis was made in 34.2% of patients, including cancer in 8.2%. A concurrent squamous diagnosis carried a risk of clinically significant lesion of 50%, compared with a risk of 25.5% for atypical glandular cells of undetermined significance alone (P =.043). Premenopausal and postmenopausal patients were both at risk for clinically important lesions, but premenopausal patients were more likely to have a high-grade SIL (30.4% versus 7.4%, P =.04). The subtype "suggestive of reactive" was a significant negative predictor of significant lesion (odds ratio = 0.09, 95% confidence interval 0.018, 0.482) in a logistic regression model controlling for age, menopausal status, and concurrent squamous diagnosis. Conclusion: Atypical glandular cells of undetermined significance is an important Papanicolaou lest diagnosis that needs appropriate and careful evaluation. Further studies are required to clarify areas of risk and to make triage algorithms. (C) 1998 by The American College of Obstetricians and Gynecologists.). C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cytopathol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Gynecol Serv, Vincent 1, Boston, MA 02114 USA. NR 8 TC 68 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1998 VL 91 IS 2 BP 278 EP 282 DI 10.1016/S0029-7844(97)00659-5 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YU010 UT WOS:000071670800022 PM 9469289 ER PT J AU Von Roenn, JH Krown, SE Benson, CA Mitsuyasu, RT Friedman-Kien, AE Scadden, DT Stelzer, KJ AF Von Roenn, JH Krown, SE Benson, CA Mitsuyasu, RT Friedman-Kien, AE Scadden, DT Stelzer, KJ TI Management of AIDS-associated Kaposi's sarcoma: A multidisciplinary perspective - Proceedings of a Roundtable Symposium, March 10, 1997, New York SO ONCOLOGY-NEW YORK LA English DT Article; Proceedings Paper CT Roundtable Symposium on Management of AIDS Associated Kaposi Sarcoma - a Multidisciplinary Perspective CY MAR 10, 1997 CL NEW YORK, NEW YORK ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; COLONY-STIMULATING FACTOR; INTERFERON-ALPHA; RADIATION-THERAPY; PHASE-II; ZIDOVUDINE; TRIAL; DOXORUBICIN; BLEOMYCIN C1 Northwestern Univ, Chicago, IL 60611 USA. Cornell Univ, Coll Med, Mem Sloan Kettering Canc Ctr, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NYU, Med Ctr, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA USA. Univ Washington, Seattle, WA 98195 USA. RP Von Roenn, JH (reprint author), Northwestern Univ, Chicago, IL 60611 USA. NR 48 TC 2 Z9 2 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD FEB PY 1998 VL 12 IS 2 SU 3 BP 9 EP 24 PG 16 WC Oncology SC Oncology GA ZC419 UT WOS:000072576100002 ER PT J AU Tripathi, RC Li, JP Tripathi, BJ Chalam, KV Adamis, AP AF Tripathi, RC Li, JP Tripathi, BJ Chalam, KV Adamis, AP TI Increased level of vascular endothelial growth factor in aqueous humor of patients with neovascular glaucoma SO OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; PERMEABILITY FACTOR; MESSENGER-RNA; FACTOR VEGF; TRABECULAR CELLS; IRIS NEOVASCULARIZATION; NONHUMAN PRIMATE; RUBEOSIS-IRIDIS; RETINAL CELLS; FACTOR FAMILY AB Purpose: This study aimed to quantitate and compare the concentration of vascular endothelial growth factor (VEGF) in aqueous humor samples from patients with neovascular glaucoma (NVG), primary open-angle glaucoma (POAG), and cataract, as well as in serum samples of healthy human subjects. Methods: The authors collected aqueous humor samples by using their previously published technique of limbal paracentesis. The authors determined the concentration of VEGF by using a competitive enzyme immunoassay system and four-parameter logistic curve fitting and performed statistical analysis by using the Mann-Whitney-Wilcoxon test. Results: The authors detected VEGF in 12 of 12 samples from patients with NVG (mean +/- standard error of the mean, 29.267 +/- 7.350 ng/ml), 15 of 28 samples from patients with POAG (0.726 +/- 0.204 ng/ml), 4 of 20 aqueous humor samples from patients with cataract (0.257 +/- 0.043 ng/ml), and 16 of 16 human serum samples (20.246 +/- 1.568 ng/ml). The mean concentration of VEGF in aqueous humor of patients with NVG was 40- and 113-fold higher than that in patients with POAG and cataract, respectively, and the difference was statistically significant (P < 0.01). The VEGF level in patients with POAG was elevated compared with that in patients with cataract (P < 0.05). Although the mean concentration of VEGF in aqueous humor of patients with NVG was approximately 1.45-fold higher than that in serum, the difference was not significant (P > 0.05). Conclusion: The authors' findings show that patients with NVG had a significantly increased level of VEGF in the aqueous humor and implicate VEGF as an important factor in the pathogenesis of intraocular neovascularization in these patients. The authors discuss the possible role of the ciliary epithelium, in addition to retina, in the production of VEGF and the complementary function of basic fibroblast growth factor and other growth factors. C1 Univ S Carolina, Sch Med, Dept Ophthalmol, Columbia, SC 29208 USA. Univ S Carolina, Sch Med, Dept Pathol, Columbia, SC 29208 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. RP Tripathi, RC (reprint author), S Carolina Eye Inst, 4 Richland Med Pk,Suite 300, Columbia, SC 29203 USA. OI Chalam, kakarla/0000-0001-9325-8665 NR 53 TC 142 Z9 148 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1998 VL 105 IS 2 BP 232 EP 237 DI 10.1016/S0161-6420(98)92782-8 PG 6 WC Ophthalmology SC Ophthalmology GA YW411 UT WOS:000071932600011 PM 9479280 ER PT J AU Chatzistefanou, K Markomichelakis, NN Christen, W Scheilian, M Foster, CS AF Chatzistefanou, K Markomichelakis, NN Christen, W Scheilian, M Foster, CS TI Characteristics of uveitis presenting for the first time in the elderly SO OPHTHALMOLOGY LA English DT Article ID RETICULUM-CELL SARCOMA; PREVALENCE; PATTERNS; DISEASE; OLDER AB Objective: This study aimed to describe the clinical characteristics of uveitis presenting de novo in the elderly, Design: The study design was a description of a retrospectively identified case series. Participants: A population of 138 patients (209 eyes) with uveitis beginning after age 60 was analyzed. Results: Uveitis in the elderly accounted for 10.4% of the authors' uveitis population. The localization of uveitis was anterior in 56.5% of patients, intermediate uveitis was diagnosed in two patients (1.4%), posterior uveitis was found in 25.4%, while 16.7% of patients presented with panuveitis. Idiopathic uveitis accounted for the majority of cases (31.2%), whereas herpes tester ophthalmicus (11.6%), herpes simplex virus (6.5%), presumed sarcoidosis (5.8%), syphilis (4.3%) ankylosing spondylitis (4.3%), and birdshot chorioretinopathy (3.6%) were the most frequent specific diagnostic entities. Secondary elevation of intraocular pressure was common (67 eyes, or 32%). The development of macular edema complicated 28.7% of cases (60 eyes). Two cases of intraocular lymphoma were identified in 19 diagnostic vitreous biopsy specimens. Fifty-two percent of eyes retained visual acuity of 20/40 or more; 32.6% had final visual acuity worse than 20/100. Conclusions: Uveitis presenting for the first time in the elderly is not uncommon. Idiopathic uveitis accounts for the majority of cases, and herpes tester ophthalmicus and herpes simplex virus are particularly prevalent. Intraocular lymphoma does not predominate in this age group. With adequate control of intraocular inflammation and its sequelae, the visual prognosis in patients in this age group with uveitis is relatively good. C1 Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1998 VL 105 IS 2 BP 347 EP 352 DI 10.1016/S0161-6420(98)93523-0 PG 6 WC Ophthalmology SC Ophthalmology GA YW411 UT WOS:000071932600030 PM 9479298 ER PT J AU Dibart, S Skobe, Z Snapp, KR Socransky, SS Smith, CM Kent, R AF Dibart, S Skobe, Z Snapp, KR Socransky, SS Smith, CM Kent, R TI Identification of bacterial species on or in crevicular epithelial cells from healthy and periodontally diseased patients using DNA-DNA hybridization SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE bacteria; crevicular epithelial cell; periodontal health; periodontal disease ID PREDOMINANT CULTIVABLE MICROBIOTA; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ATTACHMENT; LESIONS AB The purpose of this investigation was to identify bacterial species present on or in crevicular epithelial cells in healthy and diseased sites using DNA probes. In order to achieve this aim, further improvements were made in the separation of unattached bacteria from those adherent to epithelial cells isolated from the human gingival crevice or periodontal pocket. Then the DNA probes were used to determine the prevalence of detectable DNA from 15 microbial species on or in crevicular epithelial cells. One sample was taken from a single subgingival site in each of 51 individuals ranging in age from 19 to 45 years. Samples were taken from 27 sites of clinically healthy subjects and 24 samples were taken from subjects having periodontally diseased sites. DNA-DNA hybridization indicated that a majority of epithelial cells from healthy sites (63%) were in contact with or harbored Streptococcus oralis. On the other hand, species such as Bacteroides forsythus, Prevotella intermedia, Capnocytophaga ochracea and Campylobacter rectus were more frequently detected in elevated numbers in periodontally diseased sites, Cluster analysis of the microbial profiles generally aggregated subjects with and without periodontitis into separate cluster groups, The cluster patterns suggest the possibility that microbial complexes will be, in part, determined by the receptors available on the epithelial cells. C1 Boston Univ, Goldman Sch Grad Dent, Dept Periodontol, Boston, MA 02118 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Dibart, S (reprint author), Boston Univ, Goldman Sch Grad Dent, Dept Periodontol, 100 E Newton St, Boston, MA 02118 USA. FU NIDCR NIH HHS [DE04881] NR 21 TC 20 Z9 21 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1998 VL 13 IS 1 BP 30 EP 35 DI 10.1111/j.1399-302X.1998.tb00747.x PG 6 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA YU189 UT WOS:000071691200005 PM 9573819 ER PT J AU Shaniztki, B Ganeshkumar, N Weiss, EI AF Shaniztki, B Ganeshkumar, N Weiss, EI TI Characterization of a novel N-acetylneuraminic acid specific Fusobacterium nucleatum PK1594 adhesin SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE adhesin; coaggregation; N-acetylneuraminic acid; Fusobacterium; monoclonal antibody ID CAPNOCYTOPHAGA-OCHRACEA ATCC-33596; ORAL BACTERIA; BACTEROIDES-GINGIVALIS; MONOCLONAL-ANTIBODIES; COAGGREGATION; IDENTIFICATION; ADHERENCE; STRAINS; SURFACE; LECTIN AB Fusobacterium nucleatum has been identified as significantly associated with sites with active periodontal disease and, as a group, the oral fusobacteria coaggregate with members of all oral bacteria genera tested. Monoclonal antibodies were prepared and used in conjunction with other potential inhibitors, such as simple sugars and amino acids, to characterize coaggregation interactions of F. nucleatum PK1594. Four unique monoclonal antibodies, 5H11, 14C7, 19F2 and 29C12, were obtained by their ability to inhibit coaggregation of F. nucleatum PK1594 with Actinomyces israelii PK16. They were also capable of inhibiting other coaggregations including Streptococcus oralis H1, S. oralis J22, Capnocytophaga ochracea ATCC33596, Prevotella denticola PK1277 and Prevotella intermedia PK1511. All of these interactions were completely inhibited by N-acetylneuraminic acid. Neither N-acetylneuraminic acid nor monoclonal antibody 5H11 had any inhibitory effect on other F. nucleatum PK1594 interactions, including all galactose-inhibitable coaggregations. The results indicate that F. nucleatum PK1594 expresses upon its surface a distinct type of adhesin that mediates coaggregation interactions that are inhibited by N-acetylneuraminic acid. C1 Tel Aviv Univ, Maurice & Gabriela Goldschleger Sch Dent Med, Dept Oral Biol, IL-69978 Tel Aviv, Israel. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Weiss, EI (reprint author), Tel Aviv Univ, Maurice & Gabriela Goldschleger Sch Dent Med, Dept Oral Biol, IL-69978 Tel Aviv, Israel. NR 27 TC 13 Z9 13 U1 2 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1998 VL 13 IS 1 BP 47 EP 50 DI 10.1111/j.1399-302X.1998.tb00750.x PG 4 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA YU189 UT WOS:000071691200008 PM 9573822 ER PT J AU Andersen, RN Ganeshkumar, N Kolenbrander, PE AF Andersen, RN Ganeshkumar, N Kolenbrander, PE TI Helicobacter pylori adheres selectively to Fusobacterium spp. SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Helicobacter-Fusobacterium coaggregation; helicobacter oral sequestration ID POLYMERASE CHAIN-REACTION; DENTAL PLAQUE; DUODENAL-ULCER; GASTRIC-CANCER; ORAL BACTERIA; COAGGREGATION; INFECTION; CAMPYLOBACTER; SALIVA; PCR AB Helicobacter pylori strains ATCC 43504 and ATCC 43629 were tested for their ability to coaggregate with 79 strains of bacteria representing 16 genera. All except two of the strains were of human origin, and most of the strains were isolated from the oral cavity. The helicobacters failed to coaggregate with all strains except the fusobacteria. Several coaggregations were partially or completely inhibited by lactose. Strong coaggregation was seen with each of four subspecies of Fusobacterium nucleatum and with Fusobacterium periodonticum ATCC 33693, all of human dental plaque origin. In contrast, the helicobacters failed to coaggregate with non-plaque isolates, Fusobacterium mortiferum ATCC 25557 and Fusobacterium ulcerans ATCC 49185. Heat treatment of the fusobacteria inactivated their ability to coaggregate, whereas heating of the helicobacter partners had no effect, suggesting the presence of an adhesin on the fusobacteria and a corresponding receptor on the helicobacters. The potential ability of H. pylori to colonize the oral cavity by adhering selectively to the ubiquitous fusobacteria gives credence to the possibility that dental plaque may serve as a reservoir for this pathogen outside of the stomach. C1 NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Kolenbrander, PE (reprint author), NIDR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 310,30 Convent Dr MSC 4350, Bethesda, MD 20892 USA. NR 42 TC 30 Z9 32 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD FEB PY 1998 VL 13 IS 1 BP 51 EP 54 DI 10.1111/j.1399-302X.1998.tb00751.x PG 4 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA YU189 UT WOS:000071691200009 PM 9573823 ER PT J AU Gordon, BR AF Gordon, BR TI Allergy skin tests for inhalants and foods - Comparison of methods in common use SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID ATOPIC-DERMATITIS; PRICK TEST; PRECISION NEEDLE; HYPERSENSITIVITY; REPRODUCIBILITY; IMMUNOTHERAPY; REACTIVITY; DEVICES; PERFORMANCE; ANTIBODIES AB This article compares and contrasts the advantages and disadvantages of patch, scratch, prick, modified prick, single dilution intradermal, and skin endpoint titration allergy skin testing techniques. The techniques for performing these skin testing methods and their evolution are described. Skin testing strategies and antigen doses used in testing are compared, reasons for the quantitation of allergic sensitivity are discussed, and methods for quantitation are examined. Finally, the evolution of specialized skin tests to diagnose food hypersensitivity is reviewed. Common factors that are shared by all allergy techniques are stressed. C1 Cape Cod Hosp, Hyannis, MA 02601 USA. Harvard Univ, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gordon, BR (reprint author), Cape Cod Hosp, 27 Pk St, Hyannis, MA 02601 USA. NR 111 TC 14 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD FEB PY 1998 VL 31 IS 1 BP 35 EP + DI 10.1016/S0030-6665(05)70028-1 PG 20 WC Otorhinolaryngology SC Otorhinolaryngology GA ZA870 UT WOS:000072410300005 PM 9530676 ER PT J AU Freeman, GJ Boussiotis, VA Gribben, JG Sharpe, AH Nadler, LM AF Freeman, GJ Boussiotis, VA Gribben, JG Sharpe, AH Nadler, LM TI The B7/CD28: CTLA4 pathway in T cell activation and transplantation tolerance SO PATHOLOGIE BIOLOGIE LA English DT Article; Proceedings Paper CT 2nd Joseph R Coulter Symposium on Immuno-Intervention in Cancer CY APR 01-02, 1997 CL MARSEILLE, FRANCE DE B7/CD28; costimulation; tolerance C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD FEB PY 1998 VL 46 IS 2 BP 128 EP 129 PG 2 WC Pathology SC Pathology GA ZD414 UT WOS:000072682800018 ER PT J AU Anderson, P AF Anderson, P TI The fast track: RNA-binding proteins involved in signaling stress-induced apoptosis SO PATHOLOGIE BIOLOGIE LA English DT Article; Proceedings Paper CT 2nd Joseph R Coulter Symposium on Immuno-Intervention in Cancer CY APR 01-02, 1997 CL MARSEILLE, FRANCE DE apoptosis; fast kinase; RNA-binding proteins ID TIAR C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Anderson, P (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD FEB PY 1998 VL 46 IS 2 BP 135 EP 135 PG 1 WC Pathology SC Pathology GA ZD414 UT WOS:000072682800024 ER PT J AU Schlossman, SF AF Schlossman, SF TI T cell immunity: A consideration of cell surface antigens SO PATHOLOGIE BIOLOGIE LA English DT Article; Proceedings Paper CT 2nd Joseph R Coulter Symposium on Immuno-Intervention in Cancer CY APR 01-02, 1997 CL MARSEILLE, FRANCE DE T lymphocytes; antigens C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schlossman, SF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD FEB PY 1998 VL 46 IS 2 BP 140 EP 140 PG 1 WC Pathology SC Pathology GA ZD414 UT WOS:000072682800028 ER PT J AU Hack, S Jellinek, MS AF Hack, S Jellinek, MS TI Historical clues to the diagnosis of the dysfunctional child and other psychiatric disorders in children SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PEDIATRIC SYMPTOM CHECKLIST; UNINTENTIONAL INJURIES; RISK-FACTORS; ADOLESCENTS; DIVORCE; FAMILY; SCHOOL; ADJUSTMENT; BEHAVIOR; CARE AB This article focuses on selected historical clues that can help the busy pediatrician identify children who are at risk for or already suffering from psychosocial dysfunction. Certain historical elements have been chosen because they reveal either common areas of childhood dysfunction or potentially dire outcomes. The major functional realms of a child's life are covered, such as family, school, peer relationships, activities, and emotions, as well as related topics such as injury, poverty, substance abuse, and risk-taking behavior. Questions designed to elicit the relevant historical clues are suggested. Used as a set, these questions are intended to bring to light sufficient psychosocial history for pediatricians to identify most dysfunctional children. C1 Harvard Univ, Sch Med, Dept Child Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. RP Hack, S (reprint author), NYU, Med Ctr, 550 1st Ave,NB 2136, New York, NY 10016 USA. NR 58 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD FEB PY 1998 VL 45 IS 1 BP 25 EP + DI 10.1016/S0031-3955(05)70581-2 PG 25 WC Pediatrics SC Pediatrics GA YX587 UT WOS:000072055500003 PM 9491085 ER PT J AU Weissig, V Lasch, J Erdos, G Meyer, HW Rowe, TC Hughes, J AF Weissig, V Lasch, J Erdos, G Meyer, HW Rowe, TC Hughes, J TI DQAsomes: A novel potential drug and gene delivery system made from Dequalinium (TM) SO PHARMACEUTICAL RESEARCH LA English DT Article DE dequalinium; liposome; bolaform drug; non-viral transfection vector; gene therapy; drug delivery ID AGENT AB Purpose. Dequalinium, a drug known for over 30 years, is a dicationic amphiphile compound resembling bolaform electrolytes. The purpose of our work was to determine the state of aggregation of dequalinium in aqueous medium and to investigate both, its ability to bind DNA and its potential to serve as a novel non-viral transfection vector. Methods. The form of aggregation was determined employing electron microscopic techniques. The DNA binding capacity of dequalinium was assayed using SYBR(TM) Green I stain. For in vitro cell transfection experiments plasmid DNA encoding for firefly luciferase was used. Results, Dequalinium forms in aqueous medium liposome-like aggregates, which we term DQAsomes. These dequalinium vesicles bind DNA and they are able to transfect cells in vitro with an efficiency comparable to Lipofectin(TM). Conclusions. Based on the intrinsic properties of dequalinium such as the in vivo selectivity for carcinoma cells and selective accumulation in mitochondria we propose DQAsomes as a novel and unique drug and gene delivery system. C1 Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Halle Wittenberg, Inst Physiol Chem, Halle, Germany. Univ Florida, Interdisciplinary Ctr Biotechnol Res, Gainesville, FL 32611 USA. Univ Jena, Inst Ultrastruct Res, D-6900 Jena, Germany. Univ Florida, Dept Therapeut & Pharmacol, Sch Med, Gainesville, FL 32611 USA. Univ Florida, Sch Pharm, Dept Pharmaceut, Gainesville, FL 32611 USA. RP Weissig, V (reprint author), Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA USA. EM vweissig@cipr.mgh.harvard.edu FU NCI NIH HHS [CA60158]; NIGMS NIH HHS [GM47535] NR 12 TC 76 Z9 84 U1 2 U2 15 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD FEB PY 1998 VL 15 IS 2 BP 334 EP 337 DI 10.1023/A:1011991307631 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZA124 UT WOS:000072331300026 PM 9523323 ER PT J AU Tope, WD Ross, EV Kollias, N Martin, A Gillies, R Anderson, RR AF Tope, WD Ross, EV Kollias, N Martin, A Gillies, R Anderson, RR TI Protoporphyrin IX fluorescence induced in basal cell carcinoma by oral delta-aminolevulinic acid SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article; Proceedings Paper CT 6th Biennial Meeting of the International-Photodynamic-Association CY MAR 12, 1996 CL MELBOURNE, AUSTRALIA SP Int Photodynam Assoc ID 5-AMINOLEVULINIC ACID; PHOTODYNAMIC THERAPY; ENDOGENOUS PROTOPORPHYRIN; INDUCED PORPHYRIN; MURINE TUMOR; PHOTOSENSITIZATION; SKIN AB Limited depth of penetration significantly limits photodynamic therapy of nodular basal cell carcinoma (BCC) using topical delta(5)-aminolevulinic acid (ALA), To demonstrate safety and efficacy of orally administered ALA in inducing endogenous protoporphyrin IX (PpIX) production in BCC, 13 patients with BCC ingested ALA in a dose-escalation protocol, All dose ranges (10, 20 or 40 mg/kg single doses) resulted in formation of PpIX in human skin and BCC, measurable by in vivo fluorescence spectrophotometry, The PpIX fluorescence peaked in tumors before normal adjacent skin from 1 to 3 h after ALA ingestion, Gross fluorescence imaging of ex vivo specimens revealed greater PpIX fluorescence in tumor than normal skin only at the 40 mg/kg dose, Fluorescence microscopy confirmed this finding by showing distinct, full-thickness PpIX fluorescence in all subtypes of BCC only after ALA given at 40 mg/kg, Side effects were dose dependent and self limited, Photosensitivity lasting less than 24 h and nausea coinciding with peak skin PpIX fluorescence occurred at 20 and 40 mg/kg doses, After 10 mg/kg ALA, serum hepatic enzyme levels rose to a maximum within 24 h, then resolved over 13 weeks, Transient bilirubinuria occurred in two patients. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Tope, WD (reprint author), Univ Minnesota Hosp & Clin, Box 98,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 20 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD FEB PY 1998 VL 67 IS 2 BP 249 EP 255 DI 10.1562/0031-8655(1998)067<0249:PIFIIB>2.3.CO;2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YX732 UT WOS:000072071700016 PM 9487802 ER PT J AU Stanley, HE Buldyrev, SV Cruz, L Gomez-Isla, T Havlin, S Hyman, BT Knowles, R Urbanc, B Wyart, C AF Stanley, HE Buldyrev, SV Cruz, L Gomez-Isla, T Havlin, S Hyman, BT Knowles, R Urbanc, B Wyart, C TI Statistical physics and Alzheimer's disease SO PHYSICA A LA English DT Article; Proceedings Paper CT 5th International Bar-Ilan Conference on Frontiers in Condensed Matter Physics CY MAR 31-APR 03, 1997 CL BAR-ILAN UNIV, RAMAT GAN, ISRAEL SP Bar Ilan Univ, Bar Ilan Univ, Fac Nat Sci HO BAR-ILAN UNIV ID PRECURSOR; PROTEIN AB We discuss the possible utility of statistical physics in elucidating some of the puzzling phenomena that seem to occur in the brains of patients affected with Alzheimer's disease. Further, we report three specific results from this approach: (i) The size distribution of senile plaques appears to be log-normal, (ii) We develop a model for growth of senile plaques that is characterized by both aggregation and disaggregation, and (iii) We quantify neuron architecture and find quantitative evidence for the existence of microcolumns positioned at light angles to the known lamina. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. Boston Univ, Dept Phys, Boston, MA 02215 USA. Bar Ilan Univ, Dept Phys, Ramat Gan, Israel. Bar Ilan Univ, Gonda Goldschmied Ctr, Ramat Gan, Israel. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Stanley, HE (reprint author), Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. EM hes@buphyk.bu.edu RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013; Buldyrev, Sergey/I-3933-2015 OI Urbanc, Brigita/0000-0001-9159-7698; NR 9 TC 12 Z9 13 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD FEB 1 PY 1998 VL 249 IS 1-4 BP 460 EP 471 DI 10.1016/S0378-4371(97)00548-7 PG 12 WC Physics, Multidisciplinary SC Physics GA ZB572 UT WOS:000072486000066 ER PT J AU Stelnicki, EJ Vanderwall, K Harrison, MR Longaker, MT Kaban, LB Hoffman, WY AF Stelnicki, EJ Vanderwall, K Harrison, MR Longaker, MT Kaban, LB Hoffman, WY TI The in utero correction of unilateral coronal craniosynostosis SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-2; GROWTH-FACTOR-BETA; CLEFT-LIP REPAIR; SUTURE SYNOSTOSIS; RABBITS; ANOMALIES; MEMBRANES; SURGERY; MODEL AB We performed the first in utero correction of a unilateral right coronal craniosynostosis using 70-day gestation fetal lambs. The craniosynostosis was created in eight fetuses by excising their right coronal sutures, and then placing demineralized bone powder, transforming growth factor-beta, and bone morphogenetic protein-2 into the defect. Twenty-one days later, after suture fusion had occurred, four of the eight sheep were treated with a 4 mm X 12 mm strip craniectomy to open the entire synostosed right coronal suture. The edges of the excision were wrapped with 100-mu m-thick Gore-Tex (W. L. Gore & Associates, Flagstaff, Ariz.) sheets to prevent bony refusion. All eight lambs then progressed to term (140 days). The skulls of four normal, unoperated, term lambs were used as controls. At 140 days, all four treated lambs had a widely patent strip craniectomy site without any evidence of bone regeneration. This in utero correction led to a marked improvement in craniofacial morphology of three of four animals when compared with the uncorrected controls with significant (p < 0.01) correction in orbital position, skull length, and shape of the frontal bone. This was in sharp contrast to the uncorrected animals, which had marked orbital elevation, compression of the anteroposterior length of the cranial vault, frontal bone flattening, and shortening of the cranial base. The fourth corrected animal also showed evidence of improvement but had some abnormal calvarial changes secondary to the development of horns, which displaced the calvaria in a downward vector. We conclude that the in utero correction of craniosynostosis is feasible and provides a significant benefit by decreasing the severity of many of the associated deformities seen with this disorder. C1 Univ Calif San Francisco, Dept Plast Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Fetal Treatment Lab, San Francisco, CA 94143 USA. Washington Univ, St Louis, MO USA. NYU, Inst Reconstruct Plast Surg, New York, NY 10016 USA. Massachusetts Gen Hosp, Dept Oral Maxillofacial Surg, Boston, MA 02114 USA. RP Stelnicki, EJ (reprint author), Univ Calif San Francisco, Dept Plast Surg, San Francisco, CA 94143 USA. NR 30 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 1998 VL 101 IS 2 BP 287 EP 296 DI 10.1097/00006534-199802000-00004 PG 10 WC Surgery SC Surgery GA ZF104 UT WOS:000072863000004 PM 9462759 ER PT J AU Lee, WPA Strickland, JW AF Lee, WPA Strickland, JW TI Safe carpal tunnel release via a limited palmar incision SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the American-Association-of-Plastic-Surgeons CY MAY 01-03, 1995 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Plast Surgeons AB Despite its demonstrated advantages in postoperative recovery endoscopic carpal tunnel release has not been adopted by most surgeons because of the associated complications of neurovascular injury. A technique of carpal tunnel release is presented that utilizes a 1.0 to 1.5-cm palmar incision and a specially designed carpal tunnel "tome." Any aberrant anatomy of adjacent neurovascular structures may be identified under direct vision. Anatomic dissection in 28 cadaveric specimens following the procedure showed complete decompression of carpal tunnel and preservation with safe margins of the palmar cutaneous branch and thenar motor branch of median nerve, ulnar artery and nerve, and superficial palmar arch. Clinical experience with the technique in two centers consisted of 525 patients and 694 hands over a 29-month period. The great majority of patients derived complete (72.6 percent) or near-complete (19.6 percent) symptomatic relief from the procedure, and two complications (0.29 percent) of median nerve lacerations occurred. Postoperative incisional and pillar tenderness and grip, kev pinch, and three-point pinch strengths were comparable with those in published series of endoscopic carpal tunnel release. We conclude that this technique of carpal tunnel release combines the simplicity and safety of traditional open release and the reduced tissue trauma and improved postoperative recovery of the endoscopic modality. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. Indiana Univ, Sch Med, Dept Orthopaed Surg, Indianapolis, IN 46202 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Wang Ambulat Care Ctr 453, Boston, MA 02114 USA. NR 48 TC 52 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 1998 VL 101 IS 2 BP 418 EP 424 DI 10.1097/00006534-199802000-00025 PG 7 WC Surgery SC Surgery GA ZF104 UT WOS:000072863000025 PM 9462775 ER PT J AU Sachdev, D Chirgwin, JM AF Sachdev, D Chirgwin, JM TI Solubility of proteins isolated from inclusion bodies is enhanced by fusion to maltose-binding protein or thioredoxin SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID HUMAN CATHEPSIN-D; PROCATHEPSIN-D; ESCHERICHIA-COLI; PORCINE PEPSINOGEN; EXPRESSION VECTOR; IN-VITRO; ACTIVATION; PURIFICATION; SPECIFICITY; MUTAGENESIS AB When the mammalian aspartic proteinases, procathepsin D or pepsinogen, are expressed in Escherichia coli both accumulate in inclusion bodies. While pepsinogen is efficiently refolded in vitro, recovery of procathepsin D is limited by insolubility. We expressed procathepsin D and pepsinogen in E. coli, with E. coli maltose-binding protein (MBP) or thioredoxin (trx) fused to their C-termini (aspartic proteinase-MBP or aspartic proteinase-trx), The fusion proteins were still found in inclusion bodies. However, the recovery of soluble procathepsin D-MBP and procathepsin D-trx after refolding was facilitated by the bacterial fusion partners. Maltose-binding protein was more efficient than thioredoxin in increasing the recovery of soluble protein. The vector, pET23bMBPH(6), can be used for general expression of heterologous proteins in E. coli. The vector includes a histidine tag at the C-terminus of MBP to allow one-step purification of the fusion proteins under denaturing conditions. After purification, the protein of interest can be cleaved from MBP with factor Xa protease and separated from the MBP partner. Refolded pepsinogen-MBP and pepsinogen-trx were enzymatically active, but procathepsin D-MBP and procathepsin D-trx were soluble but largely inactive. The results show that the limited recovery of activity upon refolding of procathepsin D is not the consequence of competing aggregation. Thus, the fusions do not necessarily facilitate native refolding, but they do enhance the recovery of soluble protein. Such fusions could provide a system to study, in soluble form, folding states which are otherwise inaccessible because of aggregation and precipitation. (C) 1998 Academic Press. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Res Serv, San Antonio, TX 78284 USA. RP Chirgwin, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 44 TC 70 Z9 77 U1 0 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD FEB PY 1998 VL 12 IS 1 BP 122 EP 132 DI 10.1006/prep.1997.0826 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA YY157 UT WOS:000072119000017 PM 9473466 ER PT J AU Shamsi, K Balzer, T Saini, S Ros, PR Nelson, RC Carter, EC Tollerfield, S Niendorf, HP AF Shamsi, K Balzer, T Saini, S Ros, PR Nelson, RC Carter, EC Tollerfield, S Niendorf, HP TI Superparamagnetic iron oxide particles (SH U 555 A): Evaluation of efficacy in three doses for hepatic MR imaging SO RADIOLOGY LA English DT Article DE liver, MR; liver neoplasms, MR; magnetic resonance (MR), contrast enhancement ID LIVER; CONTRAST; PHARMACOKINETICS; SAFETY; TUMORS; DTPA AB PURPOSE: To evaluate the efficacy of SH U 555 A in three doses for magnetic resonance (MR) imaging in the liver and to establish the best postinjection time point for liver MR imaging. MATERIALS AND METHODS: Pre- and postcontrast image sets obtained in 169 patients after injection of SH U 555 A (randomly, 4, 8, or 16 mu mol of iron per kilogram of body weight). Three blinded readers evaluated the precontrast and 10- and 40-minute postcontrast MR images of 54, 58, and 57 patients, respectively. RESULTS: Statistically significant differences were observed in diagnostic confidence between images obtained with a dose of 4 or 16 mu mol Fe/kg (P = .011) and in good or excellent improvement, respectively, in delineation of lesions on 10-minute postcontrast images (P = .001). No apparent differences in the efficacy evaluation were seen between the 10- and 40-minute postcontrast imaging time points. CONCLUSION: There was a dose-dependent postcontrast improvement in evaluated efficacy parameters (diagnostic confidence; visual evaluations) after injection of SH U 555 A. Accumulation phase imaging could begin as early as 10 minutes after administration. C1 Schering AG, Clin Dev Diagnost, Dept Magnet Resonance & Ultrasound Contrast Media, D-13352 Berlin, Germany. Massachusetts Gen Hosp, Dept Radiol, Div Gastrointestinal Radiol, Boston, MA 02114 USA. Univ Florida, Hlth Sci Ctr, Dept Radiol, Gainesville, FL USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Schering Hlth Care, W Sussex, England. RP Shamsi, K (reprint author), Schering AG, Clin Dev Diagnost, Dept Magnet Resonance & Ultrasound Contrast Media, Mullerstr 178, D-13352 Berlin, Germany. NR 23 TC 45 Z9 58 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1998 VL 206 IS 2 BP 365 EP 371 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YT644 UT WOS:000071627700012 PM 9457187 ER PT J AU Ryan, JM Kelsey, P Ryan, BM Mueller, PR AF Ryan, JM Kelsey, P Ryan, BM Mueller, PR TI Alendronate-induced esophagitis: Case report of a recently recognized form of severe esophagitis with esophageal stricture - Radiographic features SO RADIOLOGY LA English DT Article DE drugs, effects; esophagitis; esophagus, stenosis or obstruction AB Alendronate sodium, an aminobiphosphonate used primarily to treat osteoporosis in postmenopausal women, is known to cause esophagitis. A 71-year-old woman experienced severe, acute esophagitis and severe stricture of the esophagus due to oral alendronate therapy. Unlike in previous cases, she had taken alendronate for 10 months before the onset of complications and the stricture proved resistant to dilation. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. St James Hosp, Dept Clin Med & Gastroenterol, Dublin 8, Ireland. RP Ryan, JM (reprint author), Allegheny Hahnemann Univ Hosp, Dept Radiol, Mailstop 206,Broad & Vine St, Philadelphia, PA 19102 USA. NR 13 TC 35 Z9 37 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1998 VL 206 IS 2 BP 389 EP 391 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YT644 UT WOS:000071627700015 PM 9457190 ER PT J AU Neuman, ML Murphy, BD Rosen, MP AF Neuman, ML Murphy, BD Rosen, MP TI Bedside placement of peripherally inserted central catheters: A cost-effectiveness analysis SO RADIOLOGY LA English DT Article DE catheters and catheterization; cost-effectiveness; veins, extremities AB PURPOSE: To compare two strategies for placement of peripherally inserted central catheters (PICCs). In strategy A, all PICC placements were initially attempted at the patient's bedside by trained intravenous (IV) nurses, with failures referred to the interventional radiology (IR) service. In strategy B, all PICCs were placed by interventional radiologists under fluoroscopic and/or venographic guidance. MATERIALS AND METHODS: Decision analysis and cost-effectiveness models were constructed with commercially available software. Data used in the model were obtained from a review of the authors' experience with bedside placement of PICCs by an IV team and data obtained from the literature. RESULTS: The cost-effectiveness of strategy A relative to strategy B depends on (a) the ability of the IV team to access a vein at the patient's bedside, (b) the cost of fluoroscopy or the IR suite, and (c) the intended use of the PICC. CONCLUSION: If the cost of fluoroscopy or the IR suite exceeds $100, strategy A is more cost-effective for most intended PICC uses. If the cost is less than $75, strategy B is more cost-effective for all intended PICC uses. If the cost is between $75 and $100, the most cost-effective strategy depends on the intended use of the PICC and the need to have the tip placed at the junction of the superior vena cava and right atrium. C1 Beth Israel Deaconnes Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Rosen, MP (reprint author), Beth Israel Deaconnes Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 12 TC 25 Z9 26 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1998 VL 206 IS 2 BP 423 EP 428 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YT644 UT WOS:000071627700020 PM 9457195 ER PT J AU Repace, JL Jinot, J Bayard, S Emmons, K Hammond, SK AF Repace, JL Jinot, J Bayard, S Emmons, K Hammond, SK TI Air nicotine and saliva cotinine as indicators of workplace passive smoking exposure and risk SO RISK ANALYSIS LA English DT Article DE salivary cotinine; environmental tobacco smoke; air nicotine; Monte Carlo modeling; passive smoking; workplace; lung cancer; heart disease; risk assessment ID ENVIRONMENTAL TOBACCO-SMOKE; LUNG-CANCER RISK; CORONARY HEART-DISEASE; QUALITY STANDARD; NONSMOKING WOMEN; SELF-REPORT; HEALTH; MARKERS; MULTICENTER; ABSORPTION AB We model nicotine from environmental tobacco smoke (ETS) in office air and salivary cotinine in nonsmoking U.S. workers. We estimate that: an average salivary cotinine level of 0.4 ng/ml corresponds to an increased lifetime mortality risk of 1/1000 for lung cancer, and 1/100 for heart disease; >95% of ETS-exposed office workers exceed OSHA's significant risk level for heart disease mortality, and 60% exceed significant risk for lung cancer mortality; 4000 heart disease deaths and 400 lung cancer deaths occur annually among office workers from passive smoking in the workplace, at the current 28% prevalence of unrestricted smoking in the office workplace. C1 US EPA, Off Air & Radiat, Washington, DC 20460 USA. US EPA, Off Res & Dev, Washington, DC 20460 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Repace, JL (reprint author), 101 Felicia Lane, Bowie, MD 20720 USA. EM repace@erols.com NR 68 TC 69 Z9 72 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 1998 VL 18 IS 1 BP 71 EP 83 DI 10.1111/j.1539-6924.1998.tb00917.x PG 13 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA ZB065 UT WOS:000072431500011 PM 9523445 ER PT J AU Brocke, S Hausmann, S Steinman, L Wucherpfennig, KW AF Brocke, S Hausmann, S Steinman, L Wucherpfennig, KW TI Microbial peptides and superantigens in the pathogenesis of autoimmune diseases of the central nervous system SO SEMINARS IN IMMUNOLOGY LA English DT Review DE microbial peptide antigens; superantigens; autoimmune disease ID MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; STAPHYLOCOCCAL-ENTEROTOXIN-B; T-CELL RECEPTOR; MULTIPLE-SCLEROSIS PATIENTS; MEDIATED DEMYELINATING DISEASES; MAMMARY-TUMOR VIRUS; HEAT-SHOCK-PROTEIN; MOLECULAR MIMICRY; BACTERIAL SUPERANTIGEN AB The mechanisms by which microbial peptide antigens and superantigens might initiate and perpetuate autoimmune responses against antigens of the central nervous system are discussed. A model will be proposed that includes the initial activation of naive T lymphocytes through T cell receptor-mediated recognition of microbial antigens presented by MHC class II molecules. This event might be followed by re-activation of autoreactive T cells by bacterial and viral superantigens. Bath mechanisms could lead to acute and relapsing autoimmune disease. C1 NINDS, Neurol Dis Sect, NIB, NIH, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Beckman Ctr, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Brocke, S (reprint author), NINDS, Neurol Dis Sect, NIB, NIH, 10 Ctr Dr,Bldg 10,Room 5B16, Bethesda, MD 20892 USA. NR 108 TC 28 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD FEB PY 1998 VL 10 IS 1 BP 57 EP 67 DI 10.1006/smim.1997.0105 PG 11 WC Immunology SC Immunology GA 131NE UT WOS:000076581500007 PM 9529656 ER PT J AU Roback, MG Stack, AM Thompson, C Brugnara, C Schwarz, HP Saladino, RA AF Roback, MG Stack, AM Thompson, C Brugnara, C Schwarz, HP Saladino, RA TI Activated protein C concentrate for the treatment of meningococcal endotoxin shock in rabbits SO SHOCK LA English DT Article ID PURPURA FULMINANS; SEPTIC SHOCK; DEFICIENCY; COAGULATION; SEPSIS; PATHOPHYSIOLOGY; PLASMA AB To evaluate the effects of activated protein C therapy in a rabbit model of meningococcal endotoxin-induced shock, we performed a prospective, blinded, placebo-controlled animal trial, Forty New Zealand White rabbits were challenged with intravenous meningococcal endotoxin (lipooligosaccharide) 100 mu g/kg. Ten minutes before endotoxin challenge, animals were administered either activated protein C 1600 mu g/mL (n = 20) or an equal volume of saline (n = 20) as an initial bolus, After endotoxin challenge, activated protein C treated animals were administered a continuous infusion of activated protein C 160 mu g/kg/h and saline-treated animals were administered an equal volume infusion of saline. Both activated protein C treated and saline control animals demonstrated evidence of shock after endotoxin challenge: mean arterial pressure and serum bicarbonate significantly (p < .01) declined, and heart rate significantly (p < .01) increased from baseline. In activated protein C treated animals, mean plasma activated protein C activity was 5.69 mu g/mL (+/- 3.2) 1 h after challenge, whereas plasma protein C activity was not detected in controls. Mean prothrombin and activated partial thromboplastin times were significantly (p less than or equal to. 01) prolonged compared with saline-treated controls. Other hematologic and chemical measurements did not differ between groups. Fifteen of 20 (75%) animals treated with activated protein C concentrate survived to 24 h, while 9 of 20 (45%) control animals survived to 24 h (p = .05). Those animals treated with activated protein C had improved survival, which corroborates the findings of early clinical studies in which replacement of protein C improved outcome. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Lab Med, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Denver, CO 80218 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Med,Div Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. Immuno AG Wien, Vienna, Austria. RP Saladino, RA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Med,Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 22 TC 33 Z9 34 U1 0 U2 0 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9,, AUGUSTA, GA 30901 USA SN 1073-2322 J9 SHOCK JI Shock PD FEB PY 1998 VL 9 IS 2 BP 138 EP 142 DI 10.1097/00024382-199802000-00011 PG 5 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA YU938 UT WOS:000071771700011 PM 9488260 ER PT J AU Willers, H Heilmann, HP Beck-Bornholdt, HP AF Willers, H Heilmann, HP Beck-Bornholdt, HP TI First century of radiation therapy: Historical origins and developments of fractionated irradiation in the German speaking countries SO STRAHLENTHERAPIE UND ONKOLOGIE LA German DT Article DE history; fractionation; dose per fraction; X-ray therapy ID ONCOLOGY; RADIOTHERAPY AB This review studies the historical development of fractionated X-ray therapy in the German speaking countries until World War II. Fractionated treatments appear to have their origin already in the first attempts of fractionation performed by Freund in 1896. In the following, fractionated treatments could not compete with the so-called single dose or intensive radiation treatment in Germany. However, until the 1920s there were repeated sporadic attempts of various motifs to distribute the radiation doses over a prolonged period of lime. Only with the end of the 1920s the conditions for a rise of fractionated irradiation were favourable, mainly due the fiasco of the intensive treatments and their subsequent decline. The impulse for this rise, however, came from France where Coutard had developed an individual empirical treatment regimen with great clinical success. This technique and its modifications and developments spread over Europe and America fast. In spite of the similarities between the various fractionation methods used during the first decades of the century, review of the radiological literature of that time fails to show any logical scientific connection of these methods, but rather there was a mix and overlap of irradiation attempts of various motivations. Thus, radiation therapy, and thereby the current standard fractionation scheme of 1.8 to 2 Gy per fraction 5 times per week, obviously did not grow out of a scientific basis, but originated from individual observation of patients and empirical experience. C1 Univ Hamburg, Inst Biophys & Strahlenbiol, D-20246 Hamburg, Germany. AK St Georg, Hermann Holthusen Inst Strahlentherapie, Hamburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Beck-Bornholdt, HP (reprint author), Univ Hamburg, Inst Biophys & Strahlenbiol, Martinistr 52, D-20246 Hamburg, Germany. NR 85 TC 6 Z9 7 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA LINDWURMSTRASSE 95, D-80337 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD FEB PY 1998 VL 174 IS 2 BP 53 EP 63 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 129RY UT WOS:000076477800001 PM 9487366 ER PT J AU Manno, EM Gress, DR Schwamm, LH Diringer, MN Ogilvy, CS AF Manno, EM Gress, DR Schwamm, LH Diringer, MN Ogilvy, CS TI Effects of induced hypertension on transcranial Doppler ultrasound velocities in patients after subarachnoid hemorrhage SO STROKE LA English DT Article DE ultrasonography, Doppler; subarachnoid hemorrhage; hypertension ID CEREBRAL BLOOD-FLOW; VASOSPASM; AUTOREGULATION; PRESSURE; ARTERIES; HEMODYNAMICS; PERFORMANCE; SONOGRAPHY; DIAGNOSIS; RESPONSES AB Background and Purpose-Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension, To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction and withdrawal of induced hypertension in patients after subarachnoid hemorrhage. Methods-Twenty-eight patients were studied during the induction and withdrawal of hypertension using primarily phenylephrine. Continuous monitoring was performed on the middle cerebral artery with the highest flow velocity. Treatment was based on rising TCD velocities or clinical evidence for cerebral vasospasm. Mean arterial pressure and mean TCD velocities were recorded every minute. A change of >15% from starting TCD values was considered significant. Cerebral autoregulation was calculated as a percentage of intact autoregulation. Patients were subsequently divided into groups of disturbed and intact autoregulation. Results-In 10 of 19 patients (53%), TCD velocities changed by >15% and paralleled changes in mean arterial pressure, This directly altered the TCD interpretation of the grade of vasospasm in 7 of 19 patients (36%), Three additional patients had smaller absolute changes in TCD velocities. No clinical difference could be identified between patients with disturbed and intact autoregulation. Conclusions-In patients with disturbed autoregulation after subarachnoid hemorrhage, induced hypertension can alter cerebral blood Dow velocities. The level of autoregulation needs to be considered when interpreting TCD velocities in patients after subarachnoid hemorrhage. C1 Washington Univ, Sch Med, Dept Neurol, Neurol Neurosurg Intens Care Unit, St Louis, MO 63110 USA. Univ Calif San Francisco, Neurovasc Stroke Serv, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manno, EM (reprint author), Washington Univ, Sch Med, Dept Neurol, Neurol Neurosurg Intens Care Unit, Campus Box 8111,660 S Euclid Ave, St Louis, MO 63110 USA. RI Diringer, Michael/C-1165-2008; OI Diringer, Michael/0000-0003-2337-5537; Schwamm, Lee/0000-0003-0592-9145 NR 35 TC 55 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1998 VL 29 IS 2 BP 422 EP 428 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YW406 UT WOS:000071932100014 PM 9472884 ER PT J AU Finlayson, SRG Birkmeyer, JD AF Finlayson, SRG Birkmeyer, JD TI Cost-effectiveness analysis in surgery SO SURGERY LA English DT Article ID HEALTH; OREGON; REVASCULARIZATION; ANEURYSMS; DECISION AB Background. With tighter constraint's on health care spending many recognize the need to identify and restrict clinical interventions that are not cost-effective. As a result, cost-effectiveness analysis is being used increasingly to assess the relative value of surgical interventions. Methods and Results. We first present the general concept of cost-effectiveness analysis and review a recent study of carotid endarterectomy to demonstrate the technique. We next consider the classic application of cost-effectiveness analysis to resource-allocation decisions and use the Oregon Medicaid experiment to illustrate some potential problems with this approach. We then present the current role of cost-effectiveness analysis: informing decisions about individual interventions that am new, controversial, or in direct competition with an accepted alternative treatment. Finally, we review several limitations of the methods used to measure costs and benefits and discuss problems with thp interpretation of cost-effectiveness studies. Conclusions, Cost-effectiveness analysis is a systematic approach to assessing the relative value of health care interventions. This technique is being used increasingly to frame clinical policy decisions in surgery. Because of this, surgeons need to understand cost-effectiveness analysis and be prepared to examine these studies critically. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03756 USA. Dept Vet Affairs Med Ctr, Surg Serv, White River Junction, VT USA. RP Finlayson, SRG (reprint author), Massachusetts Gen Hosp, Dept Surg, Fruit st, Boston, MA 02114 USA. NR 27 TC 18 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 1998 VL 123 IS 2 BP 151 EP 156 DI 10.1016/S0039-6060(98)70252-1 PG 6 WC Surgery SC Surgery GA YX231 UT WOS:000072019500007 PM 9481400 ER PT J AU Surgenor, DM Churchill, WH Wallace, EL Rizzo, RJ McGurk, S Goodnough, LT Kao, KJ Koerner, TAW Olson, JD Woodson, RD AF Surgenor, DM Churchill, WH Wallace, EL Rizzo, RJ McGurk, S Goodnough, LT Kao, KJ Koerner, TAW Olson, JD Woodson, RD TI The specific hospital significantly affects red cell and component transfusion practice in coronary artery bypass graft surgery: a study of five hospitals SO TRANSFUSION LA English DT Article ID NEW-YORK-STATE; MORTALITY; BLOOD; DETERMINANTS AB BACKGROUND: Interhospital differences in blood transfusion practice during coronary artery bypass graft (CABG) surgery have been noted, but the underlying issues have not been identified. STUDY DESIGN AND METHODS: Records of 3217 consecutive CABG cases in five university teaching hospitals in 1992 and 1993 were stratified by hospital, type of revascularization conduit, patients' sex, and other factors. Statistical methods were used to compare patient characteristics, transfusion outcomes, and hospital outcomes. RESULTS: Forward two-step logistic regression using patient likelihood of red cell transfusion factors in the first step and the specific hospital in the second step revealed a significant effect of hospital on the Delta odds ratios for red cell transfusion. This finding was confirmed by analyses of a highly stratified subset of cases, males in diagnosis-related group 107 (primary cases of coronary bypass without coronary catheterization) who underwent revascularization with venous and internal mammary artery grafts, revealing variations among hospitals from 109 to 457 units of red cells transfused per hundred cases. Corresponding variations in transfusions of all blood components were from 324 to 1019 units by hospital. Variation in red cell transfusion practice among surgeons in the same hospital was not responsible for these interhospital differences. CONCLUSION: The effect of the specific hospital on transfusion practice is attributed to institutional differences that, through reasons of training or hierarchy, become ingrained in hospitals. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Clin Labs,Div Hematol Oncol, Boston, MA 02115 USA. Ctr Management Syst, Snowmass Village, CO USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Barnes Hosp, Div Lab Med, St Louis, MO 63110 USA. Univ Florida, Shands Hosp, Dept Pathol & Lab Med, Gainesville, FL USA. Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. Univ Wisconsin, Dept Med, Hematol Sect, Madison, WI USA. RP Surgenor, DM (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-33774] NR 21 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 1998 VL 38 IS 2 BP 122 EP 134 DI 10.1046/j.1537-2995.1998.38298193094.x PG 13 WC Hematology SC Hematology GA ZC744 UT WOS:000072612800002 PM 9531943 ER PT J AU Nickerson, CAE Jasper, JD Asch, DA AF Nickerson, CAE Jasper, JD Asch, DA TI Comfort level, financial incentives, and consent for organ donation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 33rd Annual Congress of the Japan-Society-for-Transplantation CY SEP 16-18, 1997 CL OSAKA, JAPAN SP Japan Soc Transplantat ID TRANSPLANTATION; ATTITUDES; MARKET; EDUCATION; ETHICS C1 Vet Affairs Med Ctr, Sect 111GM, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Operat & Informat Management, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Nickerson, CAE (reprint author), Vet Affairs Med Ctr, Sect 111GM, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 35 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1998 VL 30 IS 1 BP 155 EP 159 DI 10.1016/S0041-1345(97)01218-9 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZA145 UT WOS:000072333400050 PM 9474988 ER PT J AU Zhang, M Martin, KJ Sheng, SJ Sager, R AF Zhang, M Martin, KJ Sheng, SJ Sager, R TI Expression genetics: a different approach to cancer diagnosis and prognosis SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; PROMYELOCYTIC LEUKEMIA; CARCINOMA CELLS; DOWN-REGULATION; RETINOIC ACID; MASPIN; MECHANISMS; NEOPLASIA; PARADIGM; INVASION AB Expression genetics is a new approach to the identification of cancer-related genes. Instead of studying gene mutations at the genome level, it focuses on the investigation of heredity at the RNA level. By isolating genes whose expression is up or down regulated in cancers, expression geneticists study their function in the context of gene regulation. A major goal of expression genetics in cancer is to correct gene expression in tumors by the application of potential therapeutic agents. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhang, M (reprint author), Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. EM mzhang@bcm.tmc.edu NR 36 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 1998 VL 16 IS 2 BP 66 EP 71 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YW718 UT WOS:000071965700006 PM 9487733 ER PT J AU D'Amico, AV Chang, E Garnick, M Kantoff, P Jiroutek, M Tempany, CM AF D'Amico, AV Chang, E Garnick, M Kantoff, P Jiroutek, M Tempany, CM TI Assessment of prostate cancer volume using endorectal coil magnetic resonance imaging: A new predictor of tumor response to neoadjuvant androgen suppression therapy SO UROLOGY LA English DT Article ID BLADDER-CANCER; ONCOLOGY GROUP AB Objectives. A clinical tool that can reliably assess prostate cancer response to androgen suppression is lacking. This pilot study was designed to identify the potential clinical factor(s) that correlate with tumor response after neoadjuvant therapy. Methods. Twenty-one patients managed with definitive local therapy and neoadjuvant androgen suppression (median 3 months [range 2 to 7]) between 1995 and 1997 comprise the study population. Fisher's exact test was used to test the significance of the proportion of patients with a given clinical factor and the outcome of pathologic organ-confined disease. The clinical factors tested included preoperative prostate-specific antigen, biopsy Gleason score, clinical stage, months of total androgen suppression, the change in the endorectal magnetic resonance imaging (erMRI)-defined stage, the change in erMRI-defined tumor, and the change in the erMRI-defined prostate volume during neoadjuvant androgen suppression. Results. All 21 patients had a decrease in the erMRI-determined prostate volume and prostate-specific antigen during androgen suppression, whereas only 10 of 21 (48%) had a reduction in the erMRI-determined tumor volume. There was a statistically significant increased proportion of patients with a decrease in the erMRI-determined tumor volume (P = 0.008) who had pathologic organ-confined disease. Conclusions. The results of this pilot study suggest that the changes in the erMRI-determined tumor volume occurring during androgen suppression may be predictive of the tumor response. Validation in a larger prospective study is currently underway. (C) 1998, Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. New England Deaconess Beth Israel Med Ctr, Dept Med Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD FEB PY 1998 VL 51 IS 2 BP 287 EP 292 DI 10.1016/S0090-4295(97)00610-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA YX582 UT WOS:000072055000021 PM 9495713 ER PT J AU Koenig, F Larne, R Enquist, H McGovern, FJ Schomacker, KT Kollias, N Deutsch, TF AF Koenig, F Larne, R Enquist, H McGovern, FJ Schomacker, KT Kollias, N Deutsch, TF TI Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma SO UROLOGY LA English DT Article ID CANCER AB Objectives. To assess the diagnostic potential of diffuse reflectance spectroscopy for the detection of bladder carcinoma during cystoscopy. Our hypothesis is that neovasculature in neoplastic (dysplastic and malignant) regions will lead to a blood absorption "signature" that is different from that of normal tissue. Methods. Diffuse reflectance measurements have been performed in 14 patients undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder surface. A standard cystoscopy xenon light source was used for illumination and the reflectance spectra were recorded using an optical multichannel analyzer (OMA) system. From the spectra, the relative concentrations of hemoglobin (Hb), oxyhemoglobin (HbO(2)), oxygen saturation (HbO(2)%), and the total amount of blood (arbitrary units) were calculated to assess their usefulness in differentiating between neoplastic and benign bladder areas. Results. The spectra of 26 bladder areas (9 malignant areas including 4 carcinomata in situ, 2 dysplastic lesions, and 15 benign areas) have been analyzed. Only the total amount of blood was a useful parameter for the differentiation between neoplastic and benign bladder areas. The sensitivity, specificity, and positive and negative predictive values of this method for neoplastic tissue were found to be 91%, 60%, 63%, and 90%, respectively. Conclusions. The measurement of diffuse reflectance is a fast, simple, and noninvasive method which allows in vivo determination of bladder blood perfusion. The total blood concentration was increased in neoplastic bladder tissue, making it a tool for tissue diagnosis. The relatively low specificity is a result of inflammatory areas also exhibiting an increased total blood concentration. This pilot study encourages further studies to assess the usefulness of reflectance measurements for enhanced detection of bladder cancer. (C) 1998, Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Koenig, F (reprint author), Urol Klin Char, Schumannstr 20-21, D-10117 Berlin, Germany. NR 9 TC 47 Z9 48 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD FEB PY 1998 VL 51 IS 2 BP 342 EP 345 DI 10.1016/S0090-4295(97)00612-2 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA YX582 UT WOS:000072055000034 PM 9495726 ER PT J AU Kiatboonsri, C Resnick, SC Chan, KM Barbers, RG Marboe, CC Khonsary, A Santiago, SM Sharma, OP AF Kiatboonsri, C Resnick, SC Chan, KM Barbers, RG Marboe, CC Khonsary, A Santiago, SM Sharma, OP TI The detection of recurrent sarcoidosis by FDG-PET in a lung transplant recipient SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; PULMONARY SARCOIDOSIS C1 Univ So Calif, Div Pulm & Crit Care Med, Los Angeles, CA USA. Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Sect, W Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Nucl Med Sect, W Los Angeles, CA USA. RP Chan, KM (reprint author), Henry Ford Hosp, Div Pulm & Crit Care Med, 2799 W Grand Blvd, Detroit, MI 48202 USA. NR 7 TC 11 Z9 11 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD FEB PY 1998 VL 168 IS 2 BP 130 EP 132 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YX309 UT WOS:000072027300013 PM 9499753 ER PT J AU Cooper, DKC AF Cooper, DKC TI Xenoantigens and xenoantibodies SO XENOTRANSPLANTATION LA English DT Article; Proceedings Paper CT 4th International Congress for Xenotransplantation CY SEP 07-11, 1997 CL NANTES, FRANCE DE glycosylated epitopes; pig vascular endothelial cells; antibodies ID ALPHA-GALACTOSYL EPITOPES; HUMAN NATURAL ANTIBODIES; ANTI-PIG XENOANTIBODY; KIDNEY PK15 CELLS; ORGAN XENOTRANSPLANTATION; CARBOHYDRATE ANTIGENS; THOMSEN-FRIEDENREICH; TRANSGENIC MICE; HUMAN-SERA; BABOON AB Major efforts are being directed towards determining and modifying the glycosylated epitopes on pig vascular endothelial cells, against which human natural antibodies are directed. Genetic engineering techniques are being used in an effort to knock out or replace the major alpha galactosyl (alpha Gal) epitopes in mice, but to-date these have been only modestly successful in prolonging functional survival of such modified organs. Competitive glycosylation involving insertion of the gene for alpha 1,2 fucosyltransferase results in reduction of alpha Gal expression but also of presentation of hitherto cryptic antigens against which natural human antibodies are directed or could develop. The introduction of the gene for N-acetylglucosaminyltransferase III has been demonstrated to significantly reduce alpha Gal expression, and the intracellular expression of single chain Fv antibodies against alpha 1,3 galactosyltransferase also represses this enzyme activity. Several other carbohydrate antigens have been identified that could act as targets for human natural antibodies, and these include Gal alpha 1-3Le(x), Hanganutziu-Deicher, Tn, and Forssman antigens, The alternative approach, namely, the depletion of the recipient's natural antibodies, is proving difficult, but techniques for inducing B cell tolerance are being explored. The induction of a state of mixed hematopoietic chimerism in alpha Gal knockout mice has resulted in tolerance to the alpha Gal antigen. Tolerance to the SLA antigens of miniature swine is also being attempted in baboons by the transfer of SLA Class II genes into baboon bone marrow cells, It is hoped that one or a combination of these approaches may overcome the problem created by the presence of pig antigens against which humans have xenoreactive antibodies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 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. NR 115 TC 112 Z9 114 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1998 VL 5 IS 1 BP 6 EP 17 DI 10.1111/j.1399-3089.1998.tb00003.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA ZA348 UT WOS:000072354500003 PM 9507728 ER PT J AU Chitilian, HV Laufer, TM Stenger, K Shea, S Auchincloss, H AF Chitilian, HV Laufer, TM Stenger, K Shea, S Auchincloss, H TI The strength of cell-mediated xenograft rejection in the mouse is due to the CD4+ indirect response SO XENOTRANSPLANTATION LA English DT Article; Proceedings Paper CT 4th International Congress for Xenotransplantation CY SEP 07-11, 1997 CL NANTES, FRANCE DE CD4+ T cells; xenograft rejection; indirect response ID T-CELLS; EXPRESSION; MICE AB Previous studies have shown that CD4+ T cells are responsible for the great strength of cell-mediated xenograft rejection in the mouse. In vitro studies have suggested that this CD4+ response is to xenogeneic antigens that are presented indirectly. The present studies were carried out in order to determine whether the strength of cell-mediated xenograft rejection in vivo is dependent on the CD4+ indirect response. We grafted pig skin onto mice that express class II MHC antigens only on their thymic epithelial cells (II-4+ mice). These mice have normal numbers of functional peripheral CD4+ T cells; however they lack class II MHC expression on their antigen presenting cells and are thus incapable of mounting a CD4+ T cell-mediated indirect response. Xenograft survival was prolonged on these mice. Furthermore, administration of cyclosporine and anti-CD8 monoclonal antibodies to II-4+ recipients prolonged xenograft survival to at least the same extent as allograft survival, demonstrating that the strength of cell-mediated xenograft rejection resides in the CD4+ indirect response. Despite the increased survival time, xenograft rejection still occurred in the absence of the indirect pathway. Depletion of the II-4+ recipients of their CD4+ T cell population prolonged xenograft survival even further, suggesting the presence of a weaker CD4+ direct mechanism which was virtually undetectable in vitro. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. RP Auchincloss, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Transplantat Unit, 55 Fruit St,Gray 504, Boston, MA 02114 USA. NR 16 TC 39 Z9 41 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1998 VL 5 IS 1 BP 93 EP 98 DI 10.1111/j.1399-3089.1998.tb00014.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA ZA348 UT WOS:000072354500014 PM 9507739 ER PT J AU Zhao, Y Barth, RN Swenson, K Pearson, DA Sykes, M AF Zhao, Y Barth, RN Swenson, K Pearson, DA Sykes, M TI Functionally and phenotypically mature mouse CD8(+) T cells develop in porcine thymus grafts in mice SO XENOTRANSPLANTATION LA English DT Article; Proceedings Paper CT 4th International Congress for Xenotransplantation CY SEP 07-11, 1997 CL NANTES, FRANCE DE xenogeneic transplantation; thymopoiesis; CD8; T cell; positive selection; negative selection; thymus; tolerance ID POSITIVE SELECTION; NEGATIVE SELECTION; XENOGENEIC BARRIER; CLONAL DELETION; TOLERANCE; REGIMEN; TRANSPLANTATION; DIFFERENTIATION; LYMPHOCYTES; THYMOCYTES AB Mouse CD4(+) T cells efficiently develop in fetal pig thymus (FP THY) grafts and repopulate the periphery of T cell and NK cell-depleted, thymectomized (ATX) mice. However, efficient peripheral repopulation of mouse CD8(+) T cells does not occur in these mice. We have therefore evaluated the maturation and function of mouse CD8 single positive (SP) thymocytes in fetal pig thymus and liver fragment (FP THY LIV) grafts. Phenotypic maturity, as measured by upregulated expression of TCR, class I MHC, and Qa-2, and downregulated expression of heat stable antigen (HSA) on CD8 SP cells in FP THY grafts, was similar to that in host thymi of euthymic control mice. Cytolytic T lymphocyte (CTL) activity of thymocytes from FP THY grafts was similar to that of thymocytes from host thymi of euthymic mice, indicating that functional maturation of CD8 SP cells had taken place in the grafts. Furthermore, similarly efficient deletion of V beta 5.1/5.2(+) and V beta 11(+) CD8 SP cells was observed in FP THY grafts as in host thymi of euthymic control mice. Similar percentages of V beta 6, V beta 7, and V beta 8.1/8.2 expressing cells were also detected among CD8 SP cells in FP THY grafts and host thymi of euthymic controls. Together, our results suggest that normal positive and negative selection occurs, and that mouse CD8(+) cells can undergo normal functional and phenotypic maturation in FP THY grafts. Thus, other explanations must be sought for the failure of CD8(+) cells to repopulate the peripheral lymphoid tissues of ATX, T cell-depleted, pig THY/LIV-grafted mice. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Surg Serv,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Surg Serv,Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014 FU NIAID NIH HHS [P01-AI39755] NR 28 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 1998 VL 5 IS 1 BP 99 EP 104 DI 10.1111/j.1399-3089.1998.tb00015.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA ZA348 UT WOS:000072354500015 PM 9507740 ER PT J AU Ogata, H Inoue, N Podolsky, DK AF Ogata, H Inoue, N Podolsky, DK TI Identification of a goblet cell-specific enhancer element in the rat intestinal trefoil factor gene promoter bound by a goblet cell nuclear protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; EPIDERMAL GROWTH-FACTOR; SUCRASE-ISOMALTASE GENE; MOLECULAR-CLONING; BINDING-PROTEINS; REPORTER GENE; DNA-BINDING; P-DOMAIN; EXPRESSION; PS2 AB Intestinal trefoil factor (ITF) is selectively expressed in goblet cells of the small and large intestinal mucosa. Detailed analysis of the rat ITF (RITF) promoter was undertaken by transient transfection and gel mobility shift assays (GMSAs) using the goblet cell-like LS174T colon cancer-derived cell line. Various lengths of wild-type or mutant constructs of the 5'-flanking region were linked to the pXP2 reporter gene luciferase. Expression of -118 RITF was significantly decreased compared with -154 RITF, and transfection with an 18-base pair construct (-141 to -124) resulted in more than 5-fold greater expression than transfection with the promoterless pXP2 gene construct alone. Using various synthetic oligonucleotide mutants, GMSAs revealed that only a 9-base pair sequence (CCCCTCCCC) in this element was required for specific binding, overlapping but distinct from a Spl-like element. GMSA demonstrated that this element was specifically bound by nuclear proteins from intestinal cells with a goblet cell-like phenotype. These studies demonstrate that a 9-base pair element (goblet cell response element) between -154 and -118 in the RITF promoter gene is a cis-active element bound by a distinct nuclear transcription factor and is capable of directing intestine and goblet cell-specific expression. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Fruit St, Boston, MA 02114 USA. EM Podolsky.Daniel@mgh.harvard.edu RI Ogata, Haruhiko/B-3964-2014 FU NIDDK NIH HHS [DK43351, DK46906] NR 42 TC 34 Z9 37 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 30 PY 1998 VL 273 IS 5 BP 3060 EP 3067 DI 10.1074/jbc.273.5.3060 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600077 PM 9446622 ER PT J AU Saalmuller, A Pauly, T Lunney, JK Boyd, P Aasted, B Sachs, DH Arn, S Bianchi, A Binns, RM Licence, S Whyte, A Blecha, F Chen, Z Chu, RM Davis, WC Denham, S Yang, H Whittall, T Parkhouse, RM Dominguez, J Ezquerra, A Alonso, F Horstick, G Howard, C Sopp, P Kim, YB Lipp, J Mackay, C Magyar, A McCullough, K Arriens, A Summerfield, A Murtaugh, M Nielsen, J Novikov, B Pescovitz, MD Schuberth, HJ Leibold, W Schutt, C Shimizu, M Stokes, C Haverson, K Bailey, M Tlaskalova, H Trebichavsky, I Valpotic, I Walker, J Lee, R Zuckermann, F AF Saalmuller, A Pauly, T Lunney, JK Boyd, P Aasted, B Sachs, DH Arn, S Bianchi, A Binns, RM Licence, S Whyte, A Blecha, F Chen, Z Chu, RM Davis, WC Denham, S Yang, H Whittall, T Parkhouse, RM Dominguez, J Ezquerra, A Alonso, F Horstick, G Howard, C Sopp, P Kim, YB Lipp, J Mackay, C Magyar, A McCullough, K Arriens, A Summerfield, A Murtaugh, M Nielsen, J Novikov, B Pescovitz, MD Schuberth, HJ Leibold, W Schutt, C Shimizu, M Stokes, C Haverson, K Bailey, M Tlaskalova, H Trebichavsky, I Valpotic, I Walker, J Lee, R Zuckermann, F TI Overview of the Second International Workshop to define swine cluster of differentiation (CD) antigens SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CA SP Int Union Immunol Soc, Vet Immunol Comm DE swine; Cluster of Differentiation (CD); antigens; monoclonal antibodies (mAb) ID CYTOLYTIC T-LYMPHOCYTES; MONOCLONAL-ANTIBODIES; NATURAL-KILLER; PORCINE CD44; CELLS; MOLECULES; PIG; GRANULOCYTES; EXPRESSION; SUBSETS AB The aim of the Second International Swine Cluster of Differentiation (CD) Workshop, supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (MS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters. At the summary meeting of the workshop in July, 1995, revisions in the existing nomenclature for Swine CD were approved, so that the rules are now in accord with those for human and luminant CD. Swine CD numbers will now be given to clusters of mAb to swine orthologues of human CD molecules when homology is proven by (1) suitable tissue distribution and lymphoid cell subset expression, (2) appropriate molecular mass of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned swine gene products, or cross-reactivity of the mAb on the human gene products. In some cases: this reactivity would not be fully proven, mainly due to the lack of cloned gene products; for these CD antigens, the respective clusters will be assigned by the prefix 'w' which will lead to 'wCD' antigens. As a result of the Second International Swine CD Workshop the assignment of IG mAb to existing CD groups (CD2a, CD4a, CD5a, wCD6, wCD8, CD14, CD18a, wCD21, wCD25) was confirmed. and 2 mAb to existing swine workshop clusters (SWC). More importantly, for the work an the porcine immune system, was the definition of 5 new swine CD antigens, namely CD3 (recognized by 6 new mAb and 3 epitopes), CD16 (I new mAb), wCD29 (2 mAb), CD45RA (3 mAb) and CD45RC (1 new mAb), Finally, the demarcation of two new SWC molecules in swine, SWC8 (2 mAb) and SWC9 (2 mAb) was confirmed. (C) 1998 Elsevier Science B.V. C1 Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. USDA ARS, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Royal Vet Univ, Dept Vet Virol & Immunol, Frederiksberg C, Denmark. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. CDI, Cent Vet Inst, Lelystad, Netherlands. AFRC, Inst Anim Physiol, Cambridge CB2 4AT, England. Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA. Diagn & Clin Res, Pharmingen, San Diego, CA USA. Pig Res Inst Taiwan, Chunan, Taiwan. Washington State Univ, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA. IAH Pirbright Lab, Woking, Surrey, England. CISA, INIA, Madrid, Spain. Johannes Gutenberg Univ Mainz, Med Klin 2, D-6500 Mainz, Germany. IAH, BBSRC, Newbury RG20 7NN, Berks, England. Finch Univ Hlth Sci Chicago Med Sch, Dept Microbiol & Immunol, N Chicago, IL 60064 USA. Leukosite INC, Boston, MA 02115 USA. VIRCC, Lab Transplantat Immunol, Vienna, Austria. Eotvos Lorand Univ, Dept Immunol, H-1364 Budapest, Hungary. Inst Viruskrankheiten & Immunprophylaxe, CH-3147 Mittelhausern, Switzerland. Univ Minnesota, Coll Vet Med, Dept Vet Pathobiol, St Paul, MN 55108 USA. State Vet Inst Virus Res, DK-4771 Kalvehave, Denmark. All Russian Res Inst Vet Virol & Microbiol, Pokrov, Russia. Indiana Univ Hosp, Dept Surg, Indianapolis, IN 46202 USA. TH Hannover, Hannover, Germany. EMA Univ, Inst Immunol & Transfus Med, Greifswald, Germany. Natl Inst Anim Hlth, Ibaraki, Osaka 305, Japan. Univ Bristol, Sch Med, Dept Vet Med, Bristol, Avon, England. Acad Sci Czech Republic, Inst Microbiol, Prague, Czech Republic. Gnotobiol Lab, Novy Hradek, Czech Republic. Univ Zagreb, Fac Vet, Dept Biol, Zagreb 41000, Croatia. Univ Melbourne, Sch Vet Sci, Ctr Anim Biotechnol, Parkville, Vic 3052, Australia. Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61801 USA. RP Saalmuller, A (reprint author), Fed Res Ctr Virus Dis Anim, POB 1149, D-7400 Tubingen, Germany. RI Mackay, Charles/A-9673-2008; Ezquerra, Angel/I-3440-2012; Dominguez, Javier/I-1210-2015; OI Mackay, Charles/0000-0002-6338-7340; Parkhouse, Michael/0000-0001-5967-3291; Ezquerra, Angel/0000-0002-1824-5087; Summerfield, Artur/0000-0001-8292-4634 NR 44 TC 40 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 207 EP 228 DI 10.1016/S0165-2427(97)00098-6 PG 22 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400002 PM 9589560 ER PT J AU Aasted, B Gori, K Dominguez, J Ezquerra, A Bullido, R Arn, S Bianchi, A Binns, R Chu, RM Davis, WC Denham, S Haverson, K Jensen, KT Kim, YB Magyar, A Petersen, KR Saalmuller, A Sachs, D Schutt, C Shimizu, M Stokes, C Whittall, T Yang, H Zuckermann, F AF Aasted, B Gori, K Dominguez, J Ezquerra, A Bullido, R Arn, S Bianchi, A Binns, R Chu, RM Davis, WC Denham, S Haverson, K Jensen, KT Kim, YB Magyar, A Petersen, KR Saalmuller, A Sachs, D Schutt, C Shimizu, M Stokes, C Whittall, T Yang, H Zuckermann, F TI Immunoprecipitation studies of monoclonal antibodies submitted to the Second International Swine CD Workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CALIFORNIA SP Int Union Immunol Soc, Vet Immunol Comm DE immunoprecipitation assay; monoclonal antibodies; International Swine CD workshop C1 Royal Vet & Agr Univ, Dept Vet Virol & Immunol, DK-1870 Frederiksberg C, Denmark. CISA, INIA, Valdeolmos 28130, Madrid, Spain. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Cent Vet Inst, CDI, NL-8200 AB Lelystad, Netherlands. Babraham Inst, Dept Immunol, T Cell Lab, Cambridge CB2 4AT, England. Pig Res Inst Taiwan, Chunan 35099, Taiwan. Washington State Univ, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA. AFRC, Inst Anim Hlth, Pirbright Lab, Woking GU24 0NF, Surrey, England. Univ Bristol, Sch Med, Dept Vet Med, Bristol BS18 7DV, Avon, England. Finch Univ Hlth Sci Chicago Med Sch, Dept Microbiol & Immunol, N Chicago, IL 60064 USA. Univ L Rotvos, Dept Immunol, H-2131 God, Hungary. Fed Res Ctr Virus Dis Anim, D-72001 Tubingen, Germany. Univ Greifswald, Inst Immunol & Transfus Med, D-17487 Greifswald, Germany. Natl Inst Anim Hlth, Oho, Ibaraki 305, Japan. Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61801 USA. RP Aasted, B (reprint author), Royal Vet & Agr Univ, Dept Vet Virol & Immunol, DK-1870 Frederiksberg C, Denmark. RI Ezquerra, Angel/I-3440-2012; Dominguez, Javier/I-1210-2015; OI Ezquerra, Angel/0000-0002-1824-5087 NR 2 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 229 EP 236 DI 10.1016/S0165-2427(97)00099-8 PG 8 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400003 PM 9589561 ER PT J AU Saalmuller, A Pauly, T Aasted, B Jensen, KT Sachs, DH Arn, S Davis, WC Park, YH McCullough, K Summerfield, A Murtaugh, M Pampusch, MS Burger, KD Laber, J Nielsen, J Pescovitz, MD Stokes, C Haverson, K Boyd, P Lunney, JK AF Saalmuller, A Pauly, T Aasted, B Jensen, KT Sachs, DH Arn, S Davis, WC Park, YH McCullough, K Summerfield, A Murtaugh, M Pampusch, MS Burger, KD Laber, J Nielsen, J Pescovitz, MD Stokes, C Haverson, K Boyd, P Lunney, JK TI Summary of the first round analyses of the Second International Swine CD Workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CALIFORNIA SP Int Union Immunol Soc, Vet Immunol Comm DE monoclonal antibodies; flow cytometry; clustering analysis ID CYTOLYTIC T-LYMPHOCYTES; MONOCLONAL-ANTIBODIES; DIFFERENTIATION ANTIGENS; PORCINE CD44; CELL-LINES; EXPRESSION; PIG; MOLECULES; DEFINE; MURINE AB The reactivity of 176 monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, together with 19 internal standards, was analyzed by flow cytometry on 16 different cell types as a means of establishing the proper cell subset for later detailed clustering analyses. The exact CD subset reactivity of the 19 internal standard mAb had been characterized in the First International Swine CD Workshop. The flow cytometric analyses resulted in 40 data sets which were then subjected to statistical clustering using the Leukocyte Typing Database IV (LTDB4) software, As result of this work, 22 clusters were defined. After review of these results, panels of mAb from the defined first round clusters were assigned to cell subsets. The respective mAb in those first round clusters were then distributed to subset group researchers for, further examination during the second round of the workshop. (C) 1998 Elsevier Science B.V. C1 Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. Royal Vet & Agr Univ, Dept Vet Virol & Immunol, Frederiksberg C, Denmark. Massachusetts Gen Hosp, Transplant Biol Res Ctr, Charlestown, MA USA. Washington State Univ, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA. Inst Viruskrankheiten & Immunprophylaxe, CH-3147 Mittelhausern, Switzerland. Univ Minnesota, Coll Vet Med, Dept Vet Pathobiol, St Paul, MN 55108 USA. State Vet Inst Virus Res, DK-4771 Kalvehave, Denmark. Indiana Univ Hosp, Dept Surg, Indianapolis, IN 46202 USA. Univ Bristol, Sch Med, Dept Vet Med, Bristol, Avon, England. USDA ARS, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. RP Saalmuller, A (reprint author), Fed Res Ctr Virus Dis Anim, POB 1149, D-7400 Tubingen, Germany. OI Summerfield, Artur/0000-0001-8292-4634 NR 38 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 237 EP 249 DI 10.1016/S0165-2427(97)00100-1 PG 13 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400004 PM 9589562 ER PT J AU Pescovitz, MD Book, BK Aasted, B Dominguez, J Ezquerra, A Trebichavsky, I Novikov, B Valpotic, I Sver, L Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Davis, W Barbosa, IR Zuckermann, F Saalmuller, A AF Pescovitz, MD Book, BK Aasted, B Dominguez, J Ezquerra, A Trebichavsky, I Novikov, B Valpotic, I Sver, L Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Davis, W Barbosa, IR Zuckermann, F Saalmuller, A TI Summary of workshop findings for antibodies reacting with porcine T-cells and activation antigens: results from the Second International Swine CD Workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CALIFORNIA SP Int Union Immunol Soc, Vet Immunol Comm DE monoclonal antibodies; T-cells; Swine CD Workshop; porcine ID LYMPHOCYTES AB After initial evaluation of the 176 new and 19 control monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, 57 were assigned to the T-cell/activation marker subgroup. These 57 mAb were further analyzed using flow cytometry on whole blood lymphocytes, splenocytes, Peyer's patch lymphocytes, in vitro cell lines, broncho-alveolar lavage cells, Con A and PHA blasts, fetal cell populations, and by 2-color flow cytometry against mAb to porcine CD2, CD4: and CD8. Finally, the molecular weights of the target antigens were characterized when possible. As a result of these analyses, 23 mAb were distributed into 7 CD clusters. Newly confirmed mAb assignments included: two CD2; one CD4; two CD5; one wCD6; and one wCD25. Three new mAb were found that reacted with wCD8, one of which defined a new epitope, wCD8c. For the first time, mAb against porcine CD3 were identified, including 6 mAb that reacted with three different epitopes. Several new mAb reacted with antigens whose expression varied depending on the activation state of the test cell. These will require further characterization in order to assign a CD number. (C) 1998 Elsevier Science B.V. C1 Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. Royal Vet & Agr Univ, Frederiksberg C, Denmark. INIA, Ctr Invest Sanidad Anim, Valdeolmos, Madrid, Spain. Acad Sci Czech Republ, Inst Microbiol, Prague, Czech Republic. All Russian Res Inst Vet Virol & Microbiol, Vlasimizskaya, Russia. Univ Zagreb, Fac Vet, Dept Biol, Zagreb 41000, Croatia. Danish Vet Inst Virus Res, Kalvehave, Denmark. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. USDA ARS, LPSI, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Univ Melbourne, Ctr Anim Biotechnol, Parkville, Vic 3052, Australia. Washington State Univ, Pullman, WA 99164 USA. Univ Illinois, Dept Vet Pathol, Urbana, IL 61801 USA. Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. RP Pescovitz, MD (reprint author), Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. RI Ezquerra, Angel/I-3440-2012; Dominguez, Javier/I-1210-2015; OI Ezquerra, Angel/0000-0002-1824-5087 NR 11 TC 31 Z9 32 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 251 EP 260 DI 10.1016/S0165-2427(97)00101-3 PG 10 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400005 PM 9589563 ER PT J AU Pescovitz, MD Book, BK Aasted, B Dominguez, J Ezquerra, A Trebichavsky, I Novikov, B Valpotic, I Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Lackovic, G Kirkham, P Parkhouse, RME AF Pescovitz, MD Book, BK Aasted, B Dominguez, J Ezquerra, A Trebichavsky, I Novikov, B Valpotic, I Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Lackovic, G Kirkham, P Parkhouse, RME TI Analyses of monoclonal antibodies reacting with porcine CD3: results from the Second International Swine CD Workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CALIFORNIA SP Int Union Immunol Soc, Vet Immunol Comm DE monoclonal antibodies; resting peripheral lymphocytes; epitope; porcine; CD3 ID RENAL-ALLOGRAFT REJECTION; T-CELL ACTIVATION; CORTICOSTEROIDS; POLYPEPTIDE; CD3-EPSILON; LYMPHOCYTES; EPITOPES; INVIVO AB Among the 57 monoclonal antibodies (mAb) analyzed within the T-cell group from the Second Swine CD Workshop, six mAb fell within clusters T10 and T11 (No. 088, STH164; No. 148, FY1A3; No. 149, FY2C1; No. 150, FY1H2; No. 151, FY2A11; No. 169, BB23-8E6), The mAb within these two groups gave a similar appearance on flow cytometry and stained all peripheral blood T-cells as defined by CD4 and wCD8 staining, All six mAb precipitated a 24 kDa protein. On the basis of inhibition analyses performed as part of the workshop and fi om published data, the mAb define at least three epitopes. There is only minimal stimulation of resting peripheral lymphocytes, but four of the mAb produce strong stimulation in the presence of PMA. With the exception of STH164, all have been shown to react with CD3 epsilon-transfected COS cells. The new mAb, therefore, react with three epitopes on porcine CD3 epsilon designated CD3a (BB23-8E6, FY2A11), CD3b (FY1A3, FY2C1), and CD3c (FY1H2). mAb STH164 appears to be reactive with another epitope, however, since its reactivity with CD3 has not been confirmed it is designated as wCD3. (C) 1998 Elsevier Science B.V. C1 Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. Royal Vet & Agr Univ, Frederiksberg C, Denmark. INIA, Ctr Invest Sanidad Anim, Valdeolmos, Madrid, Spain. Acad Sci Czech Republ, Inst Microbiol, Prague, Czech Republic. All Russian Res Inst Vet Virol & Microbiol, Vlasimizskaya, Russia. Univ Zagreb, Fac Vet, Dept Biol, Zagreb 41000, Croatia. Danish Vet Inst Virus Res, Kalvehave, Denmark. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. USDA ARS, LPSI, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Univ Melbourne, Ctr Anim Biotechnol, Parkville, Vic 3052, Australia. Univ Zagreb, Fac Sci, Dept Zool, Zagreb 41000, Croatia. Inst Anim Hlth, Pirbright Lab, Surrey, England. Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. RP Pescovitz, MD (reprint author), Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. RI Ezquerra, Angel/I-3440-2012; Dominguez, Javier/I-1210-2015; OI Parkhouse, Michael/0000-0001-5967-3291; Ezquerra, Angel/0000-0002-1824-5087 NR 18 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 261 EP 268 DI 10.1016/S0165-2427(97)00102-5 PG 8 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400006 PM 9589564 ER PT J AU Pescovitz, MD Book, BK Aasted, B Dominguez, J Bullido, R Trebichavsky, I Novikov, B Valpotic, I Tomaskovic, M Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Saalmuller, A AF Pescovitz, MD Book, BK Aasted, B Dominguez, J Bullido, R Trebichavsky, I Novikov, B Valpotic, I Tomaskovic, M Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Saalmuller, A TI Analyses of monoclonal antibodies reacting with porcine CD5: results from the Second International Swine CD Workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CALIFORNIA SP Int Union Immunol Soc, Vet Immunol Comm DE monoclonal antibodies; CD5; T-cell; porcine AB Among the 57 monoclonal antibodies analyzed within the T-cell group, three mAbs fell within cluster T13 including the CD5a standard b53b7 (No. 174). The two new mAbs 1H6/8 (No. 058) and BB6-9G12 (No, 166) both precipitated 55 and 60 kDa proteins that were of similar molecular weights as the standard. Staining patterns on the various cell types were similar. Both new antibodies inhibited the binding of the CD5a reference mAbs b53b7 to peripheral lymphocytes. These mAbs, therefore both react with the CD5a epitope bringing the number of anti-porcine CD5 mAbs to eight, all of which appear to recognize the same epitope. (C) 1998 Elsevier Science B.V. C1 Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. Royal Vet & Agr Univ, Frederiksberg C, Denmark. INIA, Ctr Invest Sanidad Anim, Valdeolmos, Madrid, Spain. Acad Sci Czech Republ, Inst Microbiol, Prague, Czech Republic. All Russian Res Inst Vet Virol & Microbiol, Vlasimizskaya, Russia. Univ Zagreb, Fac Vet, Dept Biol, Zagreb 41000, Croatia. Danish Vet Inst Virus Res, Kalvehave, Denmark. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. USDA ARS, LPSI, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Univ Melbourne, Ctr Anim Biotechnol, Parkville, Vic 3052, Australia. Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. RP Pescovitz, MD (reprint author), Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. RI Dominguez, Javier/I-1210-2015 NR 5 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 269 EP 273 DI 10.1016/S0165-2427(97)00103-7 PG 5 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400007 PM 9589565 ER PT J AU Pescovitz, MD Book, BK Aasted, B Dominguez, J Bullido, R Trebichavsky, I Novikov, B Valpotic, I Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Petrinec, N Saalmuller, A AF Pescovitz, MD Book, BK Aasted, B Dominguez, J Bullido, R Trebichavsky, I Novikov, B Valpotic, I Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, PC Walker, J Lee, R Petrinec, N Saalmuller, A TI Analyses of monoclonal antibodies reacting with porcine wCD6: results from the Second International Swine CD workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CA SP Int Union Immunol Soc, Vet Immunol Comm DE monoclonal antibodies; T-cells; porcine wCD6 AB Among the 57 monoclonal antibodies analyzed within the T-cell group of the Second International Swine CD Workshop, one mAb fell within cluster T14a that included the CD6 standard a38b2 (No. 175). The new mAb MIL8 (No. 082) and a38b2 both precipitated from activated T-cells a 150 kDa monomeric protein. Staining patterns on the various cell types were similar. There was no inhibition of binding of either mAb to peripheral blood T-cells with the opposite mAb. The new mAb, MIL8, reacts with a separate epitope on porcine wCD6. (C) 1998 Elsevier Science B.V. C1 Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. Royal Vet & Agr Univ, Frederiksberg C, Denmark. INIA, Ctr Invest Sanidad Anim, Madrid, Spain. Acad Sci Czech Republic, Inst Microbiol, Prague, Czech Republic. All Russian Res Inst Vet virol & Microbiol, Vlasimizskaya, Russia. Univ Zagreb, Fac Vet, Dept Biol, Zagreb 41000, Croatia. Danish Vet Inst Virus Res, Kalvehave, Denmark. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. USDA ARS, LPSI, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Univ Melbourne, Ctr Anim Biotechnol, Parkville, Vic 3052, Australia. Univ Zagreb, Inst Immunol, Zagreb, Croatia. Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. RP Pescovitz, MD (reprint author), Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46202 USA. RI Dominguez, Javier/I-1210-2015 NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 285 EP 289 DI 10.1016/S0165-2427(97)00105-0 PG 5 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400009 PM 9589567 ER PT J AU Zuckermann, FA Pescovitz, MD Aasted, B Dominguez, J Trebichavsky, I Novikov, B Valpotic, I Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, P Walker, J Lee, R Davis, WC Barbosa, IR Saalmuller, A AF Zuckermann, FA Pescovitz, MD Aasted, B Dominguez, J Trebichavsky, I Novikov, B Valpotic, I Nielsen, J Arn, S Sachs, DH Lunney, JK Boyd, P Walker, J Lee, R Davis, WC Barbosa, IR Saalmuller, A TI Report on the analyses of mAb reactive with porcine CD8 for the second international swine CD workshop SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT 2nd International Workshop on Swine Leukocyte Differentiation Antigens CY JUL 16, 1995 CL DAVIS, CALIFORNIA SP Int Union Immunol Soc, Vet Immunol Comm DE porcine CD8; peripheral blood lymphocytes; two-color cytofluorometry ID CYTOLYTIC T-LYMPHOCYTES; MONOCLONAL-ANTIBODIES; FUNCTIONAL-CHARACTERIZATION; CELL ACTIVATION; EXPRESSION; DIFFERENTIATION; BLOOD; SUBPOPULATIONS; ANTIGENS; ISOFORMS AB Based on an analysis of their reactivity with porcine peripheral blood lymphocytes (PBL), only three of the 57 mAbs assigned to the T cell/activation marker group were grouped into cluster T9 along with the two wCD8 workshop standard mAbs 76-2-11 (CD8a) and 11/295/33 (CD8b). Their placement was verified through the use of two-color cytofluorometry which established that all three mAbs (STH101, #090; UCP1H12-2, #139; and PG164A, #051) bind exclusively to CD8(+) cells. Moreover, like the CD8 standard mAbs, these three mAbs reacted with two proteins with a MW of 33 and 35 kDa from lymphocyte lysates and were, thus, given the wCD8 designation. Because the mAb STH101 inhibited the binding of mAb 76-2-11 but not of 11/295/33, it was given the wCD8a designation. The reactivity of the other two new mAbs in the T9 cluster with the various subsets of CD8(+) lymphocytes were distinct from that of the other members in this cluster including the standards. Although the characteristic porcine CD8 staining pattern consisting of CD8(low) and CD8(high) cells was obtained with the mAb UCP1H12-2: a hider gap between the fluorescence intensity of the CD8(low) and CD8(high) lymphocytes was observed. In contrast, the mAb PG164A, not only exclusively reacted with CD4(-)/CD8(high) lymphocytes, but it also failed to recognize CD4/CD8 double positive lymphocytes. It was concluded that this mAb is specific for a previously unrecognized CD8 epitope, and was, thus, given the wCD8c designation. A very similar reactivity pattern to that of PG164A was observed for two other mAbs (STH106, #094; and SwNL554.1, #009). Although these two mAbs were not originally positioned in the T cell subgroup because of their reactivity and their ability to inhibit the binding of PC164A, they were given the wCD8c designation. Overall, five new wCD8 mAbs were identified. Although the molecular basis for the differences in PBL recognition by these mAbs is not yet understood, they will be important in defining the role of CD8(+) lymphocyte subsets in health and disease. (C) 1998 Elsevier Science B.V. C1 Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61801 USA. Indiana Univ, Dept Surg & Microbiol Immunol, Indianapolis, IN 46204 USA. Royal Vet & Agr Univ, Frederiksberg C, Denmark. INIA, Dept Sanidad Anim, Madrid, Spain. Acad Sci Czech Republ, Inst Microbiol, Prague, Czech Republic. All Russian Res Inst Vet Virol & Microbiol, Vlasimizskaya, Russia. Univ Zagreb, Fac Vet, Dept Biol, Zagreb 41000, Croatia. State Vet Inst Virus Res, Kalvehave, Denmark. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Charlestown, MA USA. USDA ARS, Immunol & Dis Resistance Lab, Beltsville, MD 20705 USA. Univ Melbourne, Ctr Anim Biotechnol, Parkville, Vic 3052, Australia. Washington State Univ, Pullman, WA 99164 USA. Fed Res Ctr Virus Dis Anim, D-7400 Tubingen, Germany. RP Zuckermann, FA (reprint author), Univ Illinois, Dept Vet Pathobiol, 2001 So Lincoln Ave, Urbana, IL 61801 USA. RI Dominguez, Javier/I-1210-2015 NR 24 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN 30 PY 1998 VL 60 IS 3-4 BP 291 EP 303 DI 10.1016/S0165-2427(97)00106-2 PG 13 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA ZL333 UT WOS:000073422400010 PM 9589568 ER PT J AU Palacios, IF AF Palacios, IF TI Farewell to surgical mitral commissurotomy for many patients SO CIRCULATION LA English DT Editorial Material DE editorials; mitral valve; surgery; balloon ID PERCUTANEOUS BALLOON; CLOSED COMMISSUROTOMY; FOLLOW-UP; STENOSIS; VALVOTOMY; VALVULOPLASTY; IMMEDIATE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM palacios@olorin.mgh.harvard.edu NR 16 TC 28 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 27 PY 1998 VL 97 IS 3 BP 223 EP 226 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YT817 UT WOS:000071648000001 PM 9462519 ER PT J AU Xu, Y Lorf, T Sablinski, T Gianello, P Bailin, M Monroy, R Kozlowski, T Awwad, M Cooper, DKC Sachs, DH AF Xu, Y Lorf, T Sablinski, T Gianello, P Bailin, M Monroy, R Kozlowski, T Awwad, M Cooper, DKC Sachs, DH TI Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Gal alpha 1-3Gal beta 1-4 beta Glc-X immunoaffinity column SO TRANSPLANTATION LA English DT Article ID ALPHA-GALACTOSYL EPITOPES; IN-VIVO; GAL ANTIBODY; CELLS; IGM; XENOTRANSPLANTATION; IMMUNOADSORPTION; REJECTION; BABOONS; PK15 AB Background, Natural antibodies (NAbs) against a terminal alpha 1-3 galactosyl (alpha Gal) epitope have been identified as the major human anti-pig NAbs, Methods and Results. We used two synthetic alpha Gal trisaccharides-type 6 (alpha Gal6) and type 2(alpha Gal2)-linked to an inert matrix to remove NAbs from human plasma in vitro, Flow cytometry indicated that an average of 85% of the NAb binding activity was depleted by adsorption with alpha Gal6. By measuring the binding of NAbs to pig peripheral blood mononuclear cells and bone marrow cells, we demonstrated that alpha Gal6 was more effective than alpha Gal2 in removing NAbs, and the combination of alpha Gal6 + alpha Gal2 did not further increase removal of NAbs, The specificity of the removal of NAbs (IgM and IgG) reactive with the alpha Gal epitope by alpha Gal6 matrix was shown by enzyme-linked immunosorbent assay, In vivo studies in nonhuman primates compared plasma perfusion through a alpha Gal6 immunoaffinity column with hemoperfusion through a pig liver for changes in blood pressure, hematocrit, platelets, and NAb adsorption, Conclusions, Both methods reduced the level of anti-pig IgM and IgG xenoreactive antibodies to nearly background, but column perfusion caused less hypotension and reduction in platelets than liver perfusion, Four pig kidneys transplanted into monkeys after column perfusion did not undergo hyperacute rejection, remaining functional for 2-10 days, with a mean functional period of 7 days, demonstrating that a pig kidney can support renal function in a primate. