FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Goodfriend, TL Egan, BM AF Goodfriend, TL Egan, BM TI Nonesterified fatty acids in the pathogenesis of hypertension: theory and evidence SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PROTEIN-KINASE-C; BLOOD-PRESSURE; ALDOSTERONE SECRETION; INSULIN STIMULATION; ARTERIAL-PRESSURE; ANGIOTENSIN-II; RAT ADIPOCYTES; FISH-OIL; MECHANISM; INHIBITION AB This paper approaches the hypothesis that fatty acids contribute to hypertension by examining possible interactions of nonesterified fatty acids with renal pressure-natriuresis, peripheral vascular resistance, and the central nervous barostat, three loci where long-term regulation of blood pressure is probably controlled. By inhibiting aldosterone secretion, nonesterified fatty acids may lower blood pressure by facilitating pressure-natriuresis. Oxygenated metabolites of fatty acids appear to stimulate aldosterone secretion. In different experimental situations, fatty acids either constrict or dilate arteries. There is no evidence of an effect of fatty acids on the central nervous barostat, but they do sensitize peripheral vessels to alpha-adrenergic stimuli. Obesity and diabetes are marked by increased incidence of hypertension, and elevated levels of fatty acids or their P450 oxygenated metabolites may contribute to this association. Drugs that influence plasma fatty acids, like heparin, do not have reproducible effects on blood pressure. Experimental evidence suggests but does not prove that nonesterified fatty acids can affect the longterm set-point of blood pressure. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT PHARMACOL,MADISON,WI 53706. MED UNIV S CAROLINA,DEPT PHARMACOL,DIV CLIN PHARMACOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MED,DIV CLIN PHARMACOL,CHARLESTON,SC 29425. RP Goodfriend, TL (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NCRR NIH HHS [RR-01070]; PHS HHS [R01-43164] NR 43 TC 13 Z9 13 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JUL PY 1997 VL 57 IS 1 BP 57 EP 63 DI 10.1016/S0952-3278(97)90493-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA XM424 UT WOS:A1997XM42400010 PM 9250609 ER PT J AU Pacholczyk, T Sweadner, KJ AF Pacholczyk, T Sweadner, KJ TI Epitope and mimotope for an antibody to the Na,K-ATPase SO PROTEIN SCIENCE LA English DT Article DE antibody mapping; epitope determination; membrane protein structure; phage display of peptides; random fragment library screening; synthetic fusion proteins ID NA+,K+-ATPASE ALPHA-SUBUNIT; RANDOM PEPTIDE LIBRARY; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; CATALYTIC SUBUNIT; ANTIGENIC DETERMINANTS; MOLECULAR-CLONING; BETA-SUBUNIT; IDENTIFICATION; BINDING AB The epitope of a monoclonal antibody specific for the alpha 2 isoform of the Na,K-ATPase was determined and its accessibility in native enzyme was examined. Protein fragmentation with N-chlorosuccinimide, formic acid, trypsin, and leucine aminopeptidase indicated binding near the Na,K-ATPase N-terminus but did not unambiguously delineate the extent of the epitope. The ability of the antibody to bind to denatured enzyme made it a good candidate for screening a random peptide library displayed on M13 phage, but the consensus sequence that emerged was not found in the Na,K-ATPase. Full-length cDNA for the Na,K-ATPase was randomly fragmented and cloned into beta-galactosidase to create a lambda gt11 expression library; screening with the antibody yielded a set of overlaps spanning 23 amino acids at the N-terminus. Chimeras of Na,K-ATPase alpha 1 and alpha 2 narrowed down the epitope to 14-19 amino acids. The antibody did not recognize fusion proteins constructed with shorter segments of this epitope. It did recognize a fusion protein containing the M13 library consensus sequence, however, indicating that this sequence, which is rich in proline and hydrophobic amino acids (FPPNFLFPPPP), was a mimotope. The natural epitope, unique to the Na,K-ATPase alpha 2 isoform, was GREYSPAATTAENG. Reconstitution of antibody binding in a foreign context such as M13 PIII protein or beta-galactosidase thus required a relatively large number of amino acids, indicating that antibody mapping approaches must allow for epitopes of significant size. The epitope was accessible in native enzyme and exposed on the cytoplasmic side, documenting the surface exposure of a stretch of amino acids at the N-terminus, where the Na, K-ATPase isoforms differ most. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,LAB MEMBRANE BIOL,CHARLESTOWN,MA 02129. FU NHLBI NIH HHS [HL 36271]; NINDS NIH HHS [NS 27653] NR 38 TC 20 Z9 20 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUL PY 1997 VL 6 IS 7 BP 1537 EP 1548 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK776 UT WOS:A1997XK77600018 PM 9232655 ER PT J AU Tsuang, JW Ho, AP Eckman, TA Shaner, A AF Tsuang, JW Ho, AP Eckman, TA Shaner, A TI Dual diagnosis treatment for patients with schizophrenia who are substance dependent SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID REVOLVING-DOOR; DISORDERS C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Tsuang, JW (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,11301 WILSHIRE BLVD 00MH,LOS ANGELES,CA 90073, USA. NR 9 TC 7 Z9 7 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JUL PY 1997 VL 48 IS 7 BP 887 EP 889 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA XH532 UT WOS:A1997XH53200006 PM 9219296 ER PT J AU Perea, SG AF Perea, SG TI Culture and psychiatric diagnosis: A DSM-IV perspective - Mezzich,JE, Kleinman,A, Fabrega,H, Parron,CL SO PSYCHOSOMATICS LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,PSYCHIAT CONSULTAT SERV,BOSTON,MA 02114. RP Perea, SG (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1997 VL 38 IS 4 BP 394 EP 395 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA XH281 UT WOS:A1997XH28100015 ER PT J AU Fairclough, DL Chang, VT Hwang, SS AF Fairclough, DL Chang, VT Hwang, SS TI Quality of life in terminal cancer patients: Non-random missing data in a longitudinal study SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. DVA,DEPT MED,E ORANGE,NJ. DVA,DEPT NURSING,E ORANGE,NJ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD JUL PY 1997 VL 6 IS 5 BP 6 EP 6 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XQ858 UT WOS:A1997XQ85800010 ER PT J AU Holmes, LB AF Holmes, LB TI Bob was right SO REPRODUCTIVE TOXICOLOGY LA English DT Article; Proceedings Paper CT 1996 Symposium Festschrift for Robert L Brent CY APR 08, 1996 CL THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, PHILADELPHIA, PA HO THOMAS JEFFERSON UNIV, JEFFERSON MED COLL DE teratogen; nonteratogen; sex hormones; Bendectin ID FEMALE SEX-HORMONES; CARDIOVASCULAR BIRTH-DEFECTS; ORAL-CONTRACEPTIVES; ANTENATAL EXPOSURE; BENDECTIN; PREGNANCY AB During his career Bob Brent has been instrumental in developing the methodology to use in determining whether an exposure in pregnancy has a harmful effect on the fetus. Experience has also shown the importance of using this approach to determine when an exposure is not teratogenic, Unfortunately, the attendant debate, as illustrated in two examples reviewed, exogenous sex hormones and Bendectin, requires persistence and a thick skin, Bob has recorded in several publications how he carried out these systematic analyses, This literature will be a very valuable legacy. (C) 1997 Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Holmes, LB (reprint author), HARVARD UNIV,GENET & TERATOL UNIT,SERV PEDIAT,MASSACHUSETTS GEN HOSP,SCH MED,WARREN 801,BOSTON,MA 02114, USA. NR 27 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 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JUL-AUG PY 1997 VL 11 IS 4 BP 613 EP 616 DI 10.1016/S0890-6238(97)00001-4 PG 4 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA XH028 UT WOS:A1997XH02800018 PM 9241683 ER PT J AU Gutierrez, O Melo, M Segura, AM Angel, A Genta, RM Graham, DY AF Gutierrez, O Melo, M Segura, AM Angel, A Genta, RM Graham, DY TI Cure of Helicobacter pylori infection improves gastric acid secretion in patients with corpus gastritis SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE acid secretion; antimicrobial therapy; clinical trial; Helicobacter pylori ID DUODENAL-ULCER DISEASE; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-ALPHA; CAMPYLOBACTER-PYLORI; ANTRAL GASTRITIS; GENE-EXPRESSION; PARIETAL-CELLS; NITRIC-OXIDE; ERADICATION; INHIBITION AB Background: For more than 30 years it has been known that gastric acid secretion is inversely related to the extent and severity of corpal gastritis. We therefore evaluated the effect of cure of Helicobacter pylori infection on basal and pentagastrin-stimulated acid secretion. Methods: Basal acid output (BAG) and maximal acid output (MAO) were assessed in 11 H. pylori-infected dyspeptic patients (8 women and 3 men; mean age, 28 years) before and after successful anti-H. pylori therapy. Results: The gastritis index was significantly lower after therapy and was associated with an increase in both BAO and MAO after cure of the H. pylori infection (BAG from 0.3 mmol/h to 3.1 mmol/h and MAO from 4.8 mmol/h to 19 mmol/h). Basal and stimulated acid concentrations also increased (29.1 +/- 36.6 to 54 +/- 31 mmol/l and 72.5 +/- 46 to 120.1 +/- 30 mmol/l, respectively, for basal and stimulated acid concentrations; P < 0.05 for peak and MAO, P = 0.07 for BAG). Conclusion: Gastric acid secretion increased into the normal range after successful treatment of H. pylori infection, suggesting that gastric function can recover to normal or almost normal after cure of H. pylori infection. C1 VET AFFAIRS MED CTR 111D,DEPT PATHOL,HOUSTON,TX 77030. VET AFFAIRS MED CTR,DEPT MED,HOUSTON,TX 77030. UNIV NACL COLOMBIA,HOSP SAN JUAN DIOS,DEPT GASTROENTEROL,BOGOTA,COLOMBIA. BAYLOR COLL MED,HOUSTON,TX 77030. NR 53 TC 110 Z9 111 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD JUL PY 1997 VL 32 IS 7 BP 664 EP 668 DI 10.3109/00365529708996515 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XJ694 UT WOS:A1997XJ69400008 PM 9246705 ER PT J AU Marcus, KC Tarbell, NJ AF Marcus, KC Tarbell, NJ TI The changing role of radiation therapy in the treatment of neuroblastoma SO SEMINARS IN RADIATION ONCOLOGY LA English DT Review ID PEDIATRIC-ONCOLOGY-GROUP; CYTOMETRIC DNA ANALYSIS; HUMAN NEURO-BLASTOMA; N-MYC AMPLIFICATION; TUMOR KARYOTYPE; PROGNOSIS; STAGE; CHROMOSOME-1; HETEROZYGOSITY; CHEMOTHERAPY C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Marcus, KC (reprint author), CHILDRENS HOSP,DEPT RADIAT ONCOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 