FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wu, NX Watkins, SC Schaffer, PA DeLuca, NA AF Wu, NX Watkins, SC Schaffer, PA DeLuca, NA TI Prolonged gene expression and cell survival after infection by a herpes simplex virus mutant defective in the immediate-early genes encoding ICP4, ICP27, and ICP22 SO JOURNAL OF VIROLOGY LA English DT Article ID REGULATORY PROTEIN ICP27; TEMPERATURE-SENSITIVE MUTANTS; THYMIDINE KINASE GENE; MACROMOLECULAR-SYNTHESIS; VIRAL POLYPEPTIDES; DELETION MUTANTS; BINDING-PROTEIN; TYPE-1 ICP27; NUCLEAR-LOCALIZATION; MESSENGER-RNAS AB Very early in infection, herpes simplex virus (HSV) expresses four immediate-early (IE) regulatory proteins, ICP4, ICP0, ICP22, and ICP27. The systematic inactivation of sets of the IE proteins in cis, and the subsequent phenotypic analysis of the resulting mutants, should provide insights into how these proteins function in the HSV life cycle and also into the specific macromolecular events that are altered or perturbed in cells infected with virus strains blocked very early in infection. This approach may also provide a rational basis to assess the efficacy and safety of HSV mutants for use in gene transfer experiments. In this study, we generated and examined the phenotype of an HSV mutant simultaneously mutated in the ICP4, ICP27, and ICP22 genes of HSV. Unlike mutants deficient in ICP4 (d120), ICP4 and ICP27 (d92), and ICP4 and ICP22 (d96), mutants defective in ICP4, ICP27, and ICP22 (d95) were visually much less toxic to Vero and human embryonic lung cells. Cells infected with d95 at a multiplicity of infection of 10 PFU per cell retained a relatively normal morphology and expressed genes from the viral and cellular genomes for at least 3 days postinfection. The other mutant backgrounds were too toxic to allow examination of gene expression past 1 day postinfection. However, when cell survival was measured by the capacity of the infected cells to form colonies, d95 inhibited colony formation similarly to d92. This apparent paradox was reconciled by the observation that host cell DNA synthesis was inhibited in cells infected with d120, d92, d96, and d95. In addition, all of the mutants exhibited pronounced and distinctive alterations in nuclear morphology, as determined by electron microscopy. The appearance of d95-infected cells deviated from that of uninfected cells in that large circular structures formed in the nucleus. d95-infected cells abundantly expressed ICP0, which accumulated in fine punctate structures in the nucleus at early times postinfection and coalesced or grew to the large circular objects that were revealed by electron microscopy. Therefore, while the abundant accumulation of ICP0 in the absence of ICP4, ICP22, and ICP27 may allow for prolonged gene expression, cell survival is impaired, in part, as a result of the inhibition of cellular DNA synthesis. C1 UNIV PITTSBURGH,SCH MED,DEPT MOL GENET & BIOCHEM,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH MED,DEPT CELL BIOL & PHYSIOL,PITTSBURGH,PA 15261. DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA20260]; NIAID NIH HHS [AI30612]; NIDDK NIH HHS [DK44935] NR 84 TC 117 Z9 121 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 SEP PY 1996 VL 70 IS 9 BP 6358 EP 6369 PG 12 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500076 PM 8709264 ER PT J AU LeDoux, JM Morgan, JR Snow, RG Yarmush, ML AF LeDoux, JM Morgan, JR Snow, RG Yarmush, ML TI Proteoglycans secreted by packaging cell lines inhibit retrovirus infection SO JOURNAL OF VIROLOGY LA English DT Article ID APE LEUKEMIA-VIRUS; ECOTROPIC MURINE RETROVIRUSES; AMINO-ACID TRANSPORTER; MEDIATED GENE-TRANSFER; MOUSE FIBROBLASTS; HOST RANGE; RECEPTOR; THERAPY; ENTRY; GLYCOPROTEIN AB Using a model recombinant retrovirus encoding the Escherichia coli lacZ gene, we have found that medium conditioned with NIH 3T3 cells and packaging cell lines derived from NIH 3T3 cells inhibits infection. Most of the inhibitory activity was greater than 100 kDa and was sensitive to chondroitinase ABC digestion, which is consistent with the inhibitor being a chondroitin sulfate proteoglycan. Proteoglycans secreted by NIH 3T3 cells and purified by anion-exchange chromatography inhibited amphotropic retrovirus infection. Pretreatment of amphotropic retrovirus stocks with chondroitinase ABC boosted the level of transduction efficiency by more than twofold. The implications of these findings with respect to retrovirus-cell interactions and the production of high-titer retroviral stocks are discussed. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. SHRINERS BURN INST,BOSTON,MA 02114. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [R29 AR42012]; NICHD NIH HHS [P01 HD28528]; NIGMS NIH HHS [GM-08339] NR 45 TC 94 Z9 95 U1 0 U2 0 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 SEP PY 1996 VL 70 IS 9 BP 6468 EP 6473 PG 6 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500096 PM 8709284 ER PT J AU Kreisberg, JI Radnik, RA Kreisberg, SH AF Kreisberg, JI Radnik, RA Kreisberg, SH TI Phosphorylation of cAMP responsive element binding protein after treatment of mesangial cells with high glucose plus TGF beta or PMA SO KIDNEY INTERNATIONAL LA English DT Article ID SIGNAL TRANSDUCTION PATHWAYS; FIBRONECTIN GENE-EXPRESSION; LEUCINE ZIPPER PROTEINS; KINASE-C; TRANSCRIPTIONAL ACTIVATION; INDUCIBLE GENES; FAMILY; CREB; IDENTIFICATION; MEDIATION AB We recently showed that mesangial cells treated with high glucose plus TGF beta or PMA demonstrated activation of a cAMP-response element (CRE) located in the 5' flanking region of the fibronectin gene. Gel shift mobility assays with a CRE oligonucleotide revealed multiple complexes that did not change in mobility or abundance under conditions of high glucose plus TGF beta or PMA. Here we show that treatment with cycloheximide to inhibit protein synthesis also did not change the DNA/protein complexes. These observations led us to conclude that post-translational modification of transcription factors may be responsible for the activation of the fibronectin gene observed under our experimental conditions. We identified the proteins complexed to CRE as CRE binding protein (CREB) and activating factor 1 (ATF1). This was accomplished by supershift assays and immunoblots. Two hours of high glucose plus TGF beta or 30 minutes of PMA caused a twofold elevation in phosphorylated CREB. Neither high glucose nor TGF beta alone caused phosphorylation of CREB. ATF-1 was not phosphorylated. We also show that high glucose plus TGF beta and PMA activated protein kinase Ca; however, none of the agents tested stimulated intracellular cAMP levels, indicating that phosphorylation of CREE was independent of protein kinase A activation. These results demonstrate cross-talk between the protein kinase C and protein kinase A pathways in that agents which activate the protein kinase C pathway can stimulate phosphorylation of proteins that commonly serve as substrates for protein kinase A. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RP Kreisberg, JI (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK 29787] NR 34 TC 37 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1996 VL 50 IS 3 BP 805 EP 810 DI 10.1038/ki.1996.379 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA VD766 UT WOS:A1996VD76600010 PM 8872954 ER PT J AU Colvin, RB AF Colvin, RB TI The renal allograft biopsy SO KIDNEY INTERNATIONAL LA English DT Review ID CYCLOSPORINE-ASSOCIATED ARTERIOLOPATHY; NEEDLE ASPIRATION BIOPSY; CELL-ADHESION MOLECULE-1; NECROSIS-FACTOR-ALPHA; KIDNEY-TRANSPLANTATION; ACUTE REJECTION; INTERSTITIAL NEPHRITIS; INTERFERON-GAMMA; MONOCLONAL-ANTIBODY; VASCULAR REJECTION C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Colvin, RB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 137 TC 122 Z9 126 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1996 VL 50 IS 3 BP 1069 EP 1082 DI 10.1038/ki.1996.410 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA VD766 UT WOS:A1996VD76600041 PM 8872985 ER PT J AU Weylandt, KH Kang, JX Leaf, A AF Weylandt, KH Kang, JX Leaf, A TI Polyunsaturated fatty acids exert antiarrhythmic actions as free acids rather than in phospholipids SO LIPIDS LA English DT Article ID CARDIAC MYOCYTES; VENTRICULAR-FIBRILLATION; MYOCARDIAL-ISCHEMIA; LONG-CHAIN; ARRHYTHMIAS; MODULATION; HEART; REPERFUSION; INFARCTION; PREVENTION AB Previous studies have shown that exogenous free n-3 polyunsaturated fatty acids (PUFA) can prevent tachyarrhythmias caused by specific agents in isolated cardiac myocytes. However, the question as to whether incorporation of the n-3 PUFA into membrane phospholipids has the same immediate protective effects remained to be answered. To answer this question, we increased the content of n-3 PUFA in the phospholipids of cultured neonatal rat myocytes by growing them 2-3 d in a culture to which eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in 15 mu M concentration was added. Analysis of the fatty acid composition of membrane phospholipids revealed a significantly higher level of EPA and DHA (from 0.2 to 7.6% and from 1.2 to 6.5%) in cells supplemented with EPA or DHA, respectively. The responses of the myocytes grown in normal media or in media enriched with the PUFA to arrhythmogenic agents were examined after free fatty acids were removed from the medium and the cells. The arrhythmogenic agents used were the beta-adrenergic agonist isoproterenol or an elevated extracellular concentration of calcium. The results showed that there was no significant difference in the induction of tachyarrhythmias by isoproterenol or by elevated [Ca2+](o) in cells grown in media enriched with PUFA, as compared with cells grown in normal media in the absence of the free PUFA. Under the conditions of this study, only the unesterified PUFA were able to protect the cardiomyocytes against induced arrhythmias. There was no antiarrhythmic effect due to an increased fraction of EPA or DHA in membrane phospholipids. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,W ROXBURY,MA 02132. FU NIDDK NIH HHS [R01-DK-38165] NR 22 TC 59 Z9 60 U1 0 U2 2 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD SEP PY 1996 VL 31 IS 9 BP 977 EP 982 DI 10.1007/BF02522692 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA VG890 UT WOS:A1996VG89000009 PM 8882978 ER PT J AU Amano, S Nishiyama, T Burgeson, RE AF Amano, S Nishiyama, T Burgeson, RE TI The laminin 5 synthesis and extracellular processing by human keratinocytes SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MGH,HARVARD CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. SHISEIDO RES CTR,YOKOHAMA,KANAGAWA,JAPAN. RI Nishiyama, Toshio/C-5434-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 163 EP 163 DI 10.1016/S0945-053X(96)90030-X PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600030 ER PT J AU Sakai, LY Burgeson, RE Olsen, BR Rowe, DW Gordon, SL AF Sakai, LY Burgeson, RE Olsen, BR Rowe, DW Gordon, SL TI Current knowledge and research directions in heritable disorders of connective tissue SO MATRIX BIOLOGY LA English DT Editorial Material ID MICROFIBRIL-ASSOCIATED GLYCOPROTEIN; MULTIPLE EPIPHYSEAL DYSPLASIA; NEONATAL MARFAN-SYNDROME; GROWTH-FACTOR RECEPTOR-3; MUTATED COLLAGEN GENE; EGF-LIKE DOMAIN; OSTEOGENESIS IMPERFECTA; TRANSGENIC MICE; FIBRILLIN GENE; EXTRACELLULAR MICROFIBRILS C1 OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,PORTLAND,OR 97201. HARVARD UNIV,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,FARMINGTON,CT. OSIRIS THERAPEUT INC,BALTIMORE,MD. NIAMS,MUSCULOSKELETAL BRANCH,NIH,BETHESDA,MD. RP Sakai, LY (reprint author), OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOL BIOL,PORTLAND,OR 97201, USA. NR 90 TC 5 Z9 5 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 4 BP 211 EP 229 DI 10.1016/S0945-053X(96)90113-4 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ837 UT WOS:A1996VJ83700001 PM 8892222 ER PT J AU Haskell, CM Wong, M Williams, A Lee, LY AF Haskell, CM Wong, M Williams, A Lee, LY TI Phase I trial of extracellular adenosine 5'-triphosphate in patients with advanced cancer SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE nonsmall cell lung cancer; pharmacokinetics; biomodulation; drug resistance ID CELL-MEDIATED CYTOTOXICITY; TUMOR-CELLS; LUNG-CANCER; ATP; GROWTH; TRIPHOSPHATE AB Adenosine 5'-triphosphate (ATP) has antineoplastic activity in vitro and in murine tumor systems, but there are no data in humans defining its potential use as an antineoplastic agent. We conducted a Phase I study to determine the spectrum of toxicity, maximum safely tolerated dose (MTD), and pharmacokinetics of intravenous ATP. Fourteen men with advanced cancer received 96-hour infusions of ATP once monthly in doses ranging from 50 to 100 mu g/kg/minute. Toxicity was assessed by standard National Cancer Institute (NCI) criteria, cardiac function was monitored serially by two-dimensional echocardiography, and whole blood ATP was measured serially in a subset of patients. ATP was generally well tolerated and no significant hematologic toxicity was noted. The dose-limiting toxicity was a cardiopulmonary reaction characterized by chest tightness and dyspnea that resolved within seconds of discontinuing ATP. Dose-limiting cardiopulmonary toxicity occurred in 3 of 3 patients at 100 mu g/kg/minute, in 3 of 6 patients at 75 mu g/kg/minute, and 4 of 11 patients at 50 mu g/kg/minute. Whole blood ATP levels significantly increased with treatment, reaching a steady state by 24 hours and returning to or near baseline by 1 week after treatment. Plateau levels were 63%, 67%, and 116% above baseline at 50, 75, and 100 mu g/kg/min, respectively We conclude that prolonged infusions of ATP are feasible with acceptable toxicity and that 50 mu g/kg/minute is both the MTD and the most appropriate dose rate for subsequent Phase II testing of 96-hour infusions of ATP in patients with advanced cancer. (C) 1996 Wiley-Liss. Inc. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,HEMATOL ONCOL SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,PULM SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90073. RP Haskell, CM (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH CANC CTR W111N,LOS ANGELES,CA 90073, USA. NR 21 TC 32 Z9 33 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD SEP PY 1996 VL 27 IS 3 BP 165 EP 173 DI 10.1002/(SICI)1096-911X(199609)27:3<165::AID-MPO6>3.0.CO;2-C PG 9 WC Oncology; Pediatrics SC Oncology; Pediatrics GA VA647 UT WOS:A1996VA64700007 PM 8699994 ER PT J AU Shekelle, PG Rogers, WH Newhouse, JP AF Shekelle, PG Rogers, WH Newhouse, JP TI The effect of cost sharing on the use of chiropractic services SO MEDICAL CARE LA English DT Article DE chiropractic; cost sharing; insurance ID BACK PAIN CARE; UNITED-STATES; EPISODES AB OBJECTIVES. Chiropractic care is increasing in the United States, and there are few data about the effect of cost sharing on the use of chiropractic services. This study calculates the effect of cost sharing on chiropractice use. METHODS. The authors analyzed data from the RAND Health Insurance Experiment, a randomized controlled trial of the effect of cost sharing on the use of health services. Families in six US sites were randomized to receive fee-for-service care that was free or required one of several levels of cost sharing, or to receive care from a health maintenance organization (HMO). Enrollees were followed for 3 or 5 years. All fee-for-service plans covered chiropractic services. Persons assigned to the HMO experimental group received free fee-for-service chiropractic care; persons in the HMO control group had 95% cost sharing for chiropractic services. The authors calculated the mean annual chiropractic expense per person in each of the fee-for-service plans, and also predicted their chiropractic expenditures using a two-equation model. Chiropractic use among persons receiving HMO and fee-for-service care were compared. RESULTS. Chiropractic care is very sensitive to price, with any level of coinsurance of 25% or greater decreasing chiropractic expenditures by approximately half. Access to free chiropractic care among HMO enrollees increased chiropractic use ninefold, whereas access to free medical care decreased fee; for-service chiropractic care by 80%. CONCLUSIONS. Chiropractic care is more sensitive to price than general medical care, outpatient medical care, or dental care, and nearly as sensitive as outpatient mental health care. A substantial cross-price effect with medical care may exist. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RAND CORP,SANTA MONICA,CA. HARVARD UNIV,INST HLTH,NEW ENGLAND MED CTR,CAMBRIDGE,MA 02138. FU AHRQ HHS [TR03HS06920-01] NR 19 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1996 VL 34 IS 9 BP 863 EP 872 DI 10.1097/00005650-199609000-00001 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VF472 UT WOS:A1996VF47200001 PM 8792777 ER PT J AU Palmer, RH Louis, TA Peterson, HF Rothrock, JK Strain, R Wright, EA AF Palmer, RH Louis, TA Peterson, HF Rothrock, JK Strain, R Wright, EA TI What makes quality assurance effective? Results from a randomized, controlled trial in 16 primary care group practices SO MEDICAL CARE LA English DT Article DE practice guidelines; randomized; controlled trial; quality assurance; primary care feedback ID COST-CONTAINMENT; PHYSICIANS; SYSTEM AB OBJECTIVES. The authors estimate separately contributions of each component intervention to overall effectiveness of quality assurance cycles used to improve practice performance. METHODS. In a randomized, controlled trial, experimental cycles of quality assurance were conducted for eight patient-care guidelines, with two experimental cycles assigned to each of 16 group practices. For three separate interventions per cycle, practitioners: (1) were notified of the name of the experimental guideline, (2) discussed criteria of conformance to the guideline, and (3) received feedback on performance. Actions taken in response to interventions were documented. Using medical records data for a baseline year and for 3 months after each intervention and an additional 9 months, the authors scored each practice for conformance to two experimental guidelines and to control guidelines. RESULTS. For all patient-care guidelines combined, and for four of five guidelines showing improvement, knowledge of guidelines and review criteria alone produced no change. After feedback, performance improved and improvement persisted for at least 9 months. The number of corrective actions implemented contributed significantly to effectiveness of quality assurance. CONCLUSIONS. Feedback to providers of data on their performance is a more powerful stimulus for quality improvement than is knowledge of guidelines or discussion of review criteria. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. DANA FARBER CANC INST,BOSTON,MA 02115. MED FDN SERV INC,MIAMI,FL. BRIGHAM & WOMENS HOSP,ROBERT B BRIGHAM MULTIPURPOSE ARTHRIT CTR,BOSTON,MA 02115. RP Palmer, RH (reprint author), HARVARD UNIV,SCH PUBL HLTH,CTR QUAL CARE RES & EDUC,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU AHRQ HHS [HS 05609, HS 03087] NR 17 TC 19 Z9 19 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1996 VL 34 IS 9 SU S BP SS29 EP SS39 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VG253 UT WOS:A1996VG25300004 PM 8792787 ER PT J AU Jaffe, DL Chung, RT Friedman, LS AF Jaffe, DL Chung, RT Friedman, LS TI Management of portal hypertension and its complications SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID SPONTANEOUS BACTERIAL PERITONITIS; PORTOSYSTEMIC STENT-SHUNT; LIVER-TRANSPLANTATION; ESOPHAGEAL-VARICES; CIRRHOTIC-PATIENTS; HEPATIC-ENCEPHALOPATHY; ASCITIC FLUID; HYPERDYNAMIC CIRCULATION; SPLANCHNIC HEMODYNAMICS; ALCOHOLIC CIRRHOSIS AB Portal hypertension is the major adverse consequence of chronic Liver disease. Life-threatening sequelae of portal hypertension include gastroesophageal variceal bleeding, renal failure, infection, and hepatic encephalopathy. Recent years have seen marked progress in the medical, surgical, radiologic, and endoscopic management of these complications based on advances in our understanding of the pathophysiology of portal hypertension. Vigilant monitoring of patients with decompensated cirrhosis and portal hypertensive complications also allows determination of the optimal timing for Liver transplantation, if appropriate. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MT SINAI MED CTR,DIV GASTROENTEROL,NEW YORK,NY 10029. MT SINAI MED CTR,LIVER DIV,NEW YORK,NY 10029. MT SINAI SCH MED,NEW YORK,NY. NR 82 TC 4 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 1996 VL 80 IS 5 BP 1021 EP & PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA VF987 UT WOS:A1996VF98700008 PM 8804373 ER PT J AU Jutabha, R Jensen, DM AF Jutabha, R Jensen, DM TI Management of upper gastrointestinal bleeding in the patient with chronic liver disease SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID PORTAL-HYPERTENSIVE GASTROPATHY; RANDOMIZED CONTROLLED TRIAL; ANTRAL VASCULAR ECTASIA; INTRAHEPATIC PORTOSYSTEMIC SHUNT; DISTAL SPLENORENAL SHUNT; ENDOSCOPIC INJECTION SCLEROTHERAPY; MALLORY-WEISS SYNDROME; SPLENIC VEIN-THROMBOSIS; CANINE GASTRIC VARICES; TERM FOLLOW-UP AB This article reviews the management of severe upper gastrointestinal bleeding in the patient with chronic liver diseases. The initial assessment, diagnostic work-up, and treatment options for variceal and nonvariceal bleeding are discussed. The role of diagnostic and therapeutic endoscopy for esophagogastric varices is reviewed with special emphasis on new endoscopic techniques including variceal band ligation and cyanoacrylate injection. Various pharmacologic, surgical, and radiologic treatment options for variceal bleeding also are discussed. In addition, nonvariceal causes of severe upper gastrointestinal bleeding are reviewed including peptic ulcer diseases, Mallory-Weiss tear, portal hypertensive gastropathy, and gastric antral vascular ectasia. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CTR ULCER RES & EDUC,DIGEST DIS RES CTR,LOS ANGELES,CA 90024. RP Jutabha, R (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV DIGEST DIS,10833 LE CONTE AVE,CHS 44-138,LOS ANGELES,CA 90095, USA. FU NCRR NIH HHS [MO1-RR008658]; NIDDK NIH HHS [NIDDK R01-33273, NIDDK 41301] NR 260 TC 43 Z9 44 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 1996 VL 80 IS 5 BP 1035 EP & PG 35 WC Medicine, General & Internal SC General & Internal Medicine GA VF987 UT WOS:A1996VF98700009 PM 8804374 ER PT J AU Martin, P Friedman, LS AF Martin, P Friedman, LS TI Management of chronic liver disease - Preface SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP Martin, P (reprint author), UNIV CALIF LOS ANGELES,SCH MED,77-123D CHS,10833 LE CONTE AVE,LOS ANGELES,CA 90095, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD SEP PY 1996 VL 80 IS 5 BP R13 EP R14 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VF987 UT WOS:A1996VF98700001 ER PT J AU Carter, EA Tompkins, RG Babich, JW Correia, J Bailey, EM Fischman, AJ AF Carter, EA Tompkins, RG Babich, JW Correia, J Bailey, EM Fischman, AJ TI Thermal injury in rats alters glucose utilization by skin, wound, and small intestine, but not by skeletal muscle SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INDIVIDUAL TISSUES; BURNED PATIENTS; INSULIN; KINETICS; METABOLISM; CATABOLISM; ENDOTOXIN; SEPSIS AB The effects of thermal injury in rats on glucose utilization (Rg) by skin, wound, small intestine, and muscle in vivo has been determined using 2-[F-18]-fluoro-2-deoxy-D-glucose ((18)FDG) 6 hours, 24 hours, and 3 weeks after injury. These results were compared with serum glucose and insulin levels at the same time points and with hexokinase activity in the tissues. Thermal injury had no significant effects on serum glucose levels; however, serum insulin levels were lower than sham values 6 hours after injury, the same as sham values 24 hours after injury, and significantly higher than sham values 3 weeks after injury. Rg of unburned skin was not changed at 6 or 24 hours after injury, but was increased at 3 weeks after injury. The Rg of the wound was almost zero at 6 and 24 hours after injury; however, at 3 weeks after injury, the wound area had a Rg two to three times higher than that of the normal skin of sham animals. Small intestine Rg was decreased 6 and 24 hours after injury, but was essentially normal by 3 weeks after injury. The Rg of muscle was unchanged at all of the time points tested. Total Rg was significantly higher in the animals 3 weeks after injury, with the increase primarily due to the increases in skin and wound. The increases in Rg were associated with changes in tissue hexokinase activity. The present data suggest that thermal injury to rats results in dramatic alterations in glucose utilization by the skin and wound, changes that may contribute to the overall alterations in carbohydrate metabolism during burn trauma. Copyright (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. SHRINERS BURNS INST,BOSTON,MA. RP Carter, EA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,PEDIAT GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 30 TC 19 Z9 19 U1 0 U2 0 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 SEP PY 1996 VL 45 IS 9 BP 1161 EP 1167 DI 10.1016/S0026-0495(96)90017-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF481 UT WOS:A1996VF48100018 PM 8781305 ER PT J AU Kurohara, ML Klaustermeyer, WB Placik, IM AF Kurohara, ML Klaustermeyer, WB Placik, IM TI Asthma: Analysis of intubated patients over a one-year period SO MILITARY MEDICINE LA English DT Article ID MORTALITY; IDENTIFICATION; RISK AB Mortality rates for asthma have increased significantly since 1980. During a 12-month period (1990) at the West Los Angeles VA Medical Center, six asthma patients required intubation, Contributing factors to intubation were steroid dependence, atopy, beta-agonist overuse, infection, non-compliance, adverse drug reaction, and undertreatment with steroids. C1 W LOS ANGELES VET AFFAIRS MED CTR,ALLERGY & IMMUNOL SECT 111R,MED SERV,LOS ANGELES,CA 90073. NR 18 TC 2 Z9 2 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD SEP PY 1996 VL 161 IS 9 BP 567 EP 570 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VF858 UT WOS:A1996VF85800015 PM 8840801 ER PT J AU Clement, PB Young, RH Oliva, E Sumner, HW Scully, RE AF Clement, PB Young, RH Oliva, E Sumner, HW Scully, RE TI Hyperplastic mesothelial cells within abdominal lymph nodes: Mimic of metastatic ovarian carcinoma and serous borderline tumor - A report of two cases associated with ovarian neoplasms SO MODERN PATHOLOGY LA English DT Article DE lymph nodes; mesothelial cells; mesothelial hyperplasia; peritoneum; serous borderline tumor ID BENIGN GLANDULAR INCLUSIONS; LEIOMYOMATOSIS; METAPLASIA; LESIONS; ERROR AB Two cases of hyperplastic mesothelial cells within intra-abdominal lymph nodes were encountered in staging procedures in a 59-year-old woman with bilateral ovarian serous borderline tumors and in a 21-year-old woman with a Sertoli-Leydig cell tumor of intermediate differentiation. Both patients also had mesothelial hyperplasia of the pelvic and abdominal peritoneum; in one of them, the hyperplasia was striking, The intranodal mesothelial cells occupied the sinusoids of the lymph nodes and were initially suspected of being metastatic from the ovarian tumor in each case, The appearance of the cells on routine stains suggested the correct diagnosis, which was confirmed by histochemical and immunohistochemical staining, These cases represent the first reported examples of mesothelial cells within abdominal lymph nodes, although similar involvement of mediastinal lymph nodes has been described in three patients with pleural effusions. Intranodal mesothelial cells should be distinguished from metastatic tumor, an error that could result in inaccurate staging in a patient with a known tumor or prompt a futile search for an occult primary tumor, Moreover, it is important that in studies evaluating the frequency of nodal involvement by serous borderline tumors, intranodal mesothelial cells should not be misinterpreted as metastatic borderline tumor, a distinction that can be difficult with only routinely stained sections. C1 UNIV BRITISH COLUMBIA,DEPT PATHOL,VANCOUVER,BC,CANADA. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. PRESBYTERIAN HOSP,DEPT PATHOL,OKLAHOMA CITY,OK. RP Clement, PB (reprint author), VANCOUVER HOSP & HLTH SCI CTR,DEPT PATHOL,910 W 10TH AVE,ROOM 1302,VANCOUVER,BC V5Z 4E3,CANADA. NR 25 TC 52 Z9 53 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1996 VL 9 IS 9 BP 879 EP 886 PG 8 WC Pathology SC Pathology GA VG382 UT WOS:A1996VG38200001 PM 8878019 ER PT J AU Duncan, LM Bouffard, D Howard, C Mihm, MC Byers, HR AF Duncan, LM Bouffard, D Howard, C Mihm, MC Byers, HR TI In situ distribution of integrin alpha(2)beta(1) and alpha-actinin in melanocytic proliferations SO MODERN PATHOLOGY LA English DT Article DE alpha-actinin; cell adhesion; cell motility; integrin; melanoma ID HUMAN-MALIGNANT MELANOMA; TUMOR PROGRESSION; CELLS; ADHESION; EXPRESSION; COLLAGEN; LAMININ; METASTASIS; MIGRATION; INVITRO AB Integrin alpha(2) beta(1) is a transmembrane protein receptor for collagen and laminin previously reported as a melanoma tumor progression antigen. alpha-Actinin is an actin-binding protein reported to interact with the cytoplasmic domain of the beta(1)-integrin chain of alpha(2) beta(1). In vitro both alpha(2) beta(1) and alpha-actinin play a role in melanoma cell motility. In turn, increased melanoma cell line motility (measured as mean migration rates), correlates with metastasis. To determine the in situ distribution of these proteins, we used monoclonal antibodies directed against the alpha(2)-integrin subunit of alpha(2) beta(1) and alpha-actinin on frozen sections of 33 melanocytic proliferations, which included dermal nevi, primary melanomas, and metastatic melanomas. We found that the superficial portion of all of the melanocytic proliferations tested stained for alpha-actinin. In benign nevi and superficial spreading melanoma, there was a notable loss of staining for alpha-actinin in the cells in the deep reticular dermis. In contrast, alpha-actinin was present on almost all of the tumor cells in the nodular melanomas and the melanoma metastases. Tumors stained either uniformly positive or uniformly negative for alpha(2) beta(1); the expression of this protein correlated with the later stages of melanoma progression. Our findings suggest that alpha-actinin protein levels initially decrease and then increase during melanocytic tumor progression, whereas the alpha(2) subunit protein appears in the later stages of melanoma progression. The variable distribution of these proteins is evidence for the differential adhesive and motile properties of subpopulations of cells in melanocytic proliferations. C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MONTREAL,HOP NOTRE DAME,DEPT PATHOL,MONTREAL,PQ,CANADA. ALBANY MED COLL,DEPT DERMATOL,ALBANY,NY 12208. BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02118. RP Duncan, LM (reprint author), MASSACHUSETTS GEN HOSP,DERMATOPATHOL UNIT,WARREN 827,32 FRUIT ST,BOSTON,MA 02114, USA. NR 26 TC 15 Z9 15 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1996 VL 9 IS 9 BP 938 EP 943 PG 6 WC Pathology SC Pathology GA VG382 UT WOS:A1996VG38200009 PM 8878027 ER PT J AU Jones, RM Branda, J Johnston, KA Polymenis, M Gadd, M Rustgi, A Callanan, L Schmidt, EV AF Jones, RM Branda, J Johnston, KA Polymenis, M Gadd, M Rustgi, A Callanan, L Schmidt, EV TI An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR USF; DNA-BINDING; IMMUNOGLOBULIN ENHANCER; CELL-PROLIFERATION; TRANSGENIC MICE; SACCHAROMYCES-CEREVISIAE; MALIGNANT TRANSFORMATION; INCREASED EXPRESSION; MESSENGER-RNAS; IN-VIVO AB The mRNA cap-binding protein (eukaryotic initiation factor 4E [eIF4E]) binds the m(7)GpppN cap on mRNA, thereby initiating translation, eIF4E is essential and rate limiting for protein synthesis, Overexpression of eIF4E transforms cells, and mutations in eIF4E arrest cells in G(1) in cdc33 mutants, In this work, we identified the promoter region of the gene encoding eIF4E, because we previously identified eIF4E as a potential myc-regulated gene, In support of our previous data, a minimal, functional, 403-nucleotide promoter region of eIF4E was found to contain CACGTG E box repeats, and this core eIF4E promoter was myc responsive in cotransfections with c-myc, A direct role for myc in activating the eIF4E promoter was demonstrated by cotransfections with two dominant negative mutants of c-myc (Myc Delta TAD and Myc Delta BR) which equally suppressed promoter function, Furthermore, electrophoretic mobility shift assays demonstrated quantitative binding to the E box motifs that correlated with myc levels in the electrophoretic mobility shift assay extracts; supershift assays demonstrated max and USF binding to the same motif, cis mutations in the core or flank of the eIF4E E box simultaneously altered myc-max and USF binding and inactivated the promoter. Indeed, mutations of this E box inactivated the promoter in all cells tested, suggesting it is essential for expression of eIF4E. Furthermore, the GGCCACGTG(A/T)C(C/G) sequence is shared with other in vivo targets for c-myc, but unlike other targets, it is located in the immediate promoter region, Its critical function in the eIF4E promoter coupled with the known functional significance of eIF4E in growth regulation makes it a particularly interesting target for c-myc regulation. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEPT SURG ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NCI NIH HHS [R01-CA63117]; NINDS NIH HHS [T32NS07340-04] NR 72 TC 170 Z9 175 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 SEP PY 1996 VL 16 IS 9 BP 4754 EP 4764 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700019 PM 8756633 ER PT J AU Zhu, Y Pless, M Inhorn, R MatheyPrevot, B DAndrea, AD AF Zhu, Y Pless, M Inhorn, R MatheyPrevot, B DAndrea, AD TI The murine DUE-1 gene is specifically induced by the beta c subunit of the interleukin-3 receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; GM-CSF RECEPTOR; ERYTHROPOIETIN RECEPTOR; DNA-BINDING; EXPRESSION CLONING; MOLECULAR-CLONING; DIFFERENTIAL DISPLAY; SIGNAL-TRANSDUCTION; MAMMALIAN-CELLS; TYROSINE KINASE AB Cytokines regulate cell growth and differentiation by inducing the expression of specific target genes. We have recently isolated a cytokine-inducible, immediate-early cDNA, DUB-1, that encodes a deubiquitinating enzyme. The DUB-1 mRNA was specifically induced by the receptors for interleukin-3, granulocyte-macrophage colony-stimulating factor, and interleukin-5, suggesting a role for the beta common (beta c) subunit known to be shared by these receptors. In order to identify the mechanism of cytokine induction, we isolated a murine genomic clone for DUB-1 containing a functional promoter region. The DUB-1 gene contains two exons, and the nucleotide sequence of its coding region is identical to the sequence of DUB-1 cDNA. Various regions of the 5' flanking region of the DUB-1 gene were assayed for cytokine-inducible activity. An enhancer region that retains the beta c-specific inducible activity of the DUB-1 gene was identified. Enhancer activity was localized to a 112-bp fragment located 1.4 kb upstream from the ATG start codon. Gel mobility shift assays revealed two specific protein complexes that bound to this minimal enhancer region. One complex was induced by beta c signaling, while the other was noninducible. Finally, the membrane-proximal region of human beta c was required for DUB-1 induction. In conclusion, DUB-1 is the first example of an immediate-early gene that is induced by a specific subunit of a cytokine receptor, Further analysis of the DUB-1 enhancer element may reveal specific determinants of a beta c-specific signaling pathway. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NIDDK NIH HHS [R01DK 43889-01] NR 56 TC 42 Z9 44 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 SEP PY 1996 VL 16 IS 9 BP 4808 EP 4817 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700025 PM 8756639 ER PT J AU Brill, S Li, SH Lyman, CW Church, DM Wasmuth, JJ Weissbach, L Bernards, A Snijders, AJ AF Brill, S Li, SH Lyman, CW Church, DM Wasmuth, JJ Weissbach, L Bernards, A Snijders, AJ TI The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE; TYROSINE KINASE; FISSION YEAST; STRESS FIBERS; GROWTH-FACTOR; GENE; IDENTIFICATION; HOMOLOG; CDC42; TRANSFORMATION AB We previously described IQGAP1 as a human protein related to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe. Here we report the identification of a liver-specific human protein that is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N-terminal calponin homology motif which functions as an F-actin binding domain in members of the spectrin, filamin, and fimbrin families, Both IQGAPs also harbor several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and four IQ motifs and have 25% sequence identity with almost the entire S. pombe sar1 RasGAP homolog, As predicted by the presence of IQ motifs, IQGAP2 binds calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the GTPase activity of Ras or its close relatives, Instead, IQGAP2 binds Cdc42 and Rac1 but not RhoA. This interaction involves the C-terminal half of IQGAP2 and appears to be independent of the nucleotide binding status of the GTPases. Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain, they could play roles in the Cdc42 and Rad controlled generation of specific actin structures. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,ORTHOPED RES LABS,CHARLESTOWN,MA 02129. UNIV CALIF IRVINE,COLL MED,DEPT BIOL CHEM,IRVINE,CA 92717. FU NIAMS NIH HHS [AR16265E21]; NINDS NIH HHS [NS31747] NR 53 TC 186 Z9 189 U1 1 U2 2 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 SEP PY 1996 VL 16 IS 9 BP 4869 EP 4878 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700032 PM 8756646 ER PT J AU Nathan, DG AF Nathan, DG TI Molecular medicine society: A great start, a great future SO MOLECULAR MEDICINE LA English DT Editorial Material RP Nathan, DG (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD SEP PY 1996 VL 2 IS 5 BP 527 EP 529 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VL189 UT WOS:A1996VL18900001 PM 8898368 ER PT J AU Anisowicz, A Sotiropoulou, G Stenman, G Mok, SC Sager, R AF Anisowicz, A Sotiropoulou, G Stenman, G Mok, SC Sager, R TI A novel protease homolog differentially expressed in breast and ovarian cancer SO MOLECULAR MEDICINE LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; AMINO-ACID-SEQUENCE; NUCLEOTIDE-SEQUENCES; MOLECULAR-CLONING; ESCHERICHIA-COLI; KALLIKREIN GENE; MESSENGER-RNAS; CDNA; IDENTIFICATION; PURIFICATION AB Background: Using differential display (DD), we discovered a new member of the serine protease family of protein-cleaving enzymes, named protease M. The gene is most closely related by sequence to the kallikreins, to prostate-specific antigen (PSA), and to trypsin. The diagnostic use of PSA in prostate cancer suggested that a related molecule might be a predictor for breast or ovarian cancer. This, in turn, led to studies designed to characterize the protein and to screen for its expression in cancer. Materials and Methods: The isolation of protease M by DD, the cloning and sequencing of the cDNA, and the comparison of the predicted protein structure with related proteins are described, as are methods to produce recombinant proteins and polyclonal antibody preparations. Protease M expression was examined in mammary, prostate, and ovarian cancer, as well as normal cells and tissues. Stable transfectants expressing the protease M gene were produced in mammary carcinoma cells. Results: Protease M was localized by fluorescent in situ hybridization analysis to chromosome 19q13.3, in a region to which other kallikreins and PSA also map. The gene is expressed in the primary mammary carcinoma lines tested but not in the corresponding cell lines of metastatic origin. It is strongly expressed in ovarian cancer;tissues and cell lines. The enzyme activity could not be established, because of difficulties in producing sufficient recombinant protein, a common problem with proteases. Transfectants were selected that overexpress the mRNA, but the protein levels remained very low. Conclusions: Protease M expression (mRNA) may be a useful marker in the detection of primary mammary carcinomas, as well as primary ovarian cancers. Other medical applications are also likely, based on sequence relatedness to trypsin and PSA. C1 HARVARD UNIV,DIV CANC GENET,DANA FARBER CANC INST,SCH MED,BOSTON,MA 02115. UNIV PATRAS,SCH HLTH SCI,DEPT PHARM,PATRAS,GREECE. GOTHENBURG UNIV,DEPT PATHOL,S-41124 GOTHENBURG,SWEDEN. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,LAB GYNECOL ONCOL,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA57517, CA61253] NR 42 TC 174 Z9 179 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD SEP PY 1996 VL 2 IS 5 BP 624 EP 636 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VL189 UT WOS:A1996VL18900011 PM 8898378 ER PT J AU Schmidt, EV AF Schmidt, EV TI MYC family ties SO NATURE GENETICS LA English DT Editorial Material ID RETINOBLASTOMA GENE-PRODUCT; TATA-BINDING PROTEIN; C-MYC; TRANSACTIVATION DOMAIN; TRANSCRIPTION; ELEMENT; P107; ASSOCIATION; INHIBITION; LYMPHOMA RP Schmidt, EV (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT MOL GENET,CHARLESTOWN,MA 02129, USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1996 VL 14 IS 1 BP 8 EP 10 DI 10.1038/ng0996-8 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VF611 UT WOS:A1996VF61100005 PM 8782810 ER PT J AU Melder, RJ Koenig, GC Witwer, BP Safabakhsh, N Munn, LL Jain, RK AF Melder, RJ Koenig, GC Witwer, BP Safabakhsh, N Munn, LL Jain, RK TI During angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor regulate natural killer cell adhesion to tumor endothelium SO NATURE MEDICINE LA English DT Article ID INDUCED LEUKOCYTE ADHESION; CRANIAL WINDOWS; NECROSIS-FACTOR; E-SELECTIN; EXPRESSION; VESSELS; PERMEABILITY; METASTASIS; KINETICS; INVIVO AB Localization of activated natural killer (A-NK) cells in the microvasculature of growing tumors is the result of recognition of the intracellular and vascular cell-adhesion molecules ICAM-1 and VCAM-1 on the tumor endothelium, mediated by lymphocyte function-associated protein LFA-1 and vascular lymphocyte function-associated protein VLA-4. In vitro and in vivo studies of A-NK cell adhesion to endothelial cells showed that vascular endothelial growth factor (VEGF) promotes adhesion, whereas basic fibroblast growth factor (bFGF) inhibits adhesion through the regulation of these molecules on tumor vasculature. Thus, some angiogenic factors may facilitate lymphocyte recognition of angiogenic vessels, whereas others may provide such vessels with a mechanism that protects them from cytotoxic lymphocytes. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Melder, RJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,100 FRUIT ST,BOSTON,MA 02114, USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NCI NIH HHS [F32-CA 61631, R35-CA 56591] NR 39 TC 324 Z9 329 U1 0 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1996 VL 2 IS 9 BP 992 EP 997 DI 10.1038/nm0996-992 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VF497 UT WOS:A1996VF49700033 PM 8782456 ER PT J AU Hantraye, P Brouillet, E Ferrante, R Palfi, S Dolan, R Matthews, RT Beal, MF AF Hantraye, P Brouillet, E Ferrante, R Palfi, S Dolan, R Matthews, RT Beal, MF TI Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons SO NATURE MEDICINE LA English DT Article ID DOPAMINERGIC-NEURONS; SUPEROXIDE-DISMUTASE; 7-NITRO INDAZOLE; RAT STRIATUM; NEUROTOXICITY; DISEASE; LESIONS; MODEL; PEROXYNITRITE; MECHANISMS AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase (NOS) that blocks MPTP neurotoxicity in mice. We now show that 7-NI protects against profound striatal dopamine depletions and loss of tyrosine hydroxylase-positive neurons in the substantia nigra in MPTP-treated baboons. Furthermore, 7-NI protected against MPTP-induced motor and frontal-type cognitive deficits. These results strongly implicate a role of nitric oxide in MPTP neurotoxicity and suggest that inhibitors of neuronal NOS might be useful in treating Parkinson's disease. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. SERV HOSP FREDERIC JOLIOT,CEA,CNRS URA 2210,ORSAY,FRANCE. VET AFFAIRS MED CTR,GERIATR RES EDUC CLIN CTR,BEDFORD,MA. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. RI Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 FU NIA NIH HHS [AG 12922-01]; NINDS NIH HHS [NS 10828, NS 16367] NR 29 TC 351 Z9 355 U1 0 U2 12 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1996 VL 2 IS 9 BP 1017 EP 1021 DI 10.1038/nm0996-1017 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VF497 UT WOS:A1996VF49700037 PM 8782460 ER PT J AU Felsenfeld, AJ Rodriguez, M AF Felsenfeld, AJ Rodriguez, M TI The set point of calcium - Another view SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material ID PARATHYROID-HORMONE SECRETION; SECONDARY HYPERPARATHYROIDISM; HEMODIALYSIS-PATIENTS C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. HOSP UNIV REINA SOFIA,DEPT NEPHROL,CORDOBA 14004,SPAIN. UNIV CORDOBA,FAC MED,E-14071 CORDOBA,SPAIN. RP Felsenfeld, AJ (reprint author), HOSP UNIV REINA SOFIA,UNIT INVEST,AVDA MENENDEZ PIDAL S-N,CORDOBA 14004,SPAIN. RI Rodriguez, teresa/H-5452-2011 NR 12 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD SEP PY 1996 VL 11 IS 9 BP 1722 EP 1725 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA VJ132 UT WOS:A1996VJ13200007 PM 8918610 ER PT J AU Pralong, FP Boepple, PA Conn, PM Whitcomb, RW Butler, JP Schoenfeld, D Crowley, WF AF Pralong, FP Boepple, PA Conn, PM Whitcomb, RW Butler, JP Schoenfeld, D Crowley, WF TI Contour of the GnRH pulse independently modulates gonadotropin secretion in the human male SO NEUROENDOCRINOLOGY LA English DT Article DE gonadotropins; gonadotropin-releasing hormone; clinical neuroendocrinology; rhythms, ultradian; pulsatility ID FOLLICLE-STIMULATING-HORMONE; FREE ALPHA-SUBUNIT; MESSENGER-RIBONUCLEIC-ACID; RAT PITUITARY-CELLS; LUTEINIZING-HORMONE; RHESUS-MONKEY; DEFICIENT MEN; OVARIECTOMIZED EWES; ELECTRICAL-ACTIVITY; GENERATOR ACTIVITY AB GnRH pulse frequency, amplitude, and interpulse interval have all been demonstrated to regulate gonadotropin secretion individually. We tested the hypothesis that the contour of the GnRH pulse also modulates gonadotropin output in 10 men with isolated GnRH deficiency in whom a fixed GnRH dose was administered at a constant physiologic frequency by either instantaneous bolus or by 1-, 5-, or 30-min infusions. LH, FSH and free alpha subunit (FAS) responses were also compared to spontaneous gonadotropin secretion in normal adult men. While the LH and FAS pulses following the instantaneous bolus and 1-min infusion of GnRH were indistinguishable, further increases in the duration of gonadotrope stimulation by GnRH were associated with progressive decreases in all parameters of gonadotropin secretion (mean levels, amplitude, peak levels, AUG). FSH secretion was also decreased following variations in the contour of the GnRH pulse, although overall changes were less dramatic than for LH and FAS. The LH pulses following the bolus GnRH stimulation were indistinguishable from spontaneous LH pulses occurring in normal men whereas those stimulated by the 1-, 5-, and 30-min infusions of GnRH became progressively blunted with the lowest levels of secretion occurring after the longest infusion. In sharp contrast, FAS pulse parameters in the GnRH-deficient subjects greatly exceeded those of normal men regardless of the contour of the GnRH stimulus, whereas mean FSH levels were all modestly (although significantly) higher than those of normal adult men. These results demonstrate that the pituitary is sensitive to subtle changes in the contour of the GnRH stimulus, with a more prolonged duration of GnRH stimulation resulting in a diminished pituitary response. Alterations of the contour of endogenous GnRH secretion may represent an additional mechanism for altering gonadotrope function and provide additional evidence for the differential regulation of LH, FAS, and FSH by GnRH. However, the previously reported elevated levels of FAS secretion in GnRH-deficient men undergoing long-term GnRH replacement are not explained by abnormalities of GnRH contour. C1 MASSACHUSETTS GEN HOSP,REPROD ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,GEN CLIN RES CTR,BOSTON,MA 02114. OREGON REG PRIMATE RES CTR,BEAVERTON,OR 97006. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. HARVARD UNIV,SCH PUBL HLTH,DEPT RESP PHYSIOL,BOSTON,MA 02115. FU NICHD NIH HHS [R01-HD-15788, R01 HD015788, R01-HD-18169, P30 HD028138]; PHS HHS [U54 29164] NR 53 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD SEP PY 1996 VL 64 IS 3 BP 247 EP 256 DI 10.1159/000127125 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA VF150 UT WOS:A1996VF15000010 PM 8875443 ER PT J AU Hochberg, F Miller, G Valenzuela, R McNelis, S Crump, KS Covington, T Valdivia, G Hochberg, B Trustman, JW AF Hochberg, F Miller, G Valenzuela, R McNelis, S Crump, KS Covington, T Valdivia, G Hochberg, B Trustman, JW TI Late motor deficits of Chilean manganese miners: A blinded control study SO NEUROLOGY LA English DT Article ID WORKERS; PERFORMANCE; SYSTEM AB High-level chronic manganese (Mn) exposure produces dystonic rigidity and proximal tremor. The late effects of asymptomatic exposure are uncertain. To evaluate hand movements of asymptomatic Chilean miners, we utilized a manual tremormeter (EAP) and a digitizing tablet (MOVEMAP). In Andacollo, Chile, we examined 59 individuals aged >50 years (mean age, 64.4 years). Twenty-seven exposed miners had heavy Mn dust exposure in Mn mines for more than 5 years (mean duration, 20.25 years), ending at least 5 years previously. Thirty-two control miners had never worked in Mn mines or had short-term Mn employment. Tests of resting tremor (EAP Tremormeter, MOVEMAP Steady paradigm), action tremor (MOVEMAP Square paradigm), and repetitive hand movements (EAP Tapping Test and Ortho-kinesimeter) differentiated performance of exposed miners from that of controls. Chronic asymptomatic Mn exposure results in detectable late-life abnormalities of movement. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CATHOLIC UNIV CHILE,ESCUELA MED,DEPT SALUD PUBL,SANTIAGO,CHILE. KS CRUMP DIV,RUSTON,LA. HARVARD UNIV,BOSTON,MA 02115. NR 21 TC 41 Z9 42 U1 1 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1996 VL 47 IS 3 BP 788 EP 795 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA VG596 UT WOS:A1996VG59600029 PM 8797481 ER PT J AU Weiss, S Cataltepe, O Cole, AJ AF Weiss, S Cataltepe, O Cole, AJ TI Anatomical studies of DNA fragmentation in rat brain after systemic kainate administration SO NEUROSCIENCE LA English DT Article DE seizures; kainate; status epilepticus; DNA fragmentation; in situ nick translation; apoptosis ID APOPTOTIC CELL-DEATH; FIBER SYNAPTIC REORGANIZATION; DOMOIC ACID INTOXICATION; TEMPORAL-LOBE EPILEPSY; DELAYED NEURONAL DEATH; KAINIC ACID; NICK TRANSLATION; HIPPOCAMPAL SCLEROSIS; DAMAGE SYNDROME; NERVOUS-SYSTEM AB Rats treated systemically with kainate develop stereotyped epileptic seizures involving mainly limbic structures that may last for hours. This model of limbic status epilepticus has been widely studied using classical neuropathological techniques. We used in situ nick translation histochemistry to examine patterns of DNA fragmentation in this model. We found a stereotyped and reproducible pattern of neuronal populations that demonstrate evidence of DNA fragmentation from 24 h to one week after kainate treatment. Neither blockade of new protein synthesis nor blockade of the N-methyl-D-aspartate-type glutamate receptors significantly altered this response. Moreover, we saw no evidence of the regular internucleosomal cleavage of DNA that produces a characteristic laddered appearance of 180-200 bp DNA fragments after gel electrophoresis in samples obtained from microdissected affected regions. These studies suggest that DNA fragmentation after systemic kainate-induced seizures is not the result of programmed cell death. This assay may be useful for quantitative testing of both neuroprotective agents and mechanistic hypotheses. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,EPILEPSY RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. FU NINDS NIH HHS [NS 01360] NR 67 TC 62 Z9 62 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 SEP PY 1996 VL 74 IS 2 BP 541 EP 551 DI 10.1016/0306-4522(96)00148-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA VC755 UT WOS:A1996VC75500023 PM 8865204 ER PT J AU Scott, JA AF Scott, JA TI Artificial neural networks and image interpretation SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Editorial Material ID VENTILATION-PERFUSION; PULMONARY-EMBOLISM; CROSSROADS; DIAGNOSIS; SCANS RP Scott, JA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD SEP PY 1996 VL 17 IS 9 BP 739 EP 741 DI 10.1097/00006231-199609000-00003 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VK455 UT WOS:A1996VK45500003 PM 8895900 ER PT J AU Portillo, CJ Stevens, PE Henry, S Saunders, JM Corless, IB Munjas, BA AF Portillo, CJ Stevens, PE Henry, S Saunders, JM Corless, IB Munjas, BA TI American Academy of Nursing's HIV/AIDS Nursing Care Summit: The final synthesis SO NURSING OUTLOOK LA English DT Article ID HIV; AIDS AB The American Academy of Nursing HIV/AIDS Nursing Care Summit convened nurse leaders from across the United States to discuss nursing responses to the HIV/AIDS epidemic. This final synthesis of the Summit includes recommendations regarding clinical practice, administration and policy, education, and research in the area of HIV/AIDS. C1 UNIV WISCONSIN,SCH NURSING,MILWAUKEE,WI 53201. UNIV SO CALIF,DEPT NURSING,LOS ANGELES,CA. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114. VIRGINIA COMMONWEALTH UNIV,SCH NURSING,RICHMOND,VA. RP Portillo, CJ (reprint author), UNIV CALIF SAN FRANCISCO,SCH NURSING,SAN FRANCISCO,CA 94143, USA. OI Corless, Inge/0000-0003-0438-2037 NR 18 TC 3 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD SEP-OCT PY 1996 VL 44 IS 5 BP 229 EP 234 DI 10.1016/S0029-6554(96)80097-2 PG 6 WC Nursing SC Nursing GA VN526 UT WOS:A1996VN52600006 PM 8905836 ER PT J AU Bouros, D Papadakis, K Siafakas, N Fuller, AF AF Bouros, D Papadakis, K Siafakas, N Fuller, AF TI Patterns of pulmonary metastasis from uterine cancer SO ONCOLOGY LA English DT Article DE uterine cancer; metastasis, pulmonary; metastasis, lung; endometrial cancer; genital malignancy; adenocarcinoma ID ENDOMETRIAL CARCINOMA AB Background: Endometrial cancer is the most common female genital cancer and approximately 90% of the cases are diagnosed while they are still confined to the uterus. However, the frequency and the pattern of pulmonary metastasis (PM) have not been studied systematically. Patients and Methods: From 1962 to 1989, 90 patients wit PM were identified by computerized search of the medical records of the 1,550 (5.8%) patients admitted to the Massachusetts General Hospital with the diagnosis of uterine cancer. The median age of the patients was 67 years (range from 42 to 88 years). The histology of the uterine neoplasms included 53 adenocarcinomas (59%), 19 sarcomas (21%), 12 adenosqamous carcinomas (13.5%), 4 adenoacanthomas (4.5%), and 2 clear cell adenocarcinomas (2%). Chest radiographs were retrospectively reviewed by two experienced readers. Results: Lung metastases were found at the time of diagnosis of the primary tumor in 20 patients (22%). The usual pattern of PM involved multiple pulmonary nodules in 65 patients (72%); solitary pulmonary nodules were found in 16 (18%), mass lesion in 10 (11%), lymphangitic spread in 3, and pleural effusion in 6 (6.7%). Cavitation and tracheal metastasis were observed in one case each. Conclusion: Pulmonary metastases represent a common site of extrapelvic spread of disease for the small number of patients with advanced or recurrent endometrial carcinoma. The usual type of PM is multiple bilateral nodules. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,GYNECOL ONCOL DIV,BOSTON,MA. RP Bouros, D (reprint author), UNIV CRETE,SCH MED,DEPT THORAC MED,GR-71110 IRAKLION,GREECE. OI BOUROS, DEMOSTHENES/0000-0002-0685-0765 NR 10 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD SEP-OCT PY 1996 VL 53 IS 5 BP 360 EP 363 PG 4 WC Oncology SC Oncology GA VF149 UT WOS:A1996VF14900003 PM 8784468 ER PT J AU Simon, AL PavanLangston, D AF Simon, AL PavanLangston, D TI Long-term oral acyclovir therapy - Effect on recurrent infectious herpes simplex keratitis in patients with and without grafts SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-of-Ophthalmology Annual Meeting CY OCT-NOV -, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID PENETRATING KERATOPLASTY; GENITAL HERPES; VIRUS-INFECTION; ERYTHEMA MULTIFORME; CORNEAL ULCERATION; ANTIVIRAL THERAPY; NORMAL ADULTS; MANAGEMENT; SUPPRESSION; TRIAL AB Purpose: To evaluate the efficacy of long-term oral acyclovir therapy in reducing recurrences of dendritic or geographic herpes simplex keratitis (HSK), Methods: Thirteen patients with a history of frequently recurring HSK were followed before (mean, 27 months) and during long-term systemic acyclovir, and eight were followed after the acyclovir was discontinued, Results: Treatment ranged from 8.5 to 62 months (mean, 34 months), During treatment, the number of recurrences per month decreased from 0.15 to 0.03, and the average duration of relapses decreased from 12.6 to 7.8 days. Recurrences correlated with daily doses of oral acyclovir of 800 mg or less, intraocular surgery within 6 weeks of initiating treatment, and discontinuation of therapy against medical advice, Conclusion: The results of this small study appear to demonstrate the efficacy of long-term oral acyclovir in prophylaxis of recurrent epithelial herpes simplex infection: therapeutic doses of oral acyclovir reduce both the rate and duration of recurrences of infectious herpetic keratitis. A multicenter, double-masked, placebo-controlled study is indicated. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02114. NR 30 TC 33 Z9 36 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 SEP PY 1996 VL 103 IS 9 BP 1399 EP 1404 PG 6 WC Ophthalmology SC Ophthalmology GA VK317 UT WOS:A1996VK31700016 PM 8841297 ER PT J AU Power, WJ Saidman, SL Zhang, DS Vamvakas, EC MerayoLloves, JM Kaufman, AH Foster, CS AF Power, WJ Saidman, SL Zhang, DS Vamvakas, EC MerayoLloves, JM Kaufman, AH Foster, CS TI HLA typing in patients with ocular manifestations of Stevens-Johnson syndrome SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-of-Ophthalmology Annual Meeting CY OCT-NOV -, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID TOXIC EPIDERMAL NECROLYSIS; ERYTHEMA MULTIFORME; IMMUNE-COMPLEXES; DNA; IMMUNOFLUORESCENCE; SUSCEPTIBILITY; HYBRIDIZATION; POLYMERASE; DISEASE AB Background: Stevens-Johnson syndrome (SJS) is an acute, self-limited, inflammatory disorder of the skin and mucous membranes. With ocular involvement, SJS has been associated with the class I human leukocyte antigen (HLA)-Bw44, This study examined HL4 class II associations in patients with SJS with ocular involvement to help identify possible molecular genetic mechanisms underlying disease susceptibility/resistance. Methods: Twenty-three white patients with ocular complications secondary to SJS had HL4 class II typing performed using polymerase chain reaction-based molecular techniques. Genotype frequency was compared with results obtained from 175 control subjects, Results: HLA-DQB1*0601 was present in four (17%) patients with SJS and in five (3%) control subjects (P < 0.05; relative risk = 7.2). There was no association with HLA-DQB1*0301, which previously has been been strongly associated with recurrent erythema multiforme. None of the class II antigens tested appeared to offer a protective effect against the development of disease. Conclusion: HLA-DQB1*0601 was found in a significantly disproportionate number of white patients with SJS and ocular complications. The presence of this allele may confer an increased risk for the development of SJS with ocular complications and provides further evidence for an underlying immunogenetic susceptibility to the development of this disease. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT IMMUNOL & UVEITIS,BOSTON,MA 02146. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV CINCINNATI,DEPT OPHTHALMOL,CINCINNATI,OH 45221. NR 23 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD SEP PY 1996 VL 103 IS 9 BP 1406 EP 1409 PG 4 WC Ophthalmology SC Ophthalmology GA VK317 UT WOS:A1996VK31700018 PM 8841298 ER PT J AU Chandler, HP AF Chandler, HP TI Management of the bone-deficient knee - Revision total knee arthroplasty structural bone grafting: When and how SO ORTHOPEDICS LA English DT Article; Proceedings Paper CT 11th Annual Current Concepts in Joint Replacement Meeting CY DEC, 1995 CL ORLANDO, FL RP Chandler, HP (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WANG AMBULATORY CARE CTR,15 PARKMAN ST,LEVEL 5,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD SEP PY 1996 VL 19 IS 9 BP 797 EP 799 PG 3 WC Orthopedics SC Orthopedics GA VJ099 UT WOS:A1996VJ09900022 PM 8887426 ER PT J AU Davar, G Shalish, C Blumenfeld, A Breakefield, XO AF Davar, G Shalish, C Blumenfeld, A Breakefield, XO TI Exclusion of p75(NGFR) and other candidate genes in a family with hereditary sensory neuropathy Type II SO PAIN LA English DT Article DE pain; congenital sensory neuropathy; nerve growth factor ID NERVE GROWTH-FACTOR; RECEPTOR GENE; TARGETED DISRUPTION; NGF RECEPTOR; NEURONS; DYSAUTONOMIA; SYSTEM; AFFERENTS; GANGLION; LEADS AB Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75(NGFR), suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder. In this study candidate genes were evaluated by their inheritance pattern in two sisters affected with HSN II, their unaffected sister and mother in a consanguineous family. The segregation of polymorphic alleles at and around loci for p75(NGFR), TRKA, TRKB, BDNF, and familial dysautonomia (another hereditary sensory neuropathy having features in common with HSN II) virtually excluded these genes as the cause of HSN II in this family. Further evaluation of loci for other neurotrophic factors and their receptors, which will be possible when mapping information on their loci becomes available, may permit the identification of the gene responsible for HSN II. C1 MASSACHUSETTS GEN HOSP,MOL GENET UNIT,NEUROL SERV,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NINDS NIH HHS [1KO8NS01497, NS24279] NR 24 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 1996 VL 67 IS 1 BP 135 EP 139 DI 10.1016/0304-3959(96)03113-2 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA VL901 UT WOS:A1996VL90100018 PM 8895241 ER PT J AU Erickson, LC Cocalis, MW George, L AF Erickson, LC Cocalis, MW George, L TI Partial anomalous left pulmonary artery: New evidence on the development of the pulmonary artery sling SO PEDIATRIC CARDIOLOGY LA English DT Article DE pulmonary artery sling; congenital heart disease; vascular anomalies; embryology AB Clinical and angiographic data of a child with a unique form of partial anomalous left pulmonary artery are reported. Because the anomalous pulmonary artery does not run posterior to the trachea, this malformation is not associated with airway obstruction, as are all other forms of anomalous left pulmonary artery described to date. This case strengthens our understanding of the development of the pulmonary artery sling. C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,PEDIAT CARDIOL UNIT,BOSTON,MA 02114. USN,MED CTR,DIV PEDIAT CARDIOL,DEPT PEDIAT,SAN DIEGO,CA 92134. USN,MED CTR,DIV PEDIAT CARDIOL,DEPT CLIN INVEST,SAN DIEGO,CA 92134. CHILDRENS HOSP & HLTH CTR,DIV CARDIOL,SAN DIEGO,CA 92120. NR 5 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0172-0643 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD SEP-OCT PY 1996 VL 17 IS 5 BP 319 EP 321 DI 10.1007/s002469900070 PG 3 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA UY755 UT WOS:A1996UY75500007 PM 8660448 ER PT J AU Chen, HM Torchilin, V Langer, R AF Chen, HM Torchilin, V Langer, R TI Lectin-bearing polymerized liposomes as potential oral vaccine carriers SO PHARMACEUTICAL RESEARCH LA English DT Article DE lectin; polymerized liposomes; Peyer's patches; surface modification; targeted delivery ID M-CELLS; PROTEINS; SYSTEM AB Purpose. The potential of using lectin-modified polymerized liposomes as Peyer's patch targeted oral delivery vehicles was examined. Methods, Two types of lectins, Ulex Europaeus Agglutinin I (UEA I) and Wheat Germ Agglutinin (WGA), were modified with a hydrophobic anchor N-glutaryl-phosphotidylethanolamine (NGPE). The modified lectins were incorporated into liposome bilayers and the liposomes were subsequently stabilized through polymerization. The presence of the lectins on the liposome surfaces was first confirmed with X-ray photoelectron spectroscopy. Surface-immobilized lectins were then shown to retain their carbohydrate binding activities as well as specificities based on an in vitro aggregation assay. Finally, delivery efficiencies of lectin-bearing liposomes were determined in mice. Results. About 10.5% UEA I liposomes and 5.8% WGA liposomes were taken up from the gastrointestinal tract. These numbers are significantly higher than the 3.2% observed in the case of lectin-free liposomes. At the same time, UEA I liposomes exhibited the most effective Peyer's patch targeting among the three, which directly correlated with the highest delivery efficiency observed. Conclusions, This establishes that lectin modification of liposomes can promote binding to Peyer's patches, which will give improved efficiency for Peyer's patch targeted delivery. All these point to the potential for these lectin-modified liposomes as novel vehicles for oral vaccination. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,CHARLESTOWN,MA. FU NICHD NIH HHS [HD 29129]; NIGMS NIH HHS [GM 26698] NR 15 TC 138 Z9 146 U1 1 U2 8 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD SEP PY 1996 VL 13 IS 9 BP 1378 EP 1383 DI 10.1023/A:1016030202104 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA VL498 UT WOS:A1996VL49800019 PM 8893278 ER PT J AU Coyne, E Walenga, JM Outschoorn, AS Feyns, LV Messmore, HL Farid, S Hoppensteadt, D Koza, MJ Wehrmacher, WH Fareed, J Bermes, EW AF Coyne, E Walenga, JM Outschoorn, AS Feyns, LV Messmore, HL Farid, S Hoppensteadt, D Koza, MJ Wehrmacher, WH Fareed, J Bermes, EW TI The USP thromboplastin reference standard - Recombinant human type SO PHARMACOPEIAL FORUM LA English DT Article ID INTERNATIONAL NORMALIZED RATIO; ORAL ANTICOAGULANT CONTROL; SENSITIVITY INDEX ISI; PROTHROMBIN TIME; CALIBRATION; RELIABILITY; MULTICENTER C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. RP Coyne, E (reprint author), LOYOLA UNIV,MED CTR,CHICAGO,IL 60611, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD SEP-OCT PY 1996 VL 22 IS 5 BP 2956 EP 2960 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA VK907 UT WOS:A1996VK90700010 ER PT J AU Wood, PD Mutus, B Redmond, RW AF Wood, PD Mutus, B Redmond, RW TI The mechanism of photochemical release of nitric oxide from S-nitrosoglutathione SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SUBSTITUTED BENZENETHIYL RADICALS; THIYL RADICALS; PULSE-RADIOLYSIS; AQUEOUS-SOLUTION; FLASH-PHOTOLYSIS; MOLECULAR-OXYGEN; SINGLET-OXYGEN; ADDITION RATES; VINYL MONOMERS; SERUM-ALBUMIN AB Laser flash photolysis of S-nitroso complexes of glutathione (GSNO) and bovine serum albumin (BSANO) via excitation at 355 nn has been used to investigate the photogeneration of nitric oxide (NO) and subsequent radical reactions, In the case of GSNO, liberation of NO was confirmed by its oxidation of oxyhemoglobin to met hemoglobin, Initial NO release is via homolytic cleavage of the S-N bond to produce the glutathione thiyl radical, GS; which can subsequently, react with (a) ground-state GSNO (k = 1.7 x 10(9) M(-1)s(-1)) to yield additional NO and oxidized glutathione, GSSG; and (b) oxygen (k = 3.0 x 10(9) M(-1)s(-1)) to give the glutathione peroxy radical, GSOO; which subsequently reacts with ground-state GSNO (k = 3.8 x 10(8) M(-1)s(-1)), also producing additional NO and GSSG, The relative concentrations of oxygen and GSNO in the system determine the major pathway for removal of GS(.). These secondary reactions occur at such high rates that they preclude radical recombination under low-intensity irradiation conditions, The quantum yield of overall loss of GSNO thus varies with bath GSNO and oxygen concentrations; a value of 0.66 was determined for an aerated solution of GSNO (0.86 mM), In the case of GSNO, therefore, generation of NO is not due solely to homolysis of the S-N bond; secondary reactions of the radicals formed lead to further NO liberation, In rationalizing the known phototoxicity of GSNO, possible contributions from thiyl and thiyl-derived radicals should be considered, In contrast to GSNO, direct excitation of BSANO (containing one bound NO group per molecule) led to photodecomposition with a quantum yield of 0.09 but no evidence was obtained for liberation of NO into the bulk medium. C1 UNIV WINDSOR, DEPT CHEM & BIOCHEM, WINDSOR, ON N9B 3P4, CANADA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, WELLMAN LABS PHOTOMED,DEPT DERMATOL, BOSTON, MA USA. NR 45 TC 62 Z9 62 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP PY 1996 VL 64 IS 3 BP 518 EP 524 DI 10.1111/j.1751-1097.1996.tb03099.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VG533 UT WOS:A1996VG53300018 ER PT J AU Prokhorov, AV Emmons, KM Pallonen, UE Tsoh, JY AF Prokhorov, AV Emmons, KM Pallonen, UE Tsoh, JY TI Respiratory response to cigarette smoking among adolescent smokers: A pilot study SO PREVENTIVE MEDICINE LA English DT Article DE adolescents; smoking; respiratory symptoms; lung function ID PULMONARY-FUNCTION; LUNG-FUNCTION; CESSATION; SYMPTOMS; STUDENTS; TOBACCO; PEOPLE; WOMEN; RISK AB Background. Because cigarette smoking affects the respiratory system earlier than many other systems of the human body, an attempt was made to identify objective and subjective respiratory problems among adolescent smokers. Methods. Two studies based on a pulmonary function test (PFT), respiratory symptom assessment, and other smoking-related variables were undertaken. Study 1 involved cigarette smokers (N = 18, 22% males, mean age 18.7 years) from a freshman college class who participated in an acute smoking experiment that involved performing a PFT before and after smoking a single cigarette. Study 2 was performed on a combined group of vocational-technical high school students and; freshman college students (N = 44, 48% males, mean age 17.8 years) where PFT parameters, respiratory symptoms, and smoking-related health vulnerability were assessed among smokers vs nonsmokers. Results. In Study 1, the average reduction across PFT parameters was 4.4% and the mean estimated lung age increased from 27.15 to 29.84 years. In Study 2, a consistent trend toward reduction of PFT values among smokers vs nonsmokers was observed; the mean forced expiratory volume in 1 sec/forced vital capacity ratio (90.51% vs 94.59%), peak expiratory flow rate (80.32% vs 92.06%), and how rate of 50% of forced vital capacity (88.39% vs 102.81%) differed significantly. Significant differences in respiratory symptoms were also observed among smokers vs nonsmokers. Conclusions. The beginning of respiratory health disorders can be identified among adolescent smokers, These findings might provide important clues on how to improve outcomes from health care provider-based adolescent smoking cessation counseling. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV RHODE ISL,CANC PREVENT RES CTR,KINGSTON,RI 02881. RP Prokhorov, AV (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BEHAV SCI,1515 HOLCOMBE BLVD,BOX 243,HOUSTON,TX 77030, USA. FU NCI NIH HHS [P01 CA50087]; NHLBI NIH HHS [1RO1 HL48190] NR 27 TC 25 Z9 25 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 0091-7435 J9 PREV MED JI Prev. Med. PD SEP-OCT PY 1996 VL 25 IS 5 BP 633 EP 640 DI 10.1006/pmed.1996.0099 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VJ934 UT WOS:A1996VJ93400018 PM 8888333 ER PT J AU Weisman, AD AF Weisman, AD TI The physician in retirement: Transition and opportunity SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Editorial Material AB PHYSICIANS have been known to procrastinate and deny problems about retirement and the inevitability of aging beyond employability. The transition from what they have devoted their life to practicing, coupled with anxiety about just getting old and older than most people is enough to precipitate sadness, if not sober bereavement. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BOSTON PSYCHOANALYT SOC & INST INC,BOSTON,MA 02172. NR 12 TC 6 Z9 6 U1 1 U2 2 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 FAL PY 1996 VL 59 IS 3 BP 298 EP 306 PG 9 WC Psychiatry SC Psychiatry GA VP600 UT WOS:A1996VP60000006 PM 8912947 ER PT J AU Patenaude, AF Schneider, KA Kieffer, SA Calzone, KA Stopfer, JE Basili, LA Weber, BL Garber, JE AF Patenaude, AF Schneider, KA Kieffer, SA Calzone, KA Stopfer, JE Basili, LA Weber, BL Garber, JE TI Acceptance of invitations for p53 and BRCA1 predisposition testing: Factors influencing potential utilization of cancer genetic testing SO PSYCHO-ONCOLOGY LA English DT Article ID HUNTINGTON DISEASE; BREAST-CANCER; FAMILY HISTORY; ATTITUDES; RISK; SUSCEPTIBILITY; MUTATIONS; RELATIVES; WOMEN AB Data on uptake of two cancer predisposition testing programs is presented as the basis for discussion of factors contributing to the acceptance and refusal of genetic testing. Eighty percent (n = 29) of the 36 members of 2 BRCA1 families invited for BRCA1 predisposition testing and counseling accepted, while only 39% (n = 22) of the 57 Li-Fraumeni syndrome family members invited for p53 predisposition testing and counseling enrolled and 14% (n = 8) postponed enrollment. Factors that may influence utilization of cancer genetic testing programs include programmatic demands, nature and immediacy of cancer risk, demographic factors, perceived lethality of the cancers involved, clarity of surveillance recommendations and perceived efficacy of screening, ego-strength, and family experience with cancer. Further research is needed to determine the relative weight of these factors and to define how accepters and decliners of genetic cancer predisposition testing differ. One implication of the hypothesis that individuals seeking testing are psychologically different than those who decline is that more severe psychiatric sequelae of testing might be expected if individuals are tested who have not themselves freely chosen testing. Such subjects might in the future include children whose parents decide about testing or adults tested as a prerequisite to being employed or insured. Further research on decliners and continued psychological evaluation of the impact of cancer predisposition testing is recommended. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. RP Patenaude, AF (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 38 TC 26 Z9 26 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD SEP PY 1996 VL 5 IS 3 BP 241 EP 250 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA VJ219 UT WOS:A1996VJ21900003 ER PT J AU Seeman, T McAvay, G Merrill, S Albert, M Rodin, J AF Seeman, T McAvay, G Merrill, S Albert, M Rodin, J TI Self-efficacy beliefs and change in cognitive performance: MacArthur studies of successful aging SO PSYCHOLOGY AND AGING LA English DT Article ID COMPLEX DECISION-MAKING; ALZHEIMERS-DISEASE; ELDERLY POPULATION; MEMORY; COMMUNITY; ADULTS; QUESTIONNAIRE; INTELLIGENCE; DETERMINANTS; ABILITY AB Data from a cohort of relatively high functioning, older men and women were used to test the hypothesis that stronger self-efficacy beliefs predict better maintenance of cognitive performance. Structural equation modeling revealed that stronger baseline instrumental efficacy beliefs predicted better verbal memory performance at follow-up among men but not among women, controlling for baseline verbal memory score and sociodemographic and health status characteristics. For both men and women there were no significant associations between either type of self-efficacy beliefs and measures of nonverbal memory, abstraction, or spatial ability. Consistent with previous research showing relationships between baseline cognitive performance and change in self-efficacy beliefs, better abstraction ability was also predictive of increases in instrumental efficacy beliefs among the men. C1 YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. UNIV MICHIGAN,GERONTOL RES CTR,ANN ARBOR,MI 48109. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. HARVARD UNIV,DEPT PSYCHIAT GERONTOL,CAMBRIDGE,MA 02138. UNIV PENN,DEPT PSYCHOL,PHILADELPHIA,PA 19104. FU NIA NIH HHS [AG00586] NR 60 TC 57 Z9 58 U1 5 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 1996 VL 11 IS 3 BP 538 EP 551 DI 10.1037/0882-7974.11.3.538 PG 14 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA VK727 UT WOS:A1996VK72700014 PM 8893321 ER PT J AU Lish, JD Zimmerman, M Farber, NJ Lush, DT Kuzma, MA Plescia, G AF Lish, JD Zimmerman, M Farber, NJ Lush, DT Kuzma, MA Plescia, G TI Suicide screening in a primary care setting at a veterans affairs medical center SO PSYCHOSOMATICS LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; MENTAL-HEALTH NETWORK; PANIC DISORDER; RISK-FACTORS; GENERAL-PRACTITIONERS; PSYCHIATRIC-DISORDERS; EXCESS MORTALITY; UNITED-STATES; SELF-REPORT; DEPRESSION AB Seven-hundred and three patients from a general medical outpatient clinic at a Veterans Affairs hospital completed the SCREENER, a brief self-report questionnaire that screens for psychiatric disorders. The authors found that 7.3% of the patients had suicidal ideation. The younger and white patients were at increased risk. The risk was increased twelvefold in those patients with subjectively fair or poor mental health, sevenfold in the patients with a history of mental health treatment, and fourfold in the patients with fair or poor perceived physical health. When major depression was controlled for, anxiety and substance abuse disorders continued to show an association with suicidal ideation, The suicidal patients made more visits to their primary care physician. Screening patients for anxiety disorders and drug abuse, as well as depression, is a better approach for identifying suicidal ideation in primary care settings than screening for depression alone and may help prevent suicide and suicide attempts. C1 BROWN UNIV,SCH MED,DEPT PSYCHIAT,PROVIDENCE,RI 02912. MED COLL PENN & HAHNEMANN UNIV,DIV GEN MED,PHILADELPHIA,PA. PHILADELPHIA VET AFFAIRS MED CTR,DEPT INTERNAL MED,PHILADELPHIA,PA. RP Lish, JD (reprint author), MED COLL PENN & HAHNEMANN UNIV,EASTERN PENN PSYCHIAT INST,CLIN NEUROSCI RES UNIT,DEPT PSYCHIAT,PHILADELPHIA,PA 19129, USA. NR 73 TC 44 Z9 44 U1 5 U2 8 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1996 VL 37 IS 5 BP 413 EP 424 PG 12 WC Psychiatry; Psychology SC Psychiatry; Psychology GA VE740 UT WOS:A1996VE74000002 PM 8824120 ER PT J AU Greenberg, DB AF Greenberg, DB TI Psychological approaches to pain management: A practitioner's handbook - Gatchel,RJ, Turk,DC SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 1996 VL 37 IS 5 BP 486 EP 487 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA VE740 UT WOS:A1996VE74000012 ER PT J AU Bennett, GL Bromley, B Lieberman, E Benacerraf, BR AF Bennett, GL Bromley, B Lieberman, E Benacerraf, BR TI Subchorionic hemorrhage in first-trimester pregnancies: Prediction of pregnancy outcome with sonography SO RADIOLOGY LA English DT Article DE chorion; fetus; pregnancy, complications; pregnancy ID THREATENED-ABORTION; INTRAUTERINE HEMATOMA; PLACENTAL ABRUPTION; 1ST TRIMESTER; ULTRASOUND; DIAGNOSIS AB PURPOSE: To determine the effects of subchorionic hematoma size, gestational age, and maternal age on pregnancy outcome in patients with vaginal bleeding in the first trimester of pregnancy. MATERIALS AND METHODS: A retrospective review was performed with ultrasound images obtained in 516 patients with vaginal bleeding, a live fetus, and a subchorionic hematoma in the first trimester. Hematoma size was graded according to the percentage of the chorionic sac circumference elevated by the hematoma. Patients were also classified according to gestational age and maternal age. Logistic regression analysis was used to determine the effect of each variable on pregnancy outcome. RESULTS: The overall spontaneous abortion rate was 9.3% (48 of 516 patients). The rate nearly doubled when the separation was large (18.8%) compared with small and moderate hematomas (7.7% and 9.2%, respectively). A large separation was found to be associated with an almost threefold increase in risk of spontaneous abortion. The spontaneous abortion rate was approximately twice as high for women aged 35 years or older versus younger women (13.8% and 7.3%, respectively) and for women with bleeding at 8 weeks gestation or less compared with those with bleeding at greater than 8 weeks gestation (13.7% vs 5.9%). CONCLUSION: For women with a subchorionic hematoma that is sonographically identified, fetal outcome is dependent on size of the hematoma, maternal age, and gestational age. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NR 15 TC 63 Z9 69 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1996 VL 200 IS 3 BP 803 EP 806 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD062 UT WOS:A1996VD06200039 PM 8756935 ER PT J AU MagierowskaJung, M Cefai, D Marrakchi, H Chieze, F Agut, H Huraux, JM Seman, M AF MagierowskaJung, M Cefai, D Marrakchi, H Chieze, F Agut, H Huraux, JM Seman, M TI In vitro determination of antiviral activity of MSS209, a new amphotericin B derivative, against primary isolates of HIV1 SO RESEARCH IN VIROLOGY LA English DT Article DE HIV1, amphotericin B; derivative MS8209, antiviral activity, primary isolates ID MS-8209; ZIDOVUDINE AB MS8209. an amphotericin B derivative, was previously reported to be an inhibitor of HIV1 replication in vitro. In the present study, we determined the 50 and 90% in vitro inhibitory concentrations of MS8209 for 9 HIV1 isolates including both zidovudine-sensitive and zidovudine-resistant isolates and the reference strain Lai, using the peripheral blood mononuclear cell (PBMC) assay. We also evaluated the sensitivity of HIV1 replication to MS8209 during primary isolation from PBMCs. An inhibitory effect of MS8209 in PBMC infection was observed either when the drug was only present during the adsorption step or when the drug was initially absent but maintained throughout the culture period; the combination of these two approaches provided the highest inhibition rate. These results indicate that MS8209 can inhibit the replication of HIV1 isolates in PBMCs and suggest that it mainly acts by blocking the virus entry into cells. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,IMMUNOL LAB,BOSTON,MA 02115. UNIV PARIS 07,LAB IMMUNODIFFERENCIAT,F-75251 PARIS 05,FRANCE. HOP LA PITIE SALPETRIERE,INSERM U313,DEPT MALAD INFECT PARASITAIRES TROP & SANTE PUBL,F-75651 PARIS 13,FRANCE. RP MagierowskaJung, M (reprint author), HOP LA PITIE SALPETRIERE,CERVI,CNRS EP 57,VIROL LAB,83 BD HOP,F-75651 PARIS 13,FRANCE. NR 7 TC 5 Z9 5 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD SEP-OCT PY 1996 VL 147 IS 5 BP 313 EP 318 DI 10.1016/0923-2516(96)82289-8 PG 6 WC Virology SC Virology GA VE946 UT WOS:A1996VE94600006 PM 8881000 ER PT J AU Kraut, JA Madias, NE AF Kraut, JA Madias, NE TI Treatment of metabolic acidosis in end-stage renal failure: Is dialysis with bicarbonate sufficient? SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID HEMODIALYSIS; BASE C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV NEPHROL,MED & RES SERV,LOS ANGELES,CA 90073. NR 16 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD SEP-OCT PY 1996 VL 9 IS 5 BP 378 EP 380 DI 10.1111/j.1525-139X.1996.tb00869.x PG 3 WC Urology & Nephrology SC Urology & Nephrology GA VL364 UT WOS:A1996VL36400003 ER PT J AU Mueller, PR AF Mueller, PR TI Untitled SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP Mueller, PR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1996 VL 13 IS 3 BP 195 EP 195 DI 10.1055/s-2008-1057903 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WG203 UT WOS:A1996WG20300001 ER PT J AU Mueller, PR AF Mueller, PR TI Biliary interventions: A historical perspective SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article ID MALIGNANT OBSTRUCTIVE-JAUNDICE; ENDOPROSTHESIS; CATHETER; DRAINAGE; CHOLANGIOGRAPHY; COMPLICATIONS; DISSOLUTION; DILATATION; STRICTURES; INTUBATION RP Mueller, PR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 43 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD SEP PY 1996 VL 13 IS 3 BP 197 EP 200 DI 10.1055/s-2008-1057904 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WG203 UT WOS:A1996WG20300002 ER PT J AU Singaram, C AF Singaram, C TI Neuropathology of the gut SO SEMINARS IN NEUROLOGY LA English DT Article ID NEURONAL INTESTINAL DYSPLASIA; GENE-RELATED PEPTIDE; PIG SMALL-INTESTINE; ENTERIC NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; CELL LUNG-CARCINOMA; B RECEPTOR GENE; HIRSCHSPRUNGS-DISEASE; VISCERAL NEUROPATHY; INTERSTITIAL-CELLS C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,DIV GASTROENTEROL,MADISON,WI. RP Singaram, C (reprint author), UNIV WISCONSIN,DIV GASTROENTEROL,H6-516 CSC,600 HIGHLAND AVE,MADISON,WI 53793, USA. FU PHS HHS [KOF-02470] NR 73 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD SEP PY 1996 VL 16 IS 3 BP 227 EP 234 DI 10.1055/s-2008-1040979 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA WT276 UT WOS:A1996WT27600005 PM 9085472 ER PT J AU Peabody, JW AF Peabody, JW TI Economic reform and health sector policy: Lessons from structural adjustment programs SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT XIVth International Conference on the Social Sciences and Medicine CY SEP 02-06, 1996 CL PEEBLES, SCOTLAND DE health policy; developing countries; health economics; structural adjustment; health outcomes; quality of care ID PAPUA-NEW-GUINEA; SERVICES; AFRICA; CARE; RECESSION; CRISIS; CHILD AB From a purely economic perspective, structural adjustment programs (SAPs) and economic reform policies are viewed as short-term austerities that lead to long-term growth and development. These intertemporal trade-offs, however, are not always acceptable in health. Unique biologic events such as intrauterine development and neural development cannot be postponed even for a short period. Health policymakers need to understand the expected and unexpected impacts of economic reform on health outcomes in individuals and on the population. The interactions are complex, involve multiple sectors, and can be better understood by looking at the experience of developing countries over almost fifteen years of SAP experience. Health care budgets may be vulnerable to reduced government spending, quality of care deteriorates, nutrition will suffer more likely in urban areas, and cost-effective preventive programs may stop if labor and capital are not properly matched. Health outcomes overall do not appear to suffer but a more detailed look, with better data, shows that the incidence of preventable diseases rises and irreversible deterioration in health status does occur within countries. To prevent this from happening in the future, health policymakers need to take a multidisciplinary focus to first understand the effects of economic reform and then to plan a coordinated response. Better data, alternative financing, and strong political leadership are also important lessons. C1 RAND CORP, SANTA MONICA, CA 90407 USA. RP Peabody, JW (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, DIV GEN INTERNAL MED, 11301 WILSHIRE BLVD, LOS ANGELES, CA 90073 USA. NR 58 TC 25 Z9 27 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD SEP PY 1996 VL 43 IS 5 BP 823 EP 835 DI 10.1016/0277-9536(96)00127-X PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA VD078 UT WOS:A1996VD07800025 PM 8870147 ER PT J AU Berkman, B AF Berkman, B TI The emerging health care world: Implications for social work practice and education SO SOCIAL WORK LA English DT Article DE chronic disease; health care; managed care; primary care ID CASE-MANAGEMENT; DEPRESSION; ENVIRONMENT; PHYSICIANS; PARADIGM AB Dramatic changes in patient cave delivery have been stimulated by advances in technology and Mew approaches to the financing of health cave. Traditionally, the American health cave system has been based on a paradigm of unpredictable acute simple disease, a model that has become inappropriate as increasing numbers of patients ave presenting with multiple, chronic health problems. Because chronic illnesses ave determined by many factors, such as an individual's social, psychological, and physical environment; genetic makeup; and health cave accessibility factors, the hospital, once the dominant organization in health cave, must become part of a primary cave network of community-oriented delivery systems focused on chronic disease management. In this model, the social worker treats the patient throughout the continuum of cave. Therefore, dynamic training that addresses the changing health cave environment will be needed. In addition, social workers will need to work as members of a team in addressing the needs of patients for preventive, curative, and rehabilitative services. C1 COLUMBIA UNIV,SCH SOCIAL WORK,NEW YORK,NY. RP Berkman, B (reprint author), MASSACHUSETTS GEN HOSP,DEPT SOCIAL SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 59 TC 80 Z9 81 U1 1 U2 5 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 SN 0037-8046 J9 SOC WORK JI Soc. Work PD SEP PY 1996 VL 41 IS 5 BP 541 EP 551 PG 11 WC Social Work SC Social Work GA VM174 UT WOS:A1996VM17400010 PM 8840830 ER PT J AU Ferrara, JLM Cooke, KR Pan, LY Krenger, W AF Ferrara, JLM Cooke, KR Pan, LY Krenger, W TI The immunopathophysiology of acute graft-versus-host disease SO STEM CELLS LA English DT Review DE graft-versus-host-disease; cytokines; bone marrow transplantation; Th1/Th2 cells; review ID BONE-MARROW TRANSPLANTATION; TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; BLOOD STEM-CELLS; MINOR HISTOCOMPATIBILITY ANTIGENS; RECEPTOR MONOCLONAL-ANTIBODY; HLA-IDENTICAL SIBLINGS; ACUTE MYELOID-LEUKEMIA; CD8+ T-CELLS; PERIPHERAL-BLOOD AB The major complication after allogeneic bone marrow transplantation (BMT) is the development of graft-versus-host-disease (GVHD). This disease is initiated during the conditioning of the recipient, when host tissues are damaged, During the afferent phase of the disease, alloreactive donor T cells recognize foreign major and minor histocompatibility antigens of host tissues, The efferent phase includes activation of inflammatory effector cells as well as the secretion of cytopathic molecules which induce pathology in skin, gastrointestinal tract, liver, lung, and the immune system, Substantial experimental and clinical evidence now indicates a central role of cytokines in the immunopathophysiology of acute GVHD, which forms the basis of this review, The balance between cytokines released by T helper 1 (Th1) cells (interleukin 2, interferon-gamma) or by T helper 2 (Th2) cells (interleukin 4, interleukin 10) after allogeneic BRIT is hypothesized to govern the extent of the systemic inflammatory response, Because Th2 cytokines can inhibit the production of proinflammatory cytokines such as interleukin I and tumor necrosis factor-alpha, a Th1-->Th2 shift in the initial response of donor T cells may interrupt the cytokine cascade and thus offer a new approach to the prevention and treatment of acute GVHD, Successful interventions to modify the response of donor T cells may obviate the need for T cell depletion and thereby avoid the increased risk of relapse of malignancy and impairment of donor cell engraftment. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. FU NCI NIH HHS [CA 39592]; NHLBI NIH HHS [HL03565, HL55162] NR 139 TC 133 Z9 136 U1 0 U2 4 PU ALPHAMED PRESS PI DAYTON PA 4100 S KETTERING BLVD, DAYTON, OH 45439-2092 SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 1996 VL 14 IS 5 BP 473 EP 489 PG 17 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA VJ494 UT WOS:A1996VJ49400001 PM 8888489 ER PT J AU Scott, P Barsan, W Frederiksen, S Kronick, S Zink, BJ Domeier, RM Mitchiner, JC Judge, FP Levy, RJ Alexiou, A Reincke, H Segall, JD Walters, B Swor, R Gilroy, J Goetting, M Jackson, R Richardson, D Cisek, J Randall, J Schecter, S Wilkinson, K Walters, BL Adams, R Carl, E Nichols, F Hess, D Boop, B Earley, C Smith, DR Kaplan, P Johnson, C Morrow, C Frohman, E Porter, N Flanigan, K Morganstern, L Holland, N Stein, A Aldrich, E Oyler, G Faught, E Mitchell, V Liu, H Thomas, F Wenzel, D Dajani, BM Pan, JL Yapundich, R Futatsugi, Y Geerlings, S Moskowitz, T Nicholas, A Brockington, J Collins, A Bailey, JM Tseng, A Koroshetz, WJ Can, U Felix, A Cudkowticz, M Buonanno, F Schwamm, L Elkind, M Kistler, JP Finkelstein, S Cha, J Murphy, S Blumenfeld, H LopezBresnahan, M Can, U Goslin, K Cramer, S Suwanwela, N Homer, D Carpenter, J Wityk, R Michel, N Grufferman, S Litt, B Weiss, H Guyot, A Peterson, P Tvardek, L Schmidt, J Deshpande, A Freij, W Gandhi, B Minhas, F Shah, J Zahka, C Penn, A Sherman, J Li, YL Elleker, MG Stenerson, P Brooke, H AlJumah, M AlAyafy, H Pokroy, R Hoppe, B Pascuzzi, R Farlow, M Rightmyer, D Bales, M Caress, J Pettigrew, C Waugh, C Rockich, A Fallis, R Tikhtman, A Starkman, S Schubert, G Dobkin, B Martin, N Saver, J Hanson, S Weaver, A Porth, K Magana, R Davenport, J Taylor, F Freking, D Heros, DO Schnek, E Alter, M Ribeiro, R Lloyd, M Scheiner, S Puff, A Boyle, S Gupta, N White, K Carney, S Moulton, M LaCapra, S Hassard, D Rizwan, S Shah, A Newmark, A Gupta, A Cone, D Khan, I Cohen, B Bopari, R OConnell, J Hussian, A Patil, K Shojari, J Ribeiro, R Bell, R Gzech, D Mazer, T Grothusen, J Reyes, P Arastu, J Strassburger, T Thomas, C Wolfe, R Fang, J Scavina, M Wolfe, W Zeidwerg, D Chavin, J Shachar, O Sandler, L McGarren, D Jamieson, DG Gonnella, C Bosley, TM Pollack, DA Andrefsky, JC Hariharan, S Chang, A Lamonte, MP Champellone, J Hooker, HC Fellus, J Sosa, V Raaf, S Friedman, M Burch, G Atkins, D Foley, C Bivins, D Elias, W Nolan, D Sisk, M Wilson, J Lloyd, A Stephens, G Surrusco, R Lothes, C Humphries, W Pastemak, S Donato, M Manetta, E Mitchell, J Briggs, A Rorrer, M Offermann, P Grover, W Bolton, B Lyden, P Lewis, S Rapp, K Brody, M Rothrock, J Jackson, C Huott, P Kushida, C Liss, J Zweifer, R Caylor, L Phan, D Mahdavi, Z Tom, T Noack, H Forde, G Cameron, D Griesdale, B Makin, V Bozek, CB Sheppard, G Massey, S Zontine, D Crowe, N Gustin, K Capone, P Feasby, TE Robertson, C Rorick, M Winkelman, M Liskay, A Schmidley, J Cole, M AlJaberi, M Anagnos, A Anderson, M Bamford, C Frederickson, E Gordon, J Grosser, S Kori, A Kuntz, A Murad, M Nasreddine, W Pettee, A Riachi, N Schecht, H Stahl, J Soriano, J Sunshine, J Suarez, J Vandersluis, J AlLanham, Y Ramahi, A Shuaib, A Kadribasic, E Stewart, B Beaudry, M Boivin, D Lyons, G Dougal, RL Simsarian, JP McGarvey, M Grass, D Sigmund, L Kurtzke, R Eberly, L Lipps, D Fesenmeier, JT Viater, K Alonzo, R Cooper, W Scott, J Bustion, P Pappas, J Frazer, M Haley, EC Alves, W Kassell, NF Johnston, KC Ford, G Solenski, N Shreve, DL Wilkinson, SS Clements, S Cuccia, E Elder, L Keller, M Lackey, R Mimms, K Protzman, P Sparrow, L Lightfoot, A Lightfoot, AE Bocchicchio, BE Halley, P Polin, A Polin, R Hwang, LJ Wolf, MC Truskowski, LL Galbrieth, C Johnson, R Johnson, S Hill, C Wilson, B Bartley, A Ford, G Rumfelt, M Wingate, V Smith, M Childress, T Powers, WJ Walker, M Fleiss, JL Frankel, M Simon, RP Marler, J Adams, HP Brott, TG Choi, S Kurtzke, JF TOrner, JC Peters, GR Eckert, S Bryan, WJ Bologa, ML Legace, D Brennan, KM AF Scott, P Barsan, W Frederiksen, S Kronick, S Zink, BJ Domeier, RM Mitchiner, JC Judge, FP Levy, RJ Alexiou, A Reincke, H Segall, JD Walters, B Swor, R Gilroy, J Goetting, M Jackson, R Richardson, D Cisek, J Randall, J Schecter, S Wilkinson, K Walters, BL Adams, R Carl, E Nichols, F Hess, D Boop, B Earley, C Smith, DR Kaplan, P Johnson, C Morrow, C Frohman, E Porter, N Flanigan, K Morganstern, L Holland, N Stein, A Aldrich, E Oyler, G Faught, E Mitchell, V Liu, H Thomas, F Wenzel, D Dajani, BM Pan, JL Yapundich, R Futatsugi, Y Geerlings, S Moskowitz, T Nicholas, A Brockington, J Collins, A Bailey, JM Tseng, A Koroshetz, WJ Can, U Felix, A Cudkowticz, M Buonanno, F Schwamm, L Elkind, M Kistler, JP Finkelstein, S Cha, J Murphy, S Blumenfeld, H LopezBresnahan, M Can, U Goslin, K Cramer, S Suwanwela, N Homer, D Carpenter, J Wityk, R Michel, N Grufferman, S Litt, B Weiss, H Guyot, A Peterson, P Tvardek, L Schmidt, J Deshpande, A Freij, W Gandhi, B Minhas, F Shah, J Zahka, C Penn, A Sherman, J Li, YL Elleker, MG Stenerson, P Brooke, H AlJumah, M AlAyafy, H Pokroy, R Hoppe, B Pascuzzi, R Farlow, M Rightmyer, D Bales, M Caress, J Pettigrew, C Waugh, C Rockich, A Fallis, R Tikhtman, A Starkman, S Schubert, G Dobkin, B Martin, N Saver, J Hanson, S Weaver, A Porth, K Magana, R Davenport, J Taylor, F Freking, D Heros, DO Schnek, E Alter, M Ribeiro, R Lloyd, M Scheiner, S Puff, A Boyle, S Gupta, N White, K Carney, S Moulton, M LaCapra, S Hassard, D Rizwan, S Shah, A Newmark, A Gupta, A Cone, D Khan, I Cohen, B Bopari, R OConnell, J Hussian, A Patil, K Shojari, J Ribeiro, R Bell, R Gzech, D Mazer, T Grothusen, J Reyes, P Arastu, J Strassburger, T Thomas, C Wolfe, R Fang, J Scavina, M Wolfe, W Zeidwerg, D Chavin, J Shachar, O Sandler, L McGarren, D Jamieson, DG Gonnella, C Bosley, TM Pollack, DA Andrefsky, JC Hariharan, S Chang, A Lamonte, MP Champellone, J Hooker, HC Fellus, J Sosa, V Raaf, S Friedman, M Burch, G Atkins, D Foley, C Bivins, D Elias, W Nolan, D Sisk, M Wilson, J Lloyd, A Stephens, G Surrusco, R Lothes, C Humphries, W Pastemak, S Donato, M Manetta, E Mitchell, J Briggs, A Rorrer, M Offermann, P Grover, W Bolton, B Lyden, P Lewis, S Rapp, K Brody, M Rothrock, J Jackson, C Huott, P Kushida, C Liss, J Zweifer, R Caylor, L Phan, D Mahdavi, Z Tom, T Noack, H Forde, G Cameron, D Griesdale, B Makin, V Bozek, CB Sheppard, G Massey, S Zontine, D Crowe, N Gustin, K Capone, P Feasby, TE Robertson, C Rorick, M Winkelman, M Liskay, A Schmidley, J Cole, M AlJaberi, M Anagnos, A Anderson, M Bamford, C Frederickson, E Gordon, J Grosser, S Kori, A Kuntz, A Murad, M Nasreddine, W Pettee, A Riachi, N Schecht, H Stahl, J Soriano, J Sunshine, J Suarez, J Vandersluis, J AlLanham, Y Ramahi, A Shuaib, A Kadribasic, E Stewart, B Beaudry, M Boivin, D Lyons, G Dougal, RL Simsarian, JP McGarvey, M Grass, D Sigmund, L Kurtzke, R Eberly, L Lipps, D Fesenmeier, JT Viater, K Alonzo, R Cooper, W Scott, J Bustion, P Pappas, J Frazer, M Haley, EC Alves, W Kassell, NF Johnston, KC Ford, G Solenski, N Shreve, DL Wilkinson, SS Clements, S Cuccia, E Elder, L Keller, M Lackey, R Mimms, K Protzman, P Sparrow, L Lightfoot, A Lightfoot, AE Bocchicchio, BE Halley, P Polin, A Polin, R Hwang, LJ Wolf, MC Truskowski, LL Galbrieth, C Johnson, R Johnson, S Hill, C Wilson, B Bartley, A Ford, G Rumfelt, M Wingate, V Smith, M Childress, T Powers, WJ Walker, M Fleiss, JL Frankel, M Simon, RP Marler, J Adams, HP Brott, TG Choi, S Kurtzke, JF TOrner, JC Peters, GR Eckert, S Bryan, WJ Bologa, ML Legace, D Brennan, KM TI A randomized trial of tirilazad mesylate in patients with acute stroke (RANTTAS) SO STROKE LA English DT Article DE cerebral ischemia; lipid peroxidation; neuroprotection; stroke, acute ID NERVOUS-SYSTEM TRAUMA; ACUTE CEREBRAL INFARCTION; FREE-RADICAL SCAVENGER; LIPID-PEROXIDATION; CLINICAL-TRIALS; PHARMACOKINETICS; TOLERABILITY; ISCHEMIA AB Background and Purpose Tirilazad mesylate, a nonglucocorticoid 21-aminosteroid lipid peroxidation inhibitor, has shown promise as a neuroprotectant in experimental models of focal cerebral ischemia. Methods To test whether early treatment with tirilazad, 6 mg/kg per day for 3 days, would improve functional outcome after acute human stroke, 27 North American centers conducted a prospective, randomized, double-blinded, vehicle-controlled trial in patients with acute stroke treated within 6 hours of onset. The primary outcome measures were disability as measured by the Glasgow Outcome Scale and activities of daily living by the Barthel Index determined 3 months after stroke. Results From May 1993 through December 1994, 660 patients were randomized. The trial was prematurely terminated on the advice of an independent monitoring committee after review of outcome data at a preplanned interim analysis. In 556 fully eligible patients (276 tirilazad, 280 vehicle), the odds ratio of a favorable outcome in favor of tirilazad was 0.87 (95% confidence interval [CI], 0.60 to 1.25) for the Glasgow Outcome Scale and 0.87 (95% CI, 0.60 to 1.25) for the Barthel Index, after adjustment for imbalances between the groups in preexisting disability, prior stroke, and diabetes. Conclusions These observations suggest that tirilazad, 6 mg/kg per day for 3 days administered beginning at a median of 4.3 hours after stroke, does not improve overall functional outcome. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT NEUROL,VIRGINIA NEUROL INST,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT NEUROL SURG,VIRGINIA NEUROL INST,CHARLOTTESVILLE,VA 22908. UNIV MICHIGAN,ST JOSEPH MERCY HOSP,WILLIAM BEAUMONT HOSP,ANN ARBOR,MI. MED COLL GEORGIA,AUGUSTA,GA 30912. JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. UNIV ALABAMA,BIRMINGHAM,AL. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NORTHWESTERN UNIV,EVANSTON HOSP,SCH MED,GLENBROOK HOSP,EVANSTON,IL 60201. SINAI HOSP,BALTIMORE,MD 21215. UNIV ALBERTA,MACKENZIE HLTH SCI CTR,EDMONTON,AB,CANADA. WAYNE STATE UNIV,DETROIT RECIEVING HOSP,DETROIT,MI. INDIANA UNIV,WISHARD MEM HOSP,INDIANAPOLIS,IN 46202. UNIV KENTUCKY,VET ADM MED CTR,LEXINGTON,KY. UNIV CALIF LOS ANGELES,MED CTR,SANTA MONICA HOSP,LOS ANGELES,CA 90024. PK NICOLLET MED FDN,FAIRVIEW SOUTHDALE HOSP,METHODIST HOSP,ST LOUIS PK,MN. MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA,PA. THOMAS JEFFERSON UNIV HOSP,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. PENN HOSP,PHILADELPHIA,PA 19107. ROANOKE MEM HOSP,COMMUNITY HOSP ROANOKE VALLEY,ROANOKE NEUROL ASSOCIATES,ROANOKE,VA. UNIV CALIF SAN DIEGO,MED CTR,SCRIPPS MEM HOSP,SAN DIEGO,CA 92103. LIONS GATE HOSP,N VANCOUVER,BC,CANADA. WINCHESTER MED CTR,WINCHESTER,VA. FOOTHILLS PROV GEN HOSP,CALGARY,AB T2N 2T9,CANADA. CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,CLEVELAND,OH. ROYAL UNIV HOSP,SASKATOON,SK S7N 0W8,CANADA. HOP CHICOUTIMI,CHICOUTIMI,PQ,CANADA. ST ALPHONSUS MED CTR,BOISE,ID. FAIRFAX HOSP,FAIRFAX,VA. METHODIST HOSP,HOOSIER NEUROL GRP,INDIANAPOLIS,IN. VIRGINIA NEUROL INST,NEUROCLIN TRIALS CTR,CHARLOTTESVILLE,VA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NINCDS,DIV STROKE & TRAUMA,BETHESDA,MD 20892. COLUMBIA UNIV,NEW YORK,NY. EMORY UNIV,ATLANTA,GA 30322. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. VET ADM MED CTR,WASHINGTON,DC. UNIV IOWA,IOWA CITY,IA. NR 20 TC 138 Z9 141 U1 0 U2 14 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 1996 VL 27 IS 9 BP 1453 EP 1458 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VF032 UT WOS:A1996VF03200001 ER PT J AU Moskowitz, MA Ayata, C AF Moskowitz, MA Ayata, C TI Potentiation of oxygen-glucose deprivation-induced neuronal death after induction of iNOS - Editorial comment SO STROKE LA English DT Editorial Material RP Moskowitz, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. RI Moskowitz, Michael/D-9916-2011 NR 7 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 SEP PY 1996 VL 27 IS 9 BP 1591 EP 1591 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VF032 UT WOS:A1996VF03200026 ER PT J AU Sarac, TP Seydel, AS Ryan, CK Bessey, PQ Miller, JH Souba, WW Sax, HC AF Sarac, TP Seydel, AS Ryan, CK Bessey, PQ Miller, JH Souba, WW Sax, HC TI Sequential alterations in gut mucosal amino acid and glucose transport after 70% small bowel resection SO SURGERY LA English DT Article ID INTESTINAL RESECTION; ADAPTATION; RAT AB Background. Studied in animals with short bowel syndrome (SBS) suggest that up-regulation of nutrient transporter activity occurs as an adaptive response to the loss of absorptive area. It is unclear, however, whether nutrient transport is altered at the cell membrane in SBS. The purpose of this study is to clarify amino acid and glucose transport in small intestinal huminal mucosa after 70% small bowel resection in rabbits. Methods. New Zealand white rabbits underwent 70% jejunoileal resection (n = 27) or a sham operation (n = 19). Brush border membrane vesicles were prepared from small intestinal mucosa at 1 week, 1 month, and 3 months by magnesium aggregation-differential centrifugation. Transport of L-glutamine, L-alanine, L-leucine, L-arginne, and D-glucose was assayed by a rapid mixing filtration technique. Results. We observed no difference in uptake of all amino acids and glucose at 1 week. The uptake of amino acids and glucose was decreased by 20% to 80% in animals with SBS at 1 month. By 3 months all uptake values except that of glucose returned to normal. Kinetic studies of the system B transporter for glutamine indicate that the decrease in uptake at 1 month was caused by a reduction in the Vmax (1575 +/- 146 versus 2366 +/- 235, p < 0.05) consistent with a decrease in the number of functional carriers on the brush border membrane. Conclusions. In addition to the anatomic loss of absorptive area after massive bowel resection, alterations in enterocyte transport function may be responsible for malabsorption in patients with SBS. C1 UNIV ROCHESTER,MED CTR,DEPT SURG,ROCHESTER,NY 14642. MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114. FU NHLBI NIH HHS [5R01HL44986-05]; NIDDK NIH HHS [1R29DK47989-01A1] NR 19 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD SEP PY 1996 VL 120 IS 3 BP 503 EP 508 DI 10.1016/S0039-6060(96)80070-5 PG 6 WC Surgery SC Surgery GA VK888 UT WOS:A1996VK88800008 PM 8784404 ER PT J AU Levin, LA Avery, R Shore, JW Woog, JJ Baker, S AF Levin, LA Avery, R Shore, JW Woog, JJ Baker, S TI The spectrum of orbital aspergillosis: A clinicopathological review SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE aspergillosis; fungal infections; immunodeficiency; optic neuropathy; orbital disease ID CHRONIC GRANULOMATOUS-DISEASE; BONE-MARROW TRANSPLANTATION; ALLERGIC FUNGAL SINUSITIS; LIPOSOMAL AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; HEMATOLOGICAL MALIGNANCIES; IMMUNOCOMPROMISED PATIENTS; PAINFUL OPHTHALMOPLEGIA; ITRACONAZOLE THERAPY; NEUTROPENIC PATIENTS AB Orbital aspergillosis is an uncommon but serious infection that may first present to the ophthalmologist. Usually arising from the paranasal sinuses, it may present in manifold ways within the orbit. Some presentations, such as optic nerve involvement, can respond to systemic cortico-steroids, leading to delays in diagnosis and possibly iatrogenic potentiation of the infectious process. In this review pertinent clinical and radiographic findings are discussed, and the literature is summarized. Classic approaches to therapy include local treatment, debridement, and systemic amphotericin B. We review novel approaches to treating orbital aspergillosis and detail a flow-chart for its management. Four patients from the spectrum of orbital aspergillosis are also described: initially presenting as an infection of all exenteration socket, a complex dacryocystitis, an optic nerve tumor, and post-operative periorbital swelling. Physicians should be familiar with the clinical spectrum of disease and the variable presentation of this infection, as early diagnosis and rapid institution of appropriate therapy are crucial elements in the management of invasive aspergillosis. In the neutropenic or otherwise immunocompromised patient, a high index of suspicion must be maintained as delays in diagnosis of fulminant aspergillosis may lead to overwhelming and rapidly progressive infection. Obtaining adequate diagnostic material for pathological and microbiological examination is critical. Newer methods of therapy, particularly itraconazole and liposomal amphotericin B, may be beneficial in selected patients. C1 CLEVELAND CLIN FDN,CLEVELAND,OH 44195. TUFTS UNIV,SCH MED,BOSTON,MA 02111. MASSACHUSETTS EYE & EAR INFIRM,INFECT DIS SERV,MED UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. RP Levin, LA (reprint author), UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL,K6-456,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 118 TC 61 Z9 64 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD SEP-OCT PY 1996 VL 41 IS 2 BP 142 EP 154 DI 10.1016/S0039-6257(96)80004-X PG 13 WC Ophthalmology SC Ophthalmology GA VJ868 UT WOS:A1996VJ86800004 PM 8890440 ER PT J AU Goldman, IL Kopelberg, M Debaene, JEP Schwartz, BS AF Goldman, IL Kopelberg, M Debaene, JEP Schwartz, BS TI Antiplatelet activity in onion (Allium cepa) is sulfur dependent SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID AGGREGATION; PUNGENCY AB Plants of the genus Allium such as onion and garlic are often consumed as a source of compounds which inhibit human platelet activity, with the goal of decreasing vascular disease. Antiplatelet activity in these plants is determined in part by native concentrations of organosulfur compounds. Evaluation of four onion genotypes grown in a field study at four US locations in 1994 demonstrated onions with mild flavor and low sulfur content exhibited significantly lower antiplatelet activity than those containing high levels of sulfur. Antiplatelet activity was significantly positively correlated with genotypically determined bulb sulfur content and dissolved solids. indicating these latter factors are good predictors of antiplatelet strength, These data demonstrate antiplatelet activity is genotype dependent and correlated with bulb sulfur content. Genotype and bulb sulfur content should be taken into account in studies assessing onion antiplatelet effects. C1 UNIV WISCONSIN,DEPT BIOMOL CHEM,MADISON,WI. UNIV WISCONSIN,DEPT MED HEMATOL,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP Goldman, IL (reprint author), UNIV WISCONSIN,DEPT HORT,1575 LINDEN DR,MADISON,WI 53706, USA. FU NHLBI NIH HHS [HL43506] NR 12 TC 52 Z9 57 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD SEP PY 1996 VL 76 IS 3 BP 450 EP 452 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VG806 UT WOS:A1996VG80600026 PM 8883285 ER PT J AU Lewis, CB AF Lewis, CB TI Untitled SO TOPICS IN GERIATRIC REHABILITATION LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,WASHINGTON,DC 20052. MASSACHUSETTS GEN HOSP,INST HLTH PROF,BOSTON,MA 02114. RP Lewis, CB (reprint author), PHYS THERAPY SERV WASHINGTON DC INC,WASHINGTON,DC, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21701 SN 0882-7524 J9 TOP GERIATR REHABIL JI Top. Geriatr. Rehabil. PD SEP PY 1996 VL 12 IS 1 BP R5 EP R5 PG 1 WC Gerontology; Rehabilitation SC Geriatrics & Gerontology; Rehabilitation GA VF876 UT WOS:A1996VF87600001 ER PT J AU Webb, IJ Coral, FS Andersen, JW Elias, AD Finberg, RW Nadler, LM Ritz, J Anderson, KC AF Webb, IJ Coral, FS Andersen, JW Elias, AD Finberg, RW Nadler, LM Ritz, J Anderson, KC TI Sources and sequelae of bacterial contamination of hematopoietic stem cell components: Implications for the safety of hematotherapy and graft engineering SO TRANSFUSION LA English DT Article ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; PERIPHERAL-BLOOD; CLINICAL-SIGNIFICANCE; MULTIPLE-MYELOMA; POOR-PROGNOSIS; BREAST-CANCER; RECONSTITUTION; THERAPY; CHEMOTHERAPY AB Background: It is important to compare the incidence of bacterial contamination of components collected from the peripheral blood or bone marrow (BM), as well as of components processed with or without cell selection or depletion, and to evaluate the sequelae of such contamination. Study Design and Methods: Bacterial contamination rates were compared in 1380 untreated autologous peripheral blood progenitor cells (PBPCs), 291 untreated autologous BM samples, 916 monoclonal antibody (MoAb)-treated autologous and allogeneic BM samples, and in 45 autologous PBPC components from which the CD34+ cells were selected. Bacterial cultures were performed at sequential time points during the processing of MoAb-treated BM. Results: Bacterial contamination was documented in 44 of 2632 components from 1593 patients (1.67% of components, 2.76% of patients! before cryopreservation. Although only 0.65% of untreated PBPCs were contaminated before cryopreservation, each patient was more likely to have given a contaminated PBPC component than a contaminated BM component (2.41% vs. O%, p<0.01). Bacterial contamination of MoAb-treated BM was greater during or after manipulation than it was before (2.33% vs. 0.77%, p<0.05). At thawing, contamination was documented in 42 (1.97%) of 2136 components cultured. Ten (13.7%) of 73 patients who received hematopoietic progenitor cells that were contaminated before cryopreservation or at thawing developed fever or positive blood cultures within 48 hours of transfusion. Fever was associated with bacteremia in two cases, but no irreversible clinical sequelae were noted. Conclusion: These studies suggest that, despite careful attention to sterile procedures, low-level contamination of hematopoietic stem cell components can be introduced before or during manipulation as well as at thawing, and that standards for monitoring of the procedures for collection, processing, cryopreservation, thawing, and transfusion of hematopoietic progenitor cells are necessary. C1 DANA FARBER CANC INST,BLOOD COMPONENT LAB,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,CLIN IMMUNOL LAB,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. RP Webb, IJ (reprint author), DANA FARBER CANC INST,CRYOPRESERVAT LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010; Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA34183]; NIAID NIH HHS [AI29530] NR 37 TC 62 Z9 67 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 SEP PY 1996 VL 36 IS 9 BP 782 EP 788 DI 10.1046/j.1537-2995.1996.36996420753.x PG 7 WC Hematology SC Hematology GA VJ087 UT WOS:A1996VJ08700005 PM 8823450 ER PT J AU Carson, RA AF Carson, RA TI Effective management of hospital based donor recruitment programs. SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 36 IS 9 SU S BP A77 EP A77 PG 1 WC Hematology SC Hematology GA VK089 UT WOS:A1996VK08900336 ER PT J AU Batter, SJ McGovern, FJ Cambria, RP AF Batter, SJ McGovern, FJ Cambria, RP TI Ureteroarterial fistula: Case report and review of the literature SO UROLOGY LA English DT Article ID INDWELLING URETERAL STENTS; ILIOURETERIC FISTULA; SPONTANEOUS RUPTURE; ANEURYSM AB Ureteroarterial fistulae are rare. We report 2 cases of this clinical problem. Ureteroarterial fistulae can occur in association with prolonged ureteral stenting, radiation therapy, vascular pathology, and prior pelvic or vascular surgery. Identification of-a fistula is often difficult and requires the physician to be highly alert and vigilant. Diagnostic and therapeutic options for a ureteroarterial fistula are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT VASC SURG,BOSTON,MA 02114. NR 35 TC 49 Z9 51 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 SEP PY 1996 VL 48 IS 3 BP 481 EP 489 DI 10.1016/S0090-4295(96)00202-6 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA VG986 UT WOS:A1996VG98600029 PM 8804509 ER PT J AU Park, MK Englund, JA Glezen, WP Siber, GR Nahm, MH AF Park, MK Englund, JA Glezen, WP Siber, GR Nahm, MH TI Association of placental transfer of anti-Haemophilus influenzae type b polysaccharide antibodies with their V regions SO VACCINE LA English DT Article DE Haemophilus influenzae; vaccine; antibody ID PC ANTIBODIES; IMMUNIZATION; VACCINES AB Immunization of mothers during pregnancy may be an effective means of providing protection to infants during the first months of life against many pathogens. Previous studies have identified factors that influence the transfer of immunoglobulin across the placenta, including the time of vaccination during pregnancy and isotypes of specific immunoglobulins. By studying antibodies to Haemophilus influenzae type b polysaccharide (Hib-PS) in 26 pairs of maternal-cord sera obtained from unimmunized healthy women and 22 pairs of maternal-cord sera from women immunized with one of three different Hib vaccines, we have found that the immunoglobulin transfer is also dependent on the V region of antibodies. Anti-Hib-PS derived from the V kappa II gene ''A2'' was transferred about ten times more efficiently to the fetus than other anti-Hib-PS antibodies (20% vs 1-2%), It was found that antibodies derived from the A2 V kappa gene are primarily IgG whereas other antibodies are preferentially associated with the IgM isotype. The potential association between the antibody V region with preferential placental transfer should be considered for future studies involving maternal immunization. Copyright (C) 1996 Elsevier Science Ltd. C1 WASHINGTON UNIV,SCH MED,DIV LAB MED,ST LOUIS,MO 63110. CHONBUK NATL UNIV,DIV BIOL SCI,CHUNJOO 561756,SOUTH KOREA. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. OI Nahm, Moon/0000-0002-6922-1042 FU NIAID NIH HHS [AI-15126] NR 16 TC 8 Z9 8 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD SEP PY 1996 VL 14 IS 13 BP 1219 EP 1222 DI 10.1016/S0264-410X(96)00029-1 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VV440 UT WOS:A1996VV44000006 PM 8961508 ER PT J AU Yokozawa, T Fukata, S Kuma, K Matsuzuka, F Kobayashi, A Hirai, K Miyauchi, A Sugawara, M AF Yokozawa, T Fukata, S Kuma, K Matsuzuka, F Kobayashi, A Hirai, K Miyauchi, A Sugawara, M TI Thyroid cancer detected by ultrasound-guided fine-needle aspiration biopsy SO WORLD JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT International Surgical Week CY AUG 27-SEP 02, 1995 CL LISBON, PORTUGAL SP Int Assoc Endocrine Surgeons ID PAPILLARY CARCINOMA; NODULES; GLAND; MANAGEMENT; CYTOLOGY AB A greater percentage of thyroid cancers can be detected by ultrasound-guided fine-needle aspiration biopsy (UG-FNAB) than by ordinary FNAB. A group of 678 patients were selected sequentially as having been diagnosed with benign nodules by the conventional FNAB method. We reexamined these patients by UG-FNAB and investigated the types of thyroid cancer that were missed by the conventional FNAB. Of the 678 patients diagnosed with benign nodules (using conventional FNAB), 571 (84.2%) demonstrated the same diagnosis when UG-FNAB was used. The remaining 107 patients (15.8%) studied were suspected of having a malignancy after UG-FNAB had been performed. Surgical specimen histology proved thyroid cancer in 99 of the 107 patients: 93 had papillary carcinoma, 4 had follicular carcinoma, 1 had medullary carcinoma and 1 had anaplastic carcinoma. Two drawbacks were noted when conventional FNAB was used: (1) cancer lesions difficult to palpate (n = 55) (e.g., small cancers with or without benign lesions or cancers associated with Hashimoto's thyroiditis or Graves' disease); and (2) palpable cancers with insufficient cell material for analysis (n = 44) (e.g., cystic carcinoma and cancers,vith calcified lesions. UG-FNAB is a powerful technique for detecting microcancers, cystic carcinomas, cancers associated with benign nodules, Hashimoto's thyroiditis, or coarse calcifications. C1 KAGAWA MED SCH,DEPT SURG 2,KAGAWA,JAPAN. W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90073. RP Yokozawa, T (reprint author), KUMA HOSP,CHUO KU,8-2-35 SHIMOYAMATE DORI,KOBE 650,JAPAN. NR 21 TC 74 Z9 79 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD SEP PY 1996 VL 20 IS 7 BP 848 EP 853 PG 6 WC Surgery SC Surgery GA VD690 UT WOS:A1996VD69000019 PM 8678961 ER PT J AU Eder, PS Srinivasan, A Fishman, MC Altman, S AF Eder, PS Srinivasan, A Fishman, MC Altman, S TI The RNA subunit of ribonuclease P from the zebrafish, Danio rerio SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULE; INVITRO; MOIETY; ENZYME; CELLS AB A simple strategy has been devised to identify the gene encoding the RNA subunit of RNase P from the zebrafish, Danio rerio. The sequence obtained by amplification of genomic DNA with primers based on sequences common to two other vertebrates was confirmed by reverse transcription and amplification of RNA from a partially purified preparation of the holoenzyme. The 5' and 3' ends were determined by cyclizing the RNA, followed by reverse transcription and sequencing across the ligated RNA junction, The zebrafish sequence is 63% identical to that of Xenopus laevis nuclear RNase P RNA and 69% identical to the human RNase P RNA, A consensus secondary structure was constructed based on these nucleotide identities and on the many compensatory base changes in several regions among these three RNAs. The strategy used to obtain the zebrafish sequence should be useful in deriving analogous gene sequences from diverse classes of eukaryotes. C1 YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. NR 27 TC 14 Z9 14 U1 0 U2 3 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 AUG 30 PY 1996 VL 271 IS 35 BP 21031 EP 21036 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700013 PM 8702867 ER PT J AU Sapirstein, A Spech, RA Witzgall, R Bonventre, JV AF Sapirstein, A Spech, RA Witzgall, R Bonventre, JV TI Cytosolic phospholipase A(2), (PLA(2)), but not secretory PLA(2), potentiates hydrogen peroxide cytotoxicity in kidney epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; INDUCED DNA-DAMAGE; SUPEROXIDE-DISMUTASE; ARACHIDONIC-ACID; LIPID-PEROXIDATION; LLC-PK1 CELLS; ENZYMATIC-ACTIVITY; CALCIUM IONOPHORE; PROXIMAL TUBULES; OXIDATIVE STRESS AB Phospholipase A(2) (PLA(2)) and reactive oxygen species have been implicated both individually and synergistically in various forms of cellular injury. The form(s) of PLA(2) important for cell injury and the implications of enhanced activity of the enzyme, however, have not been discerned. Previous studies reveal an increase in PLA(2) activity associated with cell injury, but this association does not establish a causal relationship between the increase in activity and the injury. LLC-PK1 cell lines were created that express either the cytosolic PLA(2) or a group II PLA(2). The susceptibility of these cells to hydrogen peroxide toxicity was determined in order to evaluate the relative importance of these two forms of PLA(2) in oxidant injury. Expression of cytosolic PLA(2) in the LLC-cPLA(2) cell line was associated with a 50-fold increase in PLA(2) activity in the cytosolic fraction, an increase in agonist-stimulated arachidonate release, and immunodetection of the cytosolic PLA(2) protein that was undetectable in control cells. Exposure to hydrogen peroxide or menadione, but not mercuric chloride, resulted in significantly greater lactate dehydrogenase release in LLC-cPLA(2) cells when compared with control cells. Exogenous arachidonic acid (150 mu M) did not enhance hydrogen peroxide-induced injury. The intracellular calcium chelator, 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/tetra(acetoxymethyl) ester, protected the cells against injury, but the calcium ionophore, A23187, did not increase injury. Glycine conferred no protective effect against hydrogen peroxide toxicity. By contrast to these results with cytosolic PLA(2)-expressing cells, secretory PLA(2) expression to very high levels did not increase susceptibility to hydrogen peroxide. Thus, cytosolic PLA(2) may an be an important mediator of oxidant damage to renal epithelial cells. C1 MASSACHUSETTS GEN HOSP EAST,MED SERV,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP EAST,ANESTHESIA SERV,CHARLESTOWN,MA 02129. DEPT MED,CHARLESTOWN,MA 02129. DEPT ANESTHESIA,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 38452, DK39773]; NINDS NIH HHS [NS 10828] NR 77 TC 119 Z9 120 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 AUG 30 PY 1996 VL 271 IS 35 BP 21505 EP 21513 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE477 UT WOS:A1996VE47700081 PM 8702935 ER PT J AU Jiang, QB Walton, NY Gunawan, S Treiman, DM AF Jiang, QB Walton, NY Gunawan, S Treiman, DM TI High-performance liquid chromatographic determination of midazolam in rat brain SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article DE midazolam ID HUMAN PLASMA; INTRAVENOUS MIDAZOLAM; STATUS EPILEPTICUS; METABOLITES AB A high-performance liquid chromatography method for the determination of midazolam in rat brain is described. Midazolam and the internal standard halazepam were extracted with toluene and analyzed isocratically on a reversed-phase column with a mobile phase consisting of methanol, acetonitrile and potassium phosphate buffer. Detection was monitored by ultraviolet absorption at 240 nm. The standard curves were linear over the range of 25-350 ng midazolam per 50 mg brain tissue. The day-to-day coefficient of variation ranged from 1.7 to 6.9%. The limit of quantification was 80 ng/g brain tissue. The method is rapid, simple and reproducible for brain analysis. C1 DEPT VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,W LOS ANGELES DVA MED CTR,LOS ANGELES,CA 90095. RP Jiang, QB (reprint author), DEPT VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073, USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD AUG 30 PY 1996 VL 683 IS 2 BP 276 EP 280 DI 10.1016/0378-4347(95)00569-2 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VH540 UT WOS:A1996VH54000019 PM 8891927 ER PT J AU Reinherz, EL Li, J Smoylar, A Wyss, DF Knoppers, MH Willis, KJ Arulanandam, ARN Choi, JS Wagner, G AF Reinherz, EL Li, J Smoylar, A Wyss, DF Knoppers, MH Willis, KJ Arulanandam, ARN Choi, JS Wagner, G TI CD2: An exception to the immunoglobulin superfamily concept? Response SO SCIENCE LA English DT Article ID N-LINKED GLYCAN; ADHESION DOMAIN; MOLECULE CD2; GLYCOSYLATION; CONFORMATION; GLYCOPROTEIN; GLYCOFORMS; DYNAMICS; BINDING; NMR C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. PROCEPT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. RP Reinherz, EL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. NR 14 TC 3 Z9 3 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 30 PY 1996 VL 273 IS 5279 BP 1242 EP 1242 DI 10.1126/science.273.5279.1242 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VE476 UT WOS:A1996VE47600046 PM 17842602 ER PT J AU Singh, BN Lazzara, R AF Singh, BN Lazzara, R TI A new age in the pharmacologic therapy of cardiac arrhythmias - Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK. UNIV OKLAHOMA,SCH MED,OKLAHOMA CITY,OK. RP Singh, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SECT CARDIOL 111E,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 29 PY 1996 VL 78 SU 4A BP 1 EP 3 DI 10.1016/S0002-9149(96)00446-8 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WK911 UT WOS:A1996WK91100001 PM 8780322 ER PT J AU Singh, BN AF Singh, BN TI The coming of age of the class III antiarrhythmic principle: Retrospective and future trends SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; VENTRICULAR INTRACELLULAR POTENTIALS; ATRIAL-FIBRILLATION; CARDIAC-ARRHYTHMIAS; SINUS RHYTHM; SUDDEN-DEATH; DRUGS; AMIODARONE; THERAPY; MUSCLE AB Antiarrhythmic drug therapy is in a state of continuous flux In the last decade or so, numerous experimental and clinical studies have revealed that drugs that act by delaying conduction, while markedly suppressing ventricular arrhythmias, have the proclivity to increase mortality in subsets of patients with significant cardiac disease. The adverse impact on mortality was confirmed by placebo-controlled randomized trials as well as metaanalysis of smaller randomized clinical trials. The latter indicated that beta blockers exert a beneficial effect on mortality. Benefit from drugs that lengthen repolarization, especially drugs that have the additional property of blocking sympathetic excitation, was also seen in relatively small numbers of patients. Sotalol and amiodarone fell into this category of antiarrhythmic drugs. There were 2 major consequences that stemmed from the results of these trials. First, the endpoint of clinical trials shifted to total mortality from surrogates such as defined degree of suppression of ventricular arrhythmias. Second, concern regarding increases in mortality produced by class I drugs engendered a shift in favor of drugs that prolong repolarization. Such a shift was bolstered by the growing body of data that established the efficacy of sotalol and amiodarone as potent agents for the control of life-threatening ventricular arrhythmias. They were both found to be superior to class I agents. The perception that the critical factor that mediates their efficacy is the homogeneous prolongation of repolarization has led to the synthesis and characterization of so-called pure class III agents, which include d-sotalol and other IK, blockers such as dofetilide, sematilide, E-4031, and almokalant, among numerous others. The increase in mortality produced by d-sotalol in patients with myocardial infarction and lowered ejection fraction and in patients with and without heart failure has led researchers to question how to design future antiarrhythmic molecules. In the search for an ideal antifibrillatory agent, should emphasis be placed on simple molecules such as pure class III agents or on those with more complex profiles, such as sotalol and amiodarone, which exhibit antiadrenergic actions and the ability to prolong cardiac repolarization? The available data are in favor of the latter approach. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. RP Singh, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, SECT CARDIOL 691 111E, DIV CARDIOL, 11301 WILSHIRE BLVD, LOS ANGELES, CA 90073 USA. NR 48 TC 26 Z9 26 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 29 PY 1996 VL 78 IS 4A SI SI BP 17 EP 27 DI 10.1016/S0002-9149(96)00449-3 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WK911 UT WOS:A1996WK91100004 PM 8780325 ER PT J AU Singh, BN AF Singh, BN TI Antiarrhythmic actions of amiodarone: A profile of a paradoxical agent SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LOW-DOSE AMIODARONE; REFRACTORY ATRIAL-FIBRILLATION; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; IDIOPATHIC DILATED CARDIOMYOPATHY; COMPLEX VENTRICULAR ARRHYTHMIAS; CONGESTIVE-HEART-FAILURE; SUDDEN CARDIAC DEATH; MYOCARDIAL-INFARCTION; SINUS RHYTHM; INTRAVENOUS AMIODARONE AB Amiodarone, a complex compound with variegated electrophormacologic end pharmacokinetic properties and on equally complex side-effect profile, continues to have a critical role in the control of ventricular end supraventricular tachyarrhythmias as the use of class I agents has declined. Such is also the case with sotalol. Unlike other so-celled class III agents, amiodarone noncompetitively blocks sympathetic stimulation, and its effects on repolarization are not associated with reverse use dependency. Rarely does it produce torsades de pointes despite its propensity to induce significant bradycardia and marked prolongation of the QT interval. During long-term therapy with the drug, there is no impairment of ventricular function; in fact, there ore significant increases in the left ventricular ejection fraction during protracted amiodarone therapy in patients with heart failure. Long-term amiodarone administration consistently demonstrates marked efficacy in a wide spectrum of arrhythmias. The major limitation of amiodarone during long-term therapy is its unusual side-effect profile, although the increasing trend for low-dose drug therapy has demonstrated a major decline in the overall incidence of serious adverse reactions. Amiodarone is effective in controlling symptomatic ventricular tachycardia and fibrillation (VT/VF) in >60-70% of patients when conventional agents (especially doss I) are ineffective or not well tolerated. The efficacy of amiodarone compared with that of an implantable cardioverter-defibrillator in patients with VT/VF and in survivors of cardiac arrest remains uncertain when total mortality is used as the primary endpoint of comparison. Amiodarone suppresses ventricular ectopy and markedly suppresses nonsustained VT. It prevents inducible VT/VF in a smell number of patients, but slows VT rate in a larger number. The role of the drug in prolonging survival in the postmyocardial infarction patient is unclear, although preliminary data from blinded studies suggest that the drug decreases arrhythmia-related mortality. Similarly, in heart failure, amiodarone has the potential to reduce total mortality but appears to be selectively effective in nonischemic rather then in ischemic cardiomyopathy. Intravenous amiodarone was recently introduced in the United States for the control of recurrent destabilizing VT or VF resistant to conventional therapy. There is also evolving data indicating that the drug might be the most potent agent in maintaining sinus rhythm in patients with atrial fibrillation or flutter converted chemically or electrically to sinus rhythm. However, blinded controlled comparative studies involving sotalol, quinidine, or pure class III drugs have not been carried out. The available data nevertheless suggest that, barring its side-effect profile, amiodarone is a desirable prototype of a broad-spectrum antifibrillatory and antiarrhythmic compound. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. RP Singh, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SECT CARDIOL 691 111E,DIV CARDIOL,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 64 TC 86 Z9 91 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 29 PY 1996 VL 78 SU 4A BP 41 EP 53 DI 10.1016/S0002-9149(96)00452-3 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WK911 UT WOS:A1996WK91100007 PM 8780328 ER PT J AU OCallaghan, PA McGovern, BA AF OCallaghan, PA McGovern, BA TI Evolving role of sotalol in the management of ventricular tachyarrhythmias SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PROGRAMMED ELECTRICAL-STIMULATION; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; QT DISPERSION; ORAL SOTALOL; ANTIARRHYTHMIC DRUGS; DL-SOTALOL; TACHYCARDIA; EFFICACY; ARRHYTHMIAS AB Sotalol is a unique compound with several potential antiarrhythmic mechanisms, including beta blockade (class II activity), action potential duration prolongation (class III activity), and possibly reduction of QT dispersion. In recent years, trials such as the Cardiac Arrhythmia Suppression Trial (CAST) and the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial reported disappointing results with the use of class I agents in the management of ventricular arrhythmias in patients with coronary artery disease. These results have led to increased interest in class III antiarrhythmic agents, including sotalol. Sotalol is effective in suppressing ventricular premature complexes as well as nonsustained and sustained ventricular tachyarrhythmias. The interaction between sotalol and implantable cardioverter-defibrillators (ICDs) is generally favorable. As is the case with other antiarrhythmic drugs, there is no placebo-controlled trial assessing the effect of sotalol an mortality. It is not known if sotalol is more effective than placebo, conventional beta blockade, amiodarone, or ICDs in reducing mortality from life-threatening ventricular arrhythmias. In addition, the optimal method of selecting patients for sotalol therapy has yet to be determined. The safety profile of sotalol has been well established in >3,000 patients worldwide. Proarrhythmia occurs in approximately 4% of patients, and torsades de pointes occurs in approximately 2.5%. The majority of episodes of torsades de pointes occurs within 3 days of commencing sotalol therapy, and the risk of torsades de pointes increases sharply at dosages >320 mg daily. It is recommended that initiation of sotalol therapy or dosage increases be performed in a monitored setting. Overall, only 1% of patients enrolled in clinical trials of sotalol discontinued therapy as a result of drug-related congestive heart failure. However, these trials have excluded patients with poor left ventricular systolic function and/or overt heart failure. The optimal management of these patients, who are at greatest risk of sudden cardiac death, and of patients with substrates other than coronary artery disease remains to be elucidated. C1 MASSACHUSETTS GEN HOSP, CARDIAC UNIT, CARDIAC ARRHYTHMIA SERV, BOSTON, MA 02114 USA. ST PETERS HOSP, ALBANY, NY USA. NR 40 TC 8 Z9 8 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 29 PY 1996 VL 78 IS 4A SI SI BP 54 EP 60 DI 10.1016/S0002-9149(96)00453-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WK911 UT WOS:A1996WK91100008 PM 8780329 ER PT J AU Pahlavani, MA Richardson, A AF Pahlavani, MA Richardson, A TI The effect of age on the expression of Interleukin-2 SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Review DE aging; immune system; Interleukin-2; transcription; transcription factors ID T-CELL ACTIVATION; IL-2 RECEPTOR EXPRESSION; INVIVO IMMUNOPOTENTIATING ACTIVITY; CALCINEURIN PHOSPHATASE-ACTIVITY; LYMPHOCYTE-SPECIFIC FACTORS; PHORBOL-MYRISTATE ACETATE; MESSENGER-RNA EXPRESSION; IMMUNE FUNCTION; OLD MICE; INDUCED PROLIFERATION AB Interleukin-2 (IL-2) is a growth promoting cytokine that has received a great deal of attention over the past decade with respect to aging and cancer. It is produced primarily by helper T cells and regulates the growth and function of various cells that are involved in cellular and humoral immunity. The expression of IL-2 has been found to decrease with age in humans and rodents. The decline in IL-2 production has been shown to parallel the age-related decrease in immunologic function. Several studies indicate that treatment of lymphocytes from old subjects with exogenous IL-2 or infusion of IL-2 into old animals partially or completely restores some of the immune functions that decline with age. The age-related decline in IL-2 production has been shown to arise from a decline in IL-2 transcription, and a recent study suggests that the transcription factor NFAT (nuclear factor of activated T cells) may play a role in the decline in IL-2 transcription. C1 UNIV TEXAS, HLTH SCI CTR, DEPT PHYSIOL, SAN ANTONIO, TX 78284 USA. RP Pahlavani, MA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR, CTR GERIATR RES EDUC & CLIN, 7400 MERTON MINTER BLVD, SAN ANTONIO, TX 78284 USA. FU NIA NIH HHS [AG00677, AG01548] NR 188 TC 64 Z9 64 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD AUG 29 PY 1996 VL 89 IS 3 BP 125 EP 154 DI 10.1016/0047-6374(96)01725-3 PG 30 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA VA544 UT WOS:A1996VA54400001 PM 8844635 ER PT J AU Bleul, CC Farzan, M Choe, H Parolin, C ClarkLewis, I Sodroski, J Springer, TA AF Bleul, CC Farzan, M Choe, H Parolin, C ClarkLewis, I Sodroski, J Springer, TA TI The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOLECULAR-CLONING; CHROMOSOMAL LOCALIZATION; RECEPTOR CDNA; GENE; INTERLEUKIN-8; INFECTION; SEQUENCE; PROTEINS; CELLS AB CHEMOKINES are chemotactic cytokines that activate and direct the migration of leukocytes(1,2). There are two subfamilies, the CXC and the CC chemokines, We recently found that the CXC-chemokine stromal cell-derived factor-1 (SDF-1)(3,4) is a highly efficacious lymphocyte chemoattractant(5). Chemokines act on responsive leukocyte subsets through G-protein-coupled seven-transmembrane receptors', which are also used by distinct strains of HIV-1 as cofactors for viral entry. Laboratory-adapted and some T-cell-line-tropic (T-tropic) primary viruses use the orphan chemokine receptor LESTR/fusin (also known as fusin)(6-8), whereas macrophage-tropic primary HIV-1 isolates use CCR-5 and CCR-3 (refs 7-11), which are receptors for known CC chemokines, Testing of potential receptors demonstrated that SDF-1 signalled through, and hence 'adopted', the orphan receptor LESTR, which we therefore designate CXC-chemokine receptor-4 (CXCR-4). SDF-1 induced an increase in intracellular free Ca2+ and chemotaxis in CXCR-4-transfected cells. Because SDF-1 is a biological ligand for the HIV-1 entry cofactor LESTR, we tested whether it inhibited HIV-1, SDF-1 inhibited infection by T-tropic HIV-1 of HeLa-CD4 cells, CXCR-4 transfectants, and peripheral blood mononuclear cells (PBMCs), but did not affect CCR-5-mediated infection by macrophage-tropic (M-tropic) and dual-tropic primary HIV-1. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHO,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV PADUA,INST MICROBIOL,I-35121 PADUA,ITALY. UNIV BRITISH COLUMBIA,BIOMED RES CTR,VANCOUVER,BC V6T 1Z3,CANADA. NR 29 TC 1553 Z9 1588 U1 0 U2 17 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 29 PY 1996 VL 382 IS 6594 BP 829 EP 833 DI 10.1038/382829a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VE347 UT WOS:A1996VE34700053 PM 8752280 ER PT J AU Moncure, AC McDowell, RK Mark, EJ Briggs, SM Nielsen, GP AF Moncure, AC McDowell, RK Mark, EJ Briggs, SM Nielsen, GP TI A 31-year-old woman with lumbar and abdominal pain, hypertension, and a retroperitoneal mass - Idiopathic retroperitoneal fibrosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHRONIC PERIAORTITIS; INVOLVEMENT C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Moncure, AC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 17 TC 3 Z9 3 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 AUG 29 PY 1996 VL 335 IS 9 BP 650 EP 655 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VD425 UT WOS:A1996VD42500008 ER PT J AU Kraeft, SK Traincart, F Mesnildrey, S Bourdais, J Veron, M Chen, LB AF Kraeft, SK Traincart, F Mesnildrey, S Bourdais, J Veron, M Chen, LB TI Nuclear localization of nucleoside diphosphate kinase type B (nm23-H2) in cultured cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN BREAST-CANCER; TUMOR-METASTASIS; TRANSCRIPTION FACTOR; CRYSTAL-STRUCTURE; DNA-REPLICATION; DICTYOSTELIUM-DISCOIDEUM; DROSOPHILA DEVELOPMENT; MYXOCOCCUS-XANTHUS; PROTEIN EXPRESSION; GENE AB Nucleoside diphosphate (NDP) kinases are metabolic enzymes found ubiquitously in cells. Recently, two known human isoforms of NDP kinase (A and B), identical to the protein products of the genes nm23-H1 and nm23-H2, respectively, have been implicated in cancer metastasis and transcriptional regulation. To date, NDP kinase has been studied extensively in tissue sections and its cellular localization was described as being cytoplasmic, However, the recently discovered role of the nm23-H2 gene product in transcriptional activation of the c-myc proto-oncogene also suggests a nuclear localization of the protein. In this study, we used isoform-specific antibodies against NDPK-B to examine the subcellular localization of the nm23-H2 gene product. The cytoplasmic fluorescence is intense and homogeneous with pronounced labeling in the centromere region, The distribution of NDPK-B in interphase nuclei exhibits a pattern of numerous uniformly dispersed fine dots with reduced staining of the nucleoli. To further characterize the nuclear localization of NDPK-B, in situ sequential extraction of nuclear components was performed. Brief exposure to Triton X-100 and subsequent treatment with RNase A do not change the nuclear staining pattern of NDPK-B. In contrast, treatment of Triton X-100-permeabilized nuclei with DNase I results in a significant loss of fluorescence. In mitotic prophase cells, the protein segregates from forming chromosomes and reappears in newly formed daughter nuclei after cell division. Taken together, the results indicate an association of NDPK-B with chromatin in interphase nuclei, supporting its proposed role in transcription. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,SCH MED,BOSTON,MA 02115. INST PASTEUR,CNRS URA 1149,UNITE REGULAT ENZYMAT ACT CELLULAIRES,F-75724 PARIS 15,FRANCE. NR 53 TC 50 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG 25 PY 1996 VL 227 IS 1 BP 63 EP 69 DI 10.1006/excr.1996.0250 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA VF741 UT WOS:A1996VF74100008 PM 8806452 ER PT J AU Caldwell, JS Moyers, JS Doria, A Reynet, C Kahn, RC AF Caldwell, JS Moyers, JS Doria, A Reynet, C Kahn, RC TI Molecular cloning of the human rad gene: Gene structure and complete nucleotide sequence SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE GTPase; muscle; MyoD; Ras ID FAMILY; MUSCLE; MEMBER AB We have isolated and sequenced human genomic DNA clones encoding the Ras-related GTP-binding protein, Rad. The gene spans 3.75 kb and consists of five exons and four introns. Translation initiates from the first of two in-frame methionine residues in the second exon. Several potential transcription cis-elements were revealed throughout the 1.7 kb 5'-flanking region, including 'E box' and CArG binding sites for regulators of transcription in muscle. C1 HARVARD UNIV,SCH MED,DIV RES,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD AUG 23 PY 1996 VL 1316 IS 3 BP 145 EP 148 DI 10.1016/0925-4439(96)00034-8 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VD709 UT WOS:A1996VD70900001 PM 8781531 ER PT J AU Maly, P Thall, AD Petryniak, B Rogers, GE Smith, PL Marks, RM Kelly, RJ Gersten, KM Cheng, GY Saunders, TL Camper, SA Camphausen, RT Sullivan, FX Isogai, Y Hindsgaul, O vonAndrian, UH Lowe, JB AF Maly, P Thall, AD Petryniak, B Rogers, GE Smith, PL Marks, RM Kelly, RJ Gersten, KM Cheng, GY Saunders, TL Camper, SA Camphausen, RT Sullivan, FX Isogai, Y Hindsgaul, O vonAndrian, UH Lowe, JB TI The alpha(1,3)Fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis SO CELL LA English DT Article ID SIALYL-LEWIS-X; ELAM-1-DEPENDENT CELL-ADHESION; ENDOTHELIAL-DERIVED LIGAND; ALPHA(1,3)-FUCOSYL-TRANSFERASE GENE; MONOCLONAL-ANTIBODY; MESENTERIC VENULES; EXPRESSION CLONING; MOLECULAR-CLONING; DEFICIENT MICE; MOUSE AB alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate here that mice deficient in alpha(1,3)fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized by absent leukocyte E- and P-selectin ligand activity and deficient HEV L-selectin ligand activity. Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can control leukocyte trafficking in health and disease. C1 UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. GENET INST INC,CAMBRIDGE,MA 02140. LA JOLLA CANC RES CTR,BURNHAM INST,LA JOLLA,CA 92119. RP Maly, P (reprint author), UNIV MICHIGAN,SCH MED,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109, USA. RI von Andrian, Ulrich/A-5775-2008; Maly, Petr/H-5962-2014 FU NIGMS NIH HHS [GM47455] NR 54 TC 586 Z9 592 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 23 PY 1996 VL 86 IS 4 BP 643 EP 653 DI 10.1016/S0092-8674(00)80137-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE235 UT WOS:A1996VE23500014 PM 8752218 ER PT J AU Vadlamudi, RK Joung, I Strominger, JL Shin, J AF Vadlamudi, RK Joung, I Strominger, JL Shin, J TI p62, a phosphotyrosine-independent ligand of the SH2 domain of p56(lck), belongs to a new class of ubiquitin-binding proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article AB p62 is a novel cellular protein which was initially identified as a phosphotyrosine-independent ligand of the SH2 domain of p56(lck). In the yeast two-hybrid system, p62 specifically interacted with ubiquitin in vivo. Furthermore, p62 bound to ubiquitin-conjugated Sepharose beads in vitro and was efficiently competed by soluble ubiquitin. The interaction was independent of ATP hydrolysis, and its dissociation did not require a reducing agent. Thus, p62 binds to ubiquitin noncovalently. Further analysis showed that the C-terminal 80 amino acids of p62 were indispensable for its interaction with ubiquitin. However, p62 has homology neither with ubiquitin C-terminal hydrolases nor with the S5a subunit of the 26 S proteasome complex, the only proteins known to bind to ubiquitin noncovalently. These results suggest that p62 belongs to a new class of ubiquitinbinding proteins and that p62 affects signal transduction at least partly through ubiquitination-mediated protein degradation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. FU NCI NIH HHS [CA47554]; NIGMS NIH HHS [GM48961] NR 16 TC 200 Z9 206 U1 0 U2 5 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 AUG 23 PY 1996 VL 271 IS 34 BP 20235 EP 20237 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700005 PM 8702753 ER PT J AU Wang, SY Miura, M Jung, YK Zhu, H Gagliardini, V Shi, LF Greenberg, AH Yuan, JY AF Wang, SY Miura, M Jung, YK Zhu, H Gagliardini, V Shi, LF Greenberg, AH Yuan, JY TI Identification and characterization of Ich-3, a member of the interleukin-1 beta converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEATH GENE CED-3; IL-1-BETA-CONVERTING ENZYME; GRANZYME-B; MEDIATED APOPTOSIS; ICE/CED-3 PROTEASE; CYSTEINE PROTEASES; MAMMALIAN HOMOLOG; DNA FRAGMENTATION; MICE DEFICIENT; CRMA AB We report here the isolation and characterization of a new member of the ice/ced-3 family of cell death genes, named ich-3. The predicted amino acid sequence of Ich-3 protein shares 54% identity with murine interleukin-1 beta converting enzyme (ICE). Overexpression of ich-3 in Rat-1 and HeLa cells induces apoptosis, which can be inhibited by CrmA and Bcl-2. The mRNA and proteins of ich-3 are dramatically induced in vivo upon stimulation with lipopolysaccharide, an inducer of septic shock. The ich-3 gene product can be cleaved by cytotoxic T cells granule serine protease granzyme B, suggesting that Ich-3 may mediate apoptosis induced by granzyme B. Ich-3 does not process proIL-1 beta directly but does promote proIL-1 beta processing by ICE. These results suggest that Ich-3 may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV TSUKUBA,DEPT MOL NEUROBIOL,CTR TSUKUBA ADV RES ALLIANCE,TSUKUBA,IBARAKI 305,JAPAN. UNIV TSUKUBA,INST BASIC MED SCI,TSUKUBA,IBARAKI 305,JAPAN. UNIV MANITOBA,MANITOBA INST CELL BIOL,MANITOBA CANC TREATMENT & RES FDN,WINNIPEG,MB R3E 0V9,CANADA. NR 31 TC 146 Z9 150 U1 0 U2 7 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 AUG 23 PY 1996 VL 271 IS 34 BP 20580 EP 20587 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700055 PM 8702803 ER PT J AU Imbalzano, AN Schnitzler, GR Kingston, RE AF Imbalzano, AN Schnitzler, GR Kingston, RE TI Nucleosome disruption by human SWI/SNF is maintained in the absence of continued ATP hydrolysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; TUMOR VIRUS PROMOTER; RNA-POLYMERASE-II; HEAT-SHOCK FACTOR; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; DNA-BINDING; POSITIONED NUCLEOSOMES; MULTISUBUNIT COMPLEX; FACILITATED BINDING AB We have examined the requirement for ATP in human (h) SWI/SNF-mediated alteration of nucleosome structure and facilitation of transcription factor binding to nucleosomal DNA. hSWI-SNF-mediated nucleosome alteration requires hydrolysis of ATP or dATP. The alteration is stable upon removal of ATP from the reaction or upon inhibition of activity by excess ATP gamma S, indicating that continued ATP hydrolysis is not required to maintain the altered nucleosome structure, This stable alteration is sufficient to facilitate binding of a transcriptional activator protein; concurrent ATP hydrolysis was not required to facilitate binding. These data suggest sequential steps that can occur in the process by which transcription factors gain access to nucleosomal DNA. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 54 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 AUG 23 PY 1996 VL 271 IS 34 BP 20726 EP 20733 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD337 UT WOS:A1996VD33700076 PM 8702824 ER PT J AU Lepor, H Williford, WO Barry, MJ Brawer, MK Dixon, CM Gormley, G Haakenson, C Machi, M Narayan, P Padley, RJ AF Lepor, H Williford, WO Barry, MJ Brawer, MK Dixon, CM Gormley, G Haakenson, C Machi, M Narayan, P Padley, RJ TI The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ASSOCIATION SYMPTOM INDEX; MULTICENTER; MEN; DOXAZOSIN AB Background Men with benign prostatic hyperplasia can be treated with alpha(1)-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. Methods We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. Results The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo, In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. Conclusions In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone. (C) 1996, Massachusetts Medical Society. C1 VET AFFAIRS MED CTR,NEW YORK,NY. VET AFFAIRS MED CTR,COOPERAT STUDIES PROGRAM COORDINATING CTR,PERRY POINT,MD. MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114. VET AFFAIRS MED CTR,SEATTLE,WA 98108. UNIV WASHINGTON,SEATTLE,WA 98195. MERCK & CO INC,RAHWAY,NJ 07065. VET AFFAIRS MED CTR,COOPERAT STUDIES PROGRAM CLIN RES PHARM COORDINAT,ALBUQUERQUE,NM. VET AFFAIRS MED CTR,MILWAUKEE,WI. VET AFFAIRS MED CTR,SAN FRANCISCO,CA 94121. ABBOTT LABS,CARDIOVASC CLIN RES,ABBOTT PK,IL 60064. RP Lepor, H (reprint author), NYU,MED CTR,DEPT UROL,550 1ST AVE,NEW YORK,NY 10016, USA. NR 24 TC 519 Z9 530 U1 1 U2 5 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 AUG 22 PY 1996 VL 335 IS 8 BP 533 EP 539 DI 10.1056/NEJM199608223350801 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VD302 UT WOS:A1996VD30200001 PM 8684407 ER PT J AU Hylek, EM Skates, SJ Sheehan, MA Singer, DE AF Hylek, EM Skates, SJ Sheehan, MA Singer, DE TI An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RISK-FACTORS; WARFARIN; STROKE; COMPLICATIONS; OUTPATIENTS; PREVENTION; THROMBOSIS; ASPIRIN; THERAPY; SMOKING AB Background To avert major hemorrhage, physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation. Since the low rate of stroke has made it difficult to perform prospective studies to resolve this issue, we conducted a case-control study. Methods We studied 74, consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin. For each patient with stroke, three controls with nonrheumatic atrial fibrillation who were treated as our patients were randomly selected from the 1994 registry of the anticoagulant-therapy unit (222 controls). We used the international normalized ratio (INR) to measure the intensity of anticoagulation. For The patients with stroke, we used the INR at admission; for the controls, we selected the INR that was measured closest to the month and day of the matched case patient's hospital admission. Results The risk of stroke rose steeply at INRs below 2.0. At an INR of 1.7, the adjusted odds ratio for stroke, as compared with the risk at an INR of 2.0, was 2.0 (95 percent confidence interval, 1.6 to 2.4); at an INR of 1.5, it was 3.3 (95 percent confidence interval, 2.4 to 4.6); and at an INR of 1.3, it was 6.0 (95 percent confidence interval, 3.6 to 9.8). Other independent risk factors were previous stroke (odds ratio, 10.4; 95 percent confidence interval, 4.4 to 24.5), diabetes mellitus (odds ratio, 2.9; 95 percent confidence interval, 1.3 to 6.5), hypertension (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 5.7), and current smoking (odds ratio, 5.7; 95 percent confidence Interval, 1.4 to 24.0). Conclusions Among patients with atrial fibrillation, anticoagulant prophylaxis is effective at INRs of 2.0 or greater. Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0, tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower, less effective levels of anticoagulation. (C) 1996. Massachusetts Medical Society. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CLIN EPIDEMIOL UNIT,DIV GEN INTERNAL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 32 TC 551 Z9 582 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 AUG 22 PY 1996 VL 335 IS 8 BP 540 EP 546 DI 10.1056/NEJM199608223350802 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VD302 UT WOS:A1996VD30200002 PM 8678931 ER PT J AU Goto, K Heymont, JL KleinNulend, J Kronenberg, HM Demay, MB AF Goto, K Heymont, JL KleinNulend, J Kronenberg, HM Demay, MB TI Identification of an osteoblastic silencer element in the first intron of the rat osteocalcin gene SO BIOCHEMISTRY LA English DT Article ID DIFFERENTIAL UTILIZATION; COLLAGEN PROMOTER; CELL-LINES; BONE; EXPRESSION; TRANSCRIPTION; MOUSE; INDUCTION; SEQUENCES; CONTAINS AB The osteocalcin gene has been used as a model for studying the regulation of gene expression by 1,25-dihydroxyvitamin D-3, as well as for examining factors which contribute to osteoblast-specific regulation of gene expression. Most of these studies have focused on transactivation. We report the identification of a sequence in the first intron of the rat osteocalcin gene which suppresses the expression of osteocalcin-CAT fusion genes approximately 10-fold in ROS 17/2.8 and UMR 106 osteosarcoma cells. Mutation of a TTTCTTT motif in the first intron abolishes this suppression. The silencing effect of this motif is also observed after bone morphogenic protein-2 (BMP-2)-induced expression of the osteoblastic phenotype in the MLB13MYC clone 17 cell line. Mutation of the splice donor site does not affect suppression by these sequences in ROS 17/2.8 cells. When multimerized and placed upstream of the native osteocalcin promoter, these sequences retain their ability to mediate transcriptional repression. Electrophoresis mobility shift analysis demonstrates a specific protein-DNA interaction with the TTTCTTT motif in nuclear extracts from ROS 17/2.8, UMR 106, and MLB13MYC clone 17 cells but not those from COS-7 kidney cells. The mutation of this motif, which abolishes suppressing activity in the native context, also abolishes binding. The presence and activity of this suppressor in cells of the osteoblast lineage suggest that it is expressed with other cell-specific transcriptional regulators of the osteocalcin gene, coordinately regulating expression of this gene in bone cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [DK36597] NR 28 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 20 PY 1996 VL 35 IS 33 BP 11005 EP 11011 DI 10.1021/bi960723o PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VD054 UT WOS:A1996VD05400049 PM 8718894 ER PT J AU Chen, JD Yang, QC Yang, AG Marasco, WA Chen, SY AF Chen, JD Yang, QC Yang, AG Marasco, WA Chen, SY TI Intra- and extracellular immunization against HIV-1 infection with lymphocytes transduced with an AAV vector expressing a human anti-gp120 antibody SO HUMAN GENE THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; HUMAN GENE-THERAPY; CD4 BINDING-SITE; ADENOASSOCIATED VIRUS; SOLUBLE CD4; ENVELOPE GLYCOPROTEIN; T-CELLS; GP120; NEUTRALIZATION AB Recently, ae developed a novel anti-HIV-1 approach by transducing an anti-gp120 antibody gene into lymphocytes, resulting in the resistance to HIV-1 infection by the combined intra- and extracellular binding activities of the neutralizing antibody, To extend this study, we improved the co-expression of the heavy and light chains of the Fab105 fragment of the anti-gp120 antibody F105 by using an internal ribosome entry site (IRES) sequence. The Fabl05 expression cassette was then cloned into an adeno-associated virus (AAV) shuttle vector, and encapsidated recombinant AAV-Fab105 vectors were produced. The Fab105 antibody gene was shown to be transduced into human lymphocytes by using the recombinant AAV viruses, The transduced lymphocytes were able to produce and secrete the Fab105 fragments, while maintaining their normal morphology, growth rates, and responsiveness to mitogen stimulation, The infection of several primary HIV-1 patient isolates was effectively blocked in the transduced lymphocytes. This study indicates that the combined intra- and extracellular immunization approach may be useful for the treatment of HIV-1-infected patients. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT CANC BIOL,CTR COMPREHENS CANC,WINSTON SALEM,NC 27157. SALK INST BIOL STUDIES,SAN DIEGO,CA 92816. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NR 47 TC 31 Z9 31 U1 0 U2 0 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 AUG 20 PY 1996 VL 7 IS 13 BP 1515 EP 1525 DI 10.1089/hum.1996.7.13-1515 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD322 UT WOS:A1996WD32200004 PM 8864752 ER PT J AU Luo, C Shaw, KTY Raghavan, A Aramburu, J GarciaCozar, F Perrino, BA Hogan, PG Rao, A AF Luo, C Shaw, KTY Raghavan, A Aramburu, J GarciaCozar, F Perrino, BA Hogan, PG Rao, A TI Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein phosphatase; nuclear localization sequence; immunosuppression; T cell activation; signal transduction ID ACTIVATED T-CELLS; CYCLOSPORINE-A; NF-AT; IMMUNOSUPPRESSIVE DRUGS; PHOSPHATASE-ACTIVITY; LYMPHOCYTES-T; DNA-BINDING; B-CELLS; PROTEIN; INDUCTION AB The nuclear import of the nuclear factor of activated T cells (NFAT)-family transcription factors is initiated by the protein phosphatase calcineurin. Here we identify a regulatory region of NFAT1, N terminal to the DNA-binding domain, that controls nuclear import of NFAT1, The regulatory region of NFAT1 binds directly to calcineurin, is a substrate for calcineurin in vitro, and shows regulated subcellular localization identical to that of full-length NFAT1. The corresponding region of NFATc likewise binds calcineurin, suggesting that the efficient activation of NFAT1 and NFATc by calcineurin reflects a specific targeting of the phosphatase to these proteins, The presence in other NFAT-family transcription factors of several sequence motifs from the regulatory region of NFAT1, including its probable nuclear localization sequence, indicates that a conserved protein domain may control nuclear import of all NFAT proteins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. RI Garcia-Cozar, Francisco/A-6212-2013; Aramburu, J/G-8991-2014 OI Garcia-Cozar, Francisco/0000-0003-3720-259X; Aramburu, J/0000-0001-9279-9523 FU NCI NIH HHS [CA42471]; NIGMS NIH HHS [GM41292, GM46227] NR 55 TC 136 Z9 140 U1 0 U2 7 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 AUG 20 PY 1996 VL 93 IS 17 BP 8907 EP 8912 DI 10.1073/pnas.93.17.8907 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400023 PM 8799126 ER PT J AU Liang, F Romanienko, PJ Weaver, DT Jeggo, PA Jasin, M AF Liang, F Romanienko, PJ Weaver, DT Jeggo, PA Jasin, M TI Chromosomal double-strand break repair in Ku80-deficient cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE xrs-6 cell; radiation sensitive mutants; I-SceI endonuclease; homologous recombination; end-joining ID RAY SENSITIVE MUTANTS; V(D)J RECOMBINATION; DNA-REPAIR; MAMMALIAN-CELLS; HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; STEM-CELLS; MOUSE; GENE; ENDONUCLEASE AB The x-ray sensitive hamster cell line xrs-6 is deficient in DNA double-strand break (DSB) repair and exhibits impaired V(D)J recombination. The molecular defect in this line is in the 80-kDa subunit of the Ku autoantigen, a protein that binds to DNA ends and recruits the DNA-dependent protein kinase to DNA. Using an I-SceI endonu clease expression system, chromosomal DSB repair was examined in xrs-6 and parental CHO-K1 cell lines, A DSB in chromosomal DNA increased the yield of recombinants several thousand-fold above background in both the xrs-6 and CHO-K1 cells, with recombinational repair of DSBs occurring in as many as 1 of 100 cells electroporated with the endonuclease expression vector. Thus, recombinational repair of chromosomal DSBs can occur at substantial levels in mammalian cells and it is not grossly affected in our assay by a deficiency of the Ku autoantigen. Rejoining of broken chromosome ends (end-joining) near the site of the DSB was also examined. In contrast to recombinational repair, end-joining was found to be severely impaired in the xrs-6 cells, Thus, the Ku protein appears to play a critical role in only one of the chromosomal DSB repair pathways. C1 SLOAN KETTERING INST,PROGRAM MOL BIOL,NEW YORK,NY 10021. SLOAN KETTERING INST,PROGRAM GENET & CELL BIOL,NEW YORK,NY 10021. CORNELL UNIV,GRAD SCH MED SCI,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. UNIV SUSSEX,MRC,CELL MUTAT UNIT,BRIGHTON BN1 9RR,E SUSSEX,ENGLAND. NR 37 TC 145 Z9 145 U1 0 U2 4 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 AUG 20 PY 1996 VL 93 IS 17 BP 8929 EP 8933 DI 10.1073/pnas.93.17.8929 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400027 PM 8799130 ER PT J AU Grafi, G Burnett, RJ Helentjaris, T Larkins, BA DeCaprio, JA Sellers, WR Kaelin, WG AF Grafi, G Burnett, RJ Helentjaris, T Larkins, BA DeCaprio, JA Sellers, WR Kaelin, WG TI A maize cDNA encoding a member of the retinoblastoma protein family: Involvement in endoreduplication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle; RepA; wheat dwarf virus ID ONCOGENIC POINT MUTATIONS; LARGE T-ANTIGEN; INCOMPLETE PENETRANCE; GENE-PRODUCT; CELL-CYCLE; BINDING; PHASE; INACTIVATION; EXPRESSION; INHIBITORS AB Retinoblastoma (RB-1) is a tumor suppressor gene that encodes a 105-kDa nuclear phosphoprotein, To date, RE genes have been isolated only from metazoans. We have isolated a cDNA from maize endosperm whose predicted protein product (ZmRb) shows homology to the ''pocket'' A and B domains of the Rb protein family, We found ZmRb behaves as a pocket protein based on its ability to specifically interact with oncoproteins encoded by DNA tumor viruses (E7, T-Ag, E1A), ZmRb can interact in vitro and in vivo with the replication-associated protein, RepA, encoded by the wheat dwarf virus, The maize Rb-related protein undergoes changes in level and phosphorylation state concomitant with endoreduplication, and it is phosphorylated in vitro by an S-phase kinase from endoreduplicating endosperm cells, Together, our results suggest that ZmRb is a representative of the pocket protein family and may play a role in cell cycle progression, Moreover, certain plant monopartite geminiviruses may operate similarly to mammalian DNA viruses, by targeting and inactivating the retinoblastoma protein, which otherwise induces G(1) arrest. C1 UNIV ARIZONA,DEPT PLANT SCI,TUCSON,AZ 85721. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 34 TC 184 Z9 196 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 AUG 20 PY 1996 VL 93 IS 17 BP 8962 EP 8967 DI 10.1073/pnas.93.17.8962 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400033 PM 8799136 ER PT J AU Kieran, MW Perkins, AC Orkin, SH Zon, LI AF Kieran, MW Perkins, AC Orkin, SH Zon, LI TI Thrombopoietin rescues in vitro erythroid colony formation from mouse embryos lacking the erythropoietin receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-MPL LIGAND; HUMAN RECOMBINANT ERYTHROPOIETIN; BONE-MARROW-CELLS; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; HEMATOPOIETIC-CELLS; IN-VITRO; EXPRESSION; GROWTH; MICE AB The interaction of the hormone erythropoietin and its receptor (EpoR) is thought to be required for normal hematopoiesis. To define the role of EpoR in this process, the murine EpoR was disrupted by homologous recombination. Mice lacking the EpoR died in utero at embryonic day 11-12.5 with severe anemia. Embryonic erythropoiesis was markedly diminished, while fetal liver hematopoiesis was blocked at the proerythroblast stage. Other cell types known to express EpoR, including megakaryocytes, mast, and neural cells were morphologically normal. Reverse transcription-coupled PCR analysis of RNA from embryonic yolk sac, peripheral blood, and fetal liver demonstrated near normal transcripts levels for EKLF, thrombopoietin (Tpo), c-MPL, GATA-1, GATA-2, and alpha- and embryonic beta H1-globin but none for adult beta maj-globin. While colony-forming unit-erythroid (CFU-E) and burst-forming unit-erythroid (BFU-E) colonies were not present in cultures derived from EpoR-/- liver or yolk sec cells, hemoglobin-containing BFU-E colonies were detected in cultures treated with recombinant Tpo and lilt ligand or with Tpo and interleukin 3 and 11. Rescued BFU-E colonies expressed adult beta-globin and c-MPL acid appeared morphologically normal. Thus, erythroid progenitors are formed in vivo in mice lacking the EpoR, and our studies demonstrate that a signal transmitted through the Tpo receptor c-MPL stimulates proliferation and terminal differentiation of these progenitors in vitro. C1 CHILDRENS HOSP, DEPT PEDIAT, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. RI Perkins, Andrew/M-3216-2014; OI Perkins, Andrew/0000-0003-3644-7093; Kieran, Mark/0000-0003-2184-7692 NR 36 TC 128 Z9 130 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 AUG 20 PY 1996 VL 93 IS 17 BP 9126 EP 9131 DI 10.1073/pnas.93.17.9126 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400062 PM 8799165 ER PT J AU Sternini, C Spann, M Anton, B Keith, DE Bunnett, NW vonZastrow, M Evans, C Brecha, NC AF Sternini, C Spann, M Anton, B Keith, DE Bunnett, NW vonZastrow, M Evans, C Brecha, NC TI Agonist-selective endocytosis of mu opioid receptor by neurons in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE opioid receptors; opiate alkaloids; motility; enteric neurons; motor neurons ID PROTEIN-COUPLED RECEPTOR; SUBSTANCE-P; MOLECULAR-BIOLOGY; INTERNALIZATION; RESENSITIZATION; SEQUESTRATION; TRAFFICKING; MECHANISMS; ENKEPHALIN; PEPTIDES AB Opiate alkaloids are potent analgesics that exert multiple pharmacological effects in the nervous system by activating G protein-coupled receptors. Receptor internalization upon stimulation may be important for desensitization and resensitization, which affect cellular responsiveness to ligands. Here, we investigated the agonist-induced internalization of the mu opioid receptor (MOR) in vivo by using the guinea pig ileum as a model system and immunohistochemistry with an affinity-purified antibody to the C terminus of rat MOR, Antibody specificity was confirmed by the positive staining of human embryonic kidney 293 cells transfected with epitope-tagged MOR cDNA, by the lack of staining of cells transfected with the delta or kappa receptor cDNA, and by the abolition of staining when the MOR antibody was preadsorbed with the MOR peptide fragment, Abundant MOR immunoreactivity (MOR-IR) was localized to the cell body, dendrites, and axonal processes of myenteric neurons, Immunostaining was primarily confined to the plasma membrane of cell bodies and processes. Within 15 min of an intraperitoneal injection of the opiate agonist etorphine, intense MOR IR was present in vesiclelike structures, which were identified as endosomes by confocal microscopy, At 30 min, MOR-IR was throughout the cytoplasm and in perinuclear vesicles, MOR-IR was still internalized at 120 min, Agonist-induced endocytosis was completely inhibited by the opiate antagonist naloxone. Interestingly, morphine, a high-affinity MOR agonist, did not cause detectable internalization, but it partially inhibited the etorphine-induced MOR endocytosis. These results demonstrate the occurrence of agonist-selective MOR endocytosis in neurons naturally expressing this receptor in vivo and suggest the existence of different mechanisms regulating cellular responsiveness to ligands. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT NEUROBIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,OPIOID RES CTR,LOS ANGELES,CA 90024. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MOL & CELLULAR PHARMACOL,SAN FRANCISCO,CA 94143. RP Sternini, C (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CURE,DIGEST DIS RES CTR,11301 WILSHIRE BLVD,BLDG 115,ROOM 203,LOS ANGELES,CA 90073, USA. FU NIDA NIH HHS [DA 05010, P50 DA005010]; NIDDK NIH HHS [DK 39957, DK 41301] NR 42 TC 250 Z9 252 U1 0 U2 8 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 AUG 20 PY 1996 VL 93 IS 17 BP 9241 EP 9246 DI 10.1073/pnas.93.17.9241 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VD434 UT WOS:A1996VD43400082 PM 8799185 ER PT J AU Agarwal, RK Kugel, G Karuri, A Gwosdow, AR Kumar, MSA AF Agarwal, RK Kugel, G Karuri, A Gwosdow, AR Kumar, MSA TI Effect of low and high doses of nitrous oxide on preproenkephalin mRNA and its peptide methionine enkephalin levels in the hypothalamus SO BRAIN RESEARCH LA English DT Article DE preproenkephalin; mRNA; opioid; nitrous oxide; hypothalamus; met-enkephalin ID KAPPA-OPIOID RECEPTORS; RATS; ANALGESIA; MICE; BRAIN; ANTINOCICEPTION; TOLERANCE; REVERSAL; NALOXONE; EXPOSURE AB The effect of exposure to nitrous oxide (N2O) on the levels of preproenkephalin mRNA in the hypothalamus of rats was examined. In the first experiment, rats were exposed to 1000 ppm N2O for 8 h a day over 4 days. Compared with controls (which were exposed to air over the same duration), the N2O exposed animals exhibited significant elevations in preproenkephalin mRNA levels in the hypothalamus. In a second experiment, rats were exposed to 60% N2O or air for 12, 24 and 48 h duration, and hypothalamic levels of preproenkephalin mRNA as well as methionine enkephalin were analyzed. Compared with controls, N2O exposed rats exhibited significant elevations in preproenkephalin mRNA levels. The levels on preproenkephalin mRNA were significantly higher after 48 h of N2O exposure than after 12 h of N2O exposure. Similarly, the concentration of methionine enkephalin was significantly higher after 24 and 48 h of exposure to N2O than after exposure to 12 h of N2O or air. These results indicate that (a) exposure to N2O results in significant elevations in preproenkephalin mRNA levels, (b) the increased preproenkephalin mRNA levels appear to be proportional to the concentration of N2O exposure as well as the duration of N2O exposure, and (c) N2O-induced elevation in preproenkephalin mRNA levels is associated with corresponding increase in tissue concentrations of methionine enkephalin. In total, these results suggest that N2O selectively stimulates synthesis of methionine enkephalin in the diencephalic region of the brain. C1 TUFTS UNIV,SCH VET MED,DEPT ANAT & CELLULAR BIOL,NORTH GRAFTON,MA 01536. TUFTS UNIV,SCH DENT MED,DEPT RESTORAT DENT,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 31 TC 4 Z9 4 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 AUG 19 PY 1996 VL 730 IS 1-2 BP 47 EP 51 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VH291 UT WOS:A1996VH29100005 PM 8883887 ER PT J AU Benson, TE Brown, MC AF Benson, TE Brown, MC TI Synapses from medial olivocochlear branches in the inferior vestibular nucleus SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cytoarchitecture; myeloarchitecture; collateral; efferent; ultrastructure ID BRAIN-STEM; COCHLEAR-NUCLEUS; RESPONSE PROPERTIES; EFFERENT NEURONS; GRANULE CELLS; GUINEA-PIG; CAT; MOUSE; FIBERS; RAT AB Olivocochlear neurons are auditory efferent neurons that convey information from the brainstem to the auditory periphery. With light and electron microscopy, using mice, we studied the central branches of medial olivocochlear neurons that are given off to the inferior vestibular nucleus. At the level of the electron microscope, the branches form synapses. The synapses are asymmetric with round vesicles, suggesting that they are excitatory. The synapses are formed mainly onto neuronal dendrites. These dendrites have a large range of diameters, and they may emanate from several types of target neurons. These results indicate that the inferior vestibular nucleus is an integrating center for vestibular, auditory, and other types of information, but the results do not fit with current theories about the function of the olivocochlear system. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. FU NIDCD NIH HHS [DC 01089] NR 41 TC 7 Z9 7 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 19 PY 1996 VL 372 IS 2 BP 176 EP 188 DI 10.1002/(SICI)1096-9861(19960819)372:2<176::AID-CNE2>3.0.CO;2-0 PG 13 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VC486 UT WOS:A1996VC48600002 PM 8863124 ER PT J AU Si, JT Luo, ZJ Mei, L AF Si, JT Luo, ZJ Mei, L TI Induction of acetylcholine receptor gene expression by ARIA requires activation of mitogen-activated protein kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS; EPSILON-SUBUNIT GENE; NEUROMUSCULAR-JUNCTION; TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; SKELETAL-MUSCLE; NDF HEREGULIN; MAP KINASE; DIFFERENTIATION AB Transcription of genes encoding nicotinic acetylcholine receptor (AChR) subunits (alpha, beta, gamma or epsilon, and delta) is highest in nuclei localized to the synaptic region of the muscle, which contributes to maintain a high density of AChRs at the postjunctional membrane. ARIA (AChR inducing activity) is believed to be the trophic factor utilized by motor neurons to stimulate AChR synthesis in the subsynaptic area. To elucidate the signaling mechanism initiated by ARIA, we established stable C2C12 cell lines carrying the nuclear lacZ gene under the control of the mouse epsilon subunit promoter or chicken ru subunit promoter. ARIA stimulated tyrosine phosphorylation of erbB proteins in these C2C12 cells within 15 s with a peak at 5 min. Immediately following tyrosine phosphorylation of erbB proteins, mitogen-activated protein (MAP) kinase was activated which occurred within 30 s and peaked at 8 min after ARIA stimulation. Concomitantly, expression of AChR genes was induced by ARIA. ARIA-induced AChR subunit transgene expression was observed only in differentiated myotubes and not in myoblasts, suggesting that downstream signaling component(s) are regulated in a manner dependent on the myogenic program. Inhibition of the MAP kinase activity by using a specific MAP kinase kinase inhibitor or by overexpressing dominant negative mutants of Raf or MAP kinase kinase attenuated or abolished the ARIA-induced activation of AChR alpha and epsilon subunit gene expression. These results indicate that regulation of AChR gene expression by ARIA ill C2C12 cells requires activation of the MAP kinase signaling pathway. C1 UNIV VIRGINIA,SCH MED,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. MASSACHUSETTS GEN HOSP,DIABET UNIT,CHARLESTOWN,MA 02129. RI Mei, Lin/G-8755-2012 FU NINDS NIH HHS [NS34062] NR 55 TC 90 Z9 93 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 AUG 16 PY 1996 VL 271 IS 33 BP 19752 EP 19759 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900022 PM 8702681 ER PT J AU Xu, BXC Wang, XZ Darns, CJ Kopchick, JJ AF Xu, BXC Wang, XZ Darns, CJ Kopchick, JJ TI Growth hormone promotes the association of transcription factor STAT5 with the growth hormone receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE L-CELLS; TYROSINE-PHOSPHORYLATED PROTEINS; SIGNAL-TRANSDUCTION; CYTOKINE RECEPTORS; INTERFERON-GAMMA; GH RECEPTORS; DNA-BINDING; BETA-CHAIN; ACTIVATION; PROLACTIN AB Members of the cytokine/growth hormone (GH)/prolactin receptor superfamily transduce signals by association and activation of JAK tyrosine kinases. For GH receptor (GHR), both JAK2 and the GHR undergo tyrosine phosphorylation upon GH stimulation. Also, GH has recently been shown to activate the transcription factor STAT5 by tyrosine phosphorylation. In the present study, we demonstrate that GH induces rapid tyrosine phosphorylation of different isoforms of STAT5 in mouse L cells stably transfected with a cDNA encoding porcine GHR (pGHR). In this cell system, STAT5 directly interacts with the GHR in a GH-dependent manner. Additionally, GH-induced tyrosine phosphorylation of STAT5 and the interaction of STATE with GHR can be observed in mouse 3T3-F442A cells which express endogenous mouse GHR. Interestingly; when cDNAs encoding the two mouse STAT5 homologs (STAT5A and STAT5B) were individually transfected into mouse L cells expressing pGHR, only STAT5A demonstrated the ability to interact with the pGHR and subsequently underwent GH-dependent tyrosine phosphorylation. STAT5B did not. Therefore, the GH-dependent interaction of a particular STATE with tyrosine-phosphorylated GHR may play an important role in GH-mediated signal transduction. C1 OHIO UNIV,EDISON BIOTECHNOL INST,KONNEKER RES LABS THE RIDGES,MOL & CELLULAR BIOL PROGRAM,ATHENS,OH 45701. OHIO UNIV,DEPT SCI BIOL,ATHENS,OH 45701. MASSACHUSETTS GEN HOSP,GENE THERAPY CTR,BOSTON,MA 02114. NR 43 TC 39 Z9 40 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 AUG 16 PY 1996 VL 271 IS 33 BP 19768 EP 19773 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900024 PM 8702683 ER PT J AU Binder, BM OConnor, TM Bownds, MD Arshavsky, VY AF Binder, BM OConnor, TM Bownds, MD Arshavsky, VY TI Phosphorylation of non-bleached rhodopsin in intact retinas and living frogs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROD OUTER SEGMENTS; PROTEIN-KINASE-C; PHOTORECEPTOR-MEMBRANES; CYCLIC-GMP; PHOSPHODIESTERASE ACTIVATION; VERTEBRATE PHOTORECEPTORS; VISUAL TRANSDUCTION; LIGHT; PHOTOTRANSDUCTION; DEPHOSPHORYLATION AB The photoresponse in retinal photoreceptors begins when a molecule of rhodopsin is excited by a photon of light. Photoexcited rhodopsin activates an enzymatic cascade including the G-protein transducin and cyclic GMP phosphodiesterase. As a result, cytoplasmic cyclic GMP concentration is decreased and the photoresponse is initiated. This process is terminated when rhodopsin is phosphorylated by rhodopsin kinase and subsequently blocked by a protein called arrestin. It has been noted by several investigators that light can cause phosphorylation of not only photoexcited but also non-excited rhodopsin in rod photoreceptors. A goal of this study was to determine how much non-bleached rhodopsin is phosphorylated. To determine how the structural integrity of the photoreceptor influences the extent of non-breached rhodopsin phosphorylation, we studied the reaction in electropermeabilized rod outer segments, in rod outer segments still attached to isolated retinas and in living frogs. In the first two preparations, we found that the maximum extent of non-bleached rhodopsin phosphorylation was approximately 1% of the total rhodopsin pool. In living frogs, the maximal amount of non-bleached rhodopsin phosphorylation was similar to 2% of the total rhodopsin pool and occurred after prolonged illumination by the relatively dim light intensity of 20 lux. These data appear to exclude models for light adaptation that postulate high levels of phosphorylation of non-bleached rhodopsin in rod photoreceptors. C1 HARVARD UNIV, SCH MED, MASSACHUSETTS EYE & EAR INFIRM, HOWE LAB OPHTHALMOL, BOSTON, MA 02114 USA. UNIV WISCONSIN, MOL BIOL LAB, MADISON, WI 53706 USA. UNIV WISCONSIN, DEPT ZOOL, MADISON, WI 53706 USA. FU NEI NIH HHS [EY-00463, EY-10336] NR 44 TC 25 Z9 25 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 AUG 16 PY 1996 VL 271 IS 33 BP 19826 EP 19830 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900032 PM 8702691 ER PT J AU Gardella, TJ Luck, MD Jensen, GS Usdin, TB Juppner, H AF Gardella, TJ Luck, MD Jensen, GS Usdin, TB Juppner, H TI Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-8 receptor agonist SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NMR SOLUTION STRUCTURE; HUMORAL HYPERCALCEMIA; EXPRESSION CLONING; ADENYLATE-CYCLASE; PLASMA-MEMBRANE; BINDING DOMAINS; COMMON RECEPTOR; FRAGMENT 1-34; ROS 17/2.8; PROTEIN AB Most of the bone and kidney-related functions of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) are thought to be mediated by the PTH/PTHrP receptor. Recently, a homologous receptor, the PTH-2 receptor, was obtained from rat and human brain cDNA libraries. This receptor displayed the remarkable property of responding potently to PTH, but not to PTHrP. To begin to define residues involved in the ligand specificity of the PTH-2 receptor, we studied the interaction of several PTH/PTHrP hybrid ligands and other related peptide analogs with the human PTH-2 receptor The results showed that two sites in PTH and PTHrP fully account for the different potencies that the tu o ligands exhibited with PTH-2 receptors; residue 5 (His in PTHrP and Ile in PTH) determined signaling capability, while residue 23 (Phe in PTHrP and Trp in PTH) determined binding affinity. By changing these two residues of PTHrP to the corresponding residues of PTH, we were able to convert PTHrP into a ligand that avidly bound to the PTH-2 receptor and fully and potently stimulated cAMP formation, Changing residue 23 alone yielded [Trp(23)]hPTHrP-(1-36), which was an antagonist for the PTH-2 receptor, but a fall agonist for the PTH/PTHrP receptor. Residues 5 and 23 in PTH and PTHrP thus play keg roles in signaling and binding interactions, respectively, with the PTH-2 receptor. Receptor-selective agonists and antagonists derived hom these studies could help to identify the biological role of the PTH-2 receptor and to map specific sites of ligand-receptor interaction. C1 MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP Gardella, TJ (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794, DK-50708] NR 30 TC 69 Z9 69 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 16 PY 1996 VL 271 IS 33 BP 19888 EP 19893 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900042 PM 8702701 ER PT J AU Walker, WH Girardet, C Habener, JF AF Walker, WH Girardet, C Habener, JF TI Alternative exon splicing controls a translational switch from activator to repressor isoforms of transcription factor CREB during spermatogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING PROTEIN CREB; MESSENGER-RNAS; GENE; ADENOSINE-3',5'-MONOPHOSPHATE; EXPRESSION; CELLS; INITIATION; CONTAINS; ELEMENTS; ENHANCER AB The cAMP/protein kinase A signaling pathway activates the cAMP-responsive transcription factor CREB. Here we describe a unique alternative RNA splicing event that occurs during the development of germ cells in the testis, resulting in a translational switch from an mRNA encoding activator CREB to an mRNA encoding novel inhibitor CREB isoforms (I-CREBs). Alternative splicing of an additional exon into the CREB mRNA in mid to late pachytene spermatocytes results in the premature termination of translation and consequent downstream reinitiation of translation producing I-CREBs, The I-CREBs down-regulate cAMP activated gene expression by inhibiting activator CREB from binding to cAMP response elements. Further, the developmental stage-specific expression of I-CREBs in germ cells of the seminiferous tubules correlates with the cyclical down-regulation of activator CREB, suggesting that I-CREBs repress expression of the cAMP-inducible CREB gene as well as other genes transiently induced by cAMP during the 12-day cycle of spermatogenesis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,LAB MOL ENDOCRINOL,BOSTON,MA 02114. CTR MED UNIV GENEVA,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND. FU NIDDK NIH HHS [DK25532] NR 24 TC 61 Z9 61 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 AUG 16 PY 1996 VL 271 IS 33 BP 20145 EP 20150 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900079 PM 8702738 ER PT J AU Kalandadze, A Galleno, M Foncerrada, L Strominger, JL Wucherpfennig, KW AF Kalandadze, A Galleno, M Foncerrada, L Strominger, JL Wucherpfennig, KW TI Expression of recombinant HLA-DR2 molecules - Replacement of the hydrophobic transmembrane region by a leucine zipper dimerization motif allows the assembly and secretion of soluble DR alpha beta heterodimers SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; T-CELL CLONES; CLASS-II; MHC MOLECULES; PEPTIDES; ANTIGEN; SEQUENCE; BINDING; REQUIREMENTS AB Major histocompatability complex (MHC) class II molecules are membrane-anchored heterodimers that present peptides on the surface of antigen presenting cells to T cells. Soluble HLA-DR2 molecules were expressed for structural and functional characterization of the MHC/peptide/T cell receptor recognition unit. The alpha and beta chains of DR2 (encoded by the DRA, DRB1*1501 genes) did not assemble in mammalian or insect cell lines when the transmembrane regions of one or both chains were truncated. The hydrophobic transmembrane regions of DR alpha and DR beta facilitate assembly of the heterodimer and were therefore replaced by the leucine zipper dimerization motifs from the transcription factors Fos and Jun, which assemble as a soluble, tightly packed coiled coil structure. The DR alpha-Fos and DR beta-Jun constructs were expressed in a methyltrophic yeast, Pichia pastoris, using the alpha-mating factor secretion signal to direct expression to the secretory pathway. DR alpha beta heterodimers were purified from supernatants using an antibody specific for the DR alpha beta heterodimer. Kinetic and quantitative peptide binding experiments demonstrated that recombinant DR2 molecules were efficiently loaded with an antigenic peptide. Soluble DR2 molecules can be used to define structural aspects of the MHC/pepticle/T cell receptor interaction and to study the signals induced by T cell receptor recognition of soluble DR2-peptide complexes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. INVITROGEN CORP,SAN DIEGO,CA 92121. FU NCI NIH HHS [CA47554] NR 26 TC 69 Z9 71 U1 1 U2 3 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 AUG 16 PY 1996 VL 271 IS 33 BP 20156 EP 20162 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900081 PM 8702739 ER PT J AU Segal, RA Bhattacharyya, A Rua, LA Alberta, JA Stephens, RM Kaplan, DR Stiles, CD AF Segal, RA Bhattacharyya, A Rua, LA Alberta, JA Stephens, RM Kaplan, DR Stiles, CD TI Differential utilization of Trk autophosphorylation sites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; NEURONAL DIFFERENTIATION; SIGNAL-TRANSDUCTION; NEUROTROPHIC FACTOR; PC12 CELLS; MAP KINASE; INSULIN-RECEPTOR; BINDING-SITES; ACTIVATION AB Tyrosine autophosphorylation controls the catalytic and signaling activities of the neurotrophin receptors, the Trks. To analyze the regulation of distinct tyrosine sites, we generated a panel of antibodies that report the phosphorylation state of individual tyrosines within the Trk cytoplasmic domain. Using pheochromocytoma-derived cell lines, we show that individual tyrosines within the nerve growth factor receptor TrkA are phosphorylated in a non-coordinate fashion following receptor activation. The non-coordinate response of these tyrosines reflects their separate functions in regulating the catalytic and signaling activities of Trk receptors. The differential utilization of distinct sites on Trk receptor tyrosine kinases suggests that the receptor can specify both the timing and the nature of neurotrophin-stimulated signal transduction pathways. Moreover, we show that these Trk autophosphorylation sites, which have hitherto been mapped and characterized only in non-neuronal cell lines, are activated in normal neurons in response to ligand stimulation. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 41 TC 98 Z9 100 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 AUG 16 PY 1996 VL 271 IS 33 BP 20175 EP 20181 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VC669 UT WOS:A1996VC66900084 PM 8702742 ER PT J AU Morens, DM Grandinetti, A Davis, JW Ross, GW White, LR Reed, D AF Morens, DM Grandinetti, A Davis, JW Ross, GW White, LR Reed, D TI Evidence against the operation of selective mortality in explaining the association between cigarette smoking and reduced occurrence of idiopathic Parkinson disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Parkinson disease; smoking ID PROTECTION; RISK AB To investigate the association between idiopathic Parkinson disease (IPD) and reduced frequency of prior cigarette smoking, the authors compared the 29-year follow-up mortality rates and IPD incidence rates of men who were either cigarette smokers or nonsmokers at the time of enrollment in the Honolulu Heart Study (1965-1968). Based on IPD cases detected up to June 30, 1994, the age-adjusted incidence rate in smokers was less than half ?hat in nonsmokers: 34.4 versus 94.2 cases per 100,000 person-years of pre-illness follow-up, respectively. When data were stratified by 5-year age group, lower IPD incidence in smokers was observed at all ages between 50 and 90 years. Age-specific mortality trends for smokers and nonsmokers with and without IPD suggested that increased mortality in IPD patients was mostly associated with IPD itself and not with smoking. The slight excess mortality in smokers without IPD, versus nonsmokers without IPD, appeared insufficient to account for the ''missing'' incident IPD cases in smokers. These IPD incidence and mortality data are not highly consistent with the ''selective mortality'' hypothesis, which attributes reduced prior smoking frequency, typically reported by persons with IPD, to accelerated mortality in undiagnosed IPD-affected persons who smoker The ''protective'' association of cigarette smoking with IPD occurrence may thus be real, suggesting the need for further study of biologic mechanisms of protection. C1 UNIV HAWAII,SCH MED,HONOLULU,HI 96822. EAST WEST CTR,HONOLULU,HI 96848. HAWAII OSTEOPOROSIS CTR,HONOLULU,HI. NIA,NIH,HONOLULU ASIA AGING STUDY,HONOLULU,HI. US DEPT VET AFFAIRS,HONOLULU,HI. BUCK CTR RES AGING,NOVATO,CA. RP Morens, DM (reprint author), UNIV HAWAII,SCH PUBL HLTH,PROGRAM EPIDEMIOL,BIOMED D103,1960 EAST WEST RD,HONOLULU,HI 96822, USA. FU NINDS NIH HHS [NS 30371] NR 9 TC 44 Z9 46 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 1996 VL 144 IS 4 BP 400 EP 404 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VB181 UT WOS:A1996VB18100009 PM 8712197 ER PT J AU Zemishlany, Z Davidson, M AF Zemishlany, Z Davidson, M TI Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid concentration in normal subjects SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety; plasma HVA; schizophrenia; stress; cathecholamines ID SCHIZOPHRENIC-PATIENTS; PANIC DISORDER; 3,4-DIHYDROXYPHENYLACETIC ACID; NORADRENERGIC FUNCTION; PSYCHOLOGICAL STRESS; LOCUS COERULEUS; GROWTH-HORMONE; DOPAMINE; INCREASE; CORTISOL AB The present study was undertaken to investigate if acute anxiety can affect plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels have been associated with severity of schizophrenic symptoms, the results of this study will help determine if the pHVA elevations are directly related to psychosis or if anxiety is also a contributory factor. Anxiety was provoked in IO young normal subjects by a combined paradigm of mental arithmetic task and threat of electrical shock. A significant increase in self-ratings of anxiety, blood pressure, and plasma levels of norepinephrine, 3-methoxy-4-hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used was effective in provoking anxiety; however, anxiety did not affect pHVA concentrations, The results may support the notion that increased pHVA levels in severely ill schizophrenic patients are related to the schizophrenic pathophysiology rather than to anxiety. C1 BRONX VET ADM MED CTR,PSYCHIAT SERV,NEW YORK,NY. MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY. NR 42 TC 2 Z9 2 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 AUG 15 PY 1996 VL 40 IS 4 BP 247 EP 252 DI 10.1016/0006-3223(95)00390-8 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VC340 UT WOS:A1996VC34000002 PM 8871770 ER PT J AU Bakardjiev, AI Barnes, PD Goumnerova, LC Black, PM Pomeroy, SL Billett, A Loeffler, JS Tarbell, NJ AF Bakardjiev, AI Barnes, PD Goumnerova, LC Black, PM Pomeroy, SL Billett, A Loeffler, JS Tarbell, NJ TI Magnetic resonance imaging changes after stereotactic radiation therapy for childhood low grade astrocytoma SO CANCER LA English DT Article DE astrocytoma; pediatrics; radiation; stereotactic; magnetic resonance imaging ID CEREBRAL HEMISPHERES; BRAIN-TUMORS; CHILDREN; RADIOTHERAPY; MANAGEMENT; MR; IRRADIATION; SURVIVAL AB BACKGROUND. Stereotactic radiotherapy (SRT) is fractionated radiotherapy delivered under stereotactic guidance to produce highly focal and precise therapy. We studied the incidence of imaging changes that can mimic tumor progression after completion of SRT for childhood low grade astrocytoma. METHODS. Between lune 1992 and September 1994, we prospectively treated 28 children with low grade astrocytomas with SRT. The patients ranged in age from 2 to 22 years (median: 10 yrs) and none had received prior radiation therapy or radiosurgery. Routine fractionation was employed (180-200 centigray [cGy]) to a total dose of 5220-6000 cGy over 5 to 6 weeks. All of the patients underwent initial and follow-up magnetic resonance imaging (MRI) according to protocol. RESULTS. Median clinical follow-up for the 28 patients was 24 months (range, 5-32 mos) with a median radiographic follow-up of 15 months (range, 3-26 mos). Fifteen patients had reduction in tumor size, one patient had stable disease. Twelve patients (43%) developed increased size of the lesion, increased signal intensity or enhancement, cysts or cavitations, and an increase in edema or mass effect on follow-up MRI. Most of these changes occurred between 9 and 12 months after the start of SRT and resolved or decreased by 15 to 21 months. All but one patient had normal or stable neurologic examinations. CONCLUSIONS. Treatment-related MRI changes are common after conventionally fractionated schedules using stereotactic radiation techniques for patients with low grade astrocytomas. These changes can be distinguished from tumor progression by their transient nature as well as the general absence of clinical symptoms. (C) 1996 American Cancer Society. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT ONCOL HEMATOL,BOSTON,MA 02115. FU NINDS NIH HHS [NIH 1P20NS3110-01] NR 28 TC 34 Z9 35 U1 1 U2 2 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 AUG 15 PY 1996 VL 78 IS 4 BP 864 EP 873 PG 10 WC Oncology SC Oncology GA VA437 UT WOS:A1996VA43700025 PM 8756383 ER PT J AU Schully, RE Henson, DE Nielsen, ML Ruby, SG Creasman, WT Fried, A Gershenson, DM Hart, WR Kempson, RL Page, DL Selvaggi, SM Coppock, DL Farrow, GM Gorstein, F Hammond, ME Hutter, RVP Min, KW Nash, G Oberman, HA Schwartz, IS Schlosnagle, DC Travers, H Webb, JH Weiss, LL Wick, MR AF Schully, RE Henson, DE Nielsen, ML Ruby, SG Creasman, WT Fried, A Gershenson, DM Hart, WR Kempson, RL Page, DL Selvaggi, SM Coppock, DL Farrow, GM Gorstein, F Hammond, ME Hutter, RVP Min, KW Nash, G Oberman, HA Schwartz, IS Schlosnagle, DC Travers, H Webb, JH Weiss, LL Wick, MR TI Practice protocol for the examination of specimens removed from patients with ovarian tumors - A basis for checklists SO CANCER LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; CELL TUMORS; CARCINOMA; CANCER; BORDERLINE; PATHOLOGY; STAGE C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NCI,EARLY DETECT BRANCH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. PATHOL CONSULTANTS,WICHITA,KS. HINSDALE HOSP,DEPT PATHOL & LAB MED,HINSDALE,IL. RP Schully, RE (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 37 TC 0 Z9 0 U1 0 U2 2 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 AUG 15 PY 1996 VL 78 IS 4 BP 927 EP 940 PG 14 WC Oncology SC Oncology GA VA437 UT WOS:A1996VA43700033 ER PT J AU Kharbanda, S Saleem, A Yuan, ZM Kraeft, S Weichselbaum, R Chen, LB Kufe, D AF Kharbanda, S Saleem, A Yuan, ZM Kraeft, S Weichselbaum, R Chen, LB Kufe, D TI Nuclear signaling induced by ionizing radiation involves colocalization of the activated p56/p53(lyn) tyrosine kinase with p34(cdc21) SO CANCER RESEARCH LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; LEUKEMIA-CELLS; SERINE KINASE; ASSOCIATION; DNA; PHOSPHORYLATION; PP60(C-SRC); MECHANISM AB The Src-like protein-tyrosine kinase p56/pko(lyn) associates with cell membranes and transduces signals from activated cell surface receptors, In the present work, cell fractionation and confocal microscopy studies demonstrate expression of Lyn in the nucleus, We also demonstrate that exposure of intact cells to ionizing radiation is associated with selective activation of nuclear Lyn, Similar findings have been obtained following irradiation of purified nuclei, Immunoprecipitation studies of nuclear lysates demonstrate radiation-induced binding of Lyn to p34(cdc2), Nuclear colocalization of Lyn with Cdc2 has been confirmed by confocal microscopy, Other studies with glutathione S-transferase-Lyn fusion proteins demonstrate that the binding of Lyn to nuclear Cdc2 is associated with inhibition of Cdc2 activity. These findings suggest that the association of activated Lyn with Cdc2 in the nucleus may contribute to regulation of a DNA damage-dependent premitotic checkpoint. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. UNIV CHICAGO,PRITZKER SCH MED,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. FU NCI NIH HHS [CA55241] NR 42 TC 57 Z9 58 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 AUG 15 PY 1996 VL 56 IS 16 BP 3617 EP 3621 PG 5 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600002 PM 8705993 ER PT J AU Wang, FL Wang, YB Wong, WK Liu, Y Addivinola, FJ Liang, P Chen, LB Kantoff, PW Pardee, AB AF Wang, FL Wang, YB Wong, WK Liu, Y Addivinola, FJ Liang, P Chen, LB Kantoff, PW Pardee, AB TI Two differentially expressed genes in normal human prostate tissue and in carcinoma SO CANCER RESEARCH LA English DT Article ID CELLS; MITOCHONDRIA; DISPLAY; RNA; TROPOMYOSIN; ONCOGENE; NUCLEAR AB Alterations in transcriptional control may contribute directly to carcinogenesis. king the differential display technique in prostate cancer cells compared to normal prostate epithelial cells, se identified a down-regulated gene and an up-regulated gene in canter cells. The down-regulated gene encodes human epithelial tropomyosin (TMe1), a member of the family of actin filament-binding proteins, The up-regulated gene encodes cytochrome c oxidase subunit VIc (CCOSVIc), a protein of the respiration chain in the mitochondrial inner membrane, The differential display pattern was confirmed by Northern hybridization in both prostate tissue and cell lines, In situ hybridization of malignant prostate epithelial tissue using a digoxigenin-labeled antisense riboprobe detected strong staining for mRNA of COSVIc, as opposed to very weak staining in normal prostate epithelium. The expression pattern of COSVIc may be a useful marker for studying the alteration of energy metabolism in cancer tells and for the diagnosis of prostate cancer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. VANDERBILT CANC CTR,NASHVILLE,TN 37232. NR 27 TC 107 Z9 111 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 AUG 15 PY 1996 VL 56 IS 16 BP 3634 EP 3637 PG 4 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600006 PM 8705997 ER PT J AU Zhu, H Melder, RJ Baxter, LT Jain, RK AF Zhu, H Melder, RJ Baxter, LT Jain, RK TI Physiologically based kinetic model of effector cell biodistribution in mammals: Implications for adoptive immunotherapy SO CANCER RESEARCH LA English DT Article ID ACTIVATED KILLER-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; POSITRON EMISSION TOMOGRAPHY; TRANSFERRED ADHERENT; PHARMACOKINETIC MODEL; MONOCLONAL-ANTIBODIES; SCALE-UP; INVIVO; MICE; LOCALIZATION AB The goal of the present investigation was to develop a physiologically based kinetic model to describe the biodistribution of immunologically active effector cells in normal and neoplastic tissues of mammals based on the current understanding of lymphocyte trafficking pathways and signals. The model was used to extrapolate biodistribution among different animal species and to identify differences among different effector populations and between intra-arterial and systemic: injections, Most importantly, the model was used to discern critical parameters for improving the delivery of effector cells. In the model, the mammalian body was divided into 12 organ compartments, interconnected in anatomic fashion, Each compartment was characterized by blood flow rate, organ volume and lymphatic flow rate, and other physiological and immunological parameters. The resulting set of 45 differential equations was solved numerically. The model was used to simulate the following biodistribution data: (a) nonactivated T lymphocytes in rats; (b) interleukin 2-activated tumor-infiltrating lymphocytes in humans; (c) nonactivated natural killer (NK) cells in rats; and (d) interleukin 2-activated adherent NK cells in mice. Comparisons between simulations and data demonstrated the feasibility of the model and the scaling scheme. The similarities as well as differences in biodistribution of different lymphocyte populations were revealed as results of their trafficking properties. The importance of lymphocyte infiltration from surrounding normal tissues into tumor tissue was found to depend on lymphocyte migration rate, tumor size, and host organ. The study confirmed that treatment with effector cells has not been as impressive as originally promised, due, in part, to the biodistribution problems. The model simulations demonstrated that low effector concentrations in the systemic circulation greatly limited their delivery to tumor, This was due to high retention in normal tissues, especially in the lung. Reducing normal tissue retention through decreasing attachment rate or adhesion site density in the lung by 50% could increase the tumor uptake by similar to 40% for tumor-infiltrating lymphocytes and by similar to 60% for adherent NK cells. Our analysis suggested the following strategies to improve effector cell delivery to tumor: (a) bypassing the initial lung entrapment with administration to the arterial supply of tumor; (b) reducing normal tissue retention using effector cells with high deformability or blocking lymphocyte adhesion to normal vessels; and (c) enhancing tumor-specific capture and arrest by modifying the tumor microenvironment. C1 MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, STEELE LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. MIT, RADIOL SCI PROGRAM, CAMBRIDGE, MA 02139 USA. FU NCI NIH HHS [R35-CA-56591] NR 52 TC 46 Z9 46 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1996 VL 56 IS 16 BP 3771 EP 3781 PG 11 WC Oncology SC Oncology GA VB986 UT WOS:A1996VB98600032 PM 8706023 ER PT J AU Skopicki, HA Abraham, SA Weissman, NJ Mukerjee, AK Alpert, NM Fischman, AJ Picard, MH Gewirtz, H AF Skopicki, HA Abraham, SA Weissman, NJ Mukerjee, AK Alpert, NM Fischman, AJ Picard, MH Gewirtz, H TI Factors influencing regional myocardial contractile response to inotropic stimulation analysis in humans with stable ischemic heart disease SO CIRCULATION LA English DT Article DE coronary disease; myocardial contraction; adenosine; regional blood flow; echocardiography ID DOBUTAMINE STRESS ECHOCARDIOGRAPHY; POSITRON EMISSION TOMOGRAPHY; CORONARY-ARTERY DISEASE; BLOOD-FLOW; CONSCIOUS DOGS; QUANTITATIVE ARTERIOGRAPHY; COMPUTED-TOMOGRAPHY; OXYGEN-CONSUMPTION; DOMESTIC SWINE; CLOSED-CHEST AB Background We hypothesized that the response of a myocardial segment to maximal dobutamine reflects not only maximal blood flow but also tethering, metabolic, and beta-blocker status. Methods and Results patients with stable ischemic heart disease (n=27) had positron emission tomographic measurement of blood flow at rest and with adenosine, and echocardiography at rest and with dobutamine. Positron emission tomographic measurement of [F-18]fluorodeoxyglucose myocardial distribution also was made. Adenosine blood flow in segments that contracted normally at peak dobutamine was similar to that of segments that became hypokinetic (1.06+/-0.72 versus 1.02+/-0.77 mL . g(-1). min(-1)). Segments that became akinetic failed to augment blood flow (0.68+/-0.30 mL . g(-1). min(-1)). Fluorodeoxyglucose-blood flow mismatch was more common in segments with abnormal wall motion at peak dobutamine (24 of 59, 41%) versus those that contracted normally (63 of 269, 23%; chi(2), 7.40; P <.01). In patients off beta-blockers, segments that contracted normally at peak dobutamine increased blood dow with adenosine (0.70+/-0.31 to 0.86+/-0.46 mL . g(-1). min(-1); P <.05), whereas those that became abnormal did not (0.63+/-0.24 to 0.65+/-0.19 mL . g(-1). min(-1); P=NS). Segments of patients on beta-blockers that contracted normally at peak dobutamine increased blood flow with adenosine (0.78+/-0.31 to 1.10+/-0.70 mL . g(-1). min(-1); P <.05), as did segments that became abnormal (0.74+/-0.34 to 1.06+/-0.82 mL . g(-1). min(-1); P=NS). However, segments adjacent to ones with abnormal wall motion at rest had higher frequency of abnormal response at peak dobutamine in groups on (48% versus 16%; chi(2), 14.1; P <.001) and off (51% versus 21%; chi(2), 10.9; P <.01) beta-blockers. Conclusions Augmented contraction at maximal dobutamine depends not only on increased myocardial blood how but also on tethering, metabolic, and beta-blocker status. Furthermore, impaired flow reserve does not preclude a normal response to maximal dobutamine, since blood flow need not increase greatly to meet demand. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NUCL MED,BOSTON,MA 02114. OI Picard, Michael/0000-0002-9264-3243 NR 38 TC 34 Z9 34 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1996 VL 94 IS 4 BP 643 EP 650 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VC360 UT WOS:A1996VC36000016 PM 8772683 ER PT J AU Berman, M Fischman, AJ Southern, J Carter, E Mirecki, F Strauss, W Nunn, A Gewirtz, H AF Berman, M Fischman, AJ Southern, J Carter, E Mirecki, F Strauss, W Nunn, A Gewirtz, H TI Myocardial adaptation during and after sustained, demand-induced ischemia - Observations in closed-chest, domestic swine SO CIRCULATION LA English DT Article DE myocardium; metabolism; bloodflow; ischemia ID COLLATERAL-DEPENDENT MYOCARDIUM; CORONARY-ARTERY STENOSIS; VENTRICULAR DYSFUNCTION; OXYGEN-CONSUMPTION; CONSCIOUS DOGS; BLOOD-FLOW; HIBERNATION; PERFUSION; PRESSURE; DISEASE AB Background We tested the hypotheses that prolonged, demand-induced myocardial ischemia plateaus and that on relief of stress, myocardial function remains depressed, with proportionate reductions in blood flow and oxygen consumption indicative of hibernation. Methods and Results Closed-chest swine (n=20) were prepared with an 80% coronary stenosis. Hemodynamics, myocardial blood Row, oxygen, and lactate metabolism were measured in group 1 (n=9) (1) at baseline, (2) at 10 and 30 minutes of atrial pacing plus intravenous norepinephrine infusion, and (3) in 5 of 9 (group la) at approximate to 50 minutes after stress. Group la had ischemia assessed with Tc-99m-labeled EMS 181321. In group 2 (n=11), myocardial function was determined with radionuclide ventriculography (n=8), and myocardial necrosis was looked for with trichlorotetrazolium chloride staining (n=7), histology (n=10), and myocardial creatine kinase concentration (n=4). Baseline stenotic-zone endocardial blood flow was reduced versus the normal zone (0.94+/-0.33 versus 1.38+/-0.27 mL . min(-1). g(-1), mean+/-SD; P<.05), whereas epicardial flows were comparable (1.15+/-0.36 versus 1.16+/-0.26 mL . min(-1). g(-1)). Stenotic-zone endocardial flow was unchanged versus baseline at 10 and 30 minutes of stress, whereas epicardial Row increased (1.62+/-0.53 mL . min(-1). g(-1) at 10 minutes and 1.44+/-0.51 mL . min(-1). g(-1) at 30 minutes, both P<.05). Myocardial oxygen consumption increased versus baseline (10.8+/-2.9 mL . min(-1). 100 g(-1)) at 10 and 30 minutes of stress (14.9+/-5.2 and 13.9+/-4.5 mL . min(-1). 100 g(-1), both P<.05). After stress, stenotic-zone blood Row and oxygen consumption were reduced approximate to 30% (P<.01) versus baseline. In group 2, stenotic-zone contraction with stress declined versus baseline and remained depressed throughout recovery. Histological and biochemical evidence of myocardial necrosis was absent in group 2. Conclusions Myocardial ischemia induced by a sustained increase in oxygen demand may not progress to necrosis but may instead plateau. After relief of stress, myocardial function remains depressed, with a proportionate reduction in blood Row and oxygen consumption consistent with myocardial hibernation. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RHODE ISL HOSP,DIV CARDIOL,DEPT MED,PROVIDENCE,RI 02902. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,NEW BRUNSWICK,NJ. NR 27 TC 20 Z9 21 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 15 PY 1996 VL 94 IS 4 BP 755 EP 762 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VC360 UT WOS:A1996VC36000032 PM 8772699 ER PT J AU Rosa, JL CasaroliMarano, RP Buckler, AJ Vilaro, S Barbacid, M AF Rosa, JL CasaroliMarano, RP Buckler, AJ Vilaro, S Barbacid, M TI p619, A giant protein related to the chromosome condensation regulator RCC1, stimulates guanine nucleotide exchange on ARF1 and Rab proteins SO EMBO JOURNAL LA English DT Article DE Golgi apparatus; guanine nucleotide exchange factors; membrane trafficking; small GTP binding proteins ID BREFELDIN-A; GDP/GTP EXCHANGE; ADP-RIBOSYLATION; BOVINE BRAIN; RNA; TRANSPORT; ENCODES; FAMILY; IMPORT; GENE AB We report the identification of a novel human gene, designated p619, that encodes a polypeptide of 4861 amino acid residues, one of the largest human proteins known to dale, The p619 protein contains two regions of seven internal repeats highly related to the cell cycle regulator RCC1, a guanine nucleotide exchange factor for the small GTP binding protein, Ran, Ln addition, p619 possesses seven P-repeat domains characteristic of the beta-subunit of heterotrimeric G proteins, three putative SN3 binding sites, seven polar amino acid-rich regions, a putative leucine zipper and a carboxy-terminal HECT domain characteristic of E3 ubiquitin-protein ligases, p619 is expressed ubiquitously in mouse and human tissues and overexpressed in several human tumor cell Lines, Subcellular localization studies indicate that p619 is located in the cytosol and in the Golgi apparatus, Localization of p619 in the Golgi is altered by Brefeldin A, The carboxy-terminal RCC1-like domain of p619 interacts specifically with myristoylated ARF1, a small GTP binding protein also located in the Golgi, Moreover, the second RCC1-like motif located at the amino-terminus of p619 stimulates guanine nucleotide exchange on ARF1 and on members of the related Rab proteins, but not on other small GTP binding proteins such as Ran or R-Ras2/TC21. These observations suggest that p619 is a Brefeldin A-sensitive Golgi protein that functions as a guanine nucleotide exchange factor for ARF1 and, possibly, for members of the Rab family of proteins. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOL ONCOL,PRINCETON,NJ 08543. UNIV BARCELONA,DEPT CELLULAR BIOL,BARCELONA 08028,SPAIN. MASSACHUSETTS GEN HOSP,MOL GENET LAB,CHARLESTOWN,MA 02129. RI Rosa, Jose Luis/K-6685-2014 OI Rosa, Jose Luis/0000-0002-6161-5688 NR 49 TC 101 Z9 103 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 1996 VL 15 IS 16 BP 4262 EP 4273 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VE353 UT WOS:A1996VE35300019 PM 8861955 ER PT J AU Habiby, RL Boepple, P Nachtigall, L Sluss, PM Crowley, WF Jameson, JL AF Habiby, RL Boepple, P Nachtigall, L Sluss, PM Crowley, WF Jameson, JL TI Adrenal hypoplasia congenita with hypogonadotropic hypogonadism - Evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adrenal gland; DAX-1; gene mutation; hypogonadotropic hypogonadism; GnRH; gonadotropins ID STEROIDOGENIC FACTOR-I; HORMONE-RECEPTOR SUPERFAMILY; LINKED GLYCEROL KINASE; NUCLEAR RECEPTOR; KALLMANN SYNDROME; ALPHA-SUBUNIT; GONADAL AXIS; GENE; DEFICIENCY; SECRETION AB Adrenal hypoplasia congenita (AHC) is an X-linked disorder that typically presents with adrenal insufficiency during infancy. Hypogonadotropic hypogonadism (HHG) has been identified as a component of this disorder in affected individuals who survive into childhood. Recently, AHC was shown to be caused by mutations in DAX-1, a protein that is structurally similar in its carboxyterminal region to orphan nuclear receptors. We studied two kindreds with clinical features of AHC and HHG. DAX-1 mutations were identified in both families. In the JW kindred, a single base deletion at nucleotide 1219 was accompanied by an additional base substitution that resulted in a frameshift mutation at codon 329 followed by premature termination In the MH kindred, a GCAT duplication at codon 418 caused a frameshift that also resulted in truncation of DAX-1. Baseline luteinizing hormone (LH), follicle-stimulating hormone (FSH), and free-cu-subunit (FAS) levels were determined during 24 h of frequent (q10 min) venous sampling. In patient MH, baseline LH levels were low, but FAS levels were within the normal range, In contrast, in patient JW, the mean LH and FSH were within the normal range during baseline sampling, but LH secretion was erratic rather than showing typical pulses, FAS was apulsatile for much of the day, but a surge was seen over a 3-4-h period. Pulsatile gonadotropin releasing hormone (GnRH) (25 ng/kg) was administered every 2 h for 7 d to assess pituitary responsiveness to exogenous GnRH, MH did not exhibit a gonadotropin response to pulsatile GnRH. JW exhibited a normal response to the first pulse of GnRH, but there was no increase in FAS, In contrast to the priming effect of GnRH in GnRH-deficient patients with Kallmann syndrome, GnRH pulses caused minimal secretory responses of LH and no FAS responses in patient JW. The initial LH response in patient JW implies a deficiency in hypothalamic GnRH. On the other hand, the failure to respond to pulsatile GnRH is consistent with a pituitary defect in gonadotropin production These two cases exemplify the phenotypic heterogeneity of AHC/HHG, and suggest that DAX-1 mutations impair gonadotropin production by acting at both the hypothalamic and pituitary levels. C1 NORTHWESTERN UNIV, SCH MED, DIV ENDOCRINOL METAB & MOL MED, CHICAGO, IL 60611 USA. MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [P30 HD028138, P30 HD 28138, U54 HD 29164] NR 48 TC 185 Z9 197 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 15 PY 1996 VL 98 IS 4 BP 1055 EP 1062 DI 10.1172/JCI118866 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VE490 UT WOS:A1996VE49000024 PM 8770879 ER PT J AU Brubaker, JO Thompson, CM Morrison, LA Knipe, DM Siber, GR Finberg, RW AF Brubaker, JO Thompson, CM Morrison, LA Knipe, DM Siber, GR Finberg, RW TI Th1-associated immune responses to beta-galactosidase expressed by a replication-defective herpes simplex virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; CELL-MEDIATED-IMMUNITY; NATURAL-KILLER CELLS; MURINE CYTOMEGALOVIRUS-INFECTION; CD4(+) T-CELLS; LYMPHOCYTES-T; CHLAMYDIA-TRACHOMATIS; INTERFERON-GAMMA; BALB/C MICE; MUCOSAL IMMUNIZATION AB The immunogenic properties of a replication-defective herpes simplex virus HD-2, containing the Escherichia coli lacZ gene under control of the HSV ICP8 early gene promoter were studied in BALB/c mice. Experiments were designed to determine if the HD-2 virus preferentially stimulated either Th1- or Th2-associated immune responses to beta-galactosidase (beta gal). Sera from mice immunized i.p, or s.c. with virus HD-2, beta gal on aluminum phosphate adjuvant, or a control ICP8 deletion mutant, d301, were assayed for total and Ag-specific IgG1 and IgG2a Abs, beta gal-driven lymphocyte proliferation, and in vitro production of the cytokines IFN-gamma, IL-4, and IL-2. Viruses HD-2 and d301 preferentially stimulated the production of total serum IgG2a following two immunizations i.p. or a single immunization s.c., while only HD-2 virus stimulated in vivo production of beta gal-specific IgG2a serum Abs. In contrast, beta gal adsorbed on AlPO4 preferentially stimulated production of Ag specific IgG1 serum Abs. The HD-2 virus also induced a potent cellular proliferative response to beta gal, which was still pronounced 5 wk after primary immunization. Cultured lymphocytes from HD-2-immunized mice produced IFN-gamma after 5 days in culture with soluble beta gal in an Ag- and dose-dependent fashion. These results demonstrate that replication-defective mutants of HSV can be used as vectors for eliciting Th1-associated immune responses to a heterologous Ag expressed from the viral genome. C1 DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NIA NIH HHS [P0AI-AG37963]; SAMHSA HHS [P0AI-24010] NR 72 TC 39 Z9 39 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 AUG 15 PY 1996 VL 157 IS 4 BP 1598 EP 1604 PG 7 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400035 PM 8759744 ER PT J AU Kersten, CM McCluskey, RT Boyle, LA Kurnick, JT AF Kersten, CM McCluskey, RT Boyle, LA Kurnick, JT TI Escherichia coli and Pseudomonas aeruginosa induce expansion of V delta 2 cells in adult peripheral blood, but of V delta 1 cells in cord blood SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELTA-T-CELLS; RECEPTOR-GAMMA-DELTA; HEAT-SHOCK PROTEIN; MYCOBACTERIUM-TUBERCULOSIS; PLASMODIUM-FALCIPARUM; LYMPHOCYTES-T; ALPHA-BETA; STIMULATION; ACTIVATION; MICE AB Human peripheral blood T cells proliferate in response to Escherichia coli and Pseudomonas aeruginosa. We observed that during the first few days after stimulation a large percentage of the responding PBMC were gamma delta T cells. In our study we characterized the early T cell responses of freshly isolated adult and newborn PBMC to soluble preparations of heat-killed E. coli and P.aeruginosa. Specimens from all healthy adults tested showed intense proliferation in response to both bacterial preparations; at 6 days, the responding cells were mainly T cell blasts, of which high percentages (up to 80%) were gamma delta T cells, most expressing V delta 2/V gamma 9. All newborn blood specimens tested also showed T cell proliferative responses, which included a marked expansion of gamma delta T cells, mainly of the V delta 1 subset. Populations of purified V delta 1 and V delta 2 T cells were obtained from adult PBMC following stimulation with E. coli; both subsets proliferated upon rechallenge with the bacterial preparations. Protease treatment of the bacterial preparations did not appreciably affect their ability to induce expansion of gamma delta T cells in either adult or cord blood, indicating that the stimulatory components were not proteins. The response of gamma delta T cells from newborns indicates that prior exposure to bacterial products is not necessary and suggests that gamma delta T cells are important elements in natural immunity to these extracellular organisms. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,CHARLESTOWN,MA 02129. FU NHLBI NIH HHS [HL-43793] NR 42 TC 19 Z9 19 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 AUG 15 PY 1996 VL 157 IS 4 BP 1613 EP 1619 PG 7 WC Immunology SC Immunology GA VH124 UT WOS:A1996VH12400037 PM 8759746 ER PT J AU Cabral, JHM Petosa, C Sutcliffe, MJ Raza, S Byron, O Poy, F Marfatia, SM Chishti, AH Liddington, RC AF Cabral, JHM Petosa, C Sutcliffe, MJ Raza, S Byron, O Poy, F Marfatia, SM Chishti, AH Liddington, RC TI Crystal structure of a PDZ domain SO NATURE LA English DT Article ID PROTEINS; GRAPHICS; PROGRAM; ORIGIN; DHR AB PDZ domains (also known as DHR domains or GLGF repeats) are similar to 90-residue repeats found in a number of proteins implicated in ion-channel and receptor clustering, and the linking of receptors to effector enzymes(1). PDZ domains are protein-recognition modules; some recognize proteins containing the consensus carboxy-terminal tripeptide motif S/TXV with high specificity(2-4). Other PDZ domains form homotypic dimers: the PDZ domain of the neuronal enzyme nitric oxide synthase binds to the PDZ domain of PSD-95, an interaction that has been implicated in its synaptic association(5). Here we report the crystal structure of the third PDZ domain of the human homologue of the Drosophila discs-large tumour-suppressor gene product, DlgA. It consists of a five-stranded antiparallel beta-barrel flanked by three alpha-helices. A groove runs over the surface of the domain, ending in a conserved hydrophobic pocket and a buried arginine; we suggest that this is the binding site for the C-terminal peptide. C1 UNIV LEICESTER,DEPT BIOCHEM,LEICESTER LE1 7RH,LEICS,ENGLAND. UNIV LEICESTER,DEPT NCMH,LEICESTER LE1 7RH,LEICS,ENGLAND. UNIV LEICESTER,DEPT CHEM,LEICESTER LE1 7RH,LEICS,ENGLAND. DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,SCH MED,ST ELIZABETHS MED CTR,TUMOR CELL BIOL LAB,BOSTON,MA 02135. NR 28 TC 216 Z9 218 U1 0 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 15 PY 1996 VL 382 IS 6592 BP 649 EP 652 DI 10.1038/382649a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VC303 UT WOS:A1996VC30300059 ER PT J AU Khan, A Tomita, Y Sykes, M AF Khan, A Tomita, Y Sykes, M TI Thymic dependence of loss of tolerance in mixed allogeneic bone marrow chimeras after depletion of donor antigen - Peripheral mechanisms do not contribute to maintenance of tolerance SO TRANSPLANTATION LA English DT Article ID T-CELL TOLERANCE; MAJOR HISTOCOMPATIBILITY COMPLEX; INTRATHYMIC CLONAL DELETION; TRANSPLANTATION TOLERANCE; MONOCLONAL-ANTIBODIES; TRANSGENIC MICE; I-E; ANERGY; INDUCTION; REGIMEN AB A nonmyeloablative conditioning regimen has recently been developed that allows allogeneic marrow engraftment with induction of permanent mixed chimerism and donor-specific tolerance across fully MHC-mismatched, allogeneic barriers, We recently demonstrated that tolerance can be broken in these chimeras by administration of an anti-donar class I-specific monoelonal antibody that eliminates donor hematopoietic cells, We have now investigated the role of the thymus ill the loss of tolerance observed when chimerism is eliminated in this manner, Mixed chimeras were prepared in B10 (H2(b)) recipients by treatment with depleting anti-CD4 and anti-CDS mAbs, 3-Gy whole body irradiation, and 7-Gy thymic irradiation, followed by B10.A (H2(a)) bone marrow transplantation. Chimeras were thymectomized 7 weeks later, and were either untreated or were depleted of donor cells with anti-donor class I (D-d-specific) mAb 34-2-12. Control chimeras that were not thymectomized also received anti-donor monoclonal antibodies or no further treatment, Of the four groups, only euthymic animals that were depleted of donor antigen showed a loss of tolerance, as evidenced by rejection of B10.A skin grafts. In contrast to untreated central and thymectomized, anti-Dd-treated chimeras, these euthymic anti-Dd-treated chimeras showed significant recovery of V beta 11(+) T cells, which can recognize Mtv antigens presented by donor I-E molecules, The requirement for a thymus for lass of tolerance in the absence of donor antigen was verified in an adoptive transfer model, in which chimera (B10.A-->B10) spleen cells were depleted of donor-type cells ex vivo, adoptively transferred into B6 nu/nu mice, and then further depleted of donor-type antigen with monoclonal antibody treatment in vivo. These B6 nu/nu mice maintained donor-specific tolerance to B10.A skin grafts. The absence of active suppression as a potent mechanism of tolerance in long-term mixed chimeras was confirmed by the loss of mixed chimerism and of tolerance that was readily induced by injection of naive host-type spleen cells. Together, our results suggest that in mixed allogeneic chimeras, intrathymic clonal deletion, and not peripheral suppression or anergy, is the major mechanism maintaining donor-specific tolerance. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,SURG SERV,SCH MED,BOSTON,MA 02129. FU NHLBI NIH HHS [R01 HL49915]; NIAID NIH HHS [1K11AI01261-01] NR 44 TC 118 Z9 119 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 AUG 15 PY 1996 VL 62 IS 3 BP 380 EP 387 DI 10.1097/00007890-199608150-00014 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VC450 UT WOS:A1996VC45000014 PM 8779687 ER PT J AU Parolin, C Taddeo, B Palu, G Sodroski, J AF Parolin, C Taddeo, B Palu, G Sodroski, J TI Use of cis- and trans-acting viral regulatory sequences to improve expression of human immunodeficiency virus vectors in human lymphocytes SO VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; TYPE-1 ENVELOPE GLYCOPROTEIN; EMBRYONAL CARCINOMA-CELLS; HUMAN-GENE-THERAPY; ACTIVATOR GENE; LEUKEMIA-VIRUS; MURINE RETROVIRUSES; STEM-CELLS; HTLV-III; REPLICATION AB We compared the efficiency of human immunodeficiency virus (HIV-I) vectors that express a marker gene (chloramphenicol acetyltransferase, CAT) using different promoter elements. In one vector, CAT was expressed under the control of an internal murine leukemia virus (MuLV) long terminal repeat (LTR). In other vectors, CAT production was regulated by the HIV-1 LTR; these vectors also contained the HIV-I tat gene and pol sequences reported to exert cis-acting positive effects on reverse transcription or gene expression. Vectors employing the Tat-driven HIV-I LTR exhibited up to 500-foId greater CAT expression in Jurkat lymphocytes or human peripheral blood mononuclear cells compared with vectors using the internal MuLV LTR element as a promoter. This difference was not due to improved packaging of the vector RNA into virions, but to an improved level of gene expression in the target cells. Target cell CAT expression was two- to threefold higher for the vector containing the pol sequences and was only slightly less than that seen for a trans-complemented env-deleted provirus. These results indicate that defective HIV-I vectors with efficiencies of gene transfer and expression comparable with that of HIV-1 itself are feasible. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV PADUA,INST MICROBIOL,I-35121 PADUA,ITALY. FU NCI NIH HHS [CA06516]; NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI28691] NR 46 TC 50 Z9 50 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 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 1996 VL 222 IS 2 BP 415 EP 422 DI 10.1006/viro.1996.0438 PG 8 WC Virology SC Virology GA VD707 UT WOS:A1996VD70700012 PM 8806525 ER PT J AU Schieldrop, PJ Gelling, RW Elliot, R Hewitt, J Kieffer, TJ McIntosh, CHS Pederson, RA AF Schieldrop, PJ Gelling, RW Elliot, R Hewitt, J Kieffer, TJ McIntosh, CHS Pederson, RA TI Isolation of a murine glucose-dependent insulinotropic polypeptide (GIP) cDNA from a tumor cell line (STC6-14) and quantification of glucose-induced increases in GIP mRNA SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE cDNA; glucose-dependent insulinotropic polypeptide; glucose stimulus; mRNA; murine ID GASTRIC-INHIBITORY POLYPEPTIDE; GENE-EXPRESSION; PEPTIDE GIP; PRECURSOR; SEQUENCE AB A 537 base pair cDNA clone for murine GIP has been isolated. The elucidated sequence encodes an open reading frame of 432 base pairs which codes for a 144 amino acid precursor. Murine GIP is predicted to differ from the human hormone by three amino acid substitutions: arginine for histidine at position 18, arginine for lysine at position 30 and serine for lysine at position 34. GIP mRNA levels in STC6-14 cells incubated in the presence of varying glucose concentrations was investigated using a competitive-PCR method. In the presence of a 5-mM glucose stimulus, 1 x 10(5) GIP cells were found to contain 3.9 +/- 0.59 amol of GIP mRNA while the same number of cells contained 11.6 +/- 1.4 amol when subjected to a high (25 mM) glucose stimulus. C1 UNIV BRITISH COLUMBIA,DEPT PHYSIOL,VANCOUVER,BC V6T 1Z3,CANADA. UNIV BRITISH COLUMBIA,DEPT BIOCHEM,VANCOUVER,BC,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL ENDOCRINOL LAB,BOSTON,MA. NR 13 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD AUG 14 PY 1996 VL 1308 IS 2 BP 111 EP 113 DI 10.1016/0167-4781(96)00103-0 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD274 UT WOS:A1996VD27400005 PM 8764827 ER PT J AU Woodruff, PWR Benson, RR Bandettini, PA Kwong, KK Howard, RJ Talavage, T Belliveau, J Rosen, BR AF Woodruff, PWR Benson, RR Bandettini, PA Kwong, KK Howard, RJ Talavage, T Belliveau, J Rosen, BR TI Modulation of auditory and visual cortex by selective attention is modality-dependent SO NEUROREPORT LA English DT Article DE auditory attention; visual attention; functional magnetic resonance imaging ID HUMANS; BRAIN AB Using functional magnetic resonance imaging (fMRI), we investigated whether the response of auditory and visual cortex was modulated by attending selectively to either heard or seen numbers presented simultaneously. Alternating attention between modalities modulated fMRI signal within the corresponding sensory cortex. This study provides evidence that attention acts locally during early auditory cognitive sensory processing, and that modulation of auditory and visual sensory cortex by attention is modality-dependent. C1 UNIV LONDON KINGS COLL,SCH MED,DEPT PSYCHOL MED,LONDON SE5 8AF,ENGLAND. MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,CHARLESTOWN,MA 02129. RP Woodruff, PWR (reprint author), INST PSYCHIAT,DE CRESPIGNY PK, DENMARK HILL,LONDON SE5 8AF,ENGLAND. RI Woodruff, Peter/B-5998-2009; Howard, Robert/E-4890-2010; Bandettini, Peter/F-5871-2012 FU NIMH NIH HHS [5 R01 MH50054] NR 22 TC 118 Z9 118 U1 0 U2 6 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 12 PY 1996 VL 7 IS 12 BP 1909 EP 1913 DI 10.1097/00001756-199608120-00007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VP159 UT WOS:A1996VP15900007 PM 8905690 ER PT J AU Liu, R Paxton, WA Choe, S Ceradini, D Martin, SR Horuk, R MacDonald, ME Stuhlmann, H Koup, RA Landau, NR AF Liu, R Paxton, WA Choe, S Ceradini, D Martin, SR Horuk, R MacDonald, ME Stuhlmann, H Koup, RA Landau, NR TI Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection SO CELL LA English DT Article ID ERYTHROCYTE CHEMOKINE RECEPTOR; TYPE-1; DISEASE; GENE; FAMILY; REGION; PROGRESSION; REQUIREMENT; EXPRESSION; PHENOTYPE AB Rare individuals have been multiply exposed to HIV-1 but remain uninfected. The CD4(+) T-cells of two of these individuals, designated EU2 and EU3, are highly resistant in vitro to the entry of primary macrophage-tropic virus but are readily infectable with transformed T-cell line adapted viruses. We report here on the genetic basis of this resistance. We found that EU2 and EU3 have a homozygous defect in CKR-5, the gene encoding the recently described coreceptor for primary HIV-1 isolates. These individuals appear to have inherited a defective CKR-5 allele that contains an internal 32 base pair deletion. The encoded protein is severely truncated and cannot be detected at the cell surface. Surprisingly, this defect has no obvious phenotype in the affected individuals. Thus, a CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1. Heterozygous individuals are quite common (similar to 20%) in some populations. These findings indicate the importance of CKR-5 in HIV-1 transmission and suggest that targeting the HIV-1-CKR-5 interaction may provide a means of preventing or slowing disease progression. C1 BERLEX BIOSCI,DEPT IMMUNOL,RICHMOND,CA 94080. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. CUNY MT SINAI SCH MED,BROOKDALE CTR MOL BIOL,NEW YORK,NY 10029. RP Liu, R (reprint author), ROCKEFELLER UNIV,AARON DIAMOND AIDS RES CTR,1230 YORK AVE,NEW YORK,NY 10016, USA. FU NCI NIH HHS [R01CA72149]; NIAID NIH HHS [R01AI35522, R29AI36057] NR 45 TC 2051 Z9 2118 U1 16 U2 105 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 9 PY 1996 VL 86 IS 3 BP 367 EP 377 DI 10.1016/S0092-8674(00)80110-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC309 UT WOS:A1996VC30900005 PM 8756719 ER PT J AU Wang, TW Li, BY Danielson, PD Shah, PC Rockwell, S Lechleider, RJ Martin, J Manganaro, T Donahoe, PK AF Wang, TW Li, BY Danielson, PD Shah, PC Rockwell, S Lechleider, RJ Martin, J Manganaro, T Donahoe, PK TI The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors SO CELL LA English DT Article ID TRANSFORMING GROWTH-FACTOR; SERINE-THREONINE KINASE; PEPTIDYL-PROLYL ISOMERASE; ACTIVIN RECEPTOR; IMMUNOSUPPRESSANT FK506; EXPRESSION CLONING; MAMMALIAN PROTEIN; COMPLEX; CALCINEURIN; RAPAMYCIN AB The immunophilin FKBP12 is an evolutionarily conserved abundant protein; however, its physiological roles remain poorly defined. Here we report that FKBP12 is a common cytoplasmic interactor of TGF beta family type I receptors. FKBP12 binds to ligand-free TGF beta type I receptor, from which it is released upon a ligand-induced, type II receptor mediated phosphorylation of the type I receptor. Blocking FKBP12/type I receptor interaction with FK506 nonfunctional derivatives enhances the ligand activity, indicating that FKBP12 binding is inhibitory to the signaling pathways of the TGF beta family ligands. Overexpression of a myristylated FKBP12 in Mv1Lu cell specifically inhibits two separate pathways activated by TGF beta, and two point mutations on FKBP12 (G89P, 190K) abolish the inhibitory activity of FKBP12, suggesting that FKBP12 may dock a cytoplasmic protein to the type I receptors to inhibit TGF beta family mediated signaling. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP Wang, TW (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,PEDIAT SURG RES LAB,BOSTON,MA 02114, USA. FU NICHD NIH HHS [P-30 HD07396, HD 32112]; NIGMS NIH HHS [R29 GM53710] NR 47 TC 259 Z9 264 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 9 PY 1996 VL 86 IS 3 BP 435 EP 444 DI 10.1016/S0092-8674(00)80116-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC309 UT WOS:A1996VC30900011 PM 8756725 ER PT J AU Nakajima, T Fukamizu, A Takahashi, J Gage, FH Fisher, T Blenis, J Montminy, MR AF Nakajima, T Fukamizu, A Takahashi, J Gage, FH Fisher, T Blenis, J Montminy, MR TI The signal-dependent coactivator CBP is a nuclear target for pp90(RSK) SO CELL LA English DT Article ID NERVE GROWTH-FACTOR; TRANSCRIPTION FACTOR CREB; PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; BINDING PROTEIN CREB; PC12 CELLS; KINASE-II; PHOSPHORYLATION; INSULIN; CAMP; ACTIVATION AB We have examined the mechanism by which growth factor-mediated induction of the Ras pathway interferes with signaling via the second messenger cAMP. Activation of cellular Ras with insulin or NGF stimulated recruitment of the S6 kinase pp90(RSK) to the signal-dependent coactivator CBP. Formation of the pp90(RSK)-CBP complex occurred with high stoichiometry and persisted for 6-8 hr following growth factor addition. pp90(RSK) specifically recognized the E1A-binding domain of the coactivator CBP. In addition, like E1A, binding of pp90(RSK) to CBP was sufficient to repress transcription of cAMP-responsive genes via the cAMP-inducible factor CREB. By contrast with its effects on the cAMP pathway, formation of the pp90(RSK)-CBP complex was required for induction of Ras-responsive genes. These results provide a demonstration of cross-coupling between two signaling pathways that occurs at the level of a signal-dependent coactivator. C1 FDN MED RES,PEPTIDE BIOL LABS,LA JOLLA,CA 92037. SALK INST BIOL STUDIES,GENET LAB,LA JOLLA,CA 92037. RP Nakajima, T (reprint author), HARVARD UNIV,SCH MED,DEPT CELLULAR & MOL PHYSIOL,JOSLIN DIABET CTR,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA 54418]; NIA NIH HHS [AG 06088]; NIGMS NIH HHS [GM 37828] NR 39 TC 224 Z9 233 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 AUG 9 PY 1996 VL 86 IS 3 BP 465 EP 474 DI 10.1016/S0092-8674(00)80119-1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC309 UT WOS:A1996VC30900014 PM 8756728 ER PT J AU Rana, A Gallo, K Godowski, P Hirai, S Ohno, S Zon, L Kyriakis, JM Avruch, J AF Rana, A Gallo, K Godowski, P Hirai, S Ohno, S Zon, L Kyriakis, JM Avruch, J TI The mixed lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; AMINO-TERMINAL KINASES; C-JUN; MAP KINASES; IDENTIFICATION; CASCADE; GTPASES; DOMAIN; CDC42; RAS AB SPRK (also called PTK-1 and MLK-3), a member of the mixed lineage kinase subfamily of (Ser/Thr) protein kinases, encodes an amino-terminal SH3 domain followed by a kinase catalytic domain, two leucine zippers interrupted by a short spacer, a Rac/Cdc42 binding domain, and a long carboxyl-terminal proline-rich region. We report herein that SPRK activates the stress-activated protein kinases (SAPKs) but not ERK-1 during transient expression in COS cells; the p38 kinase is activated modestly (1.3-2 fold) but consistently. SPRK also activates cotransfected SEK 1/MKK-4, a dual specificity kinase which phosphorylates and activates SAPK. Reciprocally, expression of mutant, inactive SEK-1 inhibits completely the basal and SPRK-activated SAPK activity. Immunoprecipitated recombinant SPRK is able to phosphorylate and activate recombinant SEK-1 in vitro to an extent comparable to that achieved by MEK kinase-1. These results identify SPRK as a candidate upstream activator of the stress-activated protein kinases, acting through the phosphorylation and activation of SEK-1. C1 MASSACHUSETTS GEN HOSP,MED SERV,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MICHIGAN STATE UNIV,DEPT PHYSIOL,E LANSING,MI 48824. GENENTECH INC,DEPT BIOL MOL,S SAN FRANCISCO,CA 94080. YOKOHAMA CITY UNIV,SCH MED,DEPT BIOL MOL,KANAZAWA KU,YOKOHAMA,KANAGAWA 236,JAPAN. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP Rana, A (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,149 13TH ST,CHARLESTOWN,MA 02129, USA. RI Ohno, Shigeo/B-1768-2010 OI Ohno, Shigeo/0000-0002-1294-5269 NR 31 TC 185 Z9 188 U1 0 U2 5 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 AUG 9 PY 1996 VL 271 IS 32 BP 19025 EP 19028 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB684 UT WOS:A1996VB68400005 PM 8702571 ER PT J AU Golub, TR McLean, T Stegmaier, K Carroll, M Tomasson, M Gilliland, DG AF Golub, TR McLean, T Stegmaier, K Carroll, M Tomasson, M Gilliland, DG TI The TEL gene and human leukemia SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID CHRONIC MYELOMONOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-BINDING; ETS; TRANSLOCATION; FUSION; ACTIVATION; ASSOCIATION; T(12-21); PROTEIN C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP Golub, TR (reprint author), HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115, USA. NR 27 TC 23 Z9 23 U1 4 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD AUG 8 PY 1996 VL 1288 IS 1 BP M7 EP M10 DI 10.1016/0304-419X(96)00015-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA VE463 UT WOS:A1996VE46300005 PM 8764840 ER PT J AU Sellers, WR Kaelin, WG AF Sellers, WR Kaelin, WG TI xRB as a modulator of transcription SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID RETINOBLASTOMA GENE-PRODUCT; MEDIATED GROWTH SUPPRESSION; CELL-CYCLE CONTROL; S-PHASE ENTRY; RB PROTEIN; SUSCEPTIBILITY GENE; COMPLEX-FORMATION; FAMILY MEMBERS; E2F FAMILY; IN-VIVO RP Sellers, WR (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,44 BINNEY ST,BOSTON,MA 02115, USA. NR 77 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD AUG 8 PY 1996 VL 1288 IS 1 BP M1 EP M5 DI 10.1016/0304-419X(96)00014-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA VE463 UT WOS:A1996VE46300004 PM 8764839 ER PT J AU Morris, JZ Tissenbaum, HA Ruvkun, G AF Morris, JZ Tissenbaum, HA Ruvkun, G TI A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans SO NATURE LA English DT Article ID CONTROLLING DAUER FORMATION; PROTEIN-KINASE; INTERACTING GENES; 3-KINASE; WORTMANNIN; CELLS; INHIBITION; RECEPTOR; SUBUNIT; DAF-2 AB A PHEROMONE-INDUCED neurosecretory pathway in Caenorhabditis elegans triggers developmental arrest and an increase in longevity at the dauer diapause stage. The gene age-1 is required for non-dauer development and normal senescence. age-1 encodes a homologue of mammalian phosphatidylinositol-3-OH kinase (PI(3)K) catalytic subunits. Lack of both maternal and zygotic age-1 activity causes dauer formation, whereas animals with maternal but not zygotic age-1 activity develop as non-dauers that live more than twice as long as normal. These data suggest that phosphatidylinositol signalling mediated by AGE-1 protein controls lifespan and the dauer diapause decision. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. NR 30 TC 562 Z9 580 U1 3 U2 33 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 8 PY 1996 VL 382 IS 6591 BP 536 EP 539 DI 10.1038/382536a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB258 UT WOS:A1996VB25800049 PM 8700226 ER PT J AU Gelber, RD Goldhirsch, A Cole, BF Wieand, HS Schroeder, G Krook, JE AF Gelber, RD Goldhirsch, A Cole, BF Wieand, HS Schroeder, G Krook, JE TI A quality-adjusted time without symptoms or toxicity (Q-TWIST) analysis of adjuvant radiation therapy and chemotherapy for resectable rectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OPERABLE BREAST-CANCER; PREOPERATIVE RADIOTHERAPY; EUROPEAN-ORGANIZATION; SURVIVAL ANALYSIS; RANDOMIZED TRIAL; CARCINOMA; COMBINATION; IRRADIATION; INFECTION; SURGERY AB Background: Combined radiation therapy and chemotherapy after surgery, compared with postsurgical radiation therapy alone, has been shown to improve disease-free survival and overall survival significantly among patients with poor-prognosis (i.e., advanced stage disease or metastasis to regional lymph nodes) resectable rectal cancer, However, the combined therapy is associated with more toxic effects, raising the question of whether the benefits of the treatment justify its quality-of-life costs for the individual patient, Purpose: To assess the trade-offs between improved survival and increased treatment toxicity, we reanalyzed data from a randomized clinical trial that compared the efficacy of combined adjuvant chemotherapy and radiation therapy with adjuvant radiation therapy alone in the treatment of patients with poor-prognosis resectable rectal cancer, Methods: The data were from a North Central Cancer Treatment Group trial in which 204 patients with poor-prognosis rectal cancer were randomly assigned to receive either postoperative radiation therapy alone or radiation therapy plus fluorouracil-based chemotherapy, A quality-adjusted time without symptoms or toxicity (Q-TWIST) analysis was used to account for freedom from symptomatic disease and from early and late side effects of treatment, All reported P values are two-sided, Results: As reported previously, the combined therapy reduced the risk of relapse by 34% (95% confidence interval [CI] = 12%-50%; P =.0016) and reduced the overall death rate by 29% (95% CI = 7%-45%; P =.025) in comparison with adjuvant radiation therapy alone, In the 5 years following assignment to treatment, patients who received the combined therapy had more time with toxicity (3.1 months; 95% CI = 2.0-4.1 months), shorter survival after relapse (3.6 months less; 95% CI = 0.9-6.3 months less), and more TWiST (6.1 months; 95% CI 0.2-12.0 months) than patients who received adjuvant radiation therapy alone, Despite an increase in the amount of time that individuals spent with early and late toxic effects, the Q-TWIST analysis indicated that the combined therapy conferred significantly greater benefit for a wide range of patient preferences about living with the toxicity of treatment or the symptoms of overt disease, Conclusions and Implications: Use of combined chemotherapy and radiation therapy as an adjuvant to surgery for patients with poor-prognosis resectable rectal cancer is justified, since the improved outcome in terms of delayed recurrence and increased survival balances the time spent with early and late toxic effects, The Q-TWiST method is an excellent way to compare treatment outcomes that include quality-of-life considerations. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. OSPED CIVICO,INT BREAST CANC STUDY GRP,LUGANO,SWITZERLAND. BROWN UNIV,CTR STAT SCI,PROVIDENCE,RI 02912. UNIV PITTSBURGH,SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15260. N CENT CANC TREATMENT GRP,CTR STAT,ROCHESTER,MN. DULUTH CLIN,DEPT HEMATOL & ONCOL,DULUTH,MN. RP Gelber, RD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA37404, CA25224, CA06516] NR 24 TC 76 Z9 76 U1 0 U2 2 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 AUG 7 PY 1996 VL 88 IS 15 BP 1039 EP 1045 DI 10.1093/jnci/88.15.1039 PG 7 WC Oncology SC Oncology GA VA550 UT WOS:A1996VA55000010 PM 8683634 ER PT J AU Harper, SE Qiu, YB Sharp, PA AF Harper, SE Qiu, YB Sharp, PA TI Sin3 corepressor function in Myc-induced transcription and transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-MYC; DNA-BINDING; RAS COTRANSFORMATION; REPRESSOR SIN3; MAX; PROTEIN; SEQUENCE; ACTIVATION; HELIX; INTERACTS AB Many basic-helix-loop-helix-leucine zipper (b-HLH-LZ) proteins, including the Myc family and non-Myc family, bind a common DNA sequence CACGTG, yet have quite different biological actions. Myc binds this sequence as a heterodimer with Max in the activation of both transcription and transformation. The Myc family members Mad and Mxi1 are known to suppress Myc-induced transcription and transformation and to dimerize with Max to form ternary complexes with the mammalian Sin3 transcriptional corepressor (mSin3). The b-HLH-LZ domain of TFEB, which cannot heterodimerize within the Myc family, does not suppress Myc-induced transcription or transformation. However, transfer of a 25- to 36-aa region from Mad or Mxi1, which interacts with mSin3, to the b-HLH-LZ of TFEB, mediated profound suppression of Myc-induced transcription and transformation. These results suggest that the DNA binding specificities of the Myc family and non-Myc family b-HLH-LZ proteins, in the context of the cellular genes involved in Myc-induced transformation, are shared. The results also demonstrate that targeting mSin3 to CACGTG sites via a non-Myc family DNA binding domain is sufficient to oppose Myc activity in growth regulation. C1 MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. FU NCI NIH HHS [P01-CA14051, P30-CA14051, K11-CA01609] NR 39 TC 40 Z9 40 U1 2 U2 3 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 AUG 6 PY 1996 VL 93 IS 16 BP 8536 EP 8540 DI 10.1073/pnas.93.16.8536 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500070 PM 8710905 ER PT J AU FitzGerald, MG Harkin, DP SilvaArrieta, S MacDonald, DJ Lucchina, LC Unsal, H ONeill, E Koh, J Finkelstein, DM Isselbacher, KJ Sober, AJ Haber, DA AF FitzGerald, MG Harkin, DP SilvaArrieta, S MacDonald, DJ Lucchina, LC Unsal, H ONeill, E Koh, J Finkelstein, DM Isselbacher, KJ Sober, AJ Haber, DA TI Prevalence of germ-line mutations in p16, p19ARF, and CDK4 in familial melanoma: Analysis of a clinic-based population SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; CELL-CYCLE INHIBITION; TUMOR-SUPPRESSOR GENE; SUSCEPTIBILITY LOCUS; HETEROGENEITY; P16(INK4); KINDREDS; CANCER AB Five to ten percent of individuals with melanoma have another affected family member, suggesting familial predisposition. Germ-line mutations in the cyclin-dependent kinase (CDK) inhibitor p16 have been reported in a subset of melanoma pedigrees, but their prevalence is unknown in more common cases of familial melanoma that do not involve large families with multiple affected members. We screened for germ-line mutations in p16 and in two other candidate melanoma genes, p19ARF and CDK4, in 33 consecutive patients treated for melanoma; these patients had at least one affected first or second degree relative (28 independent families). Five independent, definitive p16 mutations were detected (18%, 95% confidence interval: 6%, 37%), including one nonsense, one disease-associated missense, and three small deletions. No mutations were detected in CDK4. Disease-associated mutations in p19ARF, whose transcript is derived in part from an alternative codon reading frame of p16, were only detected in patients who also had mutations inactivating p16. We conclude that germ-line p16 mutations are present in a significant fraction of individuals who have melanoma and a positive family history. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CTR CANC RISK ANAL,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT BIOSTAT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. NR 30 TC 170 Z9 172 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 AUG 6 PY 1996 VL 93 IS 16 BP 8541 EP 8545 DI 10.1073/pnas.93.16.8541 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500071 PM 8710906 ER PT J AU Delgado, JC Turbay, D Yunis, EJ Yunis, JJ Morton, ED Bhol, K Norman, R Alper, CA Good, RA Ahmed, R AF Delgado, JC Turbay, D Yunis, EJ Yunis, JJ Morton, ED Bhol, K Norman, R Alper, CA Good, RA Ahmed, R TI A common major histocompatibility complex class II allele HLA-DQB1*0301 is present in clinical variants of pemphigoid SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PCR; HLA alleles and haplotypes; autoimmunity; pemphigoid disease ID JEWISH PATIENTS; VULGARIS; SUSCEPTIBILITY; HAPLOTYPES; GENES AB Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease seen primarily in elderly persons. It is characterized clinically by the development of tense bullae and by the presence of an antibasement membrane antibody. In BP, the antigens involved in the autoimmunity are epidermal basement membrane peptides BPAg1 and BPAg2. We have compared high resolution typing of major histocompatibility complex class II loci (HLA-DRB1, DQB1) in 21 patients with BP, 17 with ocular cicatricial pemphigoid (OCP), and 22 with oral pemphigoid (OP) to a panel of 218 haplotypes of normal individuals. We found that the three diseases (BP, OCP, and OP have significant association with DQB1*0301 (P = 0.005, P < 0.0001, and P = 0.001, respectively). The frequencies of alleles DQB1*0302, *0303, and *06, which share a specific amino acid sequence from position 71 to 77 (Thr-Arg-Ala-Glu-Leu-Val-Thr) were also increased (P = 0.01). We suggest that an identical major histocompatibility complex class II allele (DQB1*0301) is a common marker for enhanced susceptibility and that the same amino acid residues in positions 71-77 (DQB1*0301, -0302, -0305, -0602, -0603 alleles) are found in patients with BP, OCP, and OP. Our findings propose that the autoimmune response in the three different clinical variants of pemphigoid, involves the recognition by T cells of a class II region of DQB1, bound to a peptide from the basement membrane of conjunctiva, oral mucosa, and skin. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. DERMATOL HLTH CARE,TAMPA,FL 33615. UNIV S FLORIDA,ALL CHILDRENS HOSP,DEPT PEDIAT,ST PETERSBURG,FL 33701. HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. RP Delgado, JC (reprint author), DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA 02115, USA. FU NEI NIH HHS [EY 08379]; NHLBI NIH HHS [HL 29583]; NIDCR NIH HHS [DE 09978] NR 19 TC 89 Z9 93 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 AUG 6 PY 1996 VL 93 IS 16 BP 8569 EP 8571 DI 10.1073/pnas.93.16.8569 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500076 PM 8710911 ER PT J AU Lipes, MA Cooper, EM Skelly, R Rhodes, CJ Boschetti, E Weir, GC Davalli, AM AF Lipes, MA Cooper, EM Skelly, R Rhodes, CJ Boschetti, E Weir, GC Davalli, AM TI Insulin-secreting non-islet cells are resistant to autoimmune destruction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transgenic models; diabetes; intermediate pituitary; insulin gene expression ID TRANSGENIC MICE; ATT20 CELLS; EXPRESSION; MOUSE; RAT; PROHORMONE; PC2; CONVERTASE; GENE; BIOSYNTHESIS AB Transgenic nonobese diabetic mice were created in which insulin expression was targeted to proopiomelanocortin-expressing pituitary cells. Proopiomelanocortin-expressing intermediate lobe pituitary cells efficiently secrete fully processed, mature insulin via a regulated secretory pathway, similar to islet beta cells. However, in contrast to the insulin-producing islet beta cells, the insulin-producing intermediate lobe pituitaries are not targeted or destroyed by cells of the immune system. Transplantation of the transgenic intermediate lobe tissues into diabetic nonobese diabetic mice resulted in the restoration of near-normoglycemia and the reversal of diabetic symptoms. The absence of autoimmunity in intermediate lobe pituitary cells engineered to secrete bona fide insulin raises the potential of these cell types for beta-cell replacement therapy for the treatment of insulin-dependent diabetes mellitus. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP Lipes, MA (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 28 TC 61 Z9 63 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 AUG 6 PY 1996 VL 93 IS 16 BP 8595 EP 8600 DI 10.1073/pnas.93.16.8595 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500081 PM 8710916 ER PT J AU Stern, CE Corkin, S Gonzalez, RG Guimaraes, AR Baker, JR Jennings, PJ Carr, CA Sugiura, RM Vedantham, V Rosen, BR AF Stern, CE Corkin, S Gonzalez, RG Guimaraes, AR Baker, JR Jennings, PJ Carr, CA Sugiura, RM Vedantham, V Rosen, BR TI The hippocampal formation participates in novel picture encoding: Evidence from functional magnetic resonance imaging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFERIOR TEMPORAL CORTEX; POSITRON EMISSION TOMOGRAPHY; ENDURING MEMORY IMPAIRMENT; RECOGNITION MEMORY; SENSORY STIMULATION; NEURONAL RESPONSES; SPATIAL LOCATION; HUMAN BRAIN; TO-SAMPLE; MONKEYS AB Considerable evidence exists to support the hypothesis that the hippocampus and related medial temporal lobe structures are crucial for the encoding and storage of information in long-term memory. Few human imaging studies, however have successfully shown signal intensity changes in these areas during encoding or retrieval. Using functional magnetic resonance imaging (fMRI), we studied normal human subjects while they performed a novel picture encoding task. High-speed echo-planar imaging techniques evaluated fMRI signal changes throughout the brain. During the encoding of novel pictures, statistically significant increases in fMRI signal were observed bilaterally in the posterior hippocampal formation and parahippocampal gyrus and in the lingual and fusiform gyri. To our knowledge, this experiment is the first fMRI study to show robust signal changes in the human hippocampal region. It also provides evidence that the encoding of noveI, complex pictures depends upon an interaction between ventral cortical regions, specialized for object vision, and the hippocampal formation and parahippocampal gyrus, specialized for long-term memory. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. RP Stern, CE (reprint author), MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129, USA. FU NIA NIH HHS [AG05134, AG06605, AG10679] NR 60 TC 451 Z9 454 U1 1 U2 24 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 AUG 6 PY 1996 VL 93 IS 16 BP 8660 EP 8665 DI 10.1073/pnas.93.16.8660 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VB325 UT WOS:A1996VB32500092 PM 8710927 ER PT J AU Satake, M Liberman, MC AF Satake, M Liberman, MC TI Morphological subclasses of lateral olivocochlear terminals? Ultrastructural analysis of inner spiral bundle in cat and guinea pig SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cochlea; efferent; synaptic vesicles; morphometry ID SUPERIOR OLIVARY COMPLEX; GENE-RELATED PEPTIDE; ENKEPHALIN-LIKE IMMUNOREACTIVITY; COCHLEAR DE-EFFERENTATION; IMMUNOELECTRON MICROSCOPY; AUDITORY-NERVE; ELECTRON-MICROSCOPY; AFFERENT-FIBERS; SERIAL SECTIONS; FINE-STRUCTURE AB The lateral olivocochlear efferent pathway terminates in vesicle-filled swellings in the inner spiral bundles under inner hair cells (IHCs) and has been suggested to include at least two chemically distinct subclasses (see, e.g., Vetter et al. [1991] Synapse 7:21-43). In the present study, the ultrastructure and peripheral targets of vesicle-filled swellings in the IHC area of the cat and guinea pig cochleas were quantitatively analyzed to determine 1) whether morphological subclasses could be defined based on swelling size or on the density, size, or shape of clear and dense-cored vesicles and 2) whether swellings with different postsynaptic targets differed morphologically. In both cat and guinea pig, all swellings contained large, round, clear vesicles and a variable number of dense-core vesicles. Although evidence of clear-cut subclasses was not compelling, the smallest swellings tended to be rich in dense-core and poor in clear vesicles and rarely formed synaptic contacts. Most of the larger swellings, which tended to contain few dense-core vesicles and a rich complement of clear round vesicles, formed synapses with radial afferent fibers. However, there were no morphological differences between swellings contacting afferents originating on the modiolar vs. pillar sides of the IHC (the source of afferents with low and high spontaneous discharge rates, respectively). We conclude that 1) if distinct gamma-amino butyric acid (GABA)ergic and cholinergic subclasses of lateral olivocochlear (LOG) fibers exist, then the vesicle morphology of their terminals does not differ as it does in the central nervous system and that 2) if peptide neurotransmitters, such as calcitonin gene-related peptide and enkephalins, are packaged in dense-core vesicles, then the LOC terminals synapsing with IHC afferent fibers are not particularly rich in these peptides. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,DEPT HLTH SCI & TECHNOL,BOSTON,MA 02115. TOHOKU UNIV,SCH MED,DEPT OTOLARYNGOL,SENDAI,MIYAGI 980,JAPAN. FU NIDCD NIH HHS [R01 DC-00188] NR 47 TC 12 Z9 13 U1 0 U2 3 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 AUG 5 PY 1996 VL 371 IS 4 BP 621 EP 632 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VA027 UT WOS:A1996VA02700010 PM 8841914 ER PT J AU Linde, K Ramirez, G Mulrow, CD Pauls, A Weidenhammer, W Melchart, D AF Linde, K Ramirez, G Mulrow, CD Pauls, A Weidenhammer, W Melchart, D TI St John's wort for depression - An overview and meta-analysis of randomised clinical trials SO BRITISH MEDICAL JOURNAL LA English DT Article ID HYPERICUM EXTRACT; UNITED-STATES; DISORDERS AB Objective-To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. Design-Systematic review and meta-analysis of trials revealed by searches. Trials-23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. Main outcome measures-A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. Results-Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. Conclusion-There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO COCHRANE CTR,SAN ANTONIO,TX 78284. PRIVATE PRACTICE NEUROL & PSYCHIAT,D-80796 MUNICH,GERMANY. RP Linde, K (reprint author), UNIV MUNICH,PROJEKT MUNCHENER MODELL,KAISERSTR 9,D-80801 MUNICH,GERMANY. OI Linde, Klaus/0000-0002-2902-970X NR 52 TC 702 Z9 728 U1 5 U2 72 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD AUG 3 PY 1996 VL 313 IS 7052 BP 253 EP 258 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VA903 UT WOS:A1996VA90300020 PM 8704532 ER PT J AU Corbett, AH Silver, PA AF Corbett, AH Silver, PA TI The NTF2 gene encodes an essential, highly conserved protein that functions in nuclear transport in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING PROTEIN; RNA-BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; IMPORT SUBSTRATE; PORE COMPLEXES; CYTOSOLIC FACTORS; MEDIATED BINDING; RAN/TC4 HOMOLOG AB The small protein p10/Ntf2p has been implicated in protein import in vitro (Moore, M, S,, and Blobel, G. (1994) Proc, Natl. Acad. Sci, U, S, A, 91, 10212-10216; Paschal, B, M,, and Gerace, L, (1995) J, Cell Biol, 129, 925-937), Here we present the first evidence that demonstrates an essential in vivo role for the NTF2 gene product in nuclear transport, The NTF2 locus was identified in a screen for temperature-sensitive Saccharomyces cerevisiae mutants defective in the localization of nuclear proteins. Genetic analysis demonstrates that the NTF2 gene is essential for viability in budding yeast. Two temperature-sensitive mutants, ntf2-1 and ntf2-2, that each contain single point mutations in highly conserved amino acid residues show defects in the localization of nuclear proteins but not in the export of poly(A)(+) RNA following a shift to the nonpermissive temperature. An epitope tagged version of Ntf2p was used to show that the protein is concentrated at the nuclear envelope, Finally, the human gene under the control of the yeast promoter fully substitutes for the deleted yeast gene, Taken together, these results demonstrate the exquisite functional conservation of this protein throughout evolution and indicate a critical in vivo role in nuclear transport. C1 DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. NR 67 TC 81 Z9 83 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 AUG 2 PY 1996 VL 271 IS 31 BP 18477 EP 18484 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300031 PM 8702493 ER PT J AU Sgroi, D Nocks, A Stamenkovic, I AF Sgroi, D Nocks, A Stamenkovic, I TI A single N-linked glycosylation site is implicated in the regulation of ligand recognition by the I-type lectins CD22 and CR33 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION MOLECULE; MYELIN-ASSOCIATED GLYCOPROTEIN; HUMAN TRANSFERRIN RECEPTORS; IMMUNOGLOBULIN SUPERFAMILY; NATURAL LIGANDS; SIALIC ACIDS; B-CELLS; BINDING; OLIGOSACCHARIDE; SIALOADHESIN AB CD22 is an immunoglobulin superfamily B lymphocyte-specific adhesion receptor and a member of the recently identified I-type class of lectins, Recent work has shown that CD22 specifically recognizes sialic acid linked alpha 2,6 to terminal N-linked oligosaccharides on selected cell surface glycoproteins, CD22-ligand interaction is regulated by the activity of a beta-galactoside alpha 2,6-sialyltransferase that can inactivate CD22-mediated binding by sialylating the CD22 receptor itself. These observations suggest that N-linked glycosylation sites on the CD22 molecule may play a role in the regulation of CD22-mediated adhesion. In this work we have performed site-specific mutagenesis of potential N-linked glycosylation sites on CD22 in an effort to determine whether they might be involved in ligand recognition. We show that mutation of a single potential N-linked glycosylation site in the first immunoglobulin domain of CD22 completely abrogates ligand recognition, Interestingly, this site is characterized by the sequence NCT, where the cysteine is thought to be involved in an intrachain disulfide bond. Site-directed mutagenesis of similar NC(T/S) motifs in the first or second Ig domains of the I-type lectins myelin-associated glycoprotein, and sialoadhesin did not disrupt their ability to mediate sialic acid binding. In contrast, mutation of a NCS motif in the first Ig domain of the I-type lectin CD33 unmasked its sialic acid binding activity. These observations suggest that a single N-linked glycosylation site located at a similar position in the CD22 and CD33 glycoproteins is critical for regulating ligand recognition by both receptors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02129. FU NIAID NIH HHS [AI/01252]; NIGMS NIH HHS [GM/AI 48614] NR 30 TC 34 Z9 35 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 AUG 2 PY 1996 VL 271 IS 31 BP 18803 EP 18809 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB683 UT WOS:A1996VB68300076 PM 8702538 ER PT J AU Vortkamp, A Lee, K Lanske, B Segre, GV Kronenberg, HM Tabin, CJ AF Vortkamp, A Lee, K Lanske, B Segre, GV Kronenberg, HM Tabin, CJ TI Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein SO SCIENCE LA English DT Article ID HORMONE-RELATED PEPTIDE; TERMINAL CLEAVAGE PRODUCT; DROSOPHILA PATCHED GENE; MOTOR-NEURON INDUCTION; SONIC-HEDGEHOG; PARATHYROID-HORMONE; SCLEROTOME INDUCTION; POLARIZING ACTIVITY; VERTEBRATE HOMOLOG; RETROVIRAL VECTORS AB Proper regulation of chondrocyte differentiation is necessary for the morphogenesis of skeletal elements, yet little is known about the molecular regulation of this process, A chicken homolog of Indian hedgehog (Ihh), a member of the conserved Hedgehog family of secreted proteins that is expressed during bone formation, has now been isolated. Ihh has biological properties similar to those of Sonic hedgehog (Shh), including the ability to regulate the conserved targets Patched (Ptc) and Gli. Ihh is expressed in the prehypertrophic chondrocytes of cartilage elements, where it regulates the rate of hypertrophic differentiation, Misexpression of Ihh prevents proliferating chondrocytes from initiating the hypertrophic differentiation process, The direct target of Ihh signaling is the perichondrium, where Gli and Ptc flank the expression domain of Ihh, Ihh induces the expression of a second signal, parathyroid hormone-related protein (PTHrP), in the periarticular perichondrium, Analysis of PTHrP (-/-) mutant mice indicated that the PTHrP protein signals to its receptor in the prehypertrophic chondrocytes, thereby blocking hypertrophic differentiation, In vitro application of Hedgehog or PTHrP protein to normal or PTHrP (-/-) limb explants demonstrated that PTHrP mediates the effects of Ihh through the formation of a negative feedback loop that modulates the rate of chondrocyte differentiation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK47038, DK4723] NR 65 TC 1319 Z9 1352 U1 1 U2 58 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 2 PY 1996 VL 273 IS 5275 BP 613 EP 622 DI 10.1126/science.273.5275.613 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VA249 UT WOS:A1996VA24900038 PM 8662546 ER PT J AU Lanske, B Karaplis, AC Lee, K Luz, A Vortkamp, A Pirro, A Karperien, M Defize, LHK Ho, C Mulligan, RC AbouSamra, AB Juppner, H Segre, GV Kronenberg, HM AF Lanske, B Karaplis, AC Lee, K Luz, A Vortkamp, A Pirro, A Karperien, M Defize, LHK Ho, C Mulligan, RC AbouSamra, AB Juppner, H Segre, GV Kronenberg, HM TI PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth SO SCIENCE LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; MESSENGER-RNA; EXPRESSION; PROTEIN; TISSUES; MOUSE; RAT; CARTILAGE; CELLS AB The PTH/PTHrP receptor binds to two ligands with distinct functions: the calcium-regulating hormone, parathyroid hormone (PTH), and the paracrine factor, PTH-related protein (PTHrP). Each ligand, in turn, is likely to activate more than one receptor. The functions of the PTH/PTHrP receptor were investigated by deletion of the murine gene by homologous recombination. Most PTH/PTHrP receptor (-/-) mutant mice died in mid-gestation, a phenotype not observed in PTHrP (-/-) mice, perhaps because of the effects of maternal PTHrP. Mice that survived exhibited accelerated differentiation of chondrocytes in bone, and their bones, grown in explant culture, were resistant to the effects of PTHrP and Sonic hedgehog. These results suggest that the PTH/PTHrP receptor mediates the effects of Indian Hedgehog and PTHrP on chondrocyte differentiation. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MCGILL UNIV,SIR MORTIMER B DAVIS JEWISH GEN HOSP,MONTREAL,PQ H3T 1E2,CANADA. GSF MUNCHEN,INST PATHOL,D-85758 MUNICH,GERMANY. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NETHERLANDS INST DEV BIOL,HUBRECHT LAB,NL-3584 CT UTRECHT,NETHERLANDS. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,CAMBRIDGE,MA 02139. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK 47038, DK 47237] NR 23 TC 882 Z9 894 U1 0 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD AUG 2 PY 1996 VL 273 IS 5275 BP 663 EP 666 DI 10.1126/science.273.5275.663 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VA249 UT WOS:A1996VA24900053 PM 8662561 ER PT J AU Koury, SI Stone, CK Thomas, SH AF Koury, SI Stone, CK Thomas, SH TI Amrinone as an antidote in experimental verapamil overdose SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE amrinone; verapamil; overdose; animal model; pharmacology; therapy; toxicology; hemodynamics ID CHANNEL BLOCKER OVERDOSE; HEART-FAILURE; CARDIOVASCULAR DEPRESSION; CALCIUM; TOXICITY; GLUCAGON; PROPRANOLOL; THERAPY; DOG; DOBUTAMINE AB Objective: To evaluate the effect of amrinone as a treatment for the hemodynamic effects of verapamil overdose in a canine model. Methods: This nonblind interventional study was performed in an established canine model of verapamil toxicity, without concurrent control animals, Pentobarbital-anesthetized and instrumented dogs (n = 8) were maintained and observed for 60 minutes or until death, The animals were overdosed with verapamil, 15 mg/kg IV, over 30 minutes. Hemodynamic parameters, including cardiac index (CI), heart rate (HR), and mean arterial pressure (MAP), were monitored. Completion of the verapamil infusion represented the defined point of toxicity; at that point, all the animals received an amrinone bolus of 2 mg/kg IV over 2 minutes followed by an amrinone drip at 10 mu g/kg/min. The hemodynamic values at the defined point of toxicity were compared with those obtained postinitiation of the amrinone infusion. Results: Two animals died before the 60-minute observation period elapsed, Baseline CI was 5.6 L/min/m(2). Following verapamil-induced toxicity, mean CI was 2.2 L/min/m(2). After administration of amrinone, a significant (p < 0.05) increase in CI was observed at 30 minutes (CI = 3.6 L/min/m(3)), 45 minutes (CI = 4.2 L/min/m(2)), and 60 minutes (CI = 4.2 L/min/m(2)). There was no statistically significant difference noted for MAP or HR compared with ''point of toxicity'' values. Conclusion: Amrinone appears to reverse the depressed cardiac index associated with verapamil overdose in a canine model while having no significant effect on the hypotension or bradycardia. C1 UNIV KENTUCKY,MED CTR,DEPT EMERGENCY MED,LEXINGTON,KY 40536. E CAROLINA UNIV,SCH MED,DEPT EMERGENCY MED,GREENVILLE,NC. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT EMERGENCY MED,BOSTON,MA. NR 33 TC 5 Z9 5 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 1996 VL 3 IS 8 BP 762 EP 767 DI 10.1111/j.1553-2712.1996.tb03512.x PG 6 WC Emergency Medicine SC Emergency Medicine GA VB385 UT WOS:A1996VB38500008 PM 8853671 ER PT J AU Goldberg, SN Gazelle, GS Solbiati, L Rittman, WJ Mueller, PR AF Goldberg, SN Gazelle, GS Solbiati, L Rittman, WJ Mueller, PR TI Radiofrequency tissue ablation: Increased lesion diameter with a perfusion electrode SO ACADEMIC RADIOLOGY LA English DT Article DE tissue ablation; lesion diameter; radiofrequency electrode; perfusion ID HEPATOCELLULAR-CARCINOMA; LIVER AB Rationale and Objectives. We sought to induce large zones of coagulation necrosis using radiofrequency (RF) with perfusion electrodes and to define optimal parameters for this system. Methods. We developed RF electrodes with internal cannulas to enable tip perfusion. Lesions were created with monopolar RF in ex vivo and in vivo liver and muscle tissue with and without perfusion of the electrode tip using 0 degrees C saline. In separate experiments, wattage, current, procedure duration, tip exposure, and perfused tip temperatures were studied. Results. In ex vivo liver tissue, a maximum lesion diameter of 3.1 cm without charring occurred with perfusion at 12 min and 50 W. In in vivo liver tissue with perfusion (tip temperature = 25-35 degrees C) and a 3-cm tip exposure, 80 W were deposited in muscle tissue and 65 W in liver tissue for 12 min without inducing charring. Lesion diameters were 4.5 cm and 2.4 cm, respectively. By comparison, without perfusion a maximum of 20 W could be deposited into either tissue type, resulting in 1.8-cm muscle lesions and 1.2-cm liver lesions, Tip temperatures between 45 degrees C and 55 degrees C resulted in charring. Smaller but predictable lesion diameters were created with a lower power, a shorter tip exposure, or both. Of all the parameters, diameter correlated best with the current applied. Conclusion. Perfusion of RF electrodes with chilled saline allows for increased power deposition without tissue charring, increasing the volume of coagulation necrosis created with a single electrode insertion. Perfusion electrodes therefore might decrease the number of probe insertions required for percutaneous tumor ablation therapy or allow for the treatment of larger lesions. C1 OSPED GEN,DEPT RADIOL,BUSTO ARSIZIO,ITALY. RADION INC,BURLINGTON,MA. RP Goldberg, SN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. OI Solbiati, Luigi/0000-0002-3109-1449 NR 23 TC 304 Z9 317 U1 0 U2 3 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 IS 8 BP 636 EP 644 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD211 UT WOS:A1996VD21100003 PM 8796727 ER PT J AU Adams Muller Panov Koenig Cavagna Roberts Runge Niemi Maly Brady Brasch Mueller AF Adams Muller Panov Koenig Cavagna Roberts Runge Niemi Maly Brady Brasch Mueller TI Characterization of proton relaxation enhancement - Discussion 6 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 RELAXOMETRY INC, MAHOPAC, NY USA. MASSACHUSETTS GEN HOSP, NMR CTR, CHARLESTOWN, MA USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. UNIV KENTUCKY, LEXINGTON, KY USA. TURKU UNIV HOSP, FIN-20520 TURKU, FINLAND. MALMO GEN HOSP, S-21401 MALMO, SWEDEN. UNIV MONS, B-7000 MONS, BELGIUM. RP Adams (reprint author), MALLINCKRODT MED INC, ST LOUIS, MO 63134 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S289 EP S291 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700038 ER PT J AU Corot Lasser Speck Maly Spinazzi Ratcliff Panov deHaen Dawson Krause Meyer Grabowski AF Corot Lasser Speck Maly Spinazzi Ratcliff Panov deHaen Dawson Krause Meyer Grabowski TI Discussion 3 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. BRACCO SPA,MILAN,ITALY. HAMMERSMITH HOSP,LONDON,ENGLAND. SCHERING AG,D-1000 BERLIN,GERMANY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MALMO GEN HOSP,S-21401 MALMO,SWEDEN. RP Corot (reprint author), GUERBET SA,ROISSY CHARLES DE GAULLE,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S223 EP S226 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700020 ER PT J AU Dawson Demsar deHaen Clement Wolf Schwickert Corot Higgins Lauffer Brasch Krause Adamzli Kawamura Watson Nunn Grabowski AF Dawson Demsar deHaen Clement Wolf Schwickert Corot Higgins Lauffer Brasch Krause Adamzli Kawamura Watson Nunn Grabowski TI Blood pool agents - Discussion 10 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 JOZEF STEFAN INST,LJUBLJANA,SLOVENIA. FAC MED NECKER ENFANTS MALAD,PARIS,FRANCE. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. MALLINCKRODT MED INC,ST LOUIS,MO. GUERBET SA,ROISSY,FRANCE. FUKUI MED SCH,FUKUI 91011,JAPAN. METASYN INC,CAMBRIDGE,MA. MASSACHUSETTS GEN HOSP EAST,CIPR,CHARLESTOWN,MA. BRACCO RES USA,PRINCETON,NJ. UNIV HOSP,MAINZ,GERMANY. RP Dawson (reprint author), HAMMERSMITH HOSP,LONDON,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S359 EP S362 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700063 ER PT J AU Fritz Grabowski deHaen Brasch Evill Wilson Corot Takahashi Speck Maly Krause Bettmann Lasser AF Fritz Grabowski deHaen Brasch Evill Wilson Corot Takahashi Speck Maly Krause Bettmann Lasser TI Toxicity of contrast media - Discussion 9 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. FLINDERS MED CTR,BEDFORD PK,SA,AUSTRALIA. GUERBET SA,ROISSY,FRANCE. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. SCHERING AG,D-1000 BERLIN,GERMANY. MALMO GEN HOSP,S-21401 MALMO,SWEDEN. DARTMOUTH HITCHCOCK MED CTR,LEBANON,NH 03766. RP Fritz (reprint author), IMARX PHARMACEUT CORP,TUCSON,AZ, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S339 EP S341 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700056 ER PT J AU Grabowski Brasch Revel Jakobsen Goldstein Wiggins Wolf Pantely Balzer AF Grabowski Brasch Revel Jakobsen Goldstein Wiggins Wolf Pantely Balzer TI Angiography and flow - Discussion 18 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. SCHERING AG,D-1000 BERLIN,GERMANY. BERLEX LABS INC,WAYNE,NJ. UNIV OSLO,NATL HOSP,OSLO,NORWAY. HOP CARDIOVASC & PNEUMOL LOUIS PRADEL,LYON,FRANCE. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. MGH CIPR,CHARLESTOWN,MA. RP Grabowski (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S471 EP S472 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700100 ER PT J AU Grabowski, EF Boor, SE Rodino, LJ Jang, IK Gold, H Michelson, AD AF Grabowski, EF Boor, SE Rodino, LJ Jang, IK Gold, H Michelson, AD TI Platelets are degranulated by some, but not all, contrast media SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Symposium CY JUN 17-22, 1995 CL NAANTALI, FINLAND ID FIBRINOLYSIS; COAGULATION; AGGREGATION; INVITRO; INVIVO; BLOOD C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. RP Grabowski, EF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC THROMBOSIS LAB,JACKSON 1306,BOSTON,MA 02114, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S328 EP S330 DI 10.1016/S1076-6332(96)80573-3 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700052 PM 8796594 ER PT J AU Koenig Miyazawa McLachlan Li, C Muller Frija Bulte Adams Mattrey Davis Brady Saini AF Koenig Miyazawa McLachlan Li, C Muller Frija Bulte Adams Mattrey Davis Brady Saini TI Superparamagnetic contrast media - Discussion 7 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 MALLINCKRODT MED INC,ST LOUIS,MO. MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA. NIH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. FAC MED NECKER ENFANTS MALAD,PARIS,FRANCE. MD ANDERSON CANC CTR,HOUSTON,TX 77030. UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. ADV MAGNET INC,PRINCETON,NJ. NIHON SCHERING KK,OSAKA,JAPAN. UNIV MONS HAINAUT,MONS,BELGIUM. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GUERBET SA,ROISSY,FRANCE. RP Koenig (reprint author), RELAXOMETRY INC,MAHOPAC,NY 10541, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S304 EP S307 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700044 ER PT J AU Koenig Siegle Frank Davis Grabowski Unger Kawamura Bulte Schlief Alexander Mattrey Bettman Muller Miyazawa Sovak AF Koenig Siegle Frank Davis Grabowski Unger Kawamura Bulte Schlief Alexander Mattrey Bettman Muller Miyazawa Sovak TI Development of new contrast agents - Discussion 11 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 NIH,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FUKUI MED SCH,FUKUI 91011,JAPAN. UNIV UTAH,SALT LAKE CITY,UT. DARTMOUTH HITCHCOCK MED CTR,LEBANON,NH 03766. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. SCHERING AG,D-1000 BERLIN,GERMANY. UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. UNIV MONS,B-7000 MONS,BELGIUM. NIHON SCHERING KK,OSAKA,JAPAN. BIOPHYSICA,LA JOLLA,CA. RP Koenig (reprint author), RELAXOMETRY INC,MAHOPAC,NY 10541, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S373 EP S375 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700067 ER PT J AU Lasser Adams Grabowski Kallio Albrecht Jakobsen Moreau MetzgerRose Mattrey Bettmann Schlief Unger Schneider Mulvagh Witter LaFrance Thomsen AF Lasser Adams Grabowski Kallio Albrecht Jakobsen Moreau MetzgerRose Mattrey Bettmann Schlief Unger Schneider Mulvagh Witter LaFrance Thomsen TI Progress in contrast enhanced ultrasonic imaging - Discussion 8 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 MALLINCKRODT MED INC,ST LOUIS,FRANCE. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TURKU UNIV HOSP,FIN-20520 TURKU,FINLAND. HAMMERSMITH HOSP,LONDON,ENGLAND. DARTMOUTH HITCHCOCK MED CTR,LEBANON,NH 03766. BRACCO DIAGNOST INC,PRINCETON,NJ. UNIV OSLO,NATL HOSP,OSLO,NORWAY. UNIV ARIZONA,TUCSON,AZ. HOP NECKER ENFANTS MALAD,PARIS,FRANCE. NIH,BETHESDA,MD 20892. BRACCO RES SA,GENEVA,SWITZERLAND. SCHERING AG,D-1000 BERLIN,GERMANY. MAYO CLIN,ROCHESTER,MN. UNIV COPENHAGEN,HERLEV HOSP,DK-2730 HERLEV,DENMARK. RP Lasser (reprint author), UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S325 EP S327 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700051 ER PT J AU Niemi, P Aronen, HJ Kwong, KK Gazit, IE Pardo, FS Rosen, BR AF Niemi, P Aronen, HJ Kwong, KK Gazit, IE Pardo, FS Rosen, BR TI Inverse correlation between T1 relaxation times before and after administration of contrast media in malignant brain tumors SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Symposium CY JUN 17-22, 1995 CL NAANTALI, FINLAND ID MAGNETIC-RESONANCE; DTPA C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,CHARLESTOWN,MA. HELSINKI UNIV HOSP,DEPT RADIOL,HELSINKI,FINLAND. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,CHARLESTOWN,MA. RP Niemi, P (reprint author), TURKU UNIV HOSP,DEPT DIAGNOST RADIOL,TURKU 20520,FINLAND. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S286 EP S288 DI 10.1016/S1076-6332(96)80558-7 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700037 PM 8796582 ER PT J AU Saini, S Edelman, RR Li, W Petersein, J Hahn, PF AF Saini, S Edelman, RR Li, W Petersein, J Hahn, PF TI Clinical evaluation of ultrasmall superparamagnetic iron oxide particles for liver imaging SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Contrast Media Research Symposium CY JUN 17-22, 1995 CL NAANTALI, FINLAND ID CONTRAST MATERIAL; MR; LESIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA. BETH ISRAEL HOSP,DEPT RADIOL,BOSTON,MA 02215. RP Saini, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 12 TC 2 Z9 2 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S409 EP S412 DI 10.1016/S1076-6332(96)80600-3 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700079 PM 8796616 ER PT J AU Wolf Morris Dawson Blomley Moreau Davis Evill Wisner Krause Tweedle Higgins Lipton Grabowski Lasser Almen Dean AF Wolf Morris Dawson Blomley Moreau Davis Evill Wisner Krause Tweedle Higgins Lipton Grabowski Lasser Almen Dean TI Contrast media pharmacokinetics - Discussion 5 SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 UNIV ROCHESTER,MED CTR,ROCHESTER,MI. HOP NECKER ENFANTS MALAD,PARIS,FRANCE. UNIV CALIF DAVIS,MED CTR,SACRAMENTO,CA 95817. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. HAMMERSMITH HOSP,LONDON,ENGLAND. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. FLINDERS MED CTR,BEDFORD PK,SA,AUSTRALIA. SCHERING AG,D-1000 BERLIN,GERMANY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. MALMO UNIV HOSP,MALMO,SWEDEN. UNIV TURKU,TURKU,FINLAND. RP Wolf (reprint author), MGH,CIPR,CHARLESTOWN,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 1996 VL 3 SU 2 BP S268 EP S272 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VD757 UT WOS:A1996VD75700033 ER PT J AU Leunig, M Yuan, F Berk, DA Gerweck, LE Jain, RK AF Leunig, M Yuan, F Berk, DA Gerweck, LE Jain, RK TI Heating or freezing bone - Effects on angiogenesis induction and growth potential in mice SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Article ID QUANTITATIVE-ANALYSIS; TRANSPLANTATION; CARTILAGE; BANKING AB We have characterized the effect of bone graft treatment by heating or freezing (with or without dimethyl sulfoxide (DMSO)). Tissue culture and dorsal skinfold chambers in mice were used as sites to quantify the effect on angiogenesis, growth and calcification of neonatal femora. Fresh femora increased in both length and cartilage diameter (calcification in vivo only), but cryopreservation or heating abolished the increase in femoral dimensions. In vivo, femora of all experimental groups elicited an angiogenic response from the host tissue, which was most pronounced for fresh femora, weaker for DMSO-preserved frozen bone and poor for unprotected frozen bone and boiled femora. Freezing in the presence of a cryopreservative (DMSO) was found to preserve the angiogenic potential of frozen bone, whereas unprotected heating or freezing significantly impaired angiogenesis induction and growth potential. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [R35-CA56591, CA22860] NR 15 TC 10 Z9 10 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD AUG PY 1996 VL 67 IS 4 BP 383 EP 388 PG 6 WC Orthopedics SC Orthopedics GA VE328 UT WOS:A1996VE32800015 PM 8792744 ER PT J AU Bohn, MJ Barton, BA Barron, KE AF Bohn, MJ Barton, BA Barron, KE TI Psychometric properties and validity of the Obsessive-Compulsive Drinking Scale SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; questionnaire; obsessions; compulsions; automatism ID ALCOHOL-ABUSE; DEPENDENCE; QUANTIFICATION; COMPONENTS; BEHAVIOR AB Abstinent alcoholics' self-reports of distressing alcohol-associated thoughts and compulsions to drink were evaluated by the Obsessive-Compulsive Drinking Scale (OCDS). Exploratory and confirmatory factor analyses on separate subject samples revealed that subjects' OCDS responses were best described by four correlated dimensions: alcohol obsessions, alcohol consumption, automaticity, and interference due to drinking. The validity of this four-factor solution was supported by the pattern of associations with drinking and coping style measures. In particular, alcohol obsessions were positively associated with alcohol dependence and use of passive/avoidant coping. Automaticity was positively associated with the intensity and salience of drinking, and inversely associated with use of active/approach coping, as well as abstinence duration. The obsession and automaticity subscales of the OCDS may be useful in evaluating cognitive-motivational processes associated with recovery from alcoholism. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,OUTPATIENT SUBST ABUSE TREATMENT PROGRAM,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PSYCHIAT SERV,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,MADISON,WI 53792. UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53706. FU NIAAA NIH HHS [R29-AA09948] NR 26 TC 60 Z9 60 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1996 VL 20 IS 5 BP 817 EP 823 DI 10.1111/j.1530-0277.1996.tb05257.x PG 7 WC Substance Abuse SC Substance Abuse GA VD037 UT WOS:A1996VD03700005 PM 8865954 ER PT J AU Lasagna, L Frei, E AF Lasagna, L Frei, E TI The impact of regulations, tradition, and experimental design on clinical cancer trials: Report and recommendations resulting from Washington cancer trials conference SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article AB On July 28-29, 1995, 45 invited participants met in Washington, D.C. to discuss clinical trials in patients suffering from cancer. The conferees represented a variety of backgrounds-academia, industry, government, contract research organizations (CROs), and patient advocates. The meeting was sponsored by CaP CURE, a nonprofit association dedicated to the cure of prostatic cancer. Formal presentations and discussion, with informal commentaries by all participants, occupied the first day's meeting. In the evening, the conferees met in small work groups and prepared recommendations for change that were presented to the full conference on the following morning. Discussions were spirited and candid, and unanimity was achieved on many points. Where controversy could not be resolved, such disagreement was duly noted and is described below. The authors of this final report take full responsibility for its content, although every participant was given an opportunity to read earlier drafts. Participants are listed in Appendix I. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Lasagna, L (reprint author), TUFTS UNIV,SACKLER SCH GRAD BIOMED SCI,TUFTS CTR STUDY DRUG DEV,136 HARRISON AVE,BOSTON,MA 02111, USA. NR 2 TC 6 Z9 6 U1 0 U2 0 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 AUG PY 1996 VL 19 IS 4 BP 325 EP 329 DI 10.1097/00000421-199608000-00001 PG 5 WC Oncology SC Oncology GA UW941 UT WOS:A1996UW94100001 PM 8677898 ER PT J AU Ruttledge, MH Andermann, AA Phelan, CM Claudio, JO Han, FY Chretien, N Rangaratnam, S MacCollin, M Short, P Parry, D Michels, V Riccardi, VM Weksberg, R Kitamura, K Bradburn, JM Hall, BD Propping, P Rouleau, GA AF Ruttledge, MH Andermann, AA Phelan, CM Claudio, JO Han, FY Chretien, N Rangaratnam, S MacCollin, M Short, P Parry, D Michels, V Riccardi, VM Weksberg, R Kitamura, K Bradburn, JM Hall, BD Propping, P Rouleau, GA TI Type of mutation in the neurofibromatosis type 2 gene (NF2) frequently determines severity of disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; TUMOR-SUPPRESSOR GENE; UNITED-KINGDOM; LENS OPACITIES; CHROMOSOME-22; DIAGNOSIS; INDIVIDUALS; ASSOCIATION; NEUROMAS; MARKERS AB The gene predisposing to neurofibromatosis type 2 (NF2) on human chromosome 22 has revealed a wide variety of different mutations in NF2 individuals. These patients display a marked variability in clinical presentation, ranging from very severe disease with numerous tumors at a young age to a relatively mild condition much later in life. To investigate whether this phenotypic heterogeneity is determined by the type of mutation in NF2, we have collected clinical information on 111 NF2 cases from 73 different families on whom we have performed mutation screening in this gene. Sixty-seven individuals (56.2%) from 41 of these kindreds revealed 36 different putative disease-causing mutations. These include 26 proposed protein-truncating alterations (frameshift deletions/insertions and nonsense mutations), 6 splice-site mutations, 2 missense mutations, 1 base substitution in the 3' UTR of the NF2 cDNA, and a single 3-bp in-frame insertion. Seventeen of these mutations are novel, whereas the remaining 19 have been described previously in other NF2 individuals or sporadic tumors. When individuals harboring protein-truncating mutations are compared with cases with single codon alterations, a significant correlation (P < .001) with clinical outcome is observed. Twenty-four of 28 patients with mutations that cause premature truncation of the NF2 protein, schwannomin, present with severe phenotypes. In contrast, all 16 cases from three families with mutations that affect only a single amino acid have mild NF2. These data provide conclusive evidence that a phenotype/genotype correlation exists for certain NF2 mutations. C1 MCGILL UNIV,UNIV DIV MED GENET,MONTREAL,PQ,CANADA. KAROLINSKA HOSP,DEPT MOL MED,ENDOCRINE TUMOR UNIT,S-10401 STOCKHOLM,SWEDEN. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. NATL CANC INST,GENET EPIDEMIOL BRANCH,BETHESDA,MD. MAYO CLIN,DEPT GENET,ROCHESTER,MN. NEUROFIBROMATOSIS INST,LA CRESCENTA,CA. HOSP SICK CHILDREN,GENET CLIN,TORONTO,ON M5G 1X8,CANADA. JICHI MED SCH,DEPT OTOLARYNGOL,MINAMI KAWACHI,TOCHIGI,JAPAN. UNIV KENTUCKY,KENTUCKY CLIN,DEPT PEDIAT GENET,LEXINGTON,KY. UNIV BONN,INST HUMAN GENET,D-5300 BONN,GERMANY. RP Ruttledge, MH (reprint author), MONTREAL GEN HOSP,RES INST,CTR RES NEUROSCI,7TH FLOOR,LIVINGSTON HALL,1650 CEDAR AVE,MONTREAL,PQ H3G 1A4,CANADA. NR 24 TC 171 Z9 176 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1996 VL 59 IS 2 BP 331 EP 342 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA VM288 UT WOS:A1996VM28800008 PM 8755919 ER PT J AU Medina, RA Pugh, JA Monterrosa, A Cornell, J AF Medina, RA Pugh, JA Monterrosa, A Cornell, J TI Minority advantage in diabetic end-stage renal disease survival on hemodialysis: Due to different proportions of diabetic type? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE diabetes mellitus; diabetic nephropathies; survival; renal replacement therapy; ethnic groups; Mexican-Americans; blacks; whites ID MEXICAN-AMERICANS; DIALYSIS PATIENTS; MORTALITY; FAILURE; DEATH; MELLITUS; IMPACT; RATES AB The objectives of this study were to identify predictors of survival on hemodialysis in patients with diabetic end-stage renal disease (ESRD) and to explain ethnic differences in survival among non-Hispanic whites, African-Americans, and Mexican-Americans. The study design was a survival analysis of an inception cohort and was conducted in dialysis centers in two urban counties in Texas. A population-based, tri-ethnic cohort of 638 adult patients with diabetic ESRD were studied. Follow-up was completed in 96% of the cohort, with a median length of follow-up of 3.8 years. Survival length on center hemodialysis was the main outcome measure. In a combined model of types I and II diabetes, Mexican-Americans (relative hazard [RH], 0.666; 95% confidence interval [CI], 0.457 to 0.944) and African-Americans (RH, 0.598; 95% CI, 0.414 to 0.864) showed a better survival than non-Hispanic whites. Other predictors independently associated with survival were age (RH, 1.015 per 10 years of age; 95% CI, 1.001 to 1.028), high self-reported physical disability (RH, 1.770; 95% CI, 1.213 to 2.583), coronary artery disease (RH, 1.445; 95% CI, 1.044 to 2.012), lower extremity amputations (RH, 2.049; 95% CI, 1.438 to 2.920), and average blood glucose levels prior to ESRD (RH, 1.002 per 1 mg/dL increment; 95% OI, 1.003 to 1.004). Non-Hispanic whites had a significantly higher rate of type I diabetes, but did not have a greater burden of any of the other predictors, In separate type I and II models, ethnicity was still a significant predictor of survival among type I but not among type II. In conclusion, we have reconfirmed the survival advantage on dialysis of African-Americans and Mexican-Americans over non-Hispanic whites with diabetic ESRD. However, among type II patients, this minority survival advantage disappears. Self-reported physical disability is an important predictor of survival among both diabetes types. Functional status at baseline is an important predictor of survival and should be assessed as an adjunct to measurement of co-morbidities. Macrovascular disease is important for type II, while educational status is important for type I. While amputation may be a marker for the severity of systemic illness, it could be a marker for quality of primary care provided to diabetic patients, since a majority of diabetic lower extremity amputations are thought to be preventable. (C) 1996 by the National Kidney Foundation, Inc. C1 AUDIE L MURPHY MEM VET ADM MED CTR,MEXICAN AMER MED TREATMENT EFFECTIVENESS RES CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [5 U01 HS07397-02]; NIDDK NIH HHS [R01 DK 38392-05S1, R01 DK 38392-05] NR 28 TC 25 Z9 25 U1 0 U2 1 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 AUG PY 1996 VL 28 IS 2 BP 226 EP 234 DI 10.1016/S0272-6386(96)90306-6 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA VA600 UT WOS:A1996VA60000010 PM 8768918 ER PT J AU Norris, KC Levine, B Ganesan, K AF Norris, KC Levine, B Ganesan, K TI Thyrotoxic periodic paralysis associated with hypokalemia and hypophosphatemia SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE thyrotoxic periodic paralysis; hypokalemia; hypophosphatemia; hyperthyroidism; African-American ID PUMP AB We report the rare case of a 43-year-old African-American man with thyrotoxic periodic paralysis associated with hypokalemia and hypophosphatemia. Both serum potassium and serum phosphate levels returned to normal after supplementation with only potassium. We consider the unusual condition of hyperthyroid-related hypokalemia and hypophosphatemia to have contributed to the acute paralysis in this patient. (C) 1996 by the National Kidney Foundation, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Norris, KC (reprint author), CHARLES R DREW UNIV MED & SCI,KING DREW MED CTR,DEPT MED,12021 S WILMINGTON BLVD,LOS ANGELES,CA 90059, USA. NR 28 TC 23 Z9 23 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 AUG PY 1996 VL 28 IS 2 BP 270 EP 273 DI 10.1016/S0272-6386(96)90312-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA VA600 UT WOS:A1996VA60000016 PM 8768924 ER PT J AU Fukui, MB Weissman, JL Curtin, HD Kanal, E AF Fukui, MB Weissman, JL Curtin, HD Kanal, E TI T2-weighted MR characteristics of internal auditory canal masses SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE neuroma; temporal bone, magnetic resonance ID ACOUSTIC NEUROMAS; CEREBELLOPONTINE ANGLE; GADOLINIUM-DTPA; DIAGNOSIS; TUMORS; CT AB PURPOSE: To determine whether masses of the internal auditory canal are hypointense relative to cerebrospinal fluid, and therefore visible, on fast spin-echo T2-weighted MR images, METHODS: Forty-six patients had 50 masses of the internal auditory canal, identified initially on contrast-enhanced MR images, that were evaluated retrospectively for signal intensity of the mass with respect to cerebrospinal fluid and for visibility of the neural elements within the internal auditory canal on T2-weighted images. RESULTS: Forty-seven of 50 masses were clearly identified on T2-weighted images. Three small abnormalities (2 to 4 mm) were not seen with confidence on T2-weighted images, However, on close inspection of these three masses, the small abnormality on contrast-enhanced MR images corresponded to a hypointense focus on T2-weighted images. All 50 masses were hypointense relative to cerebrospinal fluid on T2-weighted images. CONCLUSION: All masses of the internal auditory canal in this study were hypointense relative to cerebrospinal fluid on T2-weighted images, and were therefore visible. C1 UNIV PITTSBURGH,MED CTR,DEPT OTOLARYNGOL,PITTSBURGH,PA 15213. MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. RP Fukui, MB (reprint author), UNIV PITTSBURGH,MED CTR,DEPT RADIOL,200 LOTHROP ST,PITTSBURGH,PA 15213, USA. NR 28 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 1996 VL 17 IS 7 BP 1211 EP 1218 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VC329 UT WOS:A1996VC32900002 PM 8871701 ER PT J AU Foster, CS Alter, G DeBarge, LR Raizman, MB Crabb, JL Santos, CI Feiler, LS Friedlaender, MH AF Foster, CS Alter, G DeBarge, LR Raizman, MB Crabb, JL Santos, CI Feiler, LS Friedlaender, MH TI Efficacy and safety of rimexolone 1% ophthalmic suspension vs 1% prednisolone acetate in the treatment of uveitis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PHOSPHATE AB PURPOSE: Two multicenter studies compared the efficacy and safety of rimexolone 1% ophthalmic suspension (Vexol 1%, Alcon) and 1% prednisolone acetate (Pred Forte, Allergan). METHODS: Patients with acute uveitis, recurrent iridocyclitis, or chronic uveitis treatable by topical corticosteroid were enrolled, Treatment regimen was one or two drops every hour during Week 1, every two hours during Week 2, four times a day during Week 3, and once a day for the last three days, Efficacy and safety were determined on Days 3, 4, 7 to 10, 14, 21, and 28, A poststudy evaluation was conducted 36 to 72 hours after treatment was stopped. RESULTS: When anterior chamber cell and flare were measured, rimexolone 1% was found to be as effective as 1% prednisolone. The largest difference observed between treatments was 0.5 score unit, not clinically significant, There were no statistically significant differences in cell scores in either study (P > .05), No statistically significant differences in flare scores were found except at Day 28 in Study One (P = .04). Also, prednisolone was found to be more likely than rimexolone to cause a clinically significant increase (10 mm Hg or more) in intraocular pressure (1.7 times more likely in Study One, eight times more likely in Study Two). CONCLUSION: Rimexolone 1% ophthalmic suspension is safe and effective for the treatment of uveitis. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. CHARLOTTE EYE EAR NOSE & THROAT ASSOCIATES,CHARLOTTE,NC. UNIV TENNESSEE,CHATTANOOGA,TN. NEW ENGLAND EYE CTR,BOSTON,MA. EYE TECH MEMPHIS,MEMPHIS,TN. UNIV PUERTO RICO,RIO PIEDRAS,PR 00931. SCRIPPS CLIN MED GRP INC,LA JOLLA,CA. NR 17 TC 37 Z9 38 U1 2 U2 5 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 AUG PY 1996 VL 122 IS 2 BP 171 EP 182 PG 12 WC Ophthalmology SC Ophthalmology GA VB441 UT WOS:A1996VB44100003 PM 8694085 ER PT J AU Strahlman, E Tipping, R Vogel, R Abrantes, P Alm, A Airaksinen, PJ Barnebey, H Borgeois, A Cohen, JS CollignonBranch, J Cyrlin, MN Demailly, P Ehinger, B George, JL Greve, E Gross, RL Higginbotham, EJ Kass, MA Laibovitz, RA Lange, U Lewis, RA Maclure, G McMahon, CD Mandelkorn, RM Schuman, JS Serle, J Skuta, G Tolia, J Weinreb, R Wilensky, J Zimmerman, TJ Clineschmidt, CM Lippa, EA Reines, SA Strohmaier, KM AF Strahlman, E Tipping, R Vogel, R Abrantes, P Alm, A Airaksinen, PJ Barnebey, H Borgeois, A Cohen, JS CollignonBranch, J Cyrlin, MN Demailly, P Ehinger, B George, JL Greve, E Gross, RL Higginbotham, EJ Kass, MA Laibovitz, RA Lange, U Lewis, RA Maclure, G McMahon, CD Mandelkorn, RM Schuman, JS Serle, J Skuta, G Tolia, J Weinreb, R Wilensky, J Zimmerman, TJ Clineschmidt, CM Lippa, EA Reines, SA Strohmaier, KM TI A six-week dose-response study of the ocular hypotensive effect of dorzolamide with a one-year extension SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CARBONIC-ANHYDRASE INHIBITORS; INTRAOCULAR-PRESSURE; TIMOLOL; SEZOLAMIDE; EFFICACY; MK-507 AB PURPOSE: To investigate the efficacy and dose-response relationship of three concentrations (0.2%, 0.7%, and 2.0%) of dorzolamide hydrochloride in lowering elevated intraocular pressure (IOP) in patients during a six week period and to evaluate the efficacy of 0.7% and 2.0% dorzolamide administered for an additional year. METHODS: This prospective, double-masked, randomized, placebo-controlled, multinational study enrolled 333 adults with open-angle glaucoma or ocular hypertension, During the six week dose-response phase, patients were randomized to thrice-daily dosing of four treatments: 0.2%, 0.7%, or 2.0% dorzolamide or placebo (vehicle of dorzolamide), During a one-year extension, patients received 0.7% or 2.0% dorzolamide, and, if needed, 0.5% timolol twice daily for elevated IOP. RESULTS: In the dose-response phase, mean percent reduction of IOP (peak) was 16% to 18% for 2.0% and 0.7% dorzolamide and 4% to 7% for the placebo group, for a net reduction of IOP by dorzolamide of 11% to 14%, The 0.2% concentration of dorzolamide was not sufficiently active for further consideration, During the extension, dorzolamide maintained an adequate reduction of IOP in 55% (174 of 316) of patients, Throughout the study, the reduction in IOP was numerically great er for patients receiving 2.0% vs 0.7% dorzolamide, After 12 months of receiving dorzolamide, 20% to 28% of total carbonic anhydrase activity was observed, CONCLUSIONS: Topical dorzolamide used three times daily in concentrations of 0.7% or 2.0% lowered IOP and was generally well tolerated as monotherapy or in combination with 0.5% timolol. C1 MERCK & CO INC,W POINT,PA. HOSP SAO JOSE,LISBON,PORTUGAL. UMEA UNIV,UMEA,SWEDEN. UNIV OULU,OULU,FINLAND. VAL DE GRACE HOSP,PARIS,FRANCE. UNIV SART TILMAN,LIEGE,BELGIUM. OAKLAND UNIV,ROCHESTER,MI 48063. HOP ST JOSEPH,F-75674 PARIS,FRANCE. LUND UNIV,LUND,SWEDEN. HOP BRABOIS,NANCY,FRANCE. UNIV AMSTERDAM,ACAD MED CTR,NL-1105 AZ AMSTERDAM,NETHERLANDS. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV MICHIGAN,ANN ARBOR,MI 48109. WASHINGTON UNIV,ST LOUIS,MO. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. MT SINAI SCH MED,NEW YORK,NY. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. ILLINOIS EYE & EAR INFIRM,CHICAGO,IL. UNIV LOUISVILLE,LOUISVILLE,KY 40292. MERCK RES LABS,BLUE BELL,PA. RI Schuman, Joel/K-7304-2012 OI Schuman, Joel/0000-0002-8885-3766 NR 13 TC 60 Z9 60 U1 1 U2 2 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 AUG PY 1996 VL 122 IS 2 BP 183 EP 194 PG 12 WC Ophthalmology SC Ophthalmology GA VB441 UT WOS:A1996VB44100004 PM 8694086 ER PT J AU Nickeleit, V Kaufman, AH Zagachin, L Dutt, JE Foster, CS Colvin, RB AF Nickeleit, V Kaufman, AH Zagachin, L Dutt, JE Foster, CS Colvin, RB TI Healing corneas express embryonic fibronectin isoforms in the epithelium, subepithelial stroma, and endothelium SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ALTERNATIVELY SPLICED FIBRONECTIN; RABBIT CORNEA; CELLULAR FIBRONECTIN; RAT FIBRONECTIN; MESSENGER-RNAS; WOUNDS; CELLS; LOCALIZATION; TENASCIN; INVITRO AB The cornea is a simple, nonvascularized structure, advantageous for studying the molecular components of epithelial and stromal wound repair. Fibronectin (Fn), of uncertain source and composition, accumulates in healing corneas. We postulated that local synthesis of Fn occurs, as exogenous plasma/tear-derived Fn, which lack the embryonic EIIIA and EIIIB segments, have no consistent beneficial effect on healing Two contrasting corneal wounds were examined by in situ hybridization: a wound of the anterior stroma, basement membrane, and epithelium (anterior excimer laser keratectomy) and a superficial wound restricted to the epithelium that preserved the basement membrane (mechanical scrape). Both wounds heal without scarring. In normal corneas, only the endothelium had detectable Fn mRNA, containing the V and EIIIB domains, sporadically and at low levels. After anterior keratectomies, extensive expression of Fn mRNA occurred in a specific distribution that changed during the phases of healing. Before re-epitheliatization (days 1 and 2) V+, EIIIA(+), and EIIIB(+) isoforms were diffusely found in stromal cells under and adjacent to the wound After re-epithelialization (days 3 to 42) and reconstitution of laminin in the regenerating basement membrane zone, V+, EIIIA(+), and EIIIB(+) isoform synthesis was largely restricted to subepithelial stromal cells at the epithelial/stromal interface. In addition, the corneal epithelial cells focally expressed Fn mRNA. The endothelium showed increased levels of V+, EIIIA(+), and EIIIB(+) Fn mRNA Ln open and recently 1 e-epithelialized wounds. At 12 weeks after keratectomy, Fn mRNA expression returned to control levels. lit contrast, scrape wounds had only a modest increase of stromal and endothelial Fn mRNA (EIIIA(+), EIIIB(+), and V+) during the first 7 days and no evidence of epithelial Fn synthesis. Embryonic Fn isoforms are synthesized transiently by the cornea in response to even the most superficial wounds and are likely to be relevant to corneal healing and restoration of structure without scar formation. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,BOSTON,MA 02114. FU NCI NIH HHS [R37CA20822-17] NR 39 TC 26 Z9 27 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 AUG PY 1996 VL 149 IS 2 BP 549 EP 558 PG 10 WC Pathology SC Pathology GA UZ763 UT WOS:A1996UZ76300020 PM 8701994 ER PT J AU Platten, M Giordano, MJ Dirven, CMF Gutmann, DH Louis, DN AF Platten, M Giordano, MJ Dirven, CMF Gutmann, DH Louis, DN TI Up-regulation of specific NF1 gene transcripts in sporadic pilocytic astrocytomas SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; TUMOR-SUPPRESSOR GENE; MESSENGER-RNA; CELL-DIFFERENTIATION; BRAIN-TUMORS; EXPRESSION; PROTEIN; GAP; P53; MUTATIONS AB Pilocytic astrocytomas of the optic nerve (optic nerve gliomas) are closely associated with neurofibromatosis 1 (NF1), and allelic losses of the NF1 gene region on chromosome 17q occur in sporadic pilocytic astrocytomas. We therefore hypothesized that the NF1 gene nets as a tumor suppressor gene in pilocytic astrocytomas, and that NF1 gene expression would be reduced or absent in these tumors. To evaluate this possibility, we examined quantitative and qualitative aspects of NF1 gene expression in six sporadic pilocytic astrocytomas. Surprisingly, the NF1 gene was overexpressed up to fourfold in these tumors when compared with normal brain. This up-regulation was accompanied by immunohistochemical positivity using a carboxyl-terminal antibody and by the absence of mutations in one kilobase of the NF1 coding sequence, consistent with the expressed transcript and protein being full length and probably wild type. Pilocytic astrocytomas showed a marked predominance of transcripts containing exon 23a and lacking exon 9br, the same isoforms that are expressed by normal and reactive astrocytes and malignant astrocytomas. These data illustrate that pilocytic astrocytomas overexpress specific NF1 gene transcripts, perhaps as a regulatory response to growth stimuli. The role of the NF1 gene as a tumor suppressor in pilocytic astrocytomas, however, remains to be proven. C1 MASSACHUSETTS GEN HOSP,CS KUBIK LAB NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOL NEUROONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. WASHINGTON UNIV,SCH MED,CTR STUDY NERVOUS SYST INJURY,DEPT NEUROL,ST LOUIS,MO. WASHINGTON UNIV,SCH MED,CTR STUDY NERVOUS SYST INJURY,DEPT PEDIAT,ST LOUIS,MO. WASHINGTON UNIV,SCH MED,CTR STUDY NERVOUS SYST INJURY,DEPT GENET,ST LOUIS,MO. WASHINGTON UNIV,SCH MED,CTR STUDY NERVOUS SYST INJURY,DEPT NEUROSURG,ST LOUIS,MO. UNIV GRONINGEN HOSP,DEPT NEUROSURG,GRONINGEN,NETHERLANDS. RI Platten, Michael/F-2902-2013 FU NCI NIH HHS [CA57683]; NINDS NIH HHS [NS24279, NSO159] NR 38 TC 38 Z9 38 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 AUG PY 1996 VL 149 IS 2 BP 621 EP 627 PG 7 WC Pathology SC Pathology GA UZ763 UT WOS:A1996UZ76300026 PM 8702000 ER PT J AU Spetz, AL Strominger, J GrohSpies, V AF Spetz, AL Strominger, J GrohSpies, V TI T cell subsets in normal human epidermis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NORMAL HUMAN-SKIN; RECEPTOR-GAMMA-DELTA; LEUKOCYTE ADHESION MOLECULE-1; LYMPHOCYTE-ASSOCIATED ANTIGEN; HUMAN PERIPHERAL-BLOOD; DENDRITIC CELLS; ALPHA-BETA; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; LANGERHANS CELLS AB Freshly isolated human lymphocytes from normal epidermis were characterized with respect to distribution of subsets. The major T cell receptor-alpha beta(+) compartment was enriched for CD4(+), for CD8 alpha alpha(+), and for CD4(-) CD8(-) T lymphocytes compared with peripheral blood lymphocytes. Furthermore, the majority of epidermal T lymphocytes expressed a CD45RA(-) CD45RO(high) Fas(+) memory/effector phenotype; many also expressed early-intermediate activation markers, suggesting antigenic exposure in viva The cutaneous lymphocyte-associated antigen was expressed by almost all epidermal T lymphocytes. A large portion also expressed the mucosal-associated alpha(e) beta(7)-integrin, which may mediate retention to epithelium. These data show that T lymphocytes present in normal human epidermis constitute a distinct T cell compartment with characteristics similar to that of other epithelial-associated T cell compartments. C1 DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RI Spetz, Anna-Lena/C-3543-2016 OI Spetz, Anna-Lena/0000-0003-3964-9512 FU NCI NIH HHS [CA47554] NR 60 TC 37 Z9 38 U1 0 U2 1 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 AUG PY 1996 VL 149 IS 2 BP 665 EP 674 PG 10 WC Pathology SC Pathology GA UZ763 UT WOS:A1996UZ76300030 PM 8702004 ER PT J AU Goodyear, LJ Chang, PY Sherwood, DJ Dufresne, SD Moller, DE AF Goodyear, LJ Chang, PY Sherwood, DJ Dufresne, SD Moller, DE TI Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE ribosomal S6 kinase 2; c-jun NH2-terminal kinases; stress-activated protein kinases; p38 kinase ID MICROTUBULE-ASSOCIATED PROTEIN-2; C-JUN; MAP KINASE; GENE-EXPRESSION; PHOSPHORYLATION; IDENTIFICATION; ADAPTATIONS; STIMULATION; ISOFORMS; CASCADE AB Studies in mammalian cells have established the existence of at least three distinct mitogen-activated protein kinase (MAP kinase) signaling pathways that are activated by a variety of growth factors and/or environmental stressors. We determined whether physical exercise, a physiological stressor, and insulin, a metabolic stimulator and growth factor, activate the c-jun NH2-terminus kinase (JNK), the p38 kinase, and/or the extracellular regulatory kinases (ERK; p42(MAPK) and p44(MAPK)) signaling pathways in rat skeletal muscle. Animals were studied immediately after running on a motorized treadmill for 10-60 min (20 m/min, 10% grade) or 5-30 min after an intraperitoneal injection of insulin (20 U/rat). Exercise increased skeletal muscle JNK activity by two- to threefold throughout the time course studied, whereas insulin did not significantly increase JNK activity. The p38 activity was slightly stimulated by exercise and not by insulin. The ERK kinase pathway, as assessed by ribosomal S6 kinase-2 activity assays and phosphospecific p42(MAPK)/p44(MAPK) immunoblotting, was stimulated by both exercise and insulin. These data are the first demonstration of exercise stimulating multiple intracellular signaling pathways in skeletal muscle. Activation of these MAP kinase signaling pathways may mediate changes in skeletal muscle growth and metabolism that occur in response to exercise. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. MERCK & CO INC, MERCK SHARP & DOHME RES LABS, DEPT MOL ENDOCRINOL, RAHWAY, NJ 07065 USA. BETH ISRAEL HOSP, DEPT MED, BOSTON, MA 02215 USA. FU NIAMS NIH HHS [R29-AR-42238]; PHS HHS [R01-45874] NR 39 TC 155 Z9 168 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 1996 VL 271 IS 2 BP E403 EP E408 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VD647 UT WOS:A1996VD64700025 PM 8770036 ER PT J AU Mukai, H Fitzgibbon, WR Bozeman, G Margolius, HS Ploth, DW AF Mukai, H Fitzgibbon, WR Bozeman, G Margolius, HS Ploth, DW TI Bradykinin B-2 receptor antagonist increases chloride and water absorption in rat medullary collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE kidney; inner medullary collecting duct; Dahl salt-resistant rats; distal chloride delivery ID PAPILLARY BLOOD-FLOW; RENAL-FUNCTION; IMMUNOREACTIVE KALLIKREIN; ANGIOTENSIN-II; SODIUM; LOCALIZATION; TRANSPORT; NEPHRON; KININS; HOE-140 AB This study tested the hypothesis that intrarenal kinins play a regulatory role in electrolyte excretion by altering Cl- absorption in the collecting duct. We measured Cl- and inulin concentrations in tubular fluid samples obtained from medullary collecting ducts (MCD) of Dahl/Rapp salt-resistant (SR/ Jr) rats by microcatheterization of ducts of Bellini before and after treatment with the bradykinin receptor antagonist HOE-140. Tubular fluid was obtained from paired terminal inner medullary (t-IMCD) and outer medullary (OMCD) collecting duct sites of the left kidney. HOE-140 (n = 7) or vehicle (n = 5) was infused intravenously, and the collections were repeated. HOE-140 did not alter glomerular filtration rate but decreased urine flow rate (P < 0.05) and absolute and fractional Cl- excretion (P < 0.01). HOE-140 did not alter the fraction of filtered Cl- delivered (FDCl) to the OMCD but decreased FDCl to the t-IMCD from 2.3 +/- 0.3 to 1.3 +/- 0.3% (P < 0.05). The fraction of filtered Cl- absorbed per millimeter between the collection sites was increased from 0.2 +/- 0.1 to 0.6 +/- 0.1% (P < 0.05). Fractional absorption of water along the MCD was also increased (P < 0.05). No changes in excretory function or tubular Cl- or water absorption were observed in vehicle-treated rats. These studies show that kinin B-2 receptor blockade enhances Cl- and water absorption in the MCD, a finding that supports a role of renal kinins in the regulation of NaCl and water excretion. C1 MED UNIV S CAROLINA, DIV NEPHROL, DEPT MED, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT CELL & MOL PHARMACOL, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT EXPT THERAPEUT, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT UROL, CHARLESTON, SC 29425 USA. RALPH H JOHNSON VET AFFAIRS MED CTR, CHARLESTON, SC 29403 USA. FU NHLBI NIH HHS [HL-17705, HL-44671] NR 38 TC 26 Z9 26 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 1996 VL 271 IS 2 BP R352 EP R360 PG 9 WC Physiology SC Physiology GA VE002 UT WOS:A1996VE00200008 PM 8770134 ER PT J AU Schweitzer, M Asch, DA AF Schweitzer, M Asch, DA TI The role of employee flexible spending accounts in health care financing SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Employee flexible spending accounts for health care represent one component of the current health care financing system that merits serious reform. These accounts create a system of undesirable incentives, force employees and employers to take complicated gambles, reduce tax revenues, and fail to meet their purported policy objectives. This paper describes shortcomings in these accounts from both a theoretical and an empirical perspective. Some proposed alternatives, including medical spending accounts and zero balance accounts, resolve many of these concerns but not all of them. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,SCH MED,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. RP Schweitzer, M (reprint author), UNIV MIAMI,SCH BUSINESS,DEPT MANAGEMENT,414 JENKINS BLDG,CORAL GABLES,FL 33129, USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1996 VL 86 IS 8 BP 1079 EP 1081 DI 10.2105/AJPH.86.8_Pt_1.1079 PN 1 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VB448 UT WOS:A1996VB44800006 PM 8712264 ER PT J AU Virtanen, I Laitinen, A Tani, T Paakko, P Laitinen, LA Burgeson, RE Lehto, VP AF Virtanen, I Laitinen, A Tani, T Paakko, P Laitinen, LA Burgeson, RE Lehto, VP TI Differential expression of laminins and their integrin receptors in developing and adult human lung SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CELL-ADHESION MOLECULES; BRANCHING MORPHOGENESIS; A-CHAIN; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; MOUSE LUNG; ALPHA-6-BETA-4 INTEGRIN; CHROMOSOMAL ASSIGNMENT; NEUROMUSCULAR-JUNCTION; TISSUE DISTRIBUTION AB Laminins (Ln) appear to play an important role in the morphogenesis of airways. We studied the expression of different laminin chains and their integrin receptors in fetal and adult lung by immunohistochemistry. Special attention was focused on the changes in the expression of these proteins during the development from the pseudoglandular (PG) and canalicular stages to adult lung, and on the possible implications of the changes for the normal lung development. The most significant changes in the expression pattern were found during the development from the PG stage to the canalicular stage. Basement membranes (BM) of both the epithelial buds and the becoming bronchi showed reactivity for Ln-alpha 1, -alpha 3, and -beta 3 chains at all stages. The alpha 2 chain was expressed only in the epithelial buds at the PG stage, and could not be found in any epithelial structures at the canalicular stage. Similarly, at the PG stage the Ln-beta 2 chain was expressed in BMs of both epithelial buds and bronchi but disappeared from the bronchial BM before the canalicular stage. Ln-beta 1 chain appeared in the bronchial BM first in the mature lung, which suggests the presence of uncharacterized Ln-beta chains earlier in development. There were considerable changes in the expression of integrins (Int) comcomitantly with alterations in the composition of the BMs. At the PG stage the epithelial buds showed reactivity for Int-alpha(2), -alpha(3), and -alpha(6) subunits, but at the canalicular stage the Int-alpha(2) and -alpha(6) subunits disappeared, and only Int-alpha(3) integrin subunit was found in evolving alveolar walls; Int-alpha(6) was found in capillaries. A similar distribution of Int subunits was also found in adult alveoli. The bronchi expressed Int-alpha(2) -alpha(3) and -alpha(6) subunits at all developmental stages, but the Int-beta(4) subunit emerged first at the canalicular stage. Our results suggest that there are major changes in the expression of Ln and their Int receptors during morphogenesis of the lung, which may be important for normal development. C1 UNIV OULU,BIOCTR,OULU,FINLAND. UNIV OULU,DEPT PATHOL,OULU,FINLAND. UNIV HELSINKI,CENT HOSP,DEPT PULM MED,HELSINKI,FINLAND. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. RP Virtanen, I (reprint author), UNIV HELSINKI,INST BIOMED,DEPT ANAT,POB 9,FIN-00014 HELSINKI,FINLAND. NR 66 TC 70 Z9 70 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD AUG PY 1996 VL 15 IS 2 BP 184 EP 196 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA VB696 UT WOS:A1996VB69600005 PM 8703474 ER PT J AU Slanetz, PJ Moore, RH Hulka, CA Halpern, EF Habunek, D Whitman, GJ McCarthy, KA Hall, DA Kopans, DB AF Slanetz, PJ Moore, RH Hulka, CA Halpern, EF Habunek, D Whitman, GJ McCarthy, KA Hall, DA Kopans, DB TI Physicians' opinions on the delivery of mammographic screening services: Immediate interpretation versus double reading SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID BREAST-CANCER; PROGRAM AB OBJECTIVE. Mammographic services are delivered in many ways. Emphasis has been placed on providing women with immediate reports of their screening mammograms. We believe that double reading of mammograms is more important than an immediate report, We sought to determine physicians' attitudes toward this issue and if education affects their opinions. MATERIALS AND METHODS. Questionnaires were mailed to 1000 physicians in Massachusetts who were randomly selected from 16,000 members of the state medical society, The questionnaire had four sections, of which two were pertinent to this subject. The first section collected general information on the physician's practice and experience, The second section described two common delivery systems for mammographic screening services and asked physicians to choose the delivery system that would most benefit their patients. RESULTS. Of the 1000 physicians, 294 returned the questionnaire, giving a response rate of 29%. Of these, 16 physicians returned blank surveys, leaving 278 for analysis. Two hundred forty-nine (90%) valued off-site, delayed interpretation of mammographic screening for their patients over on-site reading by a single radiologist if an off-site, delayed reading made double reading possible. CONCLUSION. An off-site, double-reading delivery system for mammographic screening services is preferred by many physicians for their patients once they are educated as to the benefits of double reading. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BREAST IMAGING DIV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 6 TC 13 Z9 13 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 AUG PY 1996 VL 167 IS 2 BP 377 EP 379 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY821 UT WOS:A1996UY82100020 PM 8686608 ER PT J AU Shaffer, K Smith, D Kirn, D Kaplan, W Canellos, G Mauch, P Shulman, LN AF Shaffer, K Smith, D Kirn, D Kaplan, W Canellos, G Mauch, P Shulman, LN TI Primary mediastinal large-B-cell lymphoma: Radiologic findings at presentation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID EUROPEAN-AMERICAN CLASSIFICATION; NON-HODGKINS LYMPHOMA; DIFFUSE LARGE-CELL; CLINICOPATHOLOGIC ENTITY; SCLEROSIS; NEOPLASMS; DISEASE; CT; INVOLVEMENT; PROPOSAL AB OBJECTIVE. Primary mediastinal large-B-cell lymphoma was recently reclassified as a distinct clinical entity. We wished to review the imaging findings for this disease and to compare the findings with those for other disorders with a similar appearance. MATERIALS AND METHODS. We retrospectively reviewed plain films, gallium scintigrams, MR images, and CT scans for 43 patients with primary mediastinal large-B-cell lymphoma. RESULTS. All but one lesion arose in the anterior mediastinum. Areas of fluid attenuation within the masses were evident on CT scans in 50% of cases. Pleural effusions were seen by chest radiography in 33% of patients. Pericardial effusions were present in 32% of patients who underwent CT scans. Of the 21 patients who underwent gallium scintigraphy, all were reported to have positive findings. Also, MR imaging showed evidence of superior vena cava syndrome in one patient. CONCLUSION. Primary mediastinal large-B-cell lymphoma typically is seen as a bulky anterior mediastinal mass that often contains areas of necrosis. C1 BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT HEMATOL ONCOL,SAN FRANCISCO,CA 94143. DANA FARBER CANC INST,DEPT NUCL MED,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP Shaffer, K (reprint author), DANA FARBER CANC INST,DEPT RADIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 30 TC 21 Z9 24 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 AUG PY 1996 VL 167 IS 2 BP 425 EP 430 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY821 UT WOS:A1996UY82100032 PM 8686620 ER PT J AU Glickerman, DJ Obregon, RG Schmiedl, UP Harrison, SD Macaulay, SE Simon, HE Kohler, TR AF Glickerman, DJ Obregon, RG Schmiedl, UP Harrison, SD Macaulay, SE Simon, HE Kohler, TR TI Cardiac-gated MR angiography of the entire lower extremity: A prospective comparison with conventional angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ARTERIAL OCCLUSIVE DISEASE AB OBJECTIVE. The purpose of this study was to prospectively evaluate cardiac-gated two-dimensional (2D) time-of-flight MR angiography in patients with peripheral arterial occlusive disease (PAOD). SUBJECTS AND METHODS. Twenty-three patients with PAOD were studied using cardiac-gated 2D time-of-flight MR angiography in the body coil from each patient's aortic bifurcation to the pedal arches. Blinded comparison with conventional angiograms was used to determine sensitivity, specificity, and positive and negative predictive values of this MR angiography technique. Kappa statistics were used to compare treatment plans of these patients studied with MR angiography and with conventional angiography. RESULTS. In the aortoiliac region, MR angiography had a correlation coefficient of .89 for all degrees of narrowing, For hemodynamically significant lesions, MR angiography had an 89% sensitivity, 98% specificity, 84% positive predictive value, and 99% negative predictive value. In the femoral region, MR angiography had a correlation coefficient of .91 for all degrees of narrowing. For hemodynamically significant lesions, MR angiography had an 89% sensitivity, 98% specificity, 93% positive predictive value, and 97% negative predictive value. In the popliteal region, MR angiography had a correlation coefficient of .93 for all degrees of narrowing, For hemodynamically significant lesions, MR angiography had an 89% sensitivity, 98% specificity, 94%, positive predictive value, and 95% negative predictive value. In the tibioperoneal and foot regions, MR angiography had a correlation coefficient of .88 for all degrees of narrowing. For hemodynamically significant lesions, MR angiography had an 86% sensitivity, 93% specificity, 89% positive predictive value, and 91% negative predictive value, When the treatment planning data were classified into one of four outcomes (no intervention, surgery, percutaneous angioplasty, or further diagnostic study), MR angiography and conventional angiography had excellent agreement, with a Cohen's kappa value of .78. CONCLUSION. Cardiac-gated 2D time-of-flight MR angiography that uses the body coil provides a useful examination for PAOD with reasonable resolution. This imaging technique is potentially more time-efficient than techniques using extremity coils. C1 UNIV WASHINGTON,DEPT RADIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DIV VASC SURG,SEATTLE,WA 98195. PHILIPS MED SYST,SHELTON,CT 06484. RP Glickerman, DJ (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE DIV,DEPT RADIOL,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 17 TC 42 Z9 42 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 AUG PY 1996 VL 167 IS 2 BP 445 EP 451 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY821 UT WOS:A1996UY82100035 PM 8686623 ER PT J AU Gervais, DA Gazelle, GS Lu, DSK Hahn, PF Mueller, PR AF Gervais, DA Gazelle, GS Lu, DSK Hahn, PF Mueller, PR TI Percutaneous transpulmonary CT-guided liver biopsy: A safe and technically easy approach for lesions located near the diaphragm SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID THORACIC NEEDLE-BIOPSY; COMPLICATIONS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. UNIV CALIF LOS ANGELES,MED CTR HLTH SCI,DEPT RADIOL,LOS ANGELES,CA 90024. NR 8 TC 14 Z9 15 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 AUG PY 1996 VL 167 IS 2 BP 482 EP 483 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY821 UT WOS:A1996UY82100043 PM 8686631 ER PT J AU Okuno, WT Whitman, GJ Chew, FS AF Okuno, WT Whitman, GJ Chew, FS TI Recurrent pyogenic cholangiohepatitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ORIENTAL CHOLANGIOHEPATITIS C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 5 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 AUG PY 1996 VL 167 IS 2 BP 484 EP 484 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY821 UT WOS:A1996UY82100044 PM 8686632 ER PT J AU Bailey, EM Ferry, JA Harris, NL Mihm, MC Jacobson, JO Duncan, LM AF Bailey, EM Ferry, JA Harris, NL Mihm, MC Jacobson, JO Duncan, LM TI Marginal zone lymphoma (low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type) of skin and subcutaneous tissue - A study of 15 patients SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE marginal zone lymphoma; skin; subcutis; lymphoma; MALT; immunoperoxidase ID MALIGNANT-LYMPHOMA; GASTRIC LYMPHOMA; HELICOBACTER-PYLORI; UNIQUE TYPE; HYPERPLASIA; PSEUDOLYMPHOMA; DIAGNOSIS; DISTINCT; STOMACH AB Extranodal low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type occurs in the gastrointestinal tract, salivary gland, thyroid, orbit, lung, and breast. We report 15 patients with MALT-type lymphomas involving skin and subcutaneous tissue. All patients had tumors with histologic features of low-grade B-cell lymphoma of MALT type, including marginal zone cells (15 of 15 cases), plasmacytic differentiation (10 of 15 cases), Dutcher bodies (three of 15 cases), and reactive germinal centers(10 of 15 cases). All expressed pan B-cell antigens and monotypic immunoglobulin. Seven patients (five women, two men) aged 29 to 86 years (median, 53 years) had primary MALT-type lymphoma of skin (6) or subcutaneous tissue (1). One patient had persistent disease, and four patients had relapses involving skin, subcutaneous tissue, breast, orbit, and lymph node. At last follow-up (11-121 months; median, 36 months), one patient was alive with disease, and six patients had no evidence of disease. Three patients (two women, one man) aged 36 to 67 years (median, 57 years) had concurrent MALT-type lymphoma involving both subcutaneous tissue and extracutaneous sites at primary diagnosis, including lung, breast, orbit, lymph node, and bone marrow. One patient responded to treatment but relapsed with lymphoma of the skin and breast. The other two patients had persistent disease despite treatment. One patient died of disease at 25 months, and, at last follow-up (7 and 46 months), two patients were alive with disease. Five patients (four women and one man) aged 29 to 72 years (median, 63 years) had secondary skin or subcutaneous involvement by MALT-type lymphoma with primary tumors of ocular adnexa (3) or parotid gland (2). All five patients had relapses, which involved skin or subcutaneous tissue, parotid gland, lacrimal gland, breast, and lymph node. At last follow-up (61-137 months), two patients were alive with disease and three were alive with no evidence of disease. Low-grade B-cell lymphomas of MALT type may arise in or secondarily involve the skin and subcutaneous tissue and have a tendency to affect middle-aged to older women. These tumors are characterized by multiple extranodal relapses and are associated with long patient survival. Patients with primary MALT-type lymphoma of skin or subcutaneous tissue without extracutaneous involvement at diagnosis were more likely to experience prolonged disease-free survival than patients with extracutaneous spread at presentation (p < 0.03). C1 ALBANY MED CTR,DEPT DERMATOL & DERMATOPATHOL,ALBANY,NY. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP Bailey, EM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,DERMATOPATHOL UNIT,WARREN 2,BOSTON,MA 02114, USA. NR 40 TC 109 Z9 110 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 AUG PY 1996 VL 20 IS 8 BP 1011 EP 1023 DI 10.1097/00000478-199608000-00010 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA UZ126 UT WOS:A1996UZ12600010 PM 8712288 ER PT J AU Leaf, DA Reuben, DB AF Leaf, DA Reuben, DB TI ''Lifestyle'' interventions for promoting physical activity: A kilocalorie expenditure-based home feasibility study SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE physical activity; elderly ID CORONARY HEART-DISEASE; ENERGY-EXPENDITURE; OLDER ADULTS; EXERCISE; MEN; FITNESS; HEALTH; WOMEN; PREVENTION; MORTALITY AB The Centers for Disease Control and Prevention and the American College of Sports Medicine in cooperation with the President's Council of Physical Fitness and Sports recommended short periods of daily kilocalorie (calorie) expenditure with moderate-intensity physical activities to complement the currently existing recommendations. In this study the feasibility (adherence and safety) of employing calorie expenditure as the basis for prescribing a home-based walking program to healthy, community-dwelling men and women was examined. This was a 16-week pretest-posttest feasibility study of a home-based calorie-expenditure walking program conducted in an outpatient clinic in an academic medical center. Participants included 20 healthy, elderly, community-dwelling men and women. A 16-week home-based walking program was individually prescribed as a weekly amount of calorie expenditure increasing from an initial 300 calories per week to 1,200 calories per week (approximately 30 minutes of walking daily) during the final 6 weeks of the study. Adherence to the program was recorded individually in a diary (kept daily and reviewed at each visit), body weight, and walking pace. All but one participant were able to complete this 16-week program (95 percent adherence). That a calorie-based approach to promote physical activity among the elderly has a high adherence rate is suggested by these findings. Additional studies are necessary to define the potential role for this approach in promoting physical activity and improving health outcomes among the elderly. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,MULTICAMPUS PROGRAM GERIATR MED & GERONTOL,LOS ANGELES,CA 90024. RP Leaf, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. FU NIA NIH HHS [AG 10415-01] NR 42 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD AUG PY 1996 VL 312 IS 2 BP 68 EP 75 DI 10.1097/00000441-199608000-00003 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VB382 UT WOS:A1996VB38200003 PM 8701969 ER PT J AU Allison, JG Bromley, HR AF Allison, JG Bromley, HR TI Unnecessary preoperative investigations: Evaluation and cost analysis SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Midwest-Surgical-Association Meeting CY AUG 13-16, 1995 CL GRAND TRAVERSE, MI SP Midwest Surg Assoc ID ELECTROCARDIOGRAMS; UTILITY AB In keeping with national efforts to curb escalating health care costs, the necessity of multiple preoperative investigations was evaluated in 60 randomly selected ambulatory surgery patient records. Necessity for testing was assessed on clinical indications, and overall cost was calculated from the rates at both the local Department of Veterans Affairs Medical Center (VAMC) and a community hospital. Two thirds of the investigations were deemed to be inappropriate, with derived unnecessary average cost per patient of $47 and $80 for the VAMC and community hospital, respectively. Potential savings at the VAMC of $11,757.50 for the calendar year could have been realized. Education of staff and housestaff is crucial to changing obsolete practice habits. The quality and safety of care would not be compromised by limiting preoperative investigations to only those with clinical indications. C1 RALPH H JOHNSON VET AFFAIRS MED CTR,ANESTHESIOL SERV,CHARLESTON,SC 29401. RP Allison, JG (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,SURG SERV,109 BEE ST,CHARLESTON,SC 29401, USA. NR 10 TC 10 Z9 12 U1 1 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 1776 PEACHTREE RD, NW., SUITE 410N, ATLANTA, GA 30309-2352 SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD AUG PY 1996 VL 62 IS 8 BP 686 EP 689 PG 4 WC Surgery SC Surgery GA UY826 UT WOS:A1996UY82600021 PM 8712570 ER PT J AU Carter, JS Pugh, JA Monterrosa, A AF Carter, JS Pugh, JA Monterrosa, A TI Non-insulin-dependent diabetes mellitus in minorities in the United States SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; STAGE RENAL-DISEASE; NON-HISPANIC WHITES; LOWER-EXTREMITY AMPUTATIONS; CARDIOVASCULAR RISK-FACTORS; NAVAJO INDIAN COMMUNITY; MEXICAN-AMERICANS; PIMA-INDIANS; SAN-ANTONIO; RACIAL-DIFFERENCES AB Purpose: To review the available information on prevalence, complications, and mortality of non-insulin-dependent diabetes mellitus and primary and secondary prevention activities in black persons, Hispanic persons, Native Americans, and Asians and Pacific Islanders in the United States. Data Source: MEDLINE search from 1976 to 1994 through the PlusNet search system. Study Selection: Use of the key words non-insulin-dependent diabetes mellitus, the names of each specific minority group, socioeconomic status, acculturation, genetics, diet, complications, mortality, treatment, and intervention (lifestyle or medication) produced 290 unduplicated articles. Additional articles cited in the original articles were also included. Data Extraction: Risk factors, incidence, prevalence, complications, and mortality of non-insulin;dependent diabetes mellitus. Data Synthesis: All minorities, except natives of Alaska, have a prevalence of non-insulin-dependent diabetes mellitus that is two to six times greater than that of white persons. Most studies show an increased prevalence of nephropathy that can be as much as six times higher than that of white persons. Retinopathy has variably higher rates in black persons, Hispanic persons, and Native Americans. Amputations are done more frequently among black persons than among white persons (9.0 per 1000 compared with 6.3 per 1000), and Pima Indians have 3.7 times more amputations than do white persons. Diabetes-related mortality is higher for minorities than for white persons, and the rate is increasing. The relative importance of genetic heritage, diet, exercise, socioeconomic status, culture, language, and access to health care in the prevalence, incidence, and mortality of diabetes is not clear. Studies of interventions in minority populations are in progress. Conclusion: Diabetes should be treated as a public health problem for minority populations. C1 UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,SAN ANTONIO,TX 78284. VET AFFAIRS MED CTR,ALBUQUERQUE,NM 87108. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. MEXICAN AMER MED TREATMENT EFFECTIVENESS CTR,SAN ANTONIO,TX. TEXAS DIABET INST,SAN ANTONIO,TX. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [U01HS07397]; NIDDK NIH HHS [DK38392] NR 226 TC 320 Z9 322 U1 0 U2 13 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 AUG 1 PY 1996 VL 125 IS 3 BP 221 EP 232 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA UZ287 UT WOS:A1996UZ28700009 PM 8686981 ER PT J AU LopesVirella, MF Virella, G AF LopesVirella, MF Virella, G TI Modified lipoproteins, cytokines and macrovascular disease in non-insulin-dependent diabetes mellitus SO ANNALS OF MEDICINE LA English DT Article DE cytokines; endothelium damage; glycation; LDL-immune complexes; macrophages; oxidation ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; VASCULAR ENDOTHELIAL-CELLS; TUMOR NECROSIS FACTOR; CHOLESTERYL ESTER ACCUMULATION; NON-ENZYMATIC GLYCOSYLATION; MESSENGER-RNA EXPRESSION; SMOOTH-MUSCLE CELLS; IMMUNE-COMPLEXES; ATHEROSCLEROTIC LESIONS AB The processes of glycation and oxidation play a significant role in the acceleration of atherosclerosis in diabetes mellitus. Glycation is thought not only to increase the susceptibility of low-density lipoprotein (LDL) to oxidation but also to enhance the propensity of vessel wall structural proteins to bind extravasated plasma proteins, including LDL, and thus to contribute to a more marked oxidative modification of LDL. Glycated and oxidized lipoproteins induce cholesteryl ester accumulation in human macrophages and may promote platelet and endothelial cell dysfunction. Furthermore, these modified lipoproteins have the ability to trigger an autoimmune response that leads to the formation of autoantibodies and subsequently to the formation of immune complexes containing LDL. Both the modified lipoproteins and the immune complexes formed with autoantibodies reactive with modified lipoproteins may be responsible for several alternative and not mutually exclusive pathways leading to foam cell formation, macrophage activation and endothelial cell damage and may thus be of potential significance in initiating and/or contributing to the acceleration of the development of atherosclerosis. In this review we discuss how modified LDL affects lipoprotein metabolism, how immune complexes containing LDL induce the transformation of macrophages into foam cells and promote macrophage activation leading to the release of cytokines and thus initiating a sequence of events leading to endothelial cell damage and to the recruitment and activation of leucocytes. We also summarize our work showing that macrophage activation by LDL containing immune complexes leads to a paradoxical increase in LDL-receptor expression thus further impairing cholesterol homeostasis and enhancing the development of atheromatous lesions. C1 MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL DIABET & MED GENET,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425. RP LopesVirella, MF (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29403, USA. FU NHLBI NIH HHS [HL 46815] NR 78 TC 20 Z9 21 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0785-3890 J9 ANN MED JI Ann. Med. PD AUG PY 1996 VL 28 IS 4 BP 347 EP 354 DI 10.3109/07853899608999092 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VC296 UT WOS:A1996VC29600014 PM 8862690 ER PT J AU Hyman, BT AF Hyman, BT TI Alzheimer's disease or Alzheimer's diseases? Clues from molecular epidemiology SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID APOLIPOPROTEIN-E; MISSENSE MUTATIONS; GENE; CHROMOSOME-1; LOCUS; ALLELE RP Hyman, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. NR 22 TC 19 Z9 19 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1996 VL 40 IS 2 BP 135 EP 136 DI 10.1002/ana.410400202 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VC689 UT WOS:A1996VC68900001 PM 8773592 ER PT J AU Acquadro, MA Montgomery, WW AF Acquadro, MA Montgomery, WW TI Treatment of chronic paranasal sinus pain with minimal sinus disease SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE pain; paranasal sinus; sinusitis ID MEDULLARY DORSAL HORN; OROFACIAL PAIN; NEURONS; NEUROBIOLOGY; STIMULATION AB A common problem for otolaryngologists are patients who present with recurrent, persistent sinus pain that appears out of proportion to the findings on physical examination. Often these patients have a history of recurrent sinusitis that required antibiotics or surgical intervention. Many have had repeated surgical procedures because of this pain. Other common past medical histories may include allergic rhinitis, facial trauma, or dental disease. Patients who have experienced documented acute sinusitis in the past will often present de novo with similar symptoms, but lack any objective evidence of a new active sinus infection. However, the diagnosis of sinusitis is not clearly removed from the patient's or clinician's mind, and the patient is further frustrated by the lack of adequate diagnosis, treatment, and resolution of symptoms. These patients may or may not be experiencing an upper respiratory tract infection or allergy with nasal drainage. Often, they are emotionally distraught from recurrent and persistent pain, the lack of resolution of their symptoms, dependency on narcotics and other analgesics, multiple consultations with a variety of clinicians, and the impingement of their symptoms on employment, interpersonal relationships, and societal and family obligations. If sinusitis is not found to be present, the otolaryngologist must help the patient understand this point, reassure him or her that the otolaryngologist will still be vigilant for the development of sinusitis, and refocus the history and workup for some other cause of the recurrent and persistent paranasal pain. We review various treatment approaches to paranasal pains that are not the result of sinusitis. C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OTORHINOLARYNGOL,BOSTON,MA. RP Acquadro, MA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT ANESTHESIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD AUG PY 1996 VL 105 IS 8 BP 607 EP 614 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA VC010 UT WOS:A1996VC01000004 PM 8712630 ER PT J AU Wasa, M Bode, BP Abcouwer, SF Collins, CL Tanabe, KK Souba, WW AF Wasa, M Bode, BP Abcouwer, SF Collins, CL Tanabe, KK Souba, WW TI Glutamine as a regulator of DNA and protein biosynthesis in human solid tumor cell lines SO ANNALS OF SURGERY LA English DT Article ID TOTAL PARENTERAL-NUTRITION; GROWTH; METABOLISM AB Objective The transport of glutamine by six different human solid tumor-derived cell lines (e.g., breast, colon, liver) was characterized and the impact of glutamine deprivation on rates of tumor cell proliferation and DNA and protein synthesis was assayed. Summary Background Data Glutamine is added routinely to cell culture media and its importance for cellular growth has been established. However, carrier-mediated glutamine transport by solid tumors has not been studied extensively, and the mechanisms by which glutamine contributes to cell growth regulation require further investigation. Methods In a panel of different human solid tumor-derived cells, sodium-dependent glutamine transport was characterized in vitro and rates of cell proliferation, protein and DNA synthesis, as well as thymidine transport, were correlated with glutamine concentrations in the culture media. Results In all cells, regardless of tissue origin, sodium-dependent glutamine transport was mediated almost exclusively by a single carrier. There was a range of Michaelis constants (Km) and maximal transport velocities (Vmax) for the glutamine transporter in each cell type, but the amino acid inhibition profiles were nearly identical, consistent with uptake by the System ASC family of transporters. Rates of cell growth, DNA and protein synthesis, and thymidine transport correlated with the glutamine concentration in the culture media, indicating the central role of this amino acid in regulating cellular proliferation. Conclusions These data indicate that glutamine transport by all solid tumors is mediated by the System ASC family of transporters. The variation in Km values suggests that some cancers may be better suited to survive in a low glutamine environment than others. The mechanism by which glutamine supports cell proliferation and regulates cell cycle kinetics involves its modulation of DNA and protein biosynthetic rates. C1 HARVARD UNIV,DIV SURG ONCOL,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NCI NIH HHS [CA57690] NR 23 TC 50 Z9 52 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1996 VL 224 IS 2 BP 189 EP 197 DI 10.1097/00000658-199608000-00012 PG 9 WC Surgery SC Surgery GA VC539 UT WOS:A1996VC53900012 PM 8757383 ER PT J AU Ng, EY Trucksis, M Hooper, DC AF Ng, EY Trucksis, M Hooper, DC TI Quinolone resistance mutations in topoisomerase IV: Relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID POLYMERASE CHAIN-REACTION; ESCHERICHIA-COLI; A-PROTEIN; CIPROFLOXACIN RESISTANCE; METHICILLIN-RESISTANT; B-PROTEIN; PSEUDOMONAS-AERUGINOSA; NUCLEOTIDE-SEQUENCE; DETERMINING REGION; COUMARIN DRUGS AB Mutations in the flqA (formerly ofx/cfx) resistance locus of Staphylococcus aureus were previously shown to be common after first-step selections for resistance to ciprofloxacin and ofloxacin and to map on the S. aureus chromosome distinctly from gyrA, gyrB, and norA. grlA and grlB, the genes for the topoisomerase IV Of S. aureus, were identified from a genomic lambda library on a common KpnI fragment, and grlB hybridized specifically with the chromosomal SmaI A fragment, which contains the flqA locus, Amplification of grlA sequences (codons 1 to 251) by PCRs from nine independent single-step flqA mutants, one multistep mutant, and the parent strain identified mutations encoding a change from Ser to Phe at position 80 in four mutants, a novel change from Ala to either Glu or Pro at position 116 in three mutants, and no change in three mutants, In the multistep mutant, another resistance locus, flqC, was mapped by transformation to the chromosomal SmaI G fragment by linkage to Omega (chr::Tn551) 1051 (58%) and nov (97.9%), which encodes resistance to novobiocin, This fragment contains the gyrA gene, and flqC mutants had a mutation in gyrA encoding a change from Ser to Leu at position 84, a change previously found in resistant clinical isolates, In genetic outcrosses, the flqC (gyrA) mutation expressed resistance only in flqA mutants, including those with both types of grlA mutations, The silent mutant allele of gyrA was present in an flqA background and expressed resistance only upon introduction of a grlA mutation, At fourfold the MIC of ciprofloxacin, the bactericidal activity of ciprofloxacin was reduced in a grlA mutant and was abolished in gyrA grlA double mutants, These findings provide direct genetic evidence that topoisomerase IV is the primary target of current fluoroquinolones in S. aureus and that this effect may result from the greater sensitivity of topoisomerase IV relative to that of DNA gyrase to these agents, Furthermore, resistance from an altered DNA gyrase requires resistant topoisomerase IV for its expression. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [AI23988, R01 AI023988] NR 61 TC 177 Z9 181 U1 0 U2 5 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 AUG PY 1996 VL 40 IS 8 BP 1881 EP 1888 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA VA865 UT WOS:A1996VA86500021 PM 8843298 ER PT J AU Qureshi, AA Lerner, LH Lerner, EA AF Qureshi, AA Lerner, LH Lerner, EA TI From bedside to the bench and back - Nitric oxide and the cutis SO ARCHIVES OF DERMATOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; RELAXING FACTOR; MOUSE MACROPHAGES; SMOOTH-MUSCLE; L-ARGININE; SYNTHASE; ENDOTHELIUM; EXPRESSION; CELLS; CLONING AB When the discoverer of dynamite (trinitrotoluene [TNT]), Alfred Nobel, was prescribed nitroglycerin for angina in 1895, he was certainly taken aback. Almost a century later, organic nitrates and their gaseous metabolic end product, nitric oxide (NO), were implicated in a vast array of biologically diverse activities.(1) About 10 years ago, a series of discoveries from different avenues of research converged on NO, thrusting it into the limelight as a neurotransmitter, vasodilator, toxin, and modulator of immune function and inflammation.(2) Nitric oxide has thus managed to capture the interest of scientists from a number of fields and holds center stage attention. Interest in NO among dermatologists has been slow to appear, however, and the literature on NO with respect to the skin is sparse when compared with the steep escalation in the number of articles published generally on NO since 1987 (figure 1). RP Qureshi, AA (reprint author), MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129, USA. NR 38 TC 13 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 1996 VL 132 IS 8 BP 889 EP 893 DI 10.1001/archderm.132.8.889 PG 5 WC Dermatology SC Dermatology GA VB378 UT WOS:A1996VB37800004 PM 8712838 ER PT J AU To, KW Adamian, M Jakobiec, FA Berson, EL AF To, KW Adamian, M Jakobiec, FA Berson, EL TI Clinical and histopathologic findings in clumped pigmentary retinal degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LINKED RETINITIS PIGMENTOSA; ULTRASTRUCTURE AB Objective: To describe the clinical and histopathologic features of clumped pigmentary retinal degeneration (CPRD). Design: Retrospective case series. Setting: Tertiary referral center. Patients: Twenty-four-patients, aged 7 to 83 years, were identified from the medical record files of the Berman-Gund Laboratory, Boston, Mass, as having the clinical features of CPRD. The autopsy eye from a SG-year-old man with CPRD was studied with light and electron microscopy. Main Outcome Measures: Visual acuities, visual fields, dark-adaptation thresholds, and results of electroretinograms; histopathologic study of an autopsy eye. Results: The functional deficit of patients with CPRD seems to be similar to that of patients with typical retinitis pigmentosa. Different degrees of severity were observed among patients of similar age. The histopathologic data showed that the clinically distinct areas of clumped pigment are due to excessive accumulation of melanin granules in retinal pigment epithelial cells. Conclusion: Based on the distinct clinical and histopathologic appearance, CPRD should be considered as a separate form of retinal degeneration. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,OPHTHALM PATHOL SERV,BOSTON,MA. RP To, KW (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA, USA. NR 15 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 1996 VL 114 IS 8 BP 950 EP 955 PG 6 WC Ophthalmology SC Ophthalmology GA VB183 UT WOS:A1996VB18300007 PM 8694730 ER PT J AU Tolentino, MJ Miller, JW Gragoudas, ES Chatzistefanou, K Ferrara, N Adamis, AP AF Tolentino, MJ Miller, JW Gragoudas, ES Chatzistefanou, K Ferrara, N Adamis, AP TI Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a nonhuman primate SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; PERMEABILITY FACTOR; CELLS; ANGIOGENESIS; EXPRESSION; HYPOXIA; MITOGEN; INVIVO; MODEL; FLUID AB Objective: To determine whether the angiogenic peptide vascular endothelial growth factor (VEGF) is sufficient to produce iris neovascularization in a nonhuman primate (Macaca fascicularis). Methods: Eight eyes of 4 animals were studied. The 165-amino acid isoform of human recombinant VEGF (VEGF(165)) was injected into the vitreous of 5 cynomolgus monkey eyes (doses ranging from 0.25-2.5 mu g per injection). Equal amounts of inactivated human recombinant VEGF (2 eyes) or vehicle (1 eye) were injected into contralateral control eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, iris color photography, fluorescein angiography, histopathologic examination, and immunostaining with antibodies against proliferating cell nuclear antigen. Results: All 5 bioactive VEGF-injected eyes developed neovascularization with dilated and tortuous iris vessels that leaked fluorescein. None of the 3 control eyes exhibited any iris vascular changes. Inflammation was absent in both treatment groups. A dose response to VEGF was observed in the single animal that received 2.5 mu g and 0.25 mu g in the right and left eyes, respectively. Iris vessel endothelial cells were positive for proliferating cell nuclear antigen in the bioactive VEGF-injected eyes only. Injections of 1.25 mu g of VEGF every 3 days during a 30-day period produced advanced iris neovascularization, ectropion uvea, and neovascular glaucoma. Conclusions: Intravitreal injections of recombinant human VEGF(165) in amounts comparable with those measured in eyes with active neovascularization are sufficient to produce noninflammatory iris neovascularization in a nonhuman primate. Prolonged exposure to VEGF(165) can produce ectropion uveae and neovascular glaucoma. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. CHILDRENS HOSP,DEPT SURG,SURG RES LAB,BOSTON,MA. GENENTECH INC,S SAN FRANCISCO,CA 94080. NR 36 TC 207 Z9 212 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 1996 VL 114 IS 8 BP 964 EP 970 PG 7 WC Ophthalmology SC Ophthalmology GA VB183 UT WOS:A1996VB18300009 PM 8694732 ER PT J AU Husain, D Miller, JW Michaud, N Connolly, E Flotte, TJ Gragoudas, ES AF Husain, D Miller, JW Michaud, N Connolly, E Flotte, TJ Gragoudas, ES TI Intravenous infusion of liposomal benzoporphyrin derivative for photodynamic therapy of experimental choroidal neovascularization SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; AGE-RELATED MACULOPATHY; MOUSE-TUMOR MODEL; RING-A BPD; MACULAR DEGENERATION; PREVALENCE AB Objective: To compare the effectiveness of photodynamic therapy to close experimental choroidal neovascularization using an intravenous infusion of liposomal benzoporphyrin derivative (verteporfin) with previous work using a rapid intravenous injection, before initiating clinical trials. Methods: Choroidal neovascularization was induced in cynomolgus monkey eyes using argon laser. Liposomal benzoporphyrin derivative was delivered by an intravenous infusion pump for 10 or 32 minutes at a dose of 0.375 mg/kg.;Irradiation was performed with 689- or 692-nm laser light (600-mW/cm(2) irradiance and 150-J/cm(2) fluence) in 7 normal eyes and 11 eyes with choroidal neovascularization between 30 and 105 minutes-after the start of dye infusion. Findings were documented by fundus photography, fluorescein angiography, and light and electron microscopy. Results: Irradiation within 32 to 50 minutes of the start of the fast (10 minutes) or slow (32 minutes) dye infusion resulted in closure of choroidal neovascularization. In normal eyes, this technique caused choriocapillaris closure and retinal pigment epithelium damage with minimal damage to surrounding tissues. Conclusion: Photodynamic therapy using intravenous infusion of liposomal benzoporphyrin derivative selectively closed experimental choroidal neovascularization. This may be a suitable modality for clinical use. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,LASER RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 35 TC 97 Z9 101 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 1996 VL 114 IS 8 BP 978 EP 985 PG 8 WC Ophthalmology SC Ophthalmology GA VB183 UT WOS:A1996VB18300011 PM 8694734 ER PT J AU Lessell, S AF Lessell, S TI The residency review committee for ophthalmology SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material RP Lessell, S (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 1996 VL 114 IS 8 BP 1002 EP 1004 PG 3 WC Ophthalmology SC Ophthalmology GA VB183 UT WOS:A1996VB18300016 PM 8694705 ER PT J AU Wilhelm, S McNally, RJ Baer, L Florin, I AF Wilhelm, S McNally, RJ Baer, L Florin, I TI Directed forgetting in obsessive-compulsive disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article ID REDUCED COGNITIVE INHIBITION; CLINICAL ANXIETY; MEMORY; TESTS; SCALE; BIAS AB We tested whether patients with obsessive-compulsive disorder (OCD) are characterized by dysfunction in the ability to forget disturbing material. Employing a directed forgetting procedure, we presented OCD patients and healthy control subjects with a series of negative, positive, and neutral words, and instructed them either to remember or to forget each item after it was presented. Subjects received free recall and recognition tests for all words, regardless of instructions. Orthogonal planned contrasts indicated that OCD patients exhibited deficits in the ability to forget negative material relative to positive and neutral material, whereas control subjects did not. Additional analyses suggested that OCD patients elaboratively encoded negative words, regardless of instructions, thereby enhancing their memorability. Copyright (C) 1996 Elsevier Science Ltd C1 HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MARBURG,D-35032 MARBURG,GERMANY. FU NIMH NIH HHS [MH51927] NR 28 TC 48 Z9 49 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 1996 VL 34 IS 8 BP 633 EP 641 DI 10.1016/0005-7967(96)00040-X PG 9 WC Psychology, Clinical SC Psychology GA VJ036 UT WOS:A1996VJ03600004 PM 8870289 ER PT J AU Hayashi, Y Zviman, MM Brand, JG Teeter, JH Restrepo, D AF Hayashi, Y Zviman, MM Brand, JG Teeter, JH Restrepo, D TI Measurement of membrane potential and [Ca2+](i) in cell ensembles: Application to the study of glutamate taste in mice SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE; CALCIUM; FURA-2; DEPOLARIZATIONS; GROWTH; BUDS; PH AB We have studied the spectral properties of the voltage-sensitive dye, 1-(3-sulfonatopropyl)-4-[beta[2-(di-n-octylamino)-6-naphtyl]vinyl] pyridinium betaine (di-8-ANEPPS), and the Ca2+-sensitive dye, fura-2, in azolectin liposomes and in isolated taste buds from mouse, We find that the fluorescence excitation spectra of di-8-ANEPPS and fura-2 are largely nonoverlapping, allowing alternate ratio measurements of membrane potential and intracellular calcium ([Ca2+](i)), There is a small spillover of di-8-ANEPPS fluorescence at the excitation wavelengths used for fura-2 (340 and 360 nm), However, voltage-induced changes in the fluorescence of di-8-ANEPPS, excited at the fura-2 wavelengths, are small, In addition, di-8-ANEPPS fluorescence is localized to the membrane, whereas fura-2 fluorescence is distributed throughout the cytoplasm. Because of this, the effect of spillover of di-8-ANEPPS fluorescence in the [Ca2+](i) estimate is <1%, under the appropriate conditions, We have applied this method to study of the responses of multiple taste cells within isolated taste buds, We show that membrane potential and [Ca2+](i) can be measured alternately in isolated taste buds from mouse, Stimulation with glutamate and glutamate analogs indicates that taste cells express both metabotropic and ionotropic receptors, The data suggest that the receptors responding to 2-amino-4-phosphonobutyrate (L-AP4), presumably metabotropic L-glutamate receptors, do not mediate excitatory glutamate taste responses. C1 UNIV PENN, MONELL CHEM SENSES CTR, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT PHYSIOL, PHILADELPHIA, PA 19104 USA. VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. KYOTO UNIV, FOOD SCI RES INST, UJI, KYOTO 611, JAPAN. FU NIDCD NIH HHS [DC 001838, DC 00566] NR 38 TC 61 Z9 62 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1996 VL 71 IS 2 BP 1057 EP 1070 PG 14 WC Biophysics SC Biophysics GA VA410 UT WOS:A1996VA41000053 PM 8842242 ER PT J AU Kupfer, GM DAndrea, AD AF Kupfer, GM DAndrea, AD TI The effect of the Fanconi anemia polypeptide, FAC, upon p53 induction and G2 checkpoint regulation SO BLOOD LA English DT Article ID 2 COMPLEMENTATION GROUPS; DNA-DAMAGE; CELL-CYCLE; CHROMOSOME BREAKAGE; HEMATOPOIETIC-CELLS; ALKYLATING-AGENTS; INDUCED APOPTOSIS; MAMMALIAN-CELLS; PROTEIN P53; S-PHASE AB Fanconi anemia (FA) is an autosomal recessive disease marked by developmental defects, bone marrow failure, and cancer susceptibility, FA cells are hypersensitive to DNA cross-linking and alkylating agents and accumulate in the G2 phase of the cell cycle in response to these agents. FA cells also display genomic instability, suggesting a possible defect in the p53 pathway. To test the effect of heterologous expression of FAC cDNA on drug-induced cytotoxicity, G2 accumulation, and p53 induction in FA cells, we compared two isogenic FA cell lines: HSC536N (mock), a FA type C cell line sensitive to mitomycin C (MMC), and the same cell line transfected (corrected) with wild-type FAC cDNA (HSC536N [+FAC]), HSC536N (+FAC) cells showed a 30-fold increase in resistance to MMC concentration, Similarly, increases in resistance were observed following exposure to cisplatin, carboplatin, and cyclophosphamide. In addition, HSC536N (+FAC) cells showed a twofold lower G2 accumulation following MMC treatment. To analyze the possible interaction of FAC with the p53 pathway, we analyzed p53 induction in mock and corrected cell lines following exposure to MMC. HSC536N (mock) cells induced p53 at lower MMC concentrations than HSC536N (corrected). Caffeine, a known G2 checkpoint inhibitor, not only inhibited G2 accumulation seen in both cell lines but also caused the resistant HSC536N (+FAC) to become as sensitive to MMC as HSC536N (mock) cell line, We conclude that the FAC protein has a specific cytoprotective effect and may function as a cell cycle regulator of the G2 phase of the cell cycle. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV HEMATOL,BOSTON,MA. RP Kupfer, GM (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [R01-HL5725] NR 68 TC 54 Z9 54 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 AUG 1 PY 1996 VL 88 IS 3 BP 1019 EP 1025 PG 7 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300033 PM 8704210 ER PT J AU Krenger, W Falzarano, G Delmonte, J Snyder, KM Byon, JCH Ferrara, JLM AF Krenger, W Falzarano, G Delmonte, J Snyder, KM Byon, JCH Ferrara, JLM TI Interferon-gamma suppresses T-cell proliferation to mitogen via the nitric oxide pathway during experimental acute graft-versus-host disease SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; MONOCLONAL-ANTIBODY; L-ARGININE; IFN-GAMMA; PERITONEAL-MACROPHAGES; CYTOKINE DYSREGULATION; MURINE MACROPHAGES; EFFECTOR MECHANISM; TARGET-CELLS AB The development of graft-versus-host disease (GVHD) is associated with long-lasting and profound deficits in immune function that lead to increased morbidity and mortality after bone marrow transplantation (BMT). We investigated a mechanism of T-cell immunodeficiency in response to mitogen or alloantigen in an experimental model of acute GVHD by analyzing the roles of two immunosuppressive moieties: interferon gamma (IFN-gamma) and nitric oxide (NO). Splenocytes from mice with GVHD did not proliferate either to the T-cell mitogen, concanavalin A (Con A), or to host alloantigens, but only mitogen-activated cultures produced increased levels of NO. The abrogation of NO synthesis with Lc-monomethyl-arginine (NMMA) restored mitogen-induced proliferation but not the response to host antigens. The mechanism of impaired proliferation to mitogen was dependent on IFN-gamma because blockade of this cytokine in culture inhibited NO production and restored proliferation to Con A to levels similar to those in transplanted control mice without GVHD. NMMA did not substantially reduce IFN-gamma levels, demonstrating that NO acted distally to IFN-gamma in the pathway of immunosuppression in response to mitogen. Furthermore, the prevention of IFN-gamma production in vivo after allogeneic BMT, by transplantation of polarized type 2 donor T cells (secreting interleukin-4 but not IFN-gamma), also prevented NO production and restored splenocyte responses to mitogen. Our data demonstrate the existence of NO-dependent and NO-independent pathways involved in suppression of T-cell proliferation during acute GVHD. Excess NO synthesis appears to be one mechanism by which IFN-gamma induces immunodeficiency after allogeneic BMT. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. RP Krenger, W (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,D1638,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 39542]; NIAID NIH HHS [AI 30018] NR 63 TC 83 Z9 85 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 AUG 1 PY 1996 VL 88 IS 3 BP 1113 EP 1121 PG 9 WC Hematology SC Hematology GA VB323 UT WOS:A1996VB32300045 PM 8704222 ER PT J AU Hayashi, H LeGuern, C Sachs, DH Sykes, M AF Hayashi, H LeGuern, C Sachs, DH Sykes, M TI Alloresistance to K locus class I-mismatched bone marrow engraftment is mediated entirely by CD4(+) and CD8(+) T cells SO BONE MARROW TRANSPLANTATION LA English DT Article DE tolerance; bone marrow transplantation; class I MHC; alloresistance; T cells ID HEMATOPOIETIC STEM-CELLS; NATURAL-KILLER CELLS; GRAFT-REJECTION; MONOCLONAL-ANTIBODIES; MURINE MARROW; HOST DISEASE; MICE; ALLOGRAFTS; TOLERANCE; ANTIGENS AB Clinical application of approaches to inducing transplantation tolerance that involve bone marrow reconstitution will require achievement of engraftment without major toxicity to the recipient, These requirements are likely to vary according to the type of histoincompatibility between donor and recipient, We have attempted to determine the minimal conditioning required to achieve lasting mixed allogeneic chimerism and tolerance in the presence of a class I MHC disparity by evaluating the host elements that resist alloengraftment. We based our approach on a regimen that was shown to induce mixed chimerism in fully MHC-mismatched strain combinations, Recipient B10.AKM ((KIDq)-I-k-D-k) mice were treated with 7 Gy thymic irradiation (TI) and 3 Gy,whole body irradiation (WBI) and received either anti-CDS mAb alone or anti-CD4 plus anti-CDS mAbs before transplantation of K locus-disparate B10.MBR ((KIDq)-I-b-D-k) marrow, All (27 of 27) animals receiving both mAbs showed lasting multi-lineage mixed chimerism and donor-specific tolerance, In contrast, five of 22 (23%) recipients pre-treated with anti-CDS mAb alone in the same experiments failed to develop lasting multilineage mixed chimerism, suggesting that the CD4 T cell subset also participates in resistance to class I-mismatched marrow engraftment, We next attempted to determine whether or not host non-T cell elements resist allogeneic engraftment by comparing the minimum number of syngeneic vs allogeneic BMC required to achieve lasting multilineage mixed chimerism, Titrated numbers (10(6) to 10(7)) of B10.MBR ((KIDq)-I-b-D-k) bone marrow cells were administered to B10.AKM recipients treated with anti-CD4 and -CD8 mAbs, 3 Gy WBI and 7Gy TI, All recipients of each marrow dose developed lasting multilineage mixed chimerism and showed specific tolerance to B10.MBR skin grafts, The level of donor-type repopulation in recipients of each dose was not lower than that observed in similarly irradiated recipients in an Ly5 congenic, otherwise syngeneic, BMT system, Together, our results suggest that CD4(+) T cells contribute to resistance to K locus class I-mismatched marrow allografts and that resistance is mediated only by CD4 and CDS T cells, with no role for non-T cell host elements. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BONE MARROW TRANSPLANTAT SECT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU PHS HHS [R01-48049, R01-49915] NR 34 TC 5 Z9 5 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD AUG PY 1996 VL 18 IS 2 BP 285 EP 292 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA VD053 UT WOS:A1996VD05300004 PM 8864436 ER PT J AU Eng, C Foster, KA Healey, CS Houghton, C Gayther, SA Mulligan, LM Ponder, BAJ AF Eng, C Foster, KA Healey, CS Houghton, C Gayther, SA Mulligan, LM Ponder, BAJ TI Mutation analysis of the c-mos proto-oncogene and the endothelin-B receptor gene in medullary thyroid carcinoma and phaeochromocytoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE MEN 2; RET; c-mos; endothelin-B receptor; medullary thyroid carcinoma; phaeochromocytoma ID ENDOCRINE NEOPLASIA TYPE-2; TYROSINE KINASE DOMAIN; RET PROTOONCOGENE; MEN 2A; POINT MUTATION; PHEOCHROMOCYTOMAS; FMTC; PHENOTYPE; DISEASE; 2B AB The characteristic tumours of MEN 2 are medullary thyroid carcinoma (MTC) and phaeochromocytoma. Somatic RET mutations have been found in only 23-40% of sporadic IWTC and 10% of sporadic phaeochromocytomas. Thus, we sought other genes which may play a role in the pathogenesis of these tumours. We carried out direct sequence analysis of human c-mos and human ENRB in a series of sporadic MTC and phaeochromocytomas to determine if somatic mutations in these two genes could account for some of the sporadic MEN 2-related tumours in which no RET mutations are detected. No somatic mutations were found. C1 UNIV CAMBRIDGE,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. RP Eng, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,DEPT MED,M3A 31,BOSTON,MA 02115, USA. OI Eng, Charis/0000-0002-3693-5145 NR 26 TC 12 Z9 12 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG PY 1996 VL 74 IS 3 BP 339 EP 341 DI 10.1038/bjc.1996.363 PG 3 WC Oncology SC Oncology GA UZ039 UT WOS:A1996UZ03900002 PM 8695346 ER PT J AU Ottensmeier, C Swanson, L Strobel, T Druker, B Niloff, J Cannistra, SA AF Ottensmeier, C Swanson, L Strobel, T Druker, B Niloff, J Cannistra, SA TI Absence of constitutive EGF receptor activation in ovarian cancer cell lines SO BRITISH JOURNAL OF CANCER LA English DT Article DE ovarian cancer; epidermal growth factors receptor; tyrosine phosphorylation ID EPIDERMAL GROWTH-FACTOR; SIGNAL TRANSDUCTION; GENE-MUTATIONS; ASCITIC FLUID; EXPRESSION; TYROSINE; P53; EPITHELIUM; CARCINOMA; ONCOGENE AB Previous investigators have noted that certain ovarian cancer cell lines secrete and respond to transforming growth factor-alpha (TGF-alpha), suggesting that endogenous activation of the epidermal growth factor (EGF) receptor through autocrine or paracrine mechanisms might contribute to the proliferative response. In order to determine whether autocrine stimulation was partly responsible for the proliferative response in ovarian cancer, we investigated whether the EGF receptor expressed by ovarian cancer cell lines was constitutively activated as assessed by the presence of tyrosine phosphorylation. A specific anti-phosphotyrosine antibody was used in conjunction with an immunoblotting technique in order to detect EGF receptor phosphorylation in ovarian cancer cell lines in the absence and presence of exogenous EGF. The effects of neutralising anti-EGF receptor antibody on the proliferation of ovarian cancer cell lines was also examined. We found no evidence for constitutive tyrosine phosphorylation of the p170 EGF receptor in eight epithelial ovarian cancer cell lines tested, although each line demonstrated inducible phosphorylation in response to exogenous EGF. The absence of constitutive EGF receptor activation was also noted when cells were grown under high density conditions, thus excluding a role for membrane-bound EGF or TGF-alpha in this process. Media conditioned by five ovarian cancer cell lines, as well as malignant ascites obtained from 12 different ovarian cancer patients, were not capable of stimulating EGF receptor phosphorylation. Finally, the proliferation of ovarian cancer cell lines was not significantly inhibited in the presence of neutralising anti-EGF receptor antibody. These data suggest that EGF receptor activation through autocrine pathways is not a major mechanism for the growth of many ovarian cancer cell lines. Other pathways of signal transduction which bypass the requirement for EGF receptor activation may be important in the proliferation for ovarian cancer cells. Such EGF receptor-independent pathways may limit the effectiveness of strategies designed to inhibit ovarian cancer cell growth through disruption of EGF receptor function. C1 DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. BETH ISRAEL HOSP,BOSTON,MA 02215. RI Ottensmeier, Christian/E-8131-2012 OI Ottensmeier, Christian/0000-0003-3619-1657 FU NCI NIH HHS [CA 60670] NR 29 TC 14 Z9 14 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG PY 1996 VL 74 IS 3 BP 446 EP 452 DI 10.1038/bjc.1996.379 PG 7 WC Oncology SC Oncology GA UZ039 UT WOS:A1996UZ03900018 PM 8695362 ER PT J AU Kristensen, CA Nozue, M Boucher, Y Jain, RK AF Kristensen, CA Nozue, M Boucher, Y Jain, RK TI Reduction of interstitial fluid pressure after TNF-alpha treatment of three human melanoma xenografts SO BRITISH JOURNAL OF CANCER LA English DT Article DE tumour necrosis factor-alpha; interstitial fluid pressure; melanoma xenograft; blood pressure ID TUMOR-NECROSIS-FACTOR; MONOCLONAL-ANTIBODIES; ISOLATION PERFUSION; NITRIC-OXIDE; SOLID TUMORS; BLOOD-FLOW; HYPERTENSION; INTERFERON; MELPHALAN; INVIVO AB Tumour necrosis factor-alpha (TNF-alpha) reduced the interstitial fluid pressure (IFP) to 54-64% (P<0.05) and the mean arterial blood pressure (MABP) to 70% (P<0.01) of control values after 5 h in three human melanoma tumour lines transplanted to nude mice. RP Kristensen, CA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,EDWIN L STEELE LAB,100 BLOSSOM ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-56591] NR 20 TC 84 Z9 88 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG PY 1996 VL 74 IS 4 BP 533 EP 536 DI 10.1038/bjc.1996.397 PG 4 WC Oncology SC Oncology GA VC440 UT WOS:A1996VC44000007 PM 8761366 ER PT J AU Shalev, O Shinar, E Lux, SE AF Shalev, O Shinar, E Lux, SE TI Isolated beta-globin chains reproduce, in normal red cell membranes, the defective binding of spectrin to alpha-thalassaemic membranes SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thalassaemia; spectrin; ankyrin; erythrocyte membrane; globin ID HUMAN-ERYTHROCYTE MEMBRANES; PROTEIN 4.1; CYTOPLASMIC SURFACE; HEMOGLOBIN CHAINS; SELF-ASSOCIATION; CROSS-LINKING; THALASSEMIA; BAND-3; ACTIN; SITE AB Alpha-thalassaemic erythrocytes develop a specific membrane skeletal defect that is manifest as a loss of normal spectrin-binding sites on the inner surface of the thalassaemic membranes. To test whether this lesion could be caused by the excess free beta-globin chains that accumulate in alpha-thalassaemic red cells, we incubated normal red cell membranes with native, haem-containing alpha or beta globin chains or with haemoglobin A. Spectrin-depleted inside-out membrane vesicles (IOVs) derived from membranes incubated with beta-globin chains bound only 9 +/- 3% as much spectrin as IOVs from control membranes incubated with bovine serum albumin. In contrast, IOVs from membranes incubated with alpha-globin chains or haemoglobin A were nearly normal (79 +/- 3% and 86 +/- 5% of controls, respectively). This differential effect of globin chains was not seen when membranes were first transformed into spectrin-depleted IOVs and then incubated with the isolated globin chains. Under these conditions, both alpha and beta globin chains reduced the spectrin-binding capacity of the IOVs by approximately 45% (alpha 46 +/- 7%, beta 43 +/- 6%) whereas haemoglobin A had no effect. Unlike IOVs, spectrin isolated from membranes exposed to alpha or beta globin chains bound normally to IOVs and to actin (in the presence of protein 4.1). These studies show that isolated beta-globin chains (but not alpha-globin chains) can produce a spectrin-binding defect in normal red cell membranes similar to that seen in alpha thalassaemia. The existence of similar defects in the membrane skeletons of red cells from other diseases with unstable beta globins suggests a common pathophysiology for the premature destruction of these cells. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [5P01-HL32262, 5P60-HL15157]; NIDDK NIH HHS [5R01-DK34083] NR 47 TC 2 Z9 2 U1 0 U2 1 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 AUG PY 1996 VL 94 IS 2 BP 273 EP 278 DI 10.1046/j.1365-2141.1996.d01-1810.x PG 6 WC Hematology SC Hematology GA VB265 UT WOS:A1996VB26500008 PM 8759886 ER PT J AU Benson, RR Logan, WJ Cosgrove, GR Cole, AJ Jiang, H LeSueur, LL Buchbinder, BR Rosen, BR Caviness, VS AF Benson, RR Logan, WJ Cosgrove, GR Cole, AJ Jiang, H LeSueur, LL Buchbinder, BR Rosen, BR Caviness, VS TI Functional MRI localization of language in a 9-year-old child SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; BRAIN; ANATOMY; DISCRIMINATION; IMAGES; OBJECT; SPEED; FACE AB Background: Localizing critical brain functions such as language in children is difficult and generally requires invasive techniques. Recently sensory, motor and language functions in adults have been mapped to specific brain locations using functional imaging techniques. Of these techniques, functional MRI (fMRI) is the least invasive and has the highest spatial and temporal resolution. Its use in adults is well documented but application to children has not been as well described. In the present study lateralization and localization of language was evaluated with fMRI prior to epilepsy surgery in a nine-year-old male with complex partial seizures, attentional difficulty and decreased verbal proficiency. Methods: Two language paradigms well studied in adults (read, verb generation) and two additional language paradigms (antonym generation, letter fluency) were studied using whole brain fMRI after stimulus items and timing were adjusted to achieve the desired performance level during imaging. The patient was also conditioned to the magnet environment prior to imaging. Results: Word reading and letter fluency tasks produced lateralized and localized activation similar to that seen in adults. The patient had no language deficits following an anterior 2/3 dominant temporal lobe resection. Conclusions: With modifications of protocols such as those detailed in this report, this non-invasive method for localizing language function is feasible for the presurgical evaluation of children as well being applicable for a variety of developmental language issues. C1 UNIV TORONTO,HOSP SICK CHILDREN,DIV NEUROL,TORONTO,ON M5G 1X8,CANADA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. RP Benson, RR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH NMR CTR,DEPT RADIOL,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 39 TC 40 Z9 40 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 AUG PY 1996 VL 23 IS 3 BP 213 EP 219 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA VD469 UT WOS:A1996VD46900009 PM 8862845 ER PT J AU Bouros, D Papadakis, K Siafakas, N Fuller, AF AF Bouros, D Papadakis, K Siafakas, N Fuller, AF TI Natural history of patients with pulmonary metastases from uterine cancer SO CANCER LA English DT Article DE uterine cancer; carcinoma of the uterus; metastasis-pulmonary; lung metastasis; endometrial cancer; cancer; carcinoma; survival; genital malignancy; adenocarcinoma ID ENDOMETRIAL CARCINOMA; STAGE-I AB BACKGROUND. Endometrial cancer is the most common female genital cancer and approximately 90% of the cases are diagnosed while they are still confined to the uterus. However, the natural history and treated course after the development of pulmonary metastasis (PM) have not been studied systematically in a large series of patients. METHODS. Between 1962 and 1992, 100 patients (6%) with PM were identified by computerized search of the medical records from 1.665 patients admitted to our hospitals with the diagnosis of uterine cancer. The median age of the patients was 65.5 years (range: 42-87 yrs). The usual histologic types of the uterine neoplasms were 59 adenocarcinomas (59%), 21 sarcomas, and 14 adenosquamous carcinomas. Of the 83 patients with reported tumor grade, 11 had Grade 1 tumor, 12 Grade II, and 60 Grade III. RESULTS, Lung metastases were found at the time of diagnosis of the primary tumor in 22 patients. Hemoptysis was the first symptom in 3 of the 22; the majority had no respiratory symptoms. In the remaining 78 patients with PM appearing after primary therapy, the mean interval time between primary diagnosis and PM was 29.4 months, whereas between PM and death was 15.7 months. Of all patients with lung metastases, 75% did not survive 1 year; however 6% survived more than 5 years after diagnosis of metastatic disease. Patients with isolated PM had prolonged survival (36.1 mos, P = 0.001), whether treated medically or with pulmonary resection. Progestin therapy was given to 39 patients, with complete response consisting of radiographic resolution of all disease in 6 patients (15%) and prolonged stabilization in an additional 5 (13%). The histologic grade of the primary tumor was predictive of clinical response to progestine therapy. CONCLUSIONS. Asymptomatic pulmonary metastases represent a common site of extra pelvic spread of disease. The majority of patients with PM (75%) do not survive 1 year. Low grade uterine tumors are more likely to respond to progestin therapy and do so for extended periods of time. (C) 1996 American Cancer Society. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,GYNECOL ONCOL DIV,BOSTON,MA. RP Bouros, D (reprint author), UNIV CRETE,SCH MED,DEPT THORAC MED,IRAKLION 71110,GREECE. OI BOUROS, DEMOSTHENES/0000-0002-0685-0765 NR 23 TC 28 Z9 29 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 AUG 1 PY 1996 VL 78 IS 3 BP 441 EP 447 PG 7 WC Oncology SC Oncology GA UY254 UT WOS:A1996UY25400010 PM 8697389 ER PT J AU Blaney, SM Phillips, PC Packer, RJ Heideman, RL Berg, SL Adamson, PC Allen, JC Sallan, SE Jakacki, RL Lange, BJ Reaman, GH Horowitz, ME Poplack, DG Balis, FM AF Blaney, SM Phillips, PC Packer, RJ Heideman, RL Berg, SL Adamson, PC Allen, JC Sallan, SE Jakacki, RL Lange, BJ Reaman, GH Horowitz, ME Poplack, DG Balis, FM TI Phase II evaluation of topotecan for pediatric central nervous system tumors SO CANCER LA English DT Article DE topotecan; phase II trial; topoisomerase I; brain tumors ID DOSE INTENSITY; SOLID TUMORS; 9-DIMETHYLAMINOMETHYL-10-HYDROXYCAMPTOTHECIN; CHEMOTHERAPY; XENOGRAFTS; CHILDREN; MODEL; ADULT AB BACKGROUND. Topotecan is a topoisomerase I inhibitor that has good penetration across the blood-brain barrier and significant antitumor activity against human brain tumor xenografts. In a Phase I trial in children with refractory cancer, topotecan was well tolerated when administered as a 24-hour infusion. The maximum tolerated dose was 5.5 mg/m(2) and the dose-limiting toxicity was myelosuppression. This Phase II study of topotecan was performed to assess the activity of topotecan against childhood brain tumors. METHODS, Forty-five children with either a previously treated primary brain tumor that was refractory to standard therapy, or an untreated brain stem glioma or glioblastoma multiforme, received topotecan administered as a 24-hour intravenous infusion every 21 days. The initial dose was 5.5 mg/m(2) with escalation to 7.5 mg/m(2) on the second and subsequent doses in patients who did not experience dose-limiting toxicity. RESULTS, There were no complete or partial responses in the patients with high grade glioma (n = 9), medulloblastoma (n = 9), or brain stem glioma (n = 14). One of 2 patients with a low grade glioma had a partial response lasting more than 17 months; 3 patients with a brain stem glioma had stable disease for 12 to 28 weeks; and 1 patient with a malignant neuroepithelial tumor and 1 patient with an optic glioma had stable disease for 41 weeks and 22 weeks, respectively. Dose escalation from 5.5 mg/m(2) to 7.5 mg/m(2) was well tolerated in the first 11 patients enrolled on this study who had not received prior craniospinal radiation therapy. The starting dose was subsequently increased to 7.5 mg/m(2) for patients without prior craniospinal radiation. CONCLUSIONS, Topotecan administered as a 24-hour infusion every 21 days is inactive in high grade gliomas, medulloblastomas, and brain stem tumors. (C) 1996 American Cancer Society. C1 NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. CHILDRENS HOSP PHILADELPHIA, DIV NEUROL & HEMATOL ONCOL, PHILADELPHIA, PA 19104 USA. CHILDRENS NATL MED CTR, DEPT HEMATOL ONCOL, WASHINGTON, DC 20010 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA. NYU, MED CTR, DEPT NEUROL, NEW YORK, NY USA. DANA FARBER CANC INST, DIV PEDIAT HEMATOL ONCOL, BOSTON, MA 02115 USA. JAMES WHITCOMB RILEY HOSP CHILDREN, DIV PEDIAT HEMATOL ONCOL, INDIANAPOLIS, IN 46202 USA. TEXAS CHILDRENS HOSP, SERV HEMATOL, HOUSTON, TX 77030 USA. RP Blaney, SM (reprint author), TEXAS CHILDRENS CANC CTR, 6621 FANNIN MC 3-3320, HOUSTON, TX 77030 USA. NR 17 TC 60 Z9 60 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 BP 527 EP 531 PG 5 WC Oncology SC Oncology GA UY254 UT WOS:A1996UY25400021 PM 8697400 ER PT J AU Li, FP AF Li, FP TI Hereditary cancer susceptibility SO CANCER LA English DT Article ID LINE P53 MUTATIONS; TUMOR-SUPPRESSOR GENE; MOLECULAR EPIDEMIOLOGY; BREAST-CANCER; FRAUMENI SYNDROME; COLON-CANCER; WILMS TUMOR; FAMILIES; CHILDREN; CARCINOGENESIS RP Li, FP (reprint author), DANA FARBER CANC INST,MAYER 3A31,44 BINNEY ST,BOSTON,MA 02115, USA. NR 57 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 BP 553 EP 557 PG 5 WC Oncology SC Oncology GA UY254 UT WOS:A1996UY25400025 PM 8697404 ER PT J AU Harlow, E AF Harlow, E TI A research shortcut from a common cold virus to human cancer SO CANCER LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; E2F TRANSCRIPTION FACTOR; ADENOVIRUS E1A PROTEINS; DNA-BINDING ACTIVITY; LARGE TUMOR-ANTIGEN; CELL-CYCLE; SUSCEPTIBILITY GENE; SV40-TRANSFORMED CELLS; FUNCTIONAL DOMAINS; INFECTED-CELLS RP Harlow, E (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC ONCOL LAB,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 34 TC 3 Z9 3 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 AUG 1 PY 1996 VL 78 IS 3 BP 558 EP 565 DI 10.1002/(SICI)1097-0142(19960801)78:3<558::AID-CNCR26>3.0.CO;2-X PG 8 WC Oncology SC Oncology GA UY254 UT WOS:A1996UY25400026 PM 8697405 ER PT J AU Clark, JW Glicksman, AS Wanebo, HJ AF Clark, JW Glicksman, AS Wanebo, HJ TI Systemic and adjuvant therapy for patients with pancreatic carcinoma SO CANCER LA English DT Article; Proceedings Paper CT Symposium on Cancer of the Pancreas - Challenge of the Nineties CY JUN, 1994 CL NEWPORT, RI SP Eli Lilly & Co DE pancreatic cancer; chemotherapy; radiation therapy; combined modality; novel approaches ID RANDOMIZED CONTROLLED TRIAL; MONOCLONAL-ANTIBODY 17-1A; GROWTH-FACTOR RECEPTOR; P53 GENE-MUTATIONS; PHASE-II TRIAL; EXTERNAL-BEAM; RAS MUTATION; CANCER; 5-FLUOROURACIL; ADENOCARCINOMAS AB BACKGROUND. Pancreatic cancer is a highly lethal disease with less than or equal to 5% of patients surviving 5 years. There is no curative therapy for patients who cannot be surgically resected. Chemotherapy and radiation therapy can provide palliation but have not had a significant impact on 5-year survival. METHODS. Newer approaches for improving the survival of patients with pancreatic cancer integrating chemotherapy, radiation therapy, and surgery are being evaluated. New chemotherapeutic agents (e.g., gemcitabine, camptothecins, taxanes, thymydilate synthase inhibitors, and fluorouracil-related compounds) are being studied alone and in combination with each other or different agents (e.g., trimetrexate or platinum-related compounds). RESULTS. Increased knowledge about the biology of pancreatic cancer (including high frequency of ras and p53 mutations in neoplastic cells or the expression of a number of growth factor receptors on the cell surface) has lead to preclinical evaluation of novel approaches attempting to specifically target these. These novel approaches include gene therapy, vaccines, and antisense oligonucleotides targeted to genes important for proliferation or survival of pancreatic cancer cells. CONCLUSIONS. Continued development of new approaches is needed to improve the treatment and survival of patients with pancreatic cancer. (C) 1996 American Cancer Society. C1 MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. ROGERS WILLIAMS MED CTR, DEPT RADIAT THERAPY, PROVIDENCE, RI USA. BROWN UNIV, PROVIDENCE, RI 02912 USA. ROGER WILLIAMS MED CTR, DEPT SURG, PROVIDENCE, RI USA. NR 60 TC 18 Z9 22 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD AUG 1 PY 1996 VL 78 IS 3 SU S BP 688 EP 693 PG 6 WC Oncology SC Oncology GA UY778 UT WOS:A1996UY77800014 PM 8681308 ER PT J AU Tanaka, S Wands, JR AF Tanaka, S Wands, JR TI Insulin receptor substrate 1 overexpression in human hepatocellular carcinoma cells prevents transforming growth factor beta 1-induced apoptosis SO CANCER RESEARCH LA English DT Article ID HEPATOMA-CELLS; EXPRESSION; LIVER; PHOSPHORYLATION; FACTOR-BETA-1 AB Insulin-like growth factors initiate tyrosyl phosphorylation of the insulin receptor substrate 1 (IRS-1) protein and activate multiple signaling pathways essential for liver growth. This gene has been found to be up-regulated in human hepatocellular carcinomas (HCCs), and overexpression of IRS-1 in NIH3T3 cells leads to malignant transformation with activation of the mitogen-activated protein kinase cascade. To explore another possible role of IRS-1 in hepatocarcinogenesis, we examined the capability of transforming growth factor beta 1 (TGF-beta 1), a known negative regulator of hepatocyte growth, to induce programmed cell death in the context of IRS-1 overexpression. Hep3B HCC cells were stably transfected with a retroviral vector containing the IRS-1 gene. The overexpressed IRS-1 protein was highly tyrosyl phosphorylated following insulin/insulin-like growth factor I stimulation and led to constitutive activation of downstream signal transduction molecules such as phosphatidylinositol-3 kinase and mitogen-activated protein kinase. Although parental Hep3B cells were sensitive to apoptosis, the Hep3B-IRS-1-transfected cells acquired resistance to TGF-beta 1-induced programmed cell death. Our investigations suggest that IRS-1-mediated signals may act as survival factors and protect against TGF-beta 1-induced apoptosis in HCC; this phenomenon may contribute to hepatic oncogenesis. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA35711]; NIAAA NIH HHS [AA02666] NR 20 TC 115 Z9 119 U1 0 U2 2 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 AUG 1 PY 1996 VL 56 IS 15 BP 3391 EP 3394 PG 4 WC Oncology SC Oncology GA UZ288 UT WOS:A1996UZ28800002 PM 8758899 ER PT J AU Cahalin, LP Mathier, MA Semigran, MJ Dec, GW DiSalvo, TG AF Cahalin, LP Mathier, MA Semigran, MJ Dec, GW DiSalvo, TG TI The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure SO CHEST LA English DT Article DE cardiac transplantation; cardiopulmonary exercise testing; heart failure; 6-min walk test ID VENTRICULAR EJECTION FRACTION; EXERCISE CAPACITY; 6-MINUTE WALK; PROGNOSTIC VALUE; MORTALITY; CARDIOMYOPATHY; DETERMINANTS; PERFORMANCE; VARIABLES; SECONDARY AB Background: The 6-min walk test (6'WT) is a simple measure of functional capacity and predicts survival in patients with moderate heart failure (HF). Methods: To assess the role of the 6'WT in the evaluation of patients with advanced HF, 45 patients (age 49+/-8 years, mean+/-SD; New York Heart Association class 3.3+/-0.6; left ventricular ejection fraction 0.20+/-0.06; right ventricular ejection fraction 0.31+/-0.11) underwent symptom-limited cardiopulmonary exercise testing and the 6'WT during cardiac transplant evaluation. Results: Mean 6'WT distance ambulated was 310+/-100 m and peak oxygen uptake (peak V over dot o(2)) was 12.2+/-4.5 mL/kg/min. There was a significant correlation between 6'WT distance ambulated and peak V over dot o(2) (r=0.64, p<0.001). Multivariate analysis of patient characteristics, resting hemodynamics, and 6'WT results identified the distance ambulated during the 6'WT as the strongest predictor of peak V over dot o(2) (p<0.001). 6'WT distance ambulated less than 300 m predicted an increased likelihood of death or pretransplant hospital admission for continuous inotropic or mechanical support within 6 months (p=0.04), but did not predict long-term overall or event-free survival with a mean follow-up of 62 weeks. Peak V over dot o(2) was the best predictor of long-term overall and event-free survival. Conclusions: In patients with advanced HF evaluated for cardiac transplantation, distance ambulated during the 6'WT predicts (1) peak V over dot o(2) and (2) short-term event-free survival. C1 HARVARD UNIV,SCH MED,HEART FAILURE CTR,BOSTON,MA 02114. RP Cahalin, LP (reprint author), MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,BIGELOW 858,32 FRUIT ST,BOSTON,MA 02114, USA. NR 31 TC 349 Z9 378 U1 3 U2 34 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD AUG PY 1996 VL 110 IS 2 BP 325 EP 332 DI 10.1378/chest.110.2.325 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VB923 UT WOS:A1996VB92300010 PM 8697828 ER PT J AU Hess, D Fisher, D Williams, P Pooler, S Kacmarek, RM AF Hess, D Fisher, D Williams, P Pooler, S Kacmarek, RM TI Medication nebulizer performance - Effects of diluent volume, nebulizer flow, and nebulizer brand SO CHEST LA English DT Article DE aerosol therapy; inhaled bronchodilator administration; nebulizers ID JET NEBULIZERS; THERAPY; DELIVERY; SALBUTAMOL; OUTPUT; SIZE AB Background: Medication nebulizers are commonly used to delivery aerosolized medications to patients with respiratory disease, We evaluated output and respirable aerosol available to the patient (inhaled mass) for 17 medication nebulizers using a spontaneous breathing lung model. Methods: Three nebulizer fill volumes (3, 4, and 5 mL containing 2.5 mg of albuterol) and 3 oxygen flows (6, 8, and 10 L/min) were evaluated using the 17 nebulizers, A cotton plug at the nebulizer mouthpiece was used to trap aerosol during simulated spontaneous breathing, Following each trial, the amount of albuterol remaining in the nebulizer and the amount deposited in the cotton plug were determined spectrophotometrically. Aerosol particle size was determined using an 11-stage cascade impactor. Results: Increasing fill volume decreased the amount of albuterol trapped in the dead volume (p<0.001) and increased the amount delivered to the patient (p<0.001). Increasing flow increased tile mass output of particles in the respirable range of 1 to 5 mu m (p=0.004), but the respirable mass delivered to the patient was affected to a greater extent by nebulizer brand (p<0.001) than flow, Although 2.5 mg of albuterol was placed into the nebulizers, less than 0.5 mg in the respirable range of 1 to 5 mu m was delivered to the mouthpiece. Conclusions: The performance of medication nebulizers is affected by fill volume, flow, and nebulizer brand. When they are used for research applications, the nebulizer characteristics must be evaluated and reported for the conditions used in the investigation. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Hess, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT RESP CARE,ELLISON 401,BOSTON,MA 02114, USA. NR 28 TC 117 Z9 123 U1 2 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 AUG PY 1996 VL 110 IS 2 BP 498 EP & DI 10.1378/chest.110.2.498 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VB923 UT WOS:A1996VB92300039 PM 8697857 ER PT J AU Gilon, D Cape, EG Handschumacher, MD Jiang, L Sears, C Solheim, J Morris, E Strobel, JT MillerJones, SM Weyman, AE Levine, RA AF Gilon, D Cape, EG Handschumacher, MD Jiang, L Sears, C Solheim, J Morris, E Strobel, JT MillerJones, SM Weyman, AE Levine, RA TI Insights from three-dimensional echocardiographic laser stereolithography - Effect of leaflet funnel geometry on the coefficient of orifice contraction, pressure loss, and the Gorlin formula in mitral stenosis SO CIRCULATION LA English DT Article DE echocardiography; mitral valve; stenosis; pressure ID LEFT-VENTRICULAR VOLUME; IN-VIVO VALIDATION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; VALVE AREA; RECONSTRUCTION; ULTRASOUND; MORPHOLOGY; VITRO; CINEVENTRICULOGRAPHY; QUANTIFICATION AB Background Three-dimensional echocardiography can allow us to address uniquely three-dimensional scientific questions for example, the hypothesis that the impact of a stenotic valve depends not only on its limiting orifice area but also on its three-dimensional geometry proximal to the orifice. This can affect the coefficient of orifice contraction (Cc = effective/anatomic area), which is important because for a given flow rate and anatomic area, a lower Cc gives a higher velocity and pressure gradient, and Cc, routinely assumed constant in the Gorlin equation, may vary with valve shape (60% for a flat plate, 100% for a tube). To date, it has not been possible to study this with actual value shapes in patients. Methods and Results Three-dimensional echocardiography reconstructed value geometries typical of the spectrum in patients with mitral stenosis; mobile doming, intermediate conic al, and relatively flat immobile values. Each geometry was constructed with orifice areas of 0.5, 1.0 and 1.5 cm(2) by stereolithography (computerized laser polymerization) (total nine values) and studied at physiological flow rates. Cc varied prominently with shape and was larger for the longer, tapered dome (more gradual flow convergence proximal and distal to the limiting orifice); for an anatomic orifice of 1.5 cm(2), Cc increased from 0.62 to 0.75. For each shape, Cc increased with increasing orifice size relative to the proximal funnel (more tubelike). These variations translated into important differences of up to 40% in pressure gradient for the same anatomic area and flow rate (greatest for the flattest values), with a corresponding variation in calculated Gorlin area (an effective area) relative to anatomic values. Conclusions The coefficient of contraction and the related net pressure loss are importantly affected by the variations in leaflet geometry seen in patients with mitral stenosis. Three-dimensional echocardiography and stereolithography, with the use of actual information from patients, can address such uniquely three-dimensional question to provide insight into the relations between cardiac structure, pressure, and flows. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. UNIV PITTSBURGH,CHILDRENS HOSP,SCH MED & ENGN,PITTSBURGH,PA 15260. HEWLETT PACKARD CORP,ANDOVER,MA. SANTIN ENGN,PEABODY,MA. FU NHLBI NIH HHS [R01-HL-53702] NR 49 TC 30 Z9 31 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 1996 VL 94 IS 3 BP 452 EP 459 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UZ051 UT WOS:A1996UZ05100033 PM 8759088 ER PT J AU Kranzhofer, R Clinton, SK Ishii, K Coughlin, SR Fenton, JW Libby, P AF Kranzhofer, R Clinton, SK Ishii, K Coughlin, SR Fenton, JW Libby, P TI Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes SO CIRCULATION RESEARCH LA English DT Article DE atherosclerosis; thrombosis; inflammation; restenosis; monocyte chemotactic protein-1 ID TUMOR NECROSIS FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CORONARY-ARTERY DISEASE; PHOSPHOINOSITIDE HYDROLYSIS; ENDOTHELIAL-CELLS; ATHEROSCLEROTIC PLAQUE; MONOCLONAL-ANTIBODIES; PROTEOLYTIC MECHANISM; CHEMOTACTIC PROTEIN-1; RECEPTOR ACTIVATION AB Thrombosis frequently occurs during atherogenesis and in response to vascular injury. Accumulating evidence supports a role for inflammation in the same situation. The present study therefore sought links between thrombosis and inflammation by determining whether thrombin, which is present in active form at sites of thrombosis, can elicit inflammatory functions of human monocytes and vascular smooth muscle cells (SMCs), two major constituents of advanced atheroma. Human alpha-thrombin (EC(50), approximate to 500 pmol/L) potently induced interleukin (IL)-6 release from SMCs. The tethered-ligand thrombin receptor appeared to mediate this effect. Furthermore, alpha-thrombin also rapidly increased levels of mRNA encoding IL-6 and monocyte chemotactic protein-1 (MCP-1) in SMCs. In contrast, only alpha-thrombin concentrations of greater than or equal to 100 nmol/L could stimulate release of IL-6 or tumor necrosis factor-alpha (TNF alpha) in peripheral blood monocytes or monocyte-derived macrophages. Lipid loading of macrophages did not augment thrombin responsiveness. Likewise, only alpha-thrombin concentrations of greater than or equal to 100 nmol/L increased levels of IL-6, IL-1 beta, MCP-1, or TNF alpha mRNA in monocytes. Differential responses of SMCs and monocytes to thrombin extended to early agonist-mediated increases in [Ca2+](i). SMCs and endothelial cells, but not monocytes, contained abundant mRNA encoding the thrombin receptor and displayed cell surface thrombin receptor expression detected with a novel monoclonal antibody. Thus, the level of thrombin receptors appeared to account for the differential thrombin susceptibility of SMCs and monocytes. These data suggest that SMCs may be more sensitive than monocytes/macrophages to thrombin activation in human atheroma. Cytokines produced by thrombin-activated SMCs may contribute to ongoing inflammation in atheroma complicated by thrombosis or subjected to angioplasty. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,VASC MED & ATHEROSCLEROSIS UNIT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. FU NCI NIH HHS [KO7CA-01680]; NHLBI NIH HHS [HL-44907, HL-48743] NR 73 TC 83 Z9 86 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1996 VL 79 IS 2 BP 286 EP 294 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA VC257 UT WOS:A1996VC25700016 PM 8756006 ER PT J AU Vatner, DE Sato, N Ishikawa, Y Kiuchi, K Shannon, RP Vatner, SF AF Vatner, DE Sato, N Ishikawa, Y Kiuchi, K Shannon, RP Vatner, SF TI beta-adrenoceptor desensitization during the development of canine pacing-induced heart failure SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE adenylyl cyclase; beta-adrenoceptors; heart failure; ryanodine receptors ID ADRENERGIC-RECEPTOR; G-PROTEIN; DOWN-REGULATION; ALPHA; CARDIOMYOPATHY; CONTRACTION; SUBTYPES; INCREASE; SYSTEMS; COMPLEX AB 1. The goal of this review is to emphasize four major points regarding the development of catecholamine desensitization in heart Failure (HF). 2. Catecholamine desensitization occurs prior to the development of HF (i.e. after 1 day of rapid pacing, physiological responses to beta-adrenoceptor stimulation are depressed by over 50%, yet no evidence of HF is observed for 3-4 weeks of rapid pacing). 3. Multiple mechanisms in the beta-adrenoceptor cascade are involved. In HF there are decreases in beta(1)-adrenoceptors, high affinity beta-adrenoceptors, adenylyl cyclase activity and messenger RNA and increases in G(i). 4. Not all mechanisms appear simultaneously (i.e. early decreases occur in high affinity beta-adrenoceptors and adenylyl cyclase; late increases in G(i) and decreases in beta-adrenoceptor density evolves). 5. Mechanisms distal to cAMP generation also play a role (i.e. alterations in ryanodine receptor binding and excitation-contraction coupling also. occur). C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP Vatner, DE (reprint author), NEW ENGLAND REG PRIMATE RES CTR,POB 9102,SOUTHBOROUGH,MA 01772, USA. FU NHLBI NIH HHS [HL 37404, HL 38070, HL 45332] NR 22 TC 13 Z9 13 U1 0 U2 5 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD AUG PY 1996 VL 23 IS 8 BP 688 EP 692 DI 10.1111/j.1440-1681.1996.tb01760.x PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA VE531 UT WOS:A1996VE53100013 PM 8886492 ER PT J AU Sun, XC Wong, JR Song, KL Chen, LB AF Sun, XC Wong, JR Song, KL Chen, LB TI Anticarcinoma activity of a novel drug, 3-ethyl-3'-methylthiatelluracarbocyanine iodide (Te), a tellurium-containing cyanine targeted at mitochondria SO CLINICAL CANCER RESEARCH LA English DT Article ID RAT-LIVER MITOCHONDRIA; CARCINOMA-CELLS; RHODAMINE-123; ACCUMULATION; INHIBITION; RETENTION; PROBE AB Lipophilic cationic compounds such as rhodamine 123, AA1, and dequalinium chloride have been reported to constitute a new class of anticarcinoma agents based on their selective localization, accumulation, and retention within the mitochondria of certain carcinoma cells, After screening more than 1000 lipophilic cationic compounds in clonogenic assays, we found that a tellurium-containing cyanine, 3-ethyl-3'-methyl-thiatelluracarbocyanine iodide (Te), exhibits significant anticarcinoma activity, In vitro testing showed that Te was 64-fold more toxic to the carcinoma cell line CX-1 than to the normal epithelial cell line CV-1, In vivo testing showed that Te significantly prolonged the survival of mice implanted with tumors, For C57BL x DBA/2 F-1, mice implanted with the mouse bladder carcinoma cell line MB49, the treated:control (T:C) ratio ranged from 250 to 268%, For Swiss nu/nu mice implanted with the human melanoma cell line LOX, the T:C ratio ranged from 176 to 270%, For Swiss nu/nu mice implanted with the human ovarian tumor cell line OVCA-III, the T:C ratio was 344%, These anticarcinoma activities warrant further investigation of Te as a potential anticarcinoma agent. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. OREGON GRAD INST SCI & TECHNOL,DEPT CHEM BIOCHEM & MOL BIOL,PORTLAND,OR 97291. CORNELL UNIV,NEW YORK HOSP,DEPT RADIOL,COLL MED,STICH RADIAT CTR,NEW YORK,NY 10021. FU NIGMS NIH HHS [GM38318] NR 21 TC 15 Z9 16 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 1996 VL 2 IS 8 BP 1335 EP 1340 PG 6 WC Oncology SC Oncology GA VB199 UT WOS:A1996VB19900012 PM 9816305 ER PT J AU Kattapuram, AS ODonnell, RJ Huszar, M Rosenberg, AE Kattapuram, SV Mankin, HJ AF Kattapuram, AS ODonnell, RJ Huszar, M Rosenberg, AE Kattapuram, SV Mankin, HJ TI Surgical management of innominate giant cell tumor SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID BONE; RESECTION; ISCHIUM AB The surgical outcome for innominate giant cell tumors was reviewed in 7 patients; 6 (86%) were female patients and 1 (14%) was a male patient, The patients had an average age of 28.7 years (range, 16-42 years) and an average followup of 4.6 years (range, 2.0-7.3 years), Three tumors were in the ischiopubic region, 3 were acetabular, and 1 was iliosacral, The tumors ranged in size from 5 cm x 6 cm to 17 cm x 18 cm, All margins were intralesional. Reconstruction in 3 cases used osteoarticular acetabular allografts, The local recurrence rate was 3 of 7 (43%), Ischiopubic tumors accounted for all recurrences, Vascular invasion was seen in all patients who had a recurrence and only 1 patient without a recurrence, Patients with recurrences underwent subsequent resections and radiation therapy, and remain disease free at an average followup of 3.0 years (range, 0.8-4.2 years) after recurrence, There were no malignant, metastatic, or multicentric recurrences, and no patient died of disease or complications, Innominate giant cell tumor occurs most often in women and is associated with a high risk for local recurrence, Wide margins usually are not possible; intralesional margins are accepted in cases of limited accessibility or potential functional compromise. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 24 TC 9 Z9 12 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 1996 IS 329 BP 281 EP 287 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VC566 UT WOS:A1996VC56600035 PM 8769463 ER PT J AU Gervais, DA Saini, S Hahn, PF Reimer, P Goldberg, MA Weiskoff, R AF Gervais, DA Saini, S Hahn, PF Reimer, P Goldberg, MA Weiskoff, R TI Gadolinium-DTPA enhanced echoplanar MR imaging of the liver: Preliminary observations SO CLINICAL RADIOLOGY LA English DT Article ID GD-DTPA; DIFFERENTIATION; HEMANGIOMA; IMAGES AB This study describes our preliminary experience with dynamic gadopentetate dimeglumine enhanced echoplaner MR imaging (EPI) in fifteen patients with focal liver lesions. Lesion diagnosis was established by histology (n = 3) or typical imaging characteristics (exclusive of the EPI study) combined with clinical follow up (n = 12). Dynamic gadopentetate dimeglumine (0.1 mmol/kg) enhanced MR imaging was performed on a commercially available 1.5T EPI equipped MR system using a single-excitation fat-suppressed inversion recovery pulse sequence. The choice of an IR sequence allowed nulling of the lesion signal by varying T1 prior to enhancement creating the optimal conditions for qualitative inspection of the enhancement profile. Intershot delay (defined as TR) ranged from 1-5s. Image analysis was performed qualitatively by two radiologists. Benign and malignant lesions displayed temporal enhancement profiles compatible a with characteristic findings expected with conventional imaging modalities. Further refinements in our technique and expanded system capabilities will allow dynamic imaging of the entire liver with improved temporal resolution over conventional sequences. RP Gervais, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,WHITE 220,14 FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD AUG PY 1996 VL 51 IS 8 BP 545 EP 549 DI 10.1016/S0009-9260(96)80132-2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VC372 UT WOS:A1996VC37200002 PM 8761389 ER PT J AU Sykes, M AF Sykes, M TI Hematopoietic cell transplantation for the induction of allo- and xenotolerance SO CLINICAL TRANSPLANTATION LA English DT Article DE immune tolerance; xenotransplantation; bone marrow transplantation; thymus; thymic transplantation ID NONLETHAL PREPARATIVE REGIMEN; ALLOGENEIC BONE-MARROW; T-CELLS; TRANSGENIC MICE; CLONAL DELETION; NONMYELOABLATIVE REGIMEN; PECULIAR IMMUNOBIOLOGY; GRAFT-REJECTION; STEM-CELLS; TOLERANCE AB Durable tolerance can be reliably achieved by inducing engraftment of allogeneic or xenogeneic hematopoietic cells in recipients initially depleted of T lymphocytes. Engraftment of pluripotent hematopoietic stem cells (PPHSC) provides a constant supply of donor antigen to ensure the ongoing central deletion of donor-reactive T cell clones, resulting in a permanent state of donor-specific tolerance. Because of the toxicity of myeloablative therapy used to achieve allogeneic PPHSC engraftment, this approach has not yet been applied in humans. However, a non-myeloablative, relatively non-toxic conditioning regimen allowing allogeneic or concordant xenogeneic bone marrow engraftment and tolerance induction has recently been developed in a murine model. Host pre-treatment with depleting doses of anti-CD4 and anti-CD8 mAbs (and in the xenogeneic combination, anti-Thy 1.2 and anti-NK 1.1 mAbs), followed by 3 Gy whole body irradiation (WBI) and 7 Gy of thymic irradiation (TI) allows engraftment of allogeneic or xenogeneic rat bone marrow cells with mixed, multilineage lymphohematopoietic chimerism and donor-specific skin graft tolerance. TI can be omitted from the regimen if additional mAb treatments are given. Engraftment of allogeneic PPHSC is associated with early migration of donor bone marrow-derived cells to the host thymus, resulting in deletion of developing thymocytes with reactivity to donor antigens. Maintenance of long-term tolerance is purely due to this deletional mechanism. In the xenogeneic rat-->mouse species combination, mixed chimerism is also associated with deletional T cell tolerance, and also leads to tolerance at the level of B cells that make natural antibodies. In the discordant pig-->mouse species combination, we have found that physiologic preference for host hematopoiesis is a major barrier to achieving donor hematopoietic reconstitution. Pig-specific hematopoietic cytokines can at least partially overcome this barrier. Furthermore, if normal, immunocompetent mice are thymectomized, then receive T- and NK-cell-depleting mAbs, and a fetal swine thymus is grafted, murine CD4 T cells recover in the swine thymus, and demonstrate specific tolerance to the xenogeneic swine donor. These T cells appear to be able to recognize antigen in the context of host MHC, and demonstrate immunocompetence. Our studies have demonstrated for the first time that donor-specific skin graft tolerance can be induced across a discordant species barrier. RP Sykes, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,TRANSPLANTAT SECT,MGH E,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [R01HL49915] NR 48 TC 22 Z9 22 U1 0 U2 0 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 AUG PY 1996 VL 10 IS 4 BP 357 EP 363 PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA VH549 UT WOS:A1996VH54900007 PM 8884109 ER PT J AU Nguyen, DMT AF Nguyen, DMT TI The role of physical medicine and rehabilitation in pain management SO CLINICS IN GERIATRIC MEDICINE LA English DT Article ID LOW-BACK-PAIN; ANTIDEPRESSANTS; BIOFEEDBACK; EMG AB Physical medicine and rehabilitation frequently use the interdisciplinary team approach to the management of pain in the elderly because this would also address the psychosocial and functional deficits resulting from the pain symptom. The team prescribes a combination of pharmacologic agents, cognitive-behavioral therapies, physical modalities, occupational therapy, and physical therapy in the treatment plan. Management of patients with pain resulting from compression fracture and spinal stenosis is discussed also. RP Nguyen, DMT (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PHYS MED & REHABIL W117,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 59 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 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD AUG PY 1996 VL 12 IS 3 BP 517 EP & PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA UZ174 UT WOS:A1996UZ17400007 PM 8853943 ER PT J AU Evins, AE Goff, DC AF Evins, AE Goff, DC TI Adjunctive antidepressant drug therapies in the treatment of negative symptoms of schizophrenia SO CNS DRUGS LA English DT Review ID PLACEBO-CONTROLLED TRIAL; SECONDARY DEPRESSION; DEFICIT SYNDROME; DOUBLE-BLIND; DESIPRAMINE HYDROXYLATION; TRICYCLIC ANTIDEPRESSANTS; POSTPSYCHOTIC DEPRESSION; PLASMA-CONCENTRATIONS; CLINICAL SYMPTOMS; NONDEFICIT FORMS AB The negative symptoms of schizophrenia comprise one of several identified symptom clusters associated with the disorder. Although consensus on the precise components of the negative syndrome and on definitions for specific negative symptoms have not been reached, Cor the purpose of this review, negative symptoms include blunted affect, poverty of thought content and speech, apathy, social withdrawal and anergia. Negative symptoms are among the most disabling and treatment-resistant symptoms of schizophrenia, and various approaches to treatment have been taken, including augmentation of conventional antipsychotic treatment with antidepressants. Assessment of the effect of treatments an negative symptoms can be problematic and, therefore, clinical trials need to be of adequate duration and systematic attempts need to be made to rule out secondary causes of negative symptoms that may mimic or exacerbate them. Placebo-controlled studies of fluoxetine and fluvoxamine, which controlled for secondary negative symptoms, have demonstrated substantial improvement in negative symptoms compared with placebo. Significant exacerbation in psychotic symptoms was not reported in these controlled trials. This, therefore, represents a promising clinical option for treating negative symptoms. It appears that the maximum benefit of antidepressant augmentation may not be achieved until at least 12 weeks after initiation of therapy. Therefore, trials of shorter duration may understate the potential efficacy of this combination. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Evins, AE (reprint author), FREEDOM TRAIL CLIN,25 STANIFORD ST,BOSTON,MA 02114, USA. NR 120 TC 34 Z9 35 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD AUG PY 1996 VL 6 IS 2 BP 130 EP 147 DI 10.2165/00023210-199606020-00005 PG 18 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VD509 UT WOS:A1996VD50900005 ER PT J AU Corey, DP Zuker, CS AF Corey, DP Zuker, CS TI Sensory systems SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. RP Corey, DP (reprint author), HOWARD HUGHES MED INST,WELLMAN 414,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1996 VL 6 IS 4 BP 437 EP 439 DI 10.1016/S0959-4388(96)80046-8 PG 3 WC Neurosciences SC Neurosciences & Neurology GA VG349 UT WOS:A1996VG34900001 ER PT J AU Lem, J Makino, CL AF Lem, J Makino, CL TI Phototransduction in transgenic mice SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; PHOSPHODIESTERASE BETA-SUBUNIT; DOMINANT RETINITIS-PIGMENTOSA; DEGENERATION SLOW RDS; RETINAL DEGENERATION; CGMP-PHOSPHODIESTERASE; ACTIVATION STEPS; RHODOPSIN KINASE; MOUSE RETINAS; BIPOLAR CELLS AB Transgenic mice provide a powerful tool for elucidating the molecular mechanisms of phototransduction. Mice expressing a phosphorylation-deficient rhodopsin and mice deficient in arrestin are being used to study shutoff of photoactivated rhodopsin. These in vivo mouse studies indicate that shutoff is partially mediated by rhodopsin phosphorylation alone, but complete deactivation on a physiological time scale requires arrestin. Work on other transgenic mutant mice to unravel the function of recoverin and phosducin and to further define the role of the gamma subunit of phosphodiesterase is in progress. Transgenic mice are also being used to investigate how mutant proteins give rise to retinal disease and to develop therapeutic interventions. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. RP Lem, J (reprint author), TUFTS MED SCH,NEW ENGLAND EYE CTR,DEPT OPHTHALMOL,750 WASHINGTON ST,BOX 450,BOSTON,MA 02111, USA. NR 45 TC 27 Z9 27 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1996 VL 6 IS 4 BP 453 EP 458 DI 10.1016/S0959-4388(96)80049-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VG349 UT WOS:A1996VG34900004 PM 8794096 ER PT J AU Masland, RH AF Masland, RH TI Processing and encoding of visual information in the retina SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID MACAQUE MONKEY RETINA; GANGLION-CELLS; BIPOLAR CELLS; HORIZONTAL CELLS; SPATIAL STRUCTURE; MAMMALIAN RETINA; RECEPTIVE-FIELDS; TIGER SALAMANDER; PRIMATE RETINA; RABBIT RETINA AB The retina is a remarkably sophisticated instrument and much of its internal circuitry is poorly characterized. A major problem for studies aimed at better understanding the retina is that the neurons in its middle layers are varied in type and relatively inaccessible. Two approaches that have facilitated progress towards elucidating retinal function include population-based studies of the anatomy of the retina and multi-electrode recordings from its output; in combination, they enable the neuronal system of the retina to be examined as a whole. RP Masland, RH (reprint author), MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,WELLMAN 429,50 BLOSSOM ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY01075] NR 47 TC 26 Z9 26 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1996 VL 6 IS 4 BP 467 EP 474 DI 10.1016/S0959-4388(96)80051-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VG349 UT WOS:A1996VG34900006 PM 8794095 ER PT J AU Liman, ER AF Liman, ER TI Pheromone transduction in the vomeronasal organ SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID G-PROTEINS; PUTATIVE PHEROMONE; GARTER SNAKES; DIFFERENTIAL LOCALIZATION; CELLULAR-LOCALIZATION; SIGNAL-TRANSDUCTION; ODORANT RECEPTORS; URINARY PROTEINS; BINDING PROTEIN; SYSTEM AB Single-cell physiology and cloning efforts have extended studies of the vomeronasal organ to cellular and molecular levels, Recent work has shown that transduction in the vomeronasal organ is probably mediated by signalling pathways distinct from those that mediate transduction in the main olfactory system. An advance in understanding transduction has come with the cloning from rat vomeronasal organ of a family of putative pheromone receptor genes that bear no sequence similarity to previously cloned receptors. Other work has examined the expression of putative signalling components and found a zonal organization of the epithelium. Patch-clamp studies have described the basic electrical properties of vomeronasal neurons and explored second-messenger pathways. RP Liman, ER (reprint author), MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,WELLMAN 414,50 BLOSSOM ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R03 DC 02889-01] NR 63 TC 24 Z9 24 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1996 VL 6 IS 4 BP 487 EP 493 DI 10.1016/S0959-4388(96)80054-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VG349 UT WOS:A1996VG34900009 PM 8794101 ER PT J AU Kaplan, JM AF Kaplan, JM TI Sensory signaling in Caenorhabditis elegans SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID GLR-1 GLUTAMATE-RECEPTOR; C-ELEGANS; PEPTIDE COTRANSMITTERS; CHEMOSENSORY NEURONS; MOTOR-NEURON; NEMATODE; BEHAVIOR; THERMOTAXIS; RELEASE; GENES AB The simple anatomy, behavior, and genetics of the nematode Caenorhabditis elegans make it an attractive organism for studying sensory circuits and their functions in vivo. Recent advances in our understanding of C. elegans sensory signaling stem from work on topographic maps, chemosensory receptors, modality coding, and the integration of antagonistic sensory inputs. RP Kaplan, JM (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,WELLMAN 8,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 34 TC 9 Z9 15 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 1996 VL 6 IS 4 BP 494 EP 499 DI 10.1016/S0959-4388(96)80055-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VG349 UT WOS:A1996VG34900010 PM 8794103 ER PT J AU Takagi, H King, GL Aiello, LP AF Takagi, H King, GL Aiello, LP TI Identification and characterization of vascular endothelial growth factor receptor (Flt) in bovine retinal pericytes SO DIABETES LA English DT Article ID HUMAN-BREAST-CANCER; TYROSINE KINASE; SIGNAL-TRANSDUCTION; DIABETIC-RETINOPATHY; DIFFERENTIAL DISPLAY; EPITHELIAL-CELLS; MESSENGER-RNA; EXPRESSION; VEGF; KDR AB Vascular endothelial growth factor (VEGF) plays an important role in the hypoxia-stimulated neovascularization of ischemic retinal diseases such as proliferative diabetic retinopathy, VEGF exerts its effect through two known high-affinity tyrosine kinase receptors, named kinase insert domain-containing receptor (KDR) and the fms-like tyrosine kinase (Flt), VEGF receptors are located primarily on endothelial cells, although receptors on a few other nonocular cell types also have been described, In the present study, we demonstrate the expression of Flt, but not KDR, in bovine retinal pericytes (BRPCs), Although KDR is expressed predominantly in retinal endothelial cells, Northern blot analysis demonstrated substantial expression of the Flt gene in BRPCs without detection of KDR despite using polyadenylated RNA, Hypoxia increased Flt gene expression in BRPCs (2.7-fold, P < 0.01), I-125-labeled VEGF binding analysis on BRPCs demonstrated two apparent high-affinity receptor subtypes (K-d = 14 and 215 pmol/l), with 2.9 x 10(4) and 1.4 x 10(5) receptors/cell, respectively, I-125-VEGF affinity cross-linking demonstrated VEGF-specific binding complexes at 150, 172, 187, and 200 kDa under reducing conditions. Western blot analysis using an anti-phosphotyrosine antibody demonstrated VEGF-induced tyrosine phosphorylation of several proteins, VEGF stimulation had little effect on initial BRPCs growth rates but significantly increased BRPCs number after 7 days. These results suggest that two classes of high-affinity VEGF receptors are present on BRPCs, at least one of which is analogous to Flt and is capable of intracellular protein phosphorylation. Thus, VEGF might regulate the function of both retinal endothelial cells and retinal pericytes to induce pathological angiogenesis and vascular remodeling during proliferative diabetic retinopathy and other ischemic retinal diseases. C1 BEETHAM EYE INST,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. FU NEI NIH HHS [EY-05110, EY-10827]; PHS HHS [36836] NR 35 TC 96 Z9 97 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 AUG PY 1996 VL 45 IS 8 BP 1016 EP 1023 DI 10.2337/diabetes.45.8.1016 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA073 UT WOS:A1996VA07300003 PM 8690146 ER PT J AU Goodyear, LJ Hirshman, MF Napoli, R Calles, J Markuns, JF Ljungqvist, O Horton, ES AF Goodyear, LJ Hirshman, MF Napoli, R Calles, J Markuns, JF Ljungqvist, O Horton, ES TI Glucose ingestion causes GLUT4 translocation in human skeletal muscle SO DIABETES LA English DT Article ID PLASMA-MEMBRANE; TRANSPORTER NUMBER; RAT HINDLIMB; INSULIN; EXERCISE; EXPRESSION; INCREASES; PROTEIN; OBESITY; NIDDM AB In humans, ingestion of carbohydrates causes an increase in blood glucose concentration, pancreatic insulin release, and increased glucose disposal into skeletal muscle, The underlying molecular mechanism for the increase in glucose disposal in human skeletal muscle after carbohydrate ingestion is not known, We determined whether glucose ingestion increases glucose uptake in human skeletal muscle by increasing the number of glucose transporter proteins at the cell surface and/or by increasing the activity of the glucose transporter proteins in the plasma membrane, Under local anesthesia, similar to 1 g of vastus lateralis muscle was obtained from six healthy subjects before and 60 min after ingestion of a 75-g glucose load, Plasma membranes were isolated from the skeletal muscle and used to measure GLUT4 and GLUT1 content and glucose transport in plasma membrane vesicles, Glucose ingestion increased the plasma membrane content of GLUT4 per gram muscle (3,524 +/- 729 vs, 4,473 +/- 952 arbitrary units for basal and 60 min, respectively; P < 0.005). Transporter-mediated glucose transport plasma membrane vesicles was also significantly creased (130 +/- 11 vs, 224 +/- 38 pmol . mg(-1) . s(-1), P < 0.017), whereas the calculated ratio of glucose transport to GLUT4, an indication of transporter functional activity, was not significantly increased 60 min after glucose ingestion (2.3 +/- 0.4 vs, 3.0 +/- 0.5 pmol . GLUT4 arbitrary units(-1) . s(-1) P < 0.17). These results demonstrate that oral ingestion of glucose increases the rate of glucose transport across the plasma membrane and causes GLUT4 translocation in human skeletal muscle. These findings suggest that under physiological conditions the translocation of GLUT4 is an important mechanism for the stimulation of glucose uptake in human skeletal muscle. C1 NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. UNIV VERMONT,DEPT MED,DIV METAB ENDOCRINOL & NUTR,BURLINGTON,VT. KAROLINSKA HOSP & INST,DEPT SURG,STOCKHOLM,SWEDEN. RP Goodyear, LJ (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,METAB SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. OI Markuns, Jeffrey/0000-0002-8044-2575; NAPOLI, Raffaele/0000-0002-3366-2321 FU NIAMS NIH HHS [AR-42238]; NIDDK NIH HHS [DK-46188] NR 25 TC 27 Z9 28 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 AUG PY 1996 VL 45 IS 8 BP 1051 EP 1056 DI 10.2337/diabetes.45.8.1051 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA073 UT WOS:A1996VA07300008 PM 8690151 ER PT J AU Veves, A Akbari, CM Donaghue, VM Zacharoulis, D Chrzan, JS Freeman, R LoGerfo, FW AF Veves, A Akbari, CM Donaghue, VM Zacharoulis, D Chrzan, JS Freeman, R LoGerfo, FW TI The effect of diabetes, neuropathy, Charcot arthropathy and arterial disease on the foot microcirculation. SO DIABETOLOGIA LA English DT Meeting Abstract C1 DEACONESS JOSLIN FOOT CTR,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 1 EP 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300002 ER PT J AU Jiao, H Li, LS Glaser, A Galli, J Fakhrairad, H Koike, G Jacob, HJ Luthman, H AF Jiao, H Li, LS Glaser, A Galli, J Fakhrairad, H Koike, G Jacob, HJ Luthman, H TI Total genome scan for identification of NIDDM susceptibility factors in the GK rat SO DIABETOLOGIA LA English DT Meeting Abstract C1 KAROLINSKA INST,DEPT MOL MED,S-10401 STOCKHOLM,SWEDEN. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 9 EP 9 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300010 ER PT J AU Laviola, L Giorgino, F Hansen, H Chow, JC Baquero, JA Ooi, J Riedel, H Smith, RJ AF Laviola, L Giorgino, F Hansen, H Chow, JC Baquero, JA Ooi, J Riedel, H Smith, RJ TI Preferential association of the adapter protein GRB10 with insulin as compared to IGF-I receptors. SO DIABETOLOGIA LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 35 EP 35 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300035 ER PT J AU Giorgino, F Pedrini, MT Matera, L Smith, RJ AF Giorgino, F Pedrini, MT Matera, L Smith, RJ TI Specific increase in p85 alpha by dexamethasone leads to inhibition of insulin and IGF-I stimulated PI3-kinase activity SO DIABETOLOGIA LA English DT Meeting Abstract C1 IST CLIN MED ENDOCRINOL & MALATTIE METAB,BARI,ITALY. JOSLIN DIABET CTR,BOSTON,MA 02215. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 199 EP 199 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300198 ER PT J AU Brambilla, E Patti, ME Terruzzi, I Kahn, CR Luzi, L AF Brambilla, E Patti, ME Terruzzi, I Kahn, CR Luzi, L TI Amino acids (AA) stimulate protein anabolism via p70 S6 kinase phosphorylation. SO DIABETOLOGIA LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 200 EP 200 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300200 ER PT J AU Doria, A Federman, S Rich, SS Warram, JH Krolewski, AS AF Doria, A Federman, S Rich, SS Warram, JH Krolewski, AS TI DNA polymorphisms and mapping on chromosome 6q of plasma-cell antigen 1 (PC-1), an insulin signal inhibitor. SO DIABETOLOGIA 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 SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 285 EP 285 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300284 ER PT J AU Almind, K Inoue, G Pedersen, O Kahn, CR AF Almind, K Inoue, G Pedersen, O Kahn, CR TI A common amino acid polymorphism in IRS-1 causes impaired insulin signaling: Evidence from transfection studies SO DIABETOLOGIA LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. STENO DIABET CTR,DK-2820 GENTOFTE,DENMARK. 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 288 EP 288 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49300287 ER PT J AU Quinn, M Angelico, MC Warram, JH Krolewski, AS AF Quinn, M Angelico, MC Warram, JH Krolewski, AS TI Familial factors determine the development of diabetic nephropathy in patients with IDDM SO DIABETOLOGIA LA English DT Article DE insulin-dependent diabetes mellitus; genetics of diabetic nephropathy; family studies ID RISK FACTOR; MICROALBUMINURIA; MELLITUS; DISEASE; SUSCEPTIBILITY; AGGREGATION AB To evaluate familial factors in the development of diabetic nephropathy in insulin-dependent diabetes mellitus (IDDM) we examined concordance for diabetic nephropathy in families with multiple IDDM siblings. Families (n = 110) were identified through Joslin Clinic patients (probands) with a sibling having IDDM. To be eligible, the probands' and siblings' ages at IDDM diagnosis were less than 21 years, and IDDM duration was more than 15 years for probands and more than 10 years for siblings. Mean post-pubertal diabetes duration was 23 years for probands (n = 110) and 21 years for siblings (n = 125). Nephropathy history was determined by medical record review for deceased patients and those with persistent proteinuria or end-stage renal disease to ascertain the date of onset of persistent proteinuria. For patients without documented nephropathy, the albumin/creatinine ratio was measured in multiple urine samples. The cumulative incidence of persistent proteinuria according to post-pubertal duration of IDDM was determined by life-table analysis. For probands and siblings combined, the cumulative incidence of advanced diabetic nephropathy after 30 years of IDDM was 35%, but the risk in siblings varied according to the proband's renal status. The cumulative risk in siblings after 25 years of IDDM (post-puberty) was 71.5% if the proband had persistent proteinuria but only 25.4% if the proband did not (p < 0.001). A difference of nearly 50% in the risk to IDDM siblings, depending upon the IDDM proband's renal status, is consistent with a major gene effect that predisposes an individual with IDDM to develop advanced diabetic nephropathy. C1 JOSLIN DIABET CTR,SECT EPIDEMIOL & GENET,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 09116, DK 41526] NR 25 TC 339 Z9 344 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 IS 8 BP 940 EP 945 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA076 UT WOS:A1996VA07600008 PM 8858216 ER PT J AU Donaghue, VM Chrzan, JS Rosenblum, BI Giurini, JM Habershaw, GM Veves, A AF Donaghue, VM Chrzan, JS Rosenblum, BI Giurini, JM Habershaw, GM Veves, A TI A clinical evaluation of a collagen-alginate topical wound dressing in the management of diabetic foot ulcers SO DIABETOLOGIA LA English DT Meeting Abstract C1 DEACONESS JOSLIN FOOT CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1996 VL 39 SU 1 BP 1019 EP 1019 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA493 UT WOS:A1996VA49301015 ER PT J AU Craig, WA AF Craig, WA TI Antimicrobial resistance issues of the future SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article; Proceedings Paper CT Alexander Project Symposium CY NOV 01-03, 1995 CL THE HAGUE, NETHERLANDS ID OTITIS-MEDIA; EFFICACY; MODEL AB Increasing antimicrobial resistance among respiratory pathogens has the potential to reduce the efficacy of standard dosage regimens for many oral drugs. The goal of antimicrobial therapy is to maximize bactericidal activity. The duration of time that serum concentrations exceed the MIC is the pharmacokinetic/ pharmacodymamic parameter that determines efficacy for beta-lactams, macrolides, and trimethoprim/sulfamethoxazole. Studies in animal models suggest that serum levels of beta-lactams need to exceed the MIC for about half of the dosing interval to obtain maximum antimicrobial efficacy. Studies in children with acute otitis media also demonstrate that serum concentrations need to exceed the MIC for 40% or more of the dosing interval to obtain bacteriologic cure in over 85% of patients. With the oral beta-lactams used against penicillin-resistant Streptotoccus pneumoniae, this goal is obtained only with amoxicillin and amoxicillin/clavulanate. For Haemophilus influenzae, several beta-lactams including cefixime, cefpodoxime, and amoxicillin/clavulanate provide serum levels with the longest durations above the MIC. Antimicrobial resistance has also stimulated the search for new potent antimicrobials, altered but effective dosing regimens, and resistance control measures, such as the prudent use, optimal infection control practices, and vaccines to reduce colonization and subsequent infection. (C) 1996 Elsevier Science Inc. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. RP Craig, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 21 TC 78 Z9 83 U1 0 U2 2 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 AUG PY 1996 VL 25 IS 4 BP 213 EP 217 DI 10.1016/S0732-8893(96)00162-9 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA VT364 UT WOS:A1996VT36400010 PM 8937847 ER PT J AU Craig, WA AF Craig, WA TI Alexander Project Symposium, The Hague, Netherlands, November 1-3, 1995 - Closing summary SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Editorial Material RP Craig, WA (reprint author), UNIV WISCONSIN HOSP & CLIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,DEPT MED,MADISON,WI 53792, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD AUG PY 1996 VL 25 IS 4 BP 219 EP 219 DI 10.1016/S0732-8893(96)90003-6 PG 1 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA VT364 UT WOS:A1996VT36400011 ER PT J AU Okamoto, T Takeda, S Giambarella, U Murayama, Y Matsui, T Katada, T Matsuura, Y Nishimoto, I AF Okamoto, T Takeda, S Giambarella, U Murayama, Y Matsui, T Katada, T Matsuura, Y Nishimoto, I TI Intrinsic signaling function of APP as a novel target of three V642 mutations linked to familial Alzheimer's disease SO EMBO JOURNAL LA English DT Article DE amyloid precursor protein; familial Alzheimer V642 mutations; G protein coupling; mutationally activated molecule ID AMYLOID PRECURSOR PROTEIN; MANNOSE 6-PHOSPHATE RECEPTOR; LONG-TERM POTENTIATION; GROWTH-FACTOR-II; NEURITE OUTGROWTH; PERTUSSIS TOXIN; ALPHA-SUBUNITS; CELL-SURFACE; CAENORHABDITIS-ELEGANS; MISSENSE MUTATIONS AB APP(695) is a transmembrane precursor of A beta amyloid. In familial Alzheimer's disease (FAD), three mutations V642Y/F/G were discovered in APP(695), which has been suggested by multiple studies to be a cell surface signaling receptor. We previously reported that normal APP(695) encodes a potential G(o)-linked receptor with ligand-regulated function and that expression of the three FAD mutants (FAD-APPs), not normal APP, induces cellular outputs by G(o)-dependent mechanisms. This suggests that FAD-APPs are constitutively active G(o)-linked receptors. Here, we provide direct evidence for this notion. Reconstitution of either recombinant FAD-APP with G(o) into vesicles induced activation of G(o), which was inhibitable by pertussis toxin, sensitive to Mg2+ and proportional in quantity to the reconstituted amounts of FAD-APP. Consistent with the dominant inheritance of this type of FAD, this function was dominant over normal APP, because little activation was observed in APP(695)-G(o) vesicles. Experiments with antibody competition and sequence deletion indicated that His657-Lys676 of FAD-APP, which has been specified as the ligand-dependent G(o)-coupling domain of normal APP, was responsible for this constitutive activation, confirming that the three FAD-APPs are mutationally activated APP(695). This study identifies the intrinsic signaling function of APP to be a novel target of hereditary Alzheiner's disease mutations, providing an in vitro system for the screening of potential FAD inhibitors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIOVASC RES CTR,BOSTON,MA 02129. UNIV TOKYO,SCH MED,DEPT INTERNAL MED 4,BUNKYO KU,TOKYO 112,JAPAN. UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,TOKYO 113,JAPAN. NATL INST HLTH,LAB HEPATITIS VIRUSES,DEPT VIROL 2,SHINJUKU KU,TOKYO 160,JAPAN. NR 57 TC 56 Z9 57 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 1996 VL 15 IS 15 BP 3769 EP 3777 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC667 UT WOS:A1996VC66700001 PM 8670881 ER PT J AU Roodman, GD AF Roodman, GD TI Advances in bone biology: The osteoclast SO ENDOCRINE REVIEWS LA English DT Review ID COLONY-STIMULATING FACTOR; HUMAN MARROW CULTURES; TRANSFORMING GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; CARBONIC-ANHYDRASE-II; INTERLEUKIN-1 RECEPTOR ANTAGONIST; HORMONE-RELATED PROTEIN; GIANT-CELL TUMORS; ISOLATED RABBIT OSTEOCLASTS; MESSENGER-RNA EXPRESSION C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV HEMATOL, SAN ANTONIO, TX 78284 USA. RP Roodman, GD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR, RES SERV 151, 7400 MERTON MINTER BLVD, SAN ANTONIO, TX 78284 USA. FU NCI NIH HHS [CA-40035]; NIA NIH HHS [AG-13652]; NIADDK NIH HHS [AM-35188] NR 232 TC 379 Z9 396 U1 1 U2 11 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 1996 VL 17 IS 4 BP 308 EP 332 DI 10.1210/er.17.4.308 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VB427 UT WOS:A1996VB42700002 PM 8854048 ER PT J AU Maeda, S Wu, S Juppner, H Green, J Aragay, AM Fagin, JA Clemens, TL AF Maeda, S Wu, S Juppner, H Green, J Aragay, AM Fagin, JA Clemens, TL TI Cell-specific signal transduction of parathyroid hormone (PTH)-related protein through stably expressed recombinant PTH/PTHrP receptors in vascular smooth muscle cells SO ENDOCRINOLOGY LA English DT Article ID PEPTIDE GENE-EXPRESSION; OSTEOBLAST-LIKE CELLS; PHOSPHOLIPASE-C; FREE CALCIUM; OSTEOPONTIN; BINDING; STIMULATION; MECHANISMS; ACTIVATION; SECRETION AB PTH-related protein activates a G protein-coupled PTH/pTHrP receptor in many cell types and produces diverse biological actions. To study the signal transduction events associated with biological activity of the PTH/PTHrP receptor in vascular smooth muscle, a principal PTHrP-responsive tissue, rat aortic smooth muscle cells (A10) were stably transfected with a plasmid encoding a PTH/PTHrP receptor and tested for ligand binding, PTHrP-(1-34)-induced cAMP levels, inositol phosphate production, and cytosolic calcium transients. Of nineteen G418-resistant 18-resistant lines recovered, all exhibited high affinity binding [similar to dissociation constant (K-d) > 10(-10)) of iodinated [Tyr(36)]hPTHrP(1-36)NR(2) and ligand-induced cAMP accumulation (2- to 100-fold), which was directly proportional to PTH/PTHrP receptor number (range 4 x 10(3) to 7 x 10(7) sites/cell]. PTHrP had no effect on intracellular calcium or inositol phosphate formation in any cell line regardless of receptor number despite the presence of detectable G alpha(q). Transient overexpression of individual G alpha(q) proteins (G alpha(q), G alpha(11) or G alpha(14)) into PTH/PTHrP receptor-expressing A10 cells conferred the ability of PTHrP to increase intracellular calcium and inositol phosphate formation. Ligand activation of the recombinant PTH/PTHrP receptor elicited appropriate downstream biological effects in A10 cells including inhibition of DNA synthesis and osteopontin messenger RNA (mRNA) expression. Thus, a single PTH/PTHrP receptor, though capable of coupling to different G proteins, signals exclusively through a cAMP-dependent pathway in vascular smooth muscle. C1 UNIV CINCINNATI, COLL MED, DEPT MED, DIV ENDOCRINOL METAB, CINCINNATI, OH 45267 USA. UNIV CINCINNATI, COLL MED, DEPT CELLULAR & MOLEC PHYSIOL, DIV ENDOCRINOL METAB, CINCINNATI, OH 45267 USA. MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. CALTECH, DIV BIOL, PASADENA, CA 91125 USA. FU NCI NIH HHS [CA-50706]; NHLBI NIH HHS [HL-47811]; NIDDK NIH HHS [DK-42792] NR 43 TC 55 Z9 57 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1996 VL 137 IS 8 BP 3154 EP 3162 DI 10.1210/en.137.8.3154 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UY111 UT WOS:A1996UY11100002 PM 8754733 ER PT J AU Roca, AL Godson, C Weaver, DR Reppert, SM AF Roca, AL Godson, C Weaver, DR Reppert, SM TI Structure, characterization, and expression of the gene encoding the mouse Mel(1a) melatonin receptor SO ENDOCRINOLOGY LA English DT Article ID 2-IODOMELATONIN BINDING-SITES; DNA-SEQUENCES; CLONED GENES; CLONING; RAT; ORGANIZATION; PROTEIN; YEAST; ACTIVATION; ELEMENTS AB Recently, a distinct family of G protein-coupled receptors has been cloned that mediates the biological effects of melatonin. Of two subtypes cloned from mammals (Mel(1a) and Mel(1b)), the Mel(1a) receptor appears to mediate the circadian and reproductive effects of the hormone. We now report the cloning, characterization, and expression of the gene encoding the Mel(1a) receptor in mice. The receptor gene is composed of two exons, separated by an intron of greater than 13 kilobases. Exon 1 encodes the entire 5'-untranslated region and the coding region through the first cytoplasmic loop. Exon 2 encodes the rest of the coding region and the entire 3'-untranslated region. 5'-Rapid amplification of complementary DNA ends and ribonuclease protection analyses show that the major transcription start site is 103 nucleotides upstream of the translation start codon. Sequence analysis of 1.1 kilobases of the 5'-flanking region reveals that it does not contain TATA or CAAT boxes. The 5'-flanking region drives luciferase expression 114-fold over basal levels in a murine retinal cell line that endogenously expresses the Mel(1a) receptor. The mouse receptor binds 2-[(125)]iodomelatonin with high affinity (K-d = 55.6 pM) when expressed transiently in COS-7 cells. In situ hybridization studies establish that Mel(1a) receptor messenger RNA is expressed in the hypothalamic suprachiasmatic nuclei and hypophyseal pars tuberalis, presumed sites of the circadian and some of reproductive actions of melatonin, respectively. These results provide information on Mel(1a) receptor gene structure essential for designing transgenic and gene knock-out studies and analyzing the transcriptional regulation of receptor gene expression. C1 MASSACHUSETTS GEN HOSP, LAB DEV CHRONOBIOL, SERV PEDIAT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. FU NICHD NIH HHS [R37-HD-14427] NR 40 TC 96 Z9 110 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1996 VL 137 IS 8 BP 3469 EP 3477 DI 10.1210/en.137.8.3469 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UY111 UT WOS:A1996UY11100045 PM 8754776 ER PT J AU Kalkanis, SN Blumenfeld, H Sherman, JC Krebs, DE Irizarry, MC Parker, SW AF Kalkanis, SN Blumenfeld, H Sherman, JC Krebs, DE Irizarry, MC Parker, SW TI Delayed complications thirty-six years after hemispherectomy: A case report SO EPILEPSIA LA English DT Article DE hemispherectomy; intractable epilepsy; superficial cerebral hemosiderosis; ventriculoperitoneal (VP) shunting; neuropsychologic testing; locomotion testing ID HEMIPLEGIA; SEIZURES; EPILEPSY AB Purpose: To describe a late complication of hemispherectomy in a patient in whom symptoms of hydrocephalus developed 36 years after her left-sided hemispherectomy, the longest delay on record. Methods: Hemispherectomy has been successfully used in the treatment of intractable epilepsy associated with infantile-type hemiplegia for a half century. Of the patients, however, up to 33% have late increased cerebrospinal fluid pressure complications attributed to superficial cerebral hemosiderosis. Through a retrospective case analysis, we describe such complications in a 52-year-old woman with cognitive impairment, gait instability, urinary incontinence, and right hemineglect 36 years after her initial procedure. Results: Quantitative, objective measures of cognition and gait-laboratory testing confirmed the patient's favorable clinical response to ventriculoperitoneal shunting, as well as the complete resolution of her symptoms, including the atypical occurrence of right-sided hemineglect. Conclusions: This case uniquely demonstrates the clinical features of a late complication of hemispherectomy while documenting the longest reported delay for developing such adverse sequelae, We also emphasize the need for more extensive follow-up studies to assess the extent of posthemispherectomy complications. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BIOMOT LAB,BOSTON,MA 02115. RP Kalkanis, SN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,WANG ACC SUITE 331,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [R01AG11255, R01AG12561] NR 14 TC 6 Z9 7 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 1996 VL 37 IS 8 BP 758 EP 762 DI 10.1111/j.1528-1157.1996.tb00648.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA VD308 UT WOS:A1996VD30800010 PM 8764815 ER PT J AU Heiken, H Schulz, RJ Ravetch, JV Reinherz, EL Koyasu, S AF Heiken, H Schulz, RJ Ravetch, JV Reinherz, EL Koyasu, S TI T lymphocyte development in the absence of Fc epsilon receptor I gamma subunit: Analysis of thymic-dependent and independent alpha beta and gamma delta pathways SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Fc receptor; fetal thymocyte; intestinal intraepithelial lymphocyte; organ culture; large granular lymphocyte ID CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; LARGE GRANULAR LYMPHOCYTES; PROTEIN-TYROSINE KINASES; MONOCLONAL-ANTIBODY; SURFACE EXPRESSION; ZETA-CHAIN; INTRAEPITHELIAL LYMPHOCYTES; DIFFERENTIATION ANTIGENS; INTESTINAL EPITHELIUM AB During fetal development, early thymocyte progenitors transiently express low affinity Fc receptors for IgG (Fc gamma R) of both Fc gamma RII and III isoforms. Only the Fc gamma RIII isoform requires association of an Fc gamma RIII (CD16) alpha subunit with an Fc epsilon RI gamma homodimer for surface expression. To address the role of Fc gamma R in ontogeny we studied thymic development in Fc epsilon RI gamma(-/-) mice. We find that day 14.5 CD4(-)CD8(-) double-negative (DN)fetal thymocytes of Fc epsilon RI gamma(-/-) mice express mRNA of both Fc gamma RIIb, and Fc gamma RIII. Surface expression of Fc gamma RII/III is readily detected on these cells. It appears that Fc gamma RIIb(1), whose surface expression is Fc epsilon RI gamma independent, replaces Fc gamma RIII during thymic development in these animals. Moreover, subsequent development into CD4(+)CD8(+) double-positive and CD4(+)CD8(-) and CD4(-)CD8(+) single-positive subsets appears normal even in the absence of Fc epsilon RI gamma. However, alterations were noted in adult animals among the DN alpha beta TCR(+) thymocytes and peripheral splenic DN T cells as well as CD8 alpha alpha(+) intestinal intraepithelial lymphocytes (iIEL). In contrast to conventional T lymphocytes, which do not express either Fc gamma RIII or Fc epsilon RI gamma, DN alpha beta TCR(+) thymocytes and extrathymically derived alpha beta TCR(+) and gamma delta TCR(+) CD8 alpha alpha(+)beta(-) iIEL express TCR which incorporate Fc epsilon RI gamma as one of their subunits. Consistent with this, the TCR levels of these cells are lower than the TCR levels on cells from wild-type C57BL/6 mice. Despite the reduction in the level of surface TCR, the development of these cells was unaltered by the absence of Fc epsilon RI gamma. Thus, we observed alterations in adult DN alpha beta TCR(+) thymocytes, splenic DN alpha beta TCR(+) and DN gamma delta TCR(+) large granular lymphocytes (LGL), and alpha beta TCR(+) and gamma delta TCR(+) CD8 alpha alpha(+) iIEL, but no detectable changes in their major fetal thymic developmental pathways. Cultivation of peripheral DN alpha beta TCR(+) and DN gamma delta TCR(+) cells from Fc epsilon RI gamma(-/-) mice with interleukin-2 generates LGL which mediate natural killer activity. Unlike LGL from wild-type C57BL/6 mice, LGL from Fc epsilon RI gamma(-/-) mice lack Fc gamma RIII expression and could not mediate antibody-dependent cellular cytotoxicity through Fc gamma RIII. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,LAB IMMUNOL,DEPT MED,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,PROGRAM MOL BIOL,NEW YORK,NY 10021. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI34662, AI19807, AI33017] NR 54 TC 16 Z9 16 U1 0 U2 8 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 AUG PY 1996 VL 26 IS 8 BP 1935 EP 1943 DI 10.1002/eji.1830260839 PG 9 WC Immunology SC Immunology GA VB309 UT WOS:A1996VB30900038 PM 8765042 ER PT J AU Gibbons, R AF Gibbons, R TI The caries decline - A comment SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Editorial Material DE antibiotics; microflora alterations; fluoride-containing dentifrice; mutans streptococci RP Gibbons, R (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD AUG PY 1996 VL 104 IS 4 BP 424 EP 425 DI 10.1111/j.1600-0722.1996.tb00106.x PN 2 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VR976 UT WOS:A1996VR97600004 ER PT J AU Kuter, D Xia, Y Yang, C Li, JZ AF Kuter, D Xia, Y Yang, C Li, JZ TI Principles of thrombopoietin physiology: Application to disorders of altered platelet production. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 24 IS 9 BP 263 EP 263 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200262 ER PT J AU Kalina, U Behrens, E Ganser, A Hoelzer, D Griffin, JD Ottmann, OG Eder, M AF Kalina, U Behrens, E Ganser, A Hoelzer, D Griffin, JD Ottmann, OG Eder, M TI GM-CSF induced oligomerization of chimeric alpha/beta GM-CSF receptors in vitro. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. UNIV FRANKFURT,DEPT HEMATOL,FRANKFURT,GERMANY. HANNOVER MED SCH,D-3000 HANNOVER,GERMANY. RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 24 IS 9 BP 469 EP 469 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200468 ER PT J AU Tsukada, J Waterman, WR Koyama, Y Misago, M Eto, S Webb, AC Auron, PE AF Tsukada, J Waterman, WR Koyama, Y Misago, M Eto, S Webb, AC Auron, PE TI LPS, IL-1 and IL-6 signaling is mediated by a novel STAT-like factor which recognizes a gas-like element in the human proIL-1 beta gene. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV OCCUPAT & ENVIRONM HLTH,DEPT INTERNAL MED 1,KITAKYUSHU,FUKUOKA 807,JAPAN. CTR BLOOD RES,BOSTON,MA 02115. WELLESLEY COLL,DEPT BIOL SCI,WELLESLEY,MA 02181. MASSACHUSETTS GEN HOSP,DEPT MED,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 3 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 AUG PY 1996 VL 24 IS 9 BP 482 EP 482 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200481 ER PT J AU Freytes, CO Vukelja, S Salzman, D Tsai, T Callander, N Gokmen, E Rodriguez, T Castro, J Boldt, D Roodman, GD Hilsenbeck, S Adkins, D Bachier, C Craig, F Clare, N Weisner, A LeMaistre, CF AF Freytes, CO Vukelja, S Salzman, D Tsai, T Callander, N Gokmen, E Rodriguez, T Castro, J Boldt, D Roodman, GD Hilsenbeck, S Adkins, D Bachier, C Craig, F Clare, N Weisner, A LeMaistre, CF TI Autologous hematopoietic stem cell transplantation for poor prognosis low grade lymphoma. SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,AUDIE L MURPHY VET HOSP,BROOKE ARMY MED CTR,HLTH SCI CTR,SAN ANTONIO,TX. S TEXAS CANC INST,SAN ANTONIO,TX. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 24 IS 9 BP 629 EP 629 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200628 ER PT J AU Dey, B Yang, YG Pearson, DA Szot, GL Swenson, K Sykes, M AF Dey, B Yang, YG Pearson, DA Szot, GL Swenson, K Sykes, M TI Mechanisms of inhibition of acute graft-vs-host disease in mice by interleukin-12 SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 24 IS 9 BP 658 EP 658 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC092 UT WOS:A1996VC09200657 ER PT J AU Ball, TC Hirayama, F Ogawa, M AF Ball, TC Hirayama, F Ogawa, M TI Modulation of early B lymphopoiesis by interleukin-3 SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE lymphohematopoietic progenitors; B lymphopoiesis; interleukin-3 ID BONE-MARROW CULTURES; STROMAL CELL-LINE; LYMPHOHEMATOPOIETIC PROGENITORS; PRECURSOR CELLS; LYMPHOCYTES-B; PRO-B; MOUSE; GROWTH; CLONES; DIFFERENTIATION AB We recently reported that interleukin-3 (IL-3) inhibits B lymphoid lineage expression in methylcellulose culture in a dose-dependent manner. We subsequently used flow cytometric analysis of individual colonies in timed exposure to IL-3 to define more precisely the negative regulatory role of IL-3 in early B lymphopoiesis. When lymphohematopoietic progenitors isolated from 5-fluorouracil (5-FU)-treated mice were cultured in the presence of Steel factor (SF), IL-11, IL-7, and erythropoietin (Epo), B lymphopoiesis appeared to proceed through three stages: lymphohematopoietic proliferation, commitment, and early B lymphoid proliferation. When IL-3 was added to the culture for a 48-hour interval from days 4 to 6 of culture, IL-3 slightly enhanced the formation of pre-B cell colonies. These data appeared to contradict our previous observations that continued exposure to IL-3 from days 0 to 4 or longer severely inhibits B lymphoid potential of the cultured cells. A more frequently timed kinetic observation revealed that in the presence of IL-3 the peak of lymphohematopoietic progenitors was 48 hours earlier but less than one-tenth the number of lymphohematopoietic progenitors in cultures without IL-3. When added to cultures for 48 hours beyond day 6 of culture, IL-3 abrogated the B cell potential of the cultured cells. However, IL-3 failed to negatively modulate B lymphoid progenitors when added on day 14 of culture or later. These observations indicate that IL-3 is a potent negative modulator of the early B lymphopoiesis. IL-3 appears to hasten but suppress the proliferation and commitment of lymphohematopoietic progenitors to B cell lineage. It may also inhibit the proliferation of the progenitors immediately after commitment to B cell lineage. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. FU NIDDK NIH HHS [DK32294] NR 22 TC 18 Z9 18 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 AUG PY 1996 VL 24 IS 10 BP 1225 EP 1231 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA VC742 UT WOS:A1996VC74200010 PM 8765498 ER PT J AU Yu, CE Oshima, J Hisama, FM Matthews, S Trask, BJ Schellenberg, GD AF Yu, CE Oshima, J Hisama, FM Matthews, S Trask, BJ Schellenberg, GD TI A YAC, P1, and cosmid contig and 17 new polymorphic markers for the Werner syndrome region at 8p12-p21 SO GENOMICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; COLORECTAL-CARCINOMA; EXON AMPLIFICATION; HUMAN CHROMOSOME-8; BREAST-CARCINOMA; SYNDROME LOCUS; HUMAN GENOME; CELL-LINES; SHORT ARM; DNA AB A yeast artificial chromosome (YAC), P1, and cosmid clone contig was constructed for the Werner syndrome (WRN) region of chromosome 8p12-p21 and used to clone a candidate gene for WRN. This region also possibly contains a familial breast cancer locus. The contig was initiated by isolating YACs for the glutathione reductase (GSR) gene and extended in either direction by walking techniques. Sequence-tagged site (STS) markers were generated from subclones of 2 GSR YACs and used to identify P1 and cosmid clones. Additional STSs were generated from P1 and cosmid clones and from potential expressed sequences identified by cDNA selection and exon amplification methods. The final contig was assembled by typing 17 YACs, 20 P1 clones, and 109 cosmids for 54 STS markers. The WRN region could be spanned by 2 nonchimeric YACs covering approximately 1.4 Mb. A P1/cosmid contig was established covering the core 700-800 kb of the WRN region, Fifteen new short tandem repeat polymorphisms and 2 biallelic polymorphic markers were identified and included as STSs in the contig. Analysis of these markers in Werner syndrome subjects demonstrates that the candidate WRN gene is in a region of linkage disequilibrium. (C) 1996 Academic Press, Inc. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE DIV,SEATTLE,WA 98108. UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT NEUROL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. YALE UNIV,SCH MED,DEPT NEUROL,NEW HAVEN,CT 06520. FU NIA NIH HHS [R01 AG12019, R37 AG08303, T32 AG00057] NR 47 TC 14 Z9 14 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 AUG 1 PY 1996 VL 35 IS 3 BP 431 EP 440 DI 10.1006/geno.1996.0382 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800004 PM 8812476 ER PT J AU Long, KR Trofatter, JA Ramesh, V McCormick, IK Buckler, AJ AF Long, KR Trofatter, JA Ramesh, V McCormick, IK Buckler, AJ TI Cloning and characterization of a novel human clathrin heavy chain gene (CLTCL) SO GENOMICS LA English DT Article ID LIGHT CHAIN; SACCHAROMYCES-CEREVISIAE; EXON AMPLIFICATION; MOLECULAR-CLONING; EXPRESSION; CHROMOSOME-22Q11; MICRODELETIONS; TRIMERIZATION; DELETIONS; PROTEINS AB An exon representing a novel clathrin heavy chain gene (CLTCL) was isolated during gene identification studies and transcription mapping of human chromosome 22. Isolation and sequencing of cDNA clones corresponding to this exon revealed extensive similarity of the predicted amino acid sequence of this gene product to those of clathrin heavy chain genes of other species. Northern blot analysis has revealed an apparent developmental expression pattern of an approximately 6-kb mRNA. The gene appears to be expressed ubiquitously in the limited number of fetal tissues that were tested, but is selectively expressed in certain adult tissues, particularly in skeletal muscle. In addition, alternative splicing of an exon was observed near the carboxyl terminus of the predicted gene product. Its location overlaps the domain putatively involved in clathrin light chain binding and is adjacent to the heavy chain self-assembly (or trimerization) region, suggesting that alternative splicing may be involved in regulating one or both of these interactions. The expression pattern of this gene, in addition to its potential role in receptor-mediated endocytosis and signal transduction, suggests that it may be important in some developmental processes, The location of CLTCL on human chromosome 22 near the region commonly deleted in DiGeorge and other apparent haploinsufficiency syndromes warrants further investigation into its relationship with these developmental disorders. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA. FU NHGRI NIH HHS [HG00672] NR 34 TC 18 Z9 19 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD AUG 1 PY 1996 VL 35 IS 3 BP 466 EP 472 DI 10.1006/geno.1996.0386 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800008 PM 8844170 ER PT J AU Khani, SC Abitbol, M Yamamoto, S MaravicMagovcevic, I Dryja, TP AF Khani, SC Abitbol, M Yamamoto, S MaravicMagovcevic, I Dryja, TP TI Characterization and chromosomal localization of the gene for human rhodopsin kinase SO GENOMICS LA English DT Article ID ADRENERGIC-RECEPTOR KINASE; PROTEIN-KINASE; PHOTOEXCITED RHODOPSIN; 48-KDA PROTEIN; FAMILY; IDENTIFICATION; CLONING; EXPRESSION; ARRESTIN; SUBUNIT AB G-protein-dependent receptor kinases (GRKs) play a key role in the adaptation of receptors to persistent stimuli. In rod photoreceptors rhodopsin kinase (RK) mediates rapid desensitization of rod photoreceptors to light by catalyzing phosphorylation of the visual pigment rhodopsin. To study the structure and mechanism of GRKs in human photoreceptors, we have isolated and characterized cDNA and genomic clones derived from the human RK locus using a bovine rhodopsin kinase cDNA fragment as a probe. The RK locus, assigned to chromosome 13 band q34, is composed of seven exons that encode a protein 92% identical in amino acid sequence to bovine rhodopsin kinase. The marked difference between the structure of this gene and that of another recently cloned human GRK gene suggests the existence of a wide evolutionary gap between members of the GRK gene family. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, DEPT OPHTHALMOL, BOSTON, MA 02114 USA. FU NEI NIH HHS [EY 08683] NR 39 TC 16 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD AUG 1 PY 1996 VL 35 IS 3 BP 571 EP 576 DI 10.1006/geno.1996.0399 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800021 PM 8812493 ER PT J AU Lee, RL Johnson, KR Lerner, TJ AF Lee, RL Johnson, KR Lerner, TJ TI Isolation and chromosomal mapping of a mouse homolog of the Batten disease gene CLN3 SO GENOMICS LA English DT Article ID STORAGE AB We describe the isolation and chromosomal mapping of a mouse homolog of the Batten disease gene, CLN3, Like its human counterpart, the mouse cDNA contains an open reading frame of 1314 bp encoding a predicted protein product of 438 amino acids, The mouse and human coding regions are 82 and 85% identical at the nucleic acid and amino acid levels, respectively, The mouse gene maps to distal Chromosome 7, in a region containing genes whose homologs are on human chromosome 16p12, where CLN3 maps, Isolation of a mouse CLN3 homolog will facilitate the creation of a mouse model of Batten disease. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,CHARLESTOWN,MA 02129. JACKSON LAB,MOUSE MUTANT RESOURCE CTR,BAR HARBOR,ME 04609. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. FU NINDS NIH HHS [NS32099]; PHS HHS [6M46697] NR 8 TC 27 Z9 28 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 AUG 1 PY 1996 VL 35 IS 3 BP 617 EP 619 DI 10.1006/geno.1996.0410 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VB758 UT WOS:A1996VB75800032 PM 8812504 ER PT J AU Pompei, P Clyman, BB AF Pompei, P Clyman, BB TI Osteoarthritis: What to look for, and when to treat it SO GERIATRICS LA English DT Editorial Material AB In patients with suspected osteoarthritis, start with a thorough history aimed at finding the mechanical component of the condition. Ask about past and current activities that may be loading or stressing a painful joint. Conditions to consider in the differential diagnosis are those affecting soft tissues-muscles, tendons, ligaments, and bursae. Injecting the tender area with lidocaine will help identify a separate or coexisting soft tissue disorder. Before considering drug therapy, attempt to correct any mechanical factors that may be contributing to the problem. Modify the patient's exercise routine, if necessary, and begin patients on a walking aid if a weight-bearing joint is affected. C1 STANFORD HLTH SERV,SKILLED NURSING UNIT,STANFORD,CA. STANFORD UNIV,SCH MED,STANFORD,CA 94305. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. RP Pompei, P (reprint author), VET AFFAIRS HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,CLIN PROGRAMS,PALO ALTO,CA 94304, USA. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 51 IS 8 BP 36 EP & PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VC100 UT WOS:A1996VC10000014 ER PT J AU Berra, A Heiligenhaus, A Foster, CS AF Berra, A Heiligenhaus, A Foster, CS TI T-cell subsets and T-cell receptor V beta utilization by Igh-1-congenic mice in herpetic retinal necrosis SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID SIMPLEX VIRUS TYPE-1; ANTERIOR-CHAMBER INOCULATION; ADOPTIVE TRANSFER; LYMPHOCYTES-T; RETINITIS; INFECTION; GENES; PROTECTION; SPREAD; SPLEEN AB Background: After unilateral anterior chamber (AC) inoculation with herpes simplex virus type 1 (HSV-1), C.B-17 and BALB/c congenic mice, which differ only in a limited region around the Igh-1 locus on chromosome 12, show a striking difference in susceptibility to development of encephalitis and contralateral necrotizing chorioretinitis. Methods: After AC inoculation with HSV-1 (KOS), C.B-17 and BALB/c mice were followed up for the clinical signs of encephalitis and chorioretinitis. At different time points following inoculation, lymphocytes isolated from the spleen were triple-stained with antibodies directed against CD4 or CD8, IL-2R, and various V beta T-cell receptor (TCR) subsets, and were analyzed by flow cytometry. Results: These Igh-1-disparate congenic mice showed differences in the time course of splenic V beta T-cell receptor (TCR) usage in both CD4+, IL-2R+ and CD8+, IL-2R+ T cells. By day 1 post infection (p.i.), C.B-17 mice showed an increase of V beta 8 and V beta 9 TCR by both CD4+, IL-2R+ and CD8+, IL-2R+ splenic T cells. Susceptible BALB/c mice delayed the increase of splenic V beta 8 and V beta 9 TCR by CD4+, IL-2R+ T cells, which was noted by day 4 p.i. Furthermore, in BALB/c mice the usage of V beta 9 by CD8+ cells was increased by day 6 p.i. Conclusions: Our findings indicate that early preferential splenic usage of a restricted repertoire of TCR occurs after ocular inoculation with HSV-1 in resistant C.B-17 mice. Such preferential TCR usage by activated T cells may prevent viral replication in the brain and contralateral eye and may be linked to protection from development of encephalitis and destructive herpes-mediated ocular inflammation. C1 UNIV ESSEN GESAMTHSCH,DEPT OPHTHALMOL,D-45122 ESSEN,GERMANY. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA. UNIV BUENOS AIRES,DEPT PATHOL,BUENOS AIRES,DF,ARGENTINA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD AUG PY 1996 VL 234 SU 1 BP S83 EP S88 DI 10.1007/BF02343053 PG 6 WC Ophthalmology SC Ophthalmology GA VC838 UT WOS:A1996VC83800015 PM 8871155 ER PT J AU Tanaka, S Guth, PH Paulsen, G Kaunitz, JD AF Tanaka, S Guth, PH Paulsen, G Kaunitz, JD TI Gastroprotective effect of ranitidine bismuth citrate is associated with increased mucus bismuth concentration in rats SO GUT LA English DT Article DE stomach; intracellular pH; ranitidine bismuth citrate; gastric mucus; proton diffusion; mucosal blood flow ID GASTRIC-MUCOSAL LESIONS; INTRACELLULAR PH; BLOOD-FLOW; ALKALINE SECRETION; ACID-SECRETION; SURFACE CELLS; IN-VIVO; INDOMETHACIN; PROSTAGLANDIN; SUBCITRATE AB Background-Antisecretory and bismuth compounds protect the gastric mucosa from injury resulting from non-steroidal anti-inflammatory drugs. Aim-To study the mechanism underlying the gastroprotective effects of ranitidine bismuth citrate (GG311) in rats. Methods-Indomethacin rat injury model and in vivo microscopy in which acid output, surface cell intracellular pH (pH(i)), gastric mucus gel thickness, and mucosal blood how were measured simultaneously. Results-In injury studies, GG311 dose dependently protected against severe injury induced by indomethacin (60 mg/kg subcutaneously). In in vivo microscopic studies, indomethacin significantly decreased mucus gel thickness and increased the initial rate of acidification of gastric surface cells when the superfusate pH was lowered from 7.4 to 1.0, and impaired pH(i) during acid exposure. Indomethacin had no effect on mucosal blood flow or acid output. GG311 alone had no effect on gel thickness, blood flow, or pH(i) homeostasis during acid exposure, but improved the initial acidification rate and pH(i) during superfusion with pH 1.0 solutions in the presence of indomethacin. In separate experiments, indomethacin pretreatment considerably increased gastric mucus bismuth concentrations in rats given GG311. Conclusions-The gastroprotective effect of GG311 against indomethacin induced gastric injury is associated with high and prolonged gastric mucus bismuth concentrations, which may impair proton permeation across the mucus gel. C1 VET ADM WADSWORTH MED CTR,CURE DIGEST DIS RES CTR,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. NR 54 TC 13 Z9 13 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD AUG PY 1996 VL 39 IS 2 BP 164 EP 171 DI 10.1136/gut.39.2.164 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VD882 UT WOS:A1996VD88200005 PM 8977335 ER PT J AU VanHook, MP Berkman, B Dunkle, R AF VanHook, MP Berkman, B Dunkle, R TI Assessment tools for general health care settings: PRIME-MD, OARS, and SF-36 SO HEALTH & SOCIAL WORK LA English DT Editorial Material ID FUNCTIONAL ASSESSMENT; GERIATRIC ASSESSMENT; MENTAL-DISORDERS C1 MASSACHUSETTS GEN HOSP,SOCIAL SERV DEPT,BOSTON,MA 02114. UNIV MICHIGAN,SCH SOCIAL WORK,ANN ARBOR,MI 48109. RP VanHook, MP (reprint author), UNIV CENT FLORIDA,SCH SOCIAL WORK,POB 163358,ORLANDO,FL 32816, USA. NR 22 TC 14 Z9 15 U1 0 U2 3 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 SN 0360-7283 J9 HEALTH SOC WORK JI Health Soc. Work PD AUG PY 1996 VL 21 IS 3 BP 230 EP 234 PG 5 WC Social Work SC Social Work GA VB042 UT WOS:A1996VB04200010 PM 8854128 ER PT J AU Merchant, SN Ravicz, ME Rosowski, JJ AF Merchant, SN Ravicz, ME Rosowski, JJ TI Acoustic input impedance of the stapes and cochlea in human temporal bones SO HEARING RESEARCH LA English DT Article DE cochlear impedance; stapes impedance; acoustic load on middle ear ID MIDDLE-EAR MECHANICS; V TYMPANOPLASTY; VIBRATION; MODEL; CAT; IV AB The acoustic input impedance of the stapes and cochlea Z(SC) represents the mechanical load driven by the tympanic membrane, malleus and incus. Z(SC) was calculated from broad-band measurements (20 Hz to 11 kHz) of stapes displacement made with an optical motion sensor and of sound pressure at the stapes head in a human temporal-bone preparation. Measurements were made in 12 fresh temporal bones with the round window insulated from the sound stimulus. Below 1 kHz, the magnitude of Z(SC) was approximately inversely proportional to frequency, and Z(SC) angle was between -0.10 and -0.20 periods, This behavior is consistent with a mixed stiffness and resistance. Between 1 and 4 kHz, Z(SC) was resistance-dominated with a magnitude between 40 and 100 mks acoustic GR that was roughly independent of frequency, and its angle was between -0.12 and 0 periods. Between 4 and 7 kHz, the magnitude of Z(SC) was either constant or increased with frequency while Z(SC) angle was near 0. Between 7 and 8 kHz, both Z(SC) magnitude and angle decreased sharply with frequency, and both increased somewhat at higher frequencies. The input impedance of the cochlea Z, was estimated in one ear from Z(SC) measurements made before and after draining the inner ear fluids. Z(C) was stiffness-dominated below 100 Hz, and resistance-dominated from 100 Hz to 5 kHz. The frequency-dependent magnitude of Z(SC) in our bones is similar to those reported by other investigators in cadaver temporal bones (Nakamura et al., 1992; Kurokawa and Goode, 1995). Our Z(SC) measurements are qualitatively similar to theoretical predictions (Zwislocki, 1962; Kringlebotn, 1988), but are a factor of 3 greater in magnitude, implying that Z(SC) may be more resistive and stiffer than previously thought. We found inter-ear variations of a factor of 4 (12 dB), which may explain some of the clinically observed variations in size of the air-bone gap in individuals with middle ear lesions or after middle-ear reconstructive surgery. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. RP Merchant, SN (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [P01 DC 00119, K08 DC 00088, P01 DC000119] NR 37 TC 95 Z9 97 U1 1 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 AUG PY 1996 VL 97 IS 1-2 BP 30 EP 45 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA VB549 UT WOS:A1996VB54900004 PM 8844184 ER PT J AU Bush, RK AF Bush, RK TI Molecular biology of allergens SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID HOUSE-DUST MITE; BIRCH-POLLEN ALLERGEN; AMINO-ACID-SEQUENCE; ARTEMISIIFOLIA SHORT RAGWEED; T-CELL RECOGNITION; RYE-GRASS POLLEN; DER-P-I; KENTUCKY BLUEGRASS POLLEN; VENOM PHOSPHOLIPASE A(2); IGE-BINDING PROTEIN AB Molecular cloning has resulted in an ever-increasing number of purified allergens. Their functional and biologic characteristics can be determined and cross-reactivity predicted. Recombinant allergens can lead to improved diagnostic reagents. Studies of allergenic T- and B-cell epitopes may produce new therapeutic approaches to allergic diseases. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. RP Bush, RK (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT ALLERGY,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 128 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 1996 VL 16 IS 3 BP 535 EP & DI 10.1016/S0889-8561(05)70260-5 PG 30 WC Allergy; Immunology SC Allergy; Immunology GA VC478 UT WOS:A1996VC47800004 ER PT J AU Bush, RK AF Bush, RK TI Molecular biology of allergy and immunology - Preface SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Editorial Material RP Bush, RK (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 1996 VL 16 IS 3 BP R11 EP R12 DI 10.1016/S0889-8561(05)70257-5 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA VC478 UT WOS:A1996VC47800001 ER PT J AU Shankar, P Fabry, JA Fong, DM Lieberman, J AF Shankar, P Fabry, JA Fong, DM Lieberman, J TI Three regions of HIV-1 gp160 contain clusters of immunodominant CTL epitopes SO IMMUNOLOGY LETTERS LA English DT Article DE epitope; HIV; gp160; CTL; restriction; HLA Class I ID CD8+ T-CELLS; SEROPOSITIVE INDIVIDUALS; LYMPHOCYTES-T; NEF PROTEIN; VIRUS; MOLECULES; ASSOCIATION; VIREMIA; HUMANS AB HIV-1 infection stimulates a strong CTL response that coincides with resolution of viremia in acute infection and declines with development of opportunistic infections. Recognition of HIV gp160 by PBMC-derived T cell lines from 20 HIV-infected subjects is dominated by the response to a small number of peptide epitopes. Overlapping CTL epitopes restricted by multiple MHC Class I elements were identified in 3 relatively conserved regions of gp160 (amino acids 49-68, 591-600 and 844-863). CTL from five of 20 subjects recognized three overlapping immunodominant epitopes in the 49-68 a.a. region restricted by A24, B38, and B55. CTL from four subjects recognized at least three distinct epitopes in a.a. 591-600 in the context of A24, B8, B14, and B27. CTL from seven subjects recognized epitopes within a.a. 844-863 restricted by A30, B7, B8 and B35. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI Lieberman, Judy/A-2717-2015 NR 25 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD AUG PY 1996 VL 52 IS 1 BP 23 EP 30 DI 10.1016/0165-2478(96)02574-6 PG 8 WC Immunology SC Immunology GA VG236 UT WOS:A1996VG23600004 PM 8877415 ER PT J AU Smith, DJ Taubman, MA AF Smith, DJ Taubman, MA TI Experimental immunization of rats with a Streptococcus mutans 59-kilodalton glucan-binding protein protects against dental caries SO INFECTION AND IMMUNITY LA English DT Article ID LOCAL IMMUNIZATION; SYNTHETIC PEPTIDE; GLUCOSYLTRANSFERASE; SOBRINUS; GENE; SEQUENCES; DOMAIN; ANTIGENICITY; SUCROSE AB Glucan-binding proteins (GBPs) are theoretically important in the molecular pathogenesis of dental caries caused by Streptococcus mutans. The present study evaluated the ability of antibody induced by the S. mutans 59-kDa GBP (GBP(59)) to affect dental caries caused by experimental infection with S. mutans in a rodent model, Groups of 20-day-old rats were injected twice at 9-day intervals subcutaneously in the salivary gland vicinity with GBP(59), glucosyltransferase (GTF), or phosphate-buffered saline (sham injection), each incorporated in an adjuvant, Two weeks after the second injection, GBP(59)- and GTF-injected rats contained significant levels of salivary immunoglobulin A and serum immunoglobulin G antibody to the respective injected antigens, However, cross-reacting antibody to S. mutans GTF or GBP(59) was not induced by the respective antigen, Rats were then orally infected with S. mutans, After 71 days of infection, GBP(59)- and GTF-injected groups had smaller numbers of S. mutans on their molar surfaces, compared with the sham-injected infected group, Total, sulcal, and smooth-surface molar caries in the GBP(59)- and GTF-immunized S. mutans-infected groups were each significantly lower (P less than or equal to 0.003) than the respective measures of caries in the sham injected infected group, The results of this investigation demonstrate that immunization with S. mutans GBP(59) induces an immune response in rats that can interfere with the accumulation of S. mutans and can reduce the level of dental caries caused by this cariogenic streptococcus, Furthermore, the protective immunity induced by either GBP(59) or GTF appears to result from antibodies to independent epitopes since these two S. mutans components do not have a close antigenic relationship. RP Smith, DJ (reprint author), FORSYTH DENT CTR, DEPT IMMUNOL, BOSTON, MA 02115 USA. FU NIDCR NIH HHS [DE-06153] NR 24 TC 48 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1996 VL 64 IS 8 BP 3069 EP 3073 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY893 UT WOS:A1996UY89300028 PM 8757835 ER PT J AU Mahida, YR Djelloul, S Atfi, A Ciacci, C Debeaumont, M Chevalier, S Gespach, C Podolsky, DK AF Mahida, YR Djelloul, S Atfi, A Ciacci, C Debeaumont, M Chevalier, S Gespach, C Podolsky, DK TI Resistance to TGF beta in SV40 large T-immortalized rat intestinal epithelial cells is associated with down-regulation of TGF beta type I receptor SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE oncogene; kinase; growth factors; proliferation; differentiation ID GROWTH-FACTOR-BETA; NEOPLASTIC TRANSFORMATION; SIGNAL TRANSDUCTION; PROTO-ONCOGENE; EXPRESSION; MYC; ACTIVATION; LINES; PROLIFERATION; INHIBITION AB A new continuous cell line designated ESKI-1 was established by transfection of rat fetal intestinal epithelial cells with ecotropic retroviruses containing SV40 large T oncogene. The ESKI-1 cell line exhibits morphologic features of an epithelial cell line and expresses the OCI-5 and cytokeratin 8 transcripts associated with epithelial cells in the small intestine. Signal transduction and proliferation responses to TGF beta has been characterized in ESKI-1 cells, in comparison with the spontaneously-immortalized IEC cell lines originating from neonatal rat duodenum and ileum. ESKI-1 express both TGF alpha and TGF beta. However, despite a marked increase in TGF beta-stimulated p78 kinase activity observed in ESKI-1 and IEC cells, TGF beta did not modulate growth, or extracellular matrix expression in ESKI-1 cells. Resistance to growth modulation was associated with downregulation of TGF beta. Type I receptor expression in the SV40 large T-immortalized cells. Thus, proliferative resistance to TGF beta inhibition can result from depletion of the TGF beta type I receptor and disruption of the TGF beta signaling pathway downstream the p78 serine/threonine kinase. These molecular defects constitute two early events during the SV40LT-mediated immortalization and neoplastic progression of the intestinal epithelia. C1 HOP ST ANTOINE,INSERM U55,EPITHELIUM GASTROINTESTINAL,EQUIPE CANC & DIFFERENCIAT,F-75571 PARIS 12,FRANCE. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MCGILL UNIV,DEPT SURG,DIV UROL,MONTREAL,PQ H3G 1A4,CANADA. MONTREAL GEN HOSP,RES INST,MONTREAL,PQ H3G 1A4,CANADA. RI ciacci, carolina/A-2594-2012 OI ciacci, carolina/0000-0002-7426-1145 NR 55 TC 5 Z9 5 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1996 VL 9 IS 2 BP 365 EP 374 PG 10 WC Oncology SC Oncology GA UX987 UT WOS:A1996UX98700026 PM 21541524 ER PT J AU Brugge, WR AF Brugge, WR TI The role of endoscopic ultrasound in pancreatic disorders SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Article DE endoscopic ultrasound; pancreatitis; pancreatic cancer; cystic neoplasms; chronic pancreatitis ID NEEDLE ASPIRATION BIOPSY; UPPER GASTROINTESTINAL-TRACT; COMPUTED-TOMOGRAPHY; DIFFERENTIAL-DIAGNOSIS; ENDOCRINE TUMORS; ULTRASONOGRAPHY; ENDOSONOGRAPHY; LOCALIZATION; CYTOLOGY; DISEASE RP Brugge, WR (reprint author), MASSACHUSETTS GEN HOSP,GI UNIT,127 BULFINCH BLDG,BOSTON,MA 02114, USA. NR 49 TC 12 Z9 12 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD AUG PY 1996 VL 20 IS 1 BP 1 EP 10 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VE015 UT WOS:A1996VE01500001 PM 8872519 ER PT J AU Jones, L Arana, G AF Jones, L Arana, G TI Is downsizing affecting incident reports? SO JOINT COMMISSION JOURNAL ON QUALITY IMPROVEMENT LA English DT Editorial Material C1 RALPH H JOHNSON VET AFFAIRS MED CTR,MENTAL HLTH SERV,CHARLESTON,SC. MED UNIV S CAROLINA,COLL MED,CHARLESTON,SC 29425. RP Jones, L (reprint author), ORG LEARNING GRP,POB 463,MT PLEASANT,SC 29465, USA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1070-3241 J9 JOINT COMM J QUAL IM JI Jt. Comm. J. Qual. Improv. PD AUG PY 1996 VL 22 IS 8 BP 592 EP 594 PG 3 WC Health Policy & Services SC Health Care Sciences & Services GA VF431 UT WOS:A1996VF43100015 PM 8877528 ER PT J AU Park, IW Kondo, E Bergeron, L Park, J Sodroski, J AF Park, IW Kondo, E Bergeron, L Park, J Sodroski, J TI Effects of human immunodeficiency virus type 1 infection on programmed cell death in the presence or absence of Bcl-2 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; Bcl-2; programmed cell death; apoptosis; Jurkat cell ID HTLV-III/LAV ENVELOPE; T4 MOLECULE; FAS ANTIGEN; B-CELLS; HIV; GLYCOPROTEIN; EXPRESSION; RETROVIRUS; SURVIVAL; CYTOPATHICITY AB The effect of human immunodeficiency virus (HIV-I) infection on the programmed cell death of CD4 + lymphocytes was studied by using Jurkat cells stably expressing high levels of the Bcl-2 protein (Jurkat-Bcl2) or control cells (Jurkat-P). Both Jurkat-Bcl2 and Jurkat-P cells exhibited surface CD4 expression adequate to support HIV-I infection. We observed no differences between HIV-l-infected Jurkat Bcl2 cells and control cells with respect to kinetics of virus replication, protein expression, and processing. Severe cytopathic effects, which were typical of acute HIV-I infection and consisted of syncytium formation followed by single-cell lysis, were observed in both cell types. However, several lines of evidence, such as cell viability analysis by trypan blue dye exclusion, chromosomal DNA laddering, and morphologic analysis by acridine orange/ethidium bromide or Giemsa staining, indicated that HIV-1 did not induce a significant amount of programmed cell death in either cell type. These results suggest that apoptosis is at most a minor element in HIV-l-induced cytopathicity in Jurkat lymphocytes. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 06516]; NIAID NIH HHS [AI 24755, AI 28691] NR 42 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD AUG 1 PY 1996 VL 12 IS 4 BP 321 EP 328 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UY965 UT WOS:A1996UY96500001 PM 8673540 ER PT J AU McGrory, BJ Freiberg, AA Shinar, AA Harris, WH AF McGrory, BJ Freiberg, AA Shinar, AA Harris, WH TI Correlation of measured range of hip motion following total hip arthroplasty and responses to a questionnaire SO JOURNAL OF ARTHROPLASTY LA English DT Article DE hip arthroplasty; questionnaire; range of motion; outcome; WOMAC osteoarthritis index; Harris hip score ID KNEE AB Twenty-eight patients (with 30 primary and 8 revision total hip arthroplasties) completed a standardized questionnaire containing the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Harris hip score questions prior to an office visit a minimum of I year after surgery. The range of hip motion measured by an orthopaedic surgeon was compared with the responses to questions on stiffness and function as well as with global scores in the WOMAC osteoarthritis index. Patient responses to the questions asking if they could cut their toenails on the operated side and the Harris hip score question asking if they could put on socks and lie a shoe correlated significantly with postoperative hip motion (P <.005). The WOMAC global pain and stiffness scores did not correlate with range of motion. The WOMAC physical function score correlated significantly only with hip flexion (P <.05). Of the WOMAC physical function questions, difficulty bending to pick an object off the floor (P <.05) and getting on and off the toilet (P <.05) correlated with the sum of the range of motion in all planes and weighted Harris hip score range of motion calculation. These data suggest that the points allocated in the Harris hip score for range of motion can be estimated reasonably accurately from questionnaire or phone response to a series of questions on a standardized questionnaire. The question on ability to cut toenails or the Harris hip score question regarding ability to put on socks and lie a shoe correlated with the most individual planes of motion, but several WOMAC physical function questions also correlated with total and weighted range of motion calculations. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 21 TC 34 Z9 34 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 1996 VL 11 IS 5 BP 565 EP 571 DI 10.1016/S0883-5403(96)80111-2 PG 7 WC Orthopedics SC Orthopedics GA VF210 UT WOS:A1996VF21000013 PM 8872577 ER PT J AU Davies, JP Tse, MK Harris, WH AF Davies, JP Tse, MK Harris, WH TI Monitoring the integrity of the cement-metal interface of total joint components in vitro using acoustic emission and ultrasound SO JOURNAL OF ARTHROPLASTY LA English DT Article DE debonding; cement-metal interface; loosening; acoustic emission; ultrasound ID TOTAL HIP COMPONENTS; FEMORAL COMPONENTS; FINITE-ELEMENT; INITIATION; FAILURE AB Debonding of the cement-metal interface of cemented femoral components of total hip arthroplasty has been shown from clinical and autopsy material to be a common occurrence. Experimentally debonding has been shown to increase markedly the strains in the adjacent cement mantle. Studies of autopsy-retrieved specimens demonstrate that debonding of the cement-metal interface is a key initiating event in loosening of cemented femoral components of total hip arthroplasty. However, both the radiographic and autopsy evidence of cement-metal interfacial debonding exist after the fact, that is, after debonding has occurred. The lack of prospective data showing that debonding does indeed occur under physiologic loading and occurs prior to other forms of failure of fixation leaves uncertain the issue of debonding and its role in initiating loosening of cemented femoral components. Knowing when, where, and to what extent the cement-metal interface debonds is critical information in understanding the process of loosening of cemented femoral components. Such information would contribute to improving the durability of stems and improving cementing techniques. In this study, the two nondestructive techniques of acoustic emission and ultrasonic evaluation of the cement-metal interface of cemented femoral stems of total hip arthroplasty were combined to investigate when, where, and to what extent cement-metal debonding occurred in vitro in simulated femurs loaded physiologically in fatigue in simulated single-leg stance. Debonding of the cement-metal interface of a cemented femoral component in this model was both an initiating event and a major mechanism of compromise of the cement-metal interface. Additional acoustic emission signals arose from cracks that developed in the cement. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 22 TC 19 Z9 19 U1 1 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 1996 VL 11 IS 5 BP 594 EP 601 DI 10.1016/S0883-5403(96)80115-X PG 8 WC Orthopedics SC Orthopedics GA VF210 UT WOS:A1996VF21000017 PM 8872581 ER PT J AU Skare, JT Champion, CI Mirzabekov, TA Shang, ES Blanco, DR ErdjumentBromage, H Tempst, P Kagan, BL Miller, JN Lovett, MA AF Skare, JT Champion, CI Mirzabekov, TA Shang, ES Blanco, DR ErdjumentBromage, H Tempst, P Kagan, BL Miller, JN Lovett, MA TI Porin activity of the native and recombinant outer membrane protein Oms28 of Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CHRONIC NEUROLOGIC MANIFESTATIONS; LYME-DISEASE; ESCHERICHIA-COLI; TREPONEMA-PALLIDUM; PATHOGENIC LEPTOSPIRA; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; ERYTHEMA MIGRANS; EXPRESSION; IDENTIFICATION AB The outer membrane-spanning (Oms) proteins of Borrelia burgdorferi have been visualized by freeze-fracture analysis but, until recently, not further characterized. We developed a method for the isolation of B. burgdorferi outer membrane vesicles and described porin activities with single-channel conductances of 0.6 and 12.6 nS in 1 M KCl. By using both nondenaturing isoelectric focusing gel electrophoresis and fast-performance liquid chromatography separation after detergent solubilization, we found that the 0.6-nS porin activity resided in a 28-kDa protein, designated Onms28. The oms28 gene was cloned, and its nucleotide sequence was determined. The deduced amino acid sequence of Oms28 predicted a 257-amino-acid precursor protein with a putative 24-amino-acid leader peptidase I signal sequence. Processed Oms28 yielded a mature protein with a predicted molecular mass of 25,363 Da. When overproduced in Escherichia coli, the Oms28 porin fractionated in part to the outer membrane. Sodium dodecyl sulfate-polyacrylamide gel-purified recombinant Oms28 from E. coli retained functional activity as demonstrated by arm average single-channel conductance of 1.1 nS in the planar lipid bilayer assay. These findings confirmed that Oms28 is a B. burgdorferi porin, the first to be described. As such, it is of potential relevance to the pathogenesis of Lyme borreliosis and to the physiology of the spirochete. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV INFECT DIS,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST NEUROPSYCHIAT,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. MEM SLOAN KETTERING CANC CTR,PROGRAM MOL BIOL,NEW YORK,NY 10021. FU NIAID NIH HHS [AI-37312, AI-21352, AI-29733] NR 54 TC 37 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 1996 VL 178 IS 16 BP 4909 EP 4918 PG 10 WC Microbiology SC Microbiology GA VB706 UT WOS:A1996VB70600021 PM 8759855 ER PT J AU Trippel, SB Coutts, RD Einhorn, TA Mundy, GR Rosenfeld, RG AF Trippel, SB Coutts, RD Einhorn, TA Mundy, GR Rosenfeld, RG TI Growth factors as therapeutic agents SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID HORMONE RECEPTOR DEFICIENCY; CARTILAGE ORGAN-CULTURES; OSTEO-SARCOMA CELLS; FACTOR-BETA; FACTOR-I; BONE-FORMATION; ARTICULAR-CARTILAGE; CROUZON-SYNDROME; MESSENGER-RNA; FRACTURE REPAIR RP Trippel, SB (reprint author), MASSACHUSETTS GEN HOSP,PHYSICIANS OFF BLDG,SUITE 403,275 CAMBRIDGE ST,BOSTON,MA 02114, USA. NR 138 TC 85 Z9 88 U1 0 U2 2 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 AUG PY 1996 VL 78A IS 8 BP 1272 EP 1286 PG 15 WC Orthopedics; Surgery SC Orthopedics; Surgery GA VD024 UT WOS:A1996VD02400020 ER PT J AU Leach, RJ Singer, FR Lewis, TB Cody, JD Reddy, SV Whyte, MP Roodman, GD AF Leach, RJ Singer, FR Lewis, TB Cody, JD Reddy, SV Whyte, MP Roodman, GD TI Evidence of a locus for Paget's disease of bone on human chromosome 18Q. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. JOHN WAYNE CANC INST,SANTA MONICA,CA 90404. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. JEWISH HOSP ST LOUIS,ST LOUIS,MO 63110. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP 19 EP 19 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500018 ER PT J AU Phipps, KR Orwoll, ES Bevan, L AF Phipps, KR Orwoll, ES Bevan, L TI Water-borne fluoride associated with a reduction in forearm bone mineral density. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. PORTLAND VA MED CTR,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP 38 EP 38 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500039 ER PT J AU Zhao, WG Byrne, MH Tsay, A Krane, SM AF Zhao, WG Byrne, MH Tsay, A Krane, SM TI Collagenase expression at tendon/bone insertions in mice: Possible role in tendon insertion ''migration''. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP 50 EP 50 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500051 ER PT J AU Ashkar, S Weber, G Shih, S Strauss, PG Schmidt, J Cantor, H Glimcher, MJ Gerstenfeld, LC AF Ashkar, S Weber, G Shih, S Strauss, PG Schmidt, J Cantor, H Glimcher, MJ Gerstenfeld, LC TI The role of osteopontin and CD44 in the metastasis of osteosarcomas. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GSF MUNICH,INST MOL PATHOL,MUNICH,GERMANY. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP 52 EP 52 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500052 ER PT J AU Gardella, TJ Jensen, GS Luck, M Usdin, TB Juppner, H AF Gardella, TJ Jensen, GS Luck, M Usdin, TB Juppner, H TI Converting parathyroid hormone-related peptide (PTHrP) into a potent PTH-2 receptor agonist SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP 77 EP 77 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500077 ER PT J AU Kovacs, CS Ho, C Seidman, CE Seidman, JG Kronenberg, HM AF Kovacs, CS Ho, C Seidman, CE Seidman, JG Kronenberg, HM TI Parathyroid calcium sensing receptor regulates fetal blood calcium and fetal-maternal calcium gradient independently of the maternal calcium level. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP 106 EP 106 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500107 ER PT J AU Bergwitz, C Takemura, M Luck, M Segre, GV Juppner, H Gardella, TJ AF Bergwitz, C Takemura, M Luck, M Segre, GV Juppner, H Gardella, TJ TI Definition of PTH2-receptor regions that are important for binding of and activation by parathyroid hormone-related peptide (PTHRP) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP 108 EP 108 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500108 ER PT J AU Takeshige, K Kohno, H Lee, K Jemtland, R Lanske, BM Kronenberg, HM Lupu, F Efstratiadis, A Segre, GV AF Takeshige, K Kohno, H Lee, K Jemtland, R Lanske, BM Kronenberg, HM Lupu, F Efstratiadis, A Segre, GV TI Interrelationships of IGF-I and PTHrP on endochondral bone development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. COLUMBIA UNIV,DEPT GENET & DEV,NEW YORK,NY 10032. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP 124 EP 124 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500124 ER PT J AU Lee, K Vortkamp, A Tabin, C Lanske, B Kronenberg, H Segre, GV AF Lee, K Vortkamp, A Tabin, C Lanske, B Kronenberg, H Segre, GV TI Indian hedgehog delays the differentiation of growth-plate chondrocytes by stimulating expression of PTHrP. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 0 TC 2 Z9 2 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 AUG PY 1996 VL 11 SU 1 BP 125 EP 125 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500125 ER PT J AU McDougall, S Fu, YH Lowe, GN Williams, A Polendo, R Benya, PD IidaKlein, A Fang, MKA Hahn, TJ AF McDougall, S Fu, YH Lowe, GN Williams, A Polendo, R Benya, PD IidaKlein, A Fang, MKA Hahn, TJ TI Surface adhesion-mediated regulation of chondrocyte-specific gene expression in the nontransformed RCJ 3.1C5.18 rat chondrocyte cell line SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; HUMAN ARTICULAR CHONDROCYTES; OSTEOBLAST-LIKE CELLS; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; PARATHYROID-HORMONE; COLLAGEN-SYNTHESIS; RETINOIC ACID; II COLLAGEN; INDUCED REEXPRESSION AB Recent evidence suggests that decreased chondrocyte function in osteoarthritis and other articular disorders may be due to chondrocyte dedifferentiation produced by altered regulatory signals from the cartilage extracellular matrix (ECM), However, there are currently no mammalian chondrocytic cell line systems adapted to the study of this process, We therefore examined the effects of ECM growth conditions on markers of differentiated chondrocytic phenotype expression in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line, including type TI collagen expression, aggrecan production, link protein gene expression, and parathyroid hormone (PTH) receptor number, RCJ cells grown in monolayer on plastic exhibited a dedifferentiated phenotype characterized by Battened cell morphology, with >80% type I collagen and <5% type II collagen production, as determined by two-dimensional gel mapping electrophoresis of collagen cyanogen bromide peptides, Tn addition, aggrecan production was low, and link protein mRNA was not expressed at detectable levels. After transfer to growth under minimal attachment conditions on the surface of a composite type I collagen/agarose (0.15%/-0.8%) gel (GAG) for 7 days, RCJ cells developed a rounded, chondrocytic morphology and a pattern of differentiated, chondrocytic gene expression, with 79% type II and 8% type I collagen production, Steady-state type I and type II procollagen mRNA levels were altered in parallel with collagen protein expression, fn cells grown on GAG, aggrecan production increased 6-fold, and there was a marked increase in both aggrecan core protein and link protein mRNA levels, In addition, maximal PTH-stimulated cAMP generation increased 15-fold in association with an increased PTH receptor number. Therefore, the RCJ chondrocyte cell line is highly sensitive to ECR;I regulation of chondrocyte-specific gene expression. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. ORTHOPAED HOSP LOS ANGELES, J VERNON LUCK ORTHOPAED RES CTR, LOS ANGELES, CA USA. UNIV SO CALIF, DEPT ORTHOPAED, LOS ANGELES, CA USA. RP McDougall, S (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, GERIATR RES EDUC & CLIN CTR 11G, DEPT MED, 11301 WILSHIRE BLVD, LOS ANGELES, CA 90073 USA. RI Benya, Paul/I-3449-2015 OI Benya, Paul/0000-0002-1060-7127 FU NIA NIH HHS [AG00489]; NIAMS NIH HHS [AR38463, AR42894] NR 50 TC 15 Z9 15 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 AUG PY 1996 VL 11 IS 8 BP 1130 EP 1138 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UX957 UT WOS:A1996UX95700011 PM 8854249 ER PT J AU Baholyodin, T Philley, F Bormel, J Schneider, DL Silverman, SL AF Baholyodin, T Philley, F Bormel, J Schneider, DL Silverman, SL TI Decreasing secular trends in the incidence of hip fracture in women in California: 1983-1992. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. OSTEOPOROSIS MED CTR,BEVERLY HILLS,CA. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M687 EP M687 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501032 ER PT J AU Chan, KWH Williamson, KS Swindlehurst, CA Reddy, SV Roodman, GD AF Chan, KWH Williamson, KS Swindlehurst, CA Reddy, SV Roodman, GD TI Competitive assay for a novel autocrine osteoclast stimulating factor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NOVADX INC, SAN DIEGO, CA 92121 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78284 USA. VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M749 EP M749 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501095 ER PT J AU Chen, Q Goetinck, PF AF Chen, Q Goetinck, PF TI Structural analysis of cartilage matrix protein networks with a retroviral expression system. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 PENN STATE UNIV,COLL MED,HERSHEY,PA 17033. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. RI Chen, Qian/C-4354-2011 OI Chen, Qian/0000-0003-4406-5618 NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M451 EP M451 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500796 ER PT J AU Divieti, P Lanske, BM Kronenberg, HM Bringhurst, FR AF Divieti, P Lanske, BM Kronenberg, HM Bringhurst, FR TI Reconstitution of PTH responsiveness in murine calvarial osteoblasts lacking the PTH/PTHrP receptor type 1. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02140. HARVARD UNIV,SCH MED,BOSTON,MA 02140. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP M506 EP M506 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500853 ER PT J AU Elango, N Song, M Katz, MS AF Elango, N Song, M Katz, MS TI Transforming growth factor beta stimulates parathyroid hormone parathyroid hormone-related protein receptor gene expression at the transcriptional level. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M493 EP M493 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500839 ER PT J AU Guo, J Lanske, B Liu, B Kronenberg, HM Bringhurst, FR AF Guo, J Lanske, B Liu, B Kronenberg, HM Bringhurst, FR TI A functional carboxyl-terminal PTH receptor regulates growth of conditionally immortalized hypertrophic chondrocytes SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP M496 EP M496 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500842 ER PT J AU Jemtland, R Lee, K Segre, GV AF Jemtland, R Lee, K Segre, GV TI Molecular characterization distinguishes among osteoclasts in developing bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M398 EP M398 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500745 ER PT J AU Kearns, AE Goto, K Heymont, JL Demay, MB AF Kearns, AE Goto, K Heymont, JL Demay, MB TI Characterization of an osteoblastic silencer element in the first intron of the rat osteocalcin gene. SO JOURNAL OF BONE AND MINERAL RESEARCH 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 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 AUG PY 1996 VL 11 SU 1 BP M332 EP M332 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500678 ER PT J AU Lee, SK Galson, DL Goldring, SR Lorenzo, JA AF Lee, SK Galson, DL Goldring, SR Lorenzo, JA TI Calcitonin downregulates calcitonin receptor mRNA expression in osteoclast-like cells (OLC) generated from hematopoietic stem cell lines SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 DEPT VET AFFAIRS MED CTR,NEWINGTON,CT 06111. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06030. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,DEACONESS HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M381 EP M381 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500727 ER PT J AU Leung, AT Qi, LJ AbouSamra, AB AF Leung, AT Qi, LJ AbouSamra, AB TI Role of glycosylation in PTH/PTHrP receptor function. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Leung, Albert/H-6030-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 1996 VL 11 SU 1 BP M500 EP M500 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500846 ER PT J AU Li, YP Chen, W Stashenko, P AF Li, YP Chen, W Stashenko, P TI Expression of sulfatide activator protein in human osteoclasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 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 AUG PY 1996 VL 11 SU 1 BP M385 EP M385 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500731 ER PT J AU Liu, B Guo, J Lanske, B Kronenberg, HM Bringhurst, FR AF Liu, B Guo, J Lanske, B Kronenberg, HM Bringhurst, FR TI Isolation of conditionally immortalized primary stromal cells that support hormone-dependent osteoclastogenesis in vitro SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP M390 EP M390 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500737 ER PT J AU McDougall, S Lee, S Hahn, TJ AF McDougall, S Lee, S Hahn, TJ TI Adhesion-mediated regulation of fibronectin and alpha 5 beta 1 fibronectin receptor gene expression in mammalian chondrocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M457 EP M457 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500803 ER PT J AU Parfitt, AM Schipani, E Rao, DS Kupin, W Han, ZH Juppner, H AF Parfitt, AM Schipani, E Rao, DS Kupin, W Han, ZH Juppner, H TI Hypercalcemia due to constitutive activin of the PTH/PTHrP receptor-comparison with primary hyperparathyroidism. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HENRY FORD HOSP,DETROIT,MI 48202. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP M508 EP M508 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500854 ER PT J AU Polendo, R Lowe, GN McDougall, S Hahn, TJ AF Polendo, R Lowe, GN McDougall, S Hahn, TJ TI Opposing effects of the protein kinase a and protein kinase C second messenger systems on mammalian chondrocyte function. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,CTR GERIATR RES EDUC & CLIN,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M468 EP M468 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500814 ER PT J AU Qian, F Leung, A AbouSamra, AB AF Qian, F Leung, A AbouSamra, AB TI Agonist-stimulated phosphorylation of the carboxy-terminal tail of the PTH/PTHrP receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Leung, Albert/H-6030-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 1996 VL 11 SU 1 BP M497 EP M497 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500843 ER PT J AU Reddy, SV Singer, FR Anderson, JL Roodman, GD AF Reddy, SV Singer, FR Anderson, JL Roodman, GD TI Measles virus nucleocapsid transcript expression is not restricted to osteoclast lineage in patients with Paget's disease. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78284 USA. VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. ST JOHNS HOSP, JOHN WAYNE CANC CTR, SANTA MONICA, CA 90404 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M753 EP M753 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501099 ER PT J AU Rubin, DA Bergwitz, C Zon, LI Juppner, H AF Rubin, DA Bergwitz, C Zon, LI Juppner, H TI Cloning of receptors for parathyroid hormone (PTH) and PTH-related protein (PTHrP) in the zebrafish (Danio rerio). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,CHILDRENS HOSP BOSTON,BOSTON,MA. HARVARD UNIV,SCH MED,HHMI,BOSTON,MA. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M481 EP M481 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500827 ER PT J AU Schipani, E Jensen, GS Pincus, J Juppner, H AF Schipani, E Jensen, GS Pincus, J Juppner, H TI Mutational analysis of position 410 in the human PTH/PTHrP receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M495 EP M495 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500840 ER PT J AU Takemura, M IidaKlein, A Segre, GV AF Takemura, M IidaKlein, A Segre, GV TI Determinants of PTH/PTHrP receptor interactions with different G proteins SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M498 EP M498 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500845 ER PT J AU Takemura, M Bergwitz, C Usdin, TB Juppner, H Segre, GV AF Takemura, M Bergwitz, C Usdin, TB Juppner, H Segre, GV TI Specific determinants in the first and second transmembrane helices of the PTH/PTHrP receptor are necessary for stimulating phospholipase C, but not for stimulating adenylyl cyclase SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M499 EP M499 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500844 ER PT J AU Usa, T Segre, GV AF Usa, T Segre, GV TI Two alternatively spliced PTH/PTHrP receptor transcripts are expressed in rat kidney. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP M492 EP M492 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500838 ER PT J AU Grinspoon, S Askari, H Lee, K Herzog, D Klibanski, A AF Grinspoon, S Askari, H Lee, K Herzog, D Klibanski, A TI The effects of estrogen on bone turnover responses to rhIGF-I in anorexia nervosa. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP P237 EP P237 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500221 ER PT J AU Li, YC Bergwitz, C Juppner, H Demay, MB AF Li, YC Bergwitz, C Juppner, H Demay, MB TI Cloning and characterization of the vitamin D receptor from xenopus laevis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP P284 EP P284 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500268 ER PT J AU Stebler, BA Sun, WH Keller, ET Ershler, WB AF Stebler, BA Sun, WH Keller, ET Ershler, WB TI Estrogen regulation of interleukin-6 expression involves I kappa B alpha SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,MADISON,WI 53706. NORTHWESTERN UNIV,CHICAGO,IL 60614. RI Keller, Evan/M-1446-2016 OI Keller, Evan/0000-0002-7592-7535 NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP P234 EP P234 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500219 ER PT J AU Galson, DL Bloch, DB Doppalapudi, VA Owen, C Anusaksathein, O Goldring, SR AF Galson, DL Bloch, DB Doppalapudi, VA Owen, C Anusaksathein, O Goldring, SR TI Characterization of novel isoforms of the human calcitonin receptor and expression in megakaryocytes and platelets. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,DEACONESS HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP S452 EP S452 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500433 ER PT J AU Mitlak, B Smith, AP Arnold, A AF Mitlak, B Smith, AP Arnold, A TI Association of a polymorphic allele of the vitamin D receptor gene with primary hyperparathyroidism in women and men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP S489 EP S489 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500470 ER PT J AU Tirone, E Naro, F Spinella, MT Migliaccio, S Galson, DL Teti, A Goldring, SR AF Tirone, E Naro, F Spinella, MT Migliaccio, S Galson, DL Teti, A Goldring, SR TI Phosphatidycholine hydrolysis and protein kinase C pathways are activated by the calcitonin receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV LAQUILA,DEPT EXPTL MED,I-67100 LAQUILA,ITALY. UNIV ROMA LA SAPIENZA,INST HISTOL & EMBRYOL,ROME,ITALY. IST DERMOPAT IMMACOLATA,ROME,ITALY. MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEACONESS HOSP,BOSTON,MA 02215. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP S461 EP S461 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500443 ER PT J AU Uy, HL Mundy, GR Boyce, BF Story, B Dunstan, C Roodman, GD Guise, TA AF Uy, HL Mundy, GR Boyce, BF Story, B Dunstan, C Roodman, GD Guise, TA TI Tumor necrosis factor hormone-related protein (PTHrP)-induced hypercalcemia in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX 78284. RI Dunstan, Colin/G-6214-2013 OI Dunstan, Colin/0000-0001-7586-4071 NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP S447 EP S447 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500428 ER PT J AU Carolan, PJ Lee, K Segre, GV AF Carolan, PJ Lee, K Segre, GV TI Parathyroid hormone induces sequential c-fos expression in chondrocytes of developing endochondral bone in culture. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP T458 EP T458 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501276 ER PT J AU Goodman, WG Belin, T Gales, B Juppner, H Segre, GV Salusky, IB AF Goodman, WG Belin, T Gales, B Juppner, H Segre, GV Salusky, IB TI Regulation of parathyroid hormone release by calcium before and after successful long-term calcitriol therapy in secondary hyperparathyroidism. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 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 AUG PY 1996 VL 11 SU 1 BP T451 EP T451 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501267 ER PT J AU Klein, RF Vossler, M Carlos, AS Stork, PJS AF Klein, RF Vossler, M Carlos, AS Stork, PJS TI Osteoblastic mitogen-activated protein (MAP) kinase is inhibited by ethanol. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 VOLLUM INST,BONE & MINERAL RES UNIT,PORTLAND VA MED CTR,PORTLAND,OR. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP T334 EP T334 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501152 ER PT J AU Sneddon, WB Bogado, CE Demay, MB AF Sneddon, WB Bogado, CE Demay, MB TI DNA sequences downstream from the vitamin D response element of the rat osteocalcin gene enhance ligand dependent transactivation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP T502 EP T502 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501320 ER PT J AU Tahara, H Smith, AP Gaz, RD Zariwala, M Xiong, Y Arnold, A AF Tahara, H Smith, AP Gaz, RD Zariwala, M Xiong, Y Arnold, A TI Subchromosomal localization of the chromosome 1p parathyroid tumor suppressor gene and analysis of the p18 cyclin-dependent kinase inhibitor as a candidate. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. NR 0 TC 0 Z9 0 U1 0 U2 2 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 AUG PY 1996 VL 11 SU 1 BP T757 EP T757 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501574 ER PT J AU Wu, HI Arnold, A AF Wu, HI Arnold, A TI Vitamin D receptor gene as a candidate tumor suppressor gene in parathyroid adenomas. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1996 VL 11 SU 1 BP T756 EP T756 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501573 ER PT J AU Wyatt, LE IidaKlein, A Ishida, K Liu, Y Ma, D Yamaguchi, DT Miller, TA AF Wyatt, LE IidaKlein, A Ishida, K Liu, Y Ma, D Yamaguchi, DT Miller, TA TI Passage-dependent loss of osteoblast function but not proliferation markers in MC3T3-E1 cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,PLAST SURG SECT,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,GRECC,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NR 0 TC 0 Z9 0 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 AUG PY 1996 VL 11 SU 1 BP T363 EP T363 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501179 ER PT J AU Weber, C Alon, R Moser, B Springer, TA AF Weber, C Alon, R Moser, B Springer, TA TI Sequential regulation of alpha 4 beta 1 and alpha 5 beta 1 integrin avidity by CC chemokines in monocytes: Implications for transendothelial chemotaxis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-ADHESION MOLECULE-1; HUMAN ENDOTHELIAL CELLS; T-LYMPHOCYTES; ACTIVATED ENDOTHELIUM; VASCULAR ENDOTHELIUM; LEUKOCYTE EMIGRATION; CYTOPLASMIC DOMAINS; PHYSIOLOGICAL FLOW; HUMAN-NEUTROPHILS; COUNTER-RECEPTOR AB Leukocyte emigration possibly requires dynamic regulation of integrin adhesiveness for endothelial and extracellular matrix ligands. Adhesion assays on purified vascular cell adhesion molecule (VCAM)-1, fibronectin, and fibronectin fragments revealed distinct kinetic patterns for the regulation of very late antigen (VLA)-4 (alpha 4 beta 1) and VLA-5 (alpha 5 beta 1) avidity by the CC chemokines monocyte inflammatory protein (MIP)-1 alpha, RANTES (regulated on activation, normal T expressed and secreted), or monocyte chemoattractant protein (MCP)-1 in monocytes. CC chemokines induced early activation and subsequent deactivation of VLA-4, whereas upregulation of VLA-5 avidity occurred later and persisted. Controlled detachment assays in shear flow suggested that adhesive strength of VLA-4 for VCAM-1 or the 40-kD fragment of fibronectin (FN40) is more rapidly increased and subsequently reduced by MCP-1 than by MIP-1 alpha, and confirmed late and sustained activation of the adhesive strength of VLA-5 for the 120-kD fragment of fibronectin (FN120), Mn2+ or the stimulating beta 1 mAb TS2/16 strongly and stably enhanced monocyte binding to VCAM-1 or fibronectin, and locked beta 1 integrins in a high avidity state, which was not further modulated by CC chemokines, Mn2+ and mAb TS2/16 inhibited CC chemokine-induced transendothelial migration, particularly chemotaxis across stimulated endothelium that involved VLA-4 and VCAM-1. VLA-4 on Jurkat cells is of constitutively high avidity and interfered with migration across barriers expressing VCAM-1. Low but not high site densities of VCAM-1 or FN40 promoted, while FN120 impaired, beta 1 integrin-dependent monocyte chemotaxis to MCP-1 across fitters coated with these substrates. Thus, we show that CC chemokines can differentially and selectively regulate avidity of integrins sharing common beta subunits. Transient activation and deactivation of VLA-4 may serve to facilitate transendothelial diapedesis, whereas late and prolonged activation of VLA-5 may mediate subsequent interactions with the basement membrane and extracellular matrix. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV BERN,THEODOR KOCHER INST,CH-3000 BERN 9,SWITZERLAND. OI Weber, Christian/0000-0003-4610-8714 FU NCI NIH HHS [CA31798] NR 66 TC 191 Z9 193 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1996 VL 134 IS 4 BP 1063 EP 1073 DI 10.1083/jcb.134.4.1063 PG 11 WC Cell Biology SC Cell Biology GA VD431 UT WOS:A1996VD43100020 PM 8769427 ER PT J AU Clark, RA Alon, R Springer, TA AF Clark, RA Alon, R Springer, TA TI CD44 and hyaluronan-dependent rolling interactions of lymphocytes on tonsillar stroma SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN LYMPHOID-TISSUES; HOMING RECEPTOR; ENDOTHELIAL-CELLS; T-CELLS; B-CELLS; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; PHYSIOLOGICAL FLOW; HUMAN-ERYTHROCYTES; ADHESION MOLECULE AB Little is known about how lymphocytes migrate within secondary lymphoid organs, Stromal cells and their associated reticular fibers form a network of fibers that radiate from high endothelial venules to all areas of the lymph node and may provide a scaffold for lymphocyte migration, We studied interactions of lymphocytes with cultured human tonsillar stromal cells and their extracellular matrix using shear stress to distinguish transient interactions from firm adhesion. Tonsillar lymphocytes and SKW3 T lymphoma cells tethered and rolled on monolayers of cultured tonsillar stromal cells and their matrix. A significant proportion of these rolling interactions were independent of divalent cations and were mediated by CD44 binding to hyaluronan, as shown by inhibition with mAb to CD44, soluble hyaluronan, hyaluronidase treatment of the substrate, and O-glycoprotease treatment of the rolling cells. O-glycoprotease treatment of the substrate also blocked binding completely to stromal matrix and partially to stromal monolayers. SKW3 cells tethered and rolled on plastic;immobilized hyaluronan, confirming the specificity of this interaction. By contrast? monolayers of resting or stimulated human umbilical vein endothelial cells failed to support CD44- and hyaluronan-dependent rolling. SKW3 cells added under flow conditions to frozen sections of human tonsil bound and rolled along reticular fibers in the presence of EDTA. Rolling was blocked by either CD44 mAb or hyaluronan. We propose that lymphocytes migrating through secondary lymphoid organs may use CD44 to bind to hyaluronan immobilized on stromal cells and reticular fibers. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA31798] NR 77 TC 102 Z9 103 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1996 VL 134 IS 4 BP 1075 EP 1087 DI 10.1083/jcb.134.4.1075 PG 13 WC Cell Biology SC Cell Biology GA VD431 UT WOS:A1996VD43100021 PM 8769428 ER PT J AU Rudkin, GH Yamaguchi, DT Ishida, K Peterson, WJ Bahadosingh, F Thye, D Miller, TA AF Rudkin, GH Yamaguchi, DT Ishida, K Peterson, WJ Bahadosingh, F Thye, D Miller, TA TI Transforming growth factor-beta, osteogenin, and bone morphogenetic protein-2 inhibit intercellular communication and alter cell proliferation in MC3T3-E1 cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GAP-JUNCTIONAL COMMUNICATION; OSTEOBLASTIC CELLS; MODULATES PROLIFERATION; INDUCTIVE PROTEIN; GENE-EXPRESSION; DIFFERENTIATION; INVITRO; CONNEXIN43; PHENOTYPE; RABBIT AB Intercellular communication by gap junctions has been implicated to function in the control of cell growth and differentiation in osseous tissues - processes which are regulated, in part, by peptide growth factors, including transforming growth factor-beta (TGF-beta) and the bone morphogenetic proteins (BMPs). Using the osteoblastic cell line MC3T3-E1, we tested the hypothesis that the effects of TGF-beta and BMPs on cell proliferation may be correlated to changes in intercellular communication. In a series of proliferation assays, MC3T3-E1 cells were cultured in the presence of bone morphogenetic protein-2 (BMP-2) or TGF-beta for up to 48 hr. Proliferation of cells during the linear log phase (days 2 to 4) was assessed by H-3-thymidine (H-3-TdR) incorporation. After times ranging from 6 to 48 hr, BMP-2 significantly inhibited uptake of H-3-TdR at doses of 50-800 ng/ml. Similarly, TGF-beta inhibited uptake of H-3-TdR at doses of 2-32 ng/ml. In a separate group of experiments, intercellular communication through gap junctions was demonstrated by cell-cell transfer of the fluorescent tracer, lucifer yellow, after microinjection. One series of experiments showed that the gap junctional intercellular communication (GJIC) of cells, incubated for 48 hr in the presence of the higher dose of osteogenin (OG) (5.0 vs. 0.5 mu g/ml) or higher dose of TGF-beta (2.0 vs. 0.2 ng/ml), was significantly inhibited compared to control. in another series of experiments, time and dose dependent effects of BMP-2 and TGF-beta on GJIC were investigated. In The time course experiments (3, 6, 12, 24, and 48 hr), TGF-beta (2.0 ng/ml) demonstrated a statistically significant effect in inhibiting GJIC as early as 6 hr, while BMP-2 (50 ng/ml) inhibited GJIC after 24 and 48 hr of treatment. The dose-dependent effects of BMP-2 and TGF-beta on cell couplings, determined at 48 hr, showed significant inhibitory effects with BMP-2 at 25 and 50 ng/ml and with TGF-beta at 2 and 4 ng/ml. The cell count results and injection study performed at 12 hr, at a fixed cell density, confirmed that the inhibitory effect was not due to differences in cell density. The 50% effective inhibitory concentrations (EC(50)) calculated for BMP-2 and TGF-beta at 48 hr, showed no dose correlation between proliferation and GJIC, suggesting that these two events are independent occurrences. Additionally, marked morphological change was observed in the cells treated with TGF-beta. The observation may suggest that TGF-(b)eta may have effects upon cytoskeletal elements in osseous tissues. (C) 1996 Wiley-Liss, Inc. C1 W LOS ANGELES VA MED CTR,PLAST SURG LAB,GRECC,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90095. NR 36 TC 29 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1996 VL 168 IS 2 BP 433 EP 441 DI 10.1002/(SICI)1097-4652(199608)168:2<433::AID-JCP22>3.0.CO;2-2 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VA308 UT WOS:A1996VA30800022 PM 8707879 ER PT J AU Raines, DE Liberthson, RR Murray, JR AF Raines, DE Liberthson, RR Murray, JR TI Anesthetic management and outcome following noncardiac surgery in nonparturients with Eisenmenger's physiology SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE anesthesia; congenital heart disease; Eisenmenger's physiology; Eisenmenger's syndrome; surgery ID CONGENITAL HEART-DISEASE; EPIDURAL-ANESTHESIA; PATIENT; PREGNANCY; ARTERIAL; SATURATION; RESECTION; COMPLEX AB Study Objective: To evaluate the perioperative risk to nonparturients with Eisenmenger's physiology for noncardiac surgical procedures. Design: Retrospective chart review. Setting: University-affiliated hospital. Patients: 12 nonparturients with Eisenmenger's physiology who underwent 25 noncardiac surgical procedures requiring care by an anesthesiologist. Measurements and Main Results: Preoperative, intraoperative, and postoperative records were retrospectively analyzed. Data examined included patient age, gender, symptoms, laboratory values, monitors used, surgical procedure, and outcome. Twenty-five procedures were performed on 12 patients; 13 procedures were performed with general anesthesia 6 with peripheral nerve blocks, 5 with sedation by an anesthesiologist with or without local anesthetic infiltration, and one with epidural anesthesia. One patient died perioperatively. Review of the literature revealed two deaths in 32 procedures for nonparturients with Eisenmenger's physiology undergoing noncardiac surgery. Conclusions: A variety of anesthetic techniques and drugs may be used successfully in nonparturients with Eisenmenger's physiology undergoing noncardiac surgery. Although the study group is small, the perioperative mortality risk is lower than that for parturients undergoing either labor and delivery or cesarean section and is probably in the range of approximately 10%. RP Raines, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 33 TC 15 Z9 15 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 1996 VL 8 IS 5 BP 341 EP 347 DI 10.1016/0952-8180(96)00084-0 PG 7 WC Anesthesiology SC Anesthesiology GA UY469 UT WOS:A1996UY46900001 PM 8832442 ER PT J AU Kaplan, MR Plotkin, MD Brown, D Hebert, SC Delpire, E AF Kaplan, MR Plotkin, MD Brown, D Hebert, SC Delpire, E TI Expression of the mouse Na-K-2Cl cotransporter, mBSC2, in the terminal inner medullary collecting duct, the glomerular and extraglomerular mesangium, and the glomerular afferent arteriole SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE tubuloglomerular feedback; renin; inner medullary collecting duct; mesangium; macula densa ID K-CL COTRANSPORTER; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; CHLORIDE TRANSPORT; CELLS; LOCALIZATION; KIDNEY; RENIN; SECRETION; MEMBRANE AB Na-K-Cl cotransport plays an important role in the kidney in NaCl reabsorption in the thick ascending limb of Henle and a less well defined role in the inner medullary collecting duct (IMCD). Two Na-K-Cl cotransporters encoded by different genes have been identified in the mammalian kidney: BSC1/NKCC2 which localizes to the apical thick ascending limb of Henle and BSC2/NKCC1 which was isolated from a mouse IMCD cell line (mIMCD-3) but its localization has not been determined. In this study we generated a polyclonal antibody (anti-mBSC2) against the mouse BSC2/NKCC1 protein in order to characterize and localize this protein in mouse kidney. Western blot analysis with affinity-purified anti-mBSC2 showed a protein doublet of 140 and 150 kD which was most abundant in the renal papilla but also seen in cortex and outer medulla. The 140-150-kD bands were not seen with preimmune serum or with anti-mBSC2 preabsorbed with specific antigen. Immunolocalization confirmed expression of mBSC2 protein on the basolateral surface of terminal IMCD segments and demonstrated expression in the papillary surface epithelium. Immunofluorescence also revealed the unexpected presence of the BSC2 protein at the juxtaglomerular afferent arteriole, in a juxtaglomerular structure probably representing the extraglomerular mesangium, and throughout the glomerular mesangium. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,RENAL UNIT,DEPT PATHOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-08887, DK-08898, DK-42956] NR 33 TC 103 Z9 103 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1996 VL 98 IS 3 BP 723 EP 730 DI 10.1172/JCI118844 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VB698 UT WOS:A1996VB69800018 PM 8698864 ER PT J AU Chang, A Yeap, B Davis, T Blum, R Hahn, R Khanna, O Fisher, H Rosenthal, J Witte, R Schinella, R Trump, D AF Chang, A Yeap, B Davis, T Blum, R Hahn, R Khanna, O Fisher, H Rosenthal, J Witte, R Schinella, R Trump, D TI Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: Flutamide versus diethylstilbestrol SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONSTEROIDAL ANTIANDROGEN; MEDROXYPROGESTERONE ACETATE; CYPROTERONE-ACETATE; PHASE-III; CANCER; EXPERIENCE; THERAPY; TRIAL AB Purpose: Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone. Therapy with diethylstilbestrol (DES), leuprolide, or bilateral orchiectomy has been reported to be equivalent. DES is the cheapest preparation, but has the potential for serious cardiovascular or thromboembolic complications. Flutamide is a novel antiandrogen with fewer side effects. Patients and Methods: The Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, randomized study to compare the efficacy of flutamide (250 mg three times daily) to DES (1 mg three times daily) as the primary hormonal therapy for patients with stage D2 prostate cancer. Patients were stratified by performance status, disease sites, and history of cardiovascular disease at randomization. Results: Forty-eight patients received DES and 44 flutamide. Patient characteristics were evenly distributed between the two treatments. The overall response rate was similar (DES, 62%; flutamide, 50%), Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3% of patients on DES and in 17.6% on flutamide (P = .051). Other toxicities were similar between the two treatment arms. However, DES produced significantly longer rime to treatment failure (26.4 v 9.7 months, P = .016) and longer survival than flutamide (43.2 v 28.5 months, P = .040). Conclusion: As the primary hormonal therapy for stage D2 prostate cancer, DES caused more serious cardiovascular or thromboembolic complications than flutamide, Despite this, flutamide was not as active an initial agent as DES. However, the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined, and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies. (C) 1996 by American Society of Clinical Oncology. C1 UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. NYU,MED CTR,NEW YORK,NY 10012. ALBANY MED COLL,ALBANY,NY. DOWNSTATE MED CTR,BROOKLYN,NY. DANA FARBER CANC INST,BOSTON,MA 02115. STANFORD UNIV,STANFORD,CA 94305. MAYO CLIN,ROCHESTER,MN. HAHNEMANN MED COLL,PHILADELPHIA,PA. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. FU NCI NIH HHS [CA 23318, CA 11083, CA 21115] NR 33 TC 90 Z9 92 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 AUG PY 1996 VL 14 IS 8 BP 2250 EP 2257 PG 8 WC Oncology SC Oncology GA VA767 UT WOS:A1996VA76700009 PM 8708714 ER PT J AU Fowler, FJ Barry, MJ LuYao, G Wasson, JH Bin, L AF Fowler, FJ Barry, MJ LuYao, G Wasson, JH Bin, L TI Outcomes of external-beam radiation therapy for prostate cancer: A study of Medicare beneficiaries in three surveillance, epidemiology, and end results areas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; DECISION-ANALYSIS; SEQUELAE AB Purpose: This study was designed to obtain representative estimates of the quality of life and probabilities of possible adverse effects among Medicare-age patients treated with external-beam radiation therapy for prostate cancer, Methods: patients treated for local or regional prostate cancer with high-energy external-beam radiation between 1989 and 1991 were sampled from a claims data bose of the Surveillance, Epidemiology, and End Results (SEER) program from three regions, Patients were surveyed primarily by moil, with telephone follow-up evaluation of nonrespondents, There were 621 respondents (83% response rate), The results were compared with data from a previously published national survey of Medicare-age men who had undergone radical prostatectomy. Results: Although they were older at the time of treatment, radiation patients were less likely than surgical patients to wear pads for wetness (7% v 32%) and had a lower rate of impotence (23% v 56% for men < 70 years), while they were more likely to report problems with bowel dysfunction (10% v 4%), Both groups reported generally positive feelings about their treatments, Radiation and surgical patients reported similar rates of additional subsequent treatment (24% v 26% at 3 years after primary treatment), However, radiation patients were less likely to say they were cancer-free, and they reported more worry about cancer than did surgical patients, Conclusion: The health-related quality of life of radiation and surgical patients, on average, is similar, but the pattern of experience with adverse consequences of treatment differs by treatment. (C) 1996 by American Society of Clinical Oncology. C1 MASSACHUSETTS GEN HOSP, MED PRACTICE EVALUAT CTR, BOSTON, MA 02114 USA. DARTMOUTH COLL, HITCHCOCK MED CTR, DARTMOUTH MED SCH, CTR EVALUAT CLIN SCI, HANOVER, NH 03756 USA. US HLTH CARE FINANCING ADM, DIV HLTH INFORMAT & OUTCOMES, OFF RES & DEMONSTRAT, BALTIMORE, MD 21207 USA. RP Fowler, FJ (reprint author), UNIV MASSACHUSETTS, SURVEY RES CTR, 100 MORRISEY BLVD, BOSTON, MA 02125 USA. FU AHRQ HHS [HS 06336, HS 08397] NR 21 TC 161 Z9 161 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1996 VL 14 IS 8 BP 2258 EP 2265 PG 8 WC Oncology SC Oncology GA VA767 UT WOS:A1996VA76700010 PM 8708715 ER PT J AU Schiller, JH Kim, KM Hutson, P DeVore, R Glick, J Stewart, J Johnson, D AF Schiller, JH Kim, KM Hutson, P DeVore, R Glick, J Stewart, J Johnson, D TI Phase II study of topotecan in patients with extensive-stage small-cell carcinoma of the lung: An Eastern Cooperative Oncology Group trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; TOPOISOMERASE POISONS; CANCER; CAMPTOTHECIN; CHEMOTHERAPY; CPT-11; AGENTS; DRUGS AB Purpose: To determine the response rate and survival of chemotherapy-naive patients with extensive-stage small-cell lung cancer (SCLC) treated with topotecon, and to determine the relationship of topotecan pharmacokinetics with response and toxicity. Patients and Methods: Forty-eight patients with previously untreated, extensive-stage SCLC received 2.0 mg/m(2) of topotecan daily for 5 days. The first 13 patients were treated without colony-stimulating factor (CSF) support; the next 35 patients received 5 mu g/kg of granulocyte-colony-stimulating factor (G-CSF) for 10 to 14 days starting on day 6. Cycles were repeated every 3 weeks for a maximum of four cycles. patients who had a partial response to topotecan after four cycles, stable disease after two cycles, or progressive disease at any time received salvage chemotherapy with cisplatin and etoposide. Topotecan pharmacokinetics were measured using a four-point sampling scheme. Results: Of 48 patients, none had a complete response and 19 had a partial response, for an objective response rate of 39% (95% confidence interval [CI], 25.2% to 53.0%), The median response duration was 4.8 months (95% CI, 3.0 to 7.3). After a median follow-up duration of 18.2 months, the overall median survival time was 10.0 months (95% CI, 8.2 to 12.7); the 1-year survival rate was 39% (95% CI, 25.2% to 53.0%). Eight of 34 patients (24%) who received salvage chemotherapy responded. Four of 17 patients who did not respond to first-line therapy with topotecan responded to cisplatin and etoposide. The most common toxicity was hematologic. Ninety-two percent of patients treated without G-CSF developed grade 3 or 4 neutropenia, compared with 29% who received G-CSF. However, the incidence of neutropenic fevers was similar between the two groups (8% and 11%, respectively), and one patient in each group died of neutropenic fevers. There were no differences in objective tumor response, duration of response, time to treatment failure, or survival between the 13 patients who entered the study before G-CSF administration wets mandated and the 35 patients who entered after and received G-CSF. There was poor correlation between the WBC count and absolute neutrophil counts (ANCs) and both the area under the curve (AUC) and maximum concentration (C-max) of total topotecan in plasma, There was no correlation between the tumor response and either AUC or C-max of total topotecan. Conclusion: The activity of topotecan in extensive-stage SCLC noted this study warrants further investigation of this agent in phase III clinical trials. (C) 1996 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02115 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. VANDERBILT UNIV, NASHVILLE, TN USA. RP Schiller, JH (reprint author), UNIV WISCONSIN, CTR COMPREHENS CANC, CTR CLIN SCI, ROOM K4-636, 600 HIGHLAND AVE, MADISON, WI 53792 USA. FU NCI NIH HHS [CA49957, CA21076, CA23318] NR 31 TC 163 Z9 170 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1996 VL 14 IS 8 BP 2345 EP 2352 PG 8 WC Oncology SC Oncology GA VA767 UT WOS:A1996VA76700022 PM 8708727 ER PT J AU Suit, H Spiro, I Mankin, HJ Efird, J Rosenberg, AE AF Suit, H Spiro, I Mankin, HJ Efird, J Rosenberg, AE TI Radiation in management of patients with dermatofibrosarcoma protuberans SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXCISION AB Purpose: The preferred treatment of dermatofibrosarcoma protuberans (DFSP) is wide resection, namely, margins greater than or equal to 3 cm beyond the evident disease and histologically negative margins. We assess the success achieved by radiation combined with surgery for positive/close margins or by radiation alone for those tumors that are not resectable For technical/medical reasons. The literature on this point is virtually nonexistent. Materials and Methods: The outcome of treatment of 18 patients with DFSP by radiation alone (n = 3) and radiation and surgery (n = 15) at the Massachusetts General Hospital was assessed. All of the lesions at the time of the treatment by radiation alone or combined with surgery were less than 10 cm. This was the maximum dimension. The actual tumor volume was much less than indicated by this maximum dimension, as the tumors were usually relatively flat. Results: The 10-year actuarial local control rate was determined to be 88%. Local control was realized in the three patients treated by radiation alone, with follow-up periods of greater than or equal to 9 years. Among 15 patients treated by radiation and surgery, there have been three local failures; the 10-year actuarial local control rate was 84%. The three local failures occurred in 12 patients whose surgical margins were positive. One of these three local failures developed in the group of two patients whose lesions were scored as grade II. Conclusion: Radiation in well-tolerated dose schedules is an effective option in the management of patients with DFSP. This appears to be true for radiation alone or postoperatively for margin-positive disease (primary or recurrent). (C) 1996 by American Society of Clinical Oncology. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPAED SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP Suit, H (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 14 TC 77 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1996 VL 14 IS 8 BP 2365 EP 2369 PG 5 WC Oncology SC Oncology GA VA767 UT WOS:A1996VA76700024 PM 8708729 ER PT J AU Niederman, R BuyleBodin, Y Lu, BY Naleway, C Robinson, P Kent, R AF Niederman, R BuyleBodin, Y Lu, BY Naleway, C Robinson, P Kent, R TI The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE gingival inflammation; short chain carboxylic acids; propionate; butyrate ID GAS-LIQUID-CHROMATOGRAPHY; SUBGINGIVAL TEMPERATURE; GENE-EXPRESSION; BUTYRATE; CELLS; PROPIONATE; DIAGNOSIS; BACTERIA AB Short-chain carboxylic acids (SCCA; C less than or equal to 5; e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which accumulate in the gingival crevice, and exhibit significant biological activity, including the ability to alter gene expression. It has been hypothesized that among the activities of SCCAs are their ability to contribute to gingival inflammation. This concept complements the notion that specific periodontal pathogens are the causative agents of gingival inflammation. To begin testing these 2 hypotheses, we examined the relationship between SCCA concentrations, specific putative periodontal pathogens, and gingival inflammation in medically healthy periodontally diseased subjects. We reasoned that if SCCAs and/or specific periodontal pathogens were causative gingival inflammatory agents, gingival inflammation should increase with increasing concentration of the inflammatory mediator. We also recognized that other clinical variables needed to be controlled for, and an objective quantitative assessment of gingival inflammation used. To accomplish these tasks, sites within subjects were stratified by location and pocket depth, and the following quantified: bacterial presence; SCCA. concentration; and gingival inflammation. The results indicated that gingival inflammation directly and significantly correlated with SCCA concentrations in the maxillary and mandibular molars, incisors and canines (all r greater than or equal to 0.47; all p less than or equal to 0.015; too few bicuspids were available for complete analysis). The relationship between gingival inflammation and SCCA concentration was best described by a natural log relationship. Gingival inflammation did not, however, correlate positively with either the total number of specific putative periodontal pathogens, or the sum of subsets of these pathogens (-0.31 less than or equal to r less than or equal to 0.39; 0.08 less than or equal to p less than or equal to 0.75) for any of the locations. Finally the SCCA concentration did not correlate with the level of individual or groups of pathogens. These data, together with historical work and other preliminary data, support the hypothesis that SCCA, rather than specific putative periodontal pathogens, may be a causative agent in gingival inflammation. This work may, in part, begin to explain the apparent lack of a direct relationship between current gingival inflammation and the prediction of bacterially-mediated periodontal attachment loss. C1 NORTHWESTERN UNIV,DEPT STOMATOL,CHICAGO,IL. AMER DENT ASSOC HLTH FDN,CHICAGO,IL. HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. RP Niederman, R (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE08415] NR 38 TC 16 Z9 17 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD AUG PY 1996 VL 23 IS 8 BP 743 EP 749 DI 10.1111/j.1600-051X.1996.tb00604.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VD409 UT WOS:A1996VD40900006 PM 8877660 ER PT J AU OBrien, CP AF OBrien, CP TI Recent developments in the pharmacotherapy of substance abuse SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID CANNABINOID RECEPTOR; METHADONE-MAINTENANCE; COCAINE DEPENDENCE; ALCOHOL DEPENDENCE; SMOKING CESSATION; NICOTINE PATCH; NALTREXONE; BRAIN; ABSTINENCE; INPATIENT AB Modern concepts of addictive disorders emphasize the compulsive and relapsing drug-taking behaviors rather than tolerance and physical dependence. As with any chronic disorder, long-term treatment is necessary and medications may aid in the rehabilitative process. Specific medications have been demonstrated to be helpful for psychiatric disorders coexisting with addiction. Medications have also been demonstrated in controlled studies to aid in the rehabilitation of patients dependent on nicotine, alcohol, or opiates. Thus far, no medication has been clearly demonstrated to benefit patients suffering from abuse or dependence on cocaine, cannabinoids, nonalcohol sedatives, or hallucinogens. RP OBrien, CP (reprint author), UNIV PENN, PHILADELPHIA VET AFFAIRS MED CTR, 3900 CHESTNUT ST, PHILADELPHIA, PA 19104 USA. FU NIDA NIH HHS [P50DA05186-09] NR 57 TC 38 Z9 38 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 1996 VL 64 IS 4 BP 677 EP 686 PG 10 WC Psychology, Clinical SC Psychology GA VC526 UT WOS:A1996VC52600006 PM 8803357 ER PT J AU Finn, DT Jaworsky, C Chooback, L Jensen, PJ Lessin, SR AF Finn, DT Jaworsky, C Chooback, L Jensen, PJ Lessin, SR TI Correlation between clonotypic T-cell receptor beta chain variable region (TCR-V-beta) gene expression and aberrant T-cell antigen expression in cutaneous T-cell lymphoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; SKIN; ANTIBODIES; DIVERSITY; BLOOD AB Immunohistochemical studies can augment the clinicopathologic diagnosis of cutaneous T-cell lymphoma (CTCL). Our goal was to determine whether a panel of 11 T-cell receptor (TCR) beta chain variable region (V-beta) monoclonal antibodies (moAbs) could consistently identify clonal T-cell populations within CTCL skin infiltrates, and whether these cells exhibited aber-rant T-cell antigen expression, Biopsies from 24 CTCL and 3 parapsoriasis patients were analyzed. Of the 27 patients, 4 (15%) demonstrated T-cell clonality by restricted TCR-V-beta moAb staining. The V-beta(+) restricted cells expressed aberrant antigen profiles, Overall, aberrant antigen profiles were detected in 18/24 (75%) CTCL patients, V(beta)18 moAb crossreacted with a 85 kD protein produced by basal and suprabasal keratinocytes. We conclude: 1) Restricted TCR-V-beta expression correlated with aberrant T-cell antigen profiles; 2) In the absence of a complete panel of TCR-V-beta moabs, localization of aberrant T-cell antigen expression can be useful in identifying malignant T-cells within CTCL skin infiltrates; 3) The detection sensitivity and specificity of the currently available TCR-V-beta moAbs may limit their utility to consistently detect clonal T-cell populations in CTCL skin biopsies 4) A 85 kD protein present on basal and suprabasal keratinocytes is recognized by V(beta)18 moAb and may be related to immune function(s) of the epidermis. C1 VET AFFAIRS MED CTR,DEPT DERMATOL,PHILADELPHIA,PA 19104. BOSTON UNIV,DEPT DERMATOL,BOSTON,MA 02215. CASE WESTERN RESERVE UNIV,DEPT DERMATOL,CLEVELAND,OH 44106. UNIV N TEXAS,DEPT BIOCHEM,DALLAS,TX. UNIV PENN,DEPT DERMATOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [R29 CA 55017]; NIAMS NIH HHS [R01 AR 42998] NR 25 TC 7 Z9 7 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD AUG PY 1996 VL 23 IS 4 BP 306 EP 311 DI 10.1111/j.1600-0560.1996.tb01302.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA VC508 UT WOS:A1996VC50800004 PM 8864916 ER PT J AU Dietz, SB WhitakerMenezes, D Lessin, SR AF Dietz, SB WhitakerMenezes, D Lessin, SR TI The role of alpha E beta 7 integrin (CD103) and E-cadherin in epidermotropism in cutaneous T-cell lymphoma SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; SIGNAL-TRANSDUCTION PATHWAYS; MONOCLONAL-ANTIBODY HML-1; HUMAN MUCOSAL LYMPHOCYTES; EPIDERMAL-KERATINOCYTES; MEMBRANE MOLECULE; INTERFERON-GAMMA; EPITHELIAL-CELLS; EXPRESSION; ICAM-1 AB Adhesion molecules such as integrins and cadherins are thought to play a critical role in T-cell migration and localization within the epidermis (epidermotropism). The purpose of this study was to correlate T-cell expression of the integrin CD103 and E-cadherin in cutaneous T-cell lymphoma (CTCL). Serial sections of skin biopsies from 22 patients with CTCL and 13 with benign reactive dermatitis were stained with antibodies to CD4, CD103, and E-cadherin by the avidin-biotin peroxidase technique. CD103 was expressed on single epidermotropic CD4+ T-cells in 9/9 early stage (patch/plaque) CTCL and 6/10 reactive dermatitis biopsies. Less than 30% of dermal T-cells expressed CD103. All 4/4 late stage (tumor) CTCL were CD103-. Epidermal aggregates of CD4+ T-cells (Pautrier's microabscesses) were CD103-. E-cadherin was expressed on epidermal keratinocytes and follicular and sweat gland epithelia but not on T-cells. We conclude that CD103 expression on cutaneous T-cells parallels the degree of epidermotropism exhibited in both neoplastic and inflammatory disorders of the skin. E-cadherin is not expressed on T-cells infiltrating the skin. Further investigation is necessary to further elucidate the interaction between CD103 and E-cadherin in facilitating trafficking of T-cells into the epidermis. C1 VET AFFAIRS MED CTR,DEPT DERMATOL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT DERMATOL,PHILADELPHIA,PA 19104. FU NCI NIH HHS [R29 CA 55017] NR 26 TC 26 Z9 29 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD AUG PY 1996 VL 23 IS 4 BP 312 EP 318 DI 10.1111/j.1600-0560.1996.tb01303.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA VC508 UT WOS:A1996VC50800005 PM 8864917 ER PT J AU Bauman, RA Gell, G Dwyer, SJ AF Bauman, RA Gell, G Dwyer, SJ TI Large picture archiving and communication systems of the world .1. SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE computers; radiology; picture archiving and communication systems (PACS); survey AB This is the report of a worldwide survey of 82 institutions done to identify large scale picture archiving and communication systems (PACS) in clinical operation in 1995. This survey found a continuing strong trend toward the creation and operation of large PACS. In the 15 months since the first such survey, the number of clinical large PACS went from 13 to 23, almost a doubling in that short interval. New systems were added in Asia, Europe, and North America. A strong move to primary interpretation from soft copy was identified. and filmless radiology has become a reality. Copyright (C) 1996 by W.B. Saunders Company C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. GRAZ UNIV,INST MED INFORMAT,GRAZ,AUSTRIA. UNIV VIRGINIA,CHARLOTTESVILLE,VA. NR 1 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD AUG PY 1996 VL 9 IS 3 BP 99 EP 103 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VB695 UT WOS:A1996VB69500001 PM 8854258 ER PT J AU Davalli, AM Napoli, R Weitgasser, R Capotorto, JV Hirshman, MF Finegood, DT BonnerWeir, S Horton, ES Weir, GC AF Davalli, AM Napoli, R Weitgasser, R Capotorto, JV Hirshman, MF Finegood, DT BonnerWeir, S Horton, ES Weir, GC TI Long-term normalization of GLUT-4 protein content in skeletal muscle of diabetic rats following islet transplantation SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID IMPAIRED INSULIN-SECRETION; PANCREATIC-ISLETS; BETA-CELL; ENDOCRINE FUNCTION; GLUCOSE; EXPRESSION; MASS; LIVER; NORMOGLYCEMIA; REPLICATION AB Skeletal muscle GLUT-4 content is decreased in streptozotocin (STZ)-diabetic rats. This decrease is associated with impairment in glucose transport across the plasma membrane. In this study we investigated whether islet transplantation might normalize GLUT-4 content. Transplantation of syngeneic islets restored long-term near-normoglycemia in STZ-diabetic Lewis rats. Transplanted rats, followed up to 6 months, maintained slightly but significantly higher fasting and fed glucose levels when compared with age-matched normal controls. Although fasting insulin levels of transplanted rats were significantly higher than those of controls, insulin levels did not increase significantly with feeding. Plasma glucose levels following an oral glucose load (2 g/kg) were only slightly higher than in normal controls 2 months after transplantation, whereas after 6 months more severe glucose intolerance wasdetected. Transplanted rats completely lost the first-phase insulin release in response to i.v. glucose although they showed an increased second phase and preserved response to arginine. Six months after transplantation, endocrine beta cell mass of the grafts was similar to pretransplantation values. GLUT-4 protein content in skeletal muscle homogenates was reduced in untreated diabetic animals whereas it was completely restored by islet transplantation. In conclusion, achievement of long-term near-normoglycemia after islet transplantation was associated with complete normalization of skeletal muscle GLUT-4 content in the diabetic animals, even in the presence of abnormal glucose tolerance and an altered pattern of insulin secretion. C1 JOSLIN DIABET CTR,EP JOSLIN LABS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA 02215. SAN RAFFAELE SCI INST,I-20132 MILAN,ITALY. UNIV NAPLES FEDERICO II,SCH MED,NAPLES,ITALY. SALZBURG GEN HOSP,SALZBURG,AUSTRIA. UNIV ALBERTA,DEPT MED,EDMONTON,AB,CANADA. UNIV ALBERTA,DEPT PHYSIOL,EDMONTON,AB,CANADA. OI NAPOLI, Raffaele/0000-0002-3366-2321 FU NIDDK NIH HHS [DK-36836, DK-35449] NR 35 TC 3 Z9 3 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD AUG PY 1996 VL 150 IS 2 BP 255 EP 263 DI 10.1677/joe.0.1500255 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VC655 UT WOS:A1996VC65500010 PM 8869592 ER PT J AU Suh, WK Mitchell, EK Yang, Y Peterson, PA Waneck, GL Williams, DB AF Suh, WK Mitchell, EK Yang, Y Peterson, PA Waneck, GL Williams, DB TI MHC class I molecules form ternary complexes with calnexin and TAP and undergo peptide-regulated interaction with TAP via their extracellular domains SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INDUCED CONFORMATIONAL-CHANGES; T-CELL RECEPTOR; HEAVY-CHAINS; HISTOCOMPATIBILITY MOLECULES; INTRACELLULAR-TRANSPORT; ENDOPLASMIC-RETICULUM; SURFACE EXPRESSION; ALPHA-3 DOMAIN; BETA-2-MICROGLOBULIN; CHAPERONE AB Newly assembled heavy chain-beta(2)m heterodimers of class I histocompatibility molecules associate with the endoplasmic reticulum (ER) peptide transporter, TAP, and subsequently dissociate from TAP in parallel with their transport from the ER to the Golgi apparatus. It appears that TAP-associated class I molecules are waiting to bind appropriate peptides before they dissociate from TAP and leave the ER since binding of high aiffinity peptides to class I molecules in vitro leads to dissociation of TAP-class I complexes. In further support of this notion, we report that limiting peptide supply through inhibition of proteasome activities prolongs the association of mouse class I molecules with. TAP and concomitantly slows their transport to the Golgi apparatus. By using a series of deletion mutants and hybrid class I molecules we demonstrate that the extracellular domains of class I molecules are sufficient for their peptide-regulated interaction with TAP. Furthermore, based on the inability of all alpha(3) domain-specific mAb to recognize TAP-class I complexes and the fact that a point mutant of the D-d molecule at residue 222 is unable to bind to TAP, it is likely that a major site of interaction with TAP resides in the membrane-proximal region of the heavy chain alpha(3) domain. Finally, we examined the relationship between the interaction of mouse heavy chain-beta(2)m heterodimers with TAP and with the resident ER chaperone, calnexin. Most heterodimers that bound to TAP were found to associate simultaneously with calnexin. Upon delivery of peptide to class I molecules in permeabilized cells, dissociation from TAP was observed but the interaction with calnexin was largely maintained. Therefore, both TAP and calnexin may participate ill the: Ea retention of peptide-deficient class I molecules. However, since release from calnexin occurs after dissociation from TAP, it appears that calnexin ultimately determines ifa class I molecule is to be exported from the ER. C1 UNIV TORONTO, DEPT BIOCHEM, TORONTO, ON M5S 1A8, CANADA. RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. NR 49 TC 91 Z9 93 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 337 EP 348 DI 10.1084/jem.184.2.337 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700005 PM 8760787 ER PT J AU Boussiotis, VA Barber, DL Lee, BJ Gribben, JG Freeman, GJ Nadler, LM AF Boussiotis, VA Barber, DL Lee, BJ Gribben, JG Freeman, GJ Nadler, LM TI Differential association of protein tyrosine kinases with the T cell receptor is linked to the induction of anergy and its prevention by B7 family-mediated costimulation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN LYMPHOCYTES-T; INTERLEUKIN-2 GENE-EXPRESSION; TANDEM SH2 DOMAINS; ANTIGEN RECEPTOR; ZETA-CHAIN; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODIES; EFFECTOR FUNCTION; CLONAL EXPANSION; TUMOR REJECTION AB When stimulated through their antigen receptor, without costimulation, T cells enter a state of antigen-specific unresponsiveness, termed anergy. B7-mediated costimulation, signaling via CD28, is sufficient to prevent the induction of anergy. Were we show that ligation of T cell receptor (TCR) by alloantigen alone, which results ill anergy, activates tyrosine phosphorylation of TCR zeta and its association with fyn. In contrast, TCR ligation in the presence of B7 costimulation, which results in productive immunity, activates tyrosine phosphorylation of TCR zeta and CD3 chains, which associate with activated lck and zeta-associated protein (ZAP) 70. Under these conditions, CD28 associates with activated lck and TCR zeta. These data suggest that the induction of anergy is an active: signaling process characterized by the association of TCR zeta and fyn. III addition, CD28-mediated costimulation may prevent the induction of anergy by facilitating the effective association of TCR zeta and CDS epsilon with the critical protein tyrosine kinase lck, and the subsequent recruitment of ZAP-70. Strategies to inhibit or activate TCR-associated, specific protein tyrosine kinase-mediated pathways may provide a basis for drug development with potential applications in the fields of transplantation, autoimmunity, and tumor immunity. C1 DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. RP Boussiotis, VA (reprint author), DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, DANA 740, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA-40216]; NIAID NIH HHS [AI-35225]; PHS HHS [AL-54785] NR 91 TC 80 Z9 80 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 365 EP 376 DI 10.1084/jem.184.2.365 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700008 PM 8760790 ER PT J AU Mizoguchi, A Mizoguchi, E Chiba, C Bhan, AK AF Mizoguchi, A Mizoguchi, E Chiba, C Bhan, AK TI Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ULCERATIVE-COLITIS; INTRAEPITHELIAL LYMPHOCYTES; CONGENITALLY DEFICIENT; LYMPHOID DEVELOPMENT; TRANSGENIC RATS; PEYERS PATCHES; M-CELLS; GUT; AUTOIMMUNITY; EPITHELIUM AB T cell receptor-alpha mutant mice (TCR-alpha(-/-)), created by gene targeting of the TCR-alpha gene in embryonic stem cells, spontaneously develop inflammatory bowel disease (IBD) resembling human ulcerative colitis. Since gut-associated lymyhoid tissue is likely to play an important role in the development of chronic intestinal inflammation, we examined the changes in the appendix lymphoid follicle (ALF) and Peyer's patches (PP) ill these mice. We found the structure of the ALF to be remarkably similar to that of the PP ill the small intestine; in both instances, lymphoid follicles covered by surface epithelium (dome-formation) were found. The amount of proliferation in the lymphoid follicles of the appendix estimated by in vivo incorporation of 5-bromo-2'deoxyuridine was more than two times that of PP in TCR-alpha(-/-) mice. ELISPOT assay showed an increase or IgA, IgG1, and IgG2a, but not IgM-secreting B cells in ALF oi TCR alpha(-/-) mice compared to TCR-alpha(+/-) control mice. Furthermore, TCR-alpha(-/-) mice revealed an increase of autoantibody-producing B cells against the cytoskeletal protein tropomyosin in ALF as compared to PP. When TCR-alpha(-/-) mice underwent appendectomy at a young age (3-5 wk), the number of mesenteric lymph nodes cells at 6-7 mo were markedly less than in the sham-operated TCR-alpha(-/-) mice. Furthermore, appendectomy at 1 mo of age suppressed the development of IBD, with only 3.3% of these mice developing IBD in the 6-7-mo period of observation. In contrast, similar to 80% of controls, including the sham-operated TCR-alpha(-/-) mice, developed IBD during this period. These results suggest that ALF, rather than PP, is the priming site of cells involved in the disease process and plays all important role in the development of IBD in TCR-alpha(-/-) mice. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK47677, DK43551] NR 40 TC 181 Z9 182 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 707 EP 715 DI 10.1084/jem.184.2.707 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700042 PM 8760824 ER PT J AU Friedlander, RM Gagliardini, V Rotello, RJ Yuan, JY AF Friedlander, RM Gagliardini, V Rotello, RJ Yuan, JY TI Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; GENE CED-3; INTERLEUKIN-1-BETA-CONVERTING ENZYME; POLY(ADP-RIBOSE) POLYMERASE; ICE/CED-3 PROTEASE; CYSTEINE PROTEASES; MAMMALIAN HOMOLOG; CONVERTING-ENZYME AB Prointerleukin-1 beta (pro-IL-1B) is the only Known physiologic substrate of the interleukin-1B (IL-1 beta)-converting enzyme (ICE), the founding member of the ICE/ced-3 cell death gene family. Since secreted mature IL-1 beta has been detected after apoptosis, we investigated whether this cytokine, when produced endogenously, plays a role in cell death. We found that hypoxia-induced apoptosis car, be inhibited by either the IL-1 receptor antagonist (IL-1Ra) or by neutralizing antibodies to IL-1 or to its type 1 receptor. IL-1Ra also inhibits apoptosis induced by trophic factor deprivation in primary neurons, as well as by tumor necrosis factor alpha in fibroblasts. In addition, during the G(1)/S phase arrest, mature IL-1 beta induces apoptosis through a pathway independent of CmA-sensitive gene activity. We also demonstrate that Ice, when expressed in COS cells, requires the coexpression of pro-IL-1 beta for the induction of apoptosis, which is inhibited by IL-1Ra. Interestingly, we found that mature IL-1 beta has antiapoptotic activity when added exogenously before the onset of hypoxia, which we round is caused in part by its ability to downregulate the IL-1 receptor. Our findings demonstrate that pro-IL-1 beta is a substrate of ICE relevant to cell death, and depending on the temporal cellular commitment to apoptosis, mature IL-1 beta may function as a positive or negative mediator of cell death. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 49 TC 148 Z9 152 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 717 EP 724 DI 10.1084/jem.184.2.717 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700043 PM 8760825 ER PT J AU Farber, NJ Farber, HT Weiner, J Boyer, EG Davis, EB Feldman, D Johnson, C AF Farber, NJ Farber, HT Weiner, J Boyer, EG Davis, EB Feldman, D Johnson, C TI Telling patients about the diagnosis of HIV infection SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV; communication; information-sharing; patient education ID PHYSICIANS; ATTITUDES; PREVENTION; AIDS AB This study used a questionnaire to examine how patients in the HIV/AIDS Clinic at a Department of Veterans Affairs hospital were told of their diagnosis, by whom, and to what degree they were given emotional and educational support, Nearly 17% of patients were informed by someone not in the health professions (often military personnel), and 27% of patients were notified in a nonprivate setting, Forty-seven per cent indicated they received little or no educational support at the time of diagnosis, while 39% received little or no emotional support, Educational and emotional support for patients at the time of HDV diagnosis may be lacking. RP Farber, NJ (reprint author), MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA VET AFFAIRS MED CTR,GEN INTERNAL MED SECT,PHILADELPHIA,PA 19104, USA. NR 12 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 1996 VL 11 IS 8 BP 494 EP 496 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA VD947 UT WOS:A1996VD94700009 PM 8872789 ER PT J AU Kang, JX McLaughlin, M Brown, D Leaf, A AF Kang, JX McLaughlin, M Brown, D Leaf, A TI Modulation of cytoskeletal structure of cardiac myocytes by free polyunsaturated fatty acids SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 1996 VL 108 IS 2 BP 31 EP 31 PG 2 WC Physiology SC Physiology GA VA935 UT WOS:A1996VA93500035 ER PT J AU Xu, L Agosti, CG Pinney, D Beauchamp, R Hobbs, W Gusella, JF Ramesh, V AF Xu, L Agosti, CG Pinney, D Beauchamp, R Hobbs, W Gusella, JF Ramesh, V TI The NF2 tumor suppressor protein, merlin, localizes preferentially in membrane ruffles SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 1996 VL 108 IS 2 BP 52 EP 52 PG 1 WC Physiology SC Physiology GA VA935 UT WOS:A1996VA93500055 ER PT J AU Sheng, M Niethammer, M Naisbitt, S Kim, E AF Sheng, M Niethammer, M Naisbitt, S Kim, E TI Clustering of synaptic ion channels by the PSD-95 family of membrane-associated putative guanylate kinases SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 1996 VL 108 IS 2 BP 76 EP 76 PG 1 WC Physiology SC Physiology GA VA935 UT WOS:A1996VA93500079 ER PT J AU Wyszynski, M Sheng, M AF Wyszynski, M Sheng, M TI NMDA receptor anchoring to the actin cytoskeleton mediated by alpha 2-actinin in dendritic spines SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 1996 VL 108 IS 2 BP 84 EP 84 PG 1 WC Physiology SC Physiology GA VA935 UT WOS:A1996VA93500087 ER PT J AU Bruehl, RE Springer, TA Bainton, DF AF Bruehl, RE Springer, TA Bainton, DF TI Quantitation of L-selectin distribution on human leukocyte microvilli by immunogold labeling and electron microscopy SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE human; L-selectin; neutrophil; monocyte; lymphocyte; basophil; eosinophil; microvilli; cell adhesion; immunocytochemistry ID LYMPHOCYTE HOMING RECEPTOR; HIGH ENDOTHELIAL VENULES; NEUTROPHIL ADHESION; SPATIAL-DISTRIBUTION; CHEMOTACTIC FACTORS; PHYSIOLOGICAL FLOW; CYTOPLASMIC DOMAIN; CELLS; EXPRESSION; LECAM-1 AB L-Selectin is a leukocyte cell adhesion receptor that contributes to neutrophil (PMN) rolling on activated endothelium at sites of inflammation and mediates lymphocyte attachment to high endothelial venules in peripheral lymph nodes, Localization of this receptor to the tips of PMN and lymphocyte microvilli has been demonstrated. However, its distribution on these cells has not been quantified, and its localization on other leukocytes and the morphometry of microvilli on different leukocyte subpopulations have not been previously examined. In this study, PMN and mononuclear leukocytes were isolated from anticoagulated blood by dextran sedimentation and density centrifugation, fixed in 2% paraformaldehyde and 0.05% glutaraldehyde, immunogold-labeled for L-selectin, and embedded in Epon resin. The distribution of L-selectin was determined by counting gold I;articles on the plasma membrane of sectioned cells, and the surface microstructure of these cells was surveyed on two-dimensional transmission electron micrographs, On average, 78% of PMN, 72% of monocyte, and 71% of lymphocyte L-selectin was observed on the microvilli, with more variance on lymphocytes than the other cell types. Typical PMN and monocyte sections had 26 microvilli, whereas typical lymphocyte sections had 23. Quantitation of the distribution of L-selectin and leukocyte surface topology offers a foundation from which to study the requirement of microvilli or microvillus-localized L-selectin for leukocyte tethering and rolling in model systems that mimic microvascular environments. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES INC,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. RP Bruehl, RE (reprint author), UNIV CALIF SAN FRANCISCO,DEPT PATHOL,BOX 0506,SAN FRANCISCO,CA 94143, USA. FU NCI NIH HHS [CA31799]; NHLBI NIH HHS [HLB31610]; NIDDK NIH HHS [DK10486] NR 48 TC 121 Z9 122 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 1996 VL 44 IS 8 BP 835 EP 844 PG 10 WC Cell Biology SC Cell Biology GA VA927 UT WOS:A1996VA92700004 PM 8756756 ER PT J AU Ramanathan, C Wu, YT Pfleiderer, B Lizak, MJ Garrido, L Ackerman, JL AF Ramanathan, C Wu, YT Pfleiderer, B Lizak, MJ Garrido, L Ackerman, JL TI ADRF-CP surface-coil spectroscopy of synthetic calcium phosphates and bone mineral SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; TRANSFORM INFRARED-SPECTROSCOPY; CROSS-POLARIZATION; NMR-SPECTROSCOPY; TRABECULAR BONE; P-31 NMR; EARLY DEPOSITS; SOLID-PHASE; PO4 DOMAIN; MAS-NMR AB Proton to phosphorus-31 cross polarization via adiabatic demagnetization in the rotating frame (ADRF-CP) has been used, in conjunction with a surface coil, to detect monohydrogen phosphate (acid phosphate) ions in the presence of a large background of nonprotonated phosphate (orthophosphate) ions in porcine bone and synthetic calcium phosphates, Transient oscillations were observed in the transfer of polarization between the proton dipolar and phosphorus Zeeman nuclear-spin reservoirs at short times after the initiation of thermal contact, The oscillations were observed in all samples, including bone, Orthophosphate suppression was achieved by detecting the signal when the orthophosphate oscillation was passing through zero, and by adjusting the phosphorus RF field to achieve optimal cross polarization with the proton local fields of the acid phosphate ions, ADRF-CP techniques deposit less RF power than traditional spin-lock CP techniques, and are hence compatible with in vivo application. As the ratio of the protonated to nonprotonated phosphate can be used as a marker for bone-mineral maturity, ADRF-CP spectroscopy creates the possibility of characterizing bone-mineral dynamics in vivo by solid-state NMR. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,BIOMAT LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,DEPT NUCL ENGN,CAMBRIDGE,MA 02139. CHILDRENS HOSP,DEPT ORTHOPAED SURG,LAB STUDY SKELETAL DISORDERS & REHABIL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Ramanathan, Chandrasekhar/C-5207-2008; Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Ramanathan, Chandrasekhar/0000-0002-7457-3608; Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 NR 53 TC 8 Z9 8 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD AUG PY 1996 VL 121 IS 2 BP 127 EP 138 DI 10.1006/jmra.1996.0152 PG 12 WC Physics, Atomic, Molecular & Chemical SC Physics GA VB314 UT WOS:A1996VB31400005 ER PT J AU Yoshida, T Watanabe, M Engelman, DT Engelman, RM Schley, JA Maulik, N Ho, YS Oberley, TD Das, DK AF Yoshida, T Watanabe, M Engelman, DT Engelman, RM Schley, JA Maulik, N Ho, YS Oberley, TD Das, DK TI Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE transgenic mouse; antioxidants; ischemia; reperfusion; heart; glutathione peroxidase; adaptation ID ISOLATED RAT HEARTS; FREE-RADICALS; HEAT-SHOCK; SUPEROXIDE-DISMUTASE; ANTIOXIDANT ENZYMES; OXIDATIVE STRESS; EXPRESSION; CATALASE; RECOVERY; HYPERTHERMIA AB To test the authors' hypothesis that cellular antioxidant enzymes constitute a cellular defense against acute stress, myocardial ischemia reperfusion injury in transgenic mice overexpressing the cellular glutathione peroxidase (GSHPx-1) was studied. Transgenic mice were generated using the entire mouse GSHPx-1 gene including approximately 2.0 kb 5' flanking sequence. A 400% increase of GSHPx activity was found in the hearts of transgenic mice compared with non-transgenic controls. Isolated perfused hearts were prepared from two groups of mice: transgenic overexpressed; non-transgenic controls. Hearts were perfused by Langendorff mode, and after 10 min of stabilization subjected to 30 min of ischemia followed by 20 min of reperfusion. In addition, a group of hearts were perfused for 50 min without subjecting them to ischemia and reperfusion to demonstrate the stability of heart preparation. Transgenic mouse hearts demonstrated significantly improved recovery of contractile force and the rate of contraction, compared to non-transgenic control mouse hearts. The infarct size was also lower in transgenic mouse hearts compared to those of non-transgenic controls. In concert, following ischemia, release of creatine kinase from the transgenic hearts was significantly lower than the control group. The results of this study indicate that increased GSHPx-1 expression renders the heart more resistant to myocardial ischemia reperfusion injury. (C) 1996 Academic Press Limited C1 UNIV CONNECTICUT, SCH MED, DEPT SURG, DIV CARDIOVASC, FARMINGTON, CT 06030 USA. WAYNE STATE UNIV, INST CHEM TOXICOL, DETROIT, MI 48201 USA. UNIV WISCONSIN, DEPT PATHOL, MADISON, WI 53705 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, PATHOL SERV, MADISON, WI 53705 USA. FU NHLBI NIH HHS [HL 22559, HL 34360, HL 44571] NR 31 TC 118 Z9 120 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD AUG PY 1996 VL 28 IS 8 BP 1759 EP 1767 DI 10.1006/jmcc.1996.0165 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA VF059 UT WOS:A1996VF05900017 PM 8877785 ER PT J AU Huang, PL Fishman, MC AF Huang, PL Fishman, MC TI Genetic analysis of nitric oxide synthase isoforms: Targeted mutation in mice SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE nitric oxide; nitric oxide synthase; targeted disruption; animal models; homologous recombination ID LONG-TERM POTENTIATION; L-ARGININE; SEPTIC SHOCK; LACKING; MESSENGER; INHIBITOR; ROLES; HYPOTENSION; DISRUPTION; RESPONSES AB Since the discovery that nitric oxide is an endogenous vasodilator responsible for endothelium-derived relaxing factor activity, nitric oxide has been found in many different cell types and implicated in many diverse biological processes. Because pharmacological blockade does not distinguish between the three major isoforms of nitric oxide synthase, the tissue and enzyme source of nitric oxide is unclear in many situations. Targeted disruption of the genes for the various isoforms of nitric oxide synthase offers a useful genetic approach to study the roles of each isoform and to examine the effects of their deletion on physiological processes in intact animals. Here we review the phenotypes of the various nitric oxide synthase mutant mice and examine what they reveal about the complexities of the nitric oxide signaling system and about molecular and physiological compensations brought into play in the absence of individual isoforms. RP Huang, PL (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,CARDIOVASC RES CTR,149 E 13TH ST,CHARLESTOWN,MA 02129, USA. FU NINDS NIH HHS [NS33335, NS10282] NR 41 TC 48 Z9 48 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD AUG PY 1996 VL 74 IS 8 BP 415 EP 421 DI 10.1007/s001090050043 PG 7 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA VC055 UT WOS:A1996VC05500002 PM 8872855 ER PT J AU Peters, A Rosene, DL Moss, MB Kemper, TL Abraham, CR Tigges, J Albert, MS AF Peters, A Rosene, DL Moss, MB Kemper, TL Abraham, CR Tigges, J Albert, MS TI Neurobiological bases of age-related cognitive decline in the rhesus monkey SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review DE aging; behavior; cerebral cortex; hippocampal formation; macaca mulatta; mylein; neuronal loss ID UNBIASED STEREOLOGICAL ESTIMATION; PRIMARY VISUAL-CORTEX; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; RECOGNITION MEMORY; PREFRONTAL CORTEX; MACACA-MULATTA; HUMAN HIPPOCAMPUS; BEHAVIORAL DEFICITS; NONHUMAN-PRIMATES AB The rhesus monkey offers a useful model of normal human aging because when monkeys are tested on a battery of behavioral tasks that can also be used to evaluate cognition in humans, it is found that the monkeys undergo an age-related decline in several domains of cognitive function as do humans. In monkeys these changes begin at about 20 years of age. To determine what gives rise to this cognitive decline, we have examined several parameters in the brains of monkeys. Some parameters do not change with age. Examples of this are the numbers of neurons in the neocortex and hippocampal formation, and the numbers of synapses in the hippocampal formation. Changes in other parameters can be positively correlated with chronological age; examples of this are numbers of neuritic plaques, a decrease in the numbers of neurons in the striatally projecting pars compacta of the substantia nigra, and a decrease in the thickness of layer I in primary visual cortex. But the most interesting changes are those that correlate either with cognitive decline alone, or with both cognitive decline and chronological age. Among these are a breakdown in the integrity of myelin around axons, an overall reduction in the volume of white matter in the cerebral hemispheres, thinning of layer I in area 46 of prefrontal cortex, and decreases in the cell density in cortically projecting brain stem nuclei. To date then, our studies suggest that the cognitive declines evident in the rhesus monkey may be a consequence of changes in layer I and in the integrity of myelinated axons, rather than an age-related loss of cortical neurons or synapses, as has long been assumed. C1 BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02188. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02188. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. EMORY UNIV,DEPT ANAT & CELL BIOL,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP Peters, A (reprint author), BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02188, USA. RI Rosene, Douglas/G-1973-2015 FU NCRR NIH HHS [RR-00165]; NIA NIH HHS [2PO1-AG00001] NR 105 TC 204 Z9 211 U1 3 U2 14 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 AUG PY 1996 VL 55 IS 8 BP 861 EP 874 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VA570 UT WOS:A1996VA57000001 PM 8759775 ER PT J AU Irizarry, MC Kim, TW McNamara, M Tanzi, RE George, JM Clayton, DF Hyman, BT AF Irizarry, MC Kim, TW McNamara, M Tanzi, RE George, JM Clayton, DF Hyman, BT TI Characterization of the precursor protein of the non-A beta component of senile plaques (NACP) in the human central nervous system SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; amyloid; NACP; synaptophysin; synelfin; synuclein ID ALZHEIMERS-DISEASE; 14-KDA PROTEIN; POSTSYNAPTIC DENSITY; CEREBRAL-CORTEX; HUMAN BRAIN; PHOSPHOPROTEIN; SYNUCLEINS; ASSIGNMENT; SYNTAXIN-1; MEMBRANE AB A novel and highly conserved presynaptic protein has been independently described in rodents (synuclein/SYN-1), songbirds (synelfin), and humans (the precursor protein of the non-A beta component of senile plaques, NACP); a fragment of the latter has been detected in senile plaques in Alzheimer's disease (AD). We characterized the expression of NACP in human AD and non-AD brain. A subcellular fractionation study demonstrated that NACP was mainly localized to cytosolic fractions of human temporal cortex. NACP was also detectable in various membrane and vesicular fractions, suggesting that the protein was associated with membrane structures including synaptic vesicles. Pericellular immunostaining of the neuropil was observed in neocortical and limbic regions, supporting a synaptic localization. Senile plaques in AD brains were not immunoreactive, and confocal microscopy suggested a loss of NACP immunoreactivity in cored plaques. No difference was found in the amount of protein in AD and control frontal cortex, as measured by immunoblotting. PCR analysis showed that the full-length mRNA product was the major splice form in both AD and control human brains. Thus, despite the association of a hydrophobic fragment of NACP with senile plaques, our data suggest that the precursor itself is not a significant component of plaques and NACP synthesis is not substantially altered in AD. Nevertheless, the protein is an abundant component of synaptic regions prone to degeneration in AD, and may have a role in the expression or advancement of the disease. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP EAST,GENET & AGING UNIT,CHARLESTOWN,MA 02129. UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,URBANA,IL 61801. UNIV ILLINOIS,BECKMAN INST,URBANA,IL 61801. RI George, Julia/B-2169-2008; Clayton, David/B-2190-2008 OI George, Julia/0000-0001-6194-6914; Clayton, David/0000-0002-6395-3488 FU NIA NIH HHS [AG05134-11S1, AG08487]; NINDS NIH HHS [NS25742] NR 27 TC 172 Z9 172 U1 0 U2 4 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 AUG PY 1996 VL 55 IS 8 BP 889 EP 895 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA VA570 UT WOS:A1996VA57000004 PM 8759778 ER PT J AU Liman, ER Corey, DP AF Liman, ER Corey, DP TI Electrophysiological characterization of chemosensory neurons from the mouse vomeronasal organ SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mouse; olfactory; vomeronasal; sensory transduction; patch-clamp; voltage-gated channel; cyclic nucleotide-gated channel ID OLFACTORY RECEPTOR NEURONS; NUCLEOTIDE-GATED CHANNELS; SODIUM-CHANNELS; SIGNAL TRANSDUCTION; CYCLIC-NUCLEOTIDES; ODORANT DETECTION; CALCIUM CHANNELS; VERTEBRATE CELLS; MARKER PROTEIN; GARTER SNAKES AB The mechanism of sensory transduction in chemosensory neurons of the vomeronasal organ (VNO) is not known. Based on molecular data, it is likely to be different from that mediating sensory transduction in the main olfactory system. To begin to understand this system, we have characterized the electrophysiological properties of dissociated mouse VNO neurons with patch-clamp recording. Sensory neurons were distinguished from nonsensory neurons by the presence of a dendrite, by immunoreactivity for olfactory marker protein, and by the firing of action potentials. The resting potential of VNO neurons was approximately -60 mV, and the average input resistance was 3 G Omega. Current injections as small as 1-2 pA elicited steady trains of action potentials that showed no sign of adaptation during a 2 sec stimulus duration. The voltage-gated conductances in VNO neurons are distinct from those in olfactory neurons. The Na+ current is composed of two components; the major component was mt-sensitive (K-i = 3.6 nM). The outward K+ current activates at -30 mV with kinetics 10 times slower than for K+ currents in olfactory neurons. The Ca2+ current is composed of at least two components: an L-type current and a T-type current that activates at -60 mV and is not found in olfactory neurons. We find no evidence for cyclic nucleotide-gated channels in VNO neurons under a variety of experimental conditions, including those that produced large responses in mouse olfactory neurons, which is further evidence for a novel transduction pathway. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02114. RP Liman, ER (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN 414,50 BLOSSOM ST,BOSTON,MA 02114, USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [R03 DC 02889-01] NR 67 TC 83 Z9 86 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1996 VL 16 IS 15 BP 4625 EP 4637 PG 13 WC Neurosciences SC Neurosciences & Neurology GA UX955 UT WOS:A1996UX95500010 PM 8764651 ER PT J AU Sakas, DE Whittaker, KW Crowell, RM Zervas, NT AF Sakas, DE Whittaker, KW Crowell, RM Zervas, NT TI Perfluorocarbons: Recent developments and implications for neurosurgery SO JOURNAL OF NEUROSURGERY LA English DT Review DE perfluorocarbons; perfluorochemicals; cerebral protection; ischemia; magnetic resonance imaging; radiotherapy ID MAGNETIC-RESONANCE SPECTROSCOPY; FOCAL CEREBRAL-ISCHEMIA; FLUOSOL-DA 20-PERCENT; COLD-STORAGE METHOD; OXYGENATED FLUOROCARBON EMULSION; RESPIRATORY-DISTRESS SYNDROME; ARTIFICIAL BLOOD SUBSTITUTES; ANTITUMOR ALKYLATING-AGENTS; SIGNIFICANT WARM ISCHEMIA; PERFLUOROCHEMICAL EMULSION AB Over the last 30 years, perfluorocarbons (PFCs) have been extensively investigated as oxygen carriers. Early studies indicated that these compounds could be used as blood substitutes or protective agents against ischemia. Adverse characteristics such as instability, short intravascular half-life, and uncertainties concerning possible toxicity precluded wide clinical application. However, advances in PFC technology have led to the development of improved second-generation oxygen carriers that incorporate well-tolerated emulsifiers (egg-yolk phospholipids). The authors review recent developments in this field and consider the potential role of PFCs in future neurosurgical practice. Diagnostic applications could include their use to assess cerebral blood flow, local oxygen tension, and brain metabolism or to achieve enhanced imaging and precise staging of inflammatory, neoplastic, or vascular disease processes by means of computerized tomography, ultrasonography, and magnetic resonance studies. Therapeutic applications could include cerebral protection, an adjunctive role in radiotherapy of malignant brain tumors, protection against air embolism, the preservation of organs for transplantation, and ventilatory support in head-injured patients with compromised lung function. In addition, PFCs have been used successfully as a tool in ophthalmic microsurgery and potentially thy could fulfill a similar role in microneurosurgery. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. WALSGRAVE GEN HOSP,NEUROSCI UNIT,COVENTRY CV2 2DY,W MIDLANDS,ENGLAND. FU NHLBI NIH HHS [HL 22573] NR 124 TC 14 Z9 14 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1996 VL 85 IS 2 BP 248 EP 254 DI 10.3171/jns.1996.85.2.0248 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UY939 UT WOS:A1996UY93900008 PM 8755753 ER PT J AU Sanders, VJ Felisan, S Waddell, A Tourtellotte, WW AF Sanders, VJ Felisan, S Waddell, A Tourtellotte, WW TI Detection of Herpesviridae in postmortem multiple sclerosis brain tissue and controls by polymerase chain reaction SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE human herpesvirus 6; Epstein-Barr virus; varicella-zoster virus; cytomegalovirus; demyelination ID EPSTEIN-BARR-VIRUS; VARICELLA-ZOSTER VIRUS; CENTRAL-NERVOUS-SYSTEM; HERPES-SIMPLEX VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; INFECTIOUS-MONONUCLEOSIS; SCHIZOPHRENIC-PATIENTS; CYTOMEGALO-VIRUS; ENCEPHALITIS AB Objective: To test for the presence of herpesviruses in postmortem brain samples from multiple sclerosis patients and controls using polymerase chain reaction. Background: Herpes simplex virus, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus-6 are common viruses capable of persistence and latency. All have been detected in the CNS. Methods: Active and inactive plaque tissue, unaffected white matter (WM) and gray matter (GM) from MS cases, and WM and GM controls (Alzheimer's disease, Parkinson's disease and non-neurological disease) were screened for the herpesvirus by PCR. Results: (1) 37% of the MS cases were positive for herpes simplex virus (HSV). Twenty-eight percent of controls cases were positive for HSV. Forty-one percent of active plaques were positive for HSV in contrast to only 20% of inactive plaques (Sanders ef al, 1996). (2) 57% of the MS cases and 43% of the control cases were positive for HHV-6. Thirty-two percent of the active plaques contained HHV-6 compared to 17% of inactive plaques. (3) 43% of the MS cases and 32% of the control cases were positive for VZV. Fourteen percent of the active plaques and 10% ofthe inactive plaques were positive for VZV. (4) 27% of MS cases and 38% of control cases were positive for EBV. Five percent of the active plaques were positive for EBV and 10% ofthe inactive plaques were positive. (5) 16% of the MS cases and 22% ofthe controls were positive for CMV. Nine percent ofthe active plaques and 10% ofthe inactive plaques were positive. We also compared MS WM and GM with controls and found no significant difference. Conclusions: HSV, HHV-6, and VZV were present in a greater frequency of MS cases compared to controls; however, no statistical differences were noted. The presence of herpesvirus in all tissue makes an etiologic association to MS uncertain. Cellular localization of virus and its relationship to pathology and latency may reveal an association. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. NR 52 TC 107 Z9 110 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 1996 VL 2 IS 4 BP 249 EP 258 DI 10.3109/13550289609146888 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA VH076 UT WOS:A1996VH07600005 PM 8799216 ER PT J AU Agostini, HT Ryschkewitsch, CF Singer, EJ Stoner, GL AF Agostini, HT Ryschkewitsch, CF Singer, EJ Stoner, GL TI Co-infection with two JC virus genotypes in brain, cerebrospinal fluid or urinary tract detected by direct cycle sequencing of PCR products SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE AIDS; polyomavirus; progressive multifocal leukoencephalopathy; recombination; urine; viral evolution ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; BK-VIRUS; POLYOMAVIRUS; VARIANTS; EXCRETION; DISEASE; PATIENT; GENOME; AIDS AB The human polyomavirus TC (TCV), which exists in different geographically based genotypes, causes the central demyelinating disease known as progressive multifocal leukoencephalopathy (PML). A coding region recombinant ICV Type 1/Type 3 (Type 4) is excreted in the urine of some 16% of individuals in the USA. In addition, occasional 'crossovers' in viral DNA sequence at type-specific sites in the coding region occur between TCV genotypes amplified from PML brain. For recombination to occur requires the existence of two different genotypes in the same host. Here we provide evidence from direct cycle sequencing of PCR products that different genotypes of TCV can be found in a single tissue sample. After non-type-specific PCR amplification, cycle sequencing produced 'split bands' at type determining sites which were resolved into type or subtype-specific sequences by subcloning of the PCR products, PCR products with split bands at typing sites were found in two brain samples and in one cerebrospinal fluid (CSF) from AIDS patients with PML and in the urine of four immunocompetent individuals. This indicates that co-infection with two viral types does not depend on severe immunocompromise. Combinations of genotypes found were Types 1A & 1B, 1A & 2, 1B & 2 and 2 & 3. In one doubly infected patient the major TCV type excreted in the urine changed within 1 week. C1 NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. NR 25 TC 27 Z9 27 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 1996 VL 2 IS 4 BP 259 EP 267 DI 10.3109/13550289609146889 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA VH076 UT WOS:A1996VH07600006 PM 8799217 ER PT J AU Goldberg, SN Richardson, DD Palmer, EL Scott, JA AF Goldberg, SN Richardson, DD Palmer, EL Scott, JA TI Pleural effusion and ventilation/perfusion scan interpretation for acute pulmonary embolus SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE pulmonary embolus; ventilation/perfusion scan; pleural effusion ID CHEST RADIOGRAPHIC FINDINGS; PERFUSION DEFECTS AB This study was conducted to determine if pleural effusion size affects ventilation/perfusion (V/Q) scan interpretation algorithms for acute pulmonary embolus (PE), Methods: Retrospective analysis identified 163 consecutive patients undergoing angiography for PE with radiographic evidence for pleural effusion, V/Q scanning was performed in 94 (58%) of cases and reported using original Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) criteria, Effusions were classified as small, large and/or bilateral, Radiographic and scintigraphic results were correlated with regard to size and location of abnormalities, Results: Of the 163 patients, 57 (35%) had angiographically-proven PE, 77(47%) had at least one large pleural effusion and 86 (53%) had a small effusion; 33 (43%) with large effusions and 24 (28%) with small effusions had emboli at angiography. Thirty-six of 119 patients (30%) with clear chest radiographs (a control group) had PE, Thus, large effusions were associated with a higher incidence of PE than those with small effusions or clear lungs (p < 0.05), Of those with V/Q scanning, 26 of 94 (28%) had a solitary large effusion, with 12 (46%) positive for emboli, V/Q-matched abnormalities limited to effusion size were found in 16 with a solitary large effusion and 10 with a solitary small effusion, In both groups, 50% were angiographically positive for emboli, Twenty-three (66%) of 35 with bilateral effusions had corresponding V/Q-matched defects at one(n = 11) or both (n = 12) lung bases, and 9 (39%) were positive for emboli, In total, 45% with a V/Q-matched defect of equivalent size to the effusion were angiographically positive for PE. Conclusion: Pulmonary emboli are associated with pleural effusions of all sizes, Matched V/Q defects corresponding to radiographically-evident pleural effusions are of intermediate probability for PE, Thus, revision of the traditional lung scan interpretive criteria based upon pleural effusion size is not warranted. RP Goldberg, SN (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NUCL MED SECT,42 BLOSSOM ST,BOSTON,MA 02114, USA. NR 12 TC 12 Z9 12 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1996 VL 37 IS 8 BP 1310 EP 1313 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VA931 UT WOS:A1996VA93100013 PM 8708762 ER PT J AU McLean, TW Pritchard, J AF McLean, TW Pritchard, J TI Langerhans cell histiocytosis and hypercalcemia: Clinical response to indomethacin SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE Langerhans cell histiocytosis (LCH); hypercalcemia; indomethacin ID CANCER AB Purpose: Hypercalcemia is a known complication of childhood malignancies but has never been reported to be associated with Langerhans cell histiocytosis (LCH) in a pediatric patient. Patients and Methods: We describe an infant with multisystem LCH who developed hypercalcemia on two occasions. After being placed on indomethacin, the hypercalcemia did not recur despite disease progression. Conclusion: Hypercalcemia may complicate LCH. LCH is demonstrated, indomethacin should be considered as a treatment. C1 CHILDRENS HOSP,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA. GREAT ORMOND ST HOSP SICK CHILDREN,DEPT HAEMATOL ONCOL,LONDON,ENGLAND. RP McLean, TW (reprint author), DANA FARBER CANC INST,OPD 5,44 BINNEY ST,BOSTON,MA 02115, USA. NR 16 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 1996 VL 18 IS 3 BP 318 EP 320 DI 10.1097/00043426-199608000-00019 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA VA002 UT WOS:A1996VA00200019 PM 8689352 ER PT J AU Simpson, BB Ryan, DP Schnitzer, JJ Flores, A Doody, DP AF Simpson, BB Ryan, DP Schnitzer, JJ Flores, A Doody, DP TI Surgical evaluation and management of refractory constipation in older children SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 13-15, 1995 CL SAN FRANCISCO, CA SP Amer Acad Pediat DE constipation; colon innervation; Hirschsprung's disease; intestinal innervation; rectal manometry; neuronal intestinal dysplasia ID NEURONAL INTESTINAL DYSPLASIA; PULL-THROUGH PROCEDURES; HIRSCHSPRUNGS-DISEASE; ACQUIRED AGANGLIONOSIS; COLONIC MANOMETRY; DIAGNOSIS; EXPERIENCE AB Chronic constipation is a common childhood problem that accounts for 3% to 5% of pediatric visits and 10% to 25% of referrals to pediatric; gastroenterologists. The etiology of constipation can be elusive, and extensive investigation often fails to identify a specific cause. The authors conducted a fi-year retrospective review of the patients referred for deep transanal rectal biopsy to determine the usefulness of this procedure in the evaluation and subsequent surgical management of refractory constipation. Specimens obtained by transanal rectal biopsy established a diagnosis for 30 of the 70 patients, and 17 of these 30 had subsequent procedures in the treatment of their constipation. The authors conclude that transanal rectal biopsy identifies a significant number of patients with previously unidentified neuroenteric disorders who may benefit from additional surgery in the treatment of constipation refractory to medical manangement. Copyright (C) 1996 by W.B. Saunders Company C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT SURG,PEDIAT SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT GASTROENTEROL,BOSTON,MA 02114. NEWTON WELLESLEY HOSP,BOSTON,MA. NR 18 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 1996 VL 31 IS 8 BP 1040 EP 1042 DI 10.1016/S0022-3468(96)90082-2 PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA VC291 UT WOS:A1996VC29100015 PM 8863229 ER PT J AU Simpson, BB Ryan, DP Donahoe, PK Schnitzer, JJ Kim, SH Doody, DP AF Simpson, BB Ryan, DP Donahoe, PK Schnitzer, JJ Kim, SH Doody, DP TI Type IV laryngotracheoesophageal clefts: Surgical management for long-term survival SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 13-15, 1995 CL SAN FRANCISCO, CA SP Amer Acad Pediat DE esophageal anomalies; laryngeal anomalies; tracheal anomalies; laryngotracheoesophageal cleft; microgastria; tracheobronchomalacia ID ESOPHAGEAL ATRESIA; EMBRYOLOGY; REPAIR AB Complete laryngotracheoesophageal clefts (types III and IV) are rare congenital anomalies that occur when the primitive foregut fails to separate into the tracheobronchial tree and the esophagus. This article summarizes a 10-year institutional experience with six infants who had type IV clefts, presents a modification of the authors' surgical approach, and identifies pitfalls in the management of these infants. Three of the six children are long-term survivors. The recognition of specific complicating issues leads to a standardized approach, which can result in successful repair and long-term survival. Copyright (C) 1996 by W.B. Saunders Company. C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,DEPT PEDIAT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 15 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 1996 VL 31 IS 8 BP 1128 EP 1133 DI 10.1016/S0022-3468(96)90101-3 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA VC291 UT WOS:A1996VC29100052 PM 8863248 ER PT J AU Simoes, EAF Groothuis, JR Tristram, DA Allessi, K Lehr, MV Siber, GR Welliver, RC AF Simoes, EAF Groothuis, JR Tristram, DA Allessi, K Lehr, MV Siber, GR Welliver, RC TI Respiratory syncytial virus-enriched globulin for the prevention of acute otitis media in high-risk children SO JOURNAL OF PEDIATRICS LA English DT Article ID MIDDLE-EAR FLUIDS; IMMUNE GLOBULIN; HAEMOPHILUS-INFLUENZAE; PROTECTIVE ACTIVITY; ANTIBODY-RESPONSE; INFANTS; METAANALYSIS; EFFICACY; ETIOLOGY; VACCINE AB Acute otitis media (AOM) has been associated with respiratory syncytial virus (RSV) infection; AOM develops in up to one third of children with RSV illness, A masked multicenter trial used an immune globulin enriched with RSV-neutralizing antibodies (RSVIG) to prevent RSV infection of the lower respiratory tract in 249 children with either bronchopulmonary dysplasia, congenital heart disease, or prematurity, To determine whether monthly RSVIG therapy might decrease the incidence of AOM, we retrospectively analyzed the records of 109 children in two of the centers, RSVIG was administered during RSV season at a high dose of 750 mg/kg monthly or a low dose of 150 mg/kg monthly; control children received no RSVIG, Children were examined for AOM by masked observers using pneumatic otoscopy, No difference in sex, race, underlying diagnosis, number of persons in the home, exposure to smoking, or atopy was found between groups studied, In recipients of high doses of RSVIG, significantly less AOM developed per season than in control children (mean episodes, 0.15 vs 0.78; p = 0.003), and fewer episodes of RSV-related AOM occurred (0 vs 5; p = 0.047), Low doses of RSVIG did not have a clinically significant impact, High doses of RSVIG appeared to have a significant impact on preventing AOM (both RSV- and non-RSV-related AOM) in these-high risk populations, This finding may have important implications in the development of improved preventive modalities for AOM. C1 UNIV COLORADO, SCH MED, DEPT PEDIAT, DIV INFECT DIS, DENVER, CO 80202 USA. UNIV COLORADO, SCH MED, DEPT PEDIAT, DIV NEONATOL, DENVER, CO 80202 USA. SUNY BUFFALO, MED CTR HOSP, DEPT PEDIAT, DIV INFECT DIS, BUFFALO, NY 14260 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV INFECT DIS, BOSTON, MA 02115 USA. MASSACHUSETTS PUBL HLTH BIOL LABS, BOSTON, MA USA. RP Simoes, EAF (reprint author), CHILDRENS HOSP, 1056 E 19TH AVE, B070, DENVER, CO 80218 USA. FU NCRR NIH HHS [MO1 RR00069]; NIAID NIH HHS [1AI82520] NR 26 TC 71 Z9 71 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 AUG PY 1996 VL 129 IS 2 BP 214 EP 219 DI 10.1016/S0022-3476(96)70245-7 PG 6 WC Pediatrics SC Pediatrics GA VK797 UT WOS:A1996VK79700006 PM 8765618 ER PT J AU Nyby, MD Sasaki, M Ideguchi, Y Wynne, HE Hori, MT Berger, ME Golub, MS Brickman, AS Tuck, ML AF Nyby, MD Sasaki, M Ideguchi, Y Wynne, HE Hori, MT Berger, ME Golub, MS Brickman, AS Tuck, ML TI Platelet lipoxygenase inhibitors attenuate thrombin- and thromboxane mimetic-induced intracellular calcium mobilization and platelet aggregation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DIACYLGLYCEROL KINASE INHIBITION; ARACHIDONIC-ACID LIBERATION; 12S-HYDROXYEICOSATETRAENOIC ACID; CELLS; 12-LIPOXYGENASE; POTENTIATION; ACTIVATION; ADP AB Platelets metabolize arachidonic acid via cyclooxygenase and lipoxygenase (LO) enzymatic pathways. Although platelets produce large amounts of arachidonic acid metabolites via the LO pathway, little is known regarding the physiological significance of these products. We used three structurally dissimilar LO inhibitors, 5,8,11-eicosatriynoic acid (ETI), baicalein and phenidone, and found that LO inhibition attenuated thrombin- and U46619 (a thromboxane mimetic)-induced increases of platelet intracellular calcium ([Ca++](i)) in washed human platelets. LO inhibitors also reduced platelet aggregation induced by thrombin and U46619. The effect of ETI on reducing the thrombin-induced [Ca++](i) elevation persisted even when cation channels were blocked, suggesting that LO inhibitors modify release of Ca from intracellular stores. Stimulating endogenous LO product formation potentiated thrombin-induced [Ca++](i) responses and aggregation, and these effects were eliminated by ETI. ETI did not alter inositol 1,4,5-trisphosphate production in stimulated platelets, but increased platelet cyclic AMP production in thrombin- or forskolin-stimulated platelets. These results suggest that LO products are regulators of platelet [Ca++](i) mobilization and aggregation in response to some agonists, and that LO inhibitors may work in part by modifying platelet cyclic AMP metabolism. C1 US DEPT VET AFFAIRS,DEPT ENDOCRINOL 111E,SEPULVEDA,CA 91343. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. FU NHLBI NIH HHS [R01 HL41295] NR 20 TC 40 Z9 41 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1996 VL 278 IS 2 BP 503 EP 509 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA360 UT WOS:A1996VA36000007 PM 8768697 ER PT J AU Souba, WW AF Souba, WW TI No margin, no mission SO JOURNAL OF SURGICAL RESEARCH LA English DT Editorial Material RP Souba, WW (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CAMBRIDGE,MA 02138, USA. NR 4 TC 5 Z9 5 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 AUG PY 1996 VL 64 IS 2 BP 109 EP 111 DI 10.1006/jsre.1996.0334 PG 3 WC Surgery SC Surgery GA VG714 UT WOS:A1996VG71400001 PM 8812619 ER PT J AU Biederman, J Faraone, S Mick, E Wozniak, J Chen, L Ouellette, C Marrs, A Moore, P Garcia, J Mennin, D Lelon, E AF Biederman, J Faraone, S Mick, E Wozniak, J Chen, L Ouellette, C Marrs, A Moore, P Garcia, J Mennin, D Lelon, E TI Attention-deficit hyperactivity disorder and juvenile mania: An overlooked comorbidity? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; attention-deficit hyperactivity disorder; comorbidity ID DEPRESSIVE VARIANT SYNDROME; BIPOLAR AFFECTIVE-DISORDER; THERAPEUTIC CONSIDERATIONS; PREPUBERTAL CHILDREN; RISK-FACTORS; ONSET; CHILDHOOD; ADOLESCENT; PROBANDS; ILLNESS AB Objective: To evaluate the psychiatric, cognitive, and functional correlates of attention-deficit hyperactivity disorder (ADHD) children with and without comorbid bipolar disorder (BPD). Method: DSM-III-R structured diagnostic interviews and blind raters were used to examine psychiatric diagnoses at baseline and 4-year follow-up in ADHD and control children. In addition, subjects were evaluated for cognitive, academic, social, school, and family functioning. Results: BPD was diagnosed in 11% of ADHD children at baseline and in an additional 12% at 4-year follow-up. These rates were significantly higher than those of controls at each assessment. ADHD children with comorbid BPD at either baseline or follow-up assessment had significantly higher rates of additional psychopathology, psychiatric hospitalization, and severely impaired psychosocial functioning than other ADHD children. The clinical picture of bipolarity was mostly irritable and mixed. ADHD children with comorbid BPD also had a very severe symptomatic picture of ADHD as well as prototypical correlates of the disorder. Comorbidity between ADHD and BPD was not due to symptom overlap. ADHD children who developed BPD at the 4-year follow-up had higher initial rates of comorbidity, more symptoms of ADHD, worse scores on the CBCL, and a greater family history of mood disorder compared with non-BPD, ADHD children. Conclusions: The results extend previous results documenting that children with ADHD are at increased risk of developing BPD with its associated severe morbidity, dysfunction, and incapacitation. C1 HARVARD UNIV,SCH MED,INST PSYCHIAT EPIDEMIOL & GENET,BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. MASSACHUSETTS HLTH CTR,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,PSYCHIAT SERV,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 53 TC 270 Z9 281 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1996 VL 35 IS 8 BP 997 EP 1008 DI 10.1097/00004583-199608000-00010 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UY926 UT WOS:A1996UY92600010 PM 8755796 ER PT J AU Lerner, LH Wiss, K Gellis, S Barnhill, R AF Lerner, LH Wiss, K Gellis, S Barnhill, R TI An unusual pustular eruption in an infant with Down syndrome and a congenital leukemoid reaction SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CUTIS; MANIFESTATIONS; TRISOMY-21; DISORDERS; NEWBORN AB Congenital leukemia and leukemoid reactions may be indistinguishable on clinical and histologic grounds and are highly associated with trisomy 21. This report characterizes a specific vesiculopustular skin eruption in an infant with Down syndrome and a congenital leukemoid reaction. On the first day of life an unusual vesiculopustular eruption developed, starting in areas of cutaneous trauma. A biopsy revealed immature myeloid cells in an epidermal spongiotic vesiculopustule and in a perivascular distribution, suggestive of leukemia cutis. As the peripheral blood smear normalized, the eruption cleared. Myelodysplasia subsequently developed and evolved into acute myelogenous leukemia. This is the first detailed report of a specific skin infiltrate caused by the immature cells of a leukemoid reaction. Skin infiltration by immature myeloid cells during a congenital leukemoid reaction may portend an aggressive course of the myeloproliferative disorder. C1 UNIV MASSACHUSETTS,MED CTR,DIV DERMATOL,WORCESTER,MA. CHILDRENS HOSP,MED CTR,DIV DERMATOL,BOSTON,MA 02115. CHILDRENS HOSP,MED CTR,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP Lerner, LH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV DERMATOPATHOL,WARREN 827,FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 15 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1996 VL 35 IS 2 BP 330 EP 333 DI 10.1016/S0190-9622(96)90662-3 PN 2 PG 4 WC Dermatology SC Dermatology GA VA758 UT WOS:A1996VA75800014 PM 8698919 ER PT J AU Mickelson, JK Lakkis, NM VillarrealLevy, G Hughes, BJ Smith, CW AF Mickelson, JK Lakkis, NM VillarrealLevy, G Hughes, BJ Smith, CW TI Leukocyte activation with platelet adhesion after coronary angioplasty: A mechanism for recurrent disease? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE FACTOR; ENDOTHELIAL-CELLS; CARDIOPULMONARY BYPASS; UNSTABLE ANGINA; ATHEROSCLEROTIC PLAQUES; MYOCARDIAL-INFARCTION; NEUTROPHIL ADHESION; HEART-DISEASE; CARDIAC DEATH; RESTENOSIS AB Objectives. The purpose of this pilot study was to determine whether leukocyte activation occurs, whether leukocyte-platelet complexes develop and whether there is any association between these findings and clinical outcome after coronary angioplasty, Background, Increased expression of CD11b on monocytes and neutrophils promotes their adhesion to endothelial cells, extracellular matrix and smooth muscle cells, Thrombin activated plate lets adhere to monocytes and neutrophils through P-selectin, These cell complexes may affect the inflammatory process and, thus, the outcome of coronary angioplasty, Methods. During elective single-vessel coronary angioplasty in 11 men, samples were obtained for how cytometric detection of CD11b, as well as the percent of leukocytes with adherent platelets and the intensity of bound platelet fluorescence (number of platelets/leukocyte). Results. After angioplasty, there was an increase in CD11b (monocytes: p = 0.001, neutrophils: p = 0.02) and leukocytes with adherent platelets (p = 0.02), During follow-up, five patients remained in stable condition and six had subsequent clinical events: restenosis and progression of disease requiring coronary artery bypass grafting (n = 3), myocardial infarction involving the dilated artery (n = 1) and unstable angina (n = 2), Values for leukocyte CD11b expression, the percent of leukocytes with adherent platelets and the intensity of bound platelet fluorescence were higher both before and after angioplasty in the six patients experiencing clinical events, Conclusions, Despite standard aspirin and heparin therapy, leukocyte activation with platelet adherence occurs after coronary angioplasty, The magnitude of leukocyte activation and platelet adherence appears to be higher in patients experiencing late clinical events. C1 BAYLOR COLL MED,DEPT MED,CARDIOL SECT,HOUSTON,TX 77030. DEPT VET AFFAIRS MED CTR,HOUSTON,TX. RP Mickelson, JK (reprint author), TEXAS CHILDRENS HOSP,CLIN CARE CTR,SPEROS P MARTEL LAB LEUKOCYTE BIOL,SUITE 1130,6621 FANNIN,HOUSTON,TX 77030, USA. FU NIAID NIH HHS [AI23521] NR 59 TC 218 Z9 223 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1996 VL 28 IS 2 BP 345 EP 353 DI 10.1016/0735-1097(96)00164-7 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UZ529 UT WOS:A1996UZ52900010 PM 8800108 ER PT J AU Sagie, A Freitas, N Padial, LR Leavitt, M Morris, E Weyman, AE Levine, RA AF Sagie, A Freitas, N Padial, LR Leavitt, M Morris, E Weyman, AE Levine, RA TI Doppler echocardiographic assessment of long-term progression of mitral stenosis in 103 patients: Valve area and right heart disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PRESSURE HALF-TIME; TRICUSPID REGURGITATION; NATURAL-HISTORY; FOLLOW-UP; QUANTIFICATION; ULTRASOUND AB Objectives. The purpose of this study was to determine, in a large referral population, the rate of echocardiographic change in mitral valve area (MVA) without interim intervention, to deter mine which factors influence progression of narrowing and to examine associated changes in the right side of the heart. Background. Little information is currently available on the echocardiographic progression of mitral stenosis, particularly on progressive changes in the right side of the heart and the ability of a previously proposed algorithm to predict progression. Methods. We studied 103 patients (mean age 61 years; 74% female),vith serial two-dimensional and Doppler echocardiography. The average interval between entry and most recent follow-up study was 3.3 +/- 2 years (range 1 to 11). Results. During the follow up period, MVA decreased at a mean rate of 0.09 cm(2)/year. In 28 patients there was no decrease, in 40 there was only relatively little change (<0.1 cm(2)/year) and in 35 the rate of progression of mitral valve narrowing was more rapid (greater than or equal to 0.1 cm(2)/year). The rate of progression was significantly greater among patients with a larger initial MVA and milder mitral stenosis (0.12 vs. 0.06 vs. 0.03 cm(2)/year for mild, moderate and severe stenosis, p < 0.01). Although the rate of mitral valve narrowing was a weak function of initial MVA and echocardiographic score by multivariate analysis, no set of individual values or cutoff points of these variables or pressure gradients could predict this rate in individual patients. There was a significant increase in right ventricular diastolic area (17 to 18.7 cm(2)) and tricuspid regurgitation grade (2+ to 3+; p < 0.0001 between entry and follow-up studies). Progression in right heart disease occurred even in patients with minimal or no change in MVA. Patients with associated aortic regurgitation had a higher rate of decrease in;MVA than did those with trace or no aortic regurgitation (0.19 vs. 0.086 cm(2)/year, p < 0.05). Conclusions. The rate of initial valve narrowing in individual patients is variable and cannot be predicted by initial MVA, mitral valve score or transmitral gradient, alone or in combination. Right heart disease can progress independent of mitral valve narrowing. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 31 TC 34 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1996 VL 28 IS 2 BP 472 EP 479 DI 10.1016/0735-1097(96)00153-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UZ529 UT WOS:A1996UZ52900030 PM 8800128 ER PT J AU Godley, CD Warren, RL Sheridan, RL McCabe, CJ AF Godley, CD Warren, RL Sheridan, RL McCabe, CJ TI Nonoperative management of blunt splenic injury in adults: Age over 55 years as a powerful indicator for failure SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RUPTURED SPLEEN; SELECTIVE MANAGEMENT; NONSURGICAL MANAGEMENT; EARLY OPERATION; TRAUMA; SPLENECTOMY; SAFE; EXPERIENCE; CHILDREN; REPAIR AB Selective nonoperative management of adults with blunt splenic injury continues to evolve. Predictive factors associated with successful nonoperative management have primarily been clinical criteria such as hemodynamic stability and the degree of associated injuries. This study evaluates the role of patient selection in the safety and success of nonoperative management of adults with blunt splenic injury. STUDY DESIGN: Herein, we present a retrospective analysis of the management and outcome of 135 adult (16 years of age or older) patients with blunt splenic injury at a large urban Level 1 trauma center during a six-year period. RESULT: A total of 46 adult patients were treated nonoperatively after blunt splenic injury during the study period. Patient ages ranged from 16 to 93 years (mean, 36.9 years) with 11 patients 55 years of age or older. Nonoperative management was successful in 24 (52 percent) patients. Patients failing nonoperative management were significantly older than patients successfully observed (mean age, 48.1 and 26.7 years, respectively). There were ten (91 percent) failures among the 11 patients 55 years of age or older compared to 12 (34 percent) failures among younger adults despite similar mean computed tomography splenic injury grading and Injury Severity Scores (p<0.01). Complications were significantly more prevalent in older patients than in younger patients who failed observation (p<0.01). CONCLUSIONS: Nonoperative management of adults with blunt splenic injury commonly fails in older patients independent of other clinical and radiographic variables. We conclude that age over 55 years is a contraindication to nonoperative management of patients with blunt splenic injury. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 47 TC 55 Z9 57 U1 0 U2 0 PU AMER COLL SURGEONS PI CHICAGO PA 54 EAST ERIE ST, CHICAGO, IL 60611 SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 1996 VL 183 IS 2 BP 133 EP 139 PG 7 WC Surgery SC Surgery GA VA209 UT WOS:A1996VA20900008 PM 8696544 ER PT J AU Pearlman, RA AF Pearlman, RA TI Challenges facing physicians and healthcare institutions caring for patients with mental incapacity SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID PATIENTS RESUSCITATION PREFERENCES RP Pearlman, RA (reprint author), UNIV WASHINGTON,VET AFFAIRS PUGET SOUND HLTH CARE SYST,NW ETH CTR VET HLTH CARE,SEATTLE,WA 98195, USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1996 VL 44 IS 8 BP 994 EP 996 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VA563 UT WOS:A1996VA56300021 PM 8708317 ER PT J AU Cudkowicz, ME Brown, RH AF Cudkowicz, ME Brown, RH TI An update on superoxide dismutase 1 in familial amyotrophic lateral sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 6th International Symposium on MND/ALS CY OCT, 1995 CL DUBLIN, IRELAND SP Motor Neurone Dis Assoc, Irish Motor Neurone Dis Assoc, Int Alliance Motor Neuron Dis Assoc ID MOTOR-NEURON DISEASE; CENTRAL-NERVOUS-SYSTEM; NATURAL-HISTORY; POINT MUTATION; SOD-1 GENE; IDENTIFICATION; MUTANT; MICE; SUPEROXIDE-DISMUTASE-1; PEROXYNITRITE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02115. NR 61 TC 23 Z9 23 U1 0 U2 1 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 AUG PY 1996 VL 139 SU S BP 10 EP 15 DI 10.1016/0022-510X(96)00084-6 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VN554 UT WOS:A1996VN55400003 PM 8899652 ER PT J AU Jiang, N Finklestein, SP Do, TY Caday, CG Charette, M Chopp, M AF Jiang, N Finklestein, SP Do, TY Caday, CG Charette, M Chopp, M TI Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE basic fibroblast growth factor; focal cerebral ischemia; cerebral infarction ID PROGRAMMED CELL-DEATH; HEAT-SHOCK PROTEIN; ARTERY OCCLUSION; HIPPOCAMPAL-NEURONS; ENDOTHELIAL-CELLS; FGF RECEPTOR; ISCHEMIA; DAMAGE; INJURY; BRAIN AB Basic fibroblast growth factor (bFGF) is a potent neurotrophic and vasoactive peptide. Previous studies have shown that intraventricularly-administered bFGF reduces the size of cerebral infarcts following focal ischemia. In the current study, we tested the effects of intravenously-administered bFGF in a model of focal ischemia/reperfusion. The right middle cerebral artery of mature male Wistar rats was occluded by intraluminal suture. After 2 h of occlusion, the suture was removed and intravenous infusion of bFGF in vehicle (45 mu g/kg/h) or vehicle alone was begun, lasting 3 h. Animals were weighed and evaluated neurologically until sacrifice 7 days after ischemia. The volume of cerebral infarcts was then determined by H and E staining and image analysis. We found a 40% reduction in infarct volume in bFGF- vs. vehicle-treated rats (n = 11 vs. 11, P < 0.05). Reduction in infarct volume was associated with improved neurological outcome and regained body weight in bFGF-treated animals (both P < 0.05). No change in blood pressure was found during bFGF treatment. These results show that the delayed intravenous administration of bFGF reduces infarct size in this model of focal ischemia/reperfusion. The mechanisms of infarct reduction may include direct cytoprotective and/or vasoactive effects. C1 MASSACHUSETTS GEN HOSP EAST,CNS,GROWTH FACTOR RES LAB,DEPT NEUROL,CHARLESTOWN,MA 02129. HENRY FORD HOSP,DEPT NEUROL,CTR STROKE RES,DETROIT,MI 48202. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. CREAT BIOMOL,HOPKINTON,MA. FU NINDS NIH HHS [NS 29463, NS 10828, NS 33627] NR 42 TC 66 Z9 72 U1 0 U2 2 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 AUG PY 1996 VL 139 IS 2 BP 173 EP 179 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VC065 UT WOS:A1996VC06500002 PM 8856649 ER PT J AU Lukaszewicz, GC Souba, WW Abcouwer, SF AF Lukaszewicz, GC Souba, WW Abcouwer, SF TI Induction of cytokine-induced neutrophil chemoattractant (CINC) mRNA in the lungs of septic rats SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 27-30, 1995 CL HALIFAX, CANADA SP Amer Assoc Surg Trauma DE cytokine-induced neutrophil chemoattractant; chemokine; sepsis; lipopolysaccharide; lungs ID RESPIRATORY-DISTRESS SYNDROME; EPITHELIOID CELL-LINE; INTERLEUKIN-8; EXPRESSION; INJURY; MODEL; GENE; KC; PURIFICATION; FIBROBLASTS AB To study cytokine-induced neutrophil chemoattractant (CMC) mRNA induction in lungs of normal, neutropenic, and adrenalectomized rats after intraperitoneal Escherichia coli lipopolysaccharide (LPS) administration and in cultured rat pulmonary cell lines after exposure to mediators of the septic response, Materials and Methods: Northern blotting was used to assay relative CINC mRNA levels and a colorimetric myeloperoxidase assay was used as a measure of neutrophil infiltration, Results: After a single dose of LPS, rapid induction of CINC mRNA coincided with neutrophil infiltration into lungs, a response that lasted approximately 12 to 24 hours, Multiple LPS treatments resulted in a similar CINC response, but a more prolonged myeloperoxidase response. CINC mRNA induction in lungs was heightened 30% in adrenalectomized animals and 400% in nentropenic ones. LPS and cytokines induced CINC mRNA in cultured endothelial and epithelial cells, Conclusions: Induction of CINC mRNA expression in pulmonary endothelial and/or epithelial cells by systemic LPS or cytokines may play a role in mediating neutrophil infiltration into lungs during sepsis, Markedly increased CINC induction in the lungs of neutropenic animals suggests that neutrophils may act to inhibit expression of this chemoattractant via a negative feedback mechanism. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NHLBI NIH HHS [R01-HL-44986] NR 31 TC 23 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 1996 VL 41 IS 2 BP 222 EP 228 DI 10.1097/00005373-199608000-00005 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA VC511 UT WOS:A1996VC51100005 PM 8760528 ER PT J AU Cotter, G Moshkovitz, Y Barash, P Baum, A Faibel, H Segal, E AF Cotter, G Moshkovitz, Y Barash, P Baum, A Faibel, H Segal, E TI Ventricular fibrillation in the patient with blunt trauma: Not always exsanguination SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID MYOCARDIAL CONTUSION; CHEST TRAUMA; CARDIAC INJURY; CLINICAL-SIGNIFICANCE; COMMOTIO-CORDIS; DIAGNOSIS; ARREST; DYSFUNCTION; FREQUENCY; OUTCOMES AB Three cases of successful prehospital resuscitation of blunt trauma patients sustaining cardiac arrest resulting from ventricular fibrillation are reported. Although probably uncommon, ventricular fibrillation not caused by severe hypovolemia, exsanguination, or severe hypoxia in the setting of blunt trauma might be a treatable cause of cardiac arrest, Early electrocardiographic monitoring of patients with blunt trauma, including those with cardiac arrest, can detect this small, yet easily salvageable group of patients. C1 ASSAF HAROFE MED CTR,DEPT CARDIOL,IL-70300 ZERIFIN,ISRAEL. CHAIM SHEBA MED CTR,DEPT ANESTHESIOL & INTENS CARE,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,DEPT CARDIAC SURG,IL-52621 TEL HASHOMER,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL & INTENS CARE,BOSTON,MA 02114. RP Cotter, G (reprint author), ASSAF HAROFE MED CTR,DEPT MED A,IL-70300 ZERIFIN,ISRAEL. NR 38 TC 6 Z9 7 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD AUG PY 1996 VL 41 IS 2 BP 345 EP 347 DI 10.1097/00005373-199608000-00026 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA VC511 UT WOS:A1996VC51100034 PM 8760549 ER PT J AU Zhu, ZM DeLuca, NA Schaffer, PA AF Zhu, ZM DeLuca, NA Schaffer, PA TI Overexpression of the herpes simplex virus type 1 immediate-early regulatory protein, ICP27, is responsible for the aberrant localization of ICP0 and mutant forms of ICP4 in ICP4 mutant virus-infected cells SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; EARLY GENE-EXPRESSION; POLYACRYLAMIDE GELS; ELECTROPHORETIC TRANSFER; ALPHA PROTEIN-ICP27; DELETION MUTANTS; BINDING PROTEIN; TRANSACTIVATION; HSV-1; DNA AB ICP0 and ICP4 are immediate-early regulatory proteins of herpes simplex virus type 1, Previous studies by Knipe and Smith demonstrated that these two proteins are characteristically observed in the nuclei of wild-type virus-infected cells but predominantly in the cytoplasms of cells infected with several ICP4 temperature-sensitive (fs) mutant viruses at the nonpermissive temperature (NPT) (D. hi, Knipe and J. L. Smith, Mel. Cell, Biol. 6:2371-2381, 1986), Consistent with this observation, it has been shown previously that ICP0 is present predominantly in the cytoplasms of cells infected with an ICP4 null mutant virus (n12) at high multiplicities of infection and that the level of ICP27, a third viral regulatory protein, plays an important role in determining the intracellular localization of ICP0 (Z. Zhu, W. Cai, and P. A. Schaffer, J. Virol. 68:3027-3040, 1994), To address whether the cytoplasmic localization of ICP0 is a common feature of cells infected with all ICP4 mutant viruses or whether mutant ICP4 polypeptides, together with ICP27, determine the intracellular localization of ICP0, we used double-staining immunofluorescence tests to examine the intracellular staining patterns of ICP0 and ICP4 in cells infected with an extensive series of ICP4 mutant viruses, In these tests, compared with the localization pattern of ICP0 in wild-type virus-infected cells, more ICP0 was detected in the cytoplasms of cells infected with all ICP4 mutants tested at high multiplicities of infection, Each of the mutant forms of ICP 1 exhibiting predominantly cytoplasmic staining contains both the nuclear localization signal and the previously mapped ICP27-responsive region (Z. Zhu and P. A, Schaffer, J. Virol, 69:49-59, 1995). No correlation between the intracellular staining patterns of ICP0 and mutant forms of ICP4 was demonstrated, suggesting that mutant ICP4 polypeptides per se are not responsible for retention of ICP0 in the cytoplasm, This observation was confirmed in studies of cells cotransfected with plasmids expressing ICP0 and mutant forms of ICP4, in which the staining pattern of ICP0 was not changed in the presence of mutant ICP4 proteins. Studies of cells infected at low multiplicities with a variety of ICP4 ts mutant viruses at the NPT showed that both ICP0 and fs forms of ICP4 were localized predominantly within the nucleus, These observations are a further indication that the aberrant localization of the ts forms of ICP4 at the NPT is not a direct result of specific mutations in the ICP4 gene, In the final series of tests, the localization of ICP0 in cells infected with a double-mutant virus unable to express either ICP4 or ICP27 was examined. In these tests, ICP0 was detected exclusively in the nuclei of Vero cells but in both the nuclei and the cytoplasms of ICP27-expressing cells infected with the double mutant. These results demonstrate that ICP27, rather than the absence of functional ICP4, is responsible for the cytoplasmic localization of ICP0 in ICP4 mutant virus-infected cells, Taken together, these findings demonstrate that the aberrant localization of ICP0 and certain mutant forms of ICP4 in cells infected with ICP4 mutant viruses is mediated by high levels of ICP27 resulting from the inability of mutant forms of ICP4 to repress the expression of ICP27. C1 UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15261. 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 45 TC 17 Z9 17 U1 0 U2 3 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 AUG PY 1996 VL 70 IS 8 BP 5346 EP 5356 PG 11 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200056 PM 8764045 ER PT J AU Huang, JK Kwong, J Sun, ECY Liang, TJ AF Huang, JK Kwong, J Sun, ECY Liang, TJ TI Proteasome complex as a potential cellular target of hepatitis B virus X protein SO JOURNAL OF VIROLOGY LA English DT Article ID ANTIGEN PRESENTATION; MULTICATALYTIC PROTEINASE; TRANSACTIVATION FUNCTION; TRANSCRIPTION FACTOR; SEQUENCE-ANALYSIS; DNA-BINDING; GENE; EXPRESSION; MHC; DEGRADATION AB Although the biological importance of hepatitis B virus X protein (HBX) in the life cycle of hepatitis B virus has been well established, the cellular and molecular basis of its function remains largely undefined. Despite the association of multiple activities with HEX, none of them appear to provide a unifying hypothesis regarding the true biological function of HBX. Identification and characterization of cellular targets of HBX remain an essential goal in the elucidation of the molecular mechanisms of HBX. Using the Saccharomyces cerevisiae two-hybrid system, we have identified and characterized a novel subunit of the proteasome complex (XAPC7) that interacts specifically with HBX. We also showed that HEX binds specifically to XAPC7 in vitro. Mutagenesis studies have defined the domains of interaction to be critical for the function of HBX. Furthermore, overexpression of XAPC7 appeared to activate transcription by itself and antisense expression of XAPC7 was able to block transactivation by HBX. Therefore, the proteasome complex is possibly a functional target of HBX in cells. C1 NIDDK,NIH,LIVER DIS SECT,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA54524]; NIDDK NIH HHS [P30DK-43351, DK01952] NR 58 TC 134 Z9 143 U1 1 U2 5 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 AUG PY 1996 VL 70 IS 8 BP 5582 EP 5591 PG 10 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200083 PM 8764072 ER PT J AU Baradaran, K Hardwicke, MA Dabrowski, CE Schaffer, PA AF Baradaran, K Hardwicke, MA Dabrowski, CE Schaffer, PA TI Properties of the novel herpes simplex virus type 1 origin binding protein, OBPC SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-REPLICATION; UL9 PROTEIN; VIRAL-DNA; GENE-PRODUCT; DOMAIN; ORIS; IDENTIFICATION; HELICASE; HSV-1; SEQUENCE AB We have recently identified a novel 53-kDa herpes simplex virus type 1 (HSV-1) protein encoded by, and in frame with, the 3' half of the UL9 open reading frame, designated OBPC (R. Baradaran, C. Dabrowski and P. A. Schaffer, J. Virol. 68:4251-4261, 1994). Here we show that OBPC is a nuclear protein synthesized at both early and late times postinfection. In gel-shift assays in vitro-synthesized OBPC bound to oriS site I DNA to form a complex identical in mobility to complex A, generated with infected cell extracts and site I DNA. OBPC inhibited both plaque formation and viral DNA replication in transient assays, consistent with its ability to bind to site I DNA and its limited ability to interact with other essential DNA replication proteins. These properties suggest that OBPC may play a role in the initiation, elongation, or packaging of viral DNA. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM VIROL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA08749]; NIAID NIH HHS [R01 AI28537, F32AI08878] NR 59 TC 16 Z9 16 U1 0 U2 0 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 AUG PY 1996 VL 70 IS 8 BP 5673 EP 5679 PG 7 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200098 PM 8764087 ER PT J AU Heuvel, GBV Bodmer, R McConnell, KR Nagami, GT Igarashi, P AF Heuvel, GBV Bodmer, R McConnell, KR Nagami, GT Igarashi, P TI Expression of a cut-related homeobox gene in developing and polycystic mouse kidney SO KIDNEY INTERNATIONAL LA English DT Article ID CCAAT DISPLACEMENT PROTEIN; C-MYC; DROSOPHILA; DISEASE; MICE; PROMOTER; LOCUS; DIFFERENTIATION; LOCALIZATION; PATTERNS AB cut is a diverged homeobox gene that is essential for normal development of the Malpighian tubules in Drosophila melanogaster. Homologues of Drosophila cut that encode transcriptional repressors have been identified in several mammalian species and cell lineages. We examined the expression of a murine cut homologue (named Cux-1) in the developing mouse using Northern blot analysis and in situ hybridization. At 12.5 d.p.c. and 13.5 d.p.c., Cux-1 was highly expressed in a subset of embryonic tissues, including the developing metanephros. Within the metanephros, Cux-1 was expressed in the nephrogenic zone including both mesenchymal cells (uninduced and condensed mesenchyme) and epithelial cells (ureteric buds, renal vesicles, S-shaped bodies). During later stages of nephrogenesis, Cux-1 was down-regulated such that there was minimal expression in mature glomeruli and tubules. In addition, Cux-1 was detected in the mesonephros, mesonephric duct, and bladder. Expression of Cux-1 was also examined in polycystic kidneys from C57BL/6J-cpk/cpk mice. At 21 days of age, Cux-1 was highly expressed in cyst epithelium of polycystic kidneys but was minimally expressed in kidneys from phenotypically normal littermates. These results demonstrate that a cut-related homeobox gene is expressed in the developing kidney and urinary tract of the mouse. Expression of Cux-1 in the kidney is inversely related to degree of cellular differentiation. Cux-1 may encode a transcriptional repressor that inhibits terminally differentiated gene expression during early stages of nephrogenesis. C1 YALE UNIV,SCH MED,NEPHROL SECT,DEPT INTERNAL MED,NEW HAVEN,CT 06520. UNIV MICHIGAN,DEPT BIOL,ANN ARBOR,MI 48109. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. OI Igarashi, Peter/0000-0001-8698-1185 NR 38 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 1996 VL 50 IS 2 BP 453 EP 461 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA UY726 UT WOS:A1996UY72600014 ER PT J AU Los, M Jansen, GH Kaelin, WG Lips, CJM Blijham, GH Voest, EE AF Los, M Jansen, GH Kaelin, WG Lips, CJM Blijham, GH Voest, EE TI Expression pattern of the vonHippel-Lindau protein in human tissues SO LABORATORY INVESTIGATION LA English DT Article ID VON HIPPEL-LINDAU; TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; LUNG-CANCER; DISEASE; MUTATIONS; VHL; ELONGATION; DELETION AB von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disorder characterized by extensively vascularized tumors and cysts in specific organs. The VHL gene product plays a critical role in the regulation of transcription elongation by RNA polymerase II. To provide insight into which cells the VHL protein is expressed, we performed immunohistochemistry on human tissue and tumors. The VHL protein was widely expressed in normal human tissue. The cellular distribution of the protein was confined to the cytoplasm of specific cell types. High levels of expression of the protein were observed in neural tissue, especially in Purkinje cells, Golgi type II cells, and dentate nucleus of the cerebellum, pontine nuclei, the inferior olivary nucleus of the medulla oblongata, orthosympathetic ganglia, myenteric, and submucous plexus of the colon. In the other target organs of the VHL disease, high expression was observed in the renal tubule system, the exocrine pancreas, the adrenal cortex, and liver parenchyma. The VHL protein was also expressed in organs not at risk for the disease. The eosinophilic cells of the pituitary gland, epithelial cells of the follicles of the thyroid, epithelial cells of the intestines, bile ducts, and bronchial epithelia showed strong VHL immunoreactivity. Immunohistochemistry did not facilitate the discrimination of tumors obtained from VHL patients or tumors unrelated to the VHF disease. Renal cell carcinomas, hemangioblastomas, and pheochromocytomas, either VHL-related or sporadic, demonstrated positive staining for the VHL protein, which suggests that the antibody also recognizes the mutated VHL protein. The present study suggests a role for the VHL gene that goes beyond the organs involved in the disease. The recognition of cell-specific VHL expression provides a framework for further studies to elucidate the normal function of the VHL gene and to determine its role in specific cell types. C1 UNIV UTRECHT HOSP,DEPT INTERNAL MED,SECT ONCOL,NL-3508 GA UTRECHT,NETHERLANDS. UNIV UTRECHT HOSP,DEPT PATHOL,NL-3508 GA UTRECHT,NETHERLANDS. DANA FARBER CANC INST,BOSTON,MA 02115. NR 30 TC 105 Z9 107 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 1996 VL 75 IS 2 BP 231 EP 238 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA VC435 UT WOS:A1996VC43500011 PM 8765323 ER PT J AU Lazor, JB Varvares, MA Montgomery, WW Goodman, ML Mackool, BT AF Lazor, JB Varvares, MA Montgomery, WW Goodman, ML Mackool, BT TI Management of airway obstruction in cicatricial pemphigoid SO LARYNGOSCOPE LA English DT Article ID IMMUNOFLUORESCENT; ANTIBODIES AB Cicatricial pemphigoid is a chronic vesiculobullous disease of the mucosal epithelium that primarily involves the oral cavity and the eyes. The clinical and histologic features are identical to those of bullous pemphigoid, and these features often can be nonspecific for other disease processes. It is not unusual for a period of 1 year or more to elapse before a diagnosis is made. The diagnosis of cicatricial pemphigoid requires characteristic lesions and histopathologic evidence of immunoglobulin deposition along the basement membrane, as well as a high index of suspicion. The authors detail a ease of cicatricial pemphigoid resulting in airway obstruction and present the treatment required for both stabilization of the airway and resolution of the disease process. C1 MASSACHUSETTS EYE & EAR INFIRM, DEPT OTOL & LARYNGOL, BOSTON, MA 02114 USA. MASSACHUSETTS EYE & EAR INFIRM, DEPT PATHOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT DERMATOL, BOSTON, MA 02114 USA. NR 14 TC 9 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X EI 1531-4995 J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1996 VL 106 IS 8 BP 1014 EP 1017 DI 10.1097/00005537-199608000-00020 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA VA646 UT WOS:A1996VA64600019 PM 8699892 ER PT J AU Stankewich, MC Francis, SA Vu, QU Schneeberger, EE Lynch, RD AF Stankewich, MC Francis, SA Vu, QU Schneeberger, EE Lynch, RD TI Alterations in cell cholesterol content modulate Ca2+-induced tight junction assembly by MDCK cells SO LIPIDS LA English DT Article ID COENZYME-A REDUCTASE; EPITHELIAL-CELLS; SQUALENE SYNTHASE; PLASMA-MEMBRANES; LIPIDS; ACID; DEGRADATION; PROTEINS; FIBROBLASTS; LOVASTATIN AB Transepithelial electrical resistance (TER), a measure of tight junction (TJ) barrier function, develops more rapidly and reaches higher values after preincubation of MDCK cells for 24 h with 2 mu M Lovastatin (lova), an inhibitor of 3-hydroxy- 3-methylglutaryl-CoA reductase. While this effect was attributed to a 30% fall in cholesterol (CH), possible effects of lova on the supply of prenyl group precursors could not be excluded. In the current study, strategies were devised to examine effects on TER of agents that simultaneously lower CH and increase the flux of intermediates through the CH biosynthetic pathway. Zaragozic acid, 20 mu M, an inhibitor of squalene synthase known to increase the synthesis of isoprenoids and levels of prenylated proteins, lowered cell CH by 30% after 24 h, while accelerating development of TER in the same manner as lova. TER was also enhanced, despite a 23% increase in the rate of [H-3]acetate incorporation into CH, when total CH was reduced by 45% during a 2-h incubation with 2 mM methyl beta-cyclodextrin (MBCD), an agent that stimulates CH efflux from cells. The fact that the rate of TER development was diminished when cell CH content was elevated by incubation with a complex of CH and MBCD is further evidence that this sterol modulates development of the epithelial barrier. Cell associated CH derived from the complex was similar to endogenous CH with respect to its accessibility to cholesterol oxidase. Lova's effect on TER was diminished when 5 mu g/mL of CH was added to the medium during the last 11 h of incubation with lova. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV LOWELL,DEPT BIOL SCI,LOWELL,MA 01854. FU NHLBI NIH HHS [HL 25822] NR 51 TC 23 Z9 23 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD AUG PY 1996 VL 31 IS 8 BP 817 EP 828 DI 10.1007/BF02522977 PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA VD352 UT WOS:A1996VD35200004 PM 8869884 ER PT J AU Frazier, AL Grier, HE Green, DM AF Frazier, AL Grier, HE Green, DM TI Treatment of endodermal sinus tumor in children using a regimen that lacks bleomycin SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE endodermal sinus tumor; germ cell tumor; cisplatin; children ID GERM-CELL TUMORS; COMBINATION CHEMOTHERAPY; PEDIATRIC-ONCOLOGY; GOOD-PROGNOSIS; VINBLASTINE; CISPLATIN; ETOPOSIDE; EXPERIENCE; CHILDHOOD; THERAPY AB Background: The EPO-VAC protocol was initiated to study 1) the efficacy of adding a cisplatin regimen (EPO) to VAC alone (the previous standard of care) and 2) the effect of replacing bleomycin with etoposide in the treatment of pediatric endodermal sinus tumors. Methods: The eligibility requirements for entry included age <21 years at diagnosis, diagnosis of a primary gonadal or extragonadal tumor (excluding central nervous system tumors and stage I testicular tumors), and histological confirmation of endodermal sinus tumor. Children who met the eligibility criteria were treated with four courses of EPO (etoposide, cisplatin, vincristine) alternating with three courses of VAC (vincristine, dactinomycin, and cyclophosphamide). Results: Eleven children were entered on the protocol. Six patients had extragonadal disease, five patients had ovarian primaries. Seven patients had low-stage tumor (I or II) and four had advanced-stage tumor (III or IV). Three of six evaluable patients attained a complete response at 21 weeks. The three patients with a residual soft tissue mass at restaging underwent further therapy. No patient has relapsed after a median of 51 (range 14-88) months of follow-up. Conclusions: The results of this protocol suggests that a cisplatin-containing regimen that lacks bleomycin is active in childhood endodermal sinus tumors. (C) 1996 Wiley-Liss, Inc. C1 ROSWELL PK CANC INST,DEPT PEDIAT,BUFFALO,NY. RP Frazier, AL (reprint author), DANA FARBER CANC INST,DEPT PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K07CA62252-01A1] NR 22 TC 5 Z9 5 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD AUG PY 1996 VL 27 IS 2 BP 69 EP 73 DI 10.1002/(SICI)1096-911X(199608)27:2<69::AID-MPO1>3.0.CO;2-R PG 5 WC Oncology; Pediatrics SC Oncology; Pediatrics GA UT140 UT WOS:A1996UT14000001 PM 8649322 ER PT J AU Kharasch, VS Lipsitz, S Santis, W Hallowell, JA Goorin, A AF Kharasch, VS Lipsitz, S Santis, W Hallowell, JA Goorin, A TI Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE pulmonary toxicity; chemotherapy; osteosarcoma; bleomycin toxicity; cyclophosphamide toxicity; pulmonary function after chemotherapy ID DIFFUSING-CAPACITY; FUNCTION TESTS; OSTEO-SARCOMA; LUNG; IRRADIATION AB Purpose: To assess long-term pulmonary effects of multiagent chemotherapy, we studied serial pulmonary function tests (PFTs) of 35 children with osteosarcoma up to 12 years after diagnosis. Patients and Methods: We analyzed 84 sets of PFTs from 35 patients diagnosed with osteosarcoma between 1981 and 1991. They received bleomycin, cyclophosphamide, methotrexate, doxorubicin, cisplatin, and actinomycin D over 9-12 months and we performed PFTs from 3 days to 152 months after diagnosis; Time period I included 36 PFTs (43%) performed between 1 and 5 months from diagnosis, time period II included 20 PFTs (24%) performed between 8 and 12 months from diagnosis, and time period III included 28 PFTs (33%) performed between 12 and 119 months from diagnosis. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and carbon monoxide diffusing capacity (DLCO) were analyzed. Maximal respiratory pressures and arterial blood gases were measured to assess muscle weakness and gas exchange, respectively. Mean differences in PFTs were compared among the three time periods and between time period pairs. Results: All mean PFT values showed significant differences among time periods. Significant decline in DLCO; (P = .012), TLC (P = .020), and FEV1 (P = .028) between time periods I and II were noted followed by a trend towards recovery between time periods II and III. Time periods I and III were not significantly different from one another. Mean PFTs performed after 2 years of diagnosis were not different from mean PFTs performed from diagnosis to 2 years. Conclusion: This dosage regimen of multiagent chemotherapy for osteosarcoma patients caused a transient, but significant, decline in PFTs within 8-12 months after administration but appears to cause no significant long-term pulmonary function abnormalities. (C) 1996 Wiley-Liss, Inc. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Kharasch, VS (reprint author), CHILDRENS HOSP BOSTON,DIV RESP DIS,300 LONGWOOD AVE,BOSTON,MA 02158, USA. NR 29 TC 12 Z9 12 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD AUG PY 1996 VL 27 IS 2 BP 85 EP 91 PG 7 WC Oncology; Pediatrics SC Oncology; Pediatrics GA UT140 UT WOS:A1996UT14000004 PM 8649325 ER PT J AU Krumholz, HM McHorney, CA Clark, L Levesque, M Baim, DS Goldman, L AF Krumholz, HM McHorney, CA Clark, L Levesque, M Baim, DS Goldman, L TI Changes in health after elective percutaneous coronary revascularization - A comparison of generic and specific measures SO MEDICAL CARE LA English DT Article DE angioplasty; quality of life; ischemic heart disease ID QUALITY-OF-LIFE; SURVEY SF-36; DISEASE AB OBJECTIVES. This study determines changes in health-related quality of life after elective percutaneous transluminal coronary angioplasty and compares generic and specific measures. METHODS. Changes in health-related quality of life were measured in consecutive, symptomatic patients undergoing elective percutaneous coronary revascularization using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), the Specific Activity Scale (SAS), and the Canadian Cardiovascular Society Classification (CCSC). The patients were interviewed as outpatients before admission and at least 6 months later. RESULTS. There were significant changes in the following SF-36 measures: physical functioning (postscore minus prescore = 19.1 +/- 24.1), role limitations due to physical-health problems (40.4 +/- 47.2), bodily pain (19.9 +/- 29.3), vitality (12.9 +/- 25.1), social functioning (20.0 +/- 33.1), role limitations due to emotional-health problems (26.7 +/- 49.0), and general mental health (7.1 +/- 21.2). General health perceptions did not change significantly, Internal-consistency reliability coefficients for these measures ranged from 0.73 to 0.91. There also was significant improvement in the CCSC class, but the SAS class did not change significantly. Overall, the SF-36 role-physical scale was the most responsive to changes after elective percutaneous coronary revascularization, followed;by the CCSC and the SF-36 physical functioning scale. CONCLUSIONS. Although this study cannot determine the causal role of elective percutaneous coronary revascularization in these changes, it provides support for the usefulness of these measures in future evaluations of this intervention. C1 UNIV WISCONSIN,MADISON MED SCH,DEPT PREVENT MED,MADISON,WI. UNIV WISCONSIN,MADISON MED SCH,DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,HLTH SERV RES & DEV PROGRAM,MADISON,WI. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,CARDIOVASC DIV,BOSTON,MA. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. RP Krumholz, HM (reprint author), YALE UNIV,SCH MED,SECT CARDIOVASC MED,POB 208017,333 CEDAR ST,NEW HAVEN,CT 06520, USA. NR 15 TC 44 Z9 45 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1996 VL 34 IS 8 BP 754 EP 759 DI 10.1097/00005650-199608000-00003 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VB193 UT WOS:A1996VB19300003 PM 8709657 ER PT J AU Mort, EA Edwards, JN Emmons, DW Convery, K Blumenthal, D AF Mort, EA Edwards, JN Emmons, DW Convery, K Blumenthal, D TI Physician response to patient insurance status in ambulatory care clinical decision-making - Implications for quality of care SO MEDICAL CARE LA English DT Article DE primary health care; health insurance; medical indigency; quality of health care; delivery of health care; physician-patient relation ID HEALTH-INSURANCE; BREAST-CANCER; MEDICAL-CARE; HOSPITAL PATIENTS; MASSACHUSETTS; ACCESS; WOMEN; INEQUITIES; CALIFORNIA; AMERICANS AB OBJECTIVES. Individuals without health insurance in general receive fewer health services and are more likely than insured patients to experience poor outcomes. The main goal of this research was to study whether physicians' clinical recommendations vary for insured and uninsured patients, implying that physicians' choices of care may mediate insurance-related differences in health care use. METHODS. The authors designed clinical scenarios that describe routine decisions encountered by primary care physicians in ambulatory settings. Scenarios were designed to include discretionary, nondiscretionary, preventive, and diagnostic/therapeutic services. Insurance status of patients was indicated as either insured or uninsured for the service under consideration. Scenarios were presented to a nationally representative sample of primary care physicians (n = 1182) as part of the American Medical Association 1992 Socioeconomic Monitoring System Survey. Physicians were assigned randomly to receive eight scenarios in which patients were either insured or uninsured. For each scenario, physicians were asked to indicate the percentage of patients for whom they would recommend a given service. RESULTS. After controlling for variables associated with nonresponse, we found that physicians who were presented scenarios with insured patients recommended services for 72% of patients, and physicians who were presented scenarios with uninsured patients recommended the same services for 67% of patients (P < 0.001). Physicians recommended both discretionary services (50% versus 42%; P < 0.001) and nondiscretionary services more often for insured than uninsured patients (93% versus 91%; P < 0.05). CONCLUSIONS. In self-reports, physicians are more likely to recommend services for insured than for uninsured patients, and more so when services are discretionary. This provides evidence that physicians' recommendations may be important mediators of insurance-related variation in the use of health-care services. Higher rates of use among the insured may not always reflect higher quality of care, particularly when the service is discretionary in nature. C1 MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,HLTH CARE POLICY & DEV UNIT,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. AMER MED ASSOC,CTR HLTH POLICY RES,CHICAGO,IL 60610. NR 42 TC 52 Z9 52 U1 3 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1996 VL 34 IS 8 BP 783 EP 797 DI 10.1097/00005650-199608000-00006 PG 15 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VB193 UT WOS:A1996VB19300006 PM 8709660 ER PT J AU Weiss, MJS Wagner, SH Bauman, ML AF Weiss, MJS Wagner, SH Bauman, ML TI A validated case study of facilitated communication SO MENTAL RETARDATION LA English DT Article ID AUTISM; WORDS AB The case of a 13-year-old boy with autism, severe mental retardation, and a seizure disorder who was able to demonstrate valid facilitated communication was described. In three independent trials, short stories were presented to him, followed by validation test procedures with an uninformed facilitator providing physical support to the subject's arm. In Trials 1 and 3, several specific answers were provided that clearly indicated that the young man, not the uninformed facilitator, was the source of the information. Moreover, some responses seemed to imply that the subject was employing simple inferential and abstract reasoning. This case study adds to the small, but growing number of demonstrations that facilitated communication can sometimes be a valid method for at least some individuals with developmental disabilities. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP Weiss, MJS (reprint author), BEHAV PEDIAT & FAMILY DEV,205 RAWSON RD,BROOKLINE,MA 02146, USA. NR 25 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSN MENTAL RETARDATION PI WASHINGTON PA 444 N CAPITOL ST, NW, STE 846, WASHINGTON, DC 20001-1512 SN 0047-6765 J9 MENT RETARD JI Ment. Retard. PD AUG PY 1996 VL 34 IS 4 BP 220 EP 230 PG 11 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA VD965 UT WOS:A1996VD96500003 PM 8828341 ER PT J AU Golub, TR Goga, A Barker, GF Afar, DEH McLaughlin, J Bohlander, SK Rowley, JD Witte, ON Gilliland, DG AF Golub, TR Goga, A Barker, GF Afar, DEH McLaughlin, J Bohlander, SK Rowley, JD Witte, ON Gilliland, DG TI Oligomerization of the ABL tyrosine kinase by the Ets protein TEL in human leukemia SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; POSITIVE HUMAN LEUKEMIAS; ACUTE MYELOID-LEUKEMIA; P210 BCR ABL; CHROMOSOMAL TRANSLOCATION; PHILADELPHIA-CHROMOSOME; TRANSCRIPTIONAL ACTIVATION; DNA-BINDING; C-ABL; GENE AB TEL is a member of the Ets family of transcription factors which are frequently rearranged in human leukemia. The mechanism of TEL-mediated transformation, however, is unknown. We report the cloning and characterization of a chromosomal translocation associated with acute myeloid leukemia which fuses TEL to the ABL tyrosine kinase. The TEL-ABL fusion confers growth factor-independent growth to the murine hematopoietic cell line Ba/F3 and transforms Rat-1 fibroblasts and primary murine bone marrow cells. TEL-ABL is constitutively tyrosine phosphorylated and localizes to the cytoskeleton. A TEL-ABL mutant containing an ABL kinase-inactivating mutation is not constitutively phosphorylated and is nontransforming but retains cytoskeletal localization. However, constitutive phosphorylation, cytoskeletal localization, and transformation are all dependent upon a highly conserved region of TEL termed the helix-loop-helix (HLH) domain. TEL-ABL formed HLH-dependent homo-oligomers in vitro, a process critical for tyrosine kinase activation. These experiments suggest that oligomerization of TEL-ABL mediated by the TEL HLH domain is required for tyrosine kinase activation, cytoskeletal localization, and transformation. These data also suggest that oligomerization of Ets proteins through the highly conserved HLH domain may represent a previously unrecognized phenomenon. C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90095. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. OI Bohlander, Stefan/0000-0002-2202-9088 FU NCI NIH HHS [CA 57261, CA 42557, CA 53867] NR 54 TC 276 Z9 281 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 AUG PY 1996 VL 16 IS 8 BP 4107 EP 4116 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500014 PM 8754809 ER PT J AU Myers, MG Zhang, YT Aldaz, GAI Grammer, T Glasheen, EM Yenush, L Wang, LM Sun, XJ Blenis, J Pierce, JH White, MF AF Myers, MG Zhang, YT Aldaz, GAI Grammer, T Glasheen, EM Yenush, L Wang, LM Sun, XJ Blenis, J Pierce, JH White, MF TI YMXM motifs and signaling by an insulin receptor substrate 1 molecule without tyrosine phosphorylation sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; S6 KINASE; IRS-1; ACTIVATION; STIMULATION; PHOSPHOTYROSINE; 3'-KINASE; DOMAINS; CELLS AB Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) by the activated receptors for insulin, IGF-1, and various cytokines creates binding sites for signaling proteins with Src homology 2 domains (SH2 proteins). Determining the role of specific SH2 proteins during insulin signaling has been difficult because IRS-1 possesses as many as 18 potential tyrosine phosphorylation sites, several of which contain redundant motifs. Using 32D cells, which contain no endogenous IRS proteins, we compared the signaling ability of an IRS-1 molecule in which 18 potential tyrosine phosphorylation sites were replaced by phenylalanine (IRS-1(F18))) with two derivative molecules which retained three YMXM motifs (IRS-1(3YMXM)) or the two COOH-terminal SHP2-Fyn binding sites (IRS-1(YCT)). During insulin stimulation, IRS-1(F18) failed to undergo tyrosine phosphorylation or mediate activation of the phosphotidylinositol (PI) 3'-kinase or p70(s6k); IRS-1(YCT) was tyrosine phosphorylated but also failed to mediate these signaling events. Neither IRS-1(3YMXM) nor IRS-1(YCT) mediated activation of mitogen-activated protein kinases. IRS-1(F18) and IRS-1(YCT) partially mediated similar levels of insulin-stimulated mitogenesis at high insulin concentrations, however, suggesting that IRS-1 contains phosphotyrosine-independent elements which effect mitogenic signals, and that the sites in IRS-1(YCT) do not augment this signal. IRS-1(3YMXM) mediated the maximal mitogenic response to insulin, although the response to insulin was more sensitive with wild-type IRS-1. By contrast, the association of IRS-1(3YMXM) with PI 3'-kinase was more sensitive to insulin than the association with IRS-1. Thus, the binding of SH2 proteins (such as PI 3'-kinase) by YMXM moths in IRS-1 is an important element in the mitogenic response, but other elements are essential for full mitogenic sensitivity. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NCI NIH HHS [CA 46595]; NIDDK NIH HHS [DK 38712, DK 43808] NR 56 TC 69 Z9 69 U1 0 U2 4 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 AUG PY 1996 VL 16 IS 8 BP 4147 EP 4155 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500018 PM 8754813 ER PT J AU Milne, GT Jin, SF Shannon, KB Weaver, DT AF Milne, GT Jin, SF Shannon, KB Weaver, DT TI Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; HUMAN AUTOANTIGEN KU; V(D)J RECOMBINATION; ILLEGITIMATE RECOMBINATION; PROTEIN-KINASE; YEAST; GENE; TRANSFORMATION; BINDING; DISRUPTION AB DNA double-strand break (DSB) repair in mammalian cells is dependent on the Ku DNA binding protein complex. However, the mechanism of Ku-mediated repair is not understood. We discovered a Saccharomyces cerevisiae gene (KU80) that is structurally similar to the 80-kDa mammalian Ku subunit. Ku80 associates with the product of the HDFI gene, forming the major DNA end-binding complex of yeast cells. DNA end binding was absent in ku80 Delta, hdfl Delta, or ku80 Delta hdfl Delta strains. Antisera specific for epitope tags on Ku80 and Hdfl were used in supershift and immunodepletion experiments to show that both proteins are directly involved in DNA end binding. In vivo, the efficiency of two DNA end-joining processes were reduced >10-fold in ku80 Delta, hdf7 Delta, or ku80 Delta hdfl Delta strains: repair of linear plasmid DNA and repair of an HO endonuclease-induced chromesomal DSB. These DNA-joining defects correlated with DNA damage sensitivity, because ku80 Delta and hdfl Delta strains were also sensitive to methylmethane sulfonate (MMS). Ku-dependent repair is distinct from homologous recombination, because deletion of KU80 and HDFI increased the MMS sensitivity of rad52 Delta Interestingly, rad5o Delta, also shown here to be defective in end joining, was epistatic with Ku mutations for MMS repair and end joining. Therefore, Ku and Rad50 participate in an end-joining pathway that is distinct from homologous recombinational repair. Yeast DNA end joining is functionally analogous to DSB repair and V(D)J recombination in mammalian cells. C1 CHILDRENS HOSP, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MICROBIOL & MOLEC GENET, BOSTON, MA 02115 USA. NR 45 TC 231 Z9 233 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1996 VL 16 IS 8 BP 4189 EP 4198 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500023 PM 8754818 ER PT J AU Johnson, R Spiegelman, B Hanahan, D Wisdom, R AF Johnson, R Spiegelman, B Hanahan, D Wisdom, R TI Cellular transformation and malignancy induced by ras require c-jun SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATION DOMAIN; HA-RAS; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID RECEPTOR; FUNCTIONAL ANTAGONISM; EMBRYO FIBROBLASTS; PROTEIN-KINASES; FAMILY MEMBERS; T-ANTIGEN; GROWTH AB ras is an important oncogene in experimental animals and humans. In addition, activated ras proteins are potent inducers of the transcription factor AP-1, which is composed of heterodimeric complexes of Fos and Jun proteins. Together with the fact that deregulated expression of some AP-1 proteins can cause neoplastic transformation, this finding suggests that AP-1 may function as a critical ras effector. We have tested this hypothesis directly by analyzing the response to activated ras in cells that harbor a null mutation in the c-jun gene. The transcriptional response of AP-1-responsive genes to activated ras is severely impaired in c-jun null fibroblasts. Compared with wild-type cells, the c-jun null cells lack many characteristics of res transformation, including loss of contact inhibition, anchorage independence, and tumorigenicity in nude mice; these properties are restored by forced expression of c-jun. Rare tumorigenic variants of ras-expressing c-jun null fibroblasts do arise. Analysis of these variants reveals a consistent restoration of AP-1 activity. The results provide genetic evidence that c-jun is a crucial effector for transformation by activated ras proteins. C1 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,HORMONE RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. OI Johnson, Randall/0000-0002-4084-6639 NR 60 TC 235 Z9 235 U1 0 U2 2 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 AUG PY 1996 VL 16 IS 8 BP 4504 EP 4511 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500056 PM 8754851 ER PT J AU McGrew, MJ Bogdanova, N Hasegawa, K Hughes, SH Kitsis, RN Rosenthal, N AF McGrew, MJ Bogdanova, N Hasegawa, K Hughes, SH Kitsis, RN Rosenthal, N TI Distinct gene expression patterns in skeletal and cardiac muscle are dependent on common regulatory sequences in the MLC1/3 locus SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEAVY-CHAIN GENE; ENHANCER-BINDING FACTOR; LIGATION-MEDIATED PCR; TRANSCRIPTION FACTOR GATA-4; ALPHA-ACTIN PROMOTER; MYOSIN LIGHT CHAIN-1; TRANSGENIC MICE; CHLORAMPHENICOL ACETYLTRANSFERASE; MYOCARDIAL-CELLS; MOUSE EMBRYO AB The myosin light-chain 1/3 locus (MLC1/3) is regulated by two promoters and a downstream enhancer element which produce two protein isoforms in fast skeletal muscle at distinct stages of mouse embryogenesis. We have analyzed the expression of transcripts from the internal MLC3 promoter and determined that it is also expressed in the atria of the heart. Expression from the MLC3 promoter in these striated muscle lineages is differentially regulated during development. In transgenic mice, the MLC3 promoter is responsible for cardiac-specific reporter gene expression while the downstream enhancer augments expression in skeletal muscle. Examination of the methylation status of endogenous and transgenic promoter and enhancer elements indicates that the internal promoter is not regulated in a manner similar to that of the MLC1 promoter or the downstream enhancer. A GATA protein consensus sequence in the proximal MLC3 promoter but not the MLC1 promoter binds with high affinity to GATA-4, a cardiac muscle- and gut-specific transcription factor. Mutation of either the MEF2 or GATA motifs in the MLC3 promoter attenuates its activity in both heart and skeletal muscles, demonstrating that MLC3 expression in these two diverse muscle types is dependent on common regulatory elements. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED CARDIOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,BRONX,NY 10461. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NHLBI NIH HHS [HL02699]; NIAMS NIH HHS [R01AR41926] NR 76 TC 56 Z9 57 U1 0 U2 2 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 AUG PY 1996 VL 16 IS 8 BP 4524 EP 4534 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500058 PM 8754853 ER PT J AU Scheuner, D Eckman, C Jensen, M Song, X Citron, M Suzuki, N Bird, TD Hardy, J Hutton, M Kukull, W Larson, E LevyLahad, E Viitanen, M Peskind, E Poorkaj, P Schellenberg, G Tanzi, R Wasco, W Lannfelt, L Selkoe, D Younkin, S AF Scheuner, D Eckman, C Jensen, M Song, X Citron, M Suzuki, N Bird, TD Hardy, J Hutton, M Kukull, W Larson, E LevyLahad, E Viitanen, M Peskind, E Poorkaj, P Schellenberg, G Tanzi, R Wasco, W Lannfelt, L Selkoe, D Younkin, S TI Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease SO NATURE MEDICINE LA English DT Article ID PRECURSOR PROTEIN; APOLIPOPROTEIN-E; MISSENSE MUTATIONS; A-BETA; GENE; PEPTIDE; CELLS; CHROMOSOME-1; A-BETA-42(43); PATHOGENESIS AB To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0007), PS2(N141I) (P = 0.009), APP(K670N,M671L) (P < 0.0001), and APP(Y717I) (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzheimer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide. C1 CASE WESTERN RESERVE UNIV,DEPT NEUROSCI,CLEVELAND,OH 44106. MAYO CLIN JACKSONVILLE,JACKSONVILLE,FL 32224. HUDDINGE UNIV HOSP,KAROLINSKA INST,DEPT CLIN NEUROSCI & FAMILY MED,NOVUM KFC,S-14186 HUDDINGE,SWEDEN. CASE WESTERN RESERVE UNIV,DEPT PATHOL,CLEVELAND,OH 44106. HARVARD UNIV,SCH MED,CTR NEUROL DIS,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. TAKEDA CHEM IND LTD,DIV DISCOVERY RES,TSUKUBA,IBARAKI 30042,JAPAN. UNIV WASHINGTON,DEPT NEUROL,SEATTLE,WA 98185. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98185. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98185. UNIV WASHINGTON,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98185. UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98185. VET AFFAIRS PUGET SOUND HLTH CARE SYST,NEUROL SERV,SEATTLE,WA 98108. VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA 98108. UNIV S FLORIDA,DEPT PSYCHIAT,SUNCOAST ALZHEIMERS DIS LABS,TAMPA,FL 33613. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL,GENET & AGING UNIT,CHARLESTOWN,MA 02129. RI Hardy, John/C-2451-2009; OI Kukull, Walter/0000-0001-8761-9014 NR 40 TC 1832 Z9 1873 U1 18 U2 159 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 1996 VL 2 IS 8 BP 864 EP 870 DI 10.1038/nm0896-864 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UZ804 UT WOS:A1996UZ80400031 PM 8705854 ER PT J AU MartinMalo, A Rodriguez, M Martinez, ME Torres, A Felsenfeld, AJ AF MartinMalo, A Rodriguez, M Martinez, ME Torres, A Felsenfeld, AJ TI The interaction of PTH and dietary phosphorus and calcium on serum calcitriol levels in the rat with experimental renal failure SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE calcitriol; calcium; phosphorus; PTH; rat; renal failure ID PARATHYROID-HORMONE; CALCEMIC RESPONSE; 1,25-DIHYDROXYVITAMIN-D; HYPERPARATHYROIDISM; METABOLISM; MODERATE; RECEPTOR AB Background. Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phosphorus accumulation and high parathyroid hormone (PTH) levels, both inherent to renal failure, have different effects on calcitriol production; moreover, dietary calcium loading may have a separate inhibitory effect on calcitriol production. This study was designed to evaluate the relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels. Methods. Renal failure was surgically induced and rats were divided into normal, moderate renal failure, and advanced renal failure based on the serum creatinine. Each group was subdivided and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of dietary calcium and phosphorus loading on serum calcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet; both diets had negligible calcium (<0.05%). Results. With decreasing renal function, PTH increased and was greater in rats fed the HPD than the HCaD; serum calcitriol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P<0.01). The calcitriol response to a PTH infusion decreased as renal function decreased (P<0.05) but was greater on a low- (0.16%) than a high- (1%) phosphorus diet (P<0.05). Conclusions. Dietary calcium loading: either directly decreases serum calcitriol or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH on serum calcitriol is modified by dietary phosphorus; in moderate renal failure, serum calcitriol levels depend on a complex interaction between PTH and dietary calcium and phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass. C1 HOSP UNIV REINA SOFIA,UNIT INVEST,CORDOBA,SPAIN. HOSP UNIV REINA SOFIA,DEPT NEPHROL,CORDOBA,SPAIN. HOSP LA PAZ,MADRID,SPAIN. UNIV HOSP,DEPT NEPHROL,TENERIFE,SPAIN. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RI Rodriguez, teresa/H-5452-2011 NR 20 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD AUG PY 1996 VL 11 IS 8 BP 1553 EP 1558 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA VC629 UT WOS:A1996VC62900016 PM 8856210 ER PT J AU Schulz, JB Henshaw, DR MacGarvey, U Beal, MF AF Schulz, JB Henshaw, DR MacGarvey, U Beal, MF TI Involvement of oxidative stress in 3-nitropropionic acid neurotoxicity SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article; Proceedings Paper CT Workshop on Antioxidants CY NOV 12, 1994 CL HOLLYWOOD, FL ID BUTYL-ALPHA-PHENYLNITRONE; ENERGY-METABOLISM; FREE-RADICALS; BRAIN; STRIATUM; INJURY; TOXIN; GLUTAMATE; ISCHEMIA; DISEASE AB 3-Nitroproprionic acid (3-NP) is a plant mycotoxin which produces selective striatal lesions in both experimental animals and in man. We previously found evidence that its neurotoxicity may be mediated by a secondary excitotoxic mechanism. In the present study we examined whether oxidative stress plays a role in the neurotoxicity of 3-NP in vivo. We examined whether the free radical spin traps alpha-phenyl-n-tert-butyl-nitrone (PBN), n-tert-butyl-alpha-(2-sulfophenyl)-nitrone (S-PBN) or 5,5-dimethyl-1-pyrroline-n-oxide (DMPO) could attenuate the neurotoxicity of 3-NP. Striatal lesions produced by systemic administration of 3-NP were protected by pretreatment with DMPO, but the toxicity of 3-NP was increased by PBN or S-PBN pretreatment. The content of 3-NP in the plasma was increased by S-PBN, but not by DMPO consistent with an effect of S-PBN on 3-NP metabolism. Lesions produced by systemic administration of 3-NP increased the production of hydroxyl free radicals (. OH) in the striatum as assessed by the conversion of salicylate to 2,3 and 2,5 dihydroxybenzoic acid (DHBA). These results provide direct evidence that free radicals play a substantial role in the neurotoxicity of 3-NP induced neuronal injury. Copyright (C) 1996 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Schulz, Jorg/D-9786-2012 OI Schulz, Jorg/0000-0002-8903-0593 FU NINDS NIH HHS [NS10828, NS16367, NS31579] NR 25 TC 108 Z9 109 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD AUG PY 1996 VL 29 IS 2 BP 167 EP 171 DI 10.1016/0197-0186(95)00122-0 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UY764 UT WOS:A1996UY76400010 PM 8837046 ER PT J AU Morris, PP Choi, IS AF Morris, PP Choi, IS TI Cerebral vascular anatomy SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID MICROSURGICAL ANATOMY; POSTERIOR-FOSSA; ARTERY; VEINS AB The angiographic anatomy of the vascular supply to the brain is described. Commonly seen anatomic variants are discussed. Venous anatomy and its importance in the pathophysiology of certain disease states also are described. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,SECT INTERVENT NEURORADIOL,BOSTON,MA 02114. NR 21 TC 3 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 1996 VL 6 IS 3 BP 541 EP & PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VE671 UT WOS:A1996VE67100002 PM 8873092 ER PT J AU Growdon, JH Locascio, JJ Corkin, S GomezIsla, T Hyman, BT AF Growdon, JH Locascio, JJ Corkin, S GomezIsla, T Hyman, BT TI Apolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease SO NEUROLOGY LA English DT Article ID E EPSILON-2 ALLELE; TYPE-4 ALLELE; ONSET; FREQUENCY; RISK; PROGRESSION; PRECURSOR; PROTEIN; AGE AB Background: Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is a risk factor for developing Alzheimer's disease (AD) and is associated with a lower age of dementia onset. The purpose of this study was to determine whether apoE genotypes differentially influence the course of cognitive decline in AD dementia. Methods: We administered nine cognitive tests that assessed explicit memory, attention, language, visuospatial function, frontal-lobe function, and logical reasoning abilities to 66 probable AD patients every 6 to 24 months over a span of up to 5.5 years. We identified apoE genotype by a PCR-based method; there were 16 patients with epsilon 3/3, 34 with epsilon 3/4, and 16 with epsilon 4/4. Using regression statistical methods, we computed the change in performance for each test for each patient over time. We then analyzed the mean change in each test in patients grouped according to apoE genotype. Results: For the AD patients as a group, performance on all cognitive tests declined significantly over time, but the rate of decline did not vary significantly across apoE genotypes on any cognitive test. Specifically, the rate of cognitive decline was not faster in patients with an epsilon 4 allele than in those with epsilon 3/3. Conclusions: These results indicate that the mechanism placing individuals with an epsilon 4 allele at risk for developing AD does not influence the rate of cognitive decline. These observations imply that the influence of apoE epsilon 4 either precedes or occurs at an early point in the AD disease process. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. RP Growdon, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,WAC 830,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG06605, P50 AG05134]; PHS HHS [EG12406] NR 35 TC 128 Z9 129 U1 2 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1996 VL 47 IS 2 BP 444 EP 448 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA VC634 UT WOS:A1996VC63400021 PM 8757018 ER PT J AU Schacter, DL Curran, T Galluccio, L Milberg, WP Bates, JF AF Schacter, DL Curran, T Galluccio, L Milberg, WP Bates, JF TI False recognition and the right frontal lobe: A case study SO NEUROPSYCHOLOGIA LA English DT Article DE false recognition; frontal lobes; episodic memory ID SOURCE AMNESIA; RECOLLECTIVE EXPERIENCE; TEMPORAL-ORDER; MEMORY; JUDGMENTS; FREQUENCY; RETRIEVAL; RECALL; CONFABULATION; DISSOCIATION AB We described a patient, BG, who exhibited a striking pattern of false recognition after an infarction of the right frontal lobe. Seven experiments document the existence of the phenomenon, explore its characteristics, and demonstrate how it can be eliminated. BG showed pathologically high false alarm rates when stimuli were visual words (experiments 1 and 4), auditory words (experiment 2), environmental sounds (experiment 3), pseudowords (experiment 5), and pictures (experiment 7). His false alarms were not merely attributable to the semantic or physical similarity of studied and non-studied items (experiments 4 and 5). However BG's false recognitions were virtually eliminated by presenting him with categorized stimuli and testing him with new stimuli from non-studied categories (experiments 6 and 7). The results suggest that BG's false alarms may be attributable to an over-reliance on memory for general characteristics of the study episode, along with impaired memory for specific items. The damaged right frontal lobe mechanisms may normally support the monitoring and/or retrieval processes that are necessary for item-specific recognition. Copyright (C) 1996 Elsevier Science Ltd. C1 HARVARD UNIV, SCH MED, DEPT NEUROL, CTR MORPHOMETR ANAL, CAMBRIDGE, MA 02138 USA. W ROXBURY DEPT VET AFFAIRS MED CTR, CAMBRIDGE, MA USA. CTR GERIATR RES EDUC & CLIN, CAMBRIDGE, MA USA. MASSACHUSETTS GEN HOSP, CAMBRIDGE, MA USA. RP Schacter, DL (reprint author), HARVARD UNIV, DEPT PSYCHOL, 33 KIRKLAND ST, CAMBRIDGE, MA 02138 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [R01 AG08441]; NINDS NIH HHS [NS26895, P01 NS27950] NR 56 TC 210 Z9 211 U1 2 U2 10 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 AUG PY 1996 VL 34 IS 8 BP 793 EP 808 DI 10.1016/0028-3932(95)00165-4 PG 16 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA UW961 UT WOS:A1996UW96100004 PM 8817509 ER PT J AU Bruder, GE Otto, MW McGrath, PJ Stewart, JW Fava, M Rosenbaum, JF Quitkin, FM AF Bruder, GE Otto, MW McGrath, PJ Stewart, JW Fava, M Rosenbaum, JF Quitkin, FM TI Dichotic listening before and after fluoxetine treatment for major depression: Relations of laterality to therapeutic response SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE laterality; dichotic listening tests; depression; fluoxetine; antidepressive agents; treatment outcome ID COMPLEX TONE TEST; PERCEPTUAL ASYMMETRY; CEREBRAL LATERALITY; AFFECTIVE-DISORDER; WORDS TEST; PREDICTORS; MOOD; ANTIDEPRESSANTS; SCHIZOPHRENIA; SUBTYPES AB Despite the wide variance in therapeutic response to antidepressants, there are few clinical or biological predictors of treatment outcome. Studies have suggested the possible value of dichotic listening measures of perceptual asymmetry (PA) as predictors of treatment response. This study examined the relation between outcome of fluoxetine treatment and performance on verbal and nonverbal dichotic tests. As part of a multisite study, 86 outpatients with major depression were tested on dichotic fixed-words and complex-tones tests both before and during treatment. Fluoxetine responders differed from nonresponders in having greater right-ear (left-hemisphere) advantage for dichotic words and less left-ear (right-hemisphere) advantage for complex tones. There was no change in PA during fluoxetine treatment, which indicates that PA differences between treatment responders and nonresponders are stable (trait) characteristics. An aggregate, characteristic PA measure was the best predictor of responder status in a logistic regression analysis. Findings from two clinical centers support the hypothesis that a characteristic tendency for relatively greater left- than right-hemisphere activation during dichotic listening is associated with better outcome of fluoxetine treatment. C1 NEW YORK STATE PSYCHIAT INST & HOSP,DEPRESS EVALUAT SERV,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY. MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP Bruder, GE (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,DEPT BIOPSYCHOL,722 W168TH ST,NEW YORK,NY 10032, USA. RI McGrath, Patrick/I-6410-2013 OI McGrath, Patrick/0000-0001-7217-7321 FU NIMH NIH HHS [MH36295] NR 41 TC 32 Z9 35 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1996 VL 15 IS 2 BP 171 EP 179 DI 10.1016/0893-133X(95)00180-L PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UZ824 UT WOS:A1996UZ82400008 PM 8840353 ER PT J AU Ghogawala, Z Shumacher, JM Ogilvy, CS AF Ghogawala, Z Shumacher, JM Ogilvy, CS TI Distal basilar perforator artery aneurysm: Case report SO NEUROSURGERY LA English DT Article DE basilar artery; cerebral aneurysm; cerebral angiography; perforating artery; subarachnoid hemorrhage ID SUBARACHNOID HEMORRHAGE; BRANCHES; ETIOLOGY; SURGERY AB OBJECTIVE AND IMPORTANCE: Distal basilar artery aneurysms represent 5 to 8% of intracranial aneurysms. It is crucial to preserve all of the basilar apex perforating vessels when dissecting in this region. This report is the first to describe a rostral basilar perforating artery that was the anatomic origin of a cerebral aneurysm. CLINICAL PRESENTATION:A 56-year-old woman presenting with subarachnoid hemorrhage underwent initial four-vessel cerebral angiography that did not demonstrate the source of her hemorrhage. A follow-up cerebral angiogram 9 days later suggested a small aneurysm in the region of the left superior cerebellar artery. INTERVENTION: A left pterional craniotomy was performed. An aneurysm arising from the origin of a distal basilar perforating artery was identified and obliterated with a small vascular clip. Flow was preserved in the perforating vessel, and the patient had an excellent outcome. CONCLUSION: The findings in the report illustrate the novel anatomic principle that a distal basilar perforating vessel can serve as the anatomic origin of a cerebral aneurysm. Knowledge of this entity would be helpful in avoiding complications at surgery, including perforator injury or aneurysmal rupture in such cases. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT CEREBROVASC SURG,NEUROSURG SERV,BOSTON,MA 02114. LAHEY HITCHCOCK MED CTR,DEPT NEUROSURG,BURLINGTON,MA. NR 16 TC 17 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 1996 VL 39 IS 2 BP 393 EP 396 DI 10.1097/00006123-199608000-00034 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UY523 UT WOS:A1996UY52300076 PM 8832680 ER PT J AU Barker, FG AF Barker, FG TI Analysis of the relationship between long-term operative success and a transient or delayed operative side effect SO NEUROSURGERY LA English DT Article DE ablative procedures; numbness; side effect; statistical analysis; subsequent operation; toxicity ID CANCER CLINICAL-TRIALS; TRIGEMINAL NEURALGIA; SURVIVAL; RHIZOTOMY AB OBJECTIVE: Investigators sometimes correlate the success of an operative procedure with the presence of an operative side effect that is thought to reflect the efficacy of the procedure in some way. When the prevalence of the side effect increases or decreases with time, this type of analysis can introduce a systematic bias. METHODS: Monte Carlo-simulated patient cohorts with independently and randomly generated operative success and presence of side effects were generated. Kaplan-Meier analyses of operative success were stratified by the presence of side effects at various times after the ''operation.'' RESULTS: When the side effect (such as numbness after an ablative procedure) resolved during the study period in a significant proportion of patients, stratification by presence of the side effect at the end of the study period introduced a serious bias in favor of apparent better pain relief in patients without numbness. When the prevalence of the side effect increased with time (such as the requirement for a subsequent operation for radiation necrosis after brachytherapy or radiosurgical treatment of a glioma), the analysis was biased in favor of apparent longer survival for patients who experienced the side effect (i.e., those who required subsequent operations). CONCLUSION: Analyses operative success stratified by the presence of postoperative side effect with time-varying prevalence may be seriously biased anti should be interpreted with caution. RP Barker, FG (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,WARREN 905,32 FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 8 Z9 8 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 1996 VL 39 IS 2 BP 412 EP 415 DI 10.1097/00006123-199608000-00043 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UY523 UT WOS:A1996UY52300091 PM 8832685 ER PT J AU Guccione, AA Fagerson, TL Anderson, JJ AF Guccione, AA Fagerson, TL Anderson, JJ TI Regaining functional independence in the acute care setting following hip fracture SO PHYSICAL THERAPY LA English DT Article DE acute care; functional outcome; hip fractures; physical therapy; rehabilitation ID RECOVERY; OUTCOMES; PREDICTORS; DISCHARGE; SURVIVAL AB Background and Purpose. Factors that predict functional recovery in the first few days following hip fracture and that may facilitate discharge to the home directly from the acute care setting have not been identified. This study investigated the attainment of key functional milestones by patients and discharge status from an acute care hospital following hip fracture. Subjects. Subjects were 162 community-based individuals (59 men, 103 women) aged 60 years or older who were admitted to an acute care hospital following unilateral hip fracture. Methods. Data on personal, medical, surgical, hospital course, and acute rehabilitation factors as well as functional status and placement at the time of discharge were collected. Adjusted odds ratios were calculated to determine predictors of independence in seven types Of transfers and ambulation activities and discharge directly to the home. Results. Subjects who ambulated independently prior to fracture, stayed longer in the acute care setting, and received physical therapy on average more than once a day had improved odds of regaining independence in bed mobility, transfers, and ambulation. Subjects who regained independence and received physical therapy on average more than once a day had improved odds of discharge directly to the home from the acute care setting. Increasing age and postoperative complications reduced the odds of discharge directly home. Conclusion and Discussion. A substantial proportion of patients with hip fracture achieve independence in bed mobility and transfers and in ambulation with a walker during the early postoperative phase, although few progress to a higher level during a short-term stay in the acute care setting. Frequency of physical therapy, among other factors, appears to improve the odds of regaining functional independence and discharge directly to the home from the acute care setting. C1 MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,BOSTON,MA 02114. MALDEN HOSP,PHYS THERAPY DEPT,MALDEN,MA 02148. BEDFORD VET ADM MED CTR,HLTH SERV RES & DEV FIELD PROGRAM,BEDFORD,MA 01730. RP Guccione, AA (reprint author), HARVARD UNIV,SCH MED,DEPT ORTHOPAED,15 PARKMAN ST,WAC 128,BOSTON,MA 02114, USA. FU NIA NIH HHS [KO1 AG00567] NR 20 TC 47 Z9 49 U1 2 U2 3 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 AUG PY 1996 VL 76 IS 8 BP 818 EP 826 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA VB909 UT WOS:A1996VB90900002 PM 8710961 ER PT J AU Hong, L Goitein, M Bucciolini, M Comiskey, R Gottschalk, B Rosenthal, S Serago, C Urie, M AF Hong, L Goitein, M Bucciolini, M Comiskey, R Gottschalk, B Rosenthal, S Serago, C Urie, M TI A pencil beam algorithm for proton dose calculations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOTHERAPY; PATIENT AB The sharp lateral penumbra and the rapid fall-off of dose at the end of range of a proton beam are among the major advantages of proton radiation therapy. These beam characteristics depend on the position and characteristics of upstream beam-modifying devices such as apertures and compensating boluses. The extent of separation, if any, between these beam-modifying devices and the patient is particularly critical in this respect. We have developed a pencil beam algorithm for proton dose calculations which takes accurate account of the effects of materials upstream of the patient and of the air gap between them and the patient. The model includes a new approach to picking the locations of the pencil beams so as to more accurately model the penumbra and to more effectively account for the multiple-scattering effects of the media around the point of interest. We also present a faster broad-beam version of the algorithm which gives a reasonably accurate penumbra. Predictions of the algorithm and results from experiments performed in a large-field proton beam are presented. In general the algorithm agrees well with the measurements. C1 MT SINAI MED CTR,DEPT RADIAT ONCOL,NEW YORK,NY 10029. UNIV FLORENCE,DEPT MED PHYS,I-50121 FLORENCE,ITALY. HARVARD UNIV,HARVARD CYCLOTRON LAB,CAMBRIDGE,MA 02138. RP Hong, L (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. OI bucciolini, marta/0000-0002-4446-2640 FU NCI NIH HHS [CA21239, CA59267] NR 20 TC 205 Z9 207 U1 0 U2 14 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD AUG PY 1996 VL 41 IS 8 BP 1305 EP 1330 DI 10.1088/0031-9155/41/8/005 PG 26 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA VA701 UT WOS:A1996VA70100005 PM 8858722 ER PT J AU MartinezPerez, D Mulliken, JB Arceci, RJ AF MartinezPerez, D Mulliken, JB Arceci, RJ TI Langerhans cell histiocytosis: An uncommon disease commonly manifesting in the craniofacial skeleton SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID NECK MANIFESTATIONS; ORAL INVOLVEMENT; LESIONS; CHILDREN; HEAD; BONE AB Langerhans cell histiocytosis is an infrequent and enigmatic proliferative disorder that commonly presents in the head and neck region. This is an analysis of 77 patients with Langerhans cell histiocytosis treated at Children's Hospital and Dana Farber Cancer Institute from 1974 through 1993. The study focused on clinical findings, anatomic location and extent of disease, therapy, and outcome. The patients were, on average, under 5 years of age at initial presentation. Over 62 percent of the patients had signs and symptoms referred to the craniofacial skeleton. Osteolytic lesions of the cranium were the most common, followed, in frequency, by scalp rash, osteolytic mandibular tumor(s), enlarged nodes, and gingival swelling or ulceration. Single bony lesions usually were treated with curettage or radiotherapy. Chemotherapy was used commonly for advanced disease with multifocal or disseminated presentation. Initial therapy included moderate doses of single agents; other agents were added if no response was achieved. The natural history of Langerhans cell histiocytosis varied from an acute fulminant course, a waxing and waning chronic disease, to spontaneous regression. Young age at presentation and organ dysfunction predicted a poor prognosis. Statistical analysis showed that there was no significant relationship between outcome and extent of skeletal involvement when controlling for age or organ dysfunction. C1 CHILDRENS HOSP,DIV PLAST SURG,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 30 TC 9 Z9 9 U1 0 U2 0 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 AUG PY 1996 VL 98 IS 2 BP 211 EP 216 DI 10.1097/00006534-199608000-00002 PG 6 WC Surgery SC Surgery GA UY042 UT WOS:A1996UY04200002 PM 8764708 ER PT J AU Greenwald, DP Randolph, M May, JW AF Greenwald, DP Randolph, M May, JW TI Mechanical analysis of explanted silicone breast implants SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Smooth-walled silicone gel breast implants (n = 25) were removed from 15 women after implantation times that varied from 23 to 216 months (mean = 117 months; SEM = 12.9). Strips of implant shells were tested to failure by computer-controlled tensiometer. Regression analysis revealed significant negative correlation between age of implantation and shell strength (p < 0.05), shell toughness (p < 0.05), and shell elasticity (p < 0.05). These data suggest that exposure to the in vivo environment weakens silicone gel breast implant shells over time. C1 UNIV S FLORIDA,TAMPA,FL. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 8 TC 20 Z9 20 U1 0 U2 3 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 AUG PY 1996 VL 98 IS 2 BP 269 EP 272 DI 10.1097/00006534-199608000-00008 PG 4 WC Surgery SC Surgery GA UY042 UT WOS:A1996UY04200008 PM 8764714 ER PT J AU Reid, MS Ho, LB Berger, SP AF Reid, MS Ho, LB Berger, SP TI Effects of environmental conditioning on the development of nicotine sensitization: Behavioral and neurochemical analysis SO PSYCHOPHARMACOLOGY LA English DT Article DE environmental conditioning; nicotine; rat; sensitization; behavioral and neurochemical analysis ID LOCOMOTOR STIMULANT ACTION; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; TERMINAL FIELDS; TOLERANT RATS; COCAINE; AGONIST; MICROINJECTIONS; PRETREATMENT; AMPHETAMINE AB We have investigated the effects of environmental conditioning on the induction of nicotine sensitization of locomotion, stereotypy and nucleus accumbens dopamine release. Sprague-Dawley rats, some of which had been previously implanted with a microdialysis guide cannula over the nucleus accumbens, were sensitized with 5 days of repeated nicotine (0.6 mg/kg per day, SC) or saline injections (1 ml/kg per day). During nicotine treatment the drug administration was either paired with the microdialysis/activity monitor testing chamber (conditioned) (n=6) or with the animal's home cage (unconditioned) (n=6) and after 60 min the animal was returned to home cage and received a second injection of saline 15 min later. A third group received saline in the testing apparatus followed by nicotine in the home cage (pseudo-conditioned) (n=6). In the guide cannulated animals, 2 mm microdialysis probes were inserted after completing day 5 of treatment and all animals were tested for their response to nicotine (0.6 mg/kg, SC) on day 6. Both locomotor activity and nucleus accumbens dopamine release showed a larger response subsequent to nicotine challenge in the nicotine versus saline pretreated animals in the conditioned group, but not in the unconditioned group. In the pseudo-conditioned group there was an increase in the stereotypy responses to nicotine, however the locomotor and dopamine release responses were not significantly enhanced. The results from the conditioned group were confirmed in animals which were tested for behavioral activation and dopamine release simultaneously (n=5). These findings indicate that nicotine sensitization of locomotor activity and nucleus accumbens dopamine release (using a 5-day pretreatment protocol) is dependent on conditioning the animal to the testing environment during nicotine pretreatment. RP Reid, MS (reprint author), UNIV CALIF SAN FRANCISCO, DEPT PSYCHIAT, PSYCHIAT SERV 116W, SAN FRANCISCO VET AFFAIRS MED CTR, SAN FRANCISCO, CA 94121 USA. FU NIDA NIH HHS [T32 DA07250] NR 48 TC 49 Z9 49 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 1996 VL 126 IS 4 BP 301 EP 310 DI 10.1007/BF02247381 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VD849 UT WOS:A1996VD84900005 PM 8878346 ER PT J AU Kopans, DB Moore, RH McCarthy, KA Hall, DA Hulka, CA Whitman, GJ Slanetz, PJ Halpern, EF AF Kopans, DB Moore, RH McCarthy, KA Hall, DA Hulka, CA Whitman, GJ Slanetz, PJ Halpern, EF TI Positive predictive value of breast biopsy performed as a result of mammography: There is no abrupt change at age 50 years SO RADIOLOGY LA English DT Article DE breast neoplasms, diagnosis; breast radiography, utilization; cancer screening ID CANCER; WOMEN AB PURPOSE: To determine if the positive predictive value (PPV) of a biopsy initiated because of an abnormal mammogram changes abruptly at age 50 years. MATERIALS AND METHODS: The PPV and its variation with age was analyzed for 4,778 women who underwent biopsy for a clinically occult abnormality detected at mammography. The relationship of the results to the patient's age was analyzed with age represented as a continuous and two-categoried (< 50, > 50) measure. The latter measure represented an abrupt change, which distinguished those aged 49 years and younger from those aged 50 years and over. With this measure, the patients in each of the two age groups were statistically indistinguishable. RESULTS: The results were consistent with a steady increase in PPV and the yield of cancers with age, and there was no abrupt change at age 50 years. The modeled PPV for all cancers for these 4,778 patients was approximately 12% for women aged 40 years and increased to 46% by age 79 years. CONCLUSION: The PFV did not change abruptly at any age for women aged 40-79 years but increased steadily, which reflects the prior probability of breast cancer at each age. Inappropriate grouping of data can lead to misinterpretation of results. Screening guidelines should not be predicated on the false assumption that this variable changes at age 50 years. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. RP Kopans, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 12 TC 55 Z9 56 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1996 VL 200 IS 2 BP 357 EP 360 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UY078 UT WOS:A1996UY07800012 PM 8685325 ER PT J AU Zietman, AL Tibbs, MK Dallow, KC Smith, CT Althausen, AF Zlotecki, RA Shipley, WU AF Zietman, AL Tibbs, MK Dallow, KC Smith, CT Althausen, AF Zlotecki, RA Shipley, WU TI Use of PSA nadir to predict subsequent biochemical outcome following external beam radiation therapy for T1-2 adenocarcinoma of the prostate SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE prostate cancer; radiation; PSA nadir ID ANTIGEN; CANCER; RADIOTHERAPY AB Purpose. This study assessed the ability of nadir prostate-specific antigen (PSA) to act as an early surrogate for subsequent freedom from biochemical failure following radiation therapy for T1-2 prostatic adenocarcinoma. Methods and materials. A retrospective analysis was performed on the biochemicai outcome of 314 consecutive men with T1-2 disease treated by conventional external beam radiation at the Massachusetts General Hospital. Minimum follow up was 2 years, and failure was defined as three successive rises in serum PSA of greater than 10%. Kaplan-Meier actuarial analysis of outcome was employed. Results. The overall 5-year freedom from biochemical progression was 63%. For those who achieved a PSA nadir of less than or equal to 0.5 ng/ml (n = 123) it was 90%, for 0.6-1.0 ng/ml (n = 103) it was 55%, and for > 1.0 ng/ml (n = 88) it was 34%. Multivariate analysis showed an undetectable PSA nadir to be independent of Gleason grade and initial PSA in predicting subsequent outcome (P < 0.05). The likelihood of achieving an undetectable PSA nadir correlated strongly with the pretreatment value: 74% if this was below 4 ng/ml; 42% for those between 4.1 and 10 ng/ml; and 32% for those above 10 ng/ml. Conclusion. A PSA nadir of less than or equal to 0.5 ng/ml represents an early endpoint strongly predictive of a favorable outcome following radiation therapy which may be used for the rapid assessment of new radiation strategies. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,BOSTON,MA 02114. RP Zietman, AL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA 02114, USA. NR 16 TC 61 Z9 61 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 AUG PY 1996 VL 40 IS 2 BP 159 EP 162 DI 10.1016/0167-8140(96)01770-7 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VF711 UT WOS:A1996VF71100008 PM 8884970 ER PT J AU Manchanda, S Leevers, AM Wilson, CR Simon, PM Skatrud, JB Dempsey, JA AF Manchanda, S Leevers, AM Wilson, CR Simon, PM Skatrud, JB Dempsey, JA TI Frequency and volume thresholds for inhibition of inspiratory motor output during mechanical ventilation SO RESPIRATION PHYSIOLOGY LA English DT Article DE control of breathing; frequency, threshold; mammals, humans; motor output, respiratory; threshold, motor output inhibition; volume, threshold ID RESPIRATORY MUSCLE-ACTIVITY; CENTRAL APNEA; SLEEP; HUMANS; HYPOCAPNIA; WAKEFULNESS AB We quantified volume and frequency thresholds necessary for the inhibition of respiratory motor output during prolonged normocapnic mechanical ventilation in healthy subjects during wakefulness (n = 7) and NREM sleep (n = 5). Subjects were ventilated at eupneic frequency (fR) with 3 min step-wise increases in tidal volume (VT), or at eupneic VT with step-wise increases in fR, or by combinations of these two parameters. Inhibition of respiratory motor output was determined using mask pressure and, when available, esophageal pressure and diaphragmatic EMG. During wakefulness, the volume threshold (at eupneic fR) averaged 969 +/- 94 ml or 1.3-1.4 times the average eupneic tidal volume; the frequency threshold (at eupneic VT was 14.1 +/- 0.7 min(-1) or 1.2 times the average eupneic frequency. The volume threshold was reduced when MV was provided at an fR above the eupneic value, and the frequency threshold was decreased when MV was provided at a VT above the eupneic level. During NREM sleep (n = 5) the volume threshold for inhibition was 835 +/- 108 ml or 1.4-1.5 times eupneic VT. The inhibitory thresholds for VT and fR were reproducible upon repeat trials within subjects. We conclude that inhibition of respiratory motor output during prolonged normocapnic mechanical ventilation in wakefulness or NREM sleep is highly sensitive to changes in ventilator VT, fR and their combination. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED RES SERV,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,JOHN RANKIN LAB PULM MED,MADISON,WI 53705. UNIV WISCONSIN,DEPT PREVENT MED,JOHN RANKIN LAB PULM MED,MADISON,WI 53705. NR 28 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD AUG PY 1996 VL 105 IS 1-2 BP 1 EP 16 DI 10.1016/0034-5687(96)00037-0 PG 16 WC Physiology; Respiratory System SC Physiology; Respiratory System GA VK468 UT WOS:A1996VK46800001 PM 8897646 ER PT J AU Guccione, AA AF Guccione, AA TI Physical therapy for musculoskeletal syndromes SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID LOW-BACK-PAIN; CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; MEDICAL CONDITIONS; OSTEO-ARTHRITIS; CLINICAL-TRIAL; KNEE; FITNESS; DISABILITY; OSTEOARTHRITIS AB Judgments about the effectiveness of physical therapy in the treatment of musculoskeletal syndromes depend on the findings of the physical therapist's examination and the fit between the clinical problem and the intervention. Using a model of the process of disablement, this article outlines the theoretical basis for a physical therapist's role in remediating the impairments and functional limitations associated with musculoskeletal conditions. The research basis for the application of particular physical therapy procedures, including physical agents and mechanical modalities, to typical patient problems is presented. C1 HARVARD UNIV,SCH MED,DEPT ORTHOPAED,BOSTON,MA. RP Guccione, AA (reprint author), MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,15 PARKMAN ST WAC128,BOSTON,MA 02114, USA. FU NIA NIH HHS [K01AG00567] NR 53 TC 4 Z9 4 U1 1 U2 2 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 AUG PY 1996 VL 22 IS 3 BP 551 EP & DI 10.1016/S0889-857X(05)70287-8 PG 13 WC Rheumatology SC Rheumatology GA VA394 UT WOS:A1996VA39400009 PM 8844913 ER PT J AU Goldhirsch, A Gelber, RD AF Goldhirsch, A Gelber, RD TI Endocrine therapies of breast cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID LOW-DOSE AMINOGLUTETHIMIDE; PIEDMONT-ONCOLOGY-ASSOCIATION; GROWTH-FACTOR-BETA; POSTMENOPAUSAL PATIENTS; ADJUVANT TAMOXIFEN; AROMATASE INHIBITOR; RANDOMIZED TRIAL; MEDROXYPROGESTERONE ACETATE; PAST DECADE; PHASE-I C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. RP Goldhirsch, A (reprint author), OSPED CIVICO,INT BREAST CANC STUDY GRP,CH-6900 LUGANO,SWITZERLAND. NR 106 TC 36 Z9 37 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1996 VL 23 IS 4 BP 494 EP 505 PG 12 WC Oncology SC Oncology GA VD279 UT WOS:A1996VD27900013 PM 8757275 ER PT J AU Stafford, RS AF Stafford, RS TI Equal partners: A physician's call for a new spirit of medicine - Heymann,J SO SOCIAL SCIENCE & MEDICINE LA English DT Book Review RP Stafford, RS (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,HLTH CARE POLICY RES & DEV UNIT,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD AUG PY 1996 VL 43 IS 4 BP 570 EP 571 DI 10.1016/0277-9536(96)81763-1 PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA VB791 UT WOS:A1996VB79100020 ER PT J AU Hurwitz, EL Aker, PD Adams, AH Meeker, WC Shekelle, PG AF Hurwitz, EL Aker, PD Adams, AH Meeker, WC Shekelle, PG TI Manipulation and mobilization of the cervical spine - A systematic review of the literature SO SPINE LA English DT Review DE headache; neck pain; spinal manipulation ID RANDOMIZED CLINICAL-TRIAL; LOW-BACK-PAIN; EXTRACRANIAL VERTEBRAL ARTERY; CHRONIC NECK PAIN; CHIROPRACTIC MANIPULATION; MANUAL THERAPY; VERTEBROBASILAR ISCHEMIA; DIAPHRAGMATIC PARALYSIS; OUTCOME MEASURES; PERSISTENT BACK AB Study Design. Cervical spine manipulation and mobilization were reviewed in an analysis of the literature from 1966 to the present. Objectives. To assess the evidence for the efficacy and complications of cervical spine manipulation and mobilization for the treatment of neck pain and headache. Summary of Background Data. Although recent research has demonstrated the efficacy of spinal manipulation for some patients with low back pain, little is known about its efficacy for neck pain and headache. Methods. A structured search of four computerized bibliographic data bases was performed to identify articles on the efficacy and complications of cervical spine manual therapy. Data were summarized, and randomized controlled trials were critically appraised for study quality. The confidence profile method of meta-analysis was used to estimate the effect of spine manipulation on patients' pain status. Results. Two of three randomized controlled trials showed a short-term benefit for cervical mobilization for acute neck pain. The combination of three of the randomized controlled trials comparing spinal manipulation with other therapies for patients with subacute or chronic neck pain showed an improvement on a 100-mm visual analogue scale of pain at 3 weeks of 12.6 mm (95% confidence interval, -0.15, 25.5) for manipulation compared with muscle relaxants or usual medical care. The highest quality randomized controlled trial demonstrated that spinal manipulation provided short-term relief for patients with tension-type headache. The complication rate for cervical spine manipulation is estimated to be between 5 and 10 per 10 million manipulations. Conclusions. Cervical spine manipulation and mobilization probably provide at least short-term benefits for some patients with neck pain and headaches. Although the complication rate of manipulation is small, the potential for adverse outcomes must be considered because of the possibility of permanent impairment or death. C1 RAND CORP,SANTA MONICA,CA. CANADIAN MEM CHIROPRACT COLL,TORONTO,ON,CANADA. LOS ANGELES COLL CHIROPRACT,WHITTIER,CA. PALMER COLL CHIROPRACT W,SAN JOSE,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Hurwitz, EL (reprint author), UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,73-318 CTR HLTH SCI,LOS ANGELES,CA 90095, USA. NR 135 TC 236 Z9 239 U1 3 U2 20 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 1996 VL 21 IS 15 BP 1746 EP 1759 DI 10.1097/00007632-199608010-00007 PG 14 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA VA486 UT WOS:A1996VA48600007 PM 8855459 ER PT J AU Barr, JS AF Barr, JS TI Manipulation and mobilization of the cervical spine - A systematic review of the literature - Point of view SO SPINE LA English DT Editorial Material RP Barr, JS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 1996 VL 21 IS 15 BP 1759 EP 1760 DI 10.1097/00007632-199608010-00008 PG 2 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA VA486 UT WOS:A1996VA48600008 ER PT J AU Keller, RB Atlas, SJ Singer, DE Chapin, AM Mooney, NA Patrick, DL Deyo, RA AF Keller, RB Atlas, SJ Singer, DE Chapin, AM Mooney, NA Patrick, DL Deyo, RA TI The Maine Lumbar Spine Study .1. Background and concepts SO SPINE LA English DT Article DE behavior change; cohort study; feedback; lumbar disc surgery; natural history; outcomes research; sciatica; spinal stenosis; small area variations ID LOW-BACK-PAIN; SURGERY; OUTCOMES AB Study Design. This paper describes the background and factors that led to the development and implementation of the Maine Lumbar Spine Study, a prospective cohort study of patients undergoing surgical and nonsurgical treatment of herniated lumbar disc with sciatica and symptomatic spinal stenosis. Objectives. To define the factors leading to the study and the methods of designing and implementing a community-based effectiveness study to evaluate the outcomes of herniated lumbar intervertebral disc and spinal stenosis. Summary of Background Data. Variations in the utilization of surgery for these conditions and physicians' uncertainty regarding the best way to manage them resulted in support of a community-based study of the effectiveness of treatment alternatives. Methods. A prospective cohort design was used. Methods of patient enrollment, data collection, management, and analysis are described. An innovative method of ascertaining the representativeness of the enrolled versus nonenrolled patient population is presented. Results. The importance of developing community-based networks of physicians is discussed. Conclusions. These networks play an important role in analyzing practice pattern variations and in stimulating and participating in effectiveness research. Because effectiveness studies must be conducted at the community level, mechanisms must be developed with which to support and implement these efforts. C1 MAINE MED ASSESSMENT FDN,AUGUSTA,ME. MAINE HLTH INFORMAT CTR,AUGUSTA,ME. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED PRACTICES EVALUAT CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN INTERNAL MED UNIT,BOSTON,MA. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. FU AHRQ HHS [HS-06813-04, HS-06344, HS-08194] NR 17 TC 52 Z9 53 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 1996 VL 21 IS 15 BP 1769 EP 1776 DI 10.1097/00007632-199608010-00010 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA VA486 UT WOS:A1996VA48600010 PM 8855461 ER PT J AU Atlas, SJ Deyo, RA Keller, RB Chapin, AM Patrick, DL Long, JM Singer, DE AF Atlas, SJ Deyo, RA Keller, RB Chapin, AM Patrick, DL Long, JM Singer, DE TI The Maine Lumbar Spine Study .2. 1-year outcomes of surgical and nonsurgical management of sciatica SO SPINE LA English DT Article DE cohort study; lumbar disc surgery; natural history; outcomes research; sciatica ID LOW-BACK-PAIN; INTERVERTEBRAL-DISK; SURGERY; CHEMONUCLEOLYSIS; CHYMOPAPAIN; HERNIATION; TRIAL AB Study Design. The Maine Lumbar Spine Study is a prospective cohort study of patients recruited from the practices of orthopedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine. Objective. To assess 1-year outcomes of patients with sciatica believed to be due to a herniated lumbar disc treated surgically or nonsurgically. Summary of Background Data. Lumbar spine surgery rates very by geographic region and may reflect uncertainty about optimal clinical use. Methods. Eligible consenting patients participated in a baseline interview performed by study personnel and then were mailed follow-up questionnaires at 3, 6, and 12 months. Clinical data were obtained from a physician questionnaire. Outcomes included patient-reported symptoms of leg and back pain, functional status, disability, quality of life, and satisfaction with care. Results. Five hundred seven patients with sciatica 275 treated surgically and 232 treated nonsurgically initially, were enrolled. Surgically treated patients, on average, had more severe symptoms and had more severe physical and imaging findings than nonsurgically treated patients had severe symptoms, about half in each treatment group had symptoms that fell into a moderate category. At the 1-year evaluation, improvement in symptoms, functional status, and disability were found in both treatment groups. However, surgically treated patients reported significantly greater improvement. For the predominant symptom, either back or leg pain, 71% of surgically treated and 43% of nonsurgically treated patients reported definite improvement (P < 0.001). This effect was even greater after adjustment for differences between treatment groups at entry (relative odds of definite improvement, 4.3; P < 0.001). For patients with moderate symptoms and abnormal physical examination findings, surgical treatment also resulted in greater improvement than non-surgical treatment. However, there was little difference in the employment or workers' compensation status of patients treated surgically versus nonsurgically (5% vs. 7% unemployed at 1-year follow-up if employed at entry [P = 0.68]; 46% vs. 55% receiving workers' compensation at 1-year follow-up if receiving it at entry [P = 0.30] for surgical and nonsurgical management, respectively). For patients with mild symptoms, the benefits of surgical and nonsurgical treatment were similar. Conclusions. Although surgically treated patients were on a average more symptomatic at entry, there was substantial overlap in symptoms between surgically treated and nonsurgically treated patients. Surgically treated patients with sciatica reported substantially greater improvement at 1-year follow-up. However, employment and compensation outcomes were similar between the two treatment groups, and surgery appeared to provide little advantage for the subset of patients with mild symptoms. These results should be interpreted cautiously, because surgical treatment was not assigned randomly. Long-term follow-up will determine if these differences persist. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED PRACTICES EVALUAT CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,GEN INTERNAL MED UNIT,BOSTON,MA. MED MED ASSESSMENT FDN,AUGUSTA,ME. MAINE HLTH INFORMAT CTR,AUGUSTA,ME. EASTERN MAINE MED CTR,BANGOR,GWYNEDD,WALES. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. FU AHRQ HHS [HS-06344, HS-08194] NR 23 TC 206 Z9 210 U1 0 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 1996 VL 21 IS 15 BP 1777 EP 1786 DI 10.1097/00007632-199608010-00011 PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA VA486 UT WOS:A1996VA48600011 PM 8855462 ER PT J AU Atlas, SJ Deyo, RA Keller, RB Chapin, AM Patrick, DL Long, JM Singer, DE AF Atlas, SJ Deyo, RA Keller, RB Chapin, AM Patrick, DL Long, JM Singer, DE TI The Maine Lumbar Spine Study .3. 1-year outcomes of surgical and nonsurgical management of lumbar spinal stenosis SO SPINE LA English DT Article DE lumbar disc surgery; lumbar spinal stenosis; natural history; outcomes; prospective cohort study ID LOW-BACK-PAIN; METAANALYSIS AB Study Design. A prospective cohort study of patients with lumbar spinal stenosis recruited from the practices of orthopedic surgeons and neurosurgeons throughout Maine. Objective. To assess 1-year outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically. Summary of Background Data. No randomized trials and few nonexperimental studies have compared surgical and nonsurgical treatment of patients with lumbar spinal stenosis. The authors' goal was to asses 1-year outcomes of patents with lumbar spinal stenosis treated surgically or nonsurgically. Methods. Eligible, consenting patients participated in baseline interviews and were then mailed follow-up questionnaires at 3, 6, and 12 months. Clinical data were obtained from a physician questionnaire. Outcomes included patient-reported symptoms of leg and back pain, functional status, disability, and satisfaction with care. Results. One hundred forty-eight patients with lumbar spinal stenosis were enrolled, of whom 81 were treated surgically and 67 treated nonsurgically. On average, patients in the surgical group had more severe imaging findings and symptoms and worse functional status than patients in the nonsurgical group at entry. Few patients with mild symptoms were treated surgically, and few patients with severe symptoms were treated nonsurgically. However, of the patients with moderate symptoms, a similar percent were treated surgically or nonsurgically. One year after study entry, 28% of nonsurgically and 55% of surgically treated patients reported definite improvements in their predominant symptoms (P = 0.003). For patients with moderate symptoms, outcomes for surgically treated patients were also improved compared with those of nonsurgically treated patients. Surgical treatment remained a significant determinant of 1-year outcome, even after adjustment for differences between treatment groups at entry (P = 0.05). The maximal benefit of surgery was observed by the time of the first follow-up evaluation, which was at 3 months. Although few nonsurgically treated patients experienced a worsening of their condition, there was little improvement in symptoms and functional status compared with study entry. Conclusions. At a 1-year evaluation of patient-reported outcomes, patients with sever lumbar spinal stenosis who were treated surgically had greater improvement than patients treated nonsurgically. Comparisons of outcomes by treatment received must be made cautiously because of differences in baseline characteristics. A determination of whether the outcomes observed persist requires long-term follow-up. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED PRACTICES EVALUAT CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,GEN INTERNAL MED UNIT,BOSTON,MA. MAINE MED ASSESSMENT FDN,AUGUSTA,ME. MAINE HLTH INFORMAT CTR,AUGUSTA,ME. EASTERN MAINE MED CTR,BANGOR,ME. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA. FU AHRQ HHS [HS-08194, HS-06344] NR 20 TC 185 Z9 192 U1 2 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 1996 VL 21 IS 15 BP 1787 EP 1794 DI 10.1097/00007632-199608010-00012 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA VA486 UT WOS:A1996VA48600012 PM 8855463 ER PT J AU Greenberg, SM Briggs, ME Hyman, BT Kokoris, GJ Takis, C Kanter, DS Kase, CS Pessin, MS AF Greenberg, SM Briggs, ME Hyman, BT Kokoris, GJ Takis, C Kanter, DS Kase, CS Pessin, MS TI Apolipoprotein E epsilon 4 is associated with the presence and earlier onset of hemorrhage in cerebral amyloid angiopathy SO STROKE LA English DT Article DE amyloid; apolipoproteins; hemorrhage; risk factors ID SPORADIC ALZHEIMERS-DISEASE; ALLELE; PROTEIN; RISK AB Background and Purpose Cerebral amyloid angiopathy is an important cause of intracerebral hemorrhage in the elderly. The epsilon 4 allele of the apolipoprotein E gene, recently established as a genetic risk for Alzheimer's disease, has also been suggested as a possible risk factor for cerebral amyloid angiopathy. We sought to determine whether this allele is specifically associated with hemorrhages related to amyloid angiopathy and whether it correlates with the age at which first amyloid angiopathy-related hemorrhage occurs. Methods Forty-five consecutive patients presenting with lobar hemorrhage were prospectively classified according to clinical, radiological, and when available, pathological features and evaluated for apolipoprotein E genotype. They were compared with 1899 elderly patients from a population-based sample and with 18 consecutive patients with hemorrhages in deep regions typical of a hypertensive mechanism. Results Patients with multiple hemorrhages confirmed to the lobar territory demonstrated a greater than twofold overrepresentation (P<.001) in frequency of the apolipoprotein E epsilon 4 allele compared with the population-based sample. Apolipoprotein E genotypes of patients with hemorrhages in deep territories resembled the population sample. Among patients with strictly lobar hemorrhages, carriers of the epsilon 4 allele had their first hemorrhage more than 5 years earlier than noncarriers (mean age at first hemorrhage, 73.4 +/- 8.0 versus 78.9 +/- 7.4 years; P = .033). These effects were independent of the accompanying presence of Alzheimer's disease. Conclusions The data support a specific role for apolipoprotein E epsilon 4 in accelerating the process that leads to amyloid angiopathy-related hemorrhage. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT NEUROL,BOSTON,MA 02111. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. BOSTON UNIV,MED CTR,DEPT NEUROL,BOSTON,MA. RP Greenberg, SM (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,VINCENT BURNHAM 811,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG05134, AG12406] NR 25 TC 157 Z9 161 U1 1 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 1996 VL 27 IS 8 BP 1333 EP 1337 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VA092 UT WOS:A1996VA09200013 PM 8711797 ER PT J AU Lo, EH Hara, H Rogowska, J Trocha, M Pierce, AR Huang, PL Fishman, MC Wolf, GL Moskowitz, MA AF Lo, EH Hara, H Rogowska, J Trocha, M Pierce, AR Huang, PL Fishman, MC Wolf, GL Moskowitz, MA TI Temporal correlation mapping analysis of the hemodynamic penumbra in mutant mice deficient in endothelial nitric oxide synthase gene expression SO STROKE LA English DT Article DE cerebral ischemia focal; hemodynamics; nitric oxide synthase; tomography; mice ID CEREBRAL-ARTERY OCCLUSION; BLOOD-FLOW; PATHOPHYSIOLOGY; ISCHEMIA AB Background and Purpose Mice containing deletions in the genes encoding nitric oxide (NO) synthase have been useful to dissect the role of NO in cerebral ischemia. We recently reported that mice lacking expression of the endothelial isoform of NO synthase (eNOS) develop larger infarcts after middle cerebral artery occlusion. Because NO or a related product of NO synthase activity is important for relaxation of cerebral blood vessels, we examined for possible hemodynamic differences in the peri-ischemic zone of eNOS-deficient and wild-type mice after middle cerebral artery occlusion using functional CT scanning techniques. Methods Wild-type SV129 mice (n=10) and mice deficient in eNOS gene expression (n=10) were subjected to middle cerebral artery occlusion under halothane anesthesia. Thirty minutes after ischemia, functional CT scanning was performed with dynamic scanning protocols to measure the cerebral transit profiles of injected contrast agents. A temporal correlation mapping technique was used to analyze the pattern of hemodynamic perturbations based on alterations in the shape of the cerebral transit profiles. Statistical thresholds defined the hemodynamic core and penumbra Results Hemodynamic deficits were more severe in the mutant than wild-type mouse. When expressed as a percentage of the total insult, core areas were significantly increased in mutant mice (39.8+/-3.7%) Compared with wild types (28.8+/-3.4%). Conversely, areas of the hemodynamic penumbra were significantly smaller in mice deficient in eNOS activity (60.2+/-3.7%) than in wild-type mice (71.2+/-3.4%). Furthermore, the calculated relative perfusion index within the hemodynamic penumbra was significantly lower in the group with eNOS gene deletion (35.6+/-1.5% in mutants versus 43.0+/-2.4% in wild types). Conclusions These data indicate that mice lacking eNOS expression show a greater degree of hemodynamic compromise after middle cerebral artery occlusion and suggest that a product of eNOS activity (eg, NO) may protect brain after focal cerebral ischemia, possibly by improving blood flow within the penumbral zone. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE & NEUROVASC REGULAT LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS-10828, RZ9 NS-32806] NR 27 TC 82 Z9 85 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 AUG PY 1996 VL 27 IS 8 BP 1381 EP 1385 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VA092 UT WOS:A1996VA09200023 PM 8711806 ER PT J AU Abcouwer, SF Norman, J Fink, G Carter, G Lustig, RJ Souba, WW AF Abcouwer, SF Norman, J Fink, G Carter, G Lustig, RJ Souba, WW TI Tissue-specific regulation of glutamine synthetase gene expression in acute pancreatitis is confirmed by using interleukin-1 receptor knockout mice SO SURGERY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-University-Surgeons CY FEB 08-10, 1996 CL WASHINGTON, DC SP Soc Univ Surgeons ID GLUCOCORTICOID-TREATED RATS; SKELETAL-MUSCLE; NECROTIZING PANCREATITIS; METABOLISM; PLASMA; CYTOKINES; DECREASE; LUNGS AB Background, Acute pancreatitis causes a pronounced depletion of plasma and muscle glutamine pools. In several other catabolic disease states expression of the enzyme glutamine synthetase (GS) is induced in lung and muscle to support glutamine secretion by these organs. The hormonal mediators of GS induction have not been conclusively identified. We used mice deficient for the expression of the type 1 interleukin-1 receptor (IL-1R1 knockout mice) to investigate the expression of GS during acute edematous pancreatitis. Methods, Acute edematous pancreatitis was induced in adult male wild-type and IL-1R1 knockout mice by means of the intraperitoneal administration of cerulein, and their conditions were monitored. Five organs, including lung, liver, gastrocnemius muscle, spleen, and pancreas, were assayed for relative GS messenger RNA (mRNA) content by Northern blotting. Results, The ultimate severity of pancreatitis was reduced by IL-1R1 deficiency. GS mRNA levels increased during progression of pancreatitis in lung spleen, and muscle tissue from each group. No consistent increase in GS mRNA level was observed in liver. IL-IRI deficiency diet not affect GS mRNA expression in lung tissue but consistently retarded GS induction in the spleens of knockout animals. IL-1R deficiency altered the kinetics of GS induction in muscle. Conclusions, Cerulein-induced experimental pancreatitis causes an induction in GS mRNA levels in a tissue-specific fashion. IL-1R1 deficiency reduced the ultimate severity of the condition and altered the induction of GS mRNA in the spleen and muscle. C1 HARVARD UNIV,DIV SURG ONCOL,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. UNIV FLORIDA,DEPT SURG,TAMPA,FL. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NHLBI NIH HHS [R01 HL44986] NR 25 TC 10 Z9 12 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 AUG PY 1996 VL 120 IS 2 BP 255 EP 264 DI 10.1016/S0039-6060(96)80296-0 PG 10 WC Surgery SC Surgery GA VK886 UT WOS:A1996VK88600019 PM 8751591 ER PT J AU Smith, BL Gadd, MA Lawler, C MacDonald, DJ Grudberg, SC Chi, FS Carlson, K Comegno, A Souba, WW AF Smith, BL Gadd, MA Lawler, C MacDonald, DJ Grudberg, SC Chi, FS Carlson, K Comegno, A Souba, WW TI Perception of breast cancer risk among women in breast center and primary care settings: Correlation with age and family history of breast cancer SO SURGERY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-University-Surgeons CY FEB 08-10, 1996 CL WASHINGTON, DC SP Soc Univ Surgeons AB Background, A great deal of information about breast cancer risk is available to the public. The accuracy of impressions formed from this information is unknown. Methods, A total of 750 women attending a breast center and 112 women attending a primary care office completed written surveys of their perceptions of average population risk, personal lifetime risk, and personal 10-year risk of getting breast cancer. Data sufficient to apply the Gall model were obtained, and a calculated estimate of risk was generated. Ratios of perceived to calculated risk were correlated with the respondent's age, family history of breast cancer, and location in a breast center or primary care office. Results. Women in both practice settings overestimated population risk by more than twofold. Eighty percent overestimated personal lifetime risk by more than 50% and 35% by more than fivefold. Only 7% significantly underestimated risk. Ten-year risk estimates were even more inaccurate, with 69% overestimating risk by more than fivefold 46% by more than 10-fold, and 17% by more than 20-fold. Results from a primary care population were nearly identical. Women at the extremes of age were most inaccurate in estimating risk. It was surprising that family history had little impact on perception of personal risk. Conclusions, Women in both breast center and primary care settings have a falsely high perception of both short-term and long-term breast cancer risk. Health care providers should recognize these misconceptions and be aware that many women may benefit from risk counseling. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RP Smith, BL (reprint author), MGH COMPREHENS BREAST HLTH CTR,DIV SURG ONCOL,ZERO EMERSON PL 112,BOSTON,MA 02114, USA. NR 8 TC 53 Z9 53 U1 1 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 AUG PY 1996 VL 120 IS 2 BP 297 EP 303 DI 10.1016/S0039-6060(96)80301-1 PG 7 WC Surgery SC Surgery GA VK886 UT WOS:A1996VK88600024 PM 8751596 ER PT J AU Atiya, A Cohen, G Ignarro, L Brunicardi, FC AF Atiya, A Cohen, G Ignarro, L Brunicardi, FC TI Nitric oxide regulates insulin secretion in the isolated perfused human pancreas via a cholinergic mechanism SO SURGERY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-University-Surgeons CY FEB 08-10, 1996 CL WASHINGTON, DC SP Soc Univ Surgeons ID BLOOD-FLOW; SYNTHASE; NEURONS; RAT; CELLS; MONKEY AB Background. The purpose of this study Was to determine whether nitric oxide regulates insulin secretion in the isolated perfused human pancreas. Methods, Single-pass perfursion was performed in four pancreata with a modified Krebs medium. Sequential 10-minute infusions (separated by 10-minute basal periods) of (1) 25 nmol/L acetylcholine, (2) 2.5 mu mol/L acetylcholine, and (3) 16.7 mmol/L glucose were initially infused. Then 0.1 mu mol/L of N-G-monomethyl-L-arginine (NMMA) was infused during a period of 10 minutes, and steps (I) through (3) were repeated. The change in insulin secretion from basal levels during each stimulation teas calculated and compared with that see after NMMA infusion. Results. Infusion of 25 nmol/L and 2.5 mu mol/L acetylcholine resulted in a significant stimulation of insulin secretion before NMMA infusion (p < 0.05) and after NMMA infusion for acetylcholine at 25 nmol/L (p < 0.05). The was a significant decrease in acetylcholine-induced insulin secretion after NMMA infusion for acetylcholine at 25 nmol/L and 2.5 mu mol/L compared with before NMMA infusion (p < 0.05). Infusion of 16.7 mmol/L glucose significantly stimulated insulin secretion before and after NMMA infusion, but there was no significant difference seen with insulin secretion before and after NMMA infusion. Insulin secretion was significantly inhibited during NMMA infusion (p < 0.05). Conclusions, These data show that infusion of the nitric oxide synthase inhibitor NMMA suppressed cholinergic-stimulated insulin secretion but did not affect glucose-stimulated insulin secretion. We conclude that nitric oxide regulates insulin secretion in the isolated perfused human pancreas. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MOL PHARMACOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. FU NIDDK NIH HHS [1R29DK46441-01] NR 25 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 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1996 VL 120 IS 2 BP 322 EP 327 DI 10.1016/S0039-6060(96)80305-9 PG 6 WC Surgery SC Surgery GA VK886 UT WOS:A1996VK88600028 PM 8751600 ER PT J AU Burke, PA Luo, ML Zhu, JW Yaffe, MB Forse, RA AF Burke, PA Luo, ML Zhu, JW Yaffe, MB Forse, RA TI Injury induces rapid changes in hepatocyte nuclear factor-1:DNA binding SO SURGERY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-University-Surgeons CY FEB 08-10, 1996 CL WASHINGTON, DC SP Soc Univ Surgeons ID LIVER-SPECIFIC TRANSCRIPTION; ACUTE PHASE RESPONSE; 3 C/EBP ISOFORMS; CLASS-I GENE; EXPRESSION; ACTIVATION; HNF-1; INVITRO; PHOSPHORYLATION; PARTICIPATION AB Background, Transcriptional regulation in the liver plays a critical role in mediating the acute phase response to injury. The molecular mechanisms driving these transcriptional events, however, are poorly defined in vivo. The liver-specific transcription factor hepatocyte nuclear factor (HNF)-1 binds to the 5' upstream region of many acute phase genes. To explore the connection between injury and transcriptional regulatory mechanisms, we investigated the effect of injury on HNF-1 binding activity. Methods, Liver nuclear extracts were prepared from animals after burn or anesthetized sham burn injury. HNF-1 binding activity, affinity, and off rate were assessed by electrophoretic mobility shift analysis. Results, HNF-1 binding activity decreased by 28% 1 1/2 hours after injury. The dissociation constant for HNF-1 increased from 0.6 nm to 11.8 nm at 1 1/2 hours after burn injury partly because of an increase in off rate for the HNF-1:DNA complete. Conclusions, Burn injury leads to a significant decrease in HNF-1 binding activity as a result of decreased affinity of HNF-1 for DNA. These injury-induced alterations in binding of a liver-specific transcription factor for its DNA binding site represent a mechanism for vapidly modulating acute phase gene transcription in vivo. C1 HARVARD UNIV,DEACONESS HOSP,SCH MED,DEPT SURG,BOSTON,MA. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 24 TC 11 Z9 11 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 AUG PY 1996 VL 120 IS 2 BP 374 EP 381 DI 10.1016/S0039-6060(96)80312-6 PG 8 WC Surgery SC Surgery GA VK886 UT WOS:A1996VK88600035 PM 8751607 ER PT J AU Pang, XP Ross, NS Hershman, JM AF Pang, XP Ross, NS Hershman, JM TI Alterations in TNF-alpha signal transduction in resistant human papillary thyroid carcinoma cells SO THYROID LA English DT Article ID TUMOR-NECROSIS-FACTOR; MANGANOUS SUPEROXIDE-DISMUTASE; NF-KAPPA-B; FACTOR RECEPTOR; MONOCLONAL-ANTIBODIES; ACTIVATION; BINDING; LINES AB Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) inhibit the growth of the human papillary thyroid carcinoma (PTC) cell line, NP. Exposure of NP cells to TNF-alpha resulted in the development of several PTC cell lines (R30, R45, and R60) with graded loss to the TNF-alpha-induced antiproliferation, termed resistance. In contrast, the NP cells and the resistant cells were equally sensitive to the antiproliferative action of interferon-gamma. Utilizing TNF-alpha receptor-specific agonist monoclonal antibodies, we demonstrated that the TNF-alpha receptor p55 mediated the antiproliferative action of TNF-alpha, while the p75 receptor did not affect cell proliferation in the NP cell line. The resistant PTC cell lines, however, showed a graded loss of p55 receptor-mediated antiproliferation and a concomitant activation of a p75 receptor-mediated growth stimulation. Shedding of TNF receptors is an important mechanism of TNF-alpha receptor metabolism. The p55 receptor mediated the TNF-alpha-induced up-regulation of the shedding of the p75 TNF-alpha receptor. The p75 receptor mediated the TNF-alpha-induced down-regulation of the shedding of the p55 receptor. However, the shedding of the p75 receptor was decreased and the shedding of the p55 receptor was increased in the resistant R60 cell line compared with the NP cell line, in the presence and absence of TNF-alpha. In contrast, IFN-gamma increased shedding of both p55 and p75 TNF-alpha receptors in NP and R60 cell lines with equal potency. Furthermore, the resistant PTC cell lines have increased basal manganous superoxide dismutase (MnSOD) expression and blunted induction of MnSOD mRNA upon short-term TNF-alpha treatment (less than 2 h of treatment). The results indicate that a decrease in signal transduction via the p55 TNF-alpha receptor and concomitant increase in signal transduction via the p75 TNF-alpha receptor are involved in the development of MTC cell resistance. C1 W LOS ANGELES VET AFFAIRS MED CTR, DIV ENDOCRINOL & METAB, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90073 USA. COLUMBUS VA OUTPATIENT CLIN, COLUMBUS, OH 43203 USA. RP Pang, XP (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, THYROID CANC RES LAB, 11301 WILSHIRE BLVD, BLDG 114, RM 200, LOS ANGELES, CA 90073 USA. FU NCI NIH HHS [CA 61863] NR 17 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD AUG PY 1996 VL 6 IS 4 BP 313 EP 317 DI 10.1089/thy.1996.6.313 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF398 UT WOS:A1996VF39800011 PM 8875753 ER PT J AU Springer, LN McAsey, ME Flaws, JA Tilly, JL Sipes, IG Hoyer, PB AF Springer, LN McAsey, ME Flaws, JA Tilly, JL Sipes, IG Hoyer, PB TI Involvement of apoptosis in 4-vinylcyclohexene diepoxide-induced ovotoxicity in rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INTERNUCLEOSOMAL DNA FRAGMENTATION; CELL-DEATH; 4-VINYL-1-CYCLOHEXENE DIEPOXIDE; ENDONUCLEASE; OVARIAN; FOLLICLES; MICE; DESTRUCTION; MECHANISMS; GRANULOSA AB Previous studies have determined that 4-vinylcyclohexene diepoxide (VCD) causes specific destruction of oocytes contained in small pre-antral (primordial and primary) ovarian follicles of Fischer 344 rats following 30 days of daily dosing with VCD. The purposes of this study were to identify the type of VCD-induced cell death occurring in small pre-antral follicles and to determine the earliest time following the onset of dosing when evidence of follicular destruction could first be detected. A significant decrease in the number of oocytes contained in small pre-antral follicles in ovaries of rats after 15 days of daily dosing tip) with VCD (80 mg/kg) had been observed in preliminary experiments. Therefore, a study was conducted to determine the time of the onset of this follicular destruction by examination of follicular DNA integrity. Female Fischer 344 rats were dosed daily (80 mg/kg, ip) for 6, 8, 10, 12, or 14 days, and ovaries were removed 1, 4, or 24 hr after the final dose. Small pre-antral follicles (25-100 mu m) were isolated by gentle dissociation of ovaries with collagenase, and follicles were sorted with micropipets. Genomic DNA was isolated from follicles and radiolabeled with [P-32]dideoxy ATP, and the degree of fragmentation quantified by agarose gel electrophoresis and autoradiography. Degradation of DNA was evaluated by P-32 content in low-molecular-weight fragments (<4 kilobase pairs). Degradation of DNA was not observed in follicles collected 24 hr after the final dose on any day. However, a random pattern of DNA degradation was observed, and was significantly greater (p < 0.05) compared with controls, when follicles were collected 4 hr following VCD administration on Days 10 and 12, but not on Days 6 or 8, of dosing. Although not significant, there was also evidence of DNA degradation in dosed animals on Day 14. Histological evaluation of small pre-antral follicles in ovarian sections during the early stages of VCD-induced DNA degradation (Day 10; 4 hr) demonstrated margination of chromatin along the nuclear membrane in oocytes and disruptions in focal contact between granulosa cells and oocytes, both features indicative of apoptosis. Furthermore, there was no sign of ruptured membranes in granulosa cells or oocytes or of an inflammatory response, characteristics of necrosis (pathological cell death). Whereas biochemical and morphological evidence of follicular destruction was seen 4 hr after dosing on Day 10, numbers of oocyte-containing primordial and primary follicles in VCD-treated animals were not different from controls at that time. These results demonstrate that the initial evidence of impending destruction of small pre-antral follicles is first consistently visualized following 10 days of daily dosing with VCD, although a measurable reduction in oocyte numbers has not yet occurred. Despite the fact that internucleosomal cleavage of genomic DNA was not observed, morphological evaluations support that granulosa cells and oocytes in primordial and primary follicles are destroyed via the induction of apoptosis. (C) 1996 Academic Press, Inc. C1 UNIV ARIZONA,DEPT CELL BIOL ANAT,TUCSON,AZ 85724. UNIV ARIZONA,DEPT PHARMACOL TOXICOL,TUCSON,AZ 85724. UNIV ARIZONA,SW ENVIRONM HLTH SCI CTR,TUCSON,AZ 85724. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,VINCENT CTR REPROD BIOL,BOSTON,MA 02114. RP Springer, LN (reprint author), UNIV ARIZONA,DEPT PHYSIOL,TUCSON,AZ 85724, USA. FU NICHD NIH HHS [KO 4HD00907]; NIEHS NIH HHS [1-RO1-ES06999, 1 P30ES06694-01] NR 40 TC 92 Z9 92 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG PY 1996 VL 139 IS 2 BP 394 EP 401 DI 10.1006/taap.1996.0180 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VD515 UT WOS:A1996VD51500021 PM 8806857 ER PT J AU Springer, LN Tilly, JL Sipes, IG Hoyer, PB AF Springer, LN Tilly, JL Sipes, IG Hoyer, PB TI Enhanced expression of bax in small preantral follicles during 4-vinylcyclohexene diepoxide-induced ovotoxicity in the rat SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID EPOXIDE HYDROLASE GENE; CELL-DEATH; OXIDATIVE STRESS; 4-VINYL-1-CYCLOHEXENE DIEPOXIDE; STIMULATING-HORMONE; OVARIAN FOLLICLES; APOPTOSIS; DAMAGE; MICE; TOXICITY AB 4-Vinylcyclohexene diepoxide (VCD) destroys small preantral (25-100 mu m) ovarian follicles after repeated dosing in mice and rats. A previous study determined this follicular destruction is via apoptosis (physiological cell death). The purposes of this study were to examine the effects of VCD on amounts of mRNA for several genes that might be involved in this ovotoxic response and to determine the specificity of this response for small preantral follicles. The genes of interest were bax, a cell death gene; three forms of the antioxidant enzyme, superoxide dismutase (mitochondrial manganese-containing or MnSOD, cytosolic copper/zinc-containing or Cu/ZnSOD, and secreted or secSOD); and microsomal epoxide hydrolase (mEH), involved in detoxification of VCD. Female Fischer 344 rats were administered daily doses (10 days) of vehicle control (sesame oil) or VCD (80 mg/kg, ip). Four hours after the last injection, livers and ovaries were removed. Small (25-100 mu m) and large (100-250 mu m) preantral follicles were separated from the ovaries by gentle dissociation and collected by mouth pipeting. Total RNA was extracted from all tissues, reverse transcribed into first-strand cDNA, and amplified by polymerase chain reaction using oligonucieotide primers specific for each gene. Relative levels of mRNA were visualized by agarose gel electrophoresis and autoradiography and quantified by densitometric analysis. Coamplification of ribosomal protein L19 (constitutively expressed in ovarian tissue) was used for normalization in each sample. Increased levels of mRNA for box (172 +/- 20% of control, p < 0.05), MnSOD (248 +/- 708 of control, p < 0.05), and mEH (352 +/- 120% of control, p ( 0.05) were measured in 25- to 100-mu m follicles collected from VCD-treated compared with control rats. Unlike 25- to 100-mu m follicles (the targets of ovotoxicity), in 100- to 250-mu m follicles (nontargets) there were no changes (p > 0.05) in mRNA levels for bax or MnSOD in VCD-treated rats; however, mRNA levels for mEH were significantly decreased (79 +/- 48 of control, p < 0.05), compared with control. No changes in levels of mRNA for mEH were observed in liver from VCD-treated rats relative to control. Additionally, in liver VCD caused a significant decrease in mRNA levels for box (31 +/- 5% of control p < 0.05) and Cu-ZnSOD (56 +/- 17% of control, p < 0.05). In summary, dosing of rats with VCD enhanced expression of mRNA encoding several genes that might respond during the induction of ovotoxicity. The selective increase in bax in the population of follicles destroyed by repeated dosing with VCD may reflect their susceptibility to apoptosis. (C) 1996 Academic Press, Inc. C1 UNIV ARIZONA, DEPT PHYSIOL, TUCSON, AZ 85724 USA. UNIV ARIZONA, DEPT PHARMACOL TOXICOL, TUCSON, AZ 85724 USA. UNIV ARIZONA, SW ENVIRONM HLTH SCI CTR, TUCSON, AZ 85724 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, DEPT OBSTET & GYNECOL,VINCENT CTR REPROD BIOL, BOSTON, MA 02114 USA. FU NIEHS NIH HHS [1-RO1-ES06999] NR 40 TC 56 Z9 56 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG PY 1996 VL 139 IS 2 BP 402 EP 410 DI 10.1006/taap.1996.0181 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VD515 UT WOS:A1996VD51500022 PM 8806858 ER PT J AU Pascual, M Rubin, RH Cosimi, AB AF Pascual, M Rubin, RH Cosimi, AB TI Minimizing the toxicity of antilymphocyte antibody therapy SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st International Cybercongress - Transplantation in the next Millennium: A Landmark in Organ Transplantation Technology CY NOV 13-15, 1995 CL WASHINGTON, DC SP Natl Med Informat Network, Sandoz Pharm, New Jersey ID TUMOR-NECROSIS-FACTOR; TRANSPLANT RECIPIENTS; MONOCLONAL-ANTIBODY; OKT3; INTERFERON; INHIBITION; RECEPTORS; RELEASE; SERUM; TNF C1 MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-18646] NR 15 TC 4 Z9 4 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1996 VL 28 IS 4 BP 2113 EP 2114 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VD463 UT WOS:A1996VD46300033 PM 8769171 ER PT J AU Ruffolo, EF Maluf, HM Koerner, FC AF Ruffolo, EF Maluf, HM Koerner, FC TI Spindle cell endocrine carcinoma of the mammary gland SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE breast; neoplasm; neuroendocrine; spindle cells ID INFILTRATING MYOEPITHELIOMA; MALIGNANT MYOEPITHELIOMA; BREAST; ADENOMYOEPITHELIOMA; DIFFERENTIATION; GROWTH AB We report the pathological characteristics of a variant of mammary endocrine tumour, predominantly formed from cytologically bland spindle cells. This neoplasm grows as a red, well defined mass lacking the usual macroscopical characteristics of breast cancer. Within smoothly contoured aggregates arranged in an insular pattern, delicate capillaries and collagen bundles support the neoplastic epithelial cells. Most of the tumour cells possess a slender spindle shape and form a solid or fenestrated sheet, but a few appear cuboidal and create glands. Immunohistochemical studies demonstrate that the spindle cells and the glandular cells constitute a single population. Both types of cells stain for neuroendocrine markers (chromogranin, synaptophysin, and CD 57), carcinoembryonic antigen, keratin 8/18, S-100 protein, and receptors for oestrogen and progesterone. Many of the tumour cells possess argyrophilic granules, and electron microscopy may reveal dense core granules. C1 VET ADM MED CTR,PATHOL & LAB MED SERV,MEMPHIS,TN 38104. RP Ruffolo, EF (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LAB PATHOL,FRUIT ST,BOSTON,MA 02114, USA. NR 25 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD AUG PY 1996 VL 428 IS 6 BP 319 EP 324 PG 6 WC Pathology SC Pathology GA VE769 UT WOS:A1996VE76900002 PM 8797935 ER PT J AU Moradpour, D Englert, C Wakita, T Wands, JR AF Moradpour, D Englert, C Wakita, T Wands, JR TI Characterization of cell lines allowing tightly regulated expression of hepatitis C virus core protein SO VIROLOGY LA English DT Article ID NON-B-HEPATITIS; MAMMALIAN-CELLS; NON-A; ANTISENSE OLIGODEOXYNUCLEOTIDES; SUBCELLULAR-LOCALIZATION; NUCLEAR-LOCALIZATION; TRANS-SUPPRESSION; GENE-EXPRESSION; GENOME; GROWTH AB A tetracycline-regulated system was used to generate cell lines allowing tightly controlled expression of a hepatitis C virus (HCV) cDNA comprising the 5' noncoding, the core, and part of the E1 regions. Production of 21-kDa processed nucleocapsid protein could be regulated over a broad range by the concentration of tetracycline present in the culture medium. Induction ratios of over 1000-fold were found using an HCV core-luciferase fusion construct. Core protein had an intracellular half-life of 9 hr and corresponded to the product of 173 amino-terminal amino acids of the HCV open reading frame. sequential immunofluorencence microscopy revealed the presence of core antigen first in a predominantly perinuclear fine-reticular staining pattern and subsequently also in cytoplasmic granules and vesicles. By immunoelectron microscopy core protein was found on the endoplasmic reticulum membrane and on the surface of cytoplasmic lipid droplets. Growth rate analyses and colony formation efficiency assays showed no major cytotoxic effect of HCV core protein expression per se. HCV gene expression could be inhibited by an antisense oligonucleotide targeting a region immediately downstream of the translation initiation codon. These cell lines represent important tools to investigate structural and functional properties of HCV core protein and may be useful to evaluate gene therapeutic strategies against HCV in a cellular system, (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR CANC,LAB MOL GENET,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-08169] NR 37 TC 175 Z9 178 U1 1 U2 2 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 AUG 1 PY 1996 VL 222 IS 1 BP 51 EP 63 DI 10.1006/viro.1996.0397 PG 13 WC Virology SC Virology GA VB377 UT WOS:A1996VB37700006 PM 8806487 ER PT J AU Sablinski, T AF Sablinski, T TI Xenotransplantation: Lessons from nature SO XENOTRANSPLANTATION LA English DT Article DE immune system; xenograft; immunosuppressants ID HYPERACUTE XENOGRAFT REJECTION; DECAY ACCELERATING FACTOR; ADULT WORMS; PARASITE; TRANSPLANTATION; INHIBITOR; CELL; HOST; FILARIASIS; EXPRESSION RP Sablinski, T (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129, USA. NR 34 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD AUG PY 1996 VL 3 IS 3 BP 275 EP 278 DI 10.1111/j.1399-3089.1996.tb00148.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA VX270 UT WOS:A1996VX27000007 ER PT J AU Becker, T Elmer, K Schneider, F Schneider, M Grodd, W Bartels, M Heckers, S Beckmann, H AF Becker, T Elmer, K Schneider, F Schneider, M Grodd, W Bartels, M Heckers, S Beckmann, H TI Confirmation of reduced temporal limbic structure volume on magnetic resonance imaging in male patients with schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE hippocampal formation; third ventricle; temporal lobe; limbic system ID BRAIN MORPHOLOGY; LOBE; ABNORMALITIES; DISORDER; SIZE; MRI AB A structural deficit in the temporal lobes has been implicated in the pathogenesis of schizophrenia. A prospective magnetic resonance imaging (MRI) study was carried out in 20 young male patients with schizophrenia and 20 age-matched healthy male volunteers. Volumetric measurements were performed in all slices with temporal lobe cross-sections from the temporal pole to the tip of the Sylvian fissure. Volumetric assessment included the temporal lobe as a whole, hippocampal formation and amygdala complex, temporal horn and cella media of the lateral ventricle, the third ventricle, and hemispheric volume in all slices that showed temporolimbic structures. Brain structural deficit in the patients was most conspicuous in the posterior portion of the hippocampal formation. Significant effects of diagnosis were also found for the total temporal lobe and the third ventricle. Multiple regression analysis revealed posterior hippocampal volume to be significantly determined by diagnosis, but not by age or by temporal lobe or hemispheric volume. Significant correlations of morphologic and clinical parameters were restricted to negative correlations of temporal lobe volume with the global rating and sum score of the Scale for the Assessment of Negative Symptoms. The study confirms subtle temporolimbic deficit reported in previous MRI studies in patients with schizophrenia. C1 UNIV WURZBURG,DEPT PSYCHIAT,D-97080 WURZBURG,GERMANY. UNIV TUBINGEN,DEPT NEURORADIOL,D-72076 TUBINGEN,GERMANY. UNIV TUBINGEN,DEPT PSYCHIAT,D-72076 TUBINGEN,GERMANY. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RI Heckers, Stephan/F-3051-2010; Becker, Thomas/O-9769-2014 OI Heckers, Stephan/0000-0003-3601-9910; Becker, Thomas/0000-0001-8179-1219 NR 35 TC 72 Z9 73 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUL 31 PY 1996 VL 67 IS 2 BP 135 EP 143 DI 10.1016/0925-4927(96)03002-8 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VE502 UT WOS:A1996VE50200004 PM 8876013 ER PT J AU Faraone, SV Seidman, LJ Kremen, WS Toomey, R Lyons, MJ Tsuang, MT AF Faraone, SV Seidman, LJ Kremen, WS Toomey, R Lyons, MJ Tsuang, MT TI Neuropsychological functioning among the elderly nonpsychotic relatives of schizophrenic patients SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; family; neuropsychology; genetics ID VOLUNTEERS; DISORDERS; SELECTION; FAMILY AB In our prior work with a young sample (age <60), we showed that three neuropsychological functions were impaired among relatives of schizophrenic patients: abstraction, verbal memory, and auditory attention. In the present work we show that these results do not generalize to an older sample aged 60 years and greater. Thus, although we and others have put forth measures of neuropsychological function as indicators of the schizophrenia genotype, the present study suggests that conclusions may be limited to non-elderly samples. Further work is needed to address this issue definitively. C1 MASSACHUSETTS MENTAL HLTH CTR,BROCKTON,MA. MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,INST PSYCHIAT EPIDEMIOL & GENET,BROCKTON,MA 02401. BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BROCKTON,MA 02401. RP Faraone, SV (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BROCKTON W ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA, USA. RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [5 U01 MH46318-02, 1 R01MH41874-01, R 37MH43518-01] NR 31 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL 31 PY 1996 VL 21 IS 1 BP 27 EP 31 DI 10.1016/0920-9964(96)00020-5 PG 5 WC Psychiatry SC Psychiatry GA VB540 UT WOS:A1996VB54000004 PM 8998273 ER PT J AU Fishman, JA Rubin, RH Koziel, MJ Periera, BJG AF Fishman, JA Rubin, RH Koziel, MJ Periera, BJG TI Hepatitis C virus and organ transplantation SO TRANSPLANTATION LA English DT Review ID ORTHOTOPIC LIVER-TRANSPLANTATION; RENAL-ALLOGRAFT RECIPIENTS; BLOOD MONONUCLEAR-CELLS; VIRAL-HEPATITIS; KIDNEY-TRANSPLANTATION; INTERFERON THERAPY; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; REJECTION EPISODES; ALPHA-INTERFERON AB Hepatitis C virus (HCV) is both the leading cause of cirrhosis and hepatic failure leading to liver transplantation and a cause of chronic hepatitis in approximately 10% of all transplant recipients. Beginning 5-10 years or more posttransplant, HCV causes progressive liver disease in a significant fraction of infected individuals and contributes to an increased incidence of opportunistic infection and hepatocellular carcinoma. The existence of multiple genotypes of HCV with differing biologic behaviors and the generation of antigenic diversity of the virus (quasispecies) during the course of infection, limit the capacity of the immune system to generate protective immunity. Antiviral therapy with interferon-alpha is effective in only a minority of transplant patients, and since allografts from HCV infected donors are quite efficient in transmitting the virus, great attention is paid to the appropriate use of organs hom HCV-positive donors. At present, these organs should be particularly targeted for patients in emergent need of lifesaving heart, liver, or lung transplants. Issues requiring further investigation include the impact of viral superinfection on HCV-infected recipients of organs from HCV-infected donors and the use of such organs in seronegative patients who are older, diabetic, or highly sensitized, for whom quality of life issues may outweigh the long-term impact of HCV infection. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD MIT DIV HLTH SCI & TECHNOL,CTR EXPT PHARMACOL & THERAPEUT,CAMBRIDGE,MA 02142. TUFTS UNIV NEW ENGLAND MED CTR,DIV NEPHROL,BOSTON,MA 02111. RP Fishman, JA (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT INFECT DIS UNIT,BOSTON,MA 02114, USA. NR 100 TC 84 Z9 84 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 JUL 27 PY 1996 VL 62 IS 2 BP 147 EP 154 DI 10.1097/00007890-199607270-00001 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UZ031 UT WOS:A1996UZ03100001 PM 8755808 ER PT J AU Milberger, S Faraone, SV Biederman, J Testa, M Tsuang, MT AF Milberger, S Faraone, SV Biederman, J Testa, M Tsuang, MT TI New phenotype definition of attention deficit hyperactivity disorder in relatives for genetic analyses SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE psychiatric morbidity; familial transmission; logistic regression ID FAMILIAL ASSOCIATION; UNIPOLAR RELATIVES; BIPOLAR PEDIGREES; CONDUCT DISORDER; RISK-FACTORS; CHILDREN; SCHIZOPHRENIA; COMORBIDITY; PREVALENCE; DYSLEXIA AB The goal of the present investigation was to create a phenotype definition in relatives of probands that reflects a more genetic form of attention deficit hyperactivity disorder (ADHD). Logistic regression was applied to the first-degree relatives of ADHD and normal control probands to create a quantitative phenotype that combined information across psychiatric, cognitive, and demographic domains, Models were run separately in mothers, fathers, sisters, and brothers. Although there was some overlap between the variables retained in each model, no two models had exactly the same variables. Our results suggest that the use of fitted logits may be valuable as a potential index of caseness. Since different characteristics were included in different groups of relatives, our results suggest that gender and generation may moderate the expression of ADHD. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02114. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 52 TC 7 Z9 7 U1 0 U2 2 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 JUL 26 PY 1996 VL 67 IS 4 BP 369 EP 377 DI 10.1002/(SICI)1096-8628(19960726)67:4<369::AID-AJMG10>3.0.CO;2-H PG 9 WC Genetics & Heredity SC Genetics & Heredity GA UZ070 UT WOS:A1996UZ07000010 PM 8837705 ER PT J AU Kolanus, W Nagel, W Schiller, B Zeitlmann, L Godar, S Stockinger, H Seed, B AF Kolanus, W Nagel, W Schiller, B Zeitlmann, L Godar, S Stockinger, H Seed, B TI alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule SO CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; OUT SIGNAL-TRANSDUCTION; BRUTON TYROSINE KINASE; CELL-ADHESION; T-CELL; LYMPHOCYTE ADHESION; LIGAND-BINDING; GPIIB-IIIA; PH DOMAIN; PROTEIN AB The avidity of integrin adhesion receptors for extracellular ligands is subject to dynamic regulation by intracellular programs that have yet to be elucidated. We describe here a protein, cytohesin-1, which specifically interacts with the intracellular portion of the integrin beta 2 chain (CD18). The molecule shows homology to the yeast SEC7 gene product and bears a pleckstrin homology (PH) domain. Overexpression of either the full-length cytohesin-1 or the SEC7 domain induces beta 2 integrin-dependent binding of Jurkat cells to ICAM-1, whereas expression of the isolated cytohesin-1 PH domain inhibits T cell receptor-stimulated adhesion. Similar inhibition is not exhibited by PH domains taken from other proteins, showing that the interaction is specific and that individual PH domains are capable of discriminating between alternative targets. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT BIOL MOL,BOSTON,MA 02114. UNIV VIENNA,VIRCC,INST IMMUNOL,A-1235 VIENNA,AUSTRIA. RP Kolanus, W (reprint author), UNIV MUNICH,MOL BIOL LAB,GENZENTRUM,D-81375 MUNICH,GERMANY. RI Stockinger, Hannes/E-5173-2011 OI Stockinger, Hannes/0000-0001-6404-4430 FU NIDDK NIH HHS [DK43031] NR 59 TC 373 Z9 377 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 26 PY 1996 VL 86 IS 2 BP 233 EP 242 DI 10.1016/S0092-8674(00)80095-1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UZ972 UT WOS:A1996UZ97200009 PM 8706128 ER PT J AU Erhardt, P Cooper, GM AF Erhardt, P Cooper, GM TI Activation of the CPP32 apoptotic protease by distinct signaling pathways with differential sensitivity to Bcl-x(L) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRAMMED CELL-DEATH; ELEGANS; BCL-2; SURVIVAL; ENCODES AB In the absence of growth factors, many types of mam malian cells undergo apoptosis. We and others have shown recently that growth factors promote cell survival by activating phosphatidylinositol 3-kinase (PI 3-kinase) in several cell types, In the present study, we have compared downstream elements of the apoptotic pathways induced by PI 3-kinase inhibitors and other stimuli. In U937 cells, both PI 3-kinase inhibitors (wortmannin and LY294002) and etoposide activated the CPP32 apoptotic protease by cleavage to active p17 subunits, In contrast, treatment with tumor necrosis factor alpha (TNF alpha) resulted in the accumulation of a distinct active CPP32 subunit, p20. Furthermore, overexpression of Bcl-x(L) blocked DNA fragmentation, CPP32 activation and cleavage of poly(ADP ribose) polymerase in U937 cells treated with both PI 3-kinase inhibitors and etoposide, but not in cells treated with TNF alpha. Distinct patterns of CPP32 activation and differential sensitivities to Bcl-x(L) thus distinguish the cell death pathways activated by PI 3-kinase inhibition and DNA damage from that activated by TNF alpha. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA18689] NR 39 TC 115 Z9 119 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 JUL 26 PY 1996 VL 271 IS 30 BP 17601 EP 17604 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500003 PM 8663611 ER PT J AU Kradin, RL McLoud, TC Mark, EJ Kanarek, DJ AF Kradin, RL McLoud, TC Mark, EJ Kanarek, DJ TI A 62-year-old woman with progressive dyspnea and diffuse reticulonodular pulmonary infiltrates - Pulmonary amyloidosis, with diffuse alveolar septal and vascular involvement SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ASSOCIATION; PERICARDITIS; HYPERTENSION; PATTERNS C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Kradin, RL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 33 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 JUL 25 PY 1996 VL 335 IS 4 BP 266 EP 273 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UZ532 UT WOS:A1996UZ53200008 ER PT J AU Rubin, RH Baltimore, D Chen, BK Wilkinson, RA Fischman, AJ AF Rubin, RH Baltimore, D Chen, BK Wilkinson, RA Fischman, AJ TI In vivo tissue distribution of CD4 lymphocytes in mice determined by radioimmunoscintigraphy with an In-111-labeled anti-CD4 monoclonal antibody SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; INFECTIOUS LESIONS; LEUKOCYTES; CELLS; MACROPHAGES AB The tissue distribution of CD4 lymphocytes in normal C57/BL mice and CD4 knockout mice was determined by biodistribution measurements and gamma camera imaging with an In-111-labeled rat IgG(2b) monoclonal antibody directed against the murine CD-4 antigen. In normal mice, high concentrations of antibody accumulated in the spleen and lymph nodes, at 45 hr after injection, the concentrations of radiolabel in the spleen and lymph nodes of normal mice were 10- to 20-fold greater than in the corresponding tissues of the CD4 knockout mice and nonlymphoid tissues of both types of mice. At 24 and 45 hr, gamma camera images showed high concentrations of radiolabeled antibody in lymph nodes and spleen of normal but not knockout mice. These results indicate that radioimmunoscintigraphy with In-111-anti-CD4 is an excellent method for studying tissue distribution of CD4 lymphocytes in mice, Using an equivalent anti-human CD4 antibody, this method might be useful for studying the pathophysiology of conditions in which these cells play a critical role and for monitoring therapies for these disorders. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. ROCKEFELLER UNIV,NEW YORK,NY 10021. RP Rubin, RH (reprint author), HARVARD UNIV,MIT,CTR EXPTL PHARMACOL & THERAPEUT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139, USA. NR 23 TC 7 Z9 7 U1 1 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 JUL 23 PY 1996 VL 93 IS 15 BP 7460 EP 7463 DI 10.1073/pnas.93.15.7460 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000008 PM 8755495 ER PT J AU Sanderson, IR Ezzell, RM Kedinger, M Erlanger, M Xu, ZX Pringault, E LeonRobine, S Louvard, D Walker, WA AF Sanderson, IR Ezzell, RM Kedinger, M Erlanger, M Xu, ZX Pringault, E LeonRobine, S Louvard, D Walker, WA TI Human fetal enterocytes in vitro: Modulation of the phenotype by extracellular matrix SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nonmalignant; keratin; villin; Matrigel; in growth factor binding proteins ID INTESTINAL EPITHELIAL-CELLS; RAT SMALL-INTESTINE; GROWTH-FACTOR; BINDING-PROTEINS; GENE-EXPRESSION; CANCER CELLS; HUMAN VILLIN; IEC-6 CELLS; FACTOR-II; DIFFERENTIATION AB The differentiation of small intestinal epithelial cells may require stimulation by microenvironmental factors in vivo. In this study, the effects of mesenchymal and luminal elements in nonmalignant epithelial cells isolated from the human fetus were studied in vitro. Enterocytes from the human fetus were cultured and microenvironmental factors were added in stages, each stage more closely approximating the microenvironment in vivo. Four stages were examined: epithelial cells derived on plastic from intestinal culture and grown as a cell clone, the same cells grown On connective tissue support, primary epithelial explants grown on fibroblasts with a laminin base, and primary epithelial explants grown on fibroblasts and laminin with n-butyrate added to the incubation medium. The epithelial cell clone dedifferentiated when grown on plastic; however, the cells expressed cytokeratins and villin as evidence of their epithelial cell origin. Human connective tissue matrix from Engelbreth-Holm-Swarm sarcoma cells (Matrigel) modulated their phenotype: alkaline phosphatase activity increased, microvilli developed on their apical surface, and the profile of insulin-like growth factor binding proteins resembled that secreted by differentiated enterocytes. Epithelial cells taken directly from the human fetus as primary cultures and grown as explants on fibroblasts and laminin expressed greater specific enzyme activities in brush border membrane fractions than the cell clone. These activities were enhanced by the luminal molecule sodium butyrate. Thus the sequential addition of connective tissue and luminal molecules to nonmalignant epithelial cells in vitro induces a spectrum of changes in the epithelial cell phenotype toward full differentiation. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,HARVARD CLIN NUTR RES CTR,SURG RES UNIT,BOSTON,MA 02129. INSERM,U381,F-67200 STRASBOURG,FRANCE. INST CURIE,F-75231 PARIS,FRANCE. INST PASTEUR,F-75724 PARIS,FRANCE. FU FIC NIH HHS [F06-TWO 1865]; NICHD NIH HHS [R01-HD12437]; NIDDK NIH HHS [P-30 DK33506] NR 45 TC 91 Z9 93 U1 1 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 JUL 23 PY 1996 VL 93 IS 15 BP 7717 EP 7722 DI 10.1073/pnas.93.15.7717 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000055 PM 8755542 ER PT J AU Bories, JC Demengeot, J Davidson, L Alt, FW AF Bories, JC Demengeot, J Davidson, L Alt, FW TI Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: The role of enhancer elements in controlling V(D)J recombination accessibility SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CONTROL REGION; B-CELLS; REARRANGEMENT; TRANSCRIPTION; LOCUS; DOWNSTREAM; DISRUPTION; SEGMENTS; INTRON; MICE AB To assess the role of transcriptional enhancers in regulating accessibility of the T-cell receptor beta-chain (TCR beta) locus, we generated embryonic stem cell lines in which a single allelic copy of the endogenous TCR beta enhancer (E beta) was either deleted or replaced with the immunoglobulin heavy-chain intronic enhancer. We assayed the effects of these mutations on activation of the TCR beta locus in normal T- and B-lineage cells by RAG-2 (recombination-activating gene 2)-deficient blastocyst complementation. We found that E beta is required for rearrangement and germ-line transcription of the TCR beta locus in T-lineage cells. In the absence of E beta, the heavy-chain intronic enhancer partially supported joining region beta-chain rearrangement in T- but not in B-lineage cells. However, ability of the heavy-chain intronic enhancer to induce rearrangements was blocked by linkage to an expressed neomycin-resistance gene (neo(r)). These results demonstrate a critical role for E beta in promoting accessibility of the TCR beta locus and suggest that additional negative elements may cooperate to further modulate this process. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RP Bories, JC (reprint author), HOP ST LOUIS,INSERM,U93,F-75010 PARIS,FRANCE. RI demengeot, jocelyne/K-8072-2014 FU PHS HHS [A.I.20047] NR 30 TC 133 Z9 133 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 JUL 23 PY 1996 VL 93 IS 15 BP 7871 EP 7876 DI 10.1073/pnas.93.15.7871 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000083 PM 8755569 ER PT J AU Coley, CM Li, YH Medsger, AR Marrie, TJ Fine, MJ Kapoor, WN Lave, JR Detsky, AS Weinstein, MC Singer, DE AF Coley, CM Li, YH Medsger, AR Marrie, TJ Fine, MJ Kapoor, WN Lave, JR Detsky, AS Weinstein, MC Singer, DE TI Preferences for home vs hospital care among low-risk patients with community-acquired pneumonia SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID WILLINGNESS-TO-PAY; QUALITY-OF-LIFE; HEALTH; OUTCOMES AB Objective: To measure preferences for initial outpatient vs hospital care among low-risk patients who were being actively treated for community-acquired pneumonia (CAP). Methods: Study patients included 159 patients with CAP, 57 (36%) initially hospitalized, who were identified as being at low-risk for early mortality using a validated prediction model. Subjects were enrolled from university and community health care facilities located in Boston, Mass, Halifax, Nova Scotia, and Pittsburgh, Pa, participating in the Pneumonia Patient Outcome Research Team prospective cohort study of CAP. Three utility assessment techniques (category scaling, standard gamble, and willingness to pay) were used to measure the strength of patient preferences for the site of care for low-risk CAP. At the time of initial therapy or during the early recuperative period, patient preferences were assessed across a spectrum of potential clinical outcomes using 7 standardized pneumonia clinical vignettes. Results: Responses to the 7 pneumonia scenarios indicated that most patients consistently preferred outpatient-based therapy. This pattern was observed regardless of whether patients had actually been treated initially at home or in a hospital. Patients (74%) who stated that they generally preferred home care for low-risk CAP were willing to pay a mean of 24% of 1 month's household income to be assured of this preference. Preference for home care, as measured by the category scaling and the willingness to pay, persisted after adjustment for sociodemographic and baseline health status covariates. Sixty-nine percent of interviewed patients said that their physician alone determined whether they would be treated in the hospital or at home. Only 11% recalled being asked if they had a preference for either site of care. Conclusions: Most patients, even those treated initially in a hospital, who were at low risk for mortality from CAP prefer outpatient treatment. However, most physicians appear not to involve patients in the site-of-care decision. More explicit discussion of patient preferences for the location of care would likely yield more highly valued care by patients, as well as less costly treatment for CAP. C1 MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV PITTSBURGH,DEPT BIOSTAT,PITTSBURGH,PA 15261. UNIV PITTSBURGH,DEPT HLTH SERV ADM,PITTSBURGH,PA 15261. UNIV PITTSBURGH,DEPT MED,PITTSBURGH,PA 15261. VICTORIA GEN HOSP,DEPT MED,HALIFAX,NS B3H 2Y9,CANADA. VICTORIA GEN HOSP,DEPT MICROBIOL,HALIFAX,NS B3H 2Y9,CANADA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. UNIV TORONTO,DEPT HLTH ADM,TORONTO,ON M5S 1A1,CANADA. UNIV TORONTO,DEPT MED,TORONTO,ON M5S 1A1,CANADA. TORONTO HOSP,DIV GEN INTERNAL MED,TORONTO,ON,CANADA. TORONTO HOSP,DIV CLIN EPIDEMIOL,TORONTO,ON,CANADA. FU AHRQ HHS [R01 HS 06468] NR 28 TC 100 Z9 101 U1 0 U2 4 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 JUL 22 PY 1996 VL 156 IS 14 BP 1565 EP 1571 DI 10.1001/archinte.156.14.1565 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UY332 UT WOS:A1996UY33200010 PM 8687265 ER PT J AU Hollister, RD Kisiel, W Hyman, BT AF Hollister, RD Kisiel, W Hyman, BT TI Immunohistochemical localization of tissue factor pathway inhibitor-1 (TFPI-1), a Kunitz proteinase inhibitor, in Alzheimer's disease SO BRAIN RESEARCH LA English DT Article DE neurodegeneration; microglia; senile plaque; dementia; lipoprotein associated coagulation inhibitor; proteinase inhibitor ID AMYLOID PRECURSOR PROTEIN; RECEPTOR-RELATED PROTEIN; MESSENGER-RNA; COAGULATION INHIBITOR; APOLIPOPROTEIN-E; HUMAN-PLASMA; BRAIN; EXPRESSION; MICROGLIA; DOMAIN AB Senile plaques in Alzheimer's disease (AD) are composed principally of A beta, a 4 kDa fragment of the amyloid precursor protein (APP). Longer forms of APP which contain a Kunitz proteinase inhibitor (KPI) domain are elevated in aged and in AD brains. Tissue factor pathway inhibitor-1 (TFPI) contains three tandem KPI domains and has been well characterized for its role as a natural anticoagulant in the extrinsic coagulation pathway. Functionally, the first two KPI domains of TFPI bind and inhibit the activity of factor Xa and VIIa respectively. In addition, TFPI and APP-KPI share a common clearance mechanism through the low density lipoprotein receptor-related protein (LRP). As part of an ongoing study of the role of KPI-containing proteins in AD, the current study examines TFPI localization in the brain. We report here that TFPI is immunohistochemically localized to microglia in both AD and non-AD individuals and is localized to some senile plaques in AD. Western blot analyses indicate that the amount of TFPI is elevated in frontal cortex samples from AD brains. We propose that TFPI may play a cell specific role in proteinase regulation in the brain. C1 MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV NEW MEXICO, SCH MED, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. FU NHLBI NIH HHS [HL35246]; NIA NIH HHS [AG11337, AG05134] NR 50 TC 23 Z9 23 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 JUL 22 PY 1996 VL 728 IS 1 BP 13 EP 19 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VB510 UT WOS:A1996VB51000003 PM 8864292 ER PT J AU MerchanPerez, A Liberman, MC AF MerchanPerez, A Liberman, MC TI Ultrastructural differences among afferent synapses on cochlear hair cells: Correlations with spontaneous discharge rate SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cochlea; synapse; synaptic body; intracellular labeling ID AUDITORY-NERVE FIBERS; GUINEA-PIG COCHLEA; SYNAPTIC RIBBONS; CAT COCHLEA; HORSERADISH-PEROXIDASE; CENTRAL PROJECTIONS; SERIAL SECTIONS; THRESHOLDS; FREQUENCY; NEURONS AB The major class of cochlear afferent fibers, the type-I or radial-fiber (RF) population, has been subdivided into three functional groups according to spontaneous discharge rate (SR): those with low SR have the highest acoustic thresholds, high SR fibers have the lowest thresholds and medium SR fibers are of intermediate sensitivity (Liberman [1978] J. Acoust. Sec. Amer. 63:442-455). Existing evidence from intracellular labeling studies at the light microscopic level (Liberman [1982a] Science 216:1239-1241) suggests that a single cochlear inner hair cell makes synaptic contact with representatives of all three functional groups; however, low and medium SR fibers are spatially segregated from high SR fibers around the hair cell circumference, and low and medium SR fibers are smaller in caliber than those with high SR. The present study extends to the ultrastructural level the structure-function correlations available via intracellular labeling. Analysis is based on serial section reconstruction of the synaptic contacts between 11 radial fibers of known SR and their target hair cells. Results suggest systematic differences in synaptic ultrastructure among fibers of the three SR groups: with decreasing SR, the size and complexity of the synaptic body (a presynaptic specialization characteristic of the peripheral afferent synapses in all hair cell systems and some other peripheral receptors) tend to increase, as does the associated number of synaptic vesicles. The possible functional significance of these trends is discussed in the context of other known structural and functional differences among the three SR groups. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA 02139. RI Merchan-Perez, Angel/D-7417-2014 OI Merchan-Perez, Angel/0000-0002-7228-5821 FU NIDCD NIH HHS [R01 DC 00188] NR 44 TC 90 Z9 95 U1 1 U2 6 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 JUL 22 PY 1996 VL 371 IS 2 BP 208 EP 221 DI 10.1002/(SICI)1096-9861(19960722)371:2<208::AID-CNE2>3.0.CO;2-6 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UX964 UT WOS:A1996UX96400002 PM 8835727 ER PT J AU Weaver, DR AF Weaver, DR TI A(1)-adenosine receptor gene expression in fetal rat brain SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE in situ hybridization; brain mapping; caffeine; ontogeny; P-1-purinergic receptor ID ADENOSINE DOPAMINE INTERACTIONS; PRENATAL CAFFEINE; MOLECULAR-CLONING; NEONATAL EXPOSURE; MOUSE-BRAIN; G-PROTEINS; ONTOGENY; NEURONS; ALTERS; ADENOSINE-A1-RECEPTORS AB Adenosine influences neurotransmitter release, neuronal excitability, and firing rate, through A(1)-adenosine receptors (AI-R). Caffeine and related methylxanthines are adenosine receptor antagonists. Exposure of developing rodents to caffeine is associated with subtle, long-ten changes in neurochemistry and behavior. The developmental appearance of A(1)-R gene expression was examined in rats by in situ hybridization. On gestational day (GD) 10, A(1)-R mRNA was expressed at very high levels in placental mesometrium. Expression of A(1)-R mRNA in brain was first detected on GD 14. Hybridization was restricted to portions of neuroepithelium, caudate-putamen, piriform cortex, hypoglossal nucleus, and ventral horn of spinal cord. Neuroepithelial A(1)-R mRNA increased in intensity and distribution at subsequent ages, reaching a maximum on GD 20 (the latest age studied). Hybridization signal was detected, with regional variation in intensity, throughout much of the brain by GD 16, with additional increases in extent and intensity through GD 20. Generally, a caudal > rostral gradient of hybridization intensity was apparent. The distribution on GD 20 resembled the widespread yet heterogeneous pattern observed in the adult, with high levels of A(1)-R gene expression in cortex, hippocampus, thalamus, cerebellum, pontine nuclei, brainstem motor nuclei, and spinal cord. Northern blot analysis confirmed the age-related increase in abundance of A(1)-R transcripts (ca. 3.5 and 5.5 kb). The early and widespread expression of A(1)-R mRNA, coupled with previous reports of prenatal A(1)-R binding, suggests that adenosine and adenosine antagonists, including caffeine, may influence neuronal differentiation, migration or synaptogenesis, thus producing long-lasting effects on brain and behavior. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Weaver, DR (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,LAB DEV CHRONOBIOL,JACKSON 1226 GRJ 1226,BOSTON,MA 02114, USA. OI Weaver, David/0000-0001-7941-6719 NR 53 TC 60 Z9 60 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUL 20 PY 1996 VL 94 IS 2 BP 205 EP 223 DI 10.1016/0165-3806(96)00049-1 PG 19 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA UY139 UT WOS:A1996UY13900012 ER PT J AU Chen, CW Oberley, TD Roy, D AF Chen, CW Oberley, TD Roy, D TI Inhibition of stilbene estrogen-induced cell proliferation of renal epithelial cells through the modulation of insulin-like growth factor-I receptor expression SO CANCER LETTERS LA English DT Article DE stilbene estrogen; insulin-like growth factor-I receptor; renal epithelial cells ID HUMAN-BREAST-CANCER; TUBULAR CELLS; IGF-I; ANTIBODY; OVEREXPRESSION; SECRETION; INVITRO; PROTEIN; MITOGEN; CULTURE AB In the present study, we have investigated the effects of stilbene estrogen, diethylstilbestrol (DES), on the proliferative activity and expression of insulin-like growth factor-I (IGF-I) receptor in Syrian hamster renal epithelial cells. DES exposure to renal epithelial cells caused both dose- and time-dependent increases in proliferative activity. We also tested the effects of antiestrogen ICI 182780 and insulin-like growth factor-I receptor (IGF-IR) antibody on cell proliferation. Cotreatment of cells with ICI 182780 (250 nM) and DES resulted in a 50% decrease in cell growth compared to DES alone. Treatment of cells with an anti-IGF-IR antibody (alpha IR3, 1 mu g/ml) also significantly reversed the growth-stimulatory effects of DES. A nuclear binding assay revealed that an enhanced level (similar to 2-fold) of [I-125]IGF-I binding to nuclear protein occurred in DES treated renal epithelial cell nuclei compared to controls. IGF-I receptor gene expression analyzed by Northern blotting revealed that DES treatment increased the level of IGF-IR mRNA by 2-fold compared to controls. We also tested the effect of ICI compound on the induction of IGF-I receptor gene. The cotreatment of ICI 182780 strongly inhibited DES-induced IGF-I receptor gene expression (50-60% inhibition). Stimulation of the proliferative activity of renal epithelial cells by stilbene estrogen, its prevention by IGF-I receptor antibody, and inhibition of DES-induced proliferative activity and the expression of IGF-I receptors by ICI 182780 suggest the possibility that the stimulatory effect of DES on the proliferative activity of renal epithelial cells may be mediated through the up-regulation of IGF-I receptors. C1 UNIV ALABAMA,DEPT ENVIRONM HLTH SCI,ENVIRONM TOXICOL PROGRAM,BIRMINGHAM,AL 35294. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. FU NCI NIH HHS [CA52584] NR 30 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 19 PY 1996 VL 105 IS 1 BP 51 EP 59 DI 10.1016/0304-3835(96)04263-2 PG 9 WC Oncology SC Oncology GA UV573 UT WOS:A1996UV57300009 PM 8689633 ER PT J AU Gaczynska, M Goldberg, AL Tanaka, K Hendil, KB Rock, KL AF Gaczynska, M Goldberg, AL Tanaka, K Hendil, KB Rock, KL TI Proteasome subunits X and Y alter peptidase activities in opposite ways to the interferon-gamma-induced subunits LMP2 and LMP7 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MULTICATALYTIC PROTEINASE COMPLEX; CLASS-I MOLECULES; MHC; EXPRESSION; GENE; YEAST; MICE AB Most antigenic peptides presented on major histocompatibility complex class I molecules are generated by proteasomes, Interferon-gamma, which stimulates antigen presentation, induces new proteasome beta-subunits LMP2 and LMP7, which replace the homologous beta-subunits Y (delta) and X (epsilon). As a result, the capacity of the proteasome to cleave model peptides increases after hydrophobic and basic residues and falls after acidic residues, To clarify the function of these subunits, are examined the effects of overexpressing subunits X (delta) and Y (epsilon). Transfection of the Y gene into HeLa cells stimulated the proteasomal cleavage after acidic residues without altering other peptidase activities. This effect was propertional to the amount of the Y subunits and opposite to the effect of its homolog, LMP2. Y appears to promote cleavages after acidic residues, Furthermore, in mutants lacking the LMP genes (in contrast to wild-type cells), interferon-gamma treatment increased the proteasome content of Y subunits and enhanced postacidic cleavages. Transfection with cDNA for the X subunit reduced hydrolysis after hydrophobic and basic residues, an effect opposite to transfection of LMP2 and LMP7, Surprisingly, transfection of X increased the amounts not only of X, but also of Y, while decreasing LMPB content. Thus, the loss of the Y subunit upon interferon-gamma treatment or LMPB transfection accounts for the suppression of postacidic cleavages, and the loss of X contributes to the increased hydrolysis after hydrophobic and basic residues. These adaptations should favor the production of the kinds of peptides that are presented on major histocompatibility complex class I molecules. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV TOKUSHIMA,INST ENZYME RES,TOKUSHIMA 770,JAPAN. UNIV COPENHAGEN,AUGUST KROGH INST,DK-2100 COPENHAGEN 0,DENMARK. NR 42 TC 114 Z9 120 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 JUL 19 PY 1996 VL 271 IS 29 BP 17275 EP 17280 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX943 UT WOS:A1996UX94300047 PM 8663318 ER PT J AU Corey, DP GarciaAnoveros, J AF Corey, DP GarciaAnoveros, J TI Mechanosensation and the DEG/ENaC ion channels SO SCIENCE LA English DT Editorial Material ID NEMATODE CAENORHABDITIS-ELEGANS; EPITHELIAL SODIUM-CHANNEL; SENSITIVE NA+ CHANNEL; MECHANOELECTRICAL TRANSDUCTION; MEMBRANE TOPOLOGY; HAIR-CELLS; NEURONS; GENE; NEURODEGENERATION; IDENTIFICATION C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Corey, DP (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02114, USA. OI Corey, David/0000-0003-4497-6016 NR 35 TC 81 Z9 99 U1 2 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 19 PY 1996 VL 273 IS 5273 BP 323 EP 324 DI 10.1126/science.273.5273.323 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY202 UT WOS:A1996UY20200028 PM 8685718 ER PT J AU Ahima, RS Prabakaran, D Mantzoros, C Qu, DQ Lowell, B MaratosFlier, E Flier, JS AF Ahima, RS Prabakaran, D Mantzoros, C Qu, DQ Lowell, B MaratosFlier, E Flier, JS TI Role of leptin in the neuroendocrine response to fasting SO NATURE LA English DT Article ID FOOD-DEPRIVATION; SECRETION; RAT AB A TOTAL deficiency in or resistance to the protein leptin causes severe obesity(1-4). As leptin levels rise with increasing adiposity in rodents(5) and man(6,7), it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance(1,3). Starvation is also a threat to homeostasis that triggers adaptive responses(8-12), but whether leptin plays a role in the physiology of starvation is unknown. Leptin concentration falls during starvation(13) and totally leptin-deficient ob/ob mice have neuroendocrine abnormalities similar to those of starvation(14), suggesting that this may be the case. Here we show that preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starvation-induced delay in ovulation in female mice. In contrast, leptin repletion during this period of starvation has little or no effect on body weight, blood glucose or ketones. We propose that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin. C1 BETH ISRAEL HOSP,DEPT MED,DIV ENDOCRINOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. NR 24 TC 2138 Z9 2182 U1 10 U2 96 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 18 PY 1996 VL 382 IS 6588 BP 250 EP 252 DI 10.1038/382250a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UX790 UT WOS:A1996UX79000048 PM 8717038 ER PT J AU Yuan, ZM Huang, YY Whang, Y Sawyers, C Weichselbaum, R Kharbanda, S Kufe, D AF Yuan, ZM Huang, YY Whang, Y Sawyers, C Weichselbaum, R Kharbanda, S Kufe, D TI Role for c-Abl tyrosine kinase in growth arrest response to DNA damage SO NATURE LA English DT Article ID RETINOBLASTOMA PROTEIN; INHIBITION; BINDING; P53 AB THE c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents', and its overexpression causes arrest in the G1 phase of the cell cycle by a mechanism dependent on the tumour-suppressor protein p53 (refs 2-4). Here we investigate the possible role of c-Abl in growth arrest induced by DNA damage. Transient transfection experiments using wild-type or inactivated c-Abl show that both induce expression of p21, an effector of p53, but only wild-type c-Abl downregulates the activity of the cyclin-dependent kinase Cdk2 and causes growth arrest. Exposure to ionizing radiation of cells that stably express active or inactive c-Abl is associated with induction of c-Abl/p53 complexes and p21 expression. However, cells expressing the dominant-negative c-Abl mutant and cells lacking the c-abl gene are impaired in their ability to downregulate Cdk2 or undergo G1 arrest in response to ionizing radiation. We also show that expression of c-Abl kinase in p21(-/-), but not in p53(-/-), cells results in downregulation of Cdk2. Our results suggest that c-Abl kinase contributes to the regulation of growth arrest induced by ionizing radiation by a p53-dependent, p21-independent mechanism. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90095. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RI Sawyers, Charles/G-5327-2016 NR 18 TC 204 Z9 208 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 18 PY 1996 VL 382 IS 6588 BP 272 EP 274 DI 10.1038/382272a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UX790 UT WOS:A1996UX79000055 PM 8717045 ER PT J AU Greenberg, SM Edgar, MA Kunz, DP HedleyWhyte, ET Finklestein, SP Segal, AZ Vonsattel, JP AF Greenberg, SM Edgar, MA Kunz, DP HedleyWhyte, ET Finklestein, SP Segal, AZ Vonsattel, JP TI Cerebral hemorrhage in a 69-year-old woman receiving warfarin - Cerebral amyloid angiopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; CENTRAL NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; INTRACEREBRAL HEMORRHAGE; GRANULOMATOUS-ANGIITIS; THROMBOLYTIC THERAPY; CLINICAL SPECTRUM; LOBAR HEMORRHAGE; RISK-FACTORS; COMPLICATIONS C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Greenberg, SM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 48 TC 29 Z9 29 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 JUL 18 PY 1996 VL 335 IS 3 BP 189 EP 196 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UW790 UT WOS:A1996UW79000008 ER PT J AU Carlson, KJ Schiff, I AF Carlson, KJ Schiff, I TI Alternatives to hysterectomy for menorrhagia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COMPARING ENDOMETRIAL RESECTION; ABDOMINAL HYSTERECTOMY RP Carlson, KJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 9 TC 10 Z9 10 U1 1 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 JUL 18 PY 1996 VL 335 IS 3 BP 198 EP 199 DI 10.1056/NEJM199607183350309 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UW790 UT WOS:A1996UW79000009 PM 8657219 ER PT J AU Yao, R Cooper, GM AF Yao, R Cooper, GM TI Growth factor-dependent survival of rodent fibroblasts requires phosphatidylinositol 3-kinase but is independent of pp70(S6K) activity SO ONCOGENE LA English DT Article DE apoptosis; PI 3-kinase; S6 kinase ID PROGRAMMED CELL-DEATH; PROTEIN-KINASE-C; S6 KINASE; DNA-SYNTHESIS; MAMMALIAN PROTEIN; ACTIVATION; RAPAMYCIN; INSULIN; WORTMANNIN; APOPTOSIS AB A variety of mammalian cells undergo apoptosis when deprived of growth factors, but the intracellular signaling pathways responsible for cell survival remain to be characterized. In the present study, we have investigated the role of PI 3-kinase and pp70(S6K) in growth factor-dependent survival of rodent fibroblasts. As previously reported for PC12 pheochromocytoma cells, Rat-1 and REF52 cells underwent apoptosis following either serum-deprivation or treatment with the PI 3-kinase inhibitors wortmannin and LY294002. In contrast, NIH3T3 and BALB 3T3 cells were resistant to apoptosis induced by either serum-deprivation or PI 3-kinase inhibition. It thus appears that PI 3-kinase is specifically required to prevent apoptosis of fibroblast that are dependent upon growth factors survival. Consistent with this role of PI 3-kinase, serum and growth factors maintained steady state levels of PI 3-kinase activity that rapidly decreased following serum-deprivation. Serum and growth factors similarly maintained a steady state level of pp70(S6K), which is thought to be activated downstream of PI 3-kinase. However, inhibition of pp70(S6K) activation by rapamycin failed to induce apoptosis in either Rat-1 or PC12 cells. Cell survival thus appears to require a PI 3-kinase signaling pathway that is independent of pp70(S6K) activation. C1 DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01 CA18689] NR 42 TC 114 Z9 114 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 18 PY 1996 VL 13 IS 2 BP 343 EP 351 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VA252 UT WOS:A1996VA25200013 PM 8710373 ER PT J AU Garg, HG Joseph, PAM Yoshida, K Thompson, BT Hales, CA AF Garg, HG Joseph, PAM Yoshida, K Thompson, BT Hales, CA TI Antiproliferative role of 3-O-sulfate glucosamine in heparin on cultured pulmonary artery smooth muscle cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROLIFERATION; HYPERTENSION; ANTICOAGULANT; INHIBITION; SULFATE AB Heparin macromolecules inhibit vascular remodeling associated with hypoxic pulmonary hypertension. Heparin's antiproliferative effect on smooth muscle cells, based on studies of synthetic pentasaccharide fragments, has been attributed to 3-O-sulfate on the internal glucosamine. To determine the role of 3-O-sulfation in smooth muscle cell growth, we treated three heparins of varying potency with heparitinases I and II, which degrade heparin fragments containing 3-O-sulfate on the glucosamine residue to Delta-tetrassacchharides only. Our most antiproliferative heparin gave the least amount of Delta-tetrasaccharides. This heparin was then fractionated according to degree of sulfation using ETOH precipitation. Again we found no antiproliferative difference between the highly sulfated fractions and those with a lesser degree of sulfation. These studies suggest that 3-O-sulfate of glucosamine residue is not critical in whole heparins for antiproliferative activity. (C) 1996 Academic Press, Inc. C1 SEIKAGAKU CORP HIGASHIYAMATO,TOKYO RES INST,TOKYO 207,JAPAN. RP Garg, HG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CRIT CARE UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R01 HL039150] NR 26 TC 11 Z9 11 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 JUL 16 PY 1996 VL 224 IS 2 BP 468 EP 473 DI 10.1006/bbrc.1996.1050 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UY656 UT WOS:A1996UY65600029 PM 8702412 ER PT J AU Kieffer, TJ Heller, RS Habener, JF AF Kieffer, TJ Heller, RS Habener, JF TI Leptin receptors expressed on pancreatic beta-cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NECROSIS-FACTOR-ALPHA; DIABETES-OBESITY SYNDROMES; INSULIN-RESISTANCE; MICE; GENE AB Leptin (Ob protein) is a recently isolated hormone produced by adipocytes and is a powerful regulator of satiety centers in the brain. A defect in either leptin production or transmission of the leptin signal in animal models, i.e. ob/ob and db/db mice, respectively, results in a syndrome of obesity and diabetes which closely resembles that which occurs in humans. Leptin release is regulated in part by nutritional status and its expression in adipose tissue is up-regulated by insulin. Since hyperinsulinemia is a primary defect in ob/ob and db/db mice which manifests early in the disease, we postulated that leptin may also regulate insulin release as part of a 'adipoinsular' feedback loop. We demonstrate the expression of leptin receptor mRNA in primary rat pancreatic islets and in the insulinoma cell line beta TC-3. Furthermore, we find binding of I-125-leptin to beta TC-3 cells which is significantly displaced by leptin. These findings suggest the possibility that the binding of leptin to its receptor in beta-cells may modulate insulin expression in a negative feedback loop, and thereby may have an anti-obesity effect. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02114. RI Heller, R.Scott/A-7279-2008 NR 24 TC 269 Z9 271 U1 2 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 JUL 16 PY 1996 VL 224 IS 2 BP 522 EP 527 DI 10.1006/bbrc.1996.1059 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UY656 UT WOS:A1996UY65600038 PM 8702421 ER PT J AU Griffin, JD Kornfield, K AF Griffin, JD Kornfield, K TI Editor's report 1996 SO BLOOD LA English DT Editorial Material RP Griffin, JD (reprint author), DANA FARBER CANC INST,DIV HAMATOL MALIGNANCIES,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1996 VL 88 IS 2 BP 383 EP 385 PG 3 WC Hematology SC Hematology GA UW488 UT WOS:A1996UW48800001 ER PT J AU Shikama, Y Barber, DL DAndrea, AD Sieff, CA AF Shikama, Y Barber, DL DAndrea, AD Sieff, CA TI A constitutively activated chimeric cytokine receptor confers factor-independent growth in hematopoietic cell lines SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PROTEIN-TYROSINE KINASE; GM-CSF RECEPTOR; ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; BETA-SUBUNIT; FUNCTIONAL RECEPTORS; CYTOPLASMIC DOMAINS; EXPRESSION CLONING; MOLECULAR-CLONING AB The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GMR) comprises at least 2 distinct subunits, alpha and beta common (beta(c)), whereas the normal erythropoietin receptor (nEpoR) comprises only one known subunit. An arginine to cysteine (R129C) mutation of the extracytoplasmic domain of the murine EpoR leads to Epo-independent growth in transduced cells (cEpoR). To investigate the proliferative functions of the cytoplasmic regions of each GMR subunit separately and the potential of the R129C EpoR mutation to induce factor-independent growth through heterologous receptor regions, we constructed four hybrid receptors: the extracellular region of either murine nEpoR or cEpoR linked to the transmembrane and cytoplasmic regions of either the human GMR alpha or beta(c) subunit (nE alpha, nE beta, cE alpha, and cE beta). We then expressed them in an interleukin-3-dependent murine cell line, Ba/F3. Expression of nE beta led to Epo-dependent growth, whereas expression of cE beta conferred factor-independent growth. Surprisingly, expression of cE alpha also resulted in factor-independent cell growth, whereas nE alpha did not respond to Epo. Furthermore, the functional hybrid receptors showed Epo-dependent (nE beta) or constitutive (cE alpha and cE beta) tyrosine phosphorylation of the cytoplasmic kinases JAK1 and JAK2. We reasoned that the proliferative signal of cE alpha was transduced either through the alpha tail itself or through an accessory protein such as the endogenous murine beta common subunit (mu beta(c)). To distinguish these possibilities, the chimeric receptor cE alpha as expressed in the interleukin-2-dependent murine cell line, CTLL-2, that does not express mu beta(c). cE alpha did not induce cell growth in CTLL-2; however, when mu beta(c) was coexpressed with cE alpha in CTLL-2, factor-independent growth was reconstituted. In conclusion, the cytoplasmic domain of the GMB alpha subunit requires a beta chain for transduction of a proliferative signal. Furthermore, the R129C EpoR mutation can constitutively activate heterologous receptors to mediate factor-independent proliferation. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT HEMATOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA. FU NCI NIH HHS [CA45559]; NICHD NIH HHS [NIHDK 43889-04] NR 41 TC 20 Z9 20 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 JUL 15 PY 1996 VL 88 IS 2 BP 455 EP 464 PG 10 WC Hematology SC Hematology GA UW488 UT WOS:A1996UW48800009 PM 8695792 ER PT J AU Brook, A Xie, JE Du, W Dyson, N AF Brook, A Xie, JE Du, W Dyson, N TI Requirements for dE2F function in proliferating cells and in post-mitotic differentiating cells SO EMBO JOURNAL LA English DT Article DE differentiation; Drosophila; E2F; pRB; proliferation ID RETINOBLASTOMA GENE-PRODUCT; SITE-SPECIFIC RECOMBINATION; S-PHASE ENTRY; TRANSCRIPTION FACTOR; BINDING PROTEIN; G2-M TRANSITION; DNA-BINDING; DROSOPHILA; E2F; EXPRESSION AB The transcription factor E2F is a target of the retino-blastoma tumor suppressor protein (pRB) and may mediate pRB regulation of S phase entry in mammalian cells, The recent identification of mutant alleles of the Drosophila E2F gene (dE2F) has shown that dE2F is required for embryogenesis. dE2F-mutant embryos lack a co-ordinated program of gene expression which accompanies S phase entry and DNA synthesis declines to levels that are barely detectable. We have investigated the role of the dE2F gene at later stages of development, dE2F is expressed in several larval tissues and is required for cell proliferation in the eye imaginal disc, Surprisingly, dE2F expression persists in post-mitotic cells of the eye disc of third-instar larvae. The loss of dE2F function in these cells causes a novel phenotype, characterized by loss of photoreceptors and abnormal rhabdomere cell morphology. These results show that dE2F is required at multiple stages of development and suggest that E2F may have an important function in post-mitotic cells in addition to its role during cell proliferation. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. FU NIGMS NIH HHS [GM53203] NR 62 TC 56 Z9 56 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 15 PY 1996 VL 15 IS 14 BP 3676 EP 3683 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY922 UT WOS:A1996UY92200021 PM 8670871 ER PT J AU Du, W Xie, JE Dyson, N AF Du, W Xie, JE Dyson, N TI Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye SO EMBO JOURNAL LA English DT Article DE apoptosis; cell proliferation; E2F transcription factor ID S-PHASE ENTRY; RETINOBLASTOMA PROTEIN; BINDING PROTEIN; TRANSCRIPTION FACTOR-E2F; CDK4 AMPLIFICATION; DNA-BINDING; GENE; E2F; FAMILY; TRANSACTIVATION AB The deregulation of E2F activity is thought to contribute to the uncontrolled proliferation of many tumor tells, While the effects of overexpressing E2F genes have been studied extensively in tissue culture, the consequences of elevating E2F activity in vivo are unknown, To address this issue, transgenic lines of Drosophila were studied in which ectopic expression of dE2F and dDP was targeted to the developing eye, The co-expression of dDP or dE2F disrupted normal eye development, resulting in abnormal patterns of bristles, cone cells and photoreceptors. dE2F/dDP expression caused ectopic S phases in post-mitotic cells of the eye imaginal disc but did not disrupt the onset of neuronal differentiation. Most S phases were seen in uncommitted cells, although some cells that had initiated photoreceptor differentiation were also driven into the cell cycle. Elevated expression of dE2F and dDP caused apoptosis in the eve disc, The co-expression of baculo-virus p35 protein, an inhibitor of cell death, strongly enhanced the dE2F/dDP-dependent phenotype, These results show that, in this in vivo system, the elevation of E2F activity caused post-mitotic cells to enter the cell cycle, However, these cells failed to proliferate unless rescued from apoptosis. C1 MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. FU NIGMS NIH HHS [GM53203] NR 57 TC 100 Z9 100 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 15 PY 1996 VL 15 IS 14 BP 3684 EP 3692 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY922 UT WOS:A1996UY92200022 PM 8670872 ER PT J AU Fore, WW AF Fore, WW TI Managed care approaches to diabetes mellitus SO HOSPITAL PRACTICE LA English DT Article RP Fore, WW (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,WILLS EYE HOSP,JOSLIN DIABET CTR,PHILADELPHIA,PA 19107, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD JUL 15 PY 1996 VL 31 IS 7 BP 115 EP 117 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UX132 UT WOS:A1996UX13200015 PM 8682875 ER PT J AU Shipley, WU AF Shipley, WU TI PSA following irradiation for prostate cancer: The upcoming ASTRO symposium SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Shipley, WU (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA 02114, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 1996 VL 35 IS 5 BP 1115 EP 1115 DI 10.1016/0360-3016(96)00289-1 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VD588 UT WOS:A1996VD58800031 PM 8751422 ER PT J AU Janssens, SP Bloch, KD Nong, ZX Gerard, RD Zoldhelyi, P Collen, D AF Janssens, SP Bloch, KD Nong, ZX Gerard, RD Zoldhelyi, P Collen, D TI Adenoviral-mediated transfer of the human endothelial nitric oxide synthase gene reduces acute hypoxic pulmonary vasoconstriction in rats SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE adenovirus; guanylate cyclase; hypoxia; pulmonary hypertension; gene therapy ID OBSTRUCTIVE LUNG-DISEASE; DEPENDENT RELAXATION; STRUCTURAL-CHANGES; PLATELET-ADHESION; RELAXING FACTOR; HYPERTENSION; ARTERY; EXPRESSION; NEWBORN; CELLS AB Nitric oxide (NO), a vasodilator involved in the regulation of pulmonary vascular tone, is synthesized by a family of enzymes, nitric oxide synthases (NOS). To investigate whether adenoviral-mediated overexpression of constitutive endothelial NOS (ceNOS) would attenuate hypoxic pulmonary vasoconstriction, we aerosolized 3 x 10(9) plaque forming units of a recombinant adenovirus containing the ceNOS gene (AdCMVceNOS) into rat lungs. Four days after infection, transgene expression was confirmed using immunoblot techniques. Diffuse ceNOS immunostaining was detected in alveoli and medium-sized and small pulmonary vessels of AdCMVceNOS-transduced lungs. AdCMVceNOS-transduction was associated with an 86% increase in [H-3]arginine to [H-3]citrulline conversion and a rise in pulmonary cGMP levels from 7+/-1 to 59+/-9 pmol/mg protein in lungs from AdCMVceNOS versus control rats, (P < 0.05). During acute hypoxia (FIO2 = 0.10) for 25 min, mean pulmonary artery pressure (PAP) increased significantly from 17+/-1 to 27+/-1 mmHg in rats aerosolized with saline (n = 4) and from 18+1 to 28+/-1 mmHg in rats given an adenoviral vector expressing a nuclear-targeted beta-galactosidase gene (AdCMV beta gal, n = 8). In contrast, in AdCMVceNOS-transduced rats (n = 8) the hypoxia-induced increase in PAP was significantly attenuated (18+/-1 to 23+/-2 mmHg). Systemic blood pressure was not affected by aerosol gene transfer. Thus, adenoviral-mediated ceNOS gene transfer to rat lungs increases ceNOS expression and activity, and reduces acute hypoxic pulmonary vasoconstriction. Aerosolized recombinant adenovirus overexpressing vasodilatory proteins can act as a selective pulmonary vasodilator and may hold promise as a future therapeutic strategy for pulmonary hypertension. C1 KATHOLIEKE UNIV LEUVEN, CARDIAC UNIT, B-3000 LOUVAIN, BELGIUM. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CARDIOVASC RES CTR, BOSTON, MA 02115 USA. RP Janssens, SP (reprint author), KATHOLIEKE UNIV LEUVEN, CTR TRANSGENE TECHNOL & GENE THERAPY, CAMPUS GASTHUISBERG, 49 HEREST, B-3000 LOUVAIN, BELGIUM. FU NHLBI NIH HHS [HL-45895] NR 43 TC 108 Z9 117 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 15 PY 1996 VL 98 IS 2 BP 317 EP 324 DI 10.1172/JCI118795 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VA160 UT WOS:A1996VA16000013 PM 8755640 ER PT J AU Bazzoni, G Carlesso, N Griffin, JD Hemler, ME AF Bazzoni, G Carlesso, N Griffin, JD Hemler, ME TI Bcr/Abl expression stimulates integrin function in hematopoietic cell lines SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE integrin; Bcr/Abl; cell adhesion; chronic myelogenous leukemia; fibronectin ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; BONE-MARROW STROMA; PROGENITOR CELLS; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY; BCR-ABL; ADHESION MOLECULE-1; TYROSINE KINASE; CULTURE REVEALS AB Cell adhesion to the extracellular matrix is largely mediated by adhesion molecules of the integrin family and is often diminished upon oncogenic transformation. However, we show here that the chronic myelogenous leukemia oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 integrin function. The presence of Bcr/Abl in the GM-CSF- or IL-3-dependent hematopoietic cell lines MO7e, 32D, and BaF/3 enhanced cell binding to both soluble and immobilized fibronectin. The effect was due to enhanced function of the VLA-5 integrin fibronectin receptor and not to increased surface expression. In parallel, Bcr/Abl stimulated cell adhesion to the VLA-4 integrin ligand VCAM-1. Stimulation of VLA-5 function directly correlated with induction of Bcr/Abl tyrosine kinase activity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulates integrin-dependent cell adhesion, by a mechanism involving increased ligand binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role. Consistent with these results, hematopoietic precursor cells from chronic myelogenous leukemia patients also showed increased adhesion to fibronectin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,LAB HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NCI NIH HHS [CA42368, CA66996] NR 62 TC 94 Z9 95 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 15 PY 1996 VL 98 IS 2 BP 521 EP 528 DI 10.1172/JCI118820 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VA160 UT WOS:A1996VA16000038 PM 8755665 ER PT J AU Kowluru, A Seavey, SE Li, GD Sorenson, RL Weinhaus, AJ Nesher, R Rabaglia, ME Vadakekalam, J Metz, SA AF Kowluru, A Seavey, SE Li, GD Sorenson, RL Weinhaus, AJ Nesher, R Rabaglia, ME Vadakekalam, J Metz, SA TI Glucose- and GTP-dependent stimulation of the carboxyl methylation of CDC42 in rodent and human pancreatic islets and pure beta cells - Evidence for an essential role of GTP-binding proteins in nutrient-induced insulin secretion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE pancreatic beta cell; insulin secretion; GTP-binding proteins; CDC42; carboxyl methylation ID NUCLEOSIDE DIPHOSPHOKINASE ACTIVITY; GDP-DISSOCIATION INHIBITOR; ADP-RIBOSYLATION FACTORS; RAT ISLETS; FARNESYLCYSTEINE ANALOGS; SUBCELLULAR-LOCALIZATION; SIGNAL TRANSDUCTION; NUCLEOTIDE EXCHANGE; GDP/GTP EXCHANGE; PLASMA-MEMBRANE AB Several GTP-binding proteins (G-proteins) undergo posttranslational modifications (isoprenylation and carboxyl methylation) in pancreatic beta cells. Herein, two of these were identified as CDC42 and rap 1, using Western blotting and immunoprecipitation. Confocal microscopic data indicated that CDC42 is localized only in islet endocrine cells but not in acinar cells of the pancreas. CDC42 undergoes a guanine nucleotide-specific membrane association and carboxyl methylation in normal rat islets, human islets, and pure beta (HIT or INS-1) cells. GTP gamma S-dependent carboxyl methylation of a 23-kD protein was also demonstrable in secretory granule fractions from normal islets or beta cells. AFC (a specific inhibitor of prenyl-cysteine carboxyl methyl transferases) blocked the carboxyl methylation of CDC42 in five types of insulin-secreting cells, without blocking GTP gamma S-induced translocation, implying that methylation is a consequence (not a cause) of transfer to membrane sites. High glucose (but not a depolarizing concentration of K+) induced the carboxyl methylation of CDC42 in intact cells, as assessed after specific immunoprecipitation. This effect was abrogated by GTP depletion using mycophenolic acid and was restored upon GTP repletion by coprovision of guanosine. In contrast, although rap 1 was also carboxyl methylated, it was not translocated to the particulate fraction by GTP gamma S; furthermore, its methylation was also stimulated by 40 mM K+ (suggesting a role which is not specific to nutrient stimulation). AFC also impeded nutrient-induced (but not K+-induced) insulin secretion from islets and beta cells under static or perifusion conditions, whereas an inactive structural analogue of AFC failed to inhibit insulin release. These effects were reproduced not only by S-adenosylhomocysteine (another methylation inhibitor), but also by GTP depletion. Thus, the glucose- and GTP-dependent carboxyl methylation of G-proteins such as CDC42 is an obligate step in the stimulus-secretion coupling of nutrient-induced insulin secretion, but not in the exocytotic event itself. Furthermore, AFC blocked glucose-activated phosphoinositide turnover, which may provide a partial biochemical explanation for its effect on secretion, and implies that certain G-proteins must be carboxyl methylated for their interaction with signaling effector molecules, a step which can be regulated by intracellular availability of GTP. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,DIV ENDOCRINOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. UNIV MINNESOTA,SCH MED,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. HEBREW UNIV JERUSALEM,HADASSAH MED CTR,DEPT ENDOCRINOL & METAB,IL-91120 JERUSALEM,ISRAEL. FU NIDDK NIH HHS [DK33655, DK37312] NR 68 TC 99 Z9 100 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 15 PY 1996 VL 98 IS 2 BP 540 EP 555 DI 10.1172/JCI118822 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VA160 UT WOS:A1996VA16000040 PM 8755667 ER PT J AU Durstin, M Inhorn, RC Griffin, JD AF Durstin, M Inhorn, RC Griffin, JD TI Tyrosine phosphorylation of Shc is not required for proliferation or viability signaling by granulocyte-macrophage colony-stimulating factor in hematopoietic cell lines SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-NEUTROPHILS; GM-CSF; RECEPTOR; GROWTH; RAS; TRANSDUCTION; CLONING; SUBUNIT; KINASES; DOMAIN AB The receptor for human granulocyte-macrophage (GM)-CSF (GMR) is a heterodimer, consisting of an alpha-chain (GMR alpha) and a beta-chain (GMR beta). While GMR alpha is capable of binding GM-CSF, GMR beta is necessary for signal transduction. Phosphorylation of one or more tyrosine residues in GMR beta is an early event in signaling. We have recently demonstrated that tyrosine 750 (Y750) in GMR beta is a site of GM-CSF-induced phosphorylation and this site may contribute to the maintenance of cellular viability in response to GM-CSF. To investigate possible contributions made by additional GMR beta cytoplasmic tyrosine residues to receptor function, we mutated other selected tyrosine residues to phenylalanine and tested for any defects in signaling. In the present study, we show that Y577 is required for phosphorylation of Shc and an Shc-associated p140 in response to GM-CSF. Y577 is also required for association of Shc with GRB2. Y577 does not appear to be necessary for GM-CSF-induced proliferation and survival. GMR beta with a mutated Y577 is able to transduce signals leading to the activation of the Raf-1 pathway and the Jak-Stat pathway. Interestingly, mutation of Y750 reduced detectable GM-CSF-induced tyrosine phosphorylation of GMR beta, suggesting that the reduction of Shc phosphorylation associated with that mutant might be actually due to a failure to phosphorylate Y577. These data indicate that the phosphorylation of Shc in response to GM-CSF is not required for proliferation or viability signaling in these cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NCI NIH HHS [CA36167] NR 33 TC 30 Z9 30 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 JUL 15 PY 1996 VL 157 IS 2 BP 534 EP 540 PG 7 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400007 PM 8752899 ER PT J AU Fischer, MB Ma, MH Goerg, S Zhou, XN Xia, JR Finco, O Han, SH Kelsoe, G Howard, RG Rothstein, TL Kremmer, E Rosen, FS Carroll, MC AF Fischer, MB Ma, MH Goerg, S Zhou, XN Xia, JR Finco, O Han, SH Kelsoe, G Howard, RG Rothstein, TL Kremmer, E Rosen, FS Carroll, MC TI Regulation of the B cell response to T-dependent antigens by classical pathway complement SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLETE CDNA SEQUENCE; AMINO-ACID SEQUENCES; SEX-LIMITED PROTEIN; 4TH COMPONENT; LYMPHOCYTES-B; IMMUNE-RESPONSE; ANTIBODY-PRODUCTION; COMPLETE NUCLEOTIDE; MURINE COMPLEMENT; GERMINAL-CENTERS AB Mice deficient in complement components C3 (C3-/-) and C4 (C4-/-) were found to have a profound defect in their Ab response to a T-dependent Ag (bacteriophage phi X174). Characterization of the deficient mice demonstrated a diminished level of peanut agglutinin(+) germinal centers and a failure in isotype switching despite normal B cell signaling in vitro. The nature of the defect was found to lie at the B cell level, as the T cells were primed in C3- and C4-deficient mice as well as those in wild-type mice. These results, and the finding that the defect could be partly reversed by a 10-fold increase in Ag dose, support the hypothesis that covalent attachment of complement ligands, i.e., C3b and C3d to the Ag-Ab complex, increases its immunogenicity. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. IRIS,SIENA,ITALY. HEMATOLOGIKUM,INST IMMUNOL,MUNICH,GERMANY. UNIV MARYLAND,SCH MED,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. FU NIAID NIH HHS [AI-24335, AI-32544]; NICHD NIH HHS [HD-1746] NR 61 TC 282 Z9 287 U1 2 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1996 VL 157 IS 2 BP 549 EP 556 PG 8 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400009 PM 8752901 ER PT J AU Michalek, MT Grant, EP Rock, KL AF Michalek, MT Grant, EP Rock, KL TI Chemical denaturation and modification of ovalbumin alters its dependence on ubiquitin conjugation for class I antigen presentation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYCLE MUTANT TS85; ORNITHINE DECARBOXYLASE; PROTEIN-DEGRADATION; ACTIVATING ENZYME; SOLUBLE-PROTEIN; MHC; PROTEASOMES; CELLS; COMPLEX; INTERFERON AB Class I presentation of microinjected native OVA by a temperature-sensitive ubiquitin conjugation mutant, ts85, but not wild-type murine cells, was markedly inhibited following incubation at a nonpermissive temperature. In contrast, the nonpermissive temperature did not affect class I presentation of a minimal OVA peptide expressed in the cytosol. Therefore, these results provide a second example in which a temperature sensitive mutation in the ubiquitin conjugation pathway inhibits MHC class I presentation of native OVA. Surprisingly, incubation at the nonpermissive temperature did not inhibit class I presentation of chemically denatured and alkylated OVA microinjected into the cytosol of mutant cells. Similarly, the presentation of endogenously synthesized OVA (which is expressed from a recombinant vaccinia virus and, presumably, is misfolded in the cytosol) was also not inhibited in both mutant cell lines. Methylation of the lysine groups in denatured OVA, which blocks ubiquitin conjugation, reduced but did not eliminate the presentation of denatured OVA, providing evidence for both ubiquitin-dependent and ubiquitin-independent pathways for class I presentation. In contrast, a proteasome inhibitor blocked class I presentation of all forms of OVA, while a control peptide aldehyde was not inhibitory. These results indicate that modification of the structure of a protein can influence its requirements for ubiquitin conjugation for efficient class I presentation, with the key alteration possibly being the loss of proper conformation. However, regardless of the form of the Ag, the proteasome appears to be required for generating peptides from both endogenously synthesized and microinjected OVA for class I presentation. C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. ALPHA BETA TECHNOL,WORCESTER,MA 01605. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 57 TC 41 Z9 43 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 JUL 15 PY 1996 VL 157 IS 2 BP 617 EP 624 PG 8 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400017 PM 8752909 ER PT J AU Wu, MX Ao, ZH Hegen, M Morimoto, C Schlossman, SF AF Wu, MX Ao, ZH Hegen, M Morimoto, C Schlossman, SF TI Requirement of Fas(CD95), CD45, and CD11a/CD18 in monocyte-dependent apoptosis of human T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATION; LYMPHOCYTES; DEATH; FAS; MOLECULES; SUICIDE; MICE AB Our previous studies demonstrated that upon activation, monocytes (Mo) were able to sensitize peripheral blood T (PBT) cells to apoptosis induced by treatment with PMA. However, it is unknown what gene products provide the death signal to the sensitized PBT cells and how activated Mo enable PBT cells to become susceptible to apoptosis. Here, we show that PBT cells, but not Mo, express functional Fas ligand upon treatment with PMA. Moreover, this Mo-dependent T cell apoptosis could be blocked by a Fas-Ig fusion protein, as well as by a nonlytic mAb against Fas molecule. These results strongly suggest involvement of Fas-Fas ligand interaction in the death of PBT cells. Unlike Fas-induced apoptosis, however, Mo-dependent T cell death was completely inhibited by overexpression of the Bcl-2 protein, and PMA alone was sufficient to trigger apoptosis in T cells when Mo were included in culture. Furthermore, anti-CD11a, anti-CD18, or anti-CD45/CD45RA mAbs could prevent PBT cells from death triggered by PMA plus Mo, suggesting that these Ags participate in the apoptotic process. The participation of CD45RA in the death of PBT cells was further demonstrated by the observation that the J45.01 cell line, a CD45-deficient variant of Jurkat cells, did not undergo apoptosis by this Mo-dependent mechanism. When transfected with cDNA encoding CD45RA, J45.01 cells acquired apoptotic response to PMA stimulation in the presence of Mo to a similar, but lesser, degree than normal Jurkat cells. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Wu, MX (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA34183]; NIAID NIH HHS [AI12069] NR 36 TC 40 Z9 40 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 JUL 15 PY 1996 VL 157 IS 2 BP 707 EP 713 PG 7 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400028 PM 8752920 ER PT J AU Gruss, HJ Scott, C Rollins, BJ Brach, MA Herrmann, F AF Gruss, HJ Scott, C Rollins, BJ Brach, MA Herrmann, F TI Human fibroblasts express functional IL-2 receptors formed by the IL-2R alpha- and beta-chain subunits - Association of IL-2 binding with secretion of the monocyte chemoattractant protein-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN BLOOD MONOCYTES; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; INTERLEUKIN-2 RECEPTOR; GAMMA-CHAIN; GROWTH-FACTOR; CELLS; CLONING; GENE AB Expression of IL-2R was examined on human fibroblasts isolated from different tissues. By specific binding assay it is shown that [I-125]IL-2 bound to subconfluent adult bone marrow and embryonic skin and lung fibroblasts. The presence of binding sites for IL-2 was also confirmed by immunofluorescence and flow cytometry analysis using mAbs specific for the p55 IL-2R alpha (anti-CD25), p75 IL-2R beta, and p64 IL-2R gamma subunits. Fibroblasts also constitutively transcribed the genes coding for IL-2R alpha and IL-2R beta and accumulated their respective mRNAs but failed to exhibit the IL-2R gamma-chain on the mRNA and protein level. Although addition of IL-2 to fibroblast cultures did not significantly alter growth kinetics of these cells, the IL-2R complex displayed by fibroblasts appeared to be functional in that addition of IL-2 to these cells led to enhanced expression of the JE gene coding for the monocyte chemoattractant protein-1 (MCP-1). Enhancement of fibroblast MCP-1/JE gene expression by IL-2 appeared to result from delayed MCP-1/JE mRNA decay rather than as a consequence of an acceleration of the MCP-1/JE gene transcription rate. IL-2 had, however, no effect on the expression of other cytokine genes including IL-1, IL-5, IL-6, IL-7, IL-8, IL-9, granulocyte-macrophage-CSF, macrophage-CSF or TNF. These observations suggest that the range of cellular targets of IL-2 is broader than originally appreciated. IL-2 may thus serve to integrate fibroblasts and monocytes into a coordinated response of the connective tissue initiated by T lymphocytes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED,BOSTON,MA 02115. RP Gruss, HJ (reprint author), UNIV ULM,MED CTR,DEPT INTERNAL MED 3,ROBERT KOCH STR 8,D-89081 ULM,GERMANY. NR 47 TC 23 Z9 24 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 JUL 15 PY 1996 VL 157 IS 2 BP 851 EP 857 PG 7 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400046 PM 8752938 ER PT J AU GomezIsla, T Price, JL McKeel, DW Morris, JC Growdon, JH Hyman, BT AF GomezIsla, T Price, JL McKeel, DW Morris, JC Growdon, JH Hyman, BT TI Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE entorhinal cortex; stereology; neuronal loss; perforant pathway; Alzheimer's disease; aging ID DEMENTIA RATING CDR; SENILE DEMENTIA; NEUROFIBRILLARY TANGLES; HIPPOCAMPAL-FORMATION; PERFORANT PATHWAY; SYNAPSE LOSS; PATHOLOGICAL-CHANGES; DIAGNOSTIC-CRITERIA; MEMORY IMPAIRMENT; TEMPORAL-LOBE AB The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC gives rise to the perforant pathway, the major source of the excitatory input to the hippocampus, and layer IV receives a major hippocampal efferent projection. The EC is affected severely in Alzheimer disease (AD), likely contributing to memory impairment. We applied stereological principles of neuron counting to determine whether neuronal loss occurs in the EC in the very early stages of AD. We studied 20 individuals who at death had a Clinical Dementia Rating (CDR) score of 0 (cognitively normal), 0.5 (very mild), 1 (mild), or 3 (severe cognitive impairment). Lamina-specific neuronal counts were carried out on sections representing the entire EC. In the cognitively normal (CDR = 0) individuals, there were similar to 650,000 neurons in layer II, 1 million neurons in layer IV, and 7 million neurons in the entire EC. The number of neurons remained constant between 60 and 90 years of age. The group with the mildest clinically detectable dementia (CDR = 0.5), all of whom had sufficient neurofibrillary tangles (NFTs) and senile plaques for the neuropathological diagnosis of AD, had 32% fewer EC neurons than controls. Decreases in individual lamina were even more dramatic, with the number of neurons in layer II decreasing by 60% and in layer IV by 40% compared with controls. In the severe dementia cases (CDR = 3), the number of neurons in layer II decreased by similar to 90%, and the number of neurons in layer IV decreased by similar to 70% compared with controls. Neuronal number in AD was inversely proportional to NFT formation and neuritic plaques, but was not related significantly to diffuse plaques or to total plaques. These results support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. WASHINGTON UNIV,ALZHEIMERS DIS RES CTR,ST LOUIS,MO 63110. WASHINGTON UNIV,DEPT NEUROL,ST LOUIS,MO 63110. WASHINGTON UNIV,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,DEPT ANAT,ST LOUIS,MO 63110. WASHINGTON UNIV,DEPT NEUROBIOL,ST LOUIS,MO 63110. RI Morris, John/A-1686-2012 FU NIA NIH HHS [AG03991, AG05134, AG08487] NR 74 TC 940 Z9 961 U1 4 U2 33 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1996 VL 16 IS 14 BP 4491 EP 4500 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UW879 UT WOS:A1996UW87900020 PM 8699259 ER PT J AU Pollard, TR Schwesinger, WH Page, CP Schauer, PR Sirinek, KR AF Pollard, TR Schwesinger, WH Page, CP Schauer, PR Sirinek, KR TI Upper gastrointestinal bleeding following major surgical procedures: Prevalence, etiology, and outcome SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID CRITICALLY ILL PATIENTS; OPEN-HEART-SURGERY; GASTRIC PH; CIMETIDINE; COMPLICATIONS; HEMORRHAGE; FAILURE AB With continuing improvements in the medical therapy of peptic ulcer disease, the incidence of primary upper gastrointestinal bleeding (UGIB) has markedly declined. Nonetheless, in a subset of surgical patients, secondary UGIB following a major operation may still be a source of substantial morbidity, To further elucidate this problem, we reviewed 103 cases of overt UGIB following all major surgical procedures conducted in two hospitals between July 1982 and June 1994. The prevalence of postoperative UGIB during this period was 0.39%, The mean interval between initial operation and UGIB was 16 days (range 1-55 days) and there was a high incidence of associated sepsis (26%). The source of bleeding was defined endoscopically in all cases and included gastritis (69.9%), solitary ulcers (17.5%), and other causes (12.6%). Postoperative UGIB (nonvariceal) was most commonly seen following portacaval shunting operations but mortality rates were highest in patients who developed UGIB after cardiovascular operations. We conclude that: (1) postoperative UGIB has become a relatively uncommon but still formidable clinical problem; (2) erosive gastritis continues to be the major source of UGIB but acute ulcers, varices, and other causes contribute to the total; and (3) postoperative UGIB is most likely to be fatal in cardiovascular patients and those who develop concurrent sepsis and/or multiorgan failure. (C) 1996 Academic Press, Inc. C1 UNIV TEXAS,CTR HLTH SCI,SAN ANTONIO,TX 78284. RP Pollard, TR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT SURG,SAN ANTONIO,TX 78284, USA. NR 18 TC 5 Z9 6 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 JUL 15 PY 1996 VL 64 IS 1 BP 75 EP 78 DI 10.1006/jsre.1996.0309 PG 4 WC Surgery SC Surgery GA VC180 UT WOS:A1996VC18000013 PM 8806477 ER PT J AU Porcher, C Swat, W Rockwell, K Fujiwara, Y Alt, FW Orkin, SH AF Porcher, C Swat, W Rockwell, K Fujiwara, Y Alt, FW Orkin, SH TI The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages SO CELL LA English DT Article ID LOOP-HELIX PROTEINS; DNA-BINDING MOTIF; SCL GENE-PRODUCT; CHROMOSOMAL TRANSLOCATION; FUSION TRANSCRIPT; ERYTHROID-DIFFERENTIATION; DROSOPHILA-TRITHORAX; ENHANCER-BINDING; GATA-BINDING; ES CELLS AB The T cell leukemia oncoprotein SCL/tal-1, a basic-helix-loop-helix transcription factor, is required for production of embryonic red blood cells in the mouse yolk sac. To define roles in other lineages, we studied the hematopoietic potential of homozygous mutant SCL/tal-1 -/- embryonic stem cells upon in vitro differentiation and in vivo in chimeric mice. Here we show that in the absence of SCL/tal-1, hematopoiesis, including the generation of red cells, myeloid cells, megakaryocytes, mast cells, and both T and B lymphoid cells, is undetectable. These findings suggest that SCL/tal-1 functions very early in hematopoietic development, either in specification of ventral mesoderm to a blood cell fate, or in formation or maintenance of immature progenitors. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL & ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Porcher, Catherine/D-7026-2016 NR 69 TC 528 Z9 531 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 47 EP 57 DI 10.1016/S0092-8674(00)80076-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400007 PM 8689686 ER PT J AU Lee, JT Strauss, WM Dausman, JA Jaenisch, R AF Lee, JT Strauss, WM Dausman, JA Jaenisch, R TI A 450 kb transgene displays properties of the mammalian X-inactivation center SO CELL LA English DT Article ID ARTIFICIAL CHROMOSOME LIBRARY; INSITU HYBRIDIZATION; DOSAGE COMPENSATION; STEM-CELLS; MOUSE; GENE; LOCUS; DIFFERENTIATION; CONSTRUCTION; EXPRESSION AB X inactivation results in inactivation of one X chromosome to compensate for gene dosage differences between mammalian females and males. It requires the X-inactivation center (Xic) and Xist in cis. We report that introducing 450 kb of murine Xic/Xist sequences onto autosomes activates female dosage compensation in male ES cells. Xist is induced upon differentiation and can be expressed from both endogenous and ectopic loci, suggesting that elements for counting and choosing Xs are present in the transgene. Differentiating transgenic ES cells undergo excessive cell death. Postnatally, Xist is expressed only from the transgene. Ectopic Xist RNA structurally associates with the autosome and may inactivate a marker gene in cis. These results argue that the Xic is contained within 450 kb and that these sequences are sufficient for chromosome counting, choosing, and initiation of X inactivation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. RP Lee, JT (reprint author), MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142, USA. FU NCI NIH HHS [R35-CA44339] NR 42 TC 242 Z9 245 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 83 EP 94 DI 10.1016/S0092-8674(00)80079-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400010 PM 8689690 ER PT J AU Roberts, RW Crothers, DM AF Roberts, RW Crothers, DM TI Kinetic discrimination in the folding of intramolecular triple helices SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE DNA; triplex; stopped flow; melting curves; kinetics ID SOLVENT-ACCESSIBLE SURFACES; DOT-PYRIMIDINE TRIPLEXES; DNA TRIPLEX; SECONDARY STRUCTURE; DUPLEX STABILITY; NUCLEIC-ACIDS; RIBOSOMAL-RNA; H-DNA; SEQUENCE; STRAND AB We report a study of the physical properties of oligonucleotide intramolecular Pyr . Pur . Pyr triplexes modeled after H-form DNA. The experiments utilized a set of palindromic pyrimidine strands which form triplexes when combined with complementary purine strands. Triplexes of this nature have two possible isomers, one where the 3' half of the pyrimidine strand acts as the third strand (Y3) or one where the 5' end does (Y5). Kinetic studies of these triplexes revealed that the Y3 isomer folded 10 to 50 times faster than the corresponding Y5 isomer. Despite these kinetic differences, the complexes display relatively similar equilibrium stabilities, with seven of eight falling within a 1.1 kcal range. Addition of non-pairing sequence to the ends of the purine strand both reverses the kinetic bias (slowing Y3 formation >200 fold) and destabilizes the Y3 isomer 1.4 kcal/mol relative to Y5. Three features appear to lie at the source of both the kinetic and thermodynamic variability seen: (1) the prenucleation geometry of the triplexes prior to formation; (2) the accessibility of the major groove to the third strand; and (3) the nature of the tripler loop formed. Based on the data we propose a model for formation of H-form DNA that explains the biases observed for one isomer over the other in different situations. The conclusions have general implications for the tertiary folding of nucleic acids. (C) 1996 Academic Press Limited C1 YALE UNIV,DEPT CHEM,NEW HAVEN,CT 06511. RP Roberts, RW (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [GM 21966] NR 58 TC 15 Z9 15 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 12 PY 1996 VL 260 IS 2 BP 135 EP 146 DI 10.1006/jmbi.1996.0388 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX791 UT WOS:A1996UX79100004 PM 8764396 ER PT J AU Diacovo, TG Puri, KD Warnock, RA Springer, TA vonAndrian, UH AF Diacovo, TG Puri, KD Warnock, RA Springer, TA vonAndrian, UH TI Platelet-mediated lymphocyte delivery to high endothelial venules SO SCIENCE LA English DT Article ID NODE VASCULAR ADDRESSIN; L-SELECTIN; P-SELECTIN; HOMING RECEPTOR; MESENTERIC VENULES; LIGAND; MOLECULE; IDENTIFICATION; RECOGNIZE; ADHESION AB Circulating lymphocytes gain access to lymph nodes owing to their ability to initiate rolling along specialized high endothelial venules (HEVs). One mechanism of rolling involves L-selectin binding to peripheral node addressin (PNAd) on HEVs. Activated platelets are shown to bind to circulating lymphocytes and to mediate rolling in HEVs, in vivo, through another molecule, P-selectin, which also interacts with PNAd. In vitro, activated platelets enhanced tethering of lymphocytes to PNAd and sustained lymphocyte rolling, even in the absence of functional L-selectin. Thus, a platelet pathway operating through P-selectin provides a second mechanism for lymphocyte delivery to HEVs. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CARDIOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PEDIAT,DIV NEWBORN MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. STANFORD UNIV,DEPT PATHOL,STANFORD,CA 94305. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL48675, HL54936] NR 42 TC 233 Z9 238 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 12 PY 1996 VL 273 IS 5272 BP 252 EP 255 DI 10.1126/science.273.5272.252 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW787 UT WOS:A1996UW78700045 PM 8662511 ER PT J AU Dayan, CM Daniels, GH AF Dayan, CM Daniels, GH TI Chronic autoimmune thyroiditis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID TERM FOLLOW-UP; ANTITHYROID PEROXIDASE ANTIBODIES; CHRONIC LYMPHOCYTIC THYROIDITIS; L-THYROXINE THERAPY; HLA-DR EXPRESSION; LONG-TERM; HASHIMOTO THYROIDITIS; GRAVES-DISEASE; MICROSOMAL ANTIBODIES; T-CELLS C1 MASSACHUSETTS GEN HOSP,THYROID UNIT,BOSTON,MA 02114. UNIV BRISTOL,BRISTOL ROYAL INFIRM,DEPT MED,BRISTOL BS2 8HW,AVON,ENGLAND. NR 118 TC 430 Z9 445 U1 4 U2 18 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 JUL 11 PY 1996 VL 335 IS 2 BP 99 EP 107 DI 10.1056/NEJM199607113350206 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA UW353 UT WOS:A1996UW35300006 PM 8649497 ER PT J AU Aisenberg, AC Ozdemirli, M Palmer, WE Harris, NL Harmon, DC Marciniak, RA AF Aisenberg, AC Ozdemirli, M Palmer, WE Harris, NL Harmon, DC Marciniak, RA TI A 52-year-old man with back pain, fever, and abnormal imaging studies - Hodgkin's disease, nodular-sclerosis type, involving multiple bones. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MALIGNANT-LYMPHOMA; INVOLVEMENT; MARROW; SARCOMA C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Aisenberg, AC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 29 TC 3 Z9 3 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 JUL 11 PY 1996 VL 335 IS 2 BP 115 EP 122 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UW353 UT WOS:A1996UW35300008 ER PT J AU SchmidtChoudhury, A Furuta, GT Lavigne, JA Galli, SJ Wershil, BK AF SchmidtChoudhury, A Furuta, GT Lavigne, JA Galli, SJ Wershil, BK TI The regulation of tumor necrosis factor-alpha production in murine mast cells: Pentoxifylline or dexamethasone inhibits IgE-dependent production of TNF-alpha by distinct mechanisms SO CELLULAR IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; MESSENGER-RNA; CACHECTIN; MOUSE; INTERLEUKIN-3; RECRUITMENT; NEUTROPHILS; ACTIVATION; EXPRESSION; RECEPTORS AB Mast cells activated via high-affinity receptors for IgE can produce a variety of multifunctional cytokines, including TNF-alpha, which is thought to be involved in the pathophysiology of allergic diseases and other inflammatory disorders, We investigated the regulation of Fc(epsilon)RI-dependent TNF-alpha production by mouse mast cells using dexamethasone and pentoxifylline, pharmacological agents which are known to suppress TNF-alpha production by macrophages. We now report that either dexamethasone or pentoxifylline can inhibit IgE-dependent mouse mast cell production of TNF-alpha; however, the major site of action of these agents was different. Pentoxifylline inhibited mast cell TNF-alpha gene transcription, while dexamethasone inhibited TNF-alpha production predominantly by a posttranscriptional mechanism. These results demonstrate that the synthesis of mast cell TNF-alpha can be regulated pharmacologically at either the transcriptional or the translational level and that pentoxifylline and dexamethasone, two agents that are used to treat inflammatory disorders, can modulate mast cell TNF-alpha production at different points in the synthetic pathway of this cytokine. (C) 1996 Academic Press, Inc. C1 BETH ISRAEL HOSP,DIV EXPTL PATHOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIAID NIH HHS [AI22674]; NIDDK NIH HHS [DK33506, DK1543] NR 37 TC 33 Z9 33 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 1996 VL 171 IS 1 BP 140 EP 146 DI 10.1006/cimm.1996.0184 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UY134 UT WOS:A1996UY13400021 PM 8660849 ER PT J AU Boppart, SA Brezinski, ME Bouma, BE Tearney, GJ Fujimoto, JG AF Boppart, SA Brezinski, ME Bouma, BE Tearney, GJ Fujimoto, JG TI Investigation of developing embryonic morphology using optical coherence tomography SO DEVELOPMENTAL BIOLOGY LA English DT Article ID MICROSCOPY; TISSUE AB Improved imaging of morphological changes has the potential of offering new insight into the complex process of embryonic development. Optical coherence tomography (OCT) is a new imaging technique for performing in vivo cross-sectional imaging of architectural morphology by measuring backscattered infrared light. This study investigates the application of OCT for imaging developing structure in Rana pipiens, Xenopus laevis, and Brachydanio rerio. Images are compared to conventional histological baselines. Cross-sectional imaging can be performed and structural morphology identified at greater imaging depths than possible with confocal and light microscopy. Repeated OCT imaging may be performed in vivo in order to track structural changes throughout development. (C) 1996 Academic Press, Inc. C1 MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,DEPT ELECT ENGN & COMP SCI,ELECTR RES LAB,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI Boppart, Stephen/C-7338-2009 FU NEI NIH HHS [NIH-9-RO1-EY11289-10] NR 21 TC 87 Z9 88 U1 4 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 10 PY 1996 VL 177 IS 1 BP 54 EP 63 DI 10.1006/dbio.1996.0144 PG 10 WC Developmental Biology SC Developmental Biology GA VA136 UT WOS:A1996VA13600005 PM 8660876 ER PT J AU Gendron, RL Tsai, FY Paradis, H Arceci, RJ AF Gendron, RL Tsai, FY Paradis, H Arceci, RJ TI Induction of embryonic vasculogenesis by bFGF and LIF in vitro and in vivo SO DEVELOPMENTAL BIOLOGY LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; RECEPTOR TYROSINE KINASE; FIBROBLAST GROWTH-FACTOR; ENDOTHELIAL-CELL LINE; PRIMORDIAL GERM-CELLS; VASCULAR ENDOTHELIUM; IN-VITRO; DEVELOPMENTAL EXPRESSION; ADHESION MOLECULE-1; TARGETED DISRUPTION AB The de novo formation of blood vessels (vasculogenesis) is an integral part of embryogenesis. Elucidation of the role of cytokine cooperation in vasculogenesis may lead to a better understanding of organogenesis, blood vessel regulation during tumorigenesis, and tissue injury. We have used embryonic stem cells to derive an endothelial cell line, designated IEM, which expresses a range of endothelial markers, including Von Willibrand Factor VIII related antigen, vascular cell adhesion molecule, platelet-endothelial cell adhesion molecule (CD31), and receptors for acetylated low-density lipoprotein. More importantly, IEM cells can be induced upon exposure to combinations of basic fibroblast growth factor and leukemia inhibitory factor (LIF) to proliferate and undergo vasculogenesis in vitro, resulting in the formation of vascular tubes and microcapillary anastomoses. Moreover, exposure to both cytokines conditionally permits IEM cells to specifically chimerize microvascular endothelium in vivo following blastocyst injection. These results indicate that bFGF and LIF together contribute to the induction and support of embryonic vasculogenesis in an isolated endothelial cell line. Our results provide evidence that combined actions of bFGF/LIF may play a role in mechanisms controlling blood vessel development. (C) 1996 Academic Press, Inc. C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. RP Gendron, RL (reprint author), CHILDRENS HOSP RES FDN,DEPT PEDIAT,DIV HEMATOL & ONCOL,3333 BURNET AVE,CINCINNATI,OH 45229, USA. FU NICHD NIH HHS [HD27322] NR 69 TC 40 Z9 40 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 10 PY 1996 VL 177 IS 1 BP 332 EP 346 DI 10.1006/dbio.1996.0167 PG 15 WC Developmental Biology SC Developmental Biology GA VA136 UT WOS:A1996VA13600028 PM 8660899 ER PT J AU Goldmann, WH Ezzell, RM AF Goldmann, WH Ezzell, RM TI Viscoelasticity in wild-type and vinculin-deficient (5.51) mouse F9 embryonic carcinoma cells examined by atomic force microscopy and rheology SO EXPERIMENTAL CELL RESEARCH LA English DT Article AB We have been studying mouse F9 embryonic carcinoma cells which contain no detectable vinculin protein (5.51 cells), and compared them with F9 wildtype cells. Employing atomic force microscopy, we probed the elastic properties of individual F9 wildtype and 5.51 cells by measuring the dynamic response of controlled loads of the cantilever tip. An elastic modulus (Young) of similar to 3.8 and similar to 2.5 kPa was calculated for wild-type and 5.51 cells, respectively. Using disc rheometry, we detected a marked change in shear of a 1000 g pellet of similar to 55 x 10(6) cells between wild-type and 5.51 mutants, These differences are attributed to the loss of vinculin and altered cytoskeletal organization in these cells. (C) 1996 Academic Press, Inc. RP Goldmann, WH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG RES UNIT,CHARLESTOWN,MA 02129, USA. RI Goldmann, Wolfgang/H-5572-2013 NR 13 TC 53 Z9 53 U1 0 U2 6 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 JUL 10 PY 1996 VL 226 IS 1 BP 234 EP 237 DI 10.1006/excr.1996.0223 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UX592 UT WOS:A1996UX59200028 PM 8660960 ER PT J AU Kharbanda, S Bharti, A Pei, D Wang, J Pandey, P Ren, R Weichselbaum, R Walsh, CT Kufe, D AF Kharbanda, S Bharti, A Pei, D Wang, J Pandey, P Ren, R Weichselbaum, R Walsh, CT Kufe, D TI The stress response to ionizing radiation involves c-Abl-dependent phosphorylation of SHPTP1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN; JUN; PROTOONCOGENE; EXPRESSION; KINASE; EGR1; DNA AB c-Abl is a nonreceptor tyrosine kinase that is activated by certain DNA-damaging agents. The present studies demonstrate that nuclear c-Abl binds constitutively to the protein tyrosine phosphatase SHPTP1. Treatment with ionizing radiation is associated with c-Abl-dependent tyrosine phosphorylation of SHPTP1. The results demonstrate that the SH3 domain of c-Abl interacts with a WPDHGVPSEP motif (residues 417-326) in the catalytic domain of SHPTP1 and that c-Abl phosphorylates C terminal Y536 and YJ64 sites. The functional significance of the c-Abl-SHPTP1 interaction is supported hy the demonstration that, like c-Abl, SGPTP1 regulates the induction of Jun kinase activity following DNA damage. These findings indicate that SHPTP1 is involved in the response to genotoxic stress through a c-Abl-dependent mechanism. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,DEPT BIOL,WALTHAM,MA 02254. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP Kharbanda, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55241] NR 34 TC 82 Z9 85 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 9 PY 1996 VL 93 IS 14 BP 6898 EP 6901 DI 10.1073/pnas.93.14.6898 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW792 UT WOS:A1996UW79200011 PM 8692915 ER PT J AU Heller, R Jaroszeski, M Atkin, A Moradpour, D Gilbert, R Wands, J Nicolau, C AF Heller, R Jaroszeski, M Atkin, A Moradpour, D Gilbert, R Wands, J Nicolau, C TI In vivo gene electroinjection and expression in rat liver SO FEBS LETTERS LA English DT Article DE electroporation; gene transfer; rat liver; luciferase; efficiency; expression ID LIPOSOMES; CELLS; DNA; ELECTROCHEMOTHERAPY AB In vivo targeted gene transfer by non-viral vectors is subjected to anatomical constraints depending on the route of administration, Transfection efficiency and gene expression in vivo using non-viral vectors is also relatively low. We report that in vivo electropermeabilization of the liver tissue of rats in the presence of genes encoding luciferase or beta-galactosidase resulted in the strong expression of these genetic markers in rat liver cells. About 30-40% of the rat liver cells electroporated expressed the beta-galactosidase genetic marker 48 h after electroporation. The marker expression was also detected at least 21 days after transfection at about 5% of the level 48 h after electroporation, The results indicate that gene transfer by electroporation in vivo may avoid anatomical constraints and low transfection efficiency. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES LABS,BOSTON,MA 02135. UNIV S FLORIDA,COLL MED,DEPT SURG,TAMPA,FL 33612. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. UNIV S FLORIDA,COLL ENGN,DEPT CHEM ENGN,TAMPA,FL 33612. RI Heller, Richard/I-6605-2012 NR 16 TC 322 Z9 339 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 8 PY 1996 VL 389 IS 3 BP 225 EP 228 DI 10.1016/0014-5793(96)00590-X PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UX133 UT WOS:A1996UX13300001 PM 8766704 ER PT J AU Kosslyn, SM Shin, LM Thompson, WL McNally, RJ Rauch, SL Pitman, RK Alpert, NM AF Kosslyn, SM Shin, LM Thompson, WL McNally, RJ Rauch, SL Pitman, RK Alpert, NM TI Neural effects of visualizing and perceiving aversive stimuli: A PET investigation SO NEUROREPORT LA English DT Article DE mental imagery; emotion; position emission tomography ID FUNCTIONAL NEUROANATOMY; IMAGERY; CORTEX; PICTURES AB CEREBRAL blood flow was recorded (using positron emission tomography) while middle-aged subjects viewed or visualized pictures of neutral or aversive stimuli, and then determined whether auditorily presented statements correctly described the stimuli. Visualizing aversive stimuli enhanced cerebral blood flow, relative to visualizing neutral stimuli, in areas 17 (right) and 18 (bilateral), as well as the anterior insula (bilateral) and middle frontal cortex (left). Areas 17 and 18 have been identified as supporting the representations that underlie the experience of imagery, and the anterior insula is a major cortical recipient of input from the autonomic nervous system. Perceiving aversive stimuli enhanced cerebral blood flow, relative to neutral stimuli, in area 46, the angular gyrus and area 19, area 47, and the middle temporal gyrus (all in the left hemisphere). All of these areas have previously been implicated in visual object identification. It is striking that negative emotion did not modulate activation in any areas in the same way during imagery and perception. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL & PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. VA RES SERV,MANCHESTER,NH. RP Kosslyn, SM (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. NR 40 TC 98 Z9 98 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 8 PY 1996 VL 7 IS 10 BP 1569 EP 1576 DI 10.1097/00001756-199607080-00007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VM531 UT WOS:A1996VM53100007 PM 8904757 ER PT J AU Matthew, HWT Sternberg, J Stefanovich, P Morgan, JR Toner, M Tompkins, RG Yarmush, ML AF Matthew, HWT Sternberg, J Stefanovich, P Morgan, JR Toner, M Tompkins, RG Yarmush, ML TI Effects of plasma exposure on cultured hepatocytes: Implications for bioartificial liver support SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE hepatocyte culture; plasma; free fatty acids; bioartificial liver; oxygen ID FATTY-ACIDS; MICROVESICULAR STEATOSIS; LIPOPROTEIN-LIPASE; LIPID-ACCUMULATION; RAT HEPATOCYTES; OXIDATION; TRIGLYCERIDE; SECRETION; HEPARIN; PROTEIN AB In order to examine their potential for use in a bioartificial liver, hepatocytes maintained in a collagen sandwich configuration were cultured for 9 days in heparinized rat plasma. The cells exhibited a progressive accumulation of cytoplasmic lipid droplets which proved to be mainly triglyceride (TG). The rate of TG accumulation correlated with the free fatty acid (FFA) content of the plasma. Removal of FFA and TG from plasma by ether extraction significantly reduced the rate and extent of TG accumulation. A smaller reduction in the rate and extent of TG accumulation was observed when cells were maintained in an oxygen enriched environment. The lipid accumulation suppressed urea synthesis, but clearance of the drug diazepam, although constitutively depressed in plasma, appeared unaffected by the accumulation. The functional and morphological effects of plasma exposure could be fully reversed after at least 6 days of plasma exposure by returning the cells to culture medium. The results indicate that elevated FFA in plasma induces lipid accumulation, which inhibits urea synthesis in cultured hepatocytes. This suggests that estimates of the cell number needed for effective liver support should not be based upon function measurements conducted in culture media. Furthermore, optimization of bioartificial liver support device use may have to be governed by the need to limit the plasma exposure of cultured hepatocytes. However, the highly responsive nature of these cultures and the reversibility of the plasma effects suggest that the collagen sandwich culture system is a promising foundation for the development of an effective bioartificial liver support system. (C) 1996 John Wiley & Sons, Inc. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08855. OI Morgan, Jeffrey/0000-0002-7546-3443 NR 36 TC 24 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUL 5 PY 1996 VL 51 IS 1 BP 100 EP 111 DI 10.1002/(SICI)1097-0290(19960705)51:1<100::AID-BIT12>3.0.CO;2-U PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UQ521 UT WOS:A1996UQ52100012 PM 18627093 ER PT J AU Rieu, P Sugimori, T Griffith, DL Arnaout, MA AF Rieu, P Sugimori, T Griffith, DL Arnaout, MA TI Solvent-accessible residues on the metal ion-dependent adhesion site face of integrin CR3 mediate its binding to the neutrophil inhibitory factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COMPLEMENT RECEPTOR TYPE-3; MOLECULE-1 ALPHA-SUBUNIT; AMINO-ACID SEQUENCE; MONOCLONAL-ANTIBODIES; DOMAIN; GLYCOPROTEIN; CD11B/CD18; CLONING AB Neutrophil adhesion dependent functions such as chemotaxis, spreading, and phagocytosis are inhibited by neutrophil inhibitory factor (NIF), a glycoprotein produced by the hookworm Ancylostoma caninum. The NIF binding site has been localized to the A-domain of integrin CR3 (CD11b/CD18) and shown to be metal-dependent, The recently solved crystal structure of the A-domain from CD11b revealed a putative metal ion-dependent adhesion site (MIDAS) on the top of the structure. To determine if NIF binds to the A-domain at its MIDAS face, amino acid substitutions involving 24 residues present in surface loops and adjacent helices in the structure were created. The expressed CD11b A-domain and CR3 heterodimers were then tested in a blinded manner for their ability to bind to biotinylated NIF. The solvent-exposed Gly(143), Asp(149), Glu(178)-Glu(179), and Arg(208), all located on the MIDAS face, in close proximity to the metal ion, were involved in CR3-NIF interaction. These data show that the natural integrin antagonist, NIF, binds to CR3 through the MIDAS region and identify putative contact residues in this region that could be targeted therapeutically. C1 MASSACHUSETTS GEN HOSP,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,DIV NEPHROL,DEPT MED,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. NR 28 TC 49 Z9 52 U1 1 U2 4 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 JUL 5 PY 1996 VL 271 IS 27 BP 15858 EP 15861 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW352 UT WOS:A1996UW35200004 PM 8663417 ER PT J AU Strobel, RS Nagy, AK Knowles, AF Buegel, J Rosenberg, MD AF Strobel, RS Nagy, AK Knowles, AF Buegel, J Rosenberg, MD TI Chicken oviductal ecto-ATP-diphosphohydrolase - Purification and characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYACRYLAMIDE GELS; BOVINE AORTA; ASSAY; IDENTIFICATION; PHOSPHATE; PROTEINS; ELECTROPHORESIS; SYNAPTOSOMES; LOCALIZATION; MEMBRANES AB An ecto-ATP diphosphohydrolase (ATPDase) was purified to homogeneity from vesiculosomes shed from chicken oviduct, First, the ecto-ATPDase-enriched vesiculosomes were concentrated by filtration, differential centrifugation, and exclusion chromatography, Next, the nonionic detergent, Nonidet P-40, was used to extract the ecto-ATPDase from vesiculosomal membranes, and the solubilized enzyme was further purified by ion by ion exchange (DEAE-Bio-Gel) and lentil lectin-Sepharose 4B chromatography, In the final stage, immunoaffinity chromatography was utilized to obtain purified ecto-ATPDase, More than 25,000-fold purification was achieved, Specific activity of the purified enzyme was greater than 800 mu mol/min/mg of protein with MgATP as the substrate, the highest ever reported for an ATPDase, The enzyme also hydrolyzed other nucleoside triphosphates in the presence of magnesium at similar rates and CaATP and MgADP at lower rates, The molecular mass of the purified glycoprotein was 80 kDa as deter mined by SDS-polyacrylamide gel electrophoresis and Western blot analysis, Based on its enzymatic properties, the relationship of the chicken oviduct ecto-ATPDase with other reported ATPDases and ecto-ATPases is discussed. C1 UNIV MINNESOTA,DEPT GENET & CELL BIOL,ST PAUL,MN 55108. UNIV CALIF LOS ANGELES,DEPT NEUROL & MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. SUNY HLTH SCI CTR,DEPT BIOCHEM & MOLEC BIOL,SYRACUSE,NY 13210. NR 56 TC 44 Z9 44 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 JUL 5 PY 1996 VL 271 IS 27 BP 16323 EP 16331 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW352 UT WOS:A1996UW35200069 PM 8663133 ER PT J AU Frenette, PS Wagner, DD AF Frenette, PS Wagner, DD TI Adhesion molecules .2. Blood vessels and blood cells SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Frenette, Paul/J-8272-2012 NR 5 TC 238 Z9 243 U1 1 U2 2 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 JUL 4 PY 1996 VL 335 IS 1 BP 43 EP 45 DI 10.1056/NEJM199607043350108 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA UU479 UT WOS:A1996UU47900008 PM 8637541 ER PT J AU Rutberg, SE Saez, E Glick, A Dlugosz, AA Spiegelman, BM Yuspa, SH AF Rutberg, SE Saez, E Glick, A Dlugosz, AA Spiegelman, BM Yuspa, SH TI Differentiation of mouse keratinocytes is accompanied by PKC-dependent changes in AP-1 proteins SO ONCOGENE LA English DT Article DE AP-1; keratinocytes; protein kinase C; mouse skin; differentiation; c-fos ID TISSUE-SPECIFIC EXPRESSION; KINASE-C-DELTA; EPIDERMAL DIFFERENTIATION; SELECTIVE INHIBITOR; SKIN CARCINOGENESIS; BINDING-PROTEINS; GENE-EXPRESSION; PHORBOL ESTER; CYCLIC-AMP; FOS AB The conversion of cultured basal keratinocytes to the spinous and granular cell phenotypes seen in the skin can be stimulated by raising the levels of extracellular calcium, Here me show that AP-1 DNA binding activity is very low in primary cultures of basal keratinocytes, but that this activity is induced 24-48 h after increasing the concentration of extracellular calcium from 0.05 to 0.12 mM. As such, the induction of AP-1 DNA binding activity correlates with events occurring during the terminal stages of keratinocyte differentiation, Calcium-induced AP-1 DNA binding complexes consist of Pra-1, Fra-2, c-Jun, JunB and JunD and are independent of c-Fos, since the induction of DNA binding activity and the composition of the AP-1 binding complexes are identical in differentiating keratinocytes derived from c-fos null and wild type mice, The formation of calcium-induced AP-1 binding complexes is regulated by protein kinase C (PKC) and requires a functional PKC alpha isozyme, as determined through pharmacological down-modulation of specific PKC isozymes in differentiating keratinocytes, Moreover, PKC activation is required for the increased expression of Fra-2, JunB and JunD in the nucleus of differentiating cells in vitro. This observation provides a link between the obligate activation of PKC during keratinocyte differentiation and the nuclear response required to alter gene expression, In vivo expression patterns suggest that the predominant AP-1 heterodimer in the granular layer consists of Fra-2 and JunB while a JunD and Fra-1 complex predominates the spinous layer of mouse epidermis, These findings suggest distinct functions for different AP-1 proteins in the regulation of events related to keratinocyte maturation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 67 TC 111 Z9 111 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 4 PY 1996 VL 13 IS 1 BP 167 EP 176 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UX319 UT WOS:A1996UX31900019 PM 8700543 ER PT J AU Huncharek, M Muscat, J AF Huncharek, M Muscat, J TI Serum prostate-specific antigen as a predictor of staging abdominal/pelvic computed tomography in newly diagnosed prostate cancer SO ABDOMINAL IMAGING LA English DT Article DE staging; computed tomography; prostate ID CARCINOMA; CT AB Background: The standard staging evaluation for prostate cancer includes digital rectal examination, measurement of serum tumor markers, and radionuclide bone scan. In many institutions, abdominal/pelvic computed tomography (CT) scan or nuclear magnetic resonance imaging (MRI) is performed. We retrospectively reviewed 425 cases of newly diagnosed, untreated adenocarcinoma of the prostate to evaluate the ability of serum prostate-specific antigen (PSA) to predict results of staging abdominal pelvic CT. Methods: The medical records of 425 newly diagnosed, untreated prostate cancer patients were reviewed. The following information was collected on a standard data form: age, clinical stage based on digital rectal exam, method of diagnosis, histological grade, serum PSA level, and results of abdominal pelvic CT including adenopathy and abnormalities of the upper urinary tract. The results of this review were tabulated and analyzed with regard to the ability of serum PSA level to predict positive results of abdominal pelvic CT. Results: The mean PSA level of the study group was 22.1 ng/ml. Fourteen patients (3.6%) presented with a positive abdominal/pelvic CT (12 with adenopathy, one with a renal cell tumor, and one with an adrenal metastasis). Eleven of these (79%) had serum PSA levels' of 30.0 ng/ml or greater, ranging from 30.0 to 234 ng/ml. No patient with a positive study presented with a normal serum PSA level. Two patients with a positive study had a serum PSA level between 4.1 and 10.0 ng/ml (0.6%), and one had a PSA level between 10.1 and 20 ng/ml (0.3%). Conclusion: We conclude that in asymptomatic patients with newly diagnosed, untreated prostate cancer and serum PSA levels of less than 20 ng/ml the likelihood of positive findings on abdominal/pelvic CT is extremely low (<1.0%). Abdominal/pelvic CT does not appear necessary in this setting. With 200,000 cases of newly diagnosed prostate cancer each year in the United States, elimination of staging abdominal/pelvic CT in these patients could reduce medical expenditures for prostate cancer management by $20-50 million per year. C1 AMER HLTH FDN,DIV EPIDEMIOL,NEW YORK,NY 10017. RP Huncharek, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX B,BOSTON,MA 02114, USA. NR 8 TC 26 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JUL-AUG PY 1996 VL 21 IS 4 BP 364 EP 367 DI 10.1007/s002619900083 PG 4 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA UR663 UT WOS:A1996UR66300017 PM 8661585 ER PT J AU Ray, CE Kaufman, JA AF Ray, CE Kaufman, JA TI Complications of inferior vena cava filters SO ABDOMINAL IMAGING LA English DT Article DE filters; complications; vena cava ID TITANIUM GREENFIELD FILTER; CLINICAL-EXPERIENCE; PERCUTANEOUS PLACEMENT; FOLLOW-UP; MIGRATION; INSERTION; THROMBOSIS; FRACTURE; DEVICES; SITE C1 MASSACHUSETTS GEN HOSP,DIV VASC RADIOL,BOSTON,MA 02114. ROSWELL PK CANC INST,DIV ANGIOG & INTERVENT RADIOL,BUFFALO,NY 14263. NR 57 TC 75 Z9 76 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD JUL-AUG PY 1996 VL 21 IS 4 BP 368 EP 374 PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA UR663 UT WOS:A1996UR66300018 PM 8661586 ER PT J AU Robbins, AS AF Robbins, AS TI Introduction: The VA Pilot Program in Ambulatory Care and Education SO ACADEMIC MEDICINE LA English DT Editorial Material C1 MED UNIV S CAROLINA,COLL MED,CHARLESTON,SC 29425. VAMC,SEPULVEDA,CA. RP Robbins, AS (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29401, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1996 VL 71 IS 7 BP 760 EP 760 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA UX394 UT WOS:A1996UX39400022 ER PT J AU Cope, DW Sherman, S Robbins, AS AF Cope, DW Sherman, S Robbins, AS TI Restructuring VA ambulatory care and medical education: The PACE model of primary care SO ACADEMIC MEDICINE LA English DT Article ID ACADEMIC GROUP-PRACTICE; RANDOMIZED CONTROLLED TRIAL; INTERNAL-MEDICINE; PREVENTIVE MEDICINE; HEALTH MAINTENANCE; PHYSICIANS; PERSPECTIVE; RESIDENCIES; FEEDBACK; TIME AB The Veterans Health Administration (VHA) Western Region and associated medical schools formulated a set of recommendations for an improved ambulatory health care delivery system during a 1988 strategic planning conference. As a result, the Department of Veterans Affairs (VA) Medical Center in Sepulveda, California, initiated the Pilot (now Primary) Ambulatory Care and Education (PACE) program in 1990 to implement and evaluate a model program. The PACE program represents a significant departure from traditional VA and non-VA academic medical center care, shifting the focus of care from the inpatient to the outpatient setting. From its inception, the PACE program has used an interdisciplinary team approach with three independent global care firms. Each firm is interdisciplinary in composition, with a matrix management structure that expands role function and empowers team members. Emphasis is on managed primary care, stressing a biopsychosocial approach and cost-effective comprehensive care emphasizing prevention and health maintenance. Information management is provided through a network of personal computers that serve as a front end to the VHA Decentralized Hospital Computer Program (DHCP) mainframe. In addition to providing comprehensive and cost-effective care, the PACE program educates trainees in all health care disciplines, conducts research, and disseminates information about important procedures and outcomes. Undergraduate and graduate trainees from 11 health care disciplines rotate through the PACE program to learn an integrated approach to managed ambulatory care delivery. All trainees are involved in a problem-based approach to learning that emphasizes shared training experiences among health care disciplines. This paper describes the transitional phases of the PACE program (strategic planning, reorganization, and quality improvement) that are relevant for other institutions that are shifting to training programs emphasizing primary and ambulatory care. C1 RALPH H JOHNSON VET AFFAIRS MED CTR,STAFF AMBULATORY CARE,CHARLESTON,SC 29401. MED UNIV S CAROLINA,COLL MED,CHARLESTON,SC 29425. VAMC,PILOT AMBULATORY CARE & EDUC PROGRAM,SEPULVEDA,CA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. NR 52 TC 18 Z9 18 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1996 VL 71 IS 7 BP 761 EP 771 DI 10.1097/00001888-199607000-00008 PG 11 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA UX394 UT WOS:A1996UX39400023 PM 9158344 ER PT J AU Fowler, LJ Smith, SS Snider, T Schultz, MR AF Fowler, LJ Smith, SS Snider, T Schultz, MR TI Apocrine metaplasia in gynecomastia by fine needle aspiration as a possible indicator of anabolic steroid use - A report of two cases SO ACTA CYTOLOGICA LA English DT Article DE metaplasia; gynecomastia; anabolic steroids; aspiration biopsy ID MALE BREAST; CYTOLOGY; CARCINOMA; ADENOMA AB BACKGROUND: The fine needle aspiration finding of apocrine metaplasia in association with the usual cytologic findings of gynecomastia is distinctly unusual. Previous reports do not mention any historical clinical association. CASES: Two otherwise healthy adult males presented for fine needle aspiration (FNA) of new-onset breast masses. Both showed apocrine metaplasia associated with the typical clinical and cytologic features of gynecomastia on FNA. Additional questioning revealed that both patients reported recent anabolic steroid use as part of their body-building routines. CONCLUSION: The fine needle aspiration finding of apocrine metaplasia in association with the usual cytologic and clinical findings of gynecomastia in otherwise healthy adult males without a medication history may be an indicator of illicit anabolic steroid use. Anabolic steroid use often has serious consequences, so its possibility should prompt further evaluation by the patient's clinician. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV HOSP,SAN ANTONIO,TX. RP Fowler, LJ (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JUL-AUG PY 1996 VL 40 IS 4 BP 734 EP 738 PG 5 WC Pathology SC Pathology GA VQ191 UT WOS:A1996VQ19100020 PM 8693895 ER PT J AU Rollbrocker, B Waha, A Louis, DN Wiestler, OD vonDeimling, A AF Rollbrocker, B Waha, A Louis, DN Wiestler, OD vonDeimling, A TI Amplification of the cyclin-dependent kinase 4 (CDK4) gene is associated with high cdk4 protein levels in glioblastoma multiforme SO ACTA NEUROPATHOLOGICA LA English DT Article DE CDK4; gene amplification; protein level; LOH12q; brain tumors ID HUMAN SARCOMAS; CANCER AB Genetic alterations on the long arm of chromosome 12, including both gene amplification and allelic loss, are associated with malignant progression of human gliomas. The region of the chromosomal arm 12q that is amplified in malignant gliomas contains the CDK4 gene, a cell cycle regulatory gene which promotes cell division. To evaluate the frequency of CDK4 gene amplification, we analyzed a series of 355 brain tumors using a quantitative non-radioactive polymerase chain reaction assay. CDK4 gene amplification occurred in 9 of 81 glioblastomas (11%), but was rare in other neoplasms, including low-grade and anaplastic gliomas, meningiomas, medulloblastomas and metastatic carcinomas (only 6 of 274 cases). There was no correlation between CDK4 gene amplification and allelic loss of chromosome 12. To assess the significance of CDK4 gene amplification, we analyzed protein extracts from 37 glioblastomas by Western blotting with a commercially available polyclonal antibody to cdk4. All tumors with CDK4 gene amplification showed high cdk4 expression levels, whereas no increased cdk4 expression was seen in glioblastomas without CDK4 gene amplification. These data support the functional activity of CDK4 gene amplification in glioblastoma multiforme and point to an important role of CDK4 gene amplification in a subset of glioblastomas. C1 UNIV BONN,MED CTR,DEPT NEUROPATHOL,D-53105 BONN,GERMANY. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA57683] NR 24 TC 63 Z9 63 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUL PY 1996 VL 92 IS 1 BP 70 EP 74 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UT491 UT WOS:A1996UT49100011 PM 8811128 ER PT J AU Dimitri, PS Wall, C Oas, JG AF Dimitri, PS Wall, C Oas, JG TI Classification of human rotation test results using parametric modeling and multivariate statistics SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE vestibulo-ocular reflex; decision analysis; unilateral labyrinthine deficit; sinusoidal harmonic acceleration test ID SINUSOIDAL HARMONIC ACCELERATION; DIZZY PATIENT; RESPONSES AB The usefulness of vestibular testing is directly related to the accuracy of the test interpretations. Two factors, subjective analysis of large test data sets and failure to make appropriate age corrections, tend to reduce test accuracy. Correction of these problems can be accomplished by application of physiologically based models of vestibular function and multivariate classification techniques to the test data, thereby creating a more objective test interpretation procedure. Herein we report Our results on the use of this strategy for analysis of sinusoidal harmonic acceleration (SHA) test interpretation. For each patient, models reduce the large set of SHA test variables to three key parameters: asymptotic gain, vestibule-ocular reflex time constant, and bias. In addition, the new technique objectively adjusts these parameters for the patient's age. Finally, each patient's set of parameters are statistically classified as either normal or as unilateral peripheral deficit. Based on learning sets of 57 normals and 30 patients with a full unilateral peripheral deficit, this new technique resulted in a misclassification rate between the categories of normal and full unilateral loss of 3.4%, comparing favorably to the present method's misclassification rate between normal and abnormal of 13.8%. We also analyzed and classified a test group consisting of patients with possible partial unilateral deficits using the same classification function as the normal and full unilateral learning sets. Even though the classifier was not optimized for the partial group, results seemed favorable relative to the human interpreter. These results validate the accuracy and utility of physiological parametric models and multivariate statistical classification in SHA test interpretation. C1 MASSACHUSETTS EYE & EAR INFIRM,JENKS VESTIBULAR DIAGNOST LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,BOSTON,MA 02115. RI Oas, John/E-3772-2011 FU NIDCD NIH HHS [T32 DC00038, T32 DC00290] NR 18 TC 16 Z9 16 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JUL PY 1996 VL 116 IS 4 BP 497 EP 506 DI 10.3109/00016489609137880 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA UV557 UT WOS:A1996UV55700001 PM 8831833 ER PT J AU Binley, JM Ditzel, HJ Barbas, CF Sullivan, N Sodroski, J Parren, PWHI Burton, DR AF Binley, JM Ditzel, HJ Barbas, CF Sullivan, N Sodroski, J Parren, PWHI Burton, DR TI Human antibody responses to HIV type 1 glycoprotein 41 cloned in phage display libraries suggest three major epitopes are recognized and give evidence for conserved antibody motifs in antigen binding SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; 2 IMMUNODOMINANT DOMAINS; ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN; SYNTHETIC PEPTIDES; COMBINATORIAL LIBRARIES; INFECTION INVITRO; CELL EPITOPES; GP41 AB A large panel of human Fab fragments against the gp41 subunit of the HIV-1 envelope glycoprotein was isolated by panning six phage-displayed antibody libraries against recombinant gp41. The libraries were prepared from HIV-1-seropositive donors, Twenty-three Fabs recognizing conformation-dependent determinants on gp41 were isolated, Further selection of libraries against (1) gp41 ligated with Fabs from the initial selection and against (2) a recombinant gp41-containing gp140 protein yielded five additional Fabs, Competition of members of the Fab panel with one another and with previously described antibodies revealed a series of overlapping specificities that were conveniently grouped into three major epitope clusters. The majority of Fabs recognized epitopes involving residues 649-668 (previously known as the cluster II region), numbered using the Los Alamos LAI sequence, A second set of Fabs reacted with an epitope involving residues 584-609 (known as the cluster I region), Another set of Fabs appeared to recognize a third conformational epitope that has been termed the cluster III region. This third Fab epitope group demonstrated some overlap with both clusters I and II in binding assays, None of the Fabs neutralized HIV-1 laboratory strains at biologically significant concentrations, This tends to support the opinion that a vaccine based on the gp41 molecule has the drawback that neutralizing epitopes of gp41 are rare and/or unfavorably presented to the immune system, Analysis of heavy chain sequences revealed common CDR3 motif sequences in several antibodies, which appears to be an interesting consequence of a persistent immune response to conserved antigen structures. C1 Scripps Res Inst, DEPT IMMUNOL IMM2, LA JOLLA, CA 92037 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. DANA FARBER CANC INST, DEPT PATHOL, BOSTON, MA 02115 USA. OI Ditzel, Henrik J./0000-0003-3927-5135; Parren, Paul/0000-0002-4365-3859 FU NIAID NIH HHS [AI24755, AI33292, AI37470] NR 62 TC 66 Z9 70 U1 0 U2 1 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 JUL 1 PY 1996 VL 12 IS 10 BP 911 EP 924 DI 10.1089/aid.1996.12.911 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UU506 UT WOS:A1996UU50600009 PM 8798976 ER PT J AU Jiang, L DePrada, JAV Lee, MY Ba, JH Padial, LR Fallon, JT King, ME Palacios, IF Weyman, AE Levine, RA AF Jiang, L DePrada, JAV Lee, MY Ba, JH Padial, LR Fallon, JT King, ME Palacios, IF Weyman, AE Levine, RA TI Quantitative assessment of stenotic aortic valve area by using intracardiac echocardiography: In vitro validation and initial in vivo illustration SO AMERICAN HEART JOURNAL LA English DT Article ID CROSS-SECTIONAL ECHOCARDIOGRAPHY; MITRAL BALLOON VALVULOPLASTY; CARDIAC-CATHETERIZATION; ULTRASOUND CATHETER; DOPPLER ULTRASOUND; PRESSURE-GRADIENT; ORIFICE AREA; STENOSIS; SEVERITY; ADULTS AB Quantitative assessment of aortic stenosis (AS) is subject to the limitations of all current noninvasive and invasive methods. The ability to obtain a direct measure of aortic valve area with high resolution by intracardiac echocardiography (ICE) could be of great benefit to catheterized patients. To provide a fixed AS area as an ideal standard for comparison, we performed ICE in 12 sheep hearts with experimentally created AS and five human AS hearts from autopsies. ICE catheters were passed retrograde across the aortic valve, and the minimal orifice area on pullback was planimetered and compared with calibrated video imaging. The entire orifice circumference could be successfully recorded in 16 (94%) hearts. Orifice area from ICE correlated well with actual values (r = 0.98; standard error of the estimate [SEE] = 0.06 cm(2)). To illustrate the applicability in vivo, two canine models and 10 patients with AS were studied. The limiting orifice could be imaged in both animals and in 8 of 10 patients, in whom values agreed well with invasive data (r = 0.95; SEE = 0.04 cm(2)). ICE can therefore accurately measure AS orifice area in vitro; it can be applied in vivo as well. These validation studies laid the foundation for subsequent clinical studies and applications. RP Jiang, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114, USA. NR 35 TC 11 Z9 11 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 JUL PY 1996 VL 132 IS 1 BP 137 EP 144 DI 10.1016/S0002-8703(96)90402-0 PN 1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UW812 UT WOS:A1996UW81200020 PM 8701856 ER PT J AU Yu, YM Sheridan, RL Burke, JF Chapman, TE Tompkins, RG Young, VR AF Yu, YM Sheridan, RL Burke, JF Chapman, TE Tompkins, RG Young, VR TI Kinetics of plasma arginine and leucine in pediatric burn patients SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE stable isotope tracers; arginine; urea; leucine; kinetics; dispensable amino acids; indispensable amino acids; pediatric burn patients ID WHOLE-BODY PROTEIN; AMINO-ACID; METABOLISM; INJURY; TURNOVER; CHILDREN; TRAUMA; INFANTS; DIETS AB The dynamic status of whole-body arginine and leucine was investigated in eight severely burned (mean 55% of body surface area) pediatric patients (mean age 5.3 y) at a mean of 16 d after their initial injury. Plasma amino acid kinetics were estimated by using primed constant intravenous infusions of L-[C-13-guanidino]arginine and L-[1-C-13]leucine given for 4 h. Each patient was studied twice within 2 d. The patients were studied either in a ''basal'' state, which involved removal of amino acids from the the total parenteral nutrition (TPN) solution for 8 h before the tracer study, or while receiving complete TPN. Nitrogen intake was 0.58 +/- 0.08 g . kg(-1). d(-1) with nonprotein energy intake equivalent to 197 +/- 29 kJ . kg(-1). d(-1). Plasma leucine and arginine fluxes (mu mol . kg(-1). h(-1)) were 208 +/- 35 and 108 +/- 18 for basal and 290 +/- 38 and 195 +/- 22 for TPN periods, respectively. Leucine oxidation was 42 +/- 7 and 59 +/- 9 mu mol . kg(-1). h(-1) for basal and TPN periods, respectively, indicating a higher rate of leucine loss in the absence of a leucine intake than that expected for healthy individuals. The arginine kinetic data implied little net de novo arginine synthesis and further suggested increased rates of arginine degradation from burn injury. The expected rate of urea excretion, based on the basal rate of leucine oxidation, agreed closely with the measured output of urinary urea. These findings suggest that arginine is a conditionally indispensable amino acid for maintaining body protein homeostasis and nutrition in severely burned pediatric patients. The metabolic response of these children appears to be quantitatively similar to that for severely burned adult patients. C1 SHRINERS BURN INST, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, TRAUMA SERV, BOSTON, MA 02114 USA. MIT, HUMAN NUTR LAB, CAMBRIDGE, MA 02139 USA. FU NIDDK NIH HHS [DK 15856]; NIGMS NIH HHS [GM 02700] NR 42 TC 30 Z9 31 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 JUL PY 1996 VL 64 IS 1 BP 60 EP 66 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UT904 UT WOS:A1996UT90400010 PM 8669415 ER PT J AU Glanz, K Sorensen, G Farmer, A AF Glanz, K Sorensen, G Farmer, A TI The health impact of worksite nutrition and cholesterol intervention programs SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Worksite Health Promotion; nutrition intervention; hypercholesterolemia; cholesterol management; nutrition education ID RANDOMIZED CONTROLLED TRIAL; EDUCATION-PROGRAM; REDUCTION PROGRAM; PLASMA-CHOLESTEROL; EMPLOYEES DIETARY; PROMOTION PROGRAM; EATING BEHAVIORS; HEART PROJECT; SITE; CAFETERIA AB Purpose. To summarize and provide a critical review of worksite health promotion program evaluations published between 1980 and 1995 that address nutrition and hypercholesterolemia. The article discusses and critiques both intervention methods and research methodologies to identify the most effective strategies. Methods. Core articles are 26 original, data-based studies that report on measures of health status, behavior, attitudes, and knowledge as outcomes of worksite nutrition and cholesterol interventions. Only work published since 1980 that clearly describes nutrition or cholesterol interventions and that includes identifiable nutrition-related outcomes is reviewed. The main search method was the same one used for this special issue; supplementary sources included those found in earlier reviews or identified through backward searches or expert contact. Summary of Important Findings. Ten worksite nutrition education programs were reviewed and were categorized as group, education, group education plus individual counseling/instruction, cafeteria-based programs, and group education plus cafeteria-based programs. Four of these were randomized studies, and one used the worksite as the unit of randomization and analysis. Sixteen worksite cholesterol programs were reviewed in five categories: monitoring; individual counseling; group sessions or classes; mediated methods using print, audiovisual, telephone, and self-help kits; and combination approaches. Of these eight were randomized controlled trials; most tested interventions for persons with elevated cholesterol levels, although four studies reported cholesterol education programs for the general employee population. Six large controlled trials of worksite nutrition and cholesterol interventions in progress are also described. Major Conclusions. The conclusions that can be drawn from this review are limited by the study designs used, which often lacked control groups, used nonrandomized designs, or relied on self-selected high-risk or volunteer participants. Our rating for the quality of the evidence in the literature as a whole lies between suggestive and indicative. It is clear that worksite nutrition and cholesterol programs are feasible and that participants benefit in the short-term. Conclusive evidence about a causal relationship between worksite nutrition and cholesterol programs and improved behavior or health is not yet available, although studies currently underway hold promise for providing more solid evidence about the potential efficacy of these interventions. C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. RP Glanz, K (reprint author), UNIV HAWAII,1236 LAUHALA ST,HONOLULU,HI 96813, USA. NR 71 TC 63 Z9 64 U1 1 U2 9 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JUL-AUG PY 1996 VL 10 IS 6 BP 453 EP 470 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VB690 UT WOS:A1996VB69000004 PM 10163311 ER PT J AU Miller, PW Hamosh, A Macek, M Greenberger, PA MacLean, J Walden, SM Slavin, RG Cutting, GR AF Miller, PW Hamosh, A Macek, M Greenberger, PA MacLean, J Walden, SM Slavin, RG Cutting, GR TI Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CONGENITAL BILATERAL ABSENCE; VAS-DEFERENS; FAMILIAL OCCURRENCE; CHRONIC-BRONCHITIS; SWEAT CHLORIDE; MESSENGER-RNA; DIAGNOSIS; IDENTIFICATION; DISEASE; BRONCHIECTASIS AB The etiology of allergic bronchopulmonary aspergillosis (ABPA) is not well understood. A clinical phenotype resembling the pulmonary disease seen in cystic fibrosis (CF) patients can occur in some individuals with ABPA. Reports of familial occurrence of ABPA and increased incidence in CF patients suggest a possible genetic basis for the disease. To test this possibility, the entire coding region of the cystic fibrosis transmembrane regulator (CFTR) gene was analyzed in 11 individuals who met strict criteria for the diagnosis of ABPA and had normal sweat electrolytes (less than or equal to 40 mmol/liter). One patient carried two CF mutations (Delta F508/R347H), and five were found to carry one CF mutation (four Delta F508; one R117H). The frequency of the Delta F508 mutation in patients with ABPA was significantly higher than in 53 Caucasian patients with chronic bronchitis (P < .0003) and the general population (P < .003). These results suggest that CFTR plays an etiologic role in a subset of ABPA patients. C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,CMSC 1004,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21287. ST LOUIS UNIV,MED CTR,DIV ALLERGY & IMMUNOL,ST LOUIS,MO 63103. MASSACHUSETTS GEN HOSP,GEN MED SERV,CLIN IMMUNOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,ALLERGY UNIT,BOSTON,MA 02114. NORTHWESTERN UNIV,SCH MED,DIV ALLERGY IMMUNOL,CHICAGO,IL. FU NIDDK NIH HHS [DK09024, DK44003] NR 53 TC 141 Z9 144 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1996 VL 59 IS 1 BP 45 EP 51 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VL455 UT WOS:A1996VL45500008 PM 8659542 ER PT J AU Han, DP Wisniewski, SR Wilson, LA Barza, M Vine, AK Doft, BH Kelsey, SF Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russell, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M William, SM AF Han, DP Wisniewski, SR Wilson, LA Barza, M Vine, AK Doft, BH Kelsey, SF Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russell, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M William, SM TI Spectrum and susceptibilities of microbiologic isolates in the endophthalmitis vitrectomy study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID STAPHYLOCOCCUS-EPIDERMIDIS ENDOPHTHALMITIS; EXTRACAPSULAR CATARACT-EXTRACTION; ACUTE POSTOPERATIVE ENDOPHTHALMITIS; INTRAOCULAR-LENS IMPLANTATION; INFECTIOUS ENDOPHTHALMITIS; METHICILLIN-RESISTANT; PSEUDOPHAKIC ENDOPHTHALMITIS; INTRAVITREOUS CEFTAZIDIME; BACTERIAL-CONTAMINATION; AMINOGLYCOSIDE TOXICITY AB PURPOSE: To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. METHODS: Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. RESULTS: Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%), Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species, All gram-positive isolates tested were susceptible to vancomycin, Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). CONCLUSIONS: Gram-positive, coagulase-negative micrococci predominated in this series, Vancomycin was active against all gram-positive isolates tested, Amikacin and ceftazidime showed equivalent activity against gram-negative isolates, Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci. C1 MED COLL WISCONSIN,DEPT OPHTHALMOL,MILWAUKEE,WI 53226. EMORY EYE CTR,ATLANTA,GA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. UNIV MICHIGAN,WK KELLOGG EYE CTR,ANN ARBOR,MI 48105. RETINAL VITREOUS CONSULTANTS,PITTSBURGH,PA. UNIV MARYLAND EYE ASSOCIATES,BALTIMORE,MD. JOHNS HOPKINS UNIV,BALTIMORE,MD. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA GRP WASHINGTON,CHEVY CHASE,MD. RUSH UNIV,INGALLS HOSP,CHICAGO,IL 60612. RETINA ASSOCIATES CLEVELAND INC,CLEVELAND,OH. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV MINNESOTA,EDINA,MN. RETINA VITREOUS CTR PA,EDISON,NJ. UNIV FLORIDA,GAINESVILLE,FL. PENN STATE UNIV,HERSHEY,PA. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV SO CALIF,LOS ANGELES,CA. UNIV LOUISVILLE,KENTUCKY LIONS EYE RES INST,LOUISVILLE,KY 40292. UNIV S FLORIDA,N TAMPA,FL. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. ASSOCIATED RETINAL CONSULTANTS PC,ROYAL OAK,MI. RETINA CONSULTANTS,SAN DIEGO,CA. UNIV S FLORIDA,S TAMPA,FL. RETINA CONSULTANTS ASSOCIATES INC,TOLEDO,OH. GEORGETOWN UNIV,WASHINGTON,DC. UNIV WISCONSIN,MADISON,WI. NEI,PROGRAM OFF,BETHESDA,MD. RP Han, DP (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,ENDOPHTHALMITIS VIRECTOMY STUDY COORDINATING CTR,PITTSBURGH,PA 15261, USA. OI Wisniewski, Stephen/0000-0002-3877-9860 FU NEI NIH HHS [EY08150, EY08151, EY08210] NR 56 TC 350 Z9 369 U1 1 U2 17 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 JUL PY 1996 VL 122 IS 1 BP 1 EP 17 PG 17 WC Ophthalmology SC Ophthalmology GA UX374 UT WOS:A1996UX37400001 PM 8659579 ER PT J AU Weissgold, DJ Decker, PJ AF Weissgold, DJ Decker, PJ TI Retinal hemorrhages from septic emboli in a patient with a ventricular false chorda SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To demonstrate ophthalmic findings of bacterial endocarditis in a patient with a cardiac structural anomaly and to illustrate the potential usefulness of transesophageal echocardiography in the examination of such patients. METHODS: We examined a patient with bacteremia who had white-centered retinal hemorrhages. Complete clinical, laboratory, and echocardiographic evaluations were performed. RESULTS: Streptococcal bacteremia was proven and, by using transesophageal echocardiography, a ventricular false chorda was demonstrated. CONCLUSIONS: Patients with white-centered retinal hemorrhages should undergo thorough systemic examinations. In this unusual case of such hemorrhages caused by bacteremia in a patient with a ventricular false chorda, modern, high-resolution transesophageal echocardiography played an important role in confirming the diagnosis. RP Weissgold, DJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,12TH FLOOR,243 CHARLES ST,BOSTON,MA 02114, USA. NR 5 TC 4 Z9 4 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 JUL PY 1996 VL 122 IS 1 BP 117 EP 119 PG 3 WC Ophthalmology SC Ophthalmology GA UX374 UT WOS:A1996UX37400017 PM 8659585 ER PT J AU Megerian, CA McKenna, MJ Ojemann, RG AF Megerian, CA McKenna, MJ Ojemann, RG TI Delayed facial paralysis after acoustic neuroma surgery: Factors influencing recovery SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Neurotology-Society CY APR 29-30, 1995 CL PALM DESERT, CA SP Amer Neurotol Soc DE facial nerve; paralysis; acoustic neuroma ID NERVE FUNCTION; RESECTION AB Patients with satisfactory facial nerve function [House-Brackmann (HE) grade I or II] immediately after acoustic neuroma surgery are at risk for delayed facial paralysis. To study this problem, 255 consecutive patients who underwent acoustic neuroma excision with facial nerve preservation were identified. Delayed facial paralysis occurred in 62 (24.3%) patients; 90% ultimately recovered to their initial post operative HB grade, and 98.3% recovered to within one grade of their initial HB level. Paralysis occurred at an average of 3.65 postoperative days (range, 1-16 days). The average time to maximal recovery for those with changes of 1, 2, 3, and 4 HB grades was 5.6, 21.5, 39.8, and 50.5 weeks, respectively. The early onset of paralysis (<48 h after surgery) resulted in shorter average recovery times. Of patients who demonstrated nerve deterioration to grades IV-VI, 20 of 38 required tarsorrhaphy or gold-weight placement. We conclude that the overwhelming majority of patients with delayed facial paralysis after acoustic neuroma surgery do eventually recover to their postoperative HE grade. The magnitude and timecourse of delayed facial paralysis are predictive factors for subsequent recovery. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV NEUROSURG,DEPT SURG,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 11 TC 29 Z9 29 U1 0 U2 0 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 JUL PY 1996 VL 17 IS 4 BP 630 EP 633 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA UZ067 UT WOS:A1996UZ06700020 PM 8841712 ER PT J AU Dellian, M Witwer, BP Salehi, HA Yuan, F Jain, RK AF Dellian, M Witwer, BP Salehi, HA Yuan, F Jain, RK TI Quantitation and physiological characterization of angiogenic vessels in mice - Effect of basic fibroblast growth factor vascular endothelial growth factor vascular permeability factor, and host microenvironment SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN ADENOCARCINOMA LS174T; TUMOR ANGIOGENESIS; MICROVASCULAR PERMEABILITY; SCID MICE; INVIVO; INHIBITION; MEMBRANE; PRESSURE; ADHESION; TISSUES AB A prerequisite for the development of novel angiogenic and anti-angiogenic agents is the availability of routine in vivo assays that permit 1) repeated, long-term quantitation of angiogenesis and 2) physiological characterization of angiogenic vessels. We report here the development of such an assay in mice, Using this assay, we tested the hypothesis that the physiological properties of angiogenic vessels are governed by the microenvironment and vessel origin rather than the initial angiogenic stimulus. Gels containing basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) were implanted in transparent windows in the dorsal skin or cranium of mice. Vessels could be continuously and non-invasively monitored and easily quantified for more than 5 weeks after gel implantation, Newly formed vessels were first visible on day 4 in tbe cranial window and day 10 in the dorsal skinfold chamber, respectively. The number of vessels was dependent on the dose of bFGF and VEGF. At 3000 ng/ml, bFGF- and VEGF-induced blood vessels had similar diameters, red blood cell velocities, and microvascular permeability to albumin. However, red blood cell velocities and microvascular permeability to albumin were higher in the cranial window than in the dorsal skinfold chamber. Leukocyte-endothelial interaction was nearly zero in both sites. Thus, newly grown microvessels resembled vessels of granulation and neoplastic tissue in many aspects. Their physiological properties were mainly determined by the microenvironment, whereas the initial angiogenic response was stimulated by growth factors. C1 HARVARD UNIV,DEPT RADIAT ONCOL,MASSACHUSETTS GEN HOSP,SCH MED,EL STEELE LAB,BOSTON,MA 02114. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA-56591] NR 60 TC 176 Z9 179 U1 0 U2 5 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 JUL PY 1996 VL 149 IS 1 BP 59 EP 71 PG 13 WC Pathology SC Pathology GA UV051 UT WOS:A1996UV05100011 PM 8686763 ER PT J AU Russell, PS Chase, CM Colvin, RB AF Russell, PS Chase, CM Colvin, RB TI Accelerated atheromatous lesions in mouse hearts transplanted to apolipoprotein-E-deficient recipients SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE; ALLOGRAFT-REJECTION; CARDIAC ALLOGRAFTS; VCAM-1 EXPRESSION; CELLS; HYPERCHOLESTEROLEMIA; PATHOGENESIS; MICE; ATHEROSCLEROSIS; ARTERIOSCLEROSIS AB Arteriopathy, sometimes termed accelerated atherosclerosis, often impairs transplants. We employed apolipoprotein-E-deficient, hypercholesterolemic mice to determine how the hyperlipidemic environment affected transplanted hearts. Strain 129 hearts transplanted to C57BL/6 normal or C57BL/6 apolipoprotein-E-deficient recipients were evaluated by immunochemical and histological techniques. Analyses were possible both of differences in the coronary lesions that developed in a normolipidemic as compared with a hyperlipidemic environment and of the coronary atherosclerotic process in transplanted hearts compared with native hearts hearts in the same hyperlipidemic environment. Aortas and coronary arteries of transplanted hearts in both recipient groups developed florid intimal thickening by 4 to 10 weeks, with marked lipid deposition, foamy macrophages, and infiltration of smooth muscle alpha-actin-positive cells in apolipoprotein-E-deficient mice. Lipid was layered against the internal elastic lamina as in human transplants. VCAM-1 was increased in various sites in both groups. Allotransplants to apolipoprotein-E-deficient recipients had more severe aortic and coronary lesions with characteristic T cell infiltration than native hearts. In this sense, transplants suffered from accelerated atherosclerosis. The character of coronary vascular changes in transplanted hearts was distinctly affected by their lipid environment, but their severity, in terms of luminal encroachment, was not markedly different. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. FU NHLBI NIH HHS [R01-HL43340] NR 32 TC 30 Z9 30 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 JUL PY 1996 VL 149 IS 1 BP 91 EP 99 PG 9 WC Pathology SC Pathology GA UV051 UT WOS:A1996UV05100014 PM 8686767 ER PT J AU Fukayama, S Lanske, B Guo, J Kronenberg, HM Bringhurst, FR AF Fukayama, S Lanske, B Guo, J Kronenberg, HM Bringhurst, FR TI Regulation of HSP70 by PTH: A model of gene regulation not mediated by changes in cAMP levels SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE parathyroid hormone; 70-kDa heat shock protein; adenosine 3',5'-cyclic monophosphate-independent gene regulation ID HORMONE (PTH)/PTH-RELATED PEPTIDE; PROTEIN-LINKED RECEPTOR; HEAT-SHOCK PROTEINS; CELL-LINE SAOS-2; PARATHYROID-HORMONE; CALCITONIN RECEPTOR; OSTEO-SARCOMA; EXPRESSION CLONING; COMMON RECEPTOR; KIDNEY-CELLS AB Parathyroid hormone (PTH) activates both adenylate cyclase and phospholipase C in target cells, and cloned PTH/PTH-related protein (PTHrP) receptor can mediate both responses when expressed in host cells such as LLC-PK1 renal epithelial cells. Because calcitonin (CT) is known to augment 70-kDa heat shock. protein (HSP70) mRNA by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent mechanism in LLC-PK1 cells, we examined regulation of HSP70 transcription by PTH in these cells. Like CT, human PTH-(1-34) [hPTH-(1-34); 10(-10) to 10(-7) M)] increased porcine HSP70 mRNA and human HSP70 promoter-chloramphenicol acetyltransferase (CAT) expression within 4 h in LLC-PK1 cells that stably express greater than or equal to 100,000 PTH/PTHrP receptors per cell. The effect of PTH on HSP70 mRNA was not mimicked by cAMP analogues, forskolin, phorbol esters, Ca2+ ionophores, or alpha-thrombin; was insensitive to pertussis toxin; and was not due to increased mRNA stability. The upregulation of HSP70 gene transcription by hPTH (and CT) was clearly observed even after deletion of the functional heat shock consensus element in the promoter region of the human HSP70/CAT reporter. Upregulation of HSP70 transcription via endogenous PTH receptors also was observed in the osteoblastic cell lines SaOS-2 and ROS 17/2.8. Regulation of HSP70 gene transcription by PTH may be a common cellular response to the hormone, which, in some cells, may not be mediated by activation of adenylate cyclase or protein kinase C. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. RP Fukayama, S (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, FRUIT ST, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 30 TC 3 Z9 3 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1996 VL 271 IS 1 BP C121 EP C129 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UX534 UT WOS:A1996UX53400012 PM 8760037 ER PT J AU Vadakekalam, J Rabaglia, ME Chen, QH Metz, SA AF Vadakekalam, J Rabaglia, ME Chen, QH Metz, SA TI Role for GTP in glucose-induced phospholipase C activation in pancreatic islets SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE mycophenolic acid; insulin secretion; inositol phosphate; carbachol; guanosine 5'-triphosphate ID PERMEABILIZED HIT-T15 CELLS; PROTEIN-KINASE-C; INSULIN-SECRETION; B-CELLS; RAT ISLETS; INOSITOL PHOSPHATES; K+ CHANNELS; RELEASE; PHOSPHATIDYLINOSITOL; HYDROLYSIS AB We have previously demonstrated a permissive role for GTP in insulin secretion; in the current studies, we examined the effect of GTP on phospholipase C (PLC) activation to explore one possible mechanism for that observation. In rat islets preexposed to the GTP synthesis inhibitors mycophenolic acid (MPA) or mizoribine (MZ), PLC activation induced by 16.7 mM glucose (or by 20 mM alpha-ketoisocaproic acid) was inhibited 63% without altering the labeling of phosphoinositide substrates. Provision of guanine, which normalizes islet GTP content and insulin release, prevented the inhibition of PLC by MPA. Glucose-induced phosphoinositide hydrolysis was blocked by removal of extracellular Ca2+ or by diazoxide. PLC induced directly by Ca2+ influx (i.e., 40 mM K+) was reduced 42% in MPA-pretreated islets but without inhibition of the concomitant insulin release. These data indicate that glucose-induced PLC activation largely reflects Ca2+ entry and demonstrate (for the first time in intact cells) that adequate GTP is necessary for glucose (and Ca2+-)-induced PLC activation but not for maximal Ca2+-induced exocytosis. C1 UNIV WISCONSIN, DEPT MED, ENDOCRINOL SECT, MADISON, WI 53706 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53792 USA. FU NIDDK NIH HHS [DK-37312] NR 35 TC 28 Z9 28 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 1996 VL 271 IS 1 BP E85 EP E95 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA UW456 UT WOS:A1996UW45600011 PM 8760085 ER PT J AU Darmoul, D Ouellette, AJ AF Darmoul, D Ouellette, AJ TI Positional specificity of defensin gene expression reveals Paneth cell heterogeneity in mouse small intestine SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cryptdin; mucosal immunity; antimicrobial peptides ID CYSTEINE-RICH PEPTIDES; EPITHELIAL-CELL; CRYPTDIN; FAMILY; NEUTROPHILS; RENEWAL; ORIGIN; CDNA AB Cryptdins are antimicrobial peptides of the defensin family that are expressed specifically by Paneth cells in small intestinal crypts (M. E. Selsted, S. I. Miller, A. H. Henschen, and A. J. Ouellette. J. Cell Biol. 118: 929-936, 1992), and at least 17 cryptdin isoforms have been reported in mouse small intestine (A. J. Ouellette, M. M. Hsieh, M. T. Nosek, D. F. Cano-Gauci, K. M. Huttner, R. N. Buick, and M. E. Selsted. Infect. Immun. 62: 5040-5047, 1994). Analysis of cryptdin gene expression in adult mouse small bowel revealed that the cryptdin-4 isoform is differentially expressed along the proximal-to-distal intestinal axis. By peptide-specific reverse transcriptase-polymerase chain reaction-based assays, cryptdin-4 mRNA was found to be absent from the proximal small bowel, increasing to maximal levels in the ileum. In contrast, intestinal content of cryptdin-1 and -5 mRNAs was equivalent in duodenum, jejunum, and ileum, and Northern blot hybridization experiments were consistent with both sets of data. Similarly, individual crypts isolated fi om duodenum contain cryptdin-1 mRNA but not cryptdin-4 mRNA. Taken together, the results show that Paneth cells are heterogeneous, depending on their position along the longitudinal axis of the small bowel. The positional. specificity of defensin gene expression suggests that cryptdins may be useful markers for investigating the establishment and maintenance of this epithelial lineage in the mouse small intestine. C1 MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, MED SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. FU NICHD NIH HHS [HD-31852]; NIDDK NIH HHS [DK-33506, DK-44632] NR 38 TC 34 Z9 39 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JUL PY 1996 VL 271 IS 1 BP G68 EP G74 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA UW940 UT WOS:A1996UW94000010 PM 8760109 ER PT J AU Wada, H Zile, MR Ivester, CT Cooper, G McDermott, PJ AF Wada, H Zile, MR Ivester, CT Cooper, G McDermott, PJ TI Comparative effects of contraction and angiotensin II on growth of adult feline cardiocytes in primary culture SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE protein synthesis; cell culture; hypertrophy ID CONVERTING ENZYME-INHIBITION; LEFT-VENTRICULAR HYPERTROPHY; CHICK HEART-CELLS; PROTEIN-SYNTHESIS; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; RAT-HEART; RIBOSOME SYNTHESIS; GENE-EXPRESSION; STIMULATION AB The purposes of this study were 1) to determine whether angiotensin II causes growth of adult feline cardiocytes in long-term culture, 2) to compare the growth effects of angiotensin II with those resulting from electrically stimulated contraction, and 3) to determine whether the anabolic effects of contraction are exerted via the angiotensin type 1 receptor. Adult feline cardiocytes were cultured on laminin-coated trays in a serum-free medium. Cardiocytes were either electrically stimulated to contract (1 Hz, 5-ms pulse duration, alternating polarity) or were nonstimulated and quiescent. Quiescent cells were studied as controls and after treatment with angiotensin II (10(-8) M), losartan (10(-6) M; an angiotensin type 1-receptor antagonist), or angiotensin II plus losartan. Contracting cells were studied in the presence and absence of angiotensin II or losartan. In quiescent cardiocytes, angiotensin II treatment on day 7 significantly increased protein synthesis rates by 22% and protein content per cell by 17%. The effects of angiotensin II were completely blocked by losartan. Electrically stimulated contraction on days 4 and 7 in culture significantly increased protein synthesis rate by 18 and 38% and protein content per cell by 19 and 46%, respectively. Angiotensin II treatment did not further increase protein synthesis rate or protein content in contracting cardiocytes. Furthermore, losartan did not block the anabolic effects of contraction on protein synthesis rates or protein content. In conclusion, angiotensin II can exert a modest anabolic effect on adult feline cardiocytes in culture. In contracting feline cardiocytes, angiotensin II has no effect on growth. Growth caused by electrically stimulated contraction occurs more rapidly and is greater in magnitude than that caused by angiotensin II. Growth of contracting adult feline cardiocytes is not dependent on activation of the angiotensin receptor. C1 GAZES CARDIAC RES INST, DEPT MED, CHARLESTON, SC USA. GAZES CARDIAC RES INST, DEPT PHYSIOL, CHARLESTON, SC USA. GAZES CARDIAC RES INST, DEPT CELL BIOL & ANAT, CHARLESTON, SC USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29401 USA. FU NHLBI NIH HHS [P01 HL-48788] NR 38 TC 32 Z9 32 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 1996 VL 271 IS 1 BP H29 EP H37 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA UX526 UT WOS:A1996UX52600005 PM 8760154 ER PT J AU Sorensen, G Thompson, B Glanz, K Feng, ZD Kinne, S DiClemente, C Emmons, K Heimendinger, J Probart, C Lichtenstein, E AF Sorensen, G Thompson, B Glanz, K Feng, ZD Kinne, S DiClemente, C Emmons, K Heimendinger, J Probart, C Lichtenstein, E TI Work site-based cancer prevention: Primary results from the Working Well Trial SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GENERALIZED LINEAR-MODELS; SMOKING CESSATION; QUESTIONNAIRE; RECORDS; INTERVENTION; VALIDATION; WOMEN AB Objectives. This paper presents the behavioral results of the Working well Trial, the largest US work site cancer prevention and control trial to date. Methods. The Working Well Trial used a randomized, matched: pair evaluation design, with the work site as the unit of assignment and analysis. The study was conducted in 111 work sites (n = 28 000 workers). The effects of the intervention were evaluated by comparing changes in intervention and control work sites, as measured in cross-sectional surveys at baseline and follow-up. The 2-year intervention targeted both individuals and the work-site environment. Results. There occurred a net reduction in the percentage of energy obtained from fat consumption of 0.37 percentage points (P = .033), a net increase in fiber densities of 0.13 g/1000 kcal (P = .056), and an average increase in fruit and vegetable intake of 0.18 servings per day (P = .0001). Changes in tobacco use were in the desired direction but were not significant. Conclusions. Significant but small differences were observed for nutrition. Positive trends, but no significant results, were observed in trial-wide smoking outcomes. The observed net differences were small :owing to the substantial secular changes in target behaviors. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. CANC RES CTR HAWAII,HONOLULU,HI 96813. UNIV HOUSTON,HOUSTON,TX 77004. BROWN UNIV,MIRIAM HOSP,PROVIDENCE,RI 02912. NCI,ROCKVILLE,MD. PENN STATE UNIV,DEPT NUTR,UNIVERSITY PK,PA 16802. OREGON RES INST,EUGENE,OR 97403. RP Sorensen, G (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [U01 CA51686, U01 CA51687, U01 CA61771] NR 41 TC 148 Z9 151 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 939 EP 947 DI 10.2105/AJPH.86.7.939 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100007 PM 8669517 ER PT J AU Smoller, JW Pollack, MH Otto, MW Rosenbaum, JF Kradin, RL AF Smoller, JW Pollack, MH Otto, MW Rosenbaum, JF Kradin, RL TI Panic anxiety, dyspnea, and respiratory disease - Theoretical and clinical considerations SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; CARBON-DIOXIDE CHALLENGE; CHRONIC AIRWAYS OBSTRUCTION; SODIUM LACTATE INFUSION; SLEEP-APNEA; DISORDER PATIENTS; HYPERVENTILATION SYNDROME; PSYCHIATRIC-DISORDERS; VENTILATORY RESPONSE C1 MCLEAN HOSP,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PULM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CRIT CARE UNITS,BOSTON,MA 02114. NR 219 TC 122 Z9 125 U1 4 U2 9 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 JUL PY 1996 VL 154 IS 1 BP 6 EP 17 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UW827 UT WOS:A1996UW82700004 PM 8680700 ER PT J AU Sharma, SK Maclean, JA Pinto, C Kradin, RL AF Sharma, SK Maclean, JA Pinto, C Kradin, RL TI The effect of an anti-CD3 monoclonal antibody on bleomycin-induced lymphokine production and lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID INDUCED PULMONARY FIBROSIS; MARROW GRAFT-REJECTION; RECOMBINANT INTERLEUKIN-2; T-CELLS; MICE; LYMPHOCYTES; SUBPOPULATIONS; POPULATIONS; DEPLETION; PHENOTYPE AB Acute lung injury was produced in C57BL/6 mice by the intratracheal (i.t.) administration of bleomycin (BLM). Following injection of 0.1 U BLM, CD3(+) lymphocytes and the production of the T-helper-1 (Th1) lymphokines interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were increased in lung and lymph nodes. The production of the Th2 cytokine IL-4 by lung lymphocytes was decreased. Intraperitoneal (i.p.) injection of a rat antimurine CD3 (YCD3) monoclonal antibody (mAb) blocked the accumulation of pulmonary CD3(+) cells for up to 14 d and effectively suppressed IL-2 and IL-4 but not IFN-gamma production by lung lymphocytes throughout the protocol. Secretion of all of the above lymphokines by lymph node cells was inhibited by YCD3 treatment. Administration of YCD3 diminished pulmonary fibrosis and increased survival (p < 0.01) following BLM administration compared with mice treated with an isotype-matched control mAb. Initiating treatment with YCD3 at Days 5-7 following BLM also decreased pulmonary fibrosis and significantly reduced mortality (p < 0.02). We conclude that BLM yields a potentially lethal fibroinflammatory response in the lung that is markedly diminished by antagonizing the functional activities of CD3(+) cells in vivo. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NHLBI NIH HHS [HL48385]; NIAID NIH HHS [AI01245] NR 35 TC 63 Z9 63 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 JUL PY 1996 VL 154 IS 1 BP 193 EP 200 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UW827 UT WOS:A1996UW82700033 PM 8680680 ER EF