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tansplantat Biol Res Ctr, Boston, MA USA. BioTransplant Inc, Boston, MA USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 25 TC 151 Z9 152 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1998 VL 65 IS 2 BP 172 EP 179 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YU164 UT WOS:000071688700005 PM 9458010 ER PT J AU Rabkin, JM Orloff, SL Reed, MH Wheeler, LJ Corless, CL Benner, KG Flora, KD Rosen, HR Olyaei, AJ AF Rabkin, JM Orloff, SL Reed, MH Wheeler, LJ Corless, CL Benner, KG Flora, KD Rosen, HR Olyaei, AJ TI Biliary tract complications of side-to-side without T tube versus end-to-end with or without T tube choledochocholedochostomy in liver transplant recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 10-16, 1997 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID HEPATIC-ARTERY THROMBOSIS; BILE-DUCT; MANAGEMENT; ANASTOMOSIS; DRAINAGE; THERAPY; RECONSTRUCTION; CONDUIT AB Background, Biliary anastomotic complications remain a major cause of morbidity in liver transplant recipients, ranging between 10% and 50% in large clinical series, An end-to-end choledochocholedochostomy with or without T tube (CDCD EE with T tube and CDCD EE w/o T tube) and a Roux-en Y choledochojejunostomy have been standard methods for biliary drainage, Methods. The objectives of this retrospective study were to: (1) evaluate the incidence of biliary tract complications using a new method of side-to-side choledochocholedochostomy without T tube (CDCD SS w/o T tube) and (2) compare the results of CDCD SS w/o T tube with those of CDCD EE with T tube and CDCD EE w/o T tube, From September 1991 through June 1996, 279 orthotopic liver transplants were performed in 268 patients and followed through December 1996 (minimum of 6 months' follow-up). A total of 227 CDCD anastomoses in 220 patients were studied (7 retransplants >30 days): CDCD EE with T tube (n=124), CDCD EE w/o T tube (n=44), and CDCD SS w/o T tube (n=59). Results. Sixty-nine biliary complications were observed in 220 patients (30%). Anastomotic and/or T-tube leaks were seen in 43 patients (19%), and anastomotic strictures were found in 26 patients (12%). Forty patients (18%) required percutaneous or endoscopic stent placement (6%) or surgical interventions (12%). CDCD EE with T tube had the highest incidence of biliary leak requiring rehospitalization but the lowest anastomotic stricture and intervention rate and the lowest B-month mortality rate, Conclusions, CDCD EE with T tube was superior to CDCD EE or CDCD SS w/o T tube despite the increased number of rehospitalizations. CDCD SS w/o T tube did not offer significant advantages over conventional biliary anastomotic techniques. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Rabkin, JM (reprint author), Sect Liver Pancreas Transplantat, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 35 TC 55 Z9 59 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 1998 VL 65 IS 2 BP 193 EP 199 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YU164 UT WOS:000071688700008 PM 9458013 ER PT J AU Skelton, TP Zeng, CX Nocks, A Stamenkovic, I AF Skelton, TP Zeng, CX Nocks, A Stamenkovic, I TI Glycosylation provides both stimulatory and inhibitory effects on cell surface and soluble CD44 binding to hyaluronan SO JOURNAL OF CELL BIOLOGY LA English DT Article ID AFFINITY CAPILLARY ELECTROPHORESIS; HOMING RECEPTOR CD44; HAMSTER OVARY CELLS; SPLICED EXONS; HUMAN-BREAST; T-CELLS; EXPRESSION; ADHESION; PROTEIN; RECOGNITION AB Glycosylation has been implicated in the regulation of CD44-mediated cell binding of hyaluronan (HA). However, neither the relative contribution of N- and O-linked glycans nor the oligosaccharide structures that alter CD44 affinity for HA have been elucidated, To determine the effect of selective alteration of CD44 oligosaccharide composition on the affinity of CD44 for HA, we developed a novel strategy based on the use of affinity capillary electrophoresis (ACE). Soluble recombinant CD44-immunoglobulin fusion proteins were overproduced in the mutant CHO cell line ldl-D, which has reversible defects in both N- and O-linked oligosaccharide synthesis, Using this cell line, a panel of recombinant glycosidases, and metabolic glycosidase inhibitors, CD44 glycoforms with defined oligosaccharide structures were generated and tested for HA affinity by ACE. Because ldl-D cells express endogenous cell surface CD44, the effect of any given glycosylation change on the ability of cell surface and soluble CD44 to bind HA could be compared. Four distinct oligosaccharide structures were found to effect CD44-mediated HA binding: (a) the terminal alpha 2,3-linked sialic acid on N-linked oligosaccharides inhibited binding; (b) the first N-linked N-acetylglucosamine residue enhanced binding; (c) O-linked glycans on N-deglycosylated CD44 enhanced binding; and (d) N-acetylgalactosamine incorporation into non-N-linked glycans augmented HA binding by cell surface CD44. The first three structures induced up to a 30-fold alteration in the intrinsic CD44 affinity for HA (K-d = 5 to > 150 mu M). The fourth augmented CD44-mediated cellular HA avidity without changing the intrinsic HA affinity of soluble CD44. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Charlestown Navy Yard, Boston, MA 02129 USA. RP Stamenkovic, I (reprint author), Harvard Univ, Sch Med, Dept Pathol, Charlestown Navy Yard,149 13th St, Boston, MA 02129 USA. FU NCI NIH HHS [CA55735, NCD2932-CA 09216, T32 CA009216] NR 61 TC 135 Z9 139 U1 2 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 26 PY 1998 VL 140 IS 2 BP 431 EP 446 DI 10.1083/jcb.140.2.431 PG 16 WC Cell Biology SC Cell Biology GA YV186 UT WOS:000071798000018 PM 9442118 ER PT J AU Cupers, P Jadhav, AP Kirchhausen, T AF Cupers, P Jadhav, AP Kirchhausen, T TI Assembly of clathrin coats disrupts the association between Eps15 and AP-2 adaptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE SUBSTRATE; VESICLES; PROTEIN; COMPLEXES; DOMAIN; PITS AB Eps15 is a phosphorylation substrate of the epidermal growth factor receptor kinase, In vivo, it is largely found in complex with AP-2, the plasma membrane clathrin adaptor protein complex. Although AP-2 is uniformly distributed across the surface of clathrin-coated pits and vesicles, Eps15 is preferentially found in the rims of endocytic clathrin-coated pits (1), This observation suggests that Eps15 may disengage from AP-2 during coat formation. Here we use two new anti-Eps15 antibodies to show that, contrary to our own earlier suggestion, coated vesicles isolated from brain do not contain detectable amounts of Eps15. Furthermore, when AP-2 complexes that are saturated with Eps15 are used for in vitro assembly of clathrin-AP-2 coats, normal structures are formed that contain the expected amounts of clathrin and AP-2, but the amount of Eps15 present is dramatically lower than that of AP-2. We propose that during coated pit formation, addition of clathrin to the growing edge at the rim of the pit releases Eps15 from AP-2. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM36548] NR 22 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 1998 VL 273 IS 4 BP 1847 EP 1850 DI 10.1074/jbc.273.4.1847 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200003 PM 9442014 ER PT J AU Wen, Y Edelman, JL Kang, T Zeng, NX Sachs, G AF Wen, Y Edelman, JL Kang, T Zeng, NX Sachs, G TI Two functional forms of vascular endothelial growth factor receptor-2 Flk-1 mRNA are expressed in normal rat retina SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; PERMEABILITY FACTOR; CELL GROWTH; EPITHELIAL-CELLS; MESSENGER-RNA; DEVELOPMENTAL EXPRESSION; HYPOXIC INDUCTION; FACTOR FAMILY; FACTOR VEGF; ANGIOGENESIS AB Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization by exerting its endothelial specific mitogenic effects through high affinity tyrosine kinase receptors. By screening a rat retina cDNA library, we have isolated a clone encoding the full-length prototypic form of the rat VEGF receptor-2/FLk-1, as well as a short form of the mRNA that encodes the complete seven N-terminal immunoglobulin-like extracellular ligand-binding domains, transmembrane region, NH2-terminal half of the intracellular kinase domain, and kinase insert domain but does not encode the COOH-terminal half of the intracellular kinase domain and carboxyl-terminal region. Both forms of mRNA are detected in rat retina, although the short form is expressed at a lower level. VEGF induced a biphasic increase of cytoplasmic calcium with both forms in RR 293 transfected cells, indicating that both forms of the VEGF receptor-2/Flk-1 are functional and that the COOH-terminal half of the intracellular kinase domain and carboxyl region of VEGF receptor-2/Flk-1 are not strictly necessary for either Ligand binding or this biological activity. C1 W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. Allergan, Irvine, CA 92713 USA. RP Sachs, G (reprint author), W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Dept Med, 11301 Wilshire Blvd,Bldg 113,Room 324, Los Angeles, CA 90073 USA. NR 45 TC 51 Z9 52 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 23 PY 1998 VL 273 IS 4 BP 2090 EP 2097 DI 10.1074/jbc.273.4.2090 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YT367 UT WOS:000071595200037 PM 9442048 ER PT J AU Collins, KL Chen, BK Kalams, SA Walker, BD Baltimore, D AF Collins, KL Chen, BK Kalams, SA Walker, BD Baltimore, D TI HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FINE SPECIFICITY; DOWN-MODULATION; ANTIGENS; RNA AB Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes, We found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed. Resistance of infected cells to CTL killing correlated with nef-mediated downregulation of MHC class I (ref. 1) and could be overcome by adding an excess of the relevant HIV-1 epitope as soluble peptide. Thus, Nef protected infected cells by reducing the epitope density on their surface. This effect of nef may allow evasion of CTL lysis by HN-1-infected cells. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Combined Infect Dis Training Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Rockefeller Univ, New York, NY 10021 USA. RP Baltimore, D (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM baltimo@caltech.edu NR 27 TC 707 Z9 724 U1 3 U2 24 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 22 PY 1998 VL 391 IS 6665 BP 397 EP 401 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YT444 UT WOS:000071604200057 PM 9450757 ER PT J AU Sheets, EE Trotman-Dickenson, B Kalil, A Nikrui, N Smith, RN AF Sheets, EE Trotman-Dickenson, B Kalil, A Nikrui, N Smith, RN TI A 31-year-old woman with a pleural effusion, ascites, and persistent fever spikes - Tuberculous peritonitis due to M-tuberculosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS-INFECTION; ADENOSINE-DEAMINASE; OVARIAN-CANCER; EXTRAPULMONARY TUBERCULOSIS; UNITED-STATES; CA-125; DIAGNOSIS; LYMPHOMAS; CARCINOMA; MARKERS C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Sheets, EE (reprint author), Brigham & Womens Hosp, Boston, MA 02115 USA. NR 37 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 1998 VL 338 IS 4 BP 248 EP 254 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YT358 UT WOS:000071594100008 ER PT J AU Carson, JL Duff, A Berlin, JA Lawrence, VA Poses, RM Huber, EC O'Hara, DA Noveck, H Strom, BL AF Carson, JL Duff, A Berlin, JA Lawrence, VA Poses, RM Huber, EC O'Hara, DA Noveck, H Strom, BL TI Perioperative blood transfusion and postoperative mortality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MORBIDITY; DISEASE; SYSTEM; RISK AB Context.-The risks of blood transfusion have been studied extensively but the benefits and the hemoglobin concentration at which patients should receive a transfusion have not. Objective.-To determine the effect of perioperative transfusion on 30- and 90-day postoperative mortality. Design.-Retrospective cohort study. Setting.-A total of 20 US hospitals between 1983 and 1993. Participants.-A total of 8787 consecutive hip fracture patients, aged 60 years or older, who underwent surgical repair. Main Outcome Measures.-Primary outcome was 30-day postoperative mortality; secondary outcome was 90-day postoperative mortality. The "trigger" hemoglobin level was defined as the lowest hemoglobin level prior to the first transfusion during the time period or, for patients in the nontranfused group, as the lowest hemoglobin level during the time period. Results.-Overall 30-day mortality was 4.6% (n=402; 95% confidence interval [CI], 4.1%-5.0%); overall 90-day mortality was 9.0% (n=788; 95% CI, 8.4%-9.6%). A total of 42% of patients (n=3699) received a postoperative transfusion. Among patients with trigger hemoglobin levels between 80 and 100 g/L (8.0 and 10.0 g/dL), 55.6% received a transfusion, while 90.5% of patients with hemoglobin levels less than 80 g/L (8.0 g/dL) received postoperative transfusions. Postoperative transfusion did not influence 30- or 90-day mortality after adjusting for trigger hemoglobin level, cardiovascular disease, and other risk factors for death: for 30-day mortality, the adjusted odds ratio (OR) was 0.96 (95% CI, 0.74-1.26); for 90-day mortality, the adjusted hazard ratio was 1.08 (95% CI, 0.90-1.29). Similarly, 30-day mortality after surgery did not differ between those who received a preoperative transfusion and those who did not (adjusted OR, 1.23; 95% CI, 0.81-1.89). Conclusions.-Perioperative transfusion in patients with hemoglobin levels 80 g/L (8.0 g/dL) or higher did not appear to influence the risk of 30- or 90-day mortality in this elderly population, At hemoglobin concentrations of less than 80 g/L (8.0 g/dL), 90.5% of patients received a transfusion, precluding further analysis of the association of transfusion and mortality. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Dept Med, New Brunswick, NJ 08903 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Dept Anesthesia, New Brunswick, NJ 08903 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Div Gen Med, San Antonio, TX USA. Univ Texas, Dept Med, San Antonio, TX 78285 USA. Brown Univ, Sch Med, Dept Med, Div Gen Internal Med, Providence, RI 02912 USA. Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. Virginia Commonwealth Univ, Med Coll Virginia, Div Gen Internal Med, Richmond, VA 23298 USA. RP Carson, JL (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Dept Med, 125 Paterson St, New Brunswick, NJ 08903 USA. EM carson@umdnj.edu FU AHRQ HHS [1R01HS07322] NR 27 TC 258 Z9 262 U1 0 U2 4 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 JAN 21 PY 1998 VL 279 IS 3 BP 199 EP 205 DI 10.1001/jama.279.3.199 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YR124 UT WOS:000071460700029 PM 9438739 ER PT J AU Goldfeld, AE Delgado, JC Thim, S Bozon, MV Uglialoro, AM Turbay, D Cohen, C Yunis, EJ AF Goldfeld, AE Delgado, JC Thim, S Bozon, MV Uglialoro, AM Turbay, D Cohen, C Yunis, EJ TI Association of an HLA-DQ allele with clinical tuberculosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; DNA; AMPLIFICATION; POLYMORPHISM; INFECTION; RELEVANCE; HLA-DR1; VIRUS AB Context.-Although tuberculosis (TB) is the leading worldwide cause of death due to an infectious disease, the extent to which progressive clinical disease is associated with genetic host factors remains undefined. Objective.-To determine the distribution of HLA antigens and the frequency of 2 alleles of the tumor necrosis factor alpha (TNF-alpha) gene in unrelated individuals with clinical TB (cases) compared with individuals with no history of clinical TB (controls) in a population with a high prevalence of TB exposure. Design.-A 2-stage, case-control molecular typing study conducted in 1995-1996. Setting.-Three district hospitals in Svay Rieng Province in rural Cambodia. Patients.-A total of 78 patients with clinical TB and 49 controls were included in the first stage and 48 patients with TB and 39 controls from the same area and socioeconomic status were included in the second stage. Main Outcome Measures.-Presence of HLA class I and class II alleles determined by sequence-specific oligonucleotide probe hybridization and presence of 2 TNF-alpha alleles determined by restriction fragment length polymorphism analysis. Results.-In the first stage, 7 DQB1*0503 alleles were detected among 156 alleles derived from patients with TB, whereas no DQB1*0503 alleles were found among the 98 alleles derived from controls (P=.04), There was no detectable difference in the distribution of the 2 TNF-alpha alleles in patients with TB compared with controls, In the second stage, we tested for the presence of a single variable, the DQB1*0503 allele, and found 9 DQB1*0503 alleles among 96 alleles derived from patients with TB and no DQB1*0503 alleles among 78 alleles in controls (P=.005), Conclusions.-The HLA-DQB1*0503 allele is significantly associated with susceptibility to TB in Cambodian patients and, to our knowledge, is the first identified gene associated with development of clinical TB. C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Immunogenet, Boston, MA 02115 USA. Dana Farber Canc Inst, Blood Bank, Boston, MA 02115 USA. Phnom Penh, Cambodian Hlth Comm, Boston, MA USA. RP Goldfeld, AE (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL29583]; NIMH NIH HHS [MH 40279] NR 36 TC 166 Z9 172 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 JAN 21 PY 1998 VL 279 IS 3 BP 226 EP 228 DI 10.1001/jama.279.3.226 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YR124 UT WOS:000071460700034 PM 9438744 ER PT J AU Lu, S Wyatt, R Richmond, JFL Mustafa, F Wang, SX Weng, JY Montefiori, DC Sodroski, J Robinson, HL AF Lu, S Wyatt, R Richmond, JFL Mustafa, F Wang, SX Weng, JY Montefiori, DC Sodroski, J Robinson, HL TI Immunogenicity of DNA vaccines expressing human immunodeficiency virus type 1 envelope glycoprotein with and without deletions in the V1/2 and V3 regions SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID AIDS PATIENTS; HTLV-III; ANTIBODIES; GENE; PROTEIN; GP41 AB DNA vaccines that express the human immunodeficiency virus type 1 HXB-2 envelope glycoprotein (Env) with or without deletions of the major variable regions V1/V2 and V3 were tested for the ability to raise enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody in New Zealand White (NZW) rabbits, Three forms of the Envs were examined: gp120, the surface (SU) receptor-binding domain; gp140, the entire extracellular domain of Env; and gp160, the complete form of Env, For the forms of Env containing the variable regions, the gp120-expressing DNA plasmid was more immunogenic than the gp140- or gp160-expressing DNA plasmids, Removing the V1/2 and V3 variable regions increased the immunogenicity of the gp140-and gp160-expressing DNAs, Deletion of the variable regions also resulted in antibody responses against determinants that were not presented by the forms of Env containing the variable regions, Despite the improved immunogenicity, removing the V1/V2 and V3 domains did not improve the ability of Env to raise neutralizing antibodies, These results suggest that increasing the exposure of internal structures of Env that include the CD4-binding site does not necessarily result in the generation of better neutralizing antibody. C1 Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01655 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27708 USA. Duke Univ, Med Ctr, Ctr AIDS Res, Durham, NC 27708 USA. RP Lu, S (reprint author), Univ Massachusetts, Med Ctr, Dept Med, 55 Lake Ave, Worcester, MA 01655 USA. FU NCPDCID CDC HHS [NCI-6S-1649]; NIAID NIH HHS [5-T32 AI 07272-12, R01 AI 34241] NR 18 TC 73 Z9 74 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 20 PY 1998 VL 14 IS 2 BP 151 EP 155 DI 10.1089/aid.1998.14.151 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YT559 UT WOS:000071619200007 PM 9462925 ER PT J AU Raines, DE Krishnan, NS AF Raines, DE Krishnan, NS TI Transient low-affinity agonist binding to Torpedo postsynaptic membranes resolved by using sequential mixing stopped-flow fluorescence spectroscopy SO BIOCHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; FAST DESENSITIZATION; SELF-INHIBITION; LIGAND-BINDING; ION CHANNELS; BC3H-1 CELLS; KINETICS; ACTIVATION; MARMORATA; 3.0.CO;2-T PG 9 WC Oncology SC Oncology GA YQ807 UT WOS:000071425100008 PM 9445185 ER PT J AU Barbarics, E Kronauge, JF Cohen, D Davison, A Jones, AG Croop, JM AF Barbarics, E Kronauge, JF Cohen, D Davison, A Jones, AG Croop, JM TI Characterization of P-glycoprotein transport and inhibition in vivo SO CANCER RESEARCH LA English DT Article ID MEDIATED MULTIDRUG-RESISTANCE; SDZ PSC-833; IN-VIVO; CYCLOSPORINE-A; CELL-LINE; CANCER; MICE; PHARMACOKINETICS; ISONITRILE; COMPLEX AB The P-glycoprotein is an energy-dependent efflux pump capable of decreasing the intracellular concentration of a broad range of chemotherapeutic agents, [Tc-99m]Sestamibi, a P-glycoprotein transport substrate, is a sensitive probe of P-glycoprotein function both in vitro and in vivo. A human tumor model in nude mice was evaluated to determine whether [Tc-99m]Sestamibi could detect in vivo differences in P-glycoprotein expression and P-glycoprotein modulation by the reversal agent SDZ PSC 833, Differential [Tc-99m]Sestamibi accumulation based upon P-glycoprotein expression was demonstrated in xenografts in vivo, Dose-dependent inhibition of P-glycoprotein function was achieved with SDZ PSC 833, Administration of the reversal agent increased [Tc-99m]Sestamibi accumulation in the xenografts expressing P-glycoprotein. These observations show that [Tc-99m]Sestamibi as capable of detecting the modulation of P-glycoprotein in a solid tumor model by the reversal agent SDZ PSC 833. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Novartis, E Hanover, NJ 07936 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Croop, JM (reprint author), James Whitcomb Riley Hosp Children, Sect Pediat Hematol Oncol, 702 Barnhill Dr,Room 2720, Indianapolis, IN 46202 USA. EM James_Croop@iucc.iupui.edu FU NCI NIH HHS [R37 CA34970] NR 38 TC 47 Z9 48 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1998 VL 58 IS 2 BP 276 EP 282 PG 7 WC Oncology SC Oncology GA YR421 UT WOS:000071493600018 PM 9443405 ER PT J AU Dahia, PLM AF Dahia, PLM TI Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors (vol 57, pg 4710, 1997) SO CANCER RESEARCH LA English DT Correction C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dahia, PLM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1998 VL 58 IS 2 BP 375 EP 375 PG 1 WC Oncology SC Oncology GA YR421 UT WOS:000071493600034 ER PT J AU Alessi, DR Kozlowski, MT Weng, QP Morrice, N Avruch, J AF Alessi, DR Kozlowski, MT Weng, QP Morrice, N Avruch, J TI 3 Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro SO CURRENT BIOLOGY LA English DT Article ID P70(S6K); RAPAMYCIN; SITES; DOMAIN AB Background: The p70 S6 kinase, an enzyme critical for cell-cycle progression through the G1 phase, is activated in vivo by insulin and mitogens through coordinate phosphorylation at multiple sites, regulated by signaling pathways, some of which depend on and some of which are independent of phosphoinositide 3-kinase (Pi 3-kinase). It is not known which protein kinases phosphorylate and activate p70. Results: Go-expression of p70 with 3-phosphoinositide-dependent protein kinase 1 (PDK1), a protein kinase that has previously been shown to phosphorylate and activate protein kinase B (PKB, also known as c-Akt), resulted in strong activation of the S6 kinase in vivo. In vitro, PDK1 directly phosphorylated Thr252 in the activation loop of the p70 catalytic domain, the phosphorylation of which is stimulated by PI 3-kinase in vivo and is indispensable for p70 activity. Whereas PDK1-catalyzed phosphorylation and activation of PKB in vitro was highly dependent on the presence of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3), PDK1 catalyzed rapid phosphorylation and activation of p70 in vitro, independent of the presence of PtdIns(3,4,5)P-3. The ability of PDK1 to phosphorylate p70 Thr252 was strongly dependent on the phosphorylation of the p70 noncatalytic carboxy-terminal tail (amino acids 422-525) and of amino acid Thr412. Moreover, once Thr252 was phosphorylated, its ability to cause activation of the p70 S6 kinase was also controlled by the p70 carboxy-terminal tail and by phosphorylation of p70 Ser394, and most importantly, Thr412. The overriding determinant of the absolute p70 activity was the strong positive cooperativity between Thr252 and Thr412 phosphorylation; both sites must be phosphorylated to achieve substantial p70 activation. Conclusions: PDK1 is one of the components of the signaling pathway recruited by Pi a-kinase for the activation of p70 S6 kinase as well as of PKB, and serves as a multifunctional effector downstream of the Pi 3-kinase. C1 Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Dundee, Dept Biochem, MRC, Phosphorylat Unit, Dundee DD1 4HN, Scotland. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK17776] NR 28 TC 437 Z9 441 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 15 PY 1998 VL 8 IS 2 BP 69 EP 81 DI 10.1016/S0960-9822(98)70037-5 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR236 UT WOS:000071474600015 PM 9427642 ER PT J AU Raz, E van Luenen, HGAM Schaerringer, B Plasterk, RHA Driever, W AF Raz, E van Luenen, HGAM Schaerringer, B Plasterk, RHA Driever, W TI Transposition of the nematode Caenorhabditis elegans Tc3 element in the zebrafish Danio rerio SO CURRENT BIOLOGY LA English DT Article ID GERM-LINE TRANSMISSION; MEDIATED ENHANCER DETECTION; TRANSPOSABLE ELEMENT; IN-VITRO; INSERTIONAL MUTAGENESIS; DROSOPHILA GENOME; C-ELEGANS; MARINER; GENES; EXPRESSION AB Background: Transposable elements of the Tc1/mariner family are found in many species of the animal kingdom. It has been suggested that the widespread distribution of this transposon family resulted from horizontal transmission among different species. Results: To test the ability of Tc1/mariner to cross species barriers, as well as to develop molecular genetic tools for studying zebrafish development, we determined the ability of the Tc3 transposon, a member of the Tc1/mariner family, to function in zebrafish. Tc3 transposons carrying sequences encoding the green fluorescent protein (GFP) were able to integrate in the fish genome by transposition. Integrated transposons expressed the GFP marker after germline transmission, and were capable of being mobilized upon introduction of transposase protein in trans. Conclusions: Our findings support models of horizontal transmission of Tc1/mariner elements between species. The work also establishes the basis for a novel method of transposon-mediated genetic transformation and for transposon-mediated genetic screens in zebrafish and other organisms. C1 Univ Freiburg, Inst Biol 1, Dept Dev Biol, D-79104 Freiburg, Germany. Netherlands Canc Inst, Div Mol Biol, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, CVRC, Charlestown, MA 02129 USA. RP Raz, E (reprint author), Univ Freiburg, Inst Biol 1, Dept Dev Biol, Hauptstr 1, D-79104 Freiburg, Germany. EM razerez@sun2.ruf.uni-freiburg.de OI van Luenen, Henri/0000-0002-5584-7968 FU NCRR NIH HHS [5 RO1 RR10082]; NICHD NIH HHS [R01-HD29761-05] NR 46 TC 93 Z9 98 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 15 PY 1998 VL 8 IS 2 BP 82 EP 88 DI 10.1016/S0960-9822(98)70038-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR236 UT WOS:000071474600016 PM 9427643 ER PT J AU Vodicka, MA Koepp, DM Silver, PA Emerman, M AF Vodicka, MA Koepp, DM Silver, PA Emerman, M TI HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection SO GENES & DEVELOPMENT LA English DT Article DE importin-beta; lentivirus; nuclear envelope; HIV; Vpr ID HUMAN-IMMUNODEFICIENCY-VIRUS; PORE COMPLEX PROTEIN; CELL-CYCLE ARREST; MESSENGER-RNA; TYPE-1 VPR; LOCALIZATION SIGNALS; NONDIVIDING CELLS; IMPORT SUBSTRATE; MATRIX PROTEIN; IDENTIFICATION AB HIV-1 Vpr promotes nuclear entry of viral nucleic acids in nondividing macrophages and also causes a G(2) cell-cycle arrest. Consistent with its role in nuclear transport, we show Vpr localizes to the nuclear envelope in both human and yeast cells. Like the importin-beta subunit of the nuclear import receptor, Vpr also interacts with the yeast importin-alpha subunit and nucleoporins. Moreover, overexpression of either Vpr or importin-beta in yeast blocks nuclear transport of mRNAs. A mutant form of Vpr (Vpr F34I) that does not localize at the nuclear envelope, or bind to importin-alpha and nucleoporins, renders HIV-1 incapable of infecting macrophages efficiently. Vpr F34I, however, still causes a G(2) arrest, demonstrating that the dual functions of Vpr are genetically separable. Our data suggest Vpr functionally resembles importin-beta in nuclear import of the HIV-1 pre-integration complex and this function is essential for the role of Vpr in macrophage infection, but not G(2) arrest. C1 Fred Hutchinson Canc Res Ctr, Div Mol Med, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Emerman, M (reprint author), Fred Hutchinson Canc Res Ctr, Div Mol Med, Seattle, WA 98109 USA. EM memerman@fhcrc.org FU NHLBI NIH HHS [P01 HL053762, P01HL53762]; NIGMS NIH HHS [R01 GM036373, R01GM36373]; PHS HHS [R01A130927] NR 58 TC 265 Z9 266 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 1998 VL 12 IS 2 BP 175 EP 185 DI 10.1101/gad.12.2.175 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YX945 UT WOS:000072096400004 PM 9436978 ER PT J AU Verhey, LJ Smith, V Serago, CF AF Verhey, LJ Smith, V Serago, CF TI Comparison of radiosurgery treatment modalities based on physical dose distributions SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE stereotactic radiosurgery; protons; photons; dose comparisons ID STEREOTAXIC RADIOSURGERY; LINEAR-ACCELERATOR; IRRADIATION; PROTON AB Purpose: As a means of selecting the optimal stereotactic radiosurgery (SRS) treatment modality, a comparison of physical dose distributions to defined targets and nontarget brain tissue has been made for a group of test cases selected to represent a range of treatment-planning situations from small, nearly spherical volumes to large irregular volumes, Methods and Materials: Plans were developed for each case using photon beams from the Leksell Gamma Unit (LGU) multiarc bremsstrahlung photon beams from a linear accelerator (linac) and proton beams, with the objective of encompassing the target as closely as possible with the prescription isodose line, and minimizing dosage to normal tissue within the bounds of standard clinical practice. Dose-volume histograms (DVHs) were calculated for target and for nontarget brain tissue and compared for the various modalities, Results: In general, protons delivered less dosage to normal brain than other modalities for large and peripheral lesions and LGU plans were more successful at conforming to highly irregular shapes than conventional linac plans, Conclusions: Differences were observed to depend on treatment modality, target characteristics (shape, size and location), and the amount of effort expended on treatment planning and the time allotted for treatment implementation, (C) 1998 Elsevier Science Inc. C1 Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Verhey, LJ (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. NR 20 TC 94 Z9 94 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 15 PY 1998 VL 40 IS 2 BP 497 EP 505 DI 10.1016/S0360-3016(97)00720-7 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YT949 UT WOS:000071662700033 PM 9457840 ER PT J AU Smith, V Verhey, L Serago, CF AF Smith, V Verhey, L Serago, CF TI Comparison of radiosurgery treatment modalities based on complication and control probabilities SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiosurgery; complication probability; tumor control probability; treatment modality ID TUMOR-CONTROL PROBABILITY; RADIATION-THERAPY; NORMAL TISSUE; DOSE-RESPONSE; RADIOTHERAPY; OPTIMIZATION; HETEROGENEITY; IRRADIATION; ONCOLOGY; FORMULA AB Purpose: The relative efficacy of Gamma Knife, Linac, and Proton treatment modalities for stereotactic radiosurgery (SRS) was investigated on the basis of normal tissue complication probability (NTCP) and tumor control probability (TCP), calculated for representative test cases, Methods and Materials: Five radiosurgery patient cases were selected to cover a range of treatment-planning situations from small spherical volumes to large irregular volumes, A target volume consisting of contours drawn on CT transverse slices was prepared for each case. Plans were developed using the three treatment modalities for each case, with the objective of encompassing the target as closely as possible with a prescription isodose line and minimizing dose to normal tissue, within the constraints of current clinical practice, Dose-volume histograms (DVH) were calculated for the target and for normal tissue, and these histograms were used to calculate NTCP and TCP values for each plan, Results and Conclusions: Differences in NTCP and TCP values were found to depend on treatment modality, size, shape, and location of the target, the amount of effort devoted to treatment planning, and the complexity of the plan. (C) 1998 Elsevier Science Inc. C1 Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Smith, V (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. NR 41 TC 52 Z9 58 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 15 PY 1998 VL 40 IS 2 BP 507 EP 513 DI 10.1016/S0360-3016(97)00721-9 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YT949 UT WOS:000071662700034 PM 9457841 ER PT J AU Noble, A Pestano, GA Cantor, H AF Noble, A Pestano, GA Cantor, H TI Suppression of immune responses by CD8 cells. I. Superantigen-activated CD8 cells induce unidirectional Fas-mediated apoptosis of antigen-activated CD4 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MATURE T-CELLS; RECEPTOR TRANSGENIC MICE; TUMOR-NECROSIS-FACTOR; LIGAND INTERACTION; DEATH; LYMPHOCYTES; DELETION; TOLERANCE; CYTOTOXICITY; PATHWAY AB Stimulation of mature CD4 cells through the TCR induces cellular activation and expansion that are often followed by clonal elimination by a form of apoptosis(3) termed activation-induced cell death. This process of CD4 cell apoptosis is generally thought to reflect clonal suicide and to be independent of other cell types. Here we show that during the response to the superantigen Staphylococcal enterotoxin A, activated CD8 cells, but not activated CD4 cells, suppress the CD4 proliferative response. Suppression by CD8 cells reflects their ability to induce CD4 cell apoptosis via ligation of Fas. Moreover, although activated CD8 cells that express Fas ligand and Fas eliminate CD4 cells through a Fas-dependent mechanism, they are themselves resistant to Fas-dependent apoptosis. These findings indicate a fundamental difference between the two major T cell subsets with regard to sensitivity to Fas-dependent apoptosis, expression of Fas ligand, and mediation of suppressive activity following immunization with superantigen. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cantor, H (reprint author), 44 Binney St, Boston, MA 02115 USA. RI Noble, Alistair/E-9473-2010 FU NIAID NIH HHS [AI37833, AI13600] NR 32 TC 33 Z9 35 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 JAN 15 PY 1998 VL 160 IS 2 BP 559 EP 565 PG 7 WC Immunology SC Immunology GA YW267 UT WOS:000071915200006 PM 9551888 ER PT J AU Noble, A Zhao, ZS Cantor, H AF Noble, A Zhao, ZS Cantor, H TI Suppression of immune responses by CD8 cells. II. Qa-1 on activated B cells stimulates CD8 cell suppression of T helper 2 responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-SPECIFIC SUPPRESSOR; RECEPTOR ALPHA-CHAIN; CLONAL ANERGY; IFN-GAMMA; IMMUNOGLOBULIN; LYMPHOCYTES; DETERMINANTS; MOLECULES; MOUSE; MICE AB We have investigated the role of MHC class I products and CD8 T cells in regulating Ab responses using beta(2)-microglobulin deficient (beta(2)m(-/-)) mice. beta(2)m(-/-) mice produced stronger IgM and IgC responses than did control beta(2)m(+/+) mice to both cellular and viral Ags. These Ab responses could be suppressed by infusion of activated B cells from beta(2)m(+/+) mice. Further investigation showed that the beta(2)m-associated molecule on activated B cells that induced CD8 suppression was Qa-l and that the Th2 component of CD4 cells was most affected by CD8-suppressive activity. Our findings suggest a novel pathway of Th inhibition in which B cell presentation of Qa-l-associated peptides stimulates CD8 suppressive activity. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Cantor, H (reprint author), 44 Binney St, Boston, MA 02115 USA. RI Noble, Alistair/E-9473-2010 FU NIAID NIH HHS [AI13600, AI37562, AI37833] NR 44 TC 81 Z9 83 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 JAN 15 PY 1998 VL 160 IS 2 BP 566 EP 571 PG 6 WC Immunology SC Immunology GA YW267 UT WOS:000071915200007 PM 9551889 ER PT J AU Watson, A Eilers, A Lallemand, D Kyriakis, J Rubin, LL Ham, J AF Watson, A Eilers, A Lallemand, D Kyriakis, J Rubin, LL Ham, J TI Phosphorylation of c-Jun is necessary for apoptosis induced by survival signal withdrawal in cerebellar granule neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AP-1; apoptosis; cerebellar granule neurons; c-Jun; Jun kinase; signal transduction; stress-activated protein kinases ID PROGRAMMED CELL-DEATH; ACTIVATED PROTEIN-KINASES; GENE-EXPRESSION; DROSOPHILA JUN; TRANSCRIPTION FACTORS; SYMPATHETIC NEURONS; RNA-SYNTHESIS; MAP KINASES; INDUCTION; STRESS AB Cerebellar granule neurons die by apoptosis when deprived of survival signals. This death can be blocked by inhibitors of transcription or protein synthesis, suggesting that new gene expression is required. Here we show that c-jun mRNA and protein levels increase rapidly after survival signal withdrawal and that transfection of the neurons with an expression vector for a c-Jun dominant negative mutant protects them against apoptosis. Phosphorylation of serines 63 and 73 in the c-Jun transactivation domain is known to increase c-Jun activity. By using an antibody specific for c-Jun phosphorylated on serine 63, we show that this site is phosphorylated soon after survival signal withdrawal. To determine whether c-Jun phosphorylation is necessary for apoptosis, we have expressed c-Jun phosphorylation site mutants in granule neurons. c-Jun(asp), a constitutively active c-Jun mutant in which the known and potential serine and threonine phosphoacceptor sites in the transactivation domain have been mutated to aspartic acid, induces apoptosis under all conditions tested. In contrast, c-Jun(ala), which cannot be phosphorylated because the same sites have been mutated to alanine, blocks apoptosis caused by survival signal withdrawal. Finally, we show that cerebellar granule neurons contain high levels of Jun kinase activity and low levels of p38 kinase activity, neither of which increases after survival signal withdrawal. Mitogen-activated protein kinase activity decreases under the same conditions. These results suggest that c-Jun levels and c-Jun phosphorylation may be regulated by novel mechanisms in cerebellar granule neurons. C1 UCL, Eisai London Res Labs, London WC1E 6BT, England. Inst Pasteur, Dept Biotechnol, Unite Virus Oncogenes, F-75724 Paris 15, France. Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA. Ontogeny Inc, Cambridge, MA 02139 USA. RP Ham, J (reprint author), UCL, Eisai London Res Labs, Bernard Katz Bldg,Gower St, London WC1E 6BT, England. RI Ham, Jonathan/C-5164-2008 NR 52 TC 308 Z9 318 U1 0 U2 0 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 JAN 15 PY 1998 VL 18 IS 2 BP 751 EP 762 PG 12 WC Neurosciences SC Neurosciences & Neurology GA YQ697 UT WOS:000071414200018 PM 9425017 ER PT J AU Hemesath, TJ Price, ER Takemoto, C Badalian, T Fisher, DE AF Hemesath, TJ Price, ER Takemoto, C Badalian, T Fisher, DE TI MAP kinase links the transcription factor Microphthalmia to c-Kit signalling in melanocytes SO NATURE LA English DT Article ID RECEPTOR TYROSINE KINASE; CULTURED MAST-CELLS; GENE-EXPRESSION; MI/MI GENOTYPE; MELANOMA-CELLS; IN-VIVO; MOUSE; ACTIVATION; MUTATIONS; PROTEIN AB Germline mutations at loci encoding the transcription factor Microphthalmia (Mi), the cytokine receptor c-Kit, or its ligand Steel factor (Sl) result in strikingly similar defects in mast cell and melanocyte development(1-3). Here we describe a biochemical link between Kit signalling and the activity of Mi. Stimulation of melanoma cells with Sl results in activation of MAP kinase, which in turn phosphorylates Mi at a consensus target serine. This phosphorylation upregulates Mi transactivation of the tyrosinase pigmentation gene promoter. In addition to modulating pigment production, such signalling may regulate the expression of genes essential for melanocyte survival and development. The pathway represents a new application of the general MAP kinase machinery in transducing a signal between a tissue-specific receptor at the cell surface and a tissue-specific transcription factor in the nucleus. C1 Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu NR 27 TC 421 Z9 427 U1 1 U2 11 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 15 PY 1998 VL 391 IS 6664 BP 298 EP 301 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YR328 UT WOS:000071484400055 PM 9440696 ER PT J AU Rao, PM Rhea, JT Novelline, RA Mostafavi, AA McCabe, CJ AF Rao, PM Rhea, JT Novelline, RA Mostafavi, AA McCabe, CJ TI Effect of computed tomography of the appendix on treatment of patients and use of hospital resources SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DIAGNOSIS; EMERGENCY; CT; APPENDECTOMY; ACCURACY AB Background In patients with clinically suspected appendicitis, computed tomography (CT) is diagnostically accurate. However, the effect of routine CT of the appendix on the treatment of such patients and the use of hospital resources is unknown. Method's We performed appendiceal CT on 100 consecutive patients in the emergency department who, on the basis of history, physical examination, and laboratory results, were to be hospitalized for observation for suspected appendicitis or for urgent appendectomy. Outcomes were determined at surgery and by pathological examination in 59 patients, and by clinical follow-up two months later in 41 patients. Treatment plans made before CT were compared with the patients' actual treatment, We also determined the costs of surgery that revealed no appendicitis (from data on 61 patients), one day of observation in the hospital (from data on 350 patient-days in patients with suspected appendicitis), and appendiceal CT (from data on all pelvic CT examinations in 1996). Results Fifty-three patients had appendicitis, and 47 did not. The interpretations of the appendiceal CT scans were 98 percent accurate. The results of CT led to changes in the treatment of 59 patients. These changes resulted in the prevention of unnecessary appendectomy in 13 patients, admission to the hospital for observation in 18 patients, admission to the hospital for observation before necessary appendectomy in 21 patients, and admission to the hospital for observation before the diagnosis of other conditions by CT in 11 patients. The effects of performing appendiceal CT on the use of hospital resources included the prevention of unnecessary appendectomy in 13 patients (for a savings of $47,281) and the prevention of unnecessary hospital admission for 50 patient-days (for a savings of $20,250). After the cost of 100 appendiceal CT studies ($22,800) was subtracted, the overall savings was $447 per patient. Conclusions Routine appendiceal CT performed in patients who present with suspected appendicitis improves patient care and reduces the use of hospital resources. (C) 1998, Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 24 TC 425 Z9 433 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 1998 VL 338 IS 3 BP 141 EP 146 DI 10.1056/NEJM199801153380301 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YQ414 UT WOS:000071384500001 PM 9428814 ER PT J AU Edelson, MI Lau, CC Colitti, CV Welch, WR Bell, DA Berkowitz, RS Mok, SC AF Edelson, MI Lau, CC Colitti, CV Welch, WR Bell, DA Berkowitz, RS Mok, SC TI A one centimorgan deletion unit on chromosome Xq12 is commonly lost in borderline and invasive epithelial ovarian tumors SO ONCOGENE LA English DT Article DE ovary; cancer; borderline; loss of heterozygosity; chromosome Xq ID ANDROGEN-RECEPTOR GENE; HUMAN PROSTATE-CANCER; TERM FOLLOW-UP; X-CHROMOSOME; LINKAGE MAP; MALIGNANCY; MUTATION; CARCINOMAS; HETEROZYGOSITY; PROGRESSION AB We have used polymerase chain reaction (PCR) amplification of tandem repeats to study the pattern of allelic loss on chromosome X11.2-q12 in borderline and invasive epithelial ovarian tumors, Using eight microsatellite markers spanning Xq11.2-q12, 41 borderline and 65 invasive ovarian tumors, together with their corresponding normal tissues, were analysed, The highest percentage of loss of heterozygosity (LOH) was observed at the DXS1194 locus in borderline tumors (four of 16 informative cases, 25%) and at the androgen receptor (AR) locus in invasive epithelial ovarian tumors (18 of 47 informative cases, 38%), X chromosome activation studies performed in cases with LOH at the AR locus showed that the allelic loss at the AR locus is not confined to the inactive allele, A one centimorgan region including the AR locus and flanked by the primers DXS1161 and PGK1P1 was identified as the smallest common loss region in both borderline and invasive epithelial ovarian tumors. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Lab Gynecol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Texas Childrens Hosp, Div Hematol Oncol, Houston, TX 77030 USA. RP Mok, SC (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Lab Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA63381] NR 28 TC 40 Z9 40 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 15 PY 1998 VL 16 IS 2 BP 197 EP 202 DI 10.1038/sj.onc.1201479 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YQ827 UT WOS:000071427100006 PM 9464537 ER PT J AU Singh, N Gayowski, T Wannstedt, CF Shakil, AO Wagener, MM Fung, JJ Marino, IR AF Singh, N Gayowski, T Wannstedt, CF Shakil, AO Wagener, MM Fung, JJ Marino, IR TI Interferon-alpha for prophylaxis of recurrent viral hepatitis C in liver transplant recipients: A prospective, randomized, controlled trial SO TRANSPLANTATION LA English DT Article ID HUMAN-LEUKOCYTE INTERFERON; VIRUS-INFECTION; CYTOMEGALO-VIRUS; RECOMBINANT; REJECTION; ALLOGRAFT; THERAPY AB Background In a randomized, controlled trial, we sought to determine whether prophylaxis with interferon-alpha for 6 months had an impact on rate, severity, and timing of onset of recurrent hepatitis C virus (HCV hepatitis in liver transplant recipients and to assess whether interferon use was associated with re jection in liver transplant recipients. Methods. Twenty-four consecutive liver transplant recipients with HCV were randomized after transplantation to receive either interferon alpha (3 million Il three times weekly) for 6 months or no prophylaxis; median follow-up was 874 days. Results. Recurrent HCV hepatitis (histopathologically proven) developed in 50% (6 of 12) of the interferon-alpha patients versus 42% (5 of 12) of the control patients (P=NS). Severity of recurrence (as assessed by Knodell score on liver biopsies) also did not differ between the two groups (mean 4.0 for interferon-alpha patients versus 3.5 for control patients, P=NS), Interferon alpha, however, significantly delayed the timing of occurrence of HCV hepatitis; recurrent HCV hepatitis developed a median of 408 days after transplant in the interferon-alpha group versus 193 days in the control group (P=0.05). No difference in graft or patient survival was demonstrated in the two groups. Rejection episodes, treated with corticosteroids, occurred in 50% (6 of 12) of patients in the interferon-alpha group versus 42% (5 of 12) in the control group (P=NS). Corticosteroid resistant rejection (requiring OKT3) occurred in only one study patient (in the control group). Conclusions. Interferon-alpha in liver transplant recipients for 6 months delayed the occurrence of HCV hepatitis, but did not decrease the incidence nor the severity of HCV hepatitis after transplantation. Interferon-alpha use was not associated with a higher incidence of rejection compared with the control patients. C1 Vet Affairs Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. RP Singh, N (reprint author), VA Pittsburgh Hlth Care Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. RI Fung, John/A-2679-2012 NR 24 TC 117 Z9 119 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1998 VL 65 IS 1 BP 82 EP 86 DI 10.1097/00007890-199801150-00016 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YR654 UT WOS:000071516900015 PM 9448149 ER PT J AU Pascual, M Rabito, CA Tolkoff-Rubin, N Auchincloss, H Farrell, ML Delmonico, FL Cosimi, AB AF Pascual, M Rabito, CA Tolkoff-Rubin, N Auchincloss, H Farrell, ML Delmonico, FL Cosimi, AB TI Contribution of native kidney function to total glomerular filtration rate after combined kidney-pancreas transplantation SO TRANSPLANTATION LA English DT Article ID RENAL-TRANSPLANTATION; DIABETES-MELLITUS; EVOLUTION AB Background Combined kidney-pancreas transplantation (CKPT) with its associated euglycemia has been shown to prevent or reduce recurrent diabetic nephropathy in the renal allograft, There has been no evaluation of residual native kidney function after CKPT. The purpose of this study was to determine whether native kidney function may be present in diabetic recipients years after CKPT, Methods, Between 1986 and 1992, 37 patients with type 1 insulin-dependent diabetes mellitus with renal failure underwent CKPT, In each case, a single native nephrectomy was performed, We studied 16 patients who had continuing renal and pancreas function more than 4 years after CI(PT, Fourteen diabetics with a functioning renal allograft but no pancreas function were used as a control group, Simultaneous renal scans (technetium-99m diethylenetriamine pentaacetic acid) of the native and transplanted kidneys were obtained with a dual-head scintillation camera, Total glomerular filtration rate (GFR) was determined from the rate of clearance of the tracer from the extracellular space measured for 2 hr with an ambulatory renal monitor, Results, The study groups had similar pretransplant characteristics. At the time of the study, the mean serum creatinine level was not significantly different in the CKPT and control groups (1.7+/-0.7 vs, 1.5+/-0.3 mg/dl, respectively), In the CKPT and control groups, total GFRs were 70.1+/-33 vs, 72.1+/-16.5 ml/min (NS), allograft GFRs were 63+/-34.2 vs, 70.4+/-16 ml/min (NS), and native kidney GFRs were 7.1+/-7.2 vs, 1.7+/-1.9 ml/min (P<0.05), respectively, In both groups, there was a significant correlation between total GFR and allograft GFR (P<0.001), but not between total GFR and native kidney GFR, Significant single native kidney GFR (more than 8 ml/min) was found in 7/16 (44%) patients in the CKPT group, but in none of the controls. Conclusions, These results suggest that residual native kidney function can be present and contribute moderately to total GFR after CKPT, Euglycemia after CKPT may have a protective role in native kidneys. C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Box MZ-70,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1998 VL 65 IS 1 BP 99 EP 103 DI 10.1097/00007890-199801150-00019 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YR654 UT WOS:000071516900018 PM 9448152 ER PT J AU Sabatine, MS Laufer, T Glimcher, LH Widmer, M Winn, H Auchincloss, H AF Sabatine, MS Laufer, T Glimcher, LH Widmer, M Winn, H Auchincloss, H TI Delayed rejection of soluble tumor necrosis factor receptor-secreting tumor allografts SO TRANSPLANTATION LA English DT Article ID MURINE INTERLEUKIN-4 RECEPTOR; COLLAGEN-INDUCED ARTHRITIS; HUMAN-COMPLEMENT INHIBITOR; HUMAN-ENDOTHELIAL-CELLS; FACTOR BINDING-PROTEIN; TNF RECEPTOR; FACTOR-ALPHA; MONOCLONAL-ANTIBODIES; MOLECULAR-CLONING; FUSION PROTEIN AB Background. Exogenous soluble tumor necrosis factor receptor (TNFR) has been shown to be an effective immunosuppressant. It has yet to be tested whether tissues secreting soluble TNFR, when transplanted into a foreign host, could locally generate immunosuppression and therefore manifest prolonged survival. Methods. A murine tumor line was transfected with the gene encoding a chimeric protein consisting of the extracellular domain of the human 75-kDa TNFR fused to the Pc region of the human IgG1 heavy chain. This tumor line was then injected into allogeneic recipients. Results. Transfected tumor cells were shown to secrete soluble TNFR. When transplanted into minor histocompatibility antigen-disparate allogeneic recipients, these tumor cells grew as a solid tumor and resisted rejection, whereas untransfected tumors and interleukin-4 receptor transfectant controls were rejected within 4 weeks. The resistance to rejection could be reversed by coadministration of an anti-TNFR monoclonal antibody. Conclusions, Prolongation of graft survival can be achieved by genetically altering transplanted tissue to secrete soluble cytokine receptors. C1 Massachusetts Gen Hosp, Transplantat Unit, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Gen Surg Serv, GRB 504,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-18646]; NIAID NIH HHS [AI-38397] NR 78 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1998 VL 65 IS 1 BP 113 EP 120 DI 10.1097/00007890-199801150-00022 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YR654 UT WOS:000071516900021 PM 9448155 ER PT J AU Solomon, KR Mallory, MA Hanify, KA Finberg, RW AF Solomon, KR Mallory, MA Hanify, KA Finberg, RW TI The nature of membrane anchorage determines kinase associations and detergent solubility of CD4 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-TYROSINE KINASES; CELL-SURFACE; ALKALINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; EPITHELIAL-CELL; MDCK CELLS; MOLECULES; CAVEOLIN; DOMAINS; LCK AB The presence of a glycosylphosphatidylinositol (GPI) anchor on a membrane protein is thought to influence aspects of the protein's biochemistry. While it has been demonstrated that a GPI-anchor is sufficient for altering the detergent solubility of integral membrane proteins, it has not been shown that the anchor is sufficient for changing the phosphoprotein associations of membrane proteins. In order to define the influence of GPI-anchors on the biochemistry of membrane proteins we compared the phosphoprotein associations and detergent solubility of wild-type and GPI-anchored CD4 expressed on HSB cell transfectants. While wild-type CD4 was mostly associated with lck kinase, GPI-anchored CD4 was associated with the 'GPI-anchored pattern of phosphoproteins'. The Triton X-100 solubilities of the two forms of CD4 were also distinct: wild-type CD4 was > 95% soluble, whereas GPI-anchored CD4 was only 65% soluble. These results underscore the deterministic role of the GPI-anchor in the properties associated with GPI-anchored proteins. (C) 1998 Academic Press. C1 Dana Farber Canc Inst, Infect Dis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Solomon, KR (reprint author), Dana Farber Canc Inst, Infect Dis Unit, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [T32 AI 07061-19] NR 31 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC 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 JAN 14 PY 1998 VL 242 IS 2 BP 423 EP 428 DI 10.1006/bbrc.1997.7983 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YR446 UT WOS:000071496100034 PM 9446811 ER PT J AU Koch, PJ Kastowsky, M Bradaczek, H Brandenburg, K AF Koch, PJ Kastowsky, M Bradaczek, H Brandenburg, K TI Improvement of x-ray powder-diffraction patterns of Salmonella minnesota deep rough mutant bacterial lipopolysaccharide induced by heating plus hydration SO THIN SOLID FILMS LA English DT Article DE hydration of bilayers; membrane structure and order; Salmonella minnesota R595 deep rough mutant lipopolysaccharide (Re-LPS); self-aggregated membrane; X-ray powder-diffraction ID PHASE-BEHAVIOR; CONFORMATION; MEMBRANES; NEUTRON AB The effects of different sample treatments on the X-ray powder-diffraction patterns of Salmonella minnesota R595 deep rough mutant bacterial lipopolysaccharides (LPS) were investigated. Samples were obtained by slow evaporation of aqueous solutions or suspensions of sodium, lithium and natural salt form lipids. Samples were treated by hydration in moist air, heating to 60 degrees C and heating plus hydration. While after heating of samples no changes in diffraction patterns were observed, other treatments resulted in the improvement of peak intensities and sharpness of reflections. Heating plus hydration gave the most significant effects. For one natural salt form LPS sample the treatments resulted in almost doubling of the number of observable: reflections with the highest order found at 2 theta = 36 degrees. It is discussed that the effects of treatments are most probably related to perfection of the lateral and the stacking order in the samples, rather than an improved mosaic spread. The simplicity of our sample treatment:, make them suitable fur application to other than lipopolpsaccharide samples, especially for samples prepared by the Langmuir-Blodgett method. (C) 1998 Elsevier Science S.A. C1 Free Univ Berlin, Inst Kristallog, D-14195 Berlin, Germany. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Forschungsinst Borstel, D-23845 Borstel, Germany. RP Koch, PJ (reprint author), Free Univ Berlin, Inst Kristallog, Takustr 6, D-14195 Berlin, Germany. NR 16 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0040-6090 J9 THIN SOLID FILMS JI Thin Solid Films PD JAN 14 PY 1998 VL 312 IS 1-2 BP 313 EP 319 DI 10.1016/S0040-6090(97)00952-8 PG 7 WC Materials Science, Multidisciplinary; Materials Science, Coatings & Films; Physics, Applied; Physics, Condensed Matter SC Materials Science; Physics GA ZN334 UT WOS:000073635500053 ER PT J AU Reardon, LC Macpherson, DS AF Reardon, LC Macpherson, DS TI Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors - How much should we worry? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CONGESTIVE-HEART-FAILURE; CHRONIC-RENAL-FAILURE; DIABETIC HYPERTENSIVE PATIENTS; LIFE-THREATENING HYPERKALEMIA; RANDOMIZED CONTROLLED TRIAL; COMBINED THERAPY; ENALAPRIL; CAPTOPRIL; LISINOPRIL; SAFETY AB Background: Hyperkalemia is a potentially life-threatening complication resulting from the use of angiotensin-converting enzyme (ACE) inhibitors; data to guide the intensity of monitoring for or responding to hyperkalemia in outpatients are limited. Methods: Case-control methodological procedures were used to identify risk factors for hyperkalemia. Outpatients prescribed ACE inhibitors during 1992 and 1993 at a Veterans affairs medical center general medicine clinic were identified. Case patients had a potassium level higher than 5.1 mmol/L on the day of clinic visit while using an ACE inhibitor; controls had a potassium level lower than 5.0 mmol/L on the day of clinic visit while using an ACE inhibitor and had no elevated potassium level during the study period. Predictor variables measured included type and dosage of ACE inhibitor; serum chemistries; comorbidities; concurrent drug use; and age. Case patients were followed up for 1 year after the index episode of hyperkalemia. Follow-up variables included changes in therapy with ACE inhibitor, maximum potassium for each change, and mortality. Results: Of 1818 patients using ACE inhibitors, 194 (11%) developed hyperkalemia. Results of laboratory studies indicating a serum urea nitrogen level higher than 6.4 mmol/L (18 mg/dL), creatinine level higher than 136 mu mol/L (1.5 mg/dL), congestive heart failure, and long-acting ACE inhibitors were independently associated with hyperkalemia; concurrent use of loop or thiazide diuretic agent was associated with reduced risk. After 1 year of follow-up, 15 (10%) of 146 case patients remaining on a regimen of an ACE inhibitor developed severe hyperkalemia (potassium level > 6.0 mmol/L). a serum urea nitrogen level higher than 8.9 mmol/L (25 mg/dL) and age more than 70 years were independently associated with subsequent severe hyperkalemia. Conclusions: Mild hyperkalemia is common in medical outpatients using ACE inhibitors, especially in those with renal insufficiency or congestive heart failure. However, once hyperkalemia is identified during the use of ACE inhibitors, subsequent severe hyperkalemia is uncommon in patients younger than 70 years with normal renal function. C1 Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15240 USA. RP Macpherson, DS (reprint author), Univ Pittsburgh, Vet Affairs Pittsburgh Healthcare Syst, Dept Med, Univ Dr C, Pittsburgh, PA 15240 USA. NR 55 TC 125 Z9 130 U1 0 U2 1 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 JAN 12 PY 1998 VL 158 IS 1 BP 26 EP 32 DI 10.1001/archinte.158.1.26 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YQ742 UT WOS:000071418700004 PM 9437375 ER PT J AU Soriano, SG Wang, YMF Lipton, SA Dikkes, P Gutierrez-Ramos, JC Hickey, PR AF Soriano, SG Wang, YMF Lipton, SA Dikkes, P Gutierrez-Ramos, JC Hickey, PR TI ICAM-1 dependent pathway is not involved in the development of neuronal apoptosis after transient focal cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE apoptosis; cerebral ischemia; ICAM-1 ID PROGRAMMED CELL-DEATH; SUPEROXIDE; NECROSIS; MICE AB We examined brain sections from ICAM-1 deficient mice (-/-) and their nontransgenic Littermates (+/+) after focal cerebral ischemia and reperfusion (I/R) for the presence of apoptosis. Despite the reduction in necrosis, the -/- mice had apoptotic cells in the ischemic hemisphere as shown by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining and DNA laddering. ICAM-1 deficiency minimizes necrosis but not apoptosis after temporary MCAO in mice, thereby leaving the potential for delayed neuronal cell death despite ICAM-1 inactivation. (C) 1998 Elsevier Science B.V. C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Soriano, SG (reprint author), Childrens Hosp, Dept Anesthesia, 300 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL148675-02]; NICHD NIH HHS [P01 HD29587-05] NR 16 TC 9 Z9 13 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 JAN 12 PY 1998 VL 780 IS 2 BP 337 EP 341 DI 10.1016/S0006-8993(97)01298-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA YZ503 UT WOS:000072260600017 PM 9507184 ER PT J AU Voskuyl, RA Vreugdenhil, M Kang, JX Leaf, A AF Voskuyl, RA Vreugdenhil, M Kang, JX Leaf, A TI Anticonvulsant effect of polyunsaturated fatty acids in rats, using the cortical stimulation model SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE polyunsaturated fatty acid; anticonvulsant; cortical stimulation model ID VOLTAGE-DEPENDENT LIMITATION; MOUSE CENTRAL NEURONS; SODIUM-CHANNELS; CARDIAC MYOCYTES; NA+ CHANNELS; CELL-CULTURE; DRUGS DIPHENYLHYDANTOIN; DOCOSAHEXAENOIC ACID; ANTIEPILEPTIC DRUGS; ACTION-POTENTIALS AB Recent studies have shown that long-chain polyunsaturated fatty acids can prevent cardiac arrhythmias, attributed to the reduction in excitability of cardiomyocytes, owing mainly to a shift in hyperpolarizing direction of the inactivation curves of both Na+ and Ca2+ currents and to a slowed recovery from inactivation. Qualitatively similar effects of polyunsaturated fatty acids on inactivation parameters have been observed in freshly isolated hippocampal neurons. Since the same effects are presumed to underlie the action of some established anticonvulsant drugs, polyunsaturated fatty acids might have an anticonvulsant action as well. We have investigated this for eicosapentaenoic acid, docosahexaenoic acid, linoleic acid and oleic acid, employing cortical stimulation in rats, a seizure model allowing the determination of the full anticonvulsant effect-time profile in freely moving, individual animals. I.v. infusion of 40 mu mol of eicosapentaenoic acid or docosahexaenoic acid over a period of 30 min, modestly increased the threshold for localized seizure activity after 6 h by 73 +/- 13 mu A (mean +/- S.E.M.; n = 7) and 77 +/- 17 mu A (n = 7), respectively, and the threshold for generalized seizure activity by 125 +/- 20 and 130 +/- 19 mu A, respectively (P < 0.001). The thresholds remained elevated for 6 h after infusion, but returned to baseline the next day. Free plasma concentrations in rats treated with eicosapentaenoic acid or docosahexaenoic acid, averaged 5.7 +/- 1.6 mu M (n = 4) for eicosapentaenoic acid and 12.9 +/- 1.8 mu M (n = 5) for docosahexaenoic acid at the end of infusion, but declined to undetectable levels within 3 h. Linoleic acid and oleic acid were less effective. Possible mechanisms for the modest anticonvulsant effect but of long duration with the polyunsaturated fatty acids are discussed. (C) 1998 Elsevier Science B.V. C1 Leiden Univ, Dept Physiol, NL-2300 RC Leiden, Netherlands. Inst Epilepsiebestrijding, Heemstede, Netherlands. Univ Amsterdam, Inst Neurobiol, NL-1098 SM Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Voskuyl, RA (reprint author), Leiden Univ, Dept Physiol, POB 9604, NL-2300 RC Leiden, Netherlands. FU NIDDK NIH HHS [DK38165] NR 43 TC 93 Z9 93 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 12 PY 1998 VL 341 IS 2-3 BP 145 EP 152 DI 10.1016/S0014-2999(97)01467-2 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA323 UT WOS:000072352000005 PM 9543232 ER PT J AU Higgins, JMG Mandlebrot, DA Shaw, SK Russell, GJ Murphy, EA Chen, YT Nelson, WJ Parker, CM Brenner, MB AF Higgins, JMG Mandlebrot, DA Shaw, SK Russell, GJ Murphy, EA Chen, YT Nelson, WJ Parker, CM Brenner, MB TI Direct and regulated interaction of integrin alpha(E)beta(7) with E-cadherin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; FUNCTION-ASSOCIATED ANTIGEN-1; EPITHELIAL-CELLS; MONOCLONAL-ANTIBODY; T-LYMPHOCYTES; CRYSTAL-STRUCTURE; BINDING-SITE; N-CADHERIN; P-CADHERIN AB The cadherins are a family of homophilic adhesion molecules that play a vital role in the formation of cellular junctions and in tissue morphogenesis. Members of the integrin family are also involved in cell to cell adhesion, but bind heterophilically to immunoglobulin superfamily molecules such as intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, or mucosal addressin cell adhesion molecule (MadCAM)-1. Recently, an interaction between epithelial (E-) cadherin and the mucosal lymphocyte integrin, alpha(E) beta(7), has been proposed. Here, we demonstrate that a human E-cadherin-Fc fusion protein binds directly to soluble recombinant alpha(E) beta(7), and to alpha(E) beta(7) solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY' cells expressing the alpha(E) beta(7) integrin adhere strongly to purified E-cadherin-Fc coated on plastic, and the adhesion can be inhibited by antibodies to alpha(E) beta(7) or E-cadherin. The binding of alpha(E) beta(7) integrin to cadherins is selective since cell adhesion to P-cadherin-Fc through alpha(E) beta(7) requires >100-fold more fusion protein than to E-cadherin-Fc. Although the structure of the alpha(E)-chain is unique among integrins, the avidity of alpha(E) beta(7) for E-cadherin can be regulated by divalent cations or phorbol myristate acetate. Cross-linking of the T cell receptor complex on intraepithelial lymphocytes increases the avidity of alpha(E) beta(7) for E-cadherin, and may provide a mechanism for the adherence and activation of lymphocytes within the epithelium in the presence of specific foreign antigen. Thus, despite its dissimilarity to known integrin ligands, the specific molecular interaction demonstrated here indicates that E-cadherin is a direct counter receptor for the alpha(E) beta(7) integrin. C1 Harvard Univ, Brigham & Womens Hosp,Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Lymphocyte Biol Sect, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Beckman Ctr, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA. RP Brenner, MB (reprint author), Harvard Univ, Brigham & Womens Hosp,Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Lymphocyte Biol Sect, Smith Bldg,Room 552,75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI01212]; NIDDK NIH HHS [P30 DK043351, DK43351]; NIGMS NIH HHS [R01 GM035527, R29 GM49342, R37 GM035527] NR 98 TC 141 Z9 144 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 12 PY 1998 VL 140 IS 1 BP 197 EP 210 DI 10.1083/jcb.140.1.197 PG 14 WC Cell Biology SC Cell Biology GA YR491 UT WOS:000071500600019 PM 9425167 ER PT J AU Davies, SW Beardsall, K Turmaine, M DiFiglia, M Aronin, N Bates, GP AF Davies, SW Beardsall, K Turmaine, M DiFiglia, M Aronin, N Bates, GP TI Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions? SO LANCET LA English DT Article ID SPINOCEREBELLAR ATAXIA TYPE-2; BULBAR MUSCULAR-ATROPHY; ANDROGEN RECEPTOR GENE; CAG REPEAT; HYALINE INCLUSIONS; DISEASE; DEGENERATION; CLONING AB Neuronal intranuclear inclusions have been found in the brain of a transgenic mouse model of Huntington's disease and in necropsy brain tissue of patients with Huntington's disease, We suggest that neuronal intranuclear inclusions are the common neuropathology for all inherited diseases caused by expansion of polyglutamine repeats, We also suggest that patients with a pathological diagnosis of neuronal intranuclear hyaline inclusion disease may also have polyglutamine repeat expansions. C1 UCL, Dept Anat & Dev Biol, London WC1E 6JJ, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Univ Med & Dent New Jersey, Guys Hosp, Div Med & Mol Genet, London, England. RP Davies, SW (reprint author), UCL, Dept Anat & Dev Biol, Rockefeller Bldg, London WC1E 6JJ, England. RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 NR 39 TC 133 Z9 133 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 10 PY 1998 VL 351 IS 9096 BP 131 EP 133 DI 10.1016/S0140-6736(97)08360-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA YT341 UT WOS:000071591900045 PM 9439509 ER PT J AU Ottinger, EA Botfield, MC Shoelson, SE AF Ottinger, EA Botfield, MC Shoelson, SE TI Tandem SH2 domains confer high specificity in tyrosine kinase signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; GROWTH-FACTOR RECEPTOR; PHOSPHOTYROSINE-CONTAINING PEPTIDES; SRC HOMOLOGY-2 DOMAIN; T-CELL RECEPTOR; HIGH-AFFINITY BINDING; FACTOR BETA-RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHORYLATED PEPTIDES; PHOSPHATASE SH-PTP2 AB SH2 domain proteins transmit intracellular signals initiated by activated tyrosine kinase-linked receptors. Recent three-dimensional structures suggest mechanisms by which tandem SH2 domains might confer higher specificity than individual SH2 domains, To test this, binding studies were conducted with tandem domains from the five signaling enzymes: phosphatidylinositol 3-kinase p85, ZAP-70, Syk, SHP-2, and phospho; lipase C-gamma 1. Bisphosphorylated TAMs (tyrosine-based activation motifs) were derived from biologically relevant sites in platelet-derived growth factor, T cell, B cell, and high affinity IgE receptors and the receptor substrates IRS-1 (insulin receptor substrate-1) and SHPS-1/SIRP. Each tandem SH2 domain binds a distinct TAM corresponding to its appropriate biological partner with highest affinity (0.5-3.0 nM). Alternative TAMs bind the tandem SH2 domains with 1,000- to >10,000- fold lower affinity than biologically relevant TAMs. This level of specificity is significantly greater than the similar to 20-50-fold typically seen for individual SH2 domains, We conclude that high biological specificity is conferred by the simultaneous interaction of two SH2 domains in a signaling enzyme with bisphosphorylated TAMs in activated receptors and substrates. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. RP Shoelson, SE (reprint author), 130 Waverly St, Cambridge, MA 02139 USA. FU NIDDK NIH HHS [DK36836, DK43123, DK45943] NR 53 TC 141 Z9 142 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 9 PY 1998 VL 273 IS 2 BP 729 EP 735 DI 10.1074/jbc.273.2.729 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ669 UT WOS:000071411400013 PM 9422724 ER PT J AU Wilson, SB Kent, SC Patton, KT Orban, T Jackson, RA Exley, M Porcelli, S Schatz, DA Atkinson, MA Balk, SP Strominger, JL Hafler, DA AF Wilson, SB Kent, SC Patton, KT Orban, T Jackson, RA Exley, M Porcelli, S Schatz, DA Atkinson, MA Balk, SP Strominger, JL Hafler, DA TI Extreme Th1 bias of invariant V alpha 24J alpha Q T cells in type 1 diabetes SO NATURE LA English DT Article ID FIRST-DEGREE RELATIVES; MICE; LYMPHOCYTES; AUTOIMMUNITY; EXPRESSION; RESPONSES; SEARCH; GENES; MOUSE; IDDM AB Type 1 diabetes (insulin-dependent diabetes-mellitus, IDDM) is a disease controlled by the major histocompatibility complex (MHC) which results from T-cell-mediated destruction of pancreatic beta-cells(1). The incomplete concordance in identical twins and the presence of autoreactive T cells and autoantibodies in individuals who do not develop diabetes suggest that other abnormalities must occur in the immune system for disease to result(2,3). We therefore investigated a series of at-risk non-progressors and type 1 diabetic patients (including five identical twin/tripiet sets discordant for disease). The diabetic siblings had lower frequencies of CD4(-)CD8(-)V alpha 24J alpha Q(+) T cells compared with their non-diabetic sibling, All 56 V alpha 24J alpha Q(+) clones isolated from the diabetic twins/triplets secreted only interferon (IFN)-gamma upon stimulation; in contrast, 76 of 79 clones from the at-risk non-progressors and normals secreted both interleukin (IL)-4 and IFN-gamma. Half of the at-risk non-progressors had high serum levels of IL-4 and IFN-gamma. These results support a model for IDDM in which Th1-cell-mediated tissue damage is initially regulated by V alpha 24J alpha Q(+) T cells producing both cytokines; the loss of their capacity to secrete IL-4 is correlated with IDDM. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Immunol Sect, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Canc Biol Program, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Florida, Dept Pathol, Gainesville, FL 32610 USA. Univ Florida, Dept Pediat, Gainesville, FL 32610 USA. RP Hafler, DA (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. NR 27 TC 524 Z9 534 U1 0 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 8 PY 1998 VL 391 IS 6663 BP 177 EP 181 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ378 UT WOS:000071380900051 PM 9428763 ER PT J AU Dahia, PLM Aguiar, RCT Honegger, J Fahlbush, R Jordan, S Lowe, DG Lu, X Clayton, R Besser, GM Grossman, AB AF Dahia, PLM Aguiar, RCT Honegger, J Fahlbush, R Jordan, S Lowe, DG Lu, X Clayton, R Besser, GM Grossman, AB TI Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours SO ONCOGENE LA English DT Article DE Cushing's disease; ACTH-tumour; p27-kip1; mutation; carcinoid; cell cycle inhibitor; pituitary tumour ID DEPENDENT KINASE INHIBITOR; HUMAN PITUITARY-TUMORS; GROWTH-FACTOR-BETA; RETINOBLASTOMA GENE; P27(KIP1) GENE; CDK INHIBITOR; MICE LACKING; CELL-CYCLE; P27; G1 AB The molecular mechanisms leading to Cushing's disease are unclear, Inhibitors of cyclin-cyclin dependent kinase (CDK) complexes are regulators of the cell cycle and may function as tumour suppressor genes, many of which have been involved in the pathogenesis of several human malignancies, A member of this family, the p27/kip1 gene, maps to chromosome 12p13 and encodes an inhibitor of several cyclin-CDK complexes; these control the progression of the cell cycle from G1 to S-phase, Complete lack of p27/kip1 function, as occurs in the p27/kip1 'knockout' mouse, produces a complex phenotype associated with the development of pituitary tumours, specifically those of the intermediate lobe corticotrophs, We therefore investigated whether structural and functional abnormalities of the p27/kip1 gene and loss at the chromosome 12p13 region were present in human corticotrophin (ACTH)-secreting pituitary tumours, We studied 21 pituitary tumours, of which 20 were ACTH-secreting (two of these had biochemical and histological features of 'intermediate-lobe' tumours and one was malignant) while the remaining tumour was a prolactinoma; three ectopic secretors of ACTH (two bronchial and one thymic carcinoid); and a non-secretory thymic carcinoid, The whole coding region of the p27/kip1 gene was screened for mutations by PGR-SSCP analysis and/or direct sequencing, while tumour mRNA expression was analysed by means of a semi-quantitative duplex PGR, Three polymorphic microsatellite markers of the 12p13 region were used to assess loss of heterozygosity (LOH) in 12 samples, Finally, tumour p27/kip1 protein expression was assessed by immunohistochemistry using a monoclonal antibody in 12 samples suitable for analysis, No sequence abnormalities were found in any of the samples other than a previously-described polymorphism, No LOH was observed in the tumours analysed, p27/kip1 mRNA expression was similar in tumour samples in comparison with normal pituitaries, Seven of the eight corticotroph tumours analysed by immunohistochemistry stained positive for p27/kip1, including the intermediate lobe, The only malignant pituitary tumour in the original series showed an absence of staining for p27/kip1, In addition, the three carcinoid tumours studied were negative on immunohistochemistry. Of a further three malignant pituitary tumours assessed, two (including a prolactinoma) were essentially negative, while the third was moderately positive, We conclude that mutations of the p27/kip1 gene, deletions of the 12p13 area or changes in expression, are not a general feature of corticotroph tumours, even those with intermediate lobe characteristics, However, other mechanisms of p27/kip1 inactivation, such as an abnormality at the post-translational level, may be related to more aggressive histological subtypes of ACTH-secreting and possibly other pituitary tumours. C1 St Bartholomews Hosp, Dept Endocrinol, London, England. St Bartholomews Hosp, Dept Pathol, London, England. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Neurochirurg Klin, D-8520 Erlangen, Germany. St Marys Hosp, Ludwig Inst Canc Res, London, England. Univ Keele, Postgrad Med Sch, Dept Med, Stoke On Trent, Staffs, England. RP Grossman, AB (reprint author), St Bartholomews Hosp, Dept Endocrinol, London, England. NR 34 TC 75 Z9 80 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 8 PY 1998 VL 16 IS 1 BP 69 EP 76 DI 10.1038/sj.onc.1201516 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YP056 UT WOS:000071236800008 PM 9467944 ER PT J AU Albert, CM Hennekens, CH O'Donnell, CJ Ajani, UA Carey, VJ Willett, WC Ruskin, JN Manson, JE AF Albert, CM Hennekens, CH O'Donnell, CJ Ajani, UA Carey, VJ Willett, WC Ruskin, JN Manson, JE TI Fish consumption and risk of sudden cardiac death SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; POLYUNSATURATED FATTY-ACIDS; VENTRICULAR-FIBRILLATION; MYOCARDIAL-INFARCTION; MORTALITY; OMEGA-3-FATTY-ACIDS; REPRODUCIBILITY; POPULATION; PHYSICIANS AB Context.-Dietary fish intake has been associated with a reduced risk of fatal cardiac end points, but not with nonfatal end points. Dietary fish intake may have a selective benefit on fatal arrhythmias and therefore sudden cardiac death. Objective.-To investigate prospectively the association between fish consumption and the risk of sudden cardiac death. Design.-Prospective cohort study. Setting.-The US Physicians' Health Study. Patients.-A total of 20 551 US male physicians 40 to 84 years of age and free of myocardial infarction, cerebrovascular disease, and cancer at baseline who completed an abbreviated, semiquantitative food frequency questionnaire on fish consumption and were then followed up to 11 years. Main Outcome Measure.-Incidence of sudden cardiac death (death within 1 hour of symptom onset) as ascertained by hospital records and reports of next of kin. Results.-There were 133 sudden deaths over the course of the study. After controlling for age, randomized aspirin and beta carotene assignment, and coronary risk factors, dietary fish intake was associated with a reduced risk of sudden death, with an apparent threshold effect at a consumption level of 1 fish meal per week (P for trend=.03). For men who consumed fish at least once per week, the multivariate relative risk of sudden death was 0.48 (95% confidence interval, 0.24-0.96; P=.04) compared with men who consumed fish less than monthly. Estimated dietary n-3 fatty acid intake from seafood also was associated with a reduced risk of sudden death but without a significant trend across increasing categories of intake. Neither dietary fish consumption nor n-3 fatty acid intake was associated with a reduced risk of total myocardial infarction, nonsudden cardiac death, or total cardiovascular mortality. However, fish consumption was associated with a significantly reduced risk of total mortality. Conclusion.-These prospective data suggest that consumption of fish at least once per week may reduce the risk of sudden cardiac death in men. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA-34944, CA-40360]; NHLBI NIH HHS [HL-26490] NR 41 TC 592 Z9 607 U1 3 U2 27 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 JAN 7 PY 1998 VL 279 IS 1 BP 23 EP 28 DI 10.1001/jama.279.1.23 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YP607 UT WOS:000071295100030 PM 9424039 ER PT J AU Kanai, M Mullen, C Podolsky, DK AF Kanai, M Mullen, C Podolsky, DK TI Intestinal trefoil factor induces inactivation of extracellular signal-regulated protein kinase in intestinal epithelial cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IEC-6 cell; mitogen-activated protein kinase; TGF alpha; PMA; phosphatase ID EPIDERMAL GROWTH-FACTOR; SPASMOLYTIC POLYPEPTIDE; MAP-KINASE; STOMACH MUCOSA; OKADAIC ACID; PEPTIDES; EXPRESSION; PATHWAY; IDENTIFICATION; PHOSPHATASES AB Intestinal trefoil factor (ITF), a small, compact protease-resistant peptide, is abundantly expressed in goblet cells of large and small intestine, Although several biological activities of ITF have been identified, including promotion of wound healing, stimulation of epithelial cell migration, and protection of intestinal epithelial barrier, little is known about signaling events through which ITF mediates its physiological function, In this study, the effects of exogenous ITF on mitogen-activated protein kinase (MAPK) signaling cascades were examined in IEC-6 cells, a nontransformed intestinal epithelial cell line that does not express endogenous trefoil peptides, Stimulation with ITF resulted in rapid decrease in extracellular signal-related protein kinase (ERK) activity and concomitant reduced ERK tyrosine phosphorylation. ITF also decreased activation of ERK activity induced by either transforming growth factor-alpha, which links extracellular stimuli to the Ras/Raf/MEK/ERK pathway via the epidermal growth factor receptor, or phorbol 12-myristate 13-acetate, which activates Raf through protein kinase C. ITF-induced inhibition of ERK activity was blocked by an inhibitor of tyrosine and dual-specific phosphatases, sodium orthovanadate, In summary, ITF leads to inhibition of ERK and the MAPK pathway through activation of tyrosine or dual-specific phosphatase. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK041557, P30 DK043351, DK41557, DK43351, R37 DK041557] NR 40 TC 58 Z9 62 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 1998 VL 95 IS 1 BP 178 EP 182 DI 10.1073/pnas.95.1.178 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ846 UT WOS:000071429500037 PM 9419349 ER PT J AU Testa, CM Friberg, IK Weiss, SW Standaert, DG AF Testa, CM Friberg, IK Weiss, SW Standaert, DG TI Immunohistochemical localization of metabotropic glutamate receptors mGluR1a and mGluR2/3 in the rat basal ganglia SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE neostriatum; substantia nigra; globus pallidus; corticostriatal pathway; confocal microscopy ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; MOLECULAR CHARACTERIZATION; SIGNAL-TRANSDUCTION; FUNCTIONAL-ANATOMY; EXPRESSION; BRAIN; NEURONS; STRIATUM; HYBRIDIZATION AB Metabotropic glutamate receptors (mGluRs), which couple glutamate to second messengers, have important roles in the regulation of movement by the basal ganglia. We used two polyclonal antisera to mGluR1a and mGluR2/3 and confocal laser microscopy to investigate the localization of these receptors in the basal ganglia of the rat. The mGluRs were visualized in combination with an antibody to tyrosine hydroxylase (TH), an antibody to microtubule-associated protein 2 (MAPS, a dendritic marker), or SV2 (an antibody to a protein associated with presynaptic terminals). In the neostriatum, punctate mGluR1a immunoreactivity (ir) was present in the neuropil. This staining did not colocalize with MAP2-ir or SV2-ir and was not altered by decortication or unilateral B-hydroxydopamine (6-OHDA) lesions. In the globus pallidus and substantia nigra pars reticulata, however, mGluR1a-ir was tightly clustered along large MAP2-ir dendrites. In contrast to the variations in mGluR1a-ir staining, similar punctate neuropil mGluR2/3-ir staining was observed within all basal ganglia structures. In the neostriatum, these puncta were abundant; unlike mGluR1a, many mGluR2/3-ir puncta colocalized with SV2-ir, and striatal mGluR2/3-ir puncta were markedly reduced in number after decortication. Neither mGluR1a-ir nor mGluR2/3-ir could be detected in TH-ir soma within substantia nigra pars compacta, or in TH-ir striatal terminals. Overall, our observations suggest that mGluR1a and mGluR2/3 receptors have distinct cellular localizations in different components of the basal ganglia circuitry and are likely to subserve distinct functions. Our data support the presence of mGluR2/3 on the terminals of corticostriatal afferents, where they may regulate glutamate release. In contrast, mGluR1a appears to be a postsynaptic receptor of neurons in the neostriatum, globus pallidus, and substantia nigra pars reticulata. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS34361, NS31579] NR 56 TC 179 Z9 181 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 5 PY 1998 VL 390 IS 1 BP 5 EP 19 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA YM296 UT WOS:000071049400002 PM 9456172 ER PT J AU Kosinski, CM Standaert, DG Counihan, TJ Scherzer, CR Kerner, JA Daggett, LP Velicelebi, G Penney, JB Young, AB Landwehrmeyer, GB AF Kosinski, CM Standaert, DG Counihan, TJ Scherzer, CR Kerner, JA Daggett, LP Velicelebi, G Penney, JB Young, AB Landwehrmeyer, GB TI Expression of N-methyl-D-aspartate receptor subunit mRNAs in the human brain: Striatum and globus pallidus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE basal ganglia; in situ hybridization; excitotoxicity ID EXCITATORY AMINO-ACIDS; NMDA RECEPTOR; GLUTAMATE-RECEPTOR; RAT STRIATUM; MOLECULAR-CLONING; BASAL GANGLIA; MESSENGER-RNA; FUNCTIONAL-CHARACTERIZATION; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE AB N-methyl-D-aspartate receptors (NRs) play an important role in basal ganglia function. By using in situ hybridization with ribonucleotide probes, we investigated the regional and cellular distribution of NR subunit mRNA expression in the human basal ganglia: caudate nucleus, putamen, lateral globus pallidus (LGP), and medial globus pallidus (MGP). Analysis of both film autoradiograms and emulsion-dipped slides revealed distinct distribution patterns for each subunit. On film autoradiograms, the signal for NR1, NR2B, and NR2C in the striatum (STR) was higher than in globus pallidus (GP). The NR2D probe gave a stronger signal in GP than in STR. For NR2A we found a signal in all regions. Analysis of emulsion-dipped sections demonstrated that in striatal neurons, the NR2B signal was higher than in GP neurons. In GP neurons, NR2D was more abundant than in striatal neurons. Despite the relatively low signal on film for NR2C in GP, we found a slightly higher signal in GP per neuron than in STR since in the pallidal areas neurons were sparse but intensely labeled. NR1 and NR2A were more evenly distributed over neurons of STR and GP. Between the different parts of STR and GP, we observed only minor differences in the expression of NRs. In MGP a subpopulation of neurons exhibiting low NR2D signals could be separated from the majority of neurons showing an intense NR2D signal. Since the physiological properties of NRs are dependent on subunit composition, these data suggest a high degree of regional specialization of NR properties in the human basal ganglia. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. SIBIA Neurosci Inc, La Jolla, CA 92037 USA. Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany. RP Young, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG11337]; NINDS NIH HHS [NS31579] NR 80 TC 52 Z9 52 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 5 PY 1998 VL 390 IS 1 BP 63 EP 74 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA YM296 UT WOS:000071049400006 PM 9456176 ER PT J AU Scherzer, CR Landwehrmeyer, GB Kerner, JA Counihan, TJ Kosinski, CM Standaert, DG Daggett, LP Velicelebi, G Penney, JB Young, AB AF Scherzer, CR Landwehrmeyer, GB Kerner, JA Counihan, TJ Kosinski, CM Standaert, DG Daggett, LP Velicelebi, G Penney, JB Young, AB TI Expression of N-methyl-D-aspartate receptor subunit mRNAs in the human brain: Hippocampus and cortex SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NMDA; receptor subtypes; in situ hybridization; Alzheimer's disease ID ACID BINDING-SITES; NMDA RECEPTOR; FUNCTIONAL-CHARACTERIZATION; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; NERVOUS-SYSTEM; MESSENGER-RNA; PHARMACOLOGICAL CHARACTERIZATION; NEURODEGENERATIVE DISEASES; PREFRONTAL CORTEX AB N-methyl-D-aspartate receptor (NR) activation in the hippocampus and neocortex plays a central role in memory and cognitive function. We analyzed the cellular expression of the five NR subunit (NR1 and NR2A-D) mRNAs in these regions with in situ hybridization and human ribonucleotide probes. Film autoradiograms demonstrated a distinct pattern of hybridization signal in the hippocampal complex and the neocortex with probes for NR1, NR2A, and NR2B mRNA. NR2C and NR2D probes yielded scattered signals without a distinct organization. At the emulsion level, the NR1 probe produced high-density hybridization signals across the hippocampal complex. NR2A mRNA was higher in dentate granule cells and pyramidal cells in CA1 and subiculum compared to hilus neurons. NR2B mRNA expression was moderate throughout, with higher expression in dentate granule cells, CA1 and CA3 pyramidal cells than in hilus neurons. In the hippocampal complex, the NR2C probe signal was not different from background in any region, whereas the NR2D probe signal resulted in low to moderate grain densities. We analyzed NR subunit mRNA expression in the prefrontal, parietal, primary visual, and motor cortices. All areas displayed strong NR1 hybridization signals. NR2A and NR2B mRNAs were expressed in cortical areas and layers. NR2C mRNA was ex-pressed at low levels in distinct layers that differed by region and the NR2D signal was equally moderate throughout all regions. Pyramidal cells in both hippocampus and neocortex express NR1, NR2A, NR2B, and, to a lesser extent, NR2D mRNA. Interneurons or granular layer neurons and some glial cells express NR2C mRNA. (C) 1995 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany. SIBIA Neurosci Inc, La Jolla, CA 92037 USA. RP Young, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG11337]; NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS31579] NR 54 TC 83 Z9 87 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 5 PY 1998 VL 390 IS 1 BP 75 EP 90 DI 10.1002/(SICI)1096-9861(19980105)390:1<75::AID-CNE7>3.0.CO;2-N PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA YM296 UT WOS:000071049400007 PM 9456177 ER PT J AU Counihan, TJ Landwehrmeyer, GB Standaert, DG Kosinski, CM Scherzer, CR Daggett, LP Velicelebi, G Young, AB Penney, JB AF Counihan, TJ Landwehrmeyer, GB Standaert, DG Kosinski, CM Scherzer, CR Daggett, LP Velicelebi, G Young, AB Penney, JB TI Expression of N-methyl-D-aspartate receptor subunit mRNA in the human brain: Mesencephalic dopaminergic neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NMDA; receptor subtypes; Parkinson's disease; in situ hybridization; excitotoxicity ID ALTERNATIVELY SPLICED ISOFORMS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; GLUTAMATE-RECEPTOR; NMDA RECEPTORS; BASAL GANGLIA; MESSENGER-RNA; RAT STRIATUM; MOLECULAR DIVERSITY AB Evidence is accumulating that glutamate-mediated excitotoxicity plays an important role in neuronal degeneration in Parkinson's disease (PD). In addition, alterations in excitatory amino acid neurotransmission in the basal ganglia contribute to the clinical manifestations of motor dysfunction. However, detailed knowledge of the anatomical distribution and subtype specificity of glutamate receptors in the dopamine neurons of human substantia nigra (SN) has been lacking, In order to test the hypothesis that selective expression of particular N-methyl-D-aspartate receptor (NR) subunit mRNA contributes to the differential vulnerability of specific neuronal populations to excitotoxic injury in PD, we have used a quantitative dual label, in situ hybridization technique with ribonucleotide probes to examine the cellular distribution of NR subunit mRNA in postmortem human mesencephalic dopaminergic neurons from subjects with no known neurological disorder. Analysis of both film autoradiograms and emulsion-dipped sections demonstrated significant labeling of nigral neurons for each NR subunit. Neuronal labeling was most intense for the NR1 and NR2D subunits, with low level labeling for the remaining subunits. In addition, we examined four subregions of the ventral mesencephalon for differential expression of NR subunit mRNA. For all NR subunits, the pars lateralis (PL) exhibited the most intense signal, while neurons of the ventral tier substantia nigra pars compacta (SNpc) failed to demonstrate a preponderance of a particular subunit. These results demonstrate that NRs are expressed to a significant degree in dopaminergic neurons of the SN and that their distribution does not correlate with the characteristic pattern of neuronal degeneration in PD. (C) 1998 Wiley-Liss. Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Freiburg, Dept Neurol, D-7800 Freiburg, Germany. SIBIA Neurosci Inc, La Jolla, CA 92037 USA. RP Penney, JB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG 11337]; NINDS NIH HHS [NS 31579] NR 59 TC 33 Z9 33 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 5 PY 1998 VL 390 IS 1 BP 91 EP 101 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA YM296 UT WOS:000071049400008 PM 9456178 ER PT J AU Zareparsi, S Kay, J Camicioli, R Kramer, P Nutt, J Bird, T Litt, M Payami, H AF Zareparsi, S Kay, J Camicioli, R Kramer, P Nutt, J Bird, T Litt, M Payami, H TI Analysis of the alpha-synuclein G209A mutation in familial Parkinson's disease SO LANCET LA English DT Article C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Zareparsi, S (reprint author), Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. FU NIA NIH HHS [AG0817] NR 5 TC 35 Z9 35 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 3 PY 1998 VL 351 IS 9095 BP 37 EP 38 DI 10.1016/S0140-6736(05)78089-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YP205 UT WOS:000071253100021 PM 9433434 ER PT J AU Wang, JH Lim, K Smolyar, A Teng, MK Liu, JH Tse, AGD Liu, J Hussey, RE Chishti, Y Thomson, CT Sweet, RM Nathenson, SG Chang, HC Sacchettini, JC Reinherz, EL AF Wang, JH Lim, K Smolyar, A Teng, MK Liu, JH Tse, AGD Liu, J Hussey, RE Chishti, Y Thomson, CT Sweet, RM Nathenson, SG Chang, HC Sacchettini, JC Reinherz, EL TI Atomic structure of an alpha beta T cell receptor (TCR) heterodimer in complex with an anti-TCR Fab fragment derived from a mitogenic antibody SO EMBO JOURNAL LA English DT Review DE crystallography; immune receptors; quaternary structure; signal transduction ID MAJOR HISTOCOMPATIBILITY COMPLEX; ELECTRON-DENSITY MAPS; CLASS-I H-2K(B); CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; CD3 COMPLEX; T3-MOLECULAR COMPLEX; PEPTIDE VARIABILITY; SIGNAL TRANSDUCTION AB Each T cell receptor (TCR) recognizes a peptide antigen bound to a major histocompatibility complex (MHC) molecule via a clonotypic alpha beta heterodimeric structure (Ti) non-covalently associated with the monomorphic CD3 signaling components, A crystal structure of an alpha beta TCR-anti-TCR Fab complex: shows an Fab fragment derived from the H57 monoclonal antibody (mAb), interacting with the elongated FG loop of the C beta domain, situated beneath the V beta domain, This loop, along with the partially exposed ABED beta sheet of C beta, and glycans attached to both C beta and C alpha domains, forms a cavity of sufficient size to accommodate a single non-glycosylated Ig domain such as the CD3 epsilon ectodomain, That this asymmetrically localized site is embedded within the rigid constant domain module has implications for the mechanism of signal transduction in both TCR and pre-TCR complexes. Furthermore, quaternary structures of TCRs vary significantly even when they bind the same MHC molecule, as manifested by a unique twisting of the V module relative to the C module. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Reinherz, EL (reprint author), Univ Sci & Technol China, Dept Biol, Hefei 230026, Peoples R China. NR 108 TC 150 Z9 151 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 2 PY 1998 VL 17 IS 1 BP 10 EP 26 DI 10.1093/emboj/17.1.10 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YU347 UT WOS:000071708000002 PM 9427737 ER PT J AU Kim, HH Tharayil, M Rudd, CE AF Kim, HH Tharayil, M Rudd, CE TI Growth factor receptor-bound protein 2 SH2/SH3 domain binding to CD28 and its role in co-signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; SH3 DOMAINS; T-CELLS; TYROSINE KINASES; CROSS-LINKING; ACTIVATION; GRB2; ASSOCIATION; COSTIMULATION; PHOSPHORYLATION AB The co-stimulatory antigen CD28 has been shown to bind to several intracellular proteins including phosphatidylinositol S-kinase, growth factor receptor-bound protein 2 (Grb2), and ITK, Paradoxically, Grb2 and phosphatidylinositol 3-kinase binding has been mapped to a similar pYMNM motif within the CD28 cytoplasmic tail, Given the importance of CD28 co-signaling to T cell function, questions exist regarding the mechanism by which Grb2 binds to CD28, and whether the interaction plays a role in co-stimulation. To biochemically characterize Grb2/CD28 binding, we initially utilized glutathione S-transferase-Grb2 fusion proteins carrying inactivating mutations within the SH2 and SH3 domains of Grb2, and assessed their ability to bind to CD28, In vitro binding experiments indicated that the Grb2 SH2 domain is critical for the association, while the SH3 domain plays an additional role in facilitating optimal binding, Enhanced binding via the SH3 domains was not observed when the C-terminal PXXP motif within CD28 was disrupted, thereby indicating that both SH2 and SH3 domains contribute to CD28 binding. Mutations that alter Grb2 binding were found to block the CD28-dependent interleukin-a production. Further, tyrosine phosphorylation of Vav and the costimulation-dependent activation of Jun N-terminal kinase was blocked in cells defective in CD28/Grb2 binding. These results provide evidence for an alternate CD28-mediated signaling process involving Grb2 binding to the co-receptor. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA65704] NR 42 TC 91 Z9 95 U1 5 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 1998 VL 273 IS 1 BP 296 EP 301 DI 10.1074/jbc.273.1.296 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600045 PM 9417079 ER PT J AU Mari, BP Anderson, IC Mari, SE Ning, YY Lutz, Y Kobzik, L Shipp, MA AF Mari, BP Anderson, IC Mari, SE Ning, YY Lutz, Y Kobzik, L Shipp, MA TI Stromelysin-3 is induced in tumor/stroma cocultures and inactivated via a tumor-specific and basic fibroblast growth factor-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE STROMELYSIN-3; BREAST-CARCINOMA; MATRIX METALLOPROTEINASES; STRUCTURAL DETERMINANTS; GENE-EXPRESSION; CELL CARCINOMA; NUDE-MICE; ACTIVATION; CANCER; PROGRESSION AB Stromelysin-3 (STR-3) is a recently characterized matrix metalloproteinase (MIMP) with a unique pattern of expression and substrate specificity, Unlike other MMPs, STR-3 is consistently and dramatically overexpressed by multiple epithelial malignancies, including carcinomas of the breast, lung, colon, head and neck, and skin. Recent studies suggest that STR-3 promotes the local establishment of epithelial malignancies, contributing to tumor cell survival and implantation in host tissues; however, STR-3's mechanism of action remains undefined, STR-3 is a stromal cell product, prompting speculation that infiltrating stromal cells secrete STR-3 in response to tumor-derived factors, To explore this possibility, we developed a tumor/"stroma" coculture assay in which non-small cell lung cancer (NSCLC) cell lines were grown on confluent monolayers of normal pulmonary fibroblasts, In these tumor/stroma cocultures, NSCLCs stimulate normal pulmonary fibroblasts to secrete STR-8 and release extracellular basic fibroblast growth factor, Thereafter, STR-3 is processed at a unique internal sequence via a basic fibroblast growth factor-and MMP-dependent mechanism to a previously unidentified 35-kDa protein that lacks enzymatic activity. 35-kDa STR-3 is the most abundant STR-3 protein in tumor/stroma cocultures and is only detected when normal pulmonary fibroblasts are cultured with malignant bronchial epithelial cells, Therefore, the tumor-specific processing of STR-3 to the 35 kDa protein is likely to be an important regulatory mechanism. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Strasbourg 1, IGBMC, CNRS, INSERM U184, F-67404 Strasbourg, France. RP Shipp, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015 OI Mari, Bernard/0000-0002-0422-9182 NR 54 TC 53 Z9 54 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 1998 VL 273 IS 1 BP 618 EP 626 DI 10.1074/jbc.273.1.618 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP612 UT WOS:000071295600090 PM 9417124 ER PT B AU Walker, BD Rosenberg, ER Billingsly, JM Caleindo, AM Kalams, SA AF Walker, BD Rosenberg, ER Billingsly, JM Caleindo, AM Kalams, SA BE Girard, M Dodet, B TI Vigorous HIV-1-specific CD4(+) T cell responses associated with control of viremia SO 11E COLLOQUE DES CENT GARDES: RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 11th Cent Gardes Symposium CY OCT 27-29, 1997 CL MARNES COQUETTE, FRANCE C1 Massachusetts Gen Hosp, AIDS Res Ctr, Hillsborough, MA 02129 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,Room 5212D, Hillsborough, MA 02129 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-022-6 PY 1998 BP 161 EP 165 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BK85G UT WOS:000073664200023 ER PT B AU Sodroski, J Sullivan, N Cao, J Farzan, M Choe, HY Desjardins, E Moore, J Gershoni, J Wyatt, R AF Sodroski, J Sullivan, N Cao, J Farzan, M Choe, HY Desjardins, E Moore, J Gershoni, J Wyatt, R BE Girard, M Dodet, B TI Strategies of immune invasion by human immunodeficiency virus type 1 SO 11E COLLOQUE DES CENT GARDES: RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 11th Cent Gardes Symposium CY OCT 27-29, 1997 CL MARNES COQUETTE, FRANCE C1 Dana Farber Canc Inst, Div Human Retrovirol, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-022-6 PY 1998 BP 223 EP 225 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BK85G UT WOS:000073664200030 ER PT B AU Jupiter, J Ring, D AF Jupiter, J Ring, D BE Roth, JH Richards, RS TI Outcome of ulnar neurolysis during post-traumatic reconstruction of the elbow SO 7TH CONGRESS OF THE INTERNATIONAL FEDERATION OF SOCIETIES FOR SURGERY OF THE HAND (IFSSH) LA English DT Proceedings Paper CT 7th Congress of the International-Federation-of-Societies-for-Surgery-of-the-Hand CY MAY 24-28, 1998 CL VANCOUVER, CANADA SP Int Federat Soc Surg Hand C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Jupiter, J (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0524-0 PY 1998 BP 315 EP 319 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA BL91C UT WOS:000077111100054 ER PT B AU Jupiter, J Ring, D AF Jupiter, J Ring, D BE Roth, JH Richards, RS TI Operative treatment of post-traumatic proximal radioulnar synostosis SO 7TH CONGRESS OF THE INTERNATIONAL FEDERATION OF SOCIETIES FOR SURGERY OF THE HAND (IFSSH) LA English DT Proceedings Paper CT 7th Congress of the International-Federation-of-Societies-for-Surgery-of-the-Hand CY MAY 24-28, 1998 CL VANCOUVER, CANADA SP Int Federat Soc Surg Hand C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Jupiter, J (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-0524-0 PY 1998 BP 735 EP 739 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA BL91C UT WOS:000077111100127 ER PT J AU Hwang, JI Chou, YH Tsay, SH Chiang, JH Chang, CY Boland, GW Mueller, PR AF Hwang, JI Chou, YH Tsay, SH Chiang, JH Chang, CY Boland, GW Mueller, PR TI Radiologic and pathologic correlation of adenomyomatosis of the gallbladder SO ABDOMINAL IMAGING LA English DT Article DE gallbladder disease; radiologic diagnosis; adenomyomatosis ID ULTRASOUND; CHOLECYSTOGRAPHY; DISEASE AB Background: To demonstrate the radiologic-pathologic correlation of adenomyomatosis of gallbladder (GBA) and emphasize the role of high-resolution real-time ultrasound (RTUS) in the diagnosis of GBA. Methods: Ten (four male and six female, mean age = 49 years) patients with proven GBA (three diffuse, three segmental, and four fundal) diagnosed by histopathology or confirmed by oral cholecystography (OCG) were reviewed. Radiologic studies included OCG (n = 8), RTUS (n = 8), and computed tomography (CT; n = 4). Six patients subsequently underwent cholecystectomy. Results: Histopathologic correlation between pathologic specimens and OCG, RTUS, and CT was possible in six patients. The diagnostic criteria with ultrasound included numerous tiny intramural cysts containing echogenic foci with reverberation artifacts and associated segmental or diffuse gallbladder wall thickening. OCG with fatty meal demonstrated intramural diverticula. Localized fundal GBA was better visualized on RTUS and CT scan than on OCG. Conclusion: Accurate diagnosis of GBA may be made by either OCG or high-resolution RTUS preoperatively. CT scan may used as an alternative method to help make the diagnosis in equivocal cases. C1 Vet Gen Hosp, Dept Radiol, Taipei 11217, Taiwan. Natl Yang Ming Univ, Taipei 11217, Taiwan. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Vet Gen Hosp, Dept Pathol, Taipei 11217, Taiwan. RP Hwang, JI (reprint author), Vet Gen Hosp, Dept Radiol, 201 Shih Pai Rd,Sect 2, Taipei 11217, Taiwan. RI HWANG, Jahee/H-8702-2014 NR 13 TC 34 Z9 40 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JAN-FEB PY 1998 VL 23 IS 1 BP 73 EP 77 PG 5 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA YM814 UT WOS:000071103900014 PM 9437067 ER PT J AU McGibbon, CA Dupuy, DE Palmer, WE Krebs, DE AF McGibbon, CA Dupuy, DE Palmer, WE Krebs, DE TI Cartilage and subchondral bone thickness distribution with MR imaging SO ACADEMIC RADIOLOGY LA English DT Article DE acetabulum; cartilage; hip, MR imaging ID ARTICULAR-CARTILAGE; HYALINE CARTILAGE; ULTRASONIC MEASUREMENT; KNEE; QUANTIFICATION; OPTIMIZATION; DEGENERATION; SURFACES; INVITRO; JOINTS AB Rationale and Objectives. The authors mapped articular cartilage (AC) and subchondral bone (SB) thicknesses in human acetabula in vitro by using magnetic resonance (MR) imaging and validated AC measurements by using light microscopy. Materials and Methods. Left and right acetabula from a deceased patient who had undergone left hemiarthroplasty were image with fat-suppressed spoiled gradient-recalled acquisition in the steady state (repetition time = 55 msec, echo time = 15 msec, flip angle = 50 degrees, matrix = 256 x 256, field of view = 8 cm). AC and SB thickness maps were generated from image data by using analytic geometry, which enabled correction for thickness overestimation due to oblique sectioning. Cartilage bone plugs were extracted from the acetabula, and light microscopy was used to validate the thickness measurements obtained with MR imaging. Results. Standard errors between thickness measurements obtained with MR imaging and light microscopy were 0.37 and 0.33 mm for the left and right AC, respectively, which is consistent with the voxel resolution of the MR imaging sequence (0.31 x 0.31 x 0.8 mm). SB thickness of the cartilage plugs could not be reliably measured with light microscopy and, therefore, could not be validated. Contour maps showed that SB thickness gradients were rapid and focal compared with the rather smooth gradients in AC thickness; however, thicker AC was accompanied by thicker SB for left (r(2) = .261, P = 0001) and right (r(2) = .308, P = .0001) acetabula. Average thickness differences between left and right acetabular AC and SB were 0.13 mm (P = .015) and 0.11 mm (P = .026), respectively. Although it was the operated hip that had thicker articular tissues, the differences ware within the pixel resolution (<0.31 mm). Conclusion. AC and SB thickness distribution can be accurately determined by combining noninvasive MR imaging and analytic geometry, which may also provide a means for quantitative, longitudinal assessment of focal AC defects. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Rhode Isl Hosp, Dept Diagnost Radiol, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, RSH 010,40 Parkman St, Boston, MA 02114 USA. OI Dupuy, Damian/0000-0003-0524-5982 FU NICHD NIH HHS [R01-HD30063] NR 34 TC 26 Z9 27 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 1998 VL 5 IS 1 BP 20 EP 25 DI 10.1016/S1076-6332(98)80007-X PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZH425 UT WOS:000073107700004 PM 9442203 ER PT J AU Patel, MR Whitman, GJ AF Patel, MR Whitman, GJ TI Negative mammograms in symptomatic patients with breast cancer SO ACADEMIC RADIOLOGY LA English DT Article DE breast neoplasms, diagnosis; breast neoplasms, localization; breast neoplasms, radiography; breast radiography ID SCREENING MAMMOGRAPHY; DIAGNOSIS; FEATURES; LESIONS; OCCULT; TUMORS; DELAY AB Rationale and Objectives. To determine the limitations of mammography in symptomatic patients. Materials and Methods. Approximately 20,000 mammograms obtained during a 2-year period were correlated with the results of a retrospective review of the pathology database, which revealed 711 patients with breast cancer. A total of 496 of these patients underwent mammography at the authors' institution. Three observers reviewed the mammograms of patients with "normal" mammograms within 6 months of excisional biopsy. The parenchymal patterns were also assessed. Results. Mammographic abnormalities were identified in 481 cases (97%), and 15 mammograms (3%) were interpreted as "unremarkable." Fourteen of the unremarkable cases were available for review, which indicated nine true-negative findings, one technical error, two observer errors, and two combined technical and observer errors. The technical error involved the lower inner quadrant of the breast, adjacent to the chest wall. All 14 mammograms were of dense breasts. Conclusion. Mammographic abnormalities were identified in nearly all patients with proved breast cancer. Mammograms in which lesions were missed were of dense breasts, but one-third of the lesions were visible in retrospect. When examining symptomatic patients with dense breasts, radiologists should use optimal mammographic techniques and consider using nonmammographic breast imaging modalities. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patel, MR (reprint author), Beth Israel Deaconess med Ctr, Shapiro Clin Ctr, Dept Radiol, 4th Floor,330 Brookline Ave, Boston, MA 02215 USA. NR 29 TC 15 Z9 16 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 1998 VL 5 IS 1 BP 26 EP 33 DI 10.1016/S1076-6332(98)80008-1 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZH425 UT WOS:000073107700005 PM 9442204 ER PT J AU Yao, L Johnson, C Gentili, A Lee, JK Seeger, LL AF Yao, L Johnson, C Gentili, A Lee, JK Seeger, LL TI Stress injuries of bone: Analysis of MR imaging staging criteria SO ACADEMIC RADIOLOGY LA English DT Article DE bones, injuries; bones, MR; fractures; fractures, stress ID FRACTURES; CLASSIFICATION AB Rationale and Objectives. The authors examined the prognostic value of magnetic resonance (MR) imaging in stress injuries of bone. Materials and Methods. Clinical follow-up data were collected in 35 patients who underwent MR imaging because of suspected stress fractures. MR findings were correlated with total duration of symptoms, the time to return to sports activity, and findings at follow-up radiography. Results. The MR imaging finding of a "fracture" or "fatigue" line or a cortical signal intensity abnormality was predictive of a longer symptomatic period, whereas muscle edema was predictive of a shorter symptomatic period. A published grading system could be used in only 24 patients; the MR imaging grade of injury did not show correlation with clinical outcome. Conclusion. The MR imaging finding of either a medullary line or a cortical abnormality appears to indicate a more severe stress injury of bone. A previously published MR imaging grading system for stress injuries of the tibia was not prognostic in this more heterogeneous patient group. C1 Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. Univ Florida, Hlth Sci Ctr, Dept Radiol, Jacksonville, FL 32209 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Samaritan Hosp, Dept Radiol, Troy, NY USA. Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. RP Yao, L (reprint author), Georgetown Univ, Med Ctr, Dept Radiol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. RI Gentili, Amilcare/G-1238-2013 OI Gentili, Amilcare/0000-0002-5623-7512 NR 13 TC 46 Z9 46 U1 0 U2 5 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 1998 VL 5 IS 1 BP 34 EP 40 DI 10.1016/S1076-6332(98)80009-3 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZH425 UT WOS:000073107700006 PM 9442205 ER PT J AU Black, P Kathiresan, S Chung, W AF Black, P Kathiresan, S Chung, W TI Meningioma surgery in the elderly: A case-control study assessing morbidity and mortality SO ACTA NEUROCHIRURGICA LA English DT Article DE meningioma; elderly; aging; postoperative morbidity; postoperative mortality ID 70 YEARS OLD; INTRACRANIAL MENINGIOMAS; LIFE AB Goal. To assess the morbidity and mortality of meningioma surgery in patients over age 65 and compare our results with matched controls and with the present literature on meningioma surgery in the elderly. Methods. An evaluation of 114 patients undergoing meningioma resection divided into two groups: 57 patients aged 65-87, and a control group of 57 patients aged 25-64 matched by ASA status and tumor site. Operative complications, 30-day mortality, and pre- and postoperative neurologic status were assessed with follow up one to three months. Results. Complication rates in the two groups were similar and were low. Four out of fifty-seven elderly patients (7.0%) had a surgical complication compared with five younger patients (8.8%) Excluding asymptomatic DVT detected by screening, three elderly patients had medical complications (5.2%) compared with two controls (3.5%). The vast majority of patients-93% of the elderly group and 89.4% in the controls-experienced either improvement or no change in neurologic status at followup one to three months after surgery. There was one death among elderly patients within thirty days for a mortality rate of 1.8% compared with no mortality in the case control group. The elderly patient who died was an 80-year old man who died of pneumonia in a rehabilitation hospital three weeks after surgery. Our study group of 57 patients was compared by tumor site and preoperative general health status to other series in the literature. In a review from the literature of 417 patients over age 65 who underwent meningioma surgery, the average 30-day mortality was 16%. The complication rate averaged 39%. Discussion. Our lower morbidity and mortality rates after meningioma surgery in the elderly may be a result of patient selection, surgical technique, or excellent pre- and post-operative care by the resident staff, anesthesiologists, and nurses. It suggests, however, that elderly patients can have meningioma surgery safely. C1 Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Black, P (reprint author), 300 Longwood Ave, Boston, MA 02115 USA. NR 12 TC 53 Z9 56 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0001-6268 J9 ACTA NEUROCHIR JI Acta Neurochir. PY 1998 VL 140 IS 10 BP 1013 EP + DI 10.1007/s007010050209 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 136WC UT WOS:000076881300009 PM 9856244 ER PT J AU Liu, Y Brooks, BR Taniguchi, N Hartmann, HA AF Liu, Y Brooks, BR Taniguchi, N Hartmann, HA TI CuZnSOD and MnSOD immunoreactivity in brain stem motor neurons from amyotropic lateral sclerosis patients SO ACTA NEUROPATHOLOGICA LA English DT Article DE ALS; CuZnSOD; MnSOD; immunoantibodies; brain stem motor neurons ID SUPEROXIDE-DISMUTASE ACTIVITY; CENTRAL-NERVOUS-SYSTEM; CU/ZN-SUPEROXIDE; ALZHEIMERS-DISEASE; MUTATIONS; DEGENERATION; MECHANISMS; CATALASE; DECREASE; MUTANT AB Motor neurons from the brain stems of amyotrophic lateral sclerosis (ALS) and control patients were examined with immunoantibodies to CuZn-superoxide dismutase (CuZnSOD) and Mn-superoxide dismutase (MnSOD). We found that there was a marked staining for CuZnSOD in all the motor nuclei, the hypoglossus, ambiguus, facialis and trigeminus from the ALS patients, but not in the controls. The same neurons from the ALS patients also stained very intensely for MnSOD, whereas the neurons from the control patients stained weakly or not at all. Loss of neurons was also a very consistent finding and was noted in all the motor nuclei from the ALS patients, There was a proliferation of glial cells which stained strongly both for CuZnSOD and for MnSOD accompanying the loss of the neurons. These results indicated that there was an apparent increase of superoxide dismutase immunoreactivity in motor neurons of ALS patients. We conclude that CuZnSOD and MnSOD immunoreactivity is increased in motor neurons and glia in the brain stems of patients with ALS, specific for the terminal phase of this disease. C1 Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Neurol, Madison, WI 53706 USA. William S Middleton Mem Vet Hosp, Neurol Serv, Great Lakes Vet Integrated Serv Network, Madison, WI USA. Osaka Univ, Dept Biochem, Osaka, Japan. RP Hartmann, HA (reprint author), Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. NR 52 TC 17 Z9 17 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 JAN PY 1998 VL 95 IS 1 BP 63 EP 70 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA YM855 UT WOS:000071108400008 PM 9452823 ER PT J AU Willers, H Wurschmidt, F Bunemann, H Heilmann, HP AF Willers, H Wurschmidt, F Bunemann, H Heilmann, HP TI High-dose radiation therapy alone for inoperable non-small cell lung cancer - Experience with prolonged overall treatment times SO ACTA ONCOLOGICA LA English DT Article ID ONCOLOGY-GROUP; BRONCHOGENIC-CARCINOMA; FAVORABLE PATIENTS; RADIOTHERAPY; SURVIVAL; TRIALS AB The purpose of this study as to determine the impact of overall treatment time on long-term survival after high-dose radiation therapy alone for inoperable non small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I-III disease and Karnofsky Performance Scores of 80-100 received a conventionally fractionated total dose of 70 Gy through a split-course technique. After a first treatment course of 40 or 50 Gy, a restaging was performed and only patients without any contraindications, such as newly diagnosed distant metastases or serious deterioration of performance status, were given a second course. In 83% of patients this break lasted for 4-6 weeks. Overall treatment time ranged between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years (range 4.0-9.3 pears). Actuarial overall survival rates al 2 and 5 years were 28% and 7% respectively. Complete radiological tumor response was observed in 31% of patients, and was found to be the strongest positive predictor of survival with 2- and 5-year rates of 50% and 12% respectively compared with 17% and 4% for patients without complete response. Treatment duration was not found to be a significant prognostic factor in univariate or multivariate analysis. For overall treatment times of 7-11 weeks (n = 50), 12 weeks (n = 79) and > 12 weeks (n = 100), 5-year survival was 4%, 6%, and 8%, respectively (p,= 0.6). To conclude, in our experience and in contrast to other studies, prolonged overall treatment times in radiation therapy alone for inoperable NSCLC had no negative impact on long-term survival. It is hypothesized that accelerated tumor cell repopulation is absent in a significant number of these patients with the time-factor playing no apparent role for outcome of treatment. C1 Allgemeines Krankenhaus St Georg, Hermann Holthusen Inst Strahlentherapie, D-20099 Hamburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Bunemann, H (reprint author), Allgemeines Krankenhaus St Georg, Hermann Holthusen Inst Strahlentherapie, Lohmuhlenstr 5, D-20099 Hamburg, Germany. NR 23 TC 7 Z9 7 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1998 VL 37 IS 1 BP 101 EP 105 PG 5 WC Oncology SC Oncology GA ZF737 UT WOS:000072927900017 PM 9572662 ER PT J AU Cacciola, JS Alterman, AI Rutherford, MJ McKay, JR McLellan, AT AF Cacciola, JS Alterman, AI Rutherford, MJ McKay, JR McLellan, AT TI The early course of change in methadone maintenance SO ADDICTION LA English DT Article ID ADDICTION SEVERITY INDEX; ABUSE AB Aims. This study examined the functional and substance use status of methadone maintenance (MM) patients at treatment entry and 2 and 7 months later Design. Two groups of subjects were identified for longitudinal follow-up, those in continuous MM treatment and those who left treatment. Setting. The study was conducted at the Philadelphia Veterans Affairs Medical Center MM Program. Participants. Subjects were 157 men admitted to treatment. Measurements. Change was evaluated using the Addiction Severity Index and urinalysis results. Findings. Both groups of subjects reported significant reductions in drug use and increases in psychosocial functioning from admission to month 2, but demonstrated no significant changes from months 2 to 7. Subjects who left treatment, however, had more heroin use and criminal activity at all evaluation points than subjects who remained in treatment. Urinalysis data also suggested that subjects who left treatment were using drugs more frequently while in treatment than were those subjects who remained continuously enrolled in MM. Finally, subjects who left treatment spent more time in restricted environments (e.g. inpatient treatment, jail) at follow-up. Conclusions. Services may need to be enhanced to foster continuing progress in patients who remain in MM treatment and to retain those patients with more severe problems who leave treatment early. C1 Philadelphia Vet Affairs Med Ctr, PENN VA Ctr Studies Addict, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Cacciola, JS (reprint author), PENN TRC, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA-01586, DA-05858] NR 19 TC 17 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 1998 VL 93 IS 1 BP 41 EP 49 DI 10.1046/j.1360-0443.1998.931415.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA YT683 UT WOS:000071631800005 PM 9624710 ER PT J AU Laposata, M AF Laposata, M TI Fatty acid ethyl esters: nonoxidative metabolites of ethanol SO ADDICTION BIOLOGY LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; LOW-DENSITY-LIPOPROTEIN; ADIPOSE-TISSUE; SYNTHASE-III; EICOSAPENTAENOIC ACID; LIVER-MICROSOMES; CELLS; BLOOD; IDENTIFICATION; PURIFICATION AB The story of fatty acid ethyl (FAEE) encompasses nearly 40 years of research. For more than half of this time, the investigation was limited to documenting the presence of ethyl ester synthesis in different cells and tissues. In the last three years, increasing evidence has emerged that FAEE contribute to ethanol-induced organ damage, with a variety of different mechanisms proposed for mediation of this toxic effect. In addition, multiple enzymatic activities associated with FAEE formation have been described. Independent of their role in mediating cell injury, it has very recently been shown that FAEE are useful short-term and long-term serum markers of ethanol intake, given their appearance in the blood rapidly after ethanol ingestion and their presence when ethanol is no longer detectable. C1 Harvard Univ, Clin Labs, Massachusetts Gen Hosp, Sch Med,Dept Pathol, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Clin Labs, Massachusetts Gen Hosp, Sch Med,Dept Pathol, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 51 TC 18 Z9 19 U1 1 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 1998 VL 3 IS 1 BP 5 EP 14 DI 10.1080/13556219872308 PG 10 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA YT684 UT WOS:000071631900001 PM 26736076 ER PT S AU Gelber, RD Bonetti, M Cole, BF Gelber, S Goldhirsch, A AF Gelber, RD Bonetti, M Cole, BF Gelber, S Goldhirsch, A CA Int Breast Canc Sturdy Grp BE Senn, HJ Gelber, R Goldhirsch, A Thurlimann, B TI Quality of life assessment in the adjuvant setting: Is it relevant? SO ADJUVANT THERAPY OF PRIMARY BREAST CANCER VI SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT Adjuvant Therapy for Primary Breast Cancer Conference CY FEB 25-28, 1998 CL ST GALLEN, SWITZERLAND ID ADJUSTED SURVIVAL ANALYSIS; HEALTH UTILITIES INDEX; OPERABLE BREAST-CANCER; OF-LIFE; THERAPY; CHEMOTHERAPY C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Gelber, RD (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. FU NCI NIH HHS [CA-75362] NR 23 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-64085-1 J9 RECENT RES CANCER PY 1998 VL 152 BP 373 EP 389 PG 17 WC Oncology SC Oncology GA BM35K UT WOS:000078457400036 PM 9928573 ER PT S AU Beagle, JL Hoop, B Kazemi, H AF Beagle, JL Hoop, B Kazemi, H BE Hughson, RL Cunningham, DA Duffin, J TI Phrenic nerve response to glutamate antagonist microinjection in the ventral medulla SO ADVANCES IN MODELING AND CONTROL OF VENTILATION SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Canadian Conference on Modeling and Control of Ventilation CY SEP 17-21, 1997 CL HUNTSVILLE, CANADA SP Glaxo Wellcome Inc, Mississauga, Ontario, Univ Western Ontario, Sch Kinesiol, Fac Hlth Sci ID HYPOXIC VENTILATORY RESPONSE; METHYL-D-ASPARTATE; ACID NEUROTRANSMITTERS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Beagle, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46023-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 450 BP 61 EP 65 PG 5 WC Medicine, Research & Experimental; Physiology; Respiratory System SC Research & Experimental Medicine; Physiology; Respiratory System GA BL84K UT WOS:000076912200012 PM 10026964 ER PT S AU Hoop, B Krause, WL Kazemi, H AF Hoop, B Krause, WL Kazemi, H BE Hughson, RL Cunningham, DA Duffin, J TI Temporal correlation in phrenic neural activity SO ADVANCES IN MODELING AND CONTROL OF VENTILATION SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT Canadian Conference on Modeling and Control of Ventilation CY SEP 17-21, 1997 CL HUNTSVILLE, CANADA SP Glaxo Wellcome Inc, Mississauga, Ontario, Univ Western Ontario, Sch Kinesiol, Fac Hlth Sci ID TIME-SERIES; PATTERN; NOISE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Hoop, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Pulm & Crit Care Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-07874] NR 19 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46023-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 450 BP 111 EP 118 PG 8 WC Medicine, Research & Experimental; Physiology; Respiratory System SC Research & Experimental Medicine; Physiology; Respiratory System GA BL84K UT WOS:000076912200019 PM 10026971 ER PT S AU Brezinski, ME Tearney, GJ Bouma, B Boppart, SA Pitris, C Southern, JF Fujimoto, JG AF Brezinski, ME Tearney, GJ Bouma, B Boppart, SA Pitris, C Southern, JF Fujimoto, JG BE Alfano, RR TI Optical biopsy with optical coherence tomography SO ADVANCES IN OPTICAL BIOPSY AND OPTICAL MAMMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advances in Optical Biopsy and Optical Mammography CY APR 24-25, 1997 CL CUNY, NEW YORK, NEW YORK SP NY Acad Sci, NY State Ctr Adv Technol Ultrafast Photon Mat & Applicat HO CUNY ID IN-VIVO C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Brezinski, ME (reprint author), MIT, Dept Elect Engn & Comp Sci, Bldg 36-357,77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NEI NIH HHS [9-RO1-EY11289-10]; NHLBI NIH HHS [1-R29-HL55686-01A1] NR 16 TC 21 Z9 21 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-125-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 838 BP 68 EP 74 DI 10.1111/j.1749-6632.1998.tb08188.x PG 7 WC Engineering, Biomedical; Multidisciplinary Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BK58V UT WOS:000072638600006 PM 9511796 ER PT S AU Fujimoto, JG Bouma, B Tearney, GJ Boppart, SA Pitris, C Southern, JF Brezinski, ME AF Fujimoto, JG Bouma, B Tearney, GJ Boppart, SA Pitris, C Southern, JF Brezinski, ME BE Alfano, RR TI New technology for high-speed and high-resolution optical coherence tomography SO ADVANCES IN OPTICAL BIOPSY AND OPTICAL MAMMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advances in Optical Biopsy and Optical Mammography CY APR 24-25, 1997 CL CUNY, NEW YORK, NEW YORK SP NY Acad Sci, NY State Ctr Adv Technol Ultrafast Photon Mat & Applicat HO CUNY ID LASER SOURCE; EYE-LENGTH; IN-VIVO; INTERFEROMETRY; FORSTERITE; BIOPSY; LIGHT C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02114 USA. RP Fujimoto, JG (reprint author), MIT, Dept Elect Engn & Comp Sci, Bldg 36-345,77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NEI NIH HHS [9-RO1-EY11289-10]; NHLBI NIH HHS [1-R29-HL55686-01A1] NR 31 TC 59 Z9 63 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-125-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 838 BP 95 EP 107 DI 10.1111/j.1749-6632.1998.tb08190.x PG 13 WC Engineering, Biomedical; Multidisciplinary Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BK58V UT WOS:000072638600008 PM 9511798 ER PT S AU Flotte, TJ AF Flotte, TJ BE Alfano, RR TI Pathology correlations with optical biopsy techniques SO ADVANCES IN OPTICAL BIOPSY AND OPTICAL MAMMOGRAPHY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advances in Optical Biopsy and Optical Mammography CY APR 24-25, 1997 CL CUNY, NEW YORK, NEW YORK SP NY Acad Sci, NY State Ctr Adv Technol Ultrafast Photon Mat & Applicat HO CUNY ID FLUORESCENCE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs, Boston, MA 02114 USA. RP Flotte, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs, EDR 214,55 Fruit St, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-125-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 838 BP 143 EP 149 DI 10.1111/j.1749-6632.1998.tb08195.x PG 7 WC Engineering, Biomedical; Multidisciplinary Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BK58V UT WOS:000072638600013 PM 9511803 ER PT S AU Waeber, C Grailhe, R Yu, XJ Hen, R Moskowitz, MA AF Waeber, C Grailhe, R Yu, XJ Hen, R Moskowitz, MA BE Martin, GR Eglen, RM Hoyer, D Hamblin, MW Yocca, F TI Putative 5-ht(5) receptors: Localization in the mouse CNS and lack of effect in the inhibition of dural protein extravasation SO ADVANCES IN SEROTONIN RECEPTOR RESEARCH: MOLECULAR BIOLOGY, SIGNAL TRANSDUCTION, AND THERAPEUTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advances in Serotonin Receptor Research - Molecular Biology, Signal Transduction, and Therapeutics CY OCT 08-10, 1997 CL SAN FRANCISCO, CALIFORNIA SP Serotonin Club, Int Union Pharmacol, Roche Biosci, Palo Alto, Bristol Myers Squibb, Wallingford, DuPont Merck Pharmaceut Co, Wilmington, F Hoffmann La Roche, Basel, Lilly Res Labs, Indianapolis, Novartis Pharma AG, Basel, Pfizer Cent Res, Groton, SmithKline Beecham, Harlow, Glaxo Wellcome, Stevenage, Merck Res Labs, Harlow, Pierre Fabre, Castres ID GUINEA-PIG; RAT-BRAIN; SUMATRIPTAN; CP-122,288; CLONING; FAMILY AB Putative 5-ht(5) receptor binding sites were visualized by in vitro autoradiography using [I-125]LSD tin the presence of clozapine and spiperone) or [H-3]5-carboxamidotryptamine tin the presence 8-OH-DPAT, GR127935 and spiperone), Under these conditions, no [H-3]5-carboxamidotryptamine labeling was detected in the brain of mice lacking the gene encoding the putative 5-ht(5a) receptor (knockout mice), whereas intermediate densities of binding sites were seen in the olfactory bulb and neocortex of wild-type mice. [I-125]LSD labeled the same areas as [H-3]5-carboxamidotryptamine in wild-type mice. High densities of [I-125]LSD binding sites were observed in the medial habenula of wild type and knockout mice. 5-CT competed for [I-125]LSD binding sites with an affinity of 2 nM in the olfactory bulb and neocortex of wild-type mice and an affinity of 30 nM in the habenula of knockout mice, suggesting that habenular labeling might be accounted for by putative 5-ht(5b) receptors. In the presence of 5'-guanylylimidodiphosphate, 5-CT displaced [I-125]LSD from putative 5-ht(5a) and 5-ht(5b) sites with a 6-times and 3-times lower affinity respectively, suggesting that both receptor subtypes are coupled to G proteins in brain. We also studied the inhibitory effect of 5-CT on dural neurogenic inflammation in knockout mice, In wild type mice, 3 ng/kg 5-CT inhibited dural protein extravasation by 60 %. A similar effect was observed in knockout mice, even in the presence of the 5-HT1B receptor antagonist GR127935. These results suggest that the inhibitory effects of 5-CT are not mediated by a site with the characteristics of the putative 5-ht(5) receptor. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Waeber, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 9 TC 15 Z9 16 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-170-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 861 BP 85 EP 90 DI 10.1111/j.1749-6632.1998.tb10177.x PG 6 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BM29R UT WOS:000078304800011 PM 9928243 ER PT S AU Frazer, A Daws, LC AF Frazer, A Daws, LC BE Martin, GR Eglen, RM Hoyer, D Hamblin, MW Yocca, F TI Serotonin transporter function in vivo: Assessment by chronoamperometry SO ADVANCES IN SEROTONIN RECEPTOR RESEARCH: MOLECULAR BIOLOGY, SIGNAL TRANSDUCTION, AND THERAPEUTICS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Advances in Serotonin Receptor Research - Molecular Biology, Signal Transduction, and Therapeutics CY OCT 08-10, 1997 CL SAN FRANCISCO, CALIFORNIA SP Serotonin Club, Int Union Pharmacol, Roche Biosci, Palo Alto, Bristol Myers Squibb, Wallingford, DuPont Merck Pharmaceut Co, Wilmington, F Hoffmann La Roche, Basel, Lilly Res Labs, Indianapolis, Novartis Pharma AG, Basel, Pfizer Cent Res, Groton, SmithKline Beecham, Harlow, Glaxo Wellcome, Stevenage, Merck Res Labs, Harlow, Pierre Fabre, Castres ID FREELY MOVING RATS; IN-VIVO; INVIVO VOLTAMMETRY; NUCLEUS-ACCUMBENS; DOPAMINE UPTAKE; UPTAKE BLOCKERS; BIOPHASE CONCENTRATION; UPTAKE INHIBITORS; CAUDATE-PUTAMEN; RAPHE NUCLEI AB Local application of selective serotonin reuptake inhibitors, fluloxamine and citalopram, prolonged the clearance of exogenously administered serotonin (5-HT) in both the dentate gyrus and CA3 region of the dorsal hippocampus, as measured using in, vivo chronoamperometry. These effects were abolished in rats pretreated with 5,7-dihydroxytryptamine. The NE uptake inhibitors, desipramine and protriptyline, did not alter the 5-HT signal in the CA3 region, but prolonged the clearance of 5-HT in the dentate gyrus; this effect was absent in rats pretreated with 6-hydroxydopamine. From these data, it is inferred that both the SERT and NET contribute to the active clearance of exogenously applied 5-HT in the dentate gyrus. In another experiment, cyanopindolol, an antagonist of the serotonin terminal autoreceptor, also prolonged the clearance of 5-HT from the CA3 region, These and other data have generated a working hypothesis that activation of the terminal serotonin autoreceptor enhances the kinetics of 5-HT uptake through an effect on the serotonin transporter. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78250 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. Univ Adelaide, Dept Clin & Expt Pharmacol, Adelaide, SA 5005, Australia. RP Frazer, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78250 USA. EM frazer@uthscsa.edu FU NIMH NIH HHS [MH27094] NR 48 TC 12 Z9 12 U1 1 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-170-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 861 BP 217 EP 229 DI 10.1111/j.1749-6632.1998.tb10193.x PG 13 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BM29R UT WOS:000078304800027 PM 9928259 ER PT J AU Solhkhah, R Wilens, TE AF Solhkhah, R Wilens, TE TI Pharmacotherapy of adolescent alcohol and other drug use disorders SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article ID DEPENDENT DELINQUENTS; SUBSTANCE-ABUSE; OPEN TRIAL; MEDICATION; NALTREXONE C1 Massachusetts Gen Hosp, Subst Abuse Serv, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 25 TC 6 Z9 6 U1 5 U2 5 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1998 VL 22 IS 2 BP 122 EP 126 PG 5 WC Substance Abuse SC Substance Abuse GA 165AG UT WOS:000078495700005 PM 15706786 ER PT J AU Wilens, TE AF Wilens, TE TI AOD use and attention deficit hyperactivity disorder SO ALCOHOL HEALTH & RESEARCH WORLD LA English DT Article DE attention deficit disorder; hyperactive behavior; child; AODD (alcohol and other drug use disorder); comorbidity; drug therapy; disease course; AODD recovery; self administration of drugs; biochemical mechanism; adulthood; AOD prevention; psychosocial treatment method; literature review ID SUBSTANCE USE DISORDERS; ADHD; COMORBIDITY; CHILDHOOD AB Children with attention deficit/hyperactivity disorder (ADHD) often continue to exhibit significant impairment in academic, occupational, and social functioning throughout adulthood In addition, children with ADHD are at increased risk for developing alcoholism and other drug addictions, especially if;if alcoholism sr ADHD exists in other family members, Alcohol and other drug (AOD) abuse may develop earlier in life (i.e., in midadolescence) when ADHD is accompanied by certain behavioral or mood disorders, The nature of the link between ADHD and AOD use disorder is unknown, although the association may be mediated by the co-occurring disorders just mentioned In addition, ADHD-related AOD abuse may develop initially as an attempt to alleviate symptoms of mental distress;associated with chronic failure, feelings of inadequacy, and conflict with parents and peers. Therapeutic intervention should incorporate both addiction mad mental health treatment including appropriate use of psychiatric medications. C1 Massachusetts Gen Hosp, Subst Abuse Serv, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Subst Abuse Serv, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. NR 18 TC 30 Z9 31 U1 2 U2 8 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 0090-838X J9 ALCOHOL HEALTH RES W JI Alcohol Health Res. World PY 1998 VL 22 IS 2 BP 127 EP 130 PG 4 WC Substance Abuse SC Substance Abuse GA 165AG UT WOS:000078495700006 PM 15706787 ER PT J AU Plantz, SH Kreplick, LW Panacek, EA Mehta, T Adler, J McNamara, RM AF Plantz, SH Kreplick, LW Panacek, EA Mehta, T Adler, J McNamara, RM TI A national survey of board-certified emergency physicians: Quality of care and practice structure issues SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE emergency physicians; survey; quality of care; group practice; politics ID OCCUPATIONAL STRESS AB The opinions and experiences of board certified emergency physicians regarding employment structure and finances, professional society policies, and quality of patient care have never been formally studied, A survey questionnaire was sent to a random sample of 1,050 emergency physicians certified by the American Board of Emergency Medicine, The survey contained 29 multiple choice questions, Of the 1,050, 465 (44.3%) of the surveys were returned, Respondents averaged 13.5 years of emergency medicine practice, 83% were members of the American College of Emergency Physicians, and 44% were emergency medicine residency trained, Seventy five percent felt they had been financially exploited by the emergency department contract holder and 49% considered leaving their employer because of unfair business practices, Fifteen percent have been terminated without due process/peer review, and 11% have been forced to leave a position, move, or pay compensation because of noncompete clauses, The majority reported encountering instances of substandard emergency medical care, most commonly in settings with multihospital contract company coverage, The majority also believe their specialty societies should address issues of employ ment structure and quality of patient care standards. Copyright (C) 1998 by W.B. Saunders Company. C1 Chicago Med Sch, Dept Emergency Med, Chicago, IL USA. Mt Sinai Med Ctr, Chicago, IL USA. Univ Illinois, Dept Emergency Med, Oak Lawn, IL USA. Christ Hosp & Med Ctr, Oak Lawn, IL USA. Univ Calif Davis, Med Ctr, Dept Emergency Med, Sacramento, CA 95817 USA. Univ Illinois, Coll Business, Chicago, IL USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. Allegheny Univ Hlth Sci, Dept Emergency Med, Philadelphia, PA 19102 USA. RP Plantz, SH (reprint author), Suite 103,4450 Gulf Blvd, St Pete Beach, FL 33706 USA. NR 15 TC 4 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 1998 VL 16 IS 1 BP 1 EP 4 DI 10.1016/S0735-6757(98)90055-9 PG 4 WC Emergency Medicine SC Emergency Medicine GA YR508 UT WOS:000071502300001 PM 9451304 ER PT J AU Rao, PM Rhea, JT Novelline, RA McCabe, CJ AF Rao, PM Rhea, JT Novelline, RA McCabe, CJ TI The computed tomography appearance of recurrent and chronic appendicitis SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE appendicitis; appendix; computed tomography; right lower quadrant; chronic appendicitis; recurrent appendicitis ID ABDOMINAL-PAIN; UNITED-STATES; BARIUM ENEMA; DIAGNOSIS; APPENDECTOMY; EMERGENCY; CT AB The objective of this study was to determine computed tomography (CT) appearance of recurrent and chronic appendicitis. In 100 consecutive appendiceal CT examinations of proven appendicitis, 18 patients met criteria for recurrent (multiple discrete episodes) or chronic (continuous symptoms > 3 weeks, pathological findings) appendicitis. CT findings were reviewed. Ten patients had recurrent appendicitis, 3 had chronic appendicitis, 3 had both, and 2 had pathological chronic appendicitis. CT findings in 18 recurrent/chronic cases were identical to 82 acute appendicitis cases, including pericecal stranding (both 100%), dilated (> 6 mm) appendix (88.9% versus 93.9%), apical thickening (66.7% versus 69.5%), adenopathy (66.7% versus 61.0%), appendolith(s) (50% versus 42.7%), arrowhead (27.8% versus 22.0%), abscess (11.1% versus 11.0%), phlegmon (11.1% versus 6.1%), and fluid (5.6% versus 19.5%). CT findings in recurrent and chronic appendicitis are the same as those in acute appendicitis. Appendiceal CT can be beneficial for evaluating patients with suspected recurrent or chronic appendicitis. Copyright (C) 1998 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 29 TC 30 Z9 31 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 1998 VL 16 IS 1 BP 26 EP 33 DI 10.1016/S0735-6757(98)90060-2 PG 8 WC Emergency Medicine SC Emergency Medicine GA YR508 UT WOS:000071502300006 PM 9451309 ER PT J AU Chey, WD Murthy, UK Linscheer, W Barish, C Riff, D Rubin, H Safdi, M Schwartz, H Shah, U Wruble, L El-Zimaity, HMT AF Chey, WD Murthy, UK Linscheer, W Barish, C Riff, D Rubin, H Safdi, M Schwartz, H Shah, U Wruble, L El-Zimaity, HMT TI The Chemtrak Hp Chek fingerstick whole blood serology test for the detection of Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID NONULCER DYSPEPSIA; ACCURACY; DIAGNOSIS AB Objective: To evaluate a new whole blood serology test (Hp Chek; ChemTrak) that detects IgG antibodies to Helicobacter pylori. Methods: The study was conducted at 10 sites within the United States. Patients undergoing upper endoscopy for dyspepsia were recruited for enrollment. Those treated for H. pylori infection within a year of endoscopy and those who had regularly used proton pump inhibitors, bismuth compounds, or antibiotics within a month of endoscopy were not eligible. During endoscopy, specimens were obtained from the corpus and antrum for histological examination, which was performed by a single experienced pathologist, The Hp Chek was tested using whole blood and serum. Serum was also tested with a reference enzyme-linked immunosorbent assay (ELISA) at a centralized location. Test characteristics for the Hp Chek and ELISA were calculated using histology as the "gold standard." Results: Two hundred eighty-seven patients (140 women and 147 men; mean age 53 +/- 6 yr) were enrolled. The Hp Chek was easy to perform and yielded results 9 min after inoculation of the test cassette with whole blood or serum. When the Hp Chek used with whole blood was compared with histology as the gold standard, the sensitivity was 88%, specificity 85%, positive predictive value 83%, negative predictive value 90%, and percent agreement 86%. There were no statistically significant differences among the results obtained with the Hp Chek using whole blood, the E-fp Chek using serum, or reference ELISA, Conclusions: The Hp Chek whole blood serology test was easy to perform and rapid and yielded performance characteristics comparable to those of a reference ELISA or the Hp Chek used with serum. (C) 1998 by Am. Coll. of Gastroenterology. C1 Univ Michigan, Ann Arbor, MI 48109 USA. VA Med Ctr, Syracuse, NY USA. VA Med Ctr, Raleigh, NC USA. VA Med Ctr, Anaheim, CA USA. VA Med Ctr, Beverly Hills, CA USA. VA Med Ctr, Cincinnati, OH USA. VA Med Ctr, Miami, FL USA. VA Med Ctr, Leonardstown, MD 20650 USA. VA Med Ctr, Memphis, TN USA. VA Med Ctr, Houston, TX USA. RP Chey, WD (reprint author), 3912 Taubman Ctr,Box 0362, Ann Arbor, MI 48109 USA. NR 19 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 1998 VL 93 IS 1 BP 16 EP 19 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZB488 UT WOS:000072477000006 PM 9448166 ER PT J AU Sheth, SG Flamm, SL Gordon, FD Chopra, S AF Sheth, SG Flamm, SL Gordon, FD Chopra, S TI AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID TERM FOLLOW-UP; NON-B HEPATITIS; CHRONIC NON-A; ALANINE AMINOTRANSFERASE; LIVER-DISEASE; ANTI-HCV; ASPARTATE; CLASSIFICATION; DIAGNOSIS AB Objective: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection, In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio >1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices. Methods: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored. Results: The mean AST/ALT ratio in the cirrhotic patients (n = 17) was higher than in the noncirrhotic patients (n = 92) (1.06 +/- 0.06 vs 0.60 +/- 0.09; p < 0.001). A ratio greater than or equal to 1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio greater than or equal to 1. Conclusion: The AST/ALT ratio is a dependable masker of fibrosis stage and cirrhosis in patients with chronic HCV infection. (C) 1988 by Am. Coll. of Gastroenterology. C1 Beth Israel Deaconess Med Ctr Hosp, Div Gastroenterol, Dept Med, Boston, MA USA. RP Chopra, S (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol, Dana 501,330 Brookline Ave, Boston, MA 02215 USA. NR 27 TC 262 Z9 271 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 1998 VL 93 IS 1 BP 44 EP 48 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZB488 UT WOS:000072477000012 PM 9448172 ER PT J AU Ezekowitz, RAB AF Ezekowitz, RAB TI Genetic heterogeneity of mannose-binding proteins: The Jekyll and Hyde of innate immunity? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID POLYMORPHISM; ASSOCIATION; COMPLEMENT; FREQUENCY; HOMOLOGY; CHILDREN; PATHWAY; DOMAIN; DEFECT; LECTIN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, 15 Parkman St,WAC 731, Boston, MA 02114 USA. EM Ezekowitz.alan@mgh.harvard.edu NR 30 TC 32 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 1998 VL 62 IS 1 BP 6 EP 9 DI 10.1086/301696 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YY246 UT WOS:000072127900002 PM 9443889 ER PT J AU Madore, F Stampfer, MJ Rimm, EB Curhan, GC AF Madore, F Stampfer, MJ Rimm, EB Curhan, GC TI Nephrolithiasis and risk of hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT 11th Annual Scientific Meeting of the American-Society-of-Hypertension CY MAY 15-18, 1996 CL NEW YORK, NEW YORK SP Amer Soc Hypertens DE blood pressure; kidney stones; prospective study ID URINARY CALCIUM EXCRETION; BLOOD-PRESSURE; KIDNEY-STONES; DIETARY CALCIUM; UNITED-STATES; METABOLISM; RAT; SODIUM; HYPERCALCIURIA; ABNORMALITIES AB A positive association between nephrolithiasis and blood pressure has been suggested in previous studies, However, controversy remains, due to methodological problems in some of the previous studies and absence of prospective data. We evaluated the relationship between nephrolithiasis and the risk of hypertension in a cohort of 51,529 men followed prospectively for 8 years. information was obtained by biennial mailed questionnaires. Art baseline in 1986, 4111 (8.0%) subjects reported a history of nephrolithiasis and 11,623 (22.6%) a diagnosis of hypertension. A positive association was found between the two disorders (age adjusted odds ratio [OR]: 1.31; 95% confidence interval [CI]: 1.30 to 1.32). Among men who reported both disorders, 79.5% reported that the occurrence of nephrolithiasis was prior to or concomitant with the diagnosis of hypertension. Among men without hypertension at baseline, the odds ratio for incident hypertension in men with a history of nephrolithiasis compared with those without was 1.29 (95% CI: 1.12 to 1.41; adjusted for age, body mass index, and intake of calcium, sodium, potassium, magnesium, and alcohol). The occurrence of incident nephrolithiasis during follow-up was similar in men with hypertension at baseline compared with that in men without (adjusted OR: 0.99, 95% CI: 0.82 to 1.21). These data support the hypothesis that prior occurrence of nephrolithiasis increases the risk of subsequent hypertension. (C) 1998 American Journal of Hypertension, Ltd. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIDDK NIH HHS [DK45362] NR 38 TC 97 Z9 102 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 1998 VL 11 IS 1 BP 46 EP 53 DI 10.1016/S0895-7061(97)00371-3 PN 1 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YX023 UT WOS:000071998600007 PM 9504449 ER PT J AU Hauser, R Elreedy, S Ryan, PB Christiani, DC AF Hauser, R Elreedy, S Ryan, PB Christiani, DC TI Urine vanadium concentrations in workers overhauling an oil-fired boiler SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE urine vanadium; biological monitoring; fuel oil ash ID SENSITIVE DETERMINATION; ASH; EXPOSURE AB Since fuel oil ash contains vanadium (V), the measurement of urinary levels of V may provide a biological marker in workers exposed to fuel oil ash. The usefulness of urine V samples as a biological monitoring tool ultimately depends on determining the appropriate time of sampling relative to when exposure occurs. Twenty boilermakers were studied during the overhaul of a large oil-fired boiler. A total of 117 urine samples were collected, 65 start-of-shift (S-O-S) and 52 end-of-shift (E-O-S) samples. Air V exposures were estimated with personal sampling devices and work history diaries. Air V concentrations ranged from 0.36 to 32.19 mu g V/m(3), with a mean +/- SD of 19.1 +/- 10.7, and a median of 18.5. On the first day of work on the overhaul, the V urine levels at the E-O-S (mean +/- SD were 1.53 +/- 0.53, median was 1.52 mg V/g creatinine) were significantly higher than those at the S-O-S (0.87 +/- 0.32, median was 0.83), P = 0.004. However, the V concentrations of the S-O-S urine samples on the last Monday of the study were not significantly different from the S-O-S urine levels on the previous Saturday, a time interval of about 38 hr between the end of exposure and sample collection. The Spearman correlation coefficient (r) between the S-O-S urine V and the workplace concentration of V dust during the previous day was r = 0.35. In summary, the results suggest a rapid initial clearance of V (elevating the E-O-S V concentration on the first day of work relative to the S-O-S concentration), followed by a slow clearance that is not complete 38 hr after the end of exposure, as evidenced by the Monday morning urine V concentrations. The Spearman correlations suggest that the S-O-S urine is preferred to the E-O-S urine for across-shift biological monitoring of V exposure. (C) 1998 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,ENVIRONM SCI & ENGN PROGRAM,BOSTON,MA 02115. EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT ENVIRONM & OCCUPAT HLTH,ATLANTA,GA 30322. HARVARD UNIV,SCH MED,DEPT MED,MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02138. RP Hauser, R (reprint author), HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,DEPT ENVIRONM HLTH,665 HUNTINGTON AVE,BLDG 1,BOSTON,MA 02115, USA. RI Ryan, P. Barry/A-7662-2009 NR 18 TC 16 Z9 16 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JAN PY 1998 VL 33 IS 1 BP 55 EP 60 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA YJ480 UT WOS:A1998YJ48000007 PM 9408529 ER PT J AU Gilbert, K Gleason, PP Singer, DE Marrie, TJ Coley, CM Obrosky, DS Lave, JR Kapoor, WN Fine, MJ AF Gilbert, K Gleason, PP Singer, DE Marrie, TJ Coley, CM Obrosky, DS Lave, JR Kapoor, WN Fine, MJ TI Variations in antimicrobial use and cost in more than 2,000 patients with community-acquired pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ANTIBIOTIC PRESCRIBING PATTERNS; DISEASE; THERAPY AB PURPOSE: To assess the patterns of antimicrobial use, costs of antimicrobial therapy, and medical outcomes by institution in patients with community-acquired pneumonia. PATIENTS AND METHODS: The route, dose, and frequency of administration of all antimicrobial agents prescribed within 30 days of presentation were recorded for 927 outpatients and 1328 inpatients enrolled in the Pneumonia Patient Outcomes Research Team (PORT) multicenter, prospective cohort study. Total antimicrobial costs were estimated by summing drug costs, using average wholesale price for oral agents and institutional acquisition prices for parenteral agents, plus the costs associated with preparation and administration of parenteral therapy. Thirty-day outcome measures were mortality, subsequent hospitalization for outpatients, and hospital readmission for inpatients. RESULTS: Significant variation (P <0.05) in prescribing practices occurred for 17 of the 23 antimicrobial agents used in outpatients across 5 treatment sites, and for 18 of the 20 parenteral agents used in inpatients across 4 treatment sites. The median duration of antimicrobial therapy for treatment site ranged from 11 to 13 days for outpatients (P = 0.01), and from 13 to 15 days for inpatients (P = 0.49). The overall median cost of antimicrobial therapy was $12.90 for outpatients, and ranged from $10.80 to $58.90 among treatment sites (P <0.0001). The overall median cost of antimicrobial therapy was $228.70 for inpatients, and ranged from $183.70 to $315.60 among sites (P <0.0001). Mortality and hospital readmission for inpatients were not significantly different across sites after adjusting for baseline differences in patient demographic characteristics, comorbidity, and illness severity. Although subsequent hospitalization for outpatients differed by site, the rate was lowest for the site with the lowest antimicrobial costs. CONCLUSION: Variations in antimicrobial prescribing practices by treatment site exist for outpatients and inpatients with community-acquired pneumonia. Although variation in antimicrobial prescribing practices across institutions results in significant differences in antimicrobial costs, patients treated at institutions with the lowest antimicrobial costs do not demonstrate worse medical outcomes. (C) 1998 by Excerpta Medica, Inc. C1 Univ Western Ontario, Fac Med, London, ON, Canada. Univ Western Ontario, St Josephs Hlth Ctr, Dept Med, Div Gen Med, London, ON N6A 4V2, Canada. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Pittsburgh, PA USA. Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Dalhousie Univ, Victoria Gen Hosp, Dept Med, Halifax, NS, Canada. RP Fine, MJ (reprint author), Montefiore Univ Hosp, 200 Lothrop St,Unit 8 E, Pittsburgh, PA 15213 USA. FU AHRQ HHS [R01 HSO6468] NR 23 TC 75 Z9 78 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 1998 VL 104 IS 1 BP 17 EP 27 DI 10.1016/S0002-9343(97)00274-X PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA YT744 UT WOS:000071640700004 PM 9528715 ER PT J AU Graybill, JR Vazquez, J Darouiche, RO Morhart, R Greenspan, D Tuazon, C Wheat, LJ Carey, J Leviton, I Hewitt, RG MacGregor, RR Valenti, W Restrepo, M Moskovitz, BL AF Graybill, JR Vazquez, J Darouiche, RO Morhart, R Greenspan, D Tuazon, C Wheat, LJ Carey, J Leviton, I Hewitt, RG MacGregor, RR Valenti, W Restrepo, M Moskovitz, BL TI Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLOTRIMAZOLE TROCHES; FLUCONAZOLE; RESISTANCE; ALBICANS; CANDIDOSIS; INFECTION; AZOLES; AIDS; HIV AB PURPOSE: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. PATIENTS AND METHODS: This was a prospective randomized, third-party-blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semiquantitative cultures of mouth washings were also obtained on these days. RESULTS: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. CONCLUSION: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis. (C) 1998 by Excerpta Medica, Inc. C1 Audie L Murphy Mem Vet Hosp, Div Infect Dis, San Antonio, TX 78284 USA. Wayne State Univ, Dept Internal Med, Detroit, MI 48202 USA. VA Med Ctr, Infect Dis Sect, Houston, TX USA. DVA Med Ctr, Dent Res Unit, Miami, FL USA. Univ Calif San Francisco, Dept Stomatol, San Francisco, CA 94143 USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Infect Dis Res Clin, Indianapolis, IN USA. ACTU, Div Infect Dis, Cleveland, OH USA. Montefiore Hosp, Dept Med, Div Infect Dis, Bronx, NY USA. Erie Cty Med Ctr, Buffalo, NY USA. Univ Penn, Philadelphia, PA 19104 USA. Community Hlth Network, Rochester, NY USA. Janssen Pharmaceut, Titusville, NJ USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 29 TC 60 Z9 62 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 1998 VL 104 IS 1 BP 33 EP 39 DI 10.1016/S0002-9343(97)00307-0 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA YT744 UT WOS:000071640700006 PM 9528717 ER PT J AU Ubel, PA Goold, S AF Ubel, PA Goold, S TI Does bedside rationing violate patients' best interests? An exploration of "moral hazard" SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PRACTICE GUIDELINES; COST-CONTAINMENT; HEALTH-CARE; PHYSICIANS; DECISIONS; SELECTION; DOCTORS; TRIAL C1 Univ Penn, Ctr Bioeth, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Div Gen Internal Med, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Div Gen Internal Med, Ann Arbor, MI USA. Univ Michigan, Program Soc & Med, Ann Arbor, MI USA. RP Ubel, PA (reprint author), Univ Penn, Ctr Bioeth, Sch Med, Div Gen Internal Med, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. OI Goold, Susan Dorr/0000-0002-0258-9774 NR 29 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 1998 VL 104 IS 1 BP 64 EP 68 DI 10.1016/S0002-9343(97)00172-1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YT744 UT WOS:000071640700010 PM 9528721 ER PT J AU Hunter, GJ Hamberg, LM Ponzo, JA Huang-Hellinger, FR Morris, PP Rabinov, J Farkas, J Lev, MK Schaefer, PW Ogilvy, CS Schwamm, L Buonanno, FS Koroshetz, WJ Wolf, GL Gonzalez, RG AF Hunter, GJ Hamberg, LM Ponzo, JA Huang-Hellinger, FR Morris, PP Rabinov, J Farkas, J Lev, MK Schaefer, PW Ogilvy, CS Schwamm, L Buonanno, FS Koroshetz, WJ Wolf, GL Gonzalez, RG TI Assessment of cerebral perfusion and arterial anatomy in hyperacute stroke with three-dimensional functional CT: Early clinical results SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID EMISSION COMPUTED-TOMOGRAPHY; BLOOD-VOLUME; CONTRAST-MEDIA; ISCHEMIA; CIRCULATION; RECOVERY; FLOW AB PURPOSE: Our purpose was to determine the clinical feasibility of quantitative three-dimensional functional CT in patients with hyperacute stroke. METHODS: Twenty-two patients who underwent clinically indicated CT angiography were studied: nine patients had no stroke, eight had mature stroke, and five had hyperacute stroke (less than 3 hours since ictus), Maps were obtained of perfused cerebral blood volume (PBV), and CT angiograms were generated by using standard techniques. RESULTS: Normal PBV values (mean +/- SEM) were 4.6 +/- 0.15% in the gray matter, 1.75 +/- 0.09% in the white matter, 2.91 +/- 0.20% in the cerebellum, 3.18 +/- 0.10% in the caudate, 2.84 +/- 0.23% in the putamen, 2.92 +/- 0.29% in the thalamus, and 1.66 +/- 0.03% in the brain stem, For patients with mature stroke, ischemic changes were visible on noncontrast, contrast-enhanced, and PBV scans, In patients with hyperacute stroke, ischemic changes were either absent or subtle before contrast administration, but became apparent on contrast-enhanced scans, Quantitative PBV maps confirmed reduced regional perfusion, CT angiograms in the hyperacute group showed occlusion of vessels in locations appropriate to the PBV deficits seen. CONCLUSION: Quantitative three-dimensional functional CT is feasible for patients with hyperacute stroke, It is performed by using helical CT techniques, and yields measures of cerebrovascular physiological function, which are useful in this patient population. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hunter, GJ (reprint author), Ctr Imaging & Pharmaceut Res, Bldg 149,Charlestown Navy Yard, Boston, MA 02129 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 21 TC 125 Z9 132 U1 1 U2 2 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 JAN PY 1998 VL 19 IS 1 BP 29 EP 37 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YM086 UT WOS:000071026700013 PM 9432154 ER PT J AU Potter, DA Moreno, A Luther, MF Eddy, CA Siler-Khodr, TM King, TS Schenken, RS AF Potter, DA Moreno, A Luther, MF Eddy, CA Siler-Khodr, TM King, TS Schenken, RS TI Effects of follicular-phase cocaine administration on menstrual and ovarian cyclicity in rhesus monkeys SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 19-23, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Soc Gynecol Invest, NIH DE cocaine; follicular phase; menstrual cyclicity ID ANTERIOR-PITUITARY HORMONES; ESTROUS CYCLICITY; ABUSE; PROLACTIN; RAT AB OBJECTIVE: The purpose of this study was to evaluate the effects of daily follicular-phase cocaine administration on menstrual cyclicity, gonadotropin and ovarian steroid levels, ovulation rates, and corpus luteum function in cycling rhesus monkeys. STUDY DESIGN: Thirteen normally cycling, drug-naive adult rhesus monkeys were randomized to receive daily intravenous injections of either 4 mg/kg cocaine or an equal volume of saline solution. Treated animals were yoked to pair-fed controls to minimize differences in caloric intake. Daily blood samples were obtained through indwelling catheters for measurement of serum gonadotropin and ovarian steroid levels. Daily vaginal swabs were obtained to determine the onset of menses. Laparoscopy was performed 2 days after the midcycle estrogen peak to check for ovulation. Daily caloric intakes and pretreatment and posttreatment weights were recorded. RESULTS: All six of the control monkeys had laparoscopically confirmed ovulation compared with one of seven in the cocaine-treated group (p < 0.004). Cycle length was normal in five of six controls versus one of seven cocaine-treated monkeys. Estradiol levels were significantly higher in the controls versus the cocaine-treated monkeys (p = 0.01) during the first 14 days of the treatment cycle. There were no differences in basal plasma gonadotropin levels between groups. Luteal-phase lengths and luteal-phase plasma progesterone levels were similar in the controls and the single ovulatory cocaine-treated monkey. There were no significant differences in weight change or caloric intake between the two groups. CONCLUSIONS: Daily follicular-phase cocaine administration disrupts menstrual cyclicity and folliculogenesis independent of weight loss, caloric intake, and basal gonadotropin levels. C1 Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Dept Res & Dev, San Antonio, TX 78284 USA. RP Schenken, RS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDA NIH HHS [DA08295] NR 26 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1998 VL 178 IS 1 BP 118 EP 125 DI 10.1016/S0002-9378(98)70637-4 PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA YU977 UT WOS:000071776100021 PM 9465814 ER PT J AU Nickman, SL Silverman, PR Normand, C AF Nickman, SL Silverman, PR Normand, C TI Children's construction of a deceased parent: The surviving parent's contribution SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article AB Constructing a connection to the deceased is helpful to children in adjusting to the death of a parent. Using interview data from a subset of a larger study of childhood bereavement, this paper describes ways in which parents help children, ages 10-12, build this connection, provides case examples contrasting parental attitudes and behavior that are helpful and those that are not helpful to the child, and offers implications for clinical practice. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Montreal, Montreal, PQ H3C 3J7, Canada. RP Nickman, SL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. FU NIMH NIH HHS [MH41971] NR 18 TC 19 Z9 19 U1 1 U2 2 PU AMER ORTHOPSYCHIATRIC ASSOC PI NEW YORK PA 330 SEVENTH AVE, 18TH FL, NEW YORK, NY 10001 USA SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD JAN PY 1998 VL 68 IS 1 BP 126 EP 134 DI 10.1037/h0080277 PG 9 WC Psychiatry; Social Work SC Psychiatry; Social Work GA YV292 UT WOS:000071808600013 PM 9494649 ER PT J AU Vallat, AV De Girolami, U He, JL Mhashilkar, A Marasco, W Shi, B Gray, F Bell, J Keohane, C Smith, TW Gabuzda, D AF Vallat, AV De Girolami, U He, JL Mhashilkar, A Marasco, W Shi, B Gray, F Bell, J Keohane, C Smith, TW Gabuzda, D TI Localization of HIV-1 co-receptors CCR5 and CXCR4 in the brain of children with AIDS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; IMMUNE-DEFICIENCY SYNDROME; POLYMERASE CHAIN-REACTION; PROGRAMMED CELL-DEATH; DISEASE PROGRESSION; ENDOTHELIAL-CELLS; TYPE-1 INFECTION; IN-VIVO; DEMENTIA AB The chemokine receptors CCR5 and CXCR4 are coreceptors together with CD4 for human immunodeficiency virus (HIV)-1 entry into target cells. Macrophage-tropic HIV-1 viruses use CCR5 as a co-receptor, whereas T-cell-line tropic viruses use CXCR4. HIV-1 infects the brain and causes a progressive encephalopathy in 20 to 30% of infected children and adults. Most of the HIV-1-infected cells in the brain are macrophages and microglia. We examined expression of CCR5 and CXCR4 in brain tissue from 20 pediatric acquired immune deficiency syndrome (AIDS) patients in relation to neuropathological consequences of HIV-1 infection. The overall frequency of CCR5-positive perivascular mononuclear cells and macrophages was increased in the brains of children with severe HIV-1 encephalitis (HIVE) compared with children with mild HIVE or non-AIDS controls, whereas the frequency of CXCR4-positive perivascular cells did not correlate with disease severity. CCR5- and CXCR4-positive macrophages and microglia were detected in inflammatory lesions in the brain of children with severe HIVE. In addition, CXCR4 was detected in a subpopulation of neurons in autopsy brain tissue and primary human brain cultures. Similar findings were demonstrated in the brain of adult AIDS patients and controls. These findings suggest that CCR5-positive mononuclear cells, macrophages, and microglia contribute to disease progression in the central nervous system of children and adults with AIDS by serving as targets for virus replication. C1 Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA. Hop Lariboisiere, Dept Pathol, F-75475 Paris, France. Hop Raymond Poincare, Fac Med Paris Ouest, Garches, France. Univ Edinburgh, Dept Pathol, Edinburgh, Midlothian, Scotland. Cork Reg Hosp, Dept Pathol, Wilton Cork, Ireland. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, JFB712,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI07386, AI28691]; NINDS NIH HHS [NS35734] NR 67 TC 147 Z9 149 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1998 VL 152 IS 1 BP 167 EP 178 PG 12 WC Pathology SC Pathology GA YQ933 UT WOS:000071439200019 PM 9422534 ER PT J AU Kiraly, A Suto, G Guth, PH Tache, Y AF Kiraly, A Suto, G Guth, PH Tache, Y TI Peripheral mediators involved in gastric hyperemia to vagal activation by central TRH analog in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE nitric oxide; atropine; histamine; capsaicin; N-G-nitro-L-arginine methyl ester; thyrotropin-releasing hormone; blood pressure; acetylcholine; N-G-monomethyl-L-arginine; pyrilamine; gastric vascular resistance ID THYROTROPIN-RELEASING-HORMONE; MUCOSAL BLOOD-FLOW; NITRIC-OXIDE SYNTHASE; NERVOUS-SYSTEM ACTION; ARGININE METHYL-ESTER; DORSAL MOTOR NUCLEUS; STIMULATION; HISTAMINE; PENTAGASTRIN; ARTERIOLES AB Mechanisms mediating the increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracis ternally at a gastric acid secretory dose (30 ng) were investigated using hydrogen gas clearance in urethananesthetized rats. The histamine H-1 receptor antagonist pyrilamine (intravenously), capsaicin (subcutaneously, -10 days), and N-G-nitro-L-arginine methyl ester (L-NAME, intracisternally) failed to impair the 150% rise in GMBF induced by intracisternal injection of RX-77368. By contrast, atropine (subcutaneously) and N-G-monomethyl-L-arginine (intravenously) completely inhibited the increase in GMBF evoked by intracisternal RX-77368. L-NAME (intravenously) blocked the intracisternal RX-77368-induced increase in GMBF in capsaicin-pretreated rats, and the L-NAME effect was reversed by intravenous L- but not D-arginine. These findings indicate that vagal efferent activation induced by TRH analog injected intracisternally at a gastric acid secretory dose increases GMBF through atropine-sensitive mechanisms stimulating L-arginine-nitric oxide pathways, whereas HL receptors and capsaicin-sensitive afferent fibers do not play a role. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Rm 203, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-30110]; NIMH NIH HHS [MH-00663] NR 42 TC 13 Z9 13 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 JAN PY 1998 VL 274 IS 1 BP G170 EP G177 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA YR449 UT WOS:000071496400021 PM 9458786 ER PT J AU Mithofer, K Castillo, CFD Rattner, D Warshaw, AL AF Mithofer, K Castillo, CFD Rattner, D Warshaw, AL TI Subcellular kinetics of early trypsinogen activation in acute rodent pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreas; protease activation; acinar cell; experimental; cathepsin B ID CERULEIN-INDUCED PANCREATITIS; LYSOSOMAL-ENZYMES; INTRACELLULAR ACTIVATION; SUPRAMAXIMAL STIMULATION; ZYMOGEN GRANULES; CATHEPSIN B1; ACINAR CELL; RAT; PEPTIDES; ASSAY AB To investigate the debated role of intracellular trypsinogen activation and its relation to lysosomal enzyme redistribution in the pathogenesis of acute pancreatitis, rats were infused with the cholecystokinin analog caerulein at 5 mu g . kg(-1) . h(-1) for intervals up to 3 h, and the changes were contrasted with those in animals receiving saline or 0.25 mu g . kg(-1) . h(-1) caerulein. Saline or 0.25 mu g . kg(-1) . h(-1) caerulein did not induce significant changes. In contrast, 5 mu g . kg(-1) . h(-1) caerulein caused significant hyperamylasemia and pancreatic edema within 30 min. Pancreatic content of trypsinogen activation peptide (TAP) increased continuously (significant within 15 min). TAP generation was predominantly located in the zymogen fraction during the first hour but expanded to other intracellular compartments thereafter. Cathepsin B activity in the zymogen compartment increased continuously throughout the experiments and correlated significantly with TAP generation in the same compartment. Total trypsinogen content increased to 143% with marked interstitial trypsinogen accumulation after 3 h. Supramaximal caerulein stimulation causes trypsinogen activation by 15 min that originates in the zymogen compartment and is associated with increasing cathepsin B activity in this subcellular compartment. However, a much larger pool of trypsinogen survives and accumulates in the extracellular space and may become critical in the evolution of necrotizing pancreatitis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Surg Labs, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Surg Labs, 15 Parkman St,WAC 336, Boston, MA 02114 USA. NR 58 TC 55 Z9 56 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 JAN PY 1998 VL 274 IS 1 BP G71 EP G79 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA YR449 UT WOS:000071496400010 PM 9458775 ER PT J AU Freeman, GL Colston, JT Zabalgoitia, M Chandrasekar, B AF Freeman, GL Colston, JT Zabalgoitia, M Chandrasekar, B TI Contractile depression and expression of proinflammatory cytokines and iNOS in viral myocarditis SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-College-of-Cardiology CY MAR 16-19, 1997 CL ANAHEIM, CALIFORNIA SP Amer Coll Cardiol DE myocardial contraction; coxsackievirus; inducible nitric oxide synthase; mice ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; FACTOR-ALPHA; CARDIAC MYOCYTES; COXSACKIEVIRUS-B3 MYOCARDITIS; MURINE MODEL; HEART; CARDIOMYOPATHY; INDUCTION; INTERLEUKIN-1 AB We assessed two strains of mice [CD-1 and C3H.HeJ (C3H)] with different responses to cox-sackievirus B3 (CVB3) infection at 7, 14, and 21 days after inoculation with 10(5) pfu of CVBS. CD-1 mice developed inflammatory lesions at 7 days that nearly recovered by 21 days; C3H mice demonstrated persistence of infiltrates. Although there were differences in the baseline fractional shortening, it was further reduced at 7 and 14 days in both strains. It recovered in CD-1 mice but remained depressed at 21 days in C3H mice. Interleukin-6 and tumor necrosis factor-alpha transcripts were increased in both strains at 7 days. Levels dropped to near control in CD-1 mice at 21 days but remained elevated in C3H mice. Interleukin-1 beta was minimally elevated in CD-1 mice but increased progressively in C3H mice. mRNA for the inducible form of NO synthase (NOS was increased at 7 days in the CD-1 mice, returning to baseline by 14 days; it rose progressively in C3H mice, with a fivefold increase at 21 days. We conclude that mice infected with CVB3 show increased expression of proinflammatory cytokines as well as iNOS associated with reduced contractile performance. In more susceptible mice, contractile depression and cytokine and iNOS expression are more pronounced. C1 Univ Texas, Hlth Sci Ctr, Div Cardiol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Freeman, GL (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NHLBI NIH HHS [2 T32 HL-07350] NR 37 TC 35 Z9 37 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 JAN PY 1998 VL 274 IS 1 BP H249 EP H258 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA YT006 UT WOS:000071554600030 PM 9458874 ER PT J AU Jagielo, PJ Quinn, TJ Qureshi, N Schwartz, DA AF Jagielo, PJ Quinn, TJ Qureshi, N Schwartz, DA TI Grain dust-induced lung inflammation is reduced by Rhodobacter sphaeroides diphosphoryl lipid A SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE endotoxin; lipopolysaccharide inhibition; asthma ID RHODOPSEUDOMONAS-SPHAEROIDES; NONTOXIC LIPOPOLYSACCHARIDE; ENDOTOXIN; INDUCTION AB To further determine the importance of endotoxin in grain dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the lipopolysaccharide of Rhodobacter sphaeroides (RsDPLA) as a partial agonist of grain dust-induced airway inflammation. RsDPLA is a relatively inactive compound compared with lipid A derived from Escherichia coli (LPS) and has been demonstrated to act as a partial agonist of LPS-induced inflammation. To assess the potential stimulatory effect of RsDPLA in relation to LPS, we incubated THP-1 cells with RsDPLA (0.001-100 mu g/ml), LPS (0.02 mu g endotoxin activity/ml), or corn dust extract (CDE; 0.02 mu g endotoxin activity/ml). Incubation with RsDPLA revealed a tumor necrosis factor (TNF)-alpha stimulatory effect at 100 mu g/ml. In contrast, incubation with LPS or CDE resulted in TNF-alpha release at 0.02 mu g/ml. Pretreatment of THP-1 cells with varying concentrations of RsDPLA before incubation with LPS or CDE (0.02 mu g endotoxin activity/ml) resulted in a dose-dependent reduction in the LPS-or CDE-induced release of TNF-alpha with concentrations of RsDPLA of up to 10 mu g/ml but not at 100 mu g/ml. To further understand the role of endotoxin in grain dust-induced airway inflammation, we utilized the unique LPS inhibitory property of RsDPLA to determine the inflammatory response to inhaled CDE in mice in the presence of RsDPLA. Ten micrograms of RsDPLA intratracheally did not cause a significant inflammatory response compared with intratracheal saline. However, pretreatment of mice with 10 mu g of RsDPLA intratracheally before exposure to CDE (5.4 and 0.2 mu g/m(3)) or LPS (7.2 and 0.28 mu g/m(3)) resulted in significant reductions in the lung lavage concentrations of total cells, neutrophils, and specific proinflammatory cytokines compared with mice pretreated with sterile saline. These results confirm the LPS-inhibitory effect of RsDPLA and support the role of endotoxin as the principal agent in grain dust causing airway inflammation. C1 Univ Iowa, Coll Med, Dept Internal Med, Pulm Dis Crit Care & Occupat Med Div, Iowa City, IA 52242 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Dept Bacteriol, Madison, WI 53705 USA. RP Schwartz, DA (reprint author), Univ Iowa, Coll Med, Dept Internal Med, Pulm Dis Crit Care & Occupat Med Div, Iowa City, IA 52242 USA. FU NIEHS NIH HHS [ES-06537, ES-00203]; NIOSH CDC HHS [OH-00134-02] NR 19 TC 20 Z9 20 U1 0 U2 0 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 JAN PY 1998 VL 274 IS 1 BP L26 EP L31 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA YT173 UT WOS:000071572600004 PM 9458797 ER PT J AU De Angelis, C Haupert, GT AF De Angelis, C Haupert, GT TI Hypoxia triggers release of an endogenous inhibitor of Na(+)-K(+)-ATPase from midbrain and adrenal SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ouabain; endogenous digitalis; hypothalamus; natriuretic hormone ID DIGOXIN-LIKE SUBSTANCE; IMMUNOREACTIVE FACTOR; BOVINE HYPOTHALAMUS; HYPERTENSIVE RATS; HUMAN PLASMA; OUABAIN; SODIUM; TRANSPORT; BRAIN; CELLS AB An endogenous inhibitor of Na(+)-K(+)-ATPase has been isolated from bovine hypothalamus and human plasma and structurally characterized as an isomer of the plant cardiac glycoside, ouabain (A. A. Tymiak, J. A. Norman, M. Bolgar, G. C. DiDonato, H. Lee, W. L. Parker, L.-C. Lo, N. Berova, K. Nakanishi, E. Haber, and G. T. Haupert, Jr. Proc. Natl. Acad. Sci. USA 90: 8189-8193, 1993; N. Zhao, L.-C. Lo, N. Berova, K. Nakanishi, J. H. Ludens, and G. T. Haupert, Jr. Biochemistry 34: 9893-9896, 1995). This hypothalamic inhibitory factor (HIF) acts on cardiovascular and renal tissues consistent with physiological regulation in vivo. Stimuli for the release of HIF from tissue are unknown. Hypoxia may be a stimulus for the elaboration of digitalis-like activity in humans, and high NaCl concentration in central nervous system stimulates ouabain-like activity in animals. We examined the ability of low O(2) tension in viva and in vitro to stimulate HIF release from midbrain and adrenal tissues in Wistar rats. In both tissues, hypoxia stimulated a remarkable release of an inhibitor cochromatographing with HIF, and this release was enhanced by 300 mM NaCl. Plasma from hypoxic rats also showed increased levels of the purified inhibitory activity. We conclude that hypoxia is a potent stimulus for the release of HIF or HIF-like activity and discuss the possibility that an Na(+)-K(+)-ATPase inhibitor could be involved in energy-conserving cellular adaptive responses to hypoxic or ischemic insult through ATP conservation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Renal Unit, Charlestown, MA 02129 USA. Italian Air Force, Div Study Res & Experimentat, Aerosp Med Dept, I-00040 Rome, Italy. RP Haupert, GT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Renal Unit, CNY-8,149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-52282] NR 33 TC 48 Z9 49 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 1998 VL 274 IS 1 BP F182 EP F188 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA YR534 UT WOS:000071504900022 PM 9458838 ER PT J AU Smith, PR Mackler, SA Weiser, PC Brooker, DR Ahn, YJ Harte, BJ McNulty, KA Kleyman, TR AF Smith, PR Mackler, SA Weiser, PC Brooker, DR Ahn, YJ Harte, BJ McNulty, KA Kleyman, TR TI Expression and localization of epithelial sodium channel in mammalian urinary bladder SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE amiloride-sensitive sodium channel; sodium transport ID SENSITIVE NA+ CHANNEL; MEDULLARY COLLECTING DUCT; APICAL MEMBRANE; IMMUNOCYTOCHEMICAL LOCALIZATION; HOMOLOGOUS SUBUNITS; ALPHA-SUBUNITS; GAMMA-SUBUNITS; BETA-SUBUNITS; CLONING; TRANSPORT AB The mammalian urinary bladder exhibits transepithelial Na(+) absorption that contributes to Na(+) gradients established by the kidney. Electrophysiological studies have demonstrated that electrogenic Na(+) absorption across the urinary bladder is mediated in part by amiloride-sensitive Na(+) channels situated within the apical membrane of the bladder epithelium. We have used a combination of in situ hybridization, Northern blot analysis, and immunocytochemistry to examine whether the recently cloned epithelial Na(+) channel (ENaC) is expressed in the rat urinary bladder. In situ hybridization and Northern blot analyses indicate that alpha-, beta-, and gamma-rat ENaC (rENaC) are expressed in rat urinary bladder epithelial cells. Quantitation of the levels of alpha-, beta-, and gamma-rENaC mRNA expression in rat urinary bladder, relative to p-actin mRNA expression, indicates that, although comparable levels of alpha- and beta-rENaC subunits are expressed in the urinary bladder of rats maintained on standard chow, the level of gamma-rENaC mRNA expression is 5- to 10-fold lower than alpha- or beta-rENaC mRNA. Immunocytochemistry, using an antibody directed against alpha-rENaC, revealed that ENaCs are predominantly localized to the luminal membrane of the bladder epithelium. Together, these data demonstrate that ENaC is expressed in the mammalian urinary bladder and suggest that amiloride-sensitive Na(+) transport across the apical membrane of the mammalian urinary bladder epithelium is mediated primarily by ENaC. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. Allegheny Univ Hlth Sci, Dept Physiol, Philadelphia, PA 19129 USA. RP Kleyman, TR (reprint author), Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIDDK NIH HHS [DK-51391, DK-46705, DK-07006] NR 45 TC 50 Z9 50 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 1998 VL 274 IS 1 BP F91 EP F96 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA YR534 UT WOS:000071504900011 PM 9458827 ER PT J AU Eisen, JL Phillips, KA Baer, L Beer, DA Atala, KD Rasmussen, SA AF Eisen, JL Phillips, KA Baer, L Beer, DA Atala, KD Rasmussen, SA TI The Brown Assessment of Beliefs Scale: Reliability and validity SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID OBSESSIVE-COMPULSIVE DISORDER; BODY DYSMORPHIC DISORDER; DELUSIONAL EXPERIENCE; PSYCHOTIC FEATURES; BIZARRE DELUSIONS; INSIGHT; DEPRESSION AB Objective: The authors developed and evaluated the reliability and validity of the Brown Assessment of Beliefs Scale, a clinician-administered seven-item scale designed to assess delusions across a wide range of psychiatric disorders, Method: The authors developed the scale after reviewing the literature on the assessment of delusions. Four raters administered the scale to 20 patients with obsessive-compulsive disorder (OCD), 20 patients with body, dysmorphic disorder, and 10 patients with mood disorder with psychotic features. Audiotaped interviews of scale administration conducted by one rater were independently scored by the other raters to evaluate interrater reliability. The scale was administered to 27 patients twice to determine test-retest reliability. Other insight instruments as well as scales that assess symptom severity were administered to assess convergent and discriminant validity. Sensitivity to change was assessed in a multicenter treatment study of sertraline for OCD. Results: Interrater and test-retest reliability for the total score and individual item scores was excellent, with a high degree of internal consistency. One factor was obtained that accounted for 56% of the variance. Scores on the Brown Assessment of Beliefs Scale were lot correlated with symptom severity but were correlated with other measures of insight. The scale was sensitive to change in insight in OCD but was not identical to improvement in severity. Conclusions: The Brown Assessment of Beliefs Scale is a reliable and valid instrument for assessing delusionality in a number of psychiatric disorders. This scale may help clarify whether delusional and nondelusional variants of disorders constitute the same disorder as well as whether delusionality affects treatment outcome and prognosis. C1 Butler Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, OCD Clin, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. RP Eisen, JL (reprint author), Butler Hosp, 345 Blackstone Blvd, Providence, RI 02906 USA. NR 37 TC 264 Z9 270 U1 1 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1998 VL 155 IS 1 BP 102 EP 108 PG 7 WC Psychiatry SC Psychiatry GA YP421 UT WOS:000071275100017 PM 9433346 ER PT J AU Emmons, KM Wechsler, H Dowdall, G Abraham, M AF Emmons, KM Wechsler, H Dowdall, G Abraham, M TI Predictors of smoking among US college students SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BINGE-DRINKING; CIGARETTE-SMOKING; MEN AB Objectives. This study explored predictors of smoking among a large, representative national sample of students enrolled in American 4-year colleges. Methods. A sample of undergraduate students, randomly selected from 140 colleges, was sent a detailed questionnaire that included questions about smoking status. Results. The 30-day smoking prevalence was 22.3%; 25% of the participants were former smokers. Multivariate analyses suggested that, among college students, men are less likely to smoke than women. In addition, high-risk behaviors (e.g., marijuana use) and lifestyle choices (e.g., nonparticipation in athletics) increased the likelihood of being a smoker. Conclusions. This study's findings have important implications for health education and promotion among college populations. C1 Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. St Josephs Univ, Dept Sociol, Philadelphia, PA 19131 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Div Community Based Res, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 111 Z9 112 U1 4 U2 6 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 1998 VL 88 IS 1 BP 104 EP 107 DI 10.2105/AJPH.88.1.104 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZP949 UT WOS:000073804800020 PM 9584013 ER PT J AU Rosenthal, DI Chew, FS Dupuy, DE Kattapuram, SV Palmer, WE Yap, RM Levine, LA AF Rosenthal, DI Chew, FS Dupuy, DE Kattapuram, SV Palmer, WE Yap, RM Levine, LA TI Computer-based speech recognition as a replacement for medical transcription SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SYSTEM AB OBJECTIVE, We have implemented computerized speech recognition in a high-volume clinical setting using a newly developed commercial software system. This paper compares the performance of the computerized system with conventional transcription during a trial week followed by 3 months of routine clinical use. CONCLUSION. The speech recognition system was used for 97% of the cases during the trial week and 87% of cases during the months of continuous use. For a similar mixture of cases, no change occurred in the length of reports after introduction of the computerized system. Speech recognition decreased the time until the report became available by 99% and resulted in a substantial savings in transcription costs. We conclude that speech recognition by computer is practical in a high-volume clinical implementation. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 289,32 Fruit St, Boston, MA 02114 USA. NR 5 TC 37 Z9 39 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 1998 VL 170 IS 1 BP 23 EP 25 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YM600 UT WOS:000071081000007 PM 9423591 ER PT J AU Lee, SI Chew, FS AF Lee, SI Chew, FS TI Splanchnic segmental arterial mediolysis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID FIBROMUSCULAR DYSPLASIA C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chew, FS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 5 TC 8 Z9 8 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 JAN PY 1998 VL 170 IS 1 BP 122 EP 122 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YM600 UT WOS:000071081000032 PM 9423613 ER PT J AU Kearse, LA Rosow, C Zaslavsky, A Connors, P Dershwitz, M Denman, W AF Kearse, LA Rosow, C Zaslavsky, A Connors, P Dershwitz, M Denman, W TI Bispectral analysis of the electroencephalogram predicts conscious processing of information during propofol sedation and hypnosis SO ANESTHESIOLOGY LA English DT Article DE brain, intravenous anesthetics, monitoring, nitrous oxide ID NITROUS-OXIDE ANESTHESIA; BLINK REFLEX; CORNEAL REFLEX; EEG; MOVEMENT; MIDAZOLAM; PHARMACODYNAMICS AB Background: The bispectral index (BLS) measures changes in the interfrequency coupling of the electroencephalogram (EEG). The purposes of this study mere (1) to determine whether BIS correlates with responses to command during sedation and hypnosis induced by propofol or propofol and nitrous oxide, and (2) to compare BIS to targeted and measured concentrations of propofol in predicting participants' responses to commands. Methods: Twenty volunteers (15 men and 5 women, aged 22-50 yr) were given propofol by computer-controlled infusion, and EEG was recorded for off-line analysis of BIS. Responses to randomly ordered verbal commands or voice plus touch were measured with two categorical scales (CS1 and CS2, respectively). All subjects received a propofol infusion targeted to achieve effect site concentrations of 1, 2, 4, 2, 1, and 0 mu g/ml. Ten participants had repeated infusion, whereas 10 others breathed 30% nitrous oxide and oxygen and received a propofol infusion targeted for 0.5, 1, 2, 4, 2, 1, 0.5, and 0 mu g/ml. Five minutes after each targeted concentration had been reached, CS1, CS2, and arterial propofol concentration were determined. The area under the receiver operating characteristic curve was used to compare the accuracy of (1) BIS, (2) targeted propofol concentration, (3) measured concentration, and (4) treatment history as predictors of response. Results: Bispectral index was a strong predictor of CS1 and CS2 (P < 0.0001) and significantly more accurate than targeted or measured propofol concentrations (P < 0.0003 and P < 0.003, respectively), It also provided additional predictive power when combined with treatment history (P < 0.02). Nitrous oxide slightly decreased the probability of response at a given value of BIS (P < 0.05), but accuracy was unaffected. Conclusions: Bispectral index accurately predicts response to verbal commands during sedation and hypnosis with propofol or propofol plus nitrous oxide. Accuracy is maintained in situations likely to be encountered during clinical use: when propofol concentrations are increasing or decreasing and when repeated measurements are made over time. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Publ Hlth Policy, Cambridge, MA 02138 USA. RP Rosow, C (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Fruit St, Boston, MA 02114 USA. NR 36 TC 163 Z9 196 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1998 VL 88 IS 1 BP 25 EP 34 DI 10.1097/00000542-199801000-00007 PG 10 WC Anesthesiology SC Anesthesiology GA YQ733 UT WOS:000071417800008 PM 9447852 ER PT J AU Adrie, C Hirani, WM Holzmann, A Keefer, L Zapol, WM Hurford, WE AF Adrie, C Hirani, WM Holzmann, A Keefer, L Zapol, WM Hurford, WE TI Selective pulmonary vasodilation by intravenous infusion of an ultrashort half-life nucleophile nitric oxide adduct SO ANESTHESIOLOGY LA English DT Article DE nitric oxide prodrugs; pulmonary hypertension; sheep; sodium nitroprusside ID HYPERTENSION; NITROPRUSSIDE AB Background: PROLI/NO (C5H7/N3O4Na2 . CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenons administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension, Methods; in eight awake healthy sheep with pulmonary Hypertension induced by 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F-2 alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 mu g.kg(-1).min(-1) of SNP or 0.75, 1.5, 3, 6, and 12 mu g.kg(-1).min(-1) of PROLI/NB. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized. Results: Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 mu g.kg(-1).min(-1), which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 mu g.kg(-1).min(-1), PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled), Conclusions: The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Hurford, WE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL 42397] NR 15 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 1998 VL 88 IS 1 BP 190 EP 195 DI 10.1097/00000542-199801000-00027 PG 6 WC Anesthesiology SC Anesthesiology GA YQ733 UT WOS:000071417800028 PM 9447872 ER PT J AU Cutrer, FM Sorensen, AG Weisskoff, RM Ostergaard, L del Rio, MS Lee, EJ Rosen, BR Moskowitz, MA AF Cutrer, FM Sorensen, AG Weisskoff, RM Ostergaard, L del Rio, MS Lee, EJ Rosen, BR Moskowitz, MA TI Perfusion-weighted imaging defects during spontaneous migrainous aura SO ANNALS OF NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; CLASSIC MIGRAINE; SPREADING OLIGEMIA; CONTRAST AGENTS; ATTACKS; HYPOPERFUSION; HEADACHE; VOLUME AB Perfusion-and diffusion-weighted magnetic resonance imaging was performed during spontaneous visual auras in four migraineurs. Alterations in relative cerebral blood flow (16-53% decrease), cerebral blood volume (6-33% decrease), and tissue mean transit time (10-54% increase) were observed in the gray matter of occipital cortex contralateral to the affected visual hemifield. No changes in the apparent diffusion coefficient were observed either while the patients were symptomatic or after resolution of the visual symptoms but before the onset of headache. Functional magnetic resonance imaging can be a useful noninvasive tool to study hemodynamic changes during spontaneous attacks of migraine with aura. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 149 13th St,CNY 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NCI NIH HHS [P01-CA48729, R01-CA40303]; NINDS NIH HHS [K08 NS 01803] NR 28 TC 223 Z9 224 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1998 VL 43 IS 1 BP 25 EP 31 DI 10.1002/ana.410430108 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YR531 UT WOS:000071504600004 PM 9450765 ER PT J AU Mitler, MM Guilleminault, C Harsh, JR Hirshkowitz, M Becker, PM Jamieson, AO Jewel, CE Bogan, RK James, DS Sutton, JT Corser, B Mayleben, DW Bernard, SH Dinner, DS Emsellem, H Knight, E Chase, C Erwin, CW Krystal, AD Radtke, RA Farrow, S Odynski, T Pinto, J Steljes, D Feldman, NT O'Brien, M Fredrickson, PA Kaplan, J Lin, SC Burger, C Fry, JM Black, J Green, PM Schmitigal, L Gross, PT Dignan, S Harsh, J Hartwig, G Haynes, JB Hageman, M Porter-Shirley, K Hertz, G Moore, CA Iyer, V Mahowald, MM Ullevig, C Hayduk, R Erman, MK Pascualy, R Stolz, S Parman, D Richter, RW Gruenau, SP Webster, JAJ Ristanovic, RK Bergen, D Kanner, A Dyonzak, J Rogers, AE Aldrich, MS Rosenberg, R Richardson, T Lee, J Sahota, PK Dexter, JD Burger, RC Sangal, RB Sangal, JAM Belisle, C Schmidt, HS Parisot, PA Schmidt-Nowara, WW Jessup, C Schwartz, JRL Schwartz, ER Veit, C Blakely, L Scrima, L Miller, BR Shettar, SM May, RS Wilkerson, KE Stafford, C Grogan, WA Tearse, R Thein, SG Colontonio, L Vern, BA Mercer, PJ Merritt, SL Walsleben, JA O'Malley, MB Rapoport, DM Winokur, A Szuba, MD Civil, RH Dobbins, TW Kribbs, NB Laughton, WB Nelson, MT Wang, LX AF Mitler, MM Guilleminault, C Harsh, JR Hirshkowitz, M Becker, PM Jamieson, AO Jewel, CE Bogan, RK James, DS Sutton, JT Corser, B Mayleben, DW Bernard, SH Dinner, DS Emsellem, H Knight, E Chase, C Erwin, CW Krystal, AD Radtke, RA Farrow, S Odynski, T Pinto, J Steljes, D Feldman, NT O'Brien, M Fredrickson, PA Kaplan, J Lin, SC Burger, C Fry, JM Black, J Green, PM Schmitigal, L Gross, PT Dignan, S Harsh, J Hartwig, G Haynes, JB Hageman, M Porter-Shirley, K Hertz, G Moore, CA Iyer, V Mahowald, MM Ullevig, C Hayduk, R Erman, MK Pascualy, R Stolz, S Parman, D Richter, RW Gruenau, SP Webster, JAJ Ristanovic, RK Bergen, D Kanner, A Dyonzak, J Rogers, AE Aldrich, MS Rosenberg, R Richardson, T Lee, J Sahota, PK Dexter, JD Burger, RC Sangal, RB Sangal, JAM Belisle, C Schmidt, HS Parisot, PA Schmidt-Nowara, WW Jessup, C Schwartz, JRL Schwartz, ER Veit, C Blakely, L Scrima, L Miller, BR Shettar, SM May, RS Wilkerson, KE Stafford, C Grogan, WA Tearse, R Thein, SG Colontonio, L Vern, BA Mercer, PJ Merritt, SL Walsleben, JA O'Malley, MB Rapoport, DM Winokur, A Szuba, MD Civil, RH Dobbins, TW Kribbs, NB Laughton, WB Nelson, MT Wang, LX CA US Modafinil Narcolepsy Multicenter Study Grp TI Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT 121st Annual Meeting of the American-Neurological-Association CY OCT 13-16, 1996 CL MIAMI, FLORIDA SP Amer Neurol Assoc ID SLEEP LATENCY TEST; INDUCED WAKEFULNESS; AMPHETAMINE; MICE; RAT; CAT AB Narcolepsy is a central nervous system disorder characterized by excessive daytime sleepiness and cataplexy. This placebo-controlled, double-blind, randomized, parallel-group, 18-center study assessed the efficacy and safety of modafinil, a new wake-promoting drug for treating sleepiness in narcolepsy. Subjects with narcolepsy (n = 283) received daily modafinil, 200 or 400 mg, or placebo, for 9 weeks, followed by an open-label treatment period. Subjective sleepiness was measured with the Epworth Sleepiness Scale. Objective sleepiness was assessed with the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Level of illness was measured with the Clinical Global Impression of Change. Modafinil significantly reduced all measures of sleepiness and was associated with significant improvements in level of illness. Medication-related adverse experiences were few, dose-dependent, and mostly rated mild to moderate. Modafinil taken once daily was a very well tolerated and effective wake-promoting agent in the treatment of excessive daytime somnolence associated with narcolepsy. Modafinil demonstrated an excellent safety profile for up to 40 weeks of open-label treatment and efficacy was maintained, suggesting that tolerance will not develop with long-term use. Modafinil is a pharmacologically and clinically promising compound for the treatment of pathological daytime somnolence. C1 Presbyterian Med Ctr, Sleep Med Inst, Dallas, TX USA. Baptist Med Ctr, Columbia, SC USA. Christ Hosp, Cincinnati Reg Sleep Ctr, Cincinnati, OH 45219 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Neurol Ctr, Chevy Chase, MD USA. Duke Univ, Med Ctr, Durham, NC USA. Sleep Clin Nevada, Las Vegas, NV USA. Palms Pasadena Hosp, St Petersburg, FL USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Sleep Disorders Ctr, Philadelphia, PA 19129 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Kalamazoo Neurol PC, Kalamazoo, MI USA. Lahey Clin Fdn, Burlington, MA USA. Forrest Gen Hosp, Hattiesburg, MS USA. St Thomas Hosp, Sleep Disorders Ctr, Nashville, TN USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. VA Med Ctr, Houston, TX USA. Univ Louisville, Res Fdn Inc, Louisville, KY 40292 USA. Hennepin Cty Med Ctr, Minnesota Reg Sleep Disorders Ctr, Minneapolis, MN 55415 USA. Scripps Res Inst, La Jolla, CA USA. Providence Sleep Disorders Ctr, Seattle, WA USA. St Johns Hosp, Tulsa, OK USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Northside Hosp, Atlanta, GA USA. Univ Missouri, Columbia, MO USA. Sleep Disorders Inst, Troy, MI USA. Ohio Sleep Med Inst, Dublin, OH USA. Univ New Mexico Hosp, Albuquerque, NM USA. Integris SW Med Ctr, Sleep Disorders Ctr Oklahoma, Oklahoma City, OK USA. Sleep Alertness Disorder Ctr, Aurora, CO USA. UAB Stn, Ctr Psychiat Med, Birmingham, AL USA. Crozer Chester Med Ctr, Upland, PA USA. Sacred Heart Hosp, Sacred Heart Sleep Disorders Ctr, Eugene, OR USA. Pacific Res Network, San Diego, CA USA. Univ Illinois, Chicago, IL USA. NYU, Bellevue Hosp Ctr, Med Ctr, Sleep Disorders Ctr, New York, NY 10016 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Fry, JM (reprint author), Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Sleep Disorders Ctr, 3200 Henry Ave, Philadelphia, PA 19129 USA. RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 33 TC 239 Z9 240 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 1998 VL 43 IS 1 BP 88 EP 97 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YR531 UT WOS:000071504600011 ER PT J AU Canellos, GP AF Canellos, GP TI Peripheral T-cell lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 9O BP 2 EP 2 PG 1 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100010 ER PT J AU Sugarbaker, DJ AF Sugarbaker, DJ TI New surgical techniques in the management of lung cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 17O BP 4 EP 4 PG 1 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100020 ER PT J AU Winer, E Batist, G Harris, L Hooftman, L Park, Y AF Winer, E Batist, G Harris, L Hooftman, L Park, Y CA TLC D-99 Study Grp TI Phase III study of TLC D-99 (liposome encapsulated doxorubicin) vs. free doxorubicin (DOX) in patients with metastatic breast cancer (MBC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. Duke Univ, Med Ctr, Durham, NC USA. Liposome Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 59O BP 12 EP 12 PG 1 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100059 ER PT J AU Kaye, S Nemunaitis, J Ganly, I Posner, M Vokes, E Kuhn, J Heise, C Maack, C Kirn, D AF Kaye, S Nemunaitis, J Ganly, I Posner, M Vokes, E Kuhn, J Heise, C Maack, C Kirn, D TI A phase II trial of intratumoral injection with an E1B-deleted adenovirus, ONYX-015, in patients with recurrent, refractory head and neck cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland. Phys Reliance Network, Dallas, TX USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Chicago, Dept Med Oncol, Chicago, IL 60637 USA. Onyx Pharmaceut, Richmond, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 061 BP 22 EP 22 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600064 ER PT J AU Jain, RK AF Jain, RK TI Tumor microenvironment and microcirculation: Role in drug delivery SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 065 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600068 ER PT J AU Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK AF Jaffe, ES Harris, NL Diebold, J Muller-Hermelink, HK TI World Health Organization Classification of lymphomas: A work in progress SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th Symposium on Hodgkins Disease CY MAR 28-APR 01, 1998 CL COLOGNE, GERMANY DE B cell; Hodgkin's disease; leukemia; lymphoma; non-Hodgkin's lymphoma; T cell ID T-CELL LYMPHOMA; MONOCLONAL-ANTIBODY ALK1; NON-HODGKINS-LYMPHOMAS; LYMPHOPROLIFERATIVE DISORDERS; CLINICOPATHOLOGICAL ENTITY; CLINICAL-SIGNIFICANCE; TRANSLOCATION; PHENOTYPE; NEOPLASMS; PROPOSAL AB The World Health Organization (WHO) publishes classification handbooks for all neoplastic diseases. The last WHO Classification of leukemias and lymphomas was published in 1976, Since that time, through cytogenetics and molecular biology it has been shown that many hematopoietic neoplasms are associated with a unique genetic profile. Similarly, the development of widely available and routinely applied monoclonal antibodies has allowed the identification of a unique immunophenotypic profile for most leukemias and lymphomas. These techniques have permitted the recognition of a number of distinct disease entities, and also enhance both diagnostic accuracy and reproducibility. The WHO Classification has been developed under the joint auspices of the European Association for Hematopathology (EAHP) and the Society for Hematopathology (SH), First organized in 1995, the Steering Committee appointed 10 committees covering T-cell and B-cell lymphomas and leukemias, myeloid and histiocytic tumors. The committees were asked to develop a list of diseases within their topic area. and to establish definitions of each disease according to established criteria. The WHO Classification uses the principles of the R.E.A.L. Classification. which defines each disease according to its morphology, immunophenotype, genetic features, postulated normal counterpart, and clinical features. Morphologic and clinical variants of individual diseases are discussed in the text, and their use is optional. The proposed classification was presented at the USCAP meeting in 1997, the site of the first joint meeting of the EAHP and SH. The presentation was followed by an open forum attended by EAHP and SH members. The Steering Committee also appointed a Clinical Advisory Committee to ensure that the classification meets clinical needs, and to resolve questions of clinical significance. The proposed WHO Classification for lymphomas is similar to the R.E.A.L. Classification for lymphomas, with minor modifications and reassessment of provisional categories based on new data since 1993. C1 NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Hotel Dieu, Serv Cent Anat & Cytol Pathol, Paris, France. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,MSC-1500,10 Ctr Dr, Bethesda, MD 20892 USA. NR 31 TC 51 Z9 52 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 5 BP 25 EP 30 DI 10.1023/A:1008462124002 PG 6 WC Oncology SC Oncology GA 163AD UT WOS:000078379300005 ER PT J AU Rosowsky, A Papoulis, A Forsch, RA Queener, SF AF Rosowsky, A Papoulis, A Forsch, RA Queener, SF TI Synthesis and antifolate activity of new tetrahydroquinazoline and dihydrocyclopenta[d]pyrimidine analogs of piritrexim and trimetrexate as potential antitumor and antiparasitic drugs SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 120 BP 31 EP 32 PG 2 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600092 ER PT J AU Rudiger, T Jaffe, ES Delsol, G deWolf-Peeters, C Gascoyne, RD Georgii, A Harris, NL Kadin, ME MacLennan, KA Poppema, S Stein, H Weiss, LE Muller-Hermelink, HK AF Rudiger, T Jaffe, ES Delsol, G deWolf-Peeters, C Gascoyne, RD Georgii, A Harris, NL Kadin, ME MacLennan, KA Poppema, S Stein, H Weiss, LE Muller-Hermelink, HK TI Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma) SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th Symposium on Hodgkins Disease CY MAR 28-APR 01, 1998 CL COLOGNE, GERMANY DE differential diagnosis; grey zone; Hodgkin's lymphoma; immunohistochemistry; pathology; workshop report ID REED-STERNBERG CELLS; COMPOSITE LYMPHOMA; T-CELL; B-CELLS; EXPRESSION; CLASSIFICATION; DISORDERS; MARKER; ORIGIN AB Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma? anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified. C1 Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany. NCI, Pathol Lab, Bethesda, MD 20892 USA. CHU Purpan, Toulouse, France. Univ Leuven, Louvain, Belgium. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Med Hsch Hannover, Hannover, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Hosp, Boston, MA 02215 USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. Univ Groningen, NL-9700 AB Groningen, Netherlands. Univ Klinikum Benjamin Franklin, Berlin, Germany. City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Rudiger, T (reprint author), Univ Wurzburg, Inst Pathol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. RI Poppema, Sibrand/D-1204-2012 NR 27 TC 40 Z9 41 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 5 BP 31 EP 38 DI 10.1023/A:1008466208072 PG 8 WC Oncology SC Oncology GA 163AD UT WOS:000078379300006 ER PT J AU Recht, A Coleman, CN Teicher, B Ara, G Chen, YN Lowery, C Smith, M AF Recht, A Coleman, CN Teicher, B Ara, G Chen, YN Lowery, C Smith, M TI In vivo and in vitro results indicate that 'Tomudex' (raltitrexed) acts as a radiosensitizer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Joint Ctr Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Zeneca Pharmaceut, Wilmington, DE USA. Zeneca Pharmaceut, Alderley Pk, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 172P BP 36 EP 36 PG 1 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100169 ER PT J AU Harris, NL AF Harris, NL TI The many faces of Hodgkin's disease around the world: What have we learned from its pathology? SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th Symposium on Hodgkins Disease CY MAR 28-APR 01, 1998 CL COLOGNE, GERMANY DE B cell; classification; EBV; epidemiology; Hodgkin's disease; immunophenotype; lymphoma; molecular genetics; pathology ID REED-STERNBERG CELLS; EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; NODULAR LYMPHOCYTE PREDOMINANCE; TRANSFORMED GERMINAL-CENTERS; LATENT MEMBRANE-PROTEIN; ANTIGEN RECEPTOR GENES; CENTER B-CELLS; T-CELL; PROGRESSIVE TRANSFORMATION AB In the past decade there have been many advances in our understanding of Hodgkin's disease. Among the most important is the discovery that the Reed-Sternberg cell is a lymphoid cell, in most cases a B cell, and that it is clonal, and thus a true lymphoma, deserving of a name change, to 'Hodgkin's lymphoma' (HL). Based on a combination of immunophenotype and morphology, the R.E.A.L. Classification recognizes two main typos of HL: classical types (nodular sclerosis, mixed cellularity, lymphocyte-rich classical HL, and lymphocyte depletion) and nodular lymphocyte predominance type (NLPHL), which probably represent distinct biological entities. The immunophenotype and genetic features of both classical HL and NLPHL have been defined. These are useful in the subclassification of HL and in distinguishing HL from two recently-described, aggressive lymphomas that were in the past often diagnosed as HL: anaplastic large-cell lymphoma, T-cell type (ALCL), and T-cell/histiocyte-rich large B-cell lymphoma (T/HRBCL). Epstein-Barr virus has been detected in approximately 40% of the cases of classical HL, and is clonal, suggesting that this virus may play a role in the pathogenesis of at least some types of HL. The frequency of HL varies in different populations, and the frequency of EBV-positive HL appears to be inversely related to the overall frequency of HL in a given population. Thus, it is possible that its presence may simply reflect the prevalence of EBV-infected B cells in the individual. Despite the advances of the past ten years, many questions remain to be answered, and these will provide the challenges of the next decade. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2, Boston, MA 02114 USA. EM NLHarris@partners.org NR 112 TC 14 Z9 14 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 5 BP 45 EP 56 DI 10.1023/A:1008474526728 PG 12 WC Oncology SC Oncology GA 163AD UT WOS:000078379300008 ER PT J AU Miller, KD Loehrer, PJ Picus, J Blanke, C John, W Clark, J Schulman, LN Burris, H Thornton, D AF Miller, KD Loehrer, PJ Picus, J Blanke, C John, W Clark, J Schulman, LN Burris, H Thornton, D TI A phase II trial of multi-targeted antifolate (MTA) (LY231514) in patients with unresectable pancreatic cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Indiana Univ, Indianapolis, IN 46204 USA. Washington Univ, St Louis, MO USA. Vanderbilt Univ, Nashville, TN USA. Univ Kentucky, Lexington, KY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CTRC Res Fdn, San Antonio, TX USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 220O BP 46 EP 46 PG 1 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100216 ER PT J AU Villalona-Calero, M Eder, J Toppmeyer, D Allen, L Velagapudi, R Myers, M Amato, A Kagen-Hallet, K Razvillas, B O'Connor, L Fram, R Kufe, D Von Hoff, D Rowinsky, E AF Villalona-Calero, M Eder, J Toppmeyer, D Allen, L Velagapudi, R Myers, M Amato, A Kagen-Hallet, K Razvillas, B O'Connor, L Fram, R Kufe, D Von Hoff, D Rowinsky, E TI Phase I and pharmacokinetic (PK) study of LU79553, a novel bis-naphthalamide on a daily x 5 schedule SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Dana Farber Partners Canc Care, Boston, MA USA. Canc Inst New Jersey, New Brunswick, NJ USA. Knoll Pharmaceut Co, Parsippany, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 249 BP 65 EP 65 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600221 ER PT J AU Kaye, S Nemunaitis, J Ganly, I Posner, M Vokes, E Kuhn, J Heise, C Maack, C Kirn, D AF Kaye, S Nemunaitis, J Ganly, I Posner, M Vokes, E Kuhn, J Heise, C Maack, C Kirn, D TI A phase II trial of intratumoral injection with an E1B-deleted adenovirus, ONYX-015, in patients with recurrent, refractory head and neck cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Beatson Oncol Ctr, Glasgow, Lanark, Scotland. Phys Reliance Network, Dallas, TX USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Chicago, Dept Med Oncol, Chicago, IL USA. Onyx Pharmaceut, Richmond, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 326 BP 86 EP 86 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600298 ER PT J AU Canellos, GP AF Canellos, GP TI Treatment of relapsed Hodgkin's disease: Strategies and prognostic factors SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 4th Symposium on Hodgkins Disease CY MAR 28-APR 01, 1998 CL COLOGNE, GERMANY DE Hodgkins disease; prognostic factors; relapse; salvage chemotherapy ID CLINICAL STAGE-I; COMBINATION CHEMOTHERAPY; SALVAGE CHEMOTHERAPY; RADIATION-THERAPY; EUROPEAN ORGANIZATION; COMPLETE REMISSION; 2ND MALIGNANCIES; FIELD RADIATION; RISK-FACTORS; 1ST RELAPSE AB The major points in salvage therapy of patients in relapse following combination chemotherapy for advanced disease are: (1) success of any second-line approach is determined by prognostic factors which include age, duration of the initial remission, and quantity of disease at relapse; (2) induction failures (progression without remission or incomplete remission and short initial remission) require innovative therapy which currently entails high-dose chemotherapy with peripheral or bone marrow autologous support; (3) late relapse still retains an order to sensitivity to chemotherapy and can be treated with conventional dose combination with complementary radiation therapy to previously unirradiated bulky sites. The choice of regimen is empiric and can include a repeat of the regimen used for the original remission or induction. The relative advantage of HDC in this favorable group is uncertain. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 60 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 5 BP 91 EP 96 DI 10.1023/A:1008475921702 PG 6 WC Oncology SC Oncology GA 163AD UT WOS:000078379300016 ER PT J AU Demetri, GD Geiger, EA Xu, G Stefanowicz, L Joyce, R Richardson, P Elias, AD AF Demetri, GD Geiger, EA Xu, G Stefanowicz, L Joyce, R Richardson, P Elias, AD TI Outpatient tolerability of high-dose liposome-encapsulated daunorubicin (DaunoXome (R)) with filgrastim support in patients with solid tumors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Beth Israel Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 490 BP 128 EP 128 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600462 ER PT J AU Elias, A Hooftman, L Mazanet, R O'Day, S Lee, L Azarnia, N AF Elias, A Hooftman, L Mazanet, R O'Day, S Lee, L Azarnia, N TI A phase I study of TLC D-99 (liposome encapsulated doxorubicin) with G-CSF in patients with refractory solid tumours SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Liposome Co, Princeton, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 631P BP 131 EP 132 PG 2 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100623 ER PT J AU Demetri, G AF Demetri, G CA Procrit Study Grps TI Epoetin alfa treatment of anaemic breast cancer patients: Haematological and quality of life (QOL) outcomes SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Procrit Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 4 MA 676O BP 140 EP 141 PG 2 WC Oncology SC Oncology GA 137ZN UT WOS:000076947100664 ER PT J AU Recht, A Coleman, CN Teicher, B Ara, G Chen, YN Lowery, C AF Recht, A Coleman, CN Teicher, B Ara, G Chen, YN Lowery, C TI In vivo and in vitro results indicate that 'Tomudex' (raltitrexed) acts as a radiosensitizer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Oncol, Boston, MA 02115 USA. Zeneca Pharmaceut, Wilmington, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 608 BP 159 EP 159 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600580 ER PT J AU Demetri, GD Fletcher, CD Spiegelman, B Geiger, E Singer, S AF Demetri, GD Fletcher, CD Spiegelman, B Geiger, E Singer, S TI Troglitazone induces differentiation and decreases proliferation of liposarcoma in phase II trial SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 669 BP 175 EP 175 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600641 ER PT J AU Werner, J Dragotakes, SC del Castillo, CF Rivera, JA Ou, JR Rattner, DW Fischman, AJ Warshaw, AL AF Werner, J Dragotakes, SC del Castillo, CF Rivera, JA Ou, JR Rattner, DW Fischman, AJ Warshaw, AL TI Technetium-99m-labeled white blood cells - A new method to define the local and systemic role of leukocytes in acute experimental pancreatitis SO ANNALS OF SURGERY LA English DT Article ID TRYPSINOGEN-ACTIVATION PEPTIDES; ACUTE LUNG INJURY; NECROTIZING PANCREATITIS; ACINAR CELL; RAT; MODEL; STIMULATION; SEVERITY; RELEASE; MYELOPEROXIDASE AB Objective We developed a new method to quantitate leukocyte accumulation in tissues and used it to examine the time course and severity of acute experimental pancreatitis. Background Leukocyte activation and infiltration are believed to be critical steps in the progression from mild to severe pancreatitis and responsible for many of its systemic complications. Methods Pancreatitis of graded severity was induced in Sprague-Dawley rats with a combination of caerulein and controlled intraductal infusion. Technetium-99m (Tc-99m)-labeled leukocytes were quantified in pancreas, lung, liver, spleen, and kidney and compared with myeloperoxidase activity. The severity of pancreatitis was ascertained by wet/dry weight ratio, plasma amylase, and trypsinogen activation peptide in the pancreas. The time course of leukocyte accumulation was determined over 24 hours. Results Pancreatic leukocyte infiltration correlated well with tissue myeloperoxidase concentrations. in mild pancreatitis, leukocytes accumulated only in the pancreas. Moderate and severe pancreatitis were characterized by much greater leukocyte infiltration in the pancreas than in mild disease (p < 0.01), and increased Tc-99m radioactivity was detectable in the lung as early as 3 hours. Tc-99m radioactivity correlated directly with the three levels of pancreatitis. Conclusions Mild pancreatitis is characterized by low-level leukocyte activation and accumulation in the pancreas without recruitment of other organs; marked leukocyte accumulation was found in :he pancreas and in the lung in more severe grades of pancreatitis. These findings provide a basis for the pathophysiologic production of cytokines and oxygen free radicals, which potentiate organ injury in severe pancreatitis. This study validates a new tool to study local and systemic effects of leukocytes in pancreatitis as well as new therapeutic hypotheses. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 47 TC 44 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1998 VL 227 IS 1 BP 86 EP 94 DI 10.1097/00000658-199801000-00013 PG 9 WC Surgery SC Surgery GA YR054 UT WOS:000071453200013 PM 9445115 ER PT J AU Werner, J Schmidt, J Warshaw, AL Gebhard, MM Herfarth, C Klar, E AF Werner, J Schmidt, J Warshaw, AL Gebhard, MM Herfarth, C Klar, E TI The relative safety of MRI contrast agent in acute necrotizing pancreatitis SO ANNALS OF SURGERY LA English DT Article ID TRYPSINOGEN-ACTIVATION PEPTIDES; ENHANCED COMPUTED-TOMOGRAPHY; RAT; SEVERITY; MEDIA; CT; MICROCIRCULATION; ERYTHROCYTES; OXYGENATION; CAPILLARIES AB Objective To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. Background Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. Methods Necrotizing pancreatitis was induced in 14 Wister rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 mu g/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). Results The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). Conclusions intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable. C1 Univ Heidelberg, Dept Surg, D-69120 Heidelberg, Germany. Univ Heidelberg, Dept Expt Surg, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klar, E (reprint author), Univ Heidelberg, Dept Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany. NR 54 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1998 VL 227 IS 1 BP 105 EP 111 DI 10.1097/00000658-199801000-00015 PG 7 WC Surgery SC Surgery GA YR054 UT WOS:000071453200015 PM 9445117 ER PT J AU Workman, JL Kingston, RE AF Workman, JL Kingston, RE TI Alteration of nucleosome structure as a mechanism of transcriptional regulation SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE acetylation; chromatin; DNA-protein interactions ID TATA-BINDING PROTEIN; HISTONE ACETYLTRANSFERASE ACTIVITY; THYROID-HORMONE RECEPTOR; LOW IONIC-STRENGTH; DEPOSITION-RELATED ACETYLATION; CHROMATIN-REMODELING COMPLEX; NEWLY SYNTHESIZED HISTONES; ACIDIC ACTIVATION DOMAINS; YEAST PUTATIVE ADAPTERS; DNA-REPLICATION INVITRO AB The nucleosome, which is the primary building block of chromatin, is not a static structure: It can adopt alternative conformations. Changes in solution conditions or changes in histone acetylation state cause nucleosomes and nucleosomal arrays to behave with altered biophysical properties. Distinct subpopulations of nucleosomes isolated from cells have chromatographic properties and nuclease sensitivity different from those of bulk nucleosomes. Recently, proteins that were initially identified as necessary for transcriptional regulation have been shown to alter nucleosomal structure. These proteins are found in three types of multiprotein complexes that can acetylate nucleosomes, deacetylate nucleosomes, or alter nucleosome structure in an ATP-dependent manner. The direct modification of nucleosome structure by these complexes is likely to play a central role in appropriate regulation of eukaryotic genes. C1 Penn State Univ, Howard Hughes Med Inst, University Pk, PA 16802 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Workman, JL (reprint author), Penn State Univ, Howard Hughes Med Inst, University Pk, PA 16802 USA. NR 270 TC 822 Z9 835 U1 8 U2 47 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1998 VL 67 BP 545 EP 579 DI 10.1146/annurev.biochem.67.1.545 PG 35 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 116JT UT WOS:000075721700019 PM 9759497 ER PT J AU Price, DL Tanzi, RE Borchelt, DR Sisodia, SS AF Price, DL Tanzi, RE Borchelt, DR Sisodia, SS TI Alzheimer's disease: Genetic studies and transgenic models SO ANNUAL REVIEW OF GENETICS LA English DT Review DE beta-amyloid precursor protein; Tg mice; senile dementia; presenilin 1 and 2; dystrophic neurites ID AMYLOID PRECURSOR PROTEIN; RECEPTOR-RELATED PROTEIN; A-BETA DEPOSITION; PAIRED HELICAL FILAMENTS; HEREDITARY CEREBRAL-HEMORRHAGE; CARBOXYL-TERMINAL FRAGMENT; APOLIPOPROTEIN-E EPSILON-4; INBRED MOUSE STRAINS; E ALLELE EPSILON-4; NERVOUS-SYSTEM AB Recent advances in a variety of areas of research, particularly in genetics and in transgenic (Tg)/gene targeting approaches, have had a substantial impact on our understanding of Alzheimer's disease (AD) and related disorders. After briefly reviewing the progress that has been made in diagnostic assessments of patients with senile dementia and in investigations of the neuropathology of AD, we discuss some of the genes/proteins that are causative or risk factors for this disease, including those encoding amyloid precursor protein, presenilin 1 and 2, and apolipoprotein E. In addition, we comment on several potential new candidate loci/genes. Subsequently, we review selected recent reports of analyses of a variety of lines of Tg mice that show several neuropathological features of AD, including AB-amyloid deposits and dystrophic neurites. Finally, we discuss the several important issues in future investigations of Tg mice, with particular emphasis on the influences of genetic strains on phenotype, especially behavior, and strategies for making new models of neurodegenerative disorders. We believe that investigations of these Tg models will (a) enhance understanding of the relationships between impaired performance on memory tasks and the pathological/biochemical abnormalities in brain, (b) help to clarify pathogenic mechanisms in vivo, (c) lead to identification of new therapeutic targets, and (d) allow testing of new treatment strategies first in mice and then, if successful, in humans with AD. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Neuropathol, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Genet & Aging Lab, Boston, MA 02115 USA. RP Price, DL (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. EM dlprice@welchlink.welch.jhu.edu; tanzi@helix.mgh.harvard.edu; drbor@welchlink.welch.jhu.edu; ssisodia@drugs.bsd.uchicago.edu FU NIA NIH HHS [AG 05146, AG 08325]; NINDS NIH HHS [NS 20471] NR 226 TC 296 Z9 314 U1 6 U2 23 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1998 VL 32 BP 461 EP 493 DI 10.1146/annurev.genet.32.1.461 PG 33 WC Genetics & Heredity SC Genetics & Heredity GA 160GU UT WOS:000078222700017 PM 9928488 ER PT J AU Auchincloss, H Sachs, DH AF Auchincloss, H Sachs, DH TI Xenogeneic transplantation SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE xenotransplants; humoral antibody rejection; tolerance; accommodation; pigs; hyperacute rejection ID PORCINE ENDOTHELIAL-CELLS; HUMAN T-CELLS; DECAY-ACCELERATING FACTOR; NATURAL-KILLER-CELLS; BONE-MARROW TRANSPLANTATION; HUMORAL IMMUNE-RESPONSE; RAT CARDIAC XENOGRAFTS; LONG-TERM SURVIVAL; NONLETHAL PREPARATIVE REGIMEN; COMPLEMENT-MEDIATED INJURY AB This review summarizes the clinical history and rationale for xenotransplantation; recent progress in understanding the physiologic, immunologic, and infectious obstacles to the procedure's success; and some of the strategies being pursued to overcome these obstacles. The problems of xenotransplantation are complex, and a combination of approaches is required. The earliest and most striking immunologic obstacle, that of hyperacute rejection, appears to be the closest to being solved. This phenomenon depends on the binding of natural antibody to the vascular endothelium, fixation of complement by that antibody, and finally, activation of the endothelium and initiation of coagulation. Therefore, these three pathways have been targeted as sites for intervention in the process. The mechanisms responsible for the next immunologic barrier, that of delayed xenograft/acute vascular rejection, remain to be fully elucidated. They probably also involve multiple pathways, including antibody and/or immune cell binding and endothelial cell activation. The final immunologic barrier, that of the cellular immune response, involves mechanisms that are similar to those involved in allograft rejection. However, the strength of the cellular immune response to xenografts is so great that it is unlikely to be controlled by the types of nonspecific immunosuppression used routinely to prevent allograft rejection. For this reason, it may be essential to induce specific immunologic unresponsiveness to at least some of the most antigenic xenogeneic molecules. C1 Massachusetts Gen Hosp, Surg Serv, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplant Unit, Boston, MA 02114 USA. NR 202 TC 344 Z9 348 U1 1 U2 17 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1998 VL 16 BP 433 EP 470 DI 10.1146/annurev.immunol.16.1.433 PG 38 WC Immunology SC Immunology GA ZH616 UT WOS:000073129400016 PM 9597137 ER PT J AU Tsai, GC Coyle, JT AF Tsai, GC Coyle, JT TI The role of glutamatergic neurotransmission in the pathophysiology of alcoholism SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE ethanol; excitotoxicity; glutamate; N-methyl-D-aspartate ID PRENATAL ETHANOL EXPOSURE; EXCITATORY AMINO-ACIDS; D-ASPARTATE RECEPTOR; EVOKED ELECTROPHYSIOLOGICAL ACTIVITY; ACTIVATED ION CURRENT; RAT STRIATAL SLICES; NMDA RECEPTORS; EXTRACELLULAR GLUTAMATE; HIPPOCAMPAL-NEURONS; WITHDRAWAL SEIZURES AB Recent evidence suggests that ethanol abuse produces its diverse effects on the brain to a substantial degree by disrupting the function of the major excitatory neurotransmitter, glutamate. Ethanol, at concentrations associated with behavioral effects in humans, inhibits the N-methyl-D-aspartate (NMDA) receptor, which mediates the post-synaptic excitatory effects of glutamate. Tolerance to ethanol results in up-regulation of the NMDA receptor so that abrupt withdrawal produces a hyperexcitable state that leads to seizures, delerium tremens, and excitotoxic neuronal death. Ethanol's inhibition of the NMDA receptor in the fetal brain likely contributes to the CNS manifestations of fetal alcohol syndrome. Therapeutic strategies aimed at correcting glutamatergic dysregulation in alcoholism need to be explored. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Tsai, GC (reprint author), Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Belmont, MA 02178 USA. EM tsaig@helix.mgh.harvard.edu; jcoyle@warren.med.harvard.edu NR 63 TC 248 Z9 252 U1 2 U2 13 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1998 VL 49 BP 173 EP 184 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA ZG853 UT WOS:000073046600012 PM 9509257 ER PT J AU Goodyear, LJ Kahn, BB AF Goodyear, LJ Kahn, BB TI Exercise, glucose transport, and insulin sensitivity SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE skeletal muscle; GLUT4; diabetes; insulin resistance; physical training ID RAT SKELETAL-MUSCLE; DEPENDENT DIABETES-MELLITUS; OBESE ZUCKER RAT; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PROTEIN KINASE-C; MIDDLE-AGED MEN; PLASMA-MEMBRANE; INDUCED TRANSLOCATION; INDUCED INCREASE; RECEPTOR SUBSTRATE-1 AB Physical exercise can be an important adjunct in the treatment of both non-insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose transporters to the plasma membrane and transverse tubules. Exercise and insulin utilize different signaling pathways, both of which lead to the activation of glucose transport, which perhaps explains why humans with insulin resistance can increase muscle glucose transport in response to an acute bout of exercise. Exercise training in humans results in numerous beneficial adaptations in skeletal muscles, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin, although not all studies show that exercise training in patients with diabetes improves overall glucose control. However, there is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non-insulin-dependent diabetes mellitus. C1 Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Diabet Unit, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM GOODYEAL@JOSLAB.HARVARD.EDU; BKAHN@BIDMC.HARVARD.EDU FU NIAMS NIH HHS [AR-42238]; NIDDK NIH HHS [DK-43051] NR 167 TC 546 Z9 563 U1 16 U2 77 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1998 VL 49 BP 235 EP 261 PG 27 WC Medicine, General & Internal SC General & Internal Medicine GA ZG853 UT WOS:000073046600016 PM 9509261 ER PT J AU Ellisen, LW Haber, DA AF Ellisen, LW Haber, DA TI Hereditary breast cancer SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE BRCA1; BRCA2; breast cancer; genetic predisposition ID LINE P53 MUTATIONS; OVARIAN-CANCER; BRCA2 MUTATIONS; TRANSCRIPTIONAL ACTIVATION; ATAXIA-TELANGIECTASIA; FAMILIAL BREAST; JEWISH WOMEN; GENE BRCA1; DIFFERENTIATION; PROLIFERATION AB Genetic predisposition is responsible for 5-10% of all breast cancer, and a much larger percent of early-onset disease. Within the past few years, a number of genes associated with a high risk of breast cancer have been identified, including BRCA1, BRCA2, p53, and the Cowden disease gene PTEN/MMAC1. These genes appear to function as tumor suppressors, and although their mutation frequency in the general population is low, certain populations have a carrier frequency of up to 1% for particular BRCA1 and BRCA2 mutations. The isolation of these genes is likely to provide important insight into the pathogenesis of human cancer. The clinical application of these mo lecular discoveries raises controversial issues regarding presymptomatic testing for patients suspected of harboring cancer predisposing mutations. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu NR 54 TC 44 Z9 49 U1 0 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1998 VL 49 BP 425 EP 436 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA ZG853 UT WOS:000073046600028 PM 9509273 ER PT J AU Daniel, PB Walker, WH Habener, JF AF Daniel, PB Walker, WH Habener, JF TI Cyclic AMP signaling and gene regulation SO ANNUAL REVIEW OF NUTRITION LA English DT Review DE cAMP response element binding protein; cAMP response element modulator; nuclear factor kappa B; nuclear factors; spermatogenesis ID DEPENDENT PROTEIN-KINASE; ELEMENT-BINDING-PROTEIN; NF-KAPPA-B; TRANSCRIPTION FACTOR CREB; CAMP-RESPONSIVE-ELEMENT; ADENOSINE-MONOPHOSPHATE CAMP; THYROID-STIMULATING HORMONE; LONG-TERM DESENSITIZATION; ACETYL-COA CARBOXYLASE; A-PHOSPHORYLATED CREB AB Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger produced in cells in response to hormones and nutrients. The production of cAMP is dependent upon the actions of many different proteins that affect its synthesis and degradation. An important function of cAMP is to activate the phosphorylating enzyme, protein kinase A. The key roles of cAMP and protein kinase A in the phosphorylation and regulation of enzyme substrates involved in intermediary metabolism are well known. A newly discovered role for protein kinase A is in the phosphorylation and activation of transcription factors that are critical for the control of the transcription of genes in response to elevated levels of cAMP. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Daniel, PB (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. EM habenerj@a1.mgh.harvard.edu NR 242 TC 179 Z9 185 U1 2 U2 6 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 1998 VL 18 BP 353 EP 383 DI 10.1146/annurev.nutr.18.1.353 PG 31 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 106YR UT WOS:000075179500016 PM 9706229 ER PT J AU Sorensen, G Emmons, K Hunt, MK Johnston, D AF Sorensen, G Emmons, K Hunt, MK Johnston, D TI Implications of the results of community intervention trials SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE behavioral risk factor interventions; cardiovascular disease prevention; cancer prevention; community intervention research; worksite intervention research; school-based intervention research ID HEART-HEALTH-PROGRAM; STANFORD 5-CITY PROJECT; SMOKING PREVENTION PROGRAMS; ADOLESCENT DRUG-ABUSE; DISEASE RISK-FACTORS; WORKING WELL TRIAL; LONG-TERM OUTCOMES; PROMOTION PROGRAMS; SOCIOECONOMIC-STATUS; CANCER CONTROL AB This paper examines the results of population-level interventions conducted in three settings: entire communities, worksites, and schools. Four major conclusions ale discussed: (a) Directions for the next generation of community-based interventions include targeting multiple levels of influence; addressing social inequalities in disease risk; involving communities in program planning and implementation; incorporating approaches for "tailoring" interventions; and utilizing rigorous process evaluation. (b)In addition to randomized controlled trials, it is time to use the full range of research phases available, from hypothesis generation and methods development to dissemination research. (c) The public health research agenda may have contributed to observed secular trends by placing behavioral risk factors on the social and media agendas. (d) The magnitude of the results of community intervention trials must be judged according to their potential public health or population-level effects. Small changes at the individual level may result in large benefits at the population level. 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. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM Glorian-Sorensen@dfci.harvard.edu; Karen-Emmons@dfci.harvard.edu; Mary_Kay_Hunt@dfci.harvard.edu FU NCI NIH HHS [R01 CA 68087, R01 CA 59728] NR 227 TC 190 Z9 192 U1 5 U2 21 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1998 VL 19 BP 379 EP 416 DI 10.1146/annurev.publhealth.19.1.379 PG 38 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZN554 UT WOS:000073657500017 PM 9611625 ER PT J AU Fournier, B Hooper, DC AF Fournier, B Hooper, DC TI Mutations in topoisomerase IV and DNA gyrase of Staphylococcus aureus: Novel pleiotropic effects an quinolone and coumarin activity SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; RESISTANCE MUTATIONS; FLUOROQUINOLONE RESISTANCE; NOVOBIOCIN RESISTANCE; PRIMARY TARGET; GYRB GENE; B-PROTEIN; CIPROFLOXACIN; CLONING AB Previous studies have shown that topoisomerase IV and DNA gyrase interact with quinolones and coumarins in different ways. The MICs of coumarins (novobiocin and coumermycin) for MT5, a Staphylococcus aureus nov mutant, are higher than those for wild-type strains. Sequencing the gyrB gene encoding one subunit of the DNA gyrase revealed the presence of a double mutation likely to be responsible for this resistance: at codon 102 (Ile to Ser) and at codon 144 (Arg to Ile). For single-step flqA mutant MT5224c9, previously selected on ciprofloxacin, the fluoroquinolone MTC was higher and the coumarin MIC was lower than those for its parent, MT5. Sequencing the grlB and grlA genes of topoisomerase IV of MT5224c9 showed a single Asn-470-to-Asp mutation in GrlB. Genetic outcrosses by. transformation with chromosomal DNA and introduction of plasmids carrying either the wild-type or the mutated grlB gene indicated that this mutation causes both increased MICs of fluoroquinolones and decreased MICs of coumarins and that the mutant grlB allele is codominant for both phenotypes with multicopy alleles. Integration of these plasmids into the chromosome confirmed the codominance of fluoroquinolone resistance, but grlB(+) appeared dominant over grlB (Asp-470) for coumarin resistance. Finally, the gyrA (Leu-84) mutation previously described as silent for fluoroquinolone resistance increased the MIC of nalidixic acid, a nonfluorinated quinolone. Combining the grlA (Phe-80) and grlB (Asp-47O) mutations with this gyrA mutation also had differing effects. The findings indicate that alterations in topoisomerases may have pleiotropic effects on different classes of inhibitors as well as on inhibitors within the same class. A full understanding of drug action and resistance at the molecular level must take into account both inhibitor structure-activity relationships and the effects of different classes of topoisomerase mutants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI023988, R37 AI023988, AI23988] NR 42 TC 82 Z9 86 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1998 VL 42 IS 1 BP 121 EP 128 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YP659 UT WOS:000071301100019 PM 9449271 ER PT J AU Graybill, JR Najvar, LK Fothergill, A Hardin, T Rinaldi, M Lambros, C Regen, SL AF Graybill, JR Najvar, LK Fothergill, A Hardin, T Rinaldi, M Lambros, C Regen, SL TI KY-62, a polyene analog of amphotericin B, for treatment of murine candidiasis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID METHYL-ESTER; LEUKOENCEPHALOPATHY; CELLS AB KY-62 is a water-soluble analog of amphotericin B. In vitro testing of five clinical isolates of Candida albicans showed KY-62 to have potency similar to that of amphotericin B. KY-62 was administered to mice infected intravenously with C. albicans. In vivo, KY-62 was effective in immunocompetent mice, with potency similar to that of amphotericin B. KY-62 was well tolerated up to 30 mg/kg of body weight per dose, an amount that would be lethal with amphotericin B. KY-62 was less effective in mice rendered neutropenic with 5-fluorouracil. The addition of flucytosine had little effect. KY-62 may have potential for clinical development. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S TExas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Lehigh Univ, Bethlehem, PA 18015 USA. NIAID, Bethesda, MD 20892 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIAID NIH HHS [N01-AI-25141] NR 25 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1998 VL 42 IS 1 BP 147 EP 150 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YP659 UT WOS:000071301100023 PM 9449275 ER PT J AU Graybill, JR Najvar, LK Montalbo, EM Barchiesi, FJ Luther, MF Rinaldi, MG AF Graybill, JR Najvar, LK Montalbo, EM Barchiesi, FJ Luther, MF Rinaldi, MG TI Treatment of histoplasmosis with MK-991 (L-743,872) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CANDIDA-ALBICANS; ANTIFUNGAL AGENT; AMPHOTERICIN-B; CELL-WALL; PNEUMOCANDIN; FLUCONAZOLE; ITRACONAZOLE; PREVENTION; L-733560 AB BALB/c nu/+ immunocompetent and athymic (nu/nu) mice were infected intravenously with yeast cells of Histoplasma capsulatum. Mice were either given water (controls) intraperitoneally (i.p.) or given MK-991 i.p. once daily or twice daily. Protection was measured as prolonged survival or reduction in tissue counts, MK-991 was protective in immunocompetent mice, prolonging survival and reducing counts in spleen and livers at a dose as low as 0.05 mg/kg of body weight/day. MK-991 was modestly effective in athymic mice at a higher dose, 5 mg/kg/day. These studies suggest that MK-991 may be appropriate for clinical development in histoplasmosis. C1 S Texas Vet Hlth Care Syst, Audie Murphy Div 111F, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), S Texas Vet Hlth Care Syst, Audie Murphy Div 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 19 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1998 VL 42 IS 1 BP 151 EP 153 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA YP659 UT WOS:000071301100024 PM 9449276 ER PT J AU Koziel, MJ AF Koziel, MJ TI The immunopathogenesis of HBV infection SO ANTIVIRAL THERAPY LA English DT Article ID HEPATITIS-B VIRUS; CYTOTOXIC T-LYMPHOCYTE; CHRONIC ACTIVE HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMORAL IMMUNE-RESPONSE; DNA-BASED IMMUNIZATION; ACUTE VIRAL-HEPATITIS; CLASS-I MOLECULES; TRANSGENIC MICE; NUCLEOCAPSID ANTIGEN AB Clinical manifestations of hepatitis B virus (HBV) infection are a balance between viral and host factors. The immune response against any virus consists of a coordinated defence of innate immunity and acquired, virus-specific immunity. In acute HBV, immune responses associated with recovery include vigorous, polyclonal CD4 T cells directed against multiple epitopes within HBV; antibodies directed againstsurface envelope proteins (anti-HBs), the development of which requires the presence of a CD4 response; and HBV-specific cytotoxic T lymphocytes (CTLs). HBV-specific CTLs can induce death of infected hepatocytes as well as produce cytokines. Most individuals with acute HBV recover without evidence of massive liver destruction; this, plus evidence from transgenic animal models, suggests that these cytokines produced by T cells play an important role in controlling HBV replication. Individuals who fail to mount a vigorous response in acute HBV develop chronic infection. In these cases, the persisting ineffective immune response appears to be responsible for liver damage and is likely to initiate the process of hepatic fibrosis. Based on our current understanding of the immune response in acute and chronic HBV, several groups are investigating the prospect of manipulating the immune response in chronic HBV. C1 Harvard Univ, Inst Med, Beth Israel Deaconness Med Ctr, Boston, MA 02115 USA. RP Koziel, MJ (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconness Med Ctr, Boston, MA 02115 USA. NR 101 TC 23 Z9 26 U1 0 U2 2 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 1998 VL 3 SU 3 BP 13 EP 24 PG 12 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 143QP UT WOS:000077267900003 PM 10726052 ER PT J AU Haubrich, R Lalezari, J Follansbee, SE Gill, MJ Hirsch, M Richman, D Mildvan, D Burger, HU Beattie, D Donatacci, L Salgo, MP AF Haubrich, R Lalezari, J Follansbee, SE Gill, MJ Hirsch, M Richman, D Mildvan, D Burger, HU Beattie, D Donatacci, L Salgo, MP CA NV14256 Study Team TI Improved survival and reduced clinical progression in HIV-infected patients with advanced disease treated with saquinavir plus zalcitabine SO ANTIVIRAL THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 CELL COUNTS; CUBIC MILLIMETER; CONTROLLED TRIAL; ANTIRETROVIRAL THERAPY; CONTINUED ZIDOVUDINE; COMBINATION THERAPY; DOUBLE-BLIND; RO 31-8959; VIRAL LOAD AB The objective of this randomized, double-blind, controlled multicentre study was to evaluate the efficacy of saquinavir alone or in combination with zalcitabine compared to zalcitabine monotherapy in reducing progression of human immunodeficiency virus (HIV) disease. Nine hundred and forty HIV-infected patients with more than 16 weeks of prior zidovudine therapy and pre-study entry CD4 cell counts between 50 and 300 cells/mm(3) were randomized to saquinavir 600 mg every 8 h, zalcitabine 0.75 mg every 8 h or the combination of both drugs. In an intent-to-treat analysis, the treatment arms were balanced with respect to demographics, baseline HIV RNA (mean 5.0 log(10) copies/ml) and CD4 lymphocyte count (mean 170 cells/mm(3)). More patients in the zalcitabine arm stopped therapy because of toxicity than in the other two arms (25% versus 16%; P=0.005). Peripheral neuropathy was the most common treatment-limiting toxicity. Fifty-one patients in the saquinavir plus zalcitabine group developed an AIDS-defining event or died compared to 84 and 88 in the saquinavir and zalcitabine monotherapy groups respectively; Combination treatment with saquinavir plus zalcitabine reduced the risk of progression to AIDS by 49% (95% confidence interval 0.36 to 0.72, P=0.0001) and reduced death by 68% (95% confidence interval 0.16 to 0.64, P=0.001) compared to zalcitabine monotherapy. The addition of saquinavir to zalcitabine resulted in a significant reduction in progression to AIDS or death compared with zalcitabine alone. C1 Univ Calif San Diego, Treatment Ctr, Dept Med, San Diego, CA 92103 USA. Univ Calif San Francisco, Mt Zion Hosp, San Francisco, CA 94143 USA. Davies Med Ctr, San Francisco, CA USA. Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. Beth Israel Med Ctr, New York, NY 10003 USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Roche Prod Ltd, Welwyn Garden City, Herts, England. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Haubrich, R (reprint author), Univ Calif San Diego, Treatment Ctr, Dept Med, 2760 5th Ave,Suite 300, San Diego, CA 92103 USA. EM rhaubrich@ucsd.edu RI Gill, John/G-7083-2016 OI Gill, John/0000-0002-8546-8790 NR 32 TC 16 Z9 16 U1 0 U2 1 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 1998 VL 3 IS 1 BP 33 EP 42 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 111XB UT WOS:000075462800005 ER PT J AU D'Amato, RM D'Aquila, RT Wein, LM AF D'Amato, RM D'Aquila, RT Wein, LM TI Management of antiretroviral therapy for HIV infection: modelling when to change therapy SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; IN-VIVO; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITOR; TYPE-1 RNA; PLASMA; ZIDOVUDINE; RESISTANCE; INDINAVIR; MUTATIONS AB Objective: To evaluate four strategies for monitoring plasma HIV RNA levels and/or resistance genotypes to decide when to change antiretroviral therapy. The strategies include: (i) 1997 guidelines recommending a therapy switch when plasma RNA exceeds a threshold level; (ii) a viral load policy, using a fixed increase in viral load as the trigger; (iii) a genotype policy, requiring a smaller viral rebound than (ii) and detection of genotypic resistance before switching; and (iv) a proactive policy, switching drug regimens at a predetermined time if viral load has not rebounded. Design and setting: A Monte Carlo simulation tracks patients' viral loads and presence of opportunistic infection during therapy. The model uses clinical and virological data and statistical variation in patient parameters for the evaluation of therapeutic strategies. Main outcome measures: To determine which strategies minimize viral rebound detection delay while maintaining a low (prespecified) probability of switching therapy before rebound. Results: 1997 Guidelines and the viral load policy create lengthy delays in detection of rebound, particularly when patients are drug-naive and the detection limit of the viral load assay is 500 copies/ml. A detection limit of 20 copies/ml decreases this delay substantially. Genotyping achieves only minor additional delay reductions. Of the strategies tested, the proactive policy leads to the shortest delays. Conclusions: This model indicates that prolonged periods may be required for Viral load to rebound to detectable levels following prolonged suppression. Proactive switching produces the best outcome in our model because it may reduce the duration of viral replication under pressure of a failing regimen before detection of viral rebound. This strategy should be evaluated in clinical trials. C1 MIT, Ctr Operat Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr AIDS Res, Charlestown, MA USA. MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA. RP D'Aquila, RT (reprint author), Rand Corp, Santa Monica, CA 90407 USA. EM daquila@helix.mgh.harvard.edu FU NIAID NIH HHS [AI29193] NR 46 TC 19 Z9 19 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 1998 VL 3 IS 3 BP 147 EP 158 PG 12 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 134DW UT WOS:000076728500003 PM 10682132 ER PT J AU Krueger, GG Drake, LA Elias, PM Lowe, NJ Guzzo, C Weinstein, GD Lew-Kaya, DA Lue, JC Sefton, J Chandraratna, RAS AF Krueger, GG Drake, LA Elias, PM Lowe, NJ Guzzo, C Weinstein, GD Lew-Kaya, DA Lue, JC Sefton, J Chandraratna, RAS TI The safety and efficacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Meeting of the European-Academy-of-Dermatology-and-Venereology CY 1996 CL LISBON, PORTUGAL SP European Acad Dermatol & Venereol AB Objective: To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques. Design: Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study. Setting: Medical center outpatient dermatology services. Participants: One hundred fifty-three adults with 2 bilateral target plaques on the hunk, legs, or arms. Interventions: Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B). Main Outcome Measures: Treatment success and plaque elevation, scaling, and erythema vs time. Results: The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as I week. Treatment success rates (defined as >75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P<.05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily. Conclusion: The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment. C1 Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Univ Utah, Hlth Sci Ctr, Dept Dermatol, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Ft Mimley Vet Adm Hosp, Dermatol Serv, San Francisco, CA USA. Skin Res Fdn Calif, Santa Monica, CA 90034 USA. RP Lew-Kaya, DA (reprint author), Allergan Pharmaceut Inc, 2525 Dupont Dr, Irvine, CA 92715 USA. NR 6 TC 39 Z9 40 U1 0 U2 2 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 JAN PY 1998 VL 134 IS 1 BP 57 EP 60 DI 10.1001/archderm.134.1.57 PG 4 WC Dermatology SC Dermatology GA YR333 UT WOS:000071484900008 PM 9449910 ER PT J AU Uthman, BM Rowan, AJ Ahmann, PA Leppik, IE Schachter, SC Sommerville, KW Shu, V AF Uthman, BM Rowan, AJ Ahmann, PA Leppik, IE Schachter, SC Sommerville, KW Shu, V TI Tiagabine for complex partial seizures - A randomized, add-on, dose-response trial SO ARCHIVES OF NEUROLOGY LA English DT Article ID UPTAKE INHIBITOR; PHARMACOKINETICS AB Objective: To determine the efficacy and tolerability of tiagabine, a new antiepileptic drug(AED) that inhibits gamma-aminobutyric acid (GABA) uptake, at 3 dose levels vs placebo as adjunctive therapy in patients with intractable complex partial seizures (CPS). Design: Randomized, double-blind, placebo-controlled study with a parallel-group, add-on design, starting with a 12-week unblinded baseline phase followed by a 20-week double-blind treatment phase. Setting: Twenty-one US medical centers. Patients: Patients (N = 297) aged 12 to 77 years, previously diagnosed as having CPS and receiving stable regimens of 1 to 3 hepatic enzyme-inducing AEDs; dival-proex sodium or valproic acid was allowed in combination with any of these drugs. Interventions: Placebo or tiagabine 4 times a day at 16, 32, or 56 mg daily. Main Outcome Measures: Median change in 4-week CPS frequency and adverse events. Results: Median decreases in if-week CPS frequency for the 32-mg (-2.2) and 56-mg (-2.8) tiagabine groups were significantly greater than for the placebo (-0.7) group (P = .03 and P < .03, respectively); 20% and 29% of patients in the 32- and 56-mg groups had a 50% or greater reduction in the frequency of CPS vs 4% in the placebo group (P = .002 and P < .001, respectively). Adverse effects were similar for placebo and tiagabine except for a significantly greater incidence of dizziness in the 32-mg tiagabine group, tremor in the 32- and 56-mg groups, abnormal thinking (usually mental lethargy or difficulty concentrating) in the SG-mg group, and depressed mood in the 16- and 56-mg groups. Conclusions: Tiagabine is efficacious and well tolerated as adjunctive therapy for CPS; there is a clear dose-response relationship. C1 Vet Affairs Med Ctr, Neurol Serv 127, Gainesville, FL 32608 USA. Univ Florida, Coll Med, Dept Neurol, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Inst Brain, Gainesville, FL USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. Marschfield Clin, Marshfield, WI USA. MINCEP Epilepsy Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN 55455 USA. Beth Israel Hosp, Boston, MA 02215 USA. Abbott Labs, N Chicago, IL 60064 USA. RP Uthman, BM (reprint author), Vet Affairs Med Ctr, Neurol Serv 127, 1601 SW Archer Rd, Gainesville, FL 32608 USA. NR 11 TC 114 Z9 115 U1 0 U2 2 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 JAN PY 1998 VL 55 IS 1 BP 56 EP 62 DI 10.1001/archneur.55.1.56 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA YR191 UT WOS:000071469900006 PM 9443711 ER PT J AU To, KW Adamian, M Jakobiec, FA Berson, EL AF To, KW Adamian, M Jakobiec, FA Berson, EL TI Histopathologic and immunohistochemical study of an autopsy eye with X-linked cone degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 21-26, 1996 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID DYSTROPHY; CARRIERS AB We performed a histopathologic and immunohistochemical study of eyes obtained at autopsy of an 84-year-old man from a family with X-linked cone degeneration in which affected members have a 6.5-kilobase deletion in the red cone pigment gene. At his most recent ocular examination, at age 71 years, this patient had had a visual acuity of 20/200 OU, fundus changes suggestive of macular degeneration, borderline-normal full-field rod electroretinograms, and profoundly reduced full-field cone electroretinograms. Histopathologic examination demonstrated marked loss of cone and rod photoreceptors and the retinal pigment epithelium in the central macula. The peripheral cone population was reduced, while the peripheral rod population was relatively preserved, Immunohistochemical examination with an antibody to both red and green cone opsin and an antibody to blue cone opsin disclosed a prominent loss of the red and green cone population and preservation of the blue cone population. These findings show that a defect in the red cone pigment gene can result in extensive degeneration of the red and green cone population across the retina. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Pathol Serv, Boston, MA 02114 USA. RP To, KW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. NR 6 TC 9 Z9 9 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 JAN PY 1998 VL 116 IS 1 BP 100 EP 103 PG 4 WC Ophthalmology SC Ophthalmology GA YR341 UT WOS:000071485700017 PM 9445217 ER PT J AU Cunningham, MJ Eavey, RD Vlahakes, GJ Grillo, HC AF Cunningham, MJ Eavey, RD Vlahakes, GJ Grillo, HC TI Slide tracheoplasty for long-segment tracheal stenosis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 14-16, 1997 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediat Otolaryngol ID PERICARDIAL PATCH; CHILDREN; MANAGEMENT; ANASTOMOSIS; RESECTION; INFANTS; GROWTH AB Objective: To introduce a novel surgical technique for the repair of congenital long-segment tracheal stenosis. Design: Retrospective case series. Setting: Tertiary-care hospital. Patients: Three children ranging in age from 3 months to 3 years, all with complete tracheal rings, the stenotic segments representing between 36% and 49% of the total tracheal length. One patient had an anomalous right upper lobe bronchus and an associated pulmonary artery sling. Intervention: Slide tracheoplasty reconstruction. Main Outcome Measure(s): Postoperative clinical status as evidenced by day and site of extubation, duration of hospitalization, number of bronchoscopic examinations performed before discharge, and subsequent need for urgent bronchoscopic examinations, which reflects the adequacy of the reconstructed airway. Results: Two patients were extubated on the day of surgery, 1 intraoperatively; the child with the pulmonary artery sling required 3 days of elective intubation for postoperative ventilatory support. The duration of hospitalization ranged from 8 to 10 days. All patients underwent elective bronchoscopy once before discharge; none had granuloma formation. Follow-up ranged from 1 to 4 1/2 years. One patient required a single urgent bronchoscopic examination in addition to planned surveillance endoscopy. Growth of the reconstructed hemitracheal rings is demonstrable. Conclusions: Slide tracheoplasty achieves successful tracheal reconstruction using the patient's own tracheal tissues. Advantages of this method include the potential avoidance of cardiopulmonary bypass, immediate or early postoperative extubation, and the near-complete absence of granulation tissue formation. The latter obviates the need for multiple postoperative bronchoscopic examinations, as has been reported in tracheoplasty procedures using either costal cartilage or pericardium. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Thorac Surg Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Cardiac Surg Unit, Boston, MA USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 20 Z9 22 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 JAN PY 1998 VL 124 IS 1 BP 98 EP 103 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA YQ721 UT WOS:000071416600017 PM 9440789 ER PT J AU Compton, C Sobin, LH AF Compton, C Sobin, LH CA Coll Amer Pathologists Task Force Protocols Examination Specimens Pat TI Protocol for the examination of specimens removed from patients with gastric carcinoma - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MULTIVARIATE-ANALYSIS; PROGNOSTIC FACTORS; CANCER PATIENTS; SURVIVAL; UNIVARIATE; STOMACH; ADENOCARCINOMA; CLASSIFICATION; INVOLVEMENT; SURGERY AB A protocol for the pathologic examination and reporting of specimens from patients with gastric carcinoma has been developed by the Cancer Committee of the College of American Pathologists and a multidisciplinary task force of specialists dealing with patients with gastric carcinoma. The protocol incorporates all basic pathology data of diagnostic and prognostic significance appropriate for the treatment of patients with gastric carcinoma. The purpose of the protocol is to serve as a basis for the development of checklists, as on outline for full narrative reporting, as a basis for research protocols, or as a guide for other types of synoptic or reporting formats. The protocol is stratified to accommodate the surgical procedures usually employed for gastric carcinomas, including acquisition of cytologic specimens, incisional endoscopic biopsy, excisional biopsy, and gastric resection (partial or complete). Explanatory notes detailing specific procedures and rationales for documentation of specific pathologic data are included in the protocol. The protocol uses the staging system for gastric carcinoma defined by the American Joint Committee on Cancer and the International Union Against Cancer. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Armed Forces Inst Pathol, Div Gastrointestinal Pathol, Washington, DC 20306 USA. RP Compton, C (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,35 Fruit St, Boston, MA 02114 USA. NR 39 TC 13 Z9 17 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1998 VL 122 IS 1 BP 9 EP 14 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YR466 UT WOS:000071498100001 PM 9448011 ER PT J AU Passaro, E Howard, TJ Sawicki, MP Watt, PC Stabile, BE AF Passaro, E Howard, TJ Sawicki, MP Watt, PC Stabile, BE TI The origin of sporadic gastrinomas within the gastrinoma triangle - A theory SO ARCHIVES OF SURGERY LA English DT Article ID LYMPH-NODES; CELLS AB Sporadic gastrinomas are found predominantly within the gastrinoma triangle (85%), frequently within lymph nodes in the triangle (40%) and often multiple (40%). In addition, they are homologous with pancreatic polypeptidomas and express pancreatic polypeptide. We hypothesized that, if gastrinomas were of ventral pancreatic bud origin, several (7) predictions could be made. The data from the investigation of these predictions have supported the theory. We postulate that sporadic gastrinomas in the triangle arise from stem cells from the ventral pancreatic bud that become dispersed and incorporated into lymph tissue and the duodenal wall during the ventral bud's embryonic dorsal rotation within the area of the triangle. C1 W Los Angeles Vet Affairs Med Ctr, Surg Serv, Los Angeles, CA 90073 USA. Richard L Roudebush Vet Affairs Med Ctr, Los Angeles, CA USA. Harbor Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA USA. RP Passaro, E (reprint author), W Los Angeles Vet Affairs Med Ctr, Surg Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 13 TC 24 Z9 24 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JAN PY 1998 VL 133 IS 1 BP 13 EP 16 DI 10.1001/archsurg.133.1.13 PG 4 WC Surgery SC Surgery GA YQ717 UT WOS:000071416200002 PM 9438752 ER PT J AU Majde, JA Guha-Thakurta, N Chen, Z Bredow, S Krueger, JM AF Majde, JA Guha-Thakurta, N Chen, Z Bredow, S Krueger, JM TI Spontaneous release of stable viral double-stranded RNA into the extracellular medium by influenza virus-infected MDCK epithelial cells: implications for the viral acute phase response SO ARCHIVES OF VIROLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; A VIRUS; INTERFERON; ALPHA; ACTIVATION; CYTOKINES; IFN AB The viral factor responsible for triggering the acute phase response, or 'flu' syndrome, associated with many acute viral infections is not defined. One candidate viral factor is double-stranded RNA (dsRNA) generated during viral replication. In this report we demonstrate by reverse-transcriptase polymerase-chain reaction that nuclease-stable viral RNA was released from influenza-infected MDCK epithelial cells at the time of cell lysis. Removal of virion-associated RNA by ultracentrifugation left equal amounts of positive-and negative-strand viral RNA in the medium that resisted degradation by endogenous RNase in the medium and by exogenous RNase added prior to phenol extraction. These data are the first demonstration that viral RNA with characteristics of dsRNA is spontaneously released from dying influenza virus-infected cells, and thus is available to amplify cytokine induction and contribute to systemic disease. C1 Off Naval Res, Div Med Sci & Technol 341, Arlington, VA 22217 USA. Univ Tennessee, Sch Med, Dept Physiol & Biophys, Memphis, TN 38104 USA. Washington State Univ, Coll Vet Med, Dept Vet & Comparat Anat Pharmacol & Physiol, Pullman, WA 99164 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Majde, JA (reprint author), Off Naval Res, Div Med Sci & Technol 341, 800 N Quincy St, Arlington, VA 22217 USA. FU NICHD NIH HHS [HD36520] NR 23 TC 44 Z9 44 U1 0 U2 4 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1998 VL 143 IS 12 BP 2371 EP 2380 DI 10.1007/s007050050467 PG 10 WC Virology SC Virology GA 166PR UT WOS:000078586500008 PM 9930193 ER PT J AU Dunn, RB Walter, JS Lucero, Y Weaver, F Langbein, E Fehr, L Johnson, P Riedy, L AF Dunn, RB Walter, JS Lucero, Y Weaver, F Langbein, E Fehr, L Johnson, P Riedy, L TI Follow-up assessment of standing mobility device users SO ASSISTIVE TECHNOLOGY LA English DT Article DE spinal cord injury; standing wheelchair; standing frame ID SPINAL-CORD INJURIES; PARAPLEGIC PATIENTS; AMBULATION AB The use of standing devices by spinal cord-injured subjects was investigated through a national survey of a sample of individuals who returned their manufacturer's warranty card to two companies. We obtained a 32% response rate (99/310). The majority of respondents were male (87%) with a median age between 41 and 50 years. Seventy-seven percent were paraplegic and 21% were quadriplegic. Forty percent had between 1 and 5 years experience with their device, and 84% of those responding were currently using their standing device. Forty-one percent used their standing device one to six times a week; two-thirds stood between 30 minutes and 1 hour for each use. Less than 10% of subjects experienced any side effects, such as nausea or headaches, from standing. Twenty-one percent of subjects reported being able to empty their bladder more completely. There was also a favorable response by some individuals on the effects of the standing devices on bowel regularity, reduction of urinary tract infections, leg spasticity, and number of bed sores. Finally, 79% of subjects highly recommended use of standing devices to other people with spinal cord injury, The positive responses of individuals using standing devices is a strong recommendation for the assistive technology community to make these devices more available to individuals with spinal cord injury. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Rehabil Res & Dev Ctr, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Spinal Cord Injury Serv, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Loyola Med Ctr, Dept Internal Med, Maywood, IL USA. RP Dunn, RB (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv 151, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 28 TC 21 Z9 21 U1 0 U2 4 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. PY 1998 VL 10 IS 2 BP 84 EP 93 PG 10 WC Rehabilitation SC Rehabilitation GA 154JL UT WOS:000077885700003 PM 10339284 ER PT J AU Kunisaki, M Bursell, SE Umeda, F Nawata, H King, GL AF Kunisaki, Makoto Bursell, Sven-Erik Umeda, Fumio Nawata, Hajime King, George L. TI Prevention of diabetes-induced abnormal retinal blood flow by treatment with d-alpha-tocopherol SO BIOFACTORS LA English DT Article DE Vitamin E; protein kinase C; diacylglycerol; diabetes mellitus; retinal blood flow AB Hyperglycemia in diabetes mellitus has been shown to activate diacylglycerol (DAG)-protein kinase C (PKC) pathway in the vascular tissues, possibly altering vascular function. We have characterized the effects of vitamin E (d-alpha-tocopherol) on activation of PKC and DAG levels in retinal tissues of diabetic rats, and correlated its effects to retinal hemodynamics using video-based fluorescein angiography (VFA). Comparing streptozotocin-induced diabetic rats to controls, membranous PKC specific activities were increased by 71% (p < 0.05). Western blot analysis showed that the membranous PKC beta II isoform was significantly increased by 133 +/- 45% (p < 0.05). Intraperitoneal injection of d-alpha-tocopherol (40 mg/kg) every other day prevented the increases in membranous PKC specific activity and PKC beta II protein shown by immunoblots. Similar to PKC activities, total DAG levels were increased in the retina and were normalized by d-alpha-tocopherol treatment. Physiologically, abnormalities of retinal blood hemodynamics, as measured using VFA, which previously have been reported to be associated with increases of DAG and PKC levels in the diabetic rats, were prevented by d-alpha-tocopherol treatment in diabetic rats. The direct effect of d-alpha-tocopherol on total DAG and [H-3]-palmitate incorporation into DAG were also examined using cultured bovine retinal endothelial cells (REC). Exposure of REC to 22 mM glucose for three days increased total DAG and [H-3]-palmitate labeled DAG levels by 35 +/- 8% and 50 +/- 8%, respectively (p < 0.05). The presence of d-alpha-tocopherol (50 mu g/ml) prevented the increase of both total DAG and [H-3]-palmitate labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that the mechanism of the d-alpha-tocopherol's effect appears to be mediated by the normalization of the hyperglycemia-induced activation of the DAG-PKC pathway which leads to the normalization of abnormal retinal blood flow seen in diabetes mellitus. C1 [Kunisaki, Makoto; Umeda, Fumio; Nawata, Hajime] Kyushu Univ, Fac Med, Dept Internal Med 3, Fukuoka 812, Japan. [Kunisaki, Makoto; Bursell, Sven-Erik; King, George L.] Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Kunisaki, Makoto; Bursell, Sven-Erik; King, George L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Kunisaki, M (reprint author), Moji Rosai Hosp, Kitakyushu, Fukuoka 801, Japan. EM koma@ask.or.jp FU NIH [EY05110]; Diabetes and Endocrinology Research Center [DK36836]; Massachusetts Lion's Eye Research grant; Adler Foundation; Eisai Medical Research Foundation FX These studies were supported by NIH grant EY05110 (GLK), Diabetes and Endocrinology Research Center grant DK36836, in addition to the Massachusetts Lion's Eye Research grant. This fellowship was partially supported by the Adler Foundation and Eisai Medical Research Foundation. NR 42 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1998 VL 7 IS 1-2 BP 55 EP 67 DI 10.1002/biof.5520070109 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA V23MV UT WOS:000208347800008 PM 9523029 ER PT J AU Koya, D Haneda, M Kikkawa, R King, GL AF Koya, Daisuke Haneda, Masakazu Kikkawa, Ryuichi King, George L. TI d-alpha-tocopherol treatment prevents glomerular dysfunctions in diabetic rats through inhibition of protein kinase C-diacylglycerol pathway SO BIOFACTORS LA English DT Article DE Diabetic nephropathy; diacylglycerol; protein kinase C; glomerular filtration rate; albuminuria; diacylglycerol kinase AB Since diabetes now accounts for 35% of all new cases of end-stage renal disease in the United States, it is really important to prevent the onset of diabetic nephropathy. Activation of protein kinase C (PKC) is implicated to be one of the causal factors in the development of renal dysfunctions in diabetes. In this study, we have demonstrated that total diacylglycerol (DAG) contents and PKC activity in glomeruli were significantly increased in diabetic rats as compared to control rats, but intraperitoneal injection of d-alpha-tocopherol prevented these biochemical abnormalities in parallel with normalization of glomerular dysfunction such as increased glomerular filtration rate (GFR) in diabetic rats. Albuminuria in diabetic rats was also significantly increased as compared to control rats, whereas d-alpha-tocopherol treatment again ameriolated increased albuminuria in parallel with the inhibition of glomerular PKC activation by diabetes. Moreover, we have observed that the activity of DAG kinase, which metabolizes DAG to phosphatidic acid and acts as an attenuator for the DAG-PKC pathway, was enchanced by d-alpha-tocopherol treatment. These results suggest that the increase in the DAG-PKC pathway might play an important role for the development of glomerular dysfunctions in diabetes and d-alpha-tocopherol treatment could be helpful in diabetic nephropathy. C1 [King, George L.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [King, George L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [King, George L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Koya, Daisuke; Haneda, Masakazu; Kikkawa, Ryuichi] Shiga Univ Med Sci, Dept Med 3, Otsu, Shiga 52021, Japan. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Kingg@joslab.harvard.edu RI Koya, Daisuke /J-3257-2014 FU NIH [EY05110, DK36433]; Lions Eye Research Grant; Adler Foundation FX The authors thanks Ms. Joan C. Taylor for her assistance with this manuscript preparation. This study was supported by the grants: NIH EY05110, DK36433, Lions Eye Research Grant, and the Adler Foundation. NR 34 TC 30 Z9 34 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1998 VL 7 IS 1-2 BP 69 EP 76 DI 10.1002/biof.5520070110 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA V23MV UT WOS:000208347800009 PM 9523030 ER PT B AU Jain, RK AF Jain, RK BE Mihich, E Croce, C TI Tumor microcirculation - Role in delivery of molecular and cellular medicine SO BIOLOGY OF TUMORS LA English DT Proceedings Paper CT 9th Annual Pezcoller Symposium on the Biology of Tumors CY JUN 04-07, 1997 CL ROVERETO, ITALY SP Pezcoller Fdn, Bank Cassa Risparmio Trento Rovereto, Municipal, Provincial, & Regional Adm AB To reach cancer cells in a tumor, a blood-borne therapeutic molecule or cell must make its way into the tumor microcirculation and across the blood vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then integrate the resulting information in a unified theoretical. framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-45932-9 PY 1998 BP 319 EP 345 PG 27 WC Oncology; Genetics & Heredity; Immunology; Microbiology SC Oncology; Genetics & Heredity; Immunology; Microbiology GA BL93D UT WOS:000077190800023 ER PT J AU Parzen, M Lipsitz, SR Dear, KBG AF Parzen, M Lipsitz, SR Dear, KBG TI Does clustering affect the usual test statistics of no treatment effect in a randomized clinical trial? SO BIOMETRICAL JOURNAL LA English DT Article DE binary data; regression; two-sample t-test AB In many clinical trials, such as those undertaken by large cooperative cancer groups (CALGB, ECOG, SWOG, EORTC), patients are randomized to one of two treatments within an institution (a hospital or clinic), in such clinical trials, it has often occurred that outcomes of patients within institutions tend to be similar (correlated), due, possibly, to unmeasured variables such as quality of staff or quality of hospital equipment. We discuss when, in the presence of random hospital effects, the usual lest statistics for no treatment effect, which do not take these hospital effects into account, are (asymptotically) unbiased. C1 Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Newcastle, Newcastle, NSW 2308, Australia. NR 3 TC 14 Z9 14 U1 0 U2 6 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1998 VL 40 IS 4 BP 385 EP 402 DI 10.1002/(SICI)1521-4036(199808)40:4<385::AID-BIMJ385>3.3.CO;2-R PG 18 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 112VH UT WOS:000075515000001 ER PT J AU Burton, MP Schneider, BG Brown, R Escamilla-Ponce, N Gulley, ML AF Burton, MP Schneider, BG Brown, R Escamilla-Ponce, N Gulley, ML TI Comparison of histologic stains for use in PCR analysis of microdissected, paraffin-embedded tissues SO BIOTECHNIQUES LA English DT Article ID AMPLIFICATION AB We evaluated the effect of six different histologic stains on the productivity of PCR amplification of DNA isolated from paraffin-embedded tissue samples. The tissue was collected from glass slides by microdissection techniques, whereby tiny portions of tissue are visually identified through a microscope and selectively resected for subsequent DNA extraction and PCR amplification. We found that the success of PCR amplification depended on the type of histologic stain that was used to facilitate microscopic visualization of the undeparaffinized tissue section. The best results were obtained with methyl green and nuclear fast red, while Wright's stain yielded less PCR product. Two other stains, Evans blue and light-green SF yellowish (also known as the counterstain for geomori methenamine silver stain) yielded sufficient PCR products; however, their staining characteristics did not afford satisfactory visualization of nuclear chromatin to discriminate between benign and malignant cells. Our most significant finding was that a commonly used histologic stain, hematoxylin, failed to produce DNA templates that could be consistently amplified by PCR. In conclusion, it is prudent to avoid hematoxylin stains when preparing tissues as starting material for PCR. Among the remaining five strains that were evaluated, the best choice depends on the differential staining characteristics of the cells to be dissected. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Louisiana State Univ, Med Ctr, New Orleans, LA USA. RP Gulley, ML (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCI NIH HHS [R29 CA63308] NR 8 TC 59 Z9 65 U1 0 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 1998 VL 24 IS 1 BP 86 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ698 UT WOS:000071414300018 PM 9454959 ER PT S AU Fowler, AJ Toner, M AF Fowler, AJ Toner, M BE Diller, KR TI Prevention of hemolysis in rapidly frozen erythrocytes by using a laser pulse SO BIOTRANSPORT: HEAT AND MASS TRANSFER IN LIVING SYSTEMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Symposium on Heat and Mass Transfer in Biological and Medical Engineering (Biotransport 98) CY JUN 08-12, 1998 CL KUSADASI, TURKEY SP Int Ctr Heat & Mass Transfer, Univ Texas Austin, US Natl Sci Fdn ID EMBRYOS AB This paper reports on the successful recovery of rapidly frozen unprotected erythrocytes by vitrification of the intracellular solution with a laser pulse prior to thawing. Erythrocytes that were frozen at 10,000 degrees C/min exhibited 100% hemolysis when thawed unless they were first irradiated by a 7 ns, laser pulse that selectively targeted the intracellular ice so that it was melted and resolidified into a glass phase. Up to 80% of the cells treated in this way remained intact after thawing. Wright's staining confirmed a healthy cell morphology and the retention of hemoglobin in the laser treated cells. While it is well known that small amounts of intracellular ice can be tolerated by cells, the findings of this study are the first to indicate that intracellular ice may be innocuous even when formed in substantial quantities provided that crystal growth and coalescence can somehow be avoided during warming. C1 Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Ctr Engn, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Ctr Engn, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Fowler, AJ (reprint author), Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. NR 8 TC 13 Z9 13 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-172-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 858 BP 245 EP 252 DI 10.1111/j.1749-6632.1998.tb10158.x PG 8 WC Engineering, Biomedical; Multidisciplinary Sciences; Physiology SC Engineering; Science & Technology - Other Topics; Physiology GA BL74B UT WOS:000076515800024 PM 9917823 ER PT J AU Hallek, M Bergsagel, PL Anderson, KC AF Hallek, M Bergsagel, PL Anderson, KC TI Multiple myeloma: Increasing evidence for a multistep transformation process SO BLOOD LA English DT Review ID COLONY-STIMULATING FACTOR; SIGNAL TRANSDUCER GP130; PLASMA-CELL DYSCRASIAS; MARROW STROMAL CELLS; SOLUBLE INTERLEUKIN-6 RECEPTOR; TUMOR-SUPPRESSOR GENES; C-MYC GENE; TYROSINE-PHOSPHORYLATED PROTEIN; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHASE RESPONSE FACTOR/STAT3 C1 Univ Munich, Klinikum Innenstadt, Med Klin, D-80336 Munich, Germany. Cornell Univ, Coll Med, Ithaca, NY 14853 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Munich, Genzentrum, D-80336 Munich, Germany. Harvard Univ, Sch Med, Boston, MA USA. RP Hallek, M (reprint author), Univ Munich, Klinikum Innenstadt, Med Klin, Ziemssenstr 1, D-80336 Munich, Germany. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [K01 CA074265, K01 CA074265-03, K01 CA074265-05, K01 CA074265-04] NR 314 TC 564 Z9 576 U1 3 U2 33 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 3 EP 21 PG 19 WC Hematology SC Hematology GA YN358 UT WOS:000071160100002 PM 9414264 ER PT J AU David, D Bani, L Moreau, JL Demaison, C Sun, K Salvucci, O Nakarai, T de Montalembert, M Chouaib, S Joussemet, M Ritz, J Theze, J AF David, D Bani, L Moreau, JL Demaison, C Sun, K Salvucci, O Nakarai, T de Montalembert, M Chouaib, S Joussemet, M Ritz, J Theze, J TI Further analysis of interleukin-2 receptor subunit expression on the different human peripheral blood mononuclear cell subsets SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; GAMMA-CHAIN GENE; IL-2 RECEPTOR; T-CELL; HUMAN MONOCYTES; BETA-CHAIN; ALPHA-CHAIN; INTERFERON-GAMMA; ACTIVATION; GROWTH AB We have investigated the expression of the three components of the interleukin-2 receptor (IL-2R alpha, IL-2R beta, and IL-2R gamma) on the surface of the various peripheral blood mononuclear cell (PBMC) subsets by flow cytometry analysis. The PBMC were immediately isolated (ficoll) from blood collected on heparin as anticoagulant. The three IL-2R components are absent or only marginally detectable on CD4 T lymphocytes. No expression of the IL-2R chains is found for the B lymphocytes. In most donors, the three chains are not detectable on CD8 T lymphocytes, but for a few of them, IL-2R beta or IL-2R gamma are clearly expressed. CD56 high (IL-2R alpha(+)) and CD56 low (IL-2R alpha(-)) natural kilter (NK) cells express IL-2R beta, but not IL-2R gamma. IL-2R gamma is expressed by monocytes of all donors although with variable intensity. When blood is collected on other anticoagulants or when cells are isolated 1 day after collection, IL-2R alpha, IL-2R beta, and IL-2R gamma are largely expressed on the surface of most PBMC. This observation provides a possible explanation for divergent data previously reported on IL-2R expression. Finally. we show that IL-2R gamma, which is not detectable on the cell surface of lymphocytes, is nevertheless expressed and stored as an intracellular component. This result is in agreement with the constitutive expression of the IL-2R gamma gene and suggests a specific regulatory mechanism for IL-2R gamma membrane translocation. (C) 1998 by The American Society of Hematology. C1 Inst Pasteur, Dept Immunol, Unite Immunogenet Cellulaire, F-75724 Paris 15, France. Inst Gustave Roussy, Immunol Lab, Villejuif, France. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Hop Necker Enfants Malad, Site Transfus, Paris, France. Ctr Transfus Sanguine Jean Julliard, Clamart, France. RP Theze, J (reprint author), Inst Pasteur, Dept Immunol, Unite Immunogenet Cellulaire, 25 & 28 Rue Dr Roux, F-75724 Paris 15, France. RI Chouaib, Salem/F-7939-2016; Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 47 TC 42 Z9 43 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 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 165 EP 172 PG 8 WC Hematology SC Hematology GA YN358 UT WOS:000071160100019 PM 9414281 ER PT J AU Agematsu, K Nagumo, H Oguchi, Y Nakazawa, T Fukushima, K Yasui, K Ito, S Kobata, T Morimoto, C Komiyama, A AF Agematsu, K Nagumo, H Oguchi, Y Nakazawa, T Fukushima, K Yasui, K Ito, S Kobata, T Morimoto, C Komiyama, A TI Generation of plasma cells from peripheral blood memory B cells: Synergistic effect of interleukin-10 and CD27/CD70 interaction SO BLOOD LA English DT Article ID NERVE GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; DIFFERENTIATION; CD27; ACTIVATION; RECEPTOR; FAMILY; LIGAND; LYMPHOCYTES; ANTIGEN AB B cells can differentiate into the antibody-secreting cells, plasma cells, whereas the crucial signals that positively control the entry into the pathway to plasma cells have been unclear. Triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). Differentiation into plasma cells by a combination of IL-10 and CD70 transfectants occurred in CD27(+) B cells but not in CD27(-) B cells. Moreover, addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced differentiation into plasma cells. In the presence of only IL-2, IL-4, or IL-6, CD70 transfectants did not promote differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B-cell pool from peripheral blood B cells primarily activated by IL-2. IL-10, and anti-CD40 monoclonal antibody (MoAb). Finally, CD27 signaling also rescued B cells from IL-10-mediated apoptosis. These data demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10-mediated promotion of apoptosis and to direct the differentiation of CD27(+) memory B cells toward plasma cells in cooperation with IL-10. (C) 1998 by The American Society of Hematology. C1 Shinshu Univ, Sch Med, Dept Pediat, Matsumoto, Nagano 390, Japan. Shinshu Univ, Sch Med, Dept Blood Transfus, Matsumoto, Nagano 390, Japan. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Agematsu, K (reprint author), Shinshu Univ, Sch Med, Dept Pediat, Asahi 3-1-1, Matsumoto, Nagano 390, Japan. NR 37 TC 140 Z9 142 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 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 173 EP 180 PG 8 WC Hematology SC Hematology GA YN358 UT WOS:000071160100020 PM 9414282 ER PT J AU Dunussi-Joannopoulos, K Dranoff, G Weinstein, HJ Ferrara, JLM Bierer, BE Croop, JM AF Dunussi-Joannopoulos, K Dranoff, G Weinstein, HJ Ferrara, JLM Bierer, BE Croop, JM TI Gene immunotherapy in murine acute myeloid leukemia: Granulocyte-macrophage colony-stimulating factor tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokine vaccines SO BLOOD LA English DT Article ID HEMATOPOIETIC GROWTH-FACTORS; T-CELLS; MELANOMA-CELLS; MAMMARY ADENOCARCINOMA; P-GLYCOPROTEIN; GM-CSF; CTLA-4; COSTIMULATION; CANCER; LYMPHOCYTES AB In an attempt to explore novel treatment modalities in acute myeloid leukemia (AML), we studied the role of costimulatory and cytokine gene immunotherapy in murine AML. We have previously shown that leukemic mice can be cured with CD80 transfected leukemic cells (B7.1-AML vaccine) administered early in the course of the disease and that the failure B7.1-AML vaccines administered late cannot be attributed to immunosuppression induced by tumor growth, CD8(+) T cells, which are necessary for tumor rejection, are activated rather than suppressed during the first half of the leukemic course in nonvaccinated mice. In this report, we question whether CD86 (B7.2) or the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), or tumor necrosis factor-alpha (TNF-alpha) can improve the vaccination potential of AML cells. The choice of cytokines was based on their combined and alone as well ability to direct the differentiation of CD34(+) cells into potent antigen-presenting dendritic cells in vitro. Our studies show that (1) mice vaccinated with a leukemogenic number of AML cells engineered to express B7.2 (B7.2-AML) or to secrete GM-CSF, IL-4, or TNF-alpha (GM-, IL-4-, TNF-alpha-AML) do not develop leukemia; (2) GM-AML cells are tumorigenic in sublethally irradiated SJL/J mice but not in Swiss nu/nu mice, indicating that killing of tumor cells is not T-cell-dependent; (3) vaccines with irradiated GM-AML, but not B7.2-, IL-4-, or TNF-alpha-AML cells, can elicit leukemia-specific protective and therapeutic immunity; and (4) in head-to-head comparison experiments, vaccination with irradiated GM-AML is more potent than B7.1-AML, curing 80% and providing 20% prolonged survival of the leukemic mice at week 2, as opposed to cures only up to 1 week with B7.1-AML vaccines, These preclinical data emphasize that GM-CSF gene immunotherapy deserves clinical evaluation in AML. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Dunussi-Joannopoulos, K (reprint author), Genet Inst, 1 Burrt Rd, Andover, MA 01810 USA. NR 61 TC 92 Z9 94 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 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 222 EP 230 PG 9 WC Hematology SC Hematology GA YN358 UT WOS:000071160100026 PM 9414288 ER PT J AU Ghia, P Boussiotis, VA Schultze, JL Cardoso, AA Dorfman, DM Gribben, JG Freedman, AS Nadler, LM AF Ghia, P Boussiotis, VA Schultze, JL Cardoso, AA Dorfman, DM Gribben, JG Freedman, AS Nadler, LM TI Unbalanced expression of bcl-2 family proteins in follicular lymphoma: Contribution of CD40 signaling in promoting survival SO BLOOD LA English DT Article ID PROGRAMMED CELL-DEATH; IMMATURE B-CELLS; GERMINAL-CENTERS; BCL-2-DEFICIENT MICE; INDUCED APOPTOSIS; TRANSGENIC MICE; HOMOLOG BAK; BONE-MARROW; GENE BAX; IN-VITRO AB Although highly responsive, advanced stage follicular lymphoma (FL) is not curable with conventional treatment. This relative resistance is thought to be due to the t(14;18) that results in the constitutive overexpression of the death-inhibiting protein bcl-2. However, the observation that FL cells are sensitive to treatment in vivo and prone to apoptosis on in vitro culture questions whether bcl-2 alone is responsible for the pathogenesis and clinical behavior of this disease, Therefore, multiple genes are likely to be involved in both the lymphomagenesis and the clinical course of FL. We examined whether expression of other bcl-2 family genes might also be operative. Here, we show that FL cells display a different pattern of expression of bcl-2 family proteins from normal germinal center (GC) B cells that are thought to be their normal counterpart. FL cells express the death-suppressor proteins bcl-2, bcl-x(L), and mcl-1; whereas GC B cells express bcl-x(L) and mcl-1 but also the proapoptotic proteins bax-alpha and bad. Although maintaining constitutive levels of bcl-2 and mcl-1, FL cells are not protected from apoptosis when cultured in vitro. Their propensity to undergo apoptosis is temporally associated with downregulation of bcl-x(L). More importantly, activation of FL cells via CD40 not only prevents downregulation but increases the level of bcl-x(L) expression and results in promotion of survival. These results support the hypothesis that the overexpression of bcl-2 is not the only antiapoptotic mechanism responsible for the pathogenesis of FL, Survival of FL cells is determined by a number of death-inhibiting proteins, among which bcl-x(L) appears to have the most critical role, Moreover, these findings are consistent with the hypothesis that, although FL cells are malignant, they respond to microenvironmental signals such as CD40L that appear to contribute to their survival through the upregulation of death-inhibiting proteins, (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ghia, P (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, D738,44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011; Ghia, Paolo/K-7138-2016 OI Schultze, Joachim/0000-0003-2812-9853; Ghia, Paolo/0000-0003-3750-7342 FU NCI NIH HHS [CA55207, P01-CA66996] NR 62 TC 96 Z9 96 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 244 EP 251 PG 8 WC Hematology SC Hematology GA YN358 UT WOS:000071160100029 PM 9414291 ER PT J AU Heinrich, MC Hoatlin, ME Zigler, AJ Silvey, KV Bakke, AC Keeble, WW Zhi, Y Reifsteck, CA Grompe, M Brown, MG Magenis, RE Olson, SB Bagby, GC AF Heinrich, MC Hoatlin, ME Zigler, AJ Silvey, KV Bakke, AC Keeble, WW Zhi, Y Reifsteck, CA Grompe, M Brown, MG Magenis, RE Olson, SB Bagby, GC TI DNA cross-linker-induced G2/M arrest in group C Fanconi anemia lymphoblasts reflects normal checkpoint function SO BLOOD LA English DT Article ID HUMAN HEMATOPOIETIC-CELLS; SACCHAROMYCES-CEREVISIAE; ATAXIA-TELANGIECTASIA; INDUCED APOPTOSIS; CYCLE CHECKPOINT; GENE FACC; COMPLEMENTATION; PHASE; POLYPEPTIDE; CAFFEINE AB Cells from individuals with Fanconi anemia (FA) arrest excessively in the G2/M cell cycle compartment after exposure to low doses of DNA cross linking agents. The relationship of this abnormality to the fundamental genetic defect in such cells is unknown, but many investigators have speculated that the various FA genes directly regulate cell cycle checkpoints. We tested the hypothesis that the protein encoded by the FA group C complementing gene (FAG) functions to control a cell cycle checkpoint and that cells from group C patients (FA[C]) have abnormalities of cell cycle regulation directly related to the genetic mutation. We found that retroviral transduction of FA(C) lymphoblasts with wild-type FAC cDNA resulted in normalization of the cell cycle response to low-dose mitomycin C (MMC). However, when DNA damage was quantified in terms of cytogenetic damage or cellular cytotoxicity, we found similar degrees of G2/M arrest in response to equitoxic amounts of MMC in FA(C) cells as well as in normal lymphoblasts. Similar results were obtained using isogenic pairs of uncorrected, FAC or mock-corrected (neo only) FA(C) cell lines. To test the function of other checkpoints we examined the effects of hydroxyurea (HU) and ionizing radiation on cell cycle kinetics of FA(C) and normal lymphoblasts as well as with isogenic pairs of uncorrected, FAG-corrected, or mock-corrected FA(C) cell lines. In all cases the cell cycle response of FA(C) and normal lymphoblasts to these two agents were identical. Based on these studies we conclude that the aberrant G2/M arrest that typifies the response of FA(C) cells to low doses of cross-linking agents does not represent an abnormal cell cycle response but instead represents a normal cellular response to the excessive DNA damage that results in FA(C) cells following exposure to low doses of cross-linking agents. (C) 1998 by The American Society of Hematology. C1 Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Dept Med, Portland, Dorset, England. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, Dorset, England. Oregon Hlth Sci Univ, Dept Pediat, Portland, Dorset, England. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), 151B 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. FU NCI NIH HHS [CA36306]; NHLBI NIH HHS [1PO1HL48546, HL48546] NR 77 TC 51 Z9 51 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1998 VL 91 IS 1 BP 275 EP 287 PG 13 WC Hematology SC Hematology GA YN358 UT WOS:000071160100033 PM 9414295 ER PT J AU Scremin, OU Shih, TM Li, MG Jenden, DJ AF Scremin, OU Shih, TM Li, MG Jenden, DJ TI Mapping of cerebral metabolic activation in three models of cholinergic convulsions SO BRAIN RESEARCH BULLETIN LA English DT Article DE cholinesterase inhibitors; epilepsy; cerebral glucose utilization; pilocarpine; physostigmine; soman ID MUSCARINIC RECEPTOR SUBTYPES; LITHIUM PILOCARPINE MODEL; SOMAN-INDUCED SEIZURES; REGIONAL GLUCOSE USE; STATUS EPILEPTICUS; ACETYLCHOLINESTERASE INHIBITION; HYPERTENSIVE RESPONSE; BLOOD-FLOW; RAT-BRAIN; PHYSOSTIGMINE AB Glucose utilization of four cerebral cortex and 35 subcortical regions (CGU) was analyzed in three models of cholinergic seizures induced by the following compounds: 1) soman (pinacolylmethylphosphonofluoridate) an organophosphorus cholinesterase inhibitor, 100 mu g/kg SC after pretreatment with pyridostigmine 26 mu g/kg IM (n = 6); 2) physostigmine, a carbamate cholinesterase inhibitor, 1.31 mg/kg infused IV over 75 min (n = 6); and 3) pilocarpine, a direct cholinergic agonist, 30 mg/kg SC (n = 6), Physostigmine and pilocarpine were preceded by 3 mmol/kg LiCl IP 20 hrs earlier, Animals injected with saline SC (n = 6) were used as controls, Step-wise discriminant analysis successfully classified 100% of the cases into the four experimental groups with data from only six regions, Pyridostigmine-soman induced the most widespread and greatest increases in CGU. More restricted and lower levels of activation were observed with Li-pilocarpine while Li-physostigmine induced significant increases in CGU only in globus pallidus, entopeduncular nucleus, and substantia nigra, These three regions, which are functionally related, were also activated in the other two models of cholinergic convulsions and may represent the initial step in cholinergic activation of the CNS, Li-pilocarpine failed to activate most of the brainstem and the superior colliculus. All cortical regions were activated by Li-pilocarpine and pyridostigmine-soman, while they were inhibited by Li-physostigmine. This phenomenon may be due in part to the lack of activation with physostigmine of the basal forebrain nuclei (lateral septum, medial septum, vertical and horizontal limbs of the diagonal band, and substantia innominata) resulting in a decreased drive of cortical metabolism. (C) 1998 Elsevier Science Inc. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90073 USA. USA, Med Res Inst Chem Def, Neurotoxicol Branch, Aberdeen Proving Ground, MD 21010 USA. RP Scremin, OU (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 115,Room 317, Los Angeles, CA 90073 USA. NR 41 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PY 1998 VL 45 IS 2 BP 167 EP 174 DI 10.1016/S0361-9230(97)00334-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YN851 UT WOS:000071214500009 PM 9443835 ER PT J AU Clifford, SC Hewson, K Walsh, S Brinke, A Green, PM Gianelli, F Pause, A Eng, C Maher, ER AF Clifford, SC Hewson, K Walsh, S Brinke, A Green, PM Gianelli, F Pause, A Eng, C Maher, ER TI Mutation analysis of von Hippel-Lindau (VHL) tumour suppressor-associated proteins, CUL-2 and VBP-1, in renal cell carcinoma (RCC) SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 Univ Birmingham, Dept Paediat & Child Hlth, Div Med & Mol Genet, Birmingham, W Midlands, England. United Med & Dent Sch Guys & St Thomas Hosp, Guys Hosp, Div Med & Mol Genet, London SE1 9RT, England. NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PY 1998 VL 78 SU 1 MA 36 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA ZV718 UT WOS:000074334100041 ER PT J AU Cady, B Steele, GD Morrow, M Gardner, B Smith, BL Lee, NC Lawson, HW Winchester, DP AF Cady, B Steele, GD Morrow, M Gardner, B Smith, BL Lee, NC Lawson, HW Winchester, DP TI Evaluation of common breast problems: Guidance for primary care providers SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID FINE-NEEDLE ASPIRATION; SELF-EXAMINATION; CANCER; MAMMOGRAPHY; EPIDEMIOLOGY; GUIDELINES; CYTOLOGY; LESIONS; WOMEN AB The evaluation of common breast problems requires an assessment of the patient's risks and symptoms and a thorough physical examination. When indicated, appropriate imaging studies should be done, the patient should be referred to a surgeon or a breast specialist, and operative interventions should be used. C1 Brown Univ, Providence, RI 02912 USA. Women & Infants Hosp, Breast Hlth Ctr, Providence, RI USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Univ Chicago, Div Biol Sci, Chicago, IL 60637 USA. Lynn Sage Comprehens Breast Program, Chicago, IL USA. Northwestern Univ, Sch Med, Chicago, IL USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Div Surg Educ, Newark, NJ 07103 USA. Dana Farber Partners CancerCare, Womens Canc Program, Boston, MA USA. Massachusetts Gen Hosp, Comprehens Breast Hlth Ctr, Boston, MA 02114 USA. Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA 30333 USA. Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Amer Coll Surg, Canc Dept, Chicago, IL USA. Evanston NW Healthcare, Dept Surg, Evanston, IL USA. Northwestern Univ, Sch Med, Chicago, IL USA. Hlth Care Financing Adm Reg 10, Div Clin Stand & Qual, Seattle, WA USA. RP Cady, B (reprint author), Brown Univ, Providence, RI 02912 USA. NR 22 TC 38 Z9 38 U1 0 U2 0 PU AMER CANCER SOC, INC PI ATLANTA PA 1599 CLIFTON RD, NE, ATLANTA, GA 30329 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 1998 VL 48 IS 1 BP 49 EP + DI 10.3322/canjclin.48.1.49 PG 16 WC Oncology SC Oncology GA YR587 UT WOS:000071510200005 PM 9449933 ER PT J AU Macri, E Loda, M AF Macri, E Loda, M TI Role of p27 in prostate carcinogenesis SO CANCER AND METASTASIS REVIEWS LA English DT Review DE cyclin dependent kinase inhibitors; p27; prostate cancer ID DEPENDENT-KINASE INHIBITOR; TUMOR-SUPPRESSOR GENES; HUMAN P27(KIP1) GENE; CELL-CYCLE; NOBLE RATS; ANDROGEN DEPRIVATION; BREAST-CANCER; MICE LACKING; C-MYC; EXPRESSION AB The cyclin dependent kinase inhibitor p27 binds to and inhibits preferentially S-phase kinases thereby halting cell cycle progression. Loss of p27 expression has been shown to be associated with aggressive behavior in a variety of human epithelial tumors including prostate cancer. In this review, the role of p27 in cell cycle progression as well as its regulation by the ubiquitin-proteasome pathway are discussed. The experimental evidence pointing to the role of p27 as a tumor suppressor gene is outlined. The data generated to date on the prognostic significance of loss of p27 protein expression in human prostate cancers are summarized. Finally, the implications of the changes in p27 expression which occur as a result of androgen ablation in normal and neoplastic prostate are discussed. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst & Pathol,Dept Adult Oncol, Boston, MA USA. RP Loda, M (reprint author), Dana Farber Canc Inst, D740B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA77601-01] NR 70 TC 56 Z9 57 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PY 1998 VL 17 IS 4 BP 337 EP 344 DI 10.1023/A:1006133620914 PG 8 WC Oncology SC Oncology GA 209RE UT WOS:000081061700005 PM 10453277 ER PT J AU Iakoubov, LZ Torchilin, VP AF Iakoubov, LZ Torchilin, VP TI Nucleosome-releasing treatment makes surviving tumor cells better targets for nucleosome-specific anticancer antibodies SO CANCER DETECTION AND PREVENTION LA English DT Article DE antinuclear antibody; apoptosis; neoplasm; nucleosome ID PLASMA DNA; AUTOANTIBODY; SURFACE; DEATH; APOPTOSIS; RECEPTOR; MARKER; CANCER; LUPUS AB Monoclonal antibody (MoAb) 2C5, a nucleosome-specific antinuclear autoantibody (ANA) from the repertoire of aged mice, was recently reported to recognize the surface of various tumor cells but not normal cells. Surface-bound nucleosomes (NSs) were previously proven to be MoAb 2C5's target on the outer membrane of tumor cells. Furthermore, MoAb 2C5 was found to have a strong antitumor effect during the early stages of tumor development. In an attempt to further increase antitumor effect of nucleosome-specific tumorocidal monoclonal antibody against established tumors, we investigated a possible way to enhance antibody association with tumor cells. Evidence is presented here demonstrating that the in vitro treatment of tumor cells (S49 T lymphoma) resulting in a partial cell death and massive liberation of intact NSs from dead tumor cells into the culture medium was accompanied by a 50-fold increase of MoAb 2C5 binding to the surface of surviving tumor cells. Massive NS release was observed in the case of S49 T-cell treatment with dexamethasone and vincristine. However, a partial cell killing that was not accompanied with NS release (ELA lymphoma treatment with doxorubicin) did not result in the enhanced binding of MoAb 2C5 to the surface of surviving tumor cells. The use of NS-specific tumorocidal antibodies, such as MoAb 2C5, in combination with another NS release-inducing tumor therapy, should provide an enhanced antibody-tumor binding. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Iakoubov, LZ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, 149 13th St, Charlestown, MA 02129 USA. NR 19 TC 38 Z9 39 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 1998 VL 22 IS 5 BP 470 EP 475 DI 10.1046/j.1525-1500.1998.00055.x PG 6 WC Oncology SC Oncology GA 112ER UT WOS:000075481600012 PM 9727629 ER PT J AU Li, FP AF Li, FP TI Tribute to Pelayo Correa, MD, founding editor, Cancer Epidemiology Biomarkers, & Prevention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 1998 VL 7 IS 1 BP 1 EP 1 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA149 UT WOS:000072333800001 PM 9456235 ER PT J AU Kopans, DB AF Kopans, DB TI The mammography screening controversy SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Editorial Material ID WOMEN 40-49 YEARS; BREAST-CANCER; AGE C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 14 TC 2 Z9 3 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD JAN-FEB PY 1998 VL 4 IS 1 BP 22 EP 24 PG 3 WC Oncology SC Oncology GA YU910 UT WOS:000071768700004 PM 9467041 ER PT J AU Modica-Napolitano, JS Brunelli, BT Koya, K Chen, LB AF Modica-Napolitano, JS Brunelli, BT Koya, K Chen, LB TI Photoactivation enhances the mitochondrial toxicity of the cationic rhodacyanine MKT-077 SO CANCER RESEARCH LA English DT Article ID RAT-LIVER MITOCHONDRIA; ANTICARCINOMA ACTIVITY; CARCINOMA-CELLS; RHODAMINE-123; DYE; ACCUMULATION; PHOTOLYSIS; RETENTION; PHOTOCHEMOTHERAPY; SAFRANINE AB In this study, the mitochondrial phototoxicity of the cationic rhodacyanine MKT-077 was investigated by comparing its effects on the inhibition of mitochondrial respiration and the structural integrity of mitochondrial DNA (mtDNA) in the presence and absence of added high-intensity visible light (7.5 J/cm(2)), Results indicate that photoirradiation significantly enhances the mitochondrial toxicity of MKT-077 at both the biochemical and DNA levels, For example, the concentration of MKT-077 required to achieve one-half maximal inhibition of ADP-stimulated respiration was observed to he 6-fold lower in the presence versus absence of high-intensity light (one-half maximal inhibition at 2.5 versus 15 mu g MKT-077/mg, respectively), In addition, photoirradiation produced a 25-fold increase in inhibition of succinate-cytochrome c reductase activity by MKT-077 (one-half maximal inhibition at 2 versus 50 mu g MKT-077/ml, +/-light, respectively) and a 6-fold increase in inhibition of cytochrome oxidase activity (one-half maximal inhibition at 5 versus 30 mu g MKT-077/ml, +/-light, respectively), Furthermore, the combination of 25 mu g/ml MKT-077 and 7.5 J/cm(2) visible light caused significant degradation of mtDNA in isolated rat liver mitochondria, whereas the same concentration of dye in the absence of light had only a modest effect on mtDNA. Evaluation of light-induced MKT-077 lipid peroxidation in mitochondrial membrane fragments by the thiobarbituric acid test and by measurement of nonrespiratory-linked oxygen uptake suggests that mitochondrial phototoxicity by MKT-077 may be the result of lipid peroxidation via reactive oxygen species, These results have important implications with regard to the potential use of MKT-077 in photochemotherapy. C1 Merrimack Coll, Dept Biol, N Andover, MA 01845 USA. Tufts Univ, Dept Biol, Medford, MA 02155 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. RP Modica-Napolitano, JS (reprint author), Merrimack Coll, Dept Biol, N Andover, MA 01845 USA. NR 35 TC 36 Z9 37 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1998 VL 58 IS 1 BP 71 EP 75 PG 5 WC Oncology SC Oncology GA YN977 UT WOS:000071229000015 PM 9426060 ER PT J AU Tsao, H Benoit, E Sober, AJ Thiele, C Haluska, FG AF Tsao, H Benoit, E Sober, AJ Thiele, C Haluska, FG TI Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; FAMILIAL MELANOMA; CELL-LINES; HOMOZYGOUS DELETIONS; CDK4; P16; INHIBITOR; P16(INK4); CANCER; GLIOMA AB Mutations in genes that lie in the retinoblastoma pathway have been implicated in the pathogenesis of many tumor types, Two critical components that determine progression from G(1) to S include p16/CDKN2A and CDK4 Alterations in p16/CDKN2A have been well documented in multiple cancers, including melanoma, However, changes in CDK4 are apparently more rare. Only two alterations, both at codon 24, have been identified in CDK4: an activating arginine-to-cysteine transition and a germ-line arginine-to-histidine substitution in one French kindred, In a survey of 20 neuroblastomas, 17 uncultured metastatic melanomas, 33 uncultured primary uveal melanomas, 8 colon cancer cell lines, and 20 primary colon cancer samples, we found no evidence of mutations in exon 2 of CDK4. From our cell lines derived from metastatic melanomas, we detected two alterations in the functionally critical exon 2 of CDK4: a lysine-to-glutamine transition at codon 22 and the arginine-to-histidine mutation at codon 24. These findings document several novel changes in the p16-binding region of CDK4. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Dana Farber Canc Inst, Partner Canc Care, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Jackson 1021,Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [5T32AR07098-23] NR 37 TC 66 Z9 67 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1998 VL 58 IS 1 BP 109 EP 113 PG 5 WC Oncology SC Oncology GA YN977 UT WOS:000071229000021 PM 9426066 ER PT J AU Bates, RC Elith, CA Thorne, RF Burns, GF AF Bates, RC Elith, CA Thorne, RF Burns, GF TI Engagement of variant CD44 confers resistance to anti-integrin antibody-mediated apoptosis in a colon carcinoma cell line SO CELL ADHESION AND COMMUNICATION LA English DT Article DE apoptosis; CD44; colon carcinoma; metastasis ID EXTRACELLULAR-MATRIX; RECEPTOR; HYALURONATE; EXPRESSION; SURVIVAL; BCL-2; COLLAGEN; TRIGGERS; FIBROBLASTS; FIBRONECTIN AB The LIM 1863 colon carcinoma cell line grows as structured organoids around a central lumen, and we have previously demonstrated that the three-dimensional arrangement protects the individual cells from apoptosis induced by an anti-alpha integrin antibody, 23C6 (Bates et al., 1994). Here we show that the intercellular forces which drive spheroid formation can be overcome by exposure of the cells to a collagen substrate, or more specifically through ligation of the CD44 receptor by a monoclonal antibody. Binding to immobilized anti-CD44 antibody induced a monolayer morphology which is accompanied by fibronectin production and secretion, and expression of the integrin alpha v beta(6). Significantly, the cells of the monolayer acquired resistance to 23C6 antibody-mediated apoptosis over time and this property was sustained even after removal from the monolayer. We provide data to show that this resistance is not dependent on monolayer morphology, constant engagement of the CD44 receptor, loss of the 23C6 antigen, or elevation of Bcl-2 or Bcl-X-L protein. The CD44 expressed by LIM 1863 is shown to be the metastatic variant of the molecule therefore these results provide a possible explanation for the selective advantages conferred by expression of this variant for metastasizing colon cancer cells. Overall, the findings of this study support a model for the development of malignancy through the production of specific survival and growth signals as a direct consequence of a signaling event induced by stimulation of an epithelial variant of CD44. C1 Univ Newcastle, Fac Med, Canc Res Unit, Newcastle, NSW 2308, Australia. RP Bates, RC (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, Room D630,44 Binney St, Boston, MA 02115 USA. NR 43 TC 21 Z9 21 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1998 VL 6 IS 1 BP 21 EP 38 DI 10.3109/15419069809069758 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 118BK UT WOS:000075817600003 PM 9759519 ER PT J AU von Andrian, UH M'Rini, C AF von Andrian, UH M'Rini, C TI In situ analysis of lymphocyte migration to lymph nodes SO CELL ADHESION AND COMMUNICATION LA English DT Article; Proceedings Paper CT 2nd Amsterdam Zoo Meeting on Cell Adhesion and Migration in Inflammation and Cancer CY OCT 22-25, 1997 CL AMSTERDAM, NETHERLANDS SP Cent Lab Netherlands Red Cross Blood Transfus Serv, Royal Netherlands Acad Arts & Sci, KNAW, Dutch Soc Immunol, Dutch Kidney Fdn, Assoc Int Cancer Res-UK, ALZA Corp-USA, Coulter Electr-NL, Cytomat Bio-Instruments GmbH-Germany, Diagnost Prod Corp-NL, Harwood Acad Publshers GmbH-NL, Hercules European Res Ctr-NL, ICOS Corp-USA, Immunex Corp-USA, Immunotech SA-France, Intersens Instruments BV-NL, Laboned-NL, Leukosite-USA, R & D Syst Europe Ltd-UK, Serotec Ltd-UK DE lymphocyte homing; lymph node; intravital microscopy; L-selectin; P-selectin; platelet ID HIGH-ENDOTHELIAL VENULES; SELECTIN-DEFICIENT MICE; MEMORY T-CELLS; P-SELECTIN; VASCULAR ADDRESSIN; MOLECULAR MECHANISMS; PLATELETS CIRCULATE; GLYCOPROTEIN LIGAND; HOMING RECEPTOR; ACTIVATED STATE AB Blood-borne lymphocytes migrate continuously to peripheral lymph nodes (PLN) and other organized lymphoid tissues where they are most likely to encounter their cognate antigen. Lymphocyte homing to PLN is a highly regulated process that occurs exclusively in specialized high endothelial venules (HEV) in the nodal paracortex. Recently, it has become possible to explore this vital aspect of peripheral immune surveillance by intravital microscopy of the subiliac lymph node microcirculation in anesthetized mice. This paper reviews technical and experimental aspects of the new model and summarizes recent advances in our understanding of the molecular mechanisms of lymphocyte homing to PLN which were derived from its use. Both lymphocytes and granulocytes initiate rolling interactions via L-selectin binding to the peripheral node addressin (PNAd) in PLN HEV, Subsequently, a G protein-coupled chemoattractant stimulus activates LFA-1 on rolling lymphocytes, but not on granulocytes. Thus, granulocytes continue to roll through the PLN, whereas LFA-1 activation allows lymphocytes to arrest and emigrate into the extravascular compartment, We have also identified a second homing pathway that allows L-selectin low/(activated/memory) lymphocytes to home to PLN. P-selectin on circulating activated platelets can mediate simultaneous platelet adhesion to PNAd in HEV and to P-selectin glycoprotein ligand (PSGL)-1 on lymphocytes, Through this mechanism, platelets call form a cellular bridge which can effectively substitute for the loss of L-selectin on memory cell subsets. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL48675, HL54936, HL56949] NR 49 TC 63 Z9 64 U1 0 U2 3 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1998 VL 6 IS 2-3 BP 85 EP 96 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 138KP UT WOS:000076971300002 PM 9823458 ER PT J AU Li, ZH Carraro, R Gregerman, RI Lau, DCW AF Li, ZH Carraro, R Gregerman, RI Lau, DCW TI Adipocyte differentiation factor (ADF): A protein secreted by mature fat cells that induces preadipocyte differentiation in culture SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE preadipocytes; fat cells; adipocyte differentiation factor; cytokines; paracrine factor; obesity; diabetes ID TUMOR-NECROSIS-FACTOR; AMINO-ACID-SEQUENCE; GROWTH FACTOR-I; ADIPOSE-TISSUE ISLETS; PRECURSOR CELLS; GENE-EXPRESSION; INITIAL CHARACTERIZATION; ADIPOGENIC ACTIVITY; MOLECULAR-CLONING; INHIBITORY FACTOR AB A factor that is released into the culture medium of mature adipocytes and promotes the differentiation (adipogenic conversion) of preadipocytes has been partially characterized. The factor acts in a dose-dependent manner on preadipocytes to produce up to a four-fold increase in triacylglycerol (triglyceride) content and a nine-fold increase in glycerol-3-phosphate dehydrogenase (GPDH) activity, a marker of the late phase of differentiation of preadipocytes, The material appears to be a protein, since it has a molecular weight (Superose-12 gel exclusion chromatography) of about 53 kDa, an isoelectric point (pl) of 4.7-4.9, and is inactivated by the proteases papain and chymotrypsin and extremes of pH (2 and 12), Considerations of molecular weight, isoelectric point, stability to specific proteases, and especially to the action of chemical agents [the adipogenic activity is not affected by either an oxidizing (KIO4) or a reducing agent (DTT)], lead to the conclusion that the differentiation factor is distinct from known cytokines, The authors suggest that the protein be designated adipocyte differentiation factor (ADF). ADF in vivo may act as a cytokine paracrine agent to regulate the differentiation of preadipocytes. (C) 1998 Academic Press. C1 Ottawa Civic Hosp, Div Endocrinol & Metab, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Dept Med, Ottawa, ON, Canada. Univ Ottawa, Loeb Res Inst, Ottawa, ON, Canada. Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. Dept Vet Affairs, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. RP Lau, DCW (reprint author), Ottawa Civic Hosp, Div Endocrinol & Metab, 1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. EM gregerman@uthscsa.edu NR 93 TC 8 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 1998 VL 22 IS 4 BP 253 EP 270 DI 10.1006/cbir.1998.0237 PG 18 WC Cell Biology SC Cell Biology GA 174WF UT WOS:000079058800001 PM 10101042 ER PT J AU Ford, HL AF Ford, HL TI Homeobox genes: A link between development, cell cycle, and cancer? SO CELL BIOLOGY INTERNATIONAL LA English DT Review ID MESSENGER-RNA; HOX GENES; CHECKPOINT; EXPRESSION; OVEREXPRESSION; CARCINOGENESIS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Ford, HL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32-CA09361, CA61253] NR 28 TC 41 Z9 45 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PY 1998 VL 22 IS 6 BP 397 EP 400 DI 10.1006/cbir.1998.0329 PG 4 WC Cell Biology SC Cell Biology GA 196AD UT WOS:000080284900001 PM 10328847 ER PT J AU Trbovich, AM Hughes, FM Perez, GI Kugu, K Tilly, KI Cidlowski, JA Tilly, JL AF Trbovich, AM Hughes, FM Perez, GI Kugu, K Tilly, KI Cidlowski, JA Tilly, JL TI High and low molecular weight DNA cleavage in ovarian granulosa cells: characterization and protease modulation in intact cells and in cell-free nuclear autodigestion assays SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; DNA cleavage; nucleases; proteases; granulosa cell; follicle; atresia; ovary ID FOLLICLE-STIMULATING-HORMONE; EPIDERMAL GROWTH-FACTOR; DEATH GENE CED-3; CAENORHABDITIS-ELEGANS; INTERLEUKIN-1-BETA-CONVERTING ENZYME; ENDONUCLEASE ACTIVITIES; ICE/CED-3 PROTEASE; CONVERTING-ENZYME; CYSTEINE PROTEASE; SERINE PROTEASE AB To continue elucidation of the biochemical and molecular pathways involved in the induction of apoptosis in granulosa cells (GC) of ovarian follicles destined for atresia, we characterized the occurrence and protease modulation of high and low molecular weight (MW) DNA fragmentation during rat GC death, Atresia of ovarian follicles, occurring either spontaneously in vivo or induced in vitro, was associated with both high MW and internucleosomal (low MW) DNA cleavage, Incubation of follicles in the presence of a putative irreversible and non-competitive inhibitor of caspase-1 (interleukin-1 beta-converting enzyme or ICE), sodium aurothiomalate (SAM), completely prevented internucleosomal, but not high MW, DNA cleavage, As reported previously, morphological features of apoptosis (pyknosis, cellular condensation) and atresia (granulosa cell disorganization, oocyte pseudomaturation) remained detectable in SAM-treated follicles, The potential involvement of proteases in endonuclease activation was further analyzed in cell-free assays using nuclei from both GC (which autodigest their DNA) and HeLa cells (HC, which do not autodigest their DNA un less incubated with extracts prepared from other cell types). Crude cytoplasmic extracts prepared from GC induced both high MW and internucleosomal DNA cleavage in HC nuclei. The induction of low, but not high, MW DNA cleavage in HC nuclei by GC extracts was suppressed by pretreatment of the extracts with SAM or with any one of the serine protease inhibitors, dichloroisocoumarin (DCI), N-tosyl-L-leucylchloromethylketone (TLCK) or N-tosyl-L-phenylchloromethylketone (TPCK). Interestingly, SAM and DCI also prevented cation-induced low MW DNA fragmentation in GC nuclei; however, TLCK and TPCK were without effect. Our results support a role for cytoplasmic and nuclear serine proteases in the activation of the endonuclease(s) responsible for internucleosomal DNA cleavage during apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. NIEHS, Lab Integrat Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226] NR 79 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 1998 VL 5 IS 1 BP 38 EP 49 DI 10.1038/sj.cdd.4400299 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR650 UT WOS:000071516500006 PM 10200444 ER PT J AU Kugu, K Ratts, VS Piquette, GN Tilly, KI Tao, XJ Martimbeau, S Aberdeen, GW Krajewski, S Reed, JC Pepe, GJ Albrecht, ED Tilly, JL AF Kugu, K Ratts, VS Piquette, GN Tilly, KI Tao, XJ Martimbeau, S Aberdeen, GW Krajewski, S Reed, JC Pepe, GJ Albrecht, ED Tilly, JL TI Analysis of apoptosis and expression of bcl-2 gene family members in the human and baboon ovary SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; BCL-2; BCL-X; BAX; p53; caspase; ICH-1; CPP32; atresia; granulosa cell; ovary ID PROGRAMMED CELL-DEATH; GRANULOSA-CELLS; FOLLICULAR ATRESIA; IN-VIVO; DNA FRAGMENTATION; RAT OVARY; P53; PROTEASES; FOLLICLES; BAX AB Recent data support a role for apoptosis, under tight regulatory control by bcl-2, oxidative stress response, tumor suppressor, and GASP gene family members, in mediating granulosa cell demise during follicular atresia in the rodent and avian ovary. Herein we evaluated the occurrence of apoptosis in the human and baboon ovary relative to follicular health status, and analyzed expression of several cell death genes in these tissues. In situ localization of DNA strand breaks in fixed human and baboon ovarian tissue sections indicated that apoptosis was essentially restricted to granulosa cells of atretic antral follicles, Biochemical analysis of DNA oligonucleosomes in individual follicles isolated from baboon ovaries during the ovulatory phase revealed the presence of apoptotic DNA fragments in subordinate but not dominant follicles, thus substantiating the in situ labeling studies. Messenger RNA transcripts encoded by the bax death susceptibility gene, the bcl-x(long) survival gene, the bcl-x(short) pro-apoptosis gene, the p53 tumor suppressor gene, and two members of the CASP gene family (CASP-2/lch-1, CASP-3/CPP32), were detected by Northern blot analysis of total RNA prepared either from human ovaries or from Percoll-purified granulosa-lutein cells obtained from patients undergoing assisted reproductive technologies. Lastly, immunohistochemical localization of the BAX death-susceptibility protein in the human ovary revealed abundant expression in granulosa cells of early atretic follicles, whereas BAX protein was extremely low or non-detectable in healthy or grossly-atretic follicles. We conclude that apoptosis occurs during, and is probably responsible for, follicular atresia in the human and baboon ovary. Moreover, apoptosis in the human ovary is likely controlled by altered expression of the same cohort of cell death regulatory factors recently implicated as primary determinants of apoptosis induction or suppression in the rodent ovary. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept OB GYN, Boston, MA 02114 USA. Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. Univ Calif Los Angeles, Sch Med, Dept Obstet Gynecol, Los Angeles, CA 90048 USA. Univ Maryland, Sch Med, Dept Obstet Gynecol, Baltimore, MD 21201 USA. Burnham Inst, La Jolla, CA 92037 USA. Eastern Virginia Med Sch, Dept Physiol, Norfolk, VA 23501 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept OB GYN, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. EM tilly.jonathan@mgh.harvard.edu FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R55-HD31188, R01-HD34226] NR 57 TC 81 Z9 89 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 1998 VL 5 IS 1 BP 67 EP 76 DI 10.1038/sj.cdd.4400316 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YR650 UT WOS:000071516500009 PM 10200447 ER PT J AU Suzuki, K Bonner-Weir, S Hollister-Lock, J Colton, CK Weir, GC AF Suzuki, K Bonner-Weir, S Hollister-Lock, J Colton, CK Weir, GC TI Number and volume of islets transplanted in immunobarrier devices SO CELL TRANSPLANTATION LA English DT Article DE islet transplantation; diabetes; islets; immunobarrier ID XENOGRAFTS; IMMUNOSUPPRESSION; PANCREAS; GROWTH; MICE; RATS; MASS AB Immunobarrier devices may prevent immune destruction of transplanted islets, but there are concerns about survival within such devices, Islets were transplanted in diffusion chambers that employed two laminated polytetrafluoroethylene membranes held together with titanium rings, Five hundred syngeneic mouse islets placed in devices were transplanted into the epididymal fat pads of streptozotocin (STZ) diabetic mice (B6AF1). After 2 wk the devices were removed, Sections were made parallel to the membrane surface. Eight to 13 systematically selected sections of each device were analyzed by planimetry to determine the area of the device space and of the islets within that space, From these data we estimated total volume of the device, volume of islets, and number of islets in a device, The data were segregated into two groups: group I (blood glucose less than 100 mg/dL 2 wk after implantation), and group II (over 150 mg/dL), The volume (mean +/- SE) of devices implanted for 2 wk was 2.1 +/- 0.4 mu L in group I and 2.2 +/- 0.2 mu L in group II, The islet volume and number within devices were 0.30 +/- 0.06 and 0.17 +/- 0.01 mu L, or 340 +/- 50 and 230 +/- 20 islets in group I and group II, respectively, The volume of fibrous tissue in devices was about 0.50 mu L. About 10% of the islet tissue had central necrosis, The beta cell volume in a membrane device needed for cure is comparable to that required with islets under the kidney capsule (0.25-0.80 mu L) The mass of islets contained within membrane devices needed to cure diabetes is equivalent to that of a graft in an optimal transplant site such as under the kidney capsule, (C) 1998 Elsevier Science Inc. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-35449, DK-36836, DK 50657] NR 18 TC 45 Z9 46 U1 0 U2 3 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD JAN-FEB PY 1998 VL 7 IS 1 BP 47 EP 52 DI 10.1016/S0963-6897(97)00114-0 PG 6 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA YX067 UT WOS:000072003100005 PM 9489762 ER PT J AU Buczek-Thomas, JA Chen, N Hasan, T AF Buczek-Thomas, JA Chen, N Hasan, T TI Integrin-mediated adhesion and signalling in ovarian cancer cells SO CELLULAR SIGNALLING LA English DT Article DE ovarian cancer; integrins; cellular adhesion; phosphotyrosine; focal adhesion kinase ID TYROSINE PHOSPHORYLATION; KINASE; TRANSDUCTION; EXPRESSION; PROTEINS; MODEL; PHOTOIMMUNOTHERAPY; CARCINOMA; BETA-1; TUMORS AB The integrins are a family of cell surface receptors which mediate cellular adhesion and signalling events. Our goal was to evaluate integrin function and signalling pathways in ovarian cancer cells. Ovarian cancer cell lines, NIH:OVCAR-3 and NIH:OVCAR-5, exhibited distinct extracellular matrix (ECM) binding preferences which were mediated primarily through beta(1) integrin interactions. Western blot analysis was used to identify changes in cellular phosphotyrosine, focal adhesion kinase (FAK) and mitogen activated protein (MAP) kinase. Tyrosine phosphorylation of integrin-associated phosphoproteins was not enhanced in either cell type in response to adhesion onto ECM components or receptor crosslinking. FAK expression was greater in NIH:OVCAR-5 cells while MAP kinase activity was higher in NIH:OVCAR-3 cells. The data suggest that these two ovarian cancer cell lines exhibit specific ECM binding preferences and distinct differences in phosphotyrosine, focal adhesion and MAP kinase expression profiles. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Wellman 224,50 Blossom St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR403527] NR 38 TC 30 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 1998 VL 10 IS 1 BP 55 EP 63 DI 10.1016/S0898-6568(97)00074-0 PG 9 WC Cell Biology SC Cell Biology GA YM330 UT WOS:000071052800007 PM 9502118 ER PT J AU Smirnoff, M Patt, C Seckler, B Adler, JJ AF Smirnoff, M Patt, C Seckler, B Adler, JJ TI Tuberculin and anergy skin testing of patients receiving long-term hemodialysis SO CHEST LA English DT Article DE anergy; chronic renal failure; hemodialysis; tuberculin testing; tuberculosis ID DIALYSIS AB Study objectives: Immunocompromised patients with chronic renal failure requiring hemodialysis (HD) are at increased risk of developing tuberculosis (TB). Routine TB screening of this population is recommended. This study examined the frequency of TB reactions and anergy in HD patients in a community with a high prevalence of TB. Design: Outpatients in a hospital-based HD center were screened with tuberculin, Candida, and mumps antigen. Results: Forty percent of patients were anergic and 19% were tuberculin reactors. No demographic factors correlated with either test results. Conclusions: There was a high rate of TB infection and anergy in this HD center. Despite the high rate of anergy, tuberculin testing remains a useful test in this population. Anergic patients require further clinical evaluation for TB. Other HD programs should tuberculin and anergy test their patients to determine prevalence in their populations. C1 Mt Sinai Med Ctr, Dept Nursing, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. Boston Med Ctr, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Smirnoff, M (reprint author), Mt Sinai Med Ctr, Dept Nursing, New York, NY 10029 USA. NR 8 TC 77 Z9 80 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 JAN PY 1998 VL 113 IS 1 BP 25 EP 27 DI 10.1378/chest.113.1.25 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YR103 UT WOS:000071458600009 PM 9440563 ER PT J AU Sugarbaker, DJ Norberto, JJ AF Sugarbaker, DJ Norberto, JJ TI Multimodality management of malignant pleural mesothelioma SO CHEST LA English DT Article; Proceedings Paper CT International Symposium on Thoracic Malignancies CY APR 25-26, 1996 CL PITTSBURGH, PENNSYLVANIA SP Univ Pittsburgh, Sch Med, Ctr Continuing Educ Hlth Sci, Univ Pittsburgh, Canc Inst ID EXTRAPLEURAL PNEUMONECTOMY; DIFFUSE; THERAPY; CHEMOTHERAPY; TRIAL AB In this article, we explain the current trimodality approach used to treat malignant pleural mesothelioma. Our current approach employs extrapleural pneumonectomy as the cytoreductive procedure followed by combination chemoradiotherapy. Trimodality therapy was performed at the Dana-Farber Cancer Institute/Brigham and Women's Hospital Thoracic Oncology Program. From 1980 to 1995, we prospectively followed up a series of 120 patients with confirmed malignant pleural mesothelioma who underwent trimodality therapy. Two- and 5-year survival rates for the entire cohort were 45% and 22%, respectively. Survival rates were 65% and 27%, respectively, at 2 and 5 years for patients with epithelial histology. Patients with sarcomatous or mixed histology had the poorest prognosis, with 2- and 5-year survival rates of 20% and 0%, respectively. For patients with epithelial tumors and negative nodes, survival at 2 and 5 years was 74% and 39%, respectively. Extrapleural pneumonectomy in the context of trimodality therapy is a potential surgical option for a selected group of patients with malignant pleural mesothelioma. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Div Surg Serv, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. NR 22 TC 49 Z9 49 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 JAN PY 1998 VL 113 IS 1 SU S BP 61S EP 65S DI 10.1378/chest.113.1_Supplement.61S PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YT302 UT WOS:000071587100012 PM 9438692 ER PT J AU Elias, A AF Elias, A TI Dose-intensive therapy in small cell lung cancer SO CHEST LA English DT Article; Proceedings Paper CT International Symposium on Thoracic Malignancies CY APR 25-26, 1996 CL PITTSBURGH, PENNSYLVANIA SP Univ Pittsburgh, Sch Med, Ctr Continuing Educ Hlth Sci, Univ Pittsburgh, Canc Inst ID AUTOLOGOUS BONE-MARROW; COMBINED-MODALITY THERAPY; COLONY-STIMULATING FACTOR; METASTATIC BREAST-CANCER; DISEASE-FREE SURVIVAL; PHASE-I; BRONCHOGENIC-CARCINOMA; INTENSIFICATION THERAPY; SOLID TUMORS; COMBINATION CHEMOTHERAPY AB Basic to curative treatment for small cell lung cancer (SCLC) are the principles of dose response, combination chemotherapy, and combined-modality therapy. Theory and experimental and clinical data suggest that solid tumors recur, despite initially responding to chemotherapy due to drug resistance. Resistance to chemotherapy is potentially overcome by using 5- to 10-fold higher doses. To decrease the emergence of drug resistance, combinations of active non-cross-resistant agents are used. Hematopoietic stem cell support provides the opportunity to test dose response to the limits of organ tolerance. Dose-intensive therapy for lung cancer patients is complicated by the fact that this disease most often occurs in an older-aged population (median, 60 to 65 years) with underlying smoking-related comorbid disease, early metastatic spread, and enhanced risk of secondary smoking-related malignancies. In a phase II feasibility trial just activated, patients younger than 60 years of age with limited-stage SCLC are being treated with four cycles of cisplatin and etoposide and concurrent mice-daily chest radiotherapy to 45 Gy (150-cGy fractions). Those patients achieving complete or near-complete response will receive high-dose cyclophosphamide/cisplatin/ carmustine with autologous stem cell support. Upon recovery, prophylactic cranial irradiation will be given. Results could lead to a phase III trial testing the concept of dose intensification. This article reviews evidence for the contribution of dose intensification to response and survival in the treatment of SCLC, the adequacy of the clinical trial's design to address these relationships, and suggestions for future directions. The strategies of dose-intensive induction therapy, multicycle dose-intensive combination therapies, chest radiography, and stem cell purging trials will be discussed. C1 Dana Farber Canc Inst, Div Clin Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Elias, A (reprint author), Dana Farber Canc Inst, Div Clin Pharmacol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 13849] NR 78 TC 8 Z9 8 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 1998 VL 113 IS 1 SU S BP 101S EP 106S DI 10.1378/chest.113.1_Supplement.101S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YT302 UT WOS:000071587100018 PM 9438698 ER PT J AU O'Toole, JE Esseltine, D Lynch, TJ Lambert, JM Grossbard, ML AF O'Toole, JE Esseltine, D Lynch, TJ Lambert, JM Grossbard, ML TI Clinical trials with blocked ricin immunotoxins SO CLINICAL APPLICATIONS OF IMMUNOTOXINS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; PHASE-I TRIAL; B-CELL NEOPLASMS; ANTI-B4-BLOCKED RICIN; BONE-MARROW; MULTIDRUG-RESISTANT; CONTINUOUS INFUSION; A-CHAIN; THERAPY; ANTIBODY C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. ImmunoGen Inc, Cambridge, MA 02139 USA. RP O'Toole, JE (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. NR 51 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1998 VL 234 BP 35 EP 56 PG 22 WC Immunology; Microbiology SC Immunology; Microbiology GA BM12S UT WOS:000077723000003 PM 9670611 ER PT J AU Weiss, GR Poggesi, I Rocchetti, M DeMaria, D Mooneyham, T Reilly, D Vitek, LV Whaley, F Patricia, E Von Hoff, DD O'Dwyer, P AF Weiss, GR Poggesi, I Rocchetti, M DeMaria, D Mooneyham, T Reilly, D Vitek, LV Whaley, F Patricia, E Von Hoff, DD O'Dwyer, P TI A phase I and pharmacokinetic study of tallimustine [PNU152241 (FCE 24517)] in patients with advanced cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ANTITUMOR-ACTIVITY; NITROGEN-MUSTARD; DISTAMYCIN-A; DNA; FCE-24517; RESISTANT; BINDING; AGENTS AB Tallimustine [PNU 152241 (FCE 24517)] is a synthetic derivative of the DNA minor groove binder distamycin A, in which the NH2-terminal formyl group is substituted by benzoyl mustard, In this Phase I clinical trial, patients with advanced solid tumors received i.v. bolus injections of tallimustine daily for 3 consecutive days, Patients were treated at six dosage levels of 33.3 mu g/m(2)/day to 250 (mu g/m(2)/day for 3 consecutive days, with courses of therapy repeated every 28 days, Detailed pharmacokinetic blood sampling was performed during the first 3 days of the first course of tallimustine, The plasma samples were analayzed by high-performance liquid chromatography with UV detection, Forty-eight eligible patients were treated at all six dosage levels, The dominant dose-related toxicity of tallimustine was neutropenia, becoming dose limiting at 250 mu g/m(2)/day. At this dosage level, one patient experienced febrile neutropenia, and a second patient died on study of indeterminate cause, Thrombocytopenia was not observed, and only 10 patients developed anemia <8.0 gm/dl, Sporadic elevation of liver enzymes or bilirubin was observed but was not dose related. Pharmacokinetic analysis gave reliable results for 33 patients, For most patients, analysis of the data best fit a three-exponential model, Dose-related increases in areas under the concentration-time curve and end-of-infusion concentrations were observed, There was no significant plasma accumulation of tallimustine over the 3 days of administration, The terminal half-life of tallimustine in individual patients ranged from 6.83 to 39.02 h following the last dose, In summary, the recommended Phase II dosage for tallimustine is 200 mu g/m(2)/day for 3 consecutive days every 28 days, Neutropenia is the principal toxicity of this agent at this dosage and schedule. C1 Univ Texas, Hlth Sci Ctr, Div Med Oncol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Sect, San Antonio, TX USA. Pharmacia & Upjohn, Nerviano, Italy. Fox Chase Canc Ctr, Fox Chase, PA USA. Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. RP Weiss, GR (reprint author), Univ Texas, Hlth Sci Ctr, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 18 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 1998 VL 4 IS 1 BP 53 EP 59 PG 7 WC Oncology SC Oncology GA YT599 UT WOS:000071623200008 PM 9516952 ER PT J AU Bao, L Loda, M Zetter, BR AF Bao, L Loda, M Zetter, BR TI Thymosin beta 15 expression in tumor cell lines with varying metastatic potential SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE carcinomas; gene expression; metastasis; thymosin beta 15 ID MOTILITY; CANCER; ACTIN; CARCINOMA; TISSUES; SITE; GENE AB We previously isolated thymosin beta 15 from highly metastatic Dunning rat prostatic carcinoma cells. Immunohistochemical study of human prostate cancer specimens revealed a general correlation between Gleason grade and thymosin beta 15 expression,,vith high-grade (more malignant) tumors showing increased staining compared to low-grade tumors. To determine whether thymosin beta 15 may be differentially expressed in cancer cells with different metastatic potential other than in the prostatic carcinoma cells, we examined thymosin beta 15 mRNA levels in tumor cell lines from different species. We also examined thymosin beta 15 protein levels in human breast cancer samples. Thymosin beta 15 was upregulated in the highly metastatic mouse lung and human breast cancer cell lines in comparison to the nonmetastatic counterparts. Immunohistochemical staining showed the evidence of upregulation of thymosin beta 15 in malignant human breast carcinomas as compared to benign breast tumors. The expression of thymosin beta 15 was correlated with the metastatic potential of the mouse lung carcinoma and human breast carcinoma cells in addition to the prostatic carcinomas. Thymosin beta 15 may be a useful marker to predict metastatic potential of certain human cancers. (C) 1998 Lippincott-Raven Publishers. C1 Harvard Univ, Sch Med, Dept Surg & Cell Biol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Isreal Deaconess Med Ctr, Boston, MA 02115 USA. RP Zetter, BR (reprint author), Harvard Univ, Sch Med, Dept Surg & Cell Biol, Childrens Hosp, Enders 1074,300 Longwood Ave, Boston, MA 02115 USA. EM zetter@a1.tch.harvard.edu FU NCI NIH HHS [CA37393] NR 24 TC 42 Z9 43 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 1998 VL 16 IS 3 BP 227 EP 233 DI 10.1023/A:1006540824969 PG 7 WC Oncology SC Oncology GA ZF952 UT WOS:000072949700003 PM 9568640 ER PT J AU Smith, DN Shaffer, K Patz, EF AF Smith, DN Shaffer, K Patz, EF TI Imaging features of nonmyxomatous primary neoplasms of the heart and pericardium SO CLINICAL IMAGING LA English DT Article DE cardiac neoplasms; echocardiography; computed tomography; magnetic resonance imaging ID PRIMARY CARDIAC TUMORS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; MASSES; ANGIOSARCOMA; DIAGNOSIS; SARCOMAS AB We present the imaging findings in 13 patients with nonmyxomatous primary neoplasms of the heart and pericardium, Ten patients had abnormal chest films. While echocardiography was useful for determining origin of the tumor, CT (computed tomography) and MRI (magnetic resonance imaging) were better at delineating extent of disease. The radiographic appearance of these rare neoplasms of the heart and pericardium is varied. Cross-sectional imaging plays a crucial role in the surgical planning and management of these patients. (C) Elsevier Science Inc., 1998. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Duke Univ, Dept Radiol, Durham, NC 27710 USA. RP Smith, DN (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St,L-1, Boston, MA 02115 USA. NR 29 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD JAN-FEB PY 1998 VL 22 IS 1 BP 15 EP 22 DI 10.1016/S0899-7071(97)00070-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YM016 UT WOS:000071019000004 PM 9421650 ER PT J AU Craig, WA AF Craig, WA TI Pharmacokinetic/pharmacodynamic parameters: Rationale for antibacterial dosing of mice and men SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACUTE OTITIS-MEDIA; GRAM-NEGATIVE BACILLI; STREPTOCOCCUS-PNEUMONIAE; THERAPEUTIC EFFICACY; KLEBSIELLA-PNEUMONIAE; PEAK CONCENTRATION; INFECTION MODELS; THIGH-INFECTION; ANTIBIOTICS; INVIVO C1 William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI 53705 USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 64 TC 1582 Z9 1642 U1 11 U2 73 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 JAN PY 1998 VL 26 IS 1 BP 1 EP 10 DI 10.1086/516284 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YR235 UT WOS:000071474500001 PM 9455502 ER PT J AU Pegues, DA Colby, C Hibberd, PL Cohen, LG Ausubel, FM Calderwood, SB Hooper, DC AF Pegues, DA Colby, C Hibberd, PL Cohen, LG Ausubel, FM Calderwood, SB Hooper, DC TI The epidemiology of resistance to ofloxacin and oxacillin among clinical coagulase-negative staphylococcal isolates: Analysis of risk factors and strain types SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID METHICILLIN-RESISTANT; CIPROFLOXACIN-RESISTANT; QUINOLONE RESISTANCE; DNA GYRASE; UNITED-STATES; AUREUS; EPIDERMIDIS; FLUOROQUINOLONES; MUTATIONS; EMERGENCE AB Coagulase-negative staphylococci are important nosocomial pathogens that increasingly are resistant to oxacillin and fluoroquinolones. To determine predictors of acquisition of oxacillin and ofloxacin resistance, we prospectively identified 150 patients from whose clinical specimens coagulase-negative staphylococci were isolated that differed in susceptibility to oxacillin and ofloxacin. In multivariate analysis, isolation of ofloxacin-resistant coagulase-negative staphylococci was associated with receipt of aminoglycosides (odds ratio [OR] = 8.45; 95% confidence interval [CI] = 2.10-34.1; P = .001) and fluoroquinolones (OR = 11.50; 95% CI = 4.15-31.6; P < .001) within 30 days; oxacillin resistance was associated with prior receipt of beta-lactam agents (OR = 5.99; 95% CI = 2.91-12.3; P < .001), Among oxacillin-resistant strains, there was heterogeneity of pulsed-field gel electrophoresis (PFGE) types, and no type was common between ofloxacin-resistant and ofloxacin-susceptible strains. Thus ofloxacin resistance may have emerged de novo among diverse oxacillin-resistant strains following the selection pressures of antimicrobial therapy, In contrast, 50% of patients with oxacillin susceptible/ofloxacin-resistant strains had one of two PFGE types, a finding suggesting that person-to-person transmission resulted in the dissemination of some of these strains. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pharm,Infect Dis Div,Infect Control Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biol Mol, Boston, MA 02114 USA. Northeastern Univ, Bouve Coll Pharm, Dept Pharm Practice, Boston, MA 02115 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pharm,Infect Dis Div,Infect Control Unit, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI23988, 5F32AI08873] NR 40 TC 15 Z9 15 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1998 VL 26 IS 1 BP 72 EP 79 DI 10.1086/516270 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YR235 UT WOS:000071474500012 PM 9455512 ER PT J AU Tsao, HS Sober, AJ AF Tsao, HS Sober, AJ TI Ultraviolet radiation and malignant melanoma SO CLINICS IN DERMATOLOGY LA English DT Article ID INDUCED PYRIMIDINE DIMERS; SQUAMOUS-CELL CARCINOMA; EORTC CASE-CONTROL; CUTANEOUS MELANOMA; RISK-FACTORS; SKIN-CANCER; SUN EXPOSURE; MONODELPHIS-DOMESTICA; TRANSGENIC MICE; ACTIVATED RAS C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Tsao, HS (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett Hall,6th Floor, Boston, MA 02114 USA. NR 77 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD JAN-FEB PY 1998 VL 16 IS 1 BP 67 EP 73 DI 10.1016/S0738-081X(97)00191-0 PG 7 WC Dermatology SC Dermatology GA YT997 UT WOS:000071669500012 PM 9472435 ER PT S AU Kosofsky, BE Wilkins, AS AF Kosofsky, BE Wilkins, AS BE Harvey, JA Kosofsky, BE TI A mouse model of transplacental cocaine exposure - Clinical implications for exposed infants and children SO COCAINE: EFFECTS ON THE DEVELOPING BRAIN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cocaine - Effects on the Developing Brain CY SEP 16-19, 1997 CL WASHINGTON, D.C. SP New York Acad Sci, Allegheny Univ Hlth Sci, Natl Inst Drug Abuse, Nat Inst Child & Human Dev, NIMH, March Dimes, Culpeper Fdn ID PRENATAL COCAINE; SELECTIVE ATTENTION; GESTATIONAL COCAINE; CEREBRAL-CORTEX; ADULT-RATS; IN-UTERO; BEHAVIOR; PREGNANCY; CONSEQUENCES; MECHANISMS AB To characterize the effects of cocaine on developing brain me have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food nd libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting a-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dame. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior, Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero. C1 Massachusetts Gen Hosp East, Lab Mol & Dev Neurosci, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kosofsky, BE (reprint author), Massachusetts Gen Hosp East, Lab Mol & Dev Neurosci, 149 13th St, Boston, MA 02129 USA. EM Kosofsky@helix.mgh.harvard.edu; Kosofsky@helix.mgh.harvard.edu FU NIDA NIH HHS [DA00175, DA08648] NR 67 TC 35 Z9 35 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-127-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 846 BP 248 EP 261 DI 10.1111/j.1749-6632.1998.tb09742.x PG 14 WC Substance Abuse; Developmental Biology; Multidisciplinary Sciences; Clinical Neurology SC Substance Abuse; Developmental Biology; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26F UT WOS:000074931100020 PM 9668412 ER PT J AU Schnitzler, GR Sif, S Kingston, RE AF Schnitzler, GR Sif, S Kingston, RE TI A model for chromatin remodeling by the SWI SNF family SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT Cold Spring Harbor Symposium on Quantitative Biology - Mechanisms of Transcription CY 1998 CL NEW YORK, NEW YORK SP Amgren Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med Inc, Diagnost Prod Corp, Forest Labs Inc, Genentech Inc, Genet Inst, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Kyowa Hakko Kogyo Co Ltd, Eli Lilly & Co, Merck Genome Res Inst, Novartis Pharma Res, Novo Nardisk Biotech Inc, ZymoGenet Inc, OSI Pharmaceut Inc, Pall Corp, Paarke Davis Pharmaceut Res, Perkin Elmer Corp, Appl Biosyst Div, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Scherring Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC, Plant Corp Associates, Amer Cyanamid Co, Monsanto Co, Pioneer Hi-Bred Int Inc, Westvaco Corp ID YEAST SWI/SNF COMPLEX; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID RECEPTOR; RETINOBLASTOMA PROTEIN; NUCLEOSOME DISRUPTION; ESTROGEN-RECEPTOR; HUMAN HOMOLOGS; BINDING; DNA; FORM C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Schnitzler, GR (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 39 TC 15 Z9 15 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1998 VL 63 BP 535 EP 543 DI 10.1101/sqb.1998.63.535 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 208MJ UT WOS:000080994900056 PM 10384318 ER PT J AU Gray, RJ AF Gray, RJ TI On regression analysis with incomplete covariate data SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE missing at random; prognostic factors; penalized likelihood AB Approximate likelihoods are considered for regression analysis with covariate data missing at random. The methods are based on discrete approximations to the covariate distribution. In the first approximation, the covariate distribution is assumed to be concentrated on the observed complete ca,ses, with kernel averaging used for the likelihood contribution of partially complete cases. The second method places the mass of the covariate distribution on a discrete grid of points, and uses a penalty function to regularize the covariate distribution estimator. Simulations indicate the methods give reasonably good performance for estimated parameters, but that inferences based on large sample approximations may not be reliable. C1 Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. NR 12 TC 1 Z9 1 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 1998 VL 27 IS 11 BP 2641 EP 2662 DI 10.1080/03610929808832247 PG 22 WC Statistics & Probability SC Mathematics GA 132YD UT WOS:000076658500002 ER PT J AU Bisnett, T Anzueto, A Andrade, FH Rodney, GG Napier, WR Levine, SM Maxwell, LC Mureeba, P Derdak, SD Grisham, MB Jenkinson, SG AF Bisnett, T Anzueto, A Andrade, FH Rodney, GG Napier, WR Levine, SM Maxwell, LC Mureeba, P Derdak, SD Grisham, MB Jenkinson, SG TI Effect of nitric oxide synthase inhibitor on diaphragmatic function after resistive loading SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Experimental-Biology on Structure and Function in Comparative Physiology - a Tribute to Pierre Laurent CY MAR 25-26, 1996 CL UNIV LANCASTER, LANCASTER, ENGLAND SP Soc Expt Biol, Anim Respirat & Osmoregulat Grp HO UNIV LANCASTER DE nitric oxide; N-omega-nitro-L-arginine-methyl-ester; diaphragmatic fatigue; resistive loading ID SKELETAL-MUSCLE; REACTIVE OXYGEN; RAT DIAPHRAGM; INVITRO; FLOW AB We studied the effect of a nitric oxide synthase inhibitor, N-omega-Nitro-L-arginine-methyl-ester (L-NAME), on in vitro diaphragmatic function both at rest (control) or after inspiratory resistive loading (IRL). Sprague-Dawley rats were anesthetized, instrumented, and then the following experimental groups: (1) controls; (2) L-NAME (100 mg/kg/body weight intravenously alone); (3) IRL alone; and (4) L-NAME + IRL. The IRL protocol consisted of applying a variable resistor to the inspiratory limb of a two-way valve at 70% of maximal airway pressure until apnea. After the experiment, the animals were sacrificed and diaphragmatic strips were obtained for activity of constitutive nitric oxide synthase (cNOS) and measurements of in vitro contractile properties: tetanic (Po) and twitch tensions (Pt). cNOS activity was significantly decreased in the L-NAME and L- NAME + IRL groups (P less than or equal to 0.05) as compared with control and IRL groups. L-NAME alone did not affect Po or Pt. However, in both IRL groups, with and without was a significant decrease in Po and Pt. This reduction was comparable in both groups. In summary, our data showed that L-NAME resulted in a significant decrease cNOS activity, bur. in vitro contractility was impaired, COMP BIOCHEM PHYSIOL 119A;1:185-190, 1998. (C) 1998 Elsevier Science Inc. C1 Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Pulm Dis Sect 111E, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Louisiana State Univ, Shreveport, LA 71105 USA. RP Anzueto, A (reprint author), Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Pulm Dis Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Andrade, Francisco/F-1258-2011 OI Andrade, Francisco/0000-0002-2460-5798 NR 26 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD JAN PY 1998 VL 119 IS 1 BP 185 EP 190 DI 10.1016/S1095-6433(97)00420-0 PG 6 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA ZZ685 UT WOS:000074756400022 PM 11253784 ER PT J AU Holz, GG Turner, TJ AF Holz, GG Turner, TJ TI Pertussis toxin-sensitive GTP-binding proteins characterized in synaptosomal fractions of embryonic avian cerebral cortex SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE G protein; pertussis toxin; neuron; synapse ID GUANINE-NUCLEOTIDE-BINDING; ISLET-ACTIVATING PROTEIN; BETA-GAMMA-SUBUNITS; ADP-RIBOSYLATION; ADENYLATE-CYCLASE; ALPHA-SUBUNIT; BOVINE BRAIN; IMMUNOLOGICAL CHARACTERIZATION; REGULATORY COMPONENT; ADENINE-NUCLEOTIDES AB Pertussis toxin (PTX)-sensitive GTP-binding proteins (G proteins) are essential intermediaries subserving neuronal signal transduction pathways that regulate excitation-secretion coupling. Despite this established role, relatively little is known regarding the identity, subcellular distribution, and relative abundance of this class of G proteins in synaptic nerve endings. Here, sucrose density gradient centrifugation was combined with 1- and 2-dimensional gel electrophoresis to characterize PTX-sensitive G protein alpha subunits in synaptosomal fractions of embryonic (day 12) chick cerebral cortical homogenates. These findings demonstrate multiple isoforms of M(r) 40-41 kDa G(i alpha) and G(o alpha) subunits that can be identified on the basis of PTX-catalyzed ADP-ribosylation and immunoblot analysis. (C) 1998 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. RP Holz, GG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Wellman 320,50 Blossom St, Boston, MA 02114 USA. EM holz@helix.mgh.harvard.edu RI Holz, George/A-3386-2012; OI Turner, Timothy/0000-0001-9770-2647 FU NIDDK NIH HHS [DK45817, R01 DK045817-06A2, DK52166, R01 DK045817] NR 55 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 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JAN PY 1998 VL 119 IS 1 BP 201 EP 211 DI 10.1016/S0305-0491(97)00308-8 PG 11 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA YZ715 UT WOS:000072283600023 PM 9530821 ER PT S AU Grimes, RY Yoganathan, AP Levine, RA AF Grimes, RY Yoganathan, AP Levine, RA BE Murray, A Swiryn, S TI Dimensional analysis applied to the evaluation of LV function in the presence of mitral regurgitation: Computer simulations SO COMPUTERS IN CARDIOLOGY 1998, VOL 25 SE COMPUTERS IN CARDIOLOGY LA English DT Proceedings Paper CT 25th Annual Meeting on Computers in Cardiology CY SEP 13-16, 1998 CL CLEVELAND, OH SP IEEE, Engn Med & Biol, European Soc Cardiol, Cleveland Clin Fdn, Dept Cardiol, Int Ctr, NASA AB Traditional indices of LV function do not accurately reflect the true contractile state in mitral regurgitation (MR) because the low impedance systolic MR flow allows the LV ejection fraction (EF) to remain normal despite LV contractile dysfunction. It would therefore be useful to have method for predicting the EF if MR is eliminated from a given ventricle assuming contractility and blood pressure do not change. A computer model was wed to simulate ventricular hemodynamics in the presence and absence of MR. The data were then analyzed using dimensional analysis, a technique for combining;multiple variables into a compact formulation. Dimensional analysis revealed that the data could be collapsed into a single equation. This formulation potentially permits ejection fraction calculations that are corrected for the degree of MR from a specified set of ventricular function indices. Validation inpatients is the next step. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Grimes, RY (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,VBK-508, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 0-7803-5200-9 J9 COMPUT CARDIOL PY 1998 VL 25 BP 245 EP 248 DI 10.1109/CIC.1998.731779 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Medical Informatics; Medical Laboratory Technology; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Engineering; Medical Informatics; Medical Laboratory Technology; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BM07Z UT WOS:000077557100062 ER PT B AU Jain, RK AF Jain, RK BE Reed, RK Rubin, K TI Microcirculation and transport phenomena in tumours SO CONNECTIVE TISSUE BIOLOGY: INTEGRATION AND REDUCTIONISM SE WENNER-GREN INTERNATIONAL SERIES LA English DT Proceedings Paper CT Wenner-Gren Symposium on Connective Tissue Biology - Integration and Reductionism CY JUN, 1996 CL STOCKHOLM, SWEDEN SP Wenner Gren Fdn C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND BN 1-85578-118-2 J9 WENN GR INT PY 1998 VL 71 BP 269 EP 293 PG 25 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA BK35X UT WOS:000071899100021 ER PT J AU Hu, CC Simmer, JP Bartlett, JD Qian, Q Zhang, C Ryu, OH Xue, J Fukae, M Uchida, T MacDougall, M AF Hu, C. -C. Simmer, J. P. Bartlett, J. D. Qian, Q. Zhang, C. Ryu, O. H. Xue, J. Fukae, M. Uchida, T. MacDougall, M. TI Murine Enamelin: cDNA and Derived Protein Sequences SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE Enamelin; enamel; tooth; biomineralization AB Enamelin is the largest enamel protein. Recently we reported the characterization of a cDNA clone encoding porcine enamelin. The secreted protein has 1104 amino acids-over 6 times the length of amelogenin (173 amino acids) and almost 3 times the lengths of sheathlin (395 amino acids) and tuftelin (389 amino acids). Immunohistochemistry has shown that uncleaved porcine enamelin concentrates at the growing tips of the enamel crystallites while its cleavage products localize to rod and interrod enamel. Here we report the isolation and characterization of cDNA encoding murine amelogenin and demonstrate the tooth specificity of porcine enamelin. The murine clone is 4154 nucleotides in length and encodes a protein of 1274 amino acids. In the absence of post-translational modifications murine enamelin has an isotope averaged molecular mass of 137 kDa and an isoelectric point of 9.4. Multiple tissue Northern blot analyses detect porcine enamelin mRNA in developing teeth but not in liver, heart, brain, spleen, skeletal muscle and lung. Mouse and porcine enamelin share 61% amino acid identity and 75% DNA sequence identity. Mouse enamelin has 14 tandemly arranged copies of an 11 amino acid segment that is found only once in porcine enamelin. C1 [Hu, C. -C.; Simmer, J. P.; Qian, Q.; Zhang, C.; Ryu, O. H.; MacDougall, M.] Univ Texas Hlth Sci Ctr San Antonio, Sch Dent, Dept Pediat Dent, San Antonio, TX 78284 USA. [Bartlett, J. D.; Xue, J.] Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. [Fukae, M.] Tsurumi Univ, Sch Dent Med, Dept Biochem, Tsurumi Ku, Yokohama, Kanagawa 230, Japan. [Uchida, T.] Hiroshima Univ, Sch Dent, Dept Anat, Minami Ku, Hiroshima, Japan. RP Hu, CC (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM huj@uthscsa.edu FU NIDCR NIH HHS [DE09875, DE10721, DE11301, R29 DE012098] NR 26 TC 18 Z9 19 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1998 VL 39 IS 1-3 BP 47 EP 61 DI 10.3109/03008209809023911 PG 15 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA V13AS UT WOS:000207640300008 PM 11062988 ER PT J AU Bartlett, JD Ryu, OH Xue, J Simmer, JP Margolis, HC AF Bartlett, John D. Ryu, Ok Hee Xue, Jun Simmer, James P. Margolis, Henry C. TI Enamelysin mRNA Displays a Developmentally Defined Pattern of Expression and Encodes a Protein which Degrades Amelogenin SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE Matrix metalloproteinase; prokaryotic expression; zymography; dental enamel; dentin AB Previously, a cDNA encoding a novel matrix metalloproteinase (enamelysin) was isolated from a porcine enamel organ-specific cDNA library. The cloned mRNA is tooth-specific and contains an open reading frame encoding a protein composed of 483 amino acids (Gene, 183:(1-2), p123-128, 1996). Here, we show that: 1) The expression of enamelysin mRNA is not limited to the enamel organ as previously reported. The enamelysin message is also expressed at very low levels in the pulp organ. 2) Northern analysis reveals that the enamelysin mRNA displays a developmentally defined pattern of expression in the enamel organ. The message is expressed at relatively high levels during the pre-secretory and early transition stages of development. However, during late maturation, the quantity of enamelysin mRNA is greatly reduced. Conversely, the low message levels in the pulp organ remain relatively constant throughout these developmental stages. 3) The enamelysin cDNA was ligated into a prokaryotic expression vector and recombinant enamelysin containing a His tag was purified from E. coli. Zymographic analysis utilizing recombinant murine amelogenin as the substrate, reveals that the purified enamelysin degrades amelogenin. Since enamelysin is developmentally regulated and is capable of degrading amelogenin, it is likely to play a significant role during enamel bio-mineralization. C1 [Bartlett, John D.; Xue, Jun; Margolis, Henry C.] Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. [Ryu, Ok Hee; Simmer, James P.] Univ Texas San Antonio, Dept Pediat Dent, San Antonio, TX 78284 USA. RP Bartlett, JD (reprint author), Forsyth Dent Ctr, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org FU NIDCR NIH HHS [DE-12098, R29 DE012098] NR 30 TC 35 Z9 37 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1998 VL 39 IS 1-3 BP 101 EP + DI 10.3109/03008209809023916 PG 11 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA V13AS UT WOS:000207640300013 PM 11062992 ER PT J AU Scully, JL Bartlett, JD Chaparian, MG Fukae, M Uchida, T Xue, J Hu, CC Simmer, JP AF Scully, J. L. Bartlett, J. D. Chaparian, M. G. Fukae, M. Uchida, T. Xue, J. Hu, C. -C. Simmer, J. P. TI Enamel Matrix Serine Proteinase 1: Stage-Specific Expression and Molecular Modeling SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE Enamel; serine proteinase; EMSP1; amelogenin; porcine AB Enamel proteins are cleaved by proteinases soon after their secretion by ameloblasts. Intact proteins concentrate in the outer enamel at or near the growing tips of the enamel crystallites while cleavage products accumulate in the deeper enamel. In the transition and early maturation stages there is a dramatic increase in proteolytic activity. This activity, coupled with the diminished secretory and increased reabsorptive functions of ameloblasts, leads to a precipitous fall in the amount of enamel protein in the matrix. Recently we have cloned and characterized an mRNA encoding a tooth-specific serine proteinase designated enamel matrix serine proteinase 1 (EMSP1) [Simmer et al., JDR (1998) 77: 377]. EMSP1 can be detected in the inner enamel during the secretory stage and its activity increases sharply during the transition stage. Stage-specific Northern blot analysis demonstrates this increase is accompanied by a parallel increase in the amount EMSP1 mRNA. A 3-dimensional computer model of EMSP1, based upon the crystal structure of bovine trypsin, has been generated and analyzed. AN six disulfide bridges as well as the active site are conserved. Changes in the peptide binding region and the specificity pocket suggest that interaction of the proteinase with protein substrates is altered, potentially causing a shift in substrate specificity. The calcium binding region of trypsin is thoroughly modified suggesting that the calcium independence of EMSPl activity is due to an inability to bind calcium. The three potential N-linked glycosylation sites, N104, N139 and N184, are in surface accessible positions away from the active site. C1 [Hu, C. -C.; Simmer, J. P.] Univ Texas Hlth Sci Ctr San Antonio, Sch Dent, Dept Pediat Dent, San Antonio, TX 78284 USA. [Scully, J. L.] Greenhills, Dept Chem, Ann Arbor, MI USA. [Bartlett, J. D.; Xue, J.] Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. [Chaparian, M. G.] OmniSci Pharmaceut Inc, Troy, MI 48098 USA. [Fukae, M.] Tsurumi Univ, Sch Dent Med, Dept Biochem, Tsurumi Ku, Yokohama, Kanagawa 230, Japan. [Uchida, T.] Hiroshima Univ, Sch Dent, Dept Anat, Minami Ku, Hiroshima, Japan. RP Simmer, JP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE 10721, R29 DE012098] NR 46 TC 16 Z9 19 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1998 VL 39 IS 1-3 BP 111 EP + DI 10.3109/03008209809023917 PG 15 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA V13AS UT WOS:000207640300014 PM 11062993 ER PT J AU Robinson, C Boyde, A Hubbard, MJ Rosenbloom, J Deutsch, D Bonass, WA MacDougall, M Paine, CT Lee Snead, ML Wright Bartlett, JD Bashir, MM Zeichner-David, M Gibson, C Simmer, JP Mednieks, MI AF Robinson, C Boyde, A Hubbard, MJ Rosenbloom, J Deutsch, D Bonass, WA MacDougall, M Paine, CT Lee Snead, ML Wright Bartlett, JD Bashir, MM Zeichner-David, M Gibson, C Simmer, JP Mednieks, MI TI Session 6: Ameloblast gene products: 2 - Discussion SO CONNECTIVE TISSUE RESEARCH LA English DT Editorial Material C1 Univ Leeds, Sch Dent, Dept Oral Biol, Leeds LS2 9LU, W Yorkshire, England. UCL, Dept Anat & Dev Biol, London WC1E 6BT, England. Univ Otago, Dept Biochem, Dunedin, New Zealand. Univ Penn, Sch Dent Med, Dept Anat & Histol, Philadelphia, PA 19104 USA. Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Jerusalem, Israel. Univ Texas, Dept Pediat Dent, Sch Dent, San Antonio, TX 78284 USA. Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. NIDR, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC 27599 USA. Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. Univ Illinois, Coll Dent, Dept Oral Biol, Chicago, IL 60612 USA. RP Robinson, C (reprint author), Univ Leeds, Sch Dent, Dept Oral Biol, Clarendon Way, Leeds LS2 9LU, W Yorkshire, England. RI Zeichner-David, Margarita/A-6567-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1998 VL 38 IS 1-4 BP 295 EP 303 PG 9 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 145WF UT WOS:000077394100034 ER PT S AU Nathan, DG AF Nathan, DG BE Cohen, AR TI Summary of the Seventh Cooley's Anemia Symposium SO COOLEYS ANEMIA: SEVENTH SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th Cooleys Anemia Symposium CY MAY 30-JUN 02, 1997 CL CAMBRIDGE, MASSACHUSETTS SP New York Acad Sci, Cooleys Anemia Fdn, NIH, NHLBI, NIH, Natl Inst Diabet & Digest & Kidney Dis, Apotex Res Inc, NIH, NICHHD C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-121-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 850 BP 374 EP 376 DI 10.1111/j.1749-6632.1998.tb10496.x PG 3 WC Genetics & Heredity; Hematology; Multidisciplinary Sciences; Transplantation SC Genetics & Heredity; Hematology; Science & Technology - Other Topics; Transplantation GA BL26J UT WOS:000074933900041 ER PT J AU Coulter, S Picard, MH AF Coulter, S Picard, MH TI Contrast echocardiography in coronary artery disease SO CORONARY ARTERY DISEASE LA English DT Review DE echocardiography; myocardial perfusion; contrast agents; coronary artery disease ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; ACUTE-MYOCARDIAL-INFARCTION; SONICATED ALBUMIN MICROBUBBLES; LEFT-VENTRICULAR AREA; NO-REFLOW PHENOMENON; INTRAVENOUS-INJECTION; VENOUS INJECTION; ULTRASONIC CONTRAST; DEXTROSE ALBUMIN; CANINE MODEL C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Cardiac Unit, VBK508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 52 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PY 1998 VL 9 IS 7 BP 391 EP 398 DI 10.1097/00019501-199809070-00002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 136TR UT WOS:000076875700002 PM 9822858 ER PT J AU Fry, SJ Picard, MH AF Fry, SJ Picard, MH TI Transesophageal echocardiography: the evaluation of coronary artery disease SO CORONARY ARTERY DISEASE LA English DT Review DE echocardiography; transthoracic; transesophageal; coronary artery disease; perfusion ID DOBUTAMINE STRESS ECHOCARDIOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; PROTRUDING AORTIC ATHEROMAS; VENTRICULAR SEPTAL RUPTURE; FLOW RESERVE; CONTRAST ECHOCARDIOGRAPHY; DOPPLER-ECHOCARDIOGRAPHY; 2-DIMENSIONAL ECHOCARDIOGRAPHY; ATHEROSCLEROTIC LESIONS C1 Massachusetts Gen Hosp, Adult Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Fry, SJ (reprint author), Massachusetts Gen Hosp, Adult Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. EM fry.stefanie@mgh.harvard.edu OI Picard, Michael/0000-0002-9264-3243 NR 64 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PY 1998 VL 9 IS 7 BP 399 EP 410 DI 10.1097/00019501-199809070-00003 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 136TR UT WOS:000076875700003 PM 9822859 ER PT J AU Zapol, WM AF Zapol, WM TI Nitric oxide inhalation in acute respiratory distress syndrome: It works, but can we prove it? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute respiratory distress syndrome; inhaled nitric oxide; respiratory failure C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1998 VL 26 IS 1 BP 2 EP 3 DI 10.1097/00003246-199801000-00002 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA YP433 UT WOS:000071276300002 PM 9428529 ER PT J AU D'Andrea, A Pellman, D AF D'Andrea, A Pellman, D TI Deubiquitinating enzymes: A new class of biological regulators SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review ID UBIQUITIN-SPECIFIC PROTEASE; CARBOXYL-TERMINAL HYDROLASE; CHICK SKELETAL-MUSCLE; FAT-FACETS GENE; SACCHAROMYCES-CEREVISIAE; ISOPEPTIDASE-T; DROSOPHILA-MELANOGASTER; POLYUBIQUITIN CHAINS; FUNCTIONAL-ANALYSIS; DEGRADATION AB Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. Like protein phosphorylation, protein ubiquitination is dynamic, involving enzymes that add ubiquitin (ubiquitin conjugating enzymes) and enzymes that remove ubiquitin (deubiquitinating enzymes). Considerable progress has been made in the understanding of ubiquitin conjugation and its role in regulating protein degradation. Recent studies have demonstrated that regulation also occurs at the level of deubiquitination. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. Genome sequencing projects have identified many candidate deubiquitinating enzymes, making them the largest family of enzymes in the ubiquitin system. Deubiquitinating enzymes have significant sequence diversity and therefore may have a broad range of substrate specificities. Here we explore the structural and biochemical properties of deubiquitinating enzymes and their emerging roles as cellular switches. C1 Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Cellular & Mol Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Andrea, A (reprint author), Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 58 TC 195 Z9 198 U1 1 U2 23 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PY 1998 VL 33 IS 5 BP 337 EP 352 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 134UP UT WOS:000076762300001 PM 9827704 ER PT J AU Reddy, SV Roodman, GD AF Reddy, SV Roodman, GD TI Control of osteoclast differentiation SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE osteoclast; differentiation; hormones; cytokines; stromal cells; bone resorption; transcription factors ID COLONY-STIMULATING FACTOR; HUMAN MARROW CULTURES; GROWTH-FACTOR-BETA; CALCITONIN RECEPTOR ISOFORMS; PARATHYROID-HORMONE BINDING; GIANT-CELL TUMORS; BONE-RESORPTION; IN-VITRO; OSTEOBLASTIC CELLS; INHIBITS FORMATION AB The osteoclast is the primary bone-resorbing cell and is derived from the monocyte/macrophage lineage, Bipotent osteoclast precursors, which can form both osteoclasts and monocyte-macrophages, proliferate and differentiate to become unipotent post-mitotic committed osteoclast precursors. These post-mitotic committed precursors fuse to form the multinucleated osteoclast, which is then activated to resorb bone. A variety of soluble and membrane-bound factors play a critical role in regulating osteoclast formation, including growth factors, systemic hormones, and cells in the marrow microenvironment, such as osteoblasts and marrow stromal cells. Cell-to-cell interactions are important in both the formation and activity of the osteoclast. Recent molecular biological studies have identified transcription factors, such as c-fos and PU.I, which are required for osteoclast differentiation. In this review, we discuss the phenotypic changes that are induced as the cells mature from bipotent early precursors to mature osteoclasts; factors that have been identified that are involved in this process; and the role of marrow stromal cells and osteoblasts in osteoclast differentiation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78284 USA. Audie L Murphy Vet Adm Hosp, San Antonio, TX 78284 USA. FU NCI NIH HHS [CA-40035]; NIA NIH HHS [AG-13625]; NIAMS NIH HHS [AR39529] NR 114 TC 55 Z9 58 U1 0 U2 1 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 1998 VL 8 IS 1 BP 1 EP 17 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZZ684 UT WOS:000074756300001 PM 9673448 ER PT J AU Liber, HL Phillips, EN AF Liber, HL Phillips, EN TI Interrelationships between radiation-induced mutations and modifications in gene expression linked to cancer SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE radiation carcinogenesis; radiation-induced mutation; radiation-induced genomic instability; radiation-induced gene expression ID DELAYED REPRODUCTIVE DEATH; ATOMIC-BOMB SURVIVORS; GLYCOPHORIN-A LOCUS; INDUCED GENOMIC INSTABILITY; TUMOR-SUPPRESSOR GENE; MOUSE LYMPHOMA-CELLS; ABL TYROSINE KINASE; HAMSTER OVARY CELLS; WILD-TYPE P53; INDUCED CHROMOSOMAL INSTABILITY AB Ionizing radiation induces cancer in humans, but the mechanisms are not established. One simple way by which radiation could induce cancer is by inducing a genetic mutation in one or more of the multiple steps in the oncogenic pathway. However, many investigators favor the hypothesis that a mutator phenotype is necessary for a single cell to acquire the multiple genetic changes found in cancer. The alternative idea that ionizing radiation might induce an epigenetic heritable mutator phenotype has gained momentum in the last decade or so. A number of laboratories have observed a phenomenon termed 'delayed reproductive death', which is manifested as a reduced cloning efficiency, and also increased frequencies of gene locus mutations or chromosome aberrations that persist for many generations after radiation exposure. It is theorized that these endpoints arise due to a long-lived alteration in gene expression induced by radiation. Ionizing radiation is well known to induce gene expression, as it triggers the p53 pathway, as well as a series of early response genes, including c-jun and egr-1. However, there is no model from the gene expression field that could account for an epigenetic mutator effect that persists for tens or even hundreds of generations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Utah, Eccles Inst Human Genet, Dept Oncol Sci, Salt Lake City, UT 84112 USA. Univ Utah, Eccles Inst Human Genet, Dept Radiat Oncol, Salt Lake City, UT 84112 USA. NR 210 TC 9 Z9 9 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 1998 VL 8 IS 3-4 BP 257 EP 276 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 134XL UT WOS:000076769000002 PM 9807696 ER PT J AU Lanske, B Kronenberg, HM AF Lanske, B Kronenberg, HM TI Parathyroid hormone-related peptide (PTHrP) and parathyroid hormone (PTH)/PTHrP receptor SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE homologous recombination; cartilage; transplacental calcium transport; hedgehog; chondrodysplasia; rescue ID ENDOCHONDRAL BONE-FORMATION; PLACENTAL CALCIUM-TRANSPORT; MESSENGER RIBONUCLEIC-ACIDS; SONIC-HEDGEHOG; PTH/PTHRP RECEPTOR; PROTEIN PTHRP; CELL-LINE; METAPHYSEAL CHONDRODYSPLASIA; TERMINAL DIFFERENTIATION; HUMORAL HYPERCALCEMIA AB Parathyroid hormone-related peptide (PTHrP) has been identified as the factor responsible for the humoral hypercalcemia of malignancy (HHM). Since the cloning of the cDNA, it has become clear that PTHrP is a prohormone that is posttranslationally cleaved to yield a complex family of peptides. Through its homology to parathyroid hormone (PTH) in the amino-terminus region of the protein, it is able to bind to and activate a common PTH/PTHrP receptor. PTHrP has been shown to be a normal product of many adult and fetal tissues, where it appears to act in an autocrine/paracrine fashion to regulate organogenesis. PTHrP and the PTH/PTHrP receptor seem to be co-expressed in many tissues, but their role in the various systems is uncertain. The use of transgenic and knock-out animal models has contributed to a better understanding of the physiological role of this peptide and its receptor. In this review, the structure of their genes, their expression pattern, and some of their major physiological functions are discussed. Attention is focused on their interaction in the regulation of cartilage and bone development. C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 47038] NR 107 TC 35 Z9 35 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 1998 VL 8 IS 3-4 BP 297 EP 320 PG 24 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 134XL UT WOS:000076769000004 PM 9807698 ER PT J AU Greenfield, EA Nguyen, KA Kuchroo, VK AF Greenfield, EA Nguyen, KA Kuchroo, VK TI CD28/B7 costimulation: A review SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Review DE costimulation; CD28; B7; CTLA4 ID T-CELL ACTIVATION; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN-PRESENTING CELLS; SYSTEMIC LUPUS-ERYTHEMATOSUS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BONE-MARROW TRANSPLANTATION; RECEPTOR GAMMA-CHAIN; KINASE PHOSPHATIDYLINOSITOL 3-KINASE; LYMPHOCYTE-ASSOCIATED MOLECULE-4 C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Greenfield, EA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 227 TC 298 Z9 314 U1 2 U2 10 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 1998 VL 18 IS 5 BP 389 EP 418 PG 30 WC Immunology SC Immunology GA 124HA UT WOS:000076175300001 PM 9784967 ER PT J AU Ding, HF Fisher, DE AF Ding, HF Fisher, DE TI Mechanisms of p53-mediated apoptosis SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE programmed cell death; caspases; tumor suppressors; tumorigenesis; tumor therapy ID WILD-TYPE P53; TUMOR-SUPPRESSOR GENE; PROGRAMMED CELL-DEATH; MYC-INDUCED APOPTOSIS; IN-VIVO; P53-DEPENDENT APOPTOSIS; TRANSCRIPTIONAL ACTIVATION; GROWTH ARREST; P53-INDUCED APOPTOSIS; MEDIATED APOPTOSIS AB p53-mediated apoptosis of cells with DNA damage or oncogene overexpression is a major mechanism for its function as a tumor suppressor. Both transcriptionally dependent and transcriptionally independent activities of p53 can play a role in mediating cell death. It appears that p53 can induce apoptosis by multiple pathways in a manner which is regulated in a cell type and signal-specific fashion. Understanding the biochemical mechanisms of p53-dependent apoptosis holds a promise of manipulating these pathways in cancer therapy. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Ding, HF (reprint author), Dana 630F,44 Binney St, Boston, MA 02115 USA. NR 102 TC 55 Z9 57 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1998 VL 9 IS 1 BP 83 EP 98 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA 119LW UT WOS:000075898800006 PM 9754449 ER PT J AU Chadwick, BP Helbling, LA Angrist, M Chakravarti, A Gusella, JF Slaugenhaupt, SA AF Chadwick, BP Helbling, LA Angrist, M Chakravarti, A Gusella, JF Slaugenhaupt, SA TI Assignment of persephin (PSPN), a human neurotrophic factor, to chromosome 19p13.3 by radiation hybrid mapping and somatic cell hybrid PCR SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID SURVIVAL FACTOR; GDNF; NEURONS; NEURTURIN C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Med Sch, Harvard Inst Human Genet, Boston, MA USA. Case Western Reserve Univ, Dept Genet, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Human Genet, Sch Med, Cleveland, OH 44106 USA. RP Slaugenhaupt, SA (reprint author), HIM Bldg Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NINDS NIH HHS [NS36326] NR 12 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1998 VL 83 IS 3-4 BP 236 EP 237 DI 10.1159/000015189 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 175BX UT WOS:000079073000017 PM 10072588 ER PT J AU Bosch, I Croop, JM AF Bosch, I Croop, JM TI P-glycoprotein structure and evolutionary homologies SO CYTOTECHNOLOGY LA English DT Review DE ABC transporters; MDR; multidrug resistance; P-glycoprotein ID MULTIDRUG-RESISTANCE GENE; DROSOPHILA WHITE GENE; TRANSMEMBRANE CONDUCTANCE REGULATOR; YEAST SACCHAROMYCES-CEREVISIAE; BINDING CASSETTE TRANSPORTERS; MULTIPLE-DRUG-RESISTANCE; CHINESE-HAMSTER CELLS; EHRLICH ASCITES TUMOR; BLOOD-BRAIN-BARRIER; PLASMODIUM-FALCIPARUM AB Analysis of multidrug resistant cell lines has led to the identification of the P-glycoprotein multigene family. Two of the three classes of mammalian P-glycoproteins have the ability to confer cellular resistance to a broad range of structurally and functionally diverse cytotoxic agents. P-glycoproteins are integral membrane glycoproteins comprised of two similar halves, each consisting of six membrane spanning domains followed by a cytoplasmic domain which includes a nucleotide binding fold. The P-glycoprotein is a member of a large superfamily of transport proteins which utilize ATP to translocate a wide range of substrates across biological membranes. This superfamily includes transport complexes comprised of multicomponent systems, half P-glycoproteins and P-glycoprotein-like homologs which appear to require approximately 12 alpha-helical transmembrane domains and two nucleotide binding folds for substrate transport. P-glycoprotein homologs have been isolated and characterized from a wide range of species. Amino acid sequences, the similarities between the halves and intron/exon boundaries have been compared to understand the evolutionary origins of the P-glycoprotein. C1 Indiana Univ, James Whitcomb Riley Hosp Children, Sect Pediat Hematol Oncol, Indianapolis, IN 46202 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Indiana Univ, James Whitcomb Riley Hosp Children, Sect Pediat Hematol Oncol, Room 2720,702 Barnhill Dr, Indianapolis, IN 46202 USA. NR 202 TC 7 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-9069 EI 1573-0778 J9 CYTOTECHNOLOGY JI Cytotechnology PY 1998 VL 27 IS 1-3 BP 1 EP 30 DI 10.1023/A:1008080911522 PG 30 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 155UJ UT WOS:000077964500002 PM 19002778 ER PT J AU Sun, DZ Vanderburg, CR Odierna, GS Hay, ED AF Sun, DZ Vanderburg, CR Odierna, GS Hay, ED TI TGF beta 3 promotes transformation of chicken palate medial edge epithelium to mesenchyme in vitro SO DEVELOPMENT LA English DT Article DE TGF beta; epithelial-mesenchymal transformation; medial edge epithelium; carboxyfluorescein; chicken palate development; craniofacial morphogenesis ID EPIDERMAL GROWTH-FACTOR; AVIAN SECONDARY PALATE; TGF-BETA RECEPTOR; DIFFERENTIAL EXPRESSION; EMBRYONIC HEART; RETINOIC ACID; ORGAN-CULTURE; FUSION; CELLS; INVITRO AB Epithelial-mesenchymal transformation plays an important role in the disappearance of the midline line epithelial seam in rodent palate, leading to confluence of the palate, The aim of this study was to test the potential of the naturally cleft chicken palate to become confluent under the influence of growth factors, such as TGF beta 3, which are known to promote epithelial-mesenchymal transformation, After labeling medial edge epithelia with carboxyfluorescein, palatal shelves (E8-9) with or without beak were dissected and cultured on agar gels, TGF beta 1, TGF beta 2 or TGF beta 3 was added to the chemically defined medium. By 24 hours in culture, medial edge epithelia form adherent midline seams in all paired groups without intact beaks, After 72 hours, seams in the TGF beta 3 groups disappear and palates become confluent due to epithelial-mesenchymal transformation, while seams remain mainly epithelial in control, TGF beta 1 and TGF beta 2 groups, Epithelium-derived mesenchymal cells are identified by carboxyfluorescein fluorescence with confocal microscopy and by membrane-bound carboxyfluorescein isolation bodies with electron microscopy, Labeled fibroblasts completely replace the labeled epithelia of origin in TGF beta 3-treated palates without beaks, Single palates are unable to undergo transformation, and paired palatal shelves with intact beaks do not adhere or undergo transformation, even when treated with TGF beta 3. Thus, physical contact of medial edge epithelia and formation of the midline seam are necessary for epithelial-mesenchymal transformation to be triggered, We conclude that there may be no fundamental difference in developmental potential of the medial edge epithelium for transformation to mesenchyme among reptiles, birds and mammals. The bird differs from other amniotes in having developed a beak and associated craniofacial structures that seemingly keep palatal processes separated in vivo, Even control medial edge epithelia partly transform to mesenchyme if placed in close contact, However, exogenous TGF beta 3 is required to achieve complete confluence of the chicken palate. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent, Boston, MA 02115 USA. RP Hay, ED (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 220 Longwood Ave, Boston, MA 02115 USA. EM ehay@warren.med.harvard.edu FU NIDCR NIH HHS [R01- DE 11142] NR 52 TC 97 Z9 99 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JAN PY 1998 VL 125 IS 1 BP 95 EP 105 PG 11 WC Developmental Biology SC Developmental Biology GA YT861 UT WOS:000071652400010 PM 9389667 ER PT J AU Goldstein, AM Ticho, BS Fishman, MC AF Goldstein, AM Ticho, BS Fishman, MC TI Patterning the heart's left-right axis: From zebrafish to man SO DEVELOPMENTAL GENETICS LA English DT Article DE left-right asymmetry; cardiac development; situs inversus; heterotaxia ID LEFT-RIGHT ASYMMETRY; SITUS-INVERSUS; ASPLENIA SYNDROME; NODAL EXPRESSION; HANDEDNESS; NOTOCHORD; ABNORMALITIES; EMBRYOGENESIS; SPECIFICATION; MALFORMATIONS AB Normal left-right asymmetry is highly conserved among vertebrates. Errors in the proper patterning of this axis are believed to lead to congenital anomalies of the heart and abdominal viscera, often with profound clinical consequences. We review briefly the nature of potential signals and signaling sources that lead to the break in left-right symmetry. The evidence suggests that left-right reversal, or homogenization, of these signals may lead to different consequences, and we explain some malpositions and malalignments of the atria, ventricles, and/or outflow tract thai are seen in a variety of congenital cardiac diseases. We speculate that there are units of organ assembly responsive to laterality signals, and these units may be driven independently. One crucial source of signals appears to be the notochord and floorplate. in order io examine the clinical relationship of these midline structures to putative disorders of laterality, we review all patients with disturbances of normal laterality seen at the Massachusetts General past 20 years. We find a significant association between laterality defects and anomalies of the spine and other midline structures. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [1F32HL09585, HL02922-04] NR 56 TC 20 Z9 20 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1998 VL 22 IS 3 BP 278 EP 287 DI 10.1002/(SICI)1520-6408(1998)22:3<278::AID-DVG9>3.0.CO;2-3 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA ZQ737 UT WOS:000073898000009 PM 9621434 ER PT J AU Aiello, LP Gardner, TW King, GL Blankenship, G Cavallerano, JD Ferris, FL Klein, R AF Aiello, LP Gardner, TW King, GL Blankenship, G Cavallerano, JD Ferris, FL Klein, R TI Diabetic retinopathy SO DIABETES CARE LA English DT Review ID MICROVASCULAR COMPLICATIONS; FLUORESCEIN ANGIOGRAPHY; COST-EFFECTIVENESS; PHOTO-COAGULATION; 4-YEAR INCIDENCE; PROGRESSION; DIAGNOSIS; MELLITUS; AGE; EYE C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol, Boston, MA 02215 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Hershey, PA 17033 USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol, 1 Joslin Pl, Boston, MA 02215 USA. EM aiellol@joslab.harvard.edu OI Gardner, Thomas/0000-0002-5112-5810 NR 83 TC 395 Z9 410 U1 0 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 1998 VL 21 IS 1 BP 143 EP 156 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YN892 UT WOS:000071219200027 PM 9538986 ER PT J AU Fass, R Fullerton, S Naliboff, B Hirsh, T Mayer, EA AF Fass, R Fullerton, S Naliboff, B Hirsh, T Mayer, EA TI Sexual dysfunction in patients with irritable bowel syndrome and non-ulcer dyspepsia SO DIGESTION LA English DT Article DE libido; visceral hyperalgesia; quality of life ID PITUITARY-ADRENAL AXIS; FIBROMYALGIA; DISEASE; WOMEN AB The prevalence and type of sexual dysfunction in patients with functional gastrointestinal (GI) disorders involving the upper (functional dyspepsia) or lower GI tract (irritable bowel syndrome) were studied in 683 patients seen at a tertiary referral center and a comparison group of 247 community volunteers. Associations between sexual dysfunction and type and severity of GI symptoms, and psychological symptoms were examined. All subjects were evaluated with a validated bowel syndrome questionnaire, which included questions about sexual function. Psychological symptom severity was assessed by SCL-90R, The prevalence of self-reported sexual dysfunction in patients with functional GI disorders was 43.3% and did not differ by gender, age stratification or disease subtype: irritable bowel syndrome (IBS); non-ulcer dyspepsia (NUD), and IBS+NUD, In the comparison subjects without IBS symptoms and those with IBS symptoms but not seeking health care (IBS non-patients), the reported sexual dysfunction prevalence was significantly lower (16.1 and 24.4 %, respectively, p < 0.005). Decreased sexual drive was the symptom most commonly reported by both male (36.2%) and female (28.4%) patients. Dyspareunia was reported by 16.4% of females and 4% of males with IBS, but was rarely observed in patients with NUD. Report of sexual dysfunction was positively associated with perceived GI symptom severity, but not with psychological symptom severity. Sexual dysfunction should be incorporated into the quality-of-life assessment of patients with functional GI disorders and addressed in future outcome studies. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Digest Dis Res Ctr, CURE,Neuroenter Dis Program, Los Angeles, CA 90024 USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 115,CURE, Los Angeles, CA 90073 USA. NR 28 TC 46 Z9 46 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 J9 DIGESTION JI Digestion PD JAN-FEB PY 1998 VL 59 IS 1 BP 79 EP 85 DI 10.1159/000007471 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YU105 UT WOS:000071682200011 PM 9468103 ER PT J AU Moser, AJ Karam, JA Giurgiu, DI Weber, PA Abedin, ZR Roslyn, JJ Abedin, MZ AF Moser, AJ Karam, JA Giurgiu, DI Weber, PA Abedin, ZR Roslyn, JJ Abedin, MZ TI Elevated biliary calmodulin during gallstone formation - The role of bile acids SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE gallstones; calmodulin; bile acids; phospholipids; secretion; prairie dog ID CYSTIC-FIBROSIS; GALLBLADDER ABSORPTION; CHOLESTEROL GALLSTONES; SECRETION; CALCIUM; RADIOIMMUNOASSAY; PHOSPHORYLATION; PROTEIN; DISEASE; DOG AB Hepatic bile synthesis is altered during experimental gallstone formation. In response to cholesterol, there is a hydrophobic shift in hepatic bile acid synthesis and hypersecretion of phospholipids. These changes decrease the vesicular capacity for cholesterol and favor crystallization. The mechanism for these changes in hepatic bile formation is unknown. Calmodulin (CaM), a Ca2+ receptor protein involved in cellular secretion, regulates gallbladder transport and may play an important role in alterations of hepatic bile formation during cholelithiasis. We hypothesized that biliary CaM activity is altered during gallstone formation and may be associated with changes in bile acid and phospholipid synthesis. Prairie dogs were fed either control (N = 22) or 1.2% cholesterol-enriched (N = 26) diets for one to six weeks. Cholecystectomy was performed; the common bile duct was cannulated, and hourly bile samples were collected. CaM was measured in bile and gallbladder tissues by radioimmunoassay. Bile samples were analyzed for cholesterol, phospholipids, total bile acids, total protein, calcium, and individual bile acid composition. Compared to controls, gallstone animals had elevated hepatic bile levels of CaM, phospholipids, and cholesterol. Hydrophobic bile acid synthesis was also stimulated, with increased levels of taurochenodeoxycholic acid (TCDCA) and decreased taurocholic acid (TCA). Gallbladder bile demonstrated similar changes. Although gallbladder bile CaM levels were increased, tissue levels were unchanged, suggesting that increased CaM concentration is a hepatic phenomenon. Hepatic bile CaM activity correlated linearly with TCDCA concentration (r = 0.64, P < 0.004) and phospholipid hypersecretion (r = 0.53, P < 0.03). The relationship between biliary CaM and increased concentrations of TCDCA and phospholipids suggests a role for CaM in alterations of hepatocyte secretion that may promote gallstone formation. C1 Allegheny Univ Hlth Sci, Dept Surg, Philadelphia, PA 19129 USA. Philadelphia VA Med Ctr, Res Serv, Philadelphia, PA USA. Philadelphia VA Med Ctr, Surg Serv, Philadelphia, PA USA. RP Abedin, MZ (reprint author), Allegheny Univ Hlth Sci, Dept Surg, 3300 Henry Ave, Philadelphia, PA 19129 USA. NR 47 TC 3 Z9 3 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 1998 VL 43 IS 1 BP 170 EP 177 DI 10.1023/A:1018852810678 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YX136 UT WOS:000072010000027 PM 9508521 ER PT J AU Cretin, N Buhler, L Fournier, B Caulfield, A Oberholzer, J Mentha, G Morel, P AF Cretin, N Buhler, L Fournier, B Caulfield, A Oberholzer, J Mentha, G Morel, P TI Human islet allotransplantation: World experience and current status SO DIGESTIVE SURGERY LA English DT Review DE diabetes, type I; pancreas transplantation; islet transplantation ID HUMAN PANCREATIC-ISLETS; CELL AUTO-TRANSPLANTATION; PORTAL-VEIN THROMBOSIS; RAT ISLETS; LYMPHOPROLIFERATIVE DISORDERS; ORGAN-TRANSPLANTATION; INSULIN INDEPENDENCE; PORCINE ISLETS; CRYOPRESERVATION; DOGS AB Currently type-I diabetes mellitus is treated with exogenous insulin administration, but traditional insulin therapy does not prevent long-term systemic complications and therefore alternatives should be sought. Presently the only option is to substitute the insulin-producing beta cells in order to obtain a more physiological way to deliver insulin. Simultaneous kidney and pancreas transplantation is an established procedure. Pancreas transplantation, however, is a major surgical procedure with a high rate of complications. Transplantation of the isolated insulin-secreting islets of Langerhans is an alternative approach, which is easier and safer than whole organ transplantation. Since 1990, clinical. trials of islet transplantation have begun in a few specialized centers worldwide and the International Islet Registry counting 305 human islet allografts at the end of 1995. Insulin independence at 1 year was achieved in 8% of the patients, but 20% of cases showed a graft function with a normal basal C peptide and improved glycemic regulation. We review here the different aspects of human islets of Langerhans allotransplatation, namely historical aspects, indications, isolation and purification procedures and the results obtained. C1 Univ Hosp Geneva, Dept Internal Med, Div Endocrinol & Diabetol, Geneva, Switzerland. Univ Hosp Geneva, Dept Surg, Geneva, Switzerland. RP Cretin, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Biol Res Ctr, MGH E,Bldg 140-9019,13th St, Boston, MA 02129 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 70 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-4886 J9 DIGEST SURG JI Dig. Surg. PY 1998 VL 15 IS 6 BP 656 EP 662 DI 10.1159/000018672 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 140MG UT WOS:000077090600002 PM 9845631 ER PT B AU Niklason, LT Christian, BT Niklason, LE Kopans, DB Slanetz, PJ Castleberry, DE Opsahl-Ong, BH Landberg, CE Giambattista, B AF Niklason, LT Christian, BT Niklason, LE Kopans, DB Slanetz, PJ Castleberry, DE Opsahl-Ong, BH Landberg, CE Giambattista, B BE Karssemeijer, N Thijssen, M Hendriks, J VanErning, L TI Digital breast tomosynthesis: Potentially a new method for breast cancer screening SO DIGITAL MAMMOGRAPHY SE COMPUTATIONAL IMAGING AND VISION LA English DT Proceedings Paper CT 4th International Workshop on Digital Mammography CY JUN, 1998 CL UNIV HOSP NIJMEGEN, DEPT RADIOL, NIJMEGEN, NETHERLANDS SP Agfa Gevaect, Trex Med Corp, Eastman Kodak Co, Feinfocus Med Tech, Fuji Med Syst, Ge Med Syst, Nucl Associates, Philips Med Syst, R2 Technol Inc, Siemens Ag Med Engn HO UNIV HOSP NIJMEGEN, DEPT RADIOL ID SUBTRACTION ANGIOGRAPHY; MAMMOGRAPHY C1 Massachusetts Gen Hosp, Dept Radiol Sci & Technol, Boston, MA 02114 USA. RP Niklason, LT (reprint author), Massachusetts Gen Hosp, Dept Radiol Sci & Technol, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-5274-2 J9 COMP IMAG VIS PY 1998 VL 13 BP 51 EP 56 PG 6 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BM65H UT WOS:000079341500010 ER PT J AU Willett, CG Hagan, M Daley, W Warland, G Shellito, PC Compton, CC AF Willett, CG Hagan, M Daley, W Warland, G Shellito, PC Compton, CC TI Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation SO DISEASES OF THE COLON & RECTUM LA English DT Article DE rectal cancer; peroperative irradiation and 5-fluorouracil; tumor proliferation; proliferating nuclear antigen ID METASTATIC BREAST-CANCER; ESTROGENIC RECRUITMENT; RADIATION-THERAPY; HEMATOPOIETIC STEM; CHEMOTHERAPY; CARCINOMA; CELLS; TRIAL AB PURPOSE: This study examines the effect of 5-fluorouracil administration during preoperative irradiation on rectal cancer tumor proliferation. PATIENTS AND METHODS: One hundred and fifty-three patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation with (103 patients) and without (50 patients) concurrent 5-fluorouracil, followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating cell nuclear antigen immunostaining and the number of mitoses per ten high-powered fields. Postirradiation specimens were also assessed for downstaging. RESULTS: Although 5-fluorouracil did not improve downstaging rates, marked decreases in the activity of all three markers of proliferation (mitotic counts, Ki-67, and proliferating cell nuclear antigen immunostaining) were seen in rectal cancers of patients receiving the drug. No significant decreases were noted in patients undergoing irradiation only. CONCLUSION: The addition of 5-fluorouracil to preoperative irradiation resulted in a more complete inactivation of the proliferating population frequency of downstaging, however, was unaffected. Thus, the quiescent cell population appears to represent a substantial barrier to further downstaging. New treatment strategics should be aimed at controlled recruitment of quiescent tumor cells at the time of irradiation. C1 Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. Univ Florida, Dept Radiat Oncol, Gainesville, FL USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 18 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JAN PY 1998 VL 41 IS 1 BP 62 EP 67 DI 10.1007/BF02236897 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA YQ958 UT WOS:000071442300010 PM 9510312 ER PT J AU Reid, MS Mickalian, JD Delucchi, KL Hall, SM Berger, SP AF Reid, MS Mickalian, JD Delucchi, KL Hall, SM Berger, SP TI An acute dose of nicotine enhances cue-induced cocaine craving SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE nicotine; cocaine; cue-induced; craving; relapse ID FREELY MOVING RATS; CIGARETTE-SMOKING; TRANSDERMAL NICOTINE; DEPENDENT PATIENTS; ABUSE PATIENTS; D-AMPHETAMINE; HUMANS; PERFORMANCE; REACTIVITY; TOBACCO AB The present study examined whether the active component in tobacco, nicotine, can modulate cocaine craving in patients with a history of smoking crack cocaine when exposed to crack cocaine related environmental cues. Twenty patients, all cigarette smokers, were randomly assigned to nicotine (two 22 mg transdermal patches) or placebo in a single-dose, placebo-controlled, crossover, double-blind study. Craving and anxiety were measured before and after cocaine cues with visual analog scales for desire to use cocaine and mood. Skin conductance and skin temperature were recorded before and during cocaine cues. Following exposure to cocaine cues, all patients reported an increase in cocaine craving and anxiety relative to the pre-cue measures. Cue exposure also produced an increase in skin conductance and decrease in skin temperature. The cue-induced increase in cocaine craving was strongly enhanced by nicotine, while the increase in anxiety was slightly augmented. Cue-induced skin conductance and temperature responses were unaffected by nicotine. These findings show that cue-induced cocaine craving is enhanced by nicotine. This occurred in the absence of any tobacco smoking-related cues, suggesting that nicotine may have direct psychopharmacological effects on conditioned cocaine craving. (C) 1998 Elsevier Science Ireland Ltd. C1 NYU, New York Vet Affairs Med Ctr, Dept Psychiat, New York, NY 10010 USA. Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Psychiat Serv, San Francisco, CA 94121 USA. RP Reid, MS (reprint author), NYU, New York Vet Affairs Med Ctr, Dept Psychiat, 423 E 23rd St, New York, NY 10010 USA. EM msreid@itsa.ucsf.edu OI Delucchi, Kevin/0000-0003-2195-9627 FU NIDA NIH HHS [1R18DA06097, P50 DA09253, T32 DA07250] NR 40 TC 91 Z9 92 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 1998 VL 49 IS 2 BP 95 EP 104 DI 10.1016/S0376-8716(97)00144-0 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZC149 UT WOS:000072544800003 PM 9543646 ER PT J AU Tom, T Cummings, JL AF Tom, T Cummings, JL TI Depression in Parkinson's disease - Pharmacological characteristics and treatment SO DRUGS & AGING LA English DT Review ID CATECHOL-O-METHYLTRANSFERASE; ELECTROCONVULSIVE-THERAPY; MAJOR DEPRESSION; L-DOPA; PSYCHIATRIC-SYMPTOMS; CEREBROSPINAL-FLUID; LOCUS COERULEUS; OFF PHENOMENON; BINDING-SITES; MEDICALLY ILL AB Parkinson's disease (PD) is a common neurological illness and various degrees of depression frequently complicate its course. Risk factors for developing depression with PD include right-sided hemiparkinsonism, akinesia, increased severity of disability, anxiety and psychosis. Onset of parkinsonism at a younger age, female gender and the use of levodopa are arguable risk factors. Depression may be difficult to diagnose in patients with PD because the signs of the 2 disorders overlap. In addition, patients with atypical PD more commonly have depression than patients with classical PD presentations. Antidepressant response to antiparkinsonian treatment has been limited. Enhancement of catecholamine levels in the CNS by selegiline (deprenyl), a monoamine oxidase (MAO) type B inhibitor, has shown potential antidepressant as well as neuroprotective effects. Other MAO inhibitors have shown antidepressant efficacy in animal models but have not been well tolerated by patients with PD. A catechol-O-methyltransferase (COMT) inhibitor combined with an MAO inhibitor might synergistically maximise the levels of catecholamines in the CNS. Antidepressant medications used in patients without PD include tricyclic antidepressants (TCAs) and selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), but only TCAs have been carefully studied for their antidepressant effects in PD. Electroconvulsive therapy has proven efficacy as antidepressant therapy in patients with PD, and transcranial magnetic stimulation has provided temporary-relief of depression under experimental conditions. Adverse effects of polypharmacy in the attempted treatment of depression in patients with PD are common in the elderly. A 'serotonin syndrome' has occurred frequently enough to preclude the coadministration of selegiline with SSRIs or TCAs, and multiple interactions between antiparkinsonian and antidepressant medications further complicate treatment strategies in patients with PD. An algorithmic approach to the pharmacological treatment of depression is described in this article. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Neuropsychiat & Neurobehav Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NIA NIH HHS [P30 AG010123] NR 139 TC 62 Z9 65 U1 3 U2 7 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD JAN PY 1998 VL 12 IS 1 BP 55 EP 74 DI 10.2165/00002512-199812010-00006 PG 20 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA YR568 UT WOS:000071508300006 PM 9467687 ER PT B AU Brown, D Katsura, T Gustafson, CE AF Brown, D Katsura, T Gustafson, CE BE Benavides, HAC Yacaman, MJ TI Intracellular pathways of aquaporin water channel trafficking in renal epithelial cells SO ELECTRON MICROSCOPY 1998, VOL 1: GENERAL INTEREST AND INSTRUMENTATION LA English DT Proceedings Paper CT 14th International Congress on Electron Microscopy CY AUG 31-SEP 04, 1998 CL CANCUN, MEXICO SP Mexican Soc Microscopy, Consejo Nacl Ciencia & Tecnol, Inst Nacl Invest Nucl, Univ Autonoma Estado Mexico, Univ Veracruzana, Ctr Invest & Estudios Avanzados, Univ Nacl Autonoma Mexico, Ctr Invest Mat Avanzados, Inst Politecn Nacl, Univ Autonoma Nuevo Leon C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND BN 0-7503-0564-9 PY 1998 BP 855 EP 856 PG 2 WC Materials Science, Multidisciplinary; Microscopy SC Materials Science; Microscopy GA BL87G UT WOS:000077017600397 ER PT J AU Goodfriend, TL Egan, BM Kelley, DE AF Goodfriend, TL Egan, BM Kelley, DE TI Aldosterone in obesity SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 8th Conference on the Adrenal Cortex CY JUN 13-16, 1998 CL ORFORD, CANADA SP Univ Laval, Univ Montreal, McGill Univ, Univ Sherbrooke, Univ Toronto, Univ Sherbrooke, Ctr Res, Univ Montreal, Ctr Res, Univ Laval, Ctr Res, Duglas Hosp Res Ctr, Med Res Council Canada, Merck Frosst, Bayer, BiochemPharma ID BLOOD-PRESSURE; WEIGHT-REDUCTION; HYPERTENSIVE PATIENTS; FATTY-ACIDS; RESTRICTION; INSULIN; SODIUM AB Plasma aldosterone levels were measured in adults whose body mass index ranged from lean to obese. Blood was drawn while subjects rested supine for 30-90 minutes. Aldosterone was higher in obese subjects, but could not be explained by renin or K+. The best predictors of plasma aldosterone were abdominal obesity measured as waist/hip ratio or by CT scan, and insulin resistance measured by insulin or oral glucose tolerance tests, or euglycemic clamp. In one cohort, these correlations were limited to women; in the other, they were also found in men. In the women with a strong correlation between aldosterone and visceral fat, aldosterone also correlated with cortisol and DHEA-S. The data are consistent with an effect of visceral fat on adrenal steroidogenesis. Visceral adipocytes have a high rate of triglyceride turnover, and their circulation drains directly to the liver. In an experiment based on these characteristics, rat hepatocytes responded to fatty acids by releasing an unidentified secretagogue that stimulated aldosterone production by rat adrenal glomerulosa cells. The clinical data suggest that aldosterone participates in hypertension associated with the "Insulin Resistance Syndrome". The adrenal in viscerally obese subjects may be driven by a secretagogue released from the liver by fatty acids from abdominal adipocytes. C1 Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Med Univ S Carolina, Dept Pharmacol, Div Clin Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Clin Pharmacol, Charleston, SC 29425 USA. Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA USA. RP Goodfriend, TL (reprint author), Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. NR 19 TC 110 Z9 114 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1998 VL 24 IS 3-4 BP 789 EP 796 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 150ZW UT WOS:000077697300082 PM 9888579 ER PT J AU Carsia, RV Nagele, RG Morita, Y Tilly, KI Tilly, JL AF Carsia, RV Nagele, RG Morita, Y Tilly, KI Tilly, JL TI Models to elucidate the regulation of adrenal cell death SO ENDOCRINE RESEARCH LA English DT Article; Proceedings Paper CT 8th Conference on the Adrenal Cortex CY JUN 13-16, 1998 CL ORFORD, CANADA SP Univ Laval, Univ Montreal, McGill Univ, Univ Sherbrooke, Univ Toronto, Univ Sherbrooke, Ctr Res, Univ Montreal, Ctr Res, Univ Laval, Ctr Res, Duglas Hosp Res Ctr, Med Res Council Canada, Merck Frosst, Bayer, BiochemPharma ID IN-VIVO; IMMUNOHISTOCHEMICAL ANALYSIS; DIFFERENTIAL REGULATION; APOPTOSIS; EXPRESSION; ENDONUCLEASE; PROTEIN; CORTEX; FAMILY; GLAND AB Hypophysectomy-induced apoptosis in the rat adrenal gland is slow (not apparent until 12-24 h) and in-situ, 3'-end labeling (ISEL) of DNA strand breaks is restricted to a subpopulation of zona reticularis cells. In addition, it is completely blocked by ACTH. By contrast, apoptosis in the intact rat adrenal gland, cultured in the absence of trophic support, is extensive and rapid. Culture-triggered apoptosis las determined by oligonucleosome formation) is attenuated by ACTH and is largely restricted to the zonae fasciculata and reticularis even at 3 h las determined by ISEL and DAPI cytochemistry). Thus, this organ culture system may help elucidate factors that can acutely regulate adrenocortical cell survival. Quartered glands have a nearly 2-fold increase in oligonucleosome formation compared to intact glands at 3 h and are resistant to the antiapoptotic action of ACTH. In contrast, ACTH-induced corticosterone secretion is not attenuated. Angiotensin II (Ang II) enhances culture-triggered apoptosis, and its apoptotic action is attenuated by ACTH. These observations suggest that 1) acute hormonal modulation of apoptosis may require some level of gross adrenal structural integrity, and 2) ACTH and Ang II act in an antagonistic fashion to regulate adrenocortical apoptosis. The apoptotic effect of Ang II may be mediated via the type 2 receptor. C1 Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Cell Biol, Stratford, NJ 08084 USA. Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Mol Biol, Stratford, NJ 08084 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA USA. RP Carsia, RV (reprint author), Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Cell Biol, Stratford, NJ 08084 USA. FU NIA NIH HHS [R01-AG12279] NR 21 TC 11 Z9 11 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0743-5800 J9 ENDOCR RES JI Endocr. Res. PY 1998 VL 24 IS 3-4 BP 899 EP 908 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 150ZW UT WOS:000077697300098 PM 9888595 ER PT J AU Jemtland, R Lee, KC Segre, GV AF Jemtland, R Lee, KC Segre, GV TI Heterogeneity among cells that express osteoclast-associated genes in developing bone SO ENDOCRINOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MESSENGER RIBONUCLEIC-ACIDS; HORMONE-RELATED PEPTIDE; MATRIX METALLOPROTEINASES; SKELETAL DEVELOPMENT; IV COLLAGENASE; GELATINASE-B; LONG BONES; IN-VIVO; C-FOS AB In the present study, we characterized the phenotype of cells in the osteoclast lineage by in situ hybridization, using antisense complementary RNA probes that encode three genes typically expressed by osteoclasts, tartrate-resistant acid phosphatase (TRAP), type TV collagenase (matrix metalloproteinase-9), and c-fms, the receptor for macrophage colony-stimulating factor. By using complementary RNA probes labeled with S-35, digoxygenin, or a combination of the two labeling methods (dual labeling in situ hybridization), we found that each of these genes exhibited a distinct expression pattern during early stages of endochondral bone development [embryonic day 15 (ED15) to ED17] in fetal mouse hind limbs. Type IV collagenase messenger RNA (mRNA) was first expressed in or just outside of the cellular layers that define perichondrium/periosteum, earlier than transcripts for TRAP or c-fms appeared at the same sites (ED15). Although transcripts for TRAP and c-fms colocalized within the skeleton, c-fms was also found in surrounding soft tissue, whereas TRAP mRNA was never detected outside the skeleton (ED16). Type IV collagenase mRNA was uniquely distributed at the chondro-osseous border, being distinct from the distribution of TRAP or c-fms (ED17). At later stages of skeletal development (ED18 to 15-day-old postnatal bone), however, there was more overlap among TRAP, type IV collagenase, and c-fms mRNAs in cells throughout bone, except at the chondro-osseous junction, where type IV collagenase continued to be uniquely localized to some cells at all developmental stages. Whereas the levels of type IV collagenase mRNA expression was most intense at the chondro-osseous margin, the levels of c-fms and TRAP mRNA expression appeared to be more uniform throughout the developing bone. The results indicate that there is considerable heterogeneity among cells expressing osteoclast-associated genes, particularly during early stages of endochondral bone development, but that this difference becomes less pronounced later in the more mature skeleton. Distinct expression patterns of these markers may represent different stages of osteoclastogenesis. Alternatively, type IV collagenase-positive and TRAP/c-fms-positive cells may represent distinct subpopulations of cells of the osteoclast lineage. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Segre, GV (reprint author), Massachusetts Gen Hosp, Endocrine Unit, WEL 501, Boston, MA 02114 USA. EM segre@helix.mgh.harvard.edu NR 39 TC 25 Z9 27 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 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1998 VL 139 IS 1 BP 340 EP 349 DI 10.1210/en.139.1.340 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YN232 UT WOS:000071146300046 PM 9421432 ER PT S AU Qureshi, N Jarvis, B Takayama, K Sattar, N Hofman, J Stutz, P AF Qureshi, N Jarvis, B Takayama, K Sattar, N Hofman, J Stutz, P BE Levin, J Pollack, M Yokochi, T Nakano, M TI Natural and synthetic LPS and lipid A analogs or partial structures that antagonize or induce tolerance to LPS SO ENDOTOXIN AND SEPSIS: MOLECULAR MECHANISMS OF PATHOGENESIS, HOST RESISTANCE, AND THERAPY SE PROGRESS IN CLINICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 4th Conference of the International-Endotoxin-Society CY OCT 22-27, 1996 CL NAGOYA, JAPAN SP Int Endotoxin Soc ID TUMOR-NECROSIS-FACTOR; RHODOPSEUDOMONAS-SPHAEROIDES ATCC-17023; LIPOPOLYSACCHARIDE LPS; ENDOTOXIN ANTAGONIST; LETHAL ENDOTOXEMIA; A PRECURSOR; FATTY-ACIDS; GLUCOCORTICOIDS; ACTIVATION; INHIBITION C1 William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53705 USA. Coll Agr & Life Sci, Dept Bacteriol, Madison, WI 53706 USA. Acad Sci Czech Republic, Prague 4, Czech Republic. Sandoz GmbH, A-1235 Vienna, Austria. RP Qureshi, N (reprint author), William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53705 USA. FU NIGMS NIH HHS [GM-50870] NR 29 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS, INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-7742 BN 0-471-19432-8 J9 PROG CLIN BIOL RES JI Prog.Clin.Biol.Res. PY 1998 VL 397 BP 289 EP 300 PG 12 WC Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Life Sciences & Biomedicine - Other Topics; Immunology; Research & Experimental Medicine; Microbiology GA BL23U UT WOS:000074779900028 PM 9575570 ER PT B AU Kuter, DJ AF Kuter, DJ BE Boiron, M Marty, M TI Thrombopoietin: from basic biology to clinical applications SO EUROCANCER 98 LA English DT Proceedings Paper CT 11th Congress on Clinical Research Conference (EUROCANCER 98) CY JUN 03-05, 1998 CL PARIS, FRANCE SP EUROCANCER, Forum Cancerol ID HUMAN MEGAKARYOCYTE GROWTH; CHEMOTHERAPY; CANCER C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0217-0 PY 1998 BP 129 EP 130 PG 2 WC Oncology SC Oncology GA BM55Q UT WOS:000079094000042 ER PT B AU Dranoff, G AF Dranoff, G BE Boiron, M Marty, M TI Granulocyte-macrophage colony stimulating factor based cancer vaccines SO EUROCANCER 98 LA English DT Proceedings Paper CT 11th Congress on Clinical Research Conference (EUROCANCER 98) CY JUN 03-05, 1998 CL PARIS, FRANCE SP EUROCANCER, Forum Cancerol ID TUMOR C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0217-0 PY 1998 BP 297 EP 298 PG 2 WC Oncology SC Oncology GA BM55Q UT WOS:000079094000089 ER PT J AU Boglari, G Erhardt, P Cooper, GM Szeberenyi, J AF Boglari, G Erhardt, P Cooper, GM Szeberenyi, J TI Intact Ras function is required for sustained activation and nuclear translocation of extracellular signal-regulated kinases in nerve growth factor-stimulated PC12 cells SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE nerve growth factor; PC12 cells; neuronal differentiation; Ras; extracellular signalregulated kinases; nuclear translocation of ERKs ID MAP KINASE; NEURONAL DIFFERENTIATION; PROTEIN-KINASE; FACTOR RECEPTOR; CYCLIC-AMP; INSULIN; CALCIUM; RAF-1 AB PC12 pheochromocytoma cell lines expressing the dominant negative Ha-Ras Asn-17 protein at different levels were used in this study to analyze the relationship between nerve growth factor (NGF)-induced activation of members of the mitogen-activated protein kinase (MAPK) family, and neuritogenesis, In wild-type PC12 cells. NGF rapidly stimulated the extracellular signal-regulated kinases (ERKs), Kinase activation was sustained and was followed by the translocation of ERK 1 and ERK 2 into the nucleus ultimately leading to neurite outgrowth. In cells expressing relatively high levels of the inhibitory Res protein, NGF stimulation of ERK 1 and ERK 2 as well as nuclear translocation of these protein kinases were greatly inhibited, In contrast, in PC12 subclones expressing low amounts of Ha-Ras Asn-17 the peak of ERK activation was only slightly reduced, but became transient in nature and was not followed by nuclear translocation of ERKs 1 and 2. Since all PC12 subclones expressing detectable levels of the dominant inhibitory Ras protein are resistant to NGF induction of neurite formation, our observations support the notion that sustained activation and translocation of ERKs into the nucleus are essential for NGF-induced neuronal differentiation of PC12 cells. C1 Univ Pecs, Sch Med, Dept Med Biol, H-7643 Pecs, Hungary. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02115 USA. RP Boglari, G (reprint author), Univ Pecs, Sch Med, Dept Med Biol, Szigeti 12, H-7643 Pecs, Hungary. NR 25 TC 21 Z9 21 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JAN PY 1998 VL 75 IS 1 BP 54 EP 58 PG 5 WC Cell Biology SC Cell Biology GA YX176 UT WOS:000072014000007 PM 9523155 ER PT J AU Duska, LR Flynn, C Goodman, A AF Duska, LR Flynn, C Goodman, A TI Masculinizing sclerosing stromal cell tumor in pregnancy: report of a case and review of the literature SO EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY LA English DT Article DE sclerosing; stromal cell tumor; ovarian neoplasm; virilizing ID OVARY AB Purpose: To report a case of sclerosing stromal cell tumor of the ovary in pregnancy and to review the literature of this rare ovarian tumor. Methods: The patient's office record and hospital record were reviewed. Gross and microscopic pathology were reviewed by one gynecologic pathologist. A Medline literature search and literature review were performed. Results: Over eighty cases of sclerosing stromal cell tumor of the ovary have been reported in the literature since the definition of this pathologic condition in 1973. Only five cases have been reported during pregnancy and only two of these resulted in maternal virilization. This report describes severe maternal virilization with birth of a non-virilized female infant. Conclusion. Sclerosing stromal cell tumor of the ovary can result in severe virilization via androgen production. Surgery with removal of the involved ovary is required for diagnosis and cure. Prognosis is excellent. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cytopathol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Vincent 1, Boston, MA 02114 USA. NR 10 TC 13 Z9 16 U1 0 U2 0 PU S O G CANADA INC PI MONTREAL PA 1 PLACE VILLE MARIE, MONTREAL, QB 3900, CANADA SN 0392-2936 J9 EUR J GYNAECOL ONCOL JI Eur. J. Gynaecol. Oncol. PY 1998 VL 19 IS 5 BP 441 EP 443 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 145WD UT WOS:000077393800005 PM 9863907 ER PT J AU Roth, SJ Diacovo, TG Brenner, MB Rosat, JP Buccola, J Morita, CT Springer, TA AF Roth, SJ Diacovo, TG Brenner, MB Rosat, JP Buccola, J Morita, CT Springer, TA TI Transendothelial chemotaxis of human alpha/beta and gamma/delta T lymphocytes to chemokines SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE human; T lymphocyte; TCR; chemotaxis; cytokine; gamma delta T cell ID RECEPTOR-GAMMA-DELTA; CELL RECEPTOR; INDUCIBLE PROTEIN-10; ENDOTHELIAL-CELLS; IDENTIFICATION; INTERLEUKIN-8; MONOCYTES; ADHESION; CHEMOATTRACTANT; SPECIFICITY AB Two subpopulations of human T lymphocytes expressing different antigen receptors, alpha/beta and gamma/delta, emigrate into inflamed tissues in distinctive patterns. We compared the transmigration of alpha/beta and gamma/delta T cells to C-C and C-X-C chemokines using an in vitro transendothelial chemotaxis assay. The C-C chemokines monocyte chemoattractant protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta stimulated similar, dose-dependent chemotaxis of purified gamma/delta T cells, whereas MCP-1, RANTES, and MIP-1 alpha produced greater chemotaxis of purified alpha/beta T cells than MIP-1 beta. In contrast, the C-X-C chemokines interleukin (IL)-8 and interferon-gamma inducible protein-10 (IP-10) did not promote chemotaxis of either alpha/beta or gamma/delta T cells. Three gamma/delta T cell clones with differing CD4 and CD8 phenotypes also migrated exclusively to C-C chemokines. Phenotypic analysis of mononuclear cells that transmigrated from an input population of unfractionated peripheral blood mononuclear cells confirmed the results with purified gamma/delta T cells. Our data demonstrate that human peripheral blood alpha/beta and gamma/delta T cells can transmigrate to MCP-1, RANTES, MIP-1 alpha, and MIP-1 beta, and suggest that both T lymphocyte subpopulations share the capacity to emigrate in response to C-C chemokines during inflammation. C1 Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02111 USA. Brigham & Womens Hosp, Dept Rheumatol & Immunol, Lymphocyte Biol Sect, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Morita, Craig/C-1365-2011 FU NHLBI NIH HHS [HL03361, HL02776, HL48675] NR 49 TC 58 Z9 58 U1 1 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 1998 VL 28 IS 1 BP 104 EP 113 DI 10.1002/(SICI)1521-4141(199801)28:01<104::AID-IMMU104>3.0.CO;2-F PG 10 WC Immunology SC Immunology GA YW841 UT WOS:000071979400011 PM 9485190 ER PT J AU Schulz, JB Matthews, RT Heneka, M von Coellp, R Beal, MF Klockgether, T Weller, M AF Schulz, JB Matthews, RT Heneka, M von Coellp, R Beal, MF Klockgether, T Weller, M TI Extended therapeutic window for caspase inhibition and synergy with MK-801 in the treatment of cerebral histotoxic hypoxia. SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Tubingen, Dept Neurol, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 NR 0 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 1998 VL 10 SU 10 MA 803 BP 5 EP 5 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZZ630 UT WOS:000074749400027 ER PT J AU Cariani, P AF Cariani, P TI Temporal coding in the auditory system. SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 1998 VL 10 SU 10 MA 4402 BP 109 EP 109 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZZ630 UT WOS:000074749400637 ER PT J AU Rothe, F Huang, PL Wolf, G AF Rothe, F Huang, PL Wolf, G TI Ultrastructural distribution of nNOS and NADPH-diaphorase in the laterodorsal tegmental nucleus of wild type and knockout mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Magdeburg, Inst Med Neurobiol, D-39120 Magdeburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 1998 VL 10 SU 10 MA 11401 BP 287 EP 287 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZZ630 UT WOS:000074749401661 ER PT J AU Werner, A Kloss, CUA Walter, J Gutierrez-Ramos, JC Kreutzberg, GW Raivich, G AF Werner, A Kloss, CUA Walter, J Gutierrez-Ramos, JC Kreutzberg, GW Raivich, G TI Intercellular adhesion molecule 1 (ICAM1) leads to reduced astrocytic activation and a decrease in lymphocyte infiltration in the injured CNS SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Meeting Abstract C1 MPI Neurobiol, Dept Neuromorphol, D-82152 Martinsried, Germany. Ctr Blood Res, Boston, MA 02115 USA. RI Raivich, Gennadij/A-6770-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PY 1998 VL 10 SU 10 MA 14529 BP 341 EP 341 PG 1 WC Neurosciences SC Neurosciences & Neurology GA ZZ630 UT WOS:000074749401971 ER PT J AU Meyer, JS Terayama, Y Konno, S Akiyama, H Margishvili, GM Mortel, KF AF Meyer, JS Terayama, Y Konno, S Akiyama, H Margishvili, GM Mortel, KF TI Risk factors for cerebral degenerative changes and dementia SO EUROPEAN NEUROLOGY LA English DT Article; Proceedings Paper CT International Symposium on the Challenge of Cerebrovascular Aging - the Therapeutic Value of Almitrine-Raubasine CY MAY 10, 1997 CL SHANGHAI, PEOPLES R CHINA DE normal human aging; risk factors; cognitive decline; dementia; longitudinal analysis; cerebral atrophy and degenerative change; neuroimaging ID COMPUTED TOMOGRAPHIC ANALYSIS; ESTROGEN REPLACEMENT THERAPY; WHITE MATTER LUCENCIES; SCAN LEUKO-ARAIOSIS; ALZHEIMERS-DISEASE; BLOOD-FLOW; VASCULAR DEMENTIA; NEUROLOGIC FINDINGS; BRAIN; ATROPHY AB It is concluded that the most important determinants for cerebral neurodegenerative changes and cognitive decline during aging are neuronal shrinkage and/or loss, which are accelerated by certain risk factors: e.g. TIAs, hypertension, heart disease, hyperlipidemia, smoking, heavy alcohol consumption, male gender, low educational status, family history of cerebrovascular disease and absence of estrogen replacement therapy among women. Some of these risk factors are remediable by therapeutic interventions, including prevention of TIAs and medications that control hypertension, heart disease, hyperlipidemia and estrogen replacement in postmenopausal women, as well as abstention from abuse of tobacco and alcohol. Cerebral neurodegenerative changes measured by neuroimaging appear to be premorbid markers for depleted neuronal and synaptic reserves which predispose to the onset of dementias of both VAD and DAT types. Normal subjects at risk for cognitive decline include those with TIAs, hypertension and heart disease since these risk factors measurably accelerate cerebral atrophy, ventricular enlargement, leukoaraiosis, and decline in cortical perfusion. C1 Baylor Coll Med, VA Med Ctr, Cerebrovasc Res Labs, Dept Neurol, Houston, TX 77030 USA. RP Meyer, JS (reprint author), Baylor Coll Med, VA Med Ctr, Cerebrovasc Res Labs, Dept Neurol, 2002 Holcombe Blvd 151A, Houston, TX 77030 USA. OI Akiyama, Hisanao/0000-0003-4491-6064 NR 52 TC 21 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 1998 VL 39 SU 1 BP 7 EP 16 DI 10.1159/000052064 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZA243 UT WOS:000072343700003 PM 9516069 ER PT J AU Meyer, JS AF Meyer, JS TI Summary and conclusions SO EUROPEAN NEUROLOGY LA English DT Editorial Material C1 Baylor Coll Med, Cerebrovasc Res Lab, VA Med Ctr, Dept Neurol, Houston, TX 77030 USA. RP Meyer, JS (reprint author), Baylor Coll Med, Cerebrovasc Res Lab, VA Med Ctr, Dept Neurol, 2002 Holcombe Blvd 151A, Houston, TX 77030 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 1998 VL 39 SU 1 BP 45 EP 47 DI 10.1159/000052070 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZA243 UT WOS:000072343700009 ER PT J AU Hock, C Golombowski, S Muller-Spahn, F Naser, W Beyreuther, K Monning, U Schenk, D Vigo-Pelfrey, C Bush, AM Moir, R Tanzi, RE Growdon, JH Nitsch, RM AF Hock, C Golombowski, S Muller-Spahn, F Naser, W Beyreuther, K Monning, U Schenk, D Vigo-Pelfrey, C Bush, AM Moir, R Tanzi, RE Growdon, JH Nitsch, RM TI Cerebrospinal fluid levels of amyloid precursor protein and amyloid beta-peptide in Alzheimer's disease and major depression - inverse correlation with dementia severity SO EUROPEAN NEUROLOGY LA English DT Article DE dementia; biochemical markers; early diagnosis; apo E genotype ID APOLIPOPROTEIN-E GENOTYPE; MINI-MENTAL STATE; SOLUBLE DERIVATIVES; DOWNS-SYNDROME; DIAGNOSIS; PRESENILIN-1; DEPOSITION; EPSILON-4; PLAQUES; HEALTH AB Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive dementia that ultimately leads to death, Histopathological hallmarks of AD include brain amyloid deposits and neurofibrillary tangles, Major depression is a frequent diagnosis in every gerontopsychiatric clinic that sees patients with both cognitive and affective disorders, Many depressed patients, in fact, are clinically characterized by cognitive impairments. Thus, an assay that excludes -or confirms -probable AD in cognitively impaired patients is desirable, Such assays may use protein markers that are derived from such histopathologically relevant molecules as the amyloid precursor protein (APP) and its derivatives including the amyloid beta-peprides (A beta), To evaluate the differential diagnostic properties of cerebrospinal fluid (CSF) AB and secreted soluble ectodomain (APPs), we quantitated CSF levels of these measures in AD patients and compared them to age-matched control patients with major depression, CSF levels of APPs and A beta were similar in patients with AD or major depression, and the apolipoprotein E genotype had no Influence on CSF levels of A beta in AD patients. Measurement of A beta peptide using a novel zinc/copper capture ELISA that detects aggregated A beta peptides as well demonstrated similar levels in AD and major depression, In AD patients, CSF levels of total A beta (A beta 1-40 plus A beta 1-42) were inversely correlated with a functional measure of dementia severity (NOSGER), suggesting that CSF levels of A beta decrease with advancing severity of AD, Thus, CSF levels of A beta are not useful for the differentiation of AD from major depression, However, CSF levels of A beta reflect the severity of dementia and may be useful as biological markers of the stage of the disease. C1 Univ Basel, Psychiat Klin, Dept Psychiat, CH-4025 Basel, Switzerland. Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany. Boehringer Mannheim GmbH, Res Lab, Tutzing, Germany. Univ Hamburg, Ctr Mol Neurobiol, D-2000 Hamburg, Germany. Athena Neurosci Inc, S San Francisco, CA 94080 USA. Massachusetts Gen Hosp E, Genet & Aging Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hock, C (reprint author), Univ Basel, Psychiat Klin, Dept Psychiat, Wilhelm Klein Str 27, CH-4025 Basel, Switzerland. EM hock@ubaclu.unibas.ch RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 38 TC 63 Z9 64 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 1998 VL 39 IS 2 BP 111 EP 118 DI 10.1159/000007917 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YX846 UT WOS:000072085500007 PM 9520072 ER PT J AU Bech, P Peuskens, JCJR Marder, SR Chouinard, G Hoybergs, OJ Huttunen, MO Blin, O Claus, A AF Bech, P Peuskens, JCJR Marder, SR Chouinard, G Hoybergs, OJ Huttunen, MO Blin, O Claus, A TI Meta-analytic study of the benefits and risks of treating chronic schizophrenia with risperidone or conventional neuroleptics SO EUROPEAN PSYCHIATRY LA English DT Article DE meta-analysis schizophrenia; risperidone; efficacy; tolerability ID NEGATIVE SYMPTOMS; HALOPERIDOL; METAANALYSIS; CLOZAPINE; SCALE; DRUGS AB Data from six randomised, controlled, comparative studies of risperidone and conventional neuroleptics (haloperidol, zuclopenthixol and perphenazine) in the treatment of 911 patients with chronic schizophrenia were analysed to estimate the benefits and risks of treatment. Efficacy and risk of treatment were assessed by means of the Positive and Negative Syndrome Scale (PANSS) and the Extrapyramidal Symptom Rating Scale (ESRS). An effect size (difference between treatments) was calculated from the PANSS and ESRS scores. The effect size of antipsychotic effect favoured risperidone (sizes ranged from 0.22 to 0.37 on the PANSS subscales), and the effect size of safety also favoured risperidone (sizes ranged from 0.18 to 0.36 on the ESRS). An analysis of the proportions of patients requiring antiparkinsonian medication produced an effect size of 0.37 (20% of risperidone patients and 38% of patients receiving a conventional neuroleptic required antiparkinsonian medication). These data indicate that risperidone is a more effective antipsychotic than the conventional agents and causes less severe extrapyramidal symptoms. (C) 1998 Elsevier, Paris. C1 Frederiksborg Gen Hosp, Psychiat Res Unit, Hillerod Sygehus, DK-3400 Hillerod, Denmark. Univ Ctr St Jozef, Kortenberg, Belgium. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Hosp Louis H Lafontaine, Montreal, PQ, Canada. Molde Hosp, Dept Psychiat, Molde, Norway. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. Hop Enfants La Timone, Marseille, France. Univ Psychiat Hosp St Camillus, Birbeek, Belgium. RP Bech, P (reprint author), Frederiksborg Gen Hosp, Psychiat Res Unit, Hillerod Sygehus, DK-3400 Hillerod, Denmark. NR 26 TC 8 Z9 8 U1 0 U2 3 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 1998 VL 13 IS 6 BP 310 EP 314 DI 10.1016/S0924-9338(98)80049-7 PG 5 WC Psychiatry SC Psychiatry GA 134PH UT WOS:000076751400005 PM 19698646 ER PT J AU Greene, RME Saleh, A Taylor, AKM Callaghan, M Addis, BJ Nzewi, OC van Zyl, WV AF Greene, RME Saleh, A Taylor, AKM Callaghan, M Addis, BJ Nzewi, OC van Zyl, WV TI Non-invasive assessment of bleeding pulmonary artery aneurysms due to Behcet disease SO EUROPEAN RADIOLOGY LA English DT Article DE MR imaging; CT angiography; Behcet disease; pulmonary artery; aneurysm ID INVOLVEMENT AB Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behcet disease. We made exclusive use of CT angiography supplemented by MR to Identity pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral-rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream a downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behcet disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. HCI Int Med Ctr, Dept Radiol, Clydesbank G81 4HX, Scotland. HCI Int Med Ctr, Dept Cardiol, Clydesbank G81 4HX, Scotland. HCI Int Med Ctr, Dept Pathol, Clydesbank G81 4HX, Scotland. HCI Int Med Ctr, Div Cardiovasc Surg, Clydesbank G81 4HX, Scotland. RP Greene, RME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Fruit St, Boston, MA 02114 USA. NR 15 TC 18 Z9 20 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PY 1998 VL 8 IS 3 BP 359 EP 363 DI 10.1007/s003300050394 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZG433 UT WOS:000073001800004 PM 9510565 ER PT J AU Shipley, WU Kaufman, DS Heney, NM Althausen, AF Zietman, AL AF Shipley, WU Kaufman, DS Heney, NM Althausen, AF Zietman, AL TI An update of selective bladder preservation by combined modality therapy for invasive bladder cancer SO EUROPEAN UROLOGY LA English DT Article; Proceedings Paper CT 6th Heinrich Warner Symposium on Invasive Bladder Carcinoma - Progress in Basic Research, Surgical and Medical Therapy CY OCT 30-NOV 01, 1997 CL HAMBURG, GERMANY SP Heinrich Warner Fdn ID CHEMOTHERAPY; EXPERIENCE; RADIATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Radiat Oncol, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Radiat Oncol, Boston, MA 02114 USA. NR 10 TC 16 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-2838 J9 EUR UROL JI Eur. Urol. PY 1998 VL 33 SU 4 BP 32 EP 34 DI 10.1159/000052262 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA ZQ402 UT WOS:000073857600015 PM 9615208 ER PT J AU Alper, CA AF Alper, CA TI A history of complement genetics SO EXPERIMENTAL AND CLINICAL IMMUNOGENETICS LA English DT Article; Proceedings Paper CT VIIth Complement Genetics Workshop and Conference CY MAY 21-23, 1998 CL MAINZ, GERMANY SP Deutsch Forsch Gemeinschaft, Acad Sci & Literature DE complement; genetic polymorphisms; inherited deficiencies; history ID MAJOR HISTOCOMPATIBILITY COMPLEX; FRAGMENT LENGTH POLYMORPHISM; STEROID 21-HYDROXYLASE GENES; RICH BETA-GLYCOPROTEIN; FACTOR-B; DNA POLYMORPHISM; INCREASED SUSCEPTIBILITY; THIRD COMPONENT; F-SUBTYPES; HL-A AB After a brief review of the history of the complement system from the original observations in the 1880s, the history of complement genetics is outlined, beginning in 1919 with the recognition of the complement-deficient guinea pig. A highly personal view is then presented of the early days of the discovery of human complement structural gene polymorphisms and deficiencies, particularly those of C3, BF and factor I. Finally, some recent work based on features in the DNA of the MHC-encoded complement genes is outlined that sheds some light on their evolution. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Alper, CA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 14157] NR 57 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-9670 J9 EXP CLIN IMMUNOGENET JI Exp. Clin. Immunogenet. PY 1998 VL 15 IS 4 BP 203 EP 212 DI 10.1159/000019074 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Genetics & Heredity; Immunology GA 177QD UT WOS:000079221200002 PM 10072630 ER PT J AU Makinodan, T AF Makinodan, T TI Studies on the influence of age on immune response to understand the biology of immunosenescence SO EXPERIMENTAL GERONTOLOGY LA English DT Article ID AGING ANIMALS; BONE-MARROW; IMMUNOLOGICAL DEFICIENCIES; T-CELLS; MICE; RESTORATION; 2-MERCAPTOETHANOL; DIFFERENTIATION; RESPONSIVENESS; DECLINE C1 Univ Calif Los Angeles, VA Med Ctr, GRECC, Ctr Asians & Pacific Islanders,MEDTEP,RAND, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Makinodan, T (reprint author), W Los Angeles Vet Affairs Med Ctr, API, MEDTEP Ctr, RAND,VA,UCLA, 11301 Wilshire Blvd,Bldg 115,Room 328, Los Angeles, CA 90073 USA. NR 35 TC 12 Z9 12 U1 0 U2 0 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 JAN-MAR PY 1998 VL 33 IS 1-2 BP 27 EP 38 DI 10.1016/S0531-5565(97)00058-2 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA YN224 UT WOS:000071145500005 PM 9467714 ER PT J AU Deacon, T Dinsmore, J Costantini, LC Ratliff, J Isacson, O AF Deacon, T Dinsmore, J Costantini, LC Ratliff, J Isacson, O TI Blastula-stage stem cells can differentiate into dopaminergic and serotonergic neurons after transplantation SO EXPERIMENTAL NEUROLOGY LA English DT Article DE embryonic stem cells; brain tissue transplantation; cell development; dopamine; serotonin; Parkinson's disease; Lesch-Nyhan disease ID CENTRAL-NERVOUS-SYSTEM; REGION-SPECIFIC DIFFERENTIATION; FIBROBLAST GROWTH-FACTOR; ADULT-MOUSE BRAIN; PRECURSOR CELLS; IN-VITRO; LINES; RAT; PROLIFERATION; INVITRO AB In order to assess the potential of embryonic stem cells to undergo neuronal differentiation in vivo, totipotent stem cells from mouse blastocysts (D3 and E14TG2a; previously expanded in the presence of leukemia inhibitory factor) were transplanted, with or without retinoic acid pretreatment, into adult mouse brain, adult lesioned rat brain, and into the mouse kidney capsule. Intracerebral grafts survived in 61% of cyclosporine immunosuppressed rats and 100% of mouse hosts, exhibited variable size and morphology, and both intracerebral and kidney capsule grafts developed large numbers of cells exhibiting neuronal morphology and immunoreactivity for neurofilament, neuron-specific enolase, tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), and cells immunoreactive for glial fibrillary acidic protein. Though graft size and histology were variable, typical grafts of 5-10 mm(3) contained 10-20,000 TH+ neurons, whereas dopamine-beta-hydroxylase(+) cells were rare. Most grafts also in eluded nonneuronal regions. In intracerebral grafts, large numbers of astrocytes immunoreactive for glial fibrillary acidic protein were present. Both TH+ and 5-HT+ axons from intracerebral grafts grew into regions of the dopamine-lesioned host striatum. TH+ axons grew preferentially into striatal gray matter, while 5-HT+ axons showed no white/gray matter preference. These findings demonstrate that transplantation to the brain or kidney capsule can induce a significant fraction of totipotent embryonic stem cells to become putative dopaminergic or serotonergic neurons and that when transplanted to the brain these neurons are capable of innervating the adult host striatum. (C) 1998 Academic Press. C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA. Diacrin Inc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Boston Univ, Program Biol Anthropol, Boston, MA 02215 USA. RP Deacon, T (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA. NR 57 TC 167 Z9 181 U1 0 U2 3 PU ACADEMIC PRESS INC 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 JAN PY 1998 VL 149 IS 1 BP 28 EP 41 DI 10.1006/exnr.1997.6674 PG 14 WC Neurosciences SC Neurosciences & Neurology GA YU865 UT WOS:000071763800003 PM 9454612 ER PT J AU Schiff, I Schiff, M AF Schiff, I Schiff, M TI The biblical diagnostician and the anorexic bride SO FERTILITY AND STERILITY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Womens Care Div, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Schiff, I (reprint author), Massachusetts Gen Hosp, Womens Care Div, Vincent Mem Obstet & Gynecol Serv, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 1998 VL 69 IS 1 BP 8 EP 10 DI 10.1016/S0015-0282(97)00460-3 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA YU035 UT WOS:000071673300002 PM 9457924 ER PT J AU Holeman, LA Robinson, SL Szostak, JW Wilson, C AF Holeman, LA Robinson, SL Szostak, JW Wilson, C TI Isolation and characterization of fluorophore-binding RNA aptamers SO FOLDING & DESIGN LA English DT Article DE in vivo labeling; RNA localization; SELEX; sulforhodamine ID RESONANCE ENERGY-TRANSFER; IN-SITU HYBRIDIZATION; VITRO SELECTION; DNA; INVITRO; COFACTORS; MOLECULES; EVOLUTION; ARGININE; PROTEINS AB Background: In vitro selection has been shown previously to be a powerful method for isolating nucleic acids with specific ligand-binding functions ('aptamers'). Given this capacity, we have sought to isolate RNA motifs that can confer fluorescent labeling to tagged RNA transcripts, potentially allowing in vivo detection and in vitro spectroscopic analysis of RNAs. Results: Two aptamers that recognize the fluorophore sulforhodamine B were isolated by the in vitro selection process. An unusually large motif of approximately 60 nucleotides is responsible for binding in one RNA (SRB-2), This motif consists of a three-way helical junction with two large, highly conserved unpaired regions, Phosphorothioate mapping with an iodoacetamide-tagged form of the ligand shows that these two regions make close contacts with the fluorophore, suggesting that the two loops combine to form separate halves of a binding pocket. The aptamer binds the fluorophore with high affinity, recognizing both the planar aromatic ring system and a negatively charged sulfonate, a rare example of anion recognition by RNA. An aptamer (FB-I) that specifically binds fluorescein has also been isolated by mutagenesis of a sulforhodamine aptamer followed by re-selection. In a simple in vitro test, SRB-2 and FB-I have been shown to discriminate between sulforhodamine and fluorescein, specifically localizing each fluorophore to beads tagged with the corresponding aptamer. Conclusions: In addition to serving as a model system for understanding the basis of RNA folding and function, these experiments demonstrate potential applications for the aptamers in transcript double labeling or fluorescence resonance energy transfer studies. C1 Univ Calif Santa Cruz, Dept Biol, Santa Cruz, CA 95064 USA. Univ Calif Santa Cruz, Ctr Mol Biol RNA, Santa Cruz, CA 95064 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Wilson, C (reprint author), Univ Calif Santa Cruz, Dept Biol, Santa Cruz, CA 95064 USA. FU NIGMS NIH HHS [GM52707] NR 26 TC 55 Z9 56 U1 3 U2 28 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1359-0278 J9 FOLD DES JI Fold. Des. PY 1998 VL 3 IS 6 BP 423 EP 431 DI 10.1016/S1359-0278(98)00059-5 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 157CK UT WOS:000078041700004 PM 9889155 ER PT J AU Bogdanov, MB Griffin, RM Beal, MF Matson, WR AF Bogdanov, MB Griffin, RM Beal, MF Matson, WR TI Carbon column-based LCEC method for 8-hydroxy-2i-deoxyguanosine SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. ESA Inc, Chelmsford, MA 01824 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1998 VL 25 SU 1 MA 200 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400219 ER PT J AU Hampton, MB Winterbourn, CC Stamenkovic, I AF Hampton, MB Winterbourn, CC Stamenkovic, I TI Mechanisms of caspase inactivation by hydrogen peroxide SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 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. PY 1998 VL 25 SU 1 MA 254 BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400273 ER PT J AU Held, KD McCarey, YL Biaglow, JE AF Held, KD McCarey, YL Biaglow, JE TI Dual role of thiols in radiation-induced apoptosis. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1998 VL 25 SU 1 MA P5 BP S4 EP S4 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400007 ER PT J AU Kristal, BS Moskowitz, AJ Bogdanov, MB Beal, MF Vigneau-Callahan, KE Matson, WR AF Kristal, BS Moskowitz, AJ Bogdanov, MB Beal, MF Vigneau-Callahan, KE Matson, WR TI Mitochondrial-oxidant interactions SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Burke Med Res Inst, White Plains, NY USA. Cornell Univ, Coll Med, Ithaca, NY 14853 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. ESA Inc, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1998 VL 25 SU 1 MA 70 BP S34 EP S34 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400090 ER PT J AU Scott, DR Weeks, D Hong, C Postius, S Melchers, K Sachs, G AF Scott, DR Weeks, D Hong, C Postius, S Melchers, K Sachs, G TI The role of internal urease in acid resistance of Helicobacter pylori SO GASTROENTEROLOGY LA English DT Article ID HYDROGEN-ION CONCENTRATION; PROTON MOTIVE FORCE; CAMPYLOBACTER-PYLORI; GNOTOBIOTIC PIGLETS; NEGATIVE MUTANT; ULCER DISEASE; MUCUS LAYER; LOW PH; OMEPRAZOLE; GASTRITIS AB Background & Aims: The relative role of internal urease for acid protection of Helicobacter pylori is unknown, The aim of this study was to determine the comparative importance of internal and external urease under acidic conditions, Methods: The pH optimum and measured Michaelis constant for urea of external urease and urease in intact bacteria at different medium pH (pH(out)) were measured using (CO2)-C-14 release from C-14-urea, The effect of urea on membrane potential and bacterial cytoplasmic pH was measured at different fixed pH(out). S-35-methionine labeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of labeled proteins in the organism and medium measured protein synthesis at different pH(out) and mechanisms of urease externalization. Results: External urease had activity between pH 5.0 and 8.5 and internal urease between pH(out) 2.5 and 6.5, and its Michaelis constant at pH(out) 2.5 was 300 mmol/L but at pH(out) 4.5 was 0.5 mmol/L, similar to free urease, The addition of 5 mmol/L urea to bacteria at fixed pH(out) from 3.0 to 6.0 elevated potential to about -105 mV and periplasmic pH to about pH 6.2, Protein synthesis occurred mainly between pH 6.5 and 8.0, and urease activity resulted in increased protein synthesis at acidic pH, The labeling pattern of intrabacterial and released protein was similar. Conclusions: Intracellular urease activity is regulated by external pH, defends against gastric acidity by increasing periplasmic pH and membrane potential, and stimulates protein synthesis at acidic pH. External urease is produced mostly by cell lysis. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. BYK Gulden Lomberg GmbH, Dept Biol Mol, D-7750 Constance, Germany. RP Sachs, G (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 113,Room 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 40615, DK 41301] NR 59 TC 189 Z9 197 U1 0 U2 9 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 JAN PY 1998 VL 114 IS 1 BP 58 EP 70 DI 10.1016/S0016-5085(98)70633-X PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YN909 UT WOS:000071220900012 PM 9428219 ER PT S AU Martin, KJ Sager, R AF Martin, KJ Sager, R BE Walden, P Trefzer, U Sterry, W Farzaneh, F TI Expression genetics in cancer research, prognosis, and therapy SO GENE THERAPY OF CANCER SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd European Conference on Gene Therapy of Cancer CY SEP 11-13, 1997 CL HUMBOLDT UNIV, CHARITE MED FAC, BERLIN, GERMANY SP German Fed Min Educ Sci Res & Technol, Bayer, Chiron, Essex Pharma, Hoechst Marion Roussel, Karl Thomae HO HUMBOLDT UNIV, CHARITE MED FAC ID MAMMARY EPITHELIAL-CELLS; DIFFERENTIAL DISPLAY; MASPIN; RNA; SERPIN C1 Dana Farber Canc Inst, Div Canc Genet, Boston, MA 02115 USA. RP Martin, KJ (reprint author), Dana Farber Canc Inst, Div Canc Genet, 44 Binney St,D-818, Boston, MA 02115 USA. EM kmartin@mberr.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 2 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46027-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 451 BP 1 EP 7 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA BL99D UT WOS:000077389900001 PM 10026842 ER PT S AU Rainov, NG Sena-Esteves, M Fraefel, C Dobberstein, KU Chiocca, EA Breakefield, XO AF Rainov, NG Sena-Esteves, M Fraefel, C Dobberstein, KU Chiocca, EA Breakefield, XO BE Walden, P Trefzer, U Sterry, W Farzaneh, F TI A chimeric fusion protein of cytochrome CYP4B1 and green fluorescent protein for detection of pro-drug activating gene delivery and for gene therapy in malignant glioma SO GENE THERAPY OF CANCER SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 3rd European Conference on Gene Therapy of Cancer CY SEP 11-13, 1997 CL HUMBOLDT UNIV, CHARITE MED FAC, BERLIN, GERMANY SP German Fed Min Educ Sci Res & Technol, Bayer, Chiron, Essex Pharma, Hoechst Marion Roussel, Karl Thomae HO HUMBOLDT UNIV, CHARITE MED FAC ID TARGET ORGAN ALKYLATION; 2B1 GENE; 4-IPOMEANOL; CELLS; METABOLISM; CYCLOPHOSPHAMIDE; TOXICITY; VECTORS; LUNG AB Quantity and distribution of transgene-expressing tumor cells are central issues in cancer gene therapy. These are critical for the efficiency of tumor killing and for the bystander effect. In an attempt to combine the advantages of a potent bioactivating "suicide" gene with a marker gene for living cells, cDNA encoding cytochrome CYP4B1 was fused to the green fluorescent protein (GFP) cDNA. The resulting chimeric fusion protein, 4B1EGFP, was expressed in rodent and human glioma cell lines in culture. The ability of this recombinant enzyme to destroy tumor cells by converting the prodrug 4-ipomeanol (4-IM) into alkylating metabolites was evaluated in comparison with the cytotoxicity of the native CYP4B1 enzyme. The most sensitive 4B1EGFP-expressing glioma cell clone had a LD50 of 0.75 mu g/ml for 4-IM, as compared to a 4-IM LD50 of 0.5 mu g/ml in glioma cells expressing the native CYP4B1. A strong bystander effect mediated by cell-to-cell contact was present in the 4B1EGFP clones, allowing for more than 50% bystander kill at a ratio of expressing to non-expressing cells of 1:100. A herpes-simplex amplicon (pHSVPrPUC Delta Hind) was constructed with the 4B1EGFP fusion protein, and recombinant helper-free HSV particles were packaged in Vero cells. Fisher 344 rats were inoculated with 4 x 10(5) 9L tumor cells to produce epidural tumor. Recombinant HSV particles were injected into the tumor at a dose of 1 x 10(7) pfu. Tumor was resected in living anesthetized animals 24, 48, and 72 hours after virus injection, and cryostat sections were evaluated by fluorescent microscopy. HSV-mediated delivery of the fusion protein to tumor cells was successfully demonstrated. In conclusion, the chimeric fusion protein 4B1EGFP retains essentially all features of the native CYP4B1 enzyme, and, moreover, offers advantages in terms of gene transfer visualization, which may lead to improvement of gene transfer strategies. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Serv Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02129 USA. Univ Halle Wittenberg, Dept Neurosurg, Fac Med, D-06097 Halle, Germany. RP Rainov, NG (reprint author), Univ Halle Wittenberg, Dept Neurosurg, Fac Med, Magdeburger Str 16, D-06097 Halle, Germany. EM nikolai.rainov@medizin.uni-halle.de FU NCI NIH HHS [CA69246] NR 21 TC 20 Z9 22 U1 1 U2 3 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46027-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1998 VL 451 BP 393 EP 403 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA BL99D UT WOS:000077389900061 PM 10026902 ER PT J AU Marsh, DJ Dahia, PLM Coulon, V Zheng, ZM Dorion-Bonnet, F Call, KM Little, R Lin, AY Eeles, RA Goldstein, AM Hodgson, SV Richardson, AL Robinson, BG Weber, HC Longy, M Eng, C AF Marsh, DJ Dahia, PLM Coulon, V Zheng, ZM Dorion-Bonnet, F Call, KM Little, R Lin, AY Eeles, RA Goldstein, AM Hodgson, SV Richardson, AL Robinson, BG Weber, HC Longy, M Eng, C TI Allelic imbalance, including deletion of PTEN/MMACI, at the Cowden disease locus on 10q22-23, in hamartomas from patients with Cowden syndrome and germline PTEN mutation SO GENES CHROMOSOMES & CANCER LA English DT Article ID MOLECULAR-GENETICS; WILMS-TUMOR; RETINOBLASTOMA; INACTIVATION; FAMILY; CANCER; MAP AB Cowden disease (CD) is a rare, autosomal dominant inherited cancer syndrome characterized by multiple benign and malignant lesions in a wide spectrum of tissues. While individuals with CD have an increased risk of breast and thyroid neoplasms, the primary features of CD are hamartomas. The gene for CD has been mapped by linkage analysis to a 6 cM region on the long arm of chromosome 10 at 10q22-23. Loss of heterozygosity (LOH) studies of sporadic follicular thyroid adenomas and carcinomas, both component tumors of CD, have suggested that the putative susceptibility gene for CD is a tumor suppressor gene. Somatic missense and nonsense mutations have recently been identified in breast, prostate, and brain tumor cell lines in a gene encoding a dual specificity phosphatase, PTEN/MMACI, mapped at 10q23.3. Furthermore, germline PTEN/MMACI mutations are associated with CD. In the present study, 20 hamartomas from 11 individuals belonging to ten unrelated families with CD have been examined for LOH of markers flanking and within PTEN/MMACI. Eight of these ten families have germline PTEN/MMACI mutations. LOH involving microsatellite markers within the CD interval, and including PTEN/MMACI, was identified in two fibroadenomas of the breast, a thyroid adenoma, and a pulmonary hamartoma belonging to 3 of 11 (27%) of these patients. The wild-type allele was lost in these hamartomas. Semi-quantitative PCR performed on RNA from hamartomas from three different tissues from a CD patient suggested substantial reduction of PTEN/MMACI RNA levels in all of these tissues. The LOH identified in samples from individuals with CD and the suggestion of allelic loss and reduced transcription in hamartomas from a CD patient provide evidence that PTEN/MMACI functions as a tumor suppressor in CD. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med,Dept Adult Oncol, Dana Farber Canc Inst,Tradit Res Lab, Dept Med,Program Populat Sci,Human Canc Genet Uni, Boston, MA 02115 USA. Inst Bergonie, Bordeaux, France. Genome Therapeut Corp, Waltham, MA USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Royal Marsden Hosp, Canc Res Inst, Surrey, England. Guys & St Thomas Hosp, Dept Clin Genet, London SE1 9RT, England. Royal N Shore Hosp, Kolling Inst Med Res, Mol Genet Unit, St Leonards, NSW 2065, Australia. Royal N Shore Hosp, Dept Surg, St Leonards, NSW 2065, Australia. Royal N Shore Hosp, Dept Endocrinol, St Leonards, NSW 2065, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. RP Eng, C (reprint author), Harvard Univ, Sch Med,Dept Adult Oncol, Dana Farber Canc Inst,Tradit Res Lab, Dept Med,Program Populat Sci,Human Canc Genet Uni, SM822,44 Binney St, Boston, MA 02115 USA. RI Marsh, Deborah/I-1491-2014; Little, Randall/O-7172-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 24 TC 77 Z9 78 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JAN PY 1998 VL 21 IS 1 BP 61 EP 69 DI 10.1002/(SICI)1098-2264(199801)21:1<61::AID-GCC8>3.0.CO;2-6 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA YP539 UT WOS:000071288000008 PM 9443042 ER PT J AU Sellers, WR Novitch, BG Miyake, S Heith, A Otterson, GA Kaye, FJ Lassar, AB Kaelin, WG AF Sellers, WR Novitch, BG Miyake, S Heith, A Otterson, GA Kaye, FJ Lassar, AB Kaelin, WG TI Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth SO GENES & DEVELOPMENT LA English DT Article DE retinoblastoma; transcription; E2F; tumorigenesis ID ONCOGENIC POINT MUTATIONS; SKELETAL-MUSCLE CELLS; CYCLIN-E GENE; FAMILY MEMBERS; GLUCOCORTICOID RECEPTOR; INCOMPLETE PENETRANCE; RB-1 GENE; P107; PRODUCT; PRB AB The retinoblastoma tumor suppressor protein (pRB) can inhibit cell cycle progression and promote differentiation. pRB interacts with a variety of transcription factors, including members of the E2F and C-EBP protein families and MyoD, and can either repress or activate transcription depending on the promoter under study. These biological and biochemical activities of pRB have been mapped previously to a core domain, referred to as the pRB pocket. Using a panel of synthetic pRB pocket mutants, we found that the acute induction of a G(1)/S block by pRB is linked to its ability to both bind to E2F and to repress transcription. In contrast, these functions were not required for pRB to promote differentiation, which correlated with its ability to activate transcription in concert with fate-determining proteins such as MyoD. All tumor-derived PRE mutants tested to date failed to bind to E2F and did not repress transcription. Despite an inability to bind to E2F, pRB mutants associated with a low risk of retinoblastoma, unlike high-risk mutants, retained the ability to activate transcription and promote differentiation. Thus, the pRB pocket participates in dual tumor suppressor functions, one linked to cell cycle progression and the other to differentiation control, and these functions can be genetically and mechanistically dissociated. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NCI, USN, Med Oncol Branch, Div Clin Sci, Bethesda, MD 20889 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI kaye, frederic/E-2437-2011; OI Novitch, Bennett/0000-0002-2696-3708 NR 59 TC 249 Z9 255 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 1998 VL 12 IS 1 BP 95 EP 106 DI 10.1101/gad.12.1.95 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA YR072 UT WOS:000071455400010 PM 9420334 ER PT J AU Lunetta, KL Rogus, JJ AF Lunetta, KL Rogus, JJ TI Strategy for manning minor histocompatibility genes involved in graft-versus-host disease: A novel application of discordant sib pair methodology SO GENETIC EPIDEMIOLOGY LA English DT Article DE discordant sib pairs; nonparametric linkage; linkage methods; graft-versus-host disease ID BONE-MARROW TRANSPLANTATION; GENETICALLY COMPLEX TRAITS; LINKAGE STRATEGIES; ANTIGENS; POLYMORPHISM; RECIPIENTS; RISK AB We introduce a novel application for linkage analysis: using bone marrow donor-recipient sib pairs to search for genes influential in graft-versus-host disease (GVHD), a major cause of morbidity and mortality following allogeneic bone marrow transplantation. In particular, we show that transplant sib pairs in which the recipient developed severe GVHD can be used to map genes in the same way as traditional discordant (affected/unaffected) sib pairs (DSPs). For a plausible GVHD model, we demonstrate that the transplant/discordant sib pair analog of the "possible triangle test" [Holmans (1993) Am J Hum Genet 52:362-374] has similar power to that of the simpler "restricted test" proposed by Risch [(1990b) Am J Hum Genet 46:229-241; (1992) Am J Hum Genet 51:673-675]. Moreover, we show that the restricted test has superior power in much of the DSP possible triangle and significantly inferior power in only a small region. Thus, we conclude that the restricted test is preferable for localizing genes with transplant/discordant sib pairs. Finally, we examine the effects of heterogeneity on the power to detect GVHD loci and demonstrate the gain in efficiency by dividing the sample into genetically more homogeneous subgroups. (C) 1998 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Div Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. RP Lunetta, KL (reprint author), Dana Farber Canc Inst, Div Biostat Sci, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 T32 CA09337-17] NR 16 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1998 VL 15 IS 6 BP 595 EP 607 DI 10.1002/(SICI)1098-2272(1998)15:6<595::AID-GEPI4>3.0.CO;2-4 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 131TW UT WOS:000076592200004 PM 9811421 ER PT J AU Smith, WM Van Orsouw, NJ Fox, EA Kolodner, RD Vijg, J Eng, C AF Smith, WM Van Orsouw, NJ Fox, EA Kolodner, RD Vijg, J Eng, C TI Accurate, high-throughput "snapshot" detection of hMLH1 mutations by two-dimensional DNA electrophoresis SO GENETIC TESTING LA English DT Article ID NONPOLYPOSIS COLON-CANCER; GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTION; COLORECTAL-CANCER; GERMLINE MUTATIONS; MISMATCH REPAIR; BREAST-CANCER; P53 GENE; GC-CLAMP; HEREDITARY AB The human genome and related projects have resulted in the isolation of a rapidly growing number of genes that cause susceptibility to human cancer. With rare exception, these genes are large and have disease-associated mutations scattered along the length of the genes. Therefore, the development of accurate and cost-efficient mutation detection tests that can scan entire genes singly or in combination is warranted. hMLH1, encoding a mismatch repair enzyme, is a susceptibility gene for hereditary nonpolyposis colon cancer syndrome. This gene comprises 19 exons; mutations are scattered, typical of many susceptibility genes, Here, we present a strategy that combines extensive PCR multiplexing and two-dimensional DNA electrophoresis (Two-Dimensional Gene Scanning, TDGS) to scan accurately for mutations that lie within the exons and splice junctions of hMLH1, All target fragments, designed to have optimal melting characteristics, were prepared in a two-stage PCR-a four-plex long-distance PCR followed by short PCR in two multiplex groups of 10 and 11 amplicons, The mixture of amplicons was subjected to two-dimensional electrophoresis: separation by size in the first dimension and by melting characteristics in the second. Using this design, 41 samples containing known hMLH1 sequence variants or no alterations were blindly subjected to TDGS. All mutations were detected; there were no genuine false-positive or false-negative results. These results confirm that TDGS is a generally applicable, rapid, accurate, and reproducible mutation detection technology that would serve large-scale molecular epidemiologic studies as well as clinical molecular diagnostic purposes. C1 Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Program Populat Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Gerontol Div, Mol Genet Sect, Boston, MA 02115 USA. Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP Eng, C (reprint author), Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [1P30AG13314-02] NR 29 TC 9 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PY 1998 VL 2 IS 1 BP 43 EP 53 DI 10.1089/gte.1998.2.43 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 161UX UT WOS:000078309000007 PM 10464596 ER PT J AU Dhanda, RK Smith, WM Scott, CB Eng, C Vijg, J AF Dhanda, RK Smith, WM Scott, CB Eng, C Vijg, J TI A simple system for automated two-dimensional electrophoresis: Applications to genetic testing SO GENETIC TESTING LA English DT Article ID STRAND CONFORMATION POLYMORPHISM; GRADIENT GEL-ELECTROPHORESIS; MUTATIONS; PCR AB Two-dimensional gene scanning (TDGS) is a method for mutation detection based on two-dimensional electrophoretic separation of PCR-amplified DNA fragments according to size and base pair sequence. To facilitate two-dimensional electrophoresis without manual interference, a simple three-chamber unit was designed on top of an existing vertical electrophoresis instrument. Application of this system to genetic testing is demonstrated by the performance of a complete two-dimensional mutational scanning assay of one of the hereditary nonpolyposis colon cancer syndrome susceptibility genes, hMLH1. C1 Beth Israel Deaconess Med Ctr, Dept Med, Gerontol Div, Mol Genet Sect, Boston, MA 02115 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Dept Adult Oncol, Translat Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. CBS Sci Co Inc, Del Mar, CA 92014 USA. RP Vijg, J (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Gerontol Div, Mol Genet Sect, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [AG13314] NR 12 TC 9 Z9 9 U1 0 U2 0 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. PY 1998 VL 2 IS 1 BP 67 EP 70 DI 10.1089/gte.1998.2.67 PG 4 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 161UX UT WOS:000078309000010 PM 10464599 ER PT J AU Talbot, WS Egan, ES Gates, MA Walker, C Ullmann, B Neuhauss, SCF Kimmel, CB Postlethwait, JH AF Talbot, WS Egan, ES Gates, MA Walker, C Ullmann, B Neuhauss, SCF Kimmel, CB Postlethwait, JH TI Genetic analysis of chromosomal rearrangements in the cyclops region of the zebrafish genome SO GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; MUTATIONS; LOCUS; SPECIFICATION; MUTAGENESIS; FREQUENCY; BIOLOGY; MOUSE; CELLS; MAP AB Genetic screens in zebrafish have provided mutations in hundreds of genes with essential functions in die developing embryo. To investigate the possible uses of chromosomal rearrangements in the analysis of these mutations, we genetically characterized three gamma-ray induced alleles of cyclops (cyc), a gene required for development of midline structures. We show that cyc maps near one end of Linkage Group 12 (LG 12) and that this region is involved in a reciprocal translocation with LG 2 in one gamma-ray induced mutation, cyc(b213). The translocated segments together cover approximately 5% of the genetic map, and we show that this rearrangement is useful for mapping cloned genes thai reside in the affected chromosomal regions. The other two alleles, cyc(b16) and cyc(b229), have deletions in the distal region of LG 12. Interestingly, both of these mutations suppress recombination between genetic markers in LG 12, including markers al a distance from the deletion. This observation raises the possibility that these deletions affect a site required for meiotic recombination on the LG 12 chromosome. The cyc(b16) and cyc(b229) mutations may be useful for balancing other lethal mutations located in the distal region of LG 12. These results show that chromosomal rearrangements call provide useful resources for mapping and genetic analyses in zebrafish. C1 NYU, Med Ctr, Skirball Inst Biomol Med, Dev Genet Program, New York, NY 10016 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Talbot, WS (reprint author), NYU, Med Ctr, Skirball Inst Biomol Med, Dev Genet Program, 540 1st Ave, New York, NY 10016 USA. FU NCRR NIH HHS [R01 RR12349, R01 RR10715]; NICHD NIH HHS [P01 HD22486] NR 34 TC 28 Z9 28 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 1998 VL 148 IS 1 BP 373 EP 380 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YR425 UT WOS:000071494000034 PM 9475747 ER PT B AU Habener, JF Daniel, PB Walker, WH AF Habener, JF Daniel, PB Walker, WH BE Zirkin, BR TI Expression of activator and repressor isoforms of transcription factor CREB during spermatogenesis SO GERM CELL DEVELOPMENT, DIVISION, DISRUPTION AND DEATH SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT XIVth Testis Workshop on Germ Cell Development. Division, Disruption and Death CY FEB 19-22, 1997 CL BALTIMORE, MD SP Serono Symposia USA Inc C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-98368-6 J9 SERONO SYMP PY 1998 BP 96 EP 104 PG 9 WC Andrology; Cell Biology; Developmental Biology SC Endocrinology & Metabolism; Cell Biology; Developmental Biology GA BL14N UT WOS:000074440100010 ER PT J AU Barnes, CJ Cameron, IL Lee, M AF Barnes, CJ Cameron, IL Lee, M TI Immunohistochemical localization of prostaglandin endoperoxide G/H synthase isozymes in the normal rat colon epithelium and in 1,2-dimethylhydrazine-induced colon tumours SO GI CANCER LA English DT Article DE prostaglandin synthase; colon cancer; immunohistochemistry; rats ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 GENE-EXPRESSION; ASPIRIN; CANCER; ADENOCARCINOMAS; ADENOMAS; TUMORS AB Objectives Prostaglandin endoperoxide G/H synthase (PGHS) is a potential target for colon cancer chemoprevention. The aims of this study were to determine if the localization of PGHS isozymes is altered early in 1,2-dimethylhydrazine (DMH)-induced rat colon tumorigenesis and to characterize PGHS isozyme localization in DMH-induced colon tumours. Methods Male Sprague-Dawley rats were injected once a week for 8 weeks with the colon carcinogen DMH or vehicle and then sacrificed at 9 or 30 weeks. Immunohistochemical detection of PGHS isozymes was performed in normal appearing colonic mucosa and colon tumours. Results At both time points, in normal appearing colon, PGHS-1 was localized in vascular endothelial cells, smooth muscle cells, and specific cells in the lamina propria, while PGHS-2 localization was limited to a few scattered cells at the periphery of lymphatic modules. However, both isozymes were localized to carcinoma and stromal cells of DMH-induced colon tumours. Conclusions PGHS-1 is the predominant isozyme in the rat colon, and PGHS-2 is selectively upregulated in DMH-induced colon tumours. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Gastroenterol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Vet Affairs Med Ctr, San Antonio, TX 78284 USA. RP Barnes, CJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Gastroenterol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1064-9700 J9 GI CANCER JI GI Cancer PY 1998 VL 2 IS 4 BP 329 EP + PG 6 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA 123RN UT WOS:000076138300009 ER PT J AU Hsueh, YP Sheng, M AF Hsueh, YP Sheng, M TI Anchoring of glutamate receptors at the synapse SO GLUTAMATE SYNAPSE AS A THERAPEUTICAL TARGET: MOLECULAR ORGANIZATION AND PATHOLOGY OF THE GLUTAMATE SYNAPSE SE PROGRESS IN BRAIN RESEARCH LA English DT Review ID NITRIC-OXIDE SYNTHASE; TUMOR-SUPPRESSOR PROTEIN; NMDA RECEPTOR; POSTSYNAPTIC DENSITY; PDZ DOMAINS; RAT-BRAIN; GUANYLATE KINASES; PSD-95 FAMILY; NR1 SUBUNIT; K+ CHANNELS C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wel 423,50 Blossom St, Boston, MA 02114 USA. EM sheng@helix.mgh.harvard.edu OI Hsueh, Yi-Ping/0000-0002-0866-6275 FU NINDS NIH HHS [NS35050] NR 44 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES PY 1998 VL 116 BP 123 EP 131 DI 10.1016/S0079-6123(08)60434-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA BM21W UT WOS:000078045300009 PM 9932374 ER PT J AU Lancelot, E Beal, MF AF Lancelot, E Beal, MF TI Glutamate toxicity in chronic neurodegenerative disease SO GLUTAMATE SYNAPSE AS A THERAPEUTICAL TARGET: MOLECULAR ORGANIZATION AND PATHOLOGY OF THE GLUTAMATE SYNAPSE SE PROGRESS IN BRAIN RESEARCH LA English DT Review ID METHYL-D-ASPARTATE; AMYOTROPHIC-LATERAL-SCLEROSIS; NITRIC-OXIDE SYNTHASE; STRIATAL EXCITOTOXIC LESIONS; CULTURED CORTICAL-NEURONS; NMDA RECEPTOR ACTIVATION; FIBROBLAST GROWTH-FACTOR; AMINO-ACID RECEPTORS; INTRACELLULAR CALCIUM CONCENTRATIONS; DEHYDROGENASE INHIBITOR MALONATE C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Dept Neurol, Warren 408,32 Fruit St, Boston, MA 02114 USA. NR 188 TC 62 Z9 62 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES PY 1998 VL 116 BP 331 EP 347 DI 10.1016/S0079-6123(08)60446-X PG 17 WC Neurosciences SC Neurosciences & Neurology GA BM21W UT WOS:000078045300021 PM 9932386 ER PT J AU Fones, CSL Manfro, GG Pollack, MH AF Fones, CSL Manfro, GG Pollack, MH TI Social phobia: An update SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID AVOIDANT PERSONALITY-DISORDER; NATIONAL-COMORBIDITY-SURVEY; ANXIETY DISORDERS; PANIC DISORDER; PSYCHOPHARMACOLOGICAL TREATMENT; AXIS-I; PSYCHIATRIC-DISORDERS; BEHAVIORAL TREATMENTS; PHYSICAL-DISABILITY; PLACEBO AB The literature on social phobia is reviewed in this article. Social phobia has undergone considerable diagnostic evolution to reach its present form in DSM-IV. Its differential diagnosis includes panic disorder with agoraphobia, avoidant personality disorder, depression, and "shyness." Cross-cultural issues are important to consider because the disorder may manifest differently in different cultures and social settings. It is common, with a lifetime prevalence of 13.3% in the United States according to recent epidemiological studies. Underrecognition of social phobia remains an issue of concern. Comorbidity with other psychiatric disorders, including other anxiety disorders, depression, alcohol abuse, and personality disorders, frequently occurs. Current conceptualizations of the etiology of social phobia reflect psychodynamic theories and evidence from family and genetic studies, neurobiological research, and neuroimaging. Drugs such as monoamine oxidase inhibitors, selective serotonin-reuptake inhibitors, benzodiazepines, and beta-adrenergic blockers have proven to be efficacious, as has cognitive-behavioral treatment, including group approaches. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. RP Fones, CSL (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, 15 Parkman St,ACC 815, Boston, MA 02114 USA. RI Manfro, Gisele/B-7020-2009 NR 110 TC 19 Z9 20 U1 7 U2 8 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 1998 VL 5 IS 5 BP 247 EP 259 DI 10.3109/10673229809000308 PG 13 WC Psychiatry SC Psychiatry GA YV909 UT WOS:000071876500002 PM 9493947 ER PT J AU Geller, DA Biederman, J Jones, J Shapiro, S Schwartz, S Park, KS AF Geller, DA Biederman, J Jones, J Shapiro, S Schwartz, S Park, KS TI Obsessive-compulsive disorder in children and adolescents: A review SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID PROSPECTIVE FOLLOW-UP; CEREBROSPINAL-FLUID NEUROCHEMISTRY; LA-TOURETTES SYNDROME; DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; COMMUNITY SAMPLE; BEHAVIORAL PSYCHOTHERAPY; DIFFERENTIAL-DIAGNOSIS; PSYCHIATRIC-DISORDERS; GENETIC-RELATIONSHIP AB Obsessive-compulsive disorder (OCD) is a common psychiatric illness that occurs across the entire life span, Although most research on OCD pertains to adults, studies of the disorder in children and adolescents have burgeoned over the last decade, A review of this literature suggests that OCD has a bimodal incidence pattern, with one peak of onset at approximately 10 years of age and another during adulthood, and that the juvenile and adult forms are equally prevalent. Important similarities and differences between the juvenile- and adult-onset forms of OCD can be seen: both show the same clinical phenotype, diagnostic nosology, and dose responsivity, but the early-onset disorder differs in being clearly male preponderant, more highly familial, and associated with a distinct pattern of comorbid psychopathology,, including disruptive behavior and specific developmental disorders. These findings have implications both for clinical management and for future research, which could consider age of onset as an important factor in studies of all OCD patients. C1 McLean Hosp, Joint Program Pediat Psychopharmacol, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Geller, DA (reprint author), McLean Hosp, Joint Program Pediat Psychopharmacol, 115 Mill St, Belmont, MA 02178 USA. NR 118 TC 73 Z9 73 U1 10 U2 21 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 1998 VL 5 IS 5 BP 260 EP 273 DI 10.3109/10673229809000309 PG 14 WC Psychiatry SC Psychiatry GA YV909 UT WOS:000071876500003 PM 9493948 ER PT J AU Fredman, SJ Rosenbaum, JF AF Fredman, SJ Rosenbaum, JF TI Recurrent depression, resistant clinician? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID COGNITIVE BEHAVIOR-THERAPY; PROSPECTIVE FOLLOW-UP; LONG-TERM TREATMENT; MAINTENANCE THERAPY; MAJOR DEPRESSION; RELAPSE PREVENTION; DISORDER; PHARMACOTHERAPY; CONTINUATION; RECOVERY C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, 15 Parkman St,WAC 812, Boston, MA 02114 USA. NR 52 TC 3 Z9 3 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JAN-FEB PY 1998 VL 5 IS 5 BP 281 EP 285 PG 5 WC Psychiatry SC Psychiatry GA YV909 UT WOS:000071876500005 PM 9493950 ER PT J AU Cutrer, FM AF Cutrer, FM TI Me and my headache - The doctor is the patient SO HEADACHE QUARTERLY-CURRENT TREATMENT AND RESEARCH LA English DT Article AB Five years as a migraine researcher, 8 years as a neurologist, 10 years as a physician, and 25 years as a migraineur have prompted this article. The focus is on the impact of migraine as experienced first by a teenager, then by a college student, then by a neurologist, and finally, by a headache researcher. Migraine attacks as experienced from both sides of the examining table are recalled as is their evolution from a source of dread to a source of data. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Headache Unit, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DIAMOND HEADACHE CLINIC RESEARCH & EDUC FOUNDATION PI CHICAGO PA 467 WEST DEMING PLACE, CHICAGO, IL 60614 USA SN 1059-7565 J9 HEADACHE Q-CURR TREA JI Headache Q.-Curr. Treat. Res. PY 1998 VL 9 IS 1 BP 45 EP 46 PG 2 WC Neurosciences SC Neurosciences & Neurology GA ZB111 UT WOS:000072437000006 ER PT J AU Biggs, PJ AF Biggs, PJ TI Evidence for photoneutron production in the lead shielding of a dedicated intra-operative electron only facility SO HEALTH PHYSICS LA English DT Article DE electrons; neutrons; shielding; radiation protection AB A dedicated electron-only intra-operative suite has just been completed at the Massachusetts General Hospital, This suite is located on the 3rd floor with the shielding consisting entirely of lead and berated polyethylene, except for concrete in the floor and ceiling to support the lead and on the finished floor, The radiation protection barriers for this facility were calculated on the basis of a maximum permissible dose of 10 mu Sv wk(-1) for photons and 10 mu Sv wk(-1) for neutrons, based on a quality factor of 10 (this factor is specified in the regulations of the Commonwealth of Massachusetts), This even split was predicated on the basis that, except for the primary beam, the neutron leakage from the machine was generally about the same as for x rays. The initial survey showed that the neutron dose equivalent outside all barriers, except below the floor, was within the calculated values, <10 mu Sv wk(-1). However, the neutron dose equivalent measured directly below the floor was found to be 35 mu Sv wk(-1) for the highest electron energy, a difference of > 25 mu Sv wk(-1). The neutron dose equivalent, for neutrons produced by bremsstrahlung photon interactions in the lead and based on a 3% photon background in the electron beam, was calculated to be 25 mu Sv wk(-1), in good agreement with this difference. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. RP Biggs, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JAN PY 1998 VL 74 IS 1 BP 96 EP 98 DI 10.1097/00004032-199801000-00012 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA YM718 UT WOS:000071093900013 PM 9415587 ER PT J AU Ubel, PA Loewenstein, G Scanlon, D Kamlet, M AF Ubel, PA Loewenstein, G Scanlon, D Kamlet, M TI Value measurement in cost-utility analysis: Explaining the discrepancy between rating scale and person trade-off elicitations SO HEALTH POLICY LA English DT Article DE cost-effectiveness analysis; utility; person trade-off; rating scale ID HEALTH-CARE; PREFERENCES; OUTCOMES; STATES; OREGON; QALYS AB Previous studies have shown a discrepancy between common utility elicitation methods, such as rating scale (RS) elicitations, and person trade-off (PTO) elicitations. This discrepancy has generally been felt to be due to the fact that RS elicitations ask people to compare conditions to each other in terms of numbers on a visual rating scale, while PTO elicitations ask people to think in terms of numbers of people needing to be treated. However, there are three other cognitive differences between PTO and RS elicitations that might contribute to the discrepancy: In PTO elicitations, as opposed to RS elicitations: (1) people are asked to think about how conditions affect people other than themselves; (2) people are asked to think about the benefit of treating conditions; and (3) people are asked to chose who to treat among patients with different conditions. In this study, we attempt to determine whether any of these three cognitive differences contribute to the discrepancy between RS and PTO utility elicitations. We randomized prospective jurors to receive one of several survey versions in which we manipulated the RS and PTO elicitations to reduce the differences between them, while preserving their underlying structure. In the RS-self survey, we asked subjects to rate a health condition on a scale from 0 to 100 as if they had the condition. In the RS-other survey, we asked people to rate the health condition as if someone else had it. In the RS-cure survey, we asked subjects to rate the benefits of curing someone else of the health condition. In the PTO-comparison survey, we asked people to determine equivalent numbers of people needing to be cured of two conditions in order to produce equal benefits. In the PTO-choice survey, we presented people with a budget constraint and asked them to determine equivalent numbers of people needing to be cured of two conditions to help decide which group should be treated within the budget constraint. Two hundred and twenty two subjects completed surveys. Median utilities for health conditions were higher in the two PTO elicitations than in the three RS elicitations. There were no differences in utilities across the two PTO surveys, nor across the three RS surveys. In addition, the PTO elicitations allowed people to make finer distinctions among non-life threatening conditions than did the RS elicitations. The discrepancy between RS and PTO elicitations cannot be explained by shifting subjects attentions from themselves to others, nor from conditions to the benefit of treating conditions. Instead, the discrepancy occurs because of the general format of RS and PTO elicitations. (C) 1998 Published by Elsevier Science Ireland Ltd. C1 Vet Affairs Med Ctr, Philadelphia, PA USA. Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. Penn State Univ, Dept Hlth Policy & Adm, University Pk, PA 16802 USA. Carnegie Mellon Univ, H John Heinz III Sch Publ Policy & Management, Pittsburgh, PA 15213 USA. RP Ubel, PA (reprint author), Univ Penn, Ctr Bioeth, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. NR 18 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD JAN PY 1998 VL 43 IS 1 BP 33 EP 44 DI 10.1016/S0168-8510(97)00077-8 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA YZ153 UT WOS:000072225600003 PM 10178799 ER PT J AU Gulley, ML Zhang, Q Gascoyne, RD DuPont, BR Banks, PM Cho, CG Huang, JM Montalvo, EA AF Gulley, ML Zhang, Q Gascoyne, RD DuPont, BR Banks, PM Cho, CG Huang, JM Montalvo, EA TI Translocations of 11q13 in mantle cell lymphoma fail to disrupt the S mu bp-2 gene SO HEMATOPATHOLOGY AND MOLECULAR HEMATOLOGY LA English DT Article DE mantle cell lymphoma; S mu bp-2; 11q13; Epstein-Barr virus; BZLF1 ID DNA-BINDING PROTEIN; CYCLIN D1 GENE; TRANSCRIPTION FACTOR; MOLECULAR-CLONING; BCL-1 LOCUS; BREAKPOINTS; REARRANGEMENTS; OVEREXPRESSION; CHROMOSOME-11; MALIGNANCIES AB We recently cloned a gene whose protein product binds to the Epstein-Barr virus BZLF1 gene promoter. The same gene has been previously cloned by another group who named it S mu bp-2 because its protein product binds to the S mu motif of the immunoglobulin heavy chain gene where it is postulated to function in immunoglobulin class switching. In the current study, we confirm that the S mu bp-2 gene is located on chromosome 11q13, a locus known to be altered by translocation in 50-70% of mantle cell lymphomas. We used Southern blot analysis to determine whether the S mu bp-2 gene was structurally rearranged in any of 25 mantle cell lymphomas. We found no evidence of rearrangement in any of these lymphomas including 18 that were proven to contain t(11;14) by cytogenetic analysis. These data suggest that structural alteration of the S mu bp-2 gene is not an underlying mechanism of tumorigenesis in mantle cell lymphomas. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX 78284 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. RP Gulley, ML (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-8893 J9 HEMATOPATHOL MOL HEM JI Hematopathol. Mol. Hematol. PY 1998 VL 11 IS 1 BP 1 EP 11 PG 11 WC Hematology; Pathology SC Hematology; Pathology GA YM690 UT WOS:000071090300001 ER PT S AU Yablon, AD Nishioka, NS Mikic, BB Venugopalan, V AF Yablon, AD Nishioka, NS Mikic, BB Venugopalan, V BE Phipps, CR TI Physical mechanisms of pulsed infrared laser ablation of biological tissues SO HIGH-POWER LASER ABLATION, PTS 1-2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on High-Power Laser Ablation CY APR 26-30, 1998 CL SANTA FE, NM SP SPIE, Univ Illinois, Fus Studies Lab, NE Sci & Technol Inc, Photon Associates Inc, F2 Associates Inc DE laser ablation; explosive boiling; tissue ablation; interphase mass transfer AB Time-resolved measurement of the stress transients generated by pulsed infrared irradiation and ablation of tissue has demonstrated that these processes are governed primarily by photothermal processes. For ablation of porcine dermis at 2.79 mu m (Q-sw Er:YSGG) and 10.6 mu m (CO2), the onset of material removal has been shown to be delayed with respect to irradiation and the magnitude of the generated stress transients are consistent with a model for explosive material removal. Upon consideration of the threshold radiant exposure for ablation, it appears that the mechanism and dynamics of these processes are controlled by explosive boiling as the tissue water is likely to be significantly superheated. To examine this issue further, we employed time-reserved optical interferometry to measure the surface displacement generated by Q-sw Er:YSGG laser irradiation of pure water for radiant exposures below the ablation threshold. This was done to directly measure the dynamic thermal expansion and interphase mass transfer generated by pulsed laser heating. These results are compared to a model which computes the dynamic thermal field within a semi-infinite pool of water undergoing pulsed irradiation while subject to a surface heat flux condition given by kinetic theory. We find that the measured mass fluxes exceed that predicted by simple kinetic theory arguments. The implications of the experimental and model results to pulsed laser ablation of tissue are discussed. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Venugopalan, V (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 2 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-2790-X J9 P SOC PHOTO-OPT INS PY 1998 VL 3343 BP 69 EP 77 DI 10.1117/12.321609 PG 9 WC Optics SC Optics GA BL80U UT WOS:000076793000007 ER PT J AU Doria, A AF Doria, A TI Genetic markers of increased susceptibility to diabetic nephropathy SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 4th International Workshop on Diabetic Angiopathy in Children - Quality Control of Diabetes Care and Chronic Complications in Young People After St Vincent and Kos CY SEP 04-06, 1997 CL BERLIN, GERMANY SP Deutsch Forschungsgemein, Berlin Chemie AG, Berlin, Boehringer Mannheim Gmbh, Mannheim, Hoechst Marion Roussel, Bad Soden am Taunus, Lilly Deutschland GmbH, Bad Homburg, Novo Nordisk Pharma GmbH, Mainz DE insulin-dependent diabetes mellitus; diabetic nephropathy; angiotensinogen; angiotensin I-converting enzyme; angiotensin II receptor; aldose reductase; DNA polymorphisms; genetics ID CONVERTING-ENZYME GENE; INSERTION DELETION POLYMORPHISM; HUMAN ESSENTIAL-HYPERTENSION; IDDM PATIENTS; ANGIOTENSINOGEN; COMPLICATIONS; INHIBITION; MELLITUS; LINKAGE; DISEASE AB The effect of exposure to diabetes on the kidney appears to be modulated by genetic factors determining a variable degree of susceptibility to diabetic nephropathy. Multiple loci are probably involved. Some of them might be found among the genes coding for components of the renin angiotensin system (renin, angiotensinogen, angiotensin I-converting enzyme, angiotensin receptors), some may regulate the way in which cells manage hyperglycemia (e.g. aldose reductase). Various genes have been examined to date, mainly by means of association studies. Positive results have been found for some of them (e.g. ACE, AGTR1, aldose reductase), but have not been confirmed in other populations. Thus, no genetic marker of increased susceptibility to diabetic nephropathy having clinical utility is currently available. New insights are expected from the systematic scanning of the genome for linkage with diabetic nephrophathy. C1 Joslin Diabet Ctr, Sect Epidemiol & Genet, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Epidemiol & Genet, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-41526] NR 31 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 1998 VL 50 SU 1 BP 6 EP 11 DI 10.1159/000053095 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZZ812 UT WOS:000074769600003 PM 9676990 ER PT J AU Hayes, FJ Crowley, WF AF Hayes, FJ Crowley, WF TI Gonadotropin pulsations across development SO HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 40th International Henri-Pierre Klotz Symposium on Clinical Endocrinology : Endocrine Rhythms - Roles of the Sleep-Wake Cycle, the Circadian Clock and Environment CY MAY 29-30, 1997 CL PARIS, FRANCE DE gonadotropins; pulsatility; GnRH; sexual development ID HORMONE-SECRETION; MEN; STIMULATION; PATTERNS; RELEASE; PUBERTY; WOMEN; LH AB Initiation and maintenance of the reproductive axis in the human is contingent upon the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. In man, tracking endogenous GnRH secretion relies on frequent peripheral sampling of three glycoprotein products of the gonadotrope, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and free cr-subunit (FAS). FAS is superior to LH as a surrogate marker of GnRH secretory dynamics in those circumstances where GnRH secretion is rapid or where the pituitary LH response is low, The pattern of GnRH secretion is constantly changing across development; from high levels during the neonatal period, through a period of quiescence in mid-childhood, followed by sleep-entrained reactivation of the reproductive axis at the onset of puberty, ultimately culminating in the adult pattern of pulsatile secretion which in the male is approximately every 2 h and in the female varies with the stage of the menstrual cycle, This episodic mode of secretion allows differential impact of feedback mechanisms on the GnRH neurons and facilitates the maintenance of the reproductive axis during periods of stress by allowing frequency and amplitude modulations. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM crowley.william@mgh.harvard.edu FU NICHD NIH HHS [P30 HD028138, R01 HD015788, T32 HD007396] NR 22 TC 24 Z9 24 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 1998 VL 49 IS 3-4 BP 163 EP 168 DI 10.1159/000023165 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZE217 UT WOS:000072769800011 PM 9550119 ER PT J AU Guimaraes, AR Melcher, JR Talavage, TM Baker, JR Ledden, P Rosen, BR Kiang, NYS Fullerton, BC Weisskoff, RM AF Guimaraes, AR Melcher, JR Talavage, TM Baker, JR Ledden, P Rosen, BR Kiang, NYS Fullerton, BC Weisskoff, RM TI Imaging subcortical auditory activity in humans SO HUMAN BRAIN MAPPING LA English DT Article ID MEDIAL GENICULATE-BODY; BRAIN-STEM; SUPERIOR COLLICULUS; EVOKED-POTENTIALS; TONOTOPIC ORGANIZATION; RETICULAR COMPLEX; CORTEX; RESPONSES; THALAMUS; STIMULI AB There is a lack of physiological data pertaining to how listening humans process auditory information. Functional magnetic resonance imaging (fMRI) has provided some data for the auditory cortex in awake humans, but there is still a paucity of comparable data for subcortical auditory areas where the early stages of processing take place, as amply demonstrated by single-unit studies in animals. It is unclear why fMRI has been unsuccessful in imaging auditory brain-stem activity, but one problem may be cardiac-related, pulsatile brain-stem motion. To examine this, a method eliminating such motion (using cardiac gating) was applied to map sound-related activity in the auditory cortices and inferior colliculi in the brain stem. Activation in both the colliculi and cortex became more discernible when gating was used. In contrast with the cortex, the improvement in the colliculi resulted from a reduction in signal variability, rather than from an increase in percent signal change. This reduction is consistent with the hypothesis that motion or pulsatile flow is a major factor in brain-stem imaging. The way now seems clear to studying activity throughout the human auditory pathway in listening humans. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, 149 Thirteenth St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [5PO1DA09467, P01 DA009467]; NIDCD NIH HHS [P01DC00119, P01 DC000119, P01 DC000119-260023, T32 DC000038, T32DC00038-04] NR 40 TC 155 Z9 155 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 1 BP 33 EP 41 DI 10.1002/(SICI)1097-0193(1998)6:1<33::AID-HBM3>3.0.CO;2-M PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YV245 UT WOS:000071803900003 PM 9673661 ER PT J AU Krebs, HI Brashers-Krug, T Rauch, SL Savage, CR Hogan, N Rubin, RH Fischman, AJ Alpert, NM AF Krebs, HI Brashers-Krug, T Rauch, SL Savage, CR Hogan, N Rubin, RH Fischman, AJ Alpert, NM TI Robot-aided functional imaging: Application to a motor learning study SO HUMAN BRAIN MAPPING LA English DT Article DE robot-aided; functional imaging; motor learning; arm movement ID MEMORY; CORTEX; TASK AB The purpose of this study was to examine the neural activity underlying an implicit motor learning task. In particular, our goals were to determine whether initial phases of procedural learning of a motor task involve areas of the brain distinct from those involved in later phases of learning the task, and what changes in neural activity coincide with performance improvement. We describe a novel integration of robotic technology with functional brain imaging and its use in this study of implicit motor learning. A portable robotic device was used to generate forces that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that the subjects learned to manipulate. Positron emission tomography (PET) was used to measure indices of neural activity underlying learning of the motor task. Eight healthy, right-handed male subjects participated in the study. Results support the hypothesis that different stages of implicit learning (early and late implicit learning) occur in an orderly fashion, and that distinct neural structures may be involved in these different stages. In particular, neuroimaging results indicate that the cortico-striatal loop may play a significant role during early learning, and that the cortico-cerebellar loop may play a significant role during late learning. (C) 1998 Wiley-Liss, Inc. C1 MIT, Dept Ocean Engn, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Newman Lab Biomech & Human Rehabil, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol & Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, MIT, Ctr Expt Pharmacol & Therapeut, Cambridge, MA 02139 USA. RP Krebs, HI (reprint author), 77 Massachusetts Ave,3-137, Cambridge, MA 02139 USA. EM hikrebs@mit.edu FU NCRR NIH HHS [M01RR00088]; NIAMS NIH HHS [AR26710, AR40029] NR 28 TC 80 Z9 80 U1 5 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 1 BP 59 EP 72 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YV245 UT WOS:000071803900005 PM 9673663 ER PT J AU Maisog, JM Chmielowska, J AF Maisog, JM Chmielowska, J TI An efficient method for correcting the edge artifact due to smoothing SO HUMAN BRAIN MAPPING LA English DT Article DE functional neuroimaging; smoothing; convolution; artifact; correction ID PET IMAGES; ACTIVATION AB Spatial smoothing is a common pre-processing step in the analysis of functional brain imaging data. It can increase the signal to noise ratio, and specially designed smoothing filters can be used to selectively increase sensitivity to signals of specific shapes and sizes (Rosenfeld and Kak [1982]: Digital Picture Processing, vol. 2. Orlando, Fla.: Academic; Worsley et al. [1996]: Hum Brain Mapping 4:74-90). Also, some amount of spatial smoothness is required if methods from the theory of Gaussian random fields are to be used (Holmes [1994]: Statistical Issues in Functional Brain Mapping. PhD thesis, University of Glasgow). Smoothing is most often implemented as a convolution of the imaging data with a smoothing kernel, and convolution is most efficiently performed using the Convolution Theorem and the Fast Fourier Transform (Cooley and Tukey [1965]: Math Comput 19:297-301; Priestly [1981]: Spectral Analysis and Time Series. San Diego: Academic; Press et al. [1992]: Numerical Recipes in C: The Art of Scientific Computing, 2nd ed. Cambridge: Cambridge University Press). An undesirable side effect of smoothing is an artifact along the edges of the brain, where brain voxels become smoothed with non-brain voxels. This results in a dark rim which might be mistaken for hypoactivity. In this short methodological paper, we present a method for correcting functional brain images for the edge artifact due to smoothing, while retaining the use of the Convolution Theorem and the Fast Fourier Transform for efficient calculation of convolutions. (C) 1998 Wiley-Liss, Inc. C1 NIMH, Sect Funct Brian Imaging, Lab Brain & Cognit, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. RP Maisog, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND HSE 216, Boston, MA 02114 USA. NR 18 TC 5 Z9 5 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 3 BP 128 EP 136 DI 10.1002/(SICI)1097-0193(1998)6:3<128::AID-HBM2>3.0.CO;2-5 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZQ918 UT WOS:000073916100002 PM 9673668 ER PT J AU Ojemann, JG Buckner, RL Akbudak, E Snyder, AZ Ollinger, JM McKinstry, RC Rosen, BR Petersen, SE Raichle, ME Conturo, TE AF Ojemann, JG Buckner, RL Akbudak, E Snyder, AZ Ollinger, JM McKinstry, RC Rosen, BR Petersen, SE Raichle, ME Conturo, TE TI Functional MRI studies of word-stem completion: Reliability across laboratories and comparison to blood flow imaging with PET SO HUMAN BRAIN MAPPING LA English DT Article DE BOLD; cerebral blood flow; cerebral oxygen metabolism; cognition; imaging methods ID POSITRON-EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; HUMAN BRAIN; OXIDATIVE-METABOLISM; SENSORY STIMULATION; MEMORY RETRIEVAL; ACTIVATION; LANGUAGE; REGISTRATION; LOCALIZATION AB Functional magnetic resonance imaging (fMRI) based on blood oxygen level-dependent (BOLD) contrast has become an increasingly popular technique for mapping the brain. The relationship between BOLD-fMRI imaging and imaging of blood flow activation with positron emission tomography (PET) remains unclear. Moreover, BOLD imaging strategies and analysis procedures vary widely across laboratories. To examine the relationship between these different methods, we compared brain activation maps of a word-stem completion task obtained both using PET and using fMRI across two separate institutions (Washington University and Massachusetts General Hospital) with different acquisitions (gradient-refocused echo and asymmetric spin echo) and different analysis techniques. Overall, activation maps were highly similar across both fMRI methods and PET. A set of activated brain areas, in consistent locations in Talairach atlas space, were identified across all three studies, including visual striate and extrastriate, left prefrontal, supplementary motor area (SMA), and right cerebellar areas. Decreases in activation were also consistently observed in medial parietal, posterior insular, and medial inferior frontal areas. Some differences were noted that may be related to the silent performance of the task with fMRI. The largely consistent results suggest that comparisons can be made appropriately across imaging modalities and laboratory methods. A further implication of the consistencies, which extended to both increases and decreases in signal, is that the underlying brain physiology leading to BOLD contrast may be more similar to blood flow than originally appreciated Hum. Brain Mapping 6:203-215, 1998. (C) 1998 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Neurol & Neurol Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurosci, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Psychol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, McDonnell Ctr Higher Brain Funct, St Louis, MO 63110 USA. Washington Univ, Sch Med, Inst Biomed Comp, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Ojemann, JG (reprint author), Washington Univ, Sch Med, Dept Neurol Surg, Box 8057,660 S Euclid Ave, St Louis, MO 63110 USA. EM jgo@npg.wustl.edu OI Ojemann, Jeffrey/0000-0001-7580-8934 FU NHLBI NIH HHS [HL13851]; NINDS NIH HHS [NS01783, NS06833] NR 60 TC 96 Z9 96 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 4 BP 203 EP 215 DI 10.1002/(SICI)1097-0193(1998)6:4<203::AID-HBM2>3.0.CO;2-7 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 106UN UT WOS:000075169000002 PM 9704261 ER PT J AU Purdon, PL Weisskoff, RM AF Purdon, PL Weisskoff, RM TI Effect of temporal autocorrelation due to physiological noise and stimulus paradigm on voxel-level false-positive rates in fMRI SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; statistical parametric mapping; noise modeling; colored noise; brain noise AB Statistical mapping within a binary hypothesis testing framework is the most widely used analytical method in functional MRI of the brain. A common assumption in this kind of analysis is that the fMRI time series are independent and identically distributed in time, yet we know that fMRI data can have significant temporal correlation due to low-frequency physiological fluctuation (Weisskoff et al. [1993]; Proc Soc Magn Reson Med 9:7; Biswal et al. [1995]. Mag Reson Med 34:537-541). Furthermore, since the signal-to-noise ratio will vary with imaging rate, we should expect that the degree of correlation will vary with imaging rate. In this paper, we investigate the effect of temporal correlation and experimental paradigm on false-positive rates (type I error rates), using data synthesized through a simple autoregressive plus white-noise model whose parameters were estimated from real data over a range of imaging rates. We demonstrate that actual false-positive rates can be biased far above or below the assumed significance level alpha when temporal autocorrelation is ignored in a way that depends on both the degree of correlation as well as the paradigm frequency. Furthermore, we present a simple method, based on the noise model described above, for correcting such distortions, and relate this method to the extended general Linear model of Worsley and Friston ([1995]: Neuroimage 2:173-181). Hum. Brain Mapping 6:239-249, 1998. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Purdon, PL (reprint author), MGH NMR Ctr, 2nd Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA09467] NR 16 TC 179 Z9 181 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 4 BP 239 EP 249 DI 10.1002/(SICI)1097-0193(1998)6:4<239::AID-HBM4>3.0.CO;2-4 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 106UN UT WOS:000075169000004 PM 9704263 ER PT J AU Bush, G Whalen, PJ Rosen, BR Jenike, MA McInerney, SC Rauch, SL AF Bush, G Whalen, PJ Rosen, BR Jenike, MA McInerney, SC Rauch, SL TI The counting stroop: An interference task specialized for functional neuroimaging - Validation study with functional MRI SO HUMAN BRAIN MAPPING LA English DT Article; Proceedings Paper CT 4th Annual Meeting of the Cognitive-Neuroscience-Society CY MAR 23-25, 1997 CL BOSTON, MASSACHUSETTS SP Cognit Neurosci Soc DE Stroop; cognitive interference; attention; functional magnetic resonance imaging; cingulate; learning; habituation; practice; response selection; motor ID POSITRON EMISSION TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; OBSESSIVE-COMPULSIVE DISORDER; SYMPTOM PROVOCATION; RHESUS-MONKEY; BLOOD-FLOW; SELECTIVE ATTENTION; RESPONSE SELECTION; HUMAN BRAIN; ANATOMY AB The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed "Counting Stroop" to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., "two" written three times), while neutral trials contain single semantic category common animals (e.g., "bird"). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P less than or equal to 10(-4)) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories. Hum. Brain Mapping 6:270-282, 1998. a 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp East, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Boston, MA 02129 USA. MIT, Cambridge, MA 02142 USA. RP Bush, G (reprint author), Massachusetts Gen Hosp East, Psychiat Neurosci Program, CNY-9,Bldg 149,13th St, Charlestown, MA 02129 USA. EM geo@nmr.mgh.harvard.edu FU NIMH NIH HHS [MH-01215] NR 91 TC 493 Z9 502 U1 19 U2 56 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 4 BP 270 EP 282 DI 10.1002/(SICI)1097-0193(1998)6:4<270::AID-HBM6>3.0.CO;2-0 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 106UN UT WOS:000075169000006 PM 9704265 ER PT J AU Buckner, RL AF Buckner, RL TI Event-related fMRI and the hemodynamic response SO HUMAN BRAIN MAPPING LA English DT Article DE single trial; neuroimaging; MRI; fMRI; imaging ID CORTEX; TRIALS AB Event-related functional magnetic resonance imaging (ER-fMRI) methods are allowing a new spectrum of task designs to be explored with brain imaging techniques. Individual trial events can be presented rapidly, in randomly intermixed order, and the hemodynamic responses associated with individual trial events appreciated. The basis of ER-fMRI is that the hemodynamic response tracks neuronal activity on the order of seconds and, in many situations, summates over trials in a manner well predicted by a linear model-even for trials spaced as briefly as 2 sec apart. These properties are discussed, as well as certain basic characteristics of the hemodynamic response in the context of ER-fMRI. (C) 1998 Wiley-Liss, Inc. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Washington Univ, Dept Anat, St Louis, MO 63130 USA. Washington Univ, Dept Neurobiol, St Louis, MO 63130 USA. Washington Univ, Dept Radiol, St Louis, MO 63130 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Buckner, RL (reprint author), Washington Univ, Dept Psychol, Box 1125,1 Brookings Dr, St Louis, MO 63130 USA. NR 13 TC 180 Z9 187 U1 3 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1998 VL 6 IS 5-6 BP 373 EP 377 DI 10.1002/(SICI)1097-0193(1998)6:5/6<373::AID-HBM8>3.0.CO;2-P PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 126DG UT WOS:000076277200008 PM 9788075 ER PT J AU Beauchamp, RL Banwell, A McNamara, P Jacobsen, M Higgins, E Northrup, H Short, P Sims, K Ozelius, L Ramesh, V AF Beauchamp, RL Banwell, A McNamara, P Jacobsen, M Higgins, E Northrup, H Short, P Sims, K Ozelius, L Ramesh, V TI Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis SO HUMAN MUTATION LA English DT Article DE tuberous sclerosis complex; TSC2; mutations; SSCP; tuberin ID POLYCYSTIC KIDNEY-DISEASE; HETEROGENEITY; IDENTIFICATION; CHROMOSOME-9; COMPLEX; POLYMORPHISMS; HOMOLOG; MARKER; FAMILY; LOCUS AB Tuberous sclerosis complex (TSC) is a dominantly inherited multisystem disorder resulting in the development of hamartomatous growths in many organs. Genetic heterogeneity has been demonstrated linking the familial cases to either TSC1 at 9q34,3, or TSC2 at 16p13,3, About two thirds of the TSC cases are sporadic and appear to represent new mutations. While both genes are thought to account for all familial cases, with each representing approximately 50% of the mutations, the proportion of sporadic cases with mutations in TSC1 and TSC2 is yet to be determined. We have examined the entire coding sequence of the TSC2 gene in 20 familial and 20 sporadic cases and identified a total of twenty one mutations representing 50% and 55% of familial and sporadic cases respectively. Our rate of mutation detection is significantly higher than other published reports. Twenty out of 21 mutations are novel and include 6 missense, 6 nonsense, 5 frameshifts, 2 splice alterations, a 34 bp deletion resulting in abnormal splicing, and an 18 bp deletion which maintains the reading frame. The mutations are distributed throughout the coding sequence with no specific hot spots. There is no apparent correlation between mutation type and clinical severity of the disease. Our results document that at least 50% of sporadic cases arise from mutations in the TSC2 gene, The location of the mutations described here, particularly the mis sense events, should be valuable for further functional analysis of this tumor suppressor protein. Hum Mutat 12:408-416, 1998, (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp East, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. Univ Chicago, Sch Med, Dept Child Neurol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Unit, Bld 149,13th St, Charlestown, MA 02129 USA. EM ramesh@helix.mgh.harvard.edu FU NINDS NIH HHS [NS24279] NR 31 TC 44 Z9 45 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PY 1998 VL 12 IS 6 BP 408 EP 416 DI 10.1002/(SICI)1098-1004(1998)12:6<408::AID-HUMU7>3.0.CO;2-P PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 134ZM UT WOS:000076774100006 PM 9829910 ER PT J AU Poorkaj, P Sharma, V Anderson, L Nemens, E Alonso, ME Orr, H White, J Heston, L Bird, TD Schellenberg, GD AF Poorkaj, P Sharma, V Anderson, L Nemens, E Alonso, ME Orr, H White, J Heston, L Bird, TD Schellenberg, GD TI Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1 gene SO HUMAN MUTATION LA English DT Article DE Alzheimer's disease; presenilin 1; dementia; mutations; presenilin 2; STM2; S182 ID APOLIPOPROTEIN-E; IN-VIVO; PROTEIN; LOCUS; IDENTIFICATION; POLYMORPHISM; EXPRESSION; KINDREDS; TOPOLOGY AB Mutations in the presenilin genes (PS-1 and PS-2) cause early onset autosomal dominant Alzheimer's disease (AD). Eight early-onset, autopsy-documented familial AD kindreds were screened for mutations in PS-1, and seven different mutations were identified. Three of these were new mutations (G209V A426P, and E120D), two were previously reported mutations in new families, and three mutations were confirmed in previously published families. Two of these new mutations are found within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is the most C-terminal PS-1 mutation identified to date. (C) 1998 Wiley-Liss, Inc. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. Ingenex Inc, Menlo Park, CA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136, R01 AG1176] NR 36 TC 36 Z9 38 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1998 VL 11 IS 3 BP 216 EP 221 DI 10.1002/(SICI)1098-1004(1998)11:3<216::AID-HUMU6>3.0.CO;2-F PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YZ386 UT WOS:000072249200006 PM 9521423 ER PT J AU Pollock, PM Spurr, N Bishop, T Newton-Bishop, J Gruis, N van der Velden, PA Goldstein, AM Tucker, MA Foulkes, WD Barnhill, R Haber, D Fountain, J Hayward, NK AF Pollock, PM Spurr, N Bishop, T Newton-Bishop, J Gruis, N van der Velden, PA Goldstein, AM Tucker, MA Foulkes, WD Barnhill, R Haber, D Fountain, J Hayward, NK TI Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families: Evidence for common founders and independent mutations SO HUMAN MUTATION LA English DT Article DE CDKN2A; melanoma; familial; mutation; founder ID KINASE-4 INHIBITOR GENE; TUMOR-SUPPRESSOR GENE; MALIGNANT-MELANOMA; PANCREATIC-CANCER; CELL-LINES; P16; LOCUS; P16(INK4A); DELETION; KINDREDS AB Germ-line mutations in CDKN2A have been shown to predispose to cutaneous malignant melanoma. We have identified 2 new melanoma kindreds which carry a duplication of a 24bp repeat present in the 5' region of CDKN2A previously identified in melanoma families fram Australia and the United States. This mutation has now been reported in 5 melanoma families from 3 continents: Europe, North America, and Australasia, The M53I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was to determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation and 5 families carrying the 24bp duplication. There were some differences in the segregating haplotypes due primarily to recombinations and mutations within the short tandem repeat markers; however, the data provide evidence to indicate that there mere at least 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents. (C) 1998 Wiley-Liss, Inc. C1 Queensland Inst Med Res, Queensland Canc Fund Res Unit, Joint Expt Oncol Program, Brisbane, Qld 4006, Australia. St James Univ Hosp, Canc Mol Genet Lab, Leeds LS9 7TF, W Yorkshire, England. St James Univ Hosp, ICRF, Genet Epidemiol Lab, Leeds LS9 7TF, W Yorkshire, England. Leiden Univ, Med Ctr, MGC, Dept Human Genet, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. McGill Univ, Dept Med, Div Med Genet, Montreal, PQ, Canada. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Univ So Calif, Inst Med Genet, Los Angeles, CA USA. RP Hayward, NK (reprint author), PO Royal Brisbane Hosp, Queensland Inst Med Res, Herston, Qld 4029, Australia. EM nickH@qimr.edu.au RI hayward, nicholas/C-1367-2015; OI hayward, nicholas/0000-0003-4760-1033; Gruis, Nelleke/0000-0002-5210-9150; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802 FU NCI NIH HHS [CA66021] NR 40 TC 50 Z9 50 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1998 VL 11 IS 6 BP 424 EP 431 DI 10.1002/(SICI)1098-1004(1998)11:6<424::AID-HUMU2>3.0.CO;2-2 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ZK242 UT WOS:000073299600002 PM 9603434 ER PT J AU Marsh, DJ Andrew, SD Learoyd, DL Pojer, R Eng, C Robinson, BG AF Marsh, DJ Andrew, SD Learoyd, DL Pojer, R Eng, C Robinson, BG TI Deletion-insertion mutation encompassing RET codon 634 is associated with medullary thyroid carcinoma SO HUMAN MUTATION LA English DT Article ID TYROSINE KINASE DOMAIN; NEOPLASIA TYPE 2B; POINT MUTATION; PROTOONCOGENE; 2A; ACTIVATION; FMTC C1 Royal N Shore Hosp, Kolling Inst Med Res, Mol Genet Unit, St Leonards, NSW 2065, Australia. Royal N Shore Hosp, Dept Endocrinol, St Leonards, NSW 2065, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Univ Cambridge, Addenbrookes Hosp, CRC, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Robinson, BG (reprint author), Royal N Shore Hosp, Kolling Inst Med Res, Mol Genet Unit, St Leonards, NSW 2065, Australia. RI Marsh, Deborah/I-1491-2014 OI Marsh, Deborah/0000-0001-5899-4931 NR 15 TC 1 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1998 SU 1 BP S3 EP S4 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA YV593 UT WOS:000071842000002 ER PT J AU Mihm, MC Murphy, GF AF Mihm, MC Murphy, GF TI Malignant melanoma in situ: An oxymoron whose time has come SO HUMAN PATHOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Dermatopathol, Boston, MA 02114 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Mihm, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Dermatopathol, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JAN PY 1998 VL 29 IS 1 BP 6 EP 7 DI 10.1016/S0046-8177(98)90383-5 PG 2 WC Pathology SC Pathology GA YT070 UT WOS:000071561000003 PM 9445127 ER PT J AU Force, T Bonventre, JV AF Force, T Bonventre, JV TI Growth factors and mitogen activated protein kinases SO HYPERTENSION LA English DT Article; Proceedings Paper CT 51st Annual Fall Conference and Scientific Sessions of the Council-for-High-Blood-Pressure-Research of the American-Heart-Association CY SEP 16-19, 1997 CL WASHINGTON, D.C. SP Amer Heart Assoc, Council High Blood Pressure Res DE MAP kinases; stress-activated protein kinases; G-protein-coupled receptors; endothelin; angiotensin II; growth factors ID SMOOTH-MUSCLE CELLS; CYTOSOLIC PHOSPHOLIPASE A(2); MAP KINASE; C-JUN; SIGNAL-TRANSDUCTION; COUPLED RECEPTORS; ANGIOTENSIN-II; NUCLEAR TRANSLOCATION; DEPENDENT ACTIVATION; ARACHIDONIC-ACID AB Mammalian cells respond to external stimuli by activation of a variety of signal transduction pathways, which culminate in stereotypical responses, such as proliferation, growth arrest, hypertrophy, differentiation, or apoptosis. In vertebrates the actions of many stimuli resulting in proliferative or hypertrophic growth converge on a set of cellular kinase cascades, which are collectively called the mitogen-activated protein (MAP) kinase cascades. These MAP kinases have been implicated in vascular smooth muscle cell proliferation and hypertrophy, responses that are central to the pathophysiology of hypertension. In this review, we will examine how proliferative and hypertrophic stimuli activate these MAP kinase cascades, what are the consequences of that activation on gene expression, and how do these signals drive the cell into one of the stereotypical responses noted above. C1 Harvard Mit Div Hlth Sci & Technol, Div Hlth Sci & Technol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Med Serv, Charlestown, MA USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp E, Suite 4002,149 13th St, Charlestown, MA 02129 USA. EM jbonvent@warren.med.harvard.edu OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK38452, DK39773, DK50282] NR 108 TC 278 Z9 303 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 1998 VL 31 IS 1 SU S BP 152 EP 161 PN 2 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YV789 UT WOS:000071863500002 PM 9453296 ER PT J AU Kawai, T Shimauchi, H Eastcott, JW Smith, DJ Taubman, MA AF Kawai, T Shimauchi, H Eastcott, JW Smith, DJ Taubman, MA TI Antigen direction of specific T-cell clones into gingival tissues SO IMMUNOLOGY LA English DT Article ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; TRANSENDOTHELIAL MIGRATION; PERIODONTAL-DISEASE; HELPER-CELLS; LYMPHOCYTE RECIRCULATION; MOLECULAR MECHANISMS; ADOPTIVE TRANSFER; ADHESION; ACTIVATION; INTESTINE AB This study was performed to investigate T-cell traffic to periodontal tissues during infection with a periodontal pathogen Actinobacillus actinomycetemcomitans (Aa). Rowett rat T-cell clones, A3 (CD4(+) CD8(-), alpha beta TCR+, NKRP-1(-), specific to Aa) and G2 (CD4(-) CD8(-), alpha beta TCR+, NKRP-1(+), which reacts to Aa, Gram-negative and -positive bacteria), both expressed the same prominent adhesion molecules (LFA-1, VLA-4) to the same extent. Binding of bath T-cell clones to rat endothelial cells in vitro was blocked by antibody to VLA-4. Rowett rats were infected with Aa and infused with Aa-stimulated, isogenic T-clone lymphocytes that had been labelled in vitro with (125)IUdR. Radioactivity associated with recovery of clone A3, but not G2, was significantly elevated in the gingivae of infected rats, suggesting migration to infected animals' gingival tissues. Migration of radioactive Aa-specific A3 clone cells traced by autoradiography reached a maximum at 24 hr (1.2% of total lymphocytes as radiolabelled cells in infected gingiva versus 0.6% in non-infected), indicating an apparent antigen-directed retention in infected rats' gingival tissues. The G2 clone was not retained in the gingival tissues (0.20% of total lymphocytes as radiolabelled cells in infected gingiva versus 0.26% in non-infected). However, the possibility of A3 retention directed by inflammation or tissue-selective homing could not be excluded. In further experiments, other adoptively transferred T-clone lymphocytes [clones G23 (Th1) and F13 (Th2)] with specificity for the 29 000 MW outer membrane protein of Aa with the same prominent adhesion molecules could be recovered from rat gingivae previously challenged with this antigen. However, transferred T-clone lymphocytes [clone G26 (Th1)] with specificity for a different Aa antigen were not recovered. Therefore, the dynamics of cell entry into periodontal lesions vary for activated T lymphocytes with different antigenic specificities, indicating the significance of antigen in lymphocyte traffic to periodontal tissues. C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. RP Taubman, MA (reprint author), Forsyth Dent Ctr, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-03420] NR 34 TC 41 Z9 42 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 1998 VL 93 IS 1 BP 11 EP 19 PG 9 WC Immunology SC Immunology GA YR939 UT WOS:000071547000002 PM 9536113 ER PT J AU Melby, PC Yang, YZ Cheng, J Zhao, WG AF Melby, PC Yang, YZ Cheng, J Zhao, WG TI Regional differences in the cellular immune response to experimental cutaneous or visceral infection with Leishmania donovani SO INFECTION AND IMMUNITY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; IFN-GAMMA; INTERFERON-GAMMA; ANTIMICROBIAL ACTIVITY; ACTIVATED MACROPHAGES; MURINE LEISHMANIASIS; TH1 CELLS; EXPRESSION; INTERLEUKIN-12 AB Infection with the protozoan Leishmania donovani can cause serious visceral disease or subclinical infection in humans, To better understand the pathogenesis of this dichotomy, we have investigated the host cellular immune response to cutaneous or visceral infection in a murine model. Mice infected in the skin del eloped no detectable visceral parasitism, whereas intravenous inoculation resulted in hepatosplenomegaly and an increasing visceral parasite burden, Spleen cells from mice with locally controlled cutaneous infection showed strong parasite-specific proliferative and gamma interferon (IFN-gamma) responses, but spleen cells from systemically infected mice were unresponsive to parasite antigens, The in situ expression of IFN-gamma, interleukin-4 (IL-4), IL-10, IL-12, and inducible nitric oxide synthase (iNOS) mRNAs was determined in the spleen, draining lymph node (LN), and cutaneous site of inoculation, There was considerably greater expression of IPN-gamma and IL-12 p40 mRNAs in the LN draining a locally controlled cutaneous infection than in the spleen following systemic infection, Similarly, there was a high level of IFN-gamma production by LN cells following subcutaneous infection but no IFN-gamma production by spleen cells following systemic infection, Splenic IL-4 expression was transiently increased early after systemic infection, but splenic IL-IO transcripts increased throughout the course of visceral infection, IL-4 and IL-10 mRNAs were also increased in the LN following cutaneous infection, iNOS mRNA was detected earlier in the LN draining a cutaneous site of infection compared to the spleen following systemic challenge, Thus, locally controlled cutaneous infection was associated with antigen-specific spleen cell responsiveness and markedly increased levels of IFN-gamma, IL-12, and iNOS mRNA in the draining LN. Progressive splenic parasitism was associated with an early IL-4 response, markedly increased IL-10 but minimal IL-12 expression, and delayed expression of iNOS. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Med Serv, San Antonio, TX 78284 USA. RP Melby, PC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 44 TC 88 Z9 93 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 1998 VL 66 IS 1 BP 18 EP 27 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YP559 UT WOS:000071290000004 PM 9423834 ER PT J AU Hirsch, MS AF Hirsch, MS TI Reflections on the road to effective HIV therapy SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT INTERFERON-ALPHA; III REPLICATION INVITRO; HERPES-SIMPLEX VIRUS; HTLV-III; SYNERGISTIC INHIBITION; LYMPHOCYTE-T; CYTOMEGALO-VIRUS; RENAL-TRANSPLANTATION; TYPE-1 REPLICATION C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM hirsch.martin@mgh.harvard.edu NR 54 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD JAN PY 1998 VL 7 IS 1 BP 39 EP 42 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YV725 UT WOS:000071856500009 ER PT B AU Jupiter, JB Fernandez, DL Whipple, TL Richards, RR AF Jupiter, JB Fernandez, DL Whipple, TL Richards, RR BE Cannon, WD TI Intra-articular fractures of the distal radius: Contemporary perspectives SO INSTRUCTIONAL COURSE LECTURES, VOL 47 - 1998 SE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS INSTRUCTIONAL COURSE LECTURES LA English DT Proceedings Paper CT 64th Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY FEB 13-17, 1997 CL SAN FRANCISCO, CA SP Amer Acad Orthopaed Surgeons C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. NR 0 TC 11 Z9 12 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMONT PA 6300 NORTH RIVER RD, ROSEMONT, IL 60018 USA BN 0-89203-173-5 J9 AAOS INSTR COURS LEC PY 1998 VL 47 BP 191 EP 202 PG 4 WC Orthopedics SC Orthopedics GA BL27C UT WOS:000074947000022 PM 9571418 ER PT B AU Zaleske, DJ AF Zaleske, DJ BE Cannon, WD TI Cartilage and bone development SO INSTRUCTIONAL COURSE LECTURES, VOL 47 - 1998 SE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS INSTRUCTIONAL COURSE LECTURES LA English DT Proceedings Paper CT 64th Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY FEB 13-17, 1997 CL SAN FRANCISCO, CA SP Amer Acad Orthopaed Surgeons C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Zaleske, DJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMONT PA 6300 NORTH RIVER RD, ROSEMONT, IL 60018 USA BN 0-89203-173-5 J9 AAOS INSTR COURS LEC PY 1998 VL 47 BP 461 EP 468 PG 4 WC Orthopedics SC Orthopedics GA BL27C UT WOS:000074947000051 ER PT J AU Pargger, H Kaufmann, MA Drop, LJ AF Pargger, H Kaufmann, MA Drop, LJ TI Renal vascular hyperresponsiveness to elevated ionized calcium in spontaneously hypertensive rat kidneys SO INTENSIVE CARE MEDICINE LA English DT Article DE blood vessels; kidney; renal circulation; renal vascular resistance; calcium; ionized calcium; rat ID ENDOTHELIUM; RESISTANCE; REACTIVITY; HEMODYNAMICS; HYPOCALCEMIA; ANTAGONISTS; RESPONSES; ALBUMIN AB Objectives: Calcium may be indicated in critically ill patients for hemodynamic support. Its well-known action includes peripheral vasoconstriction. Vascular effects of calcium are unknown, however, in the presence of hypertension or in combination with calcium channel blocking drugs, commonly prescribed in the treatment of hypertension, The renal vessels of the spontaneously hypertensive rat (SHR) represent a suitable study model, because their vascular reactivity closely agrees with that in hypertensive humans. The present study should clarify (a) are the renal vessels of SHR responsive to high and low ionized calcium ([Ca++] within the clinical ranges? (b) because release of nitric oxide is calcium ion dependent, are renal vascular responses altered after inhibition of NO synthase? (c) are vascular responses of SHR to hypercalcemia altered by the calcium channel blocking drug verapamil? Animals and interventions: We compared isolated kidneys of SHR and those of two strains of age-matched normotensive rats (NTR) in their responses to high and low [Ca++]. They were perfused with oxygenated, warmed (37 degrees C) albumin containing Krebs-Henseleit buffer. In protocol A (n = 8 for each rat strain) steady slate high [Ca++] (1.88 mmol/l) and low [Ca++] (0.55 mmol/l) were institut- ed in randomized order, In protocol B (n = 8 for each rat strain) interventions identical to those of protocol A were instituted after inhibition of NO synthase with N-G monomethyl-L-arginine (L-NMMA). In protocol C, high and low [Ca++] levels were instituted in SHR after verapamil pretreatment. At each [Ca++] we measured changes in renal flow at constant perfusion pressures of 100 and 150 mmHg. Results: In SHR (perfusion pressure 100 mmHg), high [Ca++] induced a decrease in renal flow (-11.8 +/- 1.8 % of control), which was significantly greater (p < 0.05) than the change (-6.1 +/- 1.5 and -6.9 +/- 1.4 % of control) recorded in the two normotensive strains. In SHR (perfusion pressure 150 mmHg), high [Ca++] induced a decrease in renal flow (-12 +/- 1.3 % of control), also significantly greater (p < 0.05) than the changes (-6.2 +/- 1.1 and -5.8 +/- 1.7 % of control) in the two normotensive strains. Similar differences and significances were again observed after L-NMMA pretreatment. In SHR, verapamil prevented renal vascular responses in SHR to both high and low [Ca++]. Conclusions: First, renal vascular responses to high [Ca++] in SHR are exaggerated. At the upper end of the hypercalcemia range the observed changes in renal flow at constant perfusion pressure were modest, however, and with lesser degrees of hypercalcemia they may be anticipated to be even less pronounced, Second, effects of high [Ca++] were abolished after verapamil. If these findings are clinically applicable, they are of interest when calcium is infused in patients with hypertension. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Henry K Beecher Lab, Boston, MA 02114 USA. Kantonsspital, Dept Anaesthesia, CH-4031 Basel, Switzerland. RP Drop, LJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Henry K Beecher Lab, Boston, MA 02114 USA. EM drop@helix.mgh.harvard.edu NR 43 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JAN PY 1998 VL 24 IS 1 BP 61 EP 70 DI 10.1007/s001340050516 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA YX779 UT WOS:000072076700011 PM 9503224 ER PT J AU Stoney, CM Lentino, LM Emmons, KM AF Stoney, CM Lentino, LM Emmons, KM TI Environmental tobacco smoke: Association with cardiovascular function at rest and during stress SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE environmental tobacco smoke; blood pressure; heart rate; reactivity; stress ID CORONARY HEART-DISEASE; PASSIVE SMOKING; REACTIVITY; MORTALITY; EXPOSURE; ATHEROSCLEROSIS; HYPERTENSION; ENDOTHELIUM; PERFORMANCE; POPULATION AB Chronic exposure to environmental tobacco smoke (ETS) contributes to cardiovascular disease morbidity and mortality, and ETS alters cardiovascular performance during exercise stress. However, no study has examined whether those with ETS exposure have altered cardiovascular functioning during psychological stress, relative to those with no substantial BTS exposure. Seventy-eight healthy, nonsmoking adult men with either high levels of current EIS exposure at: home and work or no current or significant lifetime ETS exposure were tested in a stress reactivity protocol. Blood pressure and heart rate were monitored during rest and during two psychological stressors. Those with high ETS exposure had significantly elevated heart rate and blood pressure at baseline, relative to those with no exposure. The groups did not differ on their cardiovascular stress responses. These data suggest that chronic ETS exposure is associated with altered cardiovascular functioning at rest, but not during stress. Results are discussed with regard to the role of ETS on the development of heart disease among nonsmokers. C1 Ohio State Univ, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Stoney, CM (reprint author), Ohio State Univ, 210 Townshend Hall,1885 Neil Ave, Columbus, OH 43210 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 1998 VL 5 IS 3 BP 230 EP 244 DI 10.1207/s15327558ijbm0503_4 PG 15 WC Psychology, Clinical SC Psychology GA 150NH UT WOS:000077670700004 PM 16250704 ER PT J AU Sorensen, G Thompson, B Basen-Engquist, K Abrams, D Kuniyuki, A DiClemente, C Biener, L AF Sorensen, G Thompson, B Basen-Engquist, K Abrams, D Kuniyuki, A DiClemente, C Biener, L TI Durability, dissemination, and institutionalization of worksite tobacco control programs: Results from the Working Well trial SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE worksite health promotion; tobacco control; institutionalization; dissemination; program durability; program maintenance ID HEALTH AB Durability, dissemination and institutionalization of tobacco control activities are reported, based on the Working Well worksite cancer control intervention study (n = 83 worksites). Tobacco control activities increased significantly in intervention worksites as a result of research-supported activities but were not sustained 2 years after the conclusion of the intervention. Intervention sites were more likely than control sites to initiate and maintain structures for institutionalizing programs, such as assigning a committee responsibility for health-promotion programs or providing a budget for health-promoting activities. Dissemination of the program to control worksites had little impact on the level of smoking control activities in control worksites. Although program durability was not a primary aim of this intervention study, these analyses provide an important assessment of program maintenance beyond a funded intervention and underscore the need for additional research to identify effective organizational strategies for institutionalization of worksite health-promotion programs. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Worksite Coordinating Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Brown Univ, Miriam Hosp, Program Med, Dept Behav Med, Providence, RI USA. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. OI Biener, Lois/0000-0002-4130-8138 NR 22 TC 14 Z9 14 U1 2 U2 10 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PY 1998 VL 5 IS 4 BP 335 EP 351 DI 10.1207/s15327558ijbm0504_7 PG 17 WC Psychology, Clinical SC Psychology GA 189ZB UT WOS:000079935800007 PM 16250700 ER PT J AU Orkin, SH AF Orkin, SH TI Embryonic stem cells and transgenic mice in the study of hematopoiesis SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE hematopoiesis; transcriptional factors; gene targeting; GATA-1; SCL/tal-1 ID TRANSCRIPTION FACTOR GATA-1; ZINC-FINGER PROTEIN; SCL GENE-PRODUCT; DNA-BINDING; MEGAKARYOCYTIC DIFFERENTIATION; ERYTHROID-DIFFERENTIATION; YOLK-SAC; EXPRESSION; MOUSE; LINEAGES AB Blood formation (hematopoiesis) entails the generation of hematopoietic stem cells (HSCs) within the embryo and subsequent commitment of multipotential progenitors to differentiation along single lineages. These processes are controlled in large part by cell-restricted transcription factors which cooperate with more widely expressed factors to direct lineage-specific gene expression. Candidate hematopoietic transcriptional regulators have been identified by characterizing factors mediating cell-specific gene transcription and by defining genes involved in chromosomal rearrangements in leukemia. The application of transgenic and embryonic stem cell methods have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. One of the first, and best, characterized hematopoietic transcription factors is GATA-1. Herein studies of GATA-1 are reviewed to illustrate how manipulations of its locus in the mouse have contributed to current understanding in unique and unexpected ways. C1 Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol, 300 Longwood Ave, Boston, MA 02115 USA. EM Orkin@rascal.med.harvard.edu NR 49 TC 46 Z9 47 U1 0 U2 1 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 1998 VL 42 IS 7 SI SI BP 927 EP 934 PG 8 WC Developmental Biology SC Developmental Biology GA 135HK UT WOS:000076795600013 PM 9853823 ER PT J AU Kunik, ME Puryear, L Orengo, CA Molinari, V Workman, RH AF Kunik, ME Puryear, L Orengo, CA Molinari, V Workman, RH TI The efficacy and tolerability of divalproex sodium in elderly demented patients with behavioral disturbances SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE dementia; agitation; behavioral disturbance; geropsychiatry; psychotropic agent; side-effect profile ID ALZHEIMERS-DISEASE; VALPROATE; DISORDERS; AGITATION AB Behavioral disturbances are commonly encountered in elderly demented patients. The records of all patients admitted to a geropsychiatric inpatient unit within a 2-year period who had a primary diagnosis of dementia and an accompanying behavioral disturbance treated with divalproex sodium were reviewed. Of the 13 patients identified, all tolerated divalproex sodium without significant side-effects. General psychiatric symptoms, overall agitation, physical aggression and non-aggressive physical agitation decreased significantly, but verbal agitation did not. Divalproex sodium is well tolerated and may be effective in ameliorating certain behavioral disturbances in elderly demented patients with agitation. (C) 1998 John Wiley & Sons, Ltd. C1 Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Houston VAMC, Geriatr Psychiat Serv, Houston, TX USA. RP Kunik, ME (reprint author), Dept Psychiat, 1 Baylor Plaza, Houston, TX 77030 USA. NR 16 TC 42 Z9 43 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JAN PY 1998 VL 13 IS 1 BP 29 EP 34 DI 10.1002/(SICI)1099-1166(199801)13:1<29::AID-GPS726>3.0.CO;2-Z PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA YT707 UT WOS:000071635000006 PM 9489578 ER PT J AU Christian, BT Babich, JW Livni, E Alpert, NM Bonab, AA Munconi, L Polinski, R Rubin, RH Fischman, AJ AF Christian, BT Babich, JW Livni, E Alpert, NM Bonab, AA Munconi, L Polinski, R Rubin, RH Fischman, AJ TI Positron emission tomographic analysis of central dopamine D-1 receptor binding in normal subjects treated with the atypical neuroleptic, SDZ MAR 327 SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE positron emission tomography; antipsychotic drug treatment; SDZ MAR 327; SCH 23390; D-1 receptor ID CEREBRAL BLOOD-FLOW; PET; TRACERS; INVIVO AB SDZ MAR 327 is a new neuroleptic agent with high in vitro affinity for dopamine D-1 and D-2 receptors. The goal of this study was to determine the effect of time after SDZ MAR 327 administration on central dopamine D-1 receptor occupancy in healthy humans. Positron emission tomography (PET) with the dopamine D-1 receptor ligand, [C-11] SCH 23390, was performed in 6 male volunteers (age 22-34), in both the drug naive state and at 1, 2 and 4 h after a single oral dose of SDZ MAR 327 (9 mg). The pre and post drug treatment [C-11] SCH 23390 dynamic data were analyzed using two different methods, each yielding a parameter proportional to the receptor density: i) a simple regional comparison approximating the specifically bound to free fraction, B/F; and ii) a two compartment, two parameter model yielding the apparent distribution volume DV". With both methods, a metabolite corrected arterial input function was used and the vascular fraction of tissue (V-b) was fixed at a previously determined value of 4%. Method I served as a qualitative comparison of the paired studies and demonstrated little difference between the pre and post drug conditions, method II also confirmed that there was no significant change in binding of [C-11] SCH 23390 in the striatum. These data indicate that SDZ MAR 327 produces little if any effect on dopamine D-1 receptor binding at the dose used. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Ctr Expt Pharmacol & Therapeut, Cambridge, MA 02139 USA. Sandoz Pharmaceut Corp, E Hanover, NJ USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. NR 22 TC 3 Z9 3 U1 1 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD JAN PY 1998 VL 1 IS 1 BP 243 EP 247 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117DT UT WOS:000075765900035 PM 9852226 ER PT J AU Billett, AL Gelber, RD Tarbell, NJ Dalton, V Donnelly, M Sallan, SE AF Billett, AL Gelber, RD Tarbell, NJ Dalton, V Donnelly, M Sallan, SE TI Results of Dana Farber Cancer Institute-consortium childhood acute lymphoblastic leukemia protocols SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Article DE acute lymphoblastic leukemia protocols ID COMBINATION CHEMOTHERAPY; PROGNOSTIC IMPLICATIONS; INTENSIVE ASPARAGINASE; INDUCTION; CHILDREN; THERAPY C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Joint Ctr Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Sallan, SE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1998 VL 5 IS 2-4 BP 115 EP 123 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 100YQ UT WOS:000074843200006 ER PT J AU Williams, JW Bhogte, M Flinn, JF AF Williams, JW Bhogte, M Flinn, JF TI Meeting the needs of primary care physicians: A guide to content for programs on depression SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Effective Educational Techniques for Primary Care Providers - Application to the Management of Psychiatric Disorders CY JUN 27-29, 1997 CL DARTMOUTH COLL, HANOVER, NEW HAMPSHIRE SP Solvay Pharm HO DARTMOUTH COLL DE primary health care; depressive disorders; education; medical; physician's practice patterns; attitude of health personnel ID RANDOMIZED CLINICAL-TRIAL; LATE-LIFE DEPRESSION; GENERAL-PRACTITIONERS; ANTIDEPRESSANT TREATMENT; MENTAL-DISORDERS; MAJOR DEPRESSION; FAMILY MEDICINE; RECOGNITION; PREVALENCE; ILLNESS AB Objective: The purpose of this article is to identify literature-based content for the design of educational programs on depression for practicing primary care physicians. Methods: A MEDLINE search was conducted of English-language medical literature published from 1982 through July 1997 for studies describing primary care physicians' knowledge, skills, practice patterns, and perceived barriers related to care of depressed patients. Studies focusing exclusively on residency training and those describing physician practices outside North America were excluded. Of 377 articles identified, forty met inclusion and exclusion criteria. Results: Recommendations for educational content were identified from the literature review. For recognition, educators should prioritize communication skills and strategies for the use of depression questionnaires. For diagnosis, practice interpreting symptoms in the medically ill, strategies for efficient diagnosis, and systematic approaches to assessing suicide risk should be emphasized. For treatment, greater attention to the therapeutic alliance, staged therapy, and strategies for improving medication adherence are indicated. Conclusions: There is a moderately well developed literature describing self-perceived and observed gaps in the current care for depression in primary care. Addressing the entire list of needs would take more time than practicing physicians are likely to have. An important challenge for educators is to design flexible programs based on individualized needs assessment or, when not possible, to prioritize the most generalizable needs. C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Williams, JW (reprint author), Ambulatory Care 11C-6,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 61 TC 8 Z9 8 U1 2 U2 2 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1998 VL 28 IS 1 BP 123 EP 136 PG 14 WC Psychiatry SC Psychiatry GA ZQ605 UT WOS:000073884800008 PM 9617652 ER PT J AU Williams, J Mulrow, C Chiquette, E Aguilar, C Noel, P Cornell, J AF Williams, J Mulrow, C Chiquette, E Aguilar, C Noel, P Cornell, J TI Newer pharmacotherapies for depression in primary care: A literature synthesis SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1998 VL 28 IS 4 BP 405 EP 406 PG 2 WC Psychiatry SC Psychiatry GA 178YX UT WOS:000079297700033 ER PT J AU Chakrabarti, S Kassis, AI Slayter, HS Bump, EA Sahu, SK Makrigiorgos, GM AF Chakrabarti, S Kassis, AI Slayter, HS Bump, EA Sahu, SK Makrigiorgos, GM TI Continuous detection of radiation or metal generated hydroxyl radicals within core chromatin particles SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID INDUCED DNA-DAMAGE; HYDROGEN-PEROXIDE; POSITIONED NUCLEOSOME; MAMMALIAN-CELLS; PROTECTS DNA; SITE; COMPLEXES; HISTONES; REPAIR; ION AB Purpose: The aim of this work was to adapt a recently developed fluorometric method for use in the detection of hydroxyl radical (HO.) generated in the immediate vicinity of chromatin core particles reconstituted from pUC19 plasmid DNA and isolated core histones. Materials and methods: The procedure followed involves labelling nucleosomal histones with SECCA, a non-fluorescent coumarin derivative that generates the fluorescent 7-hydroxy-SECCA after reaction with HO.. Core particles are formed using histones and pUC19 DNA in a salt-dialysis procedure. Results: Electron microscopy and micrococcal nuclease digestion are consistent with successful formation of core particles. No significant differences between core particle formation in the unlabelled and SECCA-labelled samples were detected. Exposure to HO . generated by radiation or copper(--)ascorbic acid(--)hydrogen peroxide results in a gradual induction of fluorescence. Studies using dimethyl sulphoxide (DMSO) demonstrate that, unlike HO. produced by radiation, the majority of HO. generated by copper(--)ascorbic acid(--)hydrogen peroxide occurs primarily in the immediate vicinity of core particles and DNA and cannot be scavenged. Conclusions: The present procedure demonstrates the feasibility to quantitate HO. generated by several agents in the immediate vicinity of nucleosomes (chromatin-associated HO.) or associated with specific regions within the genome. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [R29 CA63334, K04 CA69296, R01 CA72046] NR 48 TC 9 Z9 9 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD JAN PY 1998 VL 73 IS 1 BP 53 EP 63 DI 10.1080/095530098142707 PG 11 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA YT713 UT WOS:000071635500006 PM 9464477 ER PT J AU Grann, A Wallner, K AF Grann, A Wallner, K TI Prostate brachytherapy in patients with inflammatory bowel disease SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostatic carcinoma; brachytherapy; inflammatory bowel disease; Crohn's; ulcerative colitis AB Purpose: There are minimal data to support the perceived contraindication of radiation therapy in patients with inflammatory bowel disease (IBD). Because of widespread concern about the possibility of radiation-related morbidity in IBD patients, the posttreatment course for 6 patients with a history of LED who were treated with I-125 prostate implantation for early stage prostate cancer are reported here. Materials and Methods: Six patients with a prior history of IBD and Stage T1c-T2c prostatic carcinoma underwent I-125 prostate brachytherapy from 1991-1996. Three patients had Crohn's disease and three had ulcerative colitis. The treatment plans were designed to treat the preimplant prostatic margin, as defined on planning CT scan, to 150 Gy. No special effort was made to minimize the rectal surface dose. Detailed records were available for all patients, and all patients were interviewed for this report, Follow-up ranged from 1 to 6 years (median: 3.7 years). Results: None of the 6 patients experienced unusual or significant gastrointestinal side effects following implantation. All 6 patients remain free of GI complications. The rectal surface area that received > 100 Gy was kept below 10 mm(2) in all patients, in accordance with previously published guidelines, Conclusions: Based on the limited information available, it appears that prostate brachytherapy is safe in patients with a history of LED. (C) 1998 Elsevier Science Inc. C1 Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, Brachytherapy Serv, New York, NY 10021 USA. RP Wallner, K (reprint author), Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Radiat Oncol Serv, 1660 S Columbian Way 174, Seattle, WA 98108 USA. NR 10 TC 21 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 1998 VL 40 IS 1 BP 135 EP 138 DI 10.1016/S0360-3016(97)00583-X PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YN393 UT WOS:000071164200021 PM 9422569 ER PT J AU Haskell, CM Mendoza, E Pisters, KMW Fossella, FV Figlin, RA AF Haskell, CM Mendoza, E Pisters, KMW Fossella, FV Figlin, RA TI Phase II study of intravenous adenosine 5 '-triphosphate in patients with previously untreated stage IIIB and stage IV non-small cell lung cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE ATP; adenosine 5 '-triphosphate; non-small cell lung cancer ID EXTRACELLULAR ATP; CLINICAL-TRIALS; TUMOR-CELLS; GROWTH AB Fifteen patients with Stage IIIB or IV non-small cell lung cancer gave informed consent to receive three or more 96-hour infusions of ATP at a dose of 50 mcg/kg/min or higher to determine whether ATP has antineoplastic activity against this tumor type and to better define the spectrum of toxicity for ATP given as a single agent. There were no objective complete or partial responses observed. The median survival of the overall group was 187 days and the median time to tumor progression was 113 days. The major toxic side effects were chest pain and dyspnea, leading to the cessation of treatment in 5 patients. We conclude that ATP at this dose and schedule of administration is an inactive agent in patients with advanced non-small cell lung cancer. C1 W Los Angeles Vet Affairs Med Ctr, Ctr Canc, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Med Oncol, Houston, TX 77030 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Haskell, CM (reprint author), W Los Angeles Vet Affairs Med Ctr, Ctr Canc, 11301 Wilshire Blvd,111-N, Los Angeles, CA 90073 USA. NR 16 TC 39 Z9 40 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 1998 VL 16 IS 1 BP 81 EP 85 DI 10.1023/A:1006018610986 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 114AM UT WOS:000075587000011 PM 9740548 ER PT J AU Witte, RS Manola, J Burch, PA Kuzel, T Weinshel, EL Loehrer, PJ AF Witte, RS Manola, J Burch, PA Kuzel, T Weinshel, EL Loehrer, PJ TI Topotecan in previously treated advanced urothelial carcinoma: an ECOG phase II trial SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE topotecan; urothelial carcinoma; bladder cancer ID COOPERATIVE-ONCOLOGY-GROUP; TRANSITIONAL CELL-CARCINOMA; CISPLATIN; CANCER; METHOTREXATE; VINBLASTINE; CHEMOTHERAPY; DOXORUBICIN; GEMCITABINE; TRACT AB Background: Chemotherapeutic agents are playing an increasing role in the management of urothelial carcinoma. Despite recent advances in the treatment of this disease there continues to be a need to identify new active agents and their toxicity spectra. Topotecan is an agent as yet unstudied in bladder cancer. Methods: Ambulatory patients with progressive advanced urothelial carcinoma following prior systemic chemotherapy were treated with topotecan 1.5 mg/m(2) intravenously (IV) daily for 5 days every three weeks for 6 cycles. Doses were modified for leukopenic fever, thrombocytopenic bleeding, and any grade 3 or 4 (NCI common toxicity criteria) toxicity. Results: Forty-four eligible patients entered the trial. There were 4 partial responses for an overall response rate of 9.1% (exact 95% two-stage binomial CI, 2.9% to 25.5%). Major identified toxicities were gastrointestinal and myelosuppression. There were no treatment-related deaths. Conclusions: Topotecan at this dose and schedule has minimal activity in previously treated patients with advanced urothelial carcinoma. Toxicities can be seven but are manageable. C1 Gundersen Clin Ltd, Med Oncol Sect, La Crosse, WI 54601 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Northwestern Univ, Chicago, IL 60611 USA. MetroMinneapolis CCOP, Minneapolis, MN USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. RP Witte, RS (reprint author), Gundersen Clin Ltd, Med Oncol Sect, 1836 South Ave, La Crosse, WI 54601 USA. FU NCI NIH HHS [CA17145, CA13650, CA23318] NR 14 TC 30 Z9 30 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 1998 VL 16 IS 2 BP 191 EP 195 DI 10.1023/A:1006159525793 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 138BQ UT WOS:000076951900013 PM 9848585 ER PT J AU Amano, S Roban, R Kuroki, M Tolentino, M Adamis, AP AF Amano, S Roban, R Kuroki, M Tolentino, M Adamis, AP TI Requirement for vascular endothelial growth factor in wound- and inflammation-related corneal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID CONJUNCTIVAL TRANSDIFFERENTIATION; IRIS NEOVASCULARIZATION; PERMEABILITY FACTOR; RETINAL ISCHEMIA; NONHUMAN PRIMATE; IN-VIVO; ANGIOGENESIS; INHIBITION; CELLS; RAT AB PURPOSE. Vascular endothelial growth factor (VEGF) is required for vascular development and for ischemia-related tumor, iris, and retinal neovascularization. The role of VEGF in inflammatory corneal neovascularization is unknown and was investigated in these studies. METHODS. A rat model was used in which removal of the corneal and limbal epithelium resulted in circumferential neovascularization. Corneal VEGF mRNA levels were quantified with ribonuclease protection assays, and VEGF protein was studied in situ using immunohistochemical analysis. Controlled-release pellets containing anti-VEGF antibodies were implanted into the corneal stroma and were used to determine the requirement for VEGF in corneal neovascularization. RESULTS. VEGF mRNB and protein were induced to high levels after corneal injury and were temporally and spatially correlated with inflammation and neovascularization. VEGF immunoreactivity was localized primarily to the inflammatory cells invading the wounded cornea. The specific inhibition of VEGF bioactivity with neutralizing antibodies potently suppressed corneal neovascularization. CONCLUSIONS. These data are the first to demonstrate that VEGF may be required for inflammatory neovascularization of the rat cornea and to identify VEGF as a functional endogenous corneal angiogenic factor. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Omiya Med Ctr, Jichi Med Sch, Omiya, Saitama, Japan. RP Adamis, AP (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 00325] NR 28 TC 236 Z9 253 U1 0 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 1998 VL 39 IS 1 BP 18 EP 22 PG 5 WC Ophthalmology SC Ophthalmology GA YQ663 UT WOS:000071410800002 PM 9430540 ER PT J AU Niethammer, M Sheng, M AF Niethammer, M Sheng, M TI Identification of ion channel-associated proteins using the yeast two-hybrid system SO ION CHANNELS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID NMDA RECEPTOR SUBUNITS; 2-HYBRID SYSTEM; POTASSIUM CHANNEL; GUANYLATE KINASES; TYROSINE KINASE; DOMAIN; TRANSFORMATION; PSD-95; FAMILY; CELLS C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Niethammer, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. NR 38 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1998 VL 293 BP 104 EP 122 PN B PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BL52B UT WOS:000075762300007 PM 9711605 ER PT B AU Cariani, P AF Cariani, P GP IEEE TI Epistemic autonomy through adaptive sensing SO JOINT CONFERENCE ON THE SCIENCE AND TECHNOLOGY OF INTELLIGENT SYSTEMS LA English DT Proceedings Paper CT Joint Conference on the Science and Technology of Intelligent Systems ISIC/CIRA/ISAS CY SEP 14-17, 1998 CL NATL INST STAND & TECHNOL, GAITHERSBURG, MD SP IEEE, Control Syst Soc, Natl Sci Fdn, USA, Army Res Off HO NATL INST STAND & TECHNOL DE evolutionary robotics; epistemic autonomy; adaptive sensing; active sensing; semiotics; sensory coding; sensory prosthesis AB Sensors and effecters determine how events in the world at large are related to the internal informational states of organisms and robotic devices. Sensors determine what kinds of distinctions (perceptual categories, features, primitives) can be made on the environment. By "evolving the sensors" perceptual repertoires can be adaptively altered and/or enlarged. To the extent that devices can adaptively choose their own feature primitives for themselves, they gain a greater measure of "epistemic autonomy" vis-a-vis their designers. Such devices are useful in ill-defined situations where the designer does not know a priori what feature primitives are adequate or optimum for solving a particular task. Several general strategies for adaptively altering or augmenting sensor function are proposed: 1) prosthesis: adaptive fabrication of new front-ends for existing sensors (e.g. telescopes), 2) active sensing: using motor-actions to alter what is sensed through interaction (poking, pushing, bending), 3) sensory evolution: adaptive construction of entirely new sensors (adaptive antibody construction, Gordon Pask's electrochemical device) and 4) internalized sensing: "bringing the world into the device" by creating internal, analog representations of the world out of which internal sensors extract newly-relevant properties (perceptual learning). Since many neural sensory representations appear to be analog and iconic in nature, neural assemblies can be adaptively formed to function as internal sensors that can switch behavior according to new perceptual categories. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Cariani, P (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-4423-5 PY 1998 BP 718 EP 723 DI 10.1109/ISIC.1998.713808 PG 6 WC Automation & Control Systems; Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Automation & Control Systems; Computer Science GA BL60A UT WOS:000075973800126 ER PT J AU Frosch, DL Shoptaw, S Jarvik, ME Rawson, RA Ling, W AF Frosch, DL Shoptaw, S Jarvik, ME Rawson, RA Ling, W TI Interest in smoking cessation among methadone maintained outpatients SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article ID TREATING CIGARETTE-SMOKING; NICOTINE DEPENDENCE; ADDICTIVE BEHAVIORS; TOBACCO USE; ALCOHOL; CANCER; MORTALITY; CLIENTS; HEALTH AB The prevalence of cigarette smoking among opiate abusers is extremely high and tobacco related diseases are a major factor associated with morbidity and mortality for this group. Yet, many treatment providers remain reluctant to address smoking cessation with their clients due in part to the belief that substance abusers are not interested in quitting smoking. The present study examined self-reported interest in smoking cessation among methadone maintenance clients (N = 120) in four clinics in Los Angeles. Fifty-eight percent of subjects rated themselves as 'Somewhat' or 'Very Interested' in a smoking cessation program. Overall subjects appeared to accurately perceive the personal risks from tobacco smoking. In conclusion we find that clients in methadone maintenance treatment programs evidence a high level of interest in quitting smoking and may well be suited for a highly structured smoking cessation intervention. C1 Matrix Ctr, Santa Fe, NM USA. Los Angeles Addict Treatment Res Ctr, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. RP Frosch, DL (reprint author), 10350 Santa Monica Blvd,330, Los Angeles, CA 90025 USA. FU NIDA NIH HHS [R18 DA-06185, P50 DA-09260] NR 34 TC 48 Z9 49 U1 0 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 1998 VL 17 IS 2 BP 9 EP 19 PG 11 WC Substance Abuse SC Substance Abuse GA ZH303 UT WOS:000073093900002 PM 9567223 ER PT J AU Shoptaw, S Reback, CJ Frosch, DL Rawson, RA AF Shoptaw, S Reback, CJ Frosch, DL Rawson, RA TI Stimulant abuse treatment as HIV prevention SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article ID INTRAVENOUS-DRUG-USERS; AIDS-RELATED KNOWLEDGE; SUBSTANCE USE; RISK BEHAVIORS; BISEXUAL MEN; COCAINE DEPENDENCE; SEXUAL-BEHAVIOR; HOMOSEXUAL MEN; SAN-FRANCISCO; SAFER SEX AB Individuals who use illicit stimulants, primarily cocaine and methamphetamine, engage in substantial amounts of HIV-related sexual risk behaviors when under the influence. This paper presents the idea that reductions in stimulant use consequent to drug treatment makes stimulant drug treatment an important HIV prevention tool for this high-risk population. Data are presented to describe many of the HIV-related sexual risks reported by out-of-treatment methamphetamine users and by cocaine and methamphetamine abusers at treatment entry and six months post treatment entry. Overall, our findings demonstrate that following initiation of a treatment episode, stimulant abusers demonstrate significant and relevant reductions in HIV-related sexual behaviors, primarily by reducing the number of sexual partners. Rea sons for why stimulant treatment corresponds to HIV transmission risk reductions and suggestions for implementing prevention messages in treatment settings are offered. C1 Matrix Ctr, Friends Res Inst Inc, Los Angeles, CA 90025 USA. Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Rawson, RA (reprint author), Matrix Ctr, Friends Res Inst Inc, 10350 Santa Monica Blvd,Suite 330, Los Angeles, CA 90025 USA. OI Shoptaw, Steven/0000-0002-3583-0026 FU NIDA NIH HHS [R44 DA08786]; PHS HHS [H204213] NR 48 TC 43 Z9 46 U1 4 U2 7 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 1998 VL 17 IS 4 BP 19 EP 32 PG 14 WC Substance Abuse SC Substance Abuse GA 142FP UT WOS:000077189700003 PM 9848029 ER PT J AU Ashofteh, A Lau, BSF Setoda, D Ling, W AF Ashofteh, A Lau, BSF Setoda, D Ling, W TI Identifying methadone abuse in patients receiving LAAM SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, MDRU, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 1998 VL 17 IS 2 MA 34A BP 170 EP 170 PG 1 WC Substance Abuse SC Substance Abuse GA ZH303 UT WOS:000073093900046 ER PT J AU Biederman, J Mick, E Faraone, SV AF Biederman, J Mick, E Faraone, SV TI Depression in attention deficit hyperactivity disorder (ADHD) children: "True" depression or demoralization? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE major Depression; ADHD; comorbidity; remission; persistence ID CO-MORBIDITY; MAJOR DEPRESSION; RISK-FACTORS; CHILDHOOD; COMORBIDITY; ADOLESCENTS; BEHAVIOR; FAMILY; PSYCHOPATHOLOGY; SPECIFICITY AB Background: The purpose of this study was to further evaluate the nature of the association between major depression (MD) and attention deficit hyperactivity disorder (ADHD) by examining predictors of persistence of MD attending to issues of familiality, adversity and comorbidity. Methods: Four years of follow-up of 76 depressed ADHD children were analyzed using multivariate regression to determine predictors of persistent MD. Results: Bipolar disorder and higher indices of interpersonal problems predicted MD persistence. In contrast, school difficulty and ADHD-associated measures of severity were not associated with persistent MD. Remission from ADHD was also not statistically significantly associated with remission from MD. Conclusions: ADHD and MD had independent and distinct courses, indicating that ADHD-associated MD reflects a depressive disorder and not merely demoralization. Limitations: This study may have reduced power due to stratification of our group of ADHD boys with persistent and remitting MD. (C) 1998 Elsevier Science B.V. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 49 TC 67 Z9 68 U1 1 U2 5 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 JAN PY 1998 VL 47 IS 1-3 BP 113 EP 122 DI 10.1016/S0165-0327(97)00127-4 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA YU154 UT WOS:000071687700014 PM 9476751 ER PT J AU Abi-Younes, SA Lamkhioued, B Garcia-Zepeda, EA Nakamura, H Lilly, CM Hamid, Q Luster, AD AF Abi-Younes, SA Lamkhioued, B Garcia-Zepeda, EA Nakamura, H Lilly, CM Hamid, Q Luster, AD TI Monocyte chemoattractant protein (MCP)-4 expression in asthmatic lungs SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 McGill Univ, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 926 BP S223 EP S223 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800923 ER PT J AU Bush, R Sanchez, H Geisler, D AF Bush, R Sanchez, H Geisler, D TI Baba ghanoush anaphylaxis due to a "hidden" food allergen. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Hosp, Madison, WI USA. Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 134 BP S31 EP S31 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800135 ER PT J AU Crawford, WW Castle, SC Klaustermeyer, WB AF Crawford, WW Castle, SC Klaustermeyer, WB TI Clinical markers of cell-mediated immunity and atopy in elderly outpatients SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 1036 BP S250 EP S250 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924801032 ER PT J AU MacLean, JA Wu, C Jiao, AP De Sanctis, GT AF MacLean, JA Wu, C Jiao, AP De Sanctis, GT TI Antigen-induced pulmonary eosinophilia and airways hyperresponsiveness in B cell-deficient mice. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 666 BP S161 EP S161 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800666 ER PT J AU Nagy, CS Smith, RN Bloch, KJ AF Nagy, CS Smith, RN Bloch, KJ TI Is there an epidemic of single or multiple low concentration monoclonal immunoglobulins (LCMI) in patients' serum? SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 320 BP S76 EP S76 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800321 ER PT J AU Sanchez, H Geisler, D Bush, R AF Sanchez, H Geisler, D Bush, R TI Detection of peanut proteins in foods by immunoblot-polymerase chain reaction (PCR) assay. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 999 BP S241 EP S241 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800995 ER PT J AU Sanchez, H Geisler, D Bush, R AF Sanchez, H Geisler, D Bush, R TI Identification of Alt a 2 in native and recombinant Alternaria preparations. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI 53706 USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 360 BP S86 EP S86 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800360 ER PT J AU Yusin, JS Crawford, WW Clements, PJ Klaustermeyer, WB AF Yusin, JS Crawford, WW Clements, PJ Klaustermeyer, WB TI Hemolytic uremic syndrome thrombotic thrombocytopenic purpura (HUS/TTP) associated renal failure in a patient with scleroderma: A case report SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1998 VL 101 IS 1 MA 506 BP S122 EP S122 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800506 ER PT J AU Taylor, E AF Taylor, E TI Jung before Freud, not Freud before Jung: the reception of Jung's work in American psychoanalytic circles between 1904 and 1909 SO JOURNAL OF ANALYTICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual American Conference of the Journal-of-Analytical-Psychology CY JUN 11-15, 1997 CL SEBASCO, MAINE SP J Anal Psychol DE nineteenth century psychology; psychotherapeutic alliance; Freud; William James; Adolf Meyer; Theodore Flournoy; Swiss psychiatry; Americanization of Jungian ideas AB A review is first presented of the new Jung scholarship - that Jung is to be properly understood, not as a disciple of Freud, but as the twentieth century exponent of the symbolic hypothesis in the tradition of the late nineteenth century psychologies of transcendence. This is followed by an outline of the so-called French-Swiss-English and American psychotherapeutic alliance, of which Jung was a part, and the cross-cultural mediumistic psychology of the subconscious it promoted, chiefly through the works of William James, F. W. H. Myers, and Theodore Flournoy. Focusing on the experimental work of the Swiss-American pathologist Adolph Meyer and the American neurologist Frederick Peterson, evidence is then produced to show that Jung, before Freud, was more important in American psychotherapeutic circles. His experimental researches into the association method and the psychogalvanic reflex, his study of mediums and connection to Swiss psychiatry had numerous unique alliances with the American scene, particularly because of their similar historical relation between psychology and religion. Therefore, to understand Jung, one must consider the archetypal significance which America held for Jung's own individuation process, as well as the Americanization of Jungian ideas that followed. C1 Massachusetts Gen Hosp, Psychol Off, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Taylor, E (reprint author), Massachusetts Gen Hosp, Psychol Off, Bulfinch 501, Boston, MA 02114 USA. NR 48 TC 13 Z9 13 U1 1 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-8774 J9 J ANAL PSYCHOL JI J. Anal. Psychol. PD JAN PY 1998 VL 43 IS 1 BP 97 EP 114 DI 10.1111/1465-5922.00011 PG 18 WC Psychology, Psychoanalysis SC Psychology GA YX348 UT WOS:000072031200010 ER PT J AU Evans, AB Tsai, LW Oelberg, DA Kazemi, H Systrom, DM AF Evans, AB Tsai, LW Oelberg, DA Kazemi, H Systrom, DM TI Skeletal muscle ECF pH error signal for exercise ventilatory control SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE acid-base; magnetic resonance spectroscopy; metaboreflex; ventilation; extracellular fluid ID NUCLEAR-MAGNETIC-RESONANCE; GROUP-IV AFFERENTS; MUSCULAR-CONTRACTION; DYNAMIC EXERCISE; HINDLIMB MUSCLE; GROUP-III; RESPONSES; TRANSPORT; FATIGUE; LACTATE AB An autonomic reflex linking exercising skeletal muscle metabolism to central ventilatory control is thought to be mediated by neural afferents having free endings that terminate in the interstitial fluid of muscle. To determine whether changes in muscle extracellular fluid pH (pH(e)) can provide an error signal for exercise ventilatory control, pH(e) was measured during electrically induced contraction by P-31-magnetic resonance spectroscopy and the chemical shift of a phosphorylated, pH-sensitive marker that distributes to the extracellular fluid (phenylphosphonic acid). Seven lightly anesthetized rats underwent unilateral continuous 5-Hz sciatic nerve stimulation in an 8.45-T nuclear magnetic resonance magnet, which resulted in a mixed lactic acidosis and respiratory alkalosis, with no net change in arterial pH. Skeletal muscle intracellular pH fell from 7.30 +/- 0.03 units at rest to 6.72 +/- 0.05 units at 2.4 min of stimulation and then rose to 7.05 +/- 0.01 units (P < 0.05), despite ongoing stimulation and muscle contraction. Despite arterial hypocapnia, pH(e) showed an immediate drop from its resting baseline of 7.40 +/- 0.01 to 7.16 +/- 0.04 units (P < 0.05) and remained acidic throughout the stimulation protocol. During the on-and off-transients for 5-Hz stimulation, changes in the pH gradient between intracellular and extracellular compartments suggested time-dependent recruitment of sarcolemmal ion-transport mechanisms, pH(e) of exercising skeletal muscle meets temporal and qualitative criteria necessary for a ventilatory metaboreflex mediator in a setting where arterial pH does not. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Nucl Magnet Resonance Lab Physiol Chem, Boston, MA 02115 USA. RP Systrom, DM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch 1, Boston, MA 02114 USA. FU NHLBI NIH HHS [K08-HL-02593-A03] NR 36 TC 10 Z9 10 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 1998 VL 84 IS 1 BP 90 EP 96 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YR127 UT WOS:000071461000012 PM 9451622 ER PT J AU Morrell, MJ Badr, MS AF Morrell, MJ Badr, MS TI Effects of NREM sleep on dynamic within-breath changes in upper airway patency in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE respiratory control; breathing; sleep apnea; obstruction ID TOTAL PULMONARY RESISTANCE; LUNG-VOLUME; APNEA; WAKEFULNESS; COLLAPSIBILITY; HYPERCAPNIA; VENTILATION; VELOPHARYNX; RESPIRATION; OCCLUSION AB The purpose of our study was to compare inspiratory-and expiratory-related changes in retropalatal cross-sectional area (CSA) during wakefulness to those during non-rapid-eye-movement (NREM) sleep. We studied 18 subjects in whom the severity of sleep-disordered breathing varied. Relative changes in CSA were visualized by using fiber-optic endoscopy. For each breath analyzed (wakefulness n = 4-13; sleep n = 7-16), the CSA was measured at fixed points within inspiration and expiration (0, 25, 50, and 100% of the inspiratory and expiratory duration); these measurements were expressed as a percentage of the CSA that occurred at the start of inspiration. During wakefulness, there was a statistically significant increase in the retropalatal CSA (compared with the start of inspiration) only during early expiration (group mean: expiration, 0% = 112.6 +/- 3.2 (SE) %; 25% = 122.8 +/- 6.2%; 50% = 110.6 +/- 3.8%). In contrast, during sleep, significant changes in CSA occurred during both inspiration and expiration (group mean: inspiration, 25% = 75.3 +/- 6.0%; 50% = 66.7 +/- 7.7%; 75% = 64.6 +/- 8.1%; expiration, 0% = 126.8 +/- 11.8%; 25% = 125.3 +/- 6.9%). The expiratory-related increase in CSA was followed by narrowing such that at end expiration the caliber of the airway was returned to that occurring at the beginning of inspiration (group mean at end expiration = 98.6 +/- 3.1%). The largest changes in CSA occurred in the subjects with an increased body mass index (BMI). We conclude that, during NREM sleep, significant changes in CSA occur during both inspiration and expiration and that the magnitude of these changes is significantly influenced by BMI. C1 William S Middleton Mem Vet Hosp, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Prevent Med, John Rankin Lab Pulm Med, Madison, WI 53705 USA. RP Morrell, MJ (reprint author), Imperial Coll, Sch Med, Natl Heart Lung Inst, St Dunstans Rd, London W6 8RP, England. EM m.morrell@cxwms.ac.uk FU PHS HHS [53443] NR 36 TC 34 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 1998 VL 84 IS 1 BP 190 EP 199 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YR127 UT WOS:000071461000025 PM 9451635 ER PT J AU Venegas, JG Harris, RS Simon, BA AF Venegas, JG Harris, RS Simon, BA TI A comprehensive equation for the pulmonary pressure-volume curve SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE mechanical properties; lung compliance; lung recoil; acute respiratory distress syndrome; pneumoconstriction ID RESPIRATORY-DISTRESS SYNDROME; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; TIDAL VOLUME; AIRWAY PRESSURE; LUNG; DISTENSIBILITY; SURFACTANT; HYPERCAPNIA; ASTHMA AB Quantification of pulmonary pressure-volume (P-V) curves is often limited to calculation of specific compliance at a given pressure or the recoil pressure (P) at a given volume (V). These parameters can be substantially different depending on the arbitrary pressure or volume used in the comparison and map lead to erroneous conclusions. We evaluated a sigmoidal equation of the form, V = alpha + b[1 + e(-(P-c)/d)](-1) for its ability to characterize lung and respiratory system P-V curves obtained under a variety of conditions including normal and hypocapnic pneumoconstricted dog lungs (n = 9), oleic acid-induced acute respiratory distress syndrome (n = 2), and mechanically ventilated patients with acute respiratory distress syndrome (n = 10). In this equation, a corresponds to the V of a lower asymptote, b to the V difference between upper and lower asymptotes, c to the P at the true inflection point of the curve, and d to a width parameter proportional to the P range within which most of the V change occurs. The equation fitted equally well inflation and deflation limbs of P-V curves with a mean goodness-of-fit coefficient (R-2) of 0.997 +/- 0.02 (SD). When the data from all analyzed P-V curves were normalized by the best-fit parameters and plotted as (V - a)/b vs. (P - c)/d, they collapsed into a single and tight relationship (R-2 = 0.997). These results demonstrate that this sigmoidal equation can fit with excellent precision inflation and deflation P-V curves of normal lungs and of lungs with alveolar derecruitment and/or a region of gas trapping while yielding robust and physiologically useful parameters. C1 Harvard Univ, Dept Anesthesia CLV255, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Unit, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Harvard Univ, Dept Anesthesia CLV255, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 32 TC 168 Z9 177 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 1998 VL 84 IS 1 BP 389 EP 395 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YR127 UT WOS:000071461000051 PM 9451661 ER PT J AU Bal, BS Maurer, BT Harris, WH AF Bal, BS Maurer, BT Harris, WH TI Trochanteric union following revision total hip arthroplasty SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; trochanter; osteotomy; reattachment; trochanteric union AB Ninety-nine patients (106 hips) with a trochanteric osteotomy during revision total hip arthroplasty were evaluated at a minimum of 5 years after surgery. Trochanteric reattachment was done with monofilament cobalt-chromium wires. The influence of the following variables on trochanteric union was examined: a prior trochanteric osteotomy, an existing trochanteric nonunion, trochanteric advancement to the lateral femur, use of vertical (in addition to horizontal) wires through the trochanter, and use of a trochanteric mesh. Overall, union occurred in 92 of the 106 trochanters (87%). Fifty-three of 61 trochanters (86.9%) healed after an initial osteotomy, whereas 34 of 38 (89.5%) healed after a repeat osteotomy. Five of the 7 trochanters with an existing nonunion healed, and 5 of 5 trochanters reattached to a bulk allograft healed. Twenty-nine of 36 trochanters (80.5%) reattached to cancellous bone healed, compared with 58 of 65 (89.2%) that were reattached to the lateral femoral cortex. Ninety percent (83/92) of the trochanters reattached in conjunction with use of a chrome-cobalt mesh healed, compared with 64.3% (9/14) of those without (P < .05). Of the variables studied, only the use of mesh was statistically significant. Osteotomy through a previously healed trochanter, advancement of the trochanter to cortical bone, existing trochanteric nonunion, trochanteric reattachment to a bulk allograft, and lack of vertical wires for fixation did not adversely affect the likelihood of obtaining trochanteric union. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,55 Fruit St, Boston, MA 02114 USA. OI Bal, B. Sonny/0000-0002-9615-8632 NR 23 TC 23 Z9 27 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 1998 VL 13 IS 1 BP 29 EP 33 DI 10.1016/S0883-5403(98)90072-9 PG 5 WC Orthopedics SC Orthopedics GA ZB698 UT WOS:000072498600005 PM 9493535 ER PT J AU Smith, SE Estok, DM Harris, WH AF Smith, SE Estok, DM Harris, WH TI Average 12-year outcome of a chrome-cobalt, beaded, bony ingrowth acetabular component SO JOURNAL OF ARTHROPLASTY LA English DT Article DE Acetabular Reconstruction Component; Porous Coated Anatomic acetabular component; aseptic loosening; acetabular revision ID TOTAL HIP-REPLACEMENT; IMPROVED CEMENTING TECHNIQUES; CONGENITAL DISLOCATION; ARTHROPLASTY AB Seventy-two hips (67 patients) were reconstructed with the Acetabular Reconstruction Component (ARC, Howmedica, Rutherford, NJ), a chrome-cobalt component with sintered ingrowth beads and peripheral flanges for screw fixation. All the materials used in the ARC (metal, porous layer, and polyethylene) are identical to those used in the Porous Coated Anatomic (PCA) acetabular component (Howmedica), but the design is different. To determine the importance of design features alone, clinical results obtained with the 2 different designs made of identical materials were compared. The average follow-up period for patients with the ARC was 12 years (range, 10-13.3 years). Seven patients (7 hips) with the ARC died prior to the minimum 10-year follow-up period, none having undergone revision procedures. Overall, 3 acetabular components (4%) in 3 patients were revised, at an average of 8.5 years (range, 7.6-9.3 years) from the index operation. The reasons for revision were aseptic loosening third-body polyethylene wear observed during a revision for femoral lysis, and acetabular component malposition and recurrent dislocation. The total incidence of acetabular aseptic loosening was 4% (3 of 72 hips). Pelvic osteolysis occurred in 3 cases (4%). In contrast, the incidence of acetabular revision of the PCA acetabular component at follow-up periods of 2-10 years is reported to be as high as 11% (range, 3-11%). Rates of aseptic loosening are as high as 30% (range, 3-30%) at substantially shorter follow-up periods, and the incidence of pelvic osteolysis associated with the PCA component is also as high as 30% (range, 5-30%). These differences may reflect differences in design between the 2 acetabular components, as the materials used were identical. In this, the longest reported average follow-up study of a successful cementless acetabular component, the aseptic loosening rate of 4% contrasts with the 42% rate at similar follow-up duration for cemented acetabular components placed by the same surgeon in patients of similar age. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Smith, SE (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 21 Z9 22 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 1998 VL 13 IS 1 BP 50 EP 60 DI 10.1016/S0883-5403(98)90075-4 PG 11 WC Orthopedics SC Orthopedics GA ZB698 UT WOS:000072498600008 PM 9493538 ER PT J AU Pal, L Shifren, JL Isaacson, KB Chang, YC Leykin, L Toth, TL AF Pal, L Shifren, JL Isaacson, KB Chang, YC Leykin, L Toth, TL TI Impact of varying stages of endometriosis on the outcome of in vitro fertilization-embryo transfer SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE endometriosis; staging; American Fertility Society classification; in vitro fertilization ID INVITRO FERTILIZATION; INFERTILE PATIENTS; IMPLANTATION; SUCCESS AB Purpose: The impact of severity of endometriosis on the outcome of in vitro fertilization (IVF) was analyzed in an uncontrolled, retrospective study in an academic IVF program. Methods: Sixty-one patients with a primary diagnosis of endometriosis undergoing 85 cycles of IVF were included in the study. Patients were divided according to the severity of disease based on the revised American Fertility Society (AFS) classification into groups A (stages I/II, or minimal/mild) and B (stages IIl/IV, or moderate/severe). Group A included 32 patients undergoing 45 IVF-embryo transfer (ET) cycles; group B included 29 patients undergoing 40 NF cycles, Exclusion criteria were age older than 40 years, basal day 3 follicle stimulating hormone (FSH) greater than 20 IU/L, male-factor infertility, assisted hatching, and gamete intrafallopian transfer cases. Stimulation for NF cycles was standard using pituitary down-regulation with gonadotropin-releasing hormone agonist in a midluteal protocol, Controlled ovarian hyperstimulation (COH) was achieved using a combination of FSH and human menopausal gonadotropin. Outcomes assessed included response to COH and number; maturity, and quality of oocytes retrieved. Fertilization, implantation, and pregnancy rates after NF-ET were also analyzed. Results: The response to COH and the number, maturity, and quality of the oocytes was comparable between patients with varying severity of endometriosis. Fertilization rates for oocytes of patients in group B (stages III/IV) were significantly impaired compared to those in group A (stages I/II) (P = 0.004). The rates for implantation, clinical pregnancy, and miscarriage were comparable between the two groups. Conclusions: The reduced fertilization potential of the oocytes obtained from patients with severe endometriosis in the absence of male-factor infertility suggests an adverse biological impact of the advanced disease on the oocytes. The outcome of IVF-ET however; is unaffected by increasing severity of endometriosis, This suggests that NF may compensate for or overcome this reduction in the biological potential of the oocytes associated with severe disease, thus accounting for a comparable outcome irrespective of the severity of endometriosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Reprod Endocrinol, Boston, MA 02114 USA. RP Pal, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Reprod Endocrinol, Vincent 1 Room 137 G, Boston, MA 02114 USA. NR 18 TC 70 Z9 76 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD JAN PY 1998 VL 15 IS 1 BP 27 EP 31 DI 10.1023/A:1022574221115 PG 5 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA YW199 UT WOS:000071908400006 PM 9493063 ER PT J AU Cao, YL Rodriguez, A Vacanti, M Ibarra, C Arevalo, C Vacanti, CA AF Cao, YL Rodriguez, A Vacanti, M Ibarra, C Arevalo, C Vacanti, CA TI Comparative study of the use of poly(glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE tissue engineering; chondrocyte; cartilage; autologous; hydrogel; poly(glycolic acid); calcium alginate; pluronic ID TISSUE; GENERATION; POLYMERS; TENDON AB New cartilage formation has been successfully achieved by a technology referred to as tissue engineering. Polymers and hydrogels such as poly(glycolic acid), calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used as cell carriers to regenerate cartilage in the nude mouse model. The next step toward human applications of engineered cartilage is to demonstrate their potential in immunocompetent animal models. This study compared the suitability of three polymers for generating tissue engineered elastic cartilage using autologous cells in an immune-competent porcine animal model. Auricular cartilage was obtained from pigs. Chondrocytes were isolated and seeded onto fiber based poly(glycolic acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at constant concentrations. Chondrocyte-polymer constructs were either implanted (PGA) or injected (calcium alginate and pluronic) as autologous implants subcutaneously into the pigs from which the cells had been isolated. Specimens were harvested and analyzed grossly and histologically after 6 weeks in vivo. All explants demonstrated cartilage formation to a variable degree. When using PGA or calcium alginate, the overall histological appearance of the tissue formed is that of fibrocartilage with thick bundles of collagen dispersed in the tissue. When using pluronics as scaffold, histologic features resemble those of native elastic cartilage, showing a more organized arrangement of the cells, which seems to correlate to functional properties as elastin presence in the tissue engineered cartilage. Elastic cartilage engineered in an immunocompetent animal model varies with the type of polymer used. The behavior of the cell-polymer constructs is not fully understood and outcome seems to be related to several factors, including inflammatory reaction. Further studies with similar models are needed to determine the feasibility of engineering tissue generated from different cell-polymer constructs prior to human application. C1 Univ Massachusetts, Med Ctr, Dept Anesthesia, Worcester, MA 01655 USA. Univ Massachusetts, Med Ctr, Lab Tissue Engn, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Cao, YL (reprint author), Univ Massachusetts, Med Ctr, Dept Anesthesia, 55 Lake Ave N, Worcester, MA 01655 USA. NR 15 TC 207 Z9 230 U1 5 U2 36 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 1998 VL 9 IS 5 BP 475 EP 487 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA ZU949 UT WOS:000074252600006 PM 9648028 ER PT J AU Bhatia, SN Balis, UJ Yarmush, ML Toner, M AF Bhatia, SN Balis, UJ Yarmush, ML Toner, M TI Probing heterotypic cell interactions: Hepatocyte function in microfabricated co-cultures SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION LA English DT Article DE co-culture; hepatocyte; micropatterning; bioartificial liver ID ADULT-RAT HEPATOCYTES; LEUKEMIA-INHIBITORY FACTOR; KERATINOCYTE GROWTH-FACTOR; FULMINANT HEPATIC-FAILURE; EXTRACELLULAR-MATRIX; SANDWICH CONFIGURATION; DIFFERENTIATED FUNCTIONS; LIVER-REGENERATION; COLLAGEN SANDWICH; EPITHELIAL-CELLS AB Replacement of liver function using extracorporeal bioartificial systems has been attempted with limited success. The instability of the hepatocyte phenotype in vitro has restricted the useful lifetime of these devices. Go-cultivation of hepatocytes with mesenchymal cells is one method that has been widely utilized to stabilize the liver-specific function of isolated cells; however, co-culture has yet to be successfully incorporated in a bioreactor setting. In this study, we probed heterotypic cell interactions in co-cultures of hepatocytes and 3T3 in order to better understand the cellular microenvironment necessary to induce and stabilize liver-specific functions. Using microfabrication and conventional techniques to control the heterotypic interface, the effects of varying degrees of heterotypic interaction on tissue function (albumin and urea synthesis) were examined. Our data indicated maximal induction of liver-specific functions in cultures with maximal initial heterotypic interaction, and that induction of hepatic functions in hepatocytes was increased in the vicinity of fibroblasts as compared to hepatocytes far from the heterotypic interface. Furthermore, our data suggested that heterotypic cell contact is necessary for induction of these functions. These studies will aid in the formation of design criteria for a co-culture based bioartificial liver, as well as provide a useful tool to study the role of heterotypic and homotypic interactions in liver physiology and pathophysiology. C1 Massachusetts Gen Hosp, Shriners Burns Inst, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Shriners Burns Inst, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RI Yu, weiting/I-7417-2013 FU NIDDK NIH HHS [DK43371] NR 59 TC 125 Z9 131 U1 2 U2 17 PU VSP BV PI ZEIST PA PO BOX 346, 3700 AH ZEIST, NETHERLANDS SN 0920-5063 J9 J BIOMAT SCI-POLYM E JI J. Biomater. Sci.