41 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 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 1997 VL 7 IS 3 BP 195 EP 203 DI 10.1016/S1053-4296(97)80003-3 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XL709 UT WOS:A1997XL70900003 ER PT J AU Greenberg, SM Vonsattel, JPG AF Greenberg, SM Vonsattel, JPG TI Diagnosis of cerebral amyloid angiopathy - Sensitivity and specificity of cortical biopsy SO STROKE LA English DT Article DE amyloid; biopsy; diagnosis; hemorrhage ID SURGICAL EXPERIENCE; ALZHEIMERS-DISEASE; HEMORRHAGE; COMPLICATIONS; PREVALENCE AB Background and Purpose Examination of cortical tissue obtained surgically is an important tool for diagnosis of cerebral amyloid angiopathy (CAA) during life. Analysis of a single sample of cortical tissue, however, might lead to conclusions that are either falsely positive (because of the high frequency of CAA in the healthy elderly) or falsely negative (because of the patchy distribution of CAA pathology). We therefore attempted to estimate the sensitivity and specificity of cortical biopsy for diagnosis of CAA as the cause of intracerebral hemorrhage. Methods To simulate biopsy in CAA, we took biopsy-sized cortical samples from postmortem brains with known extents of CAA: either CAA-related hemorrhage or mild to severe CAA without hemorrhage. Samples were stained with the use of methods routinely available in surgical pathology laboratories and blindly examined for vascular amyloid and amyloid-related vasculopathic changes. Results The presence of vascular amyloid was a sensitive marker for CAA-related hemorrhage occurring In all 28 specimens from brains with hemorrhage. Conversely, the appearance of fibrinoid necrosis in amyloid-laden vessels was relatively specific for CAA-related hemorrhage. This Ending occurred in 13 of the 28 specimens (46%) from brains with hemorrhage but in none of 27 sections from brains with mild CAA and in only 4 of 42 specimens with moderate to severe CAA without hemorrhage. Conclusions These data help to define criteria for the diagnosis of CAA-related hemorrhage from surgical specimens. C1 MASSACHUSETTS GEN HOSP,CS KUBIK LAB NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MCLEAN HOSP,BRAIN TISSUE RESOURCE CTR,BOSTON,MA. RP Greenberg, SM (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,WACC 836,BOSTON,MA 02114, USA. FU PHS HHS [31862] NR 24 TC 130 Z9 139 U1 2 U2 6 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 1997 VL 28 IS 7 BP 1418 EP 1422 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA XK482 UT WOS:A1997XK48200022 PM 9227694 ER PT J AU Carvalho, GL Wakabayashi, G Shimazu, M Karahashi, T Yoshida, M Yamamoto, S Matsushima, K Mukaida, N Clark, BD Takabayashi, T Brandt, CT Kitajima, M AF Carvalho, GL Wakabayashi, G Shimazu, M Karahashi, T Yoshida, M Yamamoto, S Matsushima, K Mukaida, N Clark, BD Takabayashi, T Brandt, CT Kitajima, M TI Anti-interleukin-8 monoclonal antibody reduces free radical production and improves hemodynamics and survival rate in endotoxic shock in rabbits SO SURGERY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RECEPTOR ANTAGONIST; ESCHERICHIA-COLI; SEPTIC SHOCK; ESSENTIAL INVOLVEMENT; THERMAL-INJURY; TISSUE-INJURY; NITRIC-OXIDE; IN-VIVO; INTERLEUKIN-8 AB Background. Although high levels of interleukin-8 (IL-8) have been found in patients with sepsis and a monoclonal antibody (MaAb) against IL-8 has been successfully used in some animal models of inflammation, no specific therapeutic agent against IL-8 has been tested for the treatment of sepsis. We studied the effects of a MoAb against IL-8 in the treatment of endotoxic shock with a prospective randomized rabbit endotoxic shock model. Methods. Twenty New Zealand white rabbits were anesthetized and divided into four groups: normal, anti-IL-8, control-Ab, and lipopolysaccharide (LPS). Anti-IL-8 and control-Ab groups received a MoAb immunoglobulin G, 3 mg/kg) 5 minutes before the LPS infection. All groups, except the normal group, received a continuous 20-minute infusion of LPS (500 mu g/kg). The normal group received NaCl (0.9%) rather than LPS. Results. The 7-day survival rates were 100% for normal group, 80% for anti-IL-8 group, 40% for control-Ab group, and 0% for LPS group. Compared with the LPS group, anti-IL-8 rabbits had a smaller decrease in mean arterial blood pressure (p < 0.05) and increased urinary volume (p < 0.05). Anti-IL-8 rabbits had lower plasmatic levels of IL-1 beta, less free radical production (p < 0.05), and a higher survival rate (p < 0.01). Conclusions. IL-8 plays a significant role in endotoxic shock, and IL-8 blockage results in attenuation of the hypotensive and tachypneic effects of LPS, reduced free radical production, and an increased survival rate after lethal endotoxic shock. C1 KEIO UNIV,SCH MED,DEPT SURG,LIVER TRANSPLANATAT DIV,SHINJUKU KU,TOKYO 160,JAPAN. UNIV FED PERNAMBUCO,MASTERS COURSE SURG,RECIFE,PE,BRAZIL. UNIV TOKYO,GRAD SCH MED,DEPT MOL PREVENT MED,TOKYO,JAPAN. KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. TUFTS UNIV,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 NR 49 TC 30 Z9 33 U1 0 U2 2 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 JUL PY 1997 VL 122 IS 1 BP 60 EP 68 DI 10.1016/S0039-6060(97)90265-8 PG 9 WC Surgery SC Surgery GA XK808 UT WOS:A1997XK80800010 PM 9225916 ER PT J AU Rivera, JA GraemeCook, F Werner, J Zgraggen, K Rustgi, AK Rattner, DW Warshaw, AL FernandezdelCastillo, C AF Rivera, JA GraemeCook, F Werner, J Zgraggen, K Rustgi, AK Rattner, DW Warshaw, AL FernandezdelCastillo, C TI A rat model of pancreatic ductal adenocarcinoma: Targeting chemical carcinogens SO SURGERY LA English DT Article ID C-K-RAS; SYRIAN-HAMSTERS; ACTIVATION; CANCER; CELLS; GENES; N-NITROSOBIS(2-OXOPROPYL)AMINE; PATHOGENESIS; MUTATIONS; FREQUENT AB Background. Current experimental models of pancreatic cancer either fail to reproduce the ductal phenotype or cause simultaneous cancers in other organs also. To develop an animal model of pancreatic cancer that accurately mimics the human condition, we restricted carcinogenic exposure to the pancreas and specifically targeted ductal epithelial cells. Three different carcinogens were either implanted directly into the pancreas or infused into the pancreatic duct, with or without near-total pancreatectomy (as a means of inducing pancreatic ductal cell proliferation). Methods. Groups of male Sprague-Dawley rats were exposed to varying doses of dimethylbenzanthracine (DMBA), methynitronitrosoguanidine, or ethylnitronitrosoguanidine either through direct implantation into the pancreas or infusion into the pancreatic duct. Near-total pancreatectomy was added in all groups except two DMBA implantation groups. Surviving rats were killed at 3, 6, 9, or 12 months, and the pancreata were evaluated histologically. Results. All three carcinogens caused pancreatic inflammation, ductal hyperplasia, atypia, and dysplasia beginning by 3 months and becoming more prominent at later time points. Only DMBA caused frequent invasive pancreatic ductal adenocarcinoma, which was first evident by 6 months. The prevalence of pancreatic cancer among DMBA-treated rats evaluated after 10 months was 39% (19 of 49). The addition of pancreatic resection did not enhance pancreatic cancer development. Conclusions. Of the strategies tested, only direct implantation of DMBA into the rat pancreas frequently produces pancreatic cancer histologically similar to human ductal adenocarcinoma. The development of hyperplastic, atypical, and dysplastic changes preceding and accompanying carcinomas suggests that these lesions are preneoplastic. This model recapitulates the progression from normal to neoplastic epithelium and is likely to be useful for the study of morphologic and molecular mechanisms underlying the early stages of pancreatic carcinogenesis and for the investigation of novel diagnostic and therapeutic techniques. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HEMATOL ONCOL UNIT,BOSTON,MA 02114. NR 42 TC 32 Z9 44 U1 0 U2 2 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 JUL PY 1997 VL 122 IS 1 BP 82 EP 90 DI 10.1016/S0039-6060(97)90268-3 PG 9 WC Surgery SC Surgery GA XK808 UT WOS:A1997XK80800013 PM 9225919 ER PT J AU Frenette, PS Wagner, DD AF Frenette, PS Wagner, DD TI Insights into selectin function from knockout mice SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID LEUKOCYTE ADHESION DEFICIENCY; P-SELECTIN; MONOCLONAL-ANTIBODY; ACTIVATED PLATELETS; IN-VIVO; LIGANDS; NEUTROPHILS; RECRUITMENT; MOLECULE RP Frenette, PS (reprint author), CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02114, USA. RI Frenette, Paul/J-8272-2012 NR 42 TC 84 Z9 85 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 JUL PY 1997 VL 78 IS 1 BP 60 EP 64 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE838 UT WOS:A1997XE83800011 PM 9198128 ER PT J AU Chae, CU Ridker, PM Manson, JE AF Chae, CU Ridker, PM Manson, JE TI Postmenopausal hormone replacement therapy and cardiovascular disease SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID CORONARY HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; ESTROGEN-PROGESTOGEN REPLACEMENT; TISSUE-PLASMINOGEN-ACTIVATOR; SMOOTH-MUSCLE CELLS; CHOLESTEROL-FED RABBITS; VEIN ENDOTHELIAL-CELLS; FACTOR-VII; MYOCARDIAL-INFARCTION; NITRIC-OXIDE C1 BRIGHAM & WOMENS HOSP,DIV PREVENT MED,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL07575] NR 181 TC 60 Z9 63 U1 0 U2 1 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 JUL PY 1997 VL 78 IS 1 BP 770 EP 780 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE838 UT WOS:A1997XE83800137 PM 9198254 ER PT J AU Vamvakas, EC Blajchman, MA AF Vamvakas, EC Blajchman, MA TI A proposal for an individual patient data based meta-analysis of randomized controlled trials of allogeneic transfusion and postoperative bacterial infection SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID PERIOPERATIVE BLOOD-TRANSFUSION; DESIGN AFFECTS OUTCOMES; CLINICAL-TRIALS; AUTOLOGOUS BLOOD; PUBLICATION BIAS; COLORECTAL-CANCER; COST-EFFECTIVENESS; IMMUNE FUNCTION; INDUCED IMMUNOSUPPRESSION; COMPLEMENT ACTIVATION C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON L8S 4L8,CANADA. MCMASTER UNIV,DEPT MED,HAMILTON,ON L8S 4L8,CANADA. RP Vamvakas, EC (reprint author), MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,GRJ 224,BOSTON,MA 02114, USA. NR 119 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 1997 VL 11 IS 3 BP 180 EP 194 DI 10.1053/tmrv.1997.0110180 PG 15 WC Hematology SC Hematology GA XL528 UT WOS:A1997XL52800003 PM 9243771 ER PT J AU Ghossein, RA Juan, RS Scher, HI Seiden, M Zhang, ZF Sun, M Chang, G Berlane, K Krithivas, K Kantoff, PW AF Ghossein, RA Juan, RS Scher, HI Seiden, M Zhang, ZF Sun, M Chang, G Berlane, K Krithivas, K Kantoff, PW TI Prognostic significance of detection of prostate-specific antigen transcripts in the peripheral blood of patients with metastatic androgen-independent prostatic carcinoma SO UROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; CIRCULATING TUMOR-CELLS; INSITU HYBRIDIZATION; CANCER; THERAPY AB Objectives. To evaluate the prognostic significance of reverse transcriptase polymerase chain reaction (RT PCR) detection of prostate-specific antigen (PSA) mRNA in relation to survival in patients with metastatic androgen-independent prostatic carcinoma (AIPC). Methods. Peripheral blood from 122 men (64 from Memorial Sloan-Kettering Cancer Center [MSKCC] and 58 from the Dana Farber Cancer Institute [DFCI]) with metastatic (Stage D2) AIPC was analyzed for PSA mRNA using RT PCR. Forty-one controls without prostatic carcinoma were also evaluated. Results. RT PCR positivity for PSA mRNA was present in 24 of the 64 (38%) patients seen at MSKCC and in 26 of the 58 (45%) patients followed at DFCI. All control individuals were PSA PCR negative. There was a significant correlation between RT PCR positivity and decreased survival in each of the Memorial and Dana Farber populations (P = 0.028 and 0.039, respectively). Serum PSA (at time of blood collection for PCR) was not predictive of survival as a continuous variable in the MSKCC (P = 0.31) and the DFCI (P = 0.09) groups. RT PCR for PSA mRNA was found to be independent from and superior to serum PSA in predicting survival in both the MSKCC and DFCI populations (P = 0.048 and P = 0.027, respectively). Conclusions. The detection of PSA mRNA in the peripheral blood by RT PCR is a predictor of survival in patients with metastatic AIPC, and PCR is superior to a single serum PSA measurement. Further studies are needed to test the value of this factor in comparison to and coupled with other prognostic parameters. (C) 1997, Elsevier Science Inc. All rights reserved. C1 DANA FARBER CANC INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Ghossein, RA (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA 05826] NR 26 TC 54 Z9 54 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 JUL PY 1997 VL 50 IS 1 BP 100 EP 105 DI 10.1016/S0090-4295(97)00127-1 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA XJ076 UT WOS:A1997XJ07600018 PM 9218026 ER PT J AU Meining, A Stolte, M Hatz, R Lehn, N Miehlke, S Morgner, A Bayerdorffer, E AF Meining, A Stolte, M Hatz, R Lehn, N Miehlke, S Morgner, A Bayerdorffer, E TI Differing degree and distribution of gastritis in Helicobacter pylori-associated diseases SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE gastritis; Helicobacter pylori; peptic ulcer; gastric cancer; MALT lymphoma ID LYMPHOID-TISSUE TYPE; GASTRODUODENAL DISEASE; INTESTINAL METAPLASIA; PEPTIC-ULCERATION; DUODENAL-ULCER; INFECTION; CANCER; RECOGNITION; ERADICATION; REGRESSION AB Infection with Helicobacter pylori (H. pylori) causes gastritis, and may be associated with gastric and duodenal ulcers and also with such malignant diseases as MALT lymphoma and gastric carcinoma. In order to determine whether there are differences in the degree and distribution of gastritis, each patient with H. pylori gastritis only (n = 50) was matched for sex and age with four patients, one each with H. pylori-associated duodenal ulcer, gastric ulcer, gastric carcinoma or MALT lymphoma. From each patient, two biopsies were taken from the antrum and two from the corpus for histopathological examination of H. pylori gastritis. The median summed gastritis score decreases in the following order: antrum: gastric ulcer > duodenal ulcer > gastritis alone > carcinoma > MALT lymphoma, and corpus: gastric ulcer > carcinoma > MALT lymphoma > gastritis alone and duodenal ulcer We conclude that the degree and distribution of H. pylori gastritis differs significantly among H. pylori-associated diseases. These differences may explain some of the underlying pathomechanisms associated with H. pylori infection. C1 KLINIKUM BAYREUTH,INST PATHOL,D-95445 BAYREUTH,GERMANY. UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT SURG,D-8000 MUNICH,GERMANY. TECH UNIV MUNICH,KLINIKUM RECHTS ISAR,DEPT MICROBIOL,D-8000 MUNICH,GERMANY. BAYLOR COLL MED,VA MED CTR,HOUSTON,TX 77030. UNIV MAGDEBURG,DEPT GASTROENTEROL HEPATOL & INFECT DIS,D-39106 MAGDEBURG,GERMANY. UNIV MUNICH,KLINIKUM GROSSHADERN,DEPT MED 2,D-8000 MUNICH,GERMANY. NR 30 TC 68 Z9 70 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 JUL PY 1997 VL 431 IS 1 BP 11 EP 15 DI 10.1007/s004280050063 PG 5 WC Pathology SC Pathology GA XL502 UT WOS:A1997XL50200002 PM 9247628 ER PT J AU Sheth, AN Bhide, PG AF Sheth, AN Bhide, PG TI Concurrent cellular output from two proliferative populations in the early embryonic mouse corpus striatum SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ganglionic eminence; neurogenesis; cell cycle; basal ganglia ID CENTRAL-NERVOUS-SYSTEM; CORTICAL NEUROGENESIS; NEURON ORIGIN; EXPRESSION; FOREBRAIN; PATTERNS; BRAIN; CELLS; TIME; TELENCEPHALON AB In mice, the striatal compartment of the forebrain is established by embryonic day 11 (E11, EO = day of conception) when a lateral ganglionic eminence emerges surrounding the lateral and ventral margins of the forebrain ventricles. The inception of the striatal compartment is evidence of altered cell cycle kinetics, especially a rapid production of postmitotic cells, within a discrete portion of the telencephalic neuroepithelium. As a step toward understanding the mechanisms which contribute to the development of a cytokinetically distinct striatal compartment, we characterized the rate and pattern of cellular output in the lateral ganglionic neuroepithelium of mice on Ell. The data show that the striatal compartment is distinguished by concurrent and equivalent levels of cell output from two proliferative populations: a dominant secondary proliferative population and a smaller, pseudostratified ventricular epithelium. In addition, although the ganglionic neuroepithelium is expanding on Ell, 30-35% of the daughter cells produced leave the cell cycle and become postmitotic. These cytogenetic events, occurring in the lateral ganglionic progenitor population, may contribute to the development of a distinct striatal compartment within the telencephalon. (C) 1997 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. OI Bhide, Pradeep/0000-0003-4236-9415 FU NINDS NIH HHS [NS 32657] NR 43 TC 36 Z9 36 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUN 30 PY 1997 VL 383 IS 2 BP 220 EP 230 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA XC614 UT WOS:A1997XC61400008 PM 9182850 ER PT J AU Bardin, T Schumacher, HR AF Bardin, T Schumacher, HR TI Special issue - Proceedings of the Symposium Bone Disease for the Rheumatologist: Osteoporosis, New Management Strategies, and Beyond - Held in Philadelphia on September 19-21, 1996 - Under the Aegis of the Societe Francaise de Rhumatologie, the American College of Rheumatology and the French Institute of the University of Pennsylvania - Foreword SO REVUE DU RHUMATISME LA English DT Editorial Material C1 UNIV PENN,VET AFFAIRS MED CTR,SCH MED,ARTHRIT IMMUNOL CTR,PHILADELPHIA,PA 19104. RP Bardin, T (reprint author), UNIV PARIS 07,HOP LARIBOISIERE,RHUMATOL CLIN,CTR VIGGO PETERSEN,PARIS,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 1169-8446 J9 REV RHUM JI Rev. Rhum. PD JUN 30 PY 1997 VL 64 IS 6 SU S BP S1 EP S1 PG 1 WC Rheumatology SC Rheumatology GA XP527 UT WOS:A1997XP52700001 ER PT J AU Simon, LS Goodman, T AF Simon, LS Goodman, T TI Normal bone, osteoporosis and the rheumatologist SO REVUE DU RHUMATISME LA English DT Article; Proceedings Paper CT Symposium on Bone Disease for the Rheumatologist - Osteoporosis, New Management Strategies, and Beyond CY SEP 19-21, 1996 CL PHILADELPHIA, PA SP Soc Francaise Rhumatol, Amer Coll Rheumatol, Univ Penn, French Inst DE osteoporosis; bone remodeling; bone densitometry ID DUAL-PHOTON-ABSORPTIOMETRY; POSTMENOPAUSAL WOMEN; CALCIUM SUPPLEMENTATION; PERIMENOPAUSAL WOMEN; ESTROGEN DEFICIENCY; CONTROLLED TRIAL; ELDERLY WOMEN; DRUG-THERAPY; HIP FRACTURE; RISK-FACTORS C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,MED SERV,ARTHRIT UNIT,BOSTON,MA 02114. NR 65 TC 0 Z9 0 U1 0 U2 0 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 1169-8446 J9 REV RHUM JI Rev. Rhum. PD JUN 30 PY 1997 VL 64 IS 6 SU S BP S3 EP S9 PG 7 WC Rheumatology SC Rheumatology GA XP527 UT WOS:A1997XP52700002 PM 9273930 ER PT J AU Jacoby, RF Schlack, S Sekhon, G Laxova, R AF Jacoby, RF Schlack, S Sekhon, G Laxova, R TI Del(10)(q22.3q24.1) associated with juvenile polyposis SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE juvenile polyps; familial cancer; gastrointestinal neoplasms; juvenile polyposis; chromosome abnormality; del(10)(q22.3q24.1) ID INTERSTITIAL DELETION; LONG ARM; CHROMOSOME-10; PATHOGENESIS; CARCINOMA; CANCER; COLI AB Juvenile polyps are the most frequent gastrointestinal polyps with a malignant potential for which the genetic basis is unknown, Juvenile polyps, with a normal epithelium but hypertrophic lamina propria, are histologically quite distinct from adenomatous polyps which have dysplastic changes in epithelial nuclei. Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis, We provide the first report indicating that a tumor suppressor gene associated with juvenile polyposis may be located at 10q22.3q24.1, Cytogenetic studies of a patient with juvenile polyposis and multiple congenital abnormalities of the head, extremities, and abdomen revealed a de novo interstitial deletion of Chr 10 as the only defect, del(10)(10q22.3q24.1). Am. J. Med. Genet. 70:361-364, 1997. (C) 1997 Wiley-Liss, Inc. C1 UNIV WISCONSIN,DEPT MED,GASTROENTEROL SECT,MADISON,WI. UNIV WISCONSIN,DEPT GENET,MADISON,WI 53706. UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI 53706. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. FU NCI NIH HHS [P30 CA14520, U01 CA59352] NR 29 TC 40 Z9 40 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUN 27 PY 1997 VL 70 IS 4 BP 361 EP 364 DI 10.1002/(SICI)1096-8628(19970627)70:4<361::AID-AJMG6>3.0.CO;2-W PG 4 WC Genetics & Heredity SC Genetics & Heredity GA XC369 UT WOS:A1997XC36900006 PM 9182775 ER PT J AU SawkaVerhelle, D Baron, V Mothe, I Filloux, C White, MF VanObberghen, E AF SawkaVerhelle, D Baron, V Mothe, I Filloux, C White, MF VanObberghen, E TI Tyr(624) and Tyr(628) in insulin receptor substrate-2 mediate its association with the insulin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSINE-DEPENDENT INTERACTION; KINASE DOMAIN AUTOPHOSPHORYLATION; FACTOR-I RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; GROWTH-HORMONE; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC-CELLS; 2-HYBRID SYSTEM; NPEY MOTIF AB In addition to the pleckstrin homology domain and the phosphotyrosine binding domain in insulin receptor substrate (IRS)-1 and IRS-2, a region between amino acids 591 and 786 in IRS-2 (IRS-2-(591-786)) binds to the insulin receptor. Based on peptide competition studies, this region interacts with the phosphorylated regulatory loop of the insulin receptor; we designate this region the kinase regulatory loop binding (KRLB) domain. Two tyrosine residues in the KRLB domain at positions 624 and 628 are crucial for this interaction. Phosphorylation of tyrosine residues in the KRLB domain by the insulin receptor inhibits the binding to the receptor. These results reveal a novel mechanism regulating the interaction of the insulin receptor and IRS-2 that may distinguish the signal of IRS-2 from IRS-1. C1 FAC MED NICE,INSERM,U145,F-06107 NICE 2,FRANCE. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. OI MOTHE-SATNEY, ISABELLE/0000-0002-2693-8385 FU NIDDK NIH HHS [DK 38712, DK 43808] NR 40 TC 44 Z9 45 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 JUN 27 PY 1997 VL 272 IS 26 BP 16414 EP 16420 DI 10.1074/jbc.272.26.16414 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG019 UT WOS:A1997XG01900053 PM 9195949 ER PT J AU Gu, HH Griffin, JD Neel, BG AF Gu, HH Griffin, JD Neel, BG TI Characterization of two SHP-2-associated binding proteins and potential substrates in hematopoietic cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSINE PHOSPHATASE SYP; COLONY-STIMULATING FACTOR; TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; MAP KINASE; PHOSPHORYLATION; INSULIN; SH-PTP2; SHPTP2; IDENTIFICATION AB Multiple studies have demonstrated an important role for the Src homology 2-containing tyrosine phosphatase 2 (SHP-2) in receptor tyrosine kinase-regulated cell proliferation and differentiation. Recent studies have identified potential SHP-2 substrates which mediate these effects. SHP-2 also is implicated in several cytokine receptor signaling pathways and in Bcr-Abl transformation. However, its precise role and targets in normal and abnormal hematopoietic cells remain to be determined. We identified two novel tyrosyl-phosphorylated proteins associated with SHP-2 in hematopoietic cells. The first, a 97-kDa cytosolic protein (p97), associates inducibly with SHP-2 upon cytokine stimulation and constitutively in Bcr-Abl-transformed cells. In contrast, p135, a 135-kDa transmembrane glycoprotein, forms a distinct complex with SHP-2, independent of cytokine stimulation or Bcr-Abl transformation. Far Western analysis reveals that SHP-2, via its Src homology 2 domains, can interact directly with either protein. In vitro dephosphorylation experiments, as well as transient transfection studies using wild type and mutant SHP-2 constructs, suggest that p97 and p135 also are SHP-2 substrates. Our results indicate that SHP-2 forms at least two separate complexes in hematopoietic cells and point to new potential SHP-2 targets. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. RP Gu, HH (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,CANC BIOL PROGRAM,HIM 1043,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [R01 CA 49152, CA 36167]; NIDDK NIH HHS [P01-DK50654] NR 53 TC 66 Z9 66 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 JUN 27 PY 1997 VL 272 IS 26 BP 16421 EP 16430 DI 10.1074/jbc.272.26.16421 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG019 UT WOS:A1997XG01900054 PM 9195950 ER PT J AU Nakagawa, H Inomoto, T Rustgi, AK AF Nakagawa, H Inomoto, T Rustgi, AK TI A CACCC box-like cis-regulatory element of the Epstein-Barr virus ED-LS promoter interacts with a novel transcriptional factor in tissue-specific squamous epithelia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KERATINOCYTE-SPECIFIC TRANSCRIPTION; BETA-GLOBIN PROMOTER; BINDING-PROTEINS; NUCLEAR PROTEINS; TRANSGENIC MICE; GENE-EXPRESSION; SV40 ENHANCER; CELLS; DIFFERENTIATION; DNA AB The Epstein-Barr (EBV) virus induces a lytic state after infecting epithelial cells. Subsequently, there is infection of B lymphocytes with two types of cycles, latent and lytic. Apart from linkage of the EBV latent membrane protein-1 (LMP-1) with benign and malignant conditions of squamous epithelial cells, little is known about other EBV gene products that may be important in these processes as well as cellular transcriptional factors that regulate EBV gene expression in these epithelial cells. The EBV ED-L2 promoter, an early lytic cycle promoter, is located upstream of a transcription start site for a short open reading frame designated BNLF2 and just downstream of the BNLF1 (LMP-1) open reading frame. We have previously used the EBV ED-L2 promoter to target oncogenes in transgenic mice, resulting in tissue-specific expression in the tongue, esophagus, forestomach, and skin, all sharing stratifying squamous epithelia, alternatively called keratinocytes. In the present study, we have functionally dissected the ED-L2 promoter by making deletion constructs fused to the luciferase reporter gene with transient transfections into squamous and nonsquamous epithelial cell lines as well as B lymphocytes. A CACCC box-like cis-regulatory element has been identified that is located between -218 and -187 base pairs of the ED-L2 promoter that confers significant promoter activity only in squamous epithelial cells. This cis-regulatory element is active in a heterologous minimal herpes simplex virus thymidine kinase promoter reporter gene construct when transfected into squamous epithelial cells but not in nonsquamous epithelial cells. DNA gel mobility shift assays have led to the identification of DNA-protein complexes that bind the CACCC box-like element. One of these proteins is a novel transcriptional factor that is uniquely active in stratified squamous epithelial cells, designated as keratinocyte specific factor (KSF). KSF may be related to Sp1 but appears to be distinct from Sp1. In addition, KSF may interact with related or identical cis-regulatory elements found in human papillomavirus-11 E6 and cytokeratin K3 promoters that are active in keratinocytes. In aggregate, KSF may be important in the transcriptional regulation of viral and eukaryotic genes in keratinocytes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HEMATOL ONCOL UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [DK43351, DK40561] NR 40 TC 23 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 JUN 27 PY 1997 VL 272 IS 26 BP 16688 EP 16699 DI 10.1074/jbc.272.26.16688 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG019 UT WOS:A1997XG01900089 PM 9195985 ER PT J AU Moghaddam, A Rosenzweig, M LeeParritz, D Annis, B Johnson, RP Wang, F AF Moghaddam, A Rosenzweig, M LeeParritz, D Annis, B Johnson, RP Wang, F TI An animal model for acute and persistent Epstein-Barr virus infection SO SCIENCE LA English DT Article ID HERPESVIRUS PAPIO; MALIGNANT-LYMPHOMA; REPLICATION; ACTIVATION; EXPRESSION; SEQUENCE; ORIGIN; CELLS; DNA AB Epstein-Barr virus (EBV) is a human lymphocryptovirus that causes infectious mononucleosis, persists asymptomatically for life in nearly all adults, and is associated with the development of B cell lymphomas and nasopharyngeal carcinomas. A highly similar rhesus lymphocryptovirus naturally endemic in rhesus monkeys was used to orally inject naive animals from a pathogen-free colony. This animal model reproduced key aspects of human EBV injection, including oral transmission, atypical lymphocytosis, lymphadenopathy, activation of CD23(+) peripheral blood B cells, sustained serologic responses to lytic and latent EBV antigens, latent infection in the peripheral blood, and virus persistence in oropharyngeal secretions. This system may be useful for studying the pathogenesis, prevention, and treatment of EBV infection and associated oncogenesis. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV IMMUNOL,SOUTHBOROUGH,MA 01172. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV PRIMATE RESOURCES,SOUTHBOROUGH,MA 01172. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,AIDS RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA65319, CA68051]; NCRR NIH HHS [P51RR00168] NR 31 TC 115 Z9 119 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 27 PY 1997 VL 276 IS 5321 BP 2030 EP 2033 DI 10.1126/science.276.5321.2030 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XG748 UT WOS:A1997XG74800061 PM 9197263 ER PT J AU Tearney, GJ Brezinski, ME Bouma, BE Boppart, SA Pitris, C Southern, JF Fujimoto, JG AF Tearney, GJ Brezinski, ME Bouma, BE Boppart, SA Pitris, C Southern, JF Fujimoto, JG TI In vivo endoscopic optical biopsy with optical coherence tomography SO SCIENCE LA English DT Article AB Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as ''optical biopsy,'' was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution. C1 MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,KNIGHT CATHETERIZAT LAB,BOSTON,MA 02114. SINAI SAMARITAN HOSP,DEPT PATHOL,MILWAUKEE,WI 53233. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NEI NIH HHS [NIH-9-RO1-EY11289]; NHLBI NIH HHS [NIH-1-R29-HL55686-01A1] NR 20 TC 875 Z9 893 U1 10 U2 94 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 27 PY 1997 VL 276 IS 5321 BP 2037 EP 2039 DI 10.1126/science.276.5321.2037 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XG748 UT WOS:A1997XG74800063 PM 9197265 ER PT J AU Alexander, SI Younes, SB Zurakowski, D Mirza, NM Dubey, DP Drew, MP Harmon, WE Yunis, EJ AF Alexander, SI Younes, SB Zurakowski, D Mirza, NM Dubey, DP Drew, MP Harmon, WE Yunis, EJ TI Cell-mediated cytotoxicity: A predictor of chronic rejection in pediatric HLA haploidentical renal transplants SO TRANSPLANTATION LA English DT Article ID ALLOGRAFT-REJECTION; RECIPIENTS; IDENTITY AB Background. Recipient antidonor cytotoxic T-cell activity has been associated with graft loss and acute rejection in renal allograft recipients, The role of immunologic mechanisms in the development of chronic graft rejection is controversial, We analyzed all living related renal transplants performed at Children's Hospital (Boston, MA) from 1983 to 1995 to assess whether cell-mediated cytotoxicity, determined in vitro and measured before transplantation, was predictive of chronic rejection. Methods. Eighty-three patients were studied retrospectively. Fifty-seven patients with one haplotype-matched renal transplants from living related donors were studied to determine the association between cell-mediated lympholysis (CML) level, acute rejection, chronic rejection, and graft failure. Acute rejection was defined by the decision to treat. Chronic rejection was defined by histology and/or the absolute serum creatinine value using an increasing serum creatinine level >1.0 mg/dl for children less than 3, a creatinine level > 1.5 mg/dl for children between 3 and 10 years of age, and a creatinine level >2.0 mg/dl for children above 10 years of age. Return to dialysis or retransplantation was considered graft failure. Results. Of the 57 haploidentical patients, there were 33 males and 24 females, The mean age at transplant was 11.1 years (SD=6.7). Twelve patients developed chronic rejection, 24 patients developed acute rejection, and 7 patients had graft failure. Pretransplant cytotoxic T lymphocyte activity was associated with chronic rejection (P=0.001) and graft failure (P=0.013) but only marginally with acute rejection (P=0.058), Controlling for age and sex, Cox's proportional hazards model revealed that CML level was predictive of time to chronic rejection (P<0.01) but not acute rejection (P=0.11). It was estimated that every 1-unit increase in CML level raises the monthly risk of chronic rejection by 7%. Ten children received HLA-identical kidneys from their siblings. There were no episodes of chronic rejection after 5 years. Two patients with high CML levels had episodes of acute rejection; both patients responded to treatment. Conclusion. Our data demonstrate an association between pretransplant cell-mediated cytotoxicity and the occurrence of chronic rejection in living related one-haploidentical renal transplants in pediatric patients. C1 CHILDRENS HOSP,DEPT RES COMP & BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RP Alexander, SI (reprint author), CHILDRENS HOSP,DIV NEPHROL,DEPT MED,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [P01 HL29583] NR 34 TC 5 Z9 5 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 JUN 27 PY 1997 VL 63 IS 12 BP 1756 EP 1761 DI 10.1097/00007890-199706270-00009 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XH444 UT WOS:A1997XH44400009 PM 9210500 ER PT J AU Johnston, LJ Redmond, RW AF Johnston, LJ Redmond, RW TI Triplet state mechanism for diphenylamine photoionization SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID LASER FLASH-PHOTOLYSIS; RADICAL-CATIONS; AQUEOUS-SOLUTION; 2-LASER PHOTOCHEMISTRY; HYDRATED ELECTRON; PULSE EXCITATION; IONIZATION; ACETONITRILE; DEPENDENCE; CHLORPROMAZINE AB The photoionization of diphenylamine has been studied using both one- and two-laser flash photolysis in acetonitrile, alcohols, and aqueous solvent mixtures with the aim of elucidating the role of the triplet in the photoionization process. Excitation of triplet diphenylamine at 532 nm lends to irreversible triplet bleaching in all solvents, although the yields decrease by approximately an order of magnitude in comparing 1:1 aqueous acetonitrile to neat methanol or 2-propanol. Photoionization to yield the diphenylamine radical cation accounts for a substantial fraction of the triplet bleaching in all cases, demonstrating that biphotonic photoionization via an upper triplet is a viable mechanism. Triplet bleaching does not lend to either N-H bond cleavage or reverse intersystem crossing in aqueous acetonitrile. Plots of the radical cation yield as a function of laser power for one-laser (308 nm) excitation of diphenylamine are linear, consistent with monophotonic ionization under these conditions. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP Johnston, LJ (reprint author), NATL RES COUNCIL CANADA,STEACIE INST MOL SCI,100 SUSSEX DR,OTTAWA,ON K1A 0R6,CANADA. NR 41 TC 20 Z9 20 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD JUN 26 PY 1997 VL 101 IS 26 BP 4660 EP 4665 DI 10.1021/jp962712a PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XG935 UT WOS:A1997XG93500002 ER PT J AU Saini, S AF Saini, S TI Imaging of the hepatobiliary tract SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HELICAL SPIRAL CT; HEPATIC METASTASES; SONOGRAPHIC DIAGNOSIS; MALIGNANT-TUMORS; LIVER; GALLBLADDER; DISEASES; EFFICACY C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Saini, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 48 TC 64 Z9 70 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 26 PY 1997 VL 336 IS 26 BP 1889 EP 1894 DI 10.1056/NEJM199706263362607 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XF756 UT WOS:A1997XF75600007 PM 9197218 ER PT J AU Kradin, RL Mark, EJ Shepard, JAO Colvin, RB AF Kradin, RL Mark, EJ Shepard, JAO Colvin, RB TI A 74-year-old man with progressive cough, dyspnea, and pleural thickening - Papillary adenocarcinoma of the lung (asbestos-related), with marked pleural mesothelial hyperplasia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EFFUSION C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Kradin, RL (reprint author), MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02114, USA. NR 25 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 JUN 26 PY 1997 VL 336 IS 26 BP 1895 EP 1903 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XF756 UT WOS:A1997XF75600008 ER PT J AU Nekrasova, ER Berman, DM Rustandi, RR Hamm, HE Gilman, AG Arshavsky, VY AF Nekrasova, ER Berman, DM Rustandi, RR Hamm, HE Gilman, AG Arshavsky, VY TI Activation of transducin guanosine triphosphatase by two proteins of the RGS family SO BIOCHEMISTRY LA English DT Article ID ROD OUTER SEGMENTS; GTPASE ACTIVITY; CGMP PHOSPHODIESTERASE; INHIBITORY SUBUNIT; PURIFICATION; MEMBRANES; BINDING; FLOW AB RGS proteins (regulators of G protein signaling) constitute a newly appreciated group of negative regulators of G protein signaling. Several members of this group stimulate the guanosine triphosphatase (GTPase) activity of various G protein alpha-subunits, including the photoreceptor G protein, transducin. In photoreceptor cells transducin GTPase is known to be substantially accelerated by the coordinated action of the gamma-subunit of its effector enzyme, cGMP phosphodiesterase (PDEgamma), and another yet unidentified membrane-associated protein factor. Here we test the possibility that this factor belongs to the RGS family of GTPase stimulators. We report a detailed kinetic analysis of transducin GTPase activation by two members of the RGS family, RGS4 and G alpha interacting protein (GAIP). RGS4, being at least 5-fold more potent than GAIP, stimulates the rate of transducin GTPase by 2 orders of magnitude. Neither RGS4 nor GAIP requires PDEgamma for activating transducin. Rather, PDEgamma causes a partial reversal of transducin GTPase activation by RGS proteins. The effect of PDEgamma is based on a decreased apparent affinity of RGS for the alpha-subunit of transducin. Our observations indicate that GTPase activity of transducin can be activated by at least two distinct mechanisms, one based on the action of RGS proteins alone and another involving the cooperative action of the effector enzyme and another protein. C1 HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. NORTHWESTERN UNIV,SCH MED,DEPT PHARMACOL & BIOL CHEM,CHICAGO,IL 60611. RI Hamm, Heidi/G-2374-2014 OI Hamm, Heidi/0000-0001-5437-5287 FU NEI NIH HHS [EY 10336]; NIGMS NIH HHS [GM 34497] NR 30 TC 55 Z9 55 U1 1 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 JUN 24 PY 1997 VL 36 IS 25 BP 7638 EP 7643 DI 10.1021/bi970427r PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XG901 UT WOS:A1997XG90100002 PM 9201904 ER PT J AU Wax, MB Saito, I Tenkova, T Krupin, T Becker, B Nelson, N Brown, D Gluck, SL AF Wax, MB Saito, I Tenkova, T Krupin, T Becker, B Nelson, N Brown, D Gluck, SL TI Vacuolar H+-ATPase in ocular ciliary epithelium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MEDULLARY COLLECTING DUCT; INTRACELLULAR PH; PLASMA-MEMBRANE; CELLS; RABBIT; LOCALIZATION; BODY; TRANSPORT; SUBUNIT; BICARBONATE AB The mechanisms controlling the production of aqueous humor and the regulation of intraocular pressure are poorly understood. Here, we provide evidence that a vacuolar H+-ATPase (V-ATPase) in the ocular ciliary epithelium is a key component of this process. In intracellular pH (pH(i)) measurements of isolated ciliary epithelium performed with 2',7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF), the selective V-ATPase inhibitor bafilomycin A(1) slowed the recovery of pH(i) in response to acute intracellular acidification, demonstrating the presence of V-ATPase preparations examined under voltage-clamped conditions, bafilomycin A(1) produced a concentration-dependent decrease in short-circuit current, and topical application of bafilomycin A(1) reduced intraocular pressure in rabbits, indicating an essential role of the V-ATPase in ciliary epithelial ion transport. Immunocytochemistry utilizing antibodies specific for the B1 isoform of the V-ATPase 56-kDa subunit revealed localization of V-ATPase in both the plasma membrane and cytoplasm of the native ciliary epithelium in both rabbit and rat eye. The regional and subcellular distribution of V-ATPase in specific regions of the ciliary process was altered profoundly by isoproterenol and phorbol esters, suggesting that change in the intracellular distribution of the enzyme is a mechanism by which drugs, hormones, and neurotransmitters modify aqueous humor production. C1 WASHINGTON UNIV,SCH MED,DEPT MED,DIV RENAL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110. NORTHWESTERN UNIV,SCH MED,DEPT OPHTHALMOL,CHICAGO,IL 60611. TEL AVIV UNIV,DEPT BIOCHEM,IL-69978 TEL AVIV,ISRAEL. MASSACHUSETTS GEN HOSP,RENAL UNIT,CHARLESTOWN,MA 02129. RP Wax, MB (reprint author), WASHINGTON UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,660 S EUCLID AVE,BOX 8096,ST LOUIS,MO 63110, USA. NR 41 TC 40 Z9 42 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 JUN 24 PY 1997 VL 94 IS 13 BP 6752 EP 6757 DI 10.1073/pnas.94.13.6752 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400031 PM 9192637 ER PT J AU McDevitt, MA Shivdasani, RA Fujiwara, Y Yang, HD Orkin, SH AF McDevitt, MA Shivdasani, RA Fujiwara, Y Yang, HD Orkin, SH TI A ''knockdown'' mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homologous recombination; hematopoiesis; gene dosage; Cre recombinase ID EMBRYONIC STEM-CELLS; DNA-BINDING FACTOR; BETA-GLOBIN LOCUS; MAMMALIAN-CELLS; FINGER PROTEIN; ZINC-FINGER; DIFFERENTIATION; PROMOTER; EXPRESSION; DELETION AB The hematopoietic-restricted transcription factor GATA-1 is required for both mammalian erythroid cell and megakaryocyte differentiation. To define the mechanisms governing its transcriptional regulation, we replaced upstream sequences including a DNase I hypersensitive (HS) region with a neomycin-resistance cassette by homologous recombination in mouse embryonic stem cells and generated mice either harboring this mutation (neo Delta HS) or lacking the selection cassette (Delta neo Delta HS). Studies of the consequences of these targeted mutations provide novel insights into GATA-1 function in erythroid cells, First, the neo Delta HS mutation leads to a marked impairment in the rate or efficiency of erythroid cell maturation due to a modest (4- to 5-fold) decrease in GATA-1 expression. Hence, erythroid differentiation is dose-dependent with respect to GATA-1, Second, since expression of GATA-1 from the Delta neo Delta HS allele in erythroid cells is largely restored, transcription interference imposed by the introduced cassette must account for the ''knockdown'' effect of the mutation, Finally, despite the potency of the upstream sequences in conferring high-level, developmentally appropriate expression of transgenes in mice, other cis-regulatory elements within the GATA-I compensate for its absence in erythroid cells, Our work illustrates the usefulness of targeted mutations to create knockdown mutations that may uncover important quantitative contributions of gene function not revealed by conventional knockouts. C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 32 TC 164 Z9 165 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 JUN 24 PY 1997 VL 94 IS 13 BP 6781 EP 6785 DI 10.1073/pnas.94.13.6781 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400036 PM 9192642 ER PT J AU Mizuta, R LaSalle, JM Cheng, HL Shinohara, A Ogawa, H Copeland, N Jenkins, NA Lalande, M Alt, FW AF Mizuta, R LaSalle, JM Cheng, HL Shinohara, A Ogawa, H Copeland, N Jenkins, NA Lalande, M Alt, FW TI RAB22 and RAB163/mouse BRCA2: Proteins that specifically interact with the RAD51 protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECA; RECOMBINATION; LOCALIZATION; CHROMOSOMES; CLONING; REPAIR; CANCER; MOUSE; GENES AB The human RAD51 protein is a homologue of the bacteria RecA and yeast RAD51 proteins that are involved in homologous recombination and DNA repair, RAD51 interacts with proteins involved in recombination and also with tumor suppressor proteins p53 and breast cancer susceptibility gene 1 (BRCA1), We have used the yeast two-hybrid system to clone murine cDNA sequences that encode two RAD51-associated molecules, RAB22 and RAB163. RAB163 encodes the C-terminal portion of mouse BRCA2, the homologue of the second breast cancer susceptibility gene protein in humans, demonstrating an in vitro association between RAD51 and BRCA2, RAB22 is a novel gene product that also interacts with RAD51 bl vitro, To detect RAD51 interactions in vivo, we developed a transient nuclear focus assay that was used to demonstrate a complete colocalization of RAB22 with RAD51 in large nuclear foci. C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. OSAKA UNIV,FAC SCI,DEPT BIOL,TOYONAKA,OSAKA 560,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,NIH,FREDERICK,MD 21702. RI LaSalle, Janine/A-4643-2008 OI LaSalle, Janine/0000-0002-3480-2031 FU NCI NIH HHS [CA42335]; NIAID NIH HHS [AI315714] NR 35 TC 191 Z9 197 U1 2 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 JUN 24 PY 1997 VL 94 IS 13 BP 6927 EP 6932 DI 10.1073/pnas.94.13.6927 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400062 PM 9192668 ER PT J AU Kharbanda, S Pandey, P Schofield, L Israels, S Roncinske, R Yoshida, K Bharti, A Yuan, ZM Saxena, S Weichselbaum, R Nalin, C Kufe, D AF Kharbanda, S Pandey, P Schofield, L Israels, S Roncinske, R Yoshida, K Bharti, A Yuan, ZM Saxena, S Weichselbaum, R Nalin, C Kufe, D TI Bole for Bcl-x(L) as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; CELL-DEATH; IONIZING-RADIATION; BCL-X; PROTEIN; IDENTIFICATION; THYMOCYTES; ACTIVATION; PREVENTION; CLEAVAGE AB Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts, Here we show that cells that overpress the Bcl-2-related protein Bcl-x(L) fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress, Coimmunoprecipitation studies demonstrate that Bcl-x(L) associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-x(L) and not to the proapoptotic Bcl-x(s) protein, The results also demonstrate that Bcl-x(s) blocks binding of cytochrome C to Bcl-x(L). Our findings support a role for Bcl-x(L) in protecting cells from apoptosis by inhibiting the availability of cytochrome C in the cytosol. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. NOVARTIS PHARMACEUT CORP,PRECLIN RES,ONCOL RES PROGRAM,E HANOVER,NJ 07936. UNIV MANITOBA,MANITOBA INST CELL BIOL,WINNIPEG,MB R3E 0V9,CANADA. FU NCI NIH HHS [CA55241, CA66996, P01 CA066996] NR 31 TC 326 Z9 337 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 JUN 24 PY 1997 VL 94 IS 13 BP 6939 EP 6942 DI 10.1073/pnas.94.13.6939 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400064 PM 9192670 ER PT J AU Tsiokas, L Kim, E Arnould, T Sukhatme, VP Walz, G AF Tsiokas, L Kim, E Arnould, T Sukhatme, VP Walz, G TI Homo- and heterodimeric interactions between the gene products of PKD1 and PKD2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE polycystic kidney disease; yeast two-hybrid system; protein-protein interactions ID POLYCYSTIC KIDNEY-DISEASE; T-CELL; TRANSGENIC MICE; 2ND GENE; PROTEIN; EXPRESSION; ACTIVATION; LOCALIZATION; CHANNELS; DOMAINS AB PKD1 and PKD2 are two recently identified genes that are responsible for the vast majority of autosomal polycystic kidney disease, a common inherited disease that causes progressive renal failure, PKD1 encodes polycystin, a large glycoprotein that contains several extracellular motifs indicative of a role in cell-cell or cell-matrix interactions, and the PKD2 encodes a protein with homology to a voltage-activated calcium channel and to PKD1, It is currently unknown how mutations of either protein functionally cause autosomal polycystic kidney disease. We show that PKD1 and PKD2 interact through their C-terminal cytoplasmic tails. This interaction resulted in an up-regulation of PKD1 but not PKD2, Furthermore, the cytoplasmic tail of PKD2 but not PKD1 formed homodimers through a coiled-coil domain distinct from the region required for interaction with PKD1, These interactions suggest that PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis and that PKD1 may require the presence of PKD2 for stable expression. C1 HARVARD UNIV,BETH ISRAEL DEACONESS MED CTR,SCH MED,DEPT MED,RENAL DIV,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL & DEV NEUROSCI,BOSTON,MA 02114. FU NIDDK NIH HHS [R01-DK-51060]; NIMH NIH HHS [MH-01147] NR 34 TC 350 Z9 356 U1 1 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 JUN 24 PY 1997 VL 94 IS 13 BP 6965 EP 6970 DI 10.1073/pnas.94.13.6965 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XH034 UT WOS:A1997XH03400069 PM 9192675 ER PT J AU Salvatore, M Morzunov, S Schwemmle, M Lipkin, WI Bunney, WE Cotman, CW Even, C Hatalski, CG Potkin, SG Portlance, ML Nichol, ST Tourtelloutte, WW Riederer, P terMeulen, V AF Salvatore, M Morzunov, S Schwemmle, M Lipkin, WI Bunney, WE Cotman, CW Even, C Hatalski, CG Potkin, SG Portlance, ML Nichol, ST Tourtelloutte, WW Riederer, P terMeulen, V TI Borna disease virus in brains of North American and European people with schizophrenia and bipolar disorder SO LANCET LA English DT Article C1 UNIV CALIF IRVINE,DEPT ANAT & NEUROBIOL,IRVINE,CA 92697. UNIV CALIF IRVINE,DEPT MICROBIOL & MOL GENET,IRVINE,CA 92697. UNIV CALIF IRVINE,DEPT PSYCHIAT & HUMAN BEHAV,IRVINE,CA 92697. CTR DIS CONTROL & PREVENT,SPECIAL PATHOGENS BRANCH,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA. W LOS ANGELES VET AFFAIRS MED CTR,NATL NEUROL RES SPECIMEN BANK,LOS ANGELES,CA 90073. UNIV NEVADA,RENO,NV 89557. UNIV WURZBURG,DEPT PSYCHIAT,D-8700 WURZBURG,GERMANY. UNIV WURZBURG,INST VIROL & IMMUNBIOL,D-8700 WURZBURG,GERMANY. RP Salvatore, M (reprint author), UNIV CALIF IRVINE,DEPT NEUROL,IRVINE,CA 92697, USA. RI Potkin, Steven/A-2021-2013; salvatore, mirella/K-6691-2016 OI salvatore, mirella/0000-0002-8296-0376 NR 5 TC 78 Z9 86 U1 1 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 21 PY 1997 VL 349 IS 9068 BP 1813 EP 1814 DI 10.1016/S0140-6736(05)61693-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XF735 UT WOS:A1997XF73500017 PM 9269221 ER PT J AU Manie, SN Astier, A Haghayeghi, N Canty, T Druker, BJ Hirai, H Freedman, AS AF Manie, SN Astier, A Haghayeghi, N Canty, T Druker, BJ Hirai, H Freedman, AS TI Regulation of integrin-mediated p130(Cas) tyrosine phosphorylation in human B cells - A role for p59(Fyn) and SHP2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; IN-VIVO; CRK; PP125(FAK); SRC; IDENTIFICATION; ACTIVATION; PROTEINS; BINDING; VLA-4 AB Engagement of beta 1 integrins in terminally differentiated human B cell lines, such as ARH-77, leads to prominent tyrosine phosphorylation of the p130 Crk-associated substrate (Cas), Cas regulates the assembly of several SH2 and SH3 domain-containing proteins into signaling complexes, which are potentially involved in the propagation of downstream signals. Ne demonstrate here that immunoprecipitated Cas from beta 1 integrin-stimulated ARH-77 cells was associated sith tyrosine kinase and phosphatase activities and that integrin ligation led to the recruitment of at least p59(Fyn) tyrosine kinase and SHP2 tyrosine phosphatase in Cas immune complexes, Cotransfection studies in COS-7 cells further indicated that Fyn/Cas physical interaction and Fyn-mediated Cas phosphorylation required amino acids 638-889 in the C-terminal region of Gas. This sequence contains both c-Src SH2 and SNS domain-binding motifs. In vitro binding studies using glutathione S-transferase fusion proteins derived from the SK2 or SH3 domains of Fyn suggested that both Fyn domains can participate in Fyn/Cas interaction. These data implicate Fyn and SHP2 as potential modulators of Cas signaling complexes in B cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. UNIV TOKYO,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 FU NCI NIH HHS [CA55207, CA66996] NR 52 TC 35 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 JUN 20 PY 1997 VL 272 IS 25 BP 15636 EP 15641 DI 10.1074/jbc.272.25.15636 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF329 UT WOS:A1997XF32900012 PM 9188452 ER PT J AU Chang, HW Aoki, M Fruman, D Auger, KR Bellacosa, A Tsichlis, PN Cantley, LC Roberts, TM Vogt, PK