FN Thomson Reuters Web of Science™ VR 1.0 PT J AU KOPANS, DB AF KOPANS, DB TI CORE BREAST BIOPSY - REPLY SO RADIOLOGY LA English DT Letter RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1994 VL 191 IS 3 BP 872 EP 872 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NM668 UT WOS:A1994NM66800058 ER PT J AU NIEMIERKO, A GOITEIN, M AF NIEMIERKO, A GOITEIN, M TI DOSE-VOLUME EFFECTS IN THE SPINAL-CORD SO RADIOTHERAPY AND ONCOLOGY LA English DT Letter ID TISSUE; TOLERANCE; RADIATION C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP NIEMIERKO, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JUN PY 1994 VL 31 IS 3 BP 265 EP 267 DI 10.1016/0167-8140(94)90434-0 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NT255 UT WOS:A1994NT25500011 PM 8066212 ER PT J AU SCHUMACHER, HR BAUTISTA, BB KRAUSER, RE MATHUR, AK GALL, EP AF SCHUMACHER, HR BAUTISTA, BB KRAUSER, RE MATHUR, AK GALL, EP TI HISTOLOGICAL APPEARANCE OF THE SYNOVIUM IN EARLY RHEUMATOID-ARTHRITIS SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article DE SYNOVIAL MEMBRANE; SYNOVIAL FLUID; MICROVASCULATURE; INFLAMMATION ID REITERS-SYNDROME; CLINICAL COURSE; MEMBRANE; FLUID; DISEASE; EXPRESSION; FEATURES; ANTIGEN; THERAPY; ONSET C1 UNIV PENN,SCH MED,DIV RHEUMATOL,PHILADELPHIA,PA 19104. PAOLI MEM HOSP,PAOLI,PA. MON VALLEY HOSP,MONONGAHELA,PA. UNIV ARIZONA,CTR HLTH SCI,DIV RHEUMATOL ALLERGY & IMMUNOL,TUCSON,AZ. RP SCHUMACHER, HR (reprint author), VET AFFAIRS MED CTR,CTR ARTHRITIS IMMUNOL,PHILADELPHIA,PA 19104, USA. FU NIAMS NIH HHS [AR 40770, AR 07062, AR 40525] NR 23 TC 32 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 1994 VL 23 IS 6 SU 2 BP 3 EP 10 DI 10.1016/0049-0172(94)90079-5 PG 8 WC Rheumatology SC Rheumatology GA NU451 UT WOS:A1994NU45100002 PM 7939728 ER PT J AU DROPCHO, EJ AF DROPCHO, EJ TI PARANEOPLASTIC DISORDERS - ANTINEURONAL ANTIBODIES AND THERAPEUTIC OPTIONS SO SEMINARS IN NEUROLOGY LA English DT Review ID NEOPLASTIC CEREBELLAR DEGENERATION; CELL LUNG-CANCER; ANTI-HU ANTIBODY; ENCEPHALOMYELITIS SENSORY NEURONOPATHY; EATON MYASTHENIC SYNDROME; CENTRAL-NERVOUS-SYSTEM; STIFF-MAN SYNDROME; NEURO-BLASTOMA; BREAST-CANCER; ANTICEREBELLAR ANTIBODIES C1 BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL. UNIV ALABAMA,CTR COMPREHENS CANC,NEUROONCOL PROGRAM,BIRMINGHAM,AL 35294. NR 115 TC 10 Z9 10 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUN PY 1994 VL 14 IS 2 BP 179 EP 187 DI 10.1055/s-2008-1041076 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA PB358 UT WOS:A1994PB35800014 PM 7984833 ER PT J AU FOITZIK, T LEWANDROWSKI, KB CASTILLO, CF RATTNER, DW WARSHAW, AL AF FOITZIK, T LEWANDROWSKI, KB CASTILLO, CF RATTNER, DW WARSHAW, AL TI EVIDENCE FOR EXTRALUMINAL TRYPSINOGEN ACTIVATION IN 3 DIFFERENT MODELS OF ACUTE-PANCREATITIS SO SURGERY LA English DT Article ID PEPTIDES; RAT; NECROSIS; MECHANISMS; THERAPY; MICE AB Background. Inappropriate extraluminal activation of trypsin is assumed to play a part in the pathogenesis of acute pancreatitis (AP), but proof has been elusive because active trypsin is transient and difficult to measure. We have previously shown increased bevels of trypsinogen activation peptides (TAP), a direct measure of trypsin activation, to correlate with severity of AP, tissue necrosis, and survival in a rodent model induced by cerulein hyperstimulation and bile salt three other models of experimental AP in rodents to give credence to the generality of the phenomenon and to its potential relevance to human AP. Methods. Experimental AP was induced in mice by a choline-deficient diet supplemented with ethionine and in rats by creation of a closed duodenal loop or by ligation of the biliopancreatic duct plus physiologic stimulation. TAP were quantified by an immunoassay in tissue and plasma at various time points after onset of AP. Results. In the group with choline-deficient diet supplemented with ethionine a significant increase in tissue and plasma TAP was found at 48 and 72 hours, respectively. In the group with closed duodenal loop significant TAP elevations were found in plasma as early as 6 hours and in the group with ligation. of the biliopancreatic duct plus physiologic stimulation at 24 hours. Conclusions. These experiments provide further evidence that extraluminal protease activation is a pathophysiologic event common to the evolution of various models of experimental acute pancreatitis and therefore increase the likelihood that this phenomenon is important in the human disease as well. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 21 TC 28 Z9 29 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 1994 VL 115 IS 6 BP 698 EP 702 PG 5 WC Surgery SC Surgery GA NP755 UT WOS:A1994NP75500007 PM 8197561 ER PT J AU HERSHMAN, JM AF HERSHMAN, JM TI HIGHLIGHTS OF THIS ISSUE SO THYROID LA English DT Editorial Material RP HERSHMAN, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BLDG 114,ROOM 200,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD SUM PY 1994 VL 4 IS 2 BP 141 EP 141 DI 10.1089/thy.1994.4.141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NV962 UT WOS:A1994NV96200001 ER PT J AU CHURCHILL, WH SURGENOR, DM WALLACE, EL AF CHURCHILL, WH SURGENOR, DM WALLACE, EL TI METHODS MUST MATCH THE MISSION SO TRANSFUSION LA English DT Editorial Material ID UNITED-STATES; TRANSFUSION; COLLECTION; BLOOD C1 HARVARD UNIV,SCH MED,BOSTON,MA. CTR BLOOD RES,BOSTON,MA 02115. CTR MANAGEMENT SYST,SNOWMASS VILLAGE,CO. RP CHURCHILL, WH (reprint author), BRIGHAM & WOMENS HOSP,BOSTON,MA 02115, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1994 VL 34 IS 6 BP 460 EP 461 DI 10.1046/j.1537-2995.1994.34694295057.x PG 2 WC Hematology SC Hematology GA NV575 UT WOS:A1994NV57500001 PM 8023384 ER PT J AU DAVALLI, AM OGAWA, Y SCAGLIA, L WU, YJ HOLLISTER, J BONNERWEIR, S WEIR, GC AF DAVALLI, AM OGAWA, Y SCAGLIA, L WU, YJ HOLLISTER, J BONNERWEIR, S WEIR, GC TI PORCINE ISLET GRAFTS IN DIABETIC NUDE-MICE - DYNAMIC INSULIN-SECRETION AND REGULATED B-CELL MASS LOWER GLUCOSE-LEVELS TO THE NORMAL PORCINE RANGE SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Xenotransplantation CY SEP 26-29, 1993 CL CAMBRIDGE, ENGLAND ID PANCREATIC-ISLETS; XENOTRANSPLANTATION; TRANSPLANTATION; LANGERHANS; ALLOGRAFTS; CANINE RP DAVALLI, AM (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1994 VL 26 IS 3 BP 1098 EP 1099 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV104 UT WOS:A1994NV10400020 PM 8029845 ER PT J AU LEE, LA SERGIO, JJ SACHS, DH SYKES, M AF LEE, LA SERGIO, JJ SACHS, DH SYKES, M TI MECHANISM OF TOLERANCE IN MIXED XENOGENEIC CHIMERAS PREPARED WITH A NONMYELOABLATIVE CONDITIONING REGIMEN SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Xenotransplantation CY SEP 26-29, 1993 CL CAMBRIDGE, ENGLAND ID NONLETHAL PREPARATIVE REGIMEN; ANTIBODIES; CELLS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NCI NIH HHS [T32 CA 09216] NR 6 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1994 VL 26 IS 3 BP 1197 EP 1198 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV104 UT WOS:A1994NV10400071 PM 8029884 ER PT J AU LEE, LA GRITSCH, HA ARN, JS EMERY, DW GLASER, RM SABLINSKI, T SACHS, DH SYKES, M AF LEE, LA GRITSCH, HA ARN, JS EMERY, DW GLASER, RM SABLINSKI, T SACHS, DH SYKES, M TI INDUCTION OF TOLERANCE TO PIG ANTIGENS IN MICE GRAFTED WITH FETAL PIG THYMUS/LIVER GRAFTS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Xenotransplantation CY SEP 26-29, 1993 CL CAMBRIDGE, ENGLAND C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA. BIOTRANSPLANT INC,BOSTON,MA. FU NCI NIH HHS [T32 CA 09216] NR 2 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1994 VL 26 IS 3 BP 1300 EP 1301 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV104 UT WOS:A1994NV10400120 PM 8029914 ER PT J AU EMERY, DW SYKES, M SACHS, DH LEGUERN, C AF EMERY, DW SYKES, M SACHS, DH LEGUERN, C TI MIXED SWINE/HUMAN LONG-TERM BONE-MARROW CULTURES SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Xenotransplantation CY SEP 26-29, 1993 CL CAMBRIDGE, ENGLAND ID CELLS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA. FU NHLBI NIH HHS [HL46532] NR 8 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1994 VL 26 IS 3 BP 1313 EP 1314 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV104 UT WOS:A1994NV10400128 PM 8029921 ER PT J AU TANAKA, M LATINNE, D GIANELLO, P SABLINSKI, T LORF, T BAILIN, M NICKELEIT, V COLVIN, R LEBOWITZ, E SYKES, M COSIMI, AB SACHS, DH AF TANAKA, M LATINNE, D GIANELLO, P SABLINSKI, T LORF, T BAILIN, M NICKELEIT, V COLVIN, R LEBOWITZ, E SYKES, M COSIMI, AB SACHS, DH TI XENOTRANSPLANTATION FROM PIG TO CYNOMOLGUS MONKEY - THE POTENTIAL FOR OVERCOMING XENOGRAFT REJECTION THROUGH INDUCTION OF CHIMERISM SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Xenotransplantation CY SEP 26-29, 1993 CL CAMBRIDGE, ENGLAND ID TOLERANCE INDUCTION; RENAL-ALLOGRAFTS; CLASS-I C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,SCH MED,DEPT SURG,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,SCH MED,DEPT ANESTHESIA & PATHOL,BOSTON,MA. BIOTRANSPLANT INC,BOSTON,MA. NR 7 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1994 VL 26 IS 3 BP 1326 EP 1327 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV104 UT WOS:A1994NV10400136 PM 8029926 ER PT J AU POWELSON, J COSIMI, AB AUSTEN, W BAILEN, M COLVIN, R GIANELLO, P SABLINSKI, T LORF, T KAWAI, T TANAKA, M SACHS, D AF POWELSON, J COSIMI, AB AUSTEN, W BAILEN, M COLVIN, R GIANELLO, P SABLINSKI, T LORF, T KAWAI, T TANAKA, M SACHS, D TI PORCINE-TO-PRIMATE ORTHOTOPIC LIVER-TRANSPLANTATION SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Xenotransplantation CY SEP 26-29, 1993 CL CAMBRIDGE, ENGLAND C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP POWELSON, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,DEPT PATHOL,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. NR 4 TC 23 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1994 VL 26 IS 3 BP 1353 EP 1354 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV104 UT WOS:A1994NV10400148 PM 8029937 ER PT J AU BALASUBRAMANIAN, V WIEGESHAUS, EH TAYLOR, BT SMITH, DW AF BALASUBRAMANIAN, V WIEGESHAUS, EH TAYLOR, BT SMITH, DW TI PATHOGENESIS OF TUBERCULOSIS - PATHWAY TO APICAL LOCALIZATION SO TUBERCLE AND LUNG DISEASE LA English DT Review ID EXPERIMENTAL AIRBORNE TUBERCULOSIS; HOST-PARASITE RELATIONSHIPS; MYCOBACTERIUM-TUBERCULOSIS; GUINEA-PIGS; EXOGENOUS REINFECTION; INFECTION; SPUTUM AB We have examined the published work of investigators which dealt with the pathogenesis of tuberculosis, especially the following: the infective dose, the yield of bacilli from the primary lesion and primary complex, the predominant location of the minimal lesion, the hypotheses of a vulnerable region in the lung and the specific pathways (endogenous or exogenous) by which tubercle bacilli cause disease. More knowledge of the pathogenic pathway to tuberculosis would provide clues to the development of new vaccines and drug regimens that can intervene at a specific stage in the pathogenesis. Based on the examination of the literature on pathogenesis of human tuberculosis and our findings in a guinea-pig model of experimental airborne tuberculosis, we have proposed an hypothesis which integrates the endogenous and exogenous pathways to tuberculosis. This hypothesis is based on the following observations: 1. The infectious dose is very low, usually 1-5 tubercle bacilli. 2. The first implant can occur anywhere in the lungs. 3. The cavitary lesion, characteristic of tuberculous disease, is often located in the apical regions in the lungs. 4. Whereas the primary implant can occur anywhere in the lungs, for the progression from infection to disease, the tubercle bacilli must gain access to the 'vulnerable' regions in the apex of the lungs. Our hypothesis states that in areas of the world where there is a low risk of infection with tubercle bacilli low incidence of vaccination or sensitization to environmental mycobacteria, or high incidence of high virulent isolates, the virulent tubercle bacilli reach the vulnerable region via a bacillemia during the first infection. In areas of the world where there is a high risk of infection with tubercle bacilli, high incidence of vaccination or sensitization to environmental mycobacteria or a high incidence of low virulent isolates, the tubercle bacilli reach the vulnerable region via the airway, which requires repeated episodes of infection as the probability of a first implant occurring in the vulnerable regions is low. C1 UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,MADISON,WI 53705. NR 48 TC 106 Z9 110 U1 1 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0962-8479 J9 TUBERCLE LUNG DIS JI Tubercle Lung Dis. PD JUN PY 1994 VL 75 IS 3 BP 168 EP 178 DI 10.1016/0962-8479(94)90002-7 PG 11 WC Respiratory System SC Respiratory System GA NV896 UT WOS:A1994NV89600002 PM 7919306 ER PT J AU ZIETMAN, AL EDELSTEIN, RA COEN, JJ BABAYAN, RK KRANE, RJ AF ZIETMAN, AL EDELSTEIN, RA COEN, JJ BABAYAN, RK KRANE, RJ TI RADICAL PROSTATECTOMY FOR ADENOCARCINOMA OF THE PROSTATE - THE INFLUENCE OF PREOPERATIVE AND PATHOLOGICAL FINDINGS ON BIOCHEMICAL DISEASE-FREE OUTCOME SO UROLOGY LA English DT Article ID CAPSULAR PENETRATION; ANTIGEN LEVELS; CANCER; RADIOTHERAPY; STAGE; MEN AB Objective. This retrospective study evaluated the outcome for a cohort of men undergoing radical retropubic prostatectomy alone as primary treatment for clinical T1-2 prostate adenocarcinoma. Methods. Sixty-two patients treated at Boston University Medical Center between 1987 and 1992 underwent radical prostatectomy alone without adjuvant or neoadjuvant endocrine therapy. Actuarial and multivariate analyses were made of disease-free outcome according to preoperative tumor T stage, prostate-specific antigen (PSA), and biopsy grade, and according to the pathologic findings at surgery. Recurrence was defined as the persistence or recurrence of detectable serum PSA four or more weeks following surgery. Results. Of all patients judged clinically to have localized disease (T1-2), 52 percent proved to have pathologic T3 tumors. Of these, 81 percent had positive surgical margins. The strongest preoperative predictors of pT3 disease were the biopsy Gleason grade and the initial serum PSA value. Actuarial analysis showed the overall likelihood of remaining free from detectable PSA at four years to be 43 percent (75% for those with organ-confined disease and 27% for those who were pT3). The poorest prognosis was seen in those with seminal vesicle involvement. Biopsy Gleason grade and initial PSA were independent preoperative predictors of biochemical failure in a Cox regression analysis but clinical T stage was not. Conclusions. The biopsy Gleason grade and initial PSA were identified as strong preoperative predictors of disease-free outcome. We confirmed the favorable prognosis of men with organ-confined disease, but emphasize the high likelihood of relapse in those with positive surgical margins or seminal vesicle invasion. C1 BOSTON UNIV,MED CTR,DEPT UROL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP ZIETMAN, AL (reprint author), BOSTON UNIV,MED CTR,DEPT RADIAT ONCOL,88 E NEWTON ST,BOSTON,MA 02118, USA. NR 21 TC 98 Z9 99 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 1994 VL 43 IS 6 BP 828 EP 833 DI 10.1016/0090-4295(94)90144-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA NQ085 UT WOS:A1994NQ08500016 PM 7515206 ER PT J AU HOGLUND, S OHAGEN, A LAWRENCE, K GABUZDA, D AF HOGLUND, S OHAGEN, A LAWRENCE, K GABUZDA, D TI ROLE OF VIF DURING PACKING OF THE CORE OF HIV-1 SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SOR GENE; SPATIAL VISUALIZATION; DNA-SYNTHESIS; TYPE-1; RNA; TRANSMISSION; MORPHOLOGY; PROTEINS; SEQUENCE AB The viral infectivity factor gene vif of human immunodeficiency virus type 1 (HIV-1) has been shown to enhance the cell-free infectivity of HIV-1 virus particles. Previous studies have demonstrated that vif increases viral infectivity at the time of virus production, most likely by affecting viral protein processing, virus assembly, or virus maturation. The effect of vif on the assembly and maturation of HIV-1 propagated in CEM, Jurkat, and SupT1 cells was examined by electron microscopy and goniometer analysis. CEM and Jurkat cells are nonpermissive and partially permissive for the replication of vif- defective viruses, respectively, while SupT1 cells are completely permissive. In CEM and Jurkat cultures, the morphology of immature vif+ and vif- virions was similar but immature virus particles were observed at a slightly higher frequency in cultures infected with the vif- virus. At later stages of virus maturation, however, nonhomogeneous packing of the core was detected in the majority of vif- virus particles produced in CEM and Jurkat cells. In the absence of vif, the cone-shaped virus core contained dense material in its broad end but, in contrast to vifi+ virions, the material inside its narrow end appeared transparent. The narrow part of the vif- virus core was surrounded by a shell and was attached to the viral envelope by a core-envelope link structure. Vif- virus particles with a lateral body of core material adjacent to the viral envelope were also observed more frequently in CEM and Jurkat cultures. In contrast, in SupT1 cultures the morphology of mature vif+ and vif- virus particles was similar. These results suggest that vif is associated with an effect during the final stages of packing of the viral nucleoprotein core. This effect may be important for the infectivity of HIV-1 virus particles. (C) 1994 Academic Press, Inc. C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HOGLUND, S (reprint author), BIOMED CTR,DEPT BIOCHEM,HIV STRUCT GRP,UPPSALA,SWEDEN. FU NIAID NIH HHS [AI33837, AI28691, AI01017] NR 27 TC 96 Z9 97 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN PY 1994 VL 201 IS 2 BP 349 EP 355 DI 10.1006/viro.1994.1300 PG 7 WC Virology SC Virology GA NL855 UT WOS:A1994NL85500016 PM 8184544 ER PT J AU BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE AF BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE TI NONHYDROLYZABLE PHOSPHOTYROSYL MIMETICS FOR THE PREPARATION OF PHOSPHATASE-RESISTANT SH2 DOMAIN INHIBITORS SO BIOCHEMISTRY LA English DT Article ID TYROSINE-PHOSPHORYLATED PEPTIDES; SOLID-PHASE SYNTHESIS; SRC HOMOLOGY-2 DOMAIN; SIGNALING COMPLEXES; INSULIN-RECEPTOR; BINDING; 3-KINASE; ANALOGS; IRS-1; TRANSDUCTION AB Src homology 2 (SH2) domains participate in protein tyrosine kinase (PTK)-mediated cellular signal transduction through their ability to bind with high affinity to phosphotyrosyl (pTyr)-bearing protein sequences. Although peptides containing pTyr competitively inhibit the binding between phosphoproteins and cognate SH2 proteins in a sequence-specific manner, such peptides are rapidly dephosphorylated by cellular phosphatases. We now describe our efforts to develop SR2 inhibitory peptides containing phosphatase-resistant pTyr Surrogates. The parent compound, (phosphonomethyl)phenylalanine (Pmp),is a phosphonate-based mimetic of pTyr in which the phosphate ester oxygen (>COPO3H2) has been replaced by a methylene unit (>CCX(2)PO(3)H(2), X(2) = H-2) Pmp analogues bearing fluorine (X(2) = H, F or X(2) = F-2) or hydroxyl (X(2) = H, OH) substituents on the phosphonate alpha-methylene carbon have been prepared and incorporated into peptides for use as SH2 domain inhibitors. In an assay using the C-terminal SH2 domain of phosphatidylinositol (PI) 3-kinase, peptides having a GXVPML sequence [where X = pTyr, Pmp, hydroxy-Pmp (HPmp), monofluoro-Pmp (FPmp), and difluoro-Pmp (F(2)Pmp)] exhibited binding potency in the order HPmp < Pmp < FPmp < F(2)Pmp = pTyr. Distinct peptide sequences which bind selectively with Src and Grb2 SH2 domains were also prepared with pTyr and F(2)Pmp. The F(2)Pmp peptides bound with high (0.2- to 5-fold) relative affinity, compared to analogous pTyr peptides. We conclude that peptides containing F(2)Pmp bind to SH2 domains with high affinity and specificity and, being resistant to cellular phosphatases, should provide a generally useful tool for disrupting SH2 domain-mediated signaling pathways in intact cells. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP BURKE, TR (reprint author), NCI,DCT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK08366] NR 35 TC 192 Z9 193 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 1994 VL 33 IS 21 BP 6490 EP 6494 DI 10.1021/bi00187a015 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP218 UT WOS:A1994NP21800015 PM 7515682 ER PT J AU CASTILLO, B DELCERRO, M BREAKEFIELD, XO FRIM, DM BARNSTABLE, CJ DEAN, DO BOHN, MC AF CASTILLO, B DELCERRO, M BREAKEFIELD, XO FRIM, DM BARNSTABLE, CJ DEAN, DO BOHN, MC TI RETINAL GANGLION-CELL SURVIVAL IS PROMOTED BY GENETICALLY-MODIFIED ASTROCYTES DESIGNED TO SECRETE BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) SO BRAIN RESEARCH LA English DT Article DE GROWTH FACTOR; NERVE GROWTH FACTOR; RETROVIRAL VECTOR; RAT RETINA ID NERVE GROWTH-FACTOR; DOPAMINERGIC-NEURONS; MESSENGER-RNA; MOTOR NEURONS; RAT; INVIVO; DEATH; DIFFERENTIATION; MOTONEURONS; RETROVIRUS AB Genetically engineered cells carrying genes for neurotrophic factors have potential application for treatment of neurodegenerative diseases and injuries to the nervous system. Brain-derived neurotrophic factor (BDNF) promotes the survival of specific neurons, including retinal ganglion cells (RGC). To determine whether genetically engineered astrocytes might be used for delivering bioactive BDNF, we infected primary type 1 rat astrocytes with a retrovirus harboring a human prepro-BDNF cDNA and assayed the medium conditioned by these astrocytes for effects on survival of rat RGCs in vitro. High levels of BDNF mRNA were expressed by infected astrocytes, but not by control astrocytes as determined by RNase protection assay using a BDNF specific probe. To test for secretion of bioactive BDNF from the transgenic astrocytes, embryonic day 17 rat retinas were dissociated and grown in medium conditioned (CM) for 24 h by astrocytes infected with a replication deficient retrovirus carrying BDNF, NGF, or alkaline phosphatase (AP) cDNA. After 3 days, the number of Thy-1 immunoreactive RGCs was counted. BDNF astrocyte CM significantly enhanced RGC survival by 15-fold compared to the AP control. NGF astrocyte CM had no significant effect. The rate of BDNF secretion was estimated at 83-166 pg/10(5) cells/h. This study demonstrates that astrocytes can be genetically engineered to synthesize and secrete bioactive BDNF. These techniques may be applicable to rescuing neurons from degenerative processes and also for enhancing their survival following transplantation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. YALE UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,NEW HAVEN,CT 06510. RP CASTILLO, B (reprint author), UNIV ROCHESTER,MED CTR,DEPT NEUROBIOL & ANAT,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. OI Barnstable, Colin/0000-0002-7011-4068 FU NINDS NIH HHS [NINDS NS24279]; PHS HHS [NEI ROI 05262] NR 40 TC 56 Z9 58 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 MAY 30 PY 1994 VL 647 IS 1 BP 30 EP 36 DI 10.1016/0006-8993(94)91395-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA NN543 UT WOS:A1994NN54300005 PM 8069702 ER PT J AU HENSHAW, R JENKINS, BG SCHULZ, JB FERRANTE, RJ KOWALL, NW ROSEN, BR BEAL, MF AF HENSHAW, R JENKINS, BG SCHULZ, JB FERRANTE, RJ KOWALL, NW ROSEN, BR BEAL, MF TI MALONATE PRODUCES STRIATAL LESIONS BY INDIRECT NMDA RECEPTOR ACTIVATION SO BRAIN RESEARCH LA English DT Note DE MALONATE; 3-NITROPROPIONIC ACID; EXCITOTOXICITY; MAGNETIC RESONANCE IMAGING; HUNTINGTONS DISEASE; PARKINSONS DISEASE ID TOXIN 3-NITROPROPIONIC ACID; SOMATOSTATIN-NEUROPEPTIDE-Y; EXCITOTOXIC LESIONS; RAT STRIATUM; MITOCHONDRIAL; ANTAGONISTS; MECHANISMS; IMPAIRMENT; INHIBITION; NEURONS AB We previously showed that local striatal injections of malonate produce age-dependent excitotoxic lesions. In the present study volumetric analysis confirmed that malonate produces age-dependent striatal lesions. Pretreatment with the non-competitive and competitive NMDA receptor antagonists, MK-801 and LY274614, and with lamotrigine resulted in significant protection in 4-month-old animals. In vivo magnetic resonance imaging of lesion area showed a significant correlation of increasing lesion size and lactate production in rats ranging from 1 to 12 months of age. Histological evaluation showed NADPH-diaphorase neurons were spared. The results provide further evidence that a subtle impairment of energy metabolism may play a role in neurodegenerative diseases. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR NMR IMAGING,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BEDFORD VA MED CTR,CTR GERIATR RES EDUC & CLIN,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Schulz, Jorg/D-9786-2012; Kowall, Neil/G-6364-2012 OI Schulz, Jorg/0000-0002-8903-0593; Kowall, Neil/0000-0002-6624-0213 FU DS NIH HHS [NINDS 16367]; NINDS NIH HHS [NS 10828, NS 31579] NR 18 TC 81 Z9 82 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 30 PY 1994 VL 647 IS 1 BP 161 EP 166 DI 10.1016/0006-8993(94)91412-5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA NN543 UT WOS:A1994NN54300022 PM 8069700 ER PT J AU KOPANS, DB AF KOPANS, DB TI PHYSICAL TRAUMA AND BREAST-CANCER SO LANCET LA English DT Letter RP KOPANS, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 28 PY 1994 VL 343 IS 8909 BP 1364 EP 1365 DI 10.1016/S0140-6736(94)92502-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NN217 UT WOS:A1994NN21700052 PM 7910355 ER PT J AU BASSING, CH HOWE, DJ SEGARINI, PR DONAHOE, PK WANG, XF AF BASSING, CH HOWE, DJ SEGARINI, PR DONAHOE, PK WANG, XF TI A SINGLE HETEROMERIC RECEPTOR COMPLEX IS SUFFICIENT TO MEDIATE BIOLOGICAL EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA LIGANDS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SERINE THREONINE KINASE; II RECEPTOR; CELL-PROLIFERATION; ACTIVIN; CLONING; EXPRESSION; FAMILY AB Transforming growth factor beta (TGF-beta), a multifunctional cytokine that regulates a variety of biological functions, signals through a heteromeric receptor complex of the type I and type II TGF-beta receptors. The type II receptor, a transmembrane serine-threonine kinase, was cloned based on its ability to directly bind TGF-beta. Recently, a number of candidate type I TGF-beta receptors have been isolated. Although only one of these transmembrane kinases (R4) has been shown to mediate TGF-beta-dependent gene activation, others bind TGF-beta when overexpressed in COS cells. Consequently, it has been postulated that the diversity of TGF-beta responses is generated through the association of distinct type I receptors with the type II TGF-beta receptor, thus creating receptor complexes of differential signaling capacities. In contrast to this model, we demonstrate that stable expression of only the R4 type I TGF-beta receptor in a mutant cell line lacking endogenous type I TGF-beta receptor was able to complex with the endogenous type II TGF-beta receptor and restore the effects of TGF-beta on inhibition of cell proliferation and activation of specific genes, regardless of which of the three mammalian isoforms of TGF-beta was used as the ligand. Therefore, R4 acts as a fully functional type I TGF-beta receptor and the differential effects of TGF-beta are likely mediated by a single receptor complex consisting of R4 and the type II receptor. C1 DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. CELTRIX PHARMACEUT,SANTA CLARA,CA 95054. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK45746] NR 20 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 1994 VL 269 IS 21 BP 14861 EP 14864 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP738 UT WOS:A1994NP73800004 PM 8195115 ER PT J AU NEUMEYER, JL WANG, SY GAO, YG MILIUS, RA KULA, NS CAMPBELL, A BALDESSARINI, RJ ZEAPONCE, Y BALDWIN, RM INNIS, RB AF NEUMEYER, JL WANG, SY GAO, YG MILIUS, RA KULA, NS CAMPBELL, A BALDESSARINI, RJ ZEAPONCE, Y BALDWIN, RM INNIS, RB TI N-OMEGA-FLUOROALKYL ANALOGS OF (1R)-2-BETA-CARBOMETHOXY-3-BETA-(4-IODOPHENYL)-TROPANE (BETA-CIT) - RADIOTRACERS FOR POSITRON EMISSION TOMOGRAPHY AND SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY IMAGING OF DOPAMINE TRANSPORTERS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID SEROTONIN TRANSPORTERS; PARKINSONS-DISEASE; NONHUMAN-PRIMATES; REUPTAKE SITES; HUMAN BRAIN; BINDING; INVIVO; PET; 2-BETA-CARBOMETHOXY-3-BETA-(4-IODOPHENYL)TROPANE; BIODISTRIBUTION C1 NORTHEASTERN UNIV,BOUVE COLL PHARM & ALLIED HLTH PROFESS,MED CHEM SECT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BELMONT,MA 02178. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BELMONT,MA 02178. YALE UNIV,SCH MED,DEPT PSYCHIAT,W HAVEN,CT 06516. VET ADM MED CTR,W HAVEN,CT 06516. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. RP NEUMEYER, JL (reprint author), RES BIOCHEM INT,1 STRATHMORE RD,NATICK,MA 01760, USA. FU NIMH NIH HHS [NIMH MH-49533, NIMH MH-47370, NIMH MH-34006] NR 25 TC 133 Z9 137 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 27 PY 1994 VL 37 IS 11 BP 1558 EP 1561 DI 10.1021/jm00037a004 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NP545 UT WOS:A1994NP54500004 PM 8201589 ER PT J AU SUGITA, K SOIFFER, RJ MURRAY, C SCHLOSSMAN, SF RITZ, J MORIMOTO, C AF SUGITA, K SOIFFER, RJ MURRAY, C SCHLOSSMAN, SF RITZ, J MORIMOTO, C TI THE PHENOTYPE AND RECONSTITUTION OF IMMUNOREGULATORY T-CELL SUBSETS AFTER T-CELL-DEPLETED ALLOGENEIC AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION SO TRANSPLANTATION LA English DT Article ID VERSUS-HOST DISEASE; SYSTEMIC LUPUS-ERYTHEMATOSUS; HELPER-INDUCER; LYMPHOCYTE-T; SUB-POPULATIONS; CYTOMEGALOVIRUS-INFECTION; IMMUNOGLOBULIN-SYNTHESIS; IMMUNE RECONSTITUTION; MONOCLONAL-ANTIBODIES; MULTIPLE-SCLEROSIS AB In the present study, we examined changes in the expression of CD45RA, CD31, and CD29 on total CD4 and CD8 lymphocytes in patients who had received CD6 T cell-depleted allogeneic marrow and received no immune suppressive drugs after engraftment in order to identify defects in reconstitution of immunoregulatory T cells after allogeneic BMT. Results following allo-BMT were compared with normal controls and patients following autologous BMT. We showed that CD4(+)CD45RA(+), CD4(+)CD29(+) (CD29(high)), and CD4(+)CD31(+) cells were markedly decreased during the first 24 months after allo- and auto-BMT. CD8(+)CD45RA(+) cells recovered to normal levels within the first month after auto-BMT, while after allo-BMT, the CD8(+)CD45RA(+) cells were at slightly low levels during the first month, but gradually increased to normal levels by 12 months post-BMT. CD8(+)CD29(+) cells were increased during the first 12 months both after allo- and auto-BMT although during the first month, a decreased percentage of CD8(+)CD29(+) cells was observed in allo-BMT patients. More important, CD4(+)CD29(+), CD8(+)CD29(+), and CD8(+)S6F1(+) cells were significantly increased in patients with moderate-to-severe acute GVHD (grades II-IV) compared with those with or without mild acute GVHD (grade I), suggesting that CD4 helper-inducer (CD4(+)CD29(high)) and CD8 killer-effector (CD8(+)CD29(high)SGF1(+)) cells play an important role in the pathophysiology of acute GVHD. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI12609, AI29530]; NIAMS NIH HHS [AR33713] NR 68 TC 33 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 27 PY 1994 VL 57 IS 10 BP 1465 EP 1473 DI 10.1097/00007890-199405270-00012 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NP057 UT WOS:A1994NP05700012 PM 7910987 ER PT J AU THIER, SO AF THIER, SO TI RESTRUCTURING THE NIH SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP THIER, SO (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 26 PY 1994 VL 330 IS 21 BP 1528 EP 1530 DI 10.1056/NEJM199405263302112 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NM068 UT WOS:A1994NM06800012 PM 8164708 ER PT J AU KAHN, CR AF KAHN, CR TI PICKING A RESEARCH PROBLEM - THE CRITICAL DECISION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP KAHN, CR (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 6 TC 23 Z9 23 U1 2 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 26 PY 1994 VL 330 IS 21 BP 1530 EP 1533 DI 10.1056/NEJM199405263302113 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NM068 UT WOS:A1994NM06800013 PM 8164709 ER PT J AU CUOMO, CA OETTINGER, MA AF CUOMO, CA OETTINGER, MA TI ANALYSIS OF REGIONS OF RAG-2 IMPORTANT FOR V(D)J RECOMBINATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID B-CELLS; GENES; EXPRESSION; MICE AB The recombinase activating genes RAG-1 and RAG-2 operate together to activate V(D)J recombination, and thus play an essential role in the generation of immune system diversity. As a first step in understanding the function of the RAG-2 protein, we have tested a series of deletion and insertion mutations for their ability to induce V(D)J joining of a variety of model substrates. Mutants were assayed for their ability to induce deletional and inversional V(D)J joining, thereby testing their proficiency at forming both signal and coding joints, and, in some cases, for their ability to carry out recombination of both extrachromosomal and integrated recombination substrates. All these reactions were affected similarly by any one mutation. Although the RAG-2 protein shows extensive evolutionary conservation across its length, we found that the carboxy-terminal portion of RAG-2, including an acidic region, is dispensable for all forms of recombination tested. In contrast, all mutations we created in the N-terminal region severely decreased recombination. Thus, the core active region required for V(D)J recombination is confined to the first three-quarters of the RAG-2 protein. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. OI Cuomo, Christina/0000-0002-5778-960X FU NIGMS NIH HHS [GM48026] NR 20 TC 113 Z9 115 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1994 VL 22 IS 10 BP 1810 EP 1814 DI 10.1093/nar/22.10.1810 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ605 UT WOS:A1994NQ60500004 PM 8208604 ER PT J AU BOTFIELD, MC JANCSO, A WEISS, MA AF BOTFIELD, MC JANCSO, A WEISS, MA TI MAPPING CRITICAL RESIDUES IN EUKARYOTIC DNA-BINDING PROTEINS - A PLASMID-BASED GENETIC SELECTION STRATEGY WITH APPLICATION TO THE OCT-2 POU MOTIF SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; REPRESSOR-OPERATOR INTERACTIONS; TRANSCRIPTION FACTOR; ANTENNAPEDIA HOMEODOMAIN; ACTIVATOR PROTEIN; ESCHERICHIA-COLI; IMMUNOGLOBULIN GENES; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; LAMBDA-REPRESSOR AB Discrimination between allowed and disallowed amino acid substitutions provides a powerful method for analysis of protein structure and function. Site-directed mutagenesis; allows specific hypotheses to be tested, but its systematic application to entire structural motifs is inefficient. This limitation may be overcome by genetic selection, which allows rapid scoring of thousands of randomly (or pseudorandomly) generated mutants. To facilitate structural dissection of DNA-binding proteins, we have designed two generally applicable bacterial selection systems: pPLUS selects for the ability of a protein to bind to a user-defined DNA sequence, whereas pMINUS selects against such binding. Complementary positive and negative selections allow rapid mapping of critical residues. To test and calibrate the systems, we have investigated the bipartite POU domain of the human B-cell-specific transcription factor Oct-2. (i) An invariant residue (Asn347) in the DNA-recognition helix bf the POU-specific homeodomain (POUHD) was substituted by each of the 19 other possible amino acids. The mutant proteins each exhibited decreased specific DNA binding as defined in vivo by genetic selection and in vitro by gel retardation; relative affinities correlate with phenotypes in the positive and negative selection systems. An essential role for Asn347 in wild-type POUHD-DNA recognition is consistent with homologous Asn-adenine interactions in cocrystal structures of canonical homeodomains. (ii) Extension of pPLUS/pMINUS selection to the POU-specific subdomain (POUS) is demonstrated by analysis of mutations in its putative helix-turn-helix (HTH) element. The altered DNA-binding properties of the mutant proteins in vivo and in vitro are in accord with a structural analogy between POUS and the operator-binding domain of phage lambda repressor. Together, our results provide a foundation for future biochemical studies of the structure and evolution of POUHD and POUS HTH sequences. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIGMS NIH HHS [GM45290] NR 62 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 24 PY 1994 VL 33 IS 20 BP 6177 EP 6185 DI 10.1021/bi00186a017 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NN472 UT WOS:A1994NN47200017 PM 8193131 ER PT J AU HOTAMISLIGIL, GS MURRAY, DL CHOY, LN SPIEGELMAN, BM AF HOTAMISLIGIL, GS MURRAY, DL CHOY, LN SPIEGELMAN, BM TI TUMOR-NECROSIS-FACTOR-ALPHA INHIBITS SIGNALING FROM THE INSULIN-RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYTOKINES; INSULIN RESISTANCE; NON-INSULIN-DEPENDENT DIABETES MELLITUS; GLUCOSE TRANSPORT; TYROSINE KINASE RECEPTORS ID TRANSPORTER MESSENGER-RNA; GLUCOSE TRANSPORTER; TYROSINE PHOSPHORYLATION; DIFFERENTIAL REGULATION; 3T3-L1 ADIPOCYTES; GENE-EXPRESSION; ADIPOSE-CELLS; RESISTANCE; PROTEIN; CANCER AB Insulin resistance is a common problem associated with infections and cancer and, most importantly, is the central component of non-insulin-dependent diabetes mellitus. We have recently shown that tumor necrosis factor (TNF) alpha is a key mediator of insulin resistance in animal models of non-insulin-dependent diabetes mellitus. Here, we investigate how TNF-alpha interferes with insulin action. Chronic exposure of adipocytes to low concentrations of TNF-alpha strongly inhibits insulin-stimulated glucose uptake. Concurrently, TNF-alpha treatment causes a moderate decrease in the insulin-stimulated autophosphorylation of the insulin receptor (IR) and a dramatic decrease in the phosphorylation of IR substrate 1, the major substrate of the IR in vivo. The IR isolated from TNF-alpha-treated cells is also defective in the ability to autophosphorylate and phosphorylate IR substrate 1 in vitro. These results show that TNF-alpha directly interferes with the signaling of insulin through its receptor and consequently blocks biological actions of insulin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 42539] NR 44 TC 744 Z9 771 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4854 EP 4858 DI 10.1073/pnas.91.11.4854 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400052 PM 8197147 ER PT J AU HALLAHAN, DE VIRUDACHALAM, S KUCHIBHOTLA, J KUFE, DW WEICHSELBAUM, RR AF HALLAHAN, DE VIRUDACHALAM, S KUCHIBHOTLA, J KUFE, DW WEICHSELBAUM, RR TI MEMBRANE-DERIVED 2ND MESSENGER REGULATES X-RAY-MEDIATED TUMOR-NECROSIS-FACTOR-ALPHA GENE INDUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-C; ARACHIDONIC-ACID RELEASE; BONE-MARROW TRANSPLANTATION; UNSATURATED FATTY-ACIDS; EPIDERMAL GROWTH-FACTOR; IONIZING-RADIATION; SACCHAROMYCES-CEREVISIAE; HYDROGEN-PEROXIDE; CELL-CYCLE; DNA DAMAGE AB Cells adapt to adverse environmental conditions through a wide range of responses that are conserved throughout evolution. Physical agents such as ionizing radiation are known to initiate a stress response that is triggered by the recognition of DNA damage. We have identified a signaling pathway involving the activation of phospholipase A(2) and protein kinase C in human cells that confers x-ray induction of the tumor necrosis factor alpha gene. Treatment of human cells with ionizing radiation or H2O2 was associated with the production of arachidonic acid. Inhibition of phospholipase A(2) abolished radiation-mediated arachidonate production as well as the subsequent activation of protein kinase C and tumor necrosis factor alpha gene expression. These findings demonstrate that ionizing radiation-mediated gene expression in human cells is regulated in part by extranuclear signal transduction. One practical application of phospholipase A(2) inhibitors is to ameliorate the adverse effects of radiotherapy associated with tumor necrosis factor alpha production. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,CHICAGO,IL 60637. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. FU NCI NIH HHS [CA58508, CA55241, CA41068] NR 53 TC 36 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4897 EP 4901 DI 10.1073/pnas.91.11.4897 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400061 PM 8197153 ER PT J AU FRIM, DM UHLER, TA GALPERN, WR BEAL, MF BREAKEFIELD, XO ISACSON, O AF FRIM, DM UHLER, TA GALPERN, WR BEAL, MF BREAKEFIELD, XO ISACSON, O TI IMPLANTED FIBROBLASTS GENETICALLY-ENGINEERED TO PRODUCE BRAIN-DERIVED NEUROTROPHIC FACTOR PREVENT 1-METHYL-4-PHENYLPYRIDINIUM TOXICITY TO DOPAMINERGIC-NEURONS IN THE RAT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUROPROTECTION; SUBSTANTIA NIGRA ID NERVE GROWTH-FACTOR; IDIOPATHIC PARKINSONS-DISEASE; EXCITATORY AMINO-ACIDS; CHOLINERGIC NEURONS; EXCITOTOXIC LESIONS; HUNTINGTONS-DISEASE; SUBSTANTIA-NIGRA; MOTOR NEURONS; GENE-TRANSFER; DEATH AB The trophism of brain-derived neurotrophic factor (BDNF) for dopaminergic cells in culture has led to significant interest in the role of BDNF in the etiology and potential treatment of Parkinson disease. Previous in vivo investigation of BDNF delivery to axotomized substantia nigra dopaminergic neurons in the adult rat has shown no protective effect. In this study, we produced nigral degeneration by infusing 1-methyl-4-phenylpyridinium (MPP(+)), a mitochondrial complex I inhibitor and the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), into the rat striatum. The subsequent loss of nigral neurons was presumably due to mitochondrial toxicity after MPP(+) uptake and retrograde transport to the substantia nigra. We engineered immortalized rat fibroblasts to secrete human BDNF and implanted these cells near the substantia nigra 7 days before striatal MPP(+) infusion. We found that BDNF-secreting fibroblasts markedly increased nigral dopaminergic neuronal survival when compared to control fibroblast implants. The observation that BDNF prevents MPTP-induced dopaminergic neuronal degeneration in the adult brain has significance for the treatment of neurodegenerative disorders, which may involve mitochondrial dysfunction, such as Parkinson disease. C1 MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL & NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP E,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. UNIV MASSACHUSETTS,SCH MED,DEPT PHARMACOL,WORCESTER,MA 01655. FU NINDS NIH HHS [NS 24279, NS 29178, NS 30064] NR 51 TC 197 Z9 204 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 5104 EP 5108 DI 10.1073/pnas.91.11.5104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400105 PM 8197193 ER PT J AU PAUL, SD KUNTZ, KM EAGLE, KA WEINSTEIN, MC AF PAUL, SD KUNTZ, KM EAGLE, KA WEINSTEIN, MC TI COSTS AND EFFECTIVENESS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IN PATIENTS WITH CONGESTIVE-HEART-FAILURE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article AB Background: Chronic heart failure is associated with a poor prognosis and reduced survival rates. The addition of vasodilator drug therapy to conventional therapy for congestive heart failure has resulted in improved survival. Methods: Adopting a societal viewpoint, we designed a decision analytic model to analyze the costs and effectiveness of three therapies available for the treatment of congestive heart failure: standard therapy (digoxin and diuretic therapy) plus (1) no vasodilator agents, (2) hydralazine hydrochloride-isosorbide dinitrate combination, and (3) enalapril. In addition, we performed sensitivity analyses to determine which model variables were influential in determining incremental cost-effectiveness ratios (cost of drug, cost of hospitalization, efficacy of agents, etc). We used data from three major randomized controlled trials to estimate treatment efficacy, mortality rates, and hospitalization rates. Results: An additional year of life gained by a patient receiving hydralazine-isosorbide combination therapy compared with standard therapy required an additional expense (incremental cost-effectiveness ratio) of $5600. Compared with the hydralazine-isosorbide combination therapy, the incremental cost-effectiveness ratio for enalapril therapy was $9700 per year of life saved. These results were insensitive to wide variations in our baseline assumptions. Conclusions: The cost per year of life saved by vasodilator therapy is much lower than that of other accepted medical therapies. Although the cost per year of life saved for hydralazine-isosorbide combination therapy is lower than that for enalapril therapy, enalapril therapy saves more lives, and the incremental cost of enalapril therapy is justified by the added benefits. C1 HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT CLIN EPIDEMIOL,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. RP PAUL, SD (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,WANG ACC 469,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 15 TC 94 Z9 94 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 23 PY 1994 VL 154 IS 10 BP 1143 EP 1149 DI 10.1001/archinte.154.10.1143 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NM394 UT WOS:A1994NM39400013 PM 8185426 ER PT J AU BLITZER, RD WONG, T NOURANIFAR, R LANDAU, EM AF BLITZER, RD WONG, T NOURANIFAR, R LANDAU, EM TI THE CHOLINERGIC INHIBITION OF AFTERHYPERPOLARIZATION IN RAT HIPPOCAMPUS IS INDEPENDENT OF CAMP-DEPENDENT PROTEIN-KINASE SO BRAIN RESEARCH LA English DT Note DE NOREPINEPHRINE; CARBACHOL; CAMP-DEPENDENT PROTEIN KINASE; WHOLE CELL RECORDING; CAI; RP-CAMPS ID PYRAMIDAL CELLS; GUINEA-PIG; NEURONS; CALCIUM; HYPERPOLARIZATION; NORADRENALINE; STIMULATION; SUBUNIT; SLICES AB The possible involvement of protein kinase A (PKA) in the muscarinic inhibition of the slow afterhyperpolarizing current (I-AHP) was investigated in rat hippocampal pyramidal cells. I-AHP was recorded using the whole cell method in hippocampal slices, and Rp-cAMPS, a PKA antagonist, was applied intracellularly. The inhibition of I-AHP by carbachol was not affected by Rp-cAMPS. In contrast, Rp-cAMPS reduced the cAMP-dependent inhibition of I-AHP by norepinephrine. The results show that phosphorylation by PKA does not contribute to the muscarinic effect on I-AHP. C1 MT SINAI MED CTR,DEPT PHARMACOL,NEW YORK,NY 10029. BRONX VET ADM MED CTR,PSYCHIAT SERV,NEW YORK,NY 10029. RP BLITZER, RD (reprint author), MT SINAI MED CTR,DEPT PSYCHIAT,BOX 1230,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. NR 26 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 23 PY 1994 VL 646 IS 2 BP 312 EP 314 DI 10.1016/0006-8993(94)90096-5 PG 3 WC Neurosciences SC Neurosciences & Neurology GA NM416 UT WOS:A1994NM41600021 PM 8069680 ER PT J AU GREENBERG, JT GUO, AL KLESSIG, DF AUSUBEL, FM AF GREENBERG, JT GUO, AL KLESSIG, DF AUSUBEL, FM TI PROGRAMMED CELL-DEATH IN PLANTS - A PATHOGEN-TRIGGERED RESPONSE ACTIVATED COORDINATELY WITH MULTIPLE DEFENSE FUNCTIONS SO CELL LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; SYRINGAE PV-SYRINGAE; TOBACCO MOSAIC-VIRUS; SALICYLIC-ACID; ARABIDOPSIS-THALIANA; HYPERSENSITIVE REACTION; DISEASE RESISTANCE; VIRAL-INFECTION; INDUCTION; APOPTOSIS AB In plants, the hypersensitive response (HR) to pathogens involves rapid cell death, which is hypothesized to arise from the activation of a cell death program. We describe mutant A. thaliana plants that contain lesions in a single accelerated cell death (ACD) gene called ACD2 and that bypass the need for pathogen exposure to induce the HR. acd2 plants that develop spontaneous lesions show typical HR characteristics both within the necrotic tissue and within the healthy part of the plant, including: modification of plant cell walls, resistance to bacterial pathogens, and accumulation of defense-related gene transcripts, the signal molecule salicylic acid and an antimicrobial compound. We propose that the ACD2 gene is involved in a pathway(s) that negatively regulates a genetically programmed HR. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT MOLEC BIOL & BIOCHEM,PISCATAWAY,NJ 08855. RP GREENBERG, JT (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114, USA. OI Greenberg, Jean/0000-0002-7213-7618 FU NIGMS NIH HHS [GM48707] NR 53 TC 509 Z9 579 U1 4 U2 26 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 20 PY 1994 VL 77 IS 4 BP 551 EP 563 DI 10.1016/0092-8674(94)90217-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM832 UT WOS:A1994NM83200010 PM 8187175 ER PT J AU LEE, YH ALBERTA, JA GONZALEZ, FJ WAXMAN, DJ AF LEE, YH ALBERTA, JA GONZALEZ, FJ WAXMAN, DJ TI MULTIPLE, FUNCTIONAL DBP SITES ON THE PROMOTER OF THE CHOLESTEROL 7-ALPHA-HYDROXYLASE P450 GENE, CYP7 - PROPOSED ROLE IN DIURNAL REGULATION OF LIVER GENE-EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENRICHED TRANSCRIPTIONAL ACTIVATOR; BILE-ACID BIOSYNTHESIS; MESSENGER-RNA LEVELS; RAT-LIVER; CIRCADIAN-RHYTHM; BINDING-PROTEIN; ALPHA-HYDROXYLASE; MOLECULAR-CLONING; HEPATOMA-CELLS; ENZYME AB Hepatic cytochrome P450 cholesterol 7 alpha-hydroxylase, CYP7, is regulated in vivo at the protein and the mRNA level in response to multiple physiological factors, including liver cholesterol synthesis, bile acid feedback inhibition, and diurnal rhythm. In the present study we investigated whether the liver transcription factor DBP (albumin promoter D-site binding protein), which undergoes a striking diurnal rhythm in rat liver (DBP levels during evening/morning similar to 100:1), contributes to the diurnal regulation of CYP7 gene expression. DNase I footprinting analysis using bacterially expressed DEP and a cloned 5'-flanking DNA segment of the rat CYP7 gene revealed five distinct DBP-binding sites, designated A-E, distributed between nucleotides (nts) -41 and -295 relative to the CYP7 transcription start site. CYP7-directed gene transcription in HepG2 cells transfected with a 5'-CYP7 promoter-chloramphenicol acetyltransferase reporter was activated up to 12-fold upon cotransfection of a DBP expression vector, whereas an HNF-1 alpha expression vector did not stimulate CYP7 gene activity. 5'-Deletion analyses and site-specific mutagenesis revealed that this stimulating effect of DBP can in part be ascribed to its functional interaction with DBP binding sites B (nts -115/-125), C (nts -172/-195), and D (nts -214/-230). C/EBP beta (LAP), another liver enriched basic-leucine zipper transcription factor, bound to these same sites but effected a more modest increase in CYP7-directed gene transcription (up to 3-4-fold) when expressed in HepG2 cells. Competition for CYP7 promoter-binding sites between C/EBP, which undergoes less than or equal to 2-fold diurnal change in rat liver, and the diurnally regulated DBP is proposed to determine the relative rates of basal versus diurnally regulated CYP7 gene transcription and thus may be a primary mechanism for setting the 3-6-fold amplitude that characterizes the circadian rhythm of liver CYP7 expression. Moreover, since DBP is first expressed in rat liver 3-4 weeks after birth, these findings may account for both the enhanced expression and the onset of the diurnal pattern of CYP7 enzyme levels at this stage of development. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK33765] NR 54 TC 75 Z9 75 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 1994 VL 269 IS 20 BP 14681 EP 14689 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500060 PM 8182075 ER PT J AU COREY, JL DAVIDSON, N LESTER, HA BRECHA, N QUICK, MW AF COREY, JL DAVIDSON, N LESTER, HA BRECHA, N QUICK, MW TI PROTEIN-KINASE-C MODULATES THE ACTIVITY OF A CLONED GAMMA-AMINOBUTYRIC-ACID TRANSPORTER EXPRESSED IN XENOPUS-OOCYTES VIA REGULATED SUBCELLULAR REDISTRIBUTION OF THE TRANSPORTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT ADIPOSE CELL; FREE FATTY-ACIDS; GLUCOSE TRANSPORTER; PLASMA-MEMBRANE; PHORBOL ESTERS; INDUCED TRANSLOCATION; INSULIN ACTION; 3T3-L1 CELLS; AFFINITY; PHOSPHORYLATION AB We report that activators and inhibitors of protein kinase C (PKC) and protein phosphatases regulate the activity of a cloned rat brain gamma-aminobutyric acid (GABA) transporter (GAT1) expressed in Xenopus oocytes. Four compounds known to activate PKC increased GABA uptake 2-3.5-fold over basal control levels. Inhibition of PKC by bisindolylmaleimide reduced basal GABA uptake 80% and blocked the phorbol 12-myristate 13-acetate (PMA)-induced stimulation of transport. Okadaic acid, a protein phosphatase inhibitor, stimulated transport 2.5-fold; a 4-fold increase in GABA uptake occurred when oocytes were treated with cyclosporin A, a specific inhibitor of protein phosphatase 2B. Modulation resulted in changes to V-max but not to K-m and was influenced by the functional expression level of the transporter protein; as expression level increased, the ability to up-regulate transporter activity decreased. Down-regulation of transporter activity was independent of expression level. Modulation did not occur through phosphorylation of the three consensus PKC sites predicted by the primary protein sequence since their removal had no effect on the susceptibility of the transporter to modulation by PMA or bisindolylmaleimide. Subcellular fractionation of oocyte membranes demonstrated that under basal level conditions, the majority of GAT1 was targeted to a cytoplasmic compartment corresponding to the trans-Golgi or low density vesicles. Stimulation of PKC with PMA resulted in a translocation of transporters from this compartment to the plasma membrane. At higher expression levels of GAT1 protein, a larger portion of GAT1 was found on the plasma membrane during basal level conditions and treatment with bisindolylmaleimide resulted in removal of these transporters from the plasma membrane. At expression levels demonstrated to be resistant to modulation by PMA, PMA-treatment still resulted in translocation of transporters from the cytoplasm to the plasma membrane. Thus, the inability of PMA to increase uptake at high expression of the GAT1 protein is due to saturation at a step subsequent to translocation. These findings 1) demonstrate the presence of a novel regulated secretory pathway in oocytes and 2) suggest a modulatory mechanism for neurotransmitter transporters that could have significant effects upon synaptic function. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,INST BRAIN RES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,CTR ULCER RES,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP COREY, JL (reprint author), CALTECH,DIV BIOL,156-29,PASADENA,CA 91125, USA. FU NINDS NIH HHS [NS-11756] NR 40 TC 184 Z9 187 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 1994 VL 269 IS 20 BP 14759 EP 14767 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500071 PM 8182081 ER PT J AU TIAN, WN PIGNATARE, JN STANTON, RC AF TIAN, WN PIGNATARE, JN STANTON, RC TI SIGNAL-TRANSDUCTION PROTEINS THAT ASSOCIATE WITH THE PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTOR MEDIATE THE (PDGF)-INDUCED RELEASE OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE FROM PERMEABILIZED CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEA-URCHIN EGGS; RAT HEPATOCYTES; TYROSINE PHOSPHORYLATION; ENZYME; BINDING; INVIVO; ADULT; GAP AB Permeabilized rat kidney cells rapidly released glucose 6-phosphate dehydrogenase (G6PD) following stimulation with peptide growth factors (Stanton, R. C., Seifter, J. L., Boxer, D. C., Zimmerman, E., and Cantley, L. C. (1991) J. Biol. Chem. 266, 12442-12448). To evaluate the signal transduction pathways mediating release of G6PD, two cell Lines transfected with wild type or mutant platelet-derived growth factor (PDGF) receptors (PDGFR) were studied using two permeabilization protocols. G6PD release was evaluated by enzyme activity and Western blot analysis. PDGF caused a significant increase in G6PD release in 1 min in cells transfected with wild type PDGFR. PDGF did not stimulate G6PD release in cells transfected with tyrosine kinase-deficient PDGFR. PDGF did not stimulate G6PD release in cells transfected with partially autophosphorylation-deficient PDGFR in which four known signaling proteins do not associate with the PDGFR The PDGF-stimulated release of G6PD was partially restored in PDGFR mutants in which either phosphatidylinositol-3-kinase or phospholipase C gamma 1 could associate with the PDGFR Lastly, there was no basal or PDGF-stimulated phosphorylation of G6PD. We conclude that release of G6PD: 1) requires intrinsic PDGFR tyrosine kinase activity; 2) requires PDGFR autophosphorylation; 3) is mediated by signaling proteins that associate with the PDGFR; 4) is not mediated by direct phosphorylation of G6PD. C1 NEW ENGLAND DEACONESS HOSP,JOSLIN DIABET CTR,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 25 TC 60 Z9 62 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 1994 VL 269 IS 20 BP 14798 EP 14805 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500076 PM 8182086 ER PT J AU MAEDA, T WURGLERMURPHY, SM SAITO, H AF MAEDA, T WURGLERMURPHY, SM SAITO, H TI A 2-COMPONENT SYSTEM THAT REGULATES AN OSMOSENSING MAP KINASE CASCADE IN YEAST SO NATURE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION; ESCHERICHIA-COLI; SHUTTLE VECTORS; PROTEIN; GENE; CHEMOTAXIS; HOMOLOGIES; STRAINS AB IN the prokaryotic two-component signal transduction systems, recognition of an environmental stimulus by a sensor molecule results in the activation of its histidine kinase domain and phosphorylation of a histidine residue within that domain(1-3). This phosphate group is then transferred to an aspartate residue in the receiver domain of a cognate response regulator molecule, resulting in the activation of its output function. Although a few eukaryotic proteins were identified recently that show sequence similarity to the prokaryotic sensors or response regulators, it has not been clear whether they constituted a part of a 'two-component' system(4-7). Here we describe a two-component system in Saccharomyces cerevisiae that regulates an osmosensing MAP kinase cascade(8,9). C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 25 TC 851 Z9 876 U1 0 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 1994 VL 369 IS 6477 BP 242 EP 245 DI 10.1038/369242a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NM067 UT WOS:A1994NM06700059 PM 8183345 ER PT J AU JANG, IK AF JANG, IK TI ACUTE MYOCARDIAL-INFARCTION AND CORONARY SPASM SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP JANG, IK (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 1994 VL 330 IS 20 BP 1420 EP 1420 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NK972 UT WOS:A1994NK97200005 PM 8159196 ER PT J AU GUSELLA, JF MACDONALD, ME AF GUSELLA, JF MACDONALD, ME TI HUNTINGTONS-DISEASE AND REPEATING TRINUCLEOTIDES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP GUSELLA, JF (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02129, USA. NR 10 TC 15 Z9 15 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 1994 VL 330 IS 20 BP 1450 EP 1451 DI 10.1056/NEJM199405193302011 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NK972 UT WOS:A1994NK97200011 PM 8159202 ER PT J AU BALDESSARINI, RJ MARSH, ER HUSTONLYONS, D AF BALDESSARINI, RJ MARSH, ER HUSTONLYONS, D TI EFFECTS OF DOPAMINE PARTIAL-AGONIST AMINOERGOLINES ON DOPAMINE METABOLISM IN LIMBIC AND EXTRAPYRAMIDAL REGIONS OF RAT-BRAIN SO BIOCHEMICAL PHARMACOLOGY LA English DT Note DE AMINOERGOLINES; AUTORECEPTORS; DOPAMINE; ERGOLINES; EXTRAPYRAMIDAL; T-DOPA; LIMBIC; PARTIAL AGONISTS; RECEPTORS; SDZ-208-911; SDZ-208-912; SDZ-212-327; SDZ-MAR-327 ID RECEPTOR; SDZ-208-911; ERGOLINES AB The aminoergolines SDZ-208-911, -208-912, and -212-327, weak partial D-2 agonists with agonist/antagonist properties, are proposed as potential atypical antipsychotic agents with limited risk of extrapyramidal effects or hyperprolactinemia. The in vivo effects on dopamine (DA) metabolism in limbic (accumbens) and extrapyramidal (striatum) regions of rat brain were evaluated by measuring the accumulation of L-dihydroxyphenylalanine (DOPA) after inhibiting decarboxylation alone (''open-loop'' model) or with added gamma-butyrolactone (GBL, autoreceptor model). All three aminoergolines markedly increased DOPA in both regions, dose-dependently, with only minor decreases when GBL was included, and so evidently lack appreciable agonist activity at D-2-like autoreceptors and resemble typical neuroleptics in stimulating DA synthesis, without regional selectivity. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA. FU NIMH NIH HHS [NIMH MH-31154, NIMH MH-47370, NIMH MH-34006] NR 13 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 18 PY 1994 VL 47 IS 10 BP 1917 EP 1919 DI 10.1016/0006-2952(94)90323-9 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NU425 UT WOS:A1994NU42500027 PM 7911303 ER PT J AU FARROW, NA MUHANDIRAM, R SINGER, AU PASCAL, SM KAY, CM GISH, G SHOELSON, SE PAWSON, T FORMANKAY, JD KAY, LE AF FARROW, NA MUHANDIRAM, R SINGER, AU PASCAL, SM KAY, CM GISH, G SHOELSON, SE PAWSON, T FORMANKAY, JD KAY, LE TI BACKBONE DYNAMICS OF A FREE AND A PHOSPHOPEPTIDE-COMPLEXED SRC HOMOLOGY-2 DOMAIN STUDIED BY N-15 NMR RELAXATION SO BIOCHEMISTRY LA English DT Article ID MODEL-FREE APPROACH; TYROSINE-PHOSPHORYLATED PEPTIDES; AFFINITY PHOSPHOTYROSYL PEPTIDE; MAGNETIC-RESONANCE RELAXATION; GROWTH-FACTOR RECEPTOR; CROSS-CORRELATION; SH2 DOMAINS; STAPHYLOCOCCAL NUCLEASE; SOLVENT SUPPRESSION; CHAIN DYNAMICS AB The backbone dynamics of the C-terminal SH2 domain of phospholipase C gamma 1 have been investigated. Two forms of the domain were studied, one in complex with a high-affinity binding peptide derived from the platelet-derived growth factor receptor and the other in the absence of this peptide. 2-D H-1-N-15 NMR methods, employing pulsed field gradients, were used to determine steady-state H-1-N-15 NOE values and T-1 and T-2 N-15 relaxation times. Backbone dynamics were characterized by the overall correlation time (tau(m)), Order parameters (S-2), effective correlation times for internal motions (tau(e)), and, if required, terms to account for motions on a microsecond-to-millisecond-time scale. An extended two-time-scale formalism was used for residues having relaxation data that could not be fit adequately using a single-time-scale formalism. The overall correlation times of the uncomplexed and complexed forms of SH2 were found to be 9.2 and 6.5 ns, respectively, suggesting that the uncomplexed form is in a monomer-dimer equilibrium. This was subsequently confirmed by hydrodynamic measurements. Analysis of order parameters reveals that residues in the so-called phosphotyrosine-binding loop exhibited higher than average disorder in both forms of SH2. Although localized differences in order parameters were observed between the uncomplexed and complexed forms of SH2, overall, higher order parameters were not found in the peptide-bound form, indicating that on average, picosecond-time-scale disorder is not reduced upon binding peptide. The relaxation data of the SH2-phosphopeptide complex were fit with fewer exchange terms than the uncomplexed form. This mat reflect the monomer-dimer equilibrium that exists in the uncomplexed form or may indicate that the complexed form has lower conformational flexibility on a microsecond-tomillisecond-time scale. C1 UNIV TORONTO,DEPT MED GENET,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,DEPT BIOCHEM,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,DEPT CHEM,TORONTO M5S 1A8,ON,CANADA. HOSP SICK CHILDREN,DIV BIOCHEM RES,TORONTO M5G 1X8,ON,CANADA. UNIV ALBERTA,DEPT BIOCHEM,MRC,PROT STRUCT & FUNCT GRP,EDMONTON T6G 2H7,AB,CANADA. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,DIV MOLEC & DEV BIOL,TORONTO M5G 1X5,ON,CANADA. RP FARROW, NA (reprint author), UNIV TORONTO,PROT ENGN NETWORK CTR EXCELLENCE,TORONTO M5S 1A8,ON,CANADA. RI Pawson, Tony/E-4578-2013; Gish, Gerald/C-7228-2017 NR 60 TC 1746 Z9 1752 U1 7 U2 89 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 17 PY 1994 VL 33 IS 19 BP 5984 EP 6003 DI 10.1021/bi00185a040 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM269 UT WOS:A1994NM26900040 PM 7514039 ER PT J AU KONG, XF SCHIPANI, E LANSKE, B JOUN, H KARPERIEN, M DEFIZE, LHK JUPPNER, H POTTS, JT SEGRE, GV KRONENBERG, HM ABOUSAMRA, AB AF KONG, XF SCHIPANI, E LANSKE, B JOUN, H KARPERIEN, M DEFIZE, LHK JUPPNER, H POTTS, JT SEGRE, GV KRONENBERG, HM ABOUSAMRA, AB TI THE RAT, MOUSE AND HUMAN GENES ENCODING THE RECEPTOR FOR PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE ARE HIGHLY HOMOLOGOUS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID POLYADENYLATION INVITRO; FUNCTIONAL EXPRESSION; TISSUE DISTRIBUTION; CLONING; AAUAAA; ORGANIZATION; DOWNSTREAM; PROTEINS; CLEAVAGE; CELLS AB The organization of the PTH/PTHrP receptor gene is highly homologous in three mammalian species, rat, human and mouse. This gene extends over 22 kb and contains at least 15 exons and 14 introns. The most 5' exon we have identified (exon U) is followed by an approximately 1kb intron. The second exon (exon S) encodes the initiator methionine and the putative signal peptide and is followed by the largest intron of this gene (about 11 kb). The amino-terminal extracellular region is encoded by 4 exons (E1, E2, E3 and G); exon G contains all 4 potential glycosylation sites. Membrane-spanning domains 1-4 and portions of their connecting intracellular and extracellular loops are encoded by 4 exons (M1, M2, M3 and M4). The second extracellular loop and portions of 4th and 5th membrane-spanning domains are encoded by one exon, EL2. The 5th membrane-spanning domain and portion of the 3rd intracellular loop are encoded by one exon, M5. The 6th membrane-spanning domain, the 3rd extracellular loop and the proximal part of the 7th membrane-spanning domain are encoded by one single exon (M6/7); the remaining sequence of the 7th membrane-spanning domain is encoded by a short exon, M7. The carboxy-terminal tail of the receptor and the 3' untranslated region are encoded by one single exon, exon T. The 3' untranslated region does not contain the classical polyadenylation signal, AATAAA. Expression in COS-7 cells of a minigene constructed of a 5' rat cDNA fragment (1.3 Kb) ligated in-frame to a 3' genomic fragment at the NsiI site, which is located in exon M6/7 resulted in a transcript that was translated into a functional receptor; it bound PTH and showed PTH-stimulated accumulation of intracellular cAMP. Therefore, the PTH/PTHrP receptor gene contains alternative 3' sequences that allow cleavage and polyadenylation of its transcript. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NETHERLANDS INST DEV BIOL,UTRECHT,NETHERLANDS. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 41 TC 78 Z9 78 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 1994 VL 200 IS 3 BP 1290 EP 1299 DI 10.1006/bbrc.1994.1591 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NL388 UT WOS:A1994NL38800018 PM 8185578 ER PT J AU ABRUTYN, E MOSSEY, J BERLIN, JA BOSCIA, J LEVISON, M PITSAKIS, P KAYE, D AF ABRUTYN, E MOSSEY, J BERLIN, JA BOSCIA, J LEVISON, M PITSAKIS, P KAYE, D TI DOES ASYMPTOMATIC BACTERIURIA PREDICT MORTALITY AND DOES ANTIMICROBIAL TREATMENT REDUCE MORTALITY IN ELDERLY AMBULATORY WOMEN SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE BACTERIURIA; URINARY TRACT INFECTIONS; RISK FACTORS; HEALTH STATUS INDICATORS; OUTCOME AND PROCESS ASSESSMENT (HEALTH CARE) ID URINARY-TRACT INFECTIONS; NO THERAPY; SURVIVAL; EPIDEMIOLOGY; POPULATION; HEALTH AB Objective: To determine whether asymptomatic bacteriuria in elderly ambulatory women is a marker of increased mortality and, if so, whether it is because of an association with other determinants of mortality or because asymptomatic bacteriuria is itself an independent cause, the removal of which might improve longevity. Design: A cohort study and a controlled clinical trial of the effect of antimicrobial treatment. Setting: A geriatric center and 21 continuing care retirement communities. Participants: Women without urinary tract catheters. Measurements: Urine cultures every 6 months (the same organism at 10(5) colony-forming units or more per mL on two midstream urine specimens defined asymptomatic bacteriuria), comorbidity, and mortality. Results: In the observational study, infected residents (n = 318) were older, and sicker, and had higher mortality (18.7 per 100 000 resident-days) than uninfected residents (n = 1173; 10.1 per 100 000 resident-days). However, in a multivariate Cox analysis, infection was not related to mortality (relative risk, 1.1; P > 0.2), whereas age at entry and self-rated health (score 1 [excellent] to 4 [bad or poor]) were strong predictors. In the clinical trial, mortality in 166 treated residents (13.8 per 100 000 resident-days) was comparable to that of 192 untreated residents (15.1 per 100 000 resident-days); the relative rate was 0.92 (95% CI, 0.57 to 1.47). The cure rates among treated and untreated residents were 82.9% and 15.6%, respectively. Conclusion: Urinary tract infection was not an independent risk factor for mortality, and its treatment did not lower the mortality rate. Screening and treatment of asymptomatic bacteriuria in ambulatory elderly women to decrease mortality do not appear warranted. C1 MED COLL PENN,EASTERN PENN PSYCHIAT INST,PHILADELPHIA,PA 19129. UNIV PENN,SCH MED,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129. RP ABRUTYN, E (reprint author), DEPT VET AFFAIRS MED CTR,38TH & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. FU NIA NIH HHS [AG03934] NR 31 TC 119 Z9 120 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1994 VL 120 IS 10 BP 827 EP 833 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NK458 UT WOS:A1994NK45800003 PM 7818631 ER PT J AU CAMERON, S TAYLOR, DS TEPAS, EC SPECK, NA MATHEYPREVOT, B AF CAMERON, S TAYLOR, DS TEPAS, EC SPECK, NA MATHEYPREVOT, B TI IDENTIFICATION OF A CRITICAL REGULATORY SITE IN THE HUMAN INTERLEUKIN-3 PROMOTER BY IN-VIVO FOOTPRINTING SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; LIGATION-MEDIATED PCR; NUCLEAR FACTOR; MESSENGER-RNA; HUMAN IL-3; GENE; TRANSCRIPTION; EXPRESSION; ENHANCER; REGION C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. DARTMOUTH COLL SCH MED,DEPT BIOCHEM,HANOVER,NH. FU NCI NIH HHS [R29CA1065]; NIDDK NIH HHS [R01 DK41758] NR 37 TC 60 Z9 60 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1994 VL 83 IS 10 BP 2851 EP 2859 PG 9 WC Hematology SC Hematology GA NL607 UT WOS:A1994NL60700012 PM 8180380 ER PT J AU HSU, LC KENNAN, WS SHEPEL, LA JACOB, HJ SZPIRER, C SZPIRER, J LANDER, ES GOULD, MN AF HSU, LC KENNAN, WS SHEPEL, LA JACOB, HJ SZPIRER, C SZPIRER, J LANDER, ES GOULD, MN TI GENETIC IDENTIFICATION OF MCS-1, A RAT MAMMARY-CARCINOMA SUPPRESSOR GENE SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; NORWAY RAT; DNA; HYBRIDIZATION; NORVEGICUS; LINKAGE; MOUSE; ADENOCARCINOGENESIS; INHERITANCE; ASSIGNMENT AB Women have inherited differences in their susceptibility to breast cancer, but the genes underlying this variation are difficult to identify. We have approached the problem of identifying breast cancer susceptibility genes by using a rat model. Inbred rat strains display differential susceptibilities to mammary carcinogenesis; the Copenhagen (COP) rat is resistant, while the Wistar-Furth (WF) rat is susceptible to induction of mammary tumors by 7,12-dimethylbenz[a]anthracene. Genetic breeding studies have shown that tumor resistance in the COP rat is a dominant phenotype, termed the rat mammary carcinoma suppressor trait. As a step toward defining the basis of this resistance, we undertook genetic mapping of this phenotype in a (WF x COP)F-1 x WF backcross by studying a large collection of microsatellite and minisatellite polymorphisms. A total of 114 genetic markers, covering approximately 75% of the rat genome, were genotyped in the backcross progeny. A marker on rat chromosome 2 was found to show linkage to the resistance phenotype. Genetic linkage was demonstrated both in a qualitative analysis (in which rats were defined as resistant if they developed 0 tumors and sensitive if they developed two or more tumors; LOD score, 4.0) and in a quantitative trait locus analysis (in which tumor number was used as the quantitative phenotype; LOD score, 3.8). We infer the existence of a gene, Mcs-1, on rat chromosome 2 that suppresses mammary carcinogenesis. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,MADISON,WI 53792. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. UNIV LIBRE BRUXELLES,DEV BIOL LAB,RHODE ST GENESE,BELGIUM. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. RI Gould, Michael/C-7414-2014; OI HSU, LIH-CHING/0000-0002-7816-3825 FU NCI NIH HHS [CA28954] NR 33 TC 52 Z9 52 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1994 VL 54 IS 10 BP 2765 EP 2770 PG 6 WC Oncology SC Oncology GA NL318 UT WOS:A1994NL31800045 PM 8168109 ER PT J AU EASTMAN, A GRANT, S LOCK, R TRITTON, T VANHOUTEN, N YUAN, JY AF EASTMAN, A GRANT, S LOCK, R TRITTON, T VANHOUTEN, N YUAN, JY TI CELL-DEATH IN CANCER AND DEVELOPMENT - AACR SPECIAL CONFERENCE IN CANCER-RESEARCH SO CANCER RESEARCH LA English DT Editorial Material C1 UNIV VERMONT,COLL MED,DEPT PHARMACOL,BURLINGTON,VT 05405. DARTMOUTH COLL SCH MED,DEPT PHARMACOL,HANOVER,NH 03756. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DIV HEMATOL ONCOL,RICHMOND,VA 23298. UNIV LOUISVILLE,JAMES GRAHAM BROWN CANC CTR,LOUISVILLE,KY 40292. UNIV TEXAS,MED BRANCH,DEPT INTERNAL MED & PEDIAT,GALVESTON,TX 77555. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. RI Lock, Richard/G-4253-2013 NR 0 TC 16 Z9 16 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1994 VL 54 IS 10 BP 2812 EP 2818 PG 7 WC Oncology SC Oncology GA NL318 UT WOS:A1994NL31800053 PM 8168115 ER PT J AU WEISS, MJ KELLER, G ORKIN, SH AF WEISS, MJ KELLER, G ORKIN, SH TI NOVEL INSIGHTS INTO ERYTHROID DEVELOPMENT REVEALED THROUGH IN-VITRO DIFFERENTIATION OF GATA-1(-) EMBRYONIC STEM-CELLS SO GENES & DEVELOPMENT LA English DT Article DE MOUSE; ES CELLS; ERYTHROID DEVELOPMENT; TRANSCRIPTION FACTOR; IN VITRO DIFFERENTIATION ID TRANSCRIPTION FACTOR GATA-1; LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS; DOMINANT CONTROL REGION; DNA-BINDING PROTEIN; C-MYB GENE; HEMATOPOIETIC DEVELOPMENT; HOMOLOGOUS RECOMBINATION; REGULATORY ELEMENT; ENDOTHELIAL-CELLS AB Mouse embryonic stem (ES) cells lacking the transcription factor GATA-1 do not produce mature red blood cells either in vivo or in vitro. To define the consequences of GATA-1 loss more precisely, we used an in vitro ES cell differentiation assay that permits enumeration of primitive (EryP) and definitive (EryD) erythroid precursors and recovery of pure erythroid colonies. In contrast to normal ES cells, GATA-1(-) ES cells fail to generate EryP precursors. EryD precursors, however, are normal in number but undergo developmental arrest and death at the proerythroblast stage. Contrary to initial expectations, arrested GATA-1(-)-definitive proerythroblasts express GATA target genes at normal levels. Transcripts of the related factor GATA-2 are remarkably elevated in GATA-1(-) proerythroblasts. These findings imply substantial interchangeability of GATA factors in vivo and suggest that GATA-1 normally serves to repress GATA-2 during erythropoiesis. The approach used here is a paradigm for the phenotypic analysis of targeted mutations affecting hematopoietic development. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. HOWARD HUGHES MED INST,BOSTON,MA. RI Weiss, Mitchell/A-1245-2013 FU NIDDK NIH HHS [R01 DK-43285] NR 83 TC 484 Z9 492 U1 2 U2 8 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1994 VL 8 IS 10 BP 1184 EP 1197 DI 10.1101/gad.8.10.1184 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NN726 UT WOS:A1994NN72600005 PM 7926723 ER PT J AU TONTONOZ, P HU, E GRAVES, RA BUDAVARI, AI SPIEGELMAN, BM AF TONTONOZ, P HU, E GRAVES, RA BUDAVARI, AI SPIEGELMAN, BM TI MPPAR-GAMMA-2 - TISSUE-SPECIFIC REGULATOR OF AN ADIPOCYTE ENHANCER SO GENES & DEVELOPMENT LA English DT Article DE ADIPOCYTE TRANSCRIPTION FACTOR; ADIPOCYTE P2 ENHANCER; ARF6; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR; RETINOID X RECEPTOR; ADIPOCYTE DIFFERENTIATION ID 9-CIS RETINOIC ACID; HORMONE RECEPTOR SUPERFAMILY; PEROXISOMAL BETA-OXIDATION; GENE-EXPRESSION; ACTIVATED RECEPTOR; BINDING-PROTEIN; TRANSGENIC MICE; ADIPOSE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; THYROID-HORMONE AB Previously, we have isolated and characterized an enhancer from the 5'-flanking region of the adipocyte P2 (aP2) gene that directs high-level adipocyte-specific gene expression in both cultured cells and transgenic mice. The key regulator of this enhancer is a cell type-restricted nuclear factor termed ARF6. Target sequences for ARF6 in the aP2 enhancer exhibit homology to a direct repeat of hormone response elements (HREs) spaced by one nucleotide; this motif (DR-1) has been demonstrated previously to be the preferred binding site for heterodimers of the retinoid X receptor (RXR) and the peroxisome proliferator-activated receptor (PPAR). We have cloned a novel member of the peroxisome proliferator-activated receptor family designated mPPAR gamma 2, and we demonstrate that a heterodimeric complex of mPPAR gamma 2 and RXR alpha constitute a functional ARF6 complex. Expression of mPPAR gamma 2 is induced very early during the differentiation of several cultured adipocyte cell lines and is strikingly adipose-specific in vivo. mPPAR gamma 2 and RXR alpha form heterodimers on ARF6-binding sites in vitro, and antiserum to RXR alpha specifically inhibits ARF6 activity in adipocyte nuclear extracts. Moreover, forced expression of mPPAR gamma 2 and RXR alpha activates the adipocyte-specific aP2 enhancer in cultured fibroblasts, and this activation is potentiated by peroxisome proliferators, fatty acids, and 9-cis retinoic acid. These results identify mPPAR gamma 2 as the first adipocyte-specific transcription factor and suggest mechanisms whereby fatty acids, peroxisome proliferators, 9-cis retinoic acid, and other lipids may regulate adipocyte gene expression and differentiation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK31405-11]; NIGMS NIH HHS [T32 GM007753, T32 GM07753-14] NR 43 TC 1676 Z9 1719 U1 7 U2 37 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1994 VL 8 IS 10 BP 1224 EP 1234 DI 10.1101/gad.8.10.1224 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NN726 UT WOS:A1994NN72600008 PM 7926726 ER PT J AU WIGGS, JL HAINES, JL PAGLINAUAN, C FINE, A SPORN, C LOU, D AF WIGGS, JL HAINES, JL PAGLINAUAN, C FINE, A SPORN, C LOU, D TI GENETIC-LINKAGE OF AUTOSOMAL-DOMINANT JUVENILE GLAUCOMA TO 1Q21-Q31 IN 3 AFFECTED PEDIGREES SO GENOMICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; ATRIAL-NATRIURETIC-FACTOR; INTRAOCULAR-PRESSURE; AQUEOUS-HUMOR; HUMAN GENOME; PREVALENCE; EYES; MAP; DNA AB Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant Juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. We describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12cM. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA. RP WIGGS, JL (reprint author), TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT OPHTHALMOL,BOX 450,750 WASHINGTON ST,BOSTON,MA 02111, USA. RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [EY09847] NR 27 TC 70 Z9 73 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1994 VL 21 IS 2 BP 299 EP 303 DI 10.1006/geno.1994.1269 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NP161 UT WOS:A1994NP16100001 PM 8088822 ER PT J AU VAITHINATHAN, R BERSON, EL DRYJA, TP AF VAITHINATHAN, R BERSON, EL DRYJA, TP TI FURTHER SCREENING OF THE RHODOPSIN GENE IN PATIENTS WITH AUTOSOMAL-DOMINANT RETINITIS-PIGMENTOSA SO GENOMICS LA English DT Note ID MUTATION; IDENTIFICATION; FAMILIES C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [EY00169, EY08683] NR 18 TC 52 Z9 53 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1994 VL 21 IS 2 BP 461 EP 463 DI 10.1006/geno.1994.1301 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NP161 UT WOS:A1994NP16100033 PM 8088850 ER PT J AU BUMP, EA BRAUNHUT, SJ PALAYOOR, ST MEDEIROS, D LAI, LL CERCE, BA LANGLEY, RE COLEMAN, CN AF BUMP, EA BRAUNHUT, SJ PALAYOOR, ST MEDEIROS, D LAI, LL CERCE, BA LANGLEY, RE COLEMAN, CN TI NOVEL CONCEPTS IN MODIFICATION OF RADIATION SENSITIVITY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD DE IONIZING RADIATION; TERT-BUTYL HYDROPEROXIDE; SR-4077; ENDOTHELIAL CELLS; APOPTOSIS ID HUMAN-ENDOTHELIAL CELLS; IONIZING-RADIATION; INDUCED APOPTOSIS; IRRADIATION; CULTURE; GROWTH; EXPOSURE; DAMAGE; RADIOSENSITIZATION; GLUTATHIONE AB Purpose: To determine whether biological effects of radiation, such as apoptosis, that differ from classical clonogenic cell killing, can be modified with agents that would not be expected to modify classical clonogenic cell killing. This would expand the range of potential modifiers of radiation therapy. Methods and Materials: EL4 murine lymphoma cell apoptosis was determined by electrophoretic analysis of deoxyribonucleic acid (DNA) fragmentation. DNA was extracted 24 h after irradiation or addition of inducing agents. Modifiers of radiation-induced apoptosis were added immediately after irradiation. The effects of radiation on wounded endothelial monolayers were studied by scraping a line across the monolayer 30 min after irradiation. Cell detachment was used as an endpoint to determine the protective effect of prolonged exposure to retinol prior to irradiation. Results: EL4 cell apoptosis can be induced by tert-butyl hydroperoxide or the glutathione oxidant SR-4077. Radiation-induced EL4 cell apoptosis can be inhibited with 3-aminobenzamide, an agent that sensitizes cells to classical clonogenic cell killing. Radiation-induced endothelial cell detachment from confluent monolayers can be modified by pretreatment with retinol. Conclusion: These results raise the possibility that radiation could induce apoptosis by an oxidative stress mechanism that is different from that involved in classical clonogenic cell killing. These and other recent findings encourage the notion that differential modification of classical clonogenic cell killing and other important endpoints of radiation action may be possible. C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP,DEPT OPHTHALMOL,BOSTON,MA 02115. RP BUMP, EA (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 42391, CA-46776] NR 47 TC 13 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 15 PY 1994 VL 29 IS 2 BP 249 EP 253 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NN512 UT WOS:A1994NN51200005 PM 8195015 ER PT J AU PALAYOOR, ST BUMP, EA MALAKER, K LANGLEY, RE SAROFF, DM DELFS, JR HURWITZ, SJ COLEMAN, CN AF PALAYOOR, ST BUMP, EA MALAKER, K LANGLEY, RE SAROFF, DM DELFS, JR HURWITZ, SJ COLEMAN, CN TI MODIFICATION OF THE AEROBIC CYTOTOXICITY OF ETANIDAZOLE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD DE SR-2508; ETANIDAZOLE; VITAMIN-E SUCCINATE; APOPTOSIS; OXIDATIVE STRESS ID PROGRAMMED CELL-DEATH; CYTO-TOXICITY; SPINAL-CORD; MISONIDAZOLE; RADIATION; RADIOSENSITIZERS; GLUTATHIONE; ENHANCEMENT; MECHANISMS; INHIBITION AB Purpose: To determine the feasibility of modifying the aerobic cytotoxicity of etanidazole without interfering with the tumoricidal action of radiation plus etanidazole. Methods and Materials: The aerobic cytotoxicity of etanidazole was studied using two different models: (1) Induction of apoptosis in EL4 cells: apoptotic DNA fragmentation was analyzed by agarose gel electrophoresis following 24 h treatment with etanidazole alone or in combination with various modifiers. (2) Spinal cord neuronal loss in organotypic roller tube cultures: Survival of acetylcholinesterase positive ventral horn neurons was analyzed morphometrically following 72 h treatment with etanidazole alone or in combination with vitamin E succinate. Results: EtanidazoIe (10 mM) induced apoptosis in EL4 cells. This effect was suppressed by 24 h treatment with TPA, IBMX, the free radical scavenger TEMPOL or vitamin E succinate. Vitamin E succinate also protected spinal cord cultures from etanidazole-induced neuronal loss. Conclusion: These results suggest that it might be possible to modify the neurotoxicity of etanidazole with agents that would not be expected to interfere with the tumoricidal action of radiation plus etanidazole. C1 DANA FARBER CANC INST,BOSTON,MA. MANNITOBA CANC FDN,WINNIPEG,MB,CANADA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. MASSACHUSETTS COLL PHARM & ALLIED HLTH SCI,BOSTON,MA. RP PALAYOOR, ST (reprint author), HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 42391] NR 30 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 15 PY 1994 VL 29 IS 2 BP 289 EP 293 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NN512 UT WOS:A1994NN51200012 PM 8195021 ER PT J AU KAWAKAMI, A TIAN, QS STREULI, M POE, M EDELHOFF, S DISTECHE, CM ANDERSON, P AF KAWAKAMI, A TIAN, QS STREULI, M POE, M EDELHOFF, S DISTECHE, CM ANDERSON, P TI INTRON-EXON ORGANIZATION AND CHROMOSOMAL LOCALIZATION OF THE HUMAN TIA-1 GENE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTE-T; TARGET-CELL LYSIS; DNA FRAGMENTATION; PERFORIN; GRANULES; CYTOLYSIS AB TIA-1 is a 40-kDa cytotoxic granule-associated RNA-binding protein (p40-TIA-1), the expression of which is restricted to cytolytic lymphocytes. The major granule-associated species is a 15-kDa protein (p15-TIA-1) that seems to be derived from the carboxyl terminus of p40-TIA-1. Although some evidence suggests that p15-TIA-1 is derived from p40-TIA-1 by proteolytic processing, it is also possible that each isoform is derived from discrete mRNA initiated from alternative promoters within the TIA-1 gene. To learn more about the relationship between p15-TIA-1 and p40-TIA-1, we have determined the complete intron-exon organization of the TIA-1 gene. The gene consists of 13 exons separated by 12 intervening sequences and spans greater than 46 kb of DNA located on chromosome 2, band p13. The transcription start site of the mRNA transcript encoding p40-TIA-1 was identified by primer extension and S1 mapping analysis. The putative promoter region preceding this transcription start site stimulated the expression of a reporter gene in transfected Jurkat and YT cells. Attempts to identify a second promoter capable of initiating an mRNA encoding p15-TIA-1 were unsuccessful, supporting the possibility that p15-TIA-1 can be derived from p40-TIA-1 proteolytically. Granule-associated serine proteases that have been implicated in cytolytic lymphocyte killing (granzyme A and granzyme B) were unable to cleave TIA-1, suggesting that processing may occur before TIA-1 enters the cytotoxic granule. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. MERCK & CO INC,MERCK SHARP & DOHME RES LABS,RAHWAY,NJ 07065. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. FU NCI NIH HHS [CA53595]; NIAID NIH HHS [AI33600] NR 22 TC 29 Z9 34 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1994 VL 152 IS 10 BP 4937 EP 4945 PG 9 WC Immunology SC Immunology GA NK925 UT WOS:A1994NK92500022 PM 8176212 ER PT J AU RUSSELL, PS CHASE, CM WINN, HJ COLVIN, RB AF RUSSELL, PS CHASE, CM WINN, HJ COLVIN, RB TI CORONARY ATHEROSCLEROSIS IN TRANSPLANTED MOUSE HEARTS .2. IMPORTANCE OF HUMORAL IMMUNITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CARDIAC TRANSPLANTATION; VASCULAR REJECTION; ALLOGRAFTS; ARTERIOSCLEROSIS; ANTIBODIES; ANTIGENS; DISEASE; RAT AB Obstructive lesions in arterial vessels of transplanted organs constitute an important factor in the late failure of these organs, especially for the heart. The absence of obstructive lesions in syngeneic donor-recipient combinations, suggests that they depend upon recipient immune responsiveness. It is controversial whether humoral or cellular aspects of the immune response predominate in the process. The present experiments employed hearts transplanted between inbred mice. After brief preoperative immunosuppression of recipients with mAbs to CD4 and CD8 determinants, hearts transplanted between mice incompatible for histocompatibility Ags survived for prolonged periods and most developed typical, obstructive coronary lesions. Our quantitative scoring of vascular changes on tissue sections of excised hearts, grades both their severity and prevalence. Transplants between strains that produced Abs to donor cells (B10.A to B10.BR), developed coronary lesions exceeding those in the reverse combination in which no detectable Ab was formed (B10.BR to B10.A; p < 0.00001), even though their histoincompatibility was similar. Treatment of B10.A recipients of B10.BR hearts with an antiserum against the donor significantly increased coronary lesions (p < 0.0003) in a dose-dependent fashion. Coronary arteries of B10.BR hearts transplanted to C.B-17 SCID mice remained largely free of lesions, whereas transplants to SCID recipients that received continuing injections of an antiserum directed to Ags of the donor developed striking, obstructive coronary lesions. We conclude that humoral immunity can be the prime instigator of atheromatous changes that occur in transplanted hearts. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP RUSSELL, PS (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R0-1 HL43340] NR 21 TC 215 Z9 216 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1994 VL 152 IS 10 BP 5135 EP 5141 PG 7 WC Immunology SC Immunology GA NK925 UT WOS:A1994NK92500045 PM 8176230 ER PT J AU LEE, CH KOMINOS, D JACQUES, S MARGOLIS, B SCHLESSINGER, J SHOELSON, SE KURIYAN, J AF LEE, CH KOMINOS, D JACQUES, S MARGOLIS, B SCHLESSINGER, J SHOELSON, SE KURIYAN, J TI CRYSTAL-STRUCTURES OF PEPTIDE COMPLEXES OF THE AMINO-TERMINAL SH2 DOMAIN OF THE SYP TYROSINE PHOSPHATASE SO STRUCTURE LA English DT Article DE CRYSTAL STRUCTURE; SH2 DOMAIN; SIGNAL TRANSDUCTION; SYP TYROSINE PHOSPHATASE; TYROSINE PHOSPHORYLATION ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; SRC HOMOLOGY-2 DOMAIN; FACTOR RECEPTOR-BETA; PHOSPHORYLATED PEPTIDES; TRANSFORMING ACTIVITY; EXPRESSION CLONING; PDGF RECEPTOR; BINDING-SITE; PI 3-KINASE; PROTEIN AB Background: Src homology 2 (SH2) domains bind to phosphotyrosine residues in a sequence-specific manner, and thereby couple tyrosine phosphorylation to changes in the localization or catalytic activity of signal transducing molecules. Current understanding of SH2 specificity is based on the structures of SH2-peptide complexes of the closely-related Src and Lck tyrosine kinases. The tyrosine phosphatase Syp contains two SH2 domains that are relatively divergent from those of the tyrosine kinases, with distinct target specificities, and is thus well suited for structural studies aimed at extending our understanding of SH2 specificity. Results: Crystal structures of the amino-terminal SH2 domain of Syp in separate complexes with two high-affinity peptides, in complex with a non-specific peptide and in the uncomplexed form have been determined at between 2 angstrom and 3 angstrom resolution. The structure of the SH2 domain and the mode of high-affinity peptide binding is essentially similar to that seen in the Src and Lck structures. However, the binding interface is more extensive in Syp. Conclusions: Most SH2 targets have hydrophobic residues at the third position following the phosphotyrosine, and the Syp structure confirms that the peptide is anchored to the SH2 surface by this residue and by the phosphotyrosine. In addition, the Syp structure has revealed that sequence specificity can extend across the five residues following the phosphotyrosine, and has shown how the SH2 domain's surface topography can be altered with resulting changes in specificity, while conserving the structure of the central core of the domain. C1 ROCKEFELLER UNIV,MOLEC BIOPHYS LABS,1230 YORK AVE,NEW YORK,NY 10021. NYU MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02115. RI Lee, Chi-Hon/G-9190-2012 NR 49 TC 199 Z9 202 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD MAY 15 PY 1994 VL 2 IS 5 BP 423 EP 438 DI 10.1016/S0969-2126(00)00044-7 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NP380 UT WOS:A1994NP38000011 PM 7521735 ER PT J AU FISHBEIN, JM ROSENGARD, BR GIANELLO, P NICKELEIT, V GUZZETTA, PC SMITH, CV NAKAJIMA, K VITIELLO, D HILL, GM SACHS, DH AF FISHBEIN, JM ROSENGARD, BR GIANELLO, P NICKELEIT, V GUZZETTA, PC SMITH, CV NAKAJIMA, K VITIELLO, D HILL, GM SACHS, DH TI DEVELOPMENT OF TOLERANCE TO CLASS-II MISMATCHED RENAL-TRANSPLANTS AFTER A SHORT-COURSE OF CYCLOSPORINE THERAPY IN MINIATURE SWINE SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ALLOGRAFT SURVIVAL; DISPARATE; ACTIVATION; MECHANISM; IMMUNITY; PATHWAYS AB Our laboratory has reported previously spontaneous acceptance of class II-matched, single haplotype (but not 2 haplotype), class I-mismatched renal allografts in miniature swine. All class II-mismatched animals rejected acutely regardless of class I matching. We have also demonstrated recently that a short course of high dose (10 mg/kg/day for 12 days) CsA uniformly induces donor-specific tolerance to 2-haplotype, class I-mismatched renal allografts. The survival of 2-haplotype, fully MHC mismatched renal allografts was prolonged by the same treatment, but tolerance was not induced, as all animals rejected eventually. We have now tested this short course of immunosuppressive therapy for its effect on renal allografts mismatched selectively for 2 haplotypes at class II. We have observed long-term graft survival in 5 of 7 animals under these conditions. Each of the 5 acceptor animals was demonstrated to be specifically tolerant by its response either to donor-matched skin grafts or to a second donor-matched kidney transplant without further immunosuppression. These data suggest the existence of a common pathway for induction of specific transplantation tolerance to MHC antigens when these antigens are recognized on vascular endothelium under conditions of altered cytokine production. They also suggest that tolerance induction under these conditions requires matching for either class I or class II antigens, which may have implications for the mechanism by which peripheral tolerance is induced, as well as practical implications for the extension of these results to potential clinical practice. C1 MASSACHUSETTS GEN HOSP EAST,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02129. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI31046] NR 18 TC 28 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1994 VL 57 IS 9 BP 1303 EP 1308 DI 10.1097/00007890-199405150-00002 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NM012 UT WOS:A1994NM01200002 PM 8184465 ER PT J AU RUSSELL, PS CHASE, CM WINN, HJ COLVIN, RB AF RUSSELL, PS CHASE, CM WINN, HJ COLVIN, RB TI CORONARY ATHEROSCLEROSIS IN TRANSPLANTED MOUSE HEARTS .III. EFFECTS OF RECIPIENT TREATMENT WITH A MONOCLONAL-ANTIBODY TO INTERFERON-GAMMA SO TRANSPLANTATION LA English DT Article ID GRAFT ARTERIOSCLEROSIS; SKIN ALLOGRAFTS; IMMUNE-RESPONSE; INVIVO; REJECTION; ANTIGENS; COMPLEX; MICE AB Obstructive coronary arterial lesions in the vessels of transplanted hearts result from a complex process in which the immune response of the recipient plays a pivotal role. We have devised an experimental system in which mouse hearts, transplanted after brief treatment with mAbs to CD4 and CD8, survive and contract for many weeks. A high percentage of such hearts develop advanced, obstructive coronary lesions by 4 weeks. Migratory cells of recipient origin localize in the linings of affected vessels, and mediators of inflammation, including adhesion molecules, are present in increased amounts in characteristic locations. Histocompatibility antigen expression is also increased, and these substances may promote the formation of vascular lesions by acting as targets for immune responses. IFN-gamma synthesis has been demonstrated in grafts where it is postulated to be important in the expression of MHC molecules and macrophage activation. Here we report that continuing treatment with R4-6A2, an mAb to IFN-gamma, strikingly inhibits the formation of obstructive vascular lesions in mouse hearts transplanted to recipients incompatible for either class I or class II antigens (P<0.0001 for the former and P<0.03 for the latter). Immunohistologic studies showed reduction of the class II-positive mononuclear infiltrate, but focally enhanced endothelial class I expression remained. The mechanism for this effect of anti-IFN-gamma probably extends beyond the influence of anti-IFN-gamma on increased expression of histocompatibility antigens. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP RUSSELL, PS (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R0-1 HL43340] NR 16 TC 70 Z9 70 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1994 VL 57 IS 9 BP 1367 EP 1371 DI 10.1097/00007890-199405150-00014 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NM012 UT WOS:A1994NM01200014 PM 7910422 ER PT J AU OKAMOTO, T MURAYAMA, Y STRITTMATTER, SM KATADA, T ASANO, S OGATA, E NISHIMOTO, I AF OKAMOTO, T MURAYAMA, Y STRITTMATTER, SM KATADA, T ASANO, S OGATA, E NISHIMOTO, I TI AN INTRINSIC GUANINE-NUCLEOTIDE EXCHANGE INHIBITOR IN G(I2)ALPHA - SIGNIFICANCE OF G-PROTEIN SELF-SUPPRESSION WHICH ANTAGONIZES RECEPTOR SIGNAL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GTP-BINDING PROTEIN; FACTOR-II RECEPTOR; ALPHA-SUBUNIT; PERTUSSIS-TOXIN; IDENTIFICATION; PURIFICATION; PEPTIDE; REGION; CELLS; BRAIN AB The alpha subunit of G(i2) (G(i2)alpha) is a member of the heterotrimeric G protein family, which transduces receptor signals as a proto-oncogene product. We have found a novel self-suppressive region in G(i2)alpha near its C terminus. A polypeptide consisting of residues 338-352 of G(i2)alpha (G(i2)alpha-338-352) antagonizes receptor- and receptor peptide stimulated G(i2)alpha activation, without affecting basal activity. Antagonism by G(i2)alpha-338-352 is attributable to an interaction with activated G(i2)alpha, which is not competitive with receptor polypeptides. Combined with the reports suggesting the presence of self-suppressive domains in a juxta-C-terminal portion of G(i2)alpha and G(o) alpha, this study sup ports the hypothesis that G(i2)alpha-338-352 constitutes an intrinsic guanine nucleotide exchange inhibitor, which in turn antagonizes receptor stimulation, suggesting that G proteins are activated by receptors through relaxation of a self suppressive conformation. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEV BIOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02129. UNIV TOKYO,SCH MED,DEPT INTERNAL MED 4,BUNKYO KU,TOKYO 112,JAPAN. TOKYO INST TECHNOL,DEPT LIFE SCI,MIDORI KU,YOKOHAMA,KANAGAWA 227,JAPAN. CANC RES INST,TOSHIMA KU,TOKYO 170,JAPAN. NR 28 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 1994 VL 269 IS 19 BP 13756 EP 13759 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600009 PM 8188651 ER PT J AU WAKITA, T WANDS, JR AF WAKITA, T WANDS, JR TI SPECIFIC-INHIBITION OF HEPATITIS-C VIRUS EXPRESSION BY ANTISENSE OLIGODEOXYNUCLEOTIDES - IN-VITRO MODEL FOR SELECTION OF TARGET SEQUENCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-B-HEPATITIS; 5' UNTRANSLATED REGION; NON-A; TRANSLATION ARREST; VIRAL-RNA; OLIGONUCLEOTIDES; COMPLEMENTARY; REPLICATION; GENOME AB The effect of sense and antisense oligodeoxynucleotides (ODNs) on hepatitis C virus (HCV) gene expression was studied to determine the role of the highly conserved 5'-untranslated region in the life cycle of the virus. It was found that antisense ODNs complementary to nucleotides (nt) 38-65, 134-175, and 312-339 in the 5' noncoding region and 341-377 in the core open reading frame efficiently blocked HCV RNA translation. Overlapping ODNs that differed by only several nucleotides showed substantially different inhibition of HCV RNA translation. Fine sequence specificity testing at nt positions 351-377 revealed that ODNs as small as a 12-mer (nt 351-363) retained a high degree (80%) of inhibitory activity compared to ODNs of longer sequences. These results suggest that there are three highly specific domains in the 5' noncoding region and a sequence immediately downstream of the HCV core initiation codon that may be critical for translation of HCV RNA. This study also provides an experimental approach for the selection of target HCV RNA sequences susceptible to antisense effects, as well as for definition of functional regions of the genome necessary for viral replication. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA-357111]; NIAAA NIH HHS [AA-02666, AA-08169] NR 41 TC 122 Z9 125 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 1994 VL 269 IS 19 BP 14205 EP 14210 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600073 PM 8188703 ER PT J AU LYNN, RB FRIEDMAN, LS AF LYNN, RB FRIEDMAN, LS TI IRRITABLE-BOWEL-SYNDROME - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID FOOD INTOLERANCE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP LYNN, RB (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 12 PY 1994 VL 330 IS 19 BP 1390 EP 1391 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NK753 UT WOS:A1994NK75300023 ER PT J AU PETERSON, RD BARTEL, DP SZOSTAK, JW HORVATH, SJ FEIGON, J AF PETERSON, RD BARTEL, DP SZOSTAK, JW HORVATH, SJ FEIGON, J TI H-1-NMR STUDIES OF THE HIGH-AFFINITY REV BINDING-SITE OF THE REV RESPONSIVE ELEMENT OF HIV-1 MESSENGER-RNA - BASE PAIRING IN THE CORE BINDING-ELEMENT SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENE-EXPRESSION REQUIRES; VIRAL MESSENGER-RNA; TARGET SEQUENCE; VIRION EXPRESSION; TRANS-ACTIVATOR; PROTEIN; SPECTROSCOPY; CONFORMATION; ADJACENT AB H-1 NMR studies of a 30-nucleotide RNA oligonucleotide (RBE3), which contains a high-affinity binding site for Rev of the HIV-1 Rev responsive element (RRE), two derivatives of RBE3 (RBE3AA and RBE3-A), and the complex of RBE3 with peptides derived from the RNA binding domain of HIV-1 Rev, are presented. The high-affinity binding site of the RRE consists of an asymmetric internal loop and surrounding Watson-Crick base pairs. In the wild-type RRE, one of the stems is closed by a loop; this is replaced in REB3 by the stable UUCG tetraloop. NOE data suggest that the internal loop of the free RNA contains structural features that have been predicted on the basis of in vitro selection experiments [Bartel, D. P., et al. (1991) Cell 67, 529-536]. The structural features include a G(syn).G(anti) base pair, a G(anti).A(anti) base pair, and a looped out U. When the Rev peptide is bound to the RNA, the base pairs in the internal loop appear to be stabilized, although the RNA chemical shifts indicate that the RNA conformation undergoes some changes when bound by Rev peptide. C1 UNIV CALIF LOS ANGELES,DEPT CHEM & BIOCHEM,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. CALTECH,DIV BIOL,PASADENA,CA 91125. FU NIGMS NIH HHS [GM 07185, P01 GM 39558] NR 58 TC 94 Z9 94 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 10 PY 1994 VL 33 IS 18 BP 5357 EP 5366 DI 10.1021/bi00184a001 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK973 UT WOS:A1994NK97300001 PM 8180157 ER PT J AU REEDQUIST, KA FUKAZAWA, T DRUKER, B PANCHAMOORTHY, G SHOELSON, SE BAND, H AF REEDQUIST, KA FUKAZAWA, T DRUKER, B PANCHAMOORTHY, G SHOELSON, SE BAND, H TI RAPID T-CELL RECEPTOR-MEDIATED TYROSINE PHOSPHORYLATION OF P120, AN FYN/LCK SRC HOMOLOGY-3 DOMAIN-BINDING PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T-CELL ACTIVATION; SIGNAL TRANSDUCTION; PROTEIN-TYROSINE KINASE; SRC-FAMILY KINASES ID ANTIGEN RECEPTOR; KINASE P59FYN; ASSOCIATION; P56LCK; CD4; RESPONSIVENESS; ACTIVATION; EXPRESSION; FAMILY; SH2 AB Tyrosine phosphorylation of cellular proteins is the earliest identifiable event following T-cell antigen receptor (TCR) stimulation and is essential for activating downstream signaling machinery. Two Src-family protein-tyrosine kinases, the TCR-associated p59(fyn) (Fyn) and the CD4/8-associated p56(lck) (Lck), have emerged as the likely mediators of early tyrosine phosphorylation in T cells. Here, we show direct binding of a 120-kDa TCR-induced phosphotyrosyl polypeptide, p120, to glutathione S-transferase fusion proteins of the Src homology 3 (SH3) domains of Fyn, Lck, and p60(Src) (Src) but not other proteins. While binding of p120 to Fyn SH2 domain was phosphotyrosine-dependent as expected, its binding to the SH3 domain was independent of tyrosine phosphorylation, as shown by lack of competition with a phosphotyrosyl competitor peptide. In contrast, an SH3-specific proline-rich peptide completely abolished p120 binding to SH3. p120 was tyrosine-phosphorylated within 10 sec following stimulation of Jurkat cells with anti-CD3 monoclonal antibody, with maximal phosphorylation at 30 sec. Importantly, p120 was found associated with Fyn and Lck proteins in unstimulated Jurkat cells and served as an in vitro substrate for these kinases. These results provide evidence for a role of the SH3 domains of Fyn and Lck in the recruitment of early tyrosine-phosphorylation substrates to the TCR-associated tyrosine kinases. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. NR 36 TC 84 Z9 84 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 1994 VL 91 IS 10 BP 4135 EP 4139 DI 10.1073/pnas.91.10.4135 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800008 PM 7514295 ER PT J AU ROTHSTEIN, JD BRISTOL, LA HOSLER, B BROWN, RH KUNCL, RW AF ROTHSTEIN, JD BRISTOL, LA HOSLER, B BROWN, RH KUNCL, RW TI CHRONIC INHIBITION OF SUPEROXIDE-DISMUTASE PRODUCES APOPTOTIC DEATH OF SPINAL NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AMYOTROPHIC LATERAL SCLEROSIS; ANTIOXIDANT; FREE RADICALS; MOTOR NEURON; ORGANOTYPE CULTURE ID CENTRAL-NERVOUS-SYSTEM; CHOLINE-ACETYLTRANSFERASE; POSTNATAL-DEVELOPMENT; GLUTAMATE; TOXICITY; RILUZOLE; NUCLEUS; ACID AB Mutations in the gene for Cu/Zn superoxide dismutase (SOD1) have been detected in some families with an autosomal dominant form of amyotrophic lateral sclerosis; these mutations appear to reduce the activity of this enzyme. To determine whether decreased SOD activity could contribute to motor neuron loss, SOD1 was inhibited chronically with either antisense oligodeoxynucleotides or diethyldithiocarbamate in spinal cord organotypic cultures. Chronic inhibition of SOD resulted in the apoptotic degeneration of spinal neurons, including motor neurons, over several weeks. Motor neuron loss was markedly potentiated by the inhibition of glutamate transport. In this paradigm, motor neuron toxicity could be entirely prevented by the antioxidant N-acetylcysteine and, to a lesser extent, by the non-N-methyl-D-aspartate glutamate receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride. These data support the hypothesis that the loss of motor neurons in familial amyotrophic lateral sclerosis could be due to a reduction in SOD1 activity, possibly potentiated by inefficient glutamate transport. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. MASSACHUSETTS GEN HOSP, DAY NEUROMUSCULAR RES LAB, BOSTON, MA 02129 USA. RP JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, MEYER 5-119, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. RI rothstein, jeffrey/C-9470-2013 NR 38 TC 284 Z9 288 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 1994 VL 91 IS 10 BP 4155 EP 4159 DI 10.1073/pnas.91.10.4155 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800012 PM 7910402 ER PT J AU AOKI, Y ISSELBACHER, KJ CHERAYIL, BJ PILLAI, S AF AOKI, Y ISSELBACHER, KJ CHERAYIL, BJ PILLAI, S TI TYROSINE PHOSPHORYLATION OF BLK AND FYN SRC HOMOLOGY-2 DOMAIN-BINDING PROTEINS OCCURS IN RESPONSE TO ANTIGEN-RECEPTOR LIGATION IN B-CELLS AND CONSTITUTIVELY IN PRE-B CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PRE-B RECEPTOR; INTRACELLULAR SIGNALING; TYROSINE KINASE ID IMMUNOGLOBULIN LIGHT CHAIN; LYMPHOCYTES-B; LAMBDA-5; ASSOCIATION; GENE; EXPRESSION; COMPLEX; SURFACE; VPREB; IDENTIFICATION AB Proteins that bind to discrete domains of the Blk, Fyn, Lyn, and Btk protein tyrosine kinases were examined in pre-B cells that had not been subjected to any external stimulation, as well as in nonstimulated and antigen-receptor-ligated B cells. Proteins that bind to the Src homology 2 domains of Blk and Fyn were identified in B cells that had been activated with anti-IgM but were not identified in unstimulated B tells. A number of Blk and Fyn Src homology 2 domain-binding phosphoproteins were also observed in pre-B cells that had not been stimulated in vitro. The phosphoproteins seen in activated B cells potentially represent substrates that play a role in the pathway of antigen-receptor-mediated signaling. Distinct signaling pathways involving distinguishable kinase substrates may be relevant in pre-B-cell-receptor-mediated cell survival during ontogeny. These results indirectly support models that predict constitutive ligand-independent signaling by the pre-antigen receptor during lymphoid ontogeny. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [AI 27835] NR 41 TC 46 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 1994 VL 91 IS 10 BP 4204 EP 4208 DI 10.1073/pnas.91.10.4204 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800022 PM 7514299 ER PT J AU BILLMAN, GE HALLAQ, H LEAF, A AF BILLMAN, GE HALLAQ, H LEAF, A TI PREVENTION OF ISCHEMIA-INDUCED VENTRICULAR-FIBRILLATION BY OMEGA-3-FATTY-ACIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FISH OIL; MYOCARDIAL INFARCTION; CORONARY HEART DISEASE; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID ID SUDDEN CARDIAC DEATH; CALCIUM-CHANNEL; HEART; MODULATION; MECHANISMS; FISH AB A specially prepared dog model of myocardial infarction was used to test the efficacy of the long-chain polyunsaturated fish oil omega 3 fatty acids eicosapentaenoic (20:5 n-3) and docosahexaenoic (22:6 n-3) acids to prevent ischemia-induced malignant cardiac arrhythmias. The dogs had sustained a prior experimental myocardial infarction from ligation of the left anterior descending coronary artery, and a hydraulic cuff was implanted around the left circumflex artery at that operation. After recovery from that procedure the animals were tested during a treadmill exercise test. With compression of the left circumflex artery sensitive animals will predictably develop ventricular fibrillation (VF). In such prepared dogs an emulsion of fish oil fatty acids was infused i.v. over a 50- to 60-min period just before the exercise-plus-ischemia test, and the effect on development of VF was recorded. The infusion was 100 ml of a 10% (vol/vol) emulsion of a fish oil concentrate containing 70% omega 3 fatty acids with free eicosapentaenoic acid and docosahexaenoic acid composing 33.9% and 25.0% of that total, respectively. Alternatively, some animals similarly received an emulsion containing 5 ml of the free fatty acid concentrate plus 5 ml of a triacylglyerol concentrate containing 65% omega 3 fatty acids with eicosapentaenoic acid and docosahexaenoic acid composing 34.0% and 23.6% of that total, respectively. In seven of eight animals the infusion of the fish oil emulsion completely prevented the acute occurrence of VF in the susceptible animals (P < 0.005). In five of five of these animals the subsequent exercise-plus ischemia test after a similar infusion of an emulsion in which soy bean oil replaced the fish oil fatty acid concentrates resulted in prompt development of VF. Possible mechanisms for this protective effect of omega 3 fatty acids against exercise and ischemia-induced malignant arrhythmias are considered. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA 02132. RP BILLMAN, GE (reprint author), OHIO STATE UNIV,DEPT PHYSIOL,COLUMBUS,OH 45210, USA. RI Billman, George/E-2758-2011 FU NIDA NIH HHS [R01-DA05917]; NIDDK NIH HHS [R01-DK38165] NR 25 TC 218 Z9 220 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 1994 VL 91 IS 10 BP 4427 EP 4430 DI 10.1073/pnas.91.10.4427 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800067 PM 8183925 ER PT J AU WULLNER, U TESTA, CM CATANIA, MV YOUNG, AB PENNEY, JB AF WULLNER, U TESTA, CM CATANIA, MV YOUNG, AB PENNEY, JB TI GLUTAMATE RECEPTORS IN STRIATUM AND SUBSTANTIA-NIGRA - EFFECTS OF MEDIAL FOREBRAIN-BUNDLE LESIONS SO BRAIN RESEARCH LA English DT Article DE GLUTAMATE RECEPTOR; AUTORADIOGRAPHY; 6-HYDROXYDOPAMINE; SUBSTANTIA NIGRA; STRIATUM; PARKINSONS DISEASE ID EXCITATORY AMINO-ACID; SUBTHALAMIC NUCLEUS; BASAL GANGLIA; RAT STRIATUM; BINDING; NEURONS AB We examined NMDA-sensitive [H-3]glutamate, [H-3]AMPA, [H-3]kainate and metabotropic-sensitive [H-3]glutamate binding sites in neostriatum and substantia nigra pars reticulata (SNr) in rats after unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. One week after the lesion, NMDA, AMPA, kainate and metabotropic receptors were decreased in the ipsilateral neostriatum, whereas at three months NMDA receptors were increased while AMPA, kainate and metabotropic receptors were not changed. In the SNr at one week, only AMPA and metabotropic receptors were significantly decreased whereas three months after the lesion NMDA, AMPA and kainate binding sites were decreased. The early decrease of excitatory amino acid receptors in the striatum is likely to reflect degeneration of dopaminergic fibers, suggesting that specific subpopulations of excitatory amino acid binding sites are located on dopaminergic terminals. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,SERV NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Catania, Maria Vincenza/E-2627-2017 OI Catania, Maria Vincenza/0000-0002-9329-8517 FU NINDS NIH HHS [NS19613] NR 17 TC 94 Z9 94 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 9 PY 1994 VL 645 IS 1-2 BP 98 EP 102 DI 10.1016/0006-8993(94)91642-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA NK540 UT WOS:A1994NK54000012 PM 8062103 ER PT J AU DUFFIN, J DOUSE, MA VANALPHEN, J AF DUFFIN, J DOUSE, MA VANALPHEN, J TI EXCITATION OF UPPER CERVICAL INSPIRATORY NEURONS BY VAGAL-STIMULATION IN THE CAT SO NEUROREPORT LA English DT Article DE UPPER CERVICAL INSPIRATORY NEURONS; VAGUS NERVE STIMULATION; PERI-STIMULUS HISTOGRAM; CAT ID EXPIRATORY NEURONS; CROSS-CORRELATION; RESPIRATORY NEURONS; NODOSE GANGLION; RAT; CONNECTIONS; NERVE; CORD AB THE responses of 57 upper cervical inspiratory neurones to single shock stimuli applied to the ipsilateral cervical vagus nerve were recorded using peri-stimulus histograms in 19 cats. Many (47%) of the histograms showed a late latency (17.9 +/- 3.4 ms; mean +/- S.D.) broad peak following the stimulation preceding a similar peak in the histogram for the phrenic activity. Nine (16%) showed a short latency (5.2 +/- 1.2 ms) peak preceding that for the phrenic activity. These peaks were of narrow half-amplitude width (1.0 +/- 0.4 ms), indicative of a paucisynaptic pathway between the cervical vagus and the ipsilateral upper cervical inspiratory neurones. Such results suggest that the upper cervical inspiratory neurones are either monosynaptically excited via vagal fibres, or disynaptically excited via dorsal group inspiratory C1 UNIV TORONTO,DEPT ANAESTHESIA,TORONTO M5S 1A8,ON,CANADA. DENVER VA MED CTR,DENVER,CO 80220. RP DUFFIN, J (reprint author), UNIV TORONTO,DEPT PHYSIOL,MED SCI BLDG,TORONTO M5S 1A8,ON,CANADA. OI Duffin, James/0000-0003-2270-7392 NR 22 TC 5 Z9 5 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 1994 VL 5 IS 9 BP 1133 EP 1136 DI 10.1097/00001756-199405000-00028 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NN159 UT WOS:A1994NN15900029 PM 8080973 ER PT J AU PASCAL, SM SINGER, AU GISH, G YAMAZAKI, T SHOELSON, SE PAWSON, T KAY, LE FORMANKAY, JD AF PASCAL, SM SINGER, AU GISH, G YAMAZAKI, T SHOELSON, SE PAWSON, T KAY, LE FORMANKAY, JD TI NUCLEAR-MAGNETIC-RESONANCE STRUCTURE OF AN SH2 DOMAIN OF PHOSPHOLIPASE C-GAMMA-1 COMPLEXED WITH A HIGH-AFFINITY BINDING PEPTIDE SO CELL LA English DT Article ID GROWTH-FACTOR-RECEPTOR; SRC HOMOLOGY-2 DOMAIN; SIGNAL TRANSDUCTION; TYROSINE KINASE; LARGER PROTEINS; POINT MUTATION; EGF RECEPTOR; C-ABL; SPECTROSCOPY; EXPRESSION AB The solution structure of the C-terminal SH2 domain of phospholipase C-gamma 1 (PLC-gamma 1), in complex with a phosphopeptide corresponding to its Tyr-1021 high affinity binding site on the platelet-derived growth factor receptor, has been determined by nuclear magnetic resonance spectroscopy. The topology of the SH2-phosphopeptide complex is similar to previously reported Src and Lck SH2 complexes. However, the binding site for residues C-terminal to the phosphotyrosine (pTyr) is an extended groove that contacts peptide residues at the +1 to +6 positions relative to the pTyr. This striking difference from Src and Lck reflects the fact that the PLC-gamma 1 complex involves binding of a phosphopeptide with predominantly hydrophobic residues C-terminal to the pTyr and therefore serves as a prototype for a second class of SH2-phosphopeptide interactions. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,DIV MOLEC & DEV BIOL,TORONTO M5G 1X5,ON,CANADA. UNIV TORONTO,PROT ENGN NETWORK CTR EXCELLENCE,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,DEPT MED GENET,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,DEPT BIOCHEM,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,DEPT CHEM,TORONTO M5S 1A8,ON,CANADA. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP PASCAL, SM (reprint author), HOSP SICK CHILDREN,DIV BIOCHEM RES,555 UNIV AVE,TORONTO M5G 1X8,ON,CANADA. RI Pawson, Tony/E-4578-2013; Gish, Gerald/C-7228-2017 NR 60 TC 226 Z9 228 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 6 PY 1994 VL 77 IS 3 BP 461 EP 472 DI 10.1016/0092-8674(94)90160-0 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK970 UT WOS:A1994NK97000016 PM 8181064 ER PT J AU SUGIMOTO, S WANDLESS, TJ SHOELSON, SE NEEL, BG WALSH, CT AF SUGIMOTO, S WANDLESS, TJ SHOELSON, SE NEEL, BG WALSH, CT TI ACTIVATION OF THE SH2-CONTAINING PROTEIN-TYROSINE-PHOSPHATASE, SH-PTP2, BY PHOSPHOTYROSINE-CONTAINING PEPTIDES DERIVED FROM INSULIN-RECEPTOR SUBSTRATE-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC HOMOLOGY-2 DOMAINS; SIGNAL TRANSDUCTION; SH2 DOMAIN; PHOSPHATIDYLINOSITOL 3'-KINASE; IRS-1; LOCALIZATION; INTERMEDIATE; ASSOCIATION; EXPRESSION; CORKSCREW AB The cytoplasmic insulin receptor substrate-1 (IRS-1), which is multiply phosphorylated in vivo on tyrosine residues, is a known binding protein for the tandem src homology 2 (SH2) domain containing protein tyrosine phosphatase, SH-PTP2. Eleven phosphotyrosyl (pY) pep- tides from IRS-1 were screened for allosteric activation of SH-PTP2 phosphatase activity toward phosphorylated, reduced, carboxyamidomethylated, and maleylated-lysozyme. Peptides IRS-1pY895, IRS-1pY1172, and IRS-1pY1222 showed up to 50-fold acceleration of dephosphorylation. Analyses of Arg to Lys mutants in either or both SH2 domains indicate that both the N-terminal (N-SH2) and C-terminal (C-SH2) domains function in allosteric activation. Direct determination by surface plasmon resonance of the dissociation constants between pY peptides and glutathione S-transferase fusions to N-SH2 and C-SH2 domains reveals a 240-fold preference of the N-SH2 domain (compared with the C-SH2 domain) for IRS-1pY1172. The N-SH2 domain prefers IRS-1pY1172>IRS-1pY895> IRS 1pY1222, whereas C-SH2 domain prefers IRS-1pY1222>IRS-1pY895>IRS-1pY1172. These data suggest that each SH2 domain can bind to a distinct pY sequence of multiply phosphorylated protein substrates such as IRS-1, while activating hydrolysis at a third pY sequence bound in the SH-PTP2 active site. In addition, proteolysis and truncation studies reveal an autoregulatory function for the C-terminal region of SH-PTP2. Limited tryptic cleavage within the C terminus results in 27-fold activation of protein tyrosine phosphatase activity. The activated tryptic fragment cannot be further activated by pY peptide binding to the SH2 do mains indicating that autoregulatory functions of the SH2 domains are dependent on the C-terminal region. These data suggest that multiple levels for control of SH-PTP2 enzymatic activity may exist in vitro and in vivo. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. BETH ISRAEL HOSP,MOLEC MED UNIT,BOSTON,MA 02115. FU NIDCR NIH HHS [DERC 36836]; NIGMS NIH HHS [GM20011]; PHS HHS [49152] NR 55 TC 168 Z9 169 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13614 EP 13622 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400081 PM 7513703 ER PT J AU GABUZDA, D BUSCIGLIO, J CHEN, LB MATSUDAIRA, P YANKNER, BA AF GABUZDA, D BUSCIGLIO, J CHEN, LB MATSUDAIRA, P YANKNER, BA TI INHIBITION OF ENERGY-METABOLISM ALTERS THE PROCESSING OF AMYLOID PRECURSOR PROTEIN AND INDUCES A POTENTIALLY AMYLOIDOGENIC DERIVATIVE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; BETA-PROTEIN; ENDOPLASMIC-RETICULUM; BREFELDIN-A; NEXIN-II; DEGRADATION; IDENTIFICATION; CLEAVAGE; PEPTIDE; DOMAIN AB The cellular mechanisms which lead to the generation and pathological deposition of beta amyloid in Alzheimer's disease are unknown. In this report we describe the proteolytic processing of the amyloid precursor protein (APP) to an 11.5-kDa COOH-terminal derivative which contains the full-length beta amyloid sequence. This processing step normally occurs at low levels in parallel with APP maturation in the secretory pathway. Inhibition of oxidative energy metabolism by sodium azide or the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone increased the proteolysis of APP to the 11.5-kDa derivative by about 80-fold with accumulation of this APP derivative in the Golgi complex. Agents which inhibit protein transport in the secretory pathway, including monensin and brefeldin A, also increased the production of the 11.5-kDa derivative. Inhibition of APP maturation demonstrated that the 11.5-kDa derivative could be produced by proteolysis of immature APP. These results demonstrate that APP processing to potentially amyloidogenic COOH-terminal derivatives occurs in either the endoplasmic reticulum or Golgi complex and can be modulated by the state of cellular energy metabolism. Deficits in oxidative energy metabolism have recently been found in the cerebral cortex of patients with Alzheimer's disease. These findings raise the possibility that energy-related metabolic stress may lead to altered metabolism of APP and contribute to amyloidosis in Alzheimer's disease. C1 HARVARD UNIV, CHILDRENS HOSP, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. MIT, WHITEHEAD INST BIOMED RES, DEPT BIOL, CAMBRIDGE, MA 02142 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. RI Matsudaira, Paul/H-1475-2012 OI Matsudaira, Paul/0000-0002-8399-3276 FU NIA NIH HHS [AG09229]; NINDS NIH HHS [NS30352] NR 46 TC 256 Z9 264 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13623 EP 13628 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400082 PM 8175797 ER PT J AU WENNBERG, JE BARRY, MJ AF WENNBERG, JE BARRY, MJ TI OUTCOMES RESEARCH SO SCIENCE LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP WENNBERG, JE (reprint author), DARTMOUTH COLL SCH MED,HANOVER,NH 03755, USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 6 PY 1994 VL 264 IS 5160 BP 758 EP 759 DI 10.1126/science.7513442 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ949 UT WOS:A1994NJ94900006 PM 7513442 ER PT J AU WOOD, WC BUDMAN, DR KORZUN, AH COOPER, MR YOUNGER, J HART, RD MOORE, A ELLERTON, JA NORTON, L FERREE, CR BALLOW, AC FREI, E HENDERSON, IC AF WOOD, WC BUDMAN, DR KORZUN, AH COOPER, MR YOUNGER, J HART, RD MOORE, A ELLERTON, JA NORTON, L FERREE, CR BALLOW, AC FREI, E HENDERSON, IC TI DOSE AND DOSE INTENSITY OF ADJUVANT CHEMOTHERAPY FOR STAGE-II, NODE-POSITIVE BREAST-CARCINOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CANCER AB Background. Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity. Methods. The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the second. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group. Results. After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P<0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity. Conclusions. The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved. C1 N SHORE UNIV HOSP,MANHASSET,NY. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ST LUKES HOSP,MILWAUKEE,WI. NEW YORK HOSP,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. S NEVADA CANC RES FDN,LAS VEGAS,NV. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. FRONTIER SCI TECHNOL & RES FDN,AMHERST,MA. DANA FARBER CANC INST,BOSTON,MA. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. RP WOOD, WC (reprint author), EMORY UNIV,SCH MED,WINSHIP CANC CTR,DEPT SURG,1364 CLIFTON RD NE,ATLANTA,GA 30322, USA. FU NCI NIH HHS [CA-33601, CA-12449, CA-35279] NR 19 TC 538 Z9 543 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 5 PY 1994 VL 330 IS 18 BP 1253 EP 1259 DI 10.1056/NEJM199405053301801 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NJ512 UT WOS:A1994NJ51200001 PM 8080512 ER PT J AU MUSS, HB THOR, AD BERRY, DA KUTE, T LIU, ET KOERNER, F CIRRINCIONE, CT BUDMAN, DR WOOD, WC BARCOS, M HENDERSON, IC AF MUSS, HB THOR, AD BERRY, DA KUTE, T LIU, ET KOERNER, F CIRRINCIONE, CT BUDMAN, DR WOOD, WC BARCOS, M HENDERSON, IC TI C-ERBB-2 EXPRESSION AND RESPONSE TO ADJUVANT THERAPY IN WOMEN WITH NODE-POSITIVE EARLY BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REQUIRING PROLONGED OBSERVATION; THYMIDINE LABELING INDEX; DNA FLOW-CYTOMETRY; PROGNOSTIC-SIGNIFICANCE; PROLIFERATIVE ACTIVITY; CELL-PROLIFERATION; BOWEL PROJECT; PROTEIN; P53; OVEREXPRESSION AB Background. The role of molecular markers in predicting the response to treatment of breast cancer is poorly defined. The Cancer and Leukemia Group B (CALGB) conducted a randomized adjuvant-chemotherapy trial (CALGB 8541) comparing three doses (high, moderate, and low) of cyclophosphamide, doxorubicin, and fluorouracil in 1572 women with node-positive breast cancer. This study (CALGB 8869) was designed to determine whether the DNA index, the S-phase fraction, c-erbB-2 expression, or p53 accumulation could be used as a marker to identify a subgroup of patients more likely than others to benefit from high doses of chemotherapy. Methods. Tissue blocks were obtained from 442 patients randomly selected from the larger CALGB trial. Paraffin sections from the primary lesions were analyzed for DNA content, S-phase fraction, c-erbB-2 expression, and p53 accumulation. Results. Patients randomly assigned to the high-dose regimen of adjuvant chemotherapy had significantly longer disease-free and overall survival if their tumors had c-erbB-2 overexpression. No further information was gained by adding the data on S-phase fraction or p53 accumulation to the analysis. There was no clear evidence of a dose-response effect in patients with minimal or no c-erbB-2 expression. Conclusions. There is a significant dose-response effect of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil in patients with overexpression of c-erbB-2 but not in patients with no c-erbB-2 expression or minimal c-erbB-2 expression. Overexpression of c-erbB-2 may be a useful marker to identify the patients who are most likely to benefit from high doses of adjuvant chemotherapy. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CANC & LEUKEMIA GRP B,STAT OFF,DURHAM,NC. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC. N SHORE UNIV HOSP,NEW YORK HOSP,NEW YORK,NY. EMORY UNIV,ATLANTA,GA 30322. ROSWELL PK MEM INST,DEPT MED,BUFFALO,NY. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA-44768, CA-03927, CA-31946] NR 51 TC 855 Z9 865 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 5 PY 1994 VL 330 IS 18 BP 1260 EP 1266 DI 10.1056/NEJM199405053301802 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NJ512 UT WOS:A1994NJ51200002 PM 7908410 ER PT J AU GOLDHIRSCH, A GELBER, RD AF GOLDHIRSCH, A GELBER, RD TI UNDERSTANDING ADJUVANT CHEMOTHERAPY FOR BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID POSITIVE AXILLARY NODES; CYCLOPHOSPHAMIDE; METHOTREXATE; FLUOROURACIL; TRIAL; CMF C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP GOLDHIRSCH, A (reprint author), INT BREAST CANC STUDY GRP,LUGANO,SWITZERLAND. NR 15 TC 13 Z9 13 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 5 PY 1994 VL 330 IS 18 BP 1308 EP 1309 DI 10.1056/NEJM199405053301811 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NJ512 UT WOS:A1994NJ51200011 PM 7908411 ER PT J AU GELBER, RD GOLDHIRSCH, A AF GELBER, RD GOLDHIRSCH, A TI RADIOTHERAPY TO THE CONSERVED BREAST - IS IT AVOIDABLE IF THE CANCER IS SMALL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PRIMARY RADIATION-THERAPY; LUMPECTOMY; IRRADIATION; RECURRENCE; TAMOXIFEN; SURGERY C1 OSPED CIVICO,DEPT ONCOL,INT BREAST CANC STUDY GRP,LUGANO,SWITZERLAND. RP GELBER, RD (reprint author), DANA FARBER CANC INST,DIV BIOSTAT,INT BREAST CANC STUDY GRP,44 BINNEY ST,BOSTON,MA 02115, USA. NR 24 TC 14 Z9 14 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 4 PY 1994 VL 86 IS 9 BP 652 EP 654 DI 10.1093/jnci/86.9.652 PG 3 WC Oncology SC Oncology GA NH714 UT WOS:A1994NH71400002 PM 8158691 ER PT J AU MORROW, NS NOVIN, D GARRICK, T AF MORROW, NS NOVIN, D GARRICK, T TI MICROINJECTION OF THYROTROPIN-RELEASING-HORMONE IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS STIMULATES GASTRIC CONTRACTILITY SO BRAIN RESEARCH LA English DT Article DE PARAVENTRICULAR NUCLEUS; THYROTROPIN-RELEASING HORMONE; GASTRIC CONTRACTILITY; VAGOTOMY ID CENTRAL NERVOUS-SYSTEM; ACID SECRETION; OXYTOCIN ANTAGONIST; RAT HYPOTHALAMUS; IMMUNOREACTIVE INNERVATION; LESION FORMATION; VAGUS NERVE; TRH; NEURONS; MOTILITY AB Changes in gastric contractility following microinjection of thyrotropin-releasing hormone (TRH) into the paraventricular nucleus of the hypothalamus (PVN) were examined in fasted, urethane-anesthetized rats. Gastric contractility was measured with extraluminal force transducers and analysed by computer. Unilateral and bilateral PVN microinjections of TRH (0.5 and 1.0 mu g) significantly increased the force index of gastric contractions from 0 to 60 min postinjection, when compared with animals microinjected with 0.1 mu g TRH, 0.1% BSA or TRH (0.5 and 1.0 mu g TRH) in sites adjacent to the PVN. The gastric force index was also significantly elevated from 61 to 120 min postinjection in rats receiving bilateral PVN microinjections of TRH (0.5 and 1.0 mu g) Peak gastric responses occurred within 10-20 min postinjection and represented an approximately eight-fold increase over basal values. In the remaining groups, the force index was not significantly altered from preinjection values. The excitatory action of TRH (1.0 mu g) on gastric contractility was completely abolished by subdiaphragmatic vagotomy. These results suggest that TRH acts within the PVN to stimulate gastric contractility via vagal-dependent pathways. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE,CTR GASTROENTER BIOL,DEPT PSYCHIAT,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT RES,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. RP MORROW, NS (reprint author), UNIV CALIF LOS ANGELES,DEPT PSYCHOL,405 HILGARD AVE,1285 FRANZ HALL,LOS ANGELES,CA 90024, USA. FU NIDDK NIH HHS [DK 41301]; NIMH NIH HHS [NIMH 5T32 M17140] NR 38 TC 10 Z9 12 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 MAY 2 PY 1994 VL 644 IS 2 BP 243 EP 250 DI 10.1016/0006-8993(94)91686-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NJ164 UT WOS:A1994NJ16400009 PM 8050036 ER PT J AU DAVIDOFF, R PICARD, MH FORCE, T THOMAS, JD GUERRERO, JL MCGLEW, S WEYMAN, AE AF DAVIDOFF, R PICARD, MH FORCE, T THOMAS, JD GUERRERO, JL MCGLEW, S WEYMAN, AE TI SPATIAL AND TEMPORAL VARIABILITY IN THE PATTERN OF RECOVERY OF VENTRICULAR GEOMETRY AND FUNCTION AFTER ACUTE OCCLUSION AND REPERFUSION SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CANINE LEFT-VENTRICLE; MECHANICAL DISADVANTAGE; CORONARY-OCCLUSION; OXYGEN-CONSUMPTION; CONSCIOUS DOGS; EXPANSION; DILATION; INJURY; MODEL AB Myocardial ischemia and infarction are known to cause changes in both ventricular shape and function. Little is known about the recovery of ventricular geometry after transient myocardial ischemia and its relationship to recovery of function. To examine the pattern of recovery of ventricular geometry following transient coronary artery occlusion and to assess the relationship of this to the return of systolic function, we used echocardiography to study 13 dogs following 15-minute occlusion of the left anterior descending coronary artery. During ischemia, total endocardial surface area (ESA) increased from 32.55 +/- 1.77 to 45.36 +/- 3.18 cm(2) (p = 0.001). The most striking increase was at the apex, where circumference increased from 5.04 +/- 0.24 at baseline to 7.86 +/- 0.43 cm at the end of occlusion (p = 0.0001), an increase of 58%. During reperfusion, ventricular geometry rapidly returned toward normal (baseline), with recovery of 80% of the increase in ESA evident by 15 minutes of reperfusion. Recovery of systolic function was substantially slower (p < 0.005 for all periods of observation during the 2 hours of reperfusion). During reperfusion, recovery of ventricular geometry and function was not uniform throughout the ischemic bed. The apex recovered most slowly, with the centroid of the area of abnormal contraction progressively moving along the long axis of the left ventricle toward the apex. There was also a progressive decrease in the radius of the area of dysfunction, from 2.0 +/- 0.15 at end occlusion to 0.13 +/- 0.07 cm at 120 minutes of reperfusion (p = 0.0001). There was no difference in blood flow between the apical and anterior segments during ischemia or reperfusion. Reperfusion favorably reduced the ischemic zone dilation before recovery of active systolic function and geometric recovery thus may be important in determining ultimate functional recovery. In addition, recovery of function proceeded inward towards the center of the ischemic territory and in a wavefront from the base to apex. This heterogeneous and asymmetric recovery suggests that sampling at one point within the ischemic zone may not reflect the true temporal pattern of recovery. C1 BOSTON UNIV,MED CTR,DEPT MED,EVANS MEM DEPT CLIN RES,BOSTON,MA. BOSTON UNIV,MED CTR,DEPT MED,DIV CARDIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Guerrero, Jorge/I-3666-2015; OI Guerrero, Jorge/0000-0003-4315-7318; Force, Thomas/0000-0002-0450-8659; Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-07535, HL-26215] NR 28 TC 14 Z9 15 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 1994 VL 127 IS 5 BP 1231 EP 1241 DI 10.1016/0002-8703(94)90041-8 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NJ879 UT WOS:A1994NJ87900005 PM 8172051 ER PT J AU MATSUURA, H PALACIOS, IF DEC, GW FALLON, JT GARAN, H RUSKIN, JN YASUDA, T AF MATSUURA, H PALACIOS, IF DEC, GW FALLON, JT GARAN, H RUSKIN, JN YASUDA, T TI INTRAVENTRICULAR-CONDUCTION ABNORMALITIES IN PATIENTS WITH CLINICALLY SUSPECTED MYOCARDITIS ARE ASSOCIATED WITH MYOCARDIAL NECROSIS SO AMERICAN HEART JOURNAL LA English DT Article ID VIRAL MYOCARDITIS; ANTIMYOSIN FAB; ANTIBODY; MICE; CARDIOMYOPATHY; DIAGNOSIS; SYSTEM; BLOCK; MODEL AB Twenty-nine patients with suspected myocarditis, either with or without intraventricular conduction abnormalities, were investigated for degree of myocardial necrosis by antimyosin scintigraphy. Among those 29 patients, 16 had intraventricular conduction abnormalities. Antimyosin scans were analyzed for heart/lung ratios and semiquantitative visual uptake scores (0 to 4+ scale). Of the 16 patients with conduction abnormalities, 15 (94%) demonstrated visual antimyosin uptake versus 7 (54%) of 13 cases without conduction abnormalities (p < 0.03). In addition, the heart/lung ratios and uptake scores were significantly higher in the group with conduction abnormalities than in the group without (1.64 +/- 0.31 vs 1.39 +/- 0.20, p < 0.03; and 2.3 +/- 0.7 vs 1.4 +/- 0.7, p < 0.005; respectively). In conclusion, intraventricular conduction abnormalities in patients with suspected myocarditis were more strongly associated with active and more severe myocardial necrosis as judged by antimyosin imaging than patients with normal electrocardiograms. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,MED SERV,DIV NUCL MED,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 22 TC 8 Z9 9 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 1994 VL 127 IS 5 BP 1290 EP 1297 DI 10.1016/0002-8703(94)90048-5 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NJ879 UT WOS:A1994NJ87900012 PM 8172058 ER PT J AU ISOBE, M SOUTHERN, JF YAZAKI, Y AF ISOBE, M SOUTHERN, JF YAZAKI, Y TI SCINTIGRAPHIC DETECTION OF EARLY CARDIAC REJECTION BY IODINE 123-LABELED MONOCLONAL-ANTIBODY DIRECTED AGAINST MONOMORPHIC DETERMINANT OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ANTIGENS SO AMERICAN HEART JOURNAL LA English DT Article ID DONOR CLASS-I; HEART-TRANSPLANTATION; INCREASED EXPRESSION; ALLOGRAFT-REJECTION; KIDNEY ALLOGRAFTS; MHC ANTIGENS; RAT; INDUCTION; CELLS; CYCLOSPORINE AB Although it has been shown that early cardiac rejection can be visualized by radioimmunoscintigraphy targeting major histocompatibility complex class II antigen, the use of antibodies that bind to a polymorphic determinant of class II antigen has certain disadvantages for clinical application. This investigation was designed to examine the feasibility of scintigraphic detection of cardiac allograft rejection by using a monoclonal antibody that reacts with a monomorphic determinant of rat IA antigens. Twenty PVG rats (RT1(C)) and five DA rats (RT1(a)) underwent heterotopic transplantation with DA hearts. Two of the 20 allografted rats were treated with FK506 (2 mg/kg/day). Seventeen rats were injected intravenously with 80 mu Ci of iodine 123-labeled monoclonal antibody reactive with a monomorphic determinant of rat major histocompatibility complex class lr antigens (0x6) 16 hours before scintigraphy, and images were compared with those obtained by injection of I-123-labeled monoclonal antibody against a polymorphic determinant of class II antigens (F17-23-6, anti-RT1(a)) (n = 8). Background activity was higher in rats injected with 0x6 than in rats injected with F17-23-6. Uptake of labeled 0x6 in the grafts reflected the severity of rejection as determined by histopathologic criteria. Rejecting allografts with lymphocyte infiltration but without myocyte necrosis could be identified by the scintigraphy with use of labeled 0x6. The ratios of radioactivity in the graft to radioactivity in the blood (percent injected dose per gram of tissue) in rats with grade IA and IB rejection (0.56 +/- 0.12, n = 4, p < 0.001) and in rats with grade IIIA and IIIB rejection (0.60 +/- 0.09, n = 4, p < 0.001) were significantly greater than in rats with nonrejecting grafts (0.24 +/- 0.08, n = 9). In conclusion, radioimmune scintigraphy with use of I-123-labeled monoclonal antibody directed against a monomorphic determinant of major histocompatibility complex class II antigen appears to be a sensitive and noninvasive method for detecting cardiac allograft rejection. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV TOKYO,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. RP ISOBE, M (reprint author), SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 1,3-1-1 ASAHI,MATSUMOTO,NAGANO 390,JAPAN. NR 34 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 1994 VL 127 IS 5 BP 1309 EP 1317 DI 10.1016/0002-8703(94)90050-7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NJ879 UT WOS:A1994NJ87900014 PM 7513490 ER PT J AU RIVERA, JM VANDERVOORT, PM MELE, D SIU, S MORRIS, E WEYMAN, AE THOMAS, JD AF RIVERA, JM VANDERVOORT, PM MELE, D SIU, S MORRIS, E WEYMAN, AE THOMAS, JD TI QUANTIFICATION OF TRICUSPID REGURGITATION BY MEANS OF THE PROXIMAL FLOW CONVERGENCE METHOD - A CLINICAL-STUDY SO AMERICAN HEART JOURNAL LA English DT Article ID DOPPLER ECHOCARDIOGRAPHIC METHOD; SYSTEMIC BLOOD-FLOW; VENTRICULAR SEPTAL-DEFECT; SURFACE-AREA METHOD; MITRAL REGURGITATION; VALVULAR REGURGITATION; REAL-TIME; ORIFICE SIZE; CANINE MODEL; VOLUME FLOW AB Quantitation of valvular regurgitation remains an important goal in clinical cardiology. It has been described previously that with the use of color Doppler flow mapping, simple measurements of apparent jet size do not correlate closely with quantitative regurgitant indices. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Assuming hemispherical convergence, flow rate Q can be calculated as Q = 2 pi r(2)v(a), where v(a) is the aliasing velocity at a distance r from the orifice. For maximal accuracy, previously validated correction factors must be used to account for the flattening effect of the isovelocity contours close to the orifice and for the actual sector angle subtended by the valve leaflets (ct), to yield a flow rate formula Q = 2 pi r(2)v(a).(v(p)/v(p) - V-a).(alpha/180), where v(p) is the orifice velocity obtained by continuous wave Doppler. In 45 patients (35 in sinus rhythm, 10 with atrial fibrillation) with tricuspid regurgitation, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated using the proximal flow convergence method and were compared with values obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (SV) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler two-dimensional method with r = 0.95 (y = 0.94x + 0.99) and Delta SV = -0.3 +/- 5.2 cm(3). Regurgitant flow rates (Q) calculated by both methods showed a similar correlation: r = 0.96 (y = 0.97x + 45) and Delta Q = 1.6 +/- 429 cm(3)/min. The correlation for regurgitant fraction (RF) calculated by both techniques was r = 0.90 (y = 1.07x - 0.02) and Delta RF = -0.002 +/- 0.008. All correlations were slightly better for the group of patients in sinus rhythm than for the group in atrial fibrillation. This study demonstrates that the proximal flow convergence method is an accurate and reproducible technique for quantifying tricuspid regurgitation. This approach is easier and less time-consuming than the Doppler two-dimensional method. While improvements of this method are to be expected, flow calculations based on the proximal flow field show excellent results and appear appropriate for clinical use. C1 MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. CLEVELAND CLIN FDN,CLEVELAND,OH. RI rivera, miguel/D-5026-2014 NR 48 TC 37 Z9 37 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 1994 VL 127 IS 5 BP 1354 EP 1362 DI 10.1016/0002-8703(94)90056-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NJ879 UT WOS:A1994NJ87900020 PM 8172065 ER PT J AU ORWOLL, E RIDDLE, M PRINCE, M AF ORWOLL, E RIDDLE, M PRINCE, M TI EFFECTS OF VITAMIN-D ON INSULIN AND GLUCAGON-SECRETION IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE VITAMIN-D; INSULIN; GLUCAGON; DIABETES ID CALCIUM-BINDING PROTEIN; PERFUSED RAT PANCREAS; D-DEFICIENT RAT; GLUCOSE-TOLERANCE; 1,25-DIHYDROXYVITAMIN-D3; MODE; RADIOIMMUNOASSAY; CALCIFEROL; REPLETION; KIDNEY AB Vitamin D has been shown to increase insulin release from pancreatic islet cells in vitro, and to improve insulin secretion in vitamin D-deficient animals. Few attempts have been made to evaluate this issue directly in humans. We studied 35 otherwise healthy diabetic subjects in the early spring at the seasonal nadir of 25-hydroxyvitamin D [25(OH)D] concentrations (mean 35 +/- 7 nmol/L). Easting glucose, insulin, C-peptide, and glucagon concentrations, and their responses to Sustacal stimulation were not related to indexes of mineral metabolism. In 20 subjects, a double-blinded, placebo-controlled, crossover trial of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] treatment (1 mu g/d for 4 d) had no effect on fasting or stimulated glucose, insulin, C-peptide, or glucagon concentrations. However, insulin and C-peptide responses to Sustacal after 1,25(OH)(2)D treatment were related to duration of diabetes (r(2) = 0.28, P = 0.052 and r(2) = 0.25, P = 0.002, respectively) in that short duration correlated with improvement after 1,25(OH)(2)D treatment. Hence, vitamin D nutrition, or 1,25(OH)(2)D therapy, had no major effect on glucose homeostasis in non-insulin-dependent diabetes mellitus. C1 PORTLAND VA MED CTR, PORTLAND, OR USA. OREGON HLTH SCI UNIV, PORTLAND, OR 97201 USA. INDIANA UNIV, DEPT MED, INDIANAPOLIS, IN USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 31 TC 106 Z9 107 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1994 VL 59 IS 5 BP 1083 EP 1087 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NJ050 UT WOS:A1994NJ05000022 PM 8172095 ER PT J AU HERBERT, V AF HERBERT, V TI VITAMIN-B-12 AND ELDERLY PEOPLE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID PROTEIN-BOUND VITAMIN-B12; MALABSORPTION RP HERBERT, V (reprint author), BRONX VET ADM MED CTR, 130 W KINGSBRIDGE RD, BRONX, NY 10468 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1994 VL 59 IS 5 BP 1093 EP 1094 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NJ050 UT WOS:A1994NJ05000025 PM 8172098 ER PT J AU HERBERT, V AF HERBERT, V TI STAGING VITAMIN-B-12 (COBALAMIN) STATUS IN VEGETARIANS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE VITAMIN B-12; SERUM HOLOTRANSCOBALAMIN II; TRANSCOBALAMIN II; COBALAMIN; VEGANS; SERUM TOTAL VITAMIN B-12; SERUM HOLOHAPTOCORRIN; B-12 HAPTOCORRIN; HAPTOCORRIN ID INTRINSIC-FACTOR; HOLOTRANSCOBALAMIN-II; TRANSCOBALAMIN-II; R-BINDER; SERUM; DEFICIENCY; AIDS; GLUTATHIONE; ABSORPTION; DEPLETION AB When one stops eating vitamin B-12 (cobalamins), one passes through four stages of negative cobalamin balance: serum depletion [low holotranscobalamin II, ie, low vitamin B-12 on transcobalamin II (TCII)], cell depletion (decreasing holohaptocorrin and low red cell vitamin B-12 concentrations), biochemical deficiency (slowed DNA synthesis, elevated serum homocysteine and methylmalonate concentrations), and, finally, clinical deficiency (anemia). Serum vitamin B-12 is on two proteins: the circulating vitamin B-12 delivery protein, TCII, and the circulating vitamin B-12 storage protein, haptocorrin. Because TCII is depleted of vitamin B-12 within days after absorption stops, the best screening test for early negative vitamin B-12 balance is a measurement of vitamin B-12 on TCII (holoTCII). HoloTCII falls below the bottom of its normal range long before total serum vitamin B-12 (which is mainly vitamin B-12 on haptocorrin) falls below the bottom of its normal range. C1 MT SINAI MED CTR, NEW YORK, NY 10029 USA. BRONX VET AFFAIRS MED CTR, NEW YORK, NY USA. NR 68 TC 142 Z9 142 U1 1 U2 9 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1994 VL 59 IS 5 SU S BP 1213S EP 1222S PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NK656 UT WOS:A1994NK65600019 PM 8172125 ER PT J AU KAPLAN, MA FERRY, JA HARRIS, NL JACOBSON, JO AF KAPLAN, MA FERRY, JA HARRIS, NL JACOBSON, JO TI CLONAL ANALYSIS OF POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS, USING BOTH EPISOMAL EPSTEIN-BARR-VIRUS AND IMMUNOGLOBULIN GENES AS MARKERS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE B-CELL LYMPHOMA; CLONALITY; EPSTEIN-BARR VIRUS; IMMUNOGLOBULIN GENES; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS ID RENAL-ALLOGRAFT REJECTION; REED-STERNBERG CELLS; HODGKINS-DISEASE; TRANSPLANT RECIPIENTS; ORGAN-TRANSPLANTATION; LYMPHOMAS; REARRANGEMENTS; CLASSIFICATION; EVOLUTION; ANTIBODY AB The authors analyzed the clonality of 15 sample's of B-cell lymphoproliferations arising in eight organ allograft recipients, using immunoglobulin (Ig) gene rearrangement and the fused terminal fragment of episomal Epstein-Barr virus (EBV) DNA as independent clonal markers. The tumors arose from 1 month to 4 years following transplantation. All tumors were monomorphous, high-grade lymphomas of immunoblastic (6 cases), large-cell noncleaved (centroblastic, 1 case), or small noncleaved (1 case) type. All tumors were highly aggressive and failed to respond to decreased immunosuppression alone. Each tumor had clonal Ig gene rearrangements, including those that were negative for surface Ig. In 13 of 15 specimens (seven of the eight cases), the tumors also contained latent, circularized EBV genome. In 10 specimens from six patients, the tumors contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. Three specimens from one patient showed more than one band of episomal EBV DNA, suggesting oligoclonal expansion, despite the detection of only a single clone by Ig gene rearrangement. Linear replicating EBV DNA was not detected in any of the cases. Synchronous or metachronous specimens from multiple sites were studied in five patients, four of which were EBV-positive cases. Two patients had identical Ig gene arrangements in each specimen, indicating a single neoplastic clone at all sites; one case was EBV-negative, and the other had identical EBV episomes in each specimen. In the other three cases, apparently different Ig gene rearrangements were found at different sites. In two of these, however, the same predominant EBV episome was present at each site, indicating a common clonal origin. The third case had oligoclonal EBV bands in each specimen, with distinct patterns in at least two different sites, suggesting true multiclonality. Analysis of EBV genomes is a useful adjunct to Ig gene analysis in assessing the clonality of these lesions. C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT MED, HEMATOL ONCOL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 43 TC 48 Z9 48 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1994 VL 101 IS 5 BP 590 EP 596 PG 7 WC Pathology SC Pathology GA NK475 UT WOS:A1994NK47500008 PM 8178765 ER PT J AU WELCH, LS MICHAELS, D ZOLOTH, SR ALEXANDER, V BALMES, J BARNHART, S BRESNITZ, E BONHAM, D CASTEN, P CHRISTIANI, D COOK, R COOPER, K CULLEN, M DEHART, D DEMERS, R FAGAN, K FRUMKIN, H FRANK, A FRIEDMAN, G GARMAN, R GIBSON, M HAKE, J HERBERT, R HESSL, S HINCAMP, D HODGSON, M HOLSTEIN, E JOHNS, RE KALAMOTO, M KERN, D KAY, K LANG, E LANGWORTHY, JR LOCKEY, J MERCHANT, J MILLER, K MORSE, L MULLOY, K OLIVER, C ROSENSTOCK, L ROUNDTREE, P SCHENKER, M SHARPE, I SCHWARTZ, D SIMMONS, J SLIWINSKI, J STEIN, C TENCZA, A WALLERSTEIN, N WAGNER, G AF WELCH, LS MICHAELS, D ZOLOTH, SR ALEXANDER, V BALMES, J BARNHART, S BRESNITZ, E BONHAM, D CASTEN, P CHRISTIANI, D COOK, R COOPER, K CULLEN, M DEHART, D DEMERS, R FAGAN, K FRUMKIN, H FRANK, A FRIEDMAN, G GARMAN, R GIBSON, M HAKE, J HERBERT, R HESSL, S HINCAMP, D HODGSON, M HOLSTEIN, E JOHNS, RE KALAMOTO, M KERN, D KAY, K LANG, E LANGWORTHY, JR LOCKEY, J MERCHANT, J MILLER, K MORSE, L MULLOY, K OLIVER, C ROSENSTOCK, L ROUNDTREE, P SCHENKER, M SHARPE, I SCHWARTZ, D SIMMONS, J SLIWINSKI, J STEIN, C TENCZA, A WALLERSTEIN, N WAGNER, G TI THE NATIONAL SHEET-METAL WORKER ASBESTOS DISEASE SCREENING-PROGRAM - RADIOLOGIC FINDINGS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE ASBESTOSIS; PLEURAL ABNORMALITIES; PARENCHYMAL ABNORMALITIES; SHIPYARD WORKER; CIGARETTE SMOKING; B READER; SHEET METAL WORKERS ID PLEURAL FIBROSIS; CIGARETTE-SMOKING; IRREGULAR OPACITIES; PULMONARY-FUNCTION; EXPOSURE; CONSTRUCTION; PNEUMOCONIOSIS; ABNORMALITIES; RADIOGRAPHS; PREVALENCE AB This report presents data gathered from a series of asbestos disease screening examinations of 9,605 United States sheet metal workers who were first employed in the trade at least 20 years before the examination. The overall prevalence of asbestos-related radiographic changes was 31.1%: 18.8% had pleural abnormalities alone, 6.6% had parenchymal abnormalities (International Labour Office (ILO) score of 110 or higher) alone, and 5.7% had both. Among those with 40 years or more since entering the trade, 41.5% had radiographic signs of asbestos-related disease, 24.2% pleural alone, 7.7% parenchymal atone, and 9.6% both pleural and parenchymal abnormalities. After controlling for several surrogates for asbestos exposure level, cigarette smoking was found to increase risk of parenchymal, and more modestly, pleural abnormalities. Each pack-year was associated with a 1% increased prevalence odds ratios for parenchymal abnormalities (ILO category 1 compared to category 0), and 0.4% increased prevalence odds ratios for pleural abnormalities. A history of shipyard employment also produced significantly increased prevalence odds ratios for each radiographic category. More that 90% of chest radiographs were classified by A or B readers; after adjustment for other risk factors, A readers were more likely to report parenchymal abnormalities of category 1, but not more likely to report category 2 or pleural abnormalities, than B readers. (C) 1994 Wiley-Liss, Inc. C1 CUNY,SCH MED,SOPHIE DAVIS SCH BIOMED EDUC,DEPT COMMUNITY HLTH & SOCIAL MED,NEW YORK,NY 10031. CUNY HUNTER COLL,SCH HLTH SCI,NEW YORK,NY 10021. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA. UNIV WASHINGTON,SEATTLE,WA 98195. MED COLL PENN,PHILADELPHIA,PA 19129. OSCHNER CLIN,NEW ORLEANS,LA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNION HLTH CARE CORP,BUFFALO,NY. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,RICHMOND,VA. YALE UNIV,NEW HAVEN,CT. UNIV OKLAHOMA,OKLAHOMA CITY,OK. WAYNE STATE UNIV,DETROIT,MI. UNIV CLEVELAND HOSP,CLEVELAND,OH 44106. EMORY UNIV,ATLANTA,GA 30322. UNIV KENTUCKY,MED CTR,LEXINGTON,KY 40536. TEXAS LUNG INST,HOUSTON,TX. GUTHRIE CLIN,SAYRE,PA. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. COOK CTY OCCUPAT HLTH CLIN,CHICAGO,IL. JOB MED,CHICAGO,IL. UNIV PITTSBURGH,PITTSBURGH,PA. ENVIRONM HLTH ASSOCIATES,EDISON,NJ. UNIV UTAH,MED CTR,SALT LAKE CITY,UT 84112. BARLOW OCCUPAT HLTH CTR,LOS ANGELES,CA. ROGER WILLIAMS GEN HOSP,PROVIDENCE,RI 02908. NATL JEWISH HOSP,DENVER,CO. UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. UNIV IOWA,IOWA CITY,IA. MARSHALL UNIV,SCH MED,HUNTINGTON,WV. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV ARKANSAS,LITTLE ROCK,AR 72204. UNIV CALIF DAVIS,DAVIS,CA 95616. MEHARRY MED COLL,NASHVILLE,TN 37208. UNIV ROCHESTER,SCH MED,ROCHESTER,NY. EASTERN NEW YORK OCCUPAT HLTH PROGRAM,LATHAM,NY. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. NIOSH,DIV RESP DIS STUDIES,MORGANTOWN,WV 26505. RP WELCH, LS (reprint author), GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC, USA. OI Frumkin, Howard/0000-0001-7079-3534 NR 35 TC 21 Z9 21 U1 0 U2 1 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 MAY PY 1994 VL 25 IS 5 BP 635 EP 648 DI 10.1002/ajim.4700250504 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NG239 UT WOS:A1994NG23900003 PM 8030635 ER PT J AU NATOWICZ, MR EVANS, JE AF NATOWICZ, MR EVANS, JE TI ABNORMAL BILE-ACIDS IN THE SMITH-LEMLI-OPITZ SYNDROME SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SMITH-LEMLI-OPITZ; BILE ACIDS; FAST ATOM BOMBARDMENT MASS SPECTROMETRY ID NOSOLOGY AB The urinary bile acids from four patients with Smith-Lemli-Opitz (SLO) syndrome were analyzed by continuous flow fast atom bombardment mass spectrometry. Two types of abnormalities were noted: (1) a deficiency of normal bile acids (cholenoates) and (2) the presence of abnormal species postulated to be cholenoates and cholestenoates. The finding of abnormal urinary bile acids in children with SLO syndrome led to further investigation of the cholesterol metabolic pathway and to the delineation of a new inborn error of metabolism, deficient conversion of 7-dehydrocholesterol to cholesterol [Irons et al., 1993]. The abnormalities of urinary bile acids, if confirmed by further structural analyses and studies of additional patients, provide an explanation for various aspects of the gastrointestinal abnormalities and growth retardation noted in SLO syndrome and suggest that exogenous bile acid replacement may play an important role in the therapy of patients with this syndrome. (C) 1994 Wiley-Liss, Inc. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV BIOMED SCI,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP NATOWICZ, MR (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. NR 21 TC 47 Z9 47 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 1994 VL 50 IS 4 BP 364 EP 367 DI 10.1002/ajmg.1320500413 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA NG003 UT WOS:A1994NG00300012 PM 8209917 ER PT J AU ZEITELS, SM VAUGHAN, CW AF ZEITELS, SM VAUGHAN, CW TI TONGUE-BASE CANCER RESECTION WITH PARTIAL SUPRAGLOTTIC LARYNGECTOMY SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOL & LARYNGOL,243 CHARLES ST,BOSTON,MA 02114. NR 0 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 SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAY-JUN PY 1994 VL 15 IS 3 BP 197 EP 203 DI 10.1016/0196-0709(94)90005-1 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA NK472 UT WOS:A1994NK47200005 PM 8024108 ER PT J AU SILLMAN, JS LEVINE, RA KOBLER, JB AF SILLMAN, JS LEVINE, RA KOBLER, JB TI LASER-DOPPLER MEASUREMENTS OF INTRATEMPORAL FACIAL-NERVE BLOOD-FLOW SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID GUINEA-PIG COCHLEA; BELLS-PALSY; PARALYSIS; FLOWMETER; RAT AB Whereas the anatomy of the vasculature supplying the intratemporal facial nerve is well known, little is known of the dynamics of blood flow within the nerve. The present study was performed to ascertain whether laser Doppler flowmetry (LDF) could detect changes in blood flow within the tympanic segment of the rabbit facial nerve. Compression of the facial nerve immediately distal to the geniculate ganglion resulted in an 80-95 percent reduction in blood flow in the tympanic segment of the nerve, whereas distal neurovascular compression had no effect. Blood flow in the tympanic segment of the nerve fell 40-60 percent during ipsilateral common carotid artery occlusion, but no change occurred with contralateral carotid occlusion. Signal-averaging techniques detected a sinusoidal amplitude modulation of the LDF flow signal that was synchronous with the cardiac cycle. The peak-to-peak amplitude of this modulation was reduced by proximal nerve compression, and the reduction in amplitude was in proportion to the overall reduction in the LDE flow signal. The authors conclude that the direction of blood flow in the tympanic segment of the rabbit facial nerve is primarily proximal to distal. Acute changes in blood flow within the tympanic segment of the nerve could readily be detected using LDF. This technique offers the possibility of monitoring human facial nerve blood flow, and may help elucidate the pathophysiology of various facial neuropathies. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 39 TC 9 Z9 10 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 1994 VL 15 IS 3 BP 327 EP 334 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA PG160 UT WOS:A1994PG16000008 PM 8579136 ER PT J AU WASIK, MA SIOUTOS, N TUTTLE, M BUTMARC, JR KAPLAN, WD KADIN, ME AF WASIK, MA SIOUTOS, N TUTTLE, M BUTMARC, JR KAPLAN, WD KADIN, ME TI CONSTITUTIVE SECRETION OF SOLUBLE INTERLEUKIN-2 RECEPTOR BY HUMAN T-CELL LYMPHOMA XENOGRAFTED INTO SCID MICE - CORRELATION OF TUMOR VOLUME WITH CONCENTRATION OF TUMOR-DERIVED SOLUBLE INTERLEUKIN-2 RECEPTOR IN BODY-FLUIDS OF THE HOST MICE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID IL-2 RECEPTOR; CYTOKINE RECEPTORS; MOLECULAR-CLONING; SURFACE-ANTIGENS; EXPRESSION; MURINE; LEUKEMIA; INVITRO; BIOLOGY; DISEASE AB Increased serum concentration of soluble ct-chain receptor for interleukin-2 (sIL-2R) has been noted inpatients with a variety of inflammatory conditions and lymphoid malignancies including T cell leukemia and lymphoma. Elevated sIL-2R serum levels seen in lymphoid malignancies appear to correlate with the clinical stage of disease. However, because sIL-2R is produced by normal activated lymphocytes, it has been uncertain whether serum sIL-2R in such conditions is derived from tumor cells or normal immune cells responding to the tumor. To address this question, we used a model of human (CD30(+)) anaplastic, large T cell lymphoma transplanted into immunodeficient SCID mice. Reverse transcription polymerase chain reaction of tumor RNA showed that the tumor, designated mJB6, contains mRNA for alpha-chain of human IL-2R. Furthermore, 15 to 25% of tumor cells stained with anti-human IL-2R alpha-chain mAb. Solid phase ELISA analysis of serum samples from mice bearing mJB6 lymphoma showed high concentrations of human sIL-2R. None of the control mice without lymphoma or with human nonlymphoid tumors (prostatic carcinoma, ovarian carcinoma, and glioblastoma multiforme) showed detectable human sIL-2R. The sIL-2R serum titers of mJB6-bearing mice cor-related strongly with tumor volume (P < 0.0001). Tumors as small as 0.4 to 0.8 mm(3) could be detected by this method. The sensitivity of sIL-2R ELISA exceeded at least 150 times the sensitivity of conventional radioisotopic tumor detection. Total resection of mJB6 tumors resulted in complete clearance of sIL-2R from the murine serum within 48 hours with a half-life of 6 hours. Accordingly, partial resection led to a significant decrease in sIL-2R followed by gradual increase with tumor regrowth, sIL-2R was also detected in the urine of mJB6-transplanted mice. As in serum, urine concentrations of sIL-2R were proportional to tumor mass (P < 0.02). Based on these findings we postulate that malignant cells are a major source of serum sIL-2R in patients with lymphoid tumors. In addition, our data further support monitoring sIL-2R concentration in body fluids as a sensitive method to detect change in tumor volume in such patients. C1 BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. DANA FARBER CANC CTR,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 35 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1994 VL 144 IS 5 BP 1089 EP 1097 PG 9 WC Pathology SC Pathology GA NK795 UT WOS:A1994NK79500026 PM 8178932 ER PT J AU FEIGIN, AM NINOMIYA, Y BEZRUKOV, SM BRYANT, BP MOORE, PA KOMAI, M WACHOWIAK, M TEETER, JH VODYANOY, I BRAND, JG AF FEIGIN, AM NINOMIYA, Y BEZRUKOV, SM BRYANT, BP MOORE, PA KOMAI, M WACHOWIAK, M TEETER, JH VODYANOY, I BRAND, JG TI ENHANCEMENT OF GUSTATORY NERVE-FIBERS TO NACL AND FORMATION OF ION CHANNELS BY COMMERCIAL NOVOBIOCIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SALT TASTE TRANSDUCTION; AMILORIDE ID ELECTRICAL TONGUE STIMULATIONS; CHORDA TYMPANI FIBERS; TASTE RECEPTOR-CELLS; AMILORIDE INHIBITION; NA+ CHANNEL; SALT TASTE; SODIUM; RESPONSES; ORGANIZATION; TRANSDUCTION AB Single fibers of the rat chorda tympani nerve were used to study the mechanism of action of the antibiotic novobiocin on salt taste transduction. In the rat, novobiocin selectively enhanced the responses of sodium-specific and amiloride-sensitive chorda tympani nerve fibers (N type) without affecting more broadly responsive cation-sensitive and amiloride-insensitive fibers (E type). In the presence of amiloride, novobiocin was ineffective at enhancing the response of N-type fibers toward sodium chloride. Novobiocin also increased the conductance of bilayers formed from neutral lipids by forming nonrectifying ion channels with low conductance (similar to 7 pS in 110 mM NaCl), long open times (several seconds and longer), and high cation selectivity. Amiloride did not alter either the conductance or kinetics of these novobiocin channels. These observations suggest that even though novobiocin is able to form cation channels in lipid bilayers, and possibly in cell membranes as well, its action on the salt-taste response is through modulation of existing amiloride-sensitive sodium channels. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. ASAHI UNIV,DEPT ORAL PHYSIOL,GIFU 50102,JAPAN. NIH,BETHESDA,MD 20892. ST PETERSBURG NUCL PHYS INST,ST PETERSBURG 188350,RUSSIA. OFF NAVAL RES,ARLINGTON,VA 22217. RP FEIGIN, AM (reprint author), UNIV PENN,MONELL CHEM SENSES CTR,3500 MARKET ST,PHILADELPHIA,PA 19104, USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1994 VL 266 IS 5 BP C1165 EP C1172 PN 1 PG 8 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500003 ER PT J AU EBERHART, GP WEST, DB BOOZER, CN ATKINSON, RL AF EBERHART, GP WEST, DB BOOZER, CN ATKINSON, RL TI INSULIN SENSITIVITY OF ADIPOCYTES FROM INBRED MOUSE STRAINS RESISTANT OR SENSITIVE TO DIET-INDUCED OBESITY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AKR/J MOUSE STRAIN; SWR/J MOUSE STRAIN; HIGH-FAT DIET; GLUCOSE TRANSPORT; 2-DEOXYGLUCOSE ID WHITE ADIPOSE-TISSUE; GLUCOSE-TRANSPORT; SKELETAL-MUSCLE; RAT ADIPOCYTES; ZUCKER RATS; CELLS; MECHANISMS; YOUNG AB We evaluated insulin sensitivity in epididymal adipocytes from two mouse strains shown to be either sensitive (AKR/J, n = 14) or resistant (SWR/J, n = 12) to the development of obesity when fed a high-fat diet. Half of each strain was fed a chow (CH) diet (12% fat), and half received a sweetened condensed milk (CM) diet (33% fat). After 1 wk, epididymal adipose depots were removed and digested with collagenase, and glucose transport was measured with labeled 2-deoxyglucose. Plasma glucose and insulin were slightly higher in AKR/J than SWR/J mice (glucose: 139.7 vs. 118.8 mg/dl, P < 0.06; insulin: 3.45 vs. 2.99 ng/ml, P < 0.04). One week of high-fat feeding increased adipose depot mass and carcass lipid in both strains to approximately the same extent. Adipocytes from AKR/J mice had greater insulin-stimulated glucose transport compared with SWR/J mice at both submaximal and maximal insulin levels (P < 0.0001). Short-term feeding of the high-fat diet increased AKR/J adipocyte insulin sensitivity but decreased the sensitivity of SWR/J adipocytes to insulin. The differences in adipocyte insulin sensitivity between strains were not explained by differences in adipocyte cell size. Access to the high-fat CM diet for 12 wk increased total dissected adipose depot size by 209% in the AKR/J mice and 82% in the SWR/J mice. These data clearly demonstrate that the two strains differ in adipocyte insulin sensitivity as well as sensitivity to dietary obesity. Increased adipocyte insulin sensitivity could contribute to a predisposition to increase adipose tissue lipid stores with diets high in fat content. C1 LOUISIANA STATE UNIV,PENNINGTON BIOMED RES CTR,OBESITY DIABET & METAB SECT,BATON ROUGE,LA 70808. MASSACHUSETTS GEN HOSP,DEPT ENDOCRINOL,BOSTON,MA 02114. DEPT VET AFFAIRS MED CTR,MED RES SERV,HAMPTON,VA 23667. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53706. NR 23 TC 23 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1994 VL 266 IS 5 BP R1423 EP R1428 PN 2 PG 6 WC Physiology SC Physiology GA NP996 UT WOS:A1994NP99600058 ER PT J AU FARAONE, SV TSUANG, MT AF FARAONE, SV TSUANG, MT TI MEASURING DIAGNOSTIC-ACCURACY IN THE ABSENCE OF A GOLD STANDARD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DSM-III-R; LATENT CLASS ANALYSIS; STRUCTURED CLINICAL INTERVIEW; INTERRATER RELIABILITY; PSYCHIATRIC-DIAGNOSIS; ATTENTION-DEFICIT; HIGH AGREEMENT; ERROR RATES; LOW KAPPA; AXIS-II AB Objective: with other medical colleagues. To defend psychiatry in the national arena, the accuracy of psychiatric diagnoses must be measured. Indexes of accuracy such as sensitivity and specificity provide valuable information, yet they are rarely computed because there is no ''gold standard'' with which to compare them. The goal of this article is to show how this problem cart be overcome and to encourage nosologists to use accuracy statistics in assessing the adequacy of psychiatric diagnoses. Method: The authors reviewed the literature on medical decision making to find methodological approaches to assessing diagnostic accuracy in the absence of gold standards. Results: A lack of such standards is not unique to psychiatry and has been addressed with a variety of novel analytic procedures. Although these methods differ in many respects, each recognizes that the conventional 2X2 table of interrater agreement does not provide data for estimating diagnostic accuracy. After defining the data needed, each method provides a mathematical model that estimates accuracy statistics and the prevalence of a disorder. Most of these methods are variants of latent class analysis. The authors reanalyzed data from one of the reviewed papers to show that similar inferences about accuracy of diagnoses could be drawn from a conventional latent class analysis. Conclusions: There are potential pitfalls in using latent structure methods, but their cautious use would provide valuable information for psychiatric nosology. These methods supplement, but do not replace, data about outcome, family history, laboratory studies, and other validating criteria in making accurate diagnoses. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,BOSTON,MA 02115. RP FARAONE, SV (reprint author), BROCKTON W ROXBURY VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,940 BELMONT ST,BROCKTON,MA 02401, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [NIMH MH-41879, NIMH MH-43518, NIMH MH-46318] NR 67 TC 145 Z9 146 U1 0 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1994 VL 151 IS 5 BP 650 EP 657 PG 8 WC Psychiatry SC Psychiatry GA NJ089 UT WOS:A1994NJ08900004 PM 8166304 ER PT J AU LIBERMAN, RP VANPUTTEN, T MARSHALL, BD MINTZ, J BOWEN, L KUEHNEL, TG ARAVAGIRI, M MARDER, SR AF LIBERMAN, RP VANPUTTEN, T MARSHALL, BD MINTZ, J BOWEN, L KUEHNEL, TG ARAVAGIRI, M MARDER, SR TI OPTIMAL DRUG AND BEHAVIOR-THERAPY FOR TREATMENT-REFRACTORY SCHIZOPHRENIC-PATIENTS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID HALOPERIDOL; PLASMA AB Thirteen treatment-refractory schizophrenic patients (10 melt and three women) who were receiving more than 50 mg/day of haloperidol and who had been hospitalized for more than 1 year successfully tolerated a mean dose reduction of 63% with consequent improvement in psychopathology and side effects. The addition of intensive behavior therapy to the optimal dose of haloperidol yielded further improvements in functional behavior, such as self-care and social interaction, C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CAMARILLO STATE HOSP,CAMARILLO RES CTR,LOS ANGELES,CA. RP LIBERMAN, RP (reprint author), UNIV CALIF LOS ANGELES,CAMARILLO RES CTR,DEPT PSYCHIAT & BIOBEHAV SCI,POB 6022,CAMARILLO,CA 93011, USA. NR 22 TC 27 Z9 27 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1994 VL 151 IS 5 BP 756 EP 759 PG 4 WC Psychiatry SC Psychiatry GA NJ089 UT WOS:A1994NJ08900022 PM 8166320 ER PT J AU LU, DSK SAINI, S HAHN, PF GOLDBERG, M LEE, MJ WEISSLEDER, R GERARD, B HALPERN, E CATS, A AF LU, DSK SAINI, S HAHN, PF GOLDBERG, M LEE, MJ WEISSLEDER, R GERARD, B HALPERN, E CATS, A TI T2-WEIGHTED MR-IMAGING OF THE UPPER PART OF THE ABDOMEN - SHOULD FAT-SUPPRESSION BE USED ROUTINELY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. Fat suppression has shown promise in improving the quality of T2-weighted spin-echo MR images of the upper part of the abdomen. The purpose of this study was to determine whether fat-suppressed images should be routinely used in lieu of conventional images. Accordingly, we prospectively compared the two techniques in a series of patients with both normal and abnormal findings in the upper part of the abdomen. MATERIALS AND METHODS. Conventional and fat-suppressed TS-weighted spin-echo images (3000/80, 160 [TR/TE]) were obtained in 45 consecutive patients referred for MR imaging of the upper part of the abdomen. Thirty-three patients had abnormal findings, and 22 of those 33 patients had histologic or follow-up confirmation of the diagnosis (14 with metastasis, one with hepatoma, four with hemangiomas, and three with cysts). Signal intensities (hepatic lesions, liver, spleen) and noise were measured to calculate signal-to-noise ratios and contrast-to-noise ratios. Qualitative comparison (liver, hepatic lesions, porta hepatis, spleen, pancreas, bowel, kidneys, adrenal glands, noise), evaluation of the number of hepatic lesions, and characterization of hepatic lesions were done by independent observers. RESULTS. Compared with conventional images, fat-suppressed images had higher signal-to-noise ratios (lesions, liver, spleen) and contrast-to-noise ratios (lesion-liver and spleen-liver) (p<.005). In qualitative comparison, three of three radiologists preferred fat-suppressed over conventional images for depiction of hepatic lesions and all upper abdominal organs except the liver, for which no clear preference was shown for either technique. Detection rates for hepatic lesions were similar with both types of images (observer 1:112 lesions on fat-suppressed vs 118 on conventional images, observer 2:142 vs 135), as was the characterization of hepatic lesions (91% accuracy on fat-suppressed images and 84% accuracy on conventional images, for 22 proved lesions and two observers). CONCLUSION. Fat-suppressed T2-weighted spin-echo MR images were better than non-fat-suppressed images for evaluation of the upper part of the abdomen. These results suggest that fat suppression should be routinely used in T2-weighted MR imaging of the upper part of the abdomen. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 8 TC 38 Z9 41 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1994 VL 162 IS 5 BP 1095 EP 1100 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NH393 UT WOS:A1994NH39300015 PM 8165989 ER PT J AU BOLAND, GW LEE, MJ MUELLER, PR DAWSON, SL GAA, JC LU, DSK GAZELLE, GS AF BOLAND, GW LEE, MJ MUELLER, PR DAWSON, SL GAA, JC LU, DSK GAZELLE, GS TI GALLSTONES IN CRITICALLY ILL PATIENTS WITH ACUTE CALCULOUS CHOLECYSTITIS TREATED BY PERCUTANEOUS CHOLECYSTOSTOMY - NONSURGICAL THERAPEUTIC OPTIONS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CYSTIC DUCT; CHOLECYSTECTOMY; LASER; OBLITERATION; LITHOTRIPSY; INVITRO; CT AB OBJECTIVE. Patients with acute calculous cholecystitis require removal of gallstones (generally cholecystectomy), as acute cholecystitis is likely to recur if gallstones are left in situ. The purpose of this study was to assess the role of nonsurgical techniques for treating gallstones in critically ill patients with acute calculous cholecystitis managed by percutaneous cholecystostomy. MATERIALS AND METHODS. Twenty-six critically ill patients with complex medical and surgical problems who were in intensive care units underwent emergent percutaneous cholecystostomy for acute calculous cholecystitis. Seven of the 26 patients subsequently died of multiple organ failure. Curative gallstone therapies were tried in the surviving 19 patients, seven of whom underwent elective surgical cholecystectomy. Nonsurgical management was attempted in 12 of 19 patients, including six with terminal disease who were treated with long-term gallbladder drainage, three who were treated with methyl tert-butyl ether for stone dissolution, two who had percutaneous cholecystolithotomy, and one who had a gallbladder stone that had passed into the common bile duct and was retrieved endoscopically. RESULTS. Long-term gallbladder drainage was successful in all six patients with terminal disease in whom it was attempted; they experienced no further episodes of cholecystitis. In four of the other six patients treated with nonsurgical therapies (percutaneous cholecystolithotomy, stone dissolution with methyl tert-butyl ether, and endoscopic removal), gallstones were successfully removed and no further therapy was required. Percutaneous therapies failed in two patients, who then had cholecystectomy. CONCLUSION. Nonsurgical gallstone therapies should be attempted in high-risk patients with acute calculous cholecystitis. Some patients may benefit form longterm catheter drainage of the gallbladder. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 20 TC 24 Z9 25 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1994 VL 162 IS 5 BP 1101 EP 1103 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NH393 UT WOS:A1994NH39300016 PM 8165990 ER PT J AU HOFFER, FA GIANTURCO, LE FLETCHER, JA GRIER, HE AF HOFFER, FA GIANTURCO, LE FLETCHER, JA GRIER, HE TI PERCUTANEOUS BIOPSY OF PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMORS AND EWINGS SARCOMAS FOR CYTOGENETIC ANALYSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID NEUROEPITHELIOMA; CHILDREN C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RP HOFFER, FA (reprint author), CHILDRENS HOSP,DEPT RADIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 7 TC 19 Z9 19 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1994 VL 162 IS 5 BP 1141 EP 1142 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NH393 UT WOS:A1994NH39300027 PM 8165999 ER PT J AU EISENBERG, PJ LEE, MJ BOLAND, GW MUELLER, PR AF EISENBERG, PJ LEE, MJ BOLAND, GW MUELLER, PR TI PERCUTANEOUS DRAINAGE OF A SUBPHRENIC ABSCESS WITH GASTRIC FISTULA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Discussion C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 13 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1994 VL 162 IS 5 BP 1233 EP 1237 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NH393 UT WOS:A1994NH39300046 PM 8166016 ER PT J AU BRENNICK, JB OCONNELL, JX DICKERSIN, GR PILCH, BZ YOUNG, RH AF BRENNICK, JB OCONNELL, JX DICKERSIN, GR PILCH, BZ YOUNG, RH TI LIPOFUSCIN PIGMENTATION (SO-CALLED MELANOSIS) OF THE PROSTATE SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE PROSTATE; LIPOFUSCIN; PIGMENT; MELANOSIS; BLUE NEVUS; SEMINAL VESICLE ID BLUE NEVUS; EPITHELIUM; GLAND; INVOLVEMENT; CARCINOMA; MELANIN; CELLS AB Although intraepithelial pigment in the prostate gland has been termed melanosis, the nature of the pigment is not entirely clear, and many pathologists are not aware of its existence. We examined 863 hematoxylin and eosin (H + E) stained slides from 150 surgical specimens of prostate (69 needle biopsies, 66 transurethral resections, 14 radical prostatectomies, and 1 suprapubic prostatectomy) from 149 patients (age range, 47 to 90 years; mean 70 years) in an effort to characterize this pigment. The 1-3 mu m in diameter, predominantly subnuclear, yellow-brown to gray-brown granules with a dark blue rim (by H + E) stained positively with Fontana-Masson, periodic acid-Schiff with diastase, Congo red, luxol fast blue, and oil-red-O and exhibited yellow autofluorescence consistent with lipofuscin. H + E stained slides revealed pigment in the benign epithelium in 86 of 150 cases (57%), within stromal macrophages in eight cases, and in atypical epithelium in two cases of high-grade prostatic intraepithelial neoplasia. Ten cases of invasive adenocarcinoma without recognizable pigment in H + E stained sections were stained by the Fontana-Masson technique, and pigment was identified in malignant epithelium in three of these cases. Ultrastructural examination of intraepithelial pigment in KII-fixed tissue from three radical prostatectomy specimens demonstrated the typical appearance of lipofuscin. Although intraepithelial pigment in prostatic biopsy or resection specimens is usually considered characteristic of seminal vesicle epithelium, our study demonstrates that lipofuscin is commonly present in epithelial cells of benign prostatic hyperplasia and less frequently in those of prostatic intraepithelial neoplasia and adenocarcinoma. The recognition of this pigment is important in preventing diagnostic confusion with seminal vesicle epithelium and with melanocytic lesions. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP BRENNICK, JB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 31 TC 28 Z9 28 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1994 VL 18 IS 5 BP 446 EP 454 DI 10.1097/00000478-199405000-00003 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA NG867 UT WOS:A1994NG86700003 PM 7513501 ER PT J AU KAUFMANN, MA ROSOW, C SCHNIEPER, P SCHNEIDER, M AF KAUFMANN, MA ROSOW, C SCHNIEPER, P SCHNEIDER, M TI PROPHYLACTIC ANTIEMETIC THERAPY WITH PATIENT-CONTROLLED ANALGESIA - A DOUBLE-BLIND, PLACEBO-CONTROLLED COMPARISON OF DROPERIDOL, METOCLOPRAMIDE, AND TROPISETRON SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSTOPERATIVE NAUSEA; GENERAL-ANESTHESIA; PREVENTION; DOMPERIDONE; ONDANSETRON; MANAGEMENT; ETIOLOGY; SURGERY; EMESIS; PAIN AB This placebo-controlled, randomized, double-blind trial was designed to evaluate the efficacy of three prophylactic antiemetic regimens on postoperative nausea and vomiting (PONV) during patient-controlled analgesia (PCA) with morphine. We studied 286 elective surgical patients for 36 h postoperatively. Group 1 was saline control. In Groups 2 and 3, metoclopramide or droperidol was administered as an intravenous (TV) bolus and then added to morphine in the PCA device. In Group 4, tropisetron, a long-acting investigational 5-hydroxytryptamine subtype 3 (5-HT5) antagonist was given as a single TV dose. We assessed the frequency and severity of PONV, as well as the need for rescue, frequency of side effects, and overall patient satisfaction. Severity of PONV was measured with a symptom-severity score (STS) which was based on both intensity and duration. The average total doses of antiemetics were metoclopramide 53.8 +/- 2.2 mg, droperidol 5.99 +/- 0.3 mg, and tropisetron 6.1 +/- 0.2 mg. Control patients had a 54% incidence of PONV. Droperidol reduced both the incidence (P < 0.001) and severity (P < 0.01) of PONV for the entire 36 h. Tropisetron reduced incidence and severity (P < 0.05), but the effect of the single bolus dose lasted only 18 h. Metoclopramide had a marginally significant effect under these conditions. Only droperidol decreased the need for rescue medication (P < 0.01), although rescue with tropisetron was highly effective. Side effects and patient satisfaction were comparable among the groups, but patients receiving droperidol were sleepier (P < 0.05) than control patients and recalled somewhat more anxiety (P = 0.03). When used together with morphine PCA, droperidol is a highly effective antiemetic for 36 h. Tropisetron is also effective, but more than one dose is required. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. UNIV BASEL,DEPT ANAESTHESIA,BASEL,SWITZERLAND. NR 19 TC 58 Z9 63 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 1994 VL 78 IS 5 BP 988 EP 994 PG 7 WC Anesthesiology SC Anesthesiology GA NJ087 UT WOS:A1994NJ08700027 PM 8161001 ER PT J AU SCHWARDT, JD NEUFELD, GR BAUMGARDNER, JE SCHERER, PW AF SCHWARDT, JD NEUFELD, GR BAUMGARDNER, JE SCHERER, PW TI NONINVASIVE RECOVERY OF ACINAR ANATOMIC INFORMATION FROM CO2 EXPIROGRAMS SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE AIRWAY CONVECTION-DIFFUSION; PULMONARY FUNCTION; EMPHYSEMA; NONINVASIVE PULMONARY MEASUREMENT ID GAS; AIRWAYS; DISPERSION; DIFFUSION; DISEASE; WASHOUT; VOLUME; MODEL AB A numerical single path model of respiratory gas exchange with distributed alveolar gas sources was used to estimate the anatomical changes in small peripheral airways such as occur in chronic obstructive pulmonary diseases (COPD). A previous sensitivity analysis of the single path model showed that decreasing total acinar airway cross-sectional area by an area reduction factor, R, results in computed gas expirograms with Phase III steepening similar to that observed in COPD patients. From experimental steady state CO2 washout data recorded from six healthy subjects and six COPD patients, optimized area reduction factors for the single path model were found that characterize peripheral airway anatomy for each subject. Area reduction factors were then combined with measured functional residual capacity data to calculate the normalized peripheral airspace diameters in a given subject, relative to the airspace diameters in the generations of an idealized standard lung. Mean area reduction factors for the patient subgroup were 63% of those for the healthy subgroup, which is related to the gas transport limitation observed in disease. Mean airspace sizes for the patient subgroup were 235% of the healthy subgroup, which characterizes the increase in size and reduction in number of peripheral airspaces due to tissue erosion in emphysema. From these results, the air-phase diffusive conductance in COPD patients was calculated to be 32% of the mean value in the healthy subjects. These findings correlated well with standard pulmonary function test data for the patients and yield the recovery of acinar airway information from gas washout by combining the single path model with experimental measurements. C1 UNIV PENN,SCH ENGN & APPL SCI,DEPT BIOENGN,220 S 33RD ST,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT ANESTHESIA,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NHLBI NIH HHS [HL 33891] NR 36 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAY-JUN PY 1994 VL 22 IS 3 BP 293 EP 306 DI 10.1007/BF02368236 PG 14 WC Engineering, Biomedical SC Engineering GA PB687 UT WOS:A1994PB68700008 PM 7978550 ER PT J AU FINE, HA MAYER, RJ AF FINE, HA MAYER, RJ TI DISTINGUISHING CENTRAL-NERVOUS-SYSTEM LYMPHOMA FROM TOXOPLASMA-ENCEPHALITIS - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP FINE, HA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1994 VL 120 IS 9 BP 813 EP 813 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NH251 UT WOS:A1994NH25100023 ER PT J AU NATHAN, B GUSTERSON, B JADAYEL, D OHARE, M ANBAZHAGAN, R JAYATILAKE, H EBBS, S MICKLEM, K PRICE, K GELBER, R REED, R SENN, HJ GOLDHIRSCH, A DYER, MJS AF NATHAN, B GUSTERSON, B JADAYEL, D OHARE, M ANBAZHAGAN, R JAYATILAKE, H EBBS, S MICKLEM, K PRICE, K GELBER, R REED, R SENN, HJ GOLDHIRSCH, A DYER, MJS TI EXPRESSION OF BCL-2 IN PRIMARY BREAST-CANCER AND ITS CORRELATION WITH TUMOR PHENOTYPE SO ANNALS OF ONCOLOGY LA English DT Article DE BCL-2; BREAST CANCER; APOPTOSIS ID PROGRAMMED CELL-DEATH; C-MYC; C-ERBB-2 EXPRESSION; APOPTOSIS; PROTEIN; CARCINOMA; SURVIVAL; ESTABLISHMENT; SEQUENCE; LYMPHOMA AB Background: The role of apoptosis (programmed cell death) in the development and progression of breast cancer is unknown. Recently the bcl-2 gene has been shown to block apoptosis and thus may promote tumour development. BCL-2 is localised to the luminal cells of the normal breast, which are considered to be the origin of malignant breast disease. Patients and methods: Immunocytochemistry using anti bcl-2- antibody was performed on 107 breast cancer specimens belonging to node-positive patients from the Ludwig Breast Cancer Studies I-IV and the results were correlated with survival, tumour grade, S-phase, oestrogen and progesterone receptor status and c-erb B-2 expression. Western and Southern blotting together with immunofluorescence were performed on the breast cancer cell lines BT-20, BT-474, MDA-MB-361, T47-D and MCF-7. Results: In the breast cancer derived cell line MCF-7 BCL-2 is expressed to a level similar to that of the B-lymphoma cell line Karpas 231 with t(14;18)(q32.3; q21.3), but no evidence of a rearrangement or gene amplification was identified. In a study of 107 breast cancers from the International Breast Cancer Study Group Trials I-IV we have demonstrated a very significant inverse correlation of BCL-2 with c-erbB-2 expression (p = 0.002), and a positive correlation with oestrogen receptors (p = 0.001) and progesterone receptors (p = 0.05). In this study there was no correlation of expression with S-phase fraction in the tumours or with any stage in the cell cycle as assessed in MCF-7 cells. Conclusion: We conclude that BCL-2 might contribute to the malignant phenotype of breast cancer by modulation of biological behaviour of cancer cells. C1 INST CANC RES, CELL BIOL & EXPTL PATHOL SECT, LONDON, ENGLAND. INST CANC RES, ACADEM HAEMATOL SECT, LONDON, ENGLAND. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02115 USA. INT BREAST CANC STUDY GRP, BERN, SWITZERLAND. JOHN RADCLIFFE HOSP, LEUKAEMIA RES FUND, IMMUNODIAGNOST UNIT, OXFORD OX3 9DU, ENGLAND. RI gusterson, barry/D-3752-2009 NR 39 TC 49 Z9 50 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 1994 VL 5 IS 5 BP 409 EP 414 PG 6 WC Oncology SC Oncology GA NT928 UT WOS:A1994NT92800007 PM 7915536 ER PT J AU DAGGETT, WM AF DAGGETT, WM TI CONCEALED RUPTURE OF THE LEFT-VENTRICLE - SUCCESSFUL SURGICAL REPAIR - COMMENT SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP DAGGETT, WM (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 1 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 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 1994 VL 57 IS 5 BP 1335 EP 1335 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NL631 UT WOS:A1994NL63100060 ER PT J AU HANDELSMAN, L BERNSTEIN, D HOLLOWAY, K SHEIKH, I TRESTMAN, R SIEVER, L COOPER, T AF HANDELSMAN, L BERNSTEIN, D HOLLOWAY, K SHEIKH, I TRESTMAN, R SIEVER, L COOPER, T TI HOSTILE IMPULSIVE TRAITS IN ADDICTS - 5-HT BEHAVIORAL PHARMACOLOGY SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,BRONX,NY. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 625 EP 625 DI 10.1016/0006-3223(94)90694-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200038 ER PT J AU SACHS, GS RENSHAW, PF LAFER, B STOLL, A THIBAULT, A ROSENBAUM, JF AF SACHS, GS RENSHAW, PF LAFER, B STOLL, A THIBAULT, A ROSENBAUM, JF TI BRAIN LITHIUM LEVELS MEASURED BY MRS - VARIABILITY DURING MAINTENANCE TREATMENT IN BIPOLAR DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 626 EP 626 DI 10.1016/0006-3223(94)90699-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200043 ER PT J AU ADLER, LE HOPE, C HOFFER, LD STEPHEN, C YOUNG, D GERHARDT, G AF ADLER, LE HOPE, C HOFFER, LD STEPHEN, C YOUNG, D GERHARDT, G TI BROMOCRIPTINE IMPAIRS P50 AUDITORY SENSORY GATING IN NORMAL CONTROL SUBJECTS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT BIOMETR,DENVER,CO. DENVER VAMC,DENVER,CO. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 630 EP 630 DI 10.1016/0006-3223(94)90714-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200058 ER PT J AU RAUCH, SL SAVAGE, CR ALPERT, NM BREITER, HCR BAER, L MIGUEL, E FISCHMAN, AJ MANZO, P MORETTI, C JENIKE, MA AF RAUCH, SL SAVAGE, CR ALPERT, NM BREITER, HCR BAER, L MIGUEL, E FISCHMAN, AJ MANZO, P MORETTI, C JENIKE, MA TI PET O-15 SYMPTOM PROVOCATION STUDIES OF ANXIETY DISORDERS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 658 EP 658 DI 10.1016/0006-3223(94)90815-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200157 ER PT J AU LI, G SILVERMAN, JM ALTSTIEL, L HAROUTUNIAN, H BIRSTEIN, S MOHS, R DAVIS, KL AF LI, G SILVERMAN, JM ALTSTIEL, L HAROUTUNIAN, H BIRSTEIN, S MOHS, R DAVIS, KL TI APOLIPOPROTEIN EPSILON-4 ALLELE AND FAMILIAL RISK IN ALZHEIMERS-DISEASE SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,NEW YORK,NY 10468. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 664 EP 664 DI 10.1016/0006-3223(94)90837-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200179 ER PT J AU GARVER, DL GRIFFITH, J HIRSCHOWITZ, J AF GARVER, DL GRIFFITH, J HIRSCHOWITZ, J TI MINIMUM EFFECTIVE DOSE OF HALOPERIDOL IN TREATMENT OF PSYCHOSES SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. DALLAS VA MED CTR,DALLAS,TX. BRONX VET ADM MED CTR,NEW YORK,NY. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 667 EP 667 DI 10.1016/0006-3223(94)90846-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200188 ER PT J AU STEINBERG, BJ TRESTMAN, RL MITROPOULOU, V COCCARO, E SIEVER, LJ AF STEINBERG, BJ TRESTMAN, RL MITROPOULOU, V COCCARO, E SIEVER, LJ TI DIURNAL MHPG, CORTISOL AND AUTONOMIC RHYTHMS IN ACUTE AND REMITTED DEPRESSION SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,BRONX,NY. MED COLL PENN,PHILADELPHIA,PA 19129. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 669 EP 669 DI 10.1016/0006-3223(94)90853-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200195 ER PT J AU TRESTMAN, RL BUCHSBAUM, M SIEGEL, B LOSONCZY, M SCHAEFER, C SIEVER, LJ AF TRESTMAN, RL BUCHSBAUM, M SIEGEL, B LOSONCZY, M SCHAEFER, C SIEVER, LJ TI FUNCTIONAL IMAGING WITH SPECT OF COGNITIVE ACTIVITY IN SCHIZOTYPALS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,BRONX,NY. MT SINAI MED CTR,NEW YORK,NY 10029. FDR VA MED CTR,MONTROSE,NY. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 683 EP 684 DI 10.1016/0006-3223(94)90905-9 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200247 ER PT J AU LAFER, B RENSHAW, PF SACHS, G CHRISTENSEN, JD YURGELUNTODD, D STOLL, AL ROSENBAUM, JF COHEN, BM AF LAFER, B RENSHAW, PF SACHS, G CHRISTENSEN, JD YURGELUNTODD, D STOLL, AL ROSENBAUM, JF COHEN, BM TI PROTON MRS OF THE BASAL GANGLIA IN BIPOLAR DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,MCLEAN HOSP,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 685 EP 685 DI 10.1016/0006-3223(94)90910-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200252 ER PT J AU AMIN, F SILVERMAN, J WENTZEL, C SMITH, CJ KNOTT, P SIEVER, LJ AF AMIN, F SILVERMAN, J WENTZEL, C SMITH, CJ KNOTT, P SIEVER, LJ TI DOPAMINE METABOLISM IN THE 1ST-DEGREE RELATIVES OF SCHIZOPHRENIC PROBANDS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,PSYCHIAT SERV 116A,BRONX,NY 10468. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 690 EP 691 DI 10.1016/0006-3223(94)90929-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200271 ER PT J AU HIRSCHOWITZ, J VALLABHAJOSULA, S INTRATOR, J HITZEMANN, R DACOSTA, M MACHAC, J AF HIRSCHOWITZ, J VALLABHAJOSULA, S INTRATOR, J HITZEMANN, R DACOSTA, M MACHAC, J TI ANTIPSYCHOTIC DRUG-THERAPY IN SCHIZOPHRENICS - STUDIES OF RECEPTOR OCCUPANCY SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,NEW YORK,NY 10468. MT SINAI MED CTR,NEW YORK,NY 10029. SUNY STONY BROOK,STONY BROOK,NY 11768. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 691 EP 691 DI 10.1016/0006-3223(94)90930-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200272 ER PT J AU ADLER, LA NIERENBERA, AA FAVA, M HANNIBAL, J ROTROSEN, J AF ADLER, LA NIERENBERA, AA FAVA, M HANNIBAL, J ROTROSEN, J TI TRAINING RATERS TO ASSESS NEUROLEPTIC-INDUCED AKATHISIA USING STANDARDIZED VIDEOTAPES SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NEW YORK DVAMC,PSYCHIAT SERV,NEW YORK,NY. NYU,SCH MED,NEW YORK,NY. MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 696 EP 696 DI 10.1016/0006-3223(94)90949-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200291 ER PT J AU AMES, D MANSCHRECK, TC BUCHANAN, RW AF AMES, D MANSCHRECK, TC BUCHANAN, RW TI NEUROLOGIC ABNORMALITIES IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W LOS ANGELES VAMC,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90073. NEW HAMPSHIRE HOSP,CONCORD,NH 03301. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 714 EP 714 DI 10.1016/0006-3223(94)91013-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200355 ER PT J AU AMES, D WIRSHING, WC WATERS, B MOHGIMI, R BERISFORD, MA AF AMES, D WIRSHING, WC WATERS, B MOHGIMI, R BERISFORD, MA TI NEUROLOGIC DEFICITS, TARDIVE-DYSKINESIA, AND MEDICATION STATUS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90073. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 715 EP 715 DI 10.1016/0006-3223(94)91018-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200360 ER PT J AU LANDAU, EM WONG, T NOURANIFAR, R IYENGAR, R BLITZER, RD AF LANDAU, EM WONG, T NOURANIFAR, R IYENGAR, R BLITZER, RD TI POSTSYNAPTIC CAMP-DEPENDENT PROTEIN-KINASE PARTICIPATES IN LONG-TERM POTENTIATION SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,BRONX,NY 10468. MT SINAI SCH MED,BRONX,NY 10468. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 733 EP 733 DI 10.1016/0006-3223(94)91082-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200424 ER PT J AU SILVERMAN, JM GREENBERG, DA ALTSTIEL, LD SMITH, CJ ZHOU, G ZACCARIO, ML YANG, XP HOLLANDER, T BELLO, J SIEVER, LJ MOHS, RC DAVIS, KL AF SILVERMAN, JM GREENBERG, DA ALTSTIEL, LD SMITH, CJ ZHOU, G ZACCARIO, ML YANG, XP HOLLANDER, T BELLO, J SIEVER, LJ MOHS, RC DAVIS, KL TI A LINKAGE MARKER FOR SCHIZOPHRENIA AND RELATED DISORDERS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,BRONX,NY 10468. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 740 EP 741 DI 10.1016/0006-3223(94)91110-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200452 ER PT J AU STEINBERG, BJ TRESTMAN, RL LOPEZ, I PAVELL, E SIEVER, LJ AF STEINBERG, BJ TRESTMAN, RL LOPEZ, I PAVELL, E SIEVER, LJ TI CHOLINERGIC CHALLENGE AND AFFECTIVE INSTABILITY IN PERSONALITY-DISORDER PATIENTS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 CUNY MT SINAI SCH MED,NEW YORK,NY 10029. BRONX VET ADM MED CTR,BRONX,NY. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 740 EP 740 DI 10.1016/0006-3223(94)91108-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200450 ER PT J AU STERN, RG SCHMEIDLER, J DAVIDSON, M AF STERN, RG SCHMEIDLER, J DAVIDSON, M TI A REVIEW OF STATISTICAL DESIGN IN CONTROLLED TREATMENT TRIALS IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY 10029. 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 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 741 EP 741 DI 10.1016/0006-3223(94)91112-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200454 ER PT J AU BAUM, MJ BROWN, JJG KICA, E RUBIN, BS JOHNSON, RS PAPAIOANNOU, VE AF BAUM, MJ BROWN, JJG KICA, E RUBIN, BS JOHNSON, RS PAPAIOANNOU, VE TI EFFECT OF A NULL MUTATION OF THE C-FOS PROTOONCOGENE ON SEXUAL-BEHAVIOR OF MALE-MICE SO BIOLOGY OF REPRODUCTION LA English DT Article ID SUPRACHIASMATIC NUCLEUS; GENE-EXPRESSION; LIGHT; STIMULATION; INDUCTION; RETENTION; MAMMALS; SYSTEM; BRAIN; RAT AB Sexual behavior was observed in male mice that were homozygous for a null mutation of the c-fos protooncogene, as well as in heterozygous mutants and wild-type controls. The onset of mounting was slower and the subsequent mounting rate was significantly lower in homozygous mutants than in either group of controls. Even so, a similar percentage of males of each genotype achieved ejaculation, and ejaculation latencies were equivalent in these mice. Likewise, in males that intromitted, the intromission efficiency and the number of intravaginal thrusts/intromission were similar among the three genotypes. The nuclear protein product (Fos) of c-fos was visualized immunocytochemically in the brains of heterozygous male mice 1 h after they exhibited a series of mounts, with or without intromission, leading to an ejaculation. As in the male of several other rodent species, nuclear Fos immunoreactivity was augmented in neurons of limbic and midbrain regions thought to convey olfactory/vomeronasal and genital/somatosensory information, respectively, to the medial preoptic area following contact with an estrous female. One interpretation of our behavioral results is that in the absence of normal neuronal c-fos expression, sensory stimuli that impinge on the male brain during mating lose their ability to initiate a cascade of further gene transcription events that otherwise control the rate at which a male reorients towards and mounts an estrous female during an ejaculatory series. Alternatively, the c-fos null mutation may disrupt normal neural development, leading to a structural change that mediates the observed deficit in mounting capacity. C1 TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT ANAT & CELL BIOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP BAUM, MJ (reprint author), BOSTON UNIV,DEPT BIOL,5 CUMMINGTON ST,BOSTON,MA 02215, USA. OI Johnson, Randall/0000-0002-4084-6639 FU NICHD NIH HHS [HD21094, HD27295]; NIMH NIH HHS [MH00392] NR 32 TC 40 Z9 40 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 1994 VL 50 IS 5 BP 1040 EP 1048 DI 10.1095/biolreprod50.5.1040 PG 9 WC Reproductive Biology SC Reproductive Biology GA NG368 UT WOS:A1994NG36800008 PM 8025159 ER PT J AU SYKES, M HARTY, MW SZOT, GL PEARSON, DA AF SYKES, M HARTY, MW SZOT, GL PEARSON, DA TI INTERLEUKIN-2 INHIBITS GRAFT-VERSUS-HOST DISEASE-PROMOTING ACTIVITY OF CD4+ CELLS WHILE PRESERVING CD4-MEDIATED AND CDS-MEDIATED GRAFT-VERSUS-LEUKEMIA EFFECTS SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY BARRIERS; CHRONIC MYELOGENOUS LEUKEMIA; TOXIC T-CELLS; LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; SELECTIVE DEPLETION; SYNGENEIC LYMPHOMA; IFN-GAMMA; MICE RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,MGH-E,BLDG 149-9019,BOSTON,MA 02129, USA. FU NCI NIH HHS [R01CA55290] NR 56 TC 79 Z9 81 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1994 VL 83 IS 9 BP 2560 EP 2569 PG 10 WC Hematology SC Hematology GA NJ298 UT WOS:A1994NJ29800022 PM 7909457 ER PT J AU ODAY, SJ RABINOWE, SN NEUBERG, D FREEDMAN, AS SOIFFER, RJ SPECTOR, NA ROBERTSON, MJ ANDERSON, K WHELAN, M PESEK, K RITZ, J NADLER, LM AF ODAY, SJ RABINOWE, SN NEUBERG, D FREEDMAN, AS SOIFFER, RJ SPECTOR, NA ROBERTSON, MJ ANDERSON, K WHELAN, M PESEK, K RITZ, J NADLER, LM TI A PHASE-II STUDY OF CONTINUOUS-INFUSION RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AS AN ADJUNCT TO AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR PATIENTS WITH NON-HODGKINS-LYMPHOMA IN FIRST REMISSION SO BLOOD LA English DT Article ID HIGH-DOSE CYCLOPHOSPHAMIDE; FACTOR GM-CSF; GROWTH-FACTORS; MALIGNANT-LYMPHOMA; PROGENITOR CELLS; CONTROLLED TRIAL; BREAST-CANCER; CHEMOTHERAPY; INTERLEUKIN-3; THERAPY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP ODAY, SJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA34183, CA06516]; PHS HHS [55207] NR 42 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1994 VL 83 IS 9 BP 2707 EP 2714 PG 8 WC Hematology SC Hematology GA NJ298 UT WOS:A1994NJ29800039 PM 8167349 ER PT J AU AYASH, LJ ELIAS, A HUNT, M DEMETRI, G WHEELER, C TEPLER, I SCHWARTZ, G MAZANET, R REICH, E MCCAULEY, M ANTMAN, K ANDERSON, KC AF AYASH, LJ ELIAS, A HUNT, M DEMETRI, G WHEELER, C TEPLER, I SCHWARTZ, G MAZANET, R REICH, E MCCAULEY, M ANTMAN, K ANDERSON, KC TI RECOMBINANT-HUMAN-ERYTHROPOIETIN FOR THE TREATMENT OF THE ANEMIA ASSOCIATED WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE ERYTHROPOIETIN; BONE MARROW TRANSPLANTATION; ANEMIA ID HEMATOPOIETIC PROGENITOR CELLS; STAGE RENAL-DISEASE; CLINICAL-TRIAL; ANEMIA; INVIVO; MEGAKARYOCYTES; HEMODIALYSIS; MECHANISMS; MALIGNANCY; GENE AB Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct less than or equal to 25% and platelets for counts < 20 000/mu l. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/1) and a haematocrit greater than or equal to 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/ 37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02115. RP AYASH, LJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA-38493] NR 32 TC 27 Z9 28 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 1994 VL 87 IS 1 BP 153 EP 161 DI 10.1111/j.1365-2141.1994.tb04886.x PG 9 WC Hematology SC Hematology GA NK999 UT WOS:A1994NK99900025 PM 7947240 ER PT J AU HILL, RA CHIAPPA, KH AF HILL, RA CHIAPPA, KH TI ELECTROPHYSIOLOGIC MONITORING IN THE INTENSIVE-CARE UNIT SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Neurocritical Care Symposium, at the XXVIII Canadian Congress of Neurological Sciences CY JUN 19, 1993 CL TORONTO, CANADA ID AUDITORY BRAIN-STEM; MULTIMODALITY EVOKED-POTENTIALS; SEVERE HEAD-INJURY; CENTRAL SOMATOSENSORY CONDUCTION; COMPRESSED SPECTRAL ARRAY; COMATOSE PATIENTS; RESPONSES; PREDICTION; DEATH; EEG AB Electroencephalography (EEG) and evoked potential studies are established monitoring tools in the neurological intensive care unit (ICU). These neurophysiologic techniques provide information on physiological state and response to therapy, and may aid diagnosis and prognosis. Serial studies or continuous monitoring may enable changes to be detected prior to irreversible deterioration in the patient's condition. Current computer technology allows simultaneous display and correlation of electrophysiologic parameters, cardiovascular state and intracranial pressure (ICP). Continuous EEG monitoring in the ICU has been shown to have a decisive or contributing impact on medical decision making in more than three-quarters of patients. In addition, continuous EEG monitoring has revealed previously unsuspected non-convulsive seizures in one-third of patients. SEPs and BAEPs can provide useful prognostic information in coma - however, these tests are etiologically nonspecific and must be carefully integrated into the clinical situation. Motor evoked potentials offer a potentially useful tool for evaluating motor system abnormalities in the ICU. C1 MASSACHUSETTS GEN HOSP,EEG EP LAB,BOSTON,MA 02114. NR 71 TC 8 Z9 9 U1 1 U2 2 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 1994 VL 21 IS 2 BP S12 EP S16 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA NN871 UT WOS:A1994NN87100017 PM 8087728 ER PT J AU YOUNG, GB BOLTON, C CHAIPPA, K MOULTON, R MUIZELAAR, JP ROPPER, A SIBBALD, W AF YOUNG, GB BOLTON, C CHAIPPA, K MOULTON, R MUIZELAAR, JP ROPPER, A SIBBALD, W TI PRECIS OF PANEL DISCUSSION - NEUROCRITICAL CARE - PRESIDENTS SYMPOSIUM XXVIII CANADIAN-CONGRESS-OF-NEUROLOGICAL-SCIENCES TORONTO, JUNE 19, 1993 SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Editorial Material C1 UNIV WESTERN ONTARIO, DEPT MED, LONDON, ON, CANADA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, EVOKED POTENTIAL LAB, BOSTON, MA USA. UNIV TORONTO, DEPT SURG, TORONTO, ON, CANADA. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA, DEPT NEUROSURG, RICHMOND, VA USA. ST ELIZABETHS HOSP BOSTON, BOSTON, MA USA. TUFTS UNIV, DEPT NEUROL, BOSTON, MA 02111 USA. UNIV WESTERN ONTARIO, DEPT MED, LONDON, ON, CANADA. UNIV WESTERN ONTARIO, DEPT SURG, LONDON, ON, CANADA. UNIV WESTERN ONTARIO, DEPT ANESTHESIA, LONDON, ON, CANADA. VICTORIA HOSP, CTR CRIT CARE TRAUMA, LONDON N6A 4G5, ON, CANADA. RP YOUNG, GB (reprint author), UNIV WESTERN ONTARIO, DEPT CLIN NEUROL SCI, LONDON, ON, CANADA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN JOURNAL NEUROLOGICAL SCIENCES INC PI CALGARY PA 709-7015 MACLEOD TRAIL SW, CALGARY, AB T2H 2K6, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 1994 VL 21 IS 2 BP S3 EP S5 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA NN871 UT WOS:A1994NN87100015 ER PT J AU SPEEG, KV MALDONADO, AL AF SPEEG, KV MALDONADO, AL TI EFFECT OF THE NONIMMUNOSUPPRESSIVE CYCLOSPORINE ANALOG SDZ PSC-833 ON COLCHICINE AND DOXORUBICIN BILIARY-SECRETION BY THE RAT IN-VIVO SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE SDZ PSC-833; COLCHICINE; DOXORUBICIN; MDR; LIVER; KIDNEY ID MEDIATED MULTIDRUG RESISTANCE; TRANSPORTER STUDIED INVIVO; P-GLYCOPROTEIN; DRUG-RESISTANCE; GENE-PRODUCT; LOCALIZATION; LEUKEMIA; ANTIBODY; TISSUES; TUMOR AB Colchicine and doxorubicin are secreted into bile as a major pathway of their elimination. Colchicine and doxorubicin are also substrates for P-glycoprotein, and P-glycoprotein has been demonstrated to be present at the liver canalicular membrane. Cyclosporin (CsA) inhibits colchicine biliary secretion in vivo. In the present study, the effects of SDZ PSC-833, a nonimmunosuppressive cyclosporin D analog, on the biliary secretion of colchicine and doxorubicin were investigated. SDZ PSC-833 given at a bolus dose of 2 mg/kg promptly decreased colchicine biliary clearance from 9.05+/-0.2 to 2.41+/-0.43 ml min(-1) kg(-1) (P<0.001) and the colchicine bile/plasma ratio from 146+/-8 to 35+/-5 (P<0.001). SDZ PSC-833 also inhibited doxorubicin biliary clearance (basal: 10.5+/-3 vs post-SDZ PSC-833: 2.48+/-0.94 m1 min(-1) kg(-1); P = 0.06) and the doxorubicin bile/plasma ratio (basal: 228+/-64 vs post-SDZ PSC-833: 48+/-22; P<0.01). Colchicine renal secretion was completely inhibited by SDZ PSC-833. Thus, SDZ PSC-833 inhibits the constitutive transport of the multidrug-resistance substrates colchicine and doxorubicin and is more potent than cyclosporin in this regard. The possibility of increased toxicity to normal tissues because of impaired elimination of cytotoxic agents will need to be considered if SDZ PSC-833 is used to chemosensitize cancer cells. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP SPEEG, KV (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GASTROENTEROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 17 TC 50 Z9 51 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1994 VL 34 IS 2 BP 133 EP 136 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NM002 UT WOS:A1994NM00200007 PM 7910787 ER PT J AU SHEPARD, JAO MATHISEN, DJ MUSE, VV BHALLA, M MCLOUD, TC AF SHEPARD, JAO MATHISEN, DJ MUSE, VV BHALLA, M MCLOUD, TC TI NEEDLE LOCALIZATION OF PERIPHERAL LUNG NODULES FOR VIDEO-ASSISTED THORACOSCOPIC SURGERY SO CHEST LA English DT Article ID PULMONARY NODULES; GUIDED MINITHORACOTOMY; RESECTION; BIOPSY; WIRE AB Video-assisted thoracoscopic surgery provides an alternative to conventional thoracotomy for resection of peripheral lung nodules. To localize small peripheral lung nodules that may not be visible or palpable by the surgeon, we have placed a Kopans hook wire percutaneously into the lung as a guide. The indications for localization included previous nondiagnostic percutaneous needle aspiration biopsy (PNAB) (n=4), nodules too small for PNAB (n=2), nodules inaccessible to PNAB (n=3), and planned resection of a known peripheral tumor less than 1 cm (n=1). The localization procedure was performed with computed tomographic guidance in all patients. The nodules ranged in size from 2 to 15 mm and were located immediately subpleural to 2-cm deep the pleura. A 20-gauge Greene biopsy needle was used as an introducer for a 35-cm-long Kopans hook wire. Patients were sent directly to the operating room in a dependent position. All ten nodules were successfully resected, including hamartoma (n=1), carcinoid tumors (n=2), granulomas (n=3), adenocarcinoma (n=1), fibrosis (n=1), benign metastasizing leiomyoma (n=1), and lymphoma (n=1). In two patients, the wire slipped out of the lung. Small focal pneumothoraces developed in five patients. There were no major complications. This procedure can safely and effectively localize nonvisible or nonpalpable pulmonary nodules for thoracoscopic surgery for diagnostic purposes or for resection of small peripheral tumors in patients who cannot tolerate a lobectomy or pneumonectomy. C1 MASSACHUSETTS GEN HOSP,DEPGEN,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP SHEPARD, JAO (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 10 TC 47 Z9 50 U1 0 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1994 VL 105 IS 5 BP 1559 EP 1563 DI 10.1378/chest.105.5.1559 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NL392 UT WOS:A1994NL39200048 PM 8181353 ER PT J AU FOLLAND, ED VOGEL, RA HARTIGAN, P BATES, ER BEAUMAN, GJ FORTIN, T BOUCHER, C PARISI, AF AF FOLLAND, ED VOGEL, RA HARTIGAN, P BATES, ER BEAUMAN, GJ FORTIN, T BOUCHER, C PARISI, AF TI RELATION BETWEEN CORONARY-ARTERY STENOSIS ASSESSED BY VISUAL, CALIPER, AND COMPUTER METHODS AND EXERCISE CAPACITY IN PATIENTS WITH SINGLE-VESSEL CORONARY-ARTERY DISEASE SO CIRCULATION LA English DT Article DE STENOSIS; EXERCISE; CORONARY DISEASE; ANGIOPLASTY; IMAGING; ANGIOGRAPHY ID PHYSIOLOGIC SIGNIFICANCE; ANGIOPLASTY AB Background Practitioners often assume a close relation between angiographic coronary artery stenosis and patient functional capacity. To test this unproven hypothesis, we analyzed the relation between coronary artery stenosis measured by different methods and maximal treadmill exercise tolerance in patients with single-vessel disease before and after intervention by percutaneous transluminal coronary angioplasty (PTCA). Methods and Results Coronary angiography and maximal exercise testing off anti-ischemic medication were performed before random assignment of 227 patients with single-vessel coronary artery disease to PTCA or drug therapy. Six months later, angiography and exercise testing were repeated with patients assigned to PTCA off anti-ischemic therapy so that the altered coronary stenosis was the only consistent variable. Patients assigned to drug therapy were exercised on drug therapy. Coronary stenosis was assessed visually by the local investigator and quantitatively by blinded caliper and computer methods in central laboratories. Variabilities of caliper and computer measurements were established in a subset read twice. Visually estimated stenosis greater than or equal to 90% at baseline was associated with shorter exercise duration (7.9 versus 9.2 minutes, P<.04). Similar segregation at baseline was not observed with caliper or computer methods. Regardless of the method of measurement used, correlation between changes of lesion severity and exercise duration from baseline to follow-up was poor. Patients were angiographically classified as ''better,'' ''unchanged,'' or ''worse'' if follow-up stenosis was below, within, or above 2 SD of mean technical variability from baseline (+/-18.8%, caliper; +/-14.6%, computer). Exercise duration for PTCA patients improved among those with better lesions (+2.4 minutes, n=50, P=.001) but also among those with unchanged lesions (+1.9 minutes, n=41, P less than or equal to .001). Unchanged medically treated patients improved less (+0.5 minutes, n=86, P=.04). Results were similar when patients were angiographically classified by minimum lumen diameter. Conclusions Handheld calipers and quantitative coronary angiography are equivalent techniques for making anatomic measurements. Neither method identified patients having reduced exercise capacity at baseline as well as visual estimation. The relation between changes of coronary stenosis and exercise duration is highly variable, at least in part because of the insensitivity of angiographic methods for detecting small but potentially important changes. Minimal anatomic improvement 6 months after PTCA does not preclude a good functional outcome. Contrary to common belief, angiographic stenosis does not correlate well with functional capacity, even in patients with single-vessel disease. C1 VET AFFAIRS MED CTR, RES SERV, BOSTON, MA 21201 USA. UNIV MARYLAND, SCH MED, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21201 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CARDIAC UNIT, BOSTON, MA USA. VET AFFAIRS MED CTR, RES SERV, W HAVEN, CT USA. VET AFFAIRS MED CTR, RES SERV, ANN ARBOR, MI USA. NR 23 TC 58 Z9 59 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY PY 1994 VL 89 IS 5 BP 2005 EP 2014 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NL675 UT WOS:A1994NL67500013 PM 8181124 ER PT J AU CONTE, MS BIRINYI, LK MIYATA, T FALLON, JT GOLD, HK WHITTEMORE, AD MULLIGAN, RC AF CONTE, MS BIRINYI, LK MIYATA, T FALLON, JT GOLD, HK WHITTEMORE, AD MULLIGAN, RC TI EFFICIENT REPOPULATION OF DENUDED RABBIT ARTERIES WITH AUTOLOGOUS GENETICALLY-MODIFIED ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Article DE GENETICS; CARDIOVASCULAR DISEASES ID VASCULAR SMOOTH-MUSCLE; LUMINAL CORONARY ANGIOPLASTY; RECOMBINANT GENE-EXPRESSION; INVIVO; PROLIFERATION; CULTURE; WALL; VECTORS; GROWTH; IDENTIFICATION AB Background In an effort to determine whether specific genetic modifications of cells of the vascular system might improve the efficacy of existing clinical procedures such as endarterectomy, atherectomy, and percutaneous angioplasty, we investigated the utility of gene transfer to rapidly and efficiently repopulate injured arteries with genetically modified cells in an animal model. Methods and Results The method involves the harvest of autologous venous-derived endothelial cells, the efficient genetic modification of the cells through the use of recombinant retroviruses, and the subsequent implantation of the genetically modified cells on the surface of balloon-denuded arterial segments. With a rabbit model, freshly isolated endothelial cells were transduced with a recombinant retrovirus encoding the bacterial enzyme beta-galactosidase. The autologous transduced cells were then implanted on the surface of balloon-denuded ileofemoral arterial segments at different cell densities; after 1 to 14 days, the animals were killed, and the vessel segments were examined. Cells expressing the bacterial gene product, as determined by in situ staining for beta-galactosidase, were found to be present on the surface of 28 of the 32 arteries seeded with genetically modified cells. Vessels examined at 4 to 7 days after seeding displayed 40% to 90% coverage with transduced cells, even when seeded at subconfluent density, and an intact endothelial cell monolayer, as evidenced by scanning electron microscopy studies. Vessels examined at 14 days after seeding revealed more variable staining for beta-galactosidase yet, again, in most cases, an intact endothelial cell monolayer. Conclusions These studies indicate the feasibility of generating segments of arterial vessels containing genetically modified cells in a rapid and efficient fashion. Further studies are now necessary to determine whether the local expression of specific polypeptides within a region of vessel for a finite period of time will be clinically useful. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA. FU NHLBI NIH HHS [HL-43771, HL-41484]; NIGMS NIH HHS [T32-GM-07560] NR 38 TC 52 Z9 57 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1994 VL 89 IS 5 BP 2161 EP 2169 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NL675 UT WOS:A1994NL67500032 PM 8181141 ER PT J AU JIANG, L SIU, SC HANDSCHUMACHER, MD GUERERRO, JL DEPRADA, JAV KING, ME PICARD, MH WEYMAN, AE LEVINE, RA AF JIANG, L SIU, SC HANDSCHUMACHER, MD GUERERRO, JL DEPRADA, JAV KING, ME PICARD, MH WEYMAN, AE LEVINE, RA TI 3-DIMENSIONAL ECHOCARDIOGRAPHY - IN-VIVO VALIDATION FOR RIGHT-VENTRICULAR VOLUME AND FUNCTION SO CIRCULATION LA English DT Article DE RIGHT VENTRICLE; VOLUME; ECHOCARDIOGRAPHY ID CORONARY-ARTERY DISEASE; CONGENITAL HEART-DISEASE; EJECTION FRACTION; REAL-TIME; 3-DIMENSIONAL RECONSTRUCTION; CHILDREN; PERFORMANCE; IMAGES; SYSTEM; SIZE AB Background Current two-dimensional echocardiographic measures of right ventricular volume are limited by the asymmetrical and crescentic shape of the ventricle and by difficulty in obtaining standardized views. Three-dimensional echocardiographic reconstruction, which does not require geometric assumptions or standardized views, may therefore have potential advantages for determining right ventricular volume. Three-dimensional techniques, however, have not been applied to the right ventricle in vivo, where cardiac motion and contraction could affect accuracy. The purpose of this study was to determine the feasibility and accuracy of three-dimensional echocardiographic reconstruction for quantifying right ventricular volume and function in vivo. In particular, it was designed to test the accuracy of a newly developed system that provides rapid, efficient, and automated three-dimensional data collection (minimizing motion effects) and takes advantage of the full three-dimensional data set to obtain volume. Methods and Results The three-dimensional system was applied to reconstruct the right ventricle and measure its volume and function during 20 hemodynamic stages created in five dogs. Actual instantaneous volumes were measured continuously by an intracavitary balloon connected to an external column. Hemodynamics were varied by volume loading and induction of ischemia. Three-dimensional reconstruction successfully reproduced right ventricular volume compared with actual values at end diastole (y=1.0x-3.4, r=.99, SEE=1.8 mL) and end systole (y=1.0x+2.0, r=.98, SEE=2.5 mL). The mean difference between calculated and actual volumes throughout the cycle was 2.1 mL, or 4.9% of the mean. Ejection fraction also correlated well with actual values (y=0.96x-0.3, r=.98, SEE=3.3%). Conclusions Despite the irregular crescentic shape of the right ventricle, this newly developed three-dimensional system and surfacing algorithm can accurately reconstruct its shape and quantitate its volume and function in vivo without geometric assumptions. The increased efficiency of the system should increase applicability to issues of clinical and research interest. RP JIANG, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,VINCENT BURNHAM 5,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-38176] NR 49 TC 121 Z9 131 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1994 VL 89 IS 5 BP 2342 EP 2350 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NL675 UT WOS:A1994NL67500054 PM 8181160 ER PT J AU GARRIDO, L WEDEEN, VJ KWONG, KK SPENCER, UM KANTOR, HL AF GARRIDO, L WEDEEN, VJ KWONG, KK SPENCER, UM KANTOR, HL TI ANISOTROPY OF WATER DIFFUSION IN THE MYOCARDIUM OF THE RAT SO CIRCULATION RESEARCH LA English DT Article DE PULSED FIELD GRADIENT NUCLEAR MAGNETIC RESONANCE; MYOCARDIUM; ANISOTROPY; DIFFUSION TENSOR ID NUCLEAR MAGNETIC-RESONANCE; LEFT-VENTRICLE; MUSCLE AB Pulsed field gradient nuclear magnetic resonance methods combined with nuclear magnetic resonance imaging were used to determine the water diffusion anisotropy in perfused rat hearts at 37 degrees C. It was found that the observed diffusion coefficient D-app (apparent diffusion coefficient) depends on the orientation of the applied gradient g. When g is parallel to the epicardial surface, the observed diffusivity is D-app parallel to=1.8+/-0.4x10(-9) m(2) s(-1), whereas when g is perpendicular to it, diffusivity is D(app)perpendicular to=2.5+/- 0.5x10(-9) m(2) s(-1). To better characterize this directional dependence, images of the second-order diffusion tenser D of the myocardium were obtained. These data demonstrate several essential features of cardiac myoarchitecture, including the helicity of fiber orientation with respect to the ventricular axis and the variation of fiber pitch angle with transmural depth. Diffusion anisotropy may be quantified in a coordinate-independent manner by the eigenvalues of the diffusion tenser. In the myocardial midwall, these eigenvalues were E(1)=3.29+/-0.57, E(2)=2.01+/-0.42, and E(3)=0.77+/-0.58x10(-9) m(2) s(-1) (mean+/-SD). These data suggest that myocardial water diffusion is essentially unrestricted parallel to the myofibers. They further show that failure to measure the complete diffusion tenser may lead to substantial underestimates of diffusion anisotropy in the myocardium. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP GARRIDO, L (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,149 13TH ST,BOSTON,MA 02129, USA. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 FU NHLBI NIH HHS [R01-HL-39371-05] NR 14 TC 92 Z9 95 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1994 VL 74 IS 5 BP 789 EP 793 PG 5 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NG968 UT WOS:A1994NG96800004 PM 8156627 ER PT J AU AOKI, Y LEE, JC PILLAI, S ISSELBACHER, KJ RUSTGI, AK AF AOKI, Y LEE, JC PILLAI, S ISSELBACHER, KJ RUSTGI, AK TI RADIOLABELED POLYMERASE CHAIN-REACTION ASSAY FOR DETECTION OF RAS ONCOGENE POINT MUTATIONS IN TUMORS SO CLINICAL CHEMISTRY LA English DT Article DE HYBRIDIZATION ASSAYS; RESTRICTION ENZYMES; CANCER; SINGLE-STRAND CONFORMATION POLYMORPHISM ID GENE-MUTATIONS; IDENTIFICATION; POLYMORPHISMS; CANCERS; COLON; DNA AB The human ras gene plays a fundamental role in the transduction of extracellular signals to the nucleus, thereby regulating cell growth and differentiation. Point mutations in the ras gene convert it into a transforming oncogene that has been found in many solid and hematologic malignancies. We describe a rapid and sensitive assay based on a radiolabeled polymerase chain reaction followed by restriction enzyme digestion that we have adapted for differentiating between the wild-type and mutant ras genes. This assay should prove useful in the analysis of ras gene point mutations in clinical tumor specimens in which ras oncogene activation is an early event in carcinogenesis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA 02129. NR 13 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1994 VL 40 IS 5 BP 705 EP 709 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NK828 UT WOS:A1994NK82800005 PM 8174240 ER PT J AU FINEGOLD, SM AF FINEGOLD, SM TI CENTENNIAL SYMPOSIUM ON ANAEROBES - A MEMORIAL TO VEILLON,ANDRE - THE SECRET PATHOGENS - INTRODUCTION SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT IMMUNOL,LOS ANGELES,CA. RP FINEGOLD, SM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,ROOM 136,BLDG 114,LOS ANGELES,CA 90073, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1994 VL 18 SU 4 BP S245 EP S247 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NL750 UT WOS:A1994NL75000001 PM 8086570 ER PT J AU FINEGOLD, SM AF FINEGOLD, SM TI REVIEW OF EARLY RESEARCH ON ANAEROBES SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Centennial Symposium on Anaerobes: A Memorial to Andre Veillon, the Secret Pathogens CY MAR 27, 1993 CL PARIS, FRANCE AB It has been one hundred years since the appearance of the first clinical paper on infection involving anaerobic bacteria, an article that also detailed recovery of and description of the organisms responsible for the infection. We pay tribute to the author of that landmark paper, Andre Veillon, in celebration of the centennial of this important occasion. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. RP FINEGOLD, SM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,ROOM 136,BLDG 114,LOS ANGELES,CA 90073, USA. NR 12 TC 1 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1994 VL 18 SU 4 BP S248 EP S249 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NL750 UT WOS:A1994NL75000002 PM 8086571 ER PT J AU JELLINEK, M AF JELLINEK, M TI REFLECTIONS ON WORTHINGTONS MODEL OF CYCLICAL GRIEF SO CLINICAL PEDIATRICS LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP JELLINEK, M (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,15 PARKMAN ST ACC 725,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAY PY 1994 VL 33 IS 5 BP 301 EP 302 DI 10.1177/000992289403300509 PG 2 WC Pediatrics SC Pediatrics GA NM013 UT WOS:A1994NM01300009 ER PT J AU SILVA, JA LEONG, GB AF SILVA, JA LEONG, GB TI UNTITLED SO COMPREHENSIVE PSYCHIATRY LA English DT Letter ID MISIDENTIFICATION SYNDROMES; CAPGRAS SYNDROME C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV,SAN ANTONIO,TX 78284, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD MAY-JUN PY 1994 VL 35 IS 3 BP 244 EP 244 DI 10.1016/0010-440X(94)90198-8 PG 1 WC Psychiatry SC Psychiatry GA NL809 UT WOS:A1994NL80900012 PM 8045116 ER PT J AU DOHLMAN, CH DOANE, MG AF DOHLMAN, CH DOANE, MG TI SOME FACTORS INFLUENCING OUTCOME AFTER KERATOPROSTHESIS SURGERY SO CORNEA LA English DT Article DE KERATOPROSTHESIS SURGERY; PROSTHESIS AB Eleven patients with severe corneal disease have been operated with a collarbutton-shaped keratoprosthesis and have been followed for 9-36 months. Two of the devices have been removed, but the remainder are securely in place. Six of the patients have benefitted substantially in terms of improved vision. The complications have been reviewed, and some factors for success have been identified. Thus, to keep the keratoprosthesis temporarily buried beneath tissue (conjunctiva or skin), application of collagenase-suppressing medication and reduction of evaporative damage to the wound around the device seem particularly important. RP DOHLMAN, CH (reprint author), MASSACHUSETTS EYE & EAR INFIRM,SCHEPENS EYE RES INST,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 52 Z9 57 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD MAY PY 1994 VL 13 IS 3 BP 214 EP 218 DI 10.1097/00003226-199405000-00004 PG 5 WC Ophthalmology SC Ophthalmology GA NG275 UT WOS:A1994NG27500004 PM 8033570 ER PT J AU BARNEY, NP FOSTER, CS AF BARNEY, NP FOSTER, CS TI PROSPECTIVE RANDOMIZED TRIAL OF ORAL ACYCLOVIR AFTER PENETRATING KERATOPLASTY FOR HERPES-SIMPLEX KERATITIS SO CORNEA LA English DT Article DE HERPES SIMPLEX; PENETRATING KERATOPLASTY; ACYCLOVIR; RECURRENCE AB Corneal graft survival in 13 patients (14 eyes) receiving oral acyclovir after penetrating keratoplasty for herpes simplex keratitis was compared with that in nine patients (nine eyes) who underwent penetrating keratoplasty for herpes simplex keratitis without postoperative acyclovir. Mean age, duration of disease, and time of follow-up did not differ in the two groups. There were no recurrences of herpes simplex keratitis in any patient receiving acyclovir during a mean follow-up of 16.5 months compared with a 44% (four of nine) recurrence rate in patients without acyclovir during a mean follow-up of 20.6 months (p < 0.01). Graft failure occurred in 14% (2 of 14) of acyclovir treatment eyes compared with 56% (five of nine) without acyclovir. Long-term prophylactic oral acyclovir signifi cantly decreased the recurrence of herpes simplex keratitis and reduced corneal graft failure in patients who had a history of recurrent herpes simplex keratitis and who had undergone penetrating keratoplasty. C1 MASSACHUSETTS EYE & EAR INFIRM,SERV IMMUNOL,BOSTON,MA 02114. NR 0 TC 53 Z9 58 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD MAY PY 1994 VL 13 IS 3 BP 232 EP 236 DI 10.1097/00003226-199405000-00007 PG 5 WC Ophthalmology SC Ophthalmology GA NG275 UT WOS:A1994NG27500007 PM 8033573 ER PT J AU CARR, DB TODRES, ID AF CARR, DB TODRES, ID TI FENTANYL INFUSION AND WEANING IN THE PEDIATRIC INTENSIVE-CARE UNIT - TOWARD SCIENCE-BASED PRACTICE SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE FENTANYL; SEDATION; ANALGESIA; INTENSIVE CARE, PEDIATRIC; MECHANICAL VENTILATION; DRUG INFUSION, INTRAVENOUS ID OPIATE-WITHDRAWAL; STRESS RESPONSES; CARDIAC-SURGERY; MORPHINE; ANESTHESIA; DEPENDENCE; ANALGESIA; TOLERANCE; NEURONS; BABIES C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP CARR, DB (reprint author), MASSACHUSETTS GEN HOSP,WANG AMBULATORY CARE CTR,DEPT ANESTHESIA,SUITE 333,BOSTON,MA 02114, USA. NR 25 TC 18 Z9 18 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1994 VL 22 IS 5 BP 725 EP 727 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA NZ174 UT WOS:A1994NZ17400001 PM 8181276 ER PT J AU MUNOZ, R KHILNANI, P ZIEGLER, J SALEM, M CATLIN, EA NUSSBAUM, S TODRES, ID CHERNOW, B AF MUNOZ, R KHILNANI, P ZIEGLER, J SALEM, M CATLIN, EA NUSSBAUM, S TODRES, ID CHERNOW, B TI ULTRAFILTERABLE HYPOMAGNESEMIA IN NEONATES ADMITTED TO THE NEONATAL INTENSIVE-CARE UNIT SO CRITICAL CARE MEDICINE LA English DT Article DE MAGNESIUM; HYPOMAGNESEMIA; NEONATES; MECHANICAL VENTILATION; HYPOKALEMIA; CALCIUM; HYPOCALCEMIA; PARATHYROID HORMONE; CALCIUM GLUCONATE; NUTRITION ID CRITICALLY ILL PATIENTS; CRITICAL ILLNESS; MAGNESIUM-DEFICIENCY; GENTAMICIN THERAPY; HYPOCALCEMIA; CALCIUM; HYPERTENSION; PREGNANCY; COMMON; MUSCLE AB Objective: To evaluate the frequency and clinical correlates of ultrafilterable hypomagnesemia in neonates admitted to the neonatal intensive care unit (ICU). Design: Prospective, observational study. Setting: Massachusetts General Hospital and Mount Auburn Hospital. Patients: A total of 117 patients (84 neonatal ICU patients and 33 normal newborns) studied over a 2-yr period of time. Measurements: Blood samples were collected during the first 48 hrs after admission. The concentrations of magnesium (total and ultrafilterable), ionized calcium, parathyroid hormone, electrolytes, glucose and arterial blood gases were determined. Results: Ultrafilterable circulating magnesium concentrations were determined in 74 of 84 neonatal ICU patients. On admission to the neonatal ICU, 23 (31.1%) of 74 neonates had ultrafilterable hypomagnesemia; two (2.7%) of 74 patients had ultrafilterable hypermagnesemia. Neonatal ICU patients had significantly lower (p < .001) ultrafilterable magnesium concentrations compared with normal neonates. Hypomagnesemic ICU patients required mechanical ventilatory support more frequently than did normomagnesemic ICU neonates (p < .05). Ionized hypocalcemia was a common finding in our patients (34 [42%] of 81). However, ultrafilterable hypomagnesemia was not statistically associated with ionized hypocalcemia (p > .05). Despite the below normal serum concentrations of ultrafilterable magnesium observed in our study, there was no impairment in parathyroid hormone secretion. Conclusions: Ultrafilterable hypomagnesemia is a common finding in neonates admitted to the ICU. Ultrafilterable hypomagnesemia is associated with the need for mechanical ventilation. To our knowledge, this is the first report of ultrafilterable magnesium concentrations in normal and sick neonates. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEONATOL UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CHILDRENS SERV,PEDIAT INSTENS CARE UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,DIV SURG INTENS CARE,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NR 32 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1994 VL 22 IS 5 BP 815 EP 820 DI 10.1097/00003246-199405000-00017 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA NZ174 UT WOS:A1994NZ17400017 PM 8181290 ER PT J AU CONN, AKT AF CONN, AKT TI CRITICAL CARE IN THE EMERGENCY DEPARTMENT - SAVING INTENSIVE-CARE UNIT FACILITIES - REPLY SO CRITICAL CARE MEDICINE LA English DT Letter RP CONN, AKT (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1994 VL 22 IS 5 BP 897 EP 898 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA NZ174 UT WOS:A1994NZ17400035 ER PT J AU ESPAILLAT, A LEE, SJ ARRUNATEGUICORREA, V FOSTER, CS VITALE, A DIMEO, S COLVIN, RB AF ESPAILLAT, A LEE, SJ ARRUNATEGUICORREA, V FOSTER, CS VITALE, A DIMEO, S COLVIN, RB TI EXPRESSION OF FIBRONECTIN ISOFORMS IN RAT CORNEA AFTER AN EPITHELIAL-SCRAPE WOUND SO CURRENT EYE RESEARCH LA English DT Article DE PCR (POLYMERASE CHAIN REACTION); FIBRONECTIN ISOFORMS; CORNEA; WOUND HEALING; EPITHELIAL WOUNDS; RAT ID GENE; RNA AB The polymerase chain reaction (PCR) technique was used to analyze the presence or absence of the EIIIB and V region fibronectin (FN) mRNA isoforms, generated by alternative splicing of the FN primary mRNA transcript during epithelial wound healing, in a rat cornea wound model. A central 4mm area of the cornea was denuded of epithelium. At 5, 15, 30, 45 minutes, 1, 2, 4, 8, 24, 48 hours, and 4 days post-wounding, the rats were euthanized and a 6mm diameter full thickness corneal biopsy was performed. cDNA was synthesized from extracted RNA, and specific FN sequences were amplified by PCR as directed by different sets of 5' and 3' primers specific for the alternatively spliced EIIIB and V region domains. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA expression was used to normalize the data. PCR products were analyzed by agarose gel electrophoresis and the identity of the bands were confirmed by direct nucleotide sequencing. The alternatively-spliced EIIIB and all three alternatively. spliced isoforms of V domain FN mRNA were observed post-wounding. Similarly, in normal tissue, EIIIB and all three V region alternatively spliced FN isoforms were expressed. These findings suggest that in situ synthesis of cellular associated EIIIB FN and FN V domain may play a role in corneal wound healing. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL SERV,RHOADS MOLEC IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,GENET MOLEC LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NCI NIH HHS [R37 CA208822] NR 19 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1994 VL 13 IS 5 BP 325 EP 330 DI 10.3109/02713689409167295 PG 6 WC Ophthalmology SC Ophthalmology GA NL282 UT WOS:A1994NL28200002 PM 8055695 ER PT J AU CUMMINGS, JL AF CUMMINGS, JL TI VASCULAR SUBCORTICAL DEMENTIAS - CLINICAL ASPECTS SO DEMENTIA LA English DT Article; Proceedings Paper CT 2nd Symposium on Ageing and Ageing Disorders CY AUG 19-20, 1993 CL STOCKHOLM, SWEDEN SP FDN GAMLA TJANARINNOR DE SUBCORTICAL DEMENTIA; LACUNES; BINSWANGERS DISEASE; FRONTAL-SUBCORTICAL CIRCUITS; EXECUTIVE FUNCTION ID MULTI-INFARCT DEMENTIA; SYMPTOMS PREDOMINATE; BINSWANGERS DISEASE; BASAL GANGLIA; PARKINSONISM; DIAGNOSIS; LACUNES AB Vascular dementia (VAD) is common, and small vessel disease is one of the most frequent etiologies of the disorder. Lacunar state and Binswanger's disease are the two types of VAD associated with small vessel disease. Lacunar state and Binswanger's disease produce a dementia syndrome with characteristics of subcortical dementia including slowing of information processing, impaired memory, and poor sustained attention. Executive dysfunction includes poor word list generation and verbal fluency (design generation), impaired motor programming with perseveration and impersistence, and difficulty with set shifting. Memory loss in subcortical VAD is characterized by poor retrieval and intact recognition. Apathy is ubiquitous in VAD and depression and psychosis are common. Parkinsonism with prominent gait disturbances in conjunction with pyramidal tract signs, dysarthria, pseudobulbar affect, and incontinence are frequent motor manifestations of VAD with small vessel disease. The lesions of subcortical VAD affect the structures - caudate nucleus, globus pallidus, thalamus - and connecting fibers of frontal-subcortical circuits and produce a clinical syndrome similar to that seen in other subcortical diseases. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,BEHAV NEUROSCI SECT,LOS ANGELES,CA. RP CUMMINGS, JL (reprint author), UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,710 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [AG10123] NR 25 TC 123 Z9 131 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1013-7424 J9 DEMENTIA JI Dementia PD MAY-AUG PY 1994 VL 5 IS 3-4 BP 177 EP 180 DI 10.1159/000106718 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NP580 UT WOS:A1994NP58000011 PM 8087175 ER PT J AU GIULIAN, D LI, J LI, X GEORGE, J RUTECKI, PA AF GIULIAN, D LI, J LI, X GEORGE, J RUTECKI, PA TI THE IMPACT OF MICROGLIA-DERIVED CYTOKINES UPON GLIOSIS IN THE CNS SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE AIDS; ALZHEIMERS DISEASE; BRAIN INJURY; CYTOKINES; GLIA; MICROGLIA; NEURON; STROKE ID TUMOR NECROSIS FACTOR; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MAMMALIAN BRAIN; AMEBOID MICROGLIA; FACTOR-ALPHA; INTERLEUKIN-1; ASTROCYTES; INJURY; CELLS AB Injury to the CNS elicits a complex cellular response involving both astrocytes and microglia. Reactive glial populations make up the so-called 'glial scar' that has long been implicated as a barrier to axonal regeneration or as a causal factor in the genesis of epilepsy. Using in vitro models involving highly enriched populations of brain cells we have observed that astroglial growth is regulated in part by an immunomodulatory growth factor, or cytokine, called interleukin-1 (IL-1). A second cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) serves as a potent microglial mitogen and regulator of the microglial component of the glial scar. Employing cytokines as tools to manipulate reactive gliosis, we found that IL-1 supported neuronal growth by action upon astroglia, while GM-CSF initiated epileptic-like discharges through mechanisms involving reactive microglia. We propose that a 'cytokine network' involving IL-1 and GM-CSF mediates the composition of glial scars at sites of CNS injury; these reactive glia, in turn, influence the survival and function of neighboring neurons, C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,FM FORSTER EPILEPSY CTR,DEPT NEUROL,MADISON,WI. RP GIULIAN, D (reprint author), BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030, USA. FU NINDS NIH HHS [NS28580, NS23113, NS25637] NR 29 TC 146 Z9 148 U1 1 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAY-AUG PY 1994 VL 16 IS 3-4 BP 128 EP 136 DI 10.1159/000112099 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PZ611 UT WOS:A1994PZ61100003 PM 7535679 ER PT J AU LIPTON, SA AF LIPTON, SA TI NEURONAL INJURY ASSOCIATED WITH HIV-1 AND POTENTIAL TREATMENT WITH CALCIUM-CHANNEL AND NMDA ANTAGONISTS SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE AIDS; ARACHIDONATE; ASTROCYTES; CYSTEINE; CYTOKINES; DEMENTIA; FREE RADICALS; GLUTAMATE; GP120; HIV-1-ASSOCIATED COGNITIVE MOTOR COMPLEX; INTERFERON-GAMMA; INTERLEUKIN-1-BETA; INTERLEUKIN-6; MACROPHAGES; MICROGLIA; NEURONS; NEUROTOXICITY; NITRIC OXIDE; N-METHYL-D-ASPARTATE RECEPTOR; PLATELET-ACTIVATING FACTOR; QUINOLINATE; TAT; TUMOR NECROSIS FACTOR-ALPHA ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR-MEDIATED NEUROTOXICITY; TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE; ARACHIDONIC-ACID; COAT PROTEIN; QUINOLINIC ACID; MONONUCLEAR PHAGOCYTES; INFECTED MACROPHAGES; CEREBROSPINAL-FLUID AB A substantial number of adults and half of the children with acquired immunodeficiency syndrome (AIDS) suffer from neurological manifestations. Among the various pathologies reported in brains of patients with AIDS is neuronal injury and loss, although neurons themselves do not appear to be infected by HIV-1. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells, especially after interacting with astrocytes, secrete neurotoxic substances. Not all of these substances are yet known, but they may include eicosanoids, platelet-activating factor, quinolinate, cysteine, cytokines, and free radicals. Macrophages activated by HIV-1 envelope protein gp120 also appear to release similar toxins. Some of these factors can lead to increased glutamate release or decreased glutamate reuptake. A final common pathway for neu ronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-asparate (NMDA) receptor-operated channels, and therefore offers hope for future pharmacological intervention, This review focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP LIPTON, SA (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI LAB,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 60 TC 57 Z9 57 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAY-AUG PY 1994 VL 16 IS 3-4 BP 145 EP 151 DI 10.1159/000112101 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PZ611 UT WOS:A1994PZ61100005 PM 7705221 ER PT J AU DORIA, A WARRAM, JH KROLEWSKI, AS AF DORIA, A WARRAM, JH KROLEWSKI, AS TI GENETIC PREDISPOSITION TO DIABETIC NEPHROPATHY - EVIDENCE FOR A ROLE OF THE ANGIOTENSIN I-CONVERTING ENZYME GENE SO DIABETES LA English DT Article ID INSERTION DELETION POLYMORPHISM; RISK FACTOR; DISEASE; SUSCEPTIBILITY; HYPERTENSION; MELLITUS; LINKAGE AB In search of genetic determinants of susceptibility to diabetic nephropathy, we examined the association between DNA sequence differences at the locus of angiotensin I-converting enzyme (ACE) and renal complications in 151 insulin-dependent diabetes mellitus (IDDM) patients with a diabetes duration of 16-21 years. This nested case-control study included 77 normoalbuminuric control subjects (albumin excretion rate <30 mu g/min) and 74 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. DNA from each of these patients was genotyped at the ACE locus by a three-allele restriction fragment-melting polymorphism (RFMP) (Dde I), which we described recently, and a two-allele insertion/deletion recognized as an Xba I restriction fragment-length polymorphism, which has been shown by other investigators to be associated with serum levels of ACE and with risk of myocardial infarction. The least common allele of the Dde I RFMP was significantly more frequent among cases with nephropathy than among normoalbuminuric control subjects (12.8 vs. 4.5%, P < 0.05). The deletion in the ACE gene was also more frequent in case than in control subjects (56.1 vs. 47.4%), but the difference was not statistically significant (P < 0,25) with this sample size. To determine the independence of these associations, the two polymorphisms were analyzed jointly to identify Xba I/Dde I haplotypes. As might be expected, carriers of the Xba I/Dde I '+=' haplotype had a fourfold risk of developing diabetic nephropathy (odds ratio [OR] 4.0, 95% confidence interval [CI] 1.5-11.0). However, this did not explain all of the excess Xba I '+' allele among cases. Carriers of the '++' haplotype were also more frequent among cases (OR 2.0, 95% CI 0.8-4.9), but this association was not statistically significant with this sample size. This study provides evidence that DNA sequence differences in the ACE gene may contribute to genetic susceptibility to diabetic nephropathy in IDDM. C1 JOSLIN DIABET CTR,DIV RES,EPIDEMIOL & GENET SECT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIDDK NIH HHS [P30-DK-36836, R01-DK-41526] NR 28 TC 189 Z9 191 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1994 VL 43 IS 5 BP 690 EP 695 DI 10.2337/diabetes.43.5.690 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK002 UT WOS:A1994NK00200013 PM 7909524 ER PT J AU MOORADIAN, AD FAILLA, M HOOGWERF, B MARYNIUK, M WYLIEROSETT, J AF MOORADIAN, AD FAILLA, M HOOGWERF, B MARYNIUK, M WYLIEROSETT, J TI SELECTED VITAMINS AND MINERALS IN DIABETES SO DIABETES CARE LA English DT Review ID TOTAL PARENTERAL-NUTRITION; ASCORBIC-ACID METABOLISM; GLUCOSE-TOLERANCE FACTOR; HIGH-DENSITY LIPOPROTEIN; ZINC STATUS; CHROMIUM SUPPLEMENTATION; SELENIUM DEFICIENCY; BREWERS-YEAST; BONE MASS; MAGNESIUM-METABOLISM C1 UNIV N CAROLINA,GREENSBORO,NC 27412. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. JOSLIN DIABET CTR,BOSTON,MA 02215. ALBERT EINSTEIN INST,BRONX,NY. RP MOORADIAN, AD (reprint author), ST LOUIS UNIV,MED CTR,ST LOUIS,MO, USA. NR 198 TC 76 Z9 82 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1994 VL 17 IS 5 BP 464 EP 479 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK271 UT WOS:A1994NK27100027 PM 8062625 ER PT J AU PFALLER, MA BUSCHELMAN, B BALE, MJ LANCASTER, M ESPINELINGROFF, A REX, JH RINALDI, MG AF PFALLER, MA BUSCHELMAN, B BALE, MJ LANCASTER, M ESPINELINGROFF, A REX, JH RINALDI, MG TI MULTICENTER COMPARISON OF A COLORIMETRIC MICRODILUTION BROTH METHOD WITH THE REFERENCE MACRODILUTION METHOD FOR IN-VITRO SUSCEPTIBILITY TESTING OF YEAST ISOLATES SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article AB This multicenter study was performed to compare a colorimetric microdilution method with the NCCLS M27-P reference macrodilution method for the testing of yeast isolates against amphotericin B, fluconazole, and 5-fluorocytosine (5FC). Testing was performed on ten yeast isolates in five independent laboratories. All sites tested each isolate a total of 20 times with both methods. MICs were read after 48 h incubation. The macrodilution MIC reference range was defined as the modal MIC +/- 1-log(2) dilution for each organism-antifungal agent combination. Agreement between the M27-P reference range results and the microdilution MICs was 86% with amphotericin B, 90% with fluconazole, and 93% with 5FC. Based on these data, it is apparent that new approaches, such as the colorimetric microdilution method, will provide MIC values comparable to the M27-P macrodilution method in a format that is more practical for use in a busy clinical laboratory. C1 ALAMAR BIOSCI,SACRAMENTO,CA. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,RICHMOND,VA. UNIV TEXAS,SCH MED,HOUSTON,TX. UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,CTR HLTH SCI,LAB SERV 113,SAN ANTONIO,TX 78285. RP PFALLER, MA (reprint author), UNIV IOWA,COLL MED,DEPT PATHOL,273 MRC,IOWA CITY,IA 52242, USA. NR 4 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAY PY 1994 VL 19 IS 1 BP 9 EP 13 DI 10.1016/0732-8893(94)90044-2 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA NX242 UT WOS:A1994NX24200003 PM 7956018 ER PT J AU HIBBERD, PL AF HIBBERD, PL TI PREVENTING CMV INFECTION IN END-STAGE RENAL-DISEASE SO DIALYSIS & TRANSPLANTATION LA English DT Article AB Cytomegalovirus (CMV) is a ubiquitous virus that rarely causes clinical disease unless the person it infects is immunosuppressed. Although patients with end-stage renal disease are at the same risk of developing symptomatic disease after infection with cytomegalovirus as a normal individual, CMV infection is important for two reasons. First, in addition to the usual ways in which CMV infection occurs, dialysis patients may also acquire infection from blood transfusions; there is increased risk following multiple transfusions. Second, dialysis patients who become transplant recipients may be at risk of morbidity and mortality due to CMV following transplantation. Preventing CMV disease remains a priority and may be achieved by a range of strategies from using erythropoietin to reducing transfusion requirements to antiviral therapy for transplant recipients at high risk of developing CMV disease. RP HIBBERD, PL (reprint author), MASSACHUSETTS GEN HOSP,PROGRAM TRANSPLANT INFECT DIS,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU CREATIVE AGE PUBL PI VAN NUYS PA 7628 DENSMORE AVE, VAN NUYS, CA 91406-2088 SN 0090-2934 J9 DIALYSIS TRANSPLANT JI Dial. Transplant. PD MAY PY 1994 VL 23 IS 5 BP 233 EP 237 PG 5 WC Engineering, Biomedical; Transplantation; Urology & Nephrology SC Engineering; Transplantation; Urology & Nephrology GA NJ313 UT WOS:A1994NJ31300004 ER PT J AU GRIFFIN, BP FLACHSKAMPF, FA REIMOLD, SC LEE, RT THOMAS, JD AF GRIFFIN, BP FLACHSKAMPF, FA REIMOLD, SC LEE, RT THOMAS, JD TI RELATIONSHIP OF AORTIC REGURGITANT VELOCITY SLOPE AND PRESSURE HALF-TIME TO SEVERITY OF AORTIC REGURGITATION UNDER CHANGING HEMODYNAMIC CONDITIONS SO EUROPEAN HEART JOURNAL LA English DT Article DE AORTIC REGURGITATION; DOPPLER-ECHOCARDIOGRAPHY ID WAVE DOPPLER ECHOCARDIOGRAPHY; IMPROVED CARDIAC-PERFORMANCE; HEMODYNAMIC CONSEQUENCES; AFTERLOAD REDUCTION; INSUFFICIENCY; ULTRASOUND C1 MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02115. NR 15 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 1994 VL 15 IS 5 BP 681 EP 685 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NP456 UT WOS:A1994NP45600016 PM 8056010 ER PT J AU POTTS, AJ CROALL, DE HEMLER, ME AF POTTS, AJ CROALL, DE HEMLER, ME TI PROTEOLYTIC CLEAVAGE OF THE INTEGRIN BETA(4), SUBUNIT SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID ACTIVATED NEUTRAL PROTEASE; ALPHA-6-BETA-4 INTEGRIN; EPIDERMAL-KERATINOCYTES; MONOCLONAL-ANTIBODIES; SQUAMOUS CARCINOMA; EPITHELIAL ANTIGEN; BETA-4 SUBUNIT; CELL; EXPRESSION; HEMIDESMOSOMES AB The integrin beta(4) subunit often undergoes proteolytic cleavage within its long cytoplasmic tail to yield a characteristic protein pattern of 205, 165, and 125 kDa. The results in this study suggest that beta(4) cleavage often occurs during or after cell lysis, where it was readily inhibitable by calcium chelators (EDTA, EGTA) and inhibitors of cysteine proteases (E64c, leupeptin). The cleavage of beta(4) is catalyzed by a calpain-like enzyme because (i) it requires calcium, (ii) it is mimicked by purified milli-calpain, and (iii) it is inhibited by several calpain inhibitors including the calpain-specific inhibitor calpastatin. Within intact cells, cleavage of beta(4) was cell type-specific and observed only when the cells were made permeable to calcium. Substantial cell viability was retained during beta(4) cleavage induced by ionomycin plus calcium, indicating that cleavage within intact cells was not necessarily a consequence of cell death. However, manipulations of cells including suspension, synchronization, and stimulation with serum, phorbol esters, or other agents all failed to induce cleavage, suggesting that if cleavage is physiologically relevant, it is not easily duplicated in vitro. Analysis of multiple cell types showed a wide variation in beta(4) sensitivity to proteolytic cleavage, suggesting that this process might be differentially regulated depending on the cellular environment. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MAINE,DEPT BIOCHEM MICROBIOL & MOLEC BIOL,ORONO,ME 04469. FU NCI NIH HHS [CA42368] NR 41 TC 40 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1994 VL 212 IS 1 BP 2 EP 9 DI 10.1006/excr.1994.1111 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA NL213 UT WOS:A1994NL21300001 PM 8174638 ER PT J AU SOKOL, L PRCHAL, JF DANDREA, A RADO, TA PRCHAL, JT AF SOKOL, L PRCHAL, JF DANDREA, A RADO, TA PRCHAL, JT TI MUTATION IN THE NEGATIVE REGULATORY ELEMENT OF THE ERYTHROPOIETIN RECEPTOR GENE IN A CASE OF SPORADIC PRIMARY POLYCYTHEMIA SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE ERYTHROPOIETIN RECEPTOR; MUTATION; PRIMARY FAMILIAL AND CONGENITAL POLYCYTHEMIA ID FAMILIAL POLYCYTHEMIA; PURE ERYTHROCYTOSIS; HUMAN MARROW; VERA; ACTIVATION; INVITRO; CELLS; SITE AB A 42-year-old Caucasian male with sporadic primary polycythemia has been followed by us for 13 years. During the time of observation, his hemoglobin had been stable, and he has never had an elevated white count or platelet count or any other stigmata of polycythemia vera (PV). Both of his parents, his three children, and all siblings have been hematologically normal. The in vitro culture of erythroid progenitors revealed an absence of autonomous erythropoietin (Epo)-independent erythroid colonies but demonstrated a marked increase in the sensitivity of erythroid progenitors to Epo. We have undertaken a study designed to determine whether a mutation in the Epo receptor (Epo-R) gene could cause the polycythemia phenotype seen in either dominant or recessive primary polycythemia described by us and others, or in polycythemia vera. We have sequenced the cytoplasmic positive and negative regulatory domains of the Epo-R genomic DNA, and a transversion of C to T in nucleotide 6148 was found in one of the patient's chromosomes. This mutation is located in the negative regulatory domain and results in a change from proline to serine (P388S). We have subsequently analyzed more than 40 chromosomes from unrelated normal subjects, as well as autosomal dominant, recessive, and sporadic primary polycythemia and polycythemia vera subjects. In no instance was the same or any other mutation in the Epo-R found. To determine if this Epo-R mutation is a cause of increased sensitivity of erythroid progenitors to erythropoietin, Ba/F3 cells (interleukin-3-dependent murine lymphoid line) were transfected with normal and mutated Epo-R cDNA, rendering the transfected cells viable and able to proliferate in Epo. Transfectants with wild-type and mutant Epo-R cDNA exhibited no difference in the presence of Epo. More recently, we were able to obtain DNA from the seven family members of the propositus and found that the nonpolycythemic mother and one of the siblings have the same Epo-R mutation. We conclude that this first described mutation of Epo-R encountered in humans does not appear on its own to explain the polycythemia phenotype; however, the possibility that it may interact with some other acquired or congenital abnormality in generating the polycythemia phenotype cannot be excluded. C1 UNIV ALABAMA,DEPT MED,DIV HEMATOL ONCOL,BIRMINGHAM,AL 35294. MCGILL UNIV,DEPT MED,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT ONCOL,MONTREAL,PQ,CANADA. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [1RO1HL50077-01] NR 36 TC 34 Z9 36 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1994 VL 22 IS 5 BP 447 EP 453 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA NJ851 UT WOS:A1994NJ85100006 PM 8174675 ER PT J AU BRUNING, R HEUCK, A NAEGELE, M SEELOS, K VAHLENSIECK, M REISER, M AF BRUNING, R HEUCK, A NAEGELE, M SEELOS, K VAHLENSIECK, M REISER, M TI FAT-SUPPRESSED STIR SEQUENCES WITH AND WITHOUT CONTRAST-MEDIUM IN MRT OF ENT TUMORS SO FORTSCHRITTE AUF DEM GEBIETE DER RONTGENSTRAHLEN UND DER NEUEN BILDGEBENDEN VERFAHREN LA German DT Article DE MRT; GD-DTPA; HNO-TUMORS ID SPIN-ECHO MR; BONE-TUMORS; METASTASES; NEURITIS; LIVER AB Fat suppressed STIR (short TI inversion recovery) sequences were compared to plain an contrast enhanced T1-weighted SE-sequences of head and neck tumours. 19 patients underwent MR imaging on a 0.5 Tesla system (T5-II, Philips). STIR imaging parameters: TR/TE = 1000/20 ms, inversion pulse 100 ms. All films were read by four radiologists. The image quality was graded: score from 0 to 5, by means that grade 5 = optimal quality. Sensitivity was 89 % in STIR, 96% in SE-sequences. Tumour delineation was graded good in the enhanced T1-weighted and enhanced fat suppression images. The unenhanced imaging was superior in STIR (STIR/T1 = 2.8/2.43). The tumour contrast was best in contrast enhanced and plain STIR sequences (STIR contrast = 3.41), and in the contrast enhanced T1-weighted SE (3.33). STIR almost equaled T1 post-contrast in respect of tumour conspicuity, but the sensitivity was lower. STIR can be a supplement to SE, but cannot substitute T1 postcontrast. The combined use is expected to have the highest assessment value. C1 KLINIKUM GROSSHADERN,INST RADIOL DIAGNOST,MUNICH,GERMANY. RP BRUNING, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,BLDG 149,MGH E,BOSTON,MA 02114, USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0936-6652 J9 ROFO FORTSCHR RONTG JI Fortschritte Geb. Rontgenstr. Neuen Bildgebenden Verfahren PD MAY PY 1994 VL 160 IS 5 BP 412 EP 416 DI 10.1055/s-2008-1032451 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NL221 UT WOS:A1994NL22100004 PM 8173051 ER PT J AU DIGNASS, AU TSUNEKAWA, S PODOLSKY, DK AF DIGNASS, AU TSUNEKAWA, S PODOLSKY, DK TI FIBROBLAST GROWTH-FACTORS MODULATE INTESTINAL EPITHELIAL-CELL GROWTH AND MIGRATION SO GASTROENTEROLOGY LA English DT Article ID COLON CANCER LINES; FACTOR-BETA; INVITRO MODEL; FACTOR-ALPHA; EXPRESSION; DIFFERENTIATION; PROLIFERATION; RESTITUTION; CULTURE; REPAIR C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK 41557, DK 43351] NR 43 TC 236 Z9 236 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1994 VL 106 IS 5 BP 1254 EP 1262 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NJ158 UT WOS:A1994NJ15800016 PM 7513666 ER PT J AU WEREMOWICZ, S KOZAKEWICH, HP HABER, D PARK, S MORTON, CC FLETCHER, JA AF WEREMOWICZ, S KOZAKEWICH, HP HABER, D PARK, S MORTON, CC FLETCHER, JA TI IDENTIFICATION OF GENETICALLY ABERRANT CELL LINEAGES IN WILMS-TUMORS SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE AB Most Wilms' tumors contain several predominant cell types, of which a primitive blastemal population is often the most prominent. Other typical components include undifferentiated mesenchymal and epithelial cells, but it has not been demonstrated that these components are neoplastic. We used a combined cytogenetic and fluorescence in situ hybridization approach to determine the clonal relationship of different cell populations within six Wilms' tumors. Clonal numerical chromosome aberrations in three Wilms' tumors were found in blastemal cells, but not in mesenchymal cells. Loss of one WT1 allele in two other tumors was detected in both blastemal and mesenchymal cells. Tetrasomy 18 in a sixth case was observed in mesenchymal and epithelial cells; blastemal cells could not be evaluated in this tumor. These findings demonstrate that mesenchymal and epithelial cells in some Wilms' tumors are neoplastic. Different histologic components in some Wilms' tumors derive from a single chromosomally aberrant ancestor which is most likely to be the primitive blastemal cell. (C) 1994 Wiley-Liss, Inc. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DIV HEMATOL ONCOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,BOSTON,MA. FU NCI NIH HHS [1K11CA01498-03] NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1994 VL 10 IS 1 BP 40 EP 48 DI 10.1002/gcc.2870100107 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA NH438 UT WOS:A1994NH43800006 PM 7519872 ER PT J AU YOUNG, F ARDMAN, B SHINKAI, Y LANSFORD, R BLACKWELL, TK MENDELSOHN, M ROLINK, A MELCHERS, F ALT, FW AF YOUNG, F ARDMAN, B SHINKAI, Y LANSFORD, R BLACKWELL, TK MENDELSOHN, M ROLINK, A MELCHERS, F ALT, FW TI INFLUENCE OF IMMUNOGLOBULIN HEAVY-CHAIN AND LIGHT-CHAIN EXPRESSION ON B-CELL DIFFERENTIATION SO GENES & DEVELOPMENT LA English DT Article DE RAG-2; B-CELL DEVELOPMENT; IMMUNOGLOBULIN TRANSGENES; PRE-B-CELLS; SURROGATE LIGHT CHAINS ID COMBINED IMMUNE-DEFICIENCY; MURINE BONE-MARROW; PRE-B; GENE REARRANGEMENT; LYMPHOCYTES-B; ANTIGEN RECEPTOR; GROWTH-FACTOR; T-CELLS; V(D)J RECOMBINATION; TARGETED DISRUPTION AB To study the influence of immunoglobulin heavy-chain (HC) and light-chain (LC) expression in promoting B-cell differentiation, we have introduced functional immunoglobulin HC and/or LC transgenes into the recombinase activating gene-2-deficient background (RAG-2(-/-)). RAG-2(-/-) mice do not undergo endogenous V(D)J rearrangement events and, therefore, are blocked in B- and T-cell development at the early pro-B- and pro-T-cell stages. Introduction of immunoglobulin HC transgenes into the RAG-2(-/-) background promotes the development of a B-lineage cell population that phenotypically has the characteristics of pre-B cells. We have shown further that this population has altered growth characteristics as measured by interleukin-7 responsiveness in culture. Bone marrow cells from immunoglobulin HC transgenic RAG-2(-/-) mice have up-regulated expression of germ-line kappa LC gene transcripts and down-regulated expression of lambda(5) surrogate LCs (SLCs). Although mu HC/SLC complexes are detectable intracellularly in HC/RAG-2(-/-) pre-B-cell populations, HC expression is not readily detectable on the surface of these cells. lambda LC RAG-2(-/-) mice had a bone marrow B-lineage cell phenotype indistinguishable from that of RAG-2(-/-) littermates, indicating that LC expression by itself has no influence on pro-B cell differentiation. Strikingly, simultaneous introduction of mu HC and lambda. LC transgenes into RAG-2(-/-) mice led to the generation of a substantial population of ''monoclonal'' peripheral B-cells that were functional with regard to immunoglobulin secretion, indicating that T cells or diverse immunoglobulin repertoires are not necessary for peripheral B-cell development. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DEPT GENET & PEDIAT,BOSTON,MA 02115. TUFTS UNIV,NEW ENGLAND MED CTR HOSP,DEPT MED,DIV HEMATOL & ONCOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. COLUMBIA UNIV,NEW YORK,NY 10032. BASEL INST IMMUNOL,BASEL,SWITZERLAND. RI Lansford, Rusty/C-6956-2014; Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 FU NCI NIH HHS [CA42335]; NIAID NIH HHS [AI20047, U01 AI31541] NR 93 TC 180 Z9 181 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1994 VL 8 IS 9 BP 1043 EP 1057 DI 10.1101/gad.8.9.1043 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NJ947 UT WOS:A1994NJ94700005 PM 7926786 ER PT J AU ALANI, E REENAN, RAG KOLODNER, RD AF ALANI, E REENAN, RAG KOLODNER, RD TI INTERACTION BETWEEN MISMATCH REPAIR AND GENETIC-RECOMBINATION IN SACCHAROMYCES-CEREVISIAE SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; HETERODUPLEX PLASMID DNA; BASE PAIR MISMATCHES; MEIOTIC RECOMBINATION; INITIATION SITE; ESCHERICHIA-COLI; HIS4 LOCUS; YEAST; CONVERSION; SEQUENCES AB The yeast Saccharomyces cerevisiae encodes a set of genes that show strong amino acid sequence similarity to MutS and MutL, proteins required for mismatch repair in Escherichia coli. We examined the role of MSH2 and PMS1, yeast homologs of mutS and mutL, respectively, in the repair of base pair mismatches formed during meiotic recombination. By using specifically marked HIS4 and ARG4 alleles, we showed that msh2 mutants displayed a severe defect in the repair of all base pair mismatches as well as 1-, 2- and 4-bp insertion/deletion mispairs. The msh2 and pms1 phenotypes were indistinguishable, suggesting that the wild-type gene products act in the same repair pathway. A comparison of gene conversion events in wild-type and msh2 mutants indicated that mismatch repair plays an important role in genetic recombination. (1) Tetrad analysis at five different loci revealed that; in msh2 mutants, the majority of aberrant segregants displayed a sectored phenotype, consistent with a failure to repair mismatches created during heteroduplex formation. In wild type, base pair mismatches were almost exclusively repaired toward conversion rather than restoration. (2) In msh2 strains 10-19% of the aberrant tetrads were Ab4:4. (3) Polarity gradients at HIS4 and ARG4 were nearly abolished in msh2 mutants. The frequency of gene conversion at the 3' end of these genes was increased and was nearly the frequency observed at the 5' end. (4) Co-conversion studies were consistent with mismatch repair acting to regulate heteroduplex DNA tract length. We favor a model proposing that recombination events occur through the formation and resolution of heteroduplex intermediates and that mismatch repair proteins specifically interact with recombination enzymes to regulate the length of symmetric heteroduplex DNA. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP ALANI, E (reprint author), DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA06516]; NHGRI NIH HHS [HG00305] NR 65 TC 209 Z9 210 U1 0 U2 5 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1994 VL 137 IS 1 BP 19 EP 39 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA NG992 UT WOS:A1994NG99200003 PM 8056309 ER PT J AU GOTTLIEB, S RUVKUN, G AF GOTTLIEB, S RUVKUN, G TI DAF-2, DAF-16 AND DAF-23 - GENETICALLY INTERACTING GENES-CONTROLLING DAUER FORMATION IN CAENORHABDITIS-ELEGANS SO GENETICS LA English DT Article ID LARVAL DEVELOPMENT; PHEROMONE; TEMPERATURE; MUTANTS AB Under conditions of high population density and low food, Caenorhabditis elegans forms an alternative third larval stage, called the dauer stage, which is resistant to desiccation and harsh environments. Genetic analysis of some dauer constitutive (Daf-c) and dauer defective (Daf-d) mutants has revealed a complex pathway that is likely to function in particular neurons and/or responding tissues. Here we analyze the genetic interactions between three genes which comprise a branch of the dauer formation pathway that acts in parallel to or downstream of the other branches of the pathway, the Daf-c genes daf-2 and daf-23 and the Daf-d gene daf-16. Unlike mutations in other Daf-c genes, mutations in both daf-2 and daf-23 cause non-conditional arrest at the dauer stage. Our epistasis analysis suggests that daf-2 and daf-23 are functioning at a similar point in the dauer pathway. First, mutations in daf-2 and daf-23 are epistatic to mutations in the same set of Daf-d genes. Second, daf-2 and daf-23 mutants are suppressed by mutations in daf-16. Mutations in daf-16 do not suppress any of the other Daf-c mutants as efficiently as they suppress daf-2 and daf-23 mutants. Third, double mutants between either daf-2 or daf-23 and several other daf-d mutants exhibit an unusual interaction. Based on these results, we present a model for the function of daf-2, daf-23 and daf-16 in dauer formation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP GOTTLIEB, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [GM44619] NR 21 TC 209 Z9 233 U1 2 U2 17 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1994 VL 137 IS 1 BP 107 EP 120 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA NG992 UT WOS:A1994NG99200011 PM 8056303 ER PT J AU LEAF, DA AF LEAF, DA TI LIPID DISORDERS - APPLYING NEW GUIDELINES TO YOUR OLDER PATIENTS SO GERIATRICS LA English DT Article ID CORONARY HEART-DISEASE; RISK-FACTORS; LIPOPROTEIN CHOLESTEROL; MYOCARDIAL-INFARCTION; FATTY-ACIDS; FRAMINGHAM; AGE; HEALTH AB The National Cholesterol Education Program Expert Panel has revised its recommendations for managing hypercholesterolemia in adults, including those at midlife and older. In utilizing these guidelines, it is important for the physician to develop an individualized approach to the older patient with hypercholesterolemia. Patient characteristics to consider include lifespan limitations, presence and severity of concomitant disease, mental status and cognitive ability, and the patient's expectations from medical care. Dietary intervention is the first step, with the major focus on restricting saturated fat and cholesterol. Lipid-lowering agents may be warranted in some patients to achieve target LDL levels. Minimize the risk of side effects by careful monitoring and using medications cautiously. C1 W LOS ANGELES VA MED CTR,LOS ANGELES,CA. RP LEAF, DA (reprint author), UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024, USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD MAY PY 1994 VL 49 IS 5 BP 35 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA NK594 UT WOS:A1994NK59400013 PM 8174939 ER PT J AU HYMAN, SE AF HYMAN, SE TI WHY DOES THE BRAIN PREFER OPIUM TO BROCCOLI SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article RP HYMAN, SE (reprint author), MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,CNY-2,149 13TH ST,BOSTON,MA 02129, USA. FU NIDA NIH HHS [DA07134]; NIMH NIH HHS [MH44160] NR 6 TC 5 Z9 5 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1994 VL 2 IS 1 BP 43 EP 46 DI 10.3109/10673229409017114 PG 4 WC Psychiatry SC Psychiatry GA NN527 UT WOS:A1994NN52700008 PM 9384879 ER PT J AU EWING, SE ROSENBAUM, JF AF EWING, SE ROSENBAUM, JF TI PHRENOTROPICS - MAKEUP FOR THE MIND SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; FLUOXETINE; PHARMACOTHERAPY; HALOPERIDOL; AMITRIPTYLINE; PHENELZINE; PLACEBO RP EWING, SE (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,ACC-815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1994 VL 2 IS 1 BP 49 EP 51 DI 10.3109/10673229409017116 PG 3 WC Psychiatry SC Psychiatry GA NN527 UT WOS:A1994NN52700010 PM 9384881 ER PT J AU BERGLUND, AM BROWN, MC AF BERGLUND, AM BROWN, MC TI CENTRAL TRAJECTORIES OF TYPE-II SPIRAL GANGLION-CELLS FROM VARIOUS COCHLEAR REGIONS IN MICE SO HEARING RESEARCH LA English DT Article DE COCHLEAR NUCLEUS; OUTER HAIR CELLS; AFFERENT ID AUDITORY-NERVE FIBERS; OUTER HAIR-CELLS; HORSERADISH-PEROXIDASE; INFERIOR COLLICULUS; ADULT CATS; INNERVATION; NUCLEUS; MOUSE; PROJECTIONS; MORPHOLOGY AB Type II spiral ganglion cells provide the afferent pathway from outer hair cells in the mammalian cochlea to neurons in the cochlear nucleus. The present study compares the projection patterns of type II fibers originating from spiral ganglion cells of apical, middle and basal cochlear regions in mice. Fibers were labeled by extracellular injections of horseradish peroxidase into the spiral ganglion. Type II fibers from all regions displayed many 'en passant' swellings (mean = 95) and had very few terminal swellings (mean = 6); fibers from the base had significantly more swellings than those from the apex. Type II fibers traveled into the cochlear nucleus together with type I fibers labeled by the same injection, and both types bifurcated in a cochleotopic manner. The bifurcations formed ascending and descending branches that traveled initially with type I branches in the magnocellular regions of the cochlear nucleus. Type II fibers differed from type I branches in that many fibers subsequently distributed collaterals and terminals to granule cell regions and to the boundaries of these regions that typically do not receive type I input. This projection into the granule cell regions depended on cochlear origin: ascending branches of type II fibers from the cochlea apex did not usually terminate in granule cell regions, whereas those from the base often ended in these regions. Descending branches of type II fibers from all regions, however, projected to the granule cell regions, particularly the granule cell lamina between ventral and dorsal cochlear nucleus. These observations suggest that afferent information from outer hair cells reaches a wide area of the magnocellular parts of the cochlear nucleus in a cochleotopic fashion, and reaches granule cell regions with a less distinct cochleotopic mapping. C1 HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. RP BERGLUND, AM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC 00119, DC 01089, DC00006-15] NR 40 TC 52 Z9 52 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1994 VL 75 IS 1-2 BP 121 EP 130 DI 10.1016/0378-5955(94)90063-9 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA NK064 UT WOS:A1994NK06400014 PM 8071139 ER PT J AU SCHUKNECHT, HF AF SCHUKNECHT, HF TI SPONTANEOUS CEREBROSPINAL-FLUID LEAKS FROM THE TYMPANOMASTOID TEGMEN SO HNO LA German DT Article DE CEREBROSPINAL FLUID LEAK; TYMPANOMASTOID TEGMEN; DURA MATER; PETROUS BONE AB The author's experience with spontaneous cerebrospinal fluid (CSF) otorrhea from the tympanomastoid tegmen is based on the management of two clinical cases, the temporal bone histopathological findings in a third case suffering fatal meningitis and a review of the literature. Characteristically, the disorder occurs in otherwise healthy ears and is the consequence of embryogenic faults in the dura mater and adjacent tegmen. After years of exposure to physiologically normal CSF pressures, these faults may fistulize into the tympanomastoid compartment. The onset may be at any age, but is more common after age 40. About 20% of cases have a history of one or more bouts of meningitis. The site of the leak is characterized by one or more defects measuring 2-5 mm in the dura mater and adjacent bony plate, usually in the area of the petrous ridge. About 25% of defects are associated with small meningoceles or meningoencephaloceles. Computed tomographic and magnetic resonance imaging, as well as testing with fluorescein dye, provide confirming diagnostic data. Corrective surgery employs transmastoid exploration. After any existing meningoceles or meningoencephaloceles have been cauterized or amputated, small grafts of autogenous fascia or cartilage are used to plug defects found. The area is covered with temporalis fascia graft, reinforced by a pedicled muscle-fascia graft and, if needed to obliterate the mastoid cavity, a free graft of subcutaneous abdominal adipose tissue. RP SCHUKNECHT, HF (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01 DC00079] NR 0 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0017-6192 J9 HNO JI HNO PD MAY PY 1994 VL 42 IS 5 BP 288 EP 293 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA NN395 UT WOS:A1994NN39500010 PM 8050917 ER PT J AU WILENS, TE BIEDERMAN, J SPENCER, TJ FRANCES, RJ AF WILENS, TE BIEDERMAN, J SPENCER, TJ FRANCES, RJ TI COMORBIDITY OF ATTENTION-DEFICIT HYPERACTIVITY AND PSYCHOACTIVE SUBSTANCE USE DISORDERS SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article C1 HACKENSACK NJ MED CTR,HACKENSACK,NJ. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE 725,PEDIAT PSYCHOPHARMACOL CLIN & RES PROGRAM,BOSTON,MA 02114, USA. NR 0 TC 77 Z9 78 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD MAY PY 1994 VL 45 IS 5 BP 421 EP & PG 0 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA NJ221 UT WOS:A1994NJ22100002 PM 8045536 ER PT J AU HARTZ, D BANYS, P HALL, SM AF HARTZ, D BANYS, P HALL, SM TI CORRELATES OF HOMELESSNESS AMONG SUBSTANCE-ABUSE PATIENTS AT A VA MEDICAL-CENTER SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Note ID MENTAL-DISORDERS; HEALTH-STATUS; DRUG-ABUSE; ALCOHOL; ADULTS C1 UNIV CALIF SAN FRANCISCO,LANGLEY PORTER PSYCHIAT INST,SAN FRANCISCO,CA 94143. SAN FRANCISCO VA MED CTR,PSYCHIAT SERV,SAN FRANCISCO,CA. FU NIDA NIH HHS [1R18-DA06097] NR 10 TC 10 Z9 10 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD MAY PY 1994 VL 45 IS 5 BP 491 EP 493 PG 3 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA NJ221 UT WOS:A1994NJ22100016 PM 8045549 ER PT J AU CHEN, SY BAGLEY, J MARASCO, WA AF CHEN, SY BAGLEY, J MARASCO, WA TI INTRACELLULAR ANTIBODIES AS A NEW CLASS OF THERAPEUTIC MOLECULES FOR GENE-THERAPY SO HUMAN GENE THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; HTLV-III/LAV ENVELOPE; T-CELLS; HIV-1; GLYCOPROTEIN; REPLICATION; EXPRESSION; MUTANTS; GP120 AB Intracellularly expressed antibodies, referred to as ''intrabodies,'' can be designed to bind and inactivate target molecules inside cells. In our previous study, mammalian cells were transduced to produce an anti-gp120 single-chain intrabody sFv105 to inactivate human immunodeficiency virus type-1 (HIV-1) infection. Here, an inducible expression vector was constructed in which the sFv105 intrabody, which reacts with the CD4-binding site of HIV-1 gp120, is under the control of the HIV-1 long terminal repeat (LTR)/promoter. The sFv105 intrabody is inducibly expressed after HIV-1 infection or in the presence of Tat protein and is retained intracellularly. A human CD4(+) lymphocyte line transformed with the expression vector exhibits resistance to the virus-mediated syncytium formation and a decreased ability to support HIV-1 production. Surface gp120 expression is markedly reduced and surface CD4 is restored to normal following HIV-1 infection in the transformed lymphocytes. Cell-surface phenotype, replication rate, morphology, and response to mitogenic stimulation of the transformed cells are also normal. Thus, intrabodies are a new class of active molecules that may be useful for the gene therapy of acquired immunodeficiency virus (AIDS) and other diseases. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, R01 AI28785] NR 31 TC 80 Z9 85 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 1994 VL 5 IS 5 BP 595 EP 601 DI 10.1089/hum.1994.5.5-595 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NN090 UT WOS:A1994NN09000005 PM 7914435 ER PT J AU KLAUCK, SM WHISENANT, E WOOD, M DRABKIN, HA SEIZINGER, BR AF KLAUCK, SM WHISENANT, E WOOD, M DRABKIN, HA SEIZINGER, BR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D3S1255 LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Note C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV COLORADO,DEPT MED ONCOL,DENVER,CO 80262. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. NR 0 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1994 VL 3 IS 5 BP 840 EP 840 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NM099 UT WOS:A1994NM09900032 PM 8081378 ER PT J AU LAWRENCE, MB BAINTON, DF SPRINGER, TA AF LAWRENCE, MB BAINTON, DF SPRINGER, TA TI NEUTROPHIL TETHERING TO AND ROLLING ON E-SELECTIN ARE SEPARABLE BY REQUIREMENT FOR L-SELECTIN SO IMMUNITY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; ENDOTHELIAL CELL RECOGNITION; NODE HOMING RECEPTOR; P-SELECTIN; GLYCOPROTEIN LIGAND; EVOLUTIONARY CONSERVATION; CHEMOTACTIC FACTORS; MYELOID CELLS; IN-VIVO; EXPRESSION AB Neutrophil tethering and rolling in shear flow are mediated by selectins and have been thought to be two indistinguishable manifestations of a single molecular interaction between selectin and ligand. However, we report that under physiologic flow conditions, tethering to E-selectin requires a ligand distinct from the one that supports neutrophil rolling. Tethering under shear to E-selectin requires a carbohydrate ligand that is closely associated with the lectin domain of L-selectin on the neutrophil surface, as enzymatic removal of L-selectin, chemotactic factor-induced shedding of L-selectin, and L-selectin MAbs effectively block tethering. In contrast, this ligand is dispensable for the ability to roll on E-selectin, since rolling adhesions formed after static incubations were not affected by the presence or absence of L-selectin. Thus, E-selectin interactions with ligands on neutrophils persist after L-selectin shedding. These findings add an additional step for regulation of leukocyte localization in inflammatory sites. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94143. RP LAWRENCE, MB (reprint author), CTR BLOOD RES INC,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HLB-48675]; NIDDK NIH HHS [DK 10486] NR 53 TC 123 Z9 123 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1994 VL 1 IS 2 BP 137 EP 145 DI 10.1016/1074-7613(94)90107-4 PG 9 WC Immunology SC Immunology GA PK162 UT WOS:A1994PK16200006 PM 7534197 ER PT J AU RUDD, CE JANSSEN, O CAI, YC DASILVA, AJ RAAB, M PRASAD, KVS AF RUDD, CE JANSSEN, O CAI, YC DASILVA, AJ RAAB, M PRASAD, KVS TI 2-STEP TCR-ZETA/CD3-CD4 AND CD28 SIGNALING IN T-CELLS - SH2/SH3 DOMAINS, PROTEIN-TYROSINE AND LIPID KINASES SO IMMUNOLOGY TODAY LA English DT Review ID RECEPTOR ZETA-CHAIN; CD45 PHOSPHOTYROSINE PHOSPHATASE; ANTIGEN RECEPTOR; LYMPHOCYTES-T; CYTOPLASMIC TAIL; TCR/CD3 COMPLEX; MICE LACKING; CD3 COMPLEX; ACTIVATION; P56LCK AB A central question in T-cell immunity concerns the nature of intracellular signaling from the antigen receptor, the CD4/CD8 co-receptors and the CD28 antigen. Since the original discovery that T-cell receptors such as CD4 can interact with intracellular protein-tyrosine Kinases such as p56(lck), remarkable progress has been made in deciphering the signaling pathways that control T-cell growth and immune function. Here, Christopher Rudd and colleagues examine the role of protein-tyrosine kinases, SH2/SH3 domains and lipid kinases in the generation of signals from the TCR zeta/CD3 complex and the CD28 antigen. RP RUDD, CE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Janssen, Ottmar/E-9735-2010 FU NCI NIH HHS [NCI CA51887-04]; NIAID NIH HHS [NCI AI33851-01] NR 106 TC 178 Z9 182 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1994 VL 15 IS 5 BP 225 EP 234 DI 10.1016/0167-5699(94)90248-8 PG 10 WC Immunology SC Immunology GA NJ948 UT WOS:A1994NJ94800008 PM 8024683 ER PT J AU CHOI, BK PASTER, BJ DEWHIRST, FE GOBEL, UB AF CHOI, BK PASTER, BJ DEWHIRST, FE GOBEL, UB TI DIVERSITY OF CULTIVABLE AND UNCULTIVABLE ORAL SPIROCHETES FROM A PATIENT WITH SEVERE DESTRUCTIVE PERIODONTITIS SO INFECTION AND IMMUNITY LA English DT Article ID NECROTIZING ULCERATIVE GINGIVITIS; OLIGODEOXYNUCLEOTIDE PROBES; TREPONEMA-PALLIDUM; WHIPPLES-DISEASE; ADULT HUMANS; IDENTIFICATION; BACTERIA; CELLS; AMPLIFICATION; MICROBIOLOGY AB To determine the genetic diversity of cultivable and uncultivable spirochetes in the gingival crevice of a patient with severe periodontitis, partial 16S rRNA genes were cloned from PCR-amplified products of DNA and RNA extracted from a subgingival plaque sample. Approximately 500 bp were amplified in PCRs by using universally conserved primers with polylinker tails. Purified PCR products were cloned into Escherichia coli by using the plasmid vector pUC19. The resultant clone library was screened by colony hybridization with a radiolabeled, treponeme-specific oligonucleotide probe. The 16S rRNA inserts of 81 spirochetal clones were then sequenced by standard procedures. Sequences were compared with 16S rRNA sequences of 35 spirochetes, including the four known cultivable oral treponeme species. The analysis revealed an unexpected diversity of oral treponemes from a single patient. When 98% or greater sequence similarity was used as the definition of a species-level cluster, the clone sequences were found to represent 23 species. When 92% similarity was used as the definition, the clones fell into eight major groups, only two of which contained named species, Treponema vincentii and Treponema denticola, while Treponema pectinovorum and Treponema socranskii mere not represented in any cluster. Seven of the 81 spirochetal clones were found to contain chimeric 16S rRNA sequences. In situ fluorescence hybridization with a fluorescein isothiocyanate-labeled oligonucleotide probe specific for one of the new species representing cluster 19 was used to identify cells of the target species directly in clinical samples. C1 KLINIKUM UNIV FREIBURG,INST MED MIKROBIOL & HYG,D-79104 FREIBURG,GERMANY. FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. FU NIDCR NIH HHS [DE 10374] NR 49 TC 171 Z9 177 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1994 VL 62 IS 5 BP 1889 EP 1895 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NH313 UT WOS:A1994NH31300053 PM 8168954 ER PT J AU PATTERSON, JE SANCHEZ, RO HERNANDEZ, J GROTA, P ROSS, KA AF PATTERSON, JE SANCHEZ, RO HERNANDEZ, J GROTA, P ROSS, KA TI SPECIAL ORGANISM ISOLATION - ATTEMPTING TO BRIDGE THE GAP SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INTENSIVE-CARE UNIT; INFECTION; RESISTANT; PRECAUTIONS; VANCOMYCIN; GENTAMICIN; ANITRATUS; OUTBREAK C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV HOSP,DEPT QUAL RISK MANAGEMENT INFECT CONTROL,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT INFECT CONTROL,SAN ANTONIO,TX 78284. VET AFFAIRS MED CTR,DEPT INFECT CONTROL,W HAVEN,CT. RP PATTERSON, JE (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED INFECT DIS,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 13 TC 8 Z9 8 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 1994 VL 15 IS 5 BP 335 EP 338 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA NM781 UT WOS:A1994NM78100015 PM 8077647 ER PT J AU PHILLIPS, I HOOPER, DC PERCIVAL, A SMITH, T THORNSBERRY, C WISE, R AF PHILLIPS, I HOOPER, DC PERCIVAL, A SMITH, T THORNSBERRY, C WISE, R TI QUINOLONE RESISTANCE IN GRAM-NEGATIVE BACTERIA - PANEL DISCUSSION SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Discussion C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ROYAL LIVERPOOL HOSP,DEPT MED MICROBIOL,LIVERPOOL L7 8XP,MERSEYSIDE,ENGLAND. UNIV LONDON SCH PHARM,DEPT PHARMACEUT,LONDON,ENGLAND. INST MICROBIOL RES,FRANKLIN,TN. DUDLEY RD GEN HOSP,BIRMINGHAM B18 7QH,W MIDLANDS,ENGLAND. RP PHILLIPS, I (reprint author), ST THOMAS HOSP,DEPT MICROBIOL,LONDON SE1 7EH,ENGLAND. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY-JUN PY 1994 VL 3 SU 3 BP S124 EP S126 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NT413 UT WOS:A1994NT41300003 ER PT J AU BIGATELLO, LM GREENE, RE SPRUNG, CL PANACEK, EA STRAUBE, RC ZIMMERMAN, JL MAUNDER, RJ LANKEN, PN PILESPELLMANN, E STANEK, KS ZASLAVSKY, A ZAPOL, WM AF BIGATELLO, LM GREENE, RE SPRUNG, CL PANACEK, EA STRAUBE, RC ZIMMERMAN, JL MAUNDER, RJ LANKEN, PN PILESPELLMANN, E STANEK, KS ZASLAVSKY, A ZAPOL, WM TI HA-1A IN SEPTIC PATIENTS WITH ARDS - RESULTS FROM THE PIVOTAL TRIAL SO INTENSIVE CARE MEDICINE LA English DT Article DE ADULT RESPIRATORY DISTRESS SYNDROME; SEPSIS; ANTIENDOTOXIN MONOCLONAL ANTIBODIES; HA-1A ID RESPIRATORY-DISTRESS SYNDROME; GRAM-NEGATIVE BACTEREMIA; ESCHERICHIA-COLI; DOUBLE-BLIND; ENDOTOXIN; SHOCK; ANTIBODY; MULTICENTER; SEPSIS AB Objective: To evaluate the effects of HA-1 A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS. Design: Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1 A in septic patients. Patients: 63 septic patients with ARDS at the time of study entry. Intervention: A single intravenous injection of HA-1 A (100 mg) or placebo. Results: A quantitative radiographic score, the PaO2/FIO2 ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1 A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1 A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p = 0.07). Using logistic regression, a significant independent effect of HA-1 A treatment was detected upon the early survival rate at 7 days (p = 0.03) but not at 14 and 28 days. Conclusion: A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT STAT,BOSTON,MA 02114. UNIV MIAMI,DEPT MED,MIAMI,FL 33152. HADASSAH HERBREW UNIV,MED CTR,JERUSALEM,ISRAEL. CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106. CENTOCOR INC,DIV RES & DEV,MALVERN,PA. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. NR 21 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAY PY 1994 VL 20 IS 5 BP 328 EP 334 DI 10.1007/BF01720904 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA NT684 UT WOS:A1994NT68400005 PM 7930026 ER PT J AU HERMAN, TS TEICHER, BA AF HERMAN, TS TEICHER, BA TI SUMMARY OF STUDIES ADDING SYSTEMIC CHEMOTHERAPY TO LOCAL HYPERTHERMIA AND RADIATION SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE HYPERTHERMIA; CHEMOTHERAPY; RADIATION ID CELL-SURVIVAL; FIBRO-SARCOMA; THERAPY; RADIOSENSITIVITY AB The Joint Center-MIT group sought to maximize the efficacy of hyperthermia plus radiation by adding systemic anticancer drugs chosen in the laboratory. After extensive laboratory investigations utilizing primarily the FSaIIC murine fibrosarcoma, we determined that cisplatin was the best drug with which to begin clinical testing and that the sequence cisplatin-hyperthermia-radiation was most efficacious. A clinical experience was then gained which found that: (1) the tolerable doses of cisplatin weekly X 6 used with local hyperthermia and radiation (limited by bone marrow suppression) were 50 mg/m2 weekly in chemotherapy naive patients and 30 mg/m2 weekly in patients having had extensive prior drug treatment, (2) apparent complete response occurred in about 50% of patients, and (3) tumour lysyis necessitating surgical repair occurred predominantly in patients with recurrent breast cancer in previously heavily irradiated fields where an incidence of 38% was observed as opposed to only 6% in breast cancer patients having had no prior radiation. In an attempt to further improve the local control potential of the combination we tested the addition of other anticancer drugs in the laboratory. Our findings were that both mitomycin C and etanidazole were far better than other agents and were able to double the tumour growth delay produced by the cisplatin/heat/radiation trimodality treatment. Since etanidazole is not marrow suppressive, clinical testing of etanidazole in the trimodality setting along with cisplatin/heat/radiation has been initiated. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP HERMAN, TS (reprint author), UNIV NEW MEXICO,CTR CANC RES & TREATMENT,900 CAMINO DE SALUD NE,ALBUQUERQUE,NM 87131, USA. NR 10 TC 11 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAY-JUN PY 1994 VL 10 IS 3 BP 443 EP 449 DI 10.3109/02656739409010290 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NP476 UT WOS:A1994NP47600018 PM 7930812 ER PT J AU LANGLEY, RE PALAYOOR, ST COLEMAN, CN BUMP, EA AF LANGLEY, RE PALAYOOR, ST COLEMAN, CN BUMP, EA TI RADIATION-INDUCED APOPTOSIS IN F9 TERATOCARCINOMA CELLS SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID RETINOIC ACID; STEM-CELLS; DNA FRAGMENTATION; LEUKEMIA-CELLS; EARLY EVENT; INDUCTION; DEATH; DIFFERENTIATION; INVITRO; EXPRESSION AB We have found that F9 murine teratocarcinoma cells undergo morphological changes and internucleosomal DNA fragmentation characteristic of apoptosis after exposure to ionizing radiation. We studied the time course, radiation dose-response, and the effects of protein and RNA synthesis inhibitors on this process. The response is dose dependent in the range 2-12 Gy. Internucleosomal DNA fragmentation can be detected as early as 6 h postirradiation and is maximal by 48 h. Cycloheximide, a protein synthesis inhibitor, and 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, an RNA synthesis inhibitor, both induced internucleosomal DNA fragmentation in the unirradiated cells and enhanced radiation-induced DNA fragmentation. F9 cells can be induced to differentiate into cells resembling endoderm with retinoic acid. After irradiation, differentiated F9 cells exhibit less DNA fragmentation than stem cells. This indicates that ionizing radiation can induce apoptosis in non-lymphoid rumours. We suggest that embryonic tumour cells may be particularly susceptible to agents that induce apoptosis. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP LANGLEY, RE (reprint author), JOINT CTR RADIAT THERAPY,JFB RM 222,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01 CA46776, 5-P30 CA06516] NR 29 TC 24 Z9 24 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD MAY PY 1994 VL 65 IS 5 BP 605 EP 610 DI 10.1080/09553009414550691 PG 6 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 NL831 UT WOS:A1994NL83100010 PM 7910198 ER PT J AU AJANI, UA WILLETT, WC SEDDON, JM AF AJANI, UA WILLETT, WC SEDDON, JM TI REPRODUCIBILITY OF A FOOD FREQUENCY QUESTIONNAIRE FOR USE IN OCULAR RESEARCH SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE REPRODUCIBILITY; FOOD FREQUENCY QUESTIONNAIRE; OCULAR RESEARCH; RELIABILITY ID DIETARY ASSESSMENT INSTRUMENTS; HISTORY QUESTIONNAIRE; VALIDITY; CANCER; RELIABILITY AB Purpose. Assessment of nutritional factors was an ancillary component of the Eye Disease Case-Control Study sponsored by the National Eye Institute, This multicenter study was designed to evaluate the role of potential risk factors for a number of retinal disorders. The authors examined the reproducibility of the food frequency questionnaire used in this study. Methods. A semiquantitative food frequency questionnaire, designed for use in this study, was self-administered by participants. To evaluate the reproducibility of this dietary questionnaire, a subsample of 325 participants completed a second questionnaire within 12 to 18 months of the first. Pearson product-moment coefficient was used to assess the correlation between the log of calorie-adjusted nutrient scores, and Spearman correlations were used for specific food items. Results. The responses for intake of 60 food items in the questionnaire were reasonably consistent. Correlation coefficients for individual food items ranged from 0.40 to 0.82. Pearson a correlation coefficients for logs of calorie-adjusted intake of nutrients ranged from 0.38 to 0.75. Nutrients of interest in eye disease include total protein (r = 0.57), total fat (r = 0.71), saturated fats (r = 0.69), carotene (r = 0.61), vitamin C (with supplements, r = 0.66), vitamin E (with supplements, r = 0.69), and zinc (with supplements, r = 0.43). Partial correlations controlling for age, sex, and clinical center were similar. Conclusions. These findings indicate that the food frequency questionnaire used in this study provides reasonably reproducible dietary information. C1 MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. FU NEI NIH HHS [EY09972] NR 26 TC 23 Z9 24 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1994 VL 35 IS 6 BP 2725 EP 2733 PG 9 WC Ophthalmology SC Ophthalmology GA NL842 UT WOS:A1994NL84200009 PM 8188466 ER PT J AU SANDBERG, MA GAUDIO, AR MILLER, S WEINER, A AF SANDBERG, MA GAUDIO, AR MILLER, S WEINER, A TI IRIS PIGMENTATION AND EXTENT OF DISEASE IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE MACULAR DEGENERATION; NEOVASCULARIZATION; IRIS PIGMENTATION; VISUAL ACUITY; VISUAL FIELD ID FELLOW EYE; 2ND EYE; DRUSEN; MACULOPATHY; PREVALENCE; BLINDNESS; PROGNOSIS; ACUITY AB Purpose. To determine whether the extent of disease in age-related macular degeneration (AMD) varies with iris pigmentation. Methods. The authors assessed visual function and macular appearance in the fellow eye or both eyes of 132 white patients with unilateral neovascular AMD. All patients had a visual acuity of 20/60 or better in the fellow eye. Eighty-nine of the patients were coded as having light irides (blue, green, or hazel) and 43 were coded as having dark irides (brown); the two groups of patients had; comparable mean ages. Results. By the Mann-Whitney test for differences in mean rank, fellow eyes with light irides showed a marginally worse visual acuity (P = .156) but significantly more visual field impairment by letter recognition perimetry (P = .011) and the macular thr eshold test of the Humphrey Field Analyzer (P = .043), and more retinal pigment epithelial atrophy (P = .017) and focal areas of hyperpigmentation (P = .002) than fellow eyes with dark irides. For eyes with a choroidal neovascular membrane (CNVM), those with light irides had significantly lower visual acuities (P = .006) and larger scars (P = .006) than eyes with dark irides. In addition, extent of disease in the eye with a CNVM was positively correlated with extent of disease in the fellow eye for most comparisons. Conclusions. These observations suggest that light iris pigmentation is associated with more extensive retinal disease in patients with unilateral neovascular AMD. Furthermore, in such patients, those with worse disease in the eye with a CNVM may tend to have more extensive atrophic disease in the fellow eye. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. FU NEI NIH HHS [EY08398] NR 26 TC 40 Z9 41 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1994 VL 35 IS 6 BP 2734 EP 2740 PG 7 WC Ophthalmology SC Ophthalmology GA NL842 UT WOS:A1994NL84200010 PM 7514581 ER PT J AU DRUY, EM MCCLENNAN, BL BETTMANN, MA JONES, JK GOLDBERG, SN KAUL, AF NEWHOUSE, JH AF DRUY, EM MCCLENNAN, BL BETTMANN, MA JONES, JK GOLDBERG, SN KAUL, AF NEWHOUSE, JH TI FACULTY DISCUSSION-2 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. DARTMOUTH HITCHCOCK MED CTR,DEPT RADIOL,LEBANON,NH 03756. DEGGE GRP LTD,ARLINGTON,VA 22209. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MED OUTCOMES MANAGEMENT INC,FOXBORO,MA 02035. COLUMBIA PRESBYTERIAN MED CTR,DEPT RADIOL,NEW YORK,NY 10032. RP DRUY, EM (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20037, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAY PY 1994 VL 29 SU 1 BP S106 EP S106 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NR592 UT WOS:A1994NR59200020 ER PT J AU FAYKUS, M COPE, C ATHANASOULIS, C DRUY, EM HEDGCOCK, M MILLER, FJ BRON, K AF FAYKUS, M COPE, C ATHANASOULIS, C DRUY, EM HEDGCOCK, M MILLER, FJ BRON, K TI DOUBLE-BLIND-STUDY OF THE SAFETY, TOLERANCE, AND DIAGNOSTIC EFFICACY OF IOPROMIDE AS COMPARED WITH IOPAMIDOL AND IOHEXOL IN PATIENTS REQUIRING AORTOGRAPHY AND VISCERAL ANGIOGRAPHY SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT International Forum on Current Considerations in Contrast Imaging CY JUN 04-06, 1993 CL AVENTURA, FL DE NONIONIC CONTRAST MEDIA; AORTOGRAPHY; VISCERAL ANGIOGRAPHY ID CONTRAST-MEDIA AB RATIONALE AND OBJECTIVES. Nonionic contrast media have been shown to be more effective, better tolerated, and safer than standard high-osmolality contrast media when given intravascularly. The aim of this study was to assess the diagnostic efficacy, tolerance, and safety of a new nonionic contrast agent, iopromide (370 mg I/mL), in comparison with two available similar agents, iopamidol (370 mg I/mL) and iohexol (350 mg I/mL), in two randomized, double-blind clinical studies of patients undergoing abdominal aortography and visceral angiography. METHODS. The iopromide group included 80 patients, and the comparator group consisted of 36 iopamidol and 45 iohexol patients. The quality and diagnostic efficacy of all three contrast agents was rated equally as either good or excellent. RESULTS. On a scale of 0 (none) to 3 (severe) for heat and pain, respectively, the mean scores were 1.08 and 0.43 for iopromide in comparison with 1.15 and 0.35 for the comparator media. Minor adverse clinical experiences were noted in 23% of the iopromide group versus 20% of the comparator group. Nausea and vomiting were more common in the comparator group (7% versus 3%), and headache was noted only in the iopromide group (4%). There were no clinically significant changes in laboratory values in any group. Three severe adverse experiences occurred, but all were deemed unrelated to the contrast agents. CONCLUSION. Based on the results of this study, iopromide appears to be efficacious, safe, well tolerated, and comparable with iohexol and iopamidol for use in abdominal aortography and visceral angiography, C1 FAYETTEVILLE XRAY ASSOCIATES,FAYETTEVILLE,NC. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGE WASHINGTON UNIV,CTR MED,WASHINGTON,DC. VET AFFAIRS MED CTR,SAN FRANCISCO,CA 94121. UNIV UTAH,SALT LAKE CITY,UT. PITTSBURG STATE UNIV,PITTSBURG,KS 66762. NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAY PY 1994 VL 29 SU 1 BP S98 EP S101 DI 10.1097/00004424-199405001-00019 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NR592 UT WOS:A1994NR59200018 PM 8071053 ER PT J AU ENOCHS, WS WEISSLEDER, R AF ENOCHS, WS WEISSLEDER, R TI MR-IMAGING OF THE PERIPHERAL NERVOUS-SYSTEM SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CONTRAST MEDIA; NERVES, PERIPHERAL; NERVOUS SYSTEM ID MAGNETIC-RESONANCE NEUROGRAPHY; RETROGRADE AXONAL-TRANSPORT; CARPAL-TUNNEL SYNDROME; LUMBAR SPINAL NERVES; NORMAL ANATOMY; GD-DTPA; CRANIAL NERVES; OPTIC NEURITIS; TARSAL TUNNEL; SHEATH TUMORS C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. NR 57 TC 14 Z9 14 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAY-JUN PY 1994 VL 4 IS 3 BP 251 EP 257 DI 10.1002/jmri.1880040306 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP292 UT WOS:A1994NP29200004 PM 7520307 ER PT J AU REIMER, P SAINI, S KWONG, KK COHEN, MS WEISSLEDER, R BRADY, TJ AF REIMER, P SAINI, S KWONG, KK COHEN, MS WEISSLEDER, R BRADY, TJ TI DYNAMIC GADOLINIUM-ENHANCED ECHO-PLANAR MR-IMAGING OF THE LIVER - EFFECT OF PULSE SEQUENCE AND DOSE ON ENHANCEMENT SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CONTRAST ENHANCEMENT; GADOLINIUM; LIVER; PULSE SEQUENCES; RAPID IMAGING ID MAGNETIC-SUSCEPTIBILITY; CONTRAST AGENT; GD-DTPA; BRAIN AB To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine-enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1. 0.2. and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine-enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine-enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 15 TC 8 Z9 9 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAY-JUN PY 1994 VL 4 IS 3 BP 331 EP 335 DI 10.1002/jmri.1880040318 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP292 UT WOS:A1994NP29200014 PM 8061430 ER PT J AU KREFT, BP TANIMOTO, A BABA, Y ZHAO, LH FINN, JP STARK, DD AF KREFT, BP TANIMOTO, A BABA, Y ZHAO, LH FINN, JP STARK, DD TI ENHANCED TUMOR-DETECTION IN THE PRESENCE OF FATTY LIVER-DISEASE - CELL-SPECIFIC CONTRAST AGENTS SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CONTRAST ENHANCEMENT; CONTRAST MEDIA, EXPERIMENTAL; LIVER, DISEASES; LIVER, FATTY; LIVER NEOPLASMS ID INFILTRATION; CT; METASTASES AB It is assumed that hepatobiliary, cell-specific contrast agents will be adversely affected by the presence of diffuse liver disease. The diagnostic efficacy for tumor detection in the presence of fatty liver disease was experimentally studied at contrast-enhanced magnetic resonance (MR) imaging with manganese-DPDP (NN'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis[phosphate]) and gadobenate dimeglumine (Gd-BOPTA/dimeg) and compared with conventional and chemical shift imaging. Carcinosarcoma was implanted into the liver of rats, and fatty liver was induced with L-ethionine. Without contrast agents. the tumor-fatty liver contrast-to-noise ratio (C/N) was increased on T1-weighted and decreased on T2-weighted MR images relative to tumor-control rats without fatty liver. Chemical shift imaging (phase-contrast method) increased the tumor-fatty liver C/N from 2.3 +/- 1.0 to 6.1 +/- 1.7 (P <.001). Mn-DPDP and Gd-BOPTA/dimeg increased the tumor-fatty liver C/N from - 5.4 +/- 1.6 to - 11.0 +/- 1.9 and - 9.8 +/- 3.4. respectively (P <.001). The hepatobiliary cell-specific contrast agents were equally effective in both fatty and non-fatty liver and outperformed both chemical shift and conventional MR imaging in detecting liver tumors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. UNIV MASSACHUSETTS,WORCESTER,MA 01605. FU NCI NIH HHS [R01 CA50353-01] NR 32 TC 10 Z9 11 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAY-JUN PY 1994 VL 4 IS 3 BP 337 EP 342 DI 10.1002/jmri.1880040319 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP292 UT WOS:A1994NP29200015 PM 8061431 ER PT J AU WOLF, GL HOOP, B CANNILLO, JA ROGOWSKA, JA HALPERN, EF AF WOLF, GL HOOP, B CANNILLO, JA ROGOWSKA, JA HALPERN, EF TI MEASUREMENT OF RENAL TRANSIT OF GADOPENTETATE DIMEGLUMINE WITH ECHO-PLANAR MR-IMAGING SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CONTRAST ENHANCEMENT; CONTRAST MEDIA, EXPERIMENTAL; KIDNEY; PERFUSION STUDIES; RAPID IMAGING ID GADOLINIUM-DTPA; BLOOD-FLOW; COMPUTED-TOMOGRAPHY; DYNAMIC MR; GD-DTPA; KIDNEY; RABBITS; TIME; DIURESIS; DOTA AB Times of peak gadolinium concentration ([Gd]) after intravenous (IV) and left ventricular (LV) bolus injection of gadopentetate dimeglumine were determined in renal cortex and medulla in normal rabbits and in rabbits after saline load (overhydration) or hemorrhage (dehydration). Magnetic resonance images were obtained with echo-planar inversion-recovery sequences, and signal intensity-versus-time curves in cortical and medullary regions of interest were converted to [Gd]-versus-time curves. Cortical perfusion measured with microspheres demonstrated that the three physiologic states were significantly different. There were three separate [Gd] peaks in both the cortex and medulla as the bolus moved from one anatomic compartment to the next. The first cortical peak occurred sooner after LV than after IV bolus injection (P < .05) and later in dehydrated than in normal and overhydrated rabbits (P < .05). The first medullary peak always followed the first cortical peak by about 6-10 seconds and mirrored the cortical patterns. The second and third cortical peaks were consistent with proximal and distal tubular transit. These peaks similarly showed faster response to LV than IV injection and were delayed by hemorrhage. The authors conclude that quantitative physiologic information can be obtained with dynamic contrast-enhanced MR imaging of the kidney. RP WOLF, GL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR IMAGING & PHARMACEUT RES,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [R01 CA49785] NR 32 TC 31 Z9 33 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAY-JUN PY 1994 VL 4 IS 3 BP 365 EP 372 DI 10.1002/jmri.1880040323 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP292 UT WOS:A1994NP29200019 PM 8061435 ER PT J AU KARLSSON, JOM CRAVALHO, EG TONER, M AF KARLSSON, JOM CRAVALHO, EG TONER, M TI A MODEL OF DIFFUSION-LIMITED ICE GROWTH INSIDE BIOLOGICAL CELLS DURING FREEZING SO JOURNAL OF APPLIED PHYSICS LA English DT Article ID COOLING RATE; CRYSTAL SIZE; GLYCEROL; DIMETHYLSULFOXIDE; EMBRYOS; CRYSTALLIZATION; PERMEABILITY; KINETICS; VISUALIZATION; VITRIFICATION AB A theoretical model for predicting the kinetics of ice crystallization inside cells during cryopreservation was developed, and applied to mouse oocytes, by coupling separate models of (1) water transport across the cell membrane, (2) ice nucleation, and (3) crystal growth. The instantaneous cell volume and cytosol composition during continuous cooling in the presence of glycerol were predicted using the water transport model. Classical nucleation theory was used to predict ice nucleation rates, and a nonisothermal diffusion-limited crystal-growth model was used to compute the resulting crystallization kinetics. The model requires knowledge of the nucleation rate parameters OMEGA and kappa, as well as the viscosity eta of a water-NaCl-glycerol solution as a function of both the composition and temperature of the solution. These dependences were estimated from data available in the literature. Cell-specific biophysical parameters were obtained from previous studies on mouse oocytes. A sensitivity analysis showed that the model was most sensitive to the values of kappa and eta. The coupled model was used to study the effect of cooling rate and initial glycerol concentration on intracellular crystal growth. The extent of crystallization, as well as the crystal size distribution, were predicted as functions of time. For rapid cooling at low to intermediate glycerol concentrations, the cells crystallized completely, while at high concentrations of glycerol, partial or total vitrification was observed. As expected, the cooling rate necessary for vitrification dropped with increasing glycerol concentration; when cells initially contained approximately 7.5 M glycerol, vitrification was achieved independent of cooling rate. For slow cooling protocols, water transport significantly affected the results. At glycerol concentrations greater than approximately 3 M, the final intracellular ice content decreased with increasing glycerol concentration at a fixed cooling rate. In this regime, the cooling rate at which a critical amount of ice was formed increased as more glycerol was used. When less than approximately 3 M glycerol was initially present in the cell, an increase in glycerol concentration was predicted to cause an increase in the final intracellular ice content at a given cooling rate. In this regime, the critical cooling rate decreased with increasing glycerol concentration. These predictions clarify previous empirical observations of slow freezing phenomena. C1 MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,SHRINERS BURN INST,SURG RES LAB,BOSTON,MA 02114. NR 55 TC 126 Z9 134 U1 2 U2 23 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD MAY 1 PY 1994 VL 75 IS 9 BP 4442 EP 4445 DI 10.1063/1.355959 PG 4 WC Physics, Applied SC Physics GA NJ734 UT WOS:A1994NJ73400017 ER PT J AU VANDERMEER, TJ MENCONI, MJ OSULLIVAN, BP LARKIN, VA WANG, HL KRADIN, RL FINK, MP AF VANDERMEER, TJ MENCONI, MJ OSULLIVAN, BP LARKIN, VA WANG, HL KRADIN, RL FINK, MP TI BACTERICIDAL PERMEABILITY-INCREASING PROTEIN AMELIORATES ACUTE LUNG INJURY IN PORCINE ENDOTOXEMIA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE POLYMORPHONUCLEAR LEUKOCYTE; NEUTROPHILS; ADULT RESPIRATORY DISTRESS SYNDROME; ENDOTOXINS; CHEMILUMINESCENCE ID RESPIRATORY-DISTRESS SYNDROME; GRAM-NEGATIVE BACTEREMIA; AMINO-TERMINAL FRAGMENT; ESCHERICHIA-COLI; SEPTIC SHOCK; LIPOPOLYSACCHARIDE; ANTIBODY; NEUTROPHILS; SEPSIS; RECEPTOR AB Bactericidal/permeability-increasing protein (BPI), a cationic protein isolated from human neutrophils, binds lipopolysaccharide (LPS), kills gram-negative bacteria, and neutralizes many of the effects of LPS in vitro and in vivo. We hypothesized that a recombinant 23-kDa NH2-terminal fragment of BPI (BPI23) would reduce acute lung injury in endotoxemic pigs. At -18 h, pigs received an intravenous priming dose of LPS (20 mu g/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 4); 2) LPS (250 mu g/kg over 50 min) and BPI23 (3-mg/kg bolus and 3 mg/kg over 60 min) (n = 6); or 3) LPS and thaumatin, a cationic protein devoid of LPS neutralizing activity that has a molecular mass and isoelectric point that are similar to that of BPI23 (n = 7). BPI23 treatment significantly ameliorated LPS-induced hypoxemia, functional upregulation of opsonin receptors on circulating phagocytes, and alveolitis but had no effect on the elaboration of tumor necrosis factor-alpha or thromboxane A(2). The salutory effects of BPI23 on acute lung injury in endotoxemic pigs may be mediated, at least in part, by inhibition of direct activation of phagocytes by LPS. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT PEDIAT,WORCESTER,MA 01655. FU NIGMS NIH HHS [R01-GM-37631-07] NR 34 TC 44 Z9 44 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1994 VL 76 IS 5 BP 2006 EP 2014 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA NL970 UT WOS:A1994NL97000026 PM 8063663 ER PT J AU ZHU, JW HANSEN, H SU, LH SHIEH, HL RIEDEL, H AF ZHU, JW HANSEN, H SU, LH SHIEH, HL RIEDEL, H TI LIGAND REGULATION OF BOVINE PROTEIN-KINASE-C-ALPHA RESPONSE VIA EITHER CYSTEINE-RICH REPEAT OF CONSERVED REGION C1 SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE CDNA EXPRESSION; PHORBOL ESTER; PHOSPHATIDYLSERINE; SIGNAL TRANSDUCTION; TUMOR PROMOTER ID PHORBOL ESTER RECEPTOR; CEREVISIAE CELL-CYCLE; PKC1 GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; CATALYTIC DOMAINS; CA-2+ CHANNELS; YEAST-CELLS; RAT-BRAIN; ACTIVATION; CALCIUM AB Based on the finding by others that the conserved region C1 of conventional protein kinase C isoforms carries two independent, cysteine-rich phorbol ester binding sites, we have mapped the structural elements of the C1 region for their role in the phorbol ester- and phospholipid regulation of PKC alpha responses. We hare prepared two amino terminal truncation mutants of bovine PKC alpha, ND91 lacking the first Cys-repeat of C1, and ND153 lacking both Cys-repeats of C1, as well as two internal deletion mutants, D162-245 lacking most of C2, and D109-263 lacking most of C2 and the second Cys-repeat of C1. The mutants were expressed in the yeast Saccharomyces cerevisiae which allows the rapid biochemical and physiological characterization of mammalian PHC isoforms. We found that all mutants displayed an elevated basal level of enzymatic activity in vitro but retained the basic catalytic PKC characteristics: regulation by Ca2+ and (except for ND153) by phospholipid or phorbol ester. In vivo we observed proportional physiological responses, the stimulation of Ca2+ uptake, and an increase in the cell doubling time for all mutants upon phorbol ester stimulation (constitutive for ND153) similar to the response of normal PKC alpha. Our findings indicate that after partial PKC activation by deletion mutagenesis, the presence of either Cys-repeat in C1 still allows phospholipid- and phorbol ester regulation of protein kinase C alpha responses. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,MOLEC BIOL SECT,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. NR 72 TC 11 Z9 11 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD MAY PY 1994 VL 115 IS 5 BP 1000 EP 1009 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL051 UT WOS:A1994NL05100033 PM 7961586 ER PT J AU RINKES, IHMB TONER, M TOMPKINS, RG YARMUSH, ML AF RINKES, IHMB TONER, M TOMPKINS, RG YARMUSH, ML TI AN EXTRACORPOREAL MICROSCOPY PERFUSION CHAMBER FOR ONLINE STUDIES OF ENVIRONMENTAL-EFFECTS ON CULTURED-HEPATOCYTES SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID BIOARTIFICIAL LIVER; COLLAGEN SANDWICH; SYSTEM AB The development of bioartificial-hybrid organ support systems is hampered by the lack of knowledge on the effects of different (in vivo) environments on cells during extracorporeal perfusion. In the present study, a perfusion chamber was designed for continuous monitoring of cultured cells during perfusion with media, as well as during plasma perfusion in an extracorporeal circuit. Chamber characterization showed satisfactory thermal and perfusion profiles and no major pH fluctuations. Further testing was performed with hepatocytes that were cultured in between two collagen layers, a configuration which was previously shown to preserve hepatocyte morphology and function for over six weeks of culture. Perfusion of the hepatocytes with culture media did not adversely affect cell morphology and function, provided the perfusion time was less-than-or-equal-to 48 hours. Perfusion of the cultures during connection of the chamber to an extracorporeal circuit involving normal rats for six hours resulted in reversible cytoplasmic changes, unaltered cell shapes indices, and a 40 percent increase in albumin secretion rate during the first post-perfusion day, followed by a return to stable control levels. We expect that this chamber will be a valuable tool for on-line studies of cells under (extracorporeal) perfusion conditions and could be used for a large variety of studies on regeneration, reperfusion damage, and detoxification. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RP RINKES, IHMB (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114, USA. NR 12 TC 7 Z9 7 U1 1 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAY PY 1994 VL 116 IS 2 BP 135 EP 139 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA NP759 UT WOS:A1994NP75900001 ER PT J AU ROUGRAFF, BT SIMON, MA KNEISL, JS GREENBERG, DB MANKIN, HJ AF ROUGRAFF, BT SIMON, MA KNEISL, JS GREENBERG, DB MANKIN, HJ TI LIMB SALVAGE COMPARED WITH AMPUTATION FOR OSTEOSARCOMA OF THE DISTAL END OF THE FEMUR - A LONG-TERM ONCOLOGICAL FUNCTIONAL AND QUALITY-OF-LIFE STUDY SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OSTEOGENIC-SARCOMA; CHEMOTHERAPY AB The outcome of treatment of nonmetastatic high-grade osteosarcoma in the distal part of the femur was studied in 227 patients from twenty-six institutions. Eight of the seventy-three patients who had had a limb-salvage procedure and nine of the 115 patients who had had an above-the-knee amputation had a local recurrence, but there was no local recurrence in the thirty-nine patients who had had a disarticulation at the hip. There were no significant differences in the rate of survival or in the duration of the postoperative disease-free period between the three groups. One hundred and nine patients (48 per cent) were alive at an average of eleven years after the operation, and ninety patients (40 per cent) remained continuously disease-free. An additional operation on the limb was necessary more often for patients who had had a limb-salvage procedure than for those who had had an amputation. Function in seventy-eight living patients was assessed with the system of the Musculoskeletal Tumor Society for evaluation of function and by the functional assessment portion of the 1989 scoring system of the Knee Society; the scores were higher for the patients who had had a limb-salvage procedure than for the two groups of patients who had had an amputation. No difference was identified between the groups with regard to the patient's acceptance of the postoperative state, the ability to walk, or the amount of pain. The quality of life was evaluated for twenty-nine patients with a series of complex questionnaires. There was no apparent difference in psychosocial outcome between the three operative groups. Compared with amputation, limb salvage for high-grade osteosarcoma of the distal part of the femur was associated with a higher rate of reoperation but it produced a better functional outcome without decreasing the rate of long-term survival. However, it did not provide a measurable benefit in the quality of life of survivors at the time of the long-term follow-up. C1 UNIV CHICAGO,MED CTR,ORTHOPAED SURG & REHABIL MED SECT,CHICAGO,IL 60637. CAROLINAS MED CTR,CHARLOTTE,NC 28232. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 29 TC 258 Z9 271 U1 1 U2 8 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 1994 VL 76A IS 5 BP 649 EP 656 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NM664 UT WOS:A1994NM66400003 PM 8175811 ER PT J AU MANKIN, HJ AF MANKIN, HJ TI METABOLIC BONE-DISEASE SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID VITAMIN-D METABOLISM; D-RESISTANT RICKETS; HEREDITARY HYPOPHOSPHATEMIC RICKETS; INTESTINAL CALCIUM-ABSORPTION; X-LINKED HYPOPHOSPHATEMIA; DOSE ORAL CALCIUM; RENAL OSTEODYSTROPHY; PRIMARY HYPERPARATHYROIDISM; RHEUMATOID-ARTHRITIS; MULTIPLE-MYELOMA RP MANKIN, HJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED SERV,BOSTON,MA 02114, USA. NR 271 TC 9 Z9 10 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 1994 VL 76A IS 5 BP 760 EP 788 PG 29 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NM664 UT WOS:A1994NM66400018 ER PT J AU MCLAUGHLIN, JR TIERNEY, M HARRIS, WH AF MCLAUGHLIN, JR TIERNEY, M HARRIS, WH TI MYCOBACTERIUM-AVIUM-INTRACELLULARE INFECTION OF HIP ARTHROPLASTIES IN AN AIDS PATIENT SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; COMPLEX INFECTION; BACTEREMIA; CIPROFLOXACIN; AMIKACIN; THERAPY C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,HIP & IMPLANT UNIT,BOSTON,MA 02114. KENNEDY CTR HIP & KNEE,NEENAH,WI 54956. MASSACHUSETTS GEN HOSP,DIV INFECT DIS,BOSTON,MA 02114. NR 16 TC 9 Z9 9 U1 0 U2 0 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON, ENGLAND WC2N 6ET SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD MAY PY 1994 VL 76B IS 3 BP 498 EP 499 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NM536 UT WOS:A1994NM53600037 PM 8175866 ER PT J AU REDDY, SV TAKAHASHI, S DALLAS, M WILLIAMS, RE NECKERS, L ROODMAN, GD AF REDDY, SV TAKAHASHI, S DALLAS, M WILLIAMS, RE NECKERS, L ROODMAN, GD TI INTERLEUKIN-6 ANTISENSE DEOXYOLIGONUCLEOTIDES INHIBIT BONE-RESORPTION BY GIANT-CELLS FROM HUMAN GIANT-CELL TUMORS OF BONE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID OSTEOBLASTS; IL-6 AB The effects of antisense constructs to IL-6 on the bone-resorbing capacity of purified giant cells from giant cell tumors of bone were examined to further define the role of IL-6 in human osteoclastic bone resorption. In addition, we wanted to determine the utility of antisense constructs to cytokines produced by osteoclasts as probes to identify the molecular events responsible for the bone-resorptive process. Giant cells were cultured on sperm whale dentin for 24 h in the presence of fluoresceinated antisense or scrambled antisense deoxyoligonucleotides complementary to IL-6 mRNA. The giant cells actively incorporated these oligonucleotides, as evidenced by their intense fluorescence. The number of resorptive lacunae formed and the area of the dentin resorbed were significantly decreased in cultures of giant cells treated with antisense IL-6 constructs compared with control cultures treated with scrambled antisense constructs to IL-6 (60 +/- 13 versus 12 +/- 6 lacunae and 1.2 +/- 0.3 versus 0.26 +/- 0.1 x 10(5) mu m(2)). IL-6 levels in conditioned media from giant cell cultures treated with IL-6 antisense constructs were fourfold lower than those in control media obtained from giant cells treated with scrambled antisense constructs to IL-6. These data confirm the capacity of IL-6 antisense oligomers to block IL-6 production by these cells. These observations show that IL-6 plays an important role in the bone-resorptive process of human osteoclasts and suggest that antisense constructs to cytokines produced by bone cells may be useful for determining the molecular events occurring during bone resorption. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED HEMATOL,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NIH,BETHESDA,MD. NR 13 TC 53 Z9 53 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1994 VL 9 IS 5 BP 753 EP 757 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NF563 UT WOS:A1994NF56300021 PM 8053406 ER PT J AU POWER, WJ NEYLAN, D COLLUM, LMT AF POWER, WJ NEYLAN, D COLLUM, LMT TI DAUNOMYCIN AS AN INHIBITOR OF HUMAN LENS EPITHELIAL-CELL PROLIFERATION IN CULTURE SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article DE DAUNOMYCIN; LENS EPITHELIAL CELL; POSTERIOR CAPSULE OPACIFICATION AB Posterior capsule opacification is still a major complication of both extracapsular cataract extraction and phacoemulsification. We evaluated the effects of the anti-proliferative agent daunomycin on cultured human and bovine lens epithelial cell viability and proliferation. After ten minutes of exposure, low concentrations of the agent markedly inhibited the proliferation of both cell types. The calculated LD50 for the drug against human cells was 2.20 mug/ml and against the bovine cells was 0.38 mug/ml. The bovine cells appeared to be slightly more susceptible to the drug's effects, although this difference was not marked. Our results indicate that daunomycin is a potent inhibitor of both human and bovine lens epithelial cells in the laboratory. RP POWER, WJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 54 Z9 60 U1 0 U2 0 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAY PY 1994 VL 20 IS 3 BP 287 EP 290 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA NM074 UT WOS:A1994NM07400004 PM 8064604 ER PT J AU OSBORNE, MA SCHLENSTEDT, G JINKS, T SILVER, PA AF OSBORNE, MA SCHLENSTEDT, G JINKS, T SILVER, PA TI NUF2, A SPINDLE POLE BODY-ASSOCIATED PROTEIN REQUIRED FOR NUCLEAR DIVISION IN YEAST SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MITOTIC CHROMOSOME TRANSMISSION; HELICAL COILED COILS; SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; GENE ENCODES; APPARATUS; SYSTEM; DNA; REARRANGEMENTS; INTRANUCLEAR AB The NUF2 gene of the yeast Saccharomyces cerevisiae encodes an essential 53-kd protein with a high content of potential coiled-coil structure similar to myosin. Nuf2 is associated with the spindle pole body (SPB) as determined by coimmunofluorescence with known SPB proteins. Nuf2 appears to be localized to the intranuclear region and is a candidate for a protein involved in SPB separation. The nuclear association of Nuf2 can be disrupted, in part, by 1 M salt but not by the detergent Triton X-100. All Nuf2 can be removed from nuclei by 8 M urea extraction. In this regard, Nuf2 is similar to other SPB-associated proteins including Nuf1/SPC110, also a coiled-coil protein. Temperature-sensitive alleles of NUF2 were generated within the coiled-coil region of Nuf2 and such NUF2 mutant cells rapidly arrest after temperature shift with a single undivided or partially divided nucleus in the bud neck, a shortened mitotic spindle and their DNA fully replicated. In sum, Nuf2 is a protein associated with the SPB that is critical for nuclear division. Anti-Nuf2 antibodies also recognize a mammalian 73-kd protein and display centrosome staining of mammalian tissue culture cells suggesting the presence of a protein with similar function. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 52 TC 58 Z9 60 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY PY 1994 VL 125 IS 4 BP 853 EP 866 DI 10.1083/jcb.125.4.853 PG 14 WC Cell Biology SC Cell Biology GA NL319 UT WOS:A1994NL31900013 PM 8188751 ER PT J AU PRICHARD, JW ROSEN, BR AF PRICHARD, JW ROSEN, BR TI STATE-OF-THE-ART REVIEW - FUNCTIONAL-STUDY OF THE BRAIN BY NMR SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review ID HUMAN VISUAL-CORTEX; MAGNETIC-RESONANCE SPECTROSCOPY; CEREBRAL BLOOD-FLOW; RAT-BRAIN; SENSORY STIMULATION; PHOTIC-STIMULATION; DIABETIC SUBJECTS; INVIVO; LACTATE; CONTRAST C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,CTR NUCL MAGNET RESONANCE,BOSTON,MA. RP PRICHARD, JW (reprint author), YALE UNIV,SCH MED,DEPT NEUROL,333 CEDAR ST,NEW HAVEN,CT 06510, USA. NR 60 TC 23 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1994 VL 14 IS 3 BP 365 EP 372 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA NG209 UT WOS:A1994NG20900001 PM 8163578 ER PT J AU SAMUELS, MH KRAMER, P WILSON, D SEXTON, G AF SAMUELS, MH KRAMER, P WILSON, D SEXTON, G TI EFFECTS OF NALOXONE INFUSIONS ON PULSATILE THYROTROPIN SECRETION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID THYROID-STIMULATING HORMONE; OPIATE RECEPTOR BLOCKADE; LUTEINIZING-HORMONE; BETA-ENDORPHIN; GROWTH-HORMONE; OPIOID-PEPTIDES; CORTISOL-LEVELS; TSH RELEASE; PITUITARY; PROLACTIN AB Endogenous opioids are known to modulate the secretion of some anterior pituitary hormones, but they are not thought to have significant effects on TSH secretion. However, dynamic TSH secretion has not been characterized during naloxone infusions. Therefore, we measured TSH levels every 15 min over 24 h in nine healthy young men at baseline and during infusions of naloxone at 2 mg/h. A TRH test was performed after each study. TSH pulses were located by Cluster analysis. Naloxone infusions decreased 24-h mean TSH levels by 28%, from 1.68 +/- 0.20 to 1.21 +/- 0.19 mU/L. Mean daytime TSH levels did not change, but nocturnal TSH levels were decreased by 39%, from 2.21 +/- 0.30 to 1.35 +/- 0.21 mU/L. There were no changes in TSH pulse frequency, but naloxone infusions decreased 24-h TSH pulse amplitude by 32%, from 2.02 +/- 0.26 to 1.37 +/- 0.21 mU/L. Daytime TSH pulse amplitude was relatively unaffected (1.27 +/- 0.15 us. 1.16 +/- 0.21 mU/L), whereas nocturnal TSH pulse amplitude was decreased by 42%, from 2.72 +/- 0.40 to 1.57 +/- 0.23 mU/L. TSH responses to acute TRH administration were decreased after naloxone infusions (12.38 +/- 1.93 us. 9.17 +/- 1.36 mU/L). Serum T-3 levels fell by 21% during naloxone infusions, from 1.9 +/- 0.1 to 1.5 +/- 0.1 nmol/L, whereas other thyroid hormone levels and cortisol levels were unchanged. These findings suggest that endogenous opioids have significant stimulatory effects on TSH secretion, predominantly during the nocturnal TSH surge. C1 AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. RP SAMUELS, MH (reprint author), OREGON HLTH SCI UNIV, DIV ENDOCRINOL, L607, 3181 SW SAM JACKSON PK RD, PORTLAND, OR 97201 USA. FU NCRR NIH HHS [MO1-RR-01-346, MO1-RR-00-334] NR 33 TC 12 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 MAY PY 1994 VL 78 IS 5 BP 1249 EP 1252 DI 10.1210/jc.78.5.1249 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK241 UT WOS:A1994NK24100044 PM 8175985 ER PT J AU ANTONIADES, HN GALANOPOULOS, T NEVILLEGOLDEN, J KIRITSY, CP LYNCH, SE AF ANTONIADES, HN GALANOPOULOS, T NEVILLEGOLDEN, J KIRITSY, CP LYNCH, SE TI P53 EXPRESSION DURING NORMAL TISSUE REGENERATION IN RESPONSE TO ACUTE CUTANEOUS INJURY IN SWINE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE SUPPRESSOR GENES; GROWTH FACTORS; P53; TISSUE REGENERATION; GENE INDUCTION ID WILD-TYPE P53; FACTOR-I IMMUNOREACTIVITY; RECEPTOR MESSENGER-RNAS; SKIN EPITHELIAL-CELLS; GROWTH-FACTOR; ENDOTHELIAL-CELLS; GENE-EXPRESSION; MONOCLONAL-ANTIBODY; BINDING PROTEIN; TRANSCRIPTION AB The present studies investigated the in vivo expression of the p53 suppressor gene and protein product in response to acute cutaneous injury in swine, along with the parallel expression of the c-sis/PDGF-B mitogen and its receptor beta (PDGF-R beta). p53 expression was shown to be suppressed during the period of active cellular proliferation in the injured tissue and to reemerge during the stages of healing. In contrast, c-sis/PDGF-B and PDGF-R beta were expressed during the early phase of active cellular proliferation and they were suppressed upon healing. This inverse relationship between mitogenic growth factors and p53 suggests the presence of well-controlled physiologic mechanisms that regulate in vivo the processes of normal tissue repair in response to injury. At the stages of tissue regeneration, these mechanisms include both the expression of growth factors that promote cell proliferation and the suppression of p53 that downregulates proliferation. At the stages of healing, the expression of the mitogenic growth factors is suppressed and that of p53 reemerges, reaching its peak at the time of complete epithelialization and healing of the injured tissue. These studies are the first to link the response of p53 protein to physiologic processes of tissue regeneration in vivo. C1 HARVARD UNIV,SCH PUBL HLTH,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT PERIODONTOL,BOSTON,MA 02115. RP ANTONIADES, HN (reprint author), INST MOLEC BIOL,1 INNOVAT DR,WORCESTER,MA 01605, USA. FU NCI NIH HHS [CA30101] NR 54 TC 51 Z9 53 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1994 VL 93 IS 5 BP 2206 EP 2214 DI 10.1172/JCI117217 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NJ960 UT WOS:A1994NJ96000043 PM 8182152 ER PT J AU FOX, JG DEWHIRST, FE FRASER, GJ PASTER, BJ SHAMES, B MURPHY, JC AF FOX, JG DEWHIRST, FE FRASER, GJ PASTER, BJ SHAMES, B MURPHY, JC TI INTRACELLULAR CAMPYLOBACTER-LIKE ORGANISM FROM FERRETS AND HAMSTERS WITH PROLIFERATIVE BOWEL-DISEASE IS A DESULFOVIBRIO SP SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SULFATE-REDUCING BACTERIA; INTESTINAL ADENOMATOSIS; COLITIS; IDENTIFICATION; REPRODUCTION; DIVERSITY; HYDROGEN; ANTIGEN; CULTURE; ILEITIS AB Proliferative bowel disease is an intestinal disorder of a variety of domestic animals associated with the presence of an intracellular Campylobacter-like organism (ICLO). We have identified the ICLO obtained from a ferret with proliferative colitis by 16S rRNA sequence analysis. In this ferret, proliferative bowel tissue containing the ICLO had translocated to the mesenteric lymph nodes, omentum, and liver. The 16S rRNA genes of the ICLO were amplified from an infected fragment of extraintestinal tissue by using universal prokaryotic primers. Approximately 1,480 bases of the amplified 16S rRNA gene were sequenced by cycle sequencing. Comparison of the sequence of the ICLO with those of over 400 bacteria in our data base indicated that the sequence of the ICLO was most closely related to that of Desulfovibrio desulfuricans (87.5% similarity). Phylogenetic analysis with 12 Desulfovibrio species and 20 species from related genera placed the ICLO in a subcluster within the genus Desulfovibrio with D. desulfuricans and 5 other Desulfovibrio species. We will refer to this organism as the intracellular Desulfovibrio organism (IDO). Specific primers were produced for PCR amplification of a 550-base Fragment of the 16S rRNA gene of the IDO in proliferative intestinal tissue samples. This unique 550-base segment was amplified from samples of frozen intestinal tissue from nine ferrets and three hamsters with ICLO-associated disease but not in four intestinal tissue samples from animals without the ICLO-associated disease. The 550-base amplified products from the bowel tissues of one hamster and one ferret were fully sequenced. The ferret IDO partial sequence was identical to the previously determined 16S rRNA sequence over its length, and the hamster IDO sequence differed by a single base. The same intracellular organism has been identified in proliferative intestinal tissues of swine and that the organism has been successfully maintained in tissue culture. The availability of specific primers for PCR-based detection of this intracellular Desulfovibrio organism will aid in the determination of its role in the pathogenesis of proliferative bowel disease in a variety of infected hosts. C1 FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. RP FOX, JG (reprint author), MIT,DIV COMPARAT MED,37 VASSAR ST,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR-01046]; NIDCR NIH HHS [DE-08303, DE-10374] NR 56 TC 79 Z9 84 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1994 VL 32 IS 5 BP 1229 EP 1237 PG 9 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700017 PM 8051249 ER PT J AU FOX, JG DEWHIRST, FE TULLY, JG PASTER, BJ YAN, L TAYLOR, NS COLLINS, MJ GORELICK, PL WARD, JM AF FOX, JG DEWHIRST, FE TULLY, JG PASTER, BJ YAN, L TAYLOR, NS COLLINS, MJ GORELICK, PL WARD, JM TI HELICOBACTER HEPATICUS SP-NOV, A MICROAEROPHILIC BACTERIUM ISOLATED FROM LIVERS AND INTESTINAL MUCOSAL SCRAPINGS FROM MICE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAMPYLOBACTER-JEJUNI; SPIRAL BACTERIUM; GASTRIC-CARCINOMA; PYLORI INFECTION; HOMOSEXUAL MEN; STOMACH; GASTROENTERITIS; PHYLOGENY; ABORTION; MUSTELAE AB A bacterium with a spiral shape and bipolar, single, sheathed flagella was isolated from the livers of mice with active, chronic hepatitis. The bacteria also colonized the cecal and colonic mucosae of mice. The bacterium grew at 37 degrees C under microaerophilic and anaerobic conditions, rapidly hydrolyzed urea, was catalase and oxidase positive, reduced nitrate to nitrite, and was resistant to cephalothin and nalidixic acid but sensitive to metronidazole. On the basis of 16S rRNA gene sequence analysis, the organism was classified as a no,el helicobacter, Helicobacter hepaticus. This new helicobacter, like two other murine Helicobacter species, fi. muridarum and ''H. rappini,'' is an efficient colonizer of the gastrointestinal tract, but in addition, it has the pathogenic potential to elicit persistent hepatitis in mice. C1 FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. NIAID,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. RP FOX, JG (reprint author), MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR-01046]; NIDCR NIH HHS [DE-08303, DE-10374] NR 41 TC 372 Z9 394 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1994 VL 32 IS 5 BP 1238 EP 1245 PG 8 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700018 PM 8051250 ER PT J AU YONG, WH MATTIA, AR FERRARO, MJ AF YONG, WH MATTIA, AR FERRARO, MJ TI COMPARISON OF FECAL LACTOFERRIN LATEX AGGLUTINATION ASSAY AND METHYLENE-BLUE MICROSCOPY FOR DETECTION OF FECAL LEUKOCYTES IN CLOSTRIDIUM-DIFFICILE-ASSOCIATED DISEASE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note AB The fecal lactoferrin assay was more sensitive (75%) than methylene blue microscopy (40%) for the detection of leukocytes in Clostridium difficile toxin-positive fecal samples. Although limited sensitivity and specificity precludes its use as a laboratory screening test, it mag. be a more useful initial test in an algorithm for clinically suspected C. difficile-associated disease. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CLIN MICROBIOL LABS,BOSTON,MA 02114. NR 10 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1994 VL 32 IS 5 BP 1360 EP 1361 PG 2 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700042 PM 8051268 ER PT J AU BRATOEVA, MP WOLF, MK MARKS, JK CANTEY, JR AF BRATOEVA, MP WOLF, MK MARKS, JK CANTEY, JR TI A CASE OF DIARRHEA, BACTEREMIA, AND FEVER CAUSED BY A NOVEL STRAIN OF ESCHERICHIA-COLI SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID TISSUE-CULTURE CELLS; DNA PROBE; EAE GENE; ADHERENCE FACTOR; HEP-2 CELLS; INVASION; CLONING; O157-H7 AB A nonenteropathogenic strain of Escherichia coli from a patient with diarrhea and bacteremia possessed the attaching-effacing ene gene, was invasive in the gentamicin invasion assay, and expressed two types of pili and K1 antigen. This unique combination places the strain in a new category of attaching-effacing E. coli. C1 MED UNIV S CAROLINA,DEPT MED,DIV INFECT DIS,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. WALTER REED ARMY INST RES,WASHINGTON,DC. NR 20 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1994 VL 32 IS 5 BP 1383 EP 1386 PG 4 WC Microbiology SC Microbiology GA NG217 UT WOS:A1994NG21700050 PM 7914208 ER PT J AU BRUNER, JMR AF BRUNER, JMR TI ON THE CALIBRATION OF ARTIFACTS SO JOURNAL OF CLINICAL MONITORING LA English DT Editorial Material ID PRESSURE C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. NR 17 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0748-1977 J9 J CLIN MONITOR JI J. Clin. Monit. PD MAY PY 1994 VL 10 IS 3 BP 143 EP 146 PG 4 WC Anesthesiology SC Anesthesiology GA NJ727 UT WOS:A1994NJ72700001 PM 8027744 ER PT J AU NIXON, AJ NEUBERG, D HAYES, DF GELMAN, R CONNOLLY, JL SCHNITT, S ABNER, A RECHT, A VICINI, F HARRIS, JR AF NIXON, AJ NEUBERG, D HAYES, DF GELMAN, R CONNOLLY, JL SCHNITT, S ABNER, A RECHT, A VICINI, F HARRIS, JR TI RELATIONSHIP OF PATIENT AGE TO PATHOLOGICAL FEATURES OF THE TUMOR AND PROGNOSIS FOR PATIENTS WITH STAGE-I OR STAGE-II BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY RADIATION-THERAPY; CONSERVATIVE SURGERY; CONSERVING THERAPY; NATURAL-HISTORY; RECURRENCE; CARCINOMA; YOUNGER; RELAPSE; PROJECT; DISCRIMINANTS C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,CTR BREAST EVALUAT,DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DIV BIOSTAT,BOSTON,MA 02115. WILLIAM BEAUMONT HOSP,DEPT RADIAT ONCOL,ROYAL OAK,MI. RP NIXON, AJ (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,JOINT CTR RADIAT THERAPY,DEPT RADIAT ONCOL,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516, CA-09001] NR 38 TC 330 Z9 342 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1994 VL 12 IS 5 BP 888 EP 894 PG 7 WC Oncology SC Oncology GA NL038 UT WOS:A1994NL03800003 PM 8164038 ER PT J AU MCINTYRE, JF SMITHSORENSEN, B FRIEND, SH KASSELL, J BORRESEN, AL YAN, YX RUSSO, C SATO, J BARBIER, N MISER, J MALKIN, D GEBHARDT, MC AF MCINTYRE, JF SMITHSORENSEN, B FRIEND, SH KASSELL, J BORRESEN, AL YAN, YX RUSSO, C SATO, J BARBIER, N MISER, J MALKIN, D GEBHARDT, MC TI GERMLINE MUTATIONS OF THE P53 TUMOR-SUPPRESSOR GENE IN CHILDREN WITH OSTEOSARCOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LI-FRAUMENI SYNDROME; DENATURANT GEL-ELECTROPHORESIS; BREAST-CANCER; TP53 MUTATIONS; FAMILY; PROTEIN; NEOPLASMS; CARCINOMA; P53-GENE; PATIENT C1 MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC GENET,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA. CHILDRENS HOSP,BOSTON,MA. NORWEGIAN RADIUM HOSP,DEPT GENET,OSLO,NORWAY. PEDIAT ONCOL GRP,ST LOUIS,MO. CHILDRENS CANC GRP,ARCADIA,CA. HOSP SICK CHILDREN,DIV HEMATOL ONCOL,TORONTO M5G 1X8,ON,CANADA. FU NCI NIH HHS [5U10CA33603-10] NR 28 TC 133 Z9 137 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1994 VL 12 IS 5 BP 925 EP 930 PG 6 WC Oncology SC Oncology GA NL038 UT WOS:A1994NL03800008 PM 8164043 ER PT J AU LABBATE, LA LAFER, B THIBAULT, A SACHS, GS AF LABBATE, LA LAFER, B THIBAULT, A SACHS, GS TI SIDE-EFFECTS INDUCED BY BRIGHT LIGHT TREATMENT FOR SEASONAL AFFECTIVE-DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PHOTOTHERAPY; DEPRESSION; PATTERNS; THERAPY; MANIA AB Background: Bright light treatment has become an accepted treatment for seasonal affective disorder (SAD), but there have been few studies about adverse effects from using this treatment. We conducted a study to examine the frequency of adverse effects of bright light treatment for SAD. Method: Thirty patients meeting DSM-III-R criteria for major depression, recurrent, with seasonal pattern as determined by the Structured Clinical interview for DSM-III-R were administered a structured interview, the 42-item Systematic Assessment for Treatment Emergent Events, to assess side effects from bright light treatment. Results: Side effects were limited and mild. They remitted with time or decreased light. No patient discontinued treatment. One patient developed mild hypomania and 3 became agitated. Sleep disturbance occurred in 62% of patients (5 of 8) using evening light. Visual side effects occurred in 26% of patients (8 of 30). Conclusion: Except for one case of mild hypomania, no other clinically significant treatment-emergent adverse effects developed. Hypomania is an uncommon, but clinically important side effect. Mild visual complaints were common and remitted promptly. In this group of patients with SAD, bright light treatment was well tolerated and resulted in a limited number of adverse effects, none of which compromised treatment. The absence of a control group limits the specificity of these side effects to bright light treatment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,15 PARKMAN ST,ACC 815,BOSTON,MA 02114. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 15 TC 53 Z9 54 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 1994 VL 55 IS 5 BP 189 EP 191 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NQ976 UT WOS:A1994NQ97600003 PM 8071268 ER PT J AU POLLACK, MH OTTO, MW KASPI, SP HAMMERNESS, PG ROSENBAUM, JF AF POLLACK, MH OTTO, MW KASPI, SP HAMMERNESS, PG ROSENBAUM, JF TI COGNITIVE-BEHAVIOR THERAPY FOR TREATMENT-REFRACTORY PANIC DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NATURALISTIC FOLLOW-UP; DEPRESSED-PATIENTS; AGORAPHOBIA; ALPRAZOLAM; ATTACKS; IMIPRAMINE; CLONAZEPAM; EXPOSURE; COMBINATION; ANXIETY AB Background: The purpose of this pilot study is to assess the efficacy of cognitive behavior therapy for the treatment of patients with panic disorder who experience an incomplete response to a trial of pharmacotherapy. Method: Fifteen consecutive patients with a DSM-III-R diagnosis of panic disorder referred for further treatment because of an incomplete response to pharmacotherapy were treated with 12-weeks of group cognitive behavior therapy. Patients were evaluated at baseline, endpoint, and at a mean of 2-months' follow-up to assess changes in panic attack frequency and global outcome. Eight of the 15 patients were deemed to have received an inadequate prior trial of medication at baseline, mainly because of a desire to control their symptoms without medication or fear of withdrawal and/or addiction. Seven of the patients were symptomatic at baseline despite an adequate prior trial of medication. Results: Overall, patients experienced a significant improvement in global function at the end of the cognitive behavior therapy intervention, as well as a decrease in panic attack frequency. Improvement was maintained at follow-up. Conclusion: This study is consistent with a growing body of evidence that many patients with panic disorder remain symptomatic over time and are receiving inadequate pharmacotherapeutic treatment. Further, we observed that patients with panic disorder who are incompletely responsive or resistant to pharmacotherapeutic management may benefit from the addition of cognitive behavior therapy. RP POLLACK, MH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,ACC-815,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH 19600] NR 45 TC 76 Z9 77 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 1994 VL 55 IS 5 BP 200 EP 205 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NQ976 UT WOS:A1994NQ97600005 PM 8071270 ER PT J AU STANDAERT, DG TESTA, CM YOUNG, AB PENNEY, JB AF STANDAERT, DG TESTA, CM YOUNG, AB PENNEY, JB TI ORGANIZATION OF N-METHYL-D-ASPARTATE GLUTAMATE-RECEPTOR GENE-EXPRESSION IN THE BASAL GANGLIA OF THE RAT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NMDA; STRIATUM; SUBTHALAMIC NUCLEUS; ALTERNATIVE SPLICING; IN SITU HYBRIDIZATION ID EXCITATORY AMINO-ACIDS; MATRIX-ENRICHED AREAS; NMDA RECEPTOR; SUBTHALAMIC NUCLEUS; HUNTINGTONS-DISEASE; MOLECULAR DIVERSITY; PROJECTION NEURONS; PARKINSONS-DISEASE; DOPAMINE RELEASE; BINDING-SITES AB Glutamate is an important neurotransmitter in the circuitry of the basal ganglia. Of the four pharmacological classes of receptors that may mediate the actions of glutamate. the N-methyl-D-aspartate (NMDA) type is of particular interest insofar as it has been implicated in the neural processes underlying long-term synaptic plasticity as well as;excitotoxic injury. NMDA ligand binding sites are abundant in the structures of the basal ganglia, and NMDA receptors have been linked to neuronal excitability, neuropeptide gene expression, and regulation of dopamine release in these regions. NMDA receptors are believed to be heterooligomers of subunits from two families: NMDAR1, encoded by a single gene but alternatively spliced to produce eight distinct isoforms (NMDAR1A-H), and NMDAR2, encoded by four separate genes (NMDAR2A-D). We have used in situ hybridization with a total of 13 oligonucleotide probes to examine the expression of these genes in the rat basal ganglia. NMDAR1 subunits are expressed throughout the basal ganglia as well as int eh rest of the brain; however, the alternatively spliced amino-terminal region Insertion I is abundantly expressed only in the subthalamic nucleus and is not detectable in the neostriatum, globus pallidus, or substantia nigra pars compacta. In contrast, expression of the carboxy terminus segment Deletion I is prominent in the striatum but is not observed in other elements of the basal ganglia. NMDAR2 subunits also exhibit differential expression: NMDAR2B is abundant in the striatum, but NMDAR2A is present within the striatum only at low levels. NMDAR2C is present in the substantia nigra pars compacta only, while NMDAR2D exhibits an unusual distribution, with high levels of expression in the substantia nigra pars compacta, the subthalamic nucleus, the globus pallidus, and the ventral pallidum. Since each isoform of the NMDAR1 and NMDAR2 subunits can confer distinct properties on the resultant NMDA receptor, these data imply that there is a high degree of regional specialization in the properties of NMDA receptors within the basal ganglia. (C) 1994 Wiley-Liss, Inc. RP STANDAERT, DG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,NEUROL SERV,WARREN 408,FRUIT ST,BOSTON,MA 02114, USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG08671]; NINDS NIH HHS [NS19613]; PHS HHS [N531579] NR 74 TC 300 Z9 304 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 1 PY 1994 VL 343 IS 1 BP 1 EP 16 DI 10.1002/cne.903430102 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA NG875 UT WOS:A1994NG87500001 PM 8027428 ER PT J AU GAZELLE, GS LEE, MJ HAHN, PF GOLDBERG, MA RAFAAT, N MUELLER, PR AF GAZELLE, GS LEE, MJ HAHN, PF GOLDBERG, MA RAFAAT, N MUELLER, PR TI US, CT, AND MRI OF PRIMARY AND SECONDARY LIVER LYMPHOMA SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE LYMPHOMA; LIVER, DISEASES; LIVER, NEOPLASMS; ULTRASOUND; COMPUTED TOMOGRAPHY; MAGNETIC RESONANCE IMAGING ID HEPATIC LYMPHOMA AB Objective: To describe the imaging findings in patients with pathologically proven hepatic lymphoma. Materials and Methods: Ultrasound, CT, and MRI studies in 23 patients with primary (11 patients) or secondary (12 patients) liver lymphoma were retrospectively reviewed. All patients had proven non-Hodgkin lymphoma; all imaging studies were obtained within 3 weeks of biopsy. Results: No finding or group of findings was specific for the diagnosis of hepatic lymphoma. In 7 of 11 cases of primary lymphoma, a single well-defined lesion was seen. Secondary liver lymphoma occurred as multiple (8 of 12) or diffusely infiltrating lesions (3 of 12) in most cases; it appeared as a solitary lesion in only 1 case. When discrete focal lesions were identified, the lesions were hypo- to anechoic on ultrasound, hypodense on CT, and had low and high signal intensity on T1- and T2-weighted MRI, respectively. Conclusion: Although no one finding appears to be diagnostic of hepatic lymphoma, ultrasound that demonstrates a homogeneous, hypoechoic, through-transmitting lesion combined with CT that demonstrates a solid, low attenuation lesion is highly suggestive of primary liver lymphoma. Secondary liver lymphoma can have a greater variety of appearances and is more likely to be multiple or diffusely infiltrating lesions than a solitary lesion. RP GAZELLE, GS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,FRUIT ST,BOSTON,MA 02114, USA. NR 6 TC 51 Z9 58 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 1994 VL 18 IS 3 BP 412 EP 415 DI 10.1097/00004728-199405000-00013 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NL657 UT WOS:A1994NL65700013 PM 8188908 ER PT J AU DOODY, DP STENGER, KS WINN, HJ AF DOODY, DP STENGER, KS WINN, HJ TI IMMUNOLOGICALLY NONSPECIFIC MECHANISMS OF TISSUE DESTRUCTION IN THE REJECTION OF SKIN-GRAFTS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PRIMARY TARGET; VASCULAR BED; ANTIGENS; ALLOGRAFTS; XENOGRAFTS; ANTISERUM; MOLECULES; MOUSE; CELLS; MICE AB When mice are lethally irradiated and reconstituted with allogeneic bone marrow cells, their skin is repopulated over a period of several months with Langerhans cells (LC) of marrow donor origin. Skin from such mice, when transplanted to unirradiated syngeneic recipients, became in many cases the sites of intense inflammatory responses that led to varying degrees of destruction of the transplanted skin and in some instances, to rejection of the entire graft. The frequency and intensity of these responses were influenced by the nature of the immunogenetic disparity between the donors and recipients of the marrow cells. Chimeric skin placed on hybrid mice derived from crosses between the marrow donors and recipients behaved in all respects as syngeneic grafts or autografts. When the recipients of the chimeric skin were presensitized to the antigens of the marrow donor, the responses were especially intense, and resulted in all cases in complete rejection. Thus the immunologically mediated attack on the allogeneic LCs was accompanied by widespread and nonspecific destruction of bystander cells. In all cases, the inflammation and tissue damage were confined sharply to the grafted skin, showing clearly that nonspecific or indirect tissue destruction is entirely consistent with highly selective destruction of grafted tissues. This finding removes a major objection to postulated mechanisms of rejection that involve indirect destruction of grafted tissues. C1 MASSACHUSETTS GEN HOSP,GEN SURG SERV,BOSTON,MA 02114. FU NIAID NIH HHS [AI-31050, AI-23413] NR 20 TC 21 Z9 22 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1994 VL 179 IS 5 BP 1645 EP 1652 DI 10.1084/jem.179.5.1645 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500025 PM 8163942 ER PT J AU KUCHROO, VK COLLINS, M ALSABBAGH, A SOBEL, RA WHITTERS, MJ ZAMVIL, SS DORF, ME HAFLER, DA SEIDMAN, JG WEINER, HL RIMM, IJ AF KUCHROO, VK COLLINS, M ALSABBAGH, A SOBEL, RA WHITTERS, MJ ZAMVIL, SS DORF, ME HAFLER, DA SEIDMAN, JG WEINER, HL RIMM, IJ TI T-CELL RECEPTOR (TCR) USAGE DETERMINES DISEASE SUSCEPTIBILITY IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - STUDIES WITH TCR V-BETA-8.2 TRANSGENIC MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID MYELIN BASIC-PROTEIN; PROTEOLIPID PROTEIN; ALPHA-CHAIN; ENCEPHALITOGENIC DETERMINANT; SJL MICE; MURINE; REGION; MOUSE; GENES; IDENTIFICATION AB Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced in laboratory animals by immunization with the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the role of the T cell receptor (TCR) repertoire in susceptibility to EAE induced by these two autoantigens. Autoreactive T cells induced after immunization with MBP use a limited set of TCR. In contrast, we demonstrate that T cell clones that recognize the encephalitogenic PLP epitope (PLP 139-151) use diverse TCR genes. When the TCR repertoire is limited by introduction of a novel rearranged TCR V beta 8.2 chain in transgenic SJL mice, EAE could be induced in the transgenic mice by immunization with the encephalitogenic epitopes of PLP, but not with the encephalitogenic epitope of MBP. Thus, skewing the TCR repertoire affects the susceptibility to EAE by immunization with MBP but not with PLP. These data demonstrate the biological consequences of the usage of a more diverse T cell repertoire in the development of an autoimmune disease. C1 GENET INST INC,CAMBRIDGE,MA 02140. HARVARD UNIV,SCH MED,CTR NEUROL DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. STANFORD UNIV,SCH MED,DEPT PATHOL,PALO ALTO,CA 94304. CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. VET AFFAIRS MED CTR,LAB SERV,PALO ALTO,CA 94304. FU NINDS NIH HHS [NS-29352, NS-26773, NS-30843] NR 27 TC 39 Z9 40 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1994 VL 179 IS 5 BP 1659 EP 1664 DI 10.1084/jem.179.5.1659 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NH655 UT WOS:A1994NH65500027 PM 8163944 ER PT J AU HEFLE, SL BUSH, RK YUNGINGER, JW CHU, FS AF HEFLE, SL BUSH, RK YUNGINGER, JW CHU, FS TI A SANDWICH ENZYME-LINKED-IMMUNOSORBENT-ASSAY (ELISA) FOR THE QUANTITATION OF SELECTED PEANUT PROTEINS IN FOODS SO JOURNAL OF FOOD PROTECTION LA English DT Article DE ALLERGENS; PEANUT; ELISA; FOOD ALLERGY; MONOCLONAL ANTIBODY ID INDUCED ANAPHYLAXIS; PRODUCTS AB A sandwich-type, enzyme-linked immunosorbent assay (ELISA) was developed for the detection of selected peanut proteins in foods. Monoclonal antibodies against a series of allergenic peanut proteins were used as the capture antibody. Food sample extracts were then added, and polyclonal rabbit antibodies directed against roasted peanut proteins were employed as secondary antibodies. The amount of allergen bound to the solid-phase was determined by a biotin and streptavidin-peroxidase system. Radioallergosorbent assay (RAST) inhibition studies of the food extracts were done as a comparison. The coefficient of determination for the ELISA and RAST assays was 0.85. Selected food samples were tested by RAST inhibition at another laboratory for comparison. Skin tests were done with selected samples in peanut-allergic adults, and the results correlated to the ELISA and RAST inhibition results. In other studies, defatted peanut protein (0.01 to 5.0%) were added to vanilla ice cream, then extracted and analyzed using ELISA and skin tests. The sensitivity of the ELISA in ice cream was approximately 40 mug/ml. In six of seven peanut-sensitive adults tested, the lowest level of added peanut protein (0.01%, 21 mug/ml) still caused a positive skin test reaction. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV WISCONSIN,INST FOOD RES,MADISON,WI 53706. MAYO CLIN & MAYO GRAD SCH MED,DEPT PEDIAT,ALLERG DIS RES LAB,ROCHESTER,MN 55901. MAYO CLIN & MAYO GRAD SCH MED,DEPT INTERNAL MED,ROCHESTER,MN 55901. NR 20 TC 41 Z9 43 U1 2 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 1994 VL 57 IS 5 BP 419 EP 423 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA NN281 UT WOS:A1994NN28100011 ER PT J AU ZIENOWICZ, RJ JUPITER, JB YAREMCHUK, MJ AF ZIENOWICZ, RJ JUPITER, JB YAREMCHUK, MJ TI A MICROSURGICAL SUCTION MAT SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Note AB We describe a suction mat used to maintain a bloodless field during microsurgery. The mat is inexpensive, can be quickly fashioned from readily available operating room items, and functions with exceptional reliability. C1 MASSACHUSETTS GEN HOSP,DIV PLAST SURG,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 1994 VL 19A IS 3 BP 519 EP 520 DI 10.1016/0363-5023(94)90074-4 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NP009 UT WOS:A1994NP00900032 PM 8056986 ER PT J AU VONWEIZSACKER, F BLUM, HE WANDS, JR AF VONWEIZSACKER, F BLUM, HE WANDS, JR TI POLYMERASE CHAIN-REACTION ANALYSIS OF HEPATITIS-B VIRUS-DNA IN FORMALIN-FIXED, PARAFFIN-EMBEDDED LIVER BIOPSIES FROM ALCOHOLICS USING A SIMPLIFIED AND STANDARDIZED AMPLIFICATION PROTOCOL SO JOURNAL OF HEPATOLOGY LA English DT Article DE ALCOHOLIC LIVER DISEASE; HEPATITIS B VIRUS; PARAFFIN-EMBEDDED TISSUE; POLYMERASE CHAIN REACTION ID DISEASE; INFECTION; CIRRHOSIS; PREVALENCE AB Sixty-seven formalin-fixed and paraffin-embedded liver biopsies from HBsAg-negative alcoholics without previous blood transfusions or intravenous drug abuse were analyzed for the presence of low-level hepatitis B virus DNA by the polymerase chain reaction. To simplify and standardize the amplification procedure, aliquots of a complete polymerase chain reaction mix were prepared and frozen for storage; random samples were tested prior to analysis of clinical material. Freezing and storage of the aliquots did not affect the activity of Tag polymerase. One large batch of ready-to-use aliquots could thus be used as a standardized polymerase chain reaction kit for all experiments. The suitability of the extracted material for polymerase chain reaction analysis was tested in two ways. First, the absence of nonspecific polymerase chain reaction inhibitors was demonstrated in all samples by amplifying cloned hepatitis B virus DNA in the presence of extracted material. Second, the integrity of the extracted DNA was tested by amplifying a segment of the beta-globin gene. Twenty-three samples were beta-globin DNA positive and thus contained sufficient amounts of nondegraded DNA. These results emphasize the importance of testing both the absence of nonspecific inhibitors and DNA integrity in DNA samples extracted from fixed tissue. Among the 23 beta-globin positive samples, 12 had cirrhosis (52.1%). Two of these samples were hepatitis B virus DNA positive (8.7%); one of these cases had cirrhosis. Thus, even in the absence of common risk factors, the incidence of hepatitis B virus in this alcoholic population was increased compared to the general population. (C) Journal of Hepatology. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC HEPATOL LAB,BOSTON,MA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 19 TC 6 Z9 6 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAY PY 1994 VL 20 IS 5 BP 646 EP 649 DI 10.1016/S0168-8278(05)80354-X PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NN432 UT WOS:A1994NN43200015 PM 8071542 ER PT J AU WEBER, GF CANTOR, H AF WEBER, GF CANTOR, H TI PHOSPHATIDYLINOSITOL SYNTHESIS IS A PROXIMAL EVENT IN INTRACELLULAR SIGNALING COUPLED TO T-CELL RECEPTOR LIGATION - DIFFERENTIAL INDUCTION BY CONVENTIONAL ANTIGEN AND RETROVIRAL SUPERANTIGEN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SHOCK SYNDROME TOXIN-1; LEYDIG TUMOR-CELLS; TRANSGENIC MICE; GENE-EXPRESSION; CYCLOSPORINE-A; ACTIVATION; HYDROLYSIS; INOSITOL; STIMULATION AB There is increasing evidence that at least two functionally distinct signal transduction pathways may be coupled to the TCR complex. A conventional signal transduction pathway coupled to TCR ligation by peptide/MHC complexes includes increased [Ca2+](i), phosphatidylinositol (PI) hydrolysis, and cytokine expression. TCR ligation by MIs-1(a)/MTV superantigens may be coupled to an alternative signal transduction pathway without increased [Ca2+](i) or detectable PI hydrolysis. We asked whether early events in the PI hydrolytic pathway might account for differential levels of PI breakdown after TCR ligation by conventional Ag and superantigen. We show that TCR ligation by conventional peptide Ag is coupled to a burst of PI synthesis in nontransformed T cells, which may represent a rate-limiting step for downstream PI hydrolysis. Incorporation of radiolabeled glucose by newly synthesized PI as well as inositol-1,4,5-trisphosphate provided direct evidence that this intracellular pool of Pi represents an important substrate for this signaling pathway. By contrast, TCR ligation of the same T cell clone by retroviral superantigen leads to similar levels of T cell proliferation without detectable PI synthesis. Increased levels of radiolabeled intracellular PI reflected de novo synthesis of PI from glucose-6-phosphate rather than recycling of inositol phosphates because labeled phosphate and glucose were incorporated into PI but extracellular [H-3]inositol was not. These findings suggest that differential PI synthesis represents an early biochemical event that distinguishes two functionally distinct signaling pathways coupled to TCR ligation by peptide Ag and retroviral superantigen. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,IMMUNOPATHOL LAB,BOSTON,MA 02115. FU NIAID NIH HHS [AI 13600, AI 12184] NR 32 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1994 VL 152 IS 9 BP 4433 EP 4443 PG 11 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900022 PM 7908918 ER PT J AU HIBBS, ML TOLVANEN, M CARPEN, O AF HIBBS, ML TOLVANEN, M CARPEN, O TI MEMBRANE-PROXIMAL IG-LIKE DOMAIN OF FC-GAMMA-RIII (CD16) CONTAINS RESIDUES CRITICAL FOR LIGAND-BINDING SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; SYSTEMIC LUPUS-ERYTHEMATOSUS; IMMUNOGLOBULIN-LIKE DOMAINS; SINGLE AMINO-ACID; HIGH-AFFINITY; MOLECULAR-CLONING; MONOCLONAL-ANTIBODY; FUNCTIONAL DOMAINS; ALPHA-SUBUNIT; RECEPTOR-II AB Ag-Ab complexes are cleared from the circulation through a complex system of receptors for the Fc portion of Ig (FcRs). Fc gamma RIII (CD16) is a low affinity FcR for IgG that is composed of two highly homologous Ig-like extracellular domains. Using secondary structure predictions, we located a strongly hydrophilic region in the second Ig-like domain of Fc gamma RIII that is predicted to lie between beta-strands C and C'. Substitutions of seven out of eight amino acids in this region abolished binding to IgG. Substitution of a conformationally adjacent amino acid in a bend just before beta-strand F and an amino acid in the B-C loop also affected ligand binding. However, amino acid substitutions in two different predicted loops in the second Ig-like domain as well as substitutions to three predicted loops in the first Ig-like domain had no effect on function. A chimeric Fc gamma RIII molecule lacking the second Ig-like domain was unable to bind IgG further, suggesting the presence of the binding site in the second domain. Neutralizing mAbs that inhibit Fc gamma RIII interaction with IgG were mapped to the E-F loop in the membrane proximal domain of Fc gamma RIII, providing further evidence of the importance of this region of the molecule in ligand interaction. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV HELSINKI,DEPT BIOCHEM,HELSINKI,FINLAND. UNIV HELSINKI,DEPT PATHOL,HELSINKI,FINLAND. RP HIBBS, ML (reprint author), ROYAL MELBOURNE HOSP,LUDWIG INST CANC RES,MELBOURNE TUMOUR BIOL BRANCH,MELBOURNE,VIC 3050,AUSTRALIA. RI Hibbs, Margaret/D-7013-2011 NR 67 TC 54 Z9 55 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1994 VL 152 IS 9 BP 4466 EP 4474 PG 9 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900025 PM 7512596 ER PT J AU WERSHIL, BK THEODOS, CM GALLI, SJ TITUS, RG AF WERSHIL, BK THEODOS, CM GALLI, SJ TITUS, RG TI MAST-CELLS AUGMENT LESION SIZE AND PERSISTENCE DURING EXPERIMENTAL LEISHMANIA-MAJOR INFECTION IN THE MOUSE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE CUTANEOUS LEISHMANIASIS; DELAYED-TYPE HYPERSENSITIVITY; NECROSIS-FACTOR-ALPHA; FC-EPSILON-RI; CONTACT SENSITIVITY; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; DEFICIENT W/WV; TNF-ALPHA; MICE AB Mast cells are a source of a variety of cytokines that may influence the host response to Leishmania major. To investigate the role of mast cells during L. major infection, we performed a morphometric analysis of mast cells at cutaneous sites in resistant C57BL/6 mice and susceptible BALB/c mice injected with L. major. Extensive dermal mast cell degranulation was found at sites of L. major infection in both strains of mice. We also examined the course of L. major infection in genetically mast cell-deficient WBB6F(1)-W/W-v or WCB6F(1)-SI/SId mice, their respective congenic normal (WBB6F(1)-+/+ or WCB6F(1)-+/+) littermates, and WBB6F(1)-W/W-v mice that had been selectively and locally repaired of their cutaneous mast cell deficiency. We found that mast cells significantly augmented the intensity and maximal size of the cutaneous lesions at sites of L. major infection, and in some cases substantially prolonged the persistence of the reactions. However, the lesions ultimately resolved in both the mast cell-deficient and the congenic normal mice. In addition, the presence or absence of mast cells had little or no effect on the numbers of viable parasites recovered from the cutaneous lesions. Moreover, mast cell-deficient W/W-v mice and the congenic normal (+/+) mice produced similar levels of IFN-gamma mRNA in lymph nodes draining the cutaneous lesions whereas no IL-4 mRNA was detectable. Taken together, these data suggest that mast cells significantly augment the size of cutaneous lesions during L. major infection in mice. However, mast cells do not appear to influence significantly either the parasite burden or the ultimate resolution of the infection. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02215. CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. FU NIAID NIH HHS [AI-22674, AI-29955]; NIDDK NIH HHS [P01 DK-33506] NR 47 TC 58 Z9 58 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1994 VL 152 IS 9 BP 4563 EP 4571 PG 9 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900036 PM 8157970 ER PT J AU BILSLAND, CAG DIAMOND, MS SPRINGER, TA AF BILSLAND, CAG DIAMOND, MS SPRINGER, TA TI THE LEUKOCYTE INTEGRIN P150,95 (CD11C/CD18) AS A RECEPTOR FOR IC3B - ACTIVATION BY A HETEROLOGOUS BETA-SUBUNIT AND LOCALIZATION OF A LIGAND RECOGNITION SITE TO THE I-DOMAIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED MOLECULE-1; INTERCELLULAR-ADHESION MOLECULE-1; AMINO-ACID SEQUENCE; MAC-1 CD11B CD18; COMPLEMENT RECEPTOR; ALPHA-SUBUNIT; COUNTER-RECEPTOR; MONOCLONAL-ANTIBODIES; VONWILLEBRAND-FACTOR; HUMAN-MONOCYTES AB p150,95 is a member of the leukocyte integrin family of adhesion proteins. Compared with LFA-1 and Mac-1, p150,95 is less well functionally characterized. Although p150,95 has complement receptor activity for iC3b and has been designated complement receptor type 4, transfected cells expressing p150,95 do not bind iC3b-sensitized cells. We report that cells cotransfected with a human p150,95 a subunit and a chicken, but not human, beta subunit bind IgM-iC3b-coated erythrocytes, suggesting that interactions between the alpha and beta subunits can regulate p150,95 adhesiveness. Furthermore, purified human p150,95 binds to cell-bound iC3b-coated erythrocytes. Because binding to iC3b by cellular and purified p150,95 is specifically abolished by mAbs that localize to the I domain of p150,95, we suggest that the I domain of the p150,95 alpha subunit is an important ligand recognition site for iC3b. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 31799] NR 55 TC 96 Z9 96 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1994 VL 152 IS 9 BP 4582 EP 4589 PG 8 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900038 PM 7512600 ER PT J AU MANDLE, R BARON, C ROUX, E SUNDEL, R GELFAND, J AULAK, K DAVIS, AE ROSEN, FS BING, DH AF MANDLE, R BARON, C ROUX, E SUNDEL, R GELFAND, J AULAK, K DAVIS, AE ROSEN, FS BING, DH TI ACQUIRED C1 INHIBITOR DEFICIENCY AS A RESULT OF AN AUTOANTIBODY TO THE REACTIVE CENTER REGION OF C1 INHIBITOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEREDITARY-ANGIO-EDEMA; C1-INHIBITOR DEFICIENCY; PURIFICATION; COMPLEMENT; ANTIBODY; SITE AB An autoantibody that we hypothesize to react with the reactive center of the plasma serine proteinase inhibitor, C1 inhibitor (C1INH), has been found in a patient with acquired C1INH deficiency. The Ab blocks the ability of C1INH to inhibit the hydrolysis of N-carbobenzyloxy-L-lysine thiobenzylester by purified C1s. A cryoprecipitate from the patient's plasma as well as the Ig fraction were able to block C1INH inhibition of C1s. The immunoaffinity purified Ab to C1INH from the patient's plasma Ig fraction neutralizes the inhibitory activity of C1INH in a dose-dependent manner and blocks the ability of normal C1INH to form a complex with C1s. The neutralizing activity of the purified Ab is reversed by a synthetic peptide that corresponds to the amino acid sequence in the P1 to P15 positions of the reactive center of C1INH but not by a 34-amino-acid trypsin peptide or 37-amino-acid elastase peptide derived from the C-terminus of C1INH. Western blot analysis indicated that the Ab is an oligoclonal Ig with kappa light chains. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. CHILDRENS HOSP RES FDN,CINCINNATI,OH 45229. UNIV CINCINNATI,COLL MED,CINCINNATI,OH. OI Sundel, Robert/0000-0002-0083-5695 FU NCRR NIH HHS [RR02172]; NICHD NIH HHS [HD22082, HD17461] NR 22 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1994 VL 152 IS 9 BP 4680 EP 4685 PG 6 WC Immunology SC Immunology GA NG719 UT WOS:A1994NG71900050 PM 7512602 ER PT J AU MEGERIAN, CA MCKENNA, MJ AF MEGERIAN, CA MCKENNA, MJ TI UNTITLED SO JOURNAL OF LARYNGOLOGY AND OTOLOGY LA English DT Letter RP MEGERIAN, CA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOL & LARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU HEADLEY BROTHERS LTD PI ASHFORD PA INVICTA PRESS, ASHFORD, KENT, ENGLAND TN24 8HH SN 0022-2151 J9 J LARYNGOL OTOL JI J. Laryngol. Otol. PD MAY PY 1994 VL 108 IS 5 BP 458 EP 458 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA NP728 UT WOS:A1994NP72800023 PM 8035135 ER PT J AU HSU, DW PARDO, FS EFIRD, JT LINGGOOD, RM HEDLEYWHYTE, ET AF HSU, DW PARDO, FS EFIRD, JT LINGGOOD, RM HEDLEYWHYTE, ET TI PROGNOSTIC-SIGNIFICANCE OF PROLIFERATIVE INDEXES IN MENINGIOMAS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE IMMUNOCYTOCHEMISTRY; LABELING INDEX; MENINGIOMA; MITOTIC INDEX; PROLIFERATING CELL NUCLEAR ANTIGEN; TUMOR RECURRENCE ID CELL NUCLEAR ANTIGEN; DNA-POLYMERASE-DELTA; RADIATION-THERAPY; INTRACRANIAL MENINGIOMAS; AUXILIARY PROTEIN; BRAIN-TUMORS; CYCLIN PCNA; ANAPLASTIC MENINGIOMA; MONOCLONAL-ANTIBODIES; RESECTED MENINGIOMAS AB The prognostic value of tumor proliferative indices in meningiomas was assessed by mitotic counts and by immunocytochemistry using a monoclonal antibody against the proliferating cell nuclear antigen (PCNA) (clone 19A2), a 36-kd nuclear protein involved in DNA synthesis. Sixty-three intracranial meningiomas were classified as benign (26), with atypical features (24) or as malignant (13). The patients included 24 men and 39 women, mean age 54.2 +/- 1.7 (mean +/- SEM) (range 15-78) at initial presentation. Twenty-four of the 63 primary tumors recurred locally, including 23.1% (6/26) of the benign, 37.5% (9/24) of the atypical, and 69.2% (9/13) of the malignant meningiomas. Among tumors that recurred, 1/9 (11%) of the atypical and 5/9 (55.5%) of the malignant tumors had had macroscopical total excision at the initial surgery. The mean interval to recurrence was 52 +/- 11.8 months. The mean progression-free follow-up period for patients without tumor recurrence was 82 +/- 8.5 months. Analysis of variance revealed that significant differences existed between tumor grades for both PCNA indices(1.16 +/- 0.29% for benign; 14.14 +/- 2.07% for atypical and 21.37 +/- 5.47% for malignant) and mitotic indices (total counts per ten high power fields) (0.08 I 0.05 for benign, 4.75 +/- 0.91 for atypical and 19.00 +/- 4.07 for malignant). Multivariate regression analysis indicated that mitotic index > 6 was the single most important factor (p < 0.05) for shorter disease-free interval. Age, sex and total surgical excision were not significant factors. PCNA index was a significant factor in the univariate model, but not in the multivariate model. However, a two-factor-interaction model with PCNA > 5% and mitoses > 6 was highly significant as a predictor of outcome (p < 0.0001). We conclude that PCNA index may be used as an adjunct with mitotic counts in predicting the clinical course of patients with meningiomas. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT THERAPY,BOSTON,MA. RP HSU, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV NEUROPATHOL,WARREN 3,BOSTON,MA 02114, USA. NR 58 TC 68 Z9 73 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1994 VL 53 IS 3 BP 247 EP 255 DI 10.1097/00005072-199405000-00005 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA NL027 UT WOS:A1994NL02700005 PM 7909837 ER PT J AU MIRRA, SS GEARING, M MCKEEL, DW CRAIN, BJ HUGHES, JP VANBELLE, G HEYMAN, A BALL, MJ CLARK, AW HANSEN, LA HEDREEN, JC JOACHIM, CL KIM, RC KIRKPATRICK, JB MARKESBERY, WR DAVIS, D MARTINEZ, AJ MILLER, CA MOOSSY, J MORRIS, J NOCHLIN, D PERL, DP PUROHIT, D PETITO, CK RAO, GR ROBITAILLE, Y SCHELPER, RL SUMI, SM VOGEL, FS WHITE, CR AF MIRRA, SS GEARING, M MCKEEL, DW CRAIN, BJ HUGHES, JP VANBELLE, G HEYMAN, A BALL, MJ CLARK, AW HANSEN, LA HEDREEN, JC JOACHIM, CL KIM, RC KIRKPATRICK, JB MARKESBERY, WR DAVIS, D MARTINEZ, AJ MILLER, CA MOOSSY, J MORRIS, J NOCHLIN, D PERL, DP PUROHIT, D PETITO, CK RAO, GR ROBITAILLE, Y SCHELPER, RL SUMI, SM VOGEL, FS WHITE, CR TI INTERLABORATORY COMPARISON OF NEUROPATHOLOGY ASSESSMENTS IN ALZHEIMERS-DISEASE - A STUDY OF THE CONSORTIUM TO ESTABLISH A REGISTRY FOR ALZHEIMERS-DISEASE (CERAD) SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ALZHEIMERS DISEASE; MULTICENTER STUDY; QUALITY IMPROVEMENT; SENILE PLAQUES; SILVER STAINS ID SENILE PLAQUES; NEUROFIBRILLARY TANGLES; SYNAPSE LOSS; DIAGNOSIS; DEMENTIA; CRITERIA AB Concerns about intercenter variation in methods and interpretation prompted CERAD investigators to examine standardization of the neuropathological assessment of Alzheimer's disease (AD). Contiguous frontal lobe sections derived from autopsy brains of eight patients clinically diagnosed as having probable AD and two cognitively normal individuals were distributed to 24 neuropathologists from 18 medical centers in the United States and Canada. Using their routine staining method(s), neuropathologists determined the rank order of severity of AD neuropathology in these cases, as well as semiquantitative and quantitative senile plaque and neurofibrillary tangle frequencies. Ranking of the ten cases revealed 75% inter-rater reliability among the 24 raters. Semiquantitative analyses showed reasonable inter-rater agreement, whereas quantitative measures yielded significant differences between raters for plaque and tangle counts (p < 0.0001). These differences reflected variation in stain sensitivity, staining technique (even when the same stain was used), and interpretation of the histological findings. Ratings on the cases with the highest proportions of diffuse plaques showed the greatest dependence upon stain sensitivity and variability in interpretation. This study indicates that greater attention to quality improvement is needed for the neuropathological evaluation of AD, particularly when pooling data in multicenter studies such as CERAD. C1 EMORY UNIV,SCH MED,ATLANTA,GA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. DUKE UNIV,MED CTR,DURHAM,NC. OREGON HLTH SCI UNIV,PORTLAND,OR. UNIV CALGARY,HLTH SCI CTR,CALGARY,AB,CANADA. UNIV CALIF SAN DIEGO,LA JOLLA,CA. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. HARVARD UNIV,BRIGHAM & WOMENS HOSP,BOSTON,MA. VET AFFAIRS MED CTR,LONG BEACH,CA. BAYLOR COLL MED,HOUSTON,TX. UNIV KENTUCKY,MED CTR,LEXINGTON,KY. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. UNIV SO CALIF,MED CTR,LOS ANGELES,CA. UNIV WASHINGTON,SCH MED,SEATTLE,WA. MT SINAI MED CTR,NEW YORK,NY. BRONX VET AFFAIRS MED CTR,NEW YORK,NY. CORNELL UNIV,MED CTR,NEW YORK,NY. VET AFFAIRS MED CTR,PITTSBURGH,PA. MONTREAL NEUROL HOSP & INST,MONTREAL,PQ,CANADA. UNIV IOWA HOSP & CLIN,IOWA CITY,IA. UNIV TEXAS,SOUTHWESTERN MED CTR,DALLAS,TX. RP MIRRA, SS (reprint author), VET AFFAIRS MED CTR,1670 CLAIRMONT RD,DECATUR,GA 30033, USA. FU NIA NIH HHS [AG05681, AG06790, AG10130] NR 25 TC 105 Z9 105 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1994 VL 53 IS 3 BP 303 EP 315 DI 10.1097/00005072-199405000-00012 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA NL027 UT WOS:A1994NL02700012 PM 8176413 ER PT J AU BROWN, MC AF BROWN, MC TI THE ANTIDROMIC COMPOUND ACTION-POTENTIAL OF THE AUDITORY-NERVE SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GUINEA-PIG COCHLEA; PHYSIOLOGICAL-PROPERTIES; ELECTRICAL-STIMULATION; SPIRAL GANGLION; FIBERS; ADAPTATION; RECORDINGS; MASKING; NEURONS; CATS AB 1. The antidromic compound action potential (ACAP) of the auditory nerve was evoked by shocks to the auditory nerve root and recorded at the round window of the cochlea in anesthetized guinea pigs. The goal of this study was to determine the characteristics of the ACAP and compare these characteristics with those of the orthodromic, sound-evoked compound action potential (CAP). 2. The ACAP consists of an initial complex of a positive peak (p(1)) followed by a negative peak (n(1)). In contrast, the CAP consists of a negative peak (N-1) followed by a positive peak (P-1). These differences in waveform are likely due to the differences in conduction direction, antidromic for the ACAP vs. orthodromic for the CAP. 3. After the initial complex, the ACAP has a second complex of peaks (p(2), n(2)) at a latency of similar to 1 ms; this complex is much smaller in amplitude than the initial complex (p(1), n(1)). It is likely that the initial ACAP complex reflects firing of auditory-nerve fibers whereas the second complex reflects firing of neurons further centrally, perhaps in the cochlear nucleus, that are activated by orthodromic firing of auditory-nerve fibers. 4. Experiments with shock pairs are consistent with the idea that for auditory nerve fibers, the absolute refractory period is <0.5 ms, and the relative refractory period is between 0.5 and at least 5 ms. 5. Experiments with click-shock pairs indicate that a shock interferes with the response to a click when the click and shock are given at about the same time. A click interferes with the response to a shock when it precedes the shock by similar to 2 ms. These time differences are present because ACAP and CAP have different latencies, the latter having a synaptic delay via the hair cells. 6. The ACAP is much more resistant than the CAP to the effects of noise masking, probably because the generation of the ACAP does not involve the hair cell-nerve fiber synapse, where adaptation arises. The ACAP is also more resistant than the CAP to the effects of asphyxia, probably because the generation of the ACAP does not involve inner hair cells, which have responses that are quickly reduced during asphyxia. C1 HARVARD UNIV,SCH MED,MIT,DEPT OTOL & LARYNGOL,DIV HLTH SCI & TECHNOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MIT,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02114. RP BROWN, MC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC-01089] NR 31 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1994 VL 71 IS 5 BP 1826 EP 1834 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA NL773 UT WOS:A1994NL77300018 PM 8064350 ER PT J AU BROWN, MC AF BROWN, MC TI ANTIDROMIC RESPONSES OF SINGLE UNITS FROM THE SPIRAL GANGLION SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STIMULATED AUDITORY-NERVE; GUINEA-PIG COCHLEA; TOPOGRAPHIC ORGANIZATION; PHYSIOLOGICAL-PROPERTIES; CENTRAL PROJECTIONS; EFFERENT NEURONS; FIBERS; CATS; MORPHOLOGY; CELLS AB 1. Antidromic responses of single units in the guinea pig spiral ganglion were recorded in response to shocks to the auditory nerve root. The orthodromic responses of these units were also recorded in response to sound. The aim of this study was 1) to classify units according to their response patterns to shocks and to sound and 2) to propose anatomic types that might correlate with these responses. The four classes of units were as follows: type I, olivo-cochlear (OC), long-latency: locked, and long-latency: jittering. 2. Type I units responded antidromically to shocks with little jitter and short latency. Their responses to sound were also of short latency and had irregular interspike intervals. Some of these units had complex spike waveforms. These units likely correspond to type I primary afferent neurons, the majority population of spiral ganglion cells. 3. One-third of the OC units responded to shocks, with little jitter and intermediate latency(2 ms). OC unit responses to sound were of long latency and had regular interspike intervals. These units likely correspond to efferent neurons that originate in the superior olivary complex of the brain and end on outer hair cells in the cochlea. 4. Long-latency: locked units responded to shocks with little jitter and long latency (4-11 ms). Many of these units had complex spike waveforms and most did not respond to high-level noise bursts. Long-latency: locked units may correspond to type II spiral ganglion neurons. 5. Long-latency: jittering units responded to shocks with a jitter of several milliseconds and long latency. Some of these units responded to sound in a pattern reminiscent of OC units. These units may constitute a subgroup of OC units that respond to shocks via activation of the reflex pathway from the cochlea to the superior olive and back out to the cochlea. 6. Further data were collected on the type I response to shocks. Antidromic spikes lacked the inflections seen on the waveforms that are typically seen on orthodromic spikes. Type I shock responses depended on shock level and duration and were reduced when a click preceded the shock by similar to 2 ms. Several type I characteristics depended on the rate of spontaneous discharge: for units of low and medium spontaneous rates(when compared with units of high rates), the shock thresholds were lower, shock latencies were longer, and the probability of firing repetitive spikes to a single shock was higher. These units also differed in that they were distributed somewhat more toward the side of the ganglion closest to scala vestibuli. C1 HARVARD UNIV,SCH MED,MIT,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MIT,DEPT OTOL & LARYNGOL,DIV HLTH SCI & TECHNOL,BOSTON,MA 02114. RP BROWN, MC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC-01089] NR 51 TC 38 Z9 38 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 1994 VL 71 IS 5 BP 1835 EP 1847 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA NL773 UT WOS:A1994NL77300019 PM 8064351 ER PT J AU TESTA, CM STANDAERT, DG YOUNG, AB PENNY, JB AF TESTA, CM STANDAERT, DG YOUNG, AB PENNY, JB TI METABOTROPIC GLUTAMATE-RECEPTOR MESSENGER-RNA EXPRESSION IN THE BASAL GANGLIA SF THE RAT SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BASAL GANGLIA; METABOTROPIC GLUTAMATE RECEPTOR; IN SITU HYBRIDIZATION; STRIATUM; SUBTHALAMIC NUCLEUS; GLUTAMATE ID EXCITATORY AMINO-ACID; NIGRA PARS RETICULATA; SUBTHALAMIC NUCLEUS; XENOPUS OOCYTES; IMMUNOCYTOCHEMICAL LOCALIZATION; CHOLINE-ACETYLTRANSFERASE; SIGNAL TRANSDUCTION; PARKINSONS-DISEASE; CORTICAL ABLATION; MOLECULAR-CLONING AB Metabotropic glutamate receptors (mGluRs) couple the actions of glutamate to intracellular second messenger systems through G-proteins. The mGluRs play an important role in the regulation of basal ganglia function. Ligand binding studies have revealed that the basal ganglia contain at least two pharmacological types of metabotropic binding sites. Agonists of mGluRs can affect both in vitro electrophysiologic responses of striatal neurons and motor behavior in vivo. Recently, cDNAs encoding five mGluRs have been cloned, each with distinct structural and pharmacological properties. In order to elucidate the function of these receptors in the biology of the extrapyramidal motor system, we have used in situ hybridization to examine the regional and cellular expression patterns of mGluR1-mGluR5 in the adult rat basal ganglia. In the striatum, all of these mGluRs were present in widely varying relative densities and cellular patterns. MGluR5 was particularly prominent, and exhibited a heterogeneous cellular distribution, with labeled and unlabeled populations of neurons. MGluR2 was expressed in a small population of large polygonal striatal neurons. The subthalamic nucleus was the only other basal ganglia structure that expressed mGluR2. Distinct cellular distributions of mGluR expression were also observed within the nucleus accumbens, globus pallidus, ventral pallidum, and substantia nigra pars reticulata. MGluR3 was expressed in glia in all basal ganglia structures, but was observed in neurons only in the striatum, substantia nigra pars reticulata, and very weakly in the subthalamic nucleus. Comparison of the restricted mGluR2 and mGluR3 mRNA distributions with that of metabotropic ligand binding sites supports a possible presynaptic location for these receptors in the basal ganglia. MGlUR1 was the only mGluR message prominently expressed in the dopaminergic neurons of the substantia nigra pars compacta, suggesting the involvement of this receptor in the regulation of dopamine release from nigrostriatal terminals. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MICHIGAN,NEUROSCI PROGRAM,ANN ARBOR,MI 48109. FU NIA NIH HHS [AG08671]; NINDS NIH HHS [NS19613] NR 84 TC 413 Z9 419 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY PY 1994 VL 14 IS 5 BP 3005 EP 3018 PN 2 PG 14 WC Neurosciences SC Neurosciences & Neurology GA NK237 UT WOS:A1994NK23700007 PM 8182455 ER PT J AU ABRAHAM, S FISCHMAN, A ALPERT, N GONZALES, E GEWIRTZ, H AF ABRAHAM, S FISCHMAN, A ALPERT, N GONZALES, E GEWIRTZ, H TI REGIONAL HETEROGENEITY OF MYOCARDIAL BLOOD-FLOW IN HUMANS WITH DILATED CARDIOMYOPATHY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P23 EP P23 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900085 ER PT J AU BABICH, JW GRAHAM, W BARROW, SA FISCHMAN, AJ AF BABICH, JW GRAHAM, W BARROW, SA FISCHMAN, AJ TI COMPARISON BETWEEN IN-111 HUMAN POLYCLONAL IGG AND A TC-99M LABELED CHEMOTACTIC PEPTIDE ANALOG FOR LOCALIZATION OF ACUTE BACTERIAL-INFECTION IN RABBITS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P174 EP P174 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900698 ER PT J AU BABICH, JW FISCHMAN, AJ AF BABICH, JW FISCHMAN, AJ TI OF THE ROLE OF ADRENERGIC-RECEPTORS ON METAIODOBENZYLGUANIDINE STORAGE AND RETENTION IN CULTURED NEUROBLASTOMA-CELLS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P66 EP P66 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900258 ER PT J AU BABICH, JW HIGGINS, JD ABRAMS, MJ GRAHAM, W BARROW, SA PIKE, M RUBIN, RH FISCHMAN, AJ MATHEY, J AF BABICH, JW HIGGINS, JD ABRAMS, MJ GRAHAM, W BARROW, SA PIKE, M RUBIN, RH FISCHMAN, AJ MATHEY, J TI INFECTION IMAGING WITH RADIOLABELED CHEMOTACTIC PEPTIDES - RELATIONSHIP BETWEEN RECEPTOR AFFINITY AND INFECTION LOCALIZATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 1 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P44 EP P44 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900170 ER PT J AU BABICH, JW FISCHMAN, AJ AF BABICH, JW FISCHMAN, AJ TI EFFECT OF CO-LIGAND ON THE BIODISTRIBUTION OF TC-99M HYDRAZINO NICOTINAMIDE CHEMOTACTIC PEPTIDE ANALOGS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P19 EP P19 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900068 ER PT J AU BHATTATHIRY, M GLASS, E KIRGAN, D MORTON, D HOH, C MADDAHI, J BROWN, C KHONSARY, A BLAHD, W AF BHATTATHIRY, M GLASS, E KIRGAN, D MORTON, D HOH, C MADDAHI, J BROWN, C KHONSARY, A BLAHD, W TI EFFICACY OF FDG WHOLE-BODY PET IN STAGING AND CLINICAL MANAGEMENT OF METASTATIC MALIGNANT-MELANOMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,MED CTR,JOHN WAYNE CANC INST,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 4 Z9 4 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P230 EP P230 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900941 ER PT J AU BROWN, CV KHONSARY, SA BHATTATHIRY, M ROPCHAN, JR FARAHI, JB QUINONES, N RIBE, JY COLOURIS, GC GLASS, EC COYLE, JJ MANDELKERN, MA BLAHD, WH AF BROWN, CV KHONSARY, SA BHATTATHIRY, M ROPCHAN, JR FARAHI, JB QUINONES, N RIBE, JY COLOURIS, GC GLASS, EC COYLE, JJ MANDELKERN, MA BLAHD, WH TI WHOLE-BODY FDG-PET ONCOLOGY ATLAS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P273 EP P273 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901111 ER PT J AU BUCHBINDER, BR JIANG, HJ ALPERT, NM COSGROVE, GR OGILVY, CS STERN, CE BAKER, JR FISCHMAN, AJ AF BUCHBINDER, BR JIANG, HJ ALPERT, NM COSGROVE, GR OGILVY, CS STERN, CE BAKER, JR FISCHMAN, AJ TI FUNCTIONAL MAPPING OF SENSORIMOTOR CORTEX IN INDIVIDUAL SUBJECTS - CORRELATION BETWEEN 0-15 PET AND INTRAOPERATIVE CORTICAL STIMULATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P107 EP P107 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900424 ER PT J AU CARTER, E TOMPKINS, RG BABICH, JW FISCHMAN, AJ AF CARTER, E TOMPKINS, RG BABICH, JW FISCHMAN, AJ TI EFFECT OF THERMAL-INJURY ON UPTAKE AND PHOSPHORYLATION OF F-18 FLUORODEOXYGLUCOSE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 SHRINERS BURN INST,BOSTON,MA 02114. RP CARTER, E (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P175 EP P175 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900702 ER PT J AU CHAUDHURI, TR ZINN, KR MORRIS, JS MCDONALD, GA LLORENS, AS CHAUDHURI, TK AF CHAUDHURI, TR ZINN, KR MORRIS, JS MCDONALD, GA LLORENS, AS CHAUDHURI, TK TI DEVELOPMENT AND CHARACTERIZATION OF RADIOLABELED HUMAN MONOCLONAL-ANTIBODY AGAINST OVARIAN-CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV MISSOURI, COLUMBIA, MO USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. VET ADM MED CTR, SAN ANTONIO, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P218 EP P219 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900889 ER PT J AU CHOI, NC HAMBERG, LM HUNTER, GJ EFIRD, JT ALPERT, NM MCLOUD, TC BABITCH, J JAIN, RK FISCHMAN, AJ AF CHOI, NC HAMBERG, LM HUNTER, GJ EFIRD, JT ALPERT, NM MCLOUD, TC BABITCH, J JAIN, RK FISCHMAN, AJ TI GLUCOSE METABOLIC-RATE MONITORED WITH PET 18-F-FDG FOR TUMOR RESPONSE TO RADIOTHERAPY (RT) OR RADIOCHEMOTHERAPY (RT+CT) IN LUNG-CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P37 EP P37 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900141 ER PT J AU CORREIA, JA BURKE, JF FISCHMAN, AJ AF CORREIA, JA BURKE, JF FISCHMAN, AJ TI STABLE-ISOTOPE CONTENT IN BIOLOGICAL SAMPLES BY NUCLEAR ACTIVATION USING A PET CYCLOTRON - A PRELIMINARY EVALUATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P177 EP P177 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900711 ER PT J AU ELMALEH, DR BROWNELL, AL SHOUP, TM ISACSON, O FISCHMAN, AJ MADRAS, B AF ELMALEH, DR BROWNELL, AL SHOUP, TM ISACSON, O FISCHMAN, AJ MADRAS, B TI PET IMAGING OF [11C]3B-ARYLTROPANE-2B-CARBOXYLIC ESTER ANALOGS IN MPTP-TREATED MONKEYS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MCLEAN HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P140 EP P140 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900563 ER PT J AU ELMALEH, DR FISCHMAN, AJ SHOUP, TM HANSON, RN MELTZER, P MADRAS, BK AF ELMALEH, DR FISCHMAN, AJ SHOUP, TM HANSON, RN MELTZER, P MADRAS, BK TI RADIOSYNTHESIS AND EVALUATION OF E-[125I]-2B-CARBOMETHOXY-3B-(4-FLUOROPHENYL)-N-(1-IODOPROP-1-EN-3-YL)NOR TROPANE AND Z-[125I]-2B-CARBOMETHOXY-3B-(4-FLUOROPHENYL)-N-(1-IODOPROP-1-EN-3-YL)NOR TROPANE (IODOALTROPANE) - A SELECTIVE SPECT AGENT FOR IMAGING DA REUPTAKE SITES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. ORGANIX,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P121 EP P121 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900484 ER PT J AU FISCHMAN, AJ LIVNI, E BABICH, JW ALPERT, NM LIU, YY THOM, E CLEELAND, R PROSSER, BL CORREIA, JA RUBIN, RH AF FISCHMAN, AJ LIVNI, E BABICH, JW ALPERT, NM LIU, YY THOM, E CLEELAND, R PROSSER, BL CORREIA, JA RUBIN, RH TI PHARMACOKINETICS OF [F-18] FLEROXACIN IN NORMAL SUBJECTS AND PATIENTS WITH URINARY-TRACT INFECTIONS AND BRONCHITIS STUDIED WITH PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HOFFMANN LA ROCHE INC,NUTLEY,NJ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P175 EP P175 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900703 ER PT J AU GEWIRTZ, H FISCHMAN, A ALPERT, N AF GEWIRTZ, H FISCHMAN, A ALPERT, N TI VALIDATION OF K1 PARAMETRIC IMAGES OBTAINED FROM DYNAMIC 13-NH3 PET IMAGES - COMPARISON TO K1 VALUES OBTAINED WITH A STANDARD NONLINEAR ESTIMATION PROGRAM SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P77 EP P77 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900304 ER PT J AU GONZALEZ, RG STERN, C GUIMARAES, A CARR, C ROSEN, B GROWDON, J FISCHMAN, AJ AF GONZALEZ, RG STERN, C GUIMARAES, A CARR, C ROSEN, B GROWDON, J FISCHMAN, AJ TI A COMPARISON OF FUNCTIONAL MRI AND PET IN THE EVALUATION OF DEMENTIA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P20 EP P20 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900073 ER PT J AU HUNTER, GJ HAMBERG, LM ALPERT, NM CHOI, NC LORING, NA FISCHMAN, AJ AF HUNTER, GJ HAMBERG, LM ALPERT, NM CHOI, NC LORING, NA FISCHMAN, AJ TI THE FDG DOSE UPTAKE RATIO CORRECTED FOR BLOOD RADIOACTIVITY (CDUR) IS A MORE ROBUST INDEX OF GLUCOSE METABOLIC-RATE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P8 EP P8 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900022 ER PT J AU JANICEK, MJ KAPLAN, WD MCLAUGHLIN, M NADLER, L AF JANICEK, MJ KAPLAN, WD MCLAUGHLIN, M NADLER, L TI SEQUENTIAL IMAGING OF NON-HODGKINS-LYMPHOMAS (NHL) WITH CT, GA-67 AND TL-201 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P230 EP P231 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900942 ER PT J AU LARSEN, SK ABRAMS, MJ HIGGINS, JD SOLOMON, HF BABICH, JW FISCHMAN, AJ MATTHEY, J AF LARSEN, SK ABRAMS, MJ HIGGINS, JD SOLOMON, HF BABICH, JW FISCHMAN, AJ MATTHEY, J TI TECHNETIUM COMPLEX OF TRICINE - USEFUL PRECURSOR FOR THE TC-99M LABELING OF HYDRAZINO NICOTINAMIDE MODIFIED HUMAN POLYCLONAL IGG SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 RW JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA 19477. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 10 Z9 10 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P105 EP P105 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900418 ER PT J AU LIVNI, E BABICH, JW ALPERT, NM CORREIA, JA WILKINSON, RA FISCHMAN, AJ AF LIVNI, E BABICH, JW ALPERT, NM CORREIA, JA WILKINSON, RA FISCHMAN, AJ TI SYNTHESIS OF A C-11 LABELED SUBSTANCE-P RECEPTOR-LIGAND FOR PET STUDIES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P254 EP P254 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901044 ER PT J AU MENG, XJ ELMALEH, DR JYAWOOK, S WEISS, S ALPERT, NM BABICH, JW TOMPKINS, RG FISCHMAN, AJ AF MENG, XJ ELMALEH, DR JYAWOOK, S WEISS, S ALPERT, NM BABICH, JW TOMPKINS, RG FISCHMAN, AJ TI SYNTHESIS OF 2-[18-F]-FLUORO-2-DEOXY-GLUCOSE - BIODISTRIBUTION IN RATS AND PRELIMINARY PET STUDIES IN MONKEYS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P254 EP P254 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90901043 ER PT J AU MOLINA, IL PALMER, EL SCOTT, JA PRINCE, MR STRAUSS, HW RUBIN, RH FISCHMAN, AJ AF MOLINA, IL PALMER, EL SCOTT, JA PRINCE, MR STRAUSS, HW RUBIN, RH FISCHMAN, AJ TI IN-111 POLYCLONAL IGG SCINTIGRAPHY IN THE EVALUATION OF COMPLICATED OSTEOMYELITIS AND SEPTIC ARTHRITIS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Prince, Martin/S-6850-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P89 EP P89 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900351 ER PT J AU NARULA, J KHAW, S NICOL, PD KHAW, BA AF NARULA, J KHAW, S NICOL, PD KHAW, BA TI QUANTITATION OF V1 AND V3 ISOFORMS OF MAMMALIAN CARDIAC MYOSIN BY RADIOIMMUNOASSAYS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P145 EP P145 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900586 ER PT J AU NARULA, J PETROV, A DITLOW, C DILLEY, J PIESLAK, I CHEN, FW KHAW, BA AF NARULA, J PETROV, A DITLOW, C DILLEY, J PIESLAK, I CHEN, FW KHAW, BA TI EARLIER EXPERIMENTAL ATHEROSCLEROTIC LESION VISUALIZATION WITH HIGH RADIOSPECIFIC-ACTIVITY, NEGATIVE CHARGE-MODIFIED CHIMERIC Z2D3 F(AB')(2) (AT 24 HOURS) VERSUS CONVENTIONALLY LABELED-ANTIBODY (AT 48 HOURS) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SCOTGEN BIOPHARMACEUT INC,MENLO PK,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P98 EP P98 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900390 ER PT J AU NARULA, J PETROV, A PAK, KY KHAW, BA AF NARULA, J PETROV, A PAK, KY KHAW, BA TI TC-99M-GLUCARATE IN ACUTE VISUALIZATION OF EXPERIMENTAL NONREPERFUSED MYOCARDIAL-INFARCTION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MOLEC TARGETING TECHNOL INC,MALVERN,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P4 EP P4 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900004 ER PT J AU PALMER, WE SCHOENBERG, OI FISCHMAN, AJ ROSENTHALL, DI POLISSON, RP AF PALMER, WE SCHOENBERG, OI FISCHMAN, AJ ROSENTHALL, DI POLISSON, RP TI FDG METABOLISM IN THE WRIST DURING TREATMENT OF INFLAMMATORY ARTHRITIS - QUANTIFICATION WITH PET AND CORRELATION WITH CLINICAL-RESPONSE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P35 EP P35 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900130 ER PT J AU RABITO, CA LOPEZ, IA MOORE, RH RUBIN, RH TOLKOFFRUBIN, NE DECARETTA, NP COLVIN, RB COSIMI, AB HAUG, CE AF RABITO, CA LOPEZ, IA MOORE, RH RUBIN, RH TOLKOFFRUBIN, NE DECARETTA, NP COLVIN, RB COSIMI, AB HAUG, CE TI REAL-TIME MONITORING OF GFR IN ISCHEMIC-INJURY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P99 EP P99 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900395 ER PT J AU RAUCH, SL ALPERT, NM SAVAGE, CR MIGUEL, EC BAER, L BREITER, HC MANZO, PA MORETTI, C FISCHMAN, AJ JENIKE, MA AF RAUCH, SL ALPERT, NM SAVAGE, CR MIGUEL, EC BAER, L BREITER, HC MANZO, PA MORETTI, C FISCHMAN, AJ JENIKE, MA TI AN O-15 PET STUDY OF SIMPLE PHOBIA DURING BEHAVIORAL CHALLENGE - A COMPARISON GROUP FOR OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P75 EP P75 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900295 ER PT J AU SHOUP, TM BROWNELL, AL FISCHMAN, AJ ELMALEH, DR MADRAS, BK AF SHOUP, TM BROWNELL, AL FISCHMAN, AJ ELMALEH, DR MADRAS, BK TI SELECTIVE DOPAMINE D-2 RECEPTOR IMAGING OF MONKEY BRAIN USING [11C]METHYL-YM-09151-2 AND PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P198 EP P199 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900803 ER PT J AU SOLOMON, HF DERIAN, CK BEBLAVY, M JESTER, D SANTULLI, R PIKE, M KROON, D HOEY, K FISCHMAN, AJ AF SOLOMON, HF DERIAN, CK BEBLAVY, M JESTER, D SANTULLI, R PIKE, M KROON, D HOEY, K FISCHMAN, AJ TI FOCAL INFECTION IMAGING USING AN IN-111 LABELED ANTAGONIST CHEMOTACTIC PEPTIDE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 RW JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA 19477. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P45 EP P45 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900172 ER PT J AU ZAKNUN, J ELMALEH, DR BABICH, JW RAPAPORT, E METELEV, V ZAMECNIK, PC FISCHMAN, AJ AF ZAKNUN, J ELMALEH, DR BABICH, JW RAPAPORT, E METELEV, V ZAMECNIK, PC FISCHMAN, AJ TI IN-VITRO UPTAKE OF I-125 IODOBENZOATE C-MYB VARIANT OLIGODEOXYNUCLEOTIDES PHOSPHOROTHIOATES IN HUMAN INTESTINAL SMOOTH-MUSCLE CELLS (HISM) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. WORCESTER FDN EXPTL BIOL INC, SHREWSBURY, MA 01545 USA. UNIV INNSBRUCK, NUCL MED CLIN, A-6020 INNSBRUCK, AUSTRIA. RI Metelev, Valeri/I-3238-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1994 VL 35 IS 5 SU S BP P151 EP P152 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NK909 UT WOS:A1994NK90900604 ER PT J AU BODE, BP AF BODE, BP TI THE ROLE OF AMINO-ACIDS IN APOB100 SYNTHESIS AND CATABOLISM IN HUMAN HEPG2 CELLS SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Note ID AMBULATORY PERITONEAL-DIALYSIS RP BODE, BP (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAY-JUN PY 1994 VL 18 IS 3 BP 280 EP 281 DI 10.1177/0148607194018003280 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NM393 UT WOS:A1994NM39300016 PM 8065006 ER PT J AU SIMEON, PS GEFFNER, ME LEVIN, SR LINDSEY, AM AF SIMEON, PS GEFFNER, ME LEVIN, SR LINDSEY, AM TI CONTINUOUS INSULIN INFUSIONS IN NEONATES - PHARMACOLOGICAL AVAILABILITY OF INSULIN IN INTRAVENOUS SOLUTIONS SO JOURNAL OF PEDIATRICS LA English DT Article ID GLUCOSE-INTOLERANCE; INFANTS AB Continuous insulin infusion is sometimes used in very low birth weight infants with glucose intolerance. We studied the availability of insulin to the neonate by means of a laboratory-simulated clinical infusion under both flushed and nonflushed conditions. Although loss of insulin was noted with both solutions (0.5 U/ml), under the nonflushed condition only 55.9% of the prescribed dose for the first 2 hours was delivered before the delivery rate of the flushed system, 71.4%, was approached. These findings have implications for neonatal insulin administration. C1 UNIV CALIF LOS ANGELES, MED CTR, SCH NURSING, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT PEDIAT, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. NR 9 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 1994 VL 124 IS 5 BP 818 EP 820 DI 10.1016/S0022-3476(05)81382-4 PN 1 PG 3 WC Pediatrics SC Pediatrics GA NK479 UT WOS:A1994NK47900030 PM 8176576 ER PT J AU BROWN, LJ GARCIA, R AF BROWN, LJ GARCIA, R TI UTILIZATION OF DENTAL SERVICES AS A RISK FACTOR FOR PERIODONTITIS SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE DELIVERY OF HEALTH CARE; ORAL HEALTH SURVEYS; PATIENT ACCEPTANCE OF HEALTH CARE; UTILIZATION REVIEW ID SUBGINGIVAL PLAQUE CONTROL; ORAL HYGIENE; LINEAR-MODELS; DISEASE; HEALTH; POPULATION; ADULTS; TEETH AB THE RELATION BETWEEN UTILIZATION OF DENTAL SERVICES from community dentists and the extent and severity of alveolar bone loss is reported for a panel of men followed for over 6 years. Oral health data were collected by the Department of Veterans Affairs, Dental Longitudinal Study, which began in 1969 and still continues. Participants have received regular oral examinations approximately every 3 years. A variety of oral health conditions were assessed, including plaque, calculus, gingival inflammation, probing depth, tooth mobility, clinical attachment level, and alveolar bone loss. Utilization data were abstracted from the dental records of dental offices that participants attended from 1979 through 1988. Multivariate modeling as well as comparisons of high utilizers and non-utilizers indicate that utilization of routine diagnostic and preventive services was not predictive of the extent and severity of periodontitis. C1 US DEPT VET AFFAIRS,WASHINGTON,DC. TUFTS UNIV,BOSTON,MA 02111. RP BROWN, LJ (reprint author), NIDR,WESTWOOD BLDG,ROOM 528,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 71 TC 14 Z9 14 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 1994 VL 65 IS 5 SU S BP 551 EP 563 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NM524 UT WOS:A1994NM52400012 PM 8046572 ER PT J AU NANJI, AA ZHAO, SP KHWAJA, S SADRZADEH, SMH WAXMAN, DJ AF NANJI, AA ZHAO, SP KHWAJA, S SADRZADEH, SMH WAXMAN, DJ TI CIMETIDINE PREVENTS ALCOHOLIC HEPATIC-INJURY IN THE INTRAGASTRIC FEEDING RAT MODEL SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ETHANOL-OXIDIZING SYSTEM; LIVER-DISEASE; THROMBOXANE SYNTHASE; LIPID-PEROXIDATION; DIETARY-FAT; CYTOCHROME-P-450; INHIBITION; EXPRESSION; FIBROSIS; ENZYMES AB Cytochrome P450 induction is believed to be important in the pathogenesis of alcoholic hepatic disease. Because cimetidine is a general inhibitor of cytochrome P450 enzymes, it was hypothesized that it could be useful in preventing alcoholic hepatic injury. An intragastric feeding model was used these studies. Experimental animals were divided into groups of four to five rats/group and fed the following diets: corn oil + dextrose, corn oil + ethanol (CE) and corn oil + ethanol + cimetidine (250 mg kg(-1) day(-1)) (CEC). The rats in each group were sacrificed at the following time intervals: 2 weeks, 1 month and 2 months. For each animal, the severity of the pathologic findings and relative protein levels of cytochromes P450 2E1, 28 and 4A were measured. In addition, plasma levels of thromboxane B-2, 6-ketoprostagiandin F-1 alpha and 8-isoprostane were also measured. The most significant finding was that cimetidine completely prevented alcoholic hepatic injury in this model system. The pathologic scores (an indication of the severity of injury) were significantly lower in the CEC groups compared with the CE group. There was however, no significant difference in cytochrome P450 2E1, 2B or 4A protein levels between CE and CEC groups. Thromboxane B-2 acid 8-isoprostane levels were significantly lower and 6-ketoprostaglandin F-1 alpha, significantly higher in the CEC group than in the CE group. These results indicate that possible mechanisms involved in the protective action of cimetidine include inhibition of thromboxane production and lipid peroxidation. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP NEW ENGLAND DEACONESS HOSP, DEPT PATHOL, 185 PILGRIM RD, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK 33765] NR 45 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1994 VL 269 IS 2 BP 832 EP 837 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB547 UT WOS:A1994PB54700053 PM 8182552 ER PT J AU HEDBERG, PS TORCHIANA, DF REYNOLDS, TR GEFFIN, GA TITUS, JS DAGGETT, WM AF HEDBERG, PS TORCHIANA, DF REYNOLDS, TR GEFFIN, GA TITUS, JS DAGGETT, WM TI REVERSAL OF VENTRICULAR CONTRACTURE DURING HYPOTHERMIC CARDIOPLEGIC ARREST SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID ISOLATED RAT-HEART; ISCHEMIC CONTRACTURE; STONE HEART; MYOCARDIAL PRESERVATION; CALCIUM; MUSCLE; HYPOXIA; CELLS; DETERMINANTS; OXYGENATION AB Ventricular contracture was produced in isolated perfused rat hearts by a novel method using repeated administration of an anoxic cold hyperkalemic cardioplegia solution. Contracture could be reversed by reperfusion with the same solution, without calcium (Group 1), oxygenated (Group 2), or oxygenated and calcium free (Group 3). Group 1 hearts underwent partial reversal of contracture; in Group 2, contracture was reversed more completely, but the effect was transient. Hearts in Group 3 had contracture reversed completely to a level lower than prearrest end diastolic pressure. Hearts in contracture were profoundly depleted of high-energy phosphates (ATP, 9% of control; creatine phosphate, 27%) and the success of contracture reversal was parallelled by the extent to which each solution repleted ATP and PCr. Ventricular contracture produced by energy depletion is rapidly reversed by restoration of oxygen to the myocardium. Reducing extracellular calcium by acalcemic perfusion is ineffective as an isolated measure but is synergistic with reoxygenation and enhances contracture reversal. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK 73126. RP HEDBERG, PS (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 12777] NR 39 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY PY 1994 VL 56 IS 5 BP 439 EP 445 DI 10.1006/jsre.1994.1069 PG 7 WC Surgery SC Surgery GA NK787 UT WOS:A1994NK78700009 PM 8170144 ER PT J AU TAYLOR, CR FLOTTE, TJ GANGE, RW ANDERSON, RR AF TAYLOR, CR FLOTTE, TJ GANGE, RW ANDERSON, RR TI TREATMENT OF NEVUS OF OTA BY Q-SWITCHED RUBY-LASER SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID GUINEA-PIG SKIN; MALIGNANT-MELANOMA; OCULODERMAL MELANOCYTOSIS; BILATERAL NEVUS; TATTOOS; RADIATION; MACULES AB Background: There are few reports on therapy for nevus of Ota. Moreover, traditional treatments are largely palliative or risk permanent pigmentary changes and/or scarring. Objective: The efficacy of the Q-switched ruby laser (694 nm, 40 nsec) as a therapy for nevus of Ota was investigated. Methods: Nine nevi or portions thereof were irradiated up to six times with 4.5 and/or 7.5 J/cm(2) at a mean exposure interval of 3 weeks. Sequential skin biopsy specimens were processed for light microscopy, immunohistochemistry, and electron microscopy. Results: Cosmetic improvement occurred at both doses in the irradiated parts of the six nevi available for follow-up. No appreciable difference was noted between single and multiple treatments. There was no gross scarring. Light microscopy revealed dose-related immediate injury with more melanophages and fewer dermal melanocytes after irradiation in comparison with control areas. Electron microscopic distinction between dermal melanocytes and melanin-laden macrophages was difficult. A monoclonal antibody to human melanosome specific antigen type 1 (HMSA-1) was used to distinguish between the two cell populations. Conclusion: Our findings suggest that the Q-switched ruby laser is useful for treating nevus of Ota. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAMS NIH HHS [1R3AR38992, R01-AR25395] NR 43 TC 44 Z9 44 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1994 VL 30 IS 5 BP 743 EP 751 PN 1 PG 9 WC Dermatology SC Dermatology GA NL044 UT WOS:A1994NL04400009 PM 8176014 ER PT J AU HULKA, JF HULKA, CA AF HULKA, JF HULKA, CA TI PREOPERATIVE SONOGRAPHIC EVALUATION AND LAPAROSCOPIC MANAGEMENT OF PERSISTENT ADNEXAL MASSES - A 1994 REVIEW SO JOURNAL OF THE AMERICAN ASSOCIATION OF GYNECOLOGIC LAPAROSCOPISTS LA English DT Review ID EPITHELIAL OVARIAN-CANCER; POSTMENOPAUSAL WOMEN; OPERATIVE LAPAROSCOPY; STAGE-I; TRANSVAGINAL DOPPLER; RELATIVE FREQUENCY; ULTRASOUND; TUMORS; CYSTS; DIAGNOSIS AB Carcinoma of the ovary is a frightening disease because it is a major cause of death due to cancer in women and is the leading cause of deaths-from gynecologic malignancies. The disease is associated with a common clinical problem: persistent adnexal masses, most of which are benign. Operative laparoscopy has become an increasingly attractive way of diagnosing and removing adnexal masses. The practicing general gynecologist thus faces two new dilemmas: not to miss an early ovarian cancer or manage an unsuspected one to the patient's detriment, and not to perform extensive major surgery for adnexal masses, most of which can be handled laparoscopically. Fortunately, pertinent data exist on which the resolution of these dilemmas may be based. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP HULKA, JF (reprint author), UNIV N CAROLINA,SCH MED,DEPT OBSTET & GYNECOL,CHAPEL HILL,NC 27514, USA. NR 67 TC 5 Z9 6 U1 0 U2 0 PU JOURNAL AMER ASSOC GYNECOLOGIC LAPAROSCOPISTS PI SANTA FE SPRINGS PA 13021 EAST FLORENCE AVE, SANTA FE SPRINGS, CA 90670-4505 SN 1074-3804 J9 J AM ASSOC GYN LAP JI J. Am. Assoc. Gynecol. Laparoscopists PD MAY PY 1994 VL 1 IS 3 BP 197 EP 205 DI 10.1016/S1074-3804(05)81010-2 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PU652 UT WOS:A1994PU65200002 PM 9050487 ER PT J AU CARLSON, S SONNENBERG, LM CUMMINGS, S AF CARLSON, S SONNENBERG, LM CUMMINGS, S TI DIETING READINESS TEST PREDICTS COMPLETION IN A SHORT-TERM WEIGHT-LOSS PROGRAM SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID OBESITY; PATTERNS C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT DIETET,AMBULATORY NUTR SERV,BOSTON,MA 02114. NR 12 TC 7 Z9 7 U1 0 U2 1 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 1994 VL 94 IS 5 BP 552 EP 554 DI 10.1016/0002-8223(94)90224-0 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NL847 UT WOS:A1994NL84700019 PM 8176135 ER PT J AU MEYER, JS TAKASHIMA, S TERAYAMA, Y OBARA, K MURAMATSU, K WEATHERS, S AF MEYER, JS TAKASHIMA, S TERAYAMA, Y OBARA, K MURAMATSU, K WEATHERS, S TI CT CHANGES ASSOCIATED WITH NORMAL AGING OF THE HUMAN BRAIN SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE COMPUTED TOMOGRAPHY; POLIO-ARAIOSIS; LEUKOARAIOSIS; CEREBRAL PERFUSION; DENSITOMETRY ID COMPUTED-TOMOGRAPHY; LEUKO-ARAIOSIS; ALZHEIMERS-DISEASE; WHITE MATTER; RISK-FACTORS; CELL COUNTS; DEMENTIA; ATROPHY; LUCENCIES; NUMBERS AB CT was used to measure changes in cerebral gray and white matter tissue densities associated with normal aging, using a cross-sectional design, in order to provide normative data for comparisons with abnormal aging such as dementias of Alzheimer's and vascular types. Cerebral compartmental densities were measured using plain CT; and their perfusion values were recorded during stable xenon inhalation (CT-CBF), among 81 neurologically and cognitively normal volunteers of different ages. Results led to the conclusion that cortical gray matter tissue densities progressively decline (polio-araiosis) after age 60. Cortical polio-araiosis is coupled with regional hypoperfusion but not with cortical atrophy. It is speculated that the cortical hypodensity identified by CT imaging parallels declines in cortical synaptic density, as reported from autopsy studies using anti-synaptophysin staining of cerebral cortex obtained from normal people above and below age 60. The coupling of cortical hypoperfusion with polio-araiosis is believed to reflect age-related reductions of cortical metabolic demands as reported by PET. During normal aging leuko-araiosis correlates directly with cortical atrophy, suggesting that anterograde axonal degeneration resulting from cortical neuronal dearborization play a role in its causation. C1 BAYLOR COLL MED & NEUROL,DEPT NEUROL,HOUSTON,TX. BAYLOR COLL MED & NEUROL,DEPT RADIOL,HOUSTON,TX. RP MEYER, JS (reprint author), DEPT VET AFFAIRS MED CTR,SERV RADIOL,CEREBAL BLOOD FLOW LAB,2002 HOLCOMBE BLVD 151A,HOUSTON,TX 77030, USA. NR 40 TC 27 Z9 27 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAY PY 1994 VL 123 IS 1-2 BP 200 EP 208 DI 10.1016/0022-510X(94)90224-0 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NL359 UT WOS:A1994NL35900031 PM 8064316 ER PT J AU KILBRIDGE, PM MAYER, JE NEWBURGER, JW HICKEY, PR WALSH, AZ NEUFELD, EJ AF KILBRIDGE, PM MAYER, JE NEWBURGER, JW HICKEY, PR WALSH, AZ NEUFELD, EJ TI INDUCTION OF INTERCELLULAR-ADHESION MOLECULE-1 AND E-SELECTIN MESSENGER-RNA IN HEART AND SKELETAL-MUSCLE OF PEDIATRIC-PATIENTS UNDERGOING CARDIOPULMONARY BYPASS SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID REDUCES ORGAN INJURY; MONOCLONAL-ANTIBODY; LEUKOCYTE ADHESION; NEUTROPHIL ADHERENCE; CARDIAC MYOCYTES; MYOCARDIAL REPERFUSION; HEMORRHAGIC-SHOCK; ACTIVATION; ISCHEMIA; ICAM-1 AB Leukocyte adhesion to vascular endothelium is an early step in inflammatory damage to tissues. To investigate the expression of endothelial adhesion molecules in the inflammatory response associated with cardiopulmonary bypass, we measured messenger ribonucleic acid (mRNA) encoding the adhesion molecules E-selectin and intercellular adhesion molecule-1 in intraoperative samples of cardiac tissue and skeletal muscle from infants undergoing cardiopulmonary bypass. Atrial tissue samples were obtained before and after bypass from II children and paired samples of rectus abdominis muscle from 15. mRNA was analyzed by ribonuclease protection with the use of nonmuscle actin as an internal control. Atrial E-selectin mRNA levels increased from before to after bypass (median increase 3.5-fold, p = 0.0002) in each of nine patients tested, and atrial intercellular adhesion molecule-1 mRNA increased in seven of nine patients (median, 2.1-fold, p = 0.025). In skeletal muscle, E-selectin mRNA increased in 11 of 12 patients (median 4.3-fold, p = 0.0018), and intercellular adhesion molecule-1 mRNA levels increased in 13 of 13 patients (median 3.2-fold, p = 0.013). E-selectin and intercellular adhesion molecule-1 induction in skeletal muscle occurred with or without circulatory arrest. We conclude that adhesion molecule mRNA induction occurs in cardiac and noncardiac tissue during cardiopulmonary bypass in man. C1 CHILDRENS HOSP,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT CARDIAC SURG,BOSTON,MA 02115. CHILDRENS HOSP,DEPT ANESTHESIA,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL48675]; NIDDK NIH HHS [DK01977] NR 39 TC 40 Z9 43 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 1994 VL 107 IS 5 BP 1183 EP 1192 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NL041 UT WOS:A1994NL04100001 PM 7513775 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI CARCINOMA OF THE PENIS SO JOURNAL OF UROLOGY LA English DT Editorial Material RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1994 VL 151 IS 5 BP 1250 EP 1250 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA NG390 UT WOS:A1994NG39000021 PM 8158768 ER PT J AU MONDA, JM BARRY, MJ OESTERLING, JE AF MONDA, JM BARRY, MJ OESTERLING, JE TI PROSTATE-SPECIFIC ANTIGEN CANNOT DISTINGUISH STAGE T1A (A1) PROSTATE-CANCER FROM BENIGN PROSTATIC HYPERPLASIA SO JOURNAL OF UROLOGY LA English DT Article DE ANTIGENS, NEOPLASM; PROSTATIC NEOPLASMS; PROSTATIC HYPERTROPHY ID FOLLOW-UP; ADENOCARCINOMA; ALPHA-1-ANTICHYMOTRYPSIN; DIAGNOSIS; CARCINOMA; DISEASE; COMPLEX; MARKER; SERUM; MEN AB To determine if serum prostate specific antigen (PSA) has decreased the prevalence of stages T1a (A1) and T1b (A2) prostate cancer, and to compare the PSA values for patients with stages T1a and T1b prostate cancer and men with symptomatic benign prostatic hyperplasia, 966 patients undergoing transurethral resection of the prostate were evaluated retrospectively. Included in the study population were 499 consecutive patients who underwent transurethral resection of the prostate for obstructive urinary symptoms in 1986 (no PSA group), and 467 consecutive patients who underwent resection in 1989 and 1990 who were evaluated with serum PSA preoperatively (PSA group). The mean age for the no PSA group was 71 years compared to 70 years for the PSA group (p = 0.36). The overall prevalence of stages T1a and T1b prostate cancer in the no PSA group was 8.6% compared to 10.3% in the PSA group (p = 0.37). The prevalence of stages T1a and T1b prostate cancer in the no PSA group was 3.6% and 5.0%, respectively, compared to 7.3% and 3.0%, respectively, for the PSA group (p = 0.01). In the PSA group the median PSA value for patients with stages T1a and T1b prostate cancer was 3.8 ng./ml. compared to 3.4 ng./ml. for the patients without cancer (p = 0.59). The median PSA level for the stage T1a cancer patients was 2.4 ng./ml., which was not statistically different from that in patients without cancer (p = 0.31), and the median PSA level for the stage T1b cancer patients was 5.9 ng./ml., which was statistically different than that in patients without cancer (p = 0.01). These findings suggest that the routine use of serum PSA does not decrease the prevalence of stage T1a prostate cancer and that PSA may decrease the prevalence of stage T1b tumors but a larger study would be necessary to document this finding. C1 MAYO CLIN & MAYO FDN,DEPT UROL,ROCHESTER,MN 55905. MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. FU AHRQ HHS [HSO6336] NR 27 TC 31 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1994 VL 151 IS 5 BP 1291 EP 1295 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA NG390 UT WOS:A1994NG39000034 PM 7512660 ER PT J AU KAUFMAN, JA YUCEL, EK WALTMAN, AC GELLER, SC PRINCE, MR CAMBRIA, RP BREWSTER, DC ABBOTT, WM AF KAUFMAN, JA YUCEL, EK WALTMAN, AC GELLER, SC PRINCE, MR CAMBRIA, RP BREWSTER, DC ABBOTT, WM TI MR-ANGIOGRAPHY IN THE PREOPERATIVE EVALUATION OF ABDOMINAL AORTIC-ANEURYSMS - A PRELIMINARY-STUDY SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE ANEURYSM, AORTIC; ANGIOGRAPHY, COMPARATIVE STUDIES; MAGNETIC RESONANCE (MR), VASCULAR STUDIES ID MAGNETIC-RESONANCE ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; RECONSTRUCTION; AORTOGRAPHY; MANAGEMENT; EXPERIENCE; STENOSIS; CT AB PURPOSE: The ability of magnetic resonance (MR) angiography to depict visceral and renal vessels was evaluated in patients with abdominal aortic aneurysms (AAAs). PATIENTS AND METHODS: MR sequences (sagittal T1-weighted, two-dimensional coronal, and three-dimensional axial time-of-flight) were compared in a prospective blinded fashion with conventional angiograms obtained preoperatively in 23 patients with AAAs. Results were correlated with surgical findings when available. RESULTS: Operative aortic clamp site was correctly predicted with conventional angiography in 95% of patients and with MR angiography in 86% (P > .1). Aneurysm neck measurements obtained with the two modalities were within 1 cm in 91% of cases. With conventional angiography as the standard of reference, 96% of all renal arteries were identified on MR angiograms but 36% of accessory arteries were missed. MR angiography enabled identification of patients who had at least one renal artery stenosis greater than 50% with a sensitivity of 100% and specificity of 89%. For identifying individual renal artery, celiac artery, and superior mesenteric artery stenoses of similar severity, the sensitivity and specificity were 67% and in excess of 96%, respectively. The celiac artery could not be evaluated in one case. CONCLUSION: The results of this small study suggest that the role of MR angiography in the preoperative evaluation of AAA warrants further investigation. C1 MASSACHUSETTS GEN HOSP,GEN SURG SERV,DIV VASC SURG,BOSTON,MA 02114. RP KAUFMAN, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. RI Prince, Martin/S-6850-2016 NR 29 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAY-JUN PY 1994 VL 5 IS 3 BP 489 EP 496 DI 10.1016/S1051-0443(94)71536-0 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA PB252 UT WOS:A1994PB25200019 PM 8054753 ER PT J AU PUSKAS, JD GERTLER, JP AF PUSKAS, JD GERTLER, JP TI INTERNAL JUGULAR TO AXILLARY VEIN BYPASS FOR SUBCLAVIAN VEIN-THROMBOSIS IN THE SETTING OF BRACHIAL ARTERIOVENOUS-FISTULA SO JOURNAL OF VASCULAR SURGERY LA English DT Note ID COMPLICATION; HEMODIALYSIS AB Placement of central venous catheter is the most common cause of subclavian vein thrombosis. In the setting of a functioning ipsilateral brachial arteriovenous fistula, venous hypertension symptoms maybe exacerbated. We report successful decompression of severe venous hypertension in the right arm of a patient whose only access for hemodialysis was a functioning right brachial arteriovenous fistula and in whom proximal subclavian vein occlusion developed from a previous percutaneous dialysis catheter. Transposition of the right internal jugular vein and end-to-side anastomosis to the right axillary vein provided prompt and effective venous outflow, with complete resolution of venous engorgement of the affected Limb and preservation of the dialysis fistula. C1 MASSACHUSETTS GEN HOSP,DIV VASC SURG,BOSTON,MA 02114. NR 15 TC 34 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 1994 VL 19 IS 5 BP 939 EP 942 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA NJ957 UT WOS:A1994NJ95700022 PM 8170051 ER PT J AU ZHU, ZM CAI, WZ SCHAFFER, PA AF ZHU, ZM CAI, WZ SCHAFFER, PA TI COOPERATIVITY AMONG HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE-EARLY REGULATORY PROTEINS - ICP4 AND ICP27 AFFECT THE INTRACELLULAR-LOCALIZATION OF ICPO SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; EARLY GENE-EXPRESSION; DNA-BINDING PROTEIN; SV40 T-ANTIGEN; NF-KAPPA-B; MACROMOLECULAR-SYNTHESIS; NUCLEAR-LOCALIZATION; POLYACRYLAMIDE GELS; DELETION MUTANTS; ELECTROPHORETIC TRANSFER AB The results of transient expression assays and studies of viral mutants have shown that three of the five immediate-early proteins of herpes simplex virus type 1 (HSV-1) perform regulatory functions, individually and cooperatively. As part of efforts designed to explore the molecular basis for the functional cooperativity among ICP0, ICP4, and ICP27 in the regulation of HSV gene expression, we have examined the intracellular localization of ICP0 in cells infected with ICP4 and ICP27 null mutant viruses by indirect immunofluorescence. Although ICP0 was localized predominantly to the nuclei of wild-type virus-infected cells, it was found exclusively in the nuclei of ICP27 mutant-infected cells and in both the cytoplasm and nuclei of ICP4 mutant-infected cells, the cytoplasmic component being especially strong. These observations indicate that both ICP4 and ICP27 can affect the intracellular localization of ICP0. Transient expression assays with plasmids that express wild-type and mutant forms of ICP0, ICP4, and ICP27 confirmed that ICP4 promotes and that ICP27 inhibits the nuclear localization of ICP0. These results confirm the observations made for mutant virus-infected cells and indicate that the localization pattern seen in infected cells can be established by these three immediate-early proteins exclusive of other viral proteins. The C-terminal half of ICP27 was shown to be required to achieve its inhibitory effect on the nuclear localization of ICP0. The region of ICPO responsive to ICP27 was mapped to the C terminus of the molecule between amino acid residues 720 and 769. In addition, the concentration of ICP27 was shown to have a significant effect on the intracellular localization of ICP0. Because the major regulatory activities of ICP0, ICP4 and ICP27 are expressed in the nucleus, the ability of these three proteins collectively to determine their own localization patterns within cells adds a new dimension to the complex process of viral gene regulation in HSV. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [R37 CA20260] NR 74 TC 58 Z9 59 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1994 VL 68 IS 5 BP 3027 EP 3040 PG 14 WC Virology SC Virology GA NF452 UT WOS:A1994NF45200029 PM 8151771 ER PT J AU SEEMAN, TE CHARPENTIER, PA BERKMAN, LF TINETTI, ME GURALNIK, JM ALBERT, M BLAZER, D ROWE, JW AF SEEMAN, TE CHARPENTIER, PA BERKMAN, LF TINETTI, ME GURALNIK, JM ALBERT, M BLAZER, D ROWE, JW TI PREDICTING CHANGES IN PHYSICAL PERFORMANCE IN A HIGH-FUNCTIONING ELDERLY COHORT - MACARTHUR STUDIES OF SUCCESSFUL AGING SO JOURNALS OF GERONTOLOGY LA English DT Article ID ALAMEDA COUNTY; RISK-FACTORS; DISABILITY; FALLS; OLD AB Background. Performance-based measures of physical performance were examined for an older cohort of relatively high-functioning men and women. Relationships between baseline physical performance and sociodemographic and health status characteristics were also examined. Three-year pattern changes in performance are described, and sociodemographic and health status predictors of change are investigated. Methods. A cohort of relatively high-functioning men and women, aged 70-79, was identified in 1988 by subsampling from three community-based studies on the basis of physical and cognitive function. Baseline in-home assessments included tests of physical performance and measurement of sociodemographic characteristics and health status. A summary measure of physical performance was developed from tests of balance, gait, lower body strength and coordination, and manual dexterity. In-home assessments were repeated at follow-up in 1991. Results. Better physical performance at baseline was more common among males, Whites, those reporting higher income and education, and those with fewer chronic conditions. In linear regression models, declines in performance were predicted by older age, lower income, higher education, relative weight and blood pressure, lower peak expiratory flow, prevalent diabetes and incident health conditions and hospitalizations during follow-up. Improvements in performance were also observed; the only significant association was with race (i.e., being Black). Conclusions. Declines in physical performance within a high-functioning cohort are predictable from sociodemographic and health status characteristics. The patterns of both decline and improvement in performance observed in this cohort suggest that older age is not uniformly associated with declines, indicating the potential for effective interventions to promote more successful aging. C1 YALE UNIV,SCH MED,DEPT MED,NEW HAVEN,CT 06510. NIA,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. RP SEEMAN, TE (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,60 COLL ST,NEW HAVEN,CT 06510, USA. NR 40 TC 208 Z9 208 U1 4 U2 16 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD MAY PY 1994 VL 49 IS 3 BP M97 EP M108 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NJ544 UT WOS:A1994NJ54400001 PM 8169338 ER PT J AU HALLEK, M ANDO, K EDER, M SLATTERY, K AJCHENBAUMCYMBALISTA, F GRIFFIN, JD AF HALLEK, M ANDO, K EDER, M SLATTERY, K AJCHENBAUMCYMBALISTA, F GRIFFIN, JD TI SIGNAL-TRANSDUCTION OF STEEL FACTOR AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR - DIFFERENTIAL REGULATION OF TRANSCRIPTION FACTOR AND G1 CYCLIN GENE-EXPRESSION, AND OF PROLIFERATION IN THE HUMAN FACTOR-DEPENDENT CELL-LINE MO7 SO LEUKEMIA LA English DT Article ID RECEPTOR TYROSINE KINASE; C-KIT PROTOONCOGENE; GROWTH-FACTOR; GM-CSF; PROGENITOR CELLS; RAPID TYROSINE; LEUKEMIA-CELLS; MYC EXPRESSION; INTERLEUKIN-3; PHOSPHORYLATION AB Steel factor (SF) synergizes with a variety of hemopoietins to support the growth and differentiation of human progenitor cells. The human factor-dependent cell line MO7 has been used as a model to study the interaction of SF with other growth factors such as GM-CSF, because both factors support the proliferation of this cell line and are synergistic in combination. Previous studies have shown that this effect is not readily explained by the synergistic activation of early, cytosolic signal transduction intermediates such as tyrosine kinases, Raf-1, MAP2 kinase, or phospholipase C gamma. In an attempt to further explore the biological and biochemical mechanisms of the synergy between SF and GM-CSF, we examined the effects of these growth factors on the regulation of nuclear proto-oncogenes, cell cycle control genes, and G1 --> S transition of MO7 cells. Individually, GM-CSF was a much more potent growth factor for MO7 cells than SF, particularly under serum-free conditions. Only GM-CSF, but not SF, was able to stimulate G1 --> S transition of MO7 cells after factor deprivation for 24 h. Northern blot analyses showed also differential effects of GM-CSF and SF on the expression of some nuclear proto-oncogenes and G1 cyclins. GM-CSF (10 ng/ml), but not SF (20 ng/ml) increased the expression of c-myc and cyclin D2 mRNA, whereas both factors caused transient increases of c-fos and cyclin D3 mRNAs. When added simultaneously, GM-CSF and SF induced an at least additive increase of c-fos mRNA expression; this effect required the presence of fetal calf serum. No additive effects of GM-CSF and SF on c-myc, cyclin D2 or D3 mRNA expression were observed. C-jun and c-myb mRNAs were constitutively expressed in the MO7 cell line, but not further increased after stimulation with GM-CSF or SF for 15 min to 48 h. The inability of SF to induce growth promoting genes such as c-myc and cyclin D2 may explain why this cytokine does not support sustained proliferation of MO7 cells. These observations suggest that SF and GM-CSF exert different effects on the expression of genes involved in regulatory pathways of cell proliferation, but the molecular mechanism of synergy remains to be elucidated. C1 DANA FARBER CANC INST, BOSTON, MA USA. FU NCI NIH HHS [CA 36167, CA 34183] NR 59 TC 15 Z9 15 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1994 VL 8 IS 5 BP 740 EP 748 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA NP119 UT WOS:A1994NP11900005 PM 7514243 ER PT J AU HAFFNER, SM VALDEZ, RA MYKKANEN, L STERN, MP KATZ, MS AF HAFFNER, SM VALDEZ, RA MYKKANEN, L STERN, MP KATZ, MS TI DECREASED TESTOSTERONE AND DEHYDROEPIANDROSTERONE-SULFATE CONCENTRATIONS ARE ASSOCIATED WITH INCREASED INSULIN AND GLUCOSE-CONCENTRATIONS IN NONDIABETIC MEN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HORMONE-BINDING GLOBULIN; BODY-FAT DISTRIBUTION; SEX-HORMONES; POSTMENOPAUSAL WOMEN; MEXICAN-AMERICANS; RESISTANCE; HYPERINSULINEMIA; ADIPOSITY; OBESITY; LIPOPROTEIN C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIAT & GERONTOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. FU NHLBI NIH HHS [R01 HL-24799, R37-HL36820] NR 38 TC 181 Z9 183 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1994 VL 43 IS 5 BP 599 EP 603 DI 10.1016/0026-0495(94)90202-X PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NL244 UT WOS:A1994NL24400013 PM 8177048 ER PT J AU RAAB, M YAMAMOTO, M RUDD, CE AF RAAB, M YAMAMOTO, M RUDD, CE TI THE T-CELL ANTIGEN CD5 ACTS AS A RECEPTOR AND SUBSTRATE FOR THE PROTEIN-TYROSINE KINASE P56(LCK) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN LYMPHOCYTES-T; INTRACELLULAR IONIZED CALCIUM; AMINO-TERMINAL DOMAIN; SIGNAL TRANSDUCTION; MEMBRANE GLYCOPROTEIN; CYTOPLASMIC DOMAINS; SURFACE-ANTIGENS; HELPER FUNCTION; CROSS-LINKING; GENE-PRODUCT AB CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T-cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this, the mechanism by which CD5 generates intracellular signals is unclear. In this study, we demonstrate that CD5 is coupled to the proteid-tyrosine kinase p56(lck) and can act as a substrate for p56(lck). Coexpression of CD5 with p56(lck) in the baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine residues. Further, anti-CD5 and anti-p56(lck) coprecipitated each other in a variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also precipitated the kinase from various T cells irrespective of the expression of TcR zeta/CD3 or CD4. No binding between p59(fyn)(T) and CD5 was detected in T cells. The binding of p56(lck) to CD5 induced a 10- to 15-fold increase in p56(lck) catalytic activity, as measured by in vitro kinase analysis. In vivo labelling with P-32(i) also showed a four- to fivefold increase in Y-394 occupancy in p56(lck) when associated with CD5. The use of glutathione S-transferase-Lck fusion proteins in precipitation analysis showed that the SH2 domain of p56(lck) could recognize CD5 as expressed in the baculovirus expression system. CD5 interaction with p56(lck) represents a novel variant of a receptor-kinase complex in which receptor can also serve as substrate. The CD5-p56(lck) interaction is likely to play roles in T-cell signalling and T-B collaboration. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 64 TC 68 Z9 68 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1994 VL 14 IS 5 BP 2862 EP 2870 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NG756 UT WOS:A1994NG75600003 PM 7513045 ER PT J AU FLEMINGTON, EK LYTLE, JP CAYROL, C BORRAS, AM SPECK, SH AF FLEMINGTON, EK LYTLE, JP CAYROL, C BORRAS, AM SPECK, SH TI DNA-BINDING-DEFECTIVE MUTANTS OF THE EPSTEIN-BARR-VIRUS LYTIC SWITCH ACTIVATOR ZTA TRANSACTIVATE WITH ALTERED SPECIFICITIES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BZLF1 PROTEIN; PRODUCTIVE INFECTION; GENE BZLF1; VIRAL-DNA; C-JUN; TRANSCRIPTION; PROMOTER; CELLS; EBV; HERPESVIRUS AB The Epstein-Barr virus BRLF1 and BZLF1 genes are the first viral genes transcribed upon induction of the viral lytic cycle. The protein products of both genes (referred to here as Rta and Zta, respectively) activate expression of other viral genes, thereby initiating the lytic cascade. Among the viral antigens expressed upon induction of the lytic cycle, however, Zta is unique in its ability to disrupt viral latency; expression of the BZLF1 gene is both necessary and sufficient for triggering the viral lytic cascade. We have previously shown that Zta can activate its own promoter (Zp), through binding to two Zta recognition sequences (ZIIIA and ZIIIB). Here we describe mutant Zta proteins that do not bind DNA (referred to as Zta DNA-binding mutants [Zdbm]) but retain the ability to transactivate Zp. Consistent with the inability of these mutants to bind DNA, transactivation of Zp by Zdbm is not dependent on the Zta recognition sequences. Instead, transactivation by Zdbm is dependent upon promoter elements that bind cellular factors. An examination of other viral and cellular promoters identified promoters that are weakly responsive or unresponsive to Zdbm. An analysis of a panel of artificial promoters containing one copy of various promoter elements demonstrated a specificity for Zdbm activation that is distinct from that of Zta. These results suggest that non-DNA-binding forms of some transactivators retain the ability to transactivate specific target promoters without direct binding to DNA. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RI CAYROL, Corinne/C-2106-2011 FU NCI NIH HHS [5R01 CA-52004]; NIGMS NIH HHS [R29 GM48045] NR 51 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1994 VL 14 IS 5 BP 3041 EP 3052 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NG756 UT WOS:A1994NG75600021 PM 8164660 ER PT J AU HANES, SD RIDDIHOUGH, G ISHHOROWICZ, D BRENT, R AF HANES, SD RIDDIHOUGH, G ISHHOROWICZ, D BRENT, R TI SPECIFIC DNA RECOGNITION AND INTERSITE SPACING ARE CRITICAL FOR ACTION OF THE BICOID MORPHOGEN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DROSOPHILA HEAD DEVELOPMENT; NUCLEAR-MAGNETIC-RESONANCE; HELIX-TURN-HELIX; ANTENNAPEDIA HOMEODOMAIN; BINDING SPECIFICITY; SEGMENTATION GENE; BICOID PROTEIN; TRANSCRIPTIONAL ACTIVATORS; ANTERIOR PATTERN; HOMEOBOX GENES AB We examined DNA site recognition by Bicoid and its importance for pattern formation in developing Drosophila embryos. Using altered DNA specificity Bicoid mutants and appropriate reporter genes, we show that Bicoid distinguishes among related DNA-binding sites in vivo by a specific contact between amino acid 9 of its recognition cy-helix (lysine 50 of the homeodomain) and bp 7 of the site. This result is consistent with our earlier results using Saccharomyces cerevisiae but differs from that predicted by crystallographic analysis of another homeodomain-DNA interaction. Our results also demonstrate that Bicoid binds directly to those genes whose transcription it regulates and that the amino acid 9 contact is necessary for Bicoid to direct anterior pattern formation. In both Drosophila embryos and yeast cells, Bicoid requires multiple binding sites to activate transcription of target genes. We find that the distance between binding sites is critical for Bicoid activation but that, unexpectedly, this critical distance differs between Drosophila and S. cerevisiae. This result suggests that Bicoid activation in Drosophila might require an ancillary protein(s) not present in S. cerevisiae. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. DEPT ZOOL,DEV BIOL UNIT,OXFORD OX1 3PS,ENGLAND. IMPERIAL CANC RES FUND,OXFORD OX1 3PS,ENGLAND. NR 82 TC 63 Z9 63 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1994 VL 14 IS 5 BP 3364 EP 3375 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NG756 UT WOS:A1994NG75600051 PM 7909358 ER PT J AU ALBANESE, C CHRISTINMAITRE, S SLUSS, PM CROWLEY, WF JAMESON, JL AF ALBANESE, C CHRISTINMAITRE, S SLUSS, PM CROWLEY, WF JAMESON, JL TI DEVELOPMENT OF A BIOASSAY FOR FSH USING A RECOMBINANT HUMAN FSH RECEPTOR AND A CAMP-RESPONSIVE LUCIFERASE REPORTER GENE SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE FSH RECEPTOR; GLYCOPROTEIN HORMONE; ALPHA GENE; LUCIFERASE; BIOASSAY; CYCLIC AMP ID FOLLICLE-STIMULATING-HORMONE; HUMAN THYROTROPIN RECEPTOR; ALPHA-SUBUNIT GENE; CYCLIC-AMP; MOLECULAR-CLONING; LUTEINIZING-HORMONE; GONADOTROPIN RECEPTORS; FUNCTIONAL EXPRESSION; SIGNAL TRANSDUCTION; BINDING INHIBITOR AB FSH exerts its actions primarily by increasing cAMP levels via a G protein-linked transmembrane receptor. We report the development of a bioassay for FSH using a cell line that stably expresses the human FSH receptor and a cAMP responsive human glycoprotein hormone ct subunit luciferase reporter construct. Receptor activation by FSH was measured by changes in luciferase activity. The cell line was shown to express 1.6 X 10(4) receptors per cell which bound FSH with high affinity (K-d 2.76 x 10(-9) M). Human pituitary FSH caused a dose-dependent increase in cAMP (ED(50), 190 mIU/ml) and luciferase (ED(50), 31.5 mIU/ml) activity. The sensitivity of the bioassay was less than 0.6 mIU/well. Postmenopausal serum, rat, ovine and bovine FSH elicited a dose-dependent increase in luciferase activity. There was no significant stimulation by highly purified human LH or recombinant human TSH. This cell line should be useful in the determination of bioactive FSH and characterization of serum FSH inhibitors. C1 NORTHWESTERN UNIV,SCH MED,DIV ENDOCRINOL METAB & MOLEC MED,CHICAGO,IL 60611. MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [U54 HD29164, P30HD28138] NR 49 TC 47 Z9 48 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1994 VL 101 IS 1-2 BP 211 EP 219 DI 10.1016/0303-7207(94)90237-2 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NJ789 UT WOS:A1994NJ78900027 PM 9397955 ER PT J AU MCCAULEY, LK BEECHER, CA MELTON, ME WERKMEISTER, JR JUPPNER, H ABOUSAMRA, AB SEGRE, GV ROSOL, TJ AF MCCAULEY, LK BEECHER, CA MELTON, ME WERKMEISTER, JR JUPPNER, H ABOUSAMRA, AB SEGRE, GV ROSOL, TJ TI TRANSFORMING GROWTH FACTOR-BETA(1) REGULATES STEADY-STATE PTH/PTHRP RECEPTOR MESSENGER-RNA LEVELS AND PTHRP BINDING IN ROS-17/2.8 OSTEOSARCOMA CELLS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE OSTEOBLAST; PARATHYROID HORMONE; RECEPTOR; TRANSFORMING GROWTH FACTOR-BETA ID PARATHYROID-HORMONE RECEPTORS; OSTEOBLAST-LIKE CELLS; FACTOR-BETA; ADENYLATE-CYCLASE; COMMON RECEPTOR; BONE-CELLS; PROTEIN; EXPRESSION; PEPTIDE; STIMULATION AB The effect of transforming growth factor beta(1) (TGF-P,) on the expression of mRNA for the parathyroid hormone receptor and binding of iodinated parathyroid hormone-related protein in ROS 17/2.8 osteosarcoma cells was evaluated. TGF-beta(1) stimulated a 2-7-fold increase in steady state mRNA levels for the parathyroid hormone receptor at a maximal dose of 5 ng/ml, with increased levels of expression at 6 h of TGF-beta(1)-incubation, and peak levels at 8-24 h. Receptor binding studies revealed a significant increase in PTHrP-specific binding with TGF-beta(1) doses as low as 0.5 ng/ml and a 55% increase in numbers of receptors with no alteration in binding affinity with 5.0 ng/ml TGF-beta(1). Time course studies indicated that receptor binding was increased at 24 h with peak levels reached at 48 h of treatment. PTH-stimulated cAMP levels were significantly increased in ROS 17/2.8 cells treated with TGF-P, (0.5 ng/ml) for 48 h. These data indicate that TGF-beta(1) upregulates steady-state mRNA, ligand binding and PTH/PTHrP receptor signaling in rat osteosarcoma cells. The effects of TGF-beta(1) on bone may be attributed in part to regulation of the PTH/PTHrP receptor at the molecular level. C1 THOMAS JEFFERSON UNIV,DEPT MED,DIV ENDOCRINOL,PHILADELPHIA,PA 19107. OHIO STATE UNIV,DEPT VET PATHOBIOL,COLUMBUS,OH 43210. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP MCCAULEY, LK (reprint author), UNIV MICHIGAN,DEPT PERIODONTOL PREVENT & GERIATR,1011 N UNIV AVE,ANN ARBOR,MI 48109, USA. RI Rosol, Thomas/G-9585-2011 OI Rosol, Thomas/0000-0003-3737-1190 NR 27 TC 39 Z9 39 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1994 VL 101 IS 1-2 BP 331 EP 336 DI 10.1016/0303-7207(94)90250-X PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NJ789 UT WOS:A1994NJ78900040 PM 9397968 ER PT J AU PEKARY, AE BERG, L SANTINI, F CHOPRA, I HERSHMAN, JM AF PEKARY, AE BERG, L SANTINI, F CHOPRA, I HERSHMAN, JM TI CYTOKINES MODULATE TYPE-I IODOTHYRONINE DEIODINASE MESSENGER-RNA LEVELS AND ENZYME-ACTIVITY IN FRTL-5 RAT-THYROID CELLS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Note DE RAT; THYROID; TYPE I IODOTHYRONINE DEIODINASE; MESSENGER RNA; ENZYME ACTIVITY; CYTOKINE ID NECROSIS-FACTOR-ALPHA AB Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (INF-gamma) have inhibitory effects on thyroid function both in vivo and in vitro. We have studied the effects of these cytokines on type I 5'-deiodinase (5'-DI) mRNA expression and enzyme activity in FRTL-5 cells maintained in standard cell culture medium containing 0 (5H) or 2 mIU/ml bovine TSH (6H). Northern blots were hybridized with 5'-DI cDNA. 5'-DI mRNA levels were reduced to 20% of control values after treating cells with 100 ng/ml TNF-alpha in 6H for 2 days while the corresponding enzyme activity was reduced 50%. Other cytokines, including IL-1 beta and interferon-gamma, also significantly inhibited expression of 5'-DI in FRTL-5 cells grown in 6H medium. Because the majority of circulating T, in the rat is secreted by the thyroid gland, the highly significant decline in the serum T-3/T-4 ratio following in vivo administration of cytokines may be due to their direct inhibitory effect on thyroidal 5'-DI expression. C1 UNIV CALIF LOS ANGELES,DEPT MED,DIV ENDOCRINOL,LOS ANGELES,CA 90073. RP PEKARY, AE (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VA MED CTR,ENDOCRINOL RES LAB,BLDG 114,RM 200,LOS ANGELES,CA 90073, USA. NR 19 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1994 VL 101 IS 1-2 BP R31 EP R35 DI 10.1016/0303-7207(94)90256-9 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NJ789 UT WOS:A1994NJ78900045 PM 9397972 ER PT J AU SAAD, MJA FOLLI, F ARAKI, E HASHIMOTO, N CSERMELY, P KAHN, CR AF SAAD, MJA FOLLI, F ARAKI, E HASHIMOTO, N CSERMELY, P KAHN, CR TI REGULATION OF INSULIN-RECEPTOR, INSULIN-RECEPTOR SUBSTRATE-1 AND PHOSPHATIDYLINOSITOL 3-KINASE IN 3T3-F442A ADIPOCYTES - EFFECTS OF DIFFERENTIATION, INSULIN, AND DEXAMETHASONE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID 3T3-L1 ADIPOCYTES; TYROSINE KINASE; ANIMAL-MODELS; MUSCLE; PROTEIN; PHOSPHORYLATION; IRS-1; LIVER; BINDING; RAT AB Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate insulin receptor substrate 1 (IRS-1), which in turn associates with and activates the enzyme phosphatidylinositol 3-kinase (PI 3-kinase). In the present study we have examined these three initial steps in insulin action during the differentiation of 313-F442A adipocytes and after treatment with dexamethasone or insulin. The differentiation of 3T3-F442A cells was characterized by a 13-fold increase in insulin receptor protein, a 9-fold increase in IRS-1, and a 10- and 4.5-fold increase in their insulin-stimulated phosphorylation, respectively. The mRNA expression of these two proteins showed a similar 8-fold increase during differentiation. In addition there was a 3.5-fold increase in PI 3-kinase protein [85 kilodalton (kDa) subunit] and a 16-fold increase in IRS-1-associated PI 3-kinase activity between day 0 and day 8 of differentiation. Dexamethasone (1 mu M) treatment of differentiated cells induced a further 48% (P < 0.05) increase in insulin receptor level, but the autophosphorylation of the receptor was decreased by 31 +/- 1% (P < 0.02). At the same time there was a decrease by 56 +/- 4% (P < 0.005) in IRS-1 protein and by 31 +/- 1% (P < 0.001) in IRS-1 phosphorylation. The expression of insulin receptor mRNA was unchanged, but the expression of IRS-1 mRNA was decreased by similar to 75% after dexamethasone. By contrast, dexamethasone induced a 69% increase in the level of PI 3-kinase as determined by immunoblotting. The combined effect of decreased IRS-1 phosphorylation and increased PI 3-kinase protein was a minimal change (15% decrease) in the association/activation between IRS-1 and PI 3-kinase. Chronic treatment with 100 nM insulin induced a time- and dose-dependent decrease in insulin receptor and IRS-1 protein levels reaching a nadir of 34 +/- 5% (P < 0.005) and 39 +/- 5% (P < 0.01) of control levels after 24 h, respectively. There was an even more marked decrease in the phosphorylation level of these proteins. Chronic insulin treatment also produced a 30% decrease in PI 3-kinase protein levels and a similar to 50% decrease in the association/ activation between IRS-1/PI 3-kinase. The expression of insulin receptor and IRS-1 mRNA was unchanged during chronic insulin treatment. Thus three of the early steps in insulin action may have an important role in the process of adipocyte differentiation and represent points of regulation in hormone-induced insulin resistance in 3T3-F442A adipocytes. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [DK-31036, DK-33201, DK-36836] NR 49 TC 57 Z9 57 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1994 VL 8 IS 5 BP 545 EP 557 DI 10.1210/me.8.5.545 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NM208 UT WOS:A1994NM20800002 PM 7520127 ER PT J AU WILDEN, PA KAHN, CR AF WILDEN, PA KAHN, CR TI THE LEVEL OF INSULIN-RECEPTOR TYROSINE KINASE-ACTIVITY MODULATES THE ACTIVITIES OF PHOSPHATIDYLINOSITOL 3-KINASE, MICROTUBULE-ASSOCIATED PROTEIN, AND S6 KINASES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SERINE THREONINE KINASES; BETA-SUBUNIT; DOMAIN AUTOPHOSPHORYLATION; SUBSTRATE PHOSPHORYLATION; MOLECULAR MECHANISM; SIGNAL TRANSDUCTION; NUCLEOTIDE EXCHANGE; MAMMALIAN-CELLS; SKELETAL-MUSCLE AB The role of insulin receptor tyrosine kinase activity in stimulation of intracellular enzymes linked to insulin action [phosphatidylinositol 3-kinase (PtdIns 3-kinase), microtubule-associated protein (MAP) kinase, and S6 kinases] was studied in Chinese hamster ovary cells which overexpress wild type human insulin receptors, receptors with reduced kinase activity due to substitution of Phe for Tyr(1146) (single-Phe), Tyr(1150,1151) (double-Phe), and Tyr(1146,1150,1151) (tri- ple-Phe), or kinase-inactive receptors with a substitution of Ala for Lys(1018) in the ATP binding site (A1018). We have previously shown that receptor autophosphorylation and kinase activity of these mutants were reduced by approximately 50, 65, 85, and 100%, respectively. Glycogen and DNA synthesis parallel the level of receptor autophosphorylation and kinase activity; however, receptor serine and threonine phosphorylation was independent of receptor tyrosine kinase activity and receptor internalization was completely dependent on maximal receptor kinase activity. Overexpression of the wild type insulin receptor increased both maximal insulin receptor substrate-1-associated and total insulin-stimulated PtdIns 3-kinase activity, as well as S6 and MAP kinase activities 2.0- to 3.6-fold. In addition there was a leftward shift of the dose-response curves for PtdIns 3-kinase and S6 kinases by approximately in-fold. Expression of the single- and double-Phe mutant receptors also enhanced maximal PtdIns 3-kinase activity, but had no effect on insulin sensitivity, whereas expression of either the triple-Phe or kinase-inactive receptors did not enhance insulin stimulation or increase insulin sensitivity as compared to the control cells. When comparing the mutant and wild type receptors, differences in insulin sensitivity were least for insulin-stimulated MAP kinase and greatest for S6 kinase; with the latter there was greater than a 1000-fold difference in insulin sensitivity when cells that overexpress wild type vs. kinase-inactive insulin receptors were compared. Thus, the level of insulin receptor tyrosine autophosphorylation and kinase activity regulate both maximal activation and insulin sensitivity of these intracellular kinases in the insulin action pathway which may lead to glycogen and/or DNA synthesis. The differential sensitivity of these enzymes to changes in receptor activation suggests that they may be differently coupled to the receptor kinase. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, DK-33201] NR 71 TC 21 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1994 VL 8 IS 5 BP 558 EP 567 DI 10.1210/me.8.5.558 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NM208 UT WOS:A1994NM20800003 PM 8058065 ER PT J AU HOTAMISLIGIL, GS GIRMEN, AS FINK, JS TIVOL, E SHALISH, C TROFATTER, J BAENZIGER, J DIAMOND, S MARKHAM, C SULLIVAN, J GROWDON, J BREAKEFIELD, XO AF HOTAMISLIGIL, GS GIRMEN, AS FINK, JS TIVOL, E SHALISH, C TROFATTER, J BAENZIGER, J DIAMOND, S MARKHAM, C SULLIVAN, J GROWDON, J BREAKEFIELD, XO TI HEREDITARY VARIATIONS IN MONOAMINE-OXIDASE AS A RISK FACTOR FOR PARKINSONS-DISEASE SO MOVEMENT DISORDERS LA English DT Article DE MONOAMINE OXIDASE; PARKINSONS DISEASE ID ENVIRONMENTAL TOXINS; DINUCLEOTIDE REPEAT; MITOCHONDRIAL-DNA; ENZYME-ACTIVITY; NORRIE DISEASE; X-CHROMOSOME; PLATELET MAO; HUMAN-LIVER; B ACTIVITY; A GENE AB Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of dopaminergic neurons in the brainstem. Recent studies suggest that several genes may have a role in determining individual susceptibility to this disease, and the degradative enzyme monoamine oxidase (MAO) has been implicated in the disease process. Wide differences in activity levels for both forms of this enzyme (MAO-A and MAO-B) exist in the human population, and levels of both are genetically determined. Here we have compared the frequency of haplotypes at the MAOA and MAOB loci an the X chromosome in 91 male patients with PD and 129 male controls. Alleles were marked using two restriction fragment length polymorphisms (RFLPs), a (GT)n repeat in the MAOA locus, and a (GT)n repeat in the MAOB locus. One particular haplotype marked by the RFLP's at MAOA was three times more frequent in patients with PD as compared with controls, and the overall distribution of these alleles was significantly different (p = 0.03) between these two groups. Another MAOA haplotype was about threefold more common in controls than in patients with PD (p = 0.005). No associations were observed between individual MAOB alleles and the disease state, but the frequency distribution for all alleles was significantly different in the two populations (p = 0.046). These findings support the idea that the MAO genes may be among the hereditary factors that influence susceptibility of individuals to PD. C1 MASSACHUSETTS GEN HOSP, NEUROL SERV, MOLEC NEUROGENET UNIT, BOSTON, MA USA. HARVARD UNIV, SCH MED, DEPT MICROBIOL & MOLEC GENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. INDIANA UNIV, MED CTR, ALCOHOL RES CTR, DEPT PSYCHIAT, INDIANAPOLIS, IN USA. INDIANA UNIV, MED CTR, ALCOHOL RES CTR, DEPT PATHOL, INDIANAPOLIS, IN USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA 90024 USA. FU NIAAA NIH HHS [ADAMHA R3AA08683]; NINDS NIH HHS [NINDS NS21921] NR 72 TC 72 Z9 75 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 1994 VL 9 IS 3 BP 305 EP 310 DI 10.1002/mds.870090304 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA NJ796 UT WOS:A1994NJ79600003 PM 7913737 ER PT J AU KURYLO, DD CORKIN, S DOLAN, RP RIZZO, JF PARKER, SW GROWDON, JH AF KURYLO, DD CORKIN, S DOLAN, RP RIZZO, JF PARKER, SW GROWDON, JH TI BROAD-BAND VISUAL CAPACITIES ARE NOT SELECTIVELY IMPAIRED IN ALZHEIMERS-DISEASE SO NEUROBIOLOGY OF AGING LA English DT Article DE ALZHEIMERS DISEASE; VISION; PRECORTICAL VISUAL CHANNELS; COLOR-OPPONENT AND BROAD-BAND CHANNELS ID GANGLION-CELL DEGENERATION; AGE-RELATED-CHANGES; COLOR-OPPONENT; CONTRAST SENSITIVITY; SENILE DEMENTIA; OPTIC-NERVE; SYSTEM; CHANNELS; DEFICITS; ACHROMATOPSIA AB Histological examination of the optic nerves of Alzheimer's disease (AD) patients has revealed a selective degeneration of large axon ganglion cells. This morphological abnormality raises the possibility of a selective impairment of broad-band channel visual function. To test this hypothesis, we administered visual psychophysical tests associated with either the color-opponent or the broad-band retinocortical channel to 14 AD patients and 29 elderly control subjects (ECS). In previous studies in monkeys, these tests had been sensitive to the effects of either parvocellular or magnocellular LGN lesions. In the present study, the color-opponent channel was assessed by tests of texture and color discrimination; the broad-band channel was assessed by tests of flicker and motion detection. Logistic regression analysis indicated that all tests collectively discriminated diagnostic groups at a borderline level of significance (p = 0.09). ANOVA also indicated a trend towards overall depressed function for AD patients on some capacities tested. Analyses comparing the prevalence of deficits in the AD and ECS groups showed that a significantly greater number of AD patients than ECS had deficits on texture discrimination, blue-violet discrimination, and 4.72-degrees/s motion detection. No individual subject demonstrated a selective impairment of broad-band channel function. The visual deficits in AD did not resemble those caused by lesions of magnocellular LGN in monkeys, indicating that the visual impairment in AD is not a functional reflection of damage limited to the broad-band channel. Rather, the perceptual deficits we observed may be due to neuropathological changes in visual association cortices, particularly the ventral visual pathway, in which parvocellular as well as magnocellular capacities are represented. The deficits are found in a subset of AD patients, suggesting that they are not an obligatory correlate of mild to moderate AD but, instead, reflect individual differences in the distribution of neuropathological changes in visual cortices. C1 MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP KURYLO, DD (reprint author), MIT,DEPT BRAIN & COGNIT SCI,E10-001,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. FU NCRR NIH HHS [RR00088] NR 45 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1994 VL 15 IS 3 BP 305 EP 311 DI 10.1016/0197-4580(94)90025-6 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA NQ033 UT WOS:A1994NQ03300003 PM 7936054 ER PT J AU HYMAN, BT GOMEZISLA, T AF HYMAN, BT GOMEZISLA, T TI ALZHEIMERS-DISEASE IS A LAMINAR, REGIONAL, AND NEURAL SYSTEM-SPECIFIC DISEASE, NOT A GLOBAL BRAIN DISEASE SO NEUROBIOLOGY OF AGING LA English DT Note ID NUCLEUS RAPHE DORSALIS; CELL LOSS; NEUROFIBRILLARY TANGLES; DEMENTIA; NEURONS; IMPAIRMENT; PLAQUES; BASALIS RP HYMAN, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. FU NIA NIH HHS [NIA AG08487] NR 22 TC 61 Z9 62 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1994 VL 15 IS 3 BP 353 EP 354 DI 10.1016/0197-4580(94)90031-0 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA NQ033 UT WOS:A1994NQ03300009 PM 7936060 ER PT J AU CRONINGOLOMB, A CORKIN, S GROWDON, JH AF CRONINGOLOMB, A CORKIN, S GROWDON, JH TI IMPAIRED PROBLEM-SOLVING IN PARKINSONS-DISEASE - IMPACT OF A SET-SHIFTING DEFICIT SO NEUROPSYCHOLOGIA LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTAL-LOBE DYSFUNCTION; COGNITIVE IMPAIRMENT; PERFORMANCE; MOTOR; COMMISSUROTOMY; INFORMATION; DEMENTIA; LESIONS; AGE AB Parkinson's disease (PD) is associated with specific cognitive deficits in the absence of dementia, including the inability to suppress previously learned responses in a changed context. Our goal was to determine whether this set-shifting deficit is sufficient to account for impaired performance on a problem-solving task, or, instead, whether it is necessary to postulate deficits in one or more other cognitive capacities, such as logical deduction. Deductive reasoning and other conceptual abilities were assessed in 15 nondemented subjects with PD who had never been medicated, 15 nondemented subjects with PD who were currently receiving medication, and 15 healthy elderly control subjects. On a deductive reasoning task, Poisoned Food Problems, the PD groups made more errors than the control group. The PD groups' error pattern was characterized by intrusions of information from previous problems. By contrast, the PD groups made appropriate assessments of redundant and irrelevant information that appeared in these problems, and performed normally on other tests of concept formation and problem solving that did not require set shifting, indicating that the capacities for logical deduction and concept formation were intact. The set-shifting deficit, conceptualized as a difficulty in suppressing a prepotent response, appears to be a primary cognitive impairment in PD and presumably arises from dysfunction of the nigrostriatal-dorsolateral prefrontal cortex complex loop. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP CRONINGOLOMB, A (reprint author), BOSTON UNIV,DEPT PSYCHOL,64 CUMMINGTON ST,BOSTON,MA 02215, USA. FU NCRR NIH HHS [RR00088]; NIA NIH HHS [AG05391]; NINDS NIH HHS [NS24778] NR 66 TC 46 Z9 47 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 1994 VL 32 IS 5 BP 579 EP 593 DI 10.1016/0028-3932(94)90146-5 PG 15 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA NN166 UT WOS:A1994NN16600007 PM 8084416 ER PT J AU COLE, DG DIFIGLIA, M AF COLE, DG DIFIGLIA, M TI RESERPINE INCREASES FOS ACTIVITY IN THE RAT BASAL GANGLIA VIA A QUINPIROLE-SENSITIVE MECHANISM SO NEUROSCIENCE LA English DT Article ID IMMEDIATE-EARLY GENES; C-FOS; PARKINSONS-DISEASE; STRIATOPALLIDAL NEURONS; SUBSTANTIA INNOMINATA; DOPAMINE; STRIATUM; EXPRESSION; RECEPTORS; AMPHETAMINE AB Expression of the immediate early gene c-fos increases acutely following neuronal depolarization. c-fos and Fos protein have been widely used to investigate basal ganglia responses to changes in dopaminergic neurotransmission. Increased dopaminergic input to D1 receptors increases Fos synthesis in striatal neurons. The role of D2 receptors in regulating Fos activity has been more difficult to establish. Because dopamine is believed to excite striatal neurons via D1 receptors and inhibit them via D2 receptors, we hypothesized that acute dopamine depletion would increase Fos activity in basal ganglia circuits normally inhibited by dopaminergic input to D2 receptors. Rats were perfused after a single dose of the dopamine-depleting drug reserpine. The brains of rats perfused 3 h after reserpine displayed numerous Fos-like immunoreactive nuclei in the striatum, entopeduncular nucleus, nucleus accumbens shell, and ventral pallidum, and sparse Fos-like immunoreactive nuclei in the globus pallidus and nucleus accumbens core. Few or no Fos-like immunoreactive nuclei were seen following perfusion 30 min, 60 min, and 24 h after reserpine. In the 3-h paradigm, pretreatment with the selective D1 antagonist SCH 23390 did not change the pattern of Fos-like immunoreactivity; pretreatment with the selective D2 agonist quinpirole completely blocked increased Fos synthesis. Acute dopamine depletion, therefore, increases Fos activity in the basal ganglia by disinhibiting D2 circuits. These results support the parallel pathway model of basal ganglia function, and show that Fos can be used to investigate the role of D2 receptors in striatal function. The findings suggest anatomic correlates for the clinical effects of acute dopamine depletion in drug therapy and advanced Parkinson's disease in humans. C1 MASSACHUSETTS GEN HOSP,CELLULAR NEUROBIOL LAB,BOSTON,MA. NR 38 TC 32 Z9 32 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1994 VL 60 IS 1 BP 115 EP 123 DI 10.1016/0306-4522(94)90207-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NG806 UT WOS:A1994NG80600011 PM 7914358 ER PT J AU MENG, J ELMALEH, DR JYAWOOK, S WEISS, S ALPERT, NM BABICH, JW TOMPKINS, RG FISCHMAN, AJ AF MENG, J ELMALEH, DR JYAWOOK, S WEISS, S ALPERT, NM BABICH, JW TOMPKINS, RG FISCHMAN, AJ TI SYNTHESIS OF 2-[F-18]FLUORO-2-DEOXY-L-GLUCOSE AND POSITRON EMISSION TOMOGRAPHY STUDIES MONKEYS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID METASTATIC BREAST-CARCINOMA; NECK TUMORS; F-18 FLUORODEOXYGLUCOSE; MUSCULOSKELETAL TUMORS; PROLIFERATIVE ACTIVITY; GLUCOSE-UTILIZATION; MALIGNANT-LYMPHOMA; FLOW-CYTOMETRY; FDG-PET; CANCER AB 2-[F-18]Fluoro-2-deoxy-L-glucose was synthesized from its trifluoromethanesulfonyl precursor. The precursor was prepared by selective acetylation and triflation of L-mannose. L-Mannose was first treated with acetic anhydride in the presence of a catalytic amount of perchloric acid and then reacted with phosphorus tribromide followed by aqueous sodium acetate to produce pure 1,3,4,6-tetra-O-acetyl-a-L-mannopyranose in 32% yield. This compound was treated with trifluoromethanesulfonic anhydride and pyridine in methylene chloride to form 1,3,4,6-tetra-O-acetyl-2-O-tritrifluoromethanesulfonyl-a-L-mannopyr in 77% yield. Nucleophilic substitution of the triflate with F-18(-) in the presence of Kryptofix(R) 2.2.2 followed by acid hydrolysis produced 2-[F-18]fluoro-2-deoxy-L-glucose with a radiochemical yield of 20-30% (EOS) within 90 min. Biodistribution studies in rats and PET imaging in Rhesus monkeys demonstrated that this sugar analog distributes in the extracellular space of most organs but is excluded from the CNS. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRAUMA SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 37 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1994 VL 21 IS 4 BP 633 EP 640 DI 10.1016/0969-8051(94)90029-9 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NL160 UT WOS:A1994NL16000008 PM 9234321 ER PT J AU LIVNI, E SATTERLEE, W ROBEY, RL ALT, CA VANMETER, EE BABICH, JW WHEELER, WJ OBANNON, DD THRALL, JH FISCHMAN, AJ AF LIVNI, E SATTERLEE, W ROBEY, RL ALT, CA VANMETER, EE BABICH, JW WHEELER, WJ OBANNON, DD THRALL, JH FISCHMAN, AJ TI SYNTHESIS OF[C-11]DAPOXETINE-CENTER-DOT-HCL, A SEROTONIN REUPTAKE INHIBITOR - BIODISTRIBUTION IN RAT AND PRELIMINARY PET IMAGING IN THE MONKEY SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID FLUOXETINE; DISORDER AB [C-11]Dapoxetine . HCl, S-(+)-N,N-dimethyl-a-[2-(naphthalenyloxy)ethyl] benzenemethanamine hydrochloride, a potent serotonin re-uptake inhibitor was prepared from its mono-methyl precursor, S-(+)-N-methyl-a-[2-(naphthalenyloxy)ethyl]benze methanamine hydrochloride. Biodistribution was determined in rats at 5, 30 and 60 min after injection and preliminary PET studies were performed in a Rhesus monkey. (CH3I)-C-11 was bubbled into a solution of S-(+)-N-methyl-alpha-[2-(naphthalenyloxy)ethyl] methanamine hydrochloride (3.0 mg in DMSO) and the mixture was heated at 110 degrees C for 8 min. [C-11]Dapoxetine . HCl was purified by HPLC on a C-18 cartridge eluted with MeOH:phosphate buffer, pH 7.2 (75:25) with a 10% yield (end of synthesis). The time required for the synthesis was 40 min, from the end of bombardment. Radiochemical purity of the final product was > 99% and specific activity was routinely > 400 mCi/mu mol [EOS]. In the biodistribution studies the highest concentration (%ID/g +/- SEM) of dapoxetine . HCl was detected in lung: 4.56 +/- 0.27 (5 min), 1.28 +/- 0.18 (30 min) and 0.67 +/- 0.04 (60 min). Brain accumulation was 0.76 +/- 0.02 (5 min), 0.46 +/- 0.04 (30 min) and 0.27 +/- 0.01 (60 min). Preliminary PET studies demonstrated significant displaceable binding in the cerebral cortex and subcortical grey matter. These results demonstrate that [C-11]dapoxetine . HCl can be prepared in high purity and may be useful for the in vivo evaluation of serotonin re-uptake mechanisms. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 24 TC 17 Z9 20 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1994 VL 21 IS 4 BP 669 EP 675 DI 10.1016/0969-8051(94)90034-5 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NL160 UT WOS:A1994NL16000013 PM 9234326 ER PT J AU VITALE, AT RODRIGUEZ, A FOSTER, CS AF VITALE, AT RODRIGUEZ, A FOSTER, CS TI LOW-DOSE CYCLOSPORINE THERAPY IN THE TREATMENT OF BIRDSHOT - RETINOCHOROIDOPATHY SO OPHTHALMOLOGY LA English DT Article ID ENDOGENOUS UVEITIS; POSTERIOR UVEITIS; DISEASE; NEPHROTOXICITY; INFLAMMATION AB Introduction: Birdshot retinochoroidopathy is an uncommon uveitic syndrome of presumed autoimmune etiology. Therapy with systemic and periocular steroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Steroid-sparing strategies with more specific agents such as cyclosporine (Cyclosporin A, CSA) have been suggested as the first line treatment for this disease. Patients and Methods: The records of 19 patients (35 eyes) with the clinical diagnosis of birdshot retinochoroidopathy were examined. Age at onset ranged from 33 to 69 years (mean, 46.1 years) in nine men and ten women. The median follow-up from disease onset was 36 months. Eight patients were treated with low-dose (2.5-5 mg/kg daily) CSA alone, six required the addition of azathioprine (1.5-2 mg/kg daily), and six received no systemic immunosuppressive therapy. Results: HLA-A29 was positive in 94% (16 of 17) of patients tested. Vitreous inflammation was controlled in 23 (88.5%) treated eyes, with fewer bouts of recurrent inflammation, and a corresponding improvement or stabilization of visual acuity in 20 (83.3%) eyes. In contrast, intraocular inflammation never was controlled fully in untreated eyes, and visual acuity decreased in six (54.5%) eyes by an average of 2.5 Snellen lines. Nephrotoxic side effects of low-dose CSA therapy were not observed, but hypertension developed in two patients. Conclusion: Although the definitive strategy for the management of birdshot retinochoroidopathy is unknown, control of intraocular inflammation with a favorable visual outcome, together with a lack of demonstrable CSA-associated nephrotoxicity and secondary side effects in these patients with birdshot retinochoroidopathy indicate that vision preservation is possible with low-dose CSA alone or in combination with other steroid-sparing immunosuppressive agents as an alternative to the long-term use of corticosteroids. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. NR 31 TC 52 Z9 58 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1994 VL 101 IS 5 BP 822 EP 831 PG 10 WC Ophthalmology SC Ophthalmology GA NL822 UT WOS:A1994NL82200017 PM 8190466 ER PT J AU OKADA, AA JOHNSON, RP LILES, WC DAMICO, DJ BAKER, AS AF OKADA, AA JOHNSON, RP LILES, WC DAMICO, DJ BAKER, AS TI ENDOGENOUS BACTERIAL ENDOPHTHALMITIS - REPORT OF A 10-YEAR RETROSPECTIVE STUDY SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Infectious-Disease-Society CY OCT, 1993 CL NEW ORLEANS, LA SP INFECTIOUS DIS SOC ID UPPER GASTROINTESTINAL ENDOSCOPY; BACILLUS-CEREUS PANOPHTHALMITIS; INFECTIOUS ENDOPHTHALMITIS; BACTEREMIA; MANAGEMENT AB Purpose: The purpose of this study is to report the predisposing factors, timing of symptoms, timing of diagnosis, causative organisms, source of infection, and visual outcome in cases of endogenous bacterial endophthalmitis. Methods: The records of 28 patients with endogenous bacterial endophthalmitis who presented to our combined ophthalmology and medicine services over a 10-year period were reviewed. Results: Ninety percent of the patients had prior medical conditions, including diabetes mellitus, gastrointestinal disorders, hypertension, cardiac disorders, and malignancy. Acute ocular symptoms were the most common reasons why the patient went to the physician (usually an ophthalmologist) rather than systemic symptoms. A correct initial diagnosis was made in 50% of patients, with a delay in diagnosis of 4 days or more in 29% of patients. Organisms were identified in 27 of the 28 patients (96% identification rate), two thirds of which were gram-positive organisms. Streptococcal species were the most common group (32% of patients), although the single most common organism was Staphylococcus aureus (25% of patients). Sources of infection were identified in 93% of patients, with endocarditis and the gastrointestinal tract being the most common. In the majority of patients, visual outcome was poor. However, six eyes that received intravenous and intravitreal antibiotics, as well as therapeutic vitrectomy, achieved visual acuities of 20/50 or better. Conclusion: These results provide a further understanding of the manner of presentation, organisms involved, and sources of infection in endogenous bacterial endophthalmitis. They also suggest that improved outcome may be associated with early initiation of combined medical and surgical treatment. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,INFECT DIS SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 25 TC 219 Z9 244 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1994 VL 101 IS 5 BP 832 EP 838 PG 7 WC Ophthalmology SC Ophthalmology GA NL822 UT WOS:A1994NL82200018 PM 8190467 ER PT J AU TSAO, TCY XIA, WJ RODBERG, GM PINTO, CE KRADIN, RL AF TSAO, TCY XIA, WJ RODBERG, GM PINTO, CE KRADIN, RL TI INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA PROMOTE THE BINDING OF DENDRITIC CELLS TO FIBRONECTIN SO PATHOBIOLOGY LA English DT Article DE INTERFERON-GAMMA; TUMOR NECROSIS FACTOR-ALPHA; DENDRITIC CELLS; FIBRONECTIN ID LEUKOCYTE ADHESION MOLECULE-1; COLONY-STIMULATING FACTOR; MEMORY T-CELLS; ARG-GLY-ASP; ACCESSORY CELLS; INTEGRIN MOLECULES; HUMAN-LYMPHOCYTES; LUNG; EXPRESSION; ACTIVATION AB Connective tissue dendritic accessory cells (DC) accumulate at sites of extracellular matrix (ECM) deposition. The adherence of DC to purified ECM proteins was examined. Splenic and pulmonary DC were purified from Lewis rats and incubated on slides coated with fibronectin (FN), laminin (LN), or collagen (COLL) types I, III and IV. In other experiments, DC were pre-incubated with selected proinflammatory cytokines (IL-1, IL-2, IFN-gamma), TNF-alpha in order to determine their abilities to modulate cell adherence to ECM. Both splenic and pulmonary DC showed dose-dependent binding to FN that was inhibited by the synthetic peptide arg-gly-asp-ser. There was minimal DC binding to LN or COLL. Pretreating DC with IFN-gamma or TNF-alpha enhanced DC binding to FN but did not increase binding to LN or COLL. IL-1 and IL-2 had no demonstrable effect on DC binding to ECM. Our results suggest that FN is a critical ligand for DC in their binding to the ECM. IFN-gamma and TNF-alpha increase adherence of DC to FN and may promote their accumulation in the lung during inflammation. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL & MED,BOSTON,MA. FU NHLBI NIH HHS [HL 48385] NR 58 TC 8 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAY-JUN PY 1994 VL 62 IS 3 BP 120 EP 126 DI 10.1159/000163888 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA PD023 UT WOS:A1994PD02300002 PM 7945918 ER PT J AU CUNNINGHAM, MJ AF CUNNINGHAM, MJ TI ACUTE OTOLARYNGOLOGIC SURGICAL CONDITIONS IN CHILDREN SO PEDIATRIC ANNALS LA English DT Article RP CUNNINGHAM, MJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,ENT PEDIAT SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD MAY PY 1994 VL 23 IS 5 BP 250 EP 256 PG 7 WC Pediatrics SC Pediatrics GA NN001 UT WOS:A1994NN00100004 PM 8065830 ER PT J AU SUEN, HC BLOCH, KD DONAHOE, PK AF SUEN, HC BLOCH, KD DONAHOE, PK TI ANTENATAL GLUCOCORTICOID CORRECTS PULMONARY IMMATURITY IN EXPERIMENTALLY-INDUCED CONGENITAL DIAPHRAGMATIC-HERNIA IN RATS SO PEDIATRIC RESEARCH LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; LUNG HYPOPLASIA; ACCELERATED APPEARANCE; NITRIC-OXIDE; FETAL; DEXAMETHASONE; BETAMETHASONE; SURFACTANT; PREVENTION; VOLUME AB Congenital diaphragmatic hernia, a highly lethal condition, displays at term the pulmonary biochemical and morphologic immaturity characteristic of premature delivery. We hypothesized that antenatal glucocorticoid, now the standard treatment to prevent hyaline membrane disease in premature human beings, might correct the parameters of the pulmonary biochemical and morphologic immaturity in severe congenital diaphragmatic hernia. A total of 112 fetal rats with or without nitrofen-induced congenital diaphragmatic hernias from 34 pregnancies were treated antenatally with either saline or dexamethasone. Antenatal dexamethasone increased the lung disaturated phosphatidylcholine content, reduced the lung glycogen concentration, reduced the saccular septal thickness, and increased the mean saccular size and volume fraction of saccules in the lungs of rats with large congenital diaphragmatic hernia in comparison with similar rats not so treated. All differences were statistically significant. Antenatal glucocorticoid therapy was efficacious in treating rats with nitrofen-induced congenital diaphragmatic hernia. This encouraging finding warrants further investigation in a large animal model with surgically created congenital diaphragmatic hernia. C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,PEDIAT SURG SERV,GEN THORAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 53 TC 84 Z9 84 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1994 VL 35 IS 5 BP 523 EP 529 DI 10.1203/00006450-199405000-00002 PG 7 WC Pediatrics SC Pediatrics GA NJ621 UT WOS:A1994NJ62100002 PM 7520565 ER PT J AU CASTILLO, L YU, YM MARCHINI, JS CHAPMAN, TE SANCHEZ, M YOUNG, VR BURKE, JF AF CASTILLO, L YU, YM MARCHINI, JS CHAPMAN, TE SANCHEZ, M YOUNG, VR BURKE, JF TI PHENYLALANINE AND TYROSINE KINETICS IN CRITICALLY ILL CHILDREN WITH SEPSIS SO PEDIATRIC RESEARCH LA English DT Article ID BIRTH-WEIGHT INFANTS; PARENTERAL-NUTRITION; GAS-CHROMATOGRAPHY; METABOLISM; PROTEIN; LEUCINE; PREDICTION; INJURY AB To better understand the impact of severe illness on the amino acid economy and nutritional needs of pediatric patients, we studied plasma phenylalanine and tyrosine kinetics in eleven critically ill patients (six full-term newborns and five young infants). Within 48 h of the diagnosis of sepsis they were given primed constant i.v. infusions of L-[1-C-13]phenylalanine and L-[3,3,H-2(2)]tyrosine for 4 h. Routine nutritional support continued during this period by parenteral administration of dextrose, lipid emulsion, and an amino acid mixture low in tyrosine. Phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation did not differ significantly between the two age groups, and so the data were combined for evaluation. For the entire group, values (mu mol.kg(-1).h(-1); mean +/- SD) for phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation were 132 +/- 24, 66 +/- 16, and 29 +/- 12, respectively. Plasma phenylalanine to tyrosine concentration ratio was 1.67 +/- 0.6. From a comparison of the rate of phenylalanine hydroxylation with measured phenylalanine intakes, it was concluded that their routine, clinical nutritional support was inadequate to achieve body phenylalanine balance. In comparison with published data, the relative rate of phenylalanine hydroxylation appears to be high. We speculate that tyrosine is a conditionally indispensable amino acid under these conditions; it would be desirable to establish the intake levels and ratio of phenylalanine to tyrosine that effectively support aromatic amino acid balance in these critically ill patients. C1 MIT,CLIN RES CTR,HUMAN NUTR LAB,CAMBRIDGE,MA 02139. MIT,SCH SCI,CAMBRIDGE,MA 02139. SHRINERS BURN INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,NEONATAL INTENS CARE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. UNIV SAO PAULO,DIV NUTR,BR-14049900 RIBEIRAO PRET,SP,BRAZIL. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. RP CASTILLO, L (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT UNIT,ELLISON 317,FRUIT ST,BOSTON,MA 02114, USA. RI Marchini, Julio/A-4006-2008; Marchini, Julio/K-1992-2016 OI Marchini, Julio/0000-0001-9999-9149 FU NCRR NIH HHS [RR88]; NIDDK NIH HHS [DK15856] NR 48 TC 35 Z9 36 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1994 VL 35 IS 5 BP 580 EP 588 DI 10.1203/00006450-199405000-00009 PG 9 WC Pediatrics SC Pediatrics GA NJ621 UT WOS:A1994NJ62100011 PM 8065841 ER PT J AU WEINBERG, JA MEDEARIS, DN AF WEINBERG, JA MEDEARIS, DN TI EMERGENCY MEDICAL-SERVICES FOR CHILDREN - THE REPORT FROM THE INSTITUTE-OF-MEDICINE SO PEDIATRICS LA English DT Article C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP WEINBERG, JA (reprint author), LEBONHEUR CHILDRENS HOSP & MED CTR,DIV EMERGENCY SERV,848 ADAMS AVE,MEMPHIS,TN 38103, USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1994 VL 93 IS 5 BP 821 EP 823 PG 3 WC Pediatrics SC Pediatrics GA NJ374 UT WOS:A1994NJ37400024 PM 8165087 ER PT J AU GUCCIONE, AA AF GUCCIONE, AA TI ARTHRITIS AND THE PROCESS OF DISABLEMENT SO PHYSICAL THERAPY LA English DT Article DE ARTHRITIS; OSTEOARTHRITIS; PHYSICAL DISABILITY; RHEUMATOID ARTHRITIS ID KNEE OSTEO-ARTHRITIS; UNITED-STATES ADULTS; RHEUMATOID-ARTHRITIS; JOINT IMPAIRMENT; MUSCULOSKELETAL IMPAIRMENTS; WORK DISABILITY; CLINICAL STATUS; MARITAL-STATUS; HEALTH-STATUS; AGE 79 AB Rheumatoid arthritis and osteoarthritis are two medical conditions that broadly alter the musculoskeletal system and influence a person's ability to perform the functional activities and tasks expected of an independent adult A burgeoning literature depicts the process of disablement in arthritis and details the relationships among disease, impairments, and functional limitations. There is, however, a substantial gap in the physical therapy literature regarding the relationships among arthritis, musculoskeletal impairment, and physical function. Furthermore, the search for the most effective ways to remediate musculoskeletal impairment and improve function remains a challenge for clinicians and researchers alike C1 MASSACHUSETTS GEN HOSP,QUAL ASSURANCE SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,RES SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,EDUC SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,BOSTON,MA 02114. RP GUCCIONE, AA (reprint author), HARVARD UNIV,SCH MED,DEPT ORTHOPAED,15 PARKMAN ST,WAC 128,BOSTON,MA 02114, USA. RI Agaliotis, Maria/G-5334-2012 FU NIA NIH HHS [K01 AG00567] NR 57 TC 52 Z9 53 U1 1 U2 2 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAY PY 1994 VL 74 IS 5 BP 408 EP 414 PG 7 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA PC522 UT WOS:A1994PC52200006 PM 8171102 ER PT J AU KWON, HB PARK, SC PENG, HP GOODMAN, HM DEWDNEY, J SHIH, MC AF KWON, HB PARK, SC PENG, HP GOODMAN, HM DEWDNEY, J SHIH, MC TI IDENTIFICATION OF A LIGHT-RESPONSIVE REGION OF THE NUCLEAR GENE ENCODING THE B-SUBUNIT OF CHLOROPLAST GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE FROM ARABIDOPSIS-THALIANA SO PLANT PHYSIOLOGY LA English DT Article ID DNA-BINDING PROTEIN; RIBULOSE-BISPHOSPHATE CARBOXYLASE; POLYMERASE CHAIN-REACTION; DIFFERENTIAL EXPRESSION; MESSENGER-RNA; HIGHER-PLANTS; RBCS-3A GENE; PROMOTER; SEQUENCES; ELEMENT AB We report here the identification of a cis-acting region involved in light regulation of the nuclear gene (GapB) encoding the B subunit of chloroplast glyceraldehyde 3-phosphate dehydrogenase from Arabidopsis thaliana. Our results show that a 664-bp GapB promoter fragment is sufficient to confer light induction and organ-specific expression of the Escherichia coli B-glucuronidase reporter gene (Gus) in transgenic tobacco (Nicotiana tabacum) plants. Deletion analysis indicates that the -261 to -173 upstream region of the GapB gene is essential for light induction. This region contains four direct repeats with the consensus sequence 5'-ATGAA(A/G)A-3' (Gap boxes). Deletion of all four repeats abolishes light induction completely. In addition, we have linked a 109-bp (-263 to -152) GapB upstream fragment containing the four direct repeats in two orientations to the -92 to +6 upstream sequence of the cauliflower mosaic virus 35S basal promoter. The resulting chimeric promoters are able to center light induction and to enhance leaf-specific expression of the Gus reporter gene in transgenic tobacco plants. Based on these results we conclude that Cap boxes are essential for light regulation and organ-specific expression of the GapB gene in A. thaliana. Using gel mobility shift assays we have also identified a nuclear factor from tobacco that interacts with GapA and GapB DNA fragments containing these Cap boxes. Competition assays indicate that Cap boxes are the binding sites for this factor. Although this binding activity is present in nuclear extracts from leaves and roots of light-grown or dark-treated tobacco plants, the activity is less abundant in nuclear extracts prepared from leaves of dark-treated plants or from roots of greenhouse-grown plants. In addition, our data show that this binding factor is distinct from the GT-1 factor, which binds to Box II and Box III within the light-responsive element of the RbcS-3A gene of pea. C1 UNIV IOWA,DEPT SCI BIOL,IOWA CITY,IA 52242. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NIGMS NIH HHS [GM41669] NR 33 TC 21 Z9 22 U1 0 U2 4 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD MAY PY 1994 VL 105 IS 1 BP 357 EP 367 DI 10.1104/pp.105.1.357 PG 11 WC Plant Sciences SC Plant Sciences GA NL641 UT WOS:A1994NL64100044 PM 8029358 ER PT J AU BUCKY, LP EHRLICH, HP SOHONI, S MAY, JW AF BUCKY, LP EHRLICH, HP SOHONI, S MAY, JW TI THE CAPSULE QUALITY OF SALINE-FILLED SMOOTH SILICONE, TEXTURED SILICONE, AND POLYURETHANE IMPLANTS IN RABBITS - A LONG-TERM STUDY SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID AUGMENTATION MAMMAPLASTY; MAMMARY PROSTHESES; BREAST IMPLANTS; CONTRACTURE AB Recently, there have been many new designs in both the surface texture and chemical composition of breast implants that claim reduced constrictive capsular formation. The purpose of this study was to utilize a quantitative method to determine the firmness of capsules formed around saline-filled smooth silicone, textured silicone, and polyurethane implants in an experimental rabbit model 1 year after implantation Our objective was to analyze the histologic, biologic, and biochemical content of the respective capsules to account for any differences in physical behavior. Forty-five smooth silicone, textured silicone, and polyurethane implants were placed in one of three positions beneath the panniculus carnosus muscle of New Zealand White rabbits. After 1 year, all capsules were palpated and classified according to firmness. Intracapsular static and dynamic pressure measurements were obtained by placing a pressure monitor (Stryker) in an injector port attached to the individual implants. Capsular firmness was significantly greater in the textured silicone implants than in the smooth silicone or polyurethane implants after 1 year. The dynamic qualities of the periprosthetic soft tissues were measured while saline was injected into the implants. The capsules around the textured silicone implants generated significantly higher pressures than the smooth silicone or polyurethane counterparts. The capsules around the polyurethane implants were the softest and most compliant in all categories. Histologically, there is a significant inflammatory response surrounding the textured silicone implants that does not exist in the capsules around the smooth silicone implants. The capsules around the polyurethane implants have the least fibrous tissue deposition. There is a decrease in the proportion of type III collagen in the capsules around the textured silicone implants versus smooth silicone or polyurethane implants. The in vitro contraction patterns of the fibroblast-populated collagen lattices do not reveal the contraction differences observed in vivo in rabbits. However, there are many components that determine contractility. This area deserves further investigation. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 28 TC 59 Z9 61 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 1994 VL 93 IS 6 BP 1123 EP 1131 DI 10.1097/00006534-199405000-00002 PG 9 WC Surgery SC Surgery GA NJ384 UT WOS:A1994NJ38400002 PM 8171130 ER PT J AU LIPKOWSKI, AW MISICKA, A HRUBY, VJ CARR, DB AF LIPKOWSKI, AW MISICKA, A HRUBY, VJ CARR, DB TI OPIOID PEPTIDE ANALOGS - RECONSIDERATION AS A POTENTIALLY NEW-GENERATION OF ANALGESICS SO POLISH JOURNAL OF CHEMISTRY LA English DT Article; Proceedings Paper CT 1st Polish-Israeli Symposium on Chemistry and Biology of Peptides CY SEP 05-08, 1993 CL GDANSK, POLAND SP MINIST NATL EDUC, UNIV GDANSK, BANK GDANSK, POLISH ISRAELI CHAMBER COMMERCE DE PEPTIDE ANALOGS; STRUCTURE ACTIVITY RELATION ID MORPHINE; AGONIST; BRAIN; SITES AB The use of opioid drugs is often accompanied by centrally mediated side effects, such as dependence, tolerance, or respiratory depression.,Additionally, all commercial opioid drugs have abuse potential. Analogues of opioid peptides with no or low blood-brain barrier permeability seem to have disadvantages because of their low likelihood of effectiveness after systemic (eg. oral or intravenous) administration. Nevertheless, such compounds offer minimal systemic side effects if delivered centrally and minimal drug abuse potential. Optimal-effectiveness of opioid peptides requires targeted techniques of delivery which are more and more common in modem pain treatment. Peripheral opioid peptide delivery to augment effects of classical drugs with mainly central actions is an additional possible therapeutic application of opioid peptide analogues with low blood-brain barrier permeability. Therefore, we believe that opioid peptide analogues have to be considered as a new generation of analgesics. C1 UNIV WARSAW, DEPT CHEM, PL-02093 WARSAW, POLAND. UNIV ARIZONA, DEPT CHEM, TUCSON, AZ 85721 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02114 USA. RP LIPKOWSKI, AW (reprint author), POLISH ACAD SCI, MED RES CTR, PL-00784 WARSAW, POLAND. NR 18 TC 12 Z9 12 U1 0 U2 1 PU POLISH CHEMICAL SOC PI WARSAW PA C/O POLISH ACAD SCIENCES, INST PHYSICAL CHEMISTRY, UL KASPRZAKA 44/52, 01-224 WARSAW, POLAND SN 0137-5083 J9 POL J CHEM JI Pol. J. Chem. PD MAY PY 1994 VL 68 IS 5 BP 907 EP 912 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA NH916 UT WOS:A1994NH91600006 ER PT J AU WEINBERGER, LE SREENIVASAN, S AF WEINBERGER, LE SREENIVASAN, S TI ETHICAL AND PROFESSIONAL CONFLICTS IN CORRECTIONAL PSYCHOLOGY SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID PRISON AB The role of the mental health professional in a prison setting has changed to reflect the prevailing ideology of the correctional administration that deemphasizes treatment and emphasizes security and custodial concerns. As a consequence, mental health professionals who work in corrections have experienced unique ethical and professional conflicts. Standards were developed to address the conflicts and provide guidelines for professional conduct, but dilemmas continue to exist. The authors believe this can be attributed to (a) the standards being vague and (b) correctional personnel not understanding or supporting the standards or the psychologist's role as a mental health professional. This article examines these propositions in more detail, using vignettes and discussion, and offers other approaches to resolving the dilemmas and improving the delivery of mental health services to incarcerated individuals. C1 W LOS ANGELES DEPT VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. RP WEINBERGER, LE (reprint author), UNIV SO CALIF,INST PSYCHIAT LAW & BEHAV SCI,POB 86125,LOS ANGELES,CA 90089, USA. NR 27 TC 15 Z9 15 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD MAY PY 1994 VL 25 IS 2 BP 161 EP 167 DI 10.1037//0735-7028.25.2.161 PG 7 WC Psychology, Multidisciplinary SC Psychology GA NL399 UT WOS:A1994NL39900011 ER PT J AU SCHILDBACH, JF SHAW, SY BRUCCOLERI, RE HABER, E HERZENBERG, LA JAGER, GC JEFFREY, PD PANKA, DJ PARKS, DR NEAR, RI NOVOTNY, J SHERIFF, S MARGOLIES, MN AF SCHILDBACH, JF SHAW, SY BRUCCOLERI, RE HABER, E HERZENBERG, LA JAGER, GC JEFFREY, PD PANKA, DJ PARKS, DR NEAR, RI NOVOTNY, J SHERIFF, S MARGOLIES, MN TI CONTRIBUTION OF A SINGLE HEAVY-CHAIN RESIDUE TO SPECIFICITY OF AN ANTIDIGOXIN MONOCLONAL-ANTIBODY SO PROTEIN SCIENCE LA English DT Article DE ANTIDIGOXIN ANTIBODY; COMPLEMENTARITY; FLUORESCENCE-ACTIVATED CELL SORTING; HAPTEN DOCKING; HYBRIDOMA VARIANT ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID-SEQUENCE; 3-DIMENSIONAL STRUCTURE; VARIABLE REGION; ARSONATE IDIOTYPE; CRYSTAL-STRUCTURE; SOMATIC MUTATION; FAB FRAGMENT; COMPLEX; BINDING AB Two distinct spontaneous variants of the murine anti-digoxin hybridoma 26-10 were isolated by fluorescence-activated cell sorting for reduced affinity of surface antibody for antigen. Nucleotide and partial amino acid sequencing of the variant antibody variable regions revealed that 1 variant had a single amino acid substitution: Lys for Asn at heavy chain position 35. The second variant antibody had 2 heavy chain substitutions: Tyr for Asn at position 35, and Met for Arg at position 38. Mutagenesis experiments confirmed that the position 35 substitutions were solely responsible for the markedly reduced affinity of both variant antibodies. Several mutants with more conservative position 35 substitutions were engineered to ascertain the contribution of Asn 35 to the binding of digoxin to antibody 26-10. Replacement of Asn with Gin reduced affinity for digoxin 10-fold relative to the wild-type antibody, but maintained wild-type fine specificity for cardiac glycoside analogues. All other substitutions (Val, Thr, Leu, Ala, and Asp) reduced affinity by at least 90-fold and caused distinct shifts in fine specificity. The Ala mutant demonstrated greatly increased relative affinities for 16-acetylated haptens and haptens with a saturated lactone. The X-ray crystal structure of the 26-10 Fab in complex with digoxin (Jeffrey PD et al., 1993, Proc Natl Acad Sci USA 90:10310-10314) reveals that the position 35 Asn contacts hapten and forms hydrogen bonds with 2 other contact residues. The reductions in affinity of the position 35 mutants for digoxin are greater than expected based upon the small hapten contact area provided by the wild-type Asn. We therefore performed molecular modeling experiments which suggested that substitution of Gin or Asp can maintain these hydrogen bonds whereas the other substituted side chains cannot. The altered binding of the Asp mutant may be due to the introduction of a negative charge. The similarities in binding of the wild-type and Gin-mutant antibodies, however, suggest that these hydrogen bonds are important for maintaining the architecture of the binding site and therefore the affinity and specificity of this antibody. The Ala mutant eliminates the wild-type hydrogen bonding, and molecular modeling suggests that the reduced side-chain volume also provides space that can accommodate a congener with a 16-acetyl group or saturated lactone, accounting for the altered fine specificity of this antibody. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,GRAD SCH ARTS & SCI,PROGRAM IMMUNOL,CAMBRIDGE,MA 02138. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. HARVARD UNIV,SCH PUBL HLTH,DIV BIOL SCI,CARDIOVASC BIOL LAB,BOSTON,MA 02115. STANFORD UNIV,DEPT GENET,STANFORD,CA 94305. FU NHLBI NIH HHS [R01 HL47415, P01 HL19259] NR 58 TC 19 Z9 19 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1994 VL 3 IS 5 BP 737 EP 749 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH623 UT WOS:A1994NH62300003 PM 8061604 ER PT J AU NIERENBERG, AA AF NIERENBERG, AA TI TREATMENT-RESISTANT DEPRESSION IN THE AGE OF SEROTONIN SO PSYCHIATRIC ANNALS LA English DT Article ID THYROID-HORMONE SUPPLEMENTATION; HIGH-DOSE FLUOXETINE; REFRACTORY DEPRESSION; LITHIUM; COMBINATION; TOXICITY; ANTIDEPRESSANTS C1 HARVARD UNIV,SCH MED,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02115. RP NIERENBERG, AA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD MAY PY 1994 VL 24 IS 5 BP 217 EP 219 PG 3 WC Psychiatry SC Psychiatry GA NM210 UT WOS:A1994NM21000002 ER PT J AU LIBERMAN, RP AF LIBERMAN, RP TI PSYCHOSOCIAL TREATMENTS FOR SCHIZOPHRENIA SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID CONTROLLED TRIAL; MAINTENANCE CHEMOTHERAPY; FAMILY PSYCHOEDUCATION; PSYCHIATRIC-PATIENTS; AFTERCARE TREATMENT; EXPRESSED EMOTION; MENTALLY-ILL; FOLLOW-UP; SKILLS; RELAPSE AB BASED upon educational and social learning principles, social skills training and family management modalities have been validated as effective in improving coping skills and symptomatic course and outcome of schizophrenia. Combined with judicious doses of antipsychotic medication, these modalities have been designed from the conceptualization of schizophrenia as a stress-related, biomedical disorder, with those afflicted having enduring vulnerability to the emergence or exacerbation of psychotic symptoms with associated social disability. Behaviorally oriented modalities require integration with a comprehensive psychiatric service delivery system to confer protection against relapse. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. CAMARILLO STATE HOSP,CAMARILLO,CA 93010. RP LIBERMAN, RP (reprint author), W LOS ANGELES VA MED CTR,REHABILITAT COMMUNITY & PSYCHIATRY B116V,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [NIMH MH 30911] NR 59 TC 54 Z9 55 U1 2 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD MAY PY 1994 VL 57 IS 2 BP 104 EP 114 PG 11 WC Psychiatry SC Psychiatry GA NX017 UT WOS:A1994NX01700003 PM 7938330 ER PT J AU SILVA, JA LEONG, GB WEINSTOCK, R SHARMA, KK KLEIN, RL AF SILVA, JA LEONG, GB WEINSTOCK, R SHARMA, KK KLEIN, RL TI DELUSIONAL MISIDENTIFICATION SYNDROMES AND DANGEROUSNESS SO PSYCHOPATHOLOGY LA English DT Article; Proceedings Paper CT Conference on Delusional Misidentification Syndromes CY 1993 CL HOSPITAL SAINTE ANNE, PARIS, FRANCE HO HOSPITAL SAINTE ANNE AB Dangerousness in the delusional misidentification syndromes is studied by reviewing a sample of 82 cases defined by either verbal threats or physical violence caused by a misidentification delusion. Eighty cases were obtained from a review of the anglophone psychiatric literature in which the patients exhibited some degree of dangerousness, to which we added 2 previously unreported cases. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. UNIV SO CALIF,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA. UNIV CALIF IRVINE,GRAD SCH MANAGEMENT,IRVINE,CA 92717. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 14 TC 20 Z9 20 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PD MAY-OCT PY 1994 VL 27 IS 3-5 BP 215 EP 219 PG 5 WC Psychiatry SC Psychiatry GA PN447 UT WOS:A1994PN44700017 PM 7846240 ER PT J AU SURMAN, OS AF SURMAN, OS TI PSYCHIATRIC ASPECTS OF LIVER-TRANSPLANTATION SO PSYCHOSOMATICS LA English DT Article ID QUALITY-OF-LIFE; HEPATIC TRANSPLANTATION; ORGAN-TRANSPLANTATION; ALCOHOLIC CIRRHOSIS; PATIENT SELECTION; RECIPIENTS; DISEASE; ENCEPHALOPATHY; COMPLICATIONS; CYCLOSPORINE AB Psychiatry plays an essential role in the selection and preoperative care of liver transplant patients. Unique to liver transplantation are the preponderance of candidates with alcoholic end-stage organ failure and also the reversibility of encephalopathy with postoperative normalization of hepatic function. The expense of liver transplantation necessitates documentation of quality of life among recipients. It can also be postulated that a ''ripple effect'' does occur, in which favorable operative outcomes provide a meaningful and beneficial effect on social networks of transplant candidates and on society in general. C1 MASSACHUSETTS GEN HOSP,TRANSPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 58 TC 35 Z9 35 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1994 VL 35 IS 3 BP 297 EP 307 PG 11 WC Psychiatry; Psychology SC Psychiatry; Psychology GA NJ604 UT WOS:A1994NJ60400007 PM 8036258 ER PT J AU HENDEE, WR BROWN, EF STANLEY, RJ THRALL, JH ZYLAK, CJ AF HENDEE, WR BROWN, EF STANLEY, RJ THRALL, JH ZYLAK, CJ TI COLLIDING FORCES IN RADIOLOGY - TECHNOLOGIC IMPERATIVE, RESOURCE LIMITATIONS, AND ACCOUNTABILITY DEMANDS SO RADIOGRAPHICS LA English DT Article DE COST EFFECTIVENESS; ECONOMICS, MEDICAL; RADIOLOGY AND RADIOLOGISTS, DEPARTMENTAL MANAGEMENT; RADIOLOGY AND RADIOLOGISTS, SOCIOECONOMIC ISSUES AB Advances in radiology over the past 20 years are the product of a technologic imperative that has produced new approaches to the acquisition of medical images and modifications to conventional approaches. The imperative has placed radiology at the leading edge of the computer-technology era of modem medicine and has also produced several big-ticket technologies that have been identified as major contributors to rising health care costs. Consequently, the demands for quantitative data on the impact and cost-effectiveness of the use of these technologies in the clinical arena are increasing. Meeting the growing demand for accountability in radiology requires that the discipline adopt innovative approaches for assessing its technologies and acquire new types of data, including documentation of cost savings accrued by selective use of radiologic technologies and demonstration of the efficiency and cost-effectiveness of triage schemes that lead to more effective decision making. The requirement of quantitative accountability represents a new way of doing business for radiology and a new approach to management for those responsible for business. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MED COLL WISCONSIN,CTR STUDY BIOETH,DEPT RADIAT ONCOL,MILWAUKEE,WI 53226. MED COLL WISCONSIN,BIOPHYS RES INST,MILWAUKEE,WI 53226. UNIV ALABAMA,DEPT RADIOL,BIRMINGHAM,AL 35233. HENRY FORD HOSP,DEPT DIAGNOST RADIOL,DETROIT,MI 48202. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP HENDEE, WR (reprint author), MED COLL WISCONSIN,CTR STUDY BIOETH,DEPT RADIOL,8701 WATERTOWN PLANK RD,MILWAUKEE,WI 53226, USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY PY 1994 VL 14 IS 3 BP 647 EP 653 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NL886 UT WOS:A1994NL88600017 PM 8066277 ER PT J AU WOLF, GL ROGOWSKA, J HANNA, GK HALPERN, EF AF WOLF, GL ROGOWSKA, J HANNA, GK HALPERN, EF TI PERCUTANEOUS CT LYMPHOGRAPHY WITH PERFLUBRON - IMAGING EFFICACY IN RABBITS AND MONKEYS SO RADIOLOGY LA English DT Article DE BROMINE; LYMPHATIC SYSTEM,; LYMPHATIC SYSTEM, CT; LYMPHOGRAPHY ID LYMPH-NODE METASTASES; COMPUTED-TOMOGRAPHY; LUNG-CANCER; PERFLUOROOCTYLBROMIDE; CARCINOMA; CRITERIA; AGENT; FLOW AB PURPOSE: To evaluate the imaging efficacy of percutaneous lymphography performed with injection of perflubron emulsions and computed tomography (CT). MATERIALS AND METHODS: Thin-section CT was used to image lymph nodes in 116 rabbits and six monkeys. Quantitative measures of regional lymph node enhancement were obtained 4 hours to 21 days after subcutaneous injection of perflubron (0.1-0.5 mt per injection site). Lymph node enhancement was calculated in Hounsfield units and converted to bromine concentration with standards that were imaged at the same time. RESULTS: Excellent enhancement of regional lymph nodes in both groups of animals was obtained. Nodal enhancement was linearly related to dose and was sustained for 20 days; maximum enhancement was seen 2 days after injection. Massage of the injection site increased delivery of the perflubron emulsion to regional lymph nodes. CONCLUSION: In rabbits and monkeys, percutaneous CT lymphography effectively depicts the intranodal distribution of macrophages in normal lymph nodes. RP WOLF, GL (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,149 13TH ST,CHARLESTON,MA 02129, USA. NR 41 TC 30 Z9 30 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1994 VL 191 IS 2 BP 501 EP 505 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NG955 UT WOS:A1994NG95500036 PM 8153329 ER PT J AU KOPANS, DB AF KOPANS, DB TI CURRENT STATUS OF AND A CRITIQUE ON METHODS USED IN THE DIAGNOSIS OF IMAGED BREAST ABNORMALITIES - A SURGEONS VIEW - REPLY SO RADIOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1994 VL 191 IS 2 BP A47 EP A50 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NG955 UT WOS:A1994NG95500002 ER PT J AU GOODMAN, TA POLISSON, RP AF GOODMAN, TA POLISSON, RP TI METHOTREXATE - ADVERSE REACTIONS AND MAJOR TOXICITIES SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS PATIENTS; FOLINIC ACID; PULSE METHOTREXATE; LIVER BIOPSIES; TRIMETHOPRIM-SULFAMETHOXAZOLE; LEUKOTRIENE-B4 SYNTHESIS; FOLATE SUPPLEMENTATION; INDUCED PNEUMONITIS; THERAPY C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GOODMAN, TA (reprint author), MASSACHUSETTS GEN HOSP,ARTHRITIS UNIT,BOSTON,MA 02114, USA. NR 90 TC 56 Z9 58 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 1994 VL 20 IS 2 BP 513 EP 528 PG 16 WC Rheumatology SC Rheumatology GA NK676 UT WOS:A1994NK67600013 PM 8016424 ER PT J AU AROSA, FA DASILVA, AJ GODINHO, IM TERSTEEGE, JCA PORTO, G RUDD, CE DESOUSA, M AF AROSA, FA DASILVA, AJ GODINHO, IM TERSTEEGE, JCA PORTO, G RUDD, CE DESOUSA, M TI DECREASED CD8-P56LCK ACTIVITY IN PERIPHERAL-BLOOD T-LYMPHOCYTES FROM PATIENTS WITH HEREDITARY HEMOCHROMATOSIS SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE-PROTEIN-KINASE; SIGNAL TRANSDUCTION; IDIOPATHIC HEMOCHROMATOSIS; CYTOPLASMIC DOMAINS; IRON OVERLOAD; CD4 RECEPTOR; P56LCK; CHAIN; ASSOCIATION; EXPRESSION AB Hereditary haemochromatosis (HH) is an autosomal recessive disease linked to certain MHC class-I specificities. The disease is characterized by increased iron absorption and, in some patients, abnormally low numbers of CD8(+) T cells in the periphery. We were interested in whether CD4- and CD8-associated p56lck kinase activities were altered in patients with HH. In a study of 18 patients with HH (with and without low numbers of CD8(+) cells), the level of autophosphorylation of the CD8-associated p56lck as well as its phosphotransferase activity, as determined by phosphorylation of an exogenous substrate, was significantly reduced by two- to three-fold relative to a control population of 23 healthy blood donors (P < 6 x 10(-7)). CD8-p56lck activity was decreased in 16 out of 18 patients (ranging from 1.5- to 10-fold decrease). By contrast, the level of CD4-p56lck activity did not show an overall decrease relative to controls. In addition to an occasional decrease in the amount of CD8-associated lck, HH patient-derived T cells showed a consistent decrease in the relative CD8-p56lck specific activity. Immunofluorescence staining showed further that the difference could not be accounted by a discrepancy in the expression of CD8 alpha alpha or CD8 alpha beta complexes or MHC class I molecules. Decreased CD8-p56lck activity was seen bath in patients undergoing intensive phlebotomy treatment and in patients in maintenance therapy (i.e. patients who had reached normal levels of iron stores), indicating that this abnormality does not appear to be corrected by iron depletion. To our knowledge, this is the first demonstration of an abnormality in a src-like receptor associated kinase in a human disease state linked to MHC class-I antigens. C1 ICBAS,P-4000 OPORTO,PORTUGAL. DANA FARBER CANC INST,DEPT TUMOR IMMUNOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RI Arosa, Fernando/E-5640-2010; Porto, Graca/J-7939-2013 OI Arosa, Fernando/0000-0002-7209-4507; Porto, Graca/0000-0002-1923-4638 NR 29 TC 42 Z9 42 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 1994 VL 39 IS 5 BP 426 EP 432 DI 10.1111/j.1365-3083.1994.tb03396.x PG 7 WC Immunology SC Immunology GA NH883 UT WOS:A1994NH88300002 PM 8191217 ER PT J AU SGROI, D STAMENKOVIC, I AF SGROI, D STAMENKOVIC, I TI THE B-CELL ADHESION MOLECULE CD22 IS CROSS-SPECIES REACTIVE AND RECOGNIZES DISTINCT SIALOGLYCOPROTEINS ON DIFFERENT FUNCTIONAL T-CELL SUBPOPULATIONS SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-B; ANTIGEN; CD45; RECEPTOR; LOCALIZATION; EXPRESSION; ISOFORMS AB CD22 is a B cell lineage restricted cell-surface adhesion glycoprotein which recognizes ligands on human T and B cells and cell lines. A soluble recombinant form of human CD22 (hCD22Rg) has been used to identify and characterize CD22-specific ligands on human T cells, one of which has been shown to be the receptor-linked phosphotyrosine phosphatase CD45. Because CD45 plays a pivotal role in lymphocyte activation, we assessed whether human CD22 might display cross-species reactivity with CD45. In the study presented here we demonstrate that human CD22Rg recognizes several murine cell-surface sialoglycoproteins, including CD45, containing sialic acid in alpha 2,6 linkage. Furthermore, hCD22Rg recognizes different ligands on functionally distinct T helper-cell subpopulations and selectively binds medullary thymocytes in vivo. Our results confirm and extend previous observations that CD22 is a sialic acid-binding lectin which interacts with CD45 and other glycoproteins capable of presenting alpha 2,6-linked sialic acid in a manner that promotes high affinity binding. The cross-species reactivity of CD22 with its ligands underscores the potential physiologic importance of CD22-mediated lymphocyte interactions. C1 MASSACHUSETTS GEN HOSP E,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [T32 CA 09216, CA55735] NR 22 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 1994 VL 39 IS 5 BP 433 EP 438 DI 10.1111/j.1365-3083.1994.tb03397.x PG 6 WC Immunology SC Immunology GA NH883 UT WOS:A1994NH88300003 PM 8191218 ER PT J AU WALDO, MC CAWTHRA, E ADLER, LE DUBESTER, S STAUNTON, M NAGAMOTO, H BAKER, N MADISON, A SIMON, J SCHERZINGER, A DREBING, C GERHARDT, G FREEDMAN, R AF WALDO, MC CAWTHRA, E ADLER, LE DUBESTER, S STAUNTON, M NAGAMOTO, H BAKER, N MADISON, A SIMON, J SCHERZINGER, A DREBING, C GERHARDT, G FREEDMAN, R TI AUDITORY SENSORY GATING, HIPPOCAMPAL VOLUME, AND CATECHOLAMINE METABOLISM IN SCHIZOPHRENICS AND THEIR SIBLINGS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE PATHOPHYSIOLOGY; AUDITORY EVOKED POTENTIAL; HIPPOCAMPUS; DOPAMINE; HOMOVANILLIC ACID; (SCHIZOPHRENIA) ID EYE-TRACKING DYSFUNCTIONS; PLASMA HOMOVANILLIC-ACID; EVOKED-RESPONSES; NEUROPHYSIOLOGICAL EVIDENCE; P50 SUPPRESSION; LIMBIC SYSTEM; POTENTIALS; NOREPINEPHRINE; ABNORMALITIES; STIMULATION AB Schizophrenia may result from the concerted action of several pathophysiological factors. This pilot study compared the distribution of measurements of three such putative factors in 11 schizophrenics and their siblings: a neurophysiological deficit in auditory sensory gating, diminished hippocampal volume, and increased catecholamine metabolism. Abnormal auditory sensory gating was found in all schizophrenics in the 11 families studied and in 8 of their 20 siblings. Compared with the schizophrenics, the clinically unaffected siblings with abnormal auditory gating had larger hippocampal volume. There was no similar difference for the siblings with normal gating. The siblings with abnormal auditory gating also had lower homovanillic acid levels than the other siblings. The data suggest that a familial neuronal deficit, identified by diminished sensory gating, may be a necessary, but not sufficient factor in the pathogenesis of schizophrenia. Individuals with this deficit are generally clinically unaffected, except for schizophrenics, who also have other abnormalities, such as diminished hippocampal volume and increased catecholamine metabolism. C1 DENVER VA MED CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR C26871,DENVER,CO 80262. DENVER VA MED CTR,DEPT PHARMACOL,DENVER,CO. DENVER VA MED CTR,DEPT RADIOL,DENVER,CO. FU NIMH NIH HHS [MH00728, MH44212, MH38321] NR 60 TC 100 Z9 100 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 1994 VL 12 IS 2 BP 93 EP 106 DI 10.1016/0920-9964(94)90067-1 PG 14 WC Psychiatry SC Psychiatry GA NK059 UT WOS:A1994NK05900001 PM 8043530 ER PT J AU HAROUTUNIAN, V DAVIDSON, M KANOF, PD PERL, DP POWCHIK, P LOSONCZY, M MCCRYSTAL, J PUROHIT, DP BIERER, LM DAVIS, KL AF HAROUTUNIAN, V DAVIDSON, M KANOF, PD PERL, DP POWCHIK, P LOSONCZY, M MCCRYSTAL, J PUROHIT, DP BIERER, LM DAVIS, KL TI CORTICAL CHOLINERGIC MARKERS IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; ACETYLCHOLINE; CHOLINERGIC; CHOLINE ACETYLTRANSFERASE; ACETYLCHOLINESTERASE; CORTEX; POSTMORTEM; (SCHIZOPHRENIA) ID ALZHEIMERS-DISEASE; NUCLEUS BASALIS; SENILE DEMENTIA; LONG-TERM; SYSTEM; MEMORY; BRAIN; IMPAIRMENT; DEFICITS; BINDING AB Cortical cholinergic deficits have been implicated in the cognitive deficits produced by a variety of neurodegenerative diseases including Alzheimer's disease (AD). Recent studies have suggested that many of the chronically institutionalized geriatric schizophrenic patients are also cognitvely impaired. In this postmortem study we compared cholinergic marker activity in six different cortical regions derived from elderly controls, chronically institutionalized geriatric schizophrenic patients, and AD patients. All of the Alzheimer's disease cases met neuropathological criteria for AD, while none of the schizophrenic cases met criteria for AD. Cholinergic marker activity (choline acetyltransferase and acetylcholinesterase) was significantly diminished in the AD cohort but not in the schizophrenic cohort. Additionally, cortical choline acetyltransferase activity was significantly and negatively correlated with Clinical Dementia Rating scores (CDR), whereas no such correlations were evident in the schizophrenic cohort. These results suggest that cognitive deficits in geriatric schizophrenics are not due to diminished cortical cholinergic activity. C1 CUNY MT SINAI SCH MED,DEPT PATHOL,NEW YORK,NY 10029. BRONX VET AFFAIRS MED CTR,BRONX,NY. PILGRIM PSYCHIAT CTR,W BRENTWOOD,NY. RP HAROUTUNIAN, V (reprint author), CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029, USA. FU NIA NIH HHS [AG00408] NR 48 TC 61 Z9 61 U1 6 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 1994 VL 12 IS 2 BP 137 EP 144 DI 10.1016/0920-9964(94)90071-X PG 8 WC Psychiatry SC Psychiatry GA NK059 UT WOS:A1994NK05900005 PM 8043524 ER PT J AU LEVY, CJ WIDOM, B SIMONSON, DC AF LEVY, CJ WIDOM, B SIMONSON, DC TI EFFECT OF THE MENSTRUAL-CYCLE ON GLUCOSE-METABOLISM AND DIABETES CONTROL IN WOMEN WITH INSULIN-DEPENDENT DIABETES-MELLITUS SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Article RP LEVY, CJ (reprint author), NEW ENGLAND DEACONESS HOSP,BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT INTERNAL MED,BOSTON,MA 02215, USA. NR 0 TC 3 Z9 3 U1 2 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PD MAY PY 1994 VL 12 IS 2 BP 110 EP 119 DI 10.1055/s-2007-1016390 PG 10 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA NW998 UT WOS:A1994NW99800010 ER PT J AU KATZ, MS LOWENTHAL, DT AF KATZ, MS LOWENTHAL, DT TI INFLUENCES OF AGE AND EXERCISE ON GLUCOSE-METABOLISM - IMPLICATIONS FOR MANAGEMENT OF OLDER DIABETICS SO SOUTHERN MEDICAL JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Exercise and Aging CY SEP, 1992 CL GAINESVILLE, FL SP GAINESVILLE VA MED CTR GERIATR RES EDUC & CLIN CTR, UNIV FLORIDA, CTR EXERCISE SCI, UNIV FLORIDA, COLL HLTH & HUMAN PERFORMANCE, UNIV FLORIDA, COLL MED, GERIATR EDUC CTR, BIRMINGHAM REG MED EDUC CTR ID PHYSICAL-ACTIVITY; INSULIN SENSITIVITY; SKELETAL-MUSCLE; TOLERANCE; MELLITUS; MEN; INTOLERANCE; TRANSPORT; MORTALITY AB The well-characterized decline in glucose tolerance during aping is due primarily to impaired insulin-mediated glucose uptake in peripheral tissues. Elderly persons with reduced insulin sensitivity are predisposed to the development of noninsulin-dependent diabetes mellitus (NIDDM), which is common in the geriatric population. Numerous studies suggest that exercise and physical training increase insulin sensitivity in young adult and middle-aged nondiabetics, older subjects with impaired glucose tolerance, and middle-aged persons with NIDDM. These investigations provide presumptive evidence that elderly persons with NIDDM may benefit from exercise training, although no published studies have specifically addressed the effects of exercise in older diabetics. Physical activity may also be effective in preventing the development of NIDDM. In addition, exercise training improves several cardiovascular risk factors, such as plasma lipid abnormalities, hypertension, and obesity. The risks of exercise in older diabetics include hypoglycemia in insulin-treated patients, exacerbation of preexisting cardiovascular disease, and worsening of long-term diabetic complications. Any exercise prescription in the older diabetic must be individualized to the patient's physical capabilities, limitations, and preferences. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV FLORIDA,COLL MED,DEPT MED,GAINESVILLE,FL. UNIV FLORIDA,COLL MED,DEPT PHARMACOL,GAINESVILLE,FL 32610. UNIV FLORIDA,COLL MED,DEPT EXERCISE SCI,GAINESVILLE,FL. VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,GAINESVILLE,FL 32608. RP KATZ, MS (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 32 TC 9 Z9 9 U1 0 U2 2 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAY PY 1994 VL 87 IS 5 BP S70 EP S73 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NL879 UT WOS:A1994NL87900016 PM 8178206 ER PT J AU MOSKOWITZ, MA AF MOSKOWITZ, MA TI TRYPTOPHAN-HYDROXYLASE ACTIVITY IN RAT-BRAIN BASE ARTERIES RELATED TO INNERVATION ORIGINATING FROM THE DORSAL RAPHE NUCLEUS - COMMENT SO STROKE LA English DT Note RP MOSKOWITZ, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1994 VL 25 IS 5 BP 1049 EP 1049 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA NH560 UT WOS:A1994NH56000024 ER PT J AU MESTER, M CARTER, EA TOMPKINS, RG GELFAND, JA DINARELLO, CA BURKE, JF CLARK, BD AF MESTER, M CARTER, EA TOMPKINS, RG GELFAND, JA DINARELLO, CA BURKE, JF CLARK, BD TI THERMAL-INJURY INDUCES VERY EARLY PRODUCTION OF INTERLEUKIN-1-ALPHA IN THE RAT BY MECHANISMS OTHER THAN ENDOTOXEMIA SO SURGERY LA English DT Article ID TUMOR NECROSIS FACTOR; BACTERIAL TRANSLOCATION; GASTROINTESTINAL TRACTS; BURN PATIENTS; SERUM LEVELS; SKIN; PROTEIN; SEPSIS; IL-1-ALPHA; INTESTINE AB Background. Cytokines are putative mediators of thermal injury-induced systemic changes. We studied the effects of thermal injury on cytokine activation in vivo with a sensitive radioimmunoassay specific for rat interleukin-1 alpha (IL-1 alpha). Methods. We characterized the organ distribution and expression kinetics of IL-1 alpha in rats submitted to either 20% total body surface area cutaneous born, muscle born, or endotoxic shock. Rats were killed at various time points, and liver, lung, spleen, ileum, thymus, kidney, skin, and plasma were harvested. Tissues were homogenized, and the supernates were assayed for rat IL-1 alpha. The assay detection limit was 1.5 ng/gm wet tissue (WT). Results. Thermal injury induced marked elevations of IL-1 alpha levels in the liver and injury, and maximal levels were reached at 2.5 hours when compared with controls. In the liver mean IL-1 alpha levels in cutaneous burn injury were 16.5 +/- 6.2 ng/gm WT, whereas in sham injury they were 1.7 +/- 0.1 ng/gm WT, p less than or equal to 0.005; in the lung IL-1 alpha levels with cutaneous burn injury were 10.3 +/- 1.3 ng/gm WT, whereas sham injury levels were 1.9 +/- 0.8 ng/gm WT, p less than or equal to 0.002). Levels in all other organs and plasma were below detection limits. Muscle burn injury had similar elevated levels of IL-1 alpha in the liver at 1 hour, indistinguishable from cutaneous burn. In contrast, endotoxin challenge resulted in dramatic elevation of IL-1 alpha levels in all organs tested except for the kidney, whereas the skin maintained its usual large amounts of IL-1 alpha. Conclusions. These data indicate that thermal or mechanical injury induce very early and organ-specific association of IL-1 alpha in vivo by mechanisms other than endotoxemia. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT GEOG MED & INFECT DIS,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SHRINERS BURNS INST,DEPT SURG,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. FU NIGMS NIH HHS [P50-GM 21700, T32-GM 07035] NR 41 TC 50 Z9 50 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 1994 VL 115 IS 5 BP 588 EP 596 PG 9 WC Surgery SC Surgery GA NJ764 UT WOS:A1994NJ76400009 PM 8178258 ER PT J AU HENSLER, JG FERRY, RC LABOW, DM KOVACHICH, GB FRAZER, A AF HENSLER, JG FERRY, RC LABOW, DM KOVACHICH, GB FRAZER, A TI QUANTITATIVE AUTORADIOGRAPHY OF THE SEROTONIN TRANSPORTER TO ASSESS THE DISTRIBUTION OF SEROTONERGIC PROJECTIONS FROM THE DORSAL RAPHE NUCLEUS SO SYNAPSE LA English DT Article DE H-3 CYANOIMIPRAMINE; PARA-CHLOROAMPHETAMINE; 5,7-DIHYDROXYTRYPTAMINE; 5-HT1A RECEPTORS ID OBSESSIVE-COMPULSIVE DISORDER; RAT-BRAIN; MIDBRAIN RAPHE; BINDING-SITES; ASCENDING PROJECTIONS; UPTAKE INHIBITORS; EXTRACELLULAR 5-HYDROXYTRYPTAMINE; DIFFERENTIAL PROJECTIONS; FILM AUTORADIOGRAPHY; CEREBRAL-CORTEX AB The binding of H-3-CN-IMI to 5-HT uptake sites, as measured by quantitative autoradiography, was used as a marker of serotonergic neurons. Within the dorsal raphe nucleus the binding of H-3-CN-IMI was compared in adjacent coronal sections of rat brain to the binding of H-3-DPAT to 5-HT1A receptors, which have a known somatodendritic localization. The heterogeneous pattern of binding of these two radioligands within the dorsal raphe nucleus was similar and corresponded to the distribution of serotonergic cell bodies as visualized by 5-HT immunohistochemistry. Intracerebroventricular administration of 5,7-dihydroxytryptamine (5,7-DHT), which caused a dramatic loss of 5-HT immunoreactivity and H-3-DPAT binding to 5-HT1A receptors, resulted in a marked reduction of H-3-CN-IMI binding in this nucleus. Treatment of rats with a dose of parachloroamphetamine (PCA) which has been reported to selectively lesion serotonergic processes arising from the dorsal raphe nucleus, while sparing serotonergic cell bodies and projections from the median raphe nucleus, did not alter the binding of H-3-DPAT or H-3-CN-IMI in the dorsal raphe nucleus; serotonergic cell bodies appeared morphologically unaffected. The lack of effect of PCA treatment on the binding of H-3-DPAT and H-3-CN-IMI is consistent with a somatodendritic localization of the 5-HT transporter in the dorsal raphe nucleus. PCA treatment appeared to produce a moderate loss of serotonergic innervation in serotonergic terminal field areas as visualized by serotonin immunohistochemistry. The reductions in H-3-CN-IMI binding observed in terminal field areas (24 to 69%) following treatment of rats with PCA did not reflect a marked differential innervation of forebrain areas by the dorsal and medial raphe nuclei as expected from previous biochemical studies, and were not entirely consistent with the findings of neuroanatomical studies using histochemical techniques. Site-specific injection of 5,7-DHT into the dorsal raphe nucleus produced an 80 +/- 11% reduction in the binding of H-3-CN-IMI in this nucleus, whereas the binding of H-3-CN-IMI in the median raphe nucleus was not reduced. The reductions in H-3-CN-IMI binding measured in the caudate putamen, frontal and entorhinal cortex as a result of specific lesion of the dorsal raphe nucleus were suggestive of a heavy innervation of these areas by the dorsal raphe nucleus as indicated in neuroanatomical studies. In the hippocampus, our data were consistent with an over-lapping innervation of these areas by both the dorsal and median raphe nuclei and are not reflective of predominant innervation by the medial raphe nucleus. (C) 1994 Wiley-Liss, Inc. C1 UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. FU NIMH NIH HHS [MH48125, MH14654] NR 64 TC 88 Z9 88 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 1994 VL 17 IS 1 BP 1 EP 15 DI 10.1002/syn.890170102 PG 15 WC Neurosciences SC Neurosciences & Neurology GA NG540 UT WOS:A1994NG54000001 PM 8042142 ER PT J AU VINCENT, SL ADAMEC, E SORENSEN, I BENES, FM AF VINCENT, SL ADAMEC, E SORENSEN, I BENES, FM TI THE EFFECTS OF CHRONIC HALOPERIDOL ADMINISTRATION ON GABA-IMMUNOREACTIVE AXON TERMINALS IN RAT MEDIAL PREFRONTAL CORTEX SO SYNAPSE LA English DT Article DE ANTIPSYCHOTIC DRUGS; DOPAMINE; INTERNEURONS; MESOCORTICAL DOPAMINE PROJECTION; RECEPTORS; SYNAPSES ID CENTRAL NERVOUS-SYSTEM; ELECTRON MICROSCOPICAL LEVEL; RECEPTOR-BINDING-SITES; ANTIPSYCHOTIC-DRUGS; AUTORADIOGRAPHIC LOCALIZATION; DOPAMINE-RECEPTORS; CEREBRAL-CORTEX; ULTRASTRUCTURAL-CHANGES; SEROTONIN RECEPTORS; CINGULATE CORTEX AB Several reports have suggested that chronic haloperidol (HAL) treatment induces ultrastructural changes in synapses of substantia nigra, corpus striatum, and medial prefrontal cortex (mPFC) of rat brain. The effects of HAL on specific cortical transmitter systems, however, are not well characterized. Recent studies have indicated that there may be a loss of gamma-aminobutyric acid (GABA)ergic cells in anterior cingulate cortex of schizophrenic subjects and this hypothesis has prompted interest in the question of whether dopamine receptor antagonists, such as HAL, may influence the activity of this transmitter system. This current report describes a quantitative light microscopic analysis of GABA-immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate (0.5 mg/kg/day, i.m.) for a period of 4 months. GABA-containing terminals were visualized with an avidin-biotin immunoperoxidase method for localizing anti-GABA antibodies. Computer-assisted image processing was employed to determine the total number of pixels representing GABA-immunoreaction product in axon terminals that were in direct apposition to pyramidal cell bodies. Drug-treated animals showed a significant increase in the number of pixels representing GABA-immunoreaction product in axosomatic terminals of layers II, III, V, and VI (93%, 63%, 31%, and 43%, respectively). These data are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mPFC. The fact that GABA-containing terminals showed the greatest increase in layer II is not consistent with the known distribution of dopamine afferents to this region which is lowest in superficial laminae. Based on the laminar distribution of non-dopaminergic receptor types that have a high affinity for HAL, the effect of this drug on GABAergic transmission could potentially involve changes that are mediated through mechanisms in which 5-HT2 or sigma opiate receptors play a role. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MCLEAN HOSP,MAILMAN RES CTR,STRUCT NEUROSCI LAB,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,HK BEECHER RES LABS,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT PHARMACOL,BOSTON,MA 02118. RP VINCENT, SL (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115, USA. FU NIMH NIH HHS [MH00423, MH31154, MH42261] NR 60 TC 48 Z9 48 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 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 1994 VL 17 IS 1 BP 26 EP 35 DI 10.1002/syn.890170104 PG 10 WC Neurosciences SC Neurosciences & Neurology GA NG540 UT WOS:A1994NG54000003 PM 8042144 ER PT J AU ATLAS, SJ SINGER, DE SKATES, SJ AF ATLAS, SJ SINGER, DE SKATES, SJ TI CHANGING BLOOD USE IN THE AIDS ERA - THE CASE OF ELECTIVE HIP-SURGERY SO TRANSFUSION LA English DT Article ID AUTOLOGOUS BLOOD; UNITED-STATES; TRANSFUSION; DONATION; REPLACEMENT; COLLECTION AB Background: Concern about the transmission of human immunodeficiency virus via blood has substantially increased the public's anxiety about the safety of the blood supply and has encouraged practices to minimize risks deriving from transfusions. Study Design and Methods: To assess changes in transfusion practices in elective surgery as awareness of transfusion-transmitted human immunodeficiency virus emerged, 80 randomly selected patients per year undergoing elective total hip replacement in five calendar years between 1977 and 1989 at a large university teaching hospital were studied. Results: Total blood use decreased significantly from an average of 3.3 units per patient in 1977 to 2.1 units per patient in 1989 (p 0.0003). Autologous blood use increased from essentially zero in 1977 to 82 percent of total blood use in 1989 (p<0.0001). The threshold hematocrit for postoperative transfusion of allogeneic blood (defined by use of logistic regression models) decreased from 30.1 percent (0.30) In 1977 to 26.7 percent (0.27) in 1989 (p = 0.01). As a result of these changes, the proportion of patients exposed to allogeneic blood decreased from 90 to 16 percent across the study period (p<0.0001). The dramatic decrease in the use of allogeneic blood in elective total hip replacement surgery during the study period was due to decreased demand for blood during and after the operation and to a striking shift in the blood supply from allogeneic to autologous sources. Conclusion: These findings demonstrate that physicians can appropriately alter practices when there are perceived health risks. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR MED PRACTICES EVALUAT,BOSTON,MA. FU BHP HRSA HHS [28PE51006] NR 26 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 1994 VL 34 IS 5 BP 386 EP 391 DI 10.1046/j.1537-2995.1994.34594249048.x PG 6 WC Hematology SC Hematology GA NP054 UT WOS:A1994NP05400006 PM 8191561 ER PT J AU DRIEVER, W STEMPLE, D SCHIER, A SOLNICAKREZEL, L AF DRIEVER, W STEMPLE, D SCHIER, A SOLNICAKREZEL, L TI ZEBRAFISH - GENETIC TOOLS FOR STUDYING VERTEBRATE DEVELOPMENT SO TRENDS IN GENETICS LA English DT Review ID GERM-LINE TRANSMISSION; BRACHYDANIO-RERIO; RECESSIVE LETHAL; NERVOUS-SYSTEM; MUTATIONS; EMBRYOS; MUTAGENESIS; NITROSOUREA; INDUCTION; FREQUENCY AB Zebrafish have entered the arena of vertebrate biology as a mainstream model system, and the use of genetic tools in this tropical fish should enhance our understanding of vertebrate development. The zebrafish system allows genetic experiments that are no possible in other vertebrates and the mutations isolated thus far attest to its usefulness, complementing knowledge obtained from other model organisms. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02129. RP DRIEVER, W (reprint author), MASSACHUSETTS GEN HOSP,CVRC,149 13TH ST,BOSTON,MA 02129, USA. NR 38 TC 217 Z9 228 U1 2 U2 24 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD MAY PY 1994 VL 10 IS 5 BP 152 EP 159 DI 10.1016/0168-9525(94)90091-4 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA NJ258 UT WOS:A1994NJ25800004 PM 8036717 ER PT J AU VINTERS, HV SECOR, DL READ, SL FRAZEE, JG TOMIYASU, U STANLEY, TM FERREIRO, JA AKERS, MA AF VINTERS, HV SECOR, DL READ, SL FRAZEE, JG TOMIYASU, U STANLEY, TM FERREIRO, JA AKERS, MA TI MICROVASCULATURE IN BRAIN BIOPSY SPECIMENS FROM PATIENTS WITH ALZHEIMERS-DISEASE - AN IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL-STUDY SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE ALZHEIMERS DISEASE; AMYLOID ANGIOPATHY; BLOOD-BRAIN BARRIER; BRAIN BIOPSY; CEREBRAL MICROVASCULATURE ID CEREBRAL AMYLOID ANGIOPATHY; BETA-PROTEIN PRECURSOR; PLAQUE CORE PROTEIN; NEURITIC PLAQUES; SENILE PLAQUES; GAMMA-TRACE; DUTCH TYPE; DEMENTIA; PEPTIDE; HEMORRHAGE AB Brain biopsy specimens from five patients with Alzheimer's disease obtained in the course of a trial of intracerebroventricular bethanechol were studied by immunohistochemical (antibody to A, peptide) and ultrastructural techniques, with particular emphasis on the microvessels. In some cases, numbers of A(4)-immunoreactive lesions (senile plaques) correlated well with numbers of plaques demonstrable by silver stains. Prominent A(4)-immunoreactive amyloid angiopathy was seen in one patient. The patient with severe cerebral amyloid angiopathy (CAA) showed extensive arteriolar deposition of amyloid filaments with apparent destruction of the media but remarkably intact endothelium. A cell of origin for amyloid filaments was not apparent, although close proximity to smooth muscle cell remnants in the arteriolar media suggested this as one possible cell of origin. Frequent vessels showed medial or adventitial collagen deposition, even when the amount of amyloid was minimal or negligible. Thus relatively severe CAA can exist in the absence of overt endothelial injury, although related studies on this tissue indicate definite abnormalities of the blood-brain barrier. Conversely, destruction of smooth muscle cells and collagen deposition in vessel walls may be the cellular correlates of arteriolar weakening that can lead to CAA-related brain hemorrhage. C1 UNIV CALIF LOS ANGELES,MED CTR,BRAIN RES INST,LOS ANGELES,CA 90024. JOHN DOUGLAS FRENCH CTR,LOS ALAMITOS,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP VINTERS, HV (reprint author), UNIV CALIF LOS ANGELES,MED CTR,DEPT PATHOL & LAB MED,CHS 18-170,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [AG 10123]; NINDS NIH HHS [R29 NS 26312] NR 74 TC 98 Z9 98 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-JUN PY 1994 VL 18 IS 3 BP 333 EP 348 PG 16 WC Microscopy; Pathology SC Microscopy; Pathology GA NL204 UT WOS:A1994NL20400003 PM 8066824 ER PT J AU GERWECK, LE ZAIDI, ST ZIETMAN, A AF GERWECK, LE ZAIDI, ST ZIETMAN, A TI MULTIVARIATE DETERMINANTS OF RADIOCURABILITY .1. PREDICTION OF SINGLE FRACTION TUMOR-CONTROL DOSES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE DETERMINANTS OF RADIOCURABILITY; INTRINSIC RADIOSENSITIVITY; HYPOXIC CELL FRACTION; CLONOGENIC FRACTION; HUMAN XENOGRAFTS ID GLIOBLASTOMA-MULTIFORME; CELL-LINES; RADIOSENSITIVITY; IRRADIATION; XENOGRAFTS; RADIATION; MURINE; SENSITIZATION; RADIOTHERAPY; BRAIN AB Purpose: The relationship between various laboratory determinants of radiocurability considered alone and in combination, and the observed 50% tumor control dose, has been examined in rodent and xenografted human tumors. Methods and Materials: The single fraction 50% tumor control dose (TCD50) under normal and clamp hypoxic conditions, 50% tumor cell transplant dose (Td(50)), and in vitro estimated tumor cell radiosensitivity parameters, were determined in each of six tumor types (four isografted murine and two xenografted human tumors). Subcutaneous transplant sites and identical or similar tumor generations were used for both the Td(50) and TCD50 studies. Radiosensitivity parameters were obtained using the clonogenic assay, after allowing cells to enter the active growth phase to recover from trypsin induced alterations of cell radiosensitivity. Both control and irradiated cells were multiplicity corrected. Results: No single parameter (InTd(50), hypoxic fraction, or intrinsic radiosensitivity) correlated with the observed tumor control doses under aerobic or hypoxic conditions. However, when considered in combination, clonogenic fraction (estimated by Td(50)(-1)), and intrinsic radiosensitivity, predicted the rank-order of tumor control doses with a significant degree of accuracy, and tumor hypoxia influenced the value of the control dose. All parameters were demonstrated to be significant determinants of radiocurability, with substantial tumor to tumor variation in the relative importance of each. For the six tumor types, the combined laboratory determinants predicted 50% tumor control doses which differed from the observed TCD(50)s by an average of approximately 9 Gy under hypoxic conditions. Conclusion: The results obtained demonstrate: (a) the necessity of simultaneously considering all determinants of radiocurability if the role of a single determinant is to be assessed; (b) laboratory determinants may accurately predict tumor radiocurability. RP GERWECK, LE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,EDWIN L STEELE LAB CELLULAR RADIAT BIOL,DEPT RADI,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-22860] NR 28 TC 36 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1994 VL 29 IS 1 BP 57 EP 66 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NJ340 UT WOS:A1994NJ34000008 PM 8175446 ER PT J AU EDGE, ASB KARASIK, A YAMADA, K KAHN, CR AF EDGE, ASB KARASIK, A YAMADA, K KAHN, CR TI EFFECT OF DEXAMETHASONE ON THE CARBOHYDRATE CHAINS OF THE INSULIN-RECEPTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID 3T3-L1 ADIPOCYTES; GENE-EXPRESSION; GLYCOSYLATION; CELLS; OLIGOSACCHARIDES; DEGLYCOSYLATION; HYDROCORTISONE; GLYCOPROTEINS; PRORECEPTOR; MACROCORTIN AB Dexamethasone treatment of IM-9 lymphocytes and Fao hepatoma cells resulted in an increase in synthesis of the insulin receptor. The receptors synthesized after stimulation with the glucocorticoid had altered carbohydrate structure. The carbohydrate side chains of the insulin receptor were less branched on the dexamethasone-treated cells; i.e.,the ratio of saccharides with three and four branches to those bearing only two branches was decreased. The predominant polymannose oligosaccharide after dexamethasone treatment was Man(9)GlcNAc (vs Man(6)GlcNAc in the control cell). Both of these changes are consistent with a less complete processing of the N-linked carbohydrate units and were not observed for the total cellular glycoproteins, whereas all glycoproteins manifested an increased sialylation in Fao cells after dexamethasone treatment. These data indicate that glucocorticoid treatment results in alterations in branching of carbohydrate side chains, in the size of polymannose chains and in sialylation of the insulin receptor. (C) 1994 Academic Press, Inc. RP EDGE, ASB (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,ELLIOT P JOSLIN RES LAB,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 31036, DK 36836, DK 38423] NR 26 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 29 PY 1994 VL 200 IS 2 BP 852 EP 859 DI 10.1006/bbrc.1994.1529 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NH738 UT WOS:A1994NH73800027 PM 8179619 ER PT J AU MOORE, SEH SPIRO, RG AF MOORE, SEH SPIRO, RG TI INTRACELLULAR COMPARTMENTALIZATION AND DEGRADATION OF FREE POLYMANNOSE OLIGOSACCHARIDES RELEASED DURING GLYCOPROTEIN-BIOSYNTHESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-LINKED OLIGOSACCHARIDES; ALPHA-D-MANNOSIDASE; RAT-LIVER; SUBSTRATE SPECIFICITIES; ENDOPLASMIC-RETICULUM; DIPHOSPHO-DOLICHOL; CATABOLIC PATHWAY; STREPTOLYSIN-O; GLUCOSIDASE-II; PROTEIN AB The intracellular site for the degradation of free polymannose oligosaccharides released during glycoprotein biosynthesis has been studied by permeabilizing the plasma membrane of metabolically radiolabeled HepG2 cells with streptolysin O. This pore-forming agent permitted us to examine the breakdown in both the cytosolic and vesicular compartments of the previously recognized (Anumula, K. R., and Spiro, R. G. (1983) J. Biol. Chem. 258, 15274-15282) polymannose components terminating in a di-N-acetylchitobiose sequence (OS-Glc-NAc2) or a single N-acetylglucosamine residue (OS-Glc-NAc1) residue. Pulse-chase studies indicated that although the OS-GlcNAc(2) saccharides were about equally distributed between vesicles and cytosol and rapidly disappeared after reaching the Man(8) stage, the OS-GlcNAc(1) species were found predominantly in the extravesicular compartment and there underwent a distinctive demannosylation sequence resulting in the formation of a Man(5)GlcNAc isomer (Man alpha 1-->2Man alpha 1--> 2Man alpha 1-->3(Man alpha 1-->6)Man beta 1-->4GlcNAc) which was different from the product of Golgi processing enzymes. Further trimming of this cytosolic limit product required its translocation into a vesicular compartment, believed to be lysosomes, in which Man(2-4)GlcNAc components appeared as the metabolic chase progressed. The accumulation of Glc(1)Man(5)GlcNAc in the cytosol during the chase suggested that glucose interferes with the cytosolic-vesicular transfer and this became even more evident by the pronounced pile-up of extravesicular Glc(3)Man(5)GlcNAc when the cells were incubated in the presence of castanospermine. Although the biological significance and mechanism of free polymannose oligosaccharide entry into the cytosol is not yet known, the possibility that it may reflect an endoplasmic reticulum-situated degradative process of glycoproteins merits consideration. C1 JOSLIN DIABET CTR,ELLIOTT P JOSLIN RES LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 17477] NR 31 TC 82 Z9 82 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 29 PY 1994 VL 269 IS 17 BP 12715 EP 12721 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NH716 UT WOS:A1994NH71600055 PM 8175683 ER PT J AU DRANOFF, G CRAWFORD, AD SADELAIN, M REAM, B RASHID, A BRONSON, RT DICKERSIN, GR BACHURSKI, CJ MARK, EL WHITSETT, JA MULLIGAN, RC AF DRANOFF, G CRAWFORD, AD SADELAIN, M REAM, B RASHID, A BRONSON, RT DICKERSIN, GR BACHURSKI, CJ MARK, EL WHITSETT, JA MULLIGAN, RC TI INVOLVEMENT OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PULMONARY HOMEOSTASIS SO SCIENCE LA English DT Article ID SURFACTANT PROTEIN-A; MURINE GM-CSF; LANGERHANS CELLS; MOUSE; PHAGOCYTOSIS; RECEPTOR; INVITRO; MICE; ENHANCEMENT; EXPRESSION AB The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis. C1 MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. CHILDRENS HOSP,DIV PULM BIOL,CINCINNATI,OH 45229. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL37569] NR 45 TC 587 Z9 596 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 29 PY 1994 VL 264 IS 5159 BP 713 EP 716 DI 10.1126/science.8171324 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NH713 UT WOS:A1994NH71300035 PM 8171324 ER PT J AU ARAKI, E HAAG, BL KAHN, CR AF ARAKI, E HAAG, BL KAHN, CR TI CLONING OF THE MOUSE INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) GENE AND COMPLETE SEQUENCE OF MOUSE IRS-1 SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Note DE IRS-1; CDNA; (MOUSE) ID SRC HOMOLOGY-2 DOMAINS; PHOSPHATIDYLINOSITOL 3'-KINASE; SIGNAL TRANSDUCTION; PROTEIN; ASSOCIATION; EXPRESSION; KINASE AB The mouse IRS-1 gene has been cloned and its structure determined. Mouse IRS-1 differs from rat by the absence of the potential C-terminal nucleotide binding site. Otherwise, the predicted IRS-1 protein is highly conserved between mouse, rat and humans, especially in the possible phosphorylation sites. The highly conserved nature of IRS-1 suggests the importance of these domains in the function of IRS-1 or its association with other proteins. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 33201, DK 36836] NR 14 TC 28 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 28 PY 1994 VL 1221 IS 3 BP 353 EP 356 DI 10.1016/0167-4889(94)90261-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NJ518 UT WOS:A1994NJ51800019 PM 8167159 ER PT J AU COTTON, DJ REGAUER, S MAYOSMITH, W SCULLY, RE BOSWELL, SL BREWER, TF AF COTTON, DJ REGAUER, S MAYOSMITH, W SCULLY, RE BOSWELL, SL BREWER, TF TI A 38-YEAR-OLD MAN WITH AIDS, SUDDEN ABDOMINAL-PAIN, AND BLEEDING FROM THE RECTUM - ACQUIRED-IMMUNODEFICIENCY-SYNDROME - CYTOMEGALOVIRUS VASCULITIS OF COLON, WITH TRANSMURAL NECROSIS AND PERITONITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID IMMUNE-DEFICIENCY-SYNDROME; KAPOSIS SARCOMA; GASTROINTESTINAL HEMORRHAGE; PSEUDOMEMBRANOUS COLITIS; INTESTINAL PERFORATION; ULCERATIVE-COLITIS; VIRUS COLITIS; INFECTION; PATIENT; ENTEROCOLITIS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP COTTON, DJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 46 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 28 PY 1994 VL 330 IS 17 BP 1218 EP 1225 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA NG586 UT WOS:A1994NG58600008 ER PT J AU CARR, MW ROTH, SJ LUTHER, E ROSE, SS SPRINGER, TA AF CARR, MW ROTH, SJ LUTHER, E ROSE, SS SPRINGER, TA TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 ACTS AS A T-LYMPHOCYTE CHEMOATTRACTANT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATING FACTOR MCAF; AMINO-ACID-SEQUENCE; CHEMOTACTIC FACTOR; ENDOTHELIAL-CELLS; PURIFICATION; ADHESION; TISSUE; LFA-1; LINE; IV AB We have utilized a transendothelial lymphocyte chemotaxis assay to identify and purify a lymphocyte chemoattractant in supernatants of mitogen-stimulated peripheral blood mononuclear cells. Amino acid sequence analysis revealed identity with monocyte chemoattractant protein 1 (MCP-1), a chemoattractant previously thought to be specific for monocytes. Recombinant MCP-1 is chemoattractive for purified T lymphocytes and for CD3(+) lymphocytes in peripheral blood lymphocyte preparations. The T-cell response to MCP-1 is dose-dependent and chemotactic, rather than chemokinetic. Phenotyping of chemoattracted T lymphocytes shows they are an activated memory subset. The response to MCP-1 by T lymphocytes can be duplicated in the absence of an endothelial monolayer and the majority of T-lymphocyte chemotactic activity in mitogen-stimulated peripheral blood mononuclear cell supernatants can be neutralized by antibody to MCP-1. Thus, MCP-1 is the major lymphocyte chemoattractant secreted by mitogen-stimulated peripheral blood mononuclear cells and is capable of acting as a potent T-lymphocyte, as well as monocyte, chemoattractant. This may help explain why monocytes and T lymphocytes of the memory subset are always found together at sites of antigen-induced inflammation. C1 HARVARD UNIV,SCH MED,COMM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. FU NHLBI NIH HHS [K08-HL02776, P01-HL48675] NR 35 TC 820 Z9 829 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 26 PY 1994 VL 91 IS 9 BP 3652 EP 3656 DI 10.1073/pnas.91.9.3652 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400038 PM 8170963 ER PT J AU REBECK, GW MAYNARD, KI HYMAN, BT MOSKOWITZ, MA AF REBECK, GW MAYNARD, KI HYMAN, BT MOSKOWITZ, MA TI SELECTIVE 5-HT(1D-ALPHA) SEROTONIN RECEPTOR GENE-EXPRESSION IN TRIGEMINAL GANGLIA - IMPLICATIONS FOR ANTIMIGRAINE DRUG DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MIGRAINE; SEROTONIN RECEPTOR SUBTYPES ID NEUROGENIC PLASMA EXTRAVASATION; RAT DURA-MATER; VASCULAR HEADACHES; ERGOT ALKALOIDS; BINDING-SITES; SUMATRIPTAN; 5-HT1B; STIMULATION; SUBFAMILY; CP-93,129 AB Pharmacological data suggest that the actions of antimigraine drugs such as sumatriptan may be mediated by 5-HT1D-like serotonin receptors on trigeminovascular nerve endings. We sought molecular evidence for the expression of an mRNA species encoding the 5-HT1D receptor subtype in guinea pig and human trigeminal ganglia, using the polymerase chain reaction with oligonucleotides uniquely homologous to the coding sequences of the 5-HT1B/D family (human 5-HT1D alpha and 5-HT1D beta; rat 5-HT1B). A Single band of predicted size was observed in samples from guinea pig trigeminal ganglia; sequence analysis revealed the presence of a single message, which was 85% and 71% identical to the human 5-HT1D alpha and 5-HT1D beta receptor DNA sequences, respectively. Similar analyses of postmortem human trigeminal ganglia revealed the presence of 5-HT1D alpha, but not 5-HT1D beta, receptor message. Inasmuch as one recent report found that mRNA encoding only the 5-HT1D beta receptor subtype was expressed by vascular smooth muscle of the central nervous system, the present findings suggest the importance of developing selective 5-HT1D alpha receptor agonists as a strategy to reduce the risk of myocardial infarction and possibly stroke that complicates the acute treatment of migraine headache. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS 21558, NS07009] NR 35 TC 127 Z9 128 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 26 PY 1994 VL 91 IS 9 BP 3666 EP 3669 DI 10.1073/pnas.91.9.3666 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400041 PM 8170966 ER PT J AU JANCSO, A BOTFIELD, MC SOWERS, LC WEISS, MA AF JANCSO, A BOTFIELD, MC SOWERS, LC WEISS, MA TI AN ALTERED-SPECIFICITY MUTATION IN A HUMAN POU DOMAIN DEMONSTRATES FUNCTIONAL ANALOGY BETWEEN THE POU-SPECIFIC SUBDOMAIN AND PHAGE-LAMBDA REPRESSOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION FACTORS; DNA-PROTEIN INTERACTIONS; MUTAGENESIS; DNA-BINDING PROTEINS; MACROMOLECULAR RECOGNITION ID BASE PAIR CONTACT; CAP-DNA COMPLEX; LAC REPRESSOR; RESTRICTION ENDONUCLEASE; IMMUNOGLOBULIN GENES; TRANSCRIPTION FACTOR; ACTIVATOR PROTEIN; CRYSTAL-STRUCTURE; OPERATOR; RECOGNITION AB The POU motif, conserved among a family of eukaryotic transcription factors, contains two DNA-binding domains: an N-terminal POU specific domain (POUs) and a C-terminal homeodomain (POUHD) Surprisingly, POUs is similar in structure to the helix-turn-helix domains of bacteriophage repressor and Cro proteins. Such similarity predicts a common mechanism of DNA recognition. To test this prediction, we have studied the DNA-binding properties of the human Oct-2 POU domain by combined application of chemical synthesis and site-directed mutagenesis. The POUs footprint of DNA contacts, identified by use of modified bases, is analogous to those of bacteriophage repressor-operator complexes. Moreover, a loss-of-contact substitution in the putative POUs recognition alpha-helix leads to relaxed specificity at one position in the DNA target site. The implied side chain-base contact is identical to that of bacteriophage repressor and Cro proteins. These results establish a functional analogy between the POUs and prokaryotic helix-turn-helix elements and suggest that their DNA specificities may be governed by a shared set of rules. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. CITY HOPE NATL MED CTR,DIV PEDIAT,DUARTE,CA 91010. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIGMS NIH HHS [GM45290, GM41336] NR 36 TC 12 Z9 12 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 26 PY 1994 VL 91 IS 9 BP 3887 EP 3891 DI 10.1073/pnas.91.9.3887 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NJ034 UT WOS:A1994NJ03400086 PM 8171007 ER PT J AU FIRST, ER PEARCE, LB BORODIC, GE AF FIRST, ER PEARCE, LB BORODIC, GE TI DOSE STANDARDIZATION OF BOTULINUM TOXIN SO LANCET LA English DT Letter ID STANDARDIZATION C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RP FIRST, ER (reprint author), BOSTON UNIV,SCH MED,DEPT PHARMACOL,BOSTON,MA 02118, USA. NR 3 TC 22 Z9 23 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 23 PY 1994 VL 343 IS 8904 BP 1035 EP 1035 DI 10.1016/S0140-6736(94)90153-8 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NG682 UT WOS:A1994NG68200035 PM 7909062 ER PT J AU GOLUB, TR BARKER, GF LOVETT, M GILLILAND, DG AF GOLUB, TR BARKER, GF LOVETT, M GILLILAND, DG TI FUSION OF PDGF RECEPTOR-BETA TO A NOVEL ETS-LIKE GENE, TEL, IN CHRONIC MYELOMONOCYTIC LEUKEMIA WITH T(512) CHROMOSOMAL TRANSLOCATION SO CELL LA English DT Article ID TYROSINE KINASE RECEPTOR; GROWTH-FACTOR RECEPTORS; MYELODYSPLASTIC SYNDROMES; TRANSFORMING GENE; MYELOID-LEUKEMIA; C-FMS; DROSOPHILA; ACTIVATION; BINDING; FAMILY AB Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML). CMML thus offers an opportunity to study early genetic events in the transition to AML. A recently recognized subgroup of CMML has a t(5;12)(q33;p13) balanced translocation. We report that the consequence of the t(5;12) translocation is expression of a fusion transcript in which the tyrosine kinase domain of the platelet-derived growth factor receptor beta (PDGFR beta) on chromosome 5 is coupled to a novel ets-like gene, tel, on chromosome 12. The tel-PDGFR beta fusion demonstrates the oncogenic potential of PDGFR beta and may provide a paradigm for early events in the pathogenesis of AML. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL & ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MCDERMOTT CTR,DALLAS,TX 75235. RP GOLUB, TR (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV HEMATOL & ONCOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-57261] NR 68 TC 978 Z9 1007 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD APR 22 PY 1994 VL 77 IS 2 BP 307 EP 316 DI 10.1016/0092-8674(94)90322-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NH634 UT WOS:A1994NH63400015 PM 8168137 ER PT J AU BRAESCHANDERSEN, S STAMENKOVIC, I AF BRAESCHANDERSEN, S STAMENKOVIC, I TI SIALYLATION OF THE B-LYMPHOCYTE MOLECULE CD22 BY ALPHA-2,6-SIALYLTRANSFERASE IS IMPLICATED IN THE REGULATION OF CD22-MEDIATED ADHESION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELLS; SURFACE EXPRESSION; ANTIGEN; PROTEIN; SIALYLTRANSFERASE; GLYCOSYLATION; ACTIVATION; RECEPTOR; CLONING; LIVER AB The B cell surface receptor CD22 binds several sialoglycoproteins containing sialic acid in alpha 2,6 linkage, on the surface of B and T lymphocytes. Because lymphocytes adhere tightly to fibroblasts transfected with CD22 cDNA, it would appear reasonable to suggest that regulatory mechanisms might have evolved which prevent undesired CD22-mediated leukocyte aggregation. Here we provide evidence for the existence of at least one mechanism that might regulate CD22 interaction with ligands on adjacent cells. We demonstrate that sialylation of CD22 by beta-galactoside alpha 2,6-sialyltransferase abrogates CD22-mediated lymphocyte adhesion, and that adhesion can be restored by removal of alpha 2,6-linked sialic acid residues from the CD22 molecule. Taken together, our results suggest that alpha 2,6-sialyltransferase can both promote and inhibit CD22-ligand interactions. These observations provide the first direct evidence that receptor-ligand interactions mediated by an Ig superfamily molecule are under the control of a specific glycosyltransferase. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,DEPT PATHOL RES,BOSTON,MA 02129. RP BRAESCHANDERSEN, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA55735] NR 19 TC 69 Z9 70 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 1994 VL 269 IS 16 BP 11783 EP 11786 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700019 PM 8163475 ER PT J AU KIM, SJ KAHN, CR AF KIM, SJ KAHN, CR TI INSULIN STIMULATES PHOSPHORYLATION OF C-JUN, C-FOS, AND FOS-RELATED PROTEINS IN CULTURED ADIPOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING; KINASE-C; NUCLEAR PROTEINS; GENE-EXPRESSION; TRANSCRIPTION; ACTIVATION; CELLS; COMPLEXES; GROWTH; SITES AB In differentiated 3T3-F442A adipocytes, insulin stimulated rapid and transient phosphorylation of c-Jun. Insulin also stimulated phosphorylation of c-Fos and several Fos-related proteins (pp72, pp45, and pp39) as indicated by precipitation with anti-c-Fos antibody following exposure to denaturating conditions. Phosphorylation of c Fos was stimulated by 7-fold by 60 min, while phosphorylation of Fos-related proteins reached maxima of 3.5-5.5-fold at 15 to 60 min. The increase in phosphorylated c-Fos was due to an increase in both c-Fos protein and the stoichiometry of c-Fos phosphorylation, and was not observed in c-fos (-/-) cells. Additionally, insulin stimulated phosphorylation of a protein with molecular mass of similar to 82 kDa on tyrosine residues by 2.5-fold within 30 min; this protein appeared to be immunologically related to c-Fos. These increases in the phosphorylation of AP-1 transcription factors correlated with a >5-fold stimulation of expression of a 12-O-tetradecanoylphorbol-13-acetate-responsive element-chloramphenicol acetyltransferase reporter gene transiently transfected into 3T3-F442A cells. These results indicate that insulin stimulates the phosphorylation of AP-1 transcription factors and several Fos-related proteins on serine and tyrosine residues. This is associated with changes in AP-1-mediated gene expression in vivo, suggesting that AP-1 phosphorylation by insulin plays a role in insulin regulated gene expression. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 36836, DK 33201] NR 37 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 1994 VL 269 IS 16 BP 11887 EP 11892 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700035 PM 7512956 ER PT J AU HARRIS, HW ZEIDEL, ML JO, IH HAMMOND, TG AF HARRIS, HW ZEIDEL, ML JO, IH HAMMOND, TG TI CHARACTERIZATION OF PURIFIED ENDOSOMES CONTAINING THE ANTIDIURETIC HORMONE-SENSITIVE WATER CHANNEL FROM RAT RENAL PAPILLA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; STIMULATED TOAD BLADDER; DUCT PRINCIPAL CELLS; COLLECTING DUCT; PERMEABILITY RESPONSE; ENDOCYTIC VESICLES; CHIP28 PROTEIN; COATED PITS; PROTON; CONTAIN AB Antidiuretic hormone (ADH) stimulation of renal epithelial cells elicits a large increase in apical membrane osmotic water permeability (P-f) produced by the fusion of water channel containing vesicles with the apical membrane. Removal of ADH stimulation results in retrieval of apical water channels into a specialized nonacidic endosomal compartment. Previous studies (Sabolic, I., Wuarin, E., and Shi, L, B. (1992) J. Cell Biol. 119, 111-122) have shown that water channel containing papillary endosomes labeled with fluorescein-dextran can be isolated from rat renal papilla. We have utilized small particle flow sorting methodology to both monitor and improve upon the purification of these water channel containing endosomes (WCV). Flow cytometry analysis on a vesicle-by-vesicle basis demonstrates that WCV are homogenous with respect to entrapped fluorescein-dextran, the apical membrane enzyme marker leucine amino peptidase and ultrastructural morphology. WCV do not acidify their luminal contents after addition of Mg-ATP but contain abundant functional water channels (P-f 0.28 cm/s at 23 degrees C) as determined by stopped flow fluorimetry. SDS-polyacrylamide gel electrophoresis analysis shows that purified WCV are composed of 20 major protein bands. To determine the identity of WCV water channels, WCV proteins were probed with affinity purified antisera recognizing two renal water channel proteins. These include Aquaporin-CHIP found in the proximal tubule and thin descending limb of Henle and the candidate ADH water channel protein WCH-1 or Aquaporin- (AQP) CD present in the ADH-responsive epithelial cells of the collecting duct. These data reveal that WCV contained little or no AQP-CHIP protein. In contrast, WCV are highly enriched for AQP-CD protein. Together, these data define the protein composition of the papillary WCV and link directly the presence of functional apical membrane water channels with the presence of the AQP-CD protein. C1 BROCKTON W ROXBURY VET ADM MED CTR,DIV NEPHROL,BOSTON,MA 02115. UNIV PITTSBURGH,SCH MED,DIV RENAL & ELECTROLYTE,PITTSBURGH,PA 15213. UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53792. RP HARRIS, HW (reprint author), CHILDRENS HOSP,DIV NEPHROL,HUNNEWELL 3,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK 43955, DK 46117, DK 38874] NR 48 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 1994 VL 269 IS 16 BP 11993 EP 12000 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700051 PM 8163502 ER PT J AU BUSH, AI PETTINGELL, WH PARADIS, MD TANZI, RE AF BUSH, AI PETTINGELL, WH PARADIS, MD TANZI, RE TI MODULATION OF A-BETA ADHESIVENESS AND SECRETASE SITE CLEAVAGE BY ZINC SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; TANGLE-BEARING NEURONS; ALZHEIMERS-DISEASE; PARKINSONISM-DEMENTIA; DOWNS-SYNDROME; NEUROFIBRILLARY TANGLES; ALUMINUM ACCUMULATION; CEREBRAL-HEMORRHAGE; BRAIN; RAT AB Abnormalities of zinc homeostasis occur in Alzheimer's disease (AD), a dementia characterized by the aggregation of A beta in the brain, and in Down syndrome, a condition characterized by premature AD, We studied the binding of Zn2+ to a synthetic peptide representing residues 1-40 (A beta(1-40)), as well as other domains of A beta. Two classes of Zn2+ binding were identified by Zn-65(2+) labeling: highly specific pH-dependent high affinity (K-alpha = 107 nM) binding, and lower affinity (K-alpha = 5.2 mu M) binding. Gel filtration chromatography identified monomeric, dimeric, and polymeric A beta species. Zinc induced a marked loss of A beta solubility upon chromatographic analysis. This was attributed to precipitation onto the column glass, which contains aluminosilicate, and was confirmed by the observation of zinc-accelerated precipitation of A beta by kaolin, a hydrated aluminum silicate suspension. Zinc binding also increased A beta resistance to tryptic cleavage at the secretase site, indicating that a small (<3 mu M) increase in brain Zn2+ concentration could significantly alter A beta metabolism, We propose that elevated brain interstitial zinc levels may increase A beta adhesiveness and interfere with A beta catabolism. Consequently, abnormalities of regional zinc concentrations in the brains of patients with AD or Down syndrome may contribute to A beta amyloidosis in these disorders. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING LAB,BOSTON,MA 02129. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 60 TC 252 Z9 264 U1 1 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 1994 VL 269 IS 16 BP 12152 EP 12158 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NG377 UT WOS:A1994NG37700073 PM 8163520 ER PT J AU LORENZO, A RAZZABONI, B WEIR, GC YANKNER, BA AF LORENZO, A RAZZABONI, B WEIR, GC YANKNER, BA TI PANCREATIC-ISLET CELL TOXICITY OF AMYLIN ASSOCIATED WITH TYPE-2 DIABETES-MELLITUS SO NATURE LA English DT Article ID AMYLOID POLYPEPTIDE; ALZHEIMERS-DISEASE; SKELETAL-MUSCLE; HORMONE; LANGERHANS; SEQUENCE; PEPTIDE; PROTEIN; DEATH AB THE 37-amino-acid polypeptide amylin is the principal constituent of the amyloid deposits that form in the islets of Langerhans in patients with type-2 diabetes menitus(1-5), but its role in the pathogenesis of this disease is unresolved(6-8). In view of the fact that the beta-amyloid protein that forms fibrils in Alzheimer's disease is toxic to neurons(9,10), we have investigated whether amylin fibrils could be toxic to pancreatic islet cells. We show here that human amylin is toxic to insulin-producing beta-cells of the adult pancreas of rats and humans. This toxicity is mediated by the fibrillar form of the amylin peptide and requires direct contact of the fibrils with the cell surface. The mechanism of cell death involves RNA and protein synthesis and is characterized by plasma membrane-blebbing, chromatin condensation and DNA fragmentation, indicating that amylin induces islet cell apoptosis. These findings indicate that amylin fibril formation in the pancreas may cause islet cell dysfunction and death in type-2 diabetes mellitus. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NR 29 TC 577 Z9 586 U1 2 U2 47 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 21 PY 1994 VL 368 IS 6473 BP 756 EP 760 DI 10.1038/368756a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NG553 UT WOS:A1994NG55300063 PM 8152488 ER PT J AU ECK, MJ ATWELL, SK SHOELSON, SE HARRISON, SC AF ECK, MJ ATWELL, SK SHOELSON, SE HARRISON, SC TI STRUCTURE OF THE REGULATORY DOMAINS OF THE SRC-FAMILY TYROSINE KINASE LCK SO NATURE LA English DT Article ID PROTEIN STRUCTURES; CRYSTAL-STRUCTURE; SH3 DOMAIN; IDENTIFICATION; P60C-SRC; BINDING AB THE kinase p56(lck) (Lck) is a T-lymphocyte-specific member of the Src family of non-receptor tyrosine kinases(1). Members of the Src family each contain unique amino-terminal regions, followed by Src-homology domains SH3 and SH2, and a tyrosine kinase domain. SH3 and SH2 domains mediate critical protein interactions in many signal-transducing pathways(2). They are small, independently folded modules of about 60 and 100 residues, respectively, and they are often but not always found together in the same molecule. Like all nine Src-family kinases (reviewed in ref. 3), Lck is regulated by phosphorylation of a tyrosine in the short C-terminal tail of its catalytic domain(4). There is evidence that binding of the phosphorylated tail to the SH2 domain inhibits catalytic activity of the kinase domain(5,6) and that the SH3 and SH2 domains may act together to effect this regulation(7). Here we report the crystal structures for a fragment of Lck bearing its SH3 and SH2 domains, alone and in complex with a phosphotyrosyl peptide containing the sequence of the Lck C-terminal regulatory tail. The latter complex represents the regulatory apparatus of Lck. The SH3-SH2 fragment forms similar dimers in both crystals, and the tail peptide binds at the intermolecular SH3/SH2 contact. The two structures show how an SH3 domain might recognize a specific target and suggest how dimerization could play a role in regulating Src-family kinases. C1 CHILDRENS HOSP MED CTR,MOLEC MED LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. RP ECK, MJ (reprint author), CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 30 TC 251 Z9 252 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 21 PY 1994 VL 368 IS 6473 BP 764 EP 769 DI 10.1038/368764a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NG553 UT WOS:A1994NG55300065 PM 7512222 ER PT J AU CHESEBRO, JH MORRISSEY, RL FALLON, JT TORCHIANA, DF MADSEN, JC EAGLE, KA AF CHESEBRO, JH MORRISSEY, RL FALLON, JT TORCHIANA, DF MADSEN, JC EAGLE, KA TI A 57-YEAR-OLD WOMAN WITH A MASS IN THE RIGHT ATRIUM - CARDIAC MYXOMA, RIGHT ATRIAL, WITH EXTENSION INTO LEFT ATRIUM AND PULMONARY TUMOR EMBOLISM SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID VASCULITIS; MIMICKING C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CHESEBRO, JH (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 51 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 1994 VL 330 IS 16 BP 1143 EP 1149 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NF699 UT WOS:A1994NF69900009 ER PT J AU NICKMAN, SL AF NICKMAN, SL TI THE INFERTILE COUPLE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP NICKMAN, SL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 1994 VL 330 IS 16 BP 1155 EP 1155 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NF699 UT WOS:A1994NF69900015 PM 8133864 ER PT J AU NITSCH, RM GROWDON, JH AF NITSCH, RM GROWDON, JH TI ROLE OF NEUROTRANSMISSION IN THE REGULATION OF AMYLOID BETA-PROTEIN PRECURSOR PROCESSING SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE ALZHEIMERS DISEASE; A-BETA; APP; CELL SURFACE RECEPTORS; PROTEIN KINASE ID FAMILIAL ALZHEIMERS-DISEASE; KINASE-C; MESSENGER-RNA; NEXIN-II; COGNITIVE IMPAIRMENT; RECEPTOR SUBTYPES; INHIBITOR DOMAIN; GENE-MUTATIONS; KUNITZ DOMAIN; CLEAVAGE SITE C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP NITSCH, RM (reprint author), MIT,DEPT BRAIN & COGNIT SCI,E25-604,CAMBRIDGE,MA 02139, USA. NR 96 TC 94 Z9 94 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 20 PY 1994 VL 47 IS 8 BP 1275 EP 1284 DI 10.1016/0006-2952(94)90325-5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NK848 UT WOS:A1994NK84800001 PM 7910457 ER PT J AU BACHINSKY, DR EMMANOUEL, D JEFFERSON, D GRUBMAN, S BROWN, D PERRONE, R AF BACHINSKY, DR EMMANOUEL, D JEFFERSON, D GRUBMAN, S BROWN, D PERRONE, R TI CHARACTERIZATION OF EPITHELIAL-CELLS FROM NORMAL AND AUTOSOMAL-DOMINANT POLYCYSTIC KIDNEY-DISEASE (ADPKD) SO FASEB JOURNAL LA English DT Meeting Abstract C1 TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT PATHOL,DIV NEPHROL,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT PEDIAT,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1457 EP A1457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601366 ER PT J AU BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE AF BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE TI PHOSPHATASE-RESISTANT SH2 DOMAIN INHIBITORS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NCI,DTP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1222 EP A1222 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600008 ER PT J AU ENDERS, G HARLOW, E LABAER, J MEYERSON, M TSAI, LH VANDENHEUVEL, S AF ENDERS, G HARLOW, E LABAER, J MEYERSON, M TSAI, LH VANDENHEUVEL, S TI CYCLIN-DEPENDENT KINASES SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1262 EP A1262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600233 ER PT J AU HUTCHCROFT, JE BIERER, BE AF HUTCHCROFT, JE BIERER, BE TI ACTIVATION-DEPENDENT PHOSPHORYLATION OF THE T-LYMPHOCYTE SURFACE-RECEPTOR CD28 AND ASSOCIATED PROTEINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1229 EP A1229 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600050 ER PT J AU KURIYAN, J LEE, CH KOMINOS, D WAKSMAN, G WU, XD KRISHNA, TSR COWBURN, D SHOELSON, SE AF KURIYAN, J LEE, CH KOMINOS, D WAKSMAN, G WU, XD KRISHNA, TSR COWBURN, D SHOELSON, SE TI CRYSTAL-STRUCTURES OF PEPTIDE COMPLEXES OF SH2 DOMAINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. RI Cowburn, David/A-8448-2008; Lee, Chi-Hon/G-9190-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1377 EP A1377 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600900 ER PT J AU KYRIAKIS, JM BANERJEE, P NIKOLAKAKI, E DAI, T RUBIE, EA AHMAD, MF AVRUCH, J WOODGETT, JR AF KYRIAKIS, JM BANERJEE, P NIKOLAKAKI, E DAI, T RUBIE, EA AHMAD, MF AVRUCH, J WOODGETT, JR TI SAPKS - A MAP KINASE SUBFAMILY THAT TRANSDUCES STRESS AND TNF-ALPHA SIGNALS TO C-JUN SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASS GEN HOSP, BOSTON, MA 02129 USA. ONTARIO CANC INST, TORONTO M4X 1K9, ONTARIO, CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1237 EP A1237 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600095 ER PT J AU LEE, YH ALBERTA, IA GONZALEZ, FI WAXMAN, DI AF LEE, YH ALBERTA, IA GONZALEZ, FI WAXMAN, DI TI MULTIPLE, FUNCTIONAL DBP SITES ON THE PROMOTER OF THE CHOLESTEROL 7-ALPHA-HYDROXYLASE-P450 GENE PROMOTER SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1252 EP A1252 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600183 ER PT J AU MILNE, GT WEAVER, DT AF MILNE, GT WEAVER, DT TI EVIDENCE FOR A REPAIR RECOMBINATION PROTEIN COMPLEX INCLUDING RAD52 AND RAD51 SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1409 EP A1409 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51601088 ER PT J AU ROLLER, PP NOMIZU, M OTAKA, A SMYTH, MS WOLF, G CASE, R SHOELSON, SE BURKE, TR AF ROLLER, PP NOMIZU, M OTAKA, A SMYTH, MS WOLF, G CASE, R SHOELSON, SE BURKE, TR TI STRUCTURE-ACTIVITY STUDIES OF SH2 DOMAIN BINDING PEPTIDES CONTAINING O-PHOSPHOTYROSINE ANALOGS SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,DTP,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1391 EP A1391 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600984 ER PT J AU WILLIAMS, KP SHOELSON, SE AF WILLIAMS, KP SHOELSON, SE TI LOOP SWAPS BETWEEN P85 AND SRC SH2 DOMAINS REVERSE SPECIFICITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1378 EP A1378 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600905 ER PT J AU YASOTHORNSRIKUL, S MCGONNIGAL, B ABRAMS, J DEAROLF, C AF YASOTHORNSRIKUL, S MCGONNIGAL, B ABRAMS, J DEAROLF, C TI IDENTIFICATION OF HEMOCYTE-SPECIFIC PROMOTER ELEMENT IN DROSOPHILA SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MIT,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1334 EP A1334 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600652 ER PT J AU ZHAO, SP WAXMAN, DJ AF ZHAO, SP WAXMAN, DJ TI INTERACTION OF SEX-DEPENDENT AND GROWTH-HORMONE (GH)-DEPENDENT LIVER NUCLEAR FACTORS WITH CYP2C12 PROMOTER SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 19 PY 1994 VL 8 IS 7 BP A1250 EP A1250 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA NH516 UT WOS:A1994NH51600170 ER PT J AU KEHOE, R WU, SY LESKE, MC CHYLACK, LT AF KEHOE, R WU, SY LESKE, MC CHYLACK, LT TI COMPARING SELF-REPORTED AND PHYSICIAN-REPORTED MEDICAL HISTORY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CARDIOVASCULAR DISEASES; DATA COLLECTION; DIABETES MELLITUS; EPIDEMIOLOGIC METHODS; INTERVIEWS ID QUESTIONNAIRE AB The authors compared self-reported medical history and medication use in a cataract case-control study of 1,380 persons (1985-1989) in Boston, Massachusetts, with information from the participants' physicians. Under- and overreporting varied by condition and type of medication. A self-reported history of hypertension had the highest sensitivity (91%), and diabetes history had the highest specificity (97%). Among different medications investigated, self-reported antihypertensive medication use was the most sensitive (88%), while self-reported use of insulin was the most specific (99%). Differences between patient- and physician-reported frequencies were very small, except for arthritis (15%) and regular aspirin use (21%). Results suggest an accurate recall of medical and drug usage history in well-defined chronic conditions. C1 SUNY STONY BROOK,SCH MED,DEPT PREVENT MED,DIV EPIDEMIOL,STONY BROOK,NY 11794. MASSACHUSETTS EYE & EAR INFIRM,BRIGHAM & WOMENS HOSP,CTR CLIN CATARACT RES,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NEI NIH HHS [EY05733] NR 7 TC 296 Z9 297 U1 0 U2 4 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 1994 VL 139 IS 8 BP 813 EP 818 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NJ044 UT WOS:A1994NJ04400010 PM 8178794 ER PT J AU SANTOS, CI HUANG, AJ ABELSON, MB FOSTER, CS FRIEDLAENDER, M MCCULLEY, JP AF SANTOS, CI HUANG, AJ ABELSON, MB FOSTER, CS FRIEDLAENDER, M MCCULLEY, JP TI EFFICACY OF LODOXAMIDE 0.1-PERCENT OPHTHALMIC SOLUTION IN RESOLVING CORNEAL EPITHELIOPATHY ASSOCIATED WITH VERNAL KERATOCONJUNCTIVITIS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MAJOR BASIC-PROTEIN; GIANT PAPILLARY CONJUNCTIVITIS; CROMOLYN SODIUM; OCULAR ALLERGY AB A multicenter, randomized, double-masked, parallel-group study compared the long-term efficacy and safety of lodoxamide 0.1% ophthalmic solution and placebo in 118 patients with vernal keratoconjunctivitis. The test drugs were instilled four times daily for 90 days. Lodoxamide 0.1% ophthalmic solution was significantly (P <.05) more effective than placebo in lowering severity scores for epithelial disease and corneal staining, evidence of the superior efficacy of lodoxamide 0.1% ophthalmic solution in reversing the corneal complications commonly associated with moderate to severe vernal keratoconjunctivitis. Additionally, lodoxamide 0.1% ophthalmic solution ameliorated the other key signs of vernal keratoconjunctivitis, including upper tarsal papillae, limbal signs (papillae, hyperemia, and Trantas' dots), and conjunctival discharge. The between-group differences in the relief of symptoms (itching, tearing, and photophobia) were clinically significant but not always statistically significant. Treatment-related adverse events were reported with similar frequency in both treatment groups, and none were serious. C1 UNIV PUERTO RICO,SCH MED,RIO PIEDRAS,PR 00931. BASCOM PALMER EYE INST,MIAMI,FL 33136. OPHTHALM RES ASSOCIATES,N ANDOVER,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. SCRIPPS CLIN MED GRP INC,LA JOLLA,CA. SW MED CTR DALLAS,DALLAS,TX. NR 23 TC 32 Z9 33 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR 15 PY 1994 VL 117 IS 4 BP 488 EP 497 PG 10 WC Ophthalmology SC Ophthalmology GA NE866 UT WOS:A1994NE86600009 PM 8154531 ER PT J AU YOUNG, LHY EGAN, KM WALSH, SM GRAGOUDAS, ES AF YOUNG, LHY EGAN, KM WALSH, SM GRAGOUDAS, ES TI FAMILIAL UVEAL MELANOMA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MALIGNANT-MELANOMA; SURVIVAL; EYE AB Because familial occurrences of uveal melanoma are rare, there have only been 15 cases of familial melanoma reported in the literature. We studied 11 additional families with a total of 24 members, in which two or more members were afflicted with uveal melanoma. The median age at diagnosis was 56.5 years, similar to the median age at diagnosis of the remaining patients treated in our institution. Thirteen were male and 11 were female, which is consistent with the slight predominance of males found in many large surveys of patients with uveal melanoma. There is a possibility of a heritable component present in these families. RP YOUNG, LHY (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 34 TC 20 Z9 20 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR 15 PY 1994 VL 117 IS 4 BP 516 EP 520 PG 5 WC Ophthalmology SC Ophthalmology GA NE866 UT WOS:A1994NE86600014 PM 8154536 ER PT J AU ROBIN, SB EPSTEIN, RJ KORNMEHL, EW AF ROBIN, SB EPSTEIN, RJ KORNMEHL, EW TI BAND-SHAPED, WHORLED MICROCYSTIC CORNEAL-DYSTROPHY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT OPHTHALMOL,CHICAGO,IL 60612. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 1 TC 14 Z9 13 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR 15 PY 1994 VL 117 IS 4 BP 543 EP 544 PG 2 WC Ophthalmology SC Ophthalmology GA NE866 UT WOS:A1994NE86600024 PM 8154546 ER PT J AU STEELE, RM SCHUNA, AA SCHREIBER, RT AF STEELE, RM SCHUNA, AA SCHREIBER, RT TI CALCIUM ANTAGONIST-INDUCED GINGIVAL HYPERPLASIA SO ANNALS OF INTERNAL MEDICINE LA English DT Note ID NIFEDIPINE; OVERGROWTH C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP STEELE, RM (reprint author), COOK CTY HOSP,DEPT PHARM,1900 W POLK,SUITE 552,CHICAGO,IL 60612, USA. NR 10 TC 32 Z9 34 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 1994 VL 120 IS 8 BP 663 EP 664 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NE850 UT WOS:A1994NE85000006 PM 8135450 ER PT J AU CARR, PL KAZIS, LE MOSKOWITZ, MA AF CARR, PL KAZIS, LE MOSKOWITZ, MA TI REWARDING WOMEN IN ACADEMIC MEDICINE - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. RP CARR, PL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 1994 VL 120 IS 8 BP 698 EP 698 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NE850 UT WOS:A1994NE85000032 ER PT J AU BESSALLE, R DANDREA, A FASMAN, G AF BESSALLE, R DANDREA, A FASMAN, G TI REFOLDING OF THE ISOLATED EXTRACELLULAR DOMAIN OF THE ERYTHROPOIETIN RECEPTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID VIRUS GP55 GLYCOPROTEIN; LIGAND-BINDING; ACTIVATION; EXPRESSION; CLONING AB Refolding of the soluble recombinant binding-active extracellular domain of the murine erythropoietin receptor (sEPO-R) was achieved with greater than 90% recovery either from urea/NaCl (1.5/0.5 M) or guanidine HCl (1 M). An expression plasmid encoding the extracellular plasma region of the human EPO-R (sEPO-R) was transfected into COS cells, and the sEPO-R so produced was labelled with [S-35]methionine and purified by EPO-affinity chromatography on a EAH-Sepharose 4B-EPO column. Rapid rates of refolding were required for recovery of the native proteins. Refolding was evaluated by rebinding of the sEPO-R to the EPO affinity column. (C) 1994 Academic Press, Inc. C1 BRANDEIS UNIV,GRAD DEPT BIOCHEM,WALTHAM,MA 02154. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 15 PY 1994 VL 200 IS 1 BP 482 EP 488 DI 10.1006/bbrc.1994.1474 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NG387 UT WOS:A1994NG38700069 PM 8166722 ER PT J AU LENHARD, RE KALISH, LA OKEN, MM ETTINGER, DS GLICK, J AF LENHARD, RE KALISH, LA OKEN, MM ETTINGER, DS GLICK, J TI TIMED-SEQUENTIAL HIGH-DOSE CYCLOPHOSPHAMIDE AND VINCRISTINE IN THE TREATMENT OF MULTIPLE-MYELOMA SO CANCER LA English DT Article DE MULTIPLE MYELOMA; CYCLOPHOSPHAMIDE; VINCRISTINE; TIME SEQUENTIAL TREATMENT AB Background. This study was designed to examine the efficacy and toxicity of high-dose cyclophosphamide (CY), and to evaluate the potential added effect of vincristine (VCR) given at a theoretic time of malignant cell stimulation in a group of patients with multiple myeloma, refractory to or relapsing after, treatment with standard doses of chemotherapy. Methods. Patients were randomly assigned to receive CY 2400 mg per M(2) as a single-day dose and VCR 1.4 mg per M(2) given on Day 1 or Day 9 after the CY. Results. There were 108 cases suitable for analysis. No difference in objective response (17.6%, 23.5%), subjective response, remission duration, or survival was observed in the two treatment arms. Conclusions. The authors conclude that a single, high dose of cyclophosphamide is more toxic and provides equal or less response than the equivalent dose given over 4 consecutive days and that no improved effect was detected using timed-sequential therapy with VCR. C1 DANA FARBER CANC INST,BOSTON,MA. VIRGINIA PIPER CANC INST,MINNEAPOLIS,MN. NW UNIV MED CTR,CHICAGO,IL. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. RP LENHARD, RE (reprint author), JOHNS HOPKINS UNIV,CTR ONCOL,SUITE 304,550 N BROADWAY,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CA 16116, CA 23318, CA 17145] NR 19 TC 4 Z9 4 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 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1994 VL 73 IS 8 BP 2113 EP 2118 DI 10.1002/1097-0142(19940415)73:8<2113::AID-CNCR2820730816>3.0.CO;2-3 PG 6 WC Oncology SC Oncology GA NF160 UT WOS:A1994NF16000015 PM 8156516 ER PT J AU CHAUHAN, D KHARBANDA, SM UCHIYAMA, H SUKHATME, VP KUFE, DW ANDERSON, KC AF CHAUHAN, D KHARBANDA, SM UCHIYAMA, H SUKHATME, VP KUFE, DW ANDERSON, KC TI INVOLVEMENT OF SERUM RESPONSE ELEMENT IN OKADAIC ACID-INDUCED EGR-1 TRANSCRIPTION IN HUMAN T-CELLS SO CANCER RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; NORMAL HUMAN-LYMPHOCYTES; IMMEDIATE-EARLY GENES; FINGER-ENCODING GENE; SWISS 3T3 CELLS; GROWTH-FACTOR; PROTEIN PHOSPHATASES; TUMOR PROMOTER; C-MYC; ANTIGEN RECEPTOR AB The present work has examined the effects of okadaic acid, an inhibitor of serine/threonine protein phosphatases, PP-1 and PP-2A, on the regulation of EGR-1 gene expression in normal peripheral blood T- and Jurkat cells. The results demonstrate that okadaic acid treatment is associated with a transient induction of EGR-1 gene expression which was detectable by 30 min to 1 h and peaked at 3-6 h. EGR-1 mRNA was superinduced in cells treated with both okadaic acid and the protein synthesis inhibitor cycloheximide. The half-life of EGR-1 mRNA was similar in both control and okadaic acid-treated cells. In contrast, treatment with both okadaic acid and cycloheximide prolonged the half-life of EGR-1 transcripts. Nuclear run-on assays demonstrated that induction of EGR-1 gene expression by okadaic acid is controlled at least in part by a transcriptional mechanism. Transient expression assays with EGR-1 promotor fragments linked to the chloramphenicol acetyltransferase gene demonstrate that okadaic acid-induced EGR-1 transcription is conferred by the 5' most distal CArG box, CC (AT)(6)GG, in the EGR-1 promoter. Moreover, chloramphenicol acetyltransferase activity was induced by okadaic acid when the 5' most distal CArG element was linked to the heterologous herpes simplex virus thymidine kinase promoter, and not induced with a similar heterologous construct containing a mutated CArG sequence. These studies demonstrate that okadaic acid regulates EGR-1 gene expression at the transcriptional level via the CArG element and suggest that PP-1 and PP-2A play a role in T-cell activation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOL DIV,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV NEPHROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 19589, CA 50947] NR 57 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1994 VL 54 IS 8 BP 2234 EP 2239 PG 6 WC Oncology SC Oncology GA NE849 UT WOS:A1994NE84900034 PM 8174132 ER PT J AU AMBROSINO, DM WANG, M CIAMARRA, A CHAN, M BOLON, DL MINN, J JACOBSOHN, DA FINBERG, RW AF AMBROSINO, DM WANG, M CIAMARRA, A CHAN, M BOLON, DL MINN, J JACOBSOHN, DA FINBERG, RW TI T-CELLS AND NATURAL-KILLER-CELLS REGULATE HUMAN-IGG SUBCLASS CONCENTRATIONS IN SCID MICE SO CELLULAR IMMUNOLOGY LA English DT Article ID IMPAIRED ANTIBODY-RESPONSE; STIMULATORY FACTOR-I; INTERFERON-GAMMA; POKEWEED MITOGEN; B-CELLS; BLOOD LYMPHOCYTES; IFN-GAMMA; POLYSACCHARIDE; CHILDREN; DIFFERENTIATION AB Cytokine regulation of human IgG subclass production is not well understood. Since T cells and natural killer (NK) cells produce IL-4 and/or IFN-gamma, we examined the effect of these cells on human IgG subclass concentration in reconstituted severe combined immunodeficient (SCID) mice. SCID mice receiving only B-cell-enriched splenocyte preparations had significantly decreased IgG concentrations and significantly decreased IgG1/IgG2 ratios compared to mice receiving B cells plus T cells (P = 0.02). IgG2 represented 58% of the total IgG at 28 days in mice receiving B-cell-enriched preparations compared to 19% of the total for the group receiving both B cells and T cells (P = 0.013). The effect of natural killer cells (CD16(+)) on IgG subclass was also studied in this model. IgG2 concentrations were twofold higher in mice receiving CD16-depleted cells compared to controls (P = 0.004). No significant differences were noted for IgG1, IgG3, or IgG4 subclass concentrations. In conclusion, T cells and natural killer cells influence human IgG subclass regulation in the SCID mouse model. We propose that the regulation of human IgG subclass production can be further examined in the SCID model. (C) 1994 Academic Press, tnc. RP AMBROSINO, DM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI29623] NR 31 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 15 PY 1994 VL 155 IS 1 BP 134 EP 143 DI 10.1006/cimm.1994.1107 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NH461 UT WOS:A1994NH46100011 PM 7909497 ER PT J AU PINTO, VB ROCK, KL AF PINTO, VB ROCK, KL TI EXTRACELLULAR MATRIX-INDUCED STIMULATION OF A CD4(-)8(-) THYMIC T-CELL LINE SO CELLULAR IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; IMMATURE THYMOCYTES; LYMPHOCYTES-T; DIFFERENTIATION; FIBRONECTIN; IDENTIFICATION; PROLIFERATION; MICE; EXPRESSION; DEFICIENT AB PBK101 was a thymic T cell line of AKR/J origin that expressed Thy I, CD44, IL-2R, and VLA-4 antigens but not CD4, CD8, or the TCR/CD3 complex. PBK101 was initially isolated growing together with adherent thymic stromal cells. The proliferation of PBK101 ceased when it was cultured in the absence of stromal cells and its proliferation was stimulated when stromal cells were added back to the culture. PBK101 cells were also stimulated when cocultured with peritoneal exudate cells (PEC). These responses appeared to require contact between PBK101 and the cellular stimulators. The stimulatory activity of the thymic stromal cell line remained in culture wells after the cellular elements were removed by mild trypsinization or detergent extraction indicating that a stimulatory molecule(s) was associated with extracellular matrix (ECM). The activity of the ECM was resistant to high salt extraction, acetic acid, and strong denaturants but was sensitive to treatment with trypsin, heat (80 degrees C), and, if cells were treated with a lathyragen, 4 M guanidine-HCl plus 2 mM dithiothreitol (DTT). The extracellular matrix produced by some other fibroblast cell lines was nonstimulatory. Stimulation of PBK101 by ECM was not inhibited by monoclonal anti-VLA4 or polyclonal anti-fibronectin antisera. Purified extracellular matrix proteins (laminin, collagen, fibronectin, and vitronectin) were either nonstimulatory or only marginally stimulated PBK101 cells. These results suggested that a potentially novel molecule(s) present in the extracellular matrix of a thymic stromal cell line and on the surface of other cellular elements stimulated a thymic T cell line of immature phenotype. The potential role of extracellular matrix-associated molecules in normal T cell development is discussed. (C) 1994 Academic Press, Inc. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA55233] NR 36 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 15 PY 1994 VL 155 IS 1 BP 144 EP 155 DI 10.1006/cimm.1994.1108 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NH461 UT WOS:A1994NH46100012 PM 8168142 ER PT J AU ECKNER, R EWEN, ME NEWSOME, D GERDES, M DECAPRIO, JA LAWRENCE, JB LIVINGSTON, DM AF ECKNER, R EWEN, ME NEWSOME, D GERDES, M DECAPRIO, JA LAWRENCE, JB LIVINGSTON, DM TI MOLECULAR-CLONING AND FUNCTIONAL ANAL OF THE ADENOVIRUS E1A-ASSOCIATED 300-KD PROTEIN (P300) REVEALS A PROTEIN WITH PROPERTIES OF A TRANSCRIPTIONAL ADAPTER SO GENES & DEVELOPMENT LA English DT Article DE P300; TRANSCRIPTIONAL ADAPTER PROTEIN; E1A-BINDING PROTEIN; CELL CYCLE REGULATORY PROTEIN ID E1A PROTEINS; CELL-CYCLE; DROSOPHILA-TRITHORAX; TERMINAL REGION; ACUTE LEUKEMIAS; DNA-SYNTHESIS; GENE; DOMAINS; REPRESSION; EXPRESSION AB The growth-controlling functions of the adenovirus E1A oncoprotein depend on its ability to interact with a set of cellular proteins. Among these are the retinoblastoma protein, p107, p130, and p300. We have isolated a cDNA encoding full-length human p300 and mapped the chromosomal location of the gene to chromosome 22q13. p300 contains three cysteine- and histidine-rich regions of which the most carboxy-terminal region interacts specifically with E1A. In its center, p300 contains a bromodomain, a hallmark of certain transcriptional coactivators. We have examined the ability of p300 to overcome the repressive effect of E1A on the SV40 enhancer. We show that p300 molecules lacking an intact E1A-binding site can bypass E1A repression and restore to a significant extent the activity of the SV40 enhancer, even in the presence of high levels of E1A protein. These results imply that p300 may function as a transcriptional adaptor protein for certain complex transcriptional regulatory elements. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,DEPT CELL BIOL,WORCESTER,MA 01655. RP ECKNER, R (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 72 TC 864 Z9 873 U1 1 U2 13 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1994 VL 8 IS 8 BP 869 EP 884 DI 10.1101/gad.8.8.869 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NK756 UT WOS:A1994NK75600001 PM 7523245 ER PT J AU GERECKE, DR WAGMAN, DW CHAMPLIAUD, MF BURGESON, RE AF GERECKE, DR WAGMAN, DW CHAMPLIAUD, MF BURGESON, RE TI THE COMPLETE PRIMARY STRUCTURE FOR A NOVEL LAMININ CHAIN, THE LAMININ-B1K CHAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID SEQUENCE; A-CHAIN; CLEAVAGE SITES; CELL-ADHESION; HEART LAMININ; PROTEIN; IDENTIFICATION; DOMAINS; VARIANT; SIGNAL AB We have isolated overlapping cDNA clones encoding the entire kalinin B1 chain. The predicted sequences are consistent with the models proposed for the structure of this chain as a truncated homologue of the B1 chain of laminin. The percent sequence homology with other laminin B1 chains is relatively low, suggesting that this chain is functionally different. The sequence of the VI domain of this chain is consistent with the possibility that it serves to bind specifically the kalinin A chain and subsequently covalently binds to it. In keeping with the accepted nomenclature for the laminin chains we name this novel polypeptide the laminin B1k chain. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BLDG 149,13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. FU NIAMS NIH HHS [AR35689, AR07098] NR 39 TC 122 Z9 123 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1994 VL 269 IS 15 BP 11073 EP 11080 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF966 UT WOS:A1994NF96600019 PM 7512558 ER PT J AU CANTIELLO, HF PRAT, AG REISIN, IL ERCOLE, LB ABRAHAM, EH AMARA, JF GREGORY, RJ AUSIELLO, DA AF CANTIELLO, HF PRAT, AG REISIN, IL ERCOLE, LB ABRAHAM, EH AMARA, JF GREGORY, RJ AUSIELLO, DA TI EXTERNAL ATP AND ITS ANALOGS ACTIVATE THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR BY A CYCLIC AMP-INDEPENDENT MECHANISM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AIRWAY EPITHELIAL-CELLS; EXTRACELLULAR ATP; CHANNELS; BINDING; PROTEINS; CL AB The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel activated by protein kinase A and regulated by ATP in a complex manner. We have applied patch-clamp techniques to C127i mouse mammary carcinoma cells transfected with human CFTR to assess the role of external ATP in the modulation of CFTR function. Extracellular ATP was sufficient to activate non-rectifying, Cl-selective whole-cell currents in CFTR-transfected, but not mock-transfected cells. The ATP-mediated activation of CFTR was independent of protein kinase A since channel activation by ATP was preserved in cells that were (a) depleted of intracellular ATP, (b) incubated with the cAMP antagonist R(p)-cAMPS, or (c) exposed to the protein kinase A inhibitor, 5-24 amide. In each of these conditions, 8-Br-cAMP was no longer capable of activating CFTR. The possibility that the extracellular ATP activation of Cl- currents in CFTR-expressing C127i cells was mediated by a P2-type purinergic receptor was supported by studies in which the effect of external ATP on the Cl- currents was mimicked by the ATP analogs, ATP-gammaS and beta,gamma-methylene ATP, but not the uridine nucleotide, UTP. Single-channel analysis of ATP-activated Cl- currents under both cell-attached and excised, inside-out patch-clamp configurations indicated that this channel is only present in CFTR-transfected cells and indistinguishable from CFTR. External ATP also activated ATP currents in CFTR-transfected cells, a novel function of CFTR. These findings are consistent with the presence of a purinergic receptor signal transduction mechanism in C127i cells whose activation by external ATP is linked to the activation of CFTR in a cAMP-independent manner. The. data provide additional support for the use of ATP and its analogs as alternative therapies in cystic fibrosis. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. GENZYME CORP,FRAMINGHAM,MA 01701. NR 23 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1994 VL 269 IS 15 BP 11224 EP 11232 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF966 UT WOS:A1994NF96600040 PM 7512560 ER PT J AU FINI, ME STRISSEL, KJ GIRARD, MT MAYS, JW RINEHART, WB AF FINI, ME STRISSEL, KJ GIRARD, MT MAYS, JW RINEHART, WB TI INTERLEUKIN-1-ALPHA MEDIATES COLLAGENASE SYNTHESIS STIMULATED BY PHORBOL 12-MYRISTATE 13-ACETATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNOVIAL CELL COLLAGENASE; MESSENGER-RNA; METALLOPROTEINASE EXPRESSION; RECEPTOR ANTAGONIST; SIGNAL TRANSDUCTION; FIBROBLASTS; GENE; STROMELYSIN; MATRIX; JUN AB Stimulation of collagenase expression in cultures of normal diploid fibroblasts by the tumor promotor phorbol 12-myristate 13-acetate (PMA) occurs secondarily to synthesis of unknown intermediary proteins. We have investigated the hypothesis that a form of the cytokine interleukin 1 (IL-1) is one intermediate controlling PMA-stimulated collagenase expression. Treatment with an IL-1 receptor antagonist inhibits the constitutive synthesis of collagenase in early passage fibroblast cultures from rabbit. Radioimmunoassay demonstrates that, of the two known IL-1 forms, IL-1alpha and IL-1beta, only IL-1alpha is synthesized and released into the medium of corneal fibroblast cultures. PMA treatment of cells increases the level of IL-1alpha mRNA; this occurs prior to the increase in collagenase mRNA and corresponds with increased synthesis and release of IL-1alpha protein. Neutralizing antiserum to EL-1alpha inhibits constitutive collagenase synthesis. Reagents that inhibit the activity of IL-1alpha (IL-1 receptor antagonist or neutralizing antibody) also inhibit the PMA-mediated stimulation of collagenase synthesis. These results indicate that constitutive and PMA-stimulated expression of collagenase is regulated through an IL-1alpha intermediate. In vivo, regulation of the lytic phase of tissue remodeling through the IL-1alpha intermediate may ensure the recruitment of cells adjacent to the one that received the initial stimulus. C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02129. RP FINI, ME (reprint author), MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,13TH ST,BOSTON,MA 02129, USA. FU NEI NIH HHS [R01-EY08408, R01-EY09828]; NIAMS NIH HHS [T32-AR07098] NR 53 TC 68 Z9 68 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1994 VL 269 IS 15 BP 11291 EP 11298 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF966 UT WOS:A1994NF96600050 PM 8157661 ER PT J AU SANZ, I WANG, SS MENESES, G FISCHBACH, M AF SANZ, I WANG, SS MENESES, G FISCHBACH, M TI MOLECULAR CHARACTERIZATION OF HUMAN IG HEAVY-CHAIN DIR GENES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; B-CELL DEVELOPMENT; D-MU PROTEIN; DIVERSITY; SEGMENT; RECOMBINATION; REARRANGEMENT; AUTOANTIBODIES; SEQUENCE; VH AB Antibody VDJ recombination is ensured by evolutionarily conserved recombination signals (RS). The 12/23 rule postulates that only gene segments with asymmetrically spaced RS recombine with one another. Two unusually long D genes (170 bp) with irregular RS (DIR) have been reported in humans and have been postulated to participate actively in VDJ recombination, thus frequently contributing to the Ab heavy chain third hypervariable region (CDR3). However, the limited sequence information retained in the CDR3 along with significant sequence diversity has precluded an accurate assessment of the actual role and genomic diversity of DIR genes. Furthermore, DIR genes pose an interesting puzzle in terms of their precise mechanism of recombination because they possess multiple and imperfect RS, often located up to 30 bp away from the recombining fragment within the DIR coding region. Here we present conclusive evidence for the existence of additional human germ-line DIR genes and preliminary evidence that suggests the absence of DIR-like sequences in nonprimate animals. We also show that DIR genes are under the transcriptional control of V-H-independent promoters and have the potential to encode a D mu protein of 105 amino acids. Finally, DIR genes seem at least in early fetal life to recombine preferentially through the conventional 3' RS. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP SANZ, I (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIAID NIH HHS [AI-29003] NR 27 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1994 VL 152 IS 8 BP 3958 EP 3969 PG 12 WC Immunology SC Immunology GA NF018 UT WOS:A1994NF01800027 PM 8144963 ER PT J AU SCHECHTER, NM WANG, ZM BLACHER, RW LESSIN, SR LAZARUS, GS RUBIN, H AF SCHECHTER, NM WANG, ZM BLACHER, RW LESSIN, SR LAZARUS, GS RUBIN, H TI DETERMINATION OF THE PRIMARY STRUCTURES OF HUMAN SKIN CHYMASE AND CATHEPSIN-G FROM CUTANEOUS MAST-CELLS OF URTICARIA PIGMENTOSA LESIONS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEUTROPHIL ELASTASE GENE; AMINO-ACID-SEQUENCE; MOLECULAR-CLONING; SERINE PROTEASE; NUCLEOTIDE-SEQUENCE; ANGIOTENSIN-II; HUMAN HEART; MCTC TYPE; HUMAN-T; MOUSE AB This study establishes the primary structure of human skin chymase and provides further evidence for the presence of a cathepsin G-like proteinase within human mast cells. The amino acid sequence of human skin chymase was established by protein methods and by analysis of PCR amplification products obtained with cDNA-derived from urticaria pigmentosa (UP) lesions. UP is a disease characterized by skin lesions containing high numbers of mast cells. Proteolytic digests of human chymase purified from normal skin yielded 10 resolvable peptides that were sequenced by automated Edman degradation. The amino acid sequences for these peptides combined with the sequence obtained for the protein's NH2-terminal region (35 residues) accounted for 137 residues of the human skin chymase sequence. This partial amino acid sequence corresponded to the sequence of human heart chymase, a proteinase isolated from heart tissue with immunologic and hydrolytic properties similar to skin chymase. PCR amplification of UP-derived cDNA with primers based on the cDNA structure of heart chymase demonstrated a single amplification product of expected size which was subcloned and sequenced. The amino acid sequence (135 residues) deduced from this product was identical to that of heart chymase in the region between the primers. This sequence, along with that established for the purified protein, constituted 99% of the heart chymase primary structure, strongly indicating that human skin and heart chymases have identical primary structures. Amplification of the same UP-cDNA with primers coding for the NH2- and COOH-terminal sequences of human neutrophil cathepsin G also produced a specific amplification product which was sequenced. The deduced amino acid sequence between the primers was identical to that reported for neutrophil cathepsin G, indicating that the protein of cutaneous mast cells previously shown to be immunologically cross-reactive with neutrophil cathepsin G has a comparable amino acid sequence. UP-cDNA demonstrating amplification products for cathepsin G did not demonstrate amplification products for human neutrophil elastase, suggesting that the cathepsin G PCR amplification product was not derived from neutrophils or monocytes possibly contaminating the lesion. These studies provide further evidence that human skin mast cells contain two different chymotrypsin-like proteinases. C1 UNIV PENN,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. PHILADELPHIA VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. ATHENA NEUROSCI INC,S SAN FRANCISCO,CA 94080. RP SCHECHTER, NM (reprint author), UNIV PENN,DEPT DERMATOL,CLIN RES BLDG,422 CURIE BLVD,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA55071]; NIAMS NIH HHS [AR39647] NR 43 TC 30 Z9 33 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1994 VL 152 IS 8 BP 4062 EP 4069 PG 8 WC Immunology SC Immunology GA NF018 UT WOS:A1994NF01800038 PM 8144971 ER PT J AU PAKZABAN, P CHIOCCA, EA AF PAKZABAN, P CHIOCCA, EA TI NERVE GROWTH-FACTOR PROTECTS AGAINST HERPES-SIMPLEX VIRUS TYPE-1 NEUROTOXICITY IN THE RAT STRIATUM SO NEUROREPORT LA English DT Article DE NERVE GROWTH FACTOR; HERPES SIMPLEX VIRUS TYPE 1; TOXICITY; NEUROPROTECTION; BRAIN; STRIATUM; RAT ID NEURONS; CELLS; ENCEPHALITIS; HYPERTROPHY; NEOSTRIATUM; INVITRO; MUTANTS; NGF AB To determine the effect of nerve growth factor (NGF) on the neurotoxicity of herpes simplex virus type 1 (HSV-1) in vivo, direct intrastriatal injection of HSV-1 in rats was followed by continuous intracerebral infusion of NGF or vehicle solution for 7 days. The mean volume of HSV-1-mediated brain tissue destruction in NGF-treated animals was significantly smaller than that in vehicle-treated animals at 1 week. Immunohistochemical staining for HSV-1 confirmed the presence of cells harboring the virus at the primary site of injection and at secondary sites of distant spread, with no significant difference in HSV-1 distribution between NGF- and vehicle-treated animals. We conclude that intrastriatal infusion of NGF locally protects against HSV-1-mediated neurolysis, but does not affect HSV-1 dissemination in the brain. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SERV NEUROSURG,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02129. FU NINDS NIH HHS [NINDS 5T32 NS 07340, NINDS NS 24279-08] NR 25 TC 10 Z9 10 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 14 PY 1994 VL 5 IS 8 BP 993 EP 996 DI 10.1097/00001756-199404000-00035 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NK709 UT WOS:A1994NK70900035 PM 8061311 ER PT J AU ELAHI, D MCALOONDYKE, M FUKAGAWA, NK MENEILLY, GS SCLATER, AL MINAKER, KL HABENER, JF ANDERSEN, DK AF ELAHI, D MCALOONDYKE, M FUKAGAWA, NK MENEILLY, GS SCLATER, AL MINAKER, KL HABENER, JF ANDERSEN, DK TI THE INSULINOTROPIC ACTIONS OF GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE (GIP) AND GLUCAGON-LIKE PEPTIDE-1(7-37) IN NORMAL AND DIABETIC SUBJECTS SO REGULATORY PEPTIDES LA English DT Article DE INCRETIN; INSULINOTROPIC; GIP; GLP-1(7-37); DIABETES; HEPATIC GLUCOSE PRODUCTION ID GASTRIC INHIBITORY POLYPEPTIDE; PERFUSED RAT PANCREAS; PREPROGLUCAGON GENE; SECRETION; SEQUENCE AB Despite similar glycemic profiles, higher insulin levels are achieved following oral versus intravenous administration of glucose. This discrepancy is due to the incretin effect and is believed to be mediated via stimulation of beta-cells by hormone(s) released from the gut. The leading gut hormone candidates are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1). To determine the relative insulinotropic activity of these peptides, we infused GLP-1(7-37) and GIP into normal subjects and patients with non-insulin dependent diabetes mellitus (NIDDM). In normal subjects during euglycemia, GLP-1(7-37) stimulated insulin release, whereas GIP did not. Using the Andres clamp technique, we established stable hyperglycemia for 2 h (5.4 mmol/l above the basal level). During the second hour, either GIP, GLP-1(7-37), or both were infused in normal healthy volunteers and in patients with NIDDM. In normal subjects, at a glucose level of 10.4 mmol/l, the 90-120 min insulin response was 279 pmol/l. GIP at a dose of 1, 2 or 4 pmol/kg/min augmented the 90-120 min insulin response by 69, 841 and 920 pmol/l, while GLP-1(7-37), at a dose of 1.5 pmol/kg/min augmented the insulin response by 2106 pmol/l. When both hormones were administered simultaneously, the augmentation was additive - 2813 pmol/l. In the diabetic subjects, GIP had no effect, while GLP-1(7-37) augmented the insulin response by 929 pmol/l. We conclude that in normal healthy subjects, GLP-1(7-37), on a molar basis, is several times more potent than GIP at equivalent glycemic conditions. The additive insulinotropic effect suggests that more than one incretin may be responsible for the greater insulin levels observed following oral administration of glucose compared to the intravenous route. In NIDDM, GIP had no insulinotropic effect, while GLP-1(7-37) had a marked effect. This suggests that GLP-1(7-37) may have therapeutic potential as a hypoglycemic agent in NIDDM patients. C1 UNIV BRITISH COLUMBIA,DEPT MED,VANCOUVER,BC,CANADA. MASSACHUSETTS GEN HOSP,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. UNIV CHICAGO,PRITZKER SCH MED,DEPT SURG,CHICAGO,IL 60637. UNIV CHICAGO,PRITZKER SCH MED,DEPT MED,CHICAGO,IL 60637. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,CHARLES A DANA RES INST,THORNDIKE LAB,DIV GERONTO,BOSTON,MA 02215. FU NIA NIH HHS [AG-00599, AG-08812]; NIDDK NIH HHS [DK-30834] NR 30 TC 211 Z9 216 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD APR 14 PY 1994 VL 51 IS 1 BP 63 EP 74 DI 10.1016/0167-0115(94)90136-8 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA NH561 UT WOS:A1994NH56100008 PM 8036284 ER PT J AU LOWE, HJ BARNETT, GO AF LOWE, HJ BARNETT, GO TI UNDERSTANDING AND USING THE MEDICAL SUBJECT-HEADINGS (MESH) VOCABULARY TO PERFORM LITERATURE SEARCHES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID END-USER; MEDLINE; INFORMATION; RETRIEVAL; STUDENTS; EDUCATION; SYSTEMS; ACCESS AB The United States National Library of Medicine's (NLM) MEDLINE database is the largest and most widely used medical bibliographic database. MEDLINE is manually indexed with NLM's Medical Subject Headings (MeSH) vocabulary. Using MeSH, a searcher can potentially create powerful and unambiguous MEDLINE queries. This article reviews the structure and use of MeSH, directed toward the nonexpert, and outlines how MeSH may help resolve a number of common difficulties encountered when searching MEDLINE. The increasing importance of the MEDLINE database as an information resource and the trend toward individuals performing their own bibliographic searches makes it crucial that health care professionals become familiar with MeSH. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,COMP SCI LAB,BOSTON,MA 02114. NR 44 TC 193 Z9 198 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 13 PY 1994 VL 271 IS 14 BP 1103 EP 1108 DI 10.1001/jama.271.14.1103 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NE228 UT WOS:A1994NE22800033 PM 8151853 ER PT J AU TANAKA, T DUKECOHAN, JS KAMEOKA, J YARON, A LEE, I SCHLOSSMAN, SF MORIMOTO, C AF TANAKA, T DUKECOHAN, JS KAMEOKA, J YARON, A LEE, I SCHLOSSMAN, SF MORIMOTO, C TI ENHANCEMENT OF ANTIGEN-INDUCED T-CELL PROLIFERATION BY SOLUBLE CD26 DIPEPTIDYL PEPTIDASE-IV SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL-MEDIATED IMMUNITY; COSTIMULATION; MEMORY T-CELLS ID LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; ACTIVATION; RECEPTOR; SURFACE; EXPRESSION; MOLECULE; COMPLEX; FAMILY; SIGNAL AB The addition of a soluble recombinant CD26 (sCD26) enhanced proliferation of peripheral blood lymphocytes induced by the recall antigen tetanus toxoid. sCD26 itself did not provide a mitogenic signal and did not augment the proliferative response of T cells to other mitogenic stimuli such as phytohemagglutinin and anti-CD3. Dipeptidyl peptidase IV-negative sCD26 did not have this enhancement effect, implying a requirement for enzyme activity. It was found that there exists a large variation in the levels of human plasma sCD26/dipeptidyl peptidase IV in vivo which may regulate T-cell activity. Peripheral blood lymphocytes from individuals whose plasma sCD26 was high and responded strongly to tetanus toxoid stimulation were insensitive to the enhancing effects of exogenously added sCD26. This suggests that plasma sCD26 had modulated the responsiveness of T cells of these individuals in vivo and that the endogenous plasma sCD26 regulates immune responses by allowing antigen-specific T cells to exert a maximal response to their specific antigen. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP TANAKA, T (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI12069]; NIAMS NIH HHS [AR33713] NR 32 TC 119 Z9 119 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 1994 VL 91 IS 8 BP 3082 EP 3086 DI 10.1073/pnas.91.8.3082 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NF968 UT WOS:A1994NF96800046 PM 7909158 ER PT J AU HARLAN, DM HENGARTNER, H HUANG, ML KANG, YH ABE, R MOREADITH, RW PIRCHER, H GRAY, GS OHASHI, PS FREEMAN, GJ NADLER, LM JUNE, CH AICHELE, P AF HARLAN, DM HENGARTNER, H HUANG, ML KANG, YH ABE, R MOREADITH, RW PIRCHER, H GRAY, GS OHASHI, PS FREEMAN, GJ NADLER, LM JUNE, CH AICHELE, P TI MICE EXPRESSING BOTH B7-1 AND VIRAL GLYCOPROTEIN ON PANCREATIC BETA-CELLS ALONG WITH GLYCOPROTEIN-SPECIFIC TRANSGENIC T-CELLS DEVELOP DIABETES DUE TO A BREAKDOWN OF T-LYMPHOCYTE UNRESPONSIVENESS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COSTIMULATORY MOLECULE; MONOCLONAL-ANTIBODIES; B-CELLS; CD28; ACTIVATION; INDUCTION; SELECTION; RECEPTOR; ANTIGEN; POPULATIONS AB T lymphocytes have been implicated in the onset of many autoimmune diseases; however, the mechanisms underlying T-cell activation toward self antigens are poorly understood. To study whether T-lymphocyte costimulation can overcome the immunologic unresponsiveness observed in an in vivo model, we have created transgenic mice expressing the costimulatory mouse molecule B7-1, a ligand for the CD28 receptor, on pancreatic beta cells. We now report that triple-transgenic mice expressing both B7-1 and a viral glycoprotein on their beta cells, along with T cells expressing the viral-glycoprotein-specific transgenic T-cell receptor, all develop insulitis (lymphocytic infiltration of the pancreatic islets) and diabetes. In striking contrast, the T cells in double-transgenic mice expressing the same viral glycoprotein (but no B7) on their pancreatic beta cells and the transgenic T-cell receptor on their T cells, reported earlier, remain indifferent to the glycoprotein-expressing beta cells. In fact, all three transgenes are required to initiate immune-mediated destruction of the beta cells. Mice expressing any of the transgenes alone, or any two in combination, maintain normal islet architecture and never spontaneously develop insulitis or diabetes. Our results show that aberrant B7 expression on peripheral tissues may play an important role in the activation of self-reactive T cells and further suggest that abnormal expression of costimulatory receptors may be involved in various T-cell-mediated autoimmune diseases. C1 UNIV ZURICH,DEPT PATHOL,INST EXPTL IMMUNOL,CH-8091 ZURICH,SWITZERLAND. REPLIGEN CORP,CAMBRIDGE,MA 02139. UNIV TEXAS,SW MED CTR,MOLEC CARDIOL LAB,DALLAS,TX 75235. UNIV TORONTO,ONTARIO CANC INST,DEPT MED BIOPHYS & IMMUNOL,TORONTO M4X 1K9,ONTARIO,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP HARLAN, DM (reprint author), USN,MED RES INST,DEPT IMMUNOBIOL,BETHESDA,MD 20889, USA. NR 42 TC 165 Z9 165 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 1994 VL 91 IS 8 BP 3137 EP 3141 DI 10.1073/pnas.91.8.3137 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NF968 UT WOS:A1994NF96800057 PM 7512724 ER PT J AU HALL, SD KOLODNER, RD AF HALL, SD KOLODNER, RD TI HOMOLOGOUS PAIRING AND STRAND EXCHANGE PROMOTED BY THE ESCHERICHIA-COLI RECT PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENETIC RECOMBINATION; RECE PATHWAY; STRAND TRANSFER ID DNA-BINDING PROTEIN; GENETIC-RECOMBINATION; BACTERIOPHAGE-LAMBDA; SACCHAROMYCES-CEREVISIAE; BETA-PROTEIN; EXONUCLEASE-VIII; PLASMID RECOMBINATION; PHAGE-LAMBDA; INTRAMOLECULAR RECOMBINATION; CONJUGATIONAL RECOMBINATION AB RecT protein of Escherichia coli promotes the formation of joint molecules between homologous linear double-stranded M13mp19 replicative-form bacteriophage DNA and circular single-stranded M13mp19 DNA in the presence of exonuclease VIII, the recE gene product. The joint molecules were formed by a mechanism involving the pairing of the complementary strand of the linear double-stranded DNA substrate with the circular single-stranded DNA substrate coupled with the displacement of the noncomplementary strand. When the homologous linear double-stranded DNA substrate had homologous 3' or 5' single-stranded tails, then RecT promoted homologous pairing and strand exchange in the absence of exonuclease VIII. Histone H1 could substitute for RecT protein; however, joint molecules formed in the presence of histone H1 did not undergo strand exchange. These results indicate that under the reaction conditions used, the observed strand exchange reaction is promoted by RecT and is not the result of spontaneous branch migration. These results are consistent with the observation that expression of RecE (exonuclease VIII) and RecT substitutes for RecA in some recombination reactions in E. coli. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM26017] NR 64 TC 62 Z9 63 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 1994 VL 91 IS 8 BP 3205 EP 3209 DI 10.1073/pnas.91.8.3205 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NF968 UT WOS:A1994NF96800071 PM 8159725 ER PT J AU HUTCHCROFT, JE BIERER, BE AF HUTCHCROFT, JE BIERER, BE TI ACTIVATION-DEPENDENT PHOSPHORYLATION OF THE T-LYMPHOCYTE SURFACE-RECEPTOR CD28 AND ASSOCIATED PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SIGNAL TRANSDUCTION; TYROSINE KINASES; COSTIMULATION; TOLERANCE ID CELL ACTIVATION; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; ANTIGEN; LIGATION; PATHWAYS AB CD28 is a costimulatory receptor that can provide the second signal necessary for T-cell activation and function in response to stimulation through the T-cell antigen receptor/CD3 complex. We found that a distinct array of proteins was phosphorylated on tyrosine following stimulation with anti-CD28 monoclonal antibody, as detected by immune-complex kinase assays. Anti-CD28 stimulation of in vitro kinase activity was detergent-dependent, occurring in immune complexes prepared with Brij 96 but not Nonidet P-40. Pretreatment of cells with low concentrations of phorbol ester increased the activation-independent phosphorylation of proteins in CD28 immune complexes. Reimmunoprecipitation studies indicated that the cytoplasmic protein-tyrosine kinases Lck and Fyn were associated with CD28. CD28 itself was phosphorylated both in vitro and in vivo in an activation-dependent manner, as detected by nonreducing/reducing SDS/PAGE analyses. The activation-stimulated phosphorylation of CD28 may play a key role in signaling through this receptor. C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP HUTCHCROFT, JE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [P01 AI35297, 1RO1 AI28554] NR 18 TC 86 Z9 86 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 1994 VL 91 IS 8 BP 3260 EP 3264 DI 10.1073/pnas.91.8.3260 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NF968 UT WOS:A1994NF96800083 PM 7512728 ER PT J AU MORT, EA WEISSMNN, JS EPSTEIN, AM AF MORT, EA WEISSMNN, JS EPSTEIN, AM TI PHYSICIAN DISCRETION AND RACIAL VARIATION IN THE USE OF SURGICAL-PROCEDURES SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CESAREAN-SECTION; UNITED-STATES; HIP FRACTURE; BLACK; RACE; MASSACHUSETTS; HYSTERECTOMY; APPENDICITIS; DIFFERENCE; AMERICANS AB Background: Racial variation in the use of surgical procedures raises concern about equitable access The goal of our study was to examine racial differences in utilization across a broad range of procedures in Massachusetts and to assess whether racial variation is related to physician discretion. Methods: We obtained fiscal year 1988 hospital discharge data for all Massachusetts residents, identified 10 clinically important surgical procedures, and calculated age- and sex-adjusted rate ratios for white and black patients. Level of discretion was determined by using a modified Delphi technique. Results: Whites had higher rates for eight procedures (abdominal aortic aneurysm repair, appendectomy, cardiac valve replacement, carotid endarterectomy, cholecystectomy, lumbar disk procedures, open reduction/ internal fixation of the femur, and tonsillectomy) and lower rates for two procedures, hysterectomy and prostatectomy. Of the eight procedures for which utilization was higher among whites, four were ranked as moderate- or high-discretion procedures and four were ranked as low-discretion procedures. Hysterectomy, the only procedure for which utilization was substantially higher among blacks (white:black rate ratio <0.90), was ranked as a high-discretion procedure. Conclusions: With the exception of hysterectomy and prostatectomy, procedure rates for whites were greater than those for blacks for a wide range of surgical procedures. Racial variation exists for low-discretion procedures as well as for those associated with moderate and high discretion. Variation among low-discretion procedures that is not explained by medical need suggests the possibility of race-related differences in access to care or in the way patients and physicians make clinical decisions. C1 HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MED SERV,GEN INTERNAL MED UNIT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,HLTH SERV & POLICY RES SECT,BOSTON,MA 02115. NR 41 TC 73 Z9 73 U1 3 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 11 PY 1994 VL 154 IS 7 BP 761 EP 767 DI 10.1001/archinte.154.7.761 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NF263 UT WOS:A1994NF26300006 PM 8147680 ER PT J AU MCENTEE, CM CANTWELLIBDAH, R HUDSON, AP AF MCENTEE, CM CANTWELLIBDAH, R HUDSON, AP TI REGULATION OF STRINGENT MITOCHONDRIAL TRANSCRIPTION IN YEAST FOLLOWING AMINO-ACID DEPRIVATION SO GENE LA English DT Note DE STARVATION; CYCLIC AMP; RNA; SACCHAROMYCES CEREVISIAE; PROTEIN KINASE ID DEPENDENT PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; RNA-POLYMERASE; GENE; PHOSPHODIESTERASE; SUBUNIT; CLONING AB In the yeast Saccharomyces cerevisiae, a phenotypically identical stringent response is induced by either nutritional downshift or starvation for a required auxotrophic amino acid (aa); in each case, the response selectively includes transcriptional curtailment for the mitochondrial (mt) genome. We have shown previously that the downshift-induced mt stringent response is governed by changing cellular cyclic AMP (cAMP) levels, via a mt cAMP-dependent protein kinase. In contrast, we demonstrate here that cAMP levels are not altered in yeast following starvation for a required aa, and we use in vitro mt transcription assays with organelles from wild-type and mutant strains to confirm that the aa starvation-induced mt stringent response is not governed by cAMP. Rather, such stringent organellar transcriptional attenuation may result from altered availability of an unidentified small molecule which is probably a product of the cytoplasmic and/or mt protein synthesis systems. C1 DEPT VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 8 PY 1994 VL 141 IS 1 BP 129 EP 132 DI 10.1016/0378-1119(94)90140-6 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA NG425 UT WOS:A1994NG42500021 PM 8163164 ER PT J AU CASE, RD PICCIONE, E WOLF, G BENETT, AM LECHLEIDER, RJ NEEL, BG SHOELSON, SE AF CASE, RD PICCIONE, E WOLF, G BENETT, AM LECHLEIDER, RJ NEEL, BG SHOELSON, SE TI SH-PTP2/SYP SH2 DOMAIN BINDING-SPECIFICITY IS DEFINED BY DIRECT INTERACTIONS WITH PLATELET-DERIVED GROWTH-FACTOR BETA-RECEPTOR, EPIDERMAL GROWTH-FACTOR RECEPTOR, AND INSULIN-RECEPTOR SUBSTRATE-1-DERIVED PHOSPHOPEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL TRANSDUCTION; AUTOPHOSPHORYLATION SITES; EGF RECEPTOR; PROTEIN; KINASE; IDENTIFICATION; SRC AB Signaling by tyrosine kinases involves direct associations between proteins with Src homology 2 (SH2) domains and sites of tyrosine phosphorylation. Specificity in signaling pathways results in part from inherent selectivity in interactions between particular SH2 domains and phosphopeptide sequences. The cytoplasmic phosphotyrosine phosphatase SH-PTP2 (Syp, PTP 1D, PTP-2C) contains two SH2 domains (N and C) which mediate its association with and activation by the platelet-derived growth factor (PDGF) and epidermal growth factor receptors and IRS-1. We have developed a competitive phosphopeptide binding assay to analyze specificity of the SH-PTP2 N-SH2 domain for phosphorylation sites of these phosphoproteins. The sequence surrounding Tyr(1009) bound with greatest affinity (ID50 = 14 mu M) of eight PDGF receptor-derived phosphopeptides tested. No peptides corresponding to known epidermal growth factor receptor phosphorylation sites bound with high affinity. However, an alternative sequence surrounding Tyr(954) bound tightly (ID50 = 21 mu M). Of the 13 IRS-1-related peptides analyzed, sequences surrounding Tyr(546), Tyr(895), and Tyr(1172) bound with highest affinity (ID50 = 11, 4, and 1 mu M, respectively). Alternative phosphopeptides generally bound with much weaker affinity (ID50 > 150 mu M). These findings are consistent with recent mutational analyses of the PDGF receptor and predict site-specific interactions between SH-PTP2 and each of these phosphoproteins. Comparisons between peptide sequences suggest that the N-terminal SH2 domain of SH-PTP2 binds with highest affinity to phosphotyrosine (pY) followed by a beta-branched residue (Val, Ile, Thr) at pY+1 and a hydrophobic residue (Val, Leu, Ile) at pY+3 positions. Peptide truncation studies also indicate that residues outside of the pY-1 to pY+4 motif are required for high affinity interactions. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,MOLEC MED UNIT,BOSTON,MA 02215. FU NIDDK NIH HHS [DK36836] NR 49 TC 129 Z9 130 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 1994 VL 269 IS 14 BP 10467 EP 10474 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF017 UT WOS:A1994NF01700044 PM 8144631 ER PT J AU HANASAKI, K VARKI, A STAMENKOVIC, I BEVILACQUA, MP AF HANASAKI, K VARKI, A STAMENKOVIC, I BEVILACQUA, MP TI CYTOKINE-INDUCED BETA-GALACTOSIDE ALPHA-2,6-SIALYLTRANSFERASE IN HUMAN ENDOTHELIAL-CELLS MEDIATES ALPHA-2,6-SIALYLATION OF ADHESION MOLECULES AND CD22 LIGANDS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE-PHASE RESPONSE; SIALIC-ACID; LINKED OLIGOSACCHARIDES; LEUKOCYTE ADHESION; ALPHA-1-ACID GLYCOPROTEIN; LIQUID-CHROMATOGRAPHY; RAT-LIVER; SIALYLTRANSFERASE; INFLAMMATION; EXPRESSION AB Sialic acids decorating blood and cell surface proteins can play important roles in various biological processes. The inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1, as well as bacterial lipopolysaccharide, can activate vascular endothelium, increasing expression of several surface glycoproteins. Here we show that treatment of cultured human endothelial cells (HEC) with TNF-alpha, interleukin-1, or lipopolysaccharide causes increased expression of the enzyme beta-galactoside alpha-2,6-sialyltransferase (alpha 2-6STN). TNF-alpha was most effective, inducing a 3.5-fold enhancement of cell-associated sialyltransferase activity by 72 h. In addition, activated HEC secreted a large portion of the induced sialyltransferase activity into the medium. Analysis of labeled HEC showed both a relative and an absolute increase of alpha 2,6-linked sialic acid on N-linked oligosaccharides after TNF-alpha stimulation. This coincided with increased expression of endothelial glycoproteins bearing N-linked glycans with alpha 2,6-linked sialic acid detected by the lectin Sambucus nigra agglutinin. The cytokine-inducible endothelial cell adhesion molecules E-selectin, ICAM-1, and VCAM-1 are among these glycoprotein substrates for alpha 2-6STN. These changes also correlated with a substantial increase in binding sites for CD22 beta, a mammalian lectin known to recognize oligosaccharides carrying multiple copies of alpha 2,6-linked sialic acid. Northern analysis revealed increased levels of mRNA encoding alpha 2-6STN. Thus, activation of endothelial cells during in flammatory and immunological processes may induce alpha 2-6STN, which can participate in sialylation of other activation-dependent molecules. C1 UNIV CALIF SAN DIEGO,CTR CANC,DIV CELLULAR & MOLEC MED,GLYCOBIOL PROGRAM,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,HOWARD HUGHES MED INST,LA JOLLA,CA 92093. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. FU NIGMS NIH HHS [R01GM32373] NR 56 TC 109 Z9 111 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 1994 VL 269 IS 14 BP 10637 EP 10643 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF017 UT WOS:A1994NF01700068 PM 8144653 ER PT J AU YUN, HY KEUTMANN, HT EIPPER, BA AF YUN, HY KEUTMANN, HT EIPPER, BA TI ALTERNATIVE SPLICING GOVERNS SULFATION OF TYROSINE OR OLIGOSACCHARIDE ON PEPTIDYLGLYCINE ALPHA-AMIDATING MONOOXYGENASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE DOMAIN; PEPTIDE AMIDATION; MESSENGER-RNA; ATT-20 CELLS; FACTOR-VIII; PROTEIN; FORMS; EXPRESSION; MEMBRANE; SECRETION AB Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the COOH-terminal alpha-amidation of neuroendocrine peptides through the sequential action of monooxygenase and lyase domains contained within this bifunctional protein. Alternative splicing leads to the expression of soluble and integral membrane bifunctional PAM proteins as well as a soluble monofunctional monooxygenase. In order to determine how alternative splicing affects post-translational modification of PAM proteins, we investigated the sulfation of PAM proteins expressed in stably transfected hEK-293 cells. Metabolic labeling with [S-35]SO42- or [S-35]methionine and immunoprecipitation demonstrated that [S-35]SO42- was efficiently incorporated into PAM proteins that have the noncatalytic exon A region following the monooxygenase domain (PAM-1 and PAM-4) and into a soluble bifunctional PAM protein (PAM-3). Alkaline hydrolysis, radiosequencing, and deglycosylation experiments demonstrated the presence of a sulfated tyrosine (Tyr(965)) in the COOH-terminal domain of PAM-3 and multiple sulfated O-glycans in the exon A region of PAM-1 and PAM-4. A mutant PAM-3 protein in which Tyr(965) was changed to Ala(965) (PAM-3/Y965A) was not sulfated and exhibited monooxygenase and lyase activities similar to those of wild type PAM-3. Pulse-chase and temperature block experiments showed that the PAM-3/Y965A protein exits the trans-Golgi network faster than wild type PAM-3. Thus inclusion of exon A results in the sulfation of O-glycans, while elimination of the transmembrane domain results in the sulfation of Tyr(965). C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. FU NIDA NIH HHS [DA-00098]; NIDDK NIH HHS [DK-32949] NR 49 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 1994 VL 269 IS 14 BP 10946 EP 10955 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NF017 UT WOS:A1994NF01700110 PM 8144680 ER PT J AU LAMURAGLIA, GM MCLOUD, TC MARK, EJ KAZEMI, H AF LAMURAGLIA, GM MCLOUD, TC MARK, EJ KAZEMI, H TI A 54-YEAR-OLD WOMAN WITH INTERMITTENT HEMOPTYSIS, INCREASING EXERTIONAL DYSPNEA, AND A LEFT MEDIASTINAL MASS - MALIGNANT FIBROUS HISTIOCYTOMA OF PULMONARY-ARTERY, WITH EMBOLISM AND PULMONARY INFARCTS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID PRIMARY SARCOMA; TRUNK; DIAGNOSIS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP LAMURAGLIA, GM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 1994 VL 330 IS 14 BP 997 EP 1002 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ND793 UT WOS:A1994ND79300009 ER PT J AU NASH, IS AF NASH, IS TI DOCTORS AND THE CLINTON PLAN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP NASH, IS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 1994 VL 330 IS 14 BP 1011 EP 1011 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ND793 UT WOS:A1994ND79300015 PM 8121445 ER PT J AU CANNISTRA, SA AF CANNISTRA, SA TI CANCER OF THE OVARY - REPLIES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP CANNISTRA, SA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 1994 VL 330 IS 14 BP 1013 EP 1014 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ND793 UT WOS:A1994ND79300025 ER PT J AU MARKOWITZ, JS AF MARKOWITZ, JS TI TRANSCATHETER VERSUS SURGICAL CLOSURE OF PATENT DUCTUS-ARTERIOSUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MARKOWITZ, JS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 1994 VL 330 IS 14 BP 1014 EP 1014 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ND793 UT WOS:A1994ND79300026 PM 8121450 ER PT J AU KOPANS, DB AF KOPANS, DB TI THE USE OF MAMMOGRAPHY FOR SCREENING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID BREAST-CANCER; MORTALITY; TRIAL RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 6 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 6 PY 1994 VL 271 IS 13 BP 982 EP 982 DI 10.1001/jama.271.13.982 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ND949 UT WOS:A1994ND94900018 PM 8139078 ER PT J AU GOLDHIRSCH, A GELBER, RD CASTIGLIONE, M AF GOLDHIRSCH, A GELBER, RD CASTIGLIONE, M TI TESTING TUMOR DORMANCY IN BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 INT BREAST CANC STUDY GRP,COMM SCI,LUGANO,SWITZERLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IBCSG STAT CTR,BOSTON,MA 02115. IBCSG,BERN,SWITZERLAND. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 6 PY 1994 VL 86 IS 7 BP 558 EP 558 DI 10.1093/jnci/86.7.558 PG 1 WC Oncology SC Oncology GA ND811 UT WOS:A1994ND81100020 PM 8133540 ER PT J AU SICKLES, EA KOPANS, DB AF SICKLES, EA KOPANS, DB TI SCREENING FOR BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SICKLES, EA (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT RADIOL,BOX 0628,SAN FRANCISCO,CA 94143, USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 6 PY 1994 VL 86 IS 7 BP 559 EP 560 DI 10.1093/jnci/86.7.559 PG 2 WC Oncology SC Oncology GA ND811 UT WOS:A1994ND81100022 ER PT J AU ZIERHUT, M HEMADY, R ZHAO, TZ MERCHANT, A FOSTER, CS AF ZIERHUT, M HEMADY, R ZHAO, TZ MERCHANT, A FOSTER, CS TI HERPES-SIMPLEX VIRUS TYPE-2 INDUCED RETINAL NECROSIS IN BALB/C MICE SO ACTA OPHTHALMOLOGICA LA English DT Article DE RETINITIS; VONSZILY MODEL; HSV-2; UVEITIS ID INTRACAMERAL INOCULATION; RETINITIS AB We injected herpes simplex virus type 2 of MS- or G-strain into the anterior chamber of BALB/c mice. In the contralateral eye inflammatory cell infiltration began in the ciliary body; focal retinitis, detected by day 8, led to total destruction of the retina by day 10. Contralateral disease was observed in 75% of mice inoculated with 8 x 10(3) pfu herpes simplex virus type 2, but in only 20% of mice receiving 80 pfu herpes simplex virus type 2. Still this low concentration, however, produced a suppressed delayed-type hypersensitivity response. Anti-herpes simplex virus type 2 antiboy, first detected on day 8, reached hight titers on day 10; by then, most of the mice had died of encephalitis. The G-strain of herpes simplex virus type 2 was more neurotoxic than the MS-strain, but produced the same incidence of contralateral retinitis. Herpes simplex virus type 2 produces contralateral necrotizing retinitis comparable to that produced by herpes simplex virus type 1. These findings, like those of other authors, suggest a role for herpes simplex virus type 2 in some cases of acute retinal necrosis in humans. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,BOSTON,MA 02115. UNIV TUBINGEN,EYE CLIN,W-7400 TUBINGEN 1,GERMANY. NR 21 TC 4 Z9 4 U1 0 U2 0 PU ARHUS UNIV HOSPITAL PI AARHUS PA DEPT OHPTHALMOLOGY, DK-8000 AARHUS, DENMARK SN 0001-639X J9 ACTA OPHTHALMOL PD APR PY 1994 VL 72 IS 2 BP 211 EP 217 PG 7 WC Ophthalmology SC Ophthalmology GA NP040 UT WOS:A1994NP04000011 PM 8079627 ER PT J AU BABA, TW KOCH, J MITTLER, ES GREENE, M WYAND, M PENNINCK, D RUPRECHT, RM AF BABA, TW KOCH, J MITTLER, ES GREENE, M WYAND, M PENNINCK, D RUPRECHT, RM TI MUCOSAL INFECTION OF NEONATAL RHESUS-MONKEYS WITH CELL-FREE SIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; INFANTS BORN; AIDS VIRUS; TRANSMISSION; TYPE-1; WOMEN; HIV-1; RISK; PREMATURITY AB Although the mechanisms for maternal transmission are unknown, approximately half of the infants congenitally infected with the human immunodeficiency virus type 1 (HIV-1) seem to become infected late in gestation or during delivery. Previously, we have developed a rhesus monkey model for congenital infection by injecting cell-free simian immunodeficiency virus (SIV) directly into amniotic fluid. Our results suggested that fetal infection may have occurred via skin or mucous membrane exposure. Mucosal surfaces have also been implicated as a portal of virus entry by a study in which the presence of serosanguinous fluid in neonatal gastric aspirates correlated with an increased rate of HIV-1 transmission. To test whether cell-free virus could traverse intact neonatal mucosal surfaces, we administered SIVmac251 orally to four rhesus monkey neonates within 1 hr following cesarean section delivery. All four neonates developed viremia and were positive by cocultivation and PCR. Seroconversion occurred in three of the four neonates. The SIV dose given was within physiological range as shown by end-point dilution of virus stock and viremic plasma samples of juvenile rhesus monkeys. This primate model for mucosal transmission of cell-free virus features a high infection rate, thus making studies of mucosal immunity and the development of strategies to prevent intrapartum virus transmission possible. C1 DANA FARBER CANC INST,VIRAL PATHOGENESIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT PROGRAM NEONATOL,DIV NEWBORN MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. DEPT OBSTET & GYNECOL,BOSTON,MA 02115. TSI MASON LABS,WORCESTER,MA 01608. TUFTS UNIV,SCH VET MED,DEPT SURG,N GRAFTON,MA 01536. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [R01-AI32330, R01-AI35533] NR 42 TC 75 Z9 76 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1994 VL 10 IS 4 BP 351 EP 357 DI 10.1089/aid.1994.10.351 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000007 PM 8068415 ER PT J AU HOLLSBERG, P RICHARDSON, JH WEBER, W DANGOND, F HAFLER, DA AF HOLLSBERG, P RICHARDSON, JH WEBER, W DANGOND, F HAFLER, DA TI INDUCTION OF ANERGY IN TAX-REACTIVE CD8 T-CELL CLONES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1994 VL 10 IS 4 BP 445 EP 445 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000027 ER PT J AU RICHARDSON, JH CARTER, NP HOLLSBERG, P CHILD, LA SODROSKI, JG HAFLER, DA LEVER, AML AF RICHARDSON, JH CARTER, NP HOLLSBERG, P CHILD, LA SODROSKI, JG HAFLER, DA LEVER, AML TI MOLECULAR AND CYTOGENETIC MAPPING OF INTEGRATED HTLV-I PROVIRUSES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,CAMBS,ENGLAND. UNIV CAMBRIDGE,DEPT MED,CAMBRIDGE CB2 2QQ,CAMBS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1994 VL 10 IS 4 BP 467 EP 467 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NK470 UT WOS:A1994NK47000106 ER PT J AU ALASSI, MT GENTA, RM GRAHAM, DY AF ALASSI, MT GENTA, RM GRAHAM, DY TI OMEPRAZOLE-TETRACYCLINE COMBINATIONS ARE INADEQUATE AS THERAPY FOR HELICOBACTER-PYLORI INFECTION SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Note ID CAMPYLOBACTER-PYLORI; DUODENAL-ULCER; ERADICATION; SUSCEPTIBILITY; LANSOPRAZOLE; AMOXICILLIN; GASTRITIS AB Background: Current triple antimicrobial therapies cure Helicobacter pylori infection in 60-90% of cases but are cumbersome. Addition of omeprazole to amoxycillin has been shown to enhance effectiveness when compared to amoxycillin alone. Method: We studied omeprazole 20 mg t.d.s. plus tetracycline 500 mg q.d.s. for 14 days (OMP/TCN) and omeprazole 40 mg in the morning plus tetracycline 500 mg q.d.s. along with bismuth subsalicylate tablets 2 q.d.s. (OMP/TCN/BSS) for 14 days. Forty-four patients (19 OMP/TCN, 25 OMP/TCN/BSS) with H. pylori peptic ulcer disease were studied. H. pylori status was evaluated at least 4 weeks after ending antimicrobial therapy. Results: In the OMP/TCN group cure of H. pylori infection was achieved in 5/19 (26%). Adding bismuth to the regimen improved the results; 4 weeks after ending therapy cure of H. pylori infection was achieved in 12/25 (48%). Conclusions: Neither regimen can be recommended for routine cure of H. pylori infection. Although one cannot predict which antimicrobial therapies will be enhanced by the addition of omeprazole, these data suggest that future studies should evaluate drugs whose effectiveness is compromised by low pH. C1 VET AFFAIRS MED CTR 111D,DEPT MED,HOUSTON,TX 77030. VET AFFAIRS MED CTR,DEPT PATHOL,HOUSTON,TX. VET AFFAIRS MED CTR,DIV MOLEC VIROL,HOUSTON,TX. BAYLOR COLL MED,HOUSTON,TX. NR 36 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD APR PY 1994 VL 8 IS 2 BP 259 EP 262 PG 4 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA NH776 UT WOS:A1994NH77600015 PM 8038358 ER PT J AU ASBURY, RF CNAAN, A JOHNSON, L HARRIS, J ZAENTZ, SD HALLER, DG AF ASBURY, RF CNAAN, A JOHNSON, L HARRIS, J ZAENTZ, SD HALLER, DG TI AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP PHASE-II STUDY OF SINGLE-AGENT DHAD, VP-16, ACLACINOMYCIN, OR SPIROGERMANIUM IN METASTATIC PANCREATIC-CANCER SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE ECOG; PANCREATIC CARCINOMA; DHAD; VP-16; ACLACINOMYCIN; SPIROGERMANIUM ID DNA AB There were 80 patients with measurable metastatic or unresectable pancreatic cancer randomly assigned to treatment with either DHAD, VP-16, aclacinomycin, or spirogermanium. There were no complete or partial responses. Two deaths from leukopenia occurred in patients treated with DHAD. One patient receiving spirogermanium experienced a seizure. No other life-threatening toxicities occurred. Maximal toxicities were not significantly more frequent with any treatment group. Median survival was 10 weeks, and median time to progression was only 6 weeks, with no difference among these four therapies. C1 UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BROWN UNIV,PROVIDENCE,RI 02912. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53706. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. FU NCI NIH HHS [CA 23318, CA 21076, CA 25988] NR 17 TC 10 Z9 11 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 1994 VL 17 IS 2 BP 166 EP 169 DI 10.1097/00000421-199404000-00016 PG 4 WC Oncology SC Oncology GA ND170 UT WOS:A1994ND17000016 PM 8141110 ER PT J AU CENTENO, BA LEWANDROWSKI, KB WARSHAW, AL COMPTON, CC SOUTHERN, JF AF CENTENO, BA LEWANDROWSKI, KB WARSHAW, AL COMPTON, CC SOUTHERN, JF TI CYST FLUID CYTOLOGIC ANALYSIS IN THE DIFFERENTIAL-DIAGNOSIS OF PANCREATIC CYSTIC LESIONS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE CYST; CYSTADENOCARCINOMA; CYTOLOGY; FINE-NEEDLE ASPIRATION; MUCINOUS CYSTIC NEOPLASM; PANCREAS, PAPILLARY CYSTADENOCARCINOMA; PSEUDOCYST; SEROUS CYSTADENOMA ID FINE-NEEDLE ASPIRATION; MUCINOUS CYSTADENOCARCINOMA; CARCINOEMBRYONIC ANTIGEN; NEOPLASMS; TUMORS AB Pancreatic cystic lesions include inflammatory pseudocysts, benign serous cystadenomas, and mucinous neoplasms, some of which are malignant. Cytologic analysis of cyst fluid has been proposed to diagnose pancreatic cysts before definitive therapy. The authors report an analysis of 31 pancreatic cyst aspirates: 9 pseudocysts, 5 serous cystadenomas, 8 mucinous cystic neoplasms, 4 mucinous cystadenocarcinomas, 2 papillary cystadenocarcinomas, 1 mucinous ductal adenocarcinoma with cystic degeneration, and 2 cystic islet cell tumors. All pseudocysts were correctly classified as probable inflammatory lesions, because of the presence of abundant acute inflammation and histiocytes and the absence of glandular epithelium. Three of five serous cystadenomas were correctly classified, based on the presence of small cuboidal cells in clusters with microvesicular cytoplasm containing glycogen. Eleven of 12 mucinous tumors contained round cells with large cytoplasmic mucin vacuoles or columnar cells containing cytoplasmic mucin. Malignancy was diagnosed in 5 of 7 carcinomas, 1 case was classified as suspicious for malignancy, and 1 case was nondiagnostic because of the absence of a cellular component. The authors concluded that pancreatic cyst fluid cytologic analysis is useful in differentiating mucinous from nonmucinous pancreatic cysts and may provide definitive evidence of malignancy. In some cases, serous cystadenoma can be diagnosed based on cytologic analysis. An inflammatory smear without epithelial cells suggests a pseudocyst, but these findings are nonspecific, as a similar pattern may occur when a cystic neoplasm undergoes degenerative changes. Therefore, pseudocyst remains a diagnosis of exclusion. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. FU NCI NIH HHS [T32-CA 09216] NR 25 TC 43 Z9 45 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 1994 VL 101 IS 4 BP 483 EP 487 PG 5 WC Pathology SC Pathology GA NE911 UT WOS:A1994NE91100017 PM 8160642 ER PT J AU MATULONIS, UA GRIFFIN, JD CANELLOS, GP AF MATULONIS, UA GRIFFIN, JD CANELLOS, GP TI AUTOLOGOUS PERIPHERAL STEM-CELL TRANSPLANTATION OF THE BLASTIC PHASE OF CHRONIC MYELOID-LEUKEMIA FOLLOWING SEQUENTIAL HIGH-DOSE CYTOSINE-ARABINOSIDE AND MELPHALAN SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE CML; AUTOTRANSPLANTS; BLAST CRISIS; STEM CELLS ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; TRANSFORMATION; CHEMOTHERAPY; CULTURE AB Blast-phase chronic myelogenous leukemia (CML) is the terminal phase in CML and is uniformly fatal. We treated 12 patients with blast-phase CML with a program of high-dose cytarabine 3.0 g/m(2) and melphalan 140 mg/m(2), followed by reinfusion of stem cells obtained from peripheral blood during the chronic phase. Seven patients achieved either a partial or complete hematologic remission, while five patients showed no response to therapy. One patient returned to chronic phase features with loss of a chromosomal abnormality acquired at blast phase, restoration of hematopoiesis, and a decrease in the amount of bone marrow blasts to less than 10%. Six patients cleared their peripheral blasts and showed recovery of their myeloid and platelet lineages, but all six required treatment for acceleration within 3 months. Of the five nonresponding patients, three died with aplastic bone marrow, one patient never cleared peripheral blasts after chemotherapy, and one patient had evidence of peripheral blasts 3 weeks after the autologous stem cell reinfusion. None of the patients returned to a normal karyotype. The ablative regimen was effective in eradicating bone marrow blasts to <10% in 8 of 10 patients in whom interpretable bone marrow samples were performed following chemotherapy. Overall, the median survival for all patients from the time of stem cell reinfusion was 5.5 months. We conclude that autotransplants with peripheral blood can successfully be used to support hematopoiesis during high-dose therapy for CML blast crisis, however, has no role by itself in the curative therapy of blast crisis CML. A small number of patients can be restored to chronic phase features, and this may provide an opportunity to administer subsequent alternative treatments designed to eradicate the malignant stem cell population. Autotransplants with stem cells may also be used as therapy for patients without a histocompatible marrow donor. However, the autotransplant may be more effective when used during the chronic phase of CML, with the use of hematopoietic growth factors, and with reinfusion of stem cells depleted of the malignant Philadelphia chromosome-positive clone. (C) 1994 Wiley-Liss, Inc. C1 DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA. NR 14 TC 7 Z9 7 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 1994 VL 45 IS 4 BP 283 EP 287 DI 10.1002/ajh.2830450403 PG 5 WC Hematology SC Hematology GA MY225 UT WOS:A1994MY22500002 PM 7909981 ER PT J AU ZUSMAN, RM HUI, KY NUSSBERGER, J CHRISTENSEN, DM HIGGINS, J CARLSON, WD SCHOENFELD, D HABER, E AF ZUSMAN, RM HUI, KY NUSSBERGER, J CHRISTENSEN, DM HIGGINS, J CARLSON, WD SCHOENFELD, D HABER, E TI R-PEP-27, A POTENT RENIN INHIBITOR, DECREASES PLASMA ANGIOTENSIN-II AND BLOOD-PRESSURE IN NORMAL VOLUNTEERS SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE R-PEP-27; RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM; RENIN INHIBITOR AB The hemodynamic and humoral effects of the specific human renin inhibitor R-PEP-27 were studied in six normal human subjects on low and high sodium intake diets. An intravenous infusion of R-PEP-27 (0.5 to 16 (mu g/min/kg body wt) reduced blood pressure in a dose-dependent fashion; the mean arterial blood pressure at the end of the infusion fell from 128 +/- 4/83 +/- 4 to 119 +/- 3/71 +/- 3 mm Hg (mean +/- SEM) (P < .01) during the low sodium intake diet. R-PEP-27 had no effect on blood pressure during the high sodium intake diet. R-PEP-27 significantly reduced plasma angiotensin II and aldosterone concentrations. The temporal response to R-PEP-27 suggests that it is a short-lived although highly potent competitive inhibitor of renin; this peptide is a valuable and specific physiologic probe of the renin-angiotensin system. RP ZUSMAN, RM (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,DIV HYPERTENS & VASC MED,CARDIAC UNIT,15 PARKMAN ST,WACC 482,BOSTON,MA 02114, USA. FU NCRR NIH HHS [RR0166-12] NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 1994 VL 7 IS 4 BP 295 EP 301 PN 1 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NG659 UT WOS:A1994NG65900001 PM 8031544 ER PT J AU COGGINS, CH DWYER, JT GREENE, T PETOT, G SNETSELAAR, LG VANLENTE, F AF COGGINS, CH DWYER, JT GREENE, T PETOT, G SNETSELAAR, LG VANLENTE, F TI SERUM-LIPID CHANGES ASSOCIATED WITH MODIFIED PROTEIN DIETS - RESULTS FROM THE FEASIBILITY PHASE OF THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE CHRONIC RENAL DISEASE; RENAL FUNCTION; DIET; LIPIDS; PROTEIN ID DENSITY-LIPOPROTEIN CHOLESTEROL; FAILURE; DEATH C1 FRANCES STERN NUTR CTR,BOSTON,MA. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,CENT BIOCHEM LAB,CLEVELAND,OH 44195. CASE WESTERN RESERVE UNIV,SCH MED,DEPT EPIDEMIOL & BIOSTAT,CLEVELAND,OH 44106. UNIV IOWA HOSP & CLIN,DEPT INTERNAL MED,IOWA CITY,IA 52242. RP COGGINS, CH (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,JACKSON 825,BOSTON,MA 02114, USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 28 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 1994 VL 23 IS 4 BP 514 EP 523 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA NF034 UT WOS:A1994NF03400004 PM 8154486 ER PT J AU BELL, NH HOLLIS, BW SHARY, JR EYRE, DR EASTELL, R COLWELL, A RUSSELL, RGG AF BELL, NH HOLLIS, BW SHARY, JR EYRE, DR EASTELL, R COLWELL, A RUSSELL, RGG TI DICLOFENAC SODIUM INHIBITS BONE-RESORPTION IN POSTMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PROSTAGLANDIN PRODUCTION; OSTEOCLASTS; COLLAGEN; ESTROGEN; RATS; 1,25-DIHYDROXYVITAMIN-D; QUANTITATION; CROSSLINKS; CALCITONIN AB Background: The results of experimental studies with animals indicated that prostaglandins stimulate bone resorption, that skeletal production of prostaglandin E, is enhanced by ovariectomy and is diminished by 17 beta-estradiol, and that the nonsteroidal anti-inflammatory drug (NSAID) naproxyn prevents bone loss after ovariectomy. Studies were carried out to investigate the effects of the NSAID diclofenac sodium on bone and mineral metabolism in premenopausal women and to compare the effects of diclofenac sodium and conjugated estrogens on bone and mineral metabolism in postmenopausal women. Patients and methods: Ten healthy premenopausal women and 17 healthy postmenopausal women were studied while not being treated and again after 4 weeks of treatment with diclofenac sodium, 150 mg per day in divided doses (both groups), and conjugated estrogens, 0.625 mg per day (postmenopausal women). Cross-linked N-telopeptides of type I collagen were measured in the urine as an index of bone resorption. The postmenopausal women were separated into two groups, responders and nonresponders, based on their response to conjugated estrogens as assessed by linear discriminant analysis for groups. Conjugated estrogens lowered urinary N-telopeptides of type I collagen in responders, but not in nonresponders. Results: Urinary cross-linked N-telopeptides were higher in the eight postmenopausal women responders than in the nine postmenopausal nonresponders or in the premenopausal women, and were not altered by diclofenac sodium in premenopausal women. In the eight postmenopausal women with higher rates of bone resorption, diclofenac sodium and conjugated estrogens significantly lowered both urinary calcium concentration and urinary cross-linked N-telopeptides. The effects of the two drugs were comparable. Conclusion: The preliminary results demonstrate that, at the dose used, diclofenac sodium is almost as effective as conjugated estrogens for decreasing bone loss in postmenopausal women. Further studies will be needed to determine whether diclofenac sodium can prevent postmenopausal bone loss. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PEDIAT,CHARLESTON,SC 29425. UNIV WASHINGTON,DEPT ORTHOPED,SEATTLE,WA 98195. UNIV SHEFFIELD,SCH MED,DEPT HUMAN METAB & CLIN BIOCHEM,SHEFFIELD S10 2UL,ENGLAND. NO GEN HOSP,CTR CLIN SCI,SHEFFIELD,S YORKSHIRE,ENGLAND. RP BELL, NH (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29401, USA. RI Eastell, Richard/G-5851-2011 OI Eastell, Richard/0000-0002-0323-3366 FU NCRR NIH HHS [M01 RR 01070]; NIAMS NIH HHS [AR 36066, R01 AR036794, R37 AR037318] NR 26 TC 34 Z9 35 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 1994 VL 96 IS 4 BP 349 EP 353 DI 10.1016/0002-9343(94)90065-5 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NG901 UT WOS:A1994NG90100009 PM 8166154 ER PT J AU ROSS, DS AF ROSS, DS TI SCREENING THYROID-FUNCTION TESTS IN AN ACUTE-CARE HOSPITAL SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID L-THYROXINE THERAPY; SUBCLINICAL HYPOTHYROIDISM; DOUBLE-BLIND; ILLNESSES C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP ROSS, DS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 1994 VL 96 IS 4 BP 393 EP 394 DI 10.1016/0002-9343(94)90077-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NG901 UT WOS:A1994NG90100020 PM 8166164 ER PT J AU KLEYMAN, TR SMITH, PR BENOS, DJ AF KLEYMAN, TR SMITH, PR BENOS, DJ TI CHARACTERIZATION AND LOCALIZATION OF EPITHELIAL NA+ CHANNELS IN TOAD URINARY-BLADDER SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE TBM CELLS; AMILORIDE; 2'-METHOXY-5'-NITROBENZAMIL; BENZAMIL; BROMOBENZAMIL; ANTI-SODIUM CHANNEL ANTIBODY ID ANTI-AMILORIDE ANTIBODIES; SODIUM-CHANNEL; PROTEIN; TRANSPORT; BINDING; PNEUMOCYTES; ANALOGS; SUBUNIT; KIDNEY; CELLS AB The toad urinary bladder and epithelial cell lines derived from the urinary bladder, including TBM, serve as model systems for the study of transepithelial Na+ transport. We examined biochemical characteristics of epithelial Na+ channels in toad urinary bladder and TBM cells and their cellular localization in the urinary bladder. The radiolabeled amiloride analogue [H-3]benzamil bound to a single class of high-affinity binding sites in membrane vesicles from toad urinary bladder with a dissociation constant (K-d) Of 10 nM. Photoactive benzamil analogues specifically labeled a 135,000-Da polypeptide in toad urinary bladder and TBM cells. A monoclonal anti-Na+ channel antibody directed against the amiloride-binding component of the channel specifically recognized a 135,000-Da polypeptide in TBM cells. Polyclonal anti-Na+ channel antibodies generated against purified bovine epithelial Na+ channel specifically recognized a 235,000-Da polypeptide in toad urinary bladder and localized Na+ channels to the apical plasma membrane of urinary bladder epithelial cells. The biochemical characteristics and the cellular localization of epithelial Na+ channels in toad urinary bladder are similar to those previously described in mammalian kidney and in the A6 cell line. C1 UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. RP KLEYMAN, TR (reprint author), DEPT VET AFFAIRS MED CTR,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 31 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1994 VL 266 IS 4 BP C1105 EP C1111 PN 1 PG 7 WC Physiology SC Physiology GA NJ994 UT WOS:A1994NJ99400025 ER PT J AU KEMNITZ, JW ROECKER, EB WEINDRUCH, R ELSON, DF BAUM, ST BERGMAN, RN AF KEMNITZ, JW ROECKER, EB WEINDRUCH, R ELSON, DF BAUM, ST BERGMAN, RN TI DIETARY RESTRICTION INCREASES INSULIN SENSITIVITY AND LOWERS BLOOD-GLUCOSE IN RHESUS-MONKEYS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AGING; MINIMAL MODEL; ADIPOSITY ID FOOD RESTRICTION; FAT DISTRIBUTION; MINIMAL-MODEL; AGE; RESISTANCE; TOLERANCE; OBESITY; HYPOTHESIS; DISEASE AB Insulin sensitivity and glucose tolerance typically decline during later life. In a multidimensional randomized trial of the effects of dietary restriction started in adulthood on the processes of aging, we are studying insulin sensitivity and glucoregulation longitudinally in control (C, n = 15, fed a defined diet ad libitum for 6-8 h/day) and restricted (R, n = 15, fed 30% less than C) monkeys using the Modified Minimal Model method. Linear rates of change were calculated for individual animals through 30 mo of diet treatment and compared between treatment groups. Basal glucose, basal insulin, and insulin responses to glucose and tolbutamide increased for C and decreased for R animals (P less than or equal to 0.002), whereas insulin sensitivity decreased for C and increased for R (P = 0.008). Glycosylated hemoglobin at 30 mo was marginally lower in R (P = 0.06) and was positively correlated with fasting plasma glucose (r = 0.508, P < 0.001). Insulin changes were significantly correlated with changes in adiposity (weight and abdominal circumference). Identification of the mechanisms through which these effects are achieved may aid in ameliorating glucose intolerance, insulin resistance, and associated illnesses in older persons. C1 UNIV WISCONSIN,WISCONSIN REG PRIMATE RES CTR,DEPT BIOSTAT,MADISON,WI 53715. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. RP KEMNITZ, JW (reprint author), UNIV WISCONSIN,WISCONSIN REG PRIMATE RES CTR,DEPT MED,1223 CAPITOL COURT,MADISON,WI 53715, USA. FU NIA NIH HHS [AG-07831, AG-00213]; NIDDK NIH HHS [DK-29867] NR 34 TC 169 Z9 172 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1994 VL 266 IS 4 BP E540 EP E547 PN 1 PG 8 WC Physiology SC Physiology GA NJ994 UT WOS:A1994NJ99400032 PM 8178974 ER PT J AU EMMONS, C STOKES, JB AF EMMONS, C STOKES, JB TI CELLULAR ACTIONS OF CAMP ON HCO(3)(-)SECRETING CELLS OF RABBIT CCD - DEPENDENCE ON IN-VIVO ACID-BASE STATUS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; INTERCALATED CELLS; ALKALOSIS; CORTICAL COLLECTING DUCT; SODIUM-DEPENDENT CHLORIDE, BICARBONATE ION EXCHANGE ID CORTICAL COLLECTING TUBULES; INTERCALATED CELLS; INTRACELLULAR PH; BICARBONATE TRANSPORT; H+-ATPASE; ALKALI LOADS; DUCT; SECRETION; EXCHANGE; BAND-3 AB HCO3- secretion by cortical collecting duct (CCD) occurs via beta-intercalated cells. In vitro CCD HCO3- secretion is modulated by both the in vivo acid-base status of the animal and by adenosine 3',5'-cyclic monophosphate (cAMP). To investigate the mechanism of cAMP-induced HCO3- secretion, we measured intracellular pH (pH(i)) of individual beta-intercalated cells of CCDs dissected from alkali-loaded rabbits perfused in vitro. beta-Intercalated cells were identified by demonstrating the presence of an apical anion exchanger (cell alkalinization in response to removal of lumen Cl-). After 180 min of perfusion to permit decrease of endogenous cAMP, acute addition of 0.1 mM 8-bromo-cAMP or 1 mu M isoproterenol to the bath caused a transient cellular alkalinization (> 0.20 pH units). In the symmetrical absence of either Na+, HCO3-, or Cl-, cAMP produced no change in pH(i). Basolateral dihydrogen 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (0.1 mM) for 15 min before cAMP addition also prevented this alkalinization. In contrast to the response of cells from alkali-loaded rabbits, addition of basolateral cAMP to CCDs dissected from normal rabbits resulted in an acidification of beta-intercalated cells (similar to 0.20 pH units). The present studies demonstrate the importance of the in vivo acid-base status of the animal in the regulation of CCD HCO3- secretion by beta-intercalated cells. The results identify the possible existence of a previously unrecognized Na+-dependent Cl-/HCO3- exchanger on the basolateral membrane of beta-intercalated cells in alkali-loaded rabbits. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,DIV NEPHROL,LOS ANGELES,CA 90024. UNIV IOWA,DEPT INTERNAL MED,EPITHELIAL TRANSPORT LAB,IOWA CITY,IA 52242. VET AFFAIRS MED CTR,IOWA CITY,IA 52242. RP EMMONS, C (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DIV NEPHROL,10833 LECONTE AVE,FACTOR 7-155,LOS ANGELES,CA 90024, USA. FU NIDDK NIH HHS [DK-25231] NR 32 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1994 VL 266 IS 4 BP F528 EP F535 PN 2 PG 8 WC Physiology SC Physiology GA NJ996 UT WOS:A1994NJ99600098 PM 8184884 ER PT J AU SALZMAN, AL WANG, HL WOLLERT, PS VANDERMEER, TJ COMPTON, CC DENENBERG, AG FINK, MP AF SALZMAN, AL WANG, HL WOLLERT, PS VANDERMEER, TJ COMPTON, CC DENENBERG, AG FINK, MP TI ENDOTOXIN-INDUCED ILEAL MUCOSAL HYPERPERMEABILITY IN PIGS - ROLE OF TISSUE ACIDOSIS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE LIPOPOLYSACCHARIDE; EPITHELIUM; ACIDOSIS; SEPSIS ID TUMOR-NECROSIS-FACTOR; SMALL-INTESTINE; TIGHT JUNCTION; BLOOD-FLOW; ION-TRANSPORT; SEPTIC SHOCK; GUT ISCHEMIA; SYSTEMIC PH; PERMEABILITY; MODEL AB Administration of lipopolysaccharide (LPS) to experimental animals leads to diminished mesenteric perfusion, increased ileal mucosal [H+], and increased gut epithelial permeability to hydrophilic solutes. We sought to determine whether these phenomena are causally related. Experiments were performed in anesthetized pigs. Permeability was assessed by measuring the plasma-to-lumen clearance of fluorescein isothiocyanate dextran (4,000 Da; FD-4) by a segment of ileum perfused with Ringer lactate solution. Mucosal perfusion (Q(mue)) and [H+] were estimated using laser Doppler flowmetry and tonometry, respectively. In an initial series of experiments, we showed that mucosal permeability was linearly correlated with mucosal [H+] in animals subjected to graded degrees of mechanically induced mesenteric ischemia (n = 14, R(2) = 0.58, P < 0.002) or injected with graded doses of LPS (n = 11, R(2) = 0.93, P < 0.0001). In a second series of experiments, we induced mucosal acidosis in normal pigs by mechanical ventilation with either a hypoxic (n = 7) or a hypercapnic (n = 5) gas mixture. In both groups, ileal mucosal permeability to FD-4 increased significantly (P < 0.05), although transmesenteric release of lactate increased significantly only in the hypoxic group. Q(mue) was unchanged in both groups. These data suggest that mucosal acidosis, even in the absence of tissue ischemia or hypoxia, increases intestinal permeability to a macromolecular hydrophilic solute. Tissue acidosis may be an important factor contributing to LPS-induced gut mucosal hyperpermeability. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NIGMS NIH HHS [5-T32-GM-07035, 2-R01-GM-37631-07] NR 42 TC 101 Z9 103 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1994 VL 266 IS 4 BP G633 EP G646 PN 1 PG 14 WC Physiology SC Physiology GA NJ994 UT WOS:A1994NJ99400062 PM 7513959 ER PT J AU VLAHAKES, GJ VERRIER, ED TURLEY, K HOFFMAN, JIE AF VLAHAKES, GJ VERRIER, ED TURLEY, K HOFFMAN, JIE TI MAXIMAL VASCULAR CONDUCTANCE IN RIGHT-VENTRICULAR MYOCARDIAL CIRCULATION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ZERO-FLOW PRESSURES; CHROMONAR; RIGHT VENTRICLE; RIGHT VENTRICULAR FAILURE; VOLUME LOADING; VASCULAR WATERFALL ID PRESSURE-FLOW RELATIONSHIPS; RIGHT CORONARY-ARTERY; ISOLATED DOG HEART; OPEN-CHEST DOGS; OXYGEN-METABOLISM; ANESTHETIZED DOGS; BLOOD-FLOW; HYPERTENSION; RESERVE; CAPACITANCE AB With acutely increasing right ventricular (RV) hypertension, failure eventually occurs because of RV ischemia. This study examines the effects of RV hypertension on the diastolic right coronary circulation. Conscious dogs instrumented to measure right coronary artery pressure and blood flow were studied after maximal coronary vasodilation with chromonar. Diastolic coronary pressure-flow relations, described by slope (conductance) and zero-flow, pressure axis intercept (P-f=0), were generated before and during RV hypertension. Diastolic P-f=0 increased from 11.8 +/- 6.5 to 17.1 +/- 7.1 (means +/- SD, P < 0.01) Torr, with no change in conductance. During RV hypertension, RV diastolic pressure increased. To examine possible mechanisms for the increase in P-f=0, pressure-flow relations were generated before and after volume loading, without systolic hypertension. Diastolic P-f=0 increased from 15.5 +/- 3.1 to 20.8 +/- 4.1 Torr, suggesting that changes in P-f=0 with RV hypertension were mediated by increased filling pressures. Pressure flow relations were derived from mean right coronary flow and RV driving pressure before and during RV hypertension. Under these conditions, P-f=0 is close to zero; the use of RV driving pressure provides a method for calculating maximal right coronary conductance. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP VLAHAKES, GJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1994 VL 266 IS 4 BP H1363 EP H1372 PN 2 PG 10 WC Physiology SC Physiology GA NJ996 UT WOS:A1994NJ99600013 ER PT J AU ANZUETO, A SUPINSKI, GS LEVINE, SM JENKINSON, SG AF ANZUETO, A SUPINSKI, GS LEVINE, SM JENKINSON, SG TI MECHANISMS OF DISEASE - ARE OXYGEN-DERIVED FREE-RADICALS INVOLVED IN DIAPHRAGMATIC DYSFUNCTION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID VITAMIN-E; LIPID-PEROXIDATION; SKELETAL-MUSCLE; SUPEROXIDE-DISMUTASE; N-ACETYLCYSTEINE; REACTIVE OXYGEN; EXERCISE; FATIGUE; RATS; METABOLISM C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. METROHLTH MED CTR,CLEVELAND,OH. RP ANZUETO, A (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 40 TC 36 Z9 36 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 1994 VL 149 IS 4 BP 1048 EP 1052 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NP836 UT WOS:A1994NP83600033 PM 8143041 ER PT J AU CHEW, FS SCHULZE, ES MATTIA, AR AF CHEW, FS SCHULZE, ES MATTIA, AR TI OSTEOMYELITIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1994 VL 162 IS 4 BP 942 EP 942 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ND136 UT WOS:A1994ND13600034 PM 8141021 ER PT J AU CHEW, FS AF CHEW, FS TI INTERACTIVE VIDEODISC FOR TEACHING RADIOLOGY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review ID INSTRUCTION; PATHOLOGY; SYSTEM AB This article reviews the development and current use of the interactive videodisc as a tool for teaching radiology. Inherent advantages of the videodisc include large image capacity with random access, ability to incorporate motion video, ability to overlay arrows and other graphics on images, quality of images, speed of retrieval and display, and ease of management of images [1, 2]. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. OI Chew, Felix/0000-0003-2711-2013 NR 56 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1994 VL 162 IS 4 BP 987 EP 991 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ND136 UT WOS:A1994ND13600046 PM 8141032 ER PT J AU HUNTSMAN, DG CLEMENT, PB GILKS, CB SCULLY, RE AF HUNTSMAN, DG CLEMENT, PB GILKS, CB SCULLY, RE TI SMALL-CELL CARCINOMA OF THE ENDOMETRIUM - A CLINICOPATHOLOGICAL STUDY OF 16 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ENDOMETRIUM; SMALL-CELL CARCINOMA; UNDIFFERENTIATED CARCINOMA; NEUROENDOCRINE CELLS ID FEMALE GENITAL-TRACT; ARGYROPHIL CELLS; UNDIFFERENTIATED CARCINOMA; VAGINA; LIGHT; UTERUS; CERVIX; OVARY AB Sixteen cases of small-cell carcinoma of the endometrium were encountered in patients who ranged in age from 30 to 78 (mean. 57.4) years. Of the 12 patients whose presenting features are known, eight had abnormal vaginal bleeding, three had pain related to metastatic tumor, and one patient had both symptoms. On pelvic examination, adnexal masses were palpable in three patients, and vaginal involvement was evident in two; one patient had a large palpable periumbilical mass. Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Extrauterine spread was documented intraoperatively in eight cases, including widespread intraabdominal and ovarian metastases in four cases, vaginal involvement in the two cases noted previously, paraaortic lymph node involvement in one case, and tubal involvement in one case. Three tumors were International Federation of Gynecology and Obstetrics (FIGO) stage I, four were stage II, two were stage III, and six were stage IV; in one case, there was insufficient information to allow staging. On gross examination, the tumors were usually described as bulky, ill-defined, and invasive of the myometrium; four were polypoid. Microscopic examination revealed sheets, cords, and nests of small or intermediate-sized cells with scanty cytoplasm, hyperchromatic nuclei, and a high mitotic rate. Single-cell and zonal necrosis and vascular invasion were typically present. Synchronous grade 1 or grade 2 endometrial endometrioid adenocarcinoma was present in eight cases, and complex atypical endometrial hyperplasia, in two others. In three cases, the adenocarcinoma merged almost imperceptibly with the small-cell component. None of the tumors contained argyrophil or argentaffin cells, although nine of 11 tumors were immunoreactive for neuron-specific enolase (one of these was also Leu-7 positive), and another was chromogranin positive. Of the 11 cases with follow-up information, seven patients died of disease (at least four with distant metastases) with a median survival of 12 months, and another patient was alive with distant metastases at 18 months. The remaining patients were clinically free of disease at postoperative intervals of less-than-or-equal-to 1 year (two cases) and 4.5 years (one case). This study confirms that small-cell carcinomas of the endometrium are a histologically distinctive subtype of endometrial carcinoma, which, like their counterparts in the uterine cervix, are aggressive tumors with a propensity for systemic s read and a poor prognosis. C1 VANCOUVER GEN HOSP,DEPT PATHOL,VANCOUVER V5Z 1M9,BC,CANADA. UNIV BRITISH COLUMBIA,DEPT PATHOL,VANCOUVER V6T 1W5,BC,CANADA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 37 TC 71 Z9 77 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 1994 VL 18 IS 4 BP 364 EP 375 DI 10.1097/00000478-199404000-00005 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA ND581 UT WOS:A1994ND58100005 PM 7511354 ER PT J AU FERRY, JA HARRIS, NL YOUNG, RH COEN, J ZIETMAN, A SCULLY, RE AF FERRY, JA HARRIS, NL YOUNG, RH COEN, J ZIETMAN, A SCULLY, RE TI MALIGNANT-LYMPHOMA OF THE TESTIS, EPIDIDYMIS, AND SPERMATIC CORD - A CLINICOPATHOLOGICAL STUDY OF 69 CASES WITH IMMUNOPHENOTYPIC ANALYSIS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE TESTIS; EPIDIDYMIS; SPERMATIC CORD; MALIGNANT LYMPHOMA; IMMUNOPEROXIDASE; SCLEROSIS; PROGNOSIS ID NON-HODGKINS LYMPHOMA; LARGE-CELL LYMPHOMA; TESTICULAR LYMPHOMAS; TUMORS; CHEMOTHERAPY AB We studied 69 cases of malignant lymphoma of the testis, epididymis, and spermatic cord, including 64 cases in which the tumor involved these sites at presentation and five cases in which lymphoma relapsed in the testis. The patients without prior lymphoma were 16 to 91 (mean, 56) years old. Fifty-two patients had diffuse large-cell lymphomas [seven large cleaved cell (two with follicular areas), 27 large noncleaved, two multilobated, six not otherwise specified (NOS), 10 immunoblastic]; six, small noncleaved cell; two, diffuse mixed small and large cell; one, diffuse small cleaved; one, follicular mixed small cleaved and large cell; and two, high grade, unclassified in the Working Formulation. Twenty-nine cases (55%) were stage I; five (9%), stage II; one (2%), stage III, and 18 (34%), stage IV. Forty patients (73%) achieved a complete remission; 23 had a relapse of tumor at 4 to 274 months (median, 13) and five were salvaged. At last follow-up, 20 (36%) patients were free of disease, six (11%) were alive with disease, and 29 (53%) had died of lymphoma. Features associated with longer disease-free actuarial survival (DFS) included stage I disease (p = 0.0001) and sclerosis (p = 0.0001). Among patients with stage I lymphoma, those with right-sided tumors (p = 0.005) or tumors with sclerosis (p = 0.0017) had longer DFS. Lymphomas with extensive sclerosis were all stage I (p = 0.0057). Four of five patients with secondary testicular lymphoma had extranodal primary sites. They ranged from 13 to 66 years (median, 35). Testicular relapses occurred 13-37 months after initial diagnosis. Three had diffuse large, noncleaved cell type; one, lymphoblastic and one, diffuse mixed small and large cell. Immunophenotyping showed B lineage in 33 cases and T lineage in one case. Most testicular lymphomas are B-lineage large-cell lymphomas, which frequently involve other extranodal sites at presentation and at relapse, and which often have an aggressive clinical course. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP FERRY, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 58 TC 114 Z9 122 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 1994 VL 18 IS 4 BP 376 EP 390 DI 10.1097/00000478-199404000-00006 PG 15 WC Pathology; Surgery SC Pathology; Surgery GA ND581 UT WOS:A1994ND58100006 PM 8141430 ER PT J AU BIGATELLO, LM HURFORD, WE KACMAREK, RM ROBERTS, JD ZAPOL, WM AF BIGATELLO, LM HURFORD, WE KACMAREK, RM ROBERTS, JD ZAPOL, WM TI PROLONGED INHALATION OF LOW CONCENTRATIONS OF NITRIC-OXIDE IN PATIENTS WITH SEVERE ADULT-RESPIRATORY-DISTRESS-SYNDROME - EFFECTS ON PULMONARY HEMODYNAMICS AND OXYGENATION SO ANESTHESIOLOGY LA English DT Article DE ENDOTHELIUM-DERIVED RELAXING FACTOR; LUNG(S), ACUTE PULMONARY HYPERTENSION, ADULT RESPIRATORY DISTRESS SYNDROME; PHARMACOLOGY, NITRIC OXIDE ID HYPERTENSION; VASOCONSTRICTION; VASODILATOR; PRESSURE; NEWBORN; SHEEP AB Background: Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of patients with severe ARDS, we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response. Methods: Thirteen patients with severe ARDS (hospital mortality 67%) inhaled 0-40 parts per million (ppm) NO. Seven of these patients continued to breathe 2-20 ppm NO for 2-27 days. Results: Inhaling 5-40 ppm NO decreased mean pulmonary artery pressure in a dose-related fashion (from 34 +/- 7 to 30 +/- 7 mmHg at 20 ppm NO). Systemic arterial pressure did not change. The ratio of arterial oxygen tension to inspired oxygen fraction increased (from 126 +/- 36 to 149 +/- 38 mmHg) and the venous admixture decreased (from 31.2 +/- 5.5 to 28.2 +/- 5.2%) without a clear dose-response effect. During prolonged NO inhalation, 2-20 ppm KO effectively reduced mean pulmonary artery pressure (38 +/- 7 vs. 31 +/- 6 mmHg) and increased arterial oxygen tension (79 +/- 10 vs. 114 +/- 27 mmHg) without evidence of tachyphylaxis. The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO (r = -0.72). The reduction of venous admixture correlated with the level of venous admixture without NO (r = -0.78). Conclusions: Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS. The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RESP CARE,BOSTON,MA 02115. RP BIGATELLO, LM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115, USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 FU NHLBI NIH HHS [HL42397] NR 27 TC 234 Z9 236 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1994 VL 80 IS 4 BP 761 EP 770 DI 10.1097/00000542-199404000-00007 PG 10 WC Anesthesiology SC Anesthesiology GA NG521 UT WOS:A1994NG52100007 PM 8024129 ER PT J AU DUTTON, RP ECKHARDT, WF SUNDER, N AF DUTTON, RP ECKHARDT, WF SUNDER, N TI TOTAL SPINAL-ANESTHESIA AFTER INTERSCALENE BLOCKADE OF THE BRACHIAL-PLEXUS SO ANESTHESIOLOGY LA English DT Note DE ANESTHESIA, REGIONAL, INTERSCALENE; COMPLICATIONS, TOTAL SPINAL ANESTHESIA ID TOXICITY C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP DUTTON, RP (reprint author), USN,NATL MED CTR,DEPT ANESTHESIOL,BETHESDA,MD 20889, USA. NR 15 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1994 VL 80 IS 4 BP 939 EP 941 DI 10.1097/00000542-199404000-00028 PG 3 WC Anesthesiology SC Anesthesiology GA NG521 UT WOS:A1994NG52100028 PM 8024148 ER PT J AU HOGAN, Q DOTSON, R ERICKSON, S KETTLER, R HOGAN, K AF HOGAN, Q DOTSON, R ERICKSON, S KETTLER, R HOGAN, K TI LOCAL-ANESTHETIC MYOTOXICITY - A CASE AND REVIEW SO ANESTHESIOLOGY LA English DT Note DE ANESTHETICS, LOCAL, BUPIVACAINE; ANESTHETICS, LOCAL, MYOTOXICITY; MUSCLE, SKELETAL, LOCAL ANESTHETIC TOXICITY; TOXICITY, LOCAL ANESTHETICS ID FROG SKELETAL-MUSCLE; CALCIUM RELEASE; SARCOPLASMIC-RETICULUM; REGENERATION; FIBERS; RHABDOMYOLYSIS; DEGENERATION; INJECTIONS; TETRACAINE; MARCAINE C1 MED COLL WISCONSIN,DEPT NEUROL,MILWAUKEE,WI 53226. MED COLL WISCONSIN,DEPT RADIOL,MILWAUKEE,WI 53226. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT ANESTHESIOL,MADISON,WI. UNIV WISCONSIN,MADISON,WI. RP HOGAN, Q (reprint author), MED COLL WISCONSIN,MILWAUKEE CTY MED COMPLEX,DEPT ANESTHESIOL,8700 W WISCONSIN AVE,MILWAUKEE,WI 53226, USA. NR 48 TC 75 Z9 76 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1994 VL 80 IS 4 BP 942 EP 947 DI 10.1097/00000542-199404000-00029 PG 6 WC Anesthesiology SC Anesthesiology GA NG521 UT WOS:A1994NG52100029 PM 8024149 ER PT J AU REYNOLDS, PP AF REYNOLDS, PP TI REAFFIRMING PROFESSIONALISM THROUGH THE EDUCATION COMMUNITY SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID INTERNAL MEDICINE; RESIDENT; IMPACT; AIDS; TIME AB Objective: To determine the role of the clinical training environment and a medical education community in reaffirming medical professionalism among physicians-in-training and faculty. Data sources: Published articles on undergraduate and graduate medical education and sociology works on professionalism were identified through research. Study selection: Studies were selected that illustrated barriers to professionalism in medical education and patient care and the professional conduct of medical students, residents, and faculty. Results: Factors that undermined the medical education community were the specialization of medicine, the faculty reward systems, and the service demands of residency because of the economics of health care. Conclusions: Establishment of a firm system with a core teaching faculty, creation of mentoring and role modeling programs, implementation of a longitudinal curriculum on medical professionalism, evaluation of physicians on professional conduct, and evaluation of the clinical training environment are suggested as strategies to re-establish an education community and reaffirm professionalism in medicine. C1 VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. RP REYNOLDS, PP (reprint author), UNIV PENN, SCH MED, ROBERT WOOD JOHNSON FDN, CLIN SCHOLARS PROGRAM, 3615 CHESTNUT ST, PHILADELPHIA, PA 19104 USA. NR 47 TC 80 Z9 80 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 1 PY 1994 VL 120 IS 7 BP 609 EP 614 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NC764 UT WOS:A1994NC76400013 PM 8117001 ER PT J AU KOKETSU, N BERLOVE, DJ MOSKOSWITZ, MA KOWALL, NW CADAY, CG FINKLESTEIN, SP AF KOKETSU, N BERLOVE, DJ MOSKOSWITZ, MA KOWALL, NW CADAY, CG FINKLESTEIN, SP TI PRETREATMENT WITH INTRAVENTRICULAR BASIC FIBROBLAST GROWTH-FACTOR DECREASES INFARCT SIZE FOLLOWING FOCAL CEREBRAL-ISCHEMIA IN RATS SO ANNALS OF NEUROLOGY LA English DT Article ID DELAYED NEURONAL DEATH; CORTICAL INFARCTION; CULTURED NEURONS; FACTOR BFGF; STROKE; BRAIN; EXCITOTOXICITY; SYSTEM; FGF; DEGENERATION AB Basic fibroblast growth factor is a polypeptide with potent multipotential trophic effects on central nervous system cells, including neurons, glia, and endothelial cells. In particular, it promotes the survival of a wide variety of brain neurons in vitro, and protects these neurons against the effects of several neurotoxins, including excitatory amino acids, hypoglycemia, and calcium ionophore. Since lack of substrate delivery, excitatory amino acid toxicity; and calcium entry into cells appear to be important processes in neuronal death after ischemia, we tested the hypothesis that: pretreatment with basic fibroblast growth fatter limits infarct Size in a model of focal cerebral ischemia in vivo. Mature male Long-Evans rats received either continuous intraventricular infusion of basic fibroblast growth factor (1.2 mu g/day; with or without heparin, added to stabilize the growth factor) or vehicle alone for 3 days before focal ischemic infarcts were made in the right lateral cerebral cortex by permanent distal middle cerebral artery occlusion and temporary (45-minute) bilateral carotid occlusion. Intraoperative measurements of core temperature, arterial blood pressure and blood gases, blood glucose concentration, and hematocrit and postoperative measurements of temperature revealed no differences among vehicle- versus basic fibroblast growth factor-treated animals: Twenty-four hours later, animals were killed, brains were removed and stained to visualize cortical infarcts, and infarct volume was determined by image analysis. Overall, we found a 25% reduction in infarct volume in basic fibroblast growth factor- (N = 25) versus vehicle-treated (N = 23) animals (P < 0.01). This reduction was riot enhanced by the addition of heparin. These data show that pretreatment with intraventricular basic fibroblast growth factor limits infarct size following focal cerebral ischemia in rats. C1 MASSACHUSETTS GEN HOSP,STROKE LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NINDS NIH HHS [NS-10828] NR 37 TC 131 Z9 134 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1994 VL 35 IS 4 BP 451 EP 457 DI 10.1002/ana.410350413 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NF250 UT WOS:A1994NF25000012 PM 8154872 ER PT J AU TAN, PE BENZ, CC DOLLBAUM, C MOORE, DH EDGERTON, SM ZAVA, DT THOR, AD AF TAN, PE BENZ, CC DOLLBAUM, C MOORE, DH EDGERTON, SM ZAVA, DT THOR, AD TI PROGNOSTIC VALUE OF CATHEPSIN-D EXPRESSION IN BREAST-CANCER - IMMUNOHISTOCHEMICAL ASSESSMENT AND CORRELATION WITH RADIOMETRIC ASSAY SO ANNALS OF ONCOLOGY LA English DT Article DE BREAST CANCER; CATHEPSIN-D; IMMUNOASSAY; IMMUNOHISTOCHEMISTRY; PROGNOSTIC MARKER ID ESTROGEN-REGULATED PROTEIN; EXTRACELLULAR-MATRIX; CELLS; OVEREXPRESSION; DISEASES; SURVIVAL; GROWTH; CARCINOMAS; ONCOGENE; MAMMARY AB Background: The prognostic significance of Cathepsin D and optimal methodologies to measure Cathepsin D in breast cancers are controversial. Patients and methods. Quantitative (immunoradiometric) and semiquantitative (immunohistochemical) assays for Cathepsin D expression were compared using 25 breast carcinomas. Immunohistochemical Cathepsin D results were derived using 3 different anti-Cathepsin D antibodies and significant associations between immunohistochemical and radiometric Cathepsin D data were observed for each reagent. Immunohistochemical analysis of Cathepsin D expression was performed on nearly 500 fixed-embedded archival breast cancers with long-term patient follow-up using 2 anti-Cathepsin D antibodies (CDR2-11/23, IC11). Results: The immunohistochemical reagents recognized generally overlapping subsets of Cathepsin D positive tumors (correlation co-efficient 0.54; p = 0.00016). Correlations between Cathepsin D data and clinical, histologic or biologic features differed for each antibody. For the node-negative patient subset, Cathepsin D immunopositivity correlated with erbB-2 and stress-response protein 27 overexpression but not survival. Cathepsin D positivity was associated with subsequent distant metastasis and estrogen receptor positivity in node positive patients. Univariate analysis of all patients suggested that Cathepsin D in-immunopositivity may be predictive of a reduced metastasis-free but not overall survival. Multivariate analysis, however, failed to confirm an independent prognostic value for Cathepsin D in breast cancer patients. Conclusions: These data do not confirm an independent prognostic significance for Cathepsin D using immunohistochemical methods on breast cancers. C1 UNIV VERMONT,DEPT PATHOL,MED ALUMNI BLDG,BURLINGTON,VT 05405. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,CANC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. AERON BIOTECHNOL INC,SAN LEANDRO,CA. LAWRENCE LIVERMORE NATL LAB,DIV BIOMED SCI,LIVERMORE,CA 94550. NR 40 TC 21 Z9 21 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. PD APR PY 1994 VL 5 IS 4 BP 329 EP 336 PG 8 WC Oncology SC Oncology GA NP846 UT WOS:A1994NP84600007 ER PT J AU BODIS, S HAREGEWOIN, A AF BODIS, S HAREGEWOIN, A TI SIGNIFICANTLY REDUCED SALIVARY NITRIC-OXIDE LEVELS IN SMOKERS SO ANNALS OF ONCOLOGY LA English DT Note DE NITRIX OXIDE; SALIVA; SMOKING AB Background: NO is a free radical gas with manifold physiologic functions primarily as a biologic messenger. Recently we reported the presence of NO in freshly secreted human saliva. We report here a significant reduction of salivary NO production in current smokers compared to non-smokers. Patients and methods: Saliva was collected from smokers (27 donors) and non-smokers (21) after rinsing the mouth with an antiseptic. Freshly secreted saliva, about 200-300 mul, was collected within the first 30-60 seconds after mouth rinsing. NO was assayed using the Griess reagent which measures its byproduct NO2. The values thus obtained were statistically analysed using the Wilcoxon test. Results: Our studies indicate significantly decreased NO levels as measured by its product NO2 in freshly secreted saliva in smokers compared to non-smokers (p = 0.0042). The median NO, level in smokers was 64.85 muM, in non-smokers 194.45 muM, respectively. Conclusions: The role of salivary NO in normal physiology is as yet unknown, however, the finding of reduced salivary NO levels in smokers suggests a potential role in the pathogenesis of smoking related morbidity of the upper aero-digestive tracts. C1 SHIELDS WARREN RES LABS, BOSTON, MA USA. RP BODIS, S (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, JOINT CTR RADIAT THERAPY, 50 BINNEY ST, BOSTON, MA 02115 USA. NR 7 TC 15 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 1994 VL 5 IS 4 BP 371 EP 372 PG 2 WC Oncology SC Oncology GA NP846 UT WOS:A1994NP84600015 PM 8075037 ER PT J AU MAZZULI, T RUSCONI, S MERRILL, DP DAQUILA, RT MOONIS, M CHOU, TC HIRSCH, MS AF MAZZULI, T RUSCONI, S MERRILL, DP DAQUILA, RT MOONIS, M CHOU, TC HIRSCH, MS TI ALTERNATING VERSUS CONTINUOUS DRUG REGIMENS IN COMBINATION CHEMOTHERAPY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN-VITRO SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RECOMBINANT INTERFERON-ALPHA; SYNERGISTIC INHIBITION; REVERSE-TRANSCRIPTASE; ZIDOVUDINE AZT; IN-VITRO; PHASE-I; REPLICATION; RESISTANCE; 2',3'-DIDEOXYCYTIDINE; DIDANOSINE AB We compared the in vitro efficacies of two-, three-, and four-drug combinations given continuously or in alternating regimens against a clinical isolate of human immunodeficiency virus type 1. In H9 cells and peripheral blood mononuclear cells, at the drug concentrations used in this study, there was greater suppression of human immunodeficiency virus type 1 infection as the number of drugs in the regimen was increased from one to four simultaneously administered agents. Although alternating drug regimens were effective, they were not better than continuous administration of either single drugs or combinations of agents and were less effective than giving all drugs of an alternating regimen simultaneously. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,GRAYS 5,FRUIT ST,BOSTON,MA 02114. MEM SLOAN KETTERING CANC CTR,BIOCHEM PHARMACOL LAB,NEW YORK,NY 10021. RI Chou, Ting-Chao/B-4111-2009; Rusconi, Stefano/H-9263-2012 OI Chou, Ting-Chao/0000-0002-3340-1594; FU NCI NIH HHS [CA-12464, CA-35020, CA-54741] NR 38 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1994 VL 38 IS 4 BP 656 EP 661 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NE046 UT WOS:A1994NE04600005 PM 8031028 ER PT J AU BADEN, HP BYERS, HR AF BADEN, HP BYERS, HR TI CLINICAL FINDINGS, CUTANEOUS PATHOLOGY, AND RESPONSE TO THERAPY IN 21 PATIENTS WITH KERATOSIS PILARIS ATROPHICANS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID FOLLICULARIS SPINULOSA DECALVANS AB Background: Keratosis pilaris atrophicans defines a group of cutaneous disorders characterized by follicular hyperkeratosis and scarring. X-linked dominant inheritance has recently been reported in a Dutch family with a form of keratosis pilaris atrophicans defined as keratosis follicularis spinulosa decalvans, with males more severely affected and having corneal involvement. The clinical manifestations observed in different families by others and ourselves did not follow that pattern, suggesting genetic heterogeneity. We report our experience with 21 unrelated individuals. Results: There were 15 male and six female patients whose onset of the skin disease was in early childhood but with scalp involvement occurring in the teen years. The cutaneous lesions consisted of follicular papules with scalp involvement present in eight individuals. Half the women had scalp involvement, and one female and one male had eye changes. Familial involvement was observed in three patients and was compatible with dominant inheritance. Histopathologic examination revealed hyperkeratosis of the upper follicle with an inflammatory response that resulted in follicular destruction. Response to therapy including keratolytics, antibiotics, corticosteroids and retinoids was limited. Conclusions: Our findings support the hypothesis that there is genetic and clinical heterogeneity among the disorders represented by the term keratosis pilaris atrophicans. The cause of these diseases may be a disorder of the keratinocyte, which is responsible for inducing both the hyperkeratosis and inflammatory changes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP BADEN, HP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,BOSTON,MA, USA. NR 22 TC 39 Z9 39 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 1994 VL 130 IS 4 BP 469 EP 475 DI 10.1001/archderm.130.4.469 PG 7 WC Dermatology SC Dermatology GA NG493 UT WOS:A1994NG49300009 PM 8166484 ER PT J AU MARDER, SR WIRSHING, WC VANPUTTEN, T MINTZ, J MCKENZIE, J JOHNSTONCRONK, K LEBELL, M LIBERMAN, RP AF MARDER, SR WIRSHING, WC VANPUTTEN, T MINTZ, J MCKENZIE, J JOHNSTONCRONK, K LEBELL, M LIBERMAN, RP TI FLUPHENAZINE VS PLACEBO SUPPLEMENTATION FOR PRODROMAL SIGNS OF RELAPSE IN SCHIZOPHRENIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID INTERMITTENT; SYMPTOMS; TRIAL AB Background: We studied the effectiveness of treating patients with low doses of fluphenazine decanoate and supplementing them with oral fluphenazine when there was evidence of prodromal symptoms of psychotic exacerbations Methods: Eighty schizophrenic patients who were receiving 5 to 10 mg of fluphenazine decanoate every 2 weeks were monitored for prodromal symptoms using an idiosyncratic prodromal rating scale. When patients met our criteria for a prodromal episode, they were randomly assigned to a double-blind comparison of oral fluphenazine hydrochloride (5 mg twice daily) or a placebo for the current and future prodromal episodes. We compared rates of psychotic exacerbations in the two treatment groups. Results: Thirty-six patients (45%) met the criteria for a prodrome at some point during the trial and were randomized to drug or placebo. Using survival analysis during the entire 2 years, we did not find a significant difference between fluphenazine and placebo in the likelihood that a prodrome would continue to an exacerbation. Survival analysis beginning at the start of the second year of treatment did indicate a significant reduction in exacerbation risk for patients receiving drug supplementation (P=.032). Similarly, there was no difference between the two groups in the proportion of time at risk spent in exacerbation during the first year, but patients receiving active drug supplementation spent less time in an exacerbated state in the second year (P=.05). Conclusions: Our treatment strategy appeared to be effective for some patients, particularly those who were able to remain in the study beyond the first year. Although the occurrence of a prodrome was a fairly good marker that a patient was at high risk of ultimate exacerbation with our low-dose maintenance protocol, prodromes were not highly sensitive indicators of imminent exacerbation. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP MARDER, SR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,PSYCHIAT SERV 116A,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [MH-41573, MH-30911] NR 20 TC 60 Z9 60 U1 8 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 1994 VL 51 IS 4 BP 280 EP 287 PG 8 WC Psychiatry SC Psychiatry GA NF265 UT WOS:A1994NF26500003 PM 8161288 ER PT J AU HISNANICK, J CODDINGTON, DA GERGEN, PJ AF HISNANICK, J CODDINGTON, DA GERGEN, PJ TI TRENDS IN ASTHMA-RELATED ADMISSIONS AMONG AMERICAN-INDIAN AND ALASKAN NATIVE CHILDREN FROM 1979 TO 1989 - UNIVERSAL HEALTH-CARE IN THE FACE OF POVERTY SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID ACUTE CHILDHOOD ASTHMA; LOW-BIRTH-WEIGHT; CHANGING PATTERNS; HOSPITALIZATION; PREVALENCE; MORTALITY; SMOKING; SEVERITY; ILLNESS; SERVICE AB Objective: To describe changes in asthma-related hospitalizations in Indian Health Service facilities and compare with national trends. Design: Trend analysis. Patients and Setting: Hospital discharge records of patients aged 17 years and younger treated by the Indian Health Service between 1979 and 1989. Main Outcome Measures: Patients discharged with asthma as the first listed diagnosis. Results: The rates of asthma-related hospitalizations increased an average of 2.6% (95% confidence interval [CI], 0.1 to 5.2) per year between 1979 and 1989 among American Indian and Alaskan Native children aged 0 to 17 years. The increase was 3.7% among the 0- to 4-year age group (95% CI, 2.0 to 5.5) and 0.3% (95% CI, 0.26 to 0.3) among the 5- to 17-year age group. Boys tended to have a higher rate of increase (4.3% [95% CI, -0.1 to 8.7]) compared with girls (2.6% [95% CI, -0.2 to 5.4]). The rates for any hospitalization decreased during this period for 0- to di-year-olds (-7.5% [95% CI, -10.5 to -4.5]). Little change was noted in hospitalization rates for lower respiratory tract diseases. Diagnostic transfer from bronchitis/bronchiolitis to asthma could not explain the increase. Both first admission and readmission for treatment of asthma contributed to the increase. Compared with previously published data, 0- to 4-year-old American Indian and Alaskan Native children more closely approximate white children than black children in both rates of hospitalization (1979-1987) and annual percentage increase in hospitalization (1979-1989 for American Indian and Alaskan Native children and 1979-1987 for white and black children) for the treatment of asthma. Conclusions: American Indian and Alaskan Native children who are cared for by the Indian Health Service have asthma-related hospitalization patterns that are similar to those seen in white children despite having socioeconomic characteristics more similar to those of black children. C1 INDIAN HLTH SERV,OFF HLTH PROGRAM,TUCSON,AZ. CHILDRENS NATL MED CTR,DEPT GEN PEDIAT,WASHINGTON,DC 20010. NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,BETHESDA,MD 20892. RP HISNANICK, J (reprint author), US DEPT VET AFFAIRS,NVCAS 008C12,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 44 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 1994 VL 148 IS 4 BP 357 EP 363 PG 7 WC Pediatrics SC Pediatrics GA NF055 UT WOS:A1994NF05500003 PM 8148934 ER PT J AU DELMONICO, FL TOLKOFFRUBIN, N AUCHINCLOSS, H FARRELL, ML FITZPATRICK, DM SAIDMAN, S HERRIN, JT COSIMI, AB AF DELMONICO, FL TOLKOFFRUBIN, N AUCHINCLOSS, H FARRELL, ML FITZPATRICK, DM SAIDMAN, S HERRIN, JT COSIMI, AB TI 2ND RENAL TRANSPLANTATIONS - ETHICAL ISSUES CLARIFIED BY OUTCOME, OUTCOME ENHANCED BY A RELIABLE CROSS-MATCH SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the New-England-Surgical-Society CY OCT 29-31, 1993 CL CAMBRIDGE, MA SP NEW ENGLAND SURG SOC ID CYCLOSPORINE; ANTIGLOBULIN; ANTIBODIES; ALLOGRAFT; REJECTION AB Objective: To determine whether the appropriate use of scarce donor resources has been accomplished by renal retransplantation by reviewing the initial and longterm outcomes of second-renal transplant recipients at the Massachusetts General Hospital, Boston. Patients and Results: With a mean follow-up of nearly 5 years following transplantation, 54 (68%) of 80 second-transplant recipients had functioning allografts (allograft failure was defined by patient death or a return to dialysis). Rejection was the most common cause of failure (14 [54%] of 26 patients). The 1-, 3-, and 5-year actuarial allograft survival rates were 86%, 78%, and 69%, respectively, which were not significantly different from the survival rates of primary allografts at this center. These results support the continued approach of providing both cadaver-donor and living-donor renal allografts for recipients whose primary renal allograft has failed. The antiglobulin crossmatch may have contributed to the successful outcome by accurately determining compatibility and by averting early rejection failures. Conclusions: Health care policy reviewers should clearly distinguish the prospects for successful second renal transplants from the outcomes of extrarenal retransplantation. Moreover, because excellent second-renal allograft survival is attainable and comparable to primary-renal allograft survival and because the costs are comparable, restricting suitable patients to subsequent lifelong dialysis becomes unethical. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP DELMONICO, FL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG GRB422,GEN SURG SERV,TRANSPLANTAT UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 22 Z9 26 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1994 VL 129 IS 4 BP 354 EP 360 PG 7 WC Surgery SC Surgery GA NE373 UT WOS:A1994NE37300003 PM 8154961 ER PT J AU MARKOWITZ, JS RATTNER, DW WARSHAW, AL AF MARKOWITZ, JS RATTNER, DW WARSHAW, AL TI FAILURE OF SYMPTOMATIC RELIEF AFTER PANCREATICOJEJUNAL DECOMPRESSION FOR CHRONIC-PANCREATITIS - STRATEGIES FOR SALVAGE SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the New-England-Surgical-Society CY OCT 29-31, 1993 CL CAMBRIDGE, MA SP NEW ENGLAND SURG SOC ID NEAR-TOTAL PANCREATECTOMY; DUCT DRAINAGE; FOLLOW-UP; PAIN; TISSUE; MANAGEMENT; RESECTION; PRESSURE AB Objective: To evaluate causes of intractable recurrent pain following pancreaticojejunostomy for chronic pancreatitis and to evaluate treatment strategies aimed at lasting pain relief. Design: Case series. Setting: Tertiary care referral center. Patients: Fifteen selected patients having severe pain associated with chronic pancreatitis with onset 0 to 60 months (median, 5 months) following pancreaticojejunostomy. Each patient underwent computed tomography and endoscopic retrograde cholangiopancreatography. Two patients (13%) were found to have pancreatic cancer, two (13%) had inadequate pancreatic duct decompression, two (13%) had biliary stenosis, and 10 (67%) had presumed neuropathy in the pancreatic head. Interventions: Fourteen (93%) of the 15 patients underwent the following reoperations: distal pancreatectomy and splenectomy (one patient), extension of the pancreaticojejunostomy and choledochojejunostomy (one patient), biliary stenting followed by choledochojejunostomy (one patient), and Whipple-type resection of the pancreatic head (14 patients). Two patients subsequently underwent a completion pancreatectomy. Main Outcome Measures: Pain relief, functional capacity, and pancreatic exocrine and endocrine status were determined. The median follow-up after reoperation was 39 months. Results: Of the 14 patients who underwent reoperation, 13 were long-term survivors. One died of pancreatic cancer. Ten of the other 13 have had satisfactory-to-excellent relief of pain, with resumption of a normal level of function. Of the 10 previously euglycemic patients who underwent pancreatic head resection, eight remain free of diabetes mellitus to date. Conclusions: The causes of recurrent or persistent pain following pancreaticojejunal decompression for chronic pancreatitis are complex and include neuropathic changes, residual or evolving pancreatic and biliary duct obstruction, and unrecognized pancreatic cancer. Acceptable outcomes can usually be achieved by following a treatment strategy aimed at addressing identified residual disease while maximally preserving pancreatic tissue. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP MARKOWITZ, JS (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,WACC-336,BOSTON,MA 02114, USA. NR 28 TC 80 Z9 83 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1994 VL 129 IS 4 BP 374 EP 380 PG 7 WC Surgery SC Surgery GA NE373 UT WOS:A1994NE37300006 PM 8154964 ER PT J AU NASIRUDDIN JEANLOZ, RW WALKERNASIR, E FAYYAZUDDIN MAHMOOD, Z MAHMOOD, K KHAN, AH RAHMANI, FS AF NASIRUDDIN JEANLOZ, RW WALKERNASIR, E FAYYAZUDDIN MAHMOOD, Z MAHMOOD, K KHAN, AH RAHMANI, FS TI A WATER-SOLUBLE FRAGMENT OF MICROCOCCUS-LYSODEIKTICUS CELL-WALL SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARBOHYDRATE RES LAB,BOSTON,MA. GANGA RAM HOSP,PAKISTAN MED RES COUNCIL CTR,LAHORE,PAKISTAN. RP NASIRUDDIN (reprint author), UNIV BALUCHISTAN,INST BIOCHEM,QUETTA,PAKISTAN. NR 21 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD APR PY 1994 VL 32 IS 6 BP 1129 EP 1137 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM262 UT WOS:A1994NM26200016 PM 8061630 ER PT J AU YELLEN, G SODICKSON, D CHEN, TY JURMAN, ME AF YELLEN, G SODICKSON, D CHEN, TY JURMAN, ME TI AN ENGINEERED CYSTEINE IN THE EXTERNAL MOUTH OF A K+ CHANNEL ALLOWS INACTIVATION TO BE MODULATED BY METAL-BINDING SO BIOPHYSICAL JOURNAL LA English DT Article ID ACETYLCHOLINE-RECEPTOR; POTASSIUM CHANNELS; MEMBRANE PATCHES; SENSORY RECEPTOR; SODIUM-CHANNELS; SITE; ION; MECHANISMS; SULFHYDRYL; ACTIVATION AB Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-Delta K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a K-d for Cd2+ of similar to 0.2 mu M. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RP YELLEN, G (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,MOLEC PHYSIOL LAB,WELLMAN 340A,50 BLOSSOM ST,BOSTON,MA, USA. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [NS29693, R01 NS029693] NR 36 TC 226 Z9 227 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1994 VL 66 IS 4 BP 1068 EP 1075 PG 8 WC Biophysics SC Biophysics GA ND194 UT WOS:A1994ND19400015 PM 8038379 ER PT J AU COREY, DP HOWARD, J AF COREY, DP HOWARD, J TI MODELS FOR ION-CHANNEL GATING WITH COMPLIANT STATES SO BIOPHYSICAL JOURNAL LA English DT Letter ID HAIR-CELLS; TRANSDUCTION C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. UNIV WASHINGTON,DEPT PHYSIOL & BIOPHYS,SEATTLE,WA 98195. RP COREY, DP (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02114, USA. RI Howard, Jonathon /D-4229-2011; Howard, Jonathon/J-7492-2016; OI Howard, Jonathon /0000-0003-0086-1196; Howard, Jonathon/0000-0003-0086-1196; Corey, David/0000-0003-4497-6016 FU NIAMS NIH HHS [NIAMSD AR40593]; NIDCD NIH HHS [NIDCD DC00304] NR 10 TC 7 Z9 7 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1994 VL 66 IS 4 BP 1254 EP 1257 PG 4 WC Biophysics SC Biophysics GA ND194 UT WOS:A1994ND19400034 PM 8038396 ER PT J AU BARNARD, GF PUDER, M BEGUM, NA CHEN, LB AF BARNARD, GF PUDER, M BEGUM, NA CHEN, LB TI PCR PRODUCT SEQUENCING WITH [ALPHA-P-33] AND [ALPHA-P-32]DATP SO BIOTECHNIQUES LA English DT Note C1 DANA FARBER CANC INST,BOSTON,MA. RP BARNARD, GF (reprint author), UNIV MASSACHUSETTS,MED CTR,DIV DIGEST DIS & NUTR,55 LAKE AVE N,WORCESTER,MA 01605, USA. FU NCI NIH HHS [CA44704, NCI 5F32CA-0900] NR 7 TC 21 Z9 21 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 1994 VL 16 IS 4 BP 572 EP 573 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NE764 UT WOS:A1994NE76400001 PM 8024769 ER PT J AU ORSON, FM AF ORSON, FM TI PHOTODOCUMENTATION OF UV SHADOWING WITH DNA GELS SO BIOTECHNIQUES LA English DT Note ID TRANSCRIPTION; INHIBITION C1 BAYLOR COLL MED,DEPT INTERNAL MED,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT VET AFFAIRS MED CTR,HOUSTON,TX 77030. NR 9 TC 2 Z9 2 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 1994 VL 16 IS 4 BP 592 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NE764 UT WOS:A1994NE76400008 PM 8024774 ER PT J AU DURANTE, W SCHINI, VB KROLL, MH CATOVSKY, S SCOTTBURDEN, T WHITE, JG VANHOUTTE, PM SCHAFER, AI AF DURANTE, W SCHINI, VB KROLL, MH CATOVSKY, S SCOTTBURDEN, T WHITE, JG VANHOUTTE, PM SCHAFER, AI TI PLATELETS INHIBIT THE INDUCTION OF NITRIC-OXIDE SYNTHESIS BY INTERLEUKIN-1-BETA IN VASCULAR SMOOTH-MUSCLE CELLS SO BLOOD LA English DT Article ID MOLECULAR-WEIGHT COMPLEX; L-ARGININE; ENDOTHELIAL-CELLS; RELAXING FACTOR; GROWTH-FACTOR; SYNTHASE ACTIVITY; RELAXATION; VASODILATORS; AGGREGATION; EXPRESSION C1 HOUSTON VET AFFAIRS MED CTR,MED SERV,2002 HOLCOMBE BLVD,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED & PHARMACOL,HOUSTON,TX 77030. BAYLOR COLL MED,CTR EXPTL THERAPEUT,HOUSTON,TX 77030. UNIV MINNESOTA,SCH MED,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,MINNEAPOLIS,MN 55455. UNIV FREIBURG,DEPT APPL PHYSIOL,W-7800 FREIBURG,GERMANY. RI Vanhoutte, Paul/B-4533-2009 FU NHLBI NIH HHS [HL-31183, HL-36045, HL-46356] NR 42 TC 20 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1994 VL 83 IS 7 BP 1831 EP 1838 PG 8 WC Hematology SC Hematology GA NE411 UT WOS:A1994NE41100016 PM 8142651 ER PT J AU RICHARDSON, EP ASTROM, KE KLEIHUES, P AF RICHARDSON, EP ASTROM, KE KLEIHUES, P TI THE DEVELOPMENT OF NEUROPATHOLOGY AT THE MASSACHUSETTS GENERAL-HOSPITAL AND HARVARD MEDICAL-SCHOOL SO BRAIN PATHOLOGY LA English DT Note AB Few institutions have shaped neuropathology as a discipline as profoundly as Massachusetts General Hospital (MGH) and Harvard Medical School. Their fascination over many decades is due to a unique accumulation of excellent, intellectually stimulating neurologists with a sincere interest in the morphologic and pathogenetic basis of nervous system diseases. Their approach was strictly case oriented and clinico-pathological conferences were developed to the highest standard. In this review, the foundations of neuropathology in Boston are recounted. C1 NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. UNIV ZURICH HOSP,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. INT AGCY RES CANC,F-69372 LYON,FRANCE. RP RICHARDSON, EP (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114, USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 1994 VL 4 IS 2 BP 181 EP 195 DI 10.1111/j.1750-3639.1994.tb00828.x PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA NH750 UT WOS:A1994NH75000008 PM 8061862 ER PT J AU RANDOLPH, ET ETH, S GLYNN, SM PAZ, GG LEONG, GB SHANER, AL STRACHAN, A VANVORT, W ESCOBAR, JI LIBERMAN, RP AF RANDOLPH, ET ETH, S GLYNN, SM PAZ, GG LEONG, GB SHANER, AL STRACHAN, A VANVORT, W ESCOBAR, JI LIBERMAN, RP TI BEHAVIORAL FAMILY MANAGEMENT IN SCHIZOPHRENIA - OUTCOME OF A CLINIC-BASED INTERVENTION SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID CONTROLLED TRIAL; PREVENTION AB To test further the highly successful outcomes of a controlled study of in-home behavioural family management (BFM) for schizophrenic patients, a clinic-based version of this intervention was compared with customary care alone for 41 schizophrenic patients in a Veterans Administration (VA) mental health clinic. Monthly Brief Psychiatric Rating Scale (BPRS) ratings, conducted by clinic psychiatrists who were 'blind' to the patients' assignment, revealed that 3 (14%) patients who received behavioural family management as well as customary care, as compared with 11 (55%) patients who received customary care alone, had symptomatic exacerbations during the first year of treatment. C1 SANTA MONICA FAMILY CONSULTANTS,SANTA MONICA,CA 90405. UNIV CONNECTICUT,DEPT PSYCHIAT,FARMINGTON,CT 06107. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,CLIN RES CTR SCHIZOPHRENIA,LOS ANGELES,CA 90025. RP RANDOLPH, ET (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 19 TC 92 Z9 95 U1 1 U2 3 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 1994 VL 164 BP 501 EP 506 DI 10.1192/bjp.164.4.501 PG 6 WC Psychiatry SC Psychiatry GA NF414 UT WOS:A1994NF41400013 PM 8038939 ER PT J AU BORSMAN, ML AF BORSMAN, ML TI FAXON-FINDER FAXON-XPRESS - REPORT FROM A BETA-TEST SITE SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the Medical-Library-Association CY MAY 14-20, 1993 CL CHICAGO, IL SP MED LIB ASSOC ID DOCUMENT DELIVERY AB In this environment of expanding information needs, spiraling journal costs, and curtailed financial resources, medical libraries must take advantage of the rapid evolution in document delivery services [1-3]. There are exciting developments in transmission technology, from fax machines to scanners to the Internet [4]. There is also a notable shift away from the traditional reliance on library networks toward use of commercial vendors as document providers. These changes require reevaluation of interlibrary loan (ILL) and document delivery systems on many levels, including pricing structures, work flow, and impact on collection development [5-7]. As commercial vendors develop increasingly effective products, librarians can test, evaluate, and incorporate them into their ILL operations to enhance service to users and relieve the pressure to acquire new resources; in this way, librarians can move from the ''just in case'' practice of building an on-site collection to the ''just in time'' model of providing timely delivery of materials to users as needed. This paper describes a beta test of the Faxon Finder/Faxon Xpress table of contents and document delivery services conducted by the Treadwell Library of the Massachusetts General Hospital. RP BORSMAN, ML (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,ACCESS SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 7 TC 1 Z9 1 U1 0 U2 1 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD APR PY 1994 VL 82 IS 2 BP 168 EP 170 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA NF278 UT WOS:A1994NF27800008 PM 8004019 ER PT J AU SIMMER, JP LAU, EC HU, CC AOBA, T LACEY, M NELSON, D ZEICHNERDAVID, M SNEAD, ML SLAVKIN, HC FINCHAM, AG AF SIMMER, JP LAU, EC HU, CC AOBA, T LACEY, M NELSON, D ZEICHNERDAVID, M SNEAD, ML SLAVKIN, HC FINCHAM, AG TI ISOLATION AND CHARACTERIZATION OF A MOUSE AMELOGENIN EXPRESSED IN ESCHERICHIA-COLI SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE AMELOGENIN; EXPRESSION; ENAMEL; RECOMBINANT DNA; TOOTH ID DESORPTION MASS-SPECTROMETRY; ENAMEL PROTEINS; MOLAR TOOTH; LOCALIZATION; IDENTIFICATION; HETEROGENEITY; ORGANOGENESIS; ANTIBODIES; TRANSCRIPT; FETAL AB A mouse cDNA encoding a 180 amino acid amelogenin was subcloned into the pET expression plasmid (Novagen, Madison, WI) for production in Escherichia coli. A simple growth and purification protocol yields 20-50 mg of 95-99% pure recombinant amelogenin from a 4.5-liter culture. This is the first heterologous expression of an enamel protein. The expressed protein was characterized by partial Edman sequencing, amino acid composition analysis, SDS-PAGE, Western blotting, laser desorption mass spectrometry, and hydroxyapatite binding. The recombinant amelogenin is 179 amino acids in length, has a molecular weight of 20,162 daltons, and hydroxyapatite binding properties similar to the porcine 173 residue amelogenin. Solubility analyses showed that the bacterially expressed protein is only sparingly soluble in the pH range of 6.4-8.0 or in solutions 20% saturated with ammonium sulfate. The purified protein was used to generate rabbit polyclonal anti-amelogenin antibodies which show specific reaction to amelogenins in both Western blot analyses of enamel extracts and in immunostaining of developing mouse molars. C1 UNIV SO CALIF,SCH DENT,CTR CRANIOFACIAL MOLEC BIOL,LOS ANGELES,CA 90033. FORSYTH DENT CTR,FORSYTH RES INST,BOSTON,MA 02115. PROCTER & GAMBLE CO,MIAMI VALLEY LABS,CINCINNATI,OH 45239. RI Zeichner-David, Margarita/A-6567-2008 FU NIDCR NIH HHS [NIDR DE-02848] NR 41 TC 160 Z9 161 U1 2 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD APR PY 1994 VL 54 IS 4 BP 312 EP 319 DI 10.1007/BF00295956 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NB462 UT WOS:A1994NB46200011 PM 8062146 ER PT J AU KRONENBERG, HM AF KRONENBERG, HM TI MECHANISMS OF REGULATION OF THE PARATHYROID-HORMONE GENE BY VITAMIN-D SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD APR PY 1994 VL 54 IS 4 BP 333 EP 333 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NB462 UT WOS:A1994NB46200026 ER PT J AU KRANE, SM AF KRANE, SM TI EFFECT OF STEROID-HORMONES ON TYPE-I COLLAGEN GENE-EXPRESSION SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD APR PY 1994 VL 54 IS 4 BP 335 EP 335 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NB462 UT WOS:A1994NB46200030 ER PT J AU MULLER, RT CALDWELL, RA HUNTER, JE AF MULLER, RT CALDWELL, RA HUNTER, JE TI FACTORS PREDICTING THE BLAMING OF VICTIMS OF PHYSICAL CHILD-ABUSE OR RAPE SO CANADIAN JOURNAL OF BEHAVIOURAL SCIENCE-REVUE CANADIENNE DES SCIENCES DU COMPORTEMENT LA English DT Article ID DEFENSIVE-ATTRIBUTION; RESPONSIBILITY; OBSERVER; PERSONALITY; RESISTANCE; ACCIDENT; EMPATHY; BELIEFS; ASSAULT; WORLD AB This study examined factors that were hypothesized to predict victim blame in the case of physical child abuse and in the case of rape. Questionnaires were completed by 897 college students. The results suggested that the defensive attribution hypothesis (particularly the notion of harm avoidance motives) was consistent with the current findings. In contrast, just world theory was not supported. Victim blame in child abuse and victim blame in rape were predicted by similar factors. The factors that best predicted victim blame were empathy, locus of control, and prior physical abuse. Personal similarity was a statistically significant predictor for both child blame and rape victim blame. Just world beliefs had virtually no predictive power, when other factors were taken into consideration. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MICHIGAN STATE UNIV,E LANSING,MI 48824. RP MULLER, RT (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 61 TC 19 Z9 19 U1 3 U2 9 PU CANADIAN PSYCHOL ASSOC PI OTTAWA PA 151 SLATER ST, STE 205, OTTAWA ON K1P 5H3, CANADA SN 0008-400X J9 CAN J BEHAV SCI JI Can. J. Behav. Sci.-Rev. Can. Sci. Comport. PD APR PY 1994 VL 26 IS 2 BP 259 EP 279 DI 10.1037/0008-400X.26.2.259 PG 21 WC Psychology, Multidisciplinary SC Psychology GA NR975 UT WOS:A1994NR97500008 ER PT J AU CONLON, MR RUBIN, PAD SAMY, CN ALBERT, DM AF CONLON, MR RUBIN, PAD SAMY, CN ALBERT, DM TI METASTATIC ORBITAL LEIOMYOSARCOMA - A CLINICOPATHOLOGICAL STUDY SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Note DE LEIOMYOSARCOMA; METASTASIS; ORBIT ID BILATERAL RETINOBLASTOMA; TISSUE C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULOPLAST & ORBIT SERV,BOSTON,MA 02114. UNIV WISCONSIN,DEPT OPHTHALMOL,MADISON,WI 53706. NR 38 TC 1 Z9 1 U1 0 U2 0 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA ON K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD APR PY 1994 VL 29 IS 2 BP 85 EP 89 PG 5 WC Ophthalmology SC Ophthalmology GA NM643 UT WOS:A1994NM64300008 PM 8069761 ER PT J AU BELL, DA SCULLY, RE AF BELL, DA SCULLY, RE TI EARLY DE-NOVO OVARIAN-CARCINOMA - A STUDY OF 14 CASES SO CANCER LA English DT Article DE OVARIAN NEOPLASMS; EARLY CARCINOMA; DE-NOVO CARCINOMA; OVARIAN INTRAEPITHELIAL NEOPLASIA ID PROPHYLACTIC OOPHORECTOMY; CANCER; BENIGN AB Background. The search for methods of early detection of ovarian carcinoma in recent years has emphasized the lack of information regarding the histologic features of early carcinoma or its precursor lesions; few examples of early de novo ovarian carcinoma have been reported. Methods. The clinicopathologic features of 14 cases of early ovarian carcinoma detected as microscopic findings in grossly normal ovaries retrieved from a consultation practice and the files of the Massachusetts General Hospital were reviewed. Results. The patients ranged in age from 27-65 years (mean, 50 years). Three women had a family history of ovarian carcinoma and six did not. The tumors ranged from microscopic to 7 mm in greatest dimension; all were unilateral and four were multifocal. One tumor involved the surface and its crypts; four, the surface and superficial cortex; eight, the superficial cortex only; and in one, surface involvement was not ascertainable. Ten carcinomas were serous; one, endometrioid; one, clear cell; and two, poorly differentiated, of undetermined cell type. Severe atypia of the noncarcinomatous surface epithelium or its inclusion cysts was additionally present in three cases. Among the seven patients whose diagnoses were made at the time of oophorectomy who had follow-up data of at least 2 years or until recurrence or death, five were alive without recurrences, one was alive with recurrence, and one died of tumor. Two of the three women died whose ovarian tumors were diagnosed retrospectively on discovery of subsequent peritoneal carcinomatosis, and the third was alive with recurrent tumor. No relation between any clinical or pathologic feature and survival was apparent in this small series except for a suggestion that well differentiated tumors had a good prognosis. Conclusions. These findings document that at least a subset of ovarian epithelial cancers develops de novo. The guarded prognosis associated with these tumors despite their minute dimensions raises questions about the value of current screening techniques for early detection of ovarian cancer. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP BELL, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 12 TC 163 Z9 165 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1994 VL 73 IS 7 BP 1859 EP 1864 DI 10.1002/1097-0142(19940401)73:7<1859::AID-CNCR2820730714>3.0.CO;2-L PG 6 WC Oncology SC Oncology GA NC857 UT WOS:A1994NC85700013 PM 8137211 ER PT J AU MATIASGUIU, X PRAT, J YOUNG, RH CAPEN, CC ROSOL, TJ DELELLIS, RA SCULLY, RE AF MATIASGUIU, X PRAT, J YOUNG, RH CAPEN, CC ROSOL, TJ DELELLIS, RA SCULLY, RE TI HUMAN PARATHYROID-HORMONE RELATED PROTEIN IN OVARIAN SMALL-CELL CARCINOMA - AN IMMUNOHISTOCHEMICAL STUDY SO CANCER LA English DT Article DE SMALL CELL CARCINOMA; OVARY; HYPERCALCEMIA; PARATHYROID HORMONE RELATED PROTEIN; IMMUNOHISTOCHEMISTRY ID HUMORAL HYPERCALCEMIA; PEPTIDE; MALIGNANCY; CANCER; IDENTIFICATION; EXPRESSION; CALCIUM; TUMORS AB Background. Small cell carcinomas (SCC) are the most common ovarian tumors associated with hypercalcemia. Parathyroid hormone-related protein (PTHrp) is the most frequent cause of hypercalcemia of malignancy. Methods. The presence of PTHrp in SCC has been studied by immunohistochemistry in formalin fixed, paraffin embedded tissues. A polyclonal antibody against a synthetic peptide corresponding to the first 36-N terminal amino acid residues of PTHrp was used. Normal dog skin, which is rich in PTHrp, was used as a positive control. Absorption tests using the synthetic peptide as antigen were done in all the cases. Results. Immunoreactivity for PTHrp was found in five of seven cases of SCC. The serum calcium levels were elevated in two of these cases, normal in two, and unknown in one. The two negative cases were associated with high serum calcium levels. Conclusion. The lack of correlation between immunoreactivity and serum calcium levels can be explained on the basis that immunohistochemistry is dependent on the peptide content of cells rather than on the capability for hormone production and/or release. The results suggest that PTHrp plays a role in the development of hypercalcemia in patients with SCC of the ovary. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. OHIO STATE UNIV,DEPT VET PATHOBIOL,COLUMBUS,OH 43210. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. RP MATIASGUIU, X (reprint author), AUTONOMOUS UNIV BARCELONA,HOSP SANTA CREU ST PAU,DEPT PATHOL,AVE ST ANTONI MA CLARET 167,E-08025 BARCELONA,SPAIN. RI Prat, Jaime/G-4679-2011; Rosol, Thomas/G-9585-2011; matias-guiu, xavier/C-3039-2009 OI Rosol, Thomas/0000-0003-3737-1190; matias-guiu, xavier/0000-0002-7201-6605 NR 18 TC 45 Z9 46 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 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1994 VL 73 IS 7 BP 1878 EP 1881 DI 10.1002/1097-0142(19940401)73:7<1878::AID-CNCR2820730717>3.0.CO;2-D PG 4 WC Oncology SC Oncology GA NC857 UT WOS:A1994NC85700016 PM 8137214 ER PT J AU RAGO, RP MILES, JM SUFIT, RL SPRIGGS, DR WILDING, G AF RAGO, RP MILES, JM SUFIT, RL SPRIGGS, DR WILDING, G TI SURAMIN-INDUCED WEAKNESS FROM HYPOPHOSPHATEMIA AND MITOCHONDRIAL MYOPATHY - ASSOCIATION OF SURAMIN WITH MITOCHONDRIAL TOXICITY IN HUMANS SO CANCER LA English DT Article DE SURAMIN; MITOCHONDRIAL MYOPATHY; HYPOPHOSPHATEMIA; FANCONIS SYNDROME; WEAKNESS; NEOPLASM ID CARCINOMA-CELLS; DISRUPTION; MECHANISM; THERAPY; DRUG AB Background. Suramin is an antiparasitic drug being evaluated as an antitumor compound. Suramin therapy commonly causes weakness and is known to cause neuropathy. Two potential causes of suramin-induced muscular weakness are described. Methods. Suramin was administered to 15 patients with advanced cancer as part of a Phase I study. Weekly dosing was adjusted to achieve mean plasma concentrations of 210 mug/ml. Results. Serum phosphate levels fell significantly (P < 0.0001) in all 15 patients on the 42nd day of treatment from a pretreatment average of 4.0 mg/dl (standard deviation [SD] +/- 0.37) to 3.0 mg/dl (SD +/- 0.20). Absolute hypophosphatemia developed in two patients with more prolonged suramin treatment due to Fanconi's syndrome. The patient who received the largest amount of suramin (19.2 g over 14 weeks) had severe proximal muscle weakness despite 6 weeks of effective phosphate repletion. A muscle biopsy was performed, which demonstrated markedly decreased cytochrome c oxidase activity by muscle histochemistry and biochemistry. Electron microscopy revealed subsarcolemmal collections of abnormal mitochondria. This mitochondrial myopathy resolved clinically 7 weeks after discontinuing suramin. Conclusions. This report indicates that suramin is associated with hypophosphatemia of Fanconi's syndrome and a mitochondrial myopathy. The clinical combination of mitochondrial myopathy and Fanconi's syndrome is similar to descriptions of congenital mitochondrial cytochrome c oxidase deficiency of de Toni-Fanconi-Debre syndrome. These findings in humans correlate with the authors' in vitro observations that suramin causes toxic mitochondrial changes, indicating a mechanism of suramin's toxicity and possibly its antitumor effect. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,K4-666 CSC,600 HIGHLAND AVE,MADISON,WI 53792. UNIV WISCONSIN HOSP & CLIN,DEPT PATHOL,MADISON,WI. UNIV WISCONSIN HOSP & CLIN,DEPT NEUROL,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. FU NCI NIH HHS [N01-CM-57735, T32-CA-09614, CA-50590] NR 21 TC 23 Z9 23 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1994 VL 73 IS 7 BP 1954 EP 1959 DI 10.1002/1097-0142(19940401)73:7<1954::AID-CNCR2820730729>3.0.CO;2-H PG 6 WC Oncology SC Oncology GA NC857 UT WOS:A1994NC85700028 PM 8137223 ER PT J AU KOPANS, DB AF KOPANS, DB TI MAMMOGRAPHY SCREENING FOR BREAST-CANCER - REPLY SO CANCER LA English DT Letter ID CARCINOMA RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1994 VL 73 IS 7 BP 2004 EP 2006 PG 3 WC Oncology SC Oncology GA NC857 UT WOS:A1994NC85700039 ER PT J AU LICHT, JD MAZANET, R LOEHRER, PJ GONIN, R ANTMAN, KH AF LICHT, JD MAZANET, R LOEHRER, PJ GONIN, R ANTMAN, KH TI PHASE-IV TRIAL OF DAILY ORAL ETOPOSIDE IN THE TREATMENT OF ADVANCED SOFT-TISSUE SARCOMA SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Note DE ETOPOSIDE; SARCOMA; CHEMOTHERAPY ID CELL LUNG-CANCER; VP-16-213 AB Intravenous-bolus etoposide has modest activity in sarcomas when given daily for 3-5 days. Low frequent doses theoretically inhibit topoisomerase II activity over a longer duration and have been reported to have increased activity in small-cell lung cancer. A phase I trial of oral etoposide resulted in partial responses in two patients with soft-tissue sarcomas. To estimate more accurately the response rate for daily oral etoposide in sarcomas, we treated 25 patients with 50 mg/m(2) per day by mouth for 21 days every 4 weeks. Treatment-related toxicity included greater than or equal to grade 2 neutropenia in 6 of the 25 patients and thrombocytopenia in 3. One brief partial response was observed (4%; 95% confidence interval for true response rate, 0-11%). Disease stabilized in five patients for periods ranging from 3 to 18 months. At this dose and on this schedule, daily oral etoposide appears to have little activity against soft-tissue sarcomas. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HOOSIER ONCOL GRP,INDIANAPOLIS,IN 46208. NR 13 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 1994 VL 34 IS 1 BP 79 EP 80 DI 10.1007/BF00686117 PG 2 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NH870 UT WOS:A1994NH87000014 PM 8174207 ER PT J AU SUIT, H ALLAM, A ALLALUNISTURNER, J BROCK, W GIRINSKY, T HILL, S HUNTER, N MILAS, L PEARCEY, R PETERS, L WELCH, DR WEST, C EFIRD, J AF SUIT, H ALLAM, A ALLALUNISTURNER, J BROCK, W GIRINSKY, T HILL, S HUNTER, N MILAS, L PEARCEY, R PETERS, L WELCH, DR WEST, C EFIRD, J TI IS TUMOR-CELL RADIATION-RESISTANCE CORRELATED WITH METASTATIC ABILITY SO CANCER RESEARCH LA English DT Article ID RECURRING MAMMARY-TUMORS; LOCAL-CONTROL; X-IRRADIATION; RAS ONCOGENE; INVITRO; CARCINOMA; CANCER; SENSITIVITY; RADIOSENSITIVITY; DISSEMINATION AB Patients who experience local failure following radiation treatment of epithelial malignancies exhibit a substantially higher rate of distant metastasis than those patients who achieve permanent local control. This fact has raised concern that the local failure to control the primary/regional tumor may serve as a marker of a particularly malignant neoplasm, i.e., high metastatic activity and radiation resistance. If this were true, there would be no gains in survival by increasing the efficacy of treating the primary/regional disease because the new local controls would develop distant metastasis. To investigate this concept, the relationship between distant metastasis probability and tumor cell radiation resistance has been studied by examining laboratory and clinical data (in vitro and in vivo assays) from six collaborating centers. TCD50s (radiation dose which inactivates half of the irradiated tumors) and incidence of distant metastasis in mice with local control have been evaluated for 24 murine tumor systems. SF2s (surviving fraction after 2 Gy) were determined in vitro for cell lines from 8 human, 13 mouse, and 15 rat tumors/tumor sublines and the metastatic activity assessed after injection of the cells into syngeneic murine hosts and xenogenic hosts for the human tumors. SF2s of cells from carcinomas of the head/neck, cervix, and endometrium which were controlled locally by radiation +/- surgery from four centers were compared for those which did and those which did not metastasize. The total number of patients studied was 222. The cumulative distributions of SFs of locally controlled tumors which did and did not metastasize were not different in each of the data sets. Similarly, there was no demonstrable relationship between TCD50s and metastatic frequency in local control mice. Furthermore, the SF2S of murine and human tumor cell lines did not track with metastatic activity. Radiation sensitivity of clinical and laboratory tumors did not correlate with metastatic activity in studies of data from six centers. C1 CROSS CANC INST,EDMONTON T6G 1Z2,ALBERTA,CANADA. UNIV TEXAS,MD ANDERSON CANC CTR,DIV RADIOTHERAPY,HOUSTON,TX 77030. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. MT VERNON HOSP,GRAY LAB,LONDON HA6 2JR,ENGLAND. CHRISTIE HOSP & HOLT RADIUM INST,NHS TRUST,PATERSON INST CANC RES,MANCHESTER M20 9BX,LANCS,ENGLAND. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DIV EXPTL PATHOL,HERSHEY,PA 17033. RP SUIT, H (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Welch, Danny/B-7310-2009; West, Catharine/J-4152-2012 OI Welch, Danny/0000-0002-1951-4947; West, Catharine/0000-0002-0839-3449 FU NCI NIH HHS [CA 06294, CA 13311, CA 50192] NR 39 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1994 VL 54 IS 7 BP 1736 EP 1741 PG 6 WC Oncology SC Oncology GA ND238 UT WOS:A1994ND23800025 PM 8137288 ER PT J AU KULA, NS BALDESSARINI, RJ KEBABIAN, JW NEUMEYER, JL AF KULA, NS BALDESSARINI, RJ KEBABIAN, JW NEUMEYER, JL TI S-(+)-APORPHINES ARE NOT SELECTIVE FOR HUMAN D-3 DOPAMINE-RECEPTORS SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE AMINOERGOLINES; AMINOTETRALINS; APORPHINES; DOPAMINE; D-2; D-3; RECEPTORS; STRIATUM; TRANSFECTION ID INSITU HYBRIDIZATION HISTOCHEMISTRY; RAT-BRAIN; D3-DOPAMINE RECEPTOR; ANTIPSYCHOTIC AGENTS; SITES; LOCALIZATION; EXPRESSION; LIGAND; D3 AB 1. Our aim was to test the hypothesis that selectivity for D-3 dopamine (DA) receptors may contribute to limbic anti-DA selectivity of S-(+)-aporphine DA partial agonists. 2. Affinity was tested with H-3-emonapride, using human D-3 receptors in mouse fibroblasts and D-2 receptors in rat striatal tissue. 3. D-3 receptors showed a picomolar affinity for H-3-emonapride, Na+ dependence, and reversible saturability, as well as stereoselectivity. Confirmatory or novel D-3/D-2, pharmacologic selectivity was found with several benzamides, thioxanthenes, buspirone, GBR-12909, and DA agonists including hydroxyaminotetralins [ADTN, (+)-7-OH-DPAT, (-)-PPHT and its fluorescein derivative], (-)-N-propylnorapomorphine, (-)-3-PPP, (-)-quinpirole, and SDZ-205-502, but neither aminoergoline nor (+)-aporphine partial agonists. 4. The results extend pharmacologic characterization of D-3-transfected cell membranes but fail to account for the high limbic anti-DA selectivity of S-(+)-aporphines. C1 MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. RES BIOCHEM INT,NATICK,MA 01760. FU NIMH NIH HHS [MH-47370, MH-34006] NR 22 TC 42 Z9 42 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 1994 VL 14 IS 2 BP 185 EP 191 DI 10.1007/BF02090784 PG 7 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA PL747 UT WOS:A1994PL74700006 PM 7842476 ER PT J AU MORRISON, BJ EAGLE, KA AF MORRISON, BJ EAGLE, KA TI LEFT ATRIAL-MYXOMA PRESENTING AS ACUTE RESPIRATORY-FAILURE SO CHEST LA English DT Note AB We report the unusual case of a young man with acute respiratory failure caused by a left atrial myxoma. The patient's rapid clinical deterioration and severe hypoxemia suggested the acute respiratory distress syndrome; however, unexpected physical examination findings and a markedly elevated pulmonary capillary wedge pressure implied cardiac abnormality. The use of echocardiography as a bedside tool allowed correct, rapid diagnosis. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MORRISON, BJ (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD APR PY 1994 VL 105 IS 4 BP 1282 EP 1283 DI 10.1378/chest.105.4.1282 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NE954 UT WOS:A1994NE95400069 PM 8162773 ER PT J AU FERNANDEZORTIZ, A MEYER, BJ MAILHAC, A FALK, E BADIMON, L FALLEN, JT FUSTER, V CHESEBRO, JH BADIMON, JJ AF FERNANDEZORTIZ, A MEYER, BJ MAILHAC, A FALK, E BADIMON, L FALLEN, JT FUSTER, V CHESEBRO, JH BADIMON, JJ TI NEW APPROACH FOR LOCAL INTRAVASCULAR DRUG-DELIVERY - IONTOPHORETIC BALLOON SO CIRCULATION LA English DT Note DE RESTENOSIS; CATHETERS; ANGIOPLASTY ID NEOINTIMAL PROLIFERATION; RESTENOSIS; HIRUDIN; HEPARIN AB Background Catheter-based systems are being developed to deliver drugs directly into the vessel wall. Pressure-mediated trauma and lack of homogeneous delivery are key limitations of these approaches. Methods and Results We studied a new catheter-based delivery system that uses electrical current to force the drug into the vessel wall. The in vivo feasibility of this approach has been assessed by delivering I-125-hirudin into porcine carotid arteries. Vascular levels of hirudin after active iontophoresis (4 mA/cm(2), 5 minutes) were 80-fold greater than those achieved by passive diffusion (without electricity). Tissue hirudin levels declined over time; by 1 hour after delivery, 80% of the drug had left the vessel wall, and by 3 hours later, the levels of hirudin within the wall were similar to those achieved by passive diffusion. Autoradiography revealed distribution of the drug throughout the entire circumference of the arterial wall within the intima, media, and adventitia. Iontophoresis-mediated vessel wall trauma was minimal (less than 10% endothelial denudation and medial smooth muscle cell damage). Balloon injury after local delivery changed neither kinetics nor distribution of the drug into the arterial wall. Conclusions (1) High local concentrations of hirudin in the arterial wall may be achieved with the iontophoretic balloon catheter. (2) The drug is distributed throughout the entire vessel wall without significant damage. (3) The retention of hirudin in the arterial wall is time dependent. (4) This technique might be useful to deliver therapeutic agents before or after percutaneous vascular interventions. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,CARDIOVASC BIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014; Falk, Erling/A-7475-2015; Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI BADIMON, LINA/0000-0002-9162-2459; Falk, Erling/0000-0001-8566-9974; Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 NR 14 TC 61 Z9 61 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1994 VL 89 IS 4 BP 1518 EP 1522 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NG469 UT WOS:A1994NG46900006 PM 8149516 ER PT J AU TOPOL, EJ FUSTER, V HARRINGTON, RA CALIFF, RM KLEIMAN, NS KEREIAKES, DJ COHEN, M CHAPEKIS, A GOLD, HK TANNENBAUM, MA RAO, AK DEBOWEY, D SCHWARTZ, D HENIS, M CHESEBRO, J AF TOPOL, EJ FUSTER, V HARRINGTON, RA CALIFF, RM KLEIMAN, NS KEREIAKES, DJ COHEN, M CHAPEKIS, A GOLD, HK TANNENBAUM, MA RAO, AK DEBOWEY, D SCHWARTZ, D HENIS, M CHESEBRO, J TI RECOMBINANT HIRUDIN FOR UNSTABLE ANGINA-PECTORIS - A MULTICENTER, RANDOMIZED ANGIOGRAPHIC TRIAL SO CIRCULATION LA English DT Article DE ANGINA; THROMBOSIS; THROMBIN; HIRUDIN; ANTICOAGULANTS ID ACUTE MYOCARDIAL-INFARCTION; PLASMINOGEN-ACTIVATOR; DOUBLE-BLIND; HEPARIN; THROMBOLYSIS; THROMBIN; PLACEBO; ASPIRIN; INHIBITION; PLATELETS AB Background Coronary artery thrombosis plays an important pathophysiological role in unstable angina and non-Q-wave myocardial infarction. To date, heparin and thrombolytic therapy has not provided complete or consistent benefit. We hypothesized that recombinant hirudin, a direct thrombin inhibitor, would prevent accumulation of coronary artery thrombus in a manner superior to heparin. Methods and Results Patients with rest ischemic pain, abnormal ECG, and baseline angiogram indicating a greater than or equal to 60% stenosis of a culprit coronary artery or saphenous vein graft with visual appearance of thrombus were randomized to one of two different doses of heparin (either a target activated partial thromboplastin time [aPTT] of 65 to 90 or 90 to 110 seconds) or one of four doses of hirudin (0.05, 0.10, 0.20, or 0.30 mg.kg(-1).h(-1) infusion) in a dose-escalating protocol. After 72 to 120 hours of study drug, a repeat coronary angiogram was obtained, and the paired studies underwent quantitative analysis. The primary end point was change in the average cross-sectional area of the culprit lesion. Other efficacy end points also involved changes in culprit lesion dimensions and TIMI flow grade. Recombinant hirudin led to a dose-dependent elevation of aPTT that appeared to plateau at the 0.2-mg/kg dose. A higher proportion of hirudin-treated patients had their aPTT within a 40-second range (16% heparin versus 71% hirudin, P<.001), Overall, the 116 patients treated with hirudin tended to show more improvement than the 50 patients receiving heparin relative to the primary efficacy variable-the average cross-sectional area (P=.08)-as well as minimal cross-sectional area (P=.028), minimal luminal diameter (P=.029), and percent diameter stenosis (P=.07). Conclusions Recombinant hirudin appears to be a promising antithrombotic intervention compared with heparin for inhibition of coronary artery thrombus. Large-scale comparative trials are warranted. C1 DUKE UNIV,MED CTR,DIV CARDIOL,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,DIV CARDIOL,BOSTON,MA 02114. BAYLOR COLL MED,DIV CARDIOL,HOUSTON,TX 77030. HAHNEMANN HOSP,PHILADELPHIA,PA. CHRIST HOSP,CINCINNATI,OH 45219. RIVERSIDE METHODIST HOSP,COLUMBUS,OH 43214. IOWA HEART CTR,DES MOINES,IA. TEMPLE UNIV,THROMBOSIS RES CTR,PHILADELPHIA,PA 19122. RP TOPOL, EJ (reprint author), CLEVELAND CLIN FDN,DEPT CARDIOL,1 CLIN CTR,9500 EUCLID AVE,DESK F25,CLEVELAND,OH 44195, USA. RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Topol, Eric/0000-0002-1478-4729 NR 32 TC 174 Z9 176 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1994 VL 89 IS 4 BP 1557 EP 1566 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NG469 UT WOS:A1994NG46900011 PM 8149521 ER PT J AU SWEENEY, MO RUSKIN, JN AF SWEENEY, MO RUSKIN, JN TI MORTALITY BENEFITS AND THE IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR SO CIRCULATION LA English DT Article DE IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; SURVIVAL; MORTALITY ID HOSPITAL VENTRICULAR-FIBRILLATION; CORONARY-ARTERY DISEASE; LONG-TERM SURVIVAL; CARDIAC-ARREST; MYOCARDIAL-INFARCTION; DEATH RATE; FOLLOW-UP; TACHYARRHYTHMIAS; ARRHYTHMIAS; RESUSCITATION AB The automatic implantable cardioverter-defibrillator (ICD) is highly effective in reducing sudden death rates in patients with life-threatening ventricular tachyarrhythmias. However, the magnitude of the ability of the ICD to improve overall survival is less certain. Data supporting the contention that the ICD prolongs survival are reviewed. It is evident that the mortality benefit consequent to the marked reduction in sudden death varies widely across subpopulations in a predictable manner. This observation reflects the powerful influence of other clinical factors that constrain survival in typical ICD patients. The implications for future studies on the ICD are discussed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC ARRHYTHMIA SERV,BOSTON,MA 02114. NR 49 TC 61 Z9 61 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1994 VL 89 IS 4 BP 1851 EP 1858 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NG469 UT WOS:A1994NG46900045 PM 8149550 ER PT J AU LEVINE, RA RODRIGUEZ, L THOMAS, JD AF LEVINE, RA RODRIGUEZ, L THOMAS, JD TI INTRACLASS CORRELATION-COEFFICIENT RATHER THAN CORRELATION-COEFFICIENT TO EXAMINE AGREEMENTS AMONG DIFFERENT METHODS MEASURING VALVULAR AREA - REPLY SO CIRCULATION LA English DT Letter C1 CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. RP LEVINE, RA (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1994 VL 89 IS 4 BP 1911 EP 1911 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NG469 UT WOS:A1994NG46900064 ER PT J AU TOBISE, K ISHIKAWA, Y HOLMER, SR IM, MJ NEWELL, JB YOSHIE, H FUJITA, M SUSANNIE, EE HOMCY, CJ AF TOBISE, K ISHIKAWA, Y HOLMER, SR IM, MJ NEWELL, JB YOSHIE, H FUJITA, M SUSANNIE, EE HOMCY, CJ TI CHANGES IN TYPE-VI ADENYLYL-CYCLASE ISOFORM EXPRESSION CORRELATE WITH A DECREASED CAPACITY FOR CAMP GENERATION IN THE AGING VENTRICLE SO CIRCULATION RESEARCH LA English DT Article DE MESSENGER RNA; G-PROTEINS; ADENYLYL CYCLASE ISOFORMS; TOXIN LABELING; IMMUNOBLOTTING; AGING ID NUCLEOTIDE REGULATORY PROTEIN; AGE-ASSOCIATED DECREASE; RAT-HEART; RECEPTOR INTERACTIONS; ADRENERGIC-RECEPTOR; COMPLEMENTARY-DNA; BINDING-PROTEINS; ALPHA-SUBUNIT; CLONING; STIMULATION AB We investigated the developmental regulation of the beta-adrenergic receptor-G(s)-adenylyl cyclase pathway in myocardial membranes from fetal, neonatal, adult, and mature adult rats by measuring the density of the beta-adrenergic receptor and the activities of the stimulatory guanine nucleotide-binding protein G(s) and the adenylyl cyclase enzyme. Total beta-adrenergic receptor content (in femtomoles per milligram protein) was greatest in the fetal (124.4+/-20.5 fmol/mg) and neonatal (122.3+/-16.1 fmol/mg) stages and gradually decreased in the adult (90.9+/-8.0 fmol/mg) and mature adult (70.0+/-9.6 fmol/mg) stages. An equivalent pattern was seen for adenylyl cyclase activity: the basal activity of the effector enzyme or that measured in the presence of 0.1 mmol/L isoproterenol with 0.1 mmol/L Gpp(NH)p, 10 mmol/L NaF, or 0.05 mmol/L forskolin was greater in the fetus and the neonate than in the adult and the mature adult. These data suggested that decreased stimulation of the catalytic unit by G(s) could be the underlying cause of diminished adenylyl cyclase activity with aging. However, quantification of G(s) by reconstitution into S49 cyc- membranes (in picomoles cAMP per microgram for 10 minutes) demonstrated no significant decrease during development from fetus (1.55+/-0.1 pmol/mug) to neonate (1.9+/-0.5 pmol/mug) and subsequent aging to adult (2.6+/-0.2 pmol/mug) and mature adult (1.9+/-0.2 pmol/mug). When Northern blot analysis was used to characterize the relative amounts of mRNA coding for G(salpha), no significant differences were seen among the developmental stages studied. Unlike G(salpha), the inhibitory protein G(ialsph2) was subject to developmental regulation; however, Concomitant evaluation of G(ialpha2) levels both by ADP-ribosylation with pertussis toxin and by immunoblotting showed the greatest amount in the fetus (0.82+/-0.07 pmol/mg) and the neonate (0.51+/-0.1 pmol/mg). The adult and mature adult both contained 0.09+/-0.02 pmol/mg. Also, the steady-state G(ialpha2), mRNA level paralleled the amount of protein. Similarly, the level of type V mRNA coding for adenylyl cyclase was greater in the mature adult than in the fetal and neonatal stages. In contrast, the level of type VI adenylyl cyclase mRNA decreased with age, paralleling the decline in the functional activity of adenylyl cyclase with age. Taken together, these data suggest that the age-related changes in the activity of the myocardial beta-adrenergic receptor-G(s)-adenylyl cyclase pathway is not primarily regulated by alteration in the level of G(s) or G(i) but by the density of beta-adrenergic receptors and by the activity of the catalyst adenylyl cyclase. In particular, steady-state mRNA measurements show that a decrease in the content of the type VI isoform of adenylyl cyclase correlates with a decrease in catalytic activity with age. C1 AMER CYANAMID CO,LEDERLE LABS,DIV MED RES,CARDIOVASC & CNS RES STN,PEARL RIVER,NY 10965. ASAHIKAWA MED COLL,DEPT MED 1,ASAHIKAWA,JAPAN. COLUMBIA UNIV COLL PHYS & SURG,DEPT PHARMACOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. UNIV REGENSBURG,INNERE MED 2,W-8400 REGENSBURG,GERMANY. CLEVELAND CLIN EDUC FDN,DEPT HEART & HYPERTENS RES,CLEVELAND,OH 44106. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-38070] NR 43 TC 87 Z9 89 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR PY 1994 VL 74 IS 4 BP 596 EP 603 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NB829 UT WOS:A1994NB82900005 PM 8137496 ER PT J AU SWEADNER, KJ HERRERA, VLM AMATO, S MOELLMANN, A GIBBONS, DK REPKE, KRH AF SWEADNER, KJ HERRERA, VLM AMATO, S MOELLMANN, A GIBBONS, DK REPKE, KRH TI IMMUNOLOGICAL IDENTIFICATION OF NA+,K+-ATPASE ISOFORMS IN MYOCARDIUM - ISOFORM CHANGE IN DEOXYCORTICOSTERONE ACETATE SALT HYPERTENSION SO CIRCULATION RESEARCH LA English DT Article DE DIGITALIS; OUABAIN; NA+,K+-ATPASE; HYPERTENSION ID NA+-K+-ATPASE; CARDIAC GLYCOSIDE RECEPTORS; OUABAIN BINDING-SITES; GUINEA-PIG HEART; CATALYTIC SUBUNIT; BETA-SUBUNIT; ALPHA-SUBUNIT; MESSENGER-RNAS; HIGH-AFFINITY; RAT HEARTS AB There are three isoforms of the catalytic (alpha) subunit of the Na+,K+-ATPase, each derived from a different gene, that differ in their sensitivity to inhibition by cardiac glycosides. Antibodies specific for the three isoforms were used to study Na+,K+-ATPase isoform expression in ventricular myocardium, where an understanding of digitalis receptor diversity is most important. In the rat heart, there is simultaneous expression of two isoforms in adult ventricle, and immunofluorescence studies demonstrated that both isoforms are expressed uniformly in cardiomyocytes. Hypertension and hypertrophy have been reported to selectively depress alpha2 isoform mRNA levels, and we show in the present study that alpha2 protein levels were correspondingly depressed in rats made hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate and a high-salt diet. In the human heart, where mRNA for all three alpha isoforms has been reported, we detected all three isoform proteins (alpha1, alpha2, and alpha3). Two isoform, (alpha1 and alpha3) predominated in the macaque heart; dissection of the heart showed uniformity of isoform expression in different ventricular regions but markedly less alpha3 in the atrium. Finally, isoform-specific antibodies were used to detect which alpha isoforms were expressed in the ventricles of several commonly used experimental animals to test the correlation of isoform expression with cardiac glycoside-response heterogeneity. Two isoforms (alpha1 and alpha3) were found in canine myocardium, whereas only one (alpha1) was found in sheep and guinea pig. Expression of Na+,K+-ATPase isoforms can thus be readily followed and related to the physiology of the digitalis receptor. C1 BOSTON UNIV,SCH MED,WHITAKER CARDIOVASC INST,MOLEC GENET SECT,BOSTON,MA 02118. RP SWEADNER, KJ (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN 427,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-36271, HL-47124]; NINDS NIH HHS [NS-27653] NR 58 TC 99 Z9 100 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR PY 1994 VL 74 IS 4 BP 669 EP 678 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NB829 UT WOS:A1994NB82900012 PM 8137503 ER PT J AU CALIENDO, AM HIRSCH, MS AF CALIENDO, AM HIRSCH, MS TI COMBINATION THERAPY FOR INFECTION DUE TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID RECOMBINANT INTERFERON-ALPHA; AIDS-RELATED COMPLEX; IMMUNE-DEFICIENCY SYNDROME; 3-DRUG SYNERGISTIC INHIBITION; HIV-1 REPLICATION INVITRO; SOLUBLE CD4; KAPOSIS SARCOMA; REVERSE-TRANSCRIPTASE; CONTROLLED TRIAL; RESISTANT HIV-1 AB The preliminary results of the Concorde trial demonstrated the transient clinical benefit of monotherapy with zidovudine (AZT) in asymptomatic persons infected with human immunodeficiency virus type 1 (HIV-1). This result, which has been widely disseminated and discussed, was predictable given the previous demonstration of the development of resistance to AZT in isolates from individuals receiving prolonged treatment with the drug and given the finding that didanosine (ddI) is more efficacious than continued therapy with AZT in individuals who have received greater-than-or-equal-to 6 months of AZT monotherapy. On the basis of these findings, interest in combinations of antiretroviral agents has continued to grow. Many in vitro studies of nucleoside and nonnucleoside inhibitors of reverse transcriptase combined with interferon-alpha or inhibitors of protease have been published. In addition, numerous clinical trials of various combinations have been completed or are under way. Dr. Martin Hirsch and his colleagues at the Massachusetts General Hospital have been among the leaders of this effort. He and Dr. Angela Caliendo review, in this AIDS Commentary, the current state of our knowledge regarding the potential utility of combination therapy for infection with HIV-1. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,FRUIT ST,BOSTON,MA 02114. NR 91 TC 43 Z9 43 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1994 VL 18 IS 4 BP 516 EP 524 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NE074 UT WOS:A1994NE07400002 PM 7518701 ER PT J AU LU, DSK PAPANICOLAOU, N GIRARD, M LEE, MJ YODER, IC AF LU, DSK PAPANICOLAOU, N GIRARD, M LEE, MJ YODER, IC TI PERCUTANEOUS INTERNAL URETERAL STENT PLACEMENT - REVIEW OF TECHNICAL ISSUES AND SOLUTIONS IN 50 CONSECUTIVE CASES SO CLINICAL RADIOLOGY LA English DT Article ID MANAGEMENT; STRICTURES; FISTULAS AB Fifty consecutive percutaneous ureteral stent placements in 40 patients over 2 1/2 years were reviewed. Thirty-seven of 50 cases were performed following failed retrograde stenting. Antegrade stenting failed in 2/37 (5%) cases of malignant obstruction, and 4/13 (31%) cases of benign ureteral disease. Causes of failure and common technical problems included poor angulation of the percutaneous track, tortuous dilated ureters, tight obstructions, wedging of stent assembly components due to high resistance, and difficulty in positioning of the proximal pigtail. Helpful technical modifications included mid-pole rather than lower pole calyceal access, urinary decompression prior to stenting, and the routine use of a peel-away sheath (success rate 23/24 placements with sheath vs 21/26 without sheath). Stent patency rates were 95% at 3 months and 54% at 6 months. With attention to technique and appropriate modifications, success rate of percutaneous stenting remained high in this series despite the large number of cases referred after retrograde stenting had failed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. NR 17 TC 21 Z9 22 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 1994 VL 49 IS 4 BP 256 EP 261 DI 10.1016/S0009-9260(05)81852-5 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ND591 UT WOS:A1994ND59100008 PM 8162683 ER PT J AU AGEMATSU, K KOBATA, T SUGITA, K FREEMAN, GJ SCHLOSSMAN, SF MORIMOTO, C AF AGEMATSU, K KOBATA, T SUGITA, K FREEMAN, GJ SCHLOSSMAN, SF MORIMOTO, C TI MOLECULAR-BASIS FOR CD27 MEDIATED T-CELL IMMUNE-RESPONSE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A310 EP A310 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001127 ER PT J AU ALCANTARA, O REDDY, SV ROODMAN, GD BOLDT, DH AF ALCANTARA, O REDDY, SV ROODMAN, GD BOLDT, DH TI HEMIN INHIBITION OF TARTRATE-RESISTANT ACID-PHOSPHATASE (TRAP) EXPRESSION IS MEDIATED BY BINDING OF A NUCLEAR-PROTEIN TO A SPECIFIC TANDEM REPEAT IN THE 5'-FLANKING REGION OF THE MTRAP GENE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A120 EP A120 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000047 ER PT J AU ALON, R SPRINGER, TA ROSSITER, H KUPPER, TS AF ALON, R SPRINGER, TA ROSSITER, H KUPPER, TS TI ROLLING OF T-CELLS ON P AND E SELECTINS UNDER PHYSIOLOGICAL FLOW IS MEDIATED BY DISTINCT CELL-SURFACE LIGANDS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A232 EP A232 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000688 ER PT J AU BISSLER, JJ CICARDI, M DONALDSON, VH GATENBY, PA ROSEN, FS DAVIS, AE AF BISSLER, JJ CICARDI, M DONALDSON, VH GATENBY, PA ROSEN, FS DAVIS, AE TI A CLUSTER OF MUTATIONS WITHIN A SHORT TRIPLET REPEAT IN THE C1 INHIBITOR GENE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV CINCINNATI,CINCINNATI,OH 45221. CHILDRENS HOSP RES FDN,CINCINNATI,OH 45229. CLIN MED,MILAN,ITALY. UNIV SYDNEY,ROYAL PRINCE ALFRED HOSP,DEPT CLIN IMMUNOL,SYDNEY,NSW 2006,AUSTRALIA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A201 EP A201 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000511 ER PT J AU BISWAS, P CHOUDHURY, GG WENZEL, U GRANDALIANO, G ABBOUD, HE AF BISWAS, P CHOUDHURY, GG WENZEL, U GRANDALIANO, G ABBOUD, HE TI DIFFERENTIAL EFFECT OF THROMBIN ON PROTEIN-KINASE-C ISOFORMS IN MESANGIAL CELLS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RI Grandaliano, Giuseppe/G-2963-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A144 EP A144 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000184 ER PT J AU DUKECOHAN, JS TANAKA, T KAMEOKA, J SCHLOSSMAN, SF MORIMOTO, C AF DUKECOHAN, JS TANAKA, T KAMEOKA, J SCHLOSSMAN, SF MORIMOTO, C TI ENHANCEMENT OF ANTIGEN-SPECIFIC T-CELL RESPONSES BY SOLUBLE RECOMBINANT CD26 SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A308 EP A308 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001119 ER PT J AU FRASER, PA LEHMAN, TJ SUNDEL, R JACKSON, J ALEXANDERTHOMAS, N DECEULAER, K AF FRASER, PA LEHMAN, TJ SUNDEL, R JACKSON, J ALEXANDERTHOMAS, N DECEULAER, K TI POLYMORPHISM OF THE HUMAN FAS GENE IS ASSOCIATED WITH EARLY-ONSET LUPUS IN BLACKS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HOSP SPECIAL SURG,NEW YORK,NY 10021. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL,BOSTON,MA 02115. HARLEM HOSP MED CTR,NEW YORK,NY 10037. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A315 EP A315 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001159 ER PT J AU GOLDFINE, AB FOLLI, F PATTI, ME SIMONSON, DC KAHN, CR AF GOLDFINE, AB FOLLI, F PATTI, ME SIMONSON, DC KAHN, CR TI EFFECTS OF SODIUM VANADATE ON IN-VIVO AND IN-VITRO INSULIN ACTION IN DIABETES SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A116 EP A116 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000026 ER PT J AU HARLAN, DM HENGARTNER, H HUANG, ML KANG, YH ABE, R MOREADITH, RW PIRCHER, H OHASHI, PS FREEMAN, GJ NADLER, LM JUNE, CH AICHELE, P AF HARLAN, DM HENGARTNER, H HUANG, ML KANG, YH ABE, R MOREADITH, RW PIRCHER, H OHASHI, PS FREEMAN, GJ NADLER, LM JUNE, CH AICHELE, P TI TRANSGENIC MICE EXPRESSING B7-1 ON PANCREATIC BETA-CELLS EXHIBIT DIABETES SUSCEPTIBILITY DUE TO A BREAKDOWN OF T-LYMPHOCYTE UNRESPONSIVENESS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. UNIV ZURICH,INST EXPTL IMMUNOL,CH-8006 ZURICH,SWITZERLAND. UNIV TEXAS,SW MED CTR,MOLEC CARDIOL LAB,DALLAS,TX 75230. UNIV TORONTO,ONTARIO CANC INST,TORONTO M5S 1A1,ONTARIO,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A343 EP A343 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001315 ER PT J AU HUANG, SC PAN, Z HARLEY, JB SCOFIELD, RH AF HUANG, SC PAN, Z HARLEY, JB SCOFIELD, RH TI IMMUNIZATION WITH VESICULAR STOMATITIS-VIRUS NUCLEOCAPSID PROTEIN INDUCES AUTOANTIBODIES TO 60 KD RO SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73190. US DEPT VET AFFAIRS,OKLAHOMA CITY,OK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A278 EP A278 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000946 ER PT J AU KASINATH, BS GRELLIER, P TERHUNE, WC GHOSHCHOUDHURY, G MALDONADO, R ABBOUD, S AF KASINATH, BS GRELLIER, P TERHUNE, WC GHOSHCHOUDHURY, G MALDONADO, R ABBOUD, S TI REGULATION OF BASEMENT-MEMBRANE (BM) HEPARAN-SULFATE PROTEOGLYCAN (HSPG) CORE PROTEIN GENE-EXPRESSION BY HIGH GLUCOSE MEDIUM IN GLOMERULAR EPITHELIAL-CELLS (GEC) SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A143 EP A143 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000181 ER PT J AU LICHTENSTEIN, MJ MONTERROSA, A ESPINO, DV HAZUDA, HP AF LICHTENSTEIN, MJ MONTERROSA, A ESPINO, DV HAZUDA, HP TI ASSOCIATION OF VISUAL-ACUITY WITH STATIC AND DYNAMIC MEASURES OF BALANCE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,GRECC,SAN ANTONIO,TX 78284. UTHSC,DEPT MED,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A218 EP A218 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000608 ER PT J AU LU, M HOLZ, GG HABENER, JF AF LU, M HOLZ, GG HABENER, JF TI DIFFERENT GLUCOSE-DEPENDENT MECHANISMS OF GLYBURIDE AND GLUCAGON-LIKE PEPTIDE-1(7-37) STIMULATION ON INSULIN-SECRETION SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HHMI,BOSTON,MA 02115. RI Holz, George/A-3386-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A211 EP A211 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000567 ER PT J AU LUYAO, GL BARRY, MJ CHANG, CH AF LUYAO, GL BARRY, MJ CHANG, CH TI TRANSURETHRAL RESECTION OF THE PROSTATE IN THE UNITED-STATES - RECENT TIME TRENDS AND OUTCOMES SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT COMMUNITY & FAMILY MED & MED,HANOVER,NH 03756. MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A229 EP A229 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000672 ER PT J AU MATSUMOTO, E ITOH, N TAKADA, Y KOBAYASHI, M CHAPMAN, VM HATTORI, M AF MATSUMOTO, E ITOH, N TAKADA, Y KOBAYASHI, M CHAPMAN, VM HATTORI, M TI COMMON DIABETOGENIC BACKGROUNDS BETWEEN IDDM AND NIDDM IN BC1[(NODXMUS-SPRETUS)F1XNOD] SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. TOYAMA MED & PHARMACEUT UNIV,TOYAMA,TOYAMA 93001,JAPAN. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,BUFFALO,NY 14263. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A211 EP A211 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000568 ER PT J AU MEIGS, JB SINGER, DE NATHAN, DM CUPPLES, LA WILSON, PWF AF MEIGS, JB SINGER, DE NATHAN, DM CUPPLES, LA WILSON, PWF TI HEMOGLOBIN A1C RELIABLY REFLECTS GLUCOSE CONTROL OVER 4 TO 6 YEARS AMONG NONDIABETIC SUBJECTS IN THE FRAMINGHAM HEART SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A246 EP A246 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000764 ER PT J AU PRALONG, FP PAVLOU, S CROWLEY, WF AF PRALONG, FP PAVLOU, S CROWLEY, WF TI ISOLATED GNRH DEFICIENCY IS ASSOCIATED WITH A PREVIOUSLY UNRECOGNIZED DEFECT IN FAS SECRETION SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NATL CTR FERTIL RES,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A269 EP A269 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000895 ER PT J AU REDDY, SV HUNDLEY, JE WINDLE, JJ LEACH, RJ ALCANTARA, O BOLDT, DH ROODMAN, GD AF REDDY, SV HUNDLEY, JE WINDLE, JJ LEACH, RJ ALCANTARA, O BOLDT, DH ROODMAN, GD TI THE MOUSE TARTRATE-RESISTANT ACID-PHOSPHATASE GENE (TRAP) CONTAINS 2 ACTIVE PROMOTERS AND IS REGULATED BY IRON SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. CANC THERAPY & RES CTR S TEXAS,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A210 EP A210 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000562 ER PT J AU SEMIGRAN, GE TRUDEAU, NR MCCARTHY, M GARCIA, M LARAIA, PJ SEMIGRAN, MJ BOUCHER, CA AF SEMIGRAN, GE TRUDEAU, NR MCCARTHY, M GARCIA, M LARAIA, PJ SEMIGRAN, MJ BOUCHER, CA TI THALLIUM IMAGING DOES NOT ADD PROGNOSTIC INFORMATION TO EXERCISE TESTING IN WOMEN SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SPAULDING REHABIL HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A293 EP A293 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001032 ER PT J AU SHIKAMA, Y LAURIE, AS JUBINSKY, PT CARROLL, M SIEFF, CA AF SHIKAMA, Y LAURIE, AS JUBINSKY, PT CARROLL, M SIEFF, CA TI THE COMMON BETA-SUBUNIT OF THE HUMAN GM-CSF RECEPTOR INTERACTS WITH A GM-CSF ERYTHROPOIETIN RECEPTOR SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A136 EP A136 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000144 ER PT J AU SILVA, P SOLOMON, R EPSTEIN, FH AF SILVA, P SOLOMON, R EPSTEIN, FH TI NUCLEOTIDES INHIBIT CHLORIDE SECRETION BY THE RECTAL GLAND SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. JOSLIN DIABET CTR,BOSTON,MA. BETH ISRAEL HOSP,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A317 EP A317 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001167 ER PT J AU TAKABAYASHI, T DINARELLO, CA MARGOLIS, NH VANNIER, E CLARK, BD BURKE, JF GELFAND, JA AF TAKABAYASHI, T DINARELLO, CA MARGOLIS, NH VANNIER, E CLARK, BD BURKE, JF GELFAND, JA TI C3A STIMULATES TRANSCRIPTION OF INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR BY MONONUCLEAR-CELLS AND INCREASES THE RESPONSE TO ENDOTOXIN SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A134 EP A134 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000131 ER PT J AU TAYLOR, AE SLUSS, P MARTIN, K MULDER, J CHRISTIN, S ALBANESE, C ADAMS, JM JAMESON, JL CROWLEY, WF AF TAYLOR, AE SLUSS, P MARTIN, K MULDER, J CHRISTIN, S ALBANESE, C ADAMS, JM JAMESON, JL CROWLEY, WF TI A MAJORITY OF WOMEN WITH PREMATURE OVARIAN FAILURE HAVE LOW FSH BIOACTIVITY SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. NORTHWESTERN UNIV,EVANSTON,IL 60201. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A270 EP A270 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000901 ER PT J AU THIEME, H AIELLO, LP FERRARA, N KING, GL AF THIEME, H AIELLO, LP FERRARA, N KING, GL TI CHARACTERIZING THE HYPOXIA MEDIATED EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) AND ITS RECEPTORS IN RETINAL CAPILLARY CELLS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. GENENTECH INC,S SAN FRANCISCO,CA 94080. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A303 EP A303 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001090 ER PT J AU UEDA, Y FREEMAN, G LEVINE, B WARD, SG HUANG, ML ABE, R NADLER, LM JUNE, CH AF UEDA, Y FREEMAN, G LEVINE, B WARD, SG HUANG, ML ABE, R NADLER, LM JUNE, CH TI DISTINCT MECHANISMS OF T-CELL SIGNAL-TRANSDUCTION BY CD28 AND CTLA4, AND BY LIGANDS B7-1 AND B7-2 SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. UNIV BATH,DEPT PHARMACOL,BATH BA2 7AY,AVON,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A309 EP A309 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02001122 ER PT J AU WENZEL, UO VALENTE, AJ ABBOUD, HE AF WENZEL, UO VALENTE, AJ ABBOUD, HE TI THROMBIN INDUCES MONOCYTE CHEMOTACTIC PEPTIDE (MCP-1) PRODUCTION IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS (VSMC) SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A266 EP A266 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000879 ER PT J AU WILLETT, CG SMITH, DI SUNDAY, ME AF WILLETT, CG SMITH, DI SUNDAY, ME TI EVIDENCE FOR HEPATOCYTE GROWTH FACTOR-LIKE PROTEIN AS AN INDUCIBLE POSSIBLE TUMOR-SUPPRESSOR GENE FOR LUNG-CANCER ON HUMAN CHROMOSOME-3P21.3 SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. WAYNE STATE UNIV,SCH MED,DETROIT,MI 48201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A203 EP A203 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000525 ER PT J AU YUNIS, JJ ALLEJANDRO, R FOSTER, CS AHMED, AR AF YUNIS, JJ ALLEJANDRO, R FOSTER, CS AHMED, AR TI IMMUNOGENETICS OF DRUG-RELATED OR PSEUDO-OCULAR CICATRICIAL PEMPHIGOID SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 BOSTON UNIV,DEPT DERMATOL,BOSTON,MA 02215. MASSACHUSETTS EYE & EAR INFIRM,DFCI,DIV IMMUNOGENET,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,UVEITIS SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1994 VL 42 IS 2 BP A231 EP A231 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NF020 UT WOS:A1994NF02000682 ER PT J AU AUCHINCLOSS, H AF AUCHINCLOSS, H TI CELL-MEDIATED XENORESPONSES - STRONG OR WEAK SO CLINICAL TRANSPLANTATION LA English DT Article DE TRANSPLANTATION; XENOGRAFTING; CELLULAR IMMUNITY AB Cell-mediated responses to xenoantigens are different from those to alloantigens. CD4+ T cells are especially important in xenoresponses and depletion of CD4+ T cells can prolong survival of xenografts better than allografts in some circumstances. The difference between the two responses is due in part to the relative weakness of direct T-cell responses stimulated by xenogeneic antigen-presenting cells. Instead, T cells tend to require that donor antigens be processed and presented indirectly in association with the MHC antigens on their own APCs. The defect in direct stimulation is due to failure of some of the several T cell/APC interactions when the receptors and ligands of these interactions come from different species. Although the cell-mediated response to xenografts is different, it remains very strong. The mechanism by which CD4+ cells cause xenograft destruction remains to be determined, but a better understanding of this mechanism may help to select the most useful types of immunosuppression for xenogeneic transplantation. RP AUCHINCLOSS, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL36372, HL18646] NR 0 TC 25 Z9 25 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD APR PY 1994 VL 8 IS 2 BP 155 EP 159 PN 2 PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA NE555 UT WOS:A1994NE55500002 PM 7912570 ER PT J AU BUCKY, LP MAY, JW AF BUCKY, LP MAY, JW TI SYNTHETIC MESH - ITS USE IN ABDOMINAL-WALL RECONSTRUCTION AFTER THE TRAM SO CLINICS IN PLASTIC SURGERY LA English DT Article AB The use of synthetic mesh for the closure of the abdominal wall after TRAM breast reconstruction offers the surgeon greater control of the abdominal wall. The technique described is based on the principles of preservation of rectus muscle blood supply, complete fascial closure, abdominal symmetry, and greater balance of forces. This technique results in a tighter closure with minimal donor site complications and yields an aesthetically superior abdominal contour. RP BUCKY, LP (reprint author), MASSACHUSETTS GEN HOSP,DEPT PLAST SURG,ACC-453,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 25 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-1298 J9 CLIN PLAST SURG JI Clin. Plast. Surg. PD APR PY 1994 VL 21 IS 2 BP 273 EP 277 PG 5 WC Surgery SC Surgery GA NE768 UT WOS:A1994NE76800010 PM 8187420 ER PT J AU FERNANDEZORTIZ, A JANG, IK FUSTER, V AF FERNANDEZORTIZ, A JANG, IK FUSTER, V TI ANTIPLATELET AND ANTITHROMBIN THERAPY SO CORONARY ARTERY DISEASE LA English DT Review DE THROMBOLYTIC THERAPY; PLATELET INHIBITION; THROMBIN; ANTITHROMBOTICS; ASPIRIN; HEPARIN; HIRUDIN; IIB/IIIA RECEPTOR BLOCKERS ID ACUTE MYOCARDIAL-INFARCTION; PLATELET CYCLOOXYGENASE INHIBITION; RANDOMIZED CONTROLLED TRIALS; CORONARY-ARTERY DISEASE; PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; ATHEROSCLEROTIC PLAQUES; THROMBIN INHIBITION; RECOMBINANT HIRUDIN; INTRAVENOUS HEPARIN C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 NR 46 TC 3 Z9 3 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD APR PY 1994 VL 5 IS 4 BP 297 EP 305 DI 10.1097/00019501-199404000-00005 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NL670 UT WOS:A1994NL67000005 PM 8044341 ER PT J AU KINGSTON, RE GREEN, MR AF KINGSTON, RE GREEN, MR TI MODELING EUKARYOTIC TRANSCRIPTIONAL ACTIVATION SO CURRENT BIOLOGY LA English DT Review ID RNA POLYMERASE-II; TATA-BINDING PROTEIN; PREINITIATION COMPLEX; DROSOPHILA-MELANOGASTER; GENE-TRANSCRIPTION; FACTOR TFIIB; PROMOTER; INVITRO; MECHANISM; DNA C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,PROGRAM MOLEC MED,WORCESTER,MA 01605. RP KINGSTON, RE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 52 TC 33 Z9 33 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 1 PY 1994 VL 4 IS 4 BP 325 EP 332 DI 10.1016/S0960-9822(00)00071-3 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NF783 UT WOS:A1994NF78300004 PM 7922341 ER PT J AU CHEN, JZ SHINKAI, Y YOUNG, F ALT, FW AF CHEN, JZ SHINKAI, Y YOUNG, F ALT, FW TI PROBING IMMUNE FUNCTIONS IN RAG-DEFICIENT MICE SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL RECEPTOR; CHAIN GENE; LYMPHOCYTES-B; THYMOCYTE DEVELOPMENT; V(D)J RECOMBINATION; TARGETED DISRUPTION; SURFACE EXPRESSION; MEMBRANE EXON; BONE-MARROW; LIGHT CHAIN AB Inactivation of recombination activating gene (RAG)-1 or RAG-2 in mice results in the inability of developing lymphocytes to initiate V(D)J recombination, leading to the arrest of lymphocyte differentiation at a very early stage. Introduction of functionally assembled antigen-receptor genes or other potentially relevant genes into the RAG-deficient background can bypass the V(D)J recombination block and promote differentiation of the lymphocytes of RAG-deficient mice to various stages. This approach offers new means for analyzing the control of lymphocyte differentiation. In addition, generation of somatic chimeric mice by injecting mutant embryonic stem cells into the RAG-2-deficient blastocysts has also provided a powerful new method for assaying the potential roles of genes or regulatory elements in lymphocyte development or function. C1 CTR BLOOD RES,BOSTON,MA. RP CHEN, JZ (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,RES LABS,300 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 FU NIAID NIH HHS [AI20047, U01 AI31541] NR 51 TC 44 Z9 45 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 1994 VL 6 IS 2 BP 313 EP 319 DI 10.1016/0952-7915(94)90107-4 PG 7 WC Immunology SC Immunology GA ND730 UT WOS:A1994ND73000016 PM 8011215 ER PT J AU RHODES, CJ ALARCON, C AF RHODES, CJ ALARCON, C TI WHAT BETA-CELL DEFECT COULD LEAD TO HYPERPROINSULINEMIA IN NIDDM - SOME CLUES FROM RECENT ADVANCES MADE IN UNDERSTANDING THE PROINSULIN-PROCESSING MECHANISM SO DIABETES LA English DT Article ID INSULIN-SECRETORY-GRANULE; MESSENGER-RNA; GENE-EXPRESSION; TRANSLATIONAL CONTROL; CARBOXYPEPTIDASE-H; SUBTILISIN FAMILY; ATT20 CELLS; ENDOPEPTIDASE; GLUCOSE; PC2 AB Pancreatic beta-cell dysfunction is a characteristic of non-insulin-dependent diabetes mellitus (NIDDM). An aspect of this dysfunction is that an increased proportion of proinsulin is secreted, but an actual beta-cell defect that leads to hyperproinsulinemia is unknown. Nevertheless, an impairment in beta-cell proinsulin conversion mechanism has been suggested as the most likely cause. Insulin is produced from its precursor molecule, proinsulin, by limited proteolytic cleavage at two dibasic sequences (Arg31, Arg32 and Lys64 , Arg65). Two endopeptidase activities catalyze this cleavage: PC2 and PC3. PC2 endopeptidase cleaves predominately at Lys64, Arg65, and PC3 endopeptidase cleaves at Arg31, Arg32. The recent identification and characterization of these endopeptidases has enabled a better understanding of the human proinsulin-processing mechanism. In particular, experimental evidence suggests that the majority of human proinsulin processing is sequential. PC3 cleaves proinsulin first to generate a proinsulin conversion intermediate that is the preferred substrate of PC2. Both PC2 and PC3 activities are influenced by Ca2+ and pH, but the more stringent Ca2+ and pH requirements of PC3 suggest it as the most likely enzyme to regulate proinsulin conversion, as well as initiate it. When an increased demand is placed on the proinsulin-processing mechanism by a glucose-stimulated increase hi proinsulin biosynthesis, there is a coordinate increase in PC3 biosynthesis (but not in PC2). This supports PC3 as the key endopeptidase that regulates proinsulin processing. In this perspective, the current concepts of the enzymology and regulation of proinsulin conversion at a molecular level are reviewed. Then, several hypothetical points of beta-cell dysfunction that might affect the proinsulin-processing mechanism and lead to hyperproinsulinemia are considered. Because the term NIDDM encompasses a wide variety of different disorders, any one or a combination of these possible points of beta-cell dysfunction could result in hyperproinsulinemia for a certain subset of NIDDM. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RHODES, CJ (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,EP JOSLIN RES LAB,ROOM 640D,1 JOSLIN PL,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK-36836] NR 68 TC 141 Z9 144 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1994 VL 43 IS 4 BP 511 EP 517 DI 10.2337/diabetes.43.4.511 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NC859 UT WOS:A1994NC85900001 PM 8138054 ER PT J AU BURKLY, LC JAKUBOWSKI, A HATTORI, M AF BURKLY, LC JAKUBOWSKI, A HATTORI, M TI PROTECTION AGAINST ADOPTIVE TRANSFER OF AUTOIMMUNE DIABETES MEDIATED THROUGH VERY LATE ANTIGEN-4 INTEGRIN SO DIABETES LA English DT Article ID TUMOR-NECROSIS-FACTOR; CELL-ADHESION MOLECULE-1; LEUKOCYTE ADHESION; FACTOR-ALPHA; T-CELLS; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; VLA-4; MICE; IDENTIFICATION AB The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes and macrophages can regulate their migration to inflammatory sites as well as control cellular activation. The role of VIA-4 in the establishment of autoimmune diabetes is not easily predicted given the multiplicity of adhesion pathways and their differential use by various cell types. The contribution of VLA-4 to insulin-dependent diabetes mellitus was investigated by administration of VLA-4-specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in NOD mice. This study shows that VIA-4-specific MoAbs profoundly inhibit the development of diabetes with protection sustained by repeated MoAb exposure. Insulitis was completely inhibited during treatment and progressed to a severe degree once MoAb treatment was suspended, yet approximately 40% of treated recipients failed to become diabetic during 1-2 months post-treatment. Although we cannot rule out depletion of a relatively minor subpopulation of cells by prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular functions leading to diabetes and demonstrates that a significant disease modifying effect can be mediated by targeting the VLA-4 integrin. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,IMMUNOL & IMMUNOGENET SECT,BOSTON,MA 02115. RP BURKLY, LC (reprint author), BIOGEN INC,DEPT IMMUNOL,14 CAMBRIDGE CTR,CAMBRIDGE,MA 02142, USA. FU NIDDK NIH HHS [R01-DK-43613] NR 36 TC 55 Z9 55 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1994 VL 43 IS 4 BP 529 EP 534 DI 10.2337/diabetes.43.4.529 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NC859 UT WOS:A1994NC85900004 PM 8138057 ER PT J AU JACOBSON, AM DEGROOT, M SAMSON, JA AF JACOBSON, AM DEGROOT, M SAMSON, JA TI THE EVALUATION OF 2 MEASURES OF QUALITY-OF-LIFE IN PATIENTS WITH TYPE-I AND TYPE-II DIABETES SO DIABETES CARE LA English DT Article ID MEDICAL OUTCOMES; OF-LIFE; INFECTION AB OBJECTIVE - To examine the effects of type I and type II diabetes on patient perceptions of their quality of life and compare the psychometric properties of a generic versus a diabetes-specific quality of life measure. RESEARCH DESIGN AND METHODS - Consecutive outpatients (n = 240) from a large multispecialty diabetes clinic were studied on a single occasion using two measures of quality of life-Diabetes Quality of Life Measure (DQOL) and the Medical Outcome Study Health Survey 36-Item Short Form (SF-36). No interventions were performed. This study examines three issues: 1) the reliability (internal consistency) of the two measures; 2) the relationship between the DQOL and SF-36 scales; and 3) the influence of clinical patient characteristics, such as number and severity of diabetes complications, on quality of life. Examination of this issue provides information about the construct validity of the two quality of life measures. RESULTS - The estimates of internal consistency (Cronbach's alpha) for the DQOL and SF-36 subscales ranged from 0.47 to 0.97. These values were very similar to the published findings from previous studies. The subscales of the two measures were variably correlated with one another (range of correlations: -0.003 to 0.60), indicating that the areas of functioning addressed by the DQOL and SF-36 overlapped only to a modest degree. Examination of the relationship of demographic factors to the DQOL measures suggests that they are not generally confounded by factors such as education, sex, or duration of diabetes. Health-related quality of life is affected by the marital status of both type I and type II diabetic patients, with separated and divorced individuals generally experiencing lower levels of quality of life. The quality of life measures were sensitive to clinical characteristics, such as frequency and severity of complications. Even after factors such as marital status and, among type II diabetic patients, type of treatment, patients' severity of diabetes complications was a significant predictor of both the diabetes-related and the more broad-based measure of quality of life. For type II diabetic patients, insulin treatment was associated with lower levels of satisfaction with diabetes and greater impact of diabetes on quality of life. CONCLUSIONS - This study provides evidence for the reliability and validity of two measures of quality of life. The two measures examine quality of life from different but complimentary perspectives. The DQOL seems more sensitive to lifestyle issues and contains special questions and worry scales oriented toward younger patients, whereas the SF-36 provides more information about functional health status. Thus, the measures may be used usefully in combination in studies of both type I and type II diabetic patients. C1 HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. MCLEAN HOSP, BELMONT, MA 02178 USA. RP JACOBSON, AM (reprint author), JOSLIN DIABET CTR, MENTAL HLTH UNIT, 1 JOSLIN PL, BOSTON, MA 02215 USA. FU NIADDK NIH HHS [AM-27845]; NIDDK NIH HHS [DK-42315-02] NR 19 TC 266 Z9 279 U1 4 U2 15 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 APR PY 1994 VL 17 IS 4 BP 267 EP 274 DI 10.2337/diacare.17.4.267 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ND201 UT WOS:A1994ND20100003 PM 8026281 ER PT J AU LOCKE, JL AF LOCKE, JL TI PHASES IN THE DEVELOPMENT OF LINGUISTIC CAPACITY SO DISCUSSIONS IN NEUROSCIENCE LA English DT Article C1 MASSACHUSETTS GEN HOSP,MGH INST HLTH PROFESS,NEUROLINGUIST LAB,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0254-8852 J9 DISCUSS NEUROSCI JI Discuss. Neurosci. PD APR PY 1994 VL 10 IS 1-2 BP 26 EP 34 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NX845 UT WOS:A1994NX84500004 ER PT J AU PHAN, HL FINLAY, JA CHU, DS TAN, PK KIRCHHAUSEN, T PAYNE, GS AF PHAN, HL FINLAY, JA CHU, DS TAN, PK KIRCHHAUSEN, T PAYNE, GS TI THE SACCHAROMYCES-CEREVISIAE APS1 GENE ENCODES A HOMOLOG OF THE SMALL-SUBUNIT OF THE MAMMALIAN CLATHRIN AP-1 COMPLEX - EVIDENCE FOR FUNCTIONAL INTERACTION WITH CLATHRIN AT THE GOLGI-COMPLEX SO EMBO JOURNAL LA English DT Article DE ALPHA-FACTOR MATURATION; AP COMPLEX; CLATHRIN; GOLGI COMPLEX; YEAST ID RECEPTOR-MEDIATED ENDOCYTOSIS; ASSEMBLY PROTEIN AP-2; COATED VESICLES; MEMBRANE-PROTEIN; HEAVY-CHAIN; PLASMA-MEMBRANE; CELL-GROWTH; YEAST; PURIFICATION; POLYPEPTIDES AB Clathrin-associated protein (AP) complexes have been implicated in the assembly of clathrin coats and the selectivity of clathrin-mediated protein transport processes. We have identified a yeast gene, APS1, encoding a homolog of the small (referred to herein as sigma) subunits of the mammalian AP-1 complex. Sequence comparisons have shown that Aps1p is more similar to the sigma subunit of the Golgi-localized mammalian AP-1 complex than Aps2p, which is more related to the plasma membrane AP-2 sigma subunit. Like their mammalian counterparts, Aps1p and Aps2p are components of distinct, large (>200 kDa) complexes and a significant portion of the Aps proteins co-fractionate with clathrin-coated vesicles during gel filtration chromatography, Unexpectedly, even though the evolutionary conservation of AP small subunits is substantial (50% identity between mammalian and yeast proteins), disruptions of APS1 (aps1 Delta) and APS2 (aps2 Delta), individually or in combination, elicit no detectable mutant phenotypes. These data indicate that the Aps proteins are not absolutely required for clathrin-mediated selective protein transport in cells expressing wild type clathrin. However, aps1 Delta accentuated the slow growth and alpha-factor pheromone maturation defect of cells carrying a temperature-sensitive allele of clathrin heavy chain (Chc) (chc1-ts). In contrast, aps1 Delta did not influence the effects of chc1-ts on vacuolar protein sorting or receptor-mediated endocytosis. The aps2 Delta mutation resulted in a sight effect on chc1-ts cell growth but had no additional effects. The growth defect of cells completely lacking Chc was compounded by aps1 Delta but not aps2 Delta. These results comprise evidence that Aps1p is involved in a subset of clathrin functions at the Golgi apparatus. The effect of aps1 Delta on cells devoid of clathrin function suggests that Aps1p also participates in clathrin-independent processes. C1 UNIV CALIF LOS ANGELES, SCH MED, INST MOLEC BIOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOL CHEM, LOS ANGELES, CA 90024 USA. HARVARD UNIV, SCH MED, DEPT CELLULAR BIOL, BOSTON, MA 02115 USA. CTR BLOOD RES, BOSTON, MA 02115 USA. FU NIGMS NIH HHS [GM 07185, GM13294, GM 39040] NR 72 TC 70 Z9 71 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 1 PY 1994 VL 13 IS 7 BP 1706 EP 1717 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NF928 UT WOS:A1994NF92800026 PM 8157009 ER PT J AU FUKAYAMA, S SCHIPANI, E JUPPNER, H LANSKE, B KRONENBERG, HM ABOUSAMRA, AB BRINGHURST, FR AF FUKAYAMA, S SCHIPANI, E JUPPNER, H LANSKE, B KRONENBERG, HM ABOUSAMRA, AB BRINGHURST, FR TI ROLE OF PROTEIN KINASE-A IN HOMOLOGOUS DOWN-REGULATION OF PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN HUMAN OSTEOBLAST-LIKE SAOS-2 CELLS SO ENDOCRINOLOGY LA English DT Article ID BETA-ADRENERGIC RECEPTORS; SARCOMA CELLS; ALKALINE-PHOSPHATASE; BETA-2-ADRENERGIC RECEPTOR; LINE SAOS-2; RNA; CAMP; DESENSITIZATION; PHOSPHORYLATION; EXPRESSION AB Homologous down-regulation of PTH/PTH-related peptide (PTHrP) receptor expression occurs in several PTH-responsive osteoblastic cell lines, but the mechanisms responsible are not well understood. We have used wild-type SaOS-2 human osteoblastic cells, in which homologous PTH/PTHrP receptor down-regulation occurs within 4 h, and a mutant cAMP-resistant subclone (Ca4A strain), to investigate the mechanisms by which PTH/PTHrP receptor mRNA is regulated. SaOS-2 cells expressed a single 2.2- to 2.5-kilobase transcript of PTH/PTHrP receptor mRNA, as assessed by Northern blot analysis of total RNA with a cDNA probe encoding the human PTH/PTHrP receptor. Homologous down-regulation of this PTH/PTHrP receptor mRNA first became significant when SaOS-2 cells had been treated with human (h) PTH-(1-34) (10(-7) M) for 8-12 h. By 24 h, steady state levels of PTH/PTHrP receptor mRNA were reduced by about 50%. This effect was mimicked by both (Bu)2cAMP (DBcAMP; 0.5 mM) and forskolin (Fsk; 10(-5) M). In contrast, down-regulation of PTH/PTHrP receptor mRNA by hPTH-(1-34), DBcAMP or Fsk was almost completely blocked in cAMP-resistant Ca4A cells. Short term (4-6 h) treatment with hPTH-(1-34), DBcAMP, or Fsk did not reduce steady state levels of PTH/PTHrP receptor mRNA in either SaOS-2 or Ca4A cells, although down-regulation was induced by 4-6 h of treatment with active phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (200 nM) or phorbol- 12,13-didecanoate (200 nM). Neither thapsigargin (1 muM) nor ionomycin (200 nM), both of which stimulate calcium transients in these cells, altered PTH/PTHrP receptor mRNA expression. Treatment with hPTH-(39-84) and hPTH-(53-84), which do not activate either cAMP-dependent protein kinase or protein kinase-C, but do stimulate Ca-45(2+) uptake in these cells, did not alter PTH/PTHrP receptor mRNA expression. In the presence of actinomycin-D (1 mug/ml), down-regulation of PTH/PTHrP receptor mRNA by hPTH-(1-34) was not observed. Cycloheximide (10 mug/ml) did not block down-regulation of PTH/PTHrP receptor mRNA induced by hPTH-(1-34). We conclude that homologous down-regulation of PTH/PTHrP receptor mRNA in SaOS-2 cells occurs later than the decline in functional surface receptors via a mechanism that does not involve enhanced mRNA degradation or new protein synthesis, but is dependent upon cAMP/cAMP-dependent protein kinase. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP FUKAYAMA, S (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,FRUIT ST,BOSTON,MA 02114, USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-11794, DK-45485-02] NR 42 TC 61 Z9 63 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1994 VL 134 IS 4 BP 1851 EP 1858 DI 10.1210/en.134.4.1851 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NC427 UT WOS:A1994NC42700036 PM 8137752 ER PT J AU BASKIN, DG SCHWARTZ, MW SIPOLS, AJ DALESSIO, DA GOLDSTEIN, BJ WHITE, MF AF BASKIN, DG SCHWARTZ, MW SIPOLS, AJ DALESSIO, DA GOLDSTEIN, BJ WHITE, MF TI INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) EXPRESSION IN RAT-BRAIN SO ENDOCRINOLOGY LA English DT Note ID GROWTH FACTOR-I; MESSENGER-RNA; INTACT RAT; PP185; PURIFICATION; ASSOCIATION; MUSCLE; KINASE; LIVER AB IRS-1 is phosphorylated on tyrosine residues after insulin stimulation and participates in the early events of signal transduction in peripheral insulin-sensitive tissues. This study determined whether neuronal populations in the rat olfactory bulb and hippocampus (brain regions which have very high concentrations of insulin receptors) also express IRS-1 and contain phosphotyrosine, using in situ hybridization, receptor binding, and immunocytochemistry. IRS-1 mRNA was colocalized with insulin receptor mRNA in neuron cell bodies of hippocampus and olfactory bulb. Similarly, IRS-1 immunoreactivity in hippocampus and olfactory bulb was concentrated in layers that contain synapses of these neurons and have both high insulin binding and phosphotyrosine levels. Thus, IRS-1 and insulin receptors are coexpressed in discrete populations of neurons, suggesting a signal transduction mechanism by which insulin may influence metabolism and gene expression in the brain. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,DIV ENDOCRINOL & METAB DIS,PHILADELPHIA,PA 19107. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP BASKIN, DG (reprint author), VET AFFAIRS MED CTR,SEATTLE,WA 98108, USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-12829, DK-17047, DK-43396] NR 18 TC 72 Z9 72 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1994 VL 134 IS 4 BP 1952 EP 1955 DI 10.1210/en.134.4.1952 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NC427 UT WOS:A1994NC42700049 PM 7511094 ER PT J AU RAZIWOLF, Z FALO, LD REISER, H AF RAZIWOLF, Z FALO, LD REISER, H TI EXPRESSION AND FUNCTION OF THE COSTIMULATORY MOLECULE B7 ON MURINE LANGERHANS CELLS - EVIDENCE FOR AN ALTERNATIVE CTLA-4 LIGAND SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B7; CTLA-4 LIGAND; LANGERHANS CELLS ID T-CELL ANTIGEN; CD4+ LYMPHOCYTES-T; DENDRITIC CELLS; ACTIVATION ANTIGEN-B7; MONOCLONAL-ANTIBODIES; PROTEIN ANTIGENS; IL-2 PRODUCTION; MESSENGER-RNA; CD28; SIGNAL AB We have previously shown, through transfection experiments, that the murine B7 (mB7) molecule, a ligand for the CD28 and CTLA-4 receptors, is a sufficient costimulatory signal for the antigen-specific and major histocompatibility complex (MHC)-restricted activation of murine CD4(+) T lymphocytes. In addition to mB7, another ligand with affinity for CTLA-4 has been described on spleen cells. Here we report our studies on the expression and function of these molecules on murine Langerhans cells (LC). Both anti-mB7 monoclonal antibody (mAb) 16-10A1 and human CTLA4Ig (hCTLA4Ig), a chimeric fusion protein consisting of the extracellular domain of human CLTA-4 and the constant domain of human IgG1, detected antigens(s) on cultured but not freshly isolated LC. Preincubation of cultured LC with anti-mB7 mAb did not significantly affect binding of hCTLA4Ig to these cells. This result demonstrate the existence of at least one other ligand for the CLTA-4 receptor on cultured LC. Functional studies revealed that the costimulatory activity of LC was inhibited better by hCTLA4Ig than by the anti-mB7 mAb. This differential effect was seen in the case of both alloreactive and antigen-specific, syngeneic T cell responses. These findings suggest that the non-mB7-ligand for CTLA-4 is functional and participates in the induction of immune responses by LC. Importantly, even synergistic combinations of anti-mB7 mAb and hCTLA4Ig did not inhibit completely the activity of LC. These findings therefore raise the possibility that LC express other costimulatory ligands besides mB7 and related family members. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. FU NIAID NIH HHS [R0I AI-33679]; NIAMS NIH HHS [KO8 ARO1884] NR 52 TC 30 Z9 31 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 1994 VL 24 IS 4 BP 805 EP 811 DI 10.1002/eji.1830240405 PG 7 WC Immunology SC Immunology GA NG465 UT WOS:A1994NG46500004 PM 7512030 ER PT J AU EISENBERG, E LACROSS, S STRASSMAN, AM AF EISENBERG, E LACROSS, S STRASSMAN, AM TI THE EFFECTS OF THE CLINICALLY TESTED NMDA RECEPTOR ANTAGONIST MEMANTINE ON CARRAGEENAN-INDUCED THERMAL HYPERALGESIA IN RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE THERMAL HYPERALGESIA; EXCITATORY AMINO ACID; GLUTAMATE RECEPTOR; INFLAMMATION; MEMANTINE; CARRAGEENAN ID METHYL-D-ASPARTATE; HORN NOCICEPTIVE NEURONS; EXCITATORY AMINO-ACIDS; DORSAL HORN; SPINAL-CORD; SUBSTANCE-P; BEHAVIORAL HYPERALGESIA; CENTRAL SENSITIZATION; TISSUE-INJURY; INFLAMMATION AB This study tested the prophylactic and the therapeutic efficacy of memantine (1-amino-3,5-dimethyl-amandate), a clinically tested N-methyl-D-aspartate (NMDA) receptor antagonist, in suppressing carrageenan-induced thermal hyperalgesia in rats. Rats were injected with 0.1 ml of 1% carrageenan solution s.c. into the right hindpaw, and exhibited hyperalgesia in the injected paw as evidenced by a significant reduction of withdrawal latencies from baseline 1, 3, 5, and 24 h following carrageenan. Prophylactic injection of memantine, 10 and 15 mg/kg, significantly suppressed the hyperalgesia 1, 3, and 5 h post-carrageenan, with maximal effects of 70% (10 mg/kg) and 90% (15 mg/kg) at 1 h post-carrageenan. Therapeutic injection of 10 mg/kg of memantine (2.5 h post-carrageenan) had no effect. The 15 mg/kg dose produced a small effect (peak of 44%) at 3.5 h but not at a statistically significant level, and had no effect 5 h post-carrageenan. This study provides evidence that memantine produces primarily a prophylactic effect (and has only a tendency to produce a therapeutic effect) on carrageenan-induced hyperalgesia at doses that do not significantly alter other motor behaviors. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,PAIN PHYSIOL LAB,BOSTON,MA 02129. NR 37 TC 48 Z9 48 U1 0 U2 1 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 APR 1 PY 1994 VL 255 IS 1-3 BP 123 EP 129 DI 10.1016/0014-2999(94)90090-6 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NE761 UT WOS:A1994NE76100016 PM 8026538 ER PT J AU ROYALL, DR AF ROYALL, DR TI PRECIS OF EXECUTIVE DYSCONTROL AS A CAUSE OF PROBLEM BEHAVIOR IN DEMENTIA SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID SUBCORTICAL DEMENTIA; FRONTAL LOBES; ALZHEIMERS-DISEASE; SCHIZOPHRENIC SYNDROMES; COGNITIVE IMPAIRMENT; VASCULAR DEMENTIA; HUMAN AUTONOMY; CORTEX; LESIONS; DYSFUNCTION AB Frontal lobe executive control functions (ECF) are proposed as a source of problem behavior in dementia. The behavior and personality changes that follow frontal lobe brain damage overlap with those seen in dementia, and frontal lobe structural and metabolic lesions can be demonstrated across a variety of dementing illnesses. ECF help explain the importance of social and environmental cues in the production of disruptive behavior and suggest interpersonal strategies for their control. This model has considerable face validity and leads to several testable hypotheses. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,DEPT PSYCHIAT,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,DEPT MED,SAN ANTONIO,TX. RP ROYALL, DR (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 90 TC 47 Z9 47 U1 6 U2 7 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD APR-JUN PY 1994 VL 20 IS 2 BP 73 EP 94 DI 10.1080/03610739408253955 PG 22 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA NE556 UT WOS:A1994NE55600001 PM 8020543 ER EF