-Polym. Ed. PY 1998 VL 9 IS 11 BP 1137 EP 1160 DI 10.1163/156856298X00695 PG 24 WC Engineering, Biomedical; Materials Science, Biomaterials; Polymer Science SC Engineering; Materials Science; Polymer Science GA 142LM UT WOS:000077202000003 PM 9860177 ER PT J AU Kurihara, N Ishizuka, S Tatsumi, J Arai, F Ikeda, K Roodman, GD AF Kurihara, N Ishizuka, S Tatsumi, J Arai, F Ikeda, K Roodman, GD TI 23(S)25(R)-1,25-dihydroxyvitamin D-3-lactone, a naturally occurring metabolite of 1,25-dihydroxyvitamin D-3, inhibits osteoclast-like cell formation in human bone marrow cultures SO JOURNAL OF BONE AND MINERAL METABOLISM LA English DT Article DE 1,25(OH)(2)D-3; 1,25(OH)(2)D-3-lactone; osteoclast-like cell ID MULTINUCLEATED CELLS; 1-ALPHA,25-DIHYDROXYVITAMIN D3-26,23-LACTONE; BIOLOGICAL-ACTIVITY; PHENOTYPE; DIASTEREOISOMERS; PRECURSORS AB We have used a human bone marrow culture system that forms multinucleated cells (MNCs), 50% of which express the osteoclast phenotype, to examine the 23(S)25(R)-1,25-dihydroxyvitamin D-3-26,23-lactone (1,25-D-3-lactone) on osteoclast-like cell formation. The 1,25-D-3-lactone is a vitamin D-3 metabolite that has recently been detected in human serum under physiological conditions at concentrations of approximately 131 pg/ml (3 x 10(-10) M) and can inhibit bone resorption induced by 1,25-dihvdroxyvitamin D-3 (1,25-D-3) in vivo and in vitro. We examined the effects of the 1,25-D-3-lactone on the formation of MNC that cross-reacted with 23C6 monoclonal antibody (23C6-positive MNC), which preferentially binds to osteoclasts. All metabolites of 1,25-D-3 except the 1,25-D-3-lactone increased both total and 23C6-positive MNC formation in a dose-dependent manner. In contrast. the 1,25 D-3-lactone inhibited both total and 23C6-positive MNC formation, whether the cultures were treated with 1,25-D-3, parathyroid hormone, or interleukin-1 beta, all potent stimulators of MNC formation. This inhibitory action of 1,25-D-3-lactone on MNC formation was very similar to the inhibitory effects of calcitonin. These data suggest that (1) 1,25-D-3-lactone is a potent natural inhibitor of formation of cells with the osteoclast phenotype at physiological concentrations and (2) the inhibition of these cells by 1,25-D-3-lactone may not result solely from its competitive binding to the 1,25-D-3 receptor. C1 Meikai Univ, Dept Periodontol, Sakado, Saitama 3500283, Japan. Audie L Murphy Mem Vet Hosp, Res Serv, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Teijin Inst Biomed Res, Hino, Tokyo 191, Japan. RP Kurihara, N (reprint author), Meikai Univ, Dept Periodontol, 1-1 Keyakidai, Sakado, Saitama 3500283, Japan. RI Arai, Fumio/J-5241-2013 OI Arai, Fumio/0000-0003-1936-4907 NR 20 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113, JAPAN SN 0914-8779 J9 J BONE MINER METAB JI J. Bone Miner. Metab. PY 1998 VL 16 IS 1 BP 5 EP 10 DI 10.1007/s007740050021 PG 6 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA 135AW UT WOS:000076778100002 ER PT J AU Sheridan, RL Choucair, RJ Donelan, MB AF Sheridan, RL Choucair, RJ Donelan, MB TI Management of massive calvarial exposure in young children SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID INJURY; RECONSTRUCTION; SCALP; BONE; FLAP AB Although small areas of exposed calvaria commonly occur in seriously burned children, these wounds are generally straightforward management problems. In contrast, management of the nearly completely exposed calvaria is an extraordinarily difficult problem-but is fortunately rare. Over the past 15 years, we have treated 119 children with full-thickness calvarial wounds requiring grafting. Pour (3.4%) of these patients (average age, 2.9 years; range, 22 months to 5.5 years) had massive exposure of nonviable calvaria, defined as 75% or more of the surface area of the calvaria. These wounds were open an average of 28 months (range, 6 to 45 months). We have concluded that optimal management involves staged debridement of the desiccated outer table with a high-speed drill, taking appropriate precautions to avoid air embolism or inadvertent dural injury in the area of sutures or fontanelles. The resulting wounds quickly granulate and can be autografted. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Burns Inst, 51 Blossom St, Boston, MA 02114 USA. NR 10 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD JAN-FEB PY 1998 VL 19 IS 1 BP 29 EP 32 DI 10.1097/00004630-199801000-00008 PN 1 PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 115UT UT WOS:000075684600005 PM 9502021 ER PT J AU Ford, HL Pardee, AB AF Ford, HL Pardee, AB TI The S phase: Beginning, middle, and end: A perspective SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE S phase; DNA replication; gene replication ID DNA-REPLICATION; CELL-CYCLE; GENE; ACTIVATION; INITIATION; YEAST; PHOSPHORYLATION; ELEMENTS; SYSTEM; CANCER AB Events in the S phase of the cell cycle have been investigated to a relatively limited extent in comparison with those in G1 and M phases. Four aspects of S are briefly discussed in this report: (1) the final biochemical step permitting initiation of DNA synthesis, (2) determination of replication timing of individual genes and its mechanism, (3) S phase processes that lead to the onset of M phase, and (4) resetting the S-phase machinery. J. Cell. Biochem. Suppls. 30/31 :1-7, 1998. (C) 1998 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 37 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1998 SU 30-31 BP 1 EP 7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 154ZV UT WOS:000077921800002 ER PT J AU VanRemmen, H Williams, MD Yang, H Walter, CA Richardson, A AF VanRemmen, H Williams, MD Yang, H Walter, CA Richardson, A TI Analysis of the transcriptional activity of the 5'-flanking region of the rat catalase gene in transiently transfected cells and in transgenic mice SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GLUTATHIONE-PEROXIDASE GENE; AMINO-ACID-SEQUENCE; SUPEROXIDE-DISMUTASE; NUCLEOTIDE-SEQUENCE; ANTIOXIDANT ENZYMES; MAMMALIAN-CELLS; DNA; EXPRESSION; LIVER; CDNA AB Transiently transfected cell lines and transgenic mice were used to study the transcriptional activity of the 5'-flanking region of the catalase gene, Fragments of the 5'-flanking region of the rat catalase gene ranging in length from 3,421 base pairs (bp) to 69 bp were fused to the chloramphenicol acetyltransferase (CAT) reporter gene, and the transcriptional activity of the reporter gene was measured following transient transfection in three cell lines: a human hepatoma cell line (HepG2), a porcine kidney epithelial cell line (LLCPK1), and a human glioma cell line (U-138 MG). The 3,421-bp fragment of the 5'-flanking region resulted in a high level of expression of the reporter gene in all three cell lines. Shorter fragments of the 5'-flanking region resulted in a decrease in the level of CAT reporter expression that varied among the three cell lines, implying the presence of tissue-specific regulatory sites. To study the tissue-specific regulation of the catalase promoter, transgenic mice containing the 3,421-bp 5'-flanking sequence attached to the CAT reporter gene were produced, and CAT expression was measured in various tissues of three independent transgenic lines. CAT activ- ity was consistently high in muscle tissue (heart, skeletal muscle, and diaphragm) and low in most other tissues studied, particularly in liver and kidney. In contrast, the endogenous expression of catalase is low in muscle and high in liver and kidney; thus, the tissue-specific expression of the reporter gene driven by the 3,421-bp fragment of the 5'-flanking region of the catalase gene was not similar to the expression of the endogenous catalase gene. (C) 1998 Wiley-Liss, Inc. C1 S TEXAS VET HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,AUDIE L MURPHY DIV,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG01548] NR 35 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 1998 VL 174 IS 1 BP 18 EP 26 DI 10.1002/(SICI)1097-4652(199801)174:1<18::AID-JCP3>3.0.CO;2-J PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA YH655 UT WOS:A1998YH65500003 PM 9397152 ER PT J AU Ancukiewicz, M AF Ancukiewicz, M TI An unsupervised and nonparametric classification procedure based on mixtures with known weights SO JOURNAL OF CLASSIFICATION LA English DT Article DE finite mixture distribution; unsupervised classification; nonparametric density estimation; myocardial infarction; creatine kinase; reperfusion AB I consider a new problem of classification into n(n greater than or equal to 2) disjoint classes based on features of unclassified data. It is assumed that the data are grouped into m(M greater than or equal to n) disjoint sets and within each set the distribution of features is a mixture of distributions corresponding to particular classes. Moreover, the mixing proportions should be known and form a matrix of rank n. The idea of solution is, first, to estimate feature densities in all the groups, then to solve the linear system for component densities. The proposed classification method is asymptotically optimal, provided a consistent method of density estimation is used. For illustration, the method is applied to determining perfusion status in myocardial infarction patients, using creatine kinase measurements. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Ancukiewicz, M (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Founders Bldg 516,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0176-4268 J9 J CLASSIF JI J. Classif. PY 1998 VL 15 IS 1 BP 129 EP 141 DI 10.1007/s003579900023 PG 13 WC Mathematics, Interdisciplinary Applications; Psychology, Mathematical SC Mathematics; Psychology GA ZN405 UT WOS:000073642600007 ER PT J AU Goodnough, LT Kuter, D McCullough, J Brecher, ME AF Goodnough, LT Kuter, D McCullough, J Brecher, ME TI Apheresis platelets: Emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose SO JOURNAL OF CLINICAL APHERESIS LA English DT Article DE apheresis platelets; platelet transfusion therapy; donor platelet count ID HUMAN MEGAKARYOCYTE GROWTH; COLONY-STIMULATING FACTOR; ADVANCED CANCER; RECOMBINANT; CHEMOTHERAPY; BLOOD AB Emerging issues in stimulating apheresis platelet donors with platelet growth factors, the relative costs of apheresis and random donor platelet concentrates, optimal platelet transfusion dose, and leucoreduction of platelet products have caused renewed debate regarding apheresis products vs. random, pooled concentrates. The future role of apheresis products in platelet transfusion therapy will in large part be determined by costs, which are increasingly recognized to be influenced by donor platelet count, apheresis yield, and platelet transfusion dose. (C) 1998 Wiley-Liss,Inc. C1 Washington Univ, Sch Med, Div Lab Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Lab Med, Dept Pathol, St Louis, MO 63110 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA USA. Univ Minnesota, Dept Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. RP Goodnough, LT (reprint author), Washington Univ, Sch Med, Div Lab Med, Dept Med, Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. EM goodnough@labmed.wustl.edu NR 34 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PY 1998 VL 13 IS 3 BP 114 EP 119 DI 10.1002/(SICI)1098-1101(1998)13:3<114::AID-JCA4>3.0.CO;2-6 PG 6 WC Hematology SC Hematology GA 134TF UT WOS:000076758800004 PM 9828021 ER PT J AU Gordon, CM Majzoub, JA Marsh, DJ Mulliken, JB Ponder, BAJ Robinson, BG Eng, C AF Gordon, CM Majzoub, JA Marsh, DJ Mulliken, JB Ponder, BAJ Robinson, BG Eng, C TI Four cases of mucosal neuroma syndrome: Multiple endocrine neoplasm 2B or not 2B? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MEDULLARY-THYROID CARCINOMA; RECEPTOR TYROSINE KINASE; RET-MUTATION-CONSORTIUM; HIRSCHSPRUNGS-DISEASE; POINT MUTATION; PROTOONCOGENE; TYPE-2; GDNF; PHENOTYPE; NEURTURIN C1 Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA 02115 USA. Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Human Canc Genet Unit,Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Human Canc Genet Unit,Dept Pediat, Boston, MA 02115 USA. Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, Genet Mol Lab, St Leonards, NSW 2065, Australia. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. RP Gordon, CM (reprint author), Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 FU NIDDK NIH HHS [5T32-DK-07699-15]; PHS HHS [MCJ-MA 259195] NR 31 TC 12 Z9 14 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 1998 VL 83 IS 1 BP 17 EP 20 DI 10.1210/jc.83.1.17 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YP375 UT WOS:000071270600005 PM 9435410 ER PT J AU Awumey, EMK Mitra, DA Hollis, BW Kumar, R Bell, NH AF Awumey, EMK Mitra, DA Hollis, BW Kumar, R Bell, NH TI Vitamin D metabolism is altered in Asian Indians in the southern United States: A clinical research center study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID D-ENDOCRINE SYSTEM; D DEFICIENCY; PLASMA 25-HYDROXYVITAMIN-D; IMMIGRANT POPULATION; NUTRITIONAL RICKETS; WHITE-CHILDREN; BONE; BLACK; RADIOIMMUNOASSAY; OSTEOMALACIA AB Asian Indians who immigrate to northern Europe have lower serum 25-hydroxyvitamin D [25(OH)D] than Caucasians, and they develop vitamin D deficiency, rickets, and osteomalacia. We investigated vitamin D metabolism, the effects of 25(OH)D, on vitamin D metabolism and activity of 25(OH)D-24-hydroxylase, the rate-limiting enzyme for degradation of 25(OK)D, from cultured skin fibroblasts of Asian Indians and compared them with cultured skin fibroblasts of Caucasians in the southern United States. Normal subjects, ages 20-40 yr, were admitted to a metabolic ward for 2.5 days and given a daily diet containing 400 mg calcium and 900 mg phosphorus. Serum vitamin D, serum 25(OH)D, urinary calcium, and urinary phosphorus were significantly lower, whereas serum immunoreactive intact parathyroid hormone (PTH) and serum 1,25-dihydroxy vitamin D [1,25(OH)(2)D] were significantly higher in Asian Indians than in Caucasians. Administration of 25(OH)D-3 increased serum 25(OH)D and urinary calcium but did not change serum PTH or serum 1,25(OK)(2)D in Asian Indians. In cultured skin fibroblasts, E-max and V-max of 25(OH)D-24-hydroxylase activity were significantly higher in Asian Indians. In summary, in Asian Indians serum vitamin D and 25(OH)D are markedly reduced, altered vitamin D metabolism is only partially reversed by 25(OH)D-3, and 25(OH)D-24-hydroxylase activity in cultured skin fibroblasts is markedly increased. Thus, Asian Indians residing in the U.S. are at risk for developing vitamin D deficiency, rickets, and osteomalacia. C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29401 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Bell, NH (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NCRR NIH HHS [MO1 RR0170]; NIAMS NIH HHS [R01 AR 36066]; NIDDK NIH HHS [DK 25409, R01 DK025409] NR 39 TC 100 Z9 102 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 1998 VL 83 IS 1 BP 169 EP 173 DI 10.1210/jc.83.1.169 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YP375 UT WOS:000071270600031 PM 9435436 ER PT J AU Lavoie, HB Martin, KA Taylor, AE Crowley, WF Hall, JE AF Lavoie, HB Martin, KA Taylor, AE Crowley, WF Hall, JE TI Exaggerated free alpha-subunit levels during pulsatile gonadotropin-releasing hormone replacement in women with idiopathic hypogonadotropic hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GNRH-DEFICIENT MEN; LUTEINIZING-HORMONE; GLYCOPROTEIN HORMONES; BETA-SUBUNIT; DIFFERENTIAL REGULATION; POSTMENOPAUSAL WOMEN; PITUITARY SECRETION; NEUROPEPTIDE-Y; EXPRESSION AB The goals of this study were to determine whether women with idiopathic hypogonadotropic hypogonadism (IHH) respond to pulsatile GnRH replacement therapy with exaggerated glycoprotein free cu-subunit (FAS) levels, as reported in GnRH-deficient men, and to determine whether this pattern is unique to congenital GnRH deficiency or is also characteristic of patients with hypogonadotropic hypogonadism caused by other factors. GnRH was administered iv at a physiologic frequency and dose (75-100 ng/kg.bolus) to women with IHH (n = 11; n = 6 with anosmia); acquired GnRH deficiency secondary to treatment for cranial tumors (AHH; n = 7); and secondary hypothalamic amenorrhea (HA; n = 8). Results were compared with 24 normal cycling women. Gonadotropins, sex steroids, and FAS levels were measured in samples drawn daily across induced or normal menstrual cycles in patients or normal women, respectively. Samples were drawn at the same time of day and were collected 45 min after a GnRH bolus in patients. All women ovulated in response to pulsatile GnRH. There were no differences in the patterns of LH or gonadal steroid secretion between any of the patient groups (IHH, AHH, and HA). The patterns of LH and FSH secretion in the induced patient cycles were not different from normal women, with the exception of lower midcycle FSH levels in IHH women (P < 0.002). However, the daily dynamic secretion of FAS was exaggerated in IHH (compared with AHH, HA, and normal) women (P < 0.002). The increase in FAS levels in IHH was dependent on cycle stage, with the greatest difference observed during the early (P < 0.005) and midfollicular phase (P < 0.05) and the early luteal phase (P < 0.05). There was no difference in FAS between groups during the late follicular phase, at the midcycle, or in the midluteal and late luteal phase. This exaggerated FAS response to GnRH replacement in IHH was demonstrated in repeat cycles in two patients. Conclusions are: 1) Women with IHH respond to pulsatile GnRH replacement with an exaggerated secretion of FAS, which seems to be modified by gonadal factors; 2) this exaggerated FAS response, which is similar to that seen in GnRH-deficient men, is unique to congenital GnRH deficiency, and it is not observed in patients with acquired or secondary hypogonadotropic hypogonadism, suggesting that IHH patients may be missing a factor, in addition to GnRH, which normally restrains FAS secretion; and 3) the FAS response may prove to be a useful marker to distinguish constitutional delay of puberty from congenital GnRH deficiency. C1 Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Dept Med, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. FU NICHD NIH HHS [R01-HD-15080, U54-HD-29164, R01 HD015788, P30 HD-28138, T32 HD007396, P30 HD028138] NR 48 TC 14 Z9 14 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 1998 VL 83 IS 1 BP 241 EP 247 DI 10.1210/jc.83.1.241 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YP375 UT WOS:000071270600045 PM 9435449 ER PT J AU Kimmel, SE Sekeres, MA Berlin, JA Goldberg, LR Strom, BL AF Kimmel, SE Sekeres, MA Berlin, JA Goldberg, LR Strom, BL TI Adverse events after protamine administration in patients undergoing cardiopulmonary bypass: Risks and predictors of under-reporting SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 11th International Conference on Pharmacoepidemiology CY AUG 20, 1995 CL MONTREAL, CANADA DE adverse drug reaction reporting systems; pharmacoepidemiology; cohort studies; risk factors; cardiopulmonary bypass; protamines ID DRUG-REACTIONS; SULFATE; SURGERY; SURVEILLANCE; HEPARIN AB A retrospective cohort study of patients undergoing cardiopulmonary bypass over 2 years at a single hospital was performed to determine the rate and predictors of attributing events to protamine and reporting them to a well-developed, hospital-based adverse drug reaction (ADR) program. Overall, 123 (12.9%) of 952 procedures were associated with an adverse event. Thirteen percent of these events were attributed to protamine in the medical record and 2.4% were reported to the ADR program. Only 19% of events attributed to protamine were reported. Even after excluding events with other measurable etiologies, the incidence of adverse events (2.6%) was still higher than that of attributed (0.8%) or reported (0.3%) events. Events that manifest as pulmonary hypertension occurred sooner after protamine, or were severe were significantly more Likely to be attributed to protamine. These predictors demonstrated similar relationships with the probability of reporting events. Reliance on reporting of adverse events could not only underestimate the risk of these events, but might bias studies by identifying non-representative events. (C) 1998 Elsevier Science Inc. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. RP Kimmel, SE (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 717 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [K08-HL03021] NR 27 TC 29 Z9 31 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JAN PY 1998 VL 51 IS 1 BP 1 EP 10 DI 10.1016/S0895-4356(97)00241-2 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YP005 UT WOS:000071231700001 PM 9467629 ER PT J AU Kim, JB Sarraf, P Wright, M Yao, KM Mueller, E Solanes, G Lowell, BB Spiegelman, BM AF Kim, JB Sarraf, P Wright, M Yao, KM Mueller, E Solanes, G Lowell, BB Spiegelman, BM TI Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ADD1/SREBP1; fatty acid synthetase; leptin; nutritional changes; insulin ID LEUCINE ZIPPER PROTEIN; NECROSIS-FACTOR-ALPHA; MOUSE OBESE GENE; ENHANCER-BINDING; GLUCOCORTICOID RECEPTOR; HORMONAL-REGULATION; 3T3-L1 CELLS; DNA-BINDING; TRANSCRIPTION; PROMOTER AB The ability to regulate specific genes of energy metabolism in response to fasting and feeding is an important adaptation allowing survival of intermittent food supplies. However, little is known about transcription factors involved in such responses in higher organisms. We show here that gene expression in adipose tissue for adipocyte determination differentiation dependent factor (ADD) 1/sterol regulatory element binding protein (SREBP) 1, a basic-helix-loop-helix protein that has a dual DNA-binding specificity, is reduced dramatically upon fasting and elevated upon refeeding; this parallels closely the regulation of two adipose cell genes that are crucial in energy homeostasis, fatty acid synthetase (FAS) and leptin. This elevation of ADD1/SREBP1, leptin, and FAS that is induced by feeding in vivo is mimicked by exposure of cultured adipocytes to insulin, the classic hormone of the fed state, We also show that the promoters for both leptin and FAS are transactivated by ADD1/SREBP1, A mutation in the basic domain of ADD1/SREBP1 that allows E-box binding but destroys sterol regulatory element-1 binding prevents leptin gene transactivation but has no effect on the increase in FAS promoter function. Molecular dissection of the FAS promoter shows that most if not all of this action of ADD1/SREBP1 is through an E-box motif at -64 to -59, contained with a sequence identified previously as the major insulin response element of this gene, These results indicate that ADD1/SREBP1 is a key transcription factor linking changes in nutritional status and insulin levels to the expression of certain genes that regulate systemic energy metabolism. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Yao, Kwok Ming/C-4457-2009 FU NIDDK NIH HHS [5-R37-DK-31405] NR 39 TC 488 Z9 504 U1 2 U2 25 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 1 PY 1998 VL 101 IS 1 BP 1 EP 9 DI 10.1172/JCI1411 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YQ513 UT WOS:000071395300001 PM 9421459 ER PT J AU Revankar, SG Kirkpatrick, WR McAtee, RK Fothergill, AW Redding, SW Rinaldi, MG Patterson, TF AF Revankar, SG Kirkpatrick, WR McAtee, RK Fothergill, AW Redding, SW Rinaldi, MG Patterson, TF TI Interpretation of trailing endpoints in antifungal susceptibility testing by the national committee for clinical laboratory standards method SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CANDIDA-ALBICANS; CHROMOGENIC AGAR; FLUCONAZOLE; RESISTANCE AB Trailing endpoints remain a problem in antifungal susceptibility testing using the National Committee for Clinical Laboratory Standards (NCCLS) method, For isolates for which trailing endpoints are found, MICs of less than or equal to 1 mu g/ml at 24 h and of >64 mu g/ml at 48 h are usually observed. In a study of human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis, we identified three patients with multiple serial isolates for which trailing endpoints were observed,vith fluconazole. At 24 h, MICs were generally less than or equal to 1 mu g/ml by both broth macro-and microdilution methods, However, at 48 h, MICs were >64 mu g/ml, while the organism remained Susceptible by agar dilution testing with fluconazole, Most episodes of oropharyngeal candidiasis with trailing-endpoint isolates responded to doses of fluconazole as low as 100 mg/day. Two patients had both susceptible and trailing-endpoint isolates by NCCLS broth macro-and microdilution testing; these isolates were found to be the same strain by pulsed-field gel electrophoresis using restriction fragment length polymorphisms, Another patient had two different strains, one for which trailing endpoints were observed and one which was susceptible at 48 h, Trailing endpoints may be seen,vith selected isolates of a strain or may be a characteristic finding for most or all isolates of a strain, In addition, with isolates for which trailing endpoints are observed, reading the endpoint for the NCCLS method at 24 h may be more appropriate. C1 Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Revankar, SG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCRR NIH HHS [M01 RR001346, MO1-RR-01346]; NIDCR NIH HHS [1 RO1 DE11381-01, R01 DE011381] NR 15 TC 74 Z9 79 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 1998 VL 36 IS 1 BP 153 EP 156 PG 4 WC Microbiology SC Microbiology GA YM068 UT WOS:000071024700031 PM 9431939 ER PT J AU Freedman, AS Neuberg, D Gribben, JG Mauch, P Soiffer, RJ Fisher, DC Anderson, KC Andersen, N Schlossman, R Kroon, M Ritz, J Aster, J Nadler, LM AF Freedman, AS Neuberg, D Gribben, JG Mauch, P Soiffer, RJ Fisher, DC Anderson, KC Andersen, N Schlossman, R Kroon, M Ritz, J Aster, J Nadler, LM TI High-dose chemoradiotherapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation in mantle-cell lymphoma: No evidence for long-term remission SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; POLYMERASE CHAIN-REACTION; INTERMEDIATE LYMPHOCYTIC LYMPHOMA; ZONE LYMPHOMA; CENTROCYTIC LYMPHOMA; BCL-2 TRANSLOCATION; RESIDUAL CELLS; THERAPY; PROGNOSIS; RELAPSE AB Purpose: The role for high-dose therapy and autologous stem-cell transplantation in mantle-cell lymphoma (MCL) is unknown. We retrospectively analyzed patients with chemosensitive disease who underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) for MCL in first remission, as well as following relapse from conventional therapy. Patients and Methods: Between August 1985 and April 1996, 28 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total-body irradiation (TBI) and a bone marrow-purging regimen. Re-review of original tissue demonstrated that all patients had morphologic, phenotypic, and genotypic characteristics of MCL. MCL was the original diagnosis in 21 patients, whereas seven patients had a prior diagnosis of diffuse small cleaved-cell lymphoma. Results: Twenty patients received multiple regimens before ABMT, while eight underwent ABMT in first complete remission (CR)/partial remission (PR) Following CHOP induction. At bone marrow harvest, only 18% of patients were in CR and overt BM infiltration wets present in 57%. Following cyclophosphamide/TBI, no treatment-related deaths were seen. Nineteen of 28 patients have relapsed at a median time of 21 months(range, 3 to 70). Of eight patients transplanted in first CR/PR, five have relapsed. Nine patients are in continuous CR with a median follow-up time of 24 months (range, 10 to 135). Disease-free survival (DFS) and overall survival (OS) are estimated to be 31% and 62% at 4 years, respectively. Conclusion: ABMT using cyclophosphamide/TBI conditioning may at best be effective in only a small fraction of patients with relapsed MCL. The lack of plateau with a median follow-up time of 24 months suggests cure may not be achievable. The role of this therapy in patients in first remission requires more study using better induction therapy to enhance the CR rate before ABMT. (C) 1998 by American Society of Clinical Oncology. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol Malignancies & Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Freedman, AS (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996] NR 43 TC 139 Z9 139 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 13 EP 18 PG 6 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500004 PM 9440717 ER PT J AU Glick, JH Young, ML Harrington, D Schilsky, RL Beck, T Neiman, R Fisher, RI Peterson, BA Oken, MM AF Glick, JH Young, ML Harrington, D Schilsky, RL Beck, T Neiman, R Fisher, RI Peterson, BA Oken, MM TI MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: The 8-year results of the Intergroup trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMBINATION CHEMOTHERAPY; ABVD AB Purpose: To compare the efficacy of sequential mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) followed by doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus the MOPP/ABV hybrid regimen in advanced-stage Hodgkin's disease. Patients and Methods: A total of 737 patients with previously untreated stages III(2)A, IIIB, IVA, or IVB Hodgkin's disease and patients in first. relapse after radiotherapy were prospectively randomized to sequential MOPP-ABV or MOPP/ABV hybrid. Of 691 eligible patients, 344 received the sequential regimen and 347 received the hybrid. Results: The overall response rate was 95%, with complete responses (CRs) in 79%: 83% on the MOPP/ABV hybrid and 75% on the sequential MOPP-ABVD arm (P = .02). With a median follow-up time of 7.3 years, the 8-year failure-free survival (FFS) rates were 64% for MOPP/ABV hybrid and 54% for sequential MOPP-ABVD (P = .01;0.69 relative risk of failure, comparing MOPP/ABV hybrid v MOPP-ABVD). The 8-year overall survival rate was significantly better for the MOPP/ABV hybrid (79%) as compared with sequential MOPP-ABVD (71%) (P = .02; relative risk, 0.65). MOPP/ABV hybrid had significantly more life-threatening or fatal neutropenia and pulmonary toxicity than the sequential MOPP-ABVD arm, which was associated with significantly greater thrombocytopenia. Nine cases of acute myelogenous leukemia or myelodysplasia were reported on the sequential regimen as compared with only one on the hybrid (P = .01). Conclusion: MOPP/ABV hybrid chemotherapy was significantly more effective than sequential MOPP-ABVD, FFS and overall survival were significantly improved on the hybrid arm, which was also associated with a lower incidence of acute leukemia or myelodysplasia. (C) 1998 by American Society of Clinical Oncology. C1 Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Med Ctr, Maywood, IL USA. Mt States Tumor Inst, Boise, ID USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Univ Minnesota, Minneapolis, MN USA. Virginia Piper Canc Inst, Minneapolis, MN USA. RP Glick, JH (reprint author), Univ Penn, Ctr Canc, 3400 Spruce St,6 Penn Tower, Philadelphia, PA 19104 USA. EM glickjh@mail.med.upenn.edu FU NCI NIH HHS [CA23318, CA31936, CA15488] NR 20 TC 67 Z9 70 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 19 EP 26 PG 8 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500005 PM 9440718 ER PT J AU Guadagnoli, E Weeks, JC Shapiro, CL Gurwitz, JH Borbas, C Soumerai, SB AF Guadagnoli, E Weeks, JC Shapiro, CL Gurwitz, JH Borbas, C Soumerai, SB TI Use of breast-conserving surgery for treatment of stage I and stage II breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GEOGRAPHIC-VARIATION; RADIATION-THERAPY; MASTECTOMY AB Purpose: To assess the use of breast-conserving surgery in two states reported to differ with respect to surgical treatment of breast cancer. Methods: A retrospective cohort study based on data collected from medical records and patients was performed among 1,514 patients diagnosed with early-stage breast cancer in Massachusetts and 1,061 patients in Minnesota. Patients were identified at 18 randomly selected hospitals in Massachusetts and at 30 hospitals in Minnesota. The rate of breast-conserving surgery in both states and the correlates of breast-conserving surgery among women eligible for the procedure were determined. Results: The rate of breast-conserving surgery in both states was much higher than previously reported, Among those eligible for the procedure, nearly 75% underwent breast-conserving surgery in Massachusetts and nearly half did so in Minnesota. Significantly (P < .003) more women who underwent mastectomy in Minnesota (27%) than in Massachusetts (15%) reported that their surgeon did not discuss breast-conserving surgery with them. Among women who underwent mastectomy and who reported being informed of both surgical alternatives, more women (P < .001) in Minnesota (74%) than in Massachusetts (62%) said they ultimately chose mastectomy because their surgeon recommended it. In Massachusetts, women treated at teaching hospitals were twice as likely as other women to undergo breast-conserving surgery. In Minnesota, women over age 70 and those who lived in rural areas were less likely than other women to undergo breast-conserving surgery. Conclusion: Although the rate of breast-conserving surgery in each state was higher than expected based on earlier reports, the rates differed considerably between states. Additional studies are needed to determine whether variation in practice between geographic areas is due to differences in patients' preferences and values or to surgeons' propensity for one type of surgery based on where they practice. (C) 1998 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Meyers Primary Care Inst, Worcester, MA USA. Healthcare Educ & Res Fdn Inc, St Paul, MN USA. RP Guadagnoli, E (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM guadagnoli@hcp.med.harvard.edu FU NCI NIH HHS [CA57755, CA59408]; NIA NIH HHS [K08 AG00510] NR 22 TC 75 Z9 79 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 101 EP 106 PG 6 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500016 PM 9440729 ER PT J AU Audrain, J Rimer, B Cella, D Garber, J Peshkin, BN Ellis, J Schildkraut, J Stefanek, M Vogel, V Lerman, C AF Audrain, J Rimer, B Cella, D Garber, J Peshkin, BN Ellis, J Schildkraut, J Stefanek, M Vogel, V Lerman, C TI Genetic counseling and testing for breast-ovarian cancer susceptibility: What do women want? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEREDITARY BREAST; FAMILIES; RISK AB Purpose: To assess preferences for the content and process of genetic counseling and testing for breast-ovarian cancer susceptibility among women at high risk for breast cancer. Methods: Ninety-eight healthy women who had a family history of breast cancer in at least two first-degree relatives participated in a structured telephone survey that evaluated preferences for type of provider and the content and process of pretest education and posttest genetic counseling. Results: Forty-two percent of women preferred that pretest education be delivered by a genetic counselor, while 22% preferred an oncologist. This preference was positively associated with a desire to discuss psychosocial issues during the session (P = .001), For posttest counseling, 38% of women preferred an oncologist, while 20% preferred a genetic counselor. However, women who desired supportive counseling during this session were significantly more likely to prefer a genetic counselor to an oncologist (P = .02). Fewer women wished to see a primary care physician or gynecologist for pretest education (11%) or posttest counseling (22%). With regard to the counseling process, 82% of women wished to self-refer for genetic counseling, but 63% desired advice and recommendations about whether to be tested. Conclusion: When feasible, the optimal approach may be for oncologists to work with genetic counselors to provide pretest education and medical recommendations, Elicitation of patients' preferences may be useful to determine the level of counseling services needed. (C) 1998 by American Society of Clinical Oncology. C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Breast Canc Fdn, Richmond, VA USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Lerman, C (reprint author), Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, 2233 Wisconsin Ave NW,Suite 535, Washington, DC 20007 USA. EM LermanC@GUNET.georgetown.edu FU NCI NIH HHS [CA63605] NR 27 TC 51 Z9 51 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 133 EP 138 PG 6 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500021 PM 9440734 ER PT J AU Talcott, JA Rieker, P Clark, JA Propert, KJ Weeks, JC Beard, CJ Wishnow, KI Kaplan, I Loughlin, KR Richie, JP Kantoff, PW AF Talcott, JA Rieker, P Clark, JA Propert, KJ Weeks, JC Beard, CJ Wishnow, KI Kaplan, I Loughlin, KR Richie, JP Kantoff, PW TI Patient-reported symptoms after primary therapy for early prostate cancer: Results of a prospective cohort study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; SEXUAL FUNCTION; URINARY CONTINENCE; OUTCOMES; COMPLICATIONS; PRESERVATION; PATTERNS; DISEASE AB Purpose: reassess complications of therapy for early (nonmetastatic) prostate cancer. Patients and Methods: A prospective study of a cohort sought treatment advice and completed required pretreatment forms. The measures were self-reported patient symptoms and other measures of quality of life before therapy and at 3 and 12 months afterward. Results: Bowel and bladder symptoms were uncommon pretreatment. Patients frequently reported irritative bowel and bladder symptoms at 3 months after radiotherapy, although these subsided somewhat at 12 months. Substantial ("a lot") urinary incontinence and wearing of absorptive pads were reported by 11% and 35% at 12 months after surgery and varied little by age. Incontinence occurred after radiotherapy infrequently, and only in men more than 65 years old. inadequate erections, present in one third of men pretreatment, were nearly universal at 3 months after surgery, although some improvement, primarily in men under 65 years of age, was evident at 12 months. Sexual dysfunction offer radiotherapy increased less but continually through 12 months, suggesting that observed treatment-related differences would decline with further follow-up. Conclusion: External-beam radiotherapy of early prostate cancer is followed by bowel and bladder irritability, by increasingly severe sexual dysfunction and, in men aged more than 65 years, occasional urinary incontinence. Greater sexual dysfunction and urinary incontinence occur in the year following radical prostatectomy. These postsurgical complication rates from patient questionnaires are greater than have been reported in other treatment series and confirm the results of two retrospective studies of patient-reported complications. (C) 1998 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. New England Deaconess Hosp, Boston, MA 02215 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes REs, B75 230,, Boston, MA 02114 USA. FU AHRQ HHS [HS08208, HS06824] NR 29 TC 213 Z9 215 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 275 EP 283 PG 9 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500040 PM 9440753 ER PT J AU Hoffman, JP Lipsitz, S Pisansky, T Weese, JL Solin, L Benson, AB AF Hoffman, JP Lipsitz, S Pisansky, T Weese, JL Solin, L Benson, AB TI Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: An eastern cooperative oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVAL; DUCTAL ADENOCARCINOMA; COMPUTED-TOMOGRAPHY; CANCER; PANCREATICODUODENECTOMY; RESECTION; CHEMORADIOTHERAPY; CHEMORADIATION; HEAD AB Purpose: A prospective, multiinstitutional trial was initiated in 1991 to examine the tolerance to and efficacy of a program of preoperative chemorcadiotherapy (CTRT) and surgical resection for patients with localized adenocarcinoma of the pancreas. Patients and Methods: Fifty-three patients were assessable for analysis, with a median follow-up of 52 months for survivors. Radiation therapy (RT) totaling 5,040 cGy in 180 cGy fractions with mitomycin 10 mg/m(2) day 2 and fluorouracil (5-FU) 1,000 mg/m(2)/d continuous infusion days 2 through 5 and 29 through 32 were given as preoperative adjuvant therapy Twelve patients did not proceed to surgery (one death, one toxicity, three local progression, six distant metastases, one intercurrent illness), whereas 41 patients underwent surgery. Of these, 17 patients did not have resection (11, hepatic and/or peritoneal metastases and six local extension that precluded resection). Twenty-four patients had tumor resection (19 Whipple, four total pancreatectomy, one distal pancreatectomy). Results: Treatment toxicity was primarily hematologic, although a comparable number suffered biliary tract complications, either from obstruction or cholangitis as a result of an occluded stent or the primary tumor. there was one postoperative death. Median survival for the entire group and for the 24 patients with resection was 9.7 and 15.7 months. This survival rate reflected the advanced state of most resected cancers (positive peritoneal cytology, three patients; margins within 2 mm, 13 patients; involved lymph nodes, four patients; and need for superior mesenteric vein (SMV) resection, four patients). tumor progression was most frequent at metastatic sites. Conclusion: This preoperative CTRT protocol was feasible and safe in a cooperative group setting. Entry of patients with advanced tumors probably accounted for the suboptimal resectability and survival results. (C) 1998 by American Society of Clinical Oncology. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Penn, Grad Hosp, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. RP Hoffman, JP (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [CA 18281, CA13650, CA23318] NR 21 TC 230 Z9 238 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 317 EP 323 PG 7 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500046 PM 9440759 ER PT J AU Alani, RM Munger, K AF Alani, RM Munger, K TI Human papillomaviruses and associated malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARCINOMA CELL-LINES; RETINOBLASTOMA PROTEIN; HUMAN KERATINOCYTES; EPITHELIAL-CELLS; ADENOVIRUS E1A; GENE-PRODUCT; LARGE-T; TYPE-16; E7; TRANSFORMATION AB The human papillomaviruses (HPVs) are smell DNA tumor viruses that infect epithelial cells and induce proliferative lesions, Substantial epidemiologic data along with in vitro and in vivo studies have led to the implication of particular HPVs with the development of epithelial malignancies. Greater than 90% of all cervical carcinomas are positive for HPV infection, Most of these lesions are caused by infection with mucosal-associated high-risk HPV subtypes, Much work has been undertaken in basic science laboratories to determine the molecular basis for HPV-associated malignancies, Although many significant advances have been made in understanding the biologic properties of these viruses using in vitro analyses, the field has been greatly hindered until recently by the inability to propagate the virus in culture, In this review, we discuss the basic biologic properties of HPVs and the current understanding of the mechanisms of cellular transformation by malignancy-associated viral subtypes, We place particular emphasis on discussion of the HPV oncogenes, E6 and E7, We also discuss premalignant and malignant disorders of squamous and mucosal epithelia, which have been associated with HPV infections, and the current understanding of the mechanism of HPV-associated carcinogenesis in these settings. We focus these discussions on cervical carcinogenesis and briefly review the particulars regarding HPV-associated malignancies in normal and immunocompromised hosts. We end with a discussion of potential targeted molecular therapies for HPV-associated malignancies that may result from the current knowledge of HPV-related cellular growth dysregulation and carcinogenesis. (C) 1998 by American Society of Clinic Oncology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Munger, K (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave,Goldenson Bldg,Room 113, Boston, MA 02115 USA. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA66980]; NIAMS NIH HHS [K08 AR01975-01A1, T32 AR07098-21] NR 52 TC 132 Z9 151 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 330 EP 337 PG 8 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500048 PM 9440761 ER PT J AU Emanuel, EJ Paterson, WB Hellman, S AF Emanuel, EJ Paterson, WB Hellman, S TI Ethics of randomized clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PATIENT C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Emanuel, EJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 21 Z9 21 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1998 VL 16 IS 1 BP 365 EP 371 PG 7 WC Oncology SC Oncology GA YQ270 UT WOS:000071368500053 PM 9440766 ER PT J AU Meltzer, HY Casey, DE Garver, DL Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Measuring outcome in schizophrenia: Differences among the atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID DOUBLE-BLIND; OLANZAPINE TRIAL; RISPERIDONE; PLACEBO; HALOPERIDOL; CLOZAPINE; QUALITY; SCALE; LIFE; MULTICENTER AB The advent of the atypical antipsychotics marked a new era in the history of the treatment of psychotic disorders. To evaluate the published literature about the available atypical antipsychotics-clozapine, risperidone, olanzapine, and quetiapine-and select the most appropriate treatment for specific patients, physicians need to understand the outcome measures used in clinical studies, the pharmacologic differences that explain varying side effect profiles, and pharmacoeconomic assessments that are used in the decision-making process. While the atypical antipsychotics have established efficacy in the overall treatment of schizophrenia, they may differ in their effects on factors such as cognitive function, overall quality of life, adverse events, and hospitalization status. Each of these factors should be considered when weighing treatment options for an individual patient. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 40 TC 35 Z9 36 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 3 EP 9 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700001 ER PT J AU Rosenbaum, JE AF Rosenbaum, JE TI Depression and its subtypes: A treatment update SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Outpatient Psychiat Div, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenbaum, JE (reprint author), Massachusetts Gen Hosp, Outpatient Psychiat Div, Clin Psychopharmacol Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 18 BP 3 EP 4 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 140BP UT WOS:000077067100001 PM 9840191 ER PT J AU Biederman, J AF Biederman, J TI Attention-deficit/hyperactivity disorder: A life-span perspective SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Current Issues in Attention Deficit Disorders CY NOV 13, 1996 CL BLOOMINGDALE, ILLINOIS SP Inst Med Studies, Wyeth Ayerst Labs ID DEFICIT-HYPERACTIVITY DISORDER; MINIMAL BRAIN-DYSFUNCTION; LA-TOURETTES SYNDROME; AGGRESSIVE NONCOMPLIANT FEATURES; NATIONAL-COMORBIDITY-SURVEY; NERVOUS-SYSTEM STIMULANTS; MOTHER CHILD INTERACTIONS; 15-YEAR FOLLOW-UP; DOUBLE-BLIND; PSYCHIATRIC STATUS AB There is increasing scientific recognition that attention-deficit/hyperactivity disorder (ADHD), a heterogeneous disorder that carries a high risk of comorbidity, continues past childhood and adolescence into adulthood in many cases and may be underidentified in girls. The etiology of ADHD is unknown, although evidence from family studies of ADHD suggests a genetic origin for some forms of this disorder. A variety of pharmacologic agents are available in treating ADHD: stimulant medications remain the first-line treatment for noncomorbid ADHD, whereas tricyclic antidepressants and bupropion are recommended for stimulant nonresponders and patients with more than one psychiatric disorder. Complex cases of ADHD, however, may require rational use of combined pharmacotherapy. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. NR 211 TC 152 Z9 158 U1 3 U2 13 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 7 BP 4 EP 16 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZY498 UT WOS:000074627800002 PM 9680048 ER PT J AU Cummings, JL AF Cummings, JL TI Alzheimer's disease management - Introduction SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID PREVALENCE C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Neurobehav & Neuropsychiat Program, Los Angeles, CA 90073 USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 13 BP 4 EP 5 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120VJ UT WOS:000075977800001 PM 9771824 ER PT J AU Small, GW Leiter, F AF Small, GW Leiter, F TI Neuroimaging for diagnosis of dementia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; E TYPE-4 ALLELE; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; EPSILON-4 ALLELE; DEPRESSION; RISK; LIFE AB Although many clinicians consider neuroimaging studies as optional for the differential diagnosis of dementia, clinical experience suggests that they can improve diagnostic accuracy. Data are limited, however, on sensitivity, specificity, and cost-effectiveness of various neuroimaging techniques. The author reviews advantages and disadvantages of neuroimaging techniques for the differential diagnosis of dementia and describes strategies used for early detection of Alzheimer's disease, including combining positron emission tomography scanning with genetic risk assessment. Such approaches could provide a means for in vivo therapeutic monitoring of brain function during experimental antidementia treatment trials. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Aging, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Small, GW (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIA NIH HHS [1T32 AG00245, 1RO1 AG13308]; NIMH NIH HHS [1RO1 MH52453] NR 32 TC 24 Z9 26 U1 2 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 11 BP 4 EP 7 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 115LE UT WOS:000075665700002 PM 9731543 ER PT J AU Nierenberg, AA Alpert, JE Pava, J Rosenbaum, JF Fava, M AF Nierenberg, AA Alpert, JE Pava, J Rosenbaum, JF Fava, M TI Course and treatment of atypical depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Depression and its Subtypes - A Treatment Update, at the Annual Meeting of the American-Psychiatric-Association CY MAY 18, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID ANTIDEPRESSANT DRUGS; MAJOR DEPRESSION; BIPOLAR; PHENELZINE; UNIPOLAR; DISORDER; EPISODES; SUBTYPES; PLACEBO AB Atypical depression is the most common form of depression in outpatients, but compared with melancholia, Little is known about its comorbidity, course, and treatment. Beyond the well-characterized constellation of symptoms that define atypical depression (mood reactivity, hypersomnia, leaden paralysis, hyperphagia, and rejection sensitivity), specific Axis I and II comorbid conditions may differentiate atypical from other depressed patients. Similarly, age at onset, duration of episodes, frequency of relapses and recurrences, and frequency of complete remission in atypical depression may be different. It has not even been established If atypical depression is a stable subtype or if it is just one of several forms of depression that an individual may express during a lifetime of recurrent depressions. Monoamine oxidase inhibitors (MAOIs) are superior to tricyclic antidepressants (TCAs) for the treatment of atypical depression, but few studies have compared MAOIs to the newer generation of antidepressants (SSRIs, bupropion, venlafaxine, nefazodone, and mirtazapine). Because of the favorable benefit/risk ratio, clinicians tend to use these newer antidepressants for all outpatients, including those with atypical depression, even though the literature is limited. A review and critique of the relevant literature on atypical depression will be presented. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 34 TC 84 Z9 86 U1 2 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 18 BP 5 EP 9 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 140BP UT WOS:000077067100002 PM 9840192 ER PT J AU Glazer, WM Dickson, RA AF Glazer, WM Dickson, RA TI Clozapine reduces violence and persistent aggression in schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PSYCHIATRIC-INPATIENTS; BEHAVIOR; SECLUSION; PREDICTION; RESTRAINT; HOSPITALIZATION; COMMUNITY; DISORDER; BRAIN AB Violence and persistent aggression are serious problems in the general population and among certain psychiatric patients. Violence and persistent aggression have been associated with suicidal ideation and substance abuse, characteristics of chronically ill, and in many instances, treatment-resistant schizophrenia individuals. Assessment of dangerousness in psychiatric patients involves evaluation of sociodemographic and clinical factors. A substantial number of neurologic and psychiatric disorders are associated with pathologic anger and aggression; of these, the association between schizophrenia and violence/aggression is the best described. Neurotransmitters that have been implicated in aggressive and violent behavior include serotonin, norepinephrine, and dopamine. Current pharmacotherapy of pathologic aggression involves the use of multiple agents on a trial-and-error basis, with varying degrees of response. Unfortunately, this approach subjects patients to numerous side effects, including the extrapyramidal symptoms associated with the use of conventional antipsychotics. This paper will review evidence for the efficacy of clozapine in the treatment of aggression and violence in the treatment-refractory patient. The reduction in violence and persistent aggression with clozapine treatment should improve the chances for integration of the schizophrenia patient into the community and provide cost savings to society. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calgary, Dept Psychiat, Calgary, AB T2N 1N4, Canada. RP Glazer, WM (reprint author), 100 Beach Plum Lane, Menemsha, MA 02552 USA. NR 68 TC 64 Z9 65 U1 3 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 3 BP 8 EP 14 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE878 UT WOS:000072840700002 PM 9541332 ER PT J AU Raskind, MA AF Raskind, MA TI The clinical interface of depression and dementia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Late Life Depression - Complex Problems, New Strategies CY MAY 20, 1997 CL SAN DIEGO, CALIFORNIA ID ALZHEIMERS-DISEASE; TRIAL AB The interface between depression and dementia is complex and has been studied primarily in Alzheimer's disease. This article discusses several aspects of this intriguing area of clinical research, including depressive pseudodementia and the possibility that depression may be a risk factor for the expression of Alzheimer's disease in later life and that depression may occur as a prodrome for this most common dementing disorder. In addition, the treatment challenges faced by clinicians when depression complicates the course of Alzheimer's disease are addressed. It is likely that a combination of behavioral treatment and use of antidepressant medication will, provide the optimal management of depression in Alzheimer's disease. C1 VA Puget Sound Hlth Care Syst, Mental Hlth Serv 116, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv 116, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 22 TC 30 Z9 32 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 10 BP 9 EP 12 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 111NF UT WOS:000075443400003 PM 9720476 ER PT J AU Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Clinical development of atypical antipsychotics: Research design and evaluation SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID BLIND OLANZAPINE TRIAL; SCHIZOPHRENIC-PATIENTS; PARALLEL-GROUP; HALOPERIDOL; PLACEBO; RISPERIDONE; MULTICENTER; QUETIAPINE; CHLORPROMAZINE; CLOZAPINE AB Clinical trials support the efficacy and safety of new drugs on the market. They provide the United States Food and Drug Administration with the information needed to approve an Investigational New Drug application and are the basis for package inserts provided by the manufacturers that guide clinicians in the use of a new drug. Because clinical trials are vital to the effective and safe use of new drugs, it is important to understand who participates in them, what questions are answered by clinical trials, and what questions are raised. The reader who asks the proper questions about issues such as methodology, affiliations of the investigators, statistical analyses performed, location of study centers, and study populations will derive the most information from the report of a clinical trial. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 25 TC 0 Z9 0 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 10 EP 16 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700002 ER PT J AU Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Adverse effects of the atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID BLIND OLANZAPINE TRIAL; SCHIZOPHRENIC PATIENTS; CLOZAPINE; HALOPERIDOL; RISPERIDONE; PLACEBO; DRUGS; SERTINDOLE; DOPAMINE; MULTICENTER AB Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely-to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 57 TC 5 Z9 8 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 17 EP 22 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700003 ER PT J AU Cohen, LS Rosenbaum, JF AF Cohen, LS Rosenbaum, JF TI Psychotropic drug use during pregnancy: Weighing the risks SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposia on Managed Care and Depression - Can Quality Be Assured/Mood and Anxiety - Disorders in the Childbearing Years CY MAY 05, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID MATERNAL DEPRESSIVE SYMPTOMS; PANIC DISORDER; ORAL CLEFTS; PRENATAL EXPOSURE; ANTIEPILEPTIC DRUGS; ELECTROCONVULSIVE-THERAPY; CONGENITAL-MALFORMATIONS; POSTPARTUM DEPRESSION; LITHIUM TREATMENT; BIPOLAR DISORDER AB Although psychotropic drugs have not been tested or approved by the Food and Drug administration for use during pregnancy, some women continue to take these medications while they are pregnant, particularly since mood and anxiety disorders cluster in women during childbearing years. The relative risks and benefits of drug therapy for these women must be weighed with each patient and treatment limited to those situations in which risks to mother and fetus from the disorder an presumed to exceed the risk of drug treatment. Risks of psychotropic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer term neurobehavioral sequelae. Of growing concern is the risk of untreated psychiatric disorder as it may potentially affect fetoplacental integrity and fetal central nervous system development. Coordination of care with the patient, her husband or partner, and the obstetrician is essential, as is careful medical record documentation when treating pregnant patients with psychiatric disorders. C1 Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. NR 190 TC 103 Z9 105 U1 3 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 18 EP 28 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200004 PM 9559756 ER PT J AU Fava, M AF Fava, M TI Depression with anger attacks SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Depression and its Subtypes - A Treatment Update, at the Annual Meeting of the American-Psychiatric-Association CY MAY 18, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID FLUOXETINE TREATMENT; UNIPOLAR DEPRESSION; AGGRESSION; HOSTILITY; DISORDERS; VIOLENCE; EFFICACY AB A number of phenomenologic studies have demonstrated the marked heterogeneity of unipolar depressive disorders. We have recently identified a subtype of depression characterized by the presence of irritability and anger attacks. These attacks are sudden spells of anger accompanied by symptoms of autonomic activation such as tachycardia, sweating, flushing, and tightness of the chest. They are experienced by depressed patients as uncharacteristic of them and inappropriate to the situations in which they occur. Approximately one third of depressed outpatients present with anger attacks. Patients with unipolar depression and anger attacks frequently experience significant anxiety and somatic symptoms, and are relatively more likely to meet criteria for avoidant, dependent, borderline, narcissistic, and antisocial personality disorders than depressed patients without these attacks. Anger attacks subside in 53% to 71% of depressed outpatients treated with antidepressants, and the degree of improvement in depressive symptoms after antidepressant treatment is comparable in depressed patients with and without anger attacks. In addition, the rate of emergence of anger attacks after treatment with antidepressants (6%-10%) appears to be lower than the rate with placebo (20%). Finally, antidepressants that affect serotonergic neurotransmission, known to be involved in the modulation of aggressive behavior in animals and humans, may be particularly effective in this subtype of depression, but further studies are needed to support this hypothesis. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 31 TC 59 Z9 61 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 18 BP 18 EP 22 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 140BP UT WOS:000077067100004 PM 9840194 ER PT J AU Marder, SR AF Marder, SR TI Facilitating compliance with antipsychotic medication SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SCHIZOPHRENIC-PATIENTS; SUBSTANCE-ABUSE; PSYCHIATRIC-SYMPTOMS; TARDIVE-DYSKINESIA; CLOZAPINE; RISPERIDONE; ADHERENCE; RELAPSE; IMPACT AB Noncompliance with medication is common among patients who have schizophrenia and is a leading cause of rehospitalization in this population. Both standard and subjective risk-factor assessments have been used to identify patients who are likely to refuse or discontinue treatment. Noncompliant patients who have schizophrenia commonly have been treated with potent D-2 dopamine-receptor antagonists and therefore may have experienced extrapyramidal side effects. The newer antipsychotics (i.e., serotonin-dopamine antagonists) are efficacious in reducing the symptoms of schizophrenia without associated dysphoria and motor side effects. Clozapine and other newer antipsychotics may improve certain aspects of cognition. The improved psychiatric state and cognitive function may facilitate "involved compliance" as a result of increased insight, awareness, and judgment. These cognitive faculties allow patients to appreciate their improved state and take steps to maintain it. The periodic visits for blood monitoring mandated for clozapine therapy also facilitate the formation of a therapeutic alliance that allows the clinician to monitor compliance. Facilitating involved compliance this way among patients who have schizophrenia may reduce the cost of this disorder to society. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Dept 116A, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Dept 116A, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 57 TC 75 Z9 78 U1 4 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 3 BP 21 EP 25 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE878 UT WOS:000072840700004 PM 9541334 ER PT J AU Peskind, ER AF Peskind, ER TI Pharmacologic approaches to cognitive deficits in Alzheimer's disease SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on New Strategies for Treating Alzheimer's Disease CY AUG 02, 1997 CL CHICAGO, ILLINOIS SP Bayer Corp ID ESTROGEN REPLACEMENT THERAPY; CONTROLLED TRIAL; DOUBLE-BLIND; CHOLINERGIC NEURONS; SELECTIVE LOSS; L-DEPRENYL; DEMENTIA; TACRINE; MEMORY; PHYSOSTIGMINE AB This article reviews placebo-controlled studies addressing drug efficacy for the cognitive deficits of Alzheimer's disease. Efforts to compensate for the presynaptic cholinergic deficiency in Alzheimer's disease by pharmacologically inhibiting acetylcholine degradation have been successful in several clinical trials. Two cholinesterase inhibitors are available for Alzheimer's disease, and others most likely will soon be available. Cholinesterase inhibitors represent the only therapy currently approved for the treatment of Alzheimer's disease. The antioxidant drugs alpha-tocopherol (vitamin E) and selegiline have been demonstrated marginally superior to placebo for slowing functional deterioration in patients with moderately advanced Alzheimer's disease. Epidemiologic studies suggest protective effects against Alzheimer's disease from postmenopausal estrogen replacement and nonsteroidal antiinflammatory drugs. Placebo-controlled studies prospectively evaluating the hypotheses generated by these epidemiologic studies are ongoing. C1 VA Puget Sound Hlth Care Syst, Mental Hlth Serv 116, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Mental Illness Res & Educ & Clin Ctr, MIRECC, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv 116, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 46 TC 22 Z9 22 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 9 BP 22 EP 27 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 113HP UT WOS:000075545200004 PM 9720483 ER PT J AU Cummings, JL Masterman, DL AF Cummings, JL Masterman, DL TI Assessment of treatment-associated changes in behavior and cholinergic therapy of neuropsychiatric symptoms in Alzheimer's disease SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Alzheimer's Disease Management - Algorithmic Strategies for Diagnosis and Treatment CY MAY 17, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID CONTROLLED TRIAL; RATING-SCALE; PSYCHIATRIC-SYMPTOMS; EXTRAPYRAMIDAL SIGNS; PRIMARY DEMENTIA; NURSING-HOMES; DOUBLE-BLIND; DELUSIONS; PSYCHOSIS; TACRINE AB Alzheimer's disease affects multiple domains of human brain function and has neuropsychological, neuropsychiatric, and neurologic manifestations. Behavioral changes should be assessed as part of a comprehensive evaluation of the effects of cholinergic treatment of Alzheimer's disease. The psychometric properties, origin, source of behavioral information, content, and administration requirements of tools used to assess behavior in Alzheimer's disease affect the type of information garnered and the conclusions that can be derived. Assessment of drug-related behavioral changes can be affected by spontaneous remission of neuropsychiatric symptoms, differing baseline severity of behavioral abnormalities, uncertain magnitude of expected treatment effects, and by the influence of disease stages, concurrent medications, and comorbid conditions. Cholinergic therapies ameliorate behavioral alteration in Alzheimer's disease, and changes in behavior should be monitored when such therapy is initiated. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Neurobehav & Neuropsychiat Program, Los Angeles, CA 90073 USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG10123] NR 80 TC 21 Z9 22 U1 4 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 13 BP 23 EP 30 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120VJ UT WOS:000075977800004 PM 9771827 ER PT J AU Glazer, WM AF Glazer, WM TI Formulary decisions and health economics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on the Routine Use of Atypical Antipsychotic Agents CY JUL 25, 1997 CL DALLAS, TEXAS SP Eli Lilly & Co ID QUALITY-OF-LIFE; NEUROLEPTIC-RESISTANT SCHIZOPHRENIA; CLOZAPINE; SCALE; HALOPERIDOL; REDUCTION; DISORDERS; COST AB Because of increasing concerns about health care costs, physicians must consider the cost-effectiveness of a treatment strategy, as well as its efficacy and safety. The question of whether the greater expense of a newer drug is justified over the cost of a generic drug deserves a comprehensive evaluation. The determination of effectiveness and tolerability of the newer antipsychotics should be expanded to include quality-of-life issues, reintegration of the patient into the community, resource utilization, and medical costs. There are clear indications that patients who take atypical antipsychotics utilize fewer medical resources than patients who take typical antipsychotics; however, the positive outcomes of the newer drugs must be translated into cost benefits if formularies are to be intelligently controlled. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Glazer, WM (reprint author), POB 121,Beach Plum Lane, Menemsha, MA 02552 USA. NR 31 TC 31 Z9 31 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 19 BP 23 EP 29 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 144JD UT WOS:000077310000005 PM 9847049 ER PT J AU Meltzer, HY Casey, DE Garver, DL Lasagna, S Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Lasagna, S Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Assessment of EPS and tardive dyskinesia in clinical trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID DOUBLE-BLIND; ANTIPSYCHOTIC-DRUGS; OLANZAPINE TRIAL; SCHIZOPHRENIA; HALOPERIDOL; RISPERIDONE; PLACEBO; CLOZAPINE; SYMPTOMS; MULTICENTER AB The incidence of acute extrapyramidal symptoms (EPS)-akathisia, dystonia, and parkinsonism-associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless; clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 27 TC 0 Z9 0 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 23 EP 27 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700004 ER PT J AU Meltzer, HY Casey, DE Garver, DL Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Assessing the effects of atypical antipsychotics on negative symptoms SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID DOUBLE-BLIND; SCHIZOPHRENIC-PATIENTS; REFRACTORY SCHIZOPHRENIA; NEUROLEPTIC TREATMENT; RISPERIDONE; HALOPERIDOL; PLACEBO; OLANZAPINE; CLOZAPINE; TRIAL AB Attempts to clarify the domains of schizophrenia gained importance when the atypical antipsychotics joined the armamentarium of schizophrenia treatments because of evidence that these agents art: superior to conventional antipsychotics for the treatment of negative symptoms. Negative symptoms can be divided into 3 components: (1) deficit or primary enduring negative symptoms that may or may not respond to treatment, (2) primary nonenduring negative symptoms, and (3) secondary negative symptoms that are associated with positive symptoms, extrapyramidal symptoms, depression, and environmental deprivation. The atypical antipsychotics have generally been found to be more effective than conventional antipsychotics against the totality of negative symptoms, but their effects on specific components are still under study. Sophisticated statistical tools such as path analysis have been used in investigations of the direct and indirect effects of atypical antipsychotics on negative symptoms, but these tools have limitations. Future study is needed to identify specific components of negative symptoms that may respond preferentially to one or another of the atypical antipsychotics. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 47 TC 7 Z9 7 U1 4 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 28 EP 34 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700005 ER PT J AU Altshuler, LL Hendrick, V Cohen, LS AF Altshuler, LL Hendrick, V Cohen, LS TI Course of mood and anxiety disorders during pregnancy and the postpartum period SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposia on Managed Care and Depression - Can Quality Be Assured/Mood and Anxiety - Disorders in the Childbearing Years CY MAY 05, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID PREEXISTING PANIC DISORDER; POSTNATAL DEPRESSION; THYROID-DYSFUNCTION; PUERPERAL PSYCHOSIS; MAINTENANCE THERAPIES; RECURRENT DEPRESSION; LITHIUM TREATMENT; OUTCOMES; WOMEN; LONG AB Because the onset of mood and anxiety disorders often occurs during the childbearing years, many women may be taking psychotropic medications for these disorders when they conceive. These medications easily diffuse across the placenta, and their impact on the fetus is of concern. But discontinuation may lead to relapse, in which case psychiatric symptoms may affect the fetus. Thoughtful treatment planning presents a dilemma to the clinician. Limited data suggest heightened vulnerability to relapse of mood and anxiety disorders in women during the postpartum period. Pregnancy appears to exacerbate symptoms of obsessive-compulsive disorder, while panic disorder patients may remain well after discontinuing medication. Future studies should address the prevalence and relapse rates of mood and anxiety disorders, particularly after medication discontinuation, among pregnant women. C1 VA Med Ctr W Los Angeles, Los Angeles, CA 90073 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Altshuler, LL (reprint author), VA Med Ctr W Los Angeles, B116AA,Bldg 158,Room 104,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 68 TC 116 Z9 119 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 29 EP 33 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200005 PM 9559757 ER PT J AU Nonacs, R Cohen, LS AF Nonacs, R Cohen, LS TI Postpartum mood disorders: Diagnosis and treatment guidelines SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposia on Managed Care and Depression - Can Quality Be Assured/Mood and Anxiety - Disorders in the Childbearing Years CY MAY 05, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID POSTNATAL DEPRESSION SCALE; PUERPERAL PSYCHOSIS; MAJOR DEPRESSION; FOLLOW-UP; INTERPERSONAL PSYCHOTHERAPY; PSYCHIATRIC-DISORDER; PROPHYLACTIC LITHIUM; MATERNITY BLUES; SOCIAL SUPPORT; LIFE EVENTS AB Mood disturbance occurs commonly during the postpartum period. The symptoms may be transient and relatively mild (as in postpartum blues) or may be associated with significant impairment of functioning (as in postpartum depression and puerperal psychosis). Despite the prevalence of postpartum mood disorders, depressive symptoms that emerge during the puerperium are often overlooked. Puerperal affective illness places the mother at risk for the development of recurrent depression and has also been associated with significant long-term effects on child development and behavior. Therefore, the prompt recognition and efficacious treatment of puerperal mood disorders are essential in order to avoid adverse outcomes for both mother and infant. This article discusses the evaluation of postpartum mood disturbance and offers guidelines for the treatment of affective illness during the puerperium. C1 Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Clin Psychopharmacol Unit, Boston, MA 02114 USA. RP Nonacs, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Clin Psychopharmacol Unit, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 78 TC 86 Z9 89 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 34 EP 40 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200006 PM 9559758 ER PT J AU Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Evaluating the effects of antipsychotics on cognition in schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID NEGATIVE SYMPTOMS; CLOZAPINE; DYSFUNCTION; RISPERIDONE; IMPROVEMENT; DEFICITS; DECLINE; AGENTS; MEMORY AB Cognitive deficits are an integral feature of schizophrenia and have a deleterious effect on the ability of schizophrenic patients to work and function in a social environment. Drugs that bring about substantial cognitive improvement represent a major contribution in improving the quality of life in schizophrenia. Recent studies have suggested that the atypical antipsychotics may be more useful than conventional agents for improving cognition. There is evidence that scores on neuropsychological assessments have improved after treatment with clozapine, risperidone, and quetiapine. Future research is needed to characterize and quantify the cognitive effects of the atypical antipsychotics. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 22 TC 2 Z9 2 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 35 EP 40 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700006 ER PT J AU Rosenbaum, JF AF Rosenbaum, JF TI Depression and its subtypes: A treatment update SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID FLUOXETINE C1 Massachusetts Gen Hosp, Outpatient Psychiat Div, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, Outpatient Psychiat Div, Clin Psychopharmacol Unit, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 18 BP 37 EP 38 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 140BP UT WOS:000077067100007 PM 9840197 ER PT J AU Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Atypical antipsychotics for treatment of depression in schizophrenia and affective disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID PSYCHOTIC MOOD DISORDERS; SCHIZOAFFECTIVE DISORDER; NEGATIVE SYMPTOMS; RISPERIDONE; CLOZAPINE; HALOPERIDOL; OLANZAPINE; SCALE; MANIA AB Depression in schizophrenia may be partially responsible for the increased suicide rate in schizophrenic patients, which is more than 20 times higher than that found in the general population. Affective disorders in patients with schizophrenia are associated with a poor outcome, an increased risk of relapse, and a high rate of suicide. There is evidence that atypical antipsychotics may contribute to a reduction in suicidality, and although the new drugs are marketed for the treatment of schizophrenia, their novel psychopharmacologic effects suggest the possibility of other therapeutic applications. Recent studies of the efficacy of the novel antipsychotics found that these agents may produce an antidepressant effect in schizophrenia and may be used as either an adjunctive medication or an alternative to mood stabilizers in patients with affective disorders. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 28 TC 1 Z9 1 U1 4 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 41 EP 45 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700007 ER PT J AU Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R AF Meltzer, HY Casey, DE Garver, DL Lasagna, L Marder, SR Masand, PS Miller, D Pickar, D Tandon, R CA Collaborative Working Grp Clinical Trial Evalua TI Treatment of special populations with the atypical antipsychotics SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium Clinical Trial Evaluations and Outcome Measures in Psychiatry CY NOV 21, 1997 CL CHICAGO, ILLINOIS ID RISPERIDONE; SCHIZOPHRENIA; CLOZAPINE; DISORDERS; PSYCHOSIS; SYMPTOMS; EFFICACY AB Atypical antipsychotics have become the treatment of choice for patients experiencing a first episode of schizophrenia. In addition, they are often prescribed for conditions such as bipolar disorder and dementia. While clinical trials have not yet established the efficacy of the atypical antipsychotics for these uses, a number of reports offer preliminary evidence that the atypical antipsychotics may be beneficial for affective disorders, substance abuse disorder, senile dementia, and pathologic aggression. Atypical agents may be particularly effective and tolerable in elderly patients who are especially susceptible to the adverse effects of conventional antipsychotic medication. Lower dosages are more necessary for the elderly than for younger adults. Current evidence suggests that clozapine is the most effective atypical antipsychotic for neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also be effective in a subset of these patients. C1 Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, Nashville, TN 37212 USA. Vet Affairs Med Ctr, Psychiat Serv, Portland, OR USA. Vet Affairs N Texas Med Ctr, Dallas, TX USA. Tufts Univ, Boston, MA 02111 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. SUNY Hlth Sci Ctr, Dept Psychiat, Syracuse, NY 13210 USA. Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Meltzer, HY (reprint author), Vanderbilt Univ, Sch Med, Dept Psychiat, Div Psychopharmacol, 1601 23rd Ave S,Suite 306, Nashville, TN 37212 USA. RI Meltzer, Herbert/E-8131-2013 NR 35 TC 1 Z9 1 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 12 BP 46 EP 52 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 120FD UT WOS:000075943700008 ER PT J AU Spencer, T Biederman, J Wilens, TE Faraone, SV AF Spencer, T Biederman, J Wilens, TE Faraone, SV TI Adults with attention-deficit/hyperactivity disorder: A controversial diagnosis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Current Issues in Attention Deficit Disorders CY NOV 13, 1996 CL BLOOMINGDALE, ILLINOIS SP Inst Med Studies, Wyeth Ayerst Labs ID DEFICIT HYPERACTIVITY DISORDER; MINIMAL BRAIN-DYSFUNCTION; 15-YEAR FOLLOW-UP; PSYCHIATRIC STATUS; CHILDHOOD HYPERACTIVITY; DOUBLE-BLIND; CONDUCT DISORDER; QUANTITATIVE MORPHOLOGY; FAMILIAL ASSOCIATION; GENERAL-POPULATION AB The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has remained controversial. This paper reviews the empirical evidence to date as to whether the diagnosis of ADHD in adults is valid and consistent with the childhood syndrome. Evidence of descriptive, divergent, pre dictive, and concurrent validity were examined. The available literature provides evidence that adult ADHD can be reliably diagnosed and that the diagnosis confers considerable power to forecast complications and treatment response. Studies of genetic transmission, specific treatment responses, and abnormalities in brain structure and function in affected individuals are also consistent with studies in childhood ADHD. There is converging evidence that adult ADHD is a not rare, valid clinical diagnosis. In addition, studies suggest that adult and child patients with ADHD may share a similar treatment-responsive, underlying neurobiological substrate. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20 MH01169-01] NR 112 TC 122 Z9 125 U1 4 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 7 BP 59 EP 68 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZY498 UT WOS:000074627800008 PM 9680054 ER PT J AU Nierenberg, AA Dougherty, D Rosenbaum, JF AF Nierenberg, AA Dougherty, D Rosenbaum, JF TI Dopaminergic agents and stimulants as antidepressant augmentation strategies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Augmentation of Antidepressant Medication CY FEB 06, 1997 CL NEW YORK, NEW YORK SP Bristol Myers Squibb ID REFRACTORY DEPRESSION; BROMOCRIPTINE; DISORDERS; PSYCHOSTIMULANTS; COMBINATION; TOMOGRAPHY; PSYCHIATRY; FLUOXETINE; INHIBITORS; BIPOLAR AB Dopaminergic agents and stimulants have been used to manage depression when conventional antidepressant treatments fail. We reviewed evidence for the role of dopaminergic dysfunction in depression, the use of dopaminergic agents as antidepressants, and the use of dopaminergic agents and stimulants as antidepressant adjuncts. Dopamine may be part of the pathophysiology of depression for a subset of patients. When used with caution and an appreciation of the potential risk of abuse, dopaminergic agents and stimulants may be useful for patients refractory to antidepressants alone. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit ACC815, 15 Parkman St, Boston, MA 02114 USA. NR 37 TC 30 Z9 30 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 5 BP 60 EP 64 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZQ083 UT WOS:000073819700008 PM 9635549 ER PT J AU Glazer, WM Rosenbaum, JF AF Glazer, WM Rosenbaum, JF TI Managed care versus managed money SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID HEALTH CAPITATION PROGRAM; OUTCOMES; RATES; MODEL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Psychopharmacol Unit,Dept Psychiat, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Psychopharmacol Unit,Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 62 EP 66 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200010 PM 9559761 ER PT J AU Glazer, WM Rosenbaum, JF AF Glazer, WM Rosenbaum, JF TI Managed care versus managed money - Introduction SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material C1 Harvard Univ, Clin Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Boston, MA 02114 USA. RP Glazer, WM (reprint author), Harvard Univ, Clin Psychopharmacol Unit, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 62 EP 62 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200009 PM 9559761 ER PT J AU Glazer, WM Rosenbaum, JF AF Glazer, WM Rosenbaum, JF TI Role of medication in managed care for depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID ANTIDEPRESSANT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Psychopharmacol Unit,Dept Psychiat, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Psychopharmacol Unit,Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 67 EP 67 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200011 PM 9559762 ER PT J AU Glazer, WM Rosenbaum, JF AF Glazer, WM Rosenbaum, JF TI Role of psychiatrists in managed care systems SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID DEPRESSION; DISORDERS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Psychopharmacol Unit,Dept Psychiat, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Psychopharmacol Unit,Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1998 VL 59 SU 2 BP 68 EP 68 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZE471 UT WOS:000072796200012 PM 9559763 ER PT J AU Duncan, LM Richards, LA Mihm, MC AF Duncan, LM Richards, LA Mihm, MC TI Increased mast cell density in invasive melanoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Dermatopathology CY FEB 02-03, 1995 CL NEW ORLEANS, LOUISIANA SP Amer Soc Dermatopathol ID C-KIT; MELANOCYTIC TUMORS; PROGNOSTIC FACTORS; GROWTH-FACTOR; CARCINOMA; BREAST; LOCALIZATION; EMPHASIS; PRODUCT; CANCER AB Mast cell participation in immune responses, tumor progression, and vascularization has been studied extensively in vitro. In situ investigation of mast cells in routinely processed tissues is hampered by difficulty in reliable detection of mast cells. We studied the tissue density of mast cells using a morphometric point-counting technique in 1 mu m-thick, Giemsa-stained, tissue sections from epon-embedded samples of skin biopsies. This technique has been demonstrated to be an accurate and reproducible method for determining mast cell density. Mast cell density in 15 cases of invasive melanoma was compared to that of 9 cases of benign melanocytic nevi and 4 cases of melanoma in situ. Mast cell density was greatest in invasive melanoma (mean density = 0.61 vol.%). The mean density of mast cells in nevi and in situ melanoma was 0.33 and 0.5 respectively. Six of 15 cases of melanoma had mast cell densities > 0.6, whereas mast cell density did not exceed 0.6 in any cases of melanoma in situ or benign melanocytic nevi (p < 0.02). Our findings confirm an increase in mast cell tissue density in some cases of invasive melanoma when compared to mast cell density in benign nevi and in situ melanoma. C1 Massachusetts Gen Hosp, Dermatopathol Univ, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Univ, WRN 827, Boston, MA 02114 USA. NR 24 TC 54 Z9 55 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 1998 VL 25 IS 1 BP 11 EP 15 DI 10.1111/j.1600-0560.1998.tb01683.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA YU625 UT WOS:000071737100002 PM 9508338 ER PT J AU Van Dijk, S Griffiths, GR Everett, MM Liu, Y You, SH Dean, DD Schwartz, Z Boyan, BD AF Van Dijk, S Griffiths, GR Everett, MM Liu, Y You, SH Dean, DD Schwartz, Z Boyan, BD TI Role of alkaline phosphatase and proteolipid in mineralization of E-coli. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Hebrew Univ Jerusalem, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 35 BP 110 EP 110 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800035 ER PT J AU Socransky, SS Goncalves, C Martin, L Haffajee, AD AF Socransky, SS Goncalves, C Martin, L Haffajee, AD TI Competitive hybridization increases specificity of whole genomic DNA probes. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 152 BP 124 EP 124 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800153 ER PT J AU Ximenez-Fyvie, LA Haffajee, AD Socransky, SS AF Ximenez-Fyvie, LA Haffajee, AD Socransky, SS TI Comparison of the microbial composition of supra- and subgingival plaque. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 150 BP 124 EP 124 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800152 ER PT J AU Ericson, RL Lau, CN Levanos, VA Paster, BJ Dewhirst, FE AF Ericson, RL Lau, CN Levanos, VA Paster, BJ Dewhirst, FE TI There are at lust forty species of human periodontal spirochetes. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 267 BP 139 EP 139 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800267 ER PT J AU Lau, CN Paster, BJ Levanos, V Ericson, RL Dewhirst, FE AF Lau, CN Paster, BJ Levanos, V Ericson, RL Dewhirst, FE TI Cultivable and uncultivable predominant bacterial species in refractory periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 269 BP 139 EP 139 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800268 ER PT J AU Uematsu, T Truong, D Stashenko, P Niederman, R AF Uematsu, T Truong, D Stashenko, P Niederman, R TI Infection susceptibility and EOP in ICAM-1 deficient mice. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 421 BP 158 EP 158 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800419 ER PT J AU Smith, DJ Heschel, RL King, WF Taubman, MA AF Smith, DJ Heschel, RL King, WF Taubman, MA TI Clostridium difficile toxin A enhances protective effect of S-mutans glucan binding protein. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 586 BP 179 EP 179 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800588 ER PT J AU Smith, DJ Heschel, RL King, WF Wise, DL Taubman, MA AF Smith, DJ Heschel, RL King, WF Wise, DL Taubman, MA TI GTF-PLG microparticle delivery vehicles for mucosal immunization. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 585 BP 179 EP 179 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800584 ER PT J AU Yaskell, T Kashket, S Winston, AE AF Yaskell, T Kashket, S Winston, AE TI Intraoral remineralization of enamel with a novel dentifrice. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Enamelon Inc, E Brunswick, NJ USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 658 BP 188 EP 188 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800660 ER PT J AU Taubman, MA Holmberg, CJ Ma, BY Smith, DJ Lees, A AF Taubman, MA Holmberg, CJ Ma, BY Smith, DJ Lees, A TI Immunogenicity of glucan synthesized by mutans streptococcal glucosyltransferase. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Vir Syst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 692 BP 192 EP 192 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800693 ER PT J AU Ottmers, V Jiang, H Bartlett, J Chen, J Hu, CC Simmer, JP AF Ottmers, V Jiang, H Bartlett, J Chen, J Hu, CC Simmer, JP TI Localization of enamel matrix serine proteinase 1 expression during tooth formation SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 698 BP 193 EP 193 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800700 ER PT J AU Colombo, AP Haffajee, AD Smith, CM Cugini, MA Socransky, SS AF Colombo, AP Haffajee, AD Smith, CM Cugini, MA Socransky, SS TI Discrimination of refractory periodontitis subjects using baseline parameters. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 714 BP 195 EP 195 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800716 ER PT J AU Feres, M Haffajee, AD Goncalves, C Allard, KA Som, S Goodson, JM Socransky, SS AF Feres, M Haffajee, AD Goncalves, C Allard, KA Som, S Goodson, JM Socransky, SS TI Systemic doxycycline administration. II. Effect on antibiotic resistance of subgingival species. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. RI Feres, Magda/H-7964-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 720 BP 195 EP 195 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800719 ER PT J AU Goodson, JM Oppenheim, R Hanson, D Doucette, D AF Goodson, JM Oppenheim, R Hanson, D Doucette, D TI A database model for periodontal disease monitoring. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. Syst Engn Inc, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 715 BP 195 EP 195 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800713 ER PT J AU Haffajee, AD Feres, M Goncalves, C Allard, KA Som, S Goodson, JM Socransky, SS AF Haffajee, AD Feres, M Goncalves, C Allard, KA Som, S Goodson, JM Socransky, SS TI Systemic doxycycline administration. I. Effect on composition of subgingival microbiota. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. RI Feres, Magda/H-7964-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 719 BP 195 EP 195 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800715 ER PT J AU Oringer, RJ Palys, MD Fiorellini, JP Iranmanesh, A Haffajee, AD Socransky, SS Giannobile, WV AF Oringer, RJ Palys, MD Fiorellini, JP Iranmanesh, A Haffajee, AD Socransky, SS Giannobile, WV TI Levels of ICTP and subgingival species around implants and teeth. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Boston, MA 02115 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 716 BP 195 EP 195 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800717 ER PT J AU Nara, Y Suda, S Tanaka, H Dogon, IL AF Nara, Y Suda, S Tanaka, H Dogon, IL TI In vivo bond strength of two adhesive systems to cervical abrasion SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Forsyth Dent Ctr, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 802 BP 206 EP 206 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800804 ER PT J AU Kwong, Y Cielinski, M Stashenko, P AF Kwong, Y Cielinski, M Stashenko, P TI Endogenous cytokine expression in developing mouse metatarsal bones. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1998 VL 77 SI A MA 859 BP 213 EP 213 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YU125 UT WOS:000071684800856 ER EF