AF Chang, HW Aoki, M Fruman, D Auger, KR Bellacosa, A Tsichlis, PN Cantley, LC Roberts, TM Vogt, PK TI Transformation of chicken cells by the gene encoding the catalytic subunit of PI 3-kinase SO SCIENCE LA English DT Article ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; NERVE GROWTH-FACTOR; PROTEIN-KINASE; PHOSPHOINOSITIDE 3-KINASE; AVIAN-SARCOMA; ACTIVATION; ONCOGENE; VIRUS; PROTOONCOGENE; ASSOCIATION AB The avian sarcoma virus 16 (ASV 16) is a retrovirus that induces hemangiosarcomas in chickens. Analysis of the ASV 16 genome revealed that it encodes an oncogene that is derived from the cellular gene for the catalytic subunit of phosphoinositide 3-kinase(PI 3-kinase). The gene is referred to as v-p3k, and like its cellular counterpart c-p3k, it is a potent transforming gene in cultured chicken embryo fibroblasts (CEFs). The products of the viral and cellular p3k genes have PI 3-kinase activity. CEFs transformed with either gene showed elevated levels of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate and activation of Akt kinase. C1 Scripps Res Inst, DEPT MOL & EXPT MED, LA JOLLA, CA 92037 USA. BETH ISRAEL DEACONESS MED CTR, DIV SIGNAL TRANSDUCT, BOSTON, MA 02215 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. FOX CHASE CANC CTR, PHILADELPHIA, PA 19111 USA. RI Cantley, Lewis/D-1800-2014; Aoki, Masahiro/A-5149-2016 OI Cantley, Lewis/0000-0002-1298-7653; FU NCI NIH HHS [CA 42564]; NIGMS NIH HHS [GM 41890, R01 GM041890] NR 36 TC 354 Z9 358 U1 1 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 JUN 20 PY 1997 VL 276 IS 5320 BP 1848 EP 1850 DI 10.1126/science.276.5320.1848 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XF103 UT WOS:A1997XF10300045 PM 9188528 ER PT J AU Rettig, MB Ma, HJ Vescio, RA Pold, M Schiller, G Belson, D Savage, A Nishikubo, C Wu, C Fraser, J Said, JW Berenson, JR AF Rettig, MB Ma, HJ Vescio, RA Pold, M Schiller, G Belson, D Savage, A Nishikubo, C Wu, C Fraser, J Said, JW Berenson, JR TI Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients SO SCIENCE LA English DT Article ID MONOCLONAL GAMMOPATHY; DNA-SEQUENCES; UNDETERMINED SIGNIFICANCE; INTERLEUKIN-6; CYTOKINES; RECEPTOR AB Kaposi's sarcoma-associated herpesvirus (KSHV) was found in the bone marrow dendritic cells of multiple myeloma patients but not in malignant plasma cells or bone marrow dendritic cells from normal individuals or patients with other malignancies. In addition the virus was detected in the bone marrow dendritic cells from two out of eight patients with monoclonal gammopathy of undetermined significance (MGUS), a precursor to myeloma. Viral interleukin-6, the human homolog of which is a growth factor for myeloma, was found to be transcribed in the myeloma bone marrow dendritic cells. KSHV may be required for transformation from MGUS to myeloma and perpetuate the growth of malignant plasma cells. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV HEMATOL & ONCOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90095. RP Rettig, MB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV HEMATOL ONCOL,11301 WILSHIRE BLVD,111-H,LOS ANGELES,CA 90073, USA. RI Fraser, John/I-7309-2013 NR 40 TC 396 Z9 409 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 20 PY 1997 VL 276 IS 5320 BP 1851 EP 1854 DI 10.1126/science.276.5320.1851 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XF103 UT WOS:A1997XF10300046 PM 9188529 ER PT J AU Lill, NL Grossman, SR Ginsberg, D DeCaprio, J Livingston, DM AF Lill, NL Grossman, SR Ginsberg, D DeCaprio, J Livingston, DM TI Binding and modulation of p53 by p300/CBP coactivators SO NATURE LA English DT Article ID CELL-CYCLE; RETINOBLASTOMA PROTEIN; E1A PROTEINS; GENE; SUPPRESSION; INDUCTION; COMPLEXES; REVEALS; GROWTH; FORMS AB The adenovirus E1A and SV40 large-T-antigen oncoproteins bind to members of the p300/CBP transcriptional coactivator family. Binding of p300/CBP is implicated in the transforming mechanisms of EIA and T-antigen oncoproteins. A common region of the T antigen is critical for binding both p300/CBP and the tumour suppressor p53 (ref. 1), suggesting a link between the functions of p53 and p300. Here we report that p300/CBP binds to p53 in the absence of viral oncoproteins, and that p300 and p53 colocalize within the nucleus and coexist in a stable DNA-binding complex. Consistent with its ability to bind to p300, E1A disrupted functions mediated by p53. It reduced p53-mediated activation of the p21 and bax promoters, and suppressed p53-induced cell-cycle arrest and apoptosis. We conclude that members of the p300/CBP family are transcriptional adaptors for p53, modulating its checkpoint function in the G1 phase of the cell cycle and its induction of apoptosis. Disruption of p300/p53-dependent growth control may be part of the mechanism by which E1A induces cell transformation. These results help to explain how p53 mediates growth and checkpoint control, and how members of the p300/CBP family affect progression from G1 to the S phase of the cell cycle. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 30 TC 551 Z9 555 U1 0 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 19 PY 1997 VL 387 IS 6635 BP 823 EP 827 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XF144 UT WOS:A1997XF14400055 PM 9194565 ER PT J AU Schwartz, MW Seeley, RJ AF Schwartz, MW Seeley, RJ TI Neuroendocrine responses to starvation and weight loss SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CORTICOTROPIN-RELEASING FACTOR; LUTEINIZING-HORMONE SECRETION; NEUROPEPTIDE GENE-EXPRESSION; CENTRAL-NERVOUS-SYSTEM; BODY-WEIGHT; PARAVENTRICULAR NUCLEUS; OBESE GENE; FOOD-DEPRIVATION; ENERGY-BALANCE; MESSENGER-RNA C1 UNIV WASHINGTON, HARBORVIEW MED CTR, DEPT MED, SEATTLE, WA 98104 USA. UNIV WASHINGTON, HARBORVIEW MED CTR, DEPT PSYCHOL, SEATTLE, WA 98104 USA. RP Schwartz, MW (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST, 1660 S COLUMBIAN WAY, SEATTLE, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-12829]; NINDS NIH HHS [NS32273] NR 88 TC 207 Z9 211 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 19 PY 1997 VL 336 IS 25 BP 1802 EP 1811 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA XE485 UT WOS:A1997XE48500007 PM 9187072 ER PT J AU Edelson, MI Scherer, SW Tsui, LC Welch, WR Bell, DA Berkowitz, RS Mok, SC AF Edelson, MI Scherer, SW Tsui, LC Welch, WR Bell, DA Berkowitz, RS Mok, SC TI Identification of a 1300 kilobase deletion unit on chromosome 7q31.3 in invasive epithelial ovarian carcinomas SO ONCOGENE LA English DT Article DE ovary; cancer; borderline; LOH; chromosome 7 ID TUMOR-SUPPRESSOR GENE; FREQUENT LOSS; HUMAN BORDERLINE; SQUAMOUS-CELL; ALLELIC LOSS; CANCER; HETEROZYGOSITY; HUMAN-CHROMOSOME-7; MALIGNANCIES; ALLELOTYPE AB We have used polymerase chain reaction (PCR) amplification of tandem repeats to study the pattern of allelic loss on chromosome 7q31 in invasive epithelial ovarian carcinomas and borderline ovarian tumors. Using 13 primer sets spanning loci from 7q31 to 7q32, 16 borderline and 54 invasive ovarian tumor tissue, together with their corresponding normal tissue, were analysed. Invasive epithelial ovarian tumors demonstrated loss of heterozygosity (LOH) at one or more loci on 7q in 32 of 54 cases (59%). The invasive epithelial ovarian tumors demonstrated the highest percentage of LOH at the loci D7S643 (20 of 40 informative cases, 50%) and GATA44F09 (18 of 42 informative cases, 43%). In contrary, only one borderline ovarian tumor showed LOH at one locus (GATA44F09, one of 14 informative cases, 7%). Our results display a sharp contrast in the pattern of LOH between invasive and borderline ovarian tumors suggesting that allelic loss at chromosome 7q31.3 may be involved in the development and progression of invasive epithelial ovarian tumors but not borderline ovarian tumors. Further analysis of the deletion map for the invasive epithelial ovarian tumors showed two regions Likely to harbor ovarian tumor suppressor genes including a novel 1300 kilobase common loss region flanked by GATA44F09 and D7S643. C1 BRIGHAM & WOMENS HOSP,LAB GYNECOL ONCOL,DIV GYNECOL ONCOL,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. RI Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Scherer, Stephen /0000-0002-8326-1999 FU NCI NIH HHS [R01CA63381, R01CA69291, R01CA69453] NR 37 TC 42 Z9 43 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 19 PY 1997 VL 14 IS 24 BP 2979 EP 2984 DI 10.1038/sj.onc.1201271 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XF555 UT WOS:A1997XF55500012 PM 9205105 ER PT J AU Goldstein, B Hammond, M AF Goldstein, B Hammond, M TI Physical medicine and rehabilitation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 UNIV WASHINGTON,SEATTLE,WA 98195. RP Goldstein, B (reprint author), VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98195, USA. NR 15 TC 4 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 18 PY 1997 VL 277 IS 23 BP 1891 EP 1892 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XD544 UT WOS:A1997XD54400039 PM 9185820 ER PT J AU Hasson, T Gillespie, PG Garcia, JA MacDonald, RB Zhao, YD Yee, AG Mooseker, MS Corey, DP AF Hasson, T Gillespie, PG Garcia, JA MacDonald, RB Zhao, YD Yee, AG Mooseker, MS Corey, DP TI Unconventional myosins in inner-ear sensory epithelia SO JOURNAL OF CELL BIOLOGY LA English DT Article ID COCHLEAR HAIR-CELLS; BULLFROGS INTERNAL EAR; ACTIN-FILAMENTS; IMMUNOCYTOCHEMICAL LOCALIZATION; MECHANOELECTRICAL TRANSDUCTION; CUTICULAR PLATE; CHICK COCHLEA; GENE ENCODES; GUINEA-PIG; STEREOCILIA AB To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes. Of the four isozymes, each from a different class, three are expressed in the hair cells of amphibia and mammals. In stereocilia, constructed of cross-linked F-actin filaments, myosin-I beta is found mostly near stereociliary tips, myosin-VI is largely absent, and myosin-VIIa colocalizes with crosslinks that connect adjacent stereocilia. In the cuticular plate, a meshwork of actin filaments, myosin-I beta is excluded, myosin-VI is concentrated, and modest amounts of myosin-VIIa are present. These three myosin isozymes are excluded from other actin-rich domains, including the circumferential actin belt and the cortical actin network. A member of a fourth class, myosin-V, is not expressed in hair cells but is present at high levels in afferent nerve cells that innervate hair cells. Substantial amounts of myosins-I beta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt. Our localization results suggest specific functions for three hair-cell myosin isozymes. As suggested previously, myosin-IP probably plays a role in adaptation; concentration of myosin-VI in cuticular plates and association with stereociliary rootlets suggest that this isozyme participates in rigidly anchoring stereocilia; and finally, colocalization with cross-links between adjacent stereocilia indicates that myosin-VIIa is required for the structural integrity of hair bundles. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. YALE UNIV,DEPT PATHOL,DEPT CELL BIOL,DEPT BIOL,NEW HAVEN,CT 06520. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,DEPT PHYSIOL,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM SPEECH & HEARING,JOINT PROGRAM HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,CAMBRIDGE,MA 02139. HOWARD HUGHES MED INST,COCONUT GROVE,FL. OI Corey, David/0000-0003-4497-6016; Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIDCD NIH HHS [R01 DC002281, DC 02368, R01 DC000304, R01 DC002368]; NIDDK NIH HHS [DK 25387, DK 38979, R01 DK025387, R37 DK025387, R56 DK025387] NR 87 TC 366 Z9 380 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 16 PY 1997 VL 137 IS 6 BP 1287 EP 1307 DI 10.1083/jcb.137.6.1287 PG 21 WC Cell Biology SC Cell Biology GA XF795 UT WOS:A1997XF79500008 PM 9182663 ER PT J AU Pilcher, BK Dumin, JA Sudbeck, BD Krane, SM Welgus, HG Parks, WC AF Pilcher, BK Dumin, JA Sudbeck, BD Krane, SM Welgus, HG Parks, WC TI The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTERSTITIAL COLLAGENASE; INTEGRIN EXPRESSION; ADHESION; GENE; METALLOPROTEINASES; REEPITHELIALIZATION; LOCALIZATION; EPIDERMIS; RECEPTORS; INDUCTION AB We have shown in a variety of human wounds that collagenase-1 (MMP-1), a matrix metalloproteinase that cleaves fibrillar type I collagen, is invariably expressed by basal keratinocytes migrating across the dermal matrix. Furthermore, we have demonstrated that MMP-1 expression is induced in primary keratinocytes by contact with native type I collagen and not by basement membrane proteins or by other components of the dermal or provisional (wound) matrix. Based on these observations, we hypothesized that the catalytic activity of MMP-1 is necessary for keratinocyte migration on type I collagen. To test this idea, we assessed keratinocyte motility on type I collagen using colony dispersion and colloidal gold migration assays. In both assays, primary human keratinocytes migrated efficiently on collagen. The specificity of MMP-1 in promoting cell movement was demonstrated in four distinct experiments. One, keratinocyte migration was completely blocked by peptide hydroxymates, which are potent inhibitors of the catalytic activity of MMPs. Two, HaCaTs, a line of human keratinocytes that do not express MMP-1 in response to collagen, did not migrate on a type I collagen matrix but moved efficiently on denatured type I collagen (gelatin). EGF, which induces MMP-1 production by HaCaT cells, resulted in the ability of these cells to migrate across a type I collagen matrix. Three, keratinocytes did not migrate on mutant type I collagen lacking the collagenase cleavage site, even though this substrate induced MMP-1 expression. Four, cell migration on collagen was completely blocked by recombinant tissue inhibitor of metalloproteinase-1 (TIMP-1) and by affinity-purified anti-MMP-1 antiserum. In addition, the collagen-mediated induction of collagenase-1 and migration of primary keratinocytes on collagen was blocked by antibodies against the alpha 2 integrin subunit but not by antibodies against the alpha 1 or alpha 3 subunits. We propose that interaction of the alpha 2 beta 1 integrin with dermal collagen mediates induction of collagenase-1 in keratinocytes at the onset of healing and that the activity of collagenase-1 is needed to initiate cell movement. Furthermore, we propose that cleavage of dermal collagen provides keratinocytes with a mechanism to maintain their directionality during reepithelialization. C1 WASHINGTON UNIV,SCH MED,DEPT MED DERMATOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PHYSIOL & CELL BIOL,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 43 TC 400 Z9 408 U1 2 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 16 PY 1997 VL 137 IS 6 BP 1445 EP 1457 DI 10.1083/jcb.137.6.1445 PG 13 WC Cell Biology SC Cell Biology GA XF795 UT WOS:A1997XF79500019 PM 9182674 ER PT J AU Hughes, MD Johnson, VA Hirsch, MS Bremer, JW Elbeik, T Erice, A Kuritzkes, DR Scott, WA Spector, SA Basgoz, N Fischl, MA DAquila, RT AF Hughes, MD Johnson, VA Hirsch, MS Bremer, JW Elbeik, T Erice, A Kuritzkes, DR Scott, WA Spector, SA Basgoz, N Fischl, MA DAquila, RT TI Monitoring plasma HIV-1 RNA levels in addition to CD4(+) lymphocyte count improves assessment of antiretroviral therapeutic response SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; TYPE-1 RNA; INFECTION; ASSAY; AIDS; QUANTIFICATION; QUANTITATION; PROGRESSION; PCR AB Background: CD4(+) lymphocyte counts and plasma HIV-1 RNA levels predict progression of HIV-related disease, but the relative importance of these and other virological factors in defining response to antiretroviral therapy is not yet clear. Objective: To determine the short-term variability of plasma HIV-1 RNA level during stable therapy; the relative importance of pretreatment values and early changes in CD4(+) count, HIV-1 RNA levels, and infectious HIV-1 titers in mononuclear cells of peripheral blood and pretreatment syncytium-inducing phenotype of an HIV-1 isolate for prediction of disease progression and decline in CD4(+) counts during therapy. Design: Data were collected prospectively in a randomized, clinical trial comparing two combination regimens (ACTG [AIDS Clinical Trials Group] Protocol 241) and pooled across treatments. Setting: 8 AIDS Clinical Trials Units. Patients: 198 adults with HIV-1 infection and no more than 350 CD4(+) lymphocytes/mm(3) who had received at least 6 months of nucleoside therapy. Interventions: All patients received zidovudine and didanosine; 100 received nevirapine and 98 received placebo. Measurements: CD4(+) lymphocyte counts, plasma HIV-1 RNA levels, and infectious HIV-1 titers in cells were measured before and 8 and 48 weeks after study treatment. Assay for the syncytium-inducing viral phenotype was done at baseline. Progression was defined as occurrence of opportunistic infection, malignancy, or death during the 48 weeks after treatment began. Results: The difference between two measurements of HIV-1 RNA levels at baseline was within +/-0.39 log(10) copies/mL (2.5-fold) for 90% of 167 patients receiving stable therapy. In a multivariate model, risk for disease progression was reduced by 56% (95% CI, 8% to 79% [P = 0.028]) for every 10-fold lower HIV-1 RNA level at baseline, by 52% (CI, 6% increase to 79% reduction [P = 0.071]) for every 10-fold reduction in HIV-1 RNA level at 8 weeks after treatment initiation, and by 67% (CI, 42% to 81% [P < 0.001]) for every 2-fold higher CD4(+) count at baseline. These risk factors and syncytium-inducing viral phenotype at baseline, but not infectious HIV-1 titers in circulating cells, were associated with change in CD4(+) counts over 48 weeks. Conclusions: For an individual patient, a change in plasma HIV-1 RNA level of 2.5-fold or more probably indicates a true biological change. Monitoring HIV-I RNA levels and CD4(+) lymphocytes before a change in antiretroviral treatment and monitoring HIV-1 RNA levers shortly thereafter improves prediction of disease progression and decline in CD4(+) counts for 1 year compared with monitoring CD4(+) counts or HIV-1 RNA levels alone. Additional monitoring of infectious HIV-1 titers in mononuclear cells of peripheral blood is not useful. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH PUBL HLTH,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH MED,BIRMINGHAM,AL 35294. RUSH MED COLL,CHICAGO,IL 60612. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MINNESOTA,SCH MED,CTR HLTH,MINNEAPOLIS,MN 55455. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. UNIV MIAMI,SCH MED,DEPT BIOCHEM & MOL BIOL,MIAMI,FL 33101. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. VET AFFAIRS MED CTR,DENVER,CO. RP Hughes, MD (reprint author), UNIV LONDON LONDON SCH HYG & TROP MED,MED STAT UNIT,KEPPEL ST,LONDON WC1E 7HT,ENGLAND. FU NIAID NIH HHS [AI-27675, AI-27661, AI-29193] NR 37 TC 206 Z9 213 U1 0 U2 3 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 JUN 15 PY 1997 VL 126 IS 12 BP 929 EP 938 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA XE549 UT WOS:A1997XE54900004 PM 9182469 ER PT J AU OBrien, WA Hartigan, PM Daar, ES Simberkoff, MS Hamilton, JD AF OBrien, WA Hartigan, PM Daar, ES Simberkoff, MS Hamilton, JD TI Changes in plasma HIV RNA levels and CD4(+) lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; ZIDOVUDINE; QUANTITATION; TUBERCULOSIS; REPLICATION; VACCINATION AB Background: Markers are needed for assessing response to antiretroviral therapy over time. The CD4(+) lymphocyte count is one such surrogate, but it is relatively weak. Objective: To assess the association of changes in plasma human immunodeficiency virus (HIV) RNA level and CD4(+) lymphocyte count with progression to the acquired immunodeficiency syndrome (AIDS). Design: Analysis of data from a subset of patients in a multicenter, randomized, clinical trial. Setting: Six Veterans Affairs medical centers and one U.S. Army medical center. Patients: 270 symptomatic HIV-infected patients from the Veterans Affairs Cooperative Study on AIDS. Intervention: Patients were randomly assigned to receive zidovudine or placebo initially; a cross-over protocol was established for patients receiving placebo who had disease progression. Measurements: Reverse transcriptase polymerase chain reaction on cryopreserved plasma samples, previously obtained CD4(+) lymphocyte counts, and clinical events. Results: For each decrease of 0.5 log(10) copies/mL in plasma HIV RNA level, averaged over the 6 months after randomization, the relative risk (RR) for progression to AIDS was 0.67 (P < 0.001). In a subset of 70 treated patients with long-term follow-up, a return to baseline plasma HIV RNA levels within 6 months of randomization was associated with progression to AIDS (RR, 4.28; P = 0.004). Plasma HIV RNA levels or CD4(+) lymphocyte counts over time were more strongly associated with progression to AIDS than were baseline levels or counts. Conclusions: An adequate virologic response after initiation of antiretroviral therapy seems to require a decrease in plasma HIV RNA level of at least 0.5 log(10) copies/mL that is sustained for at least 6 months. The independent relation between plasma HIV RNA level and CD4(+) lymphocyte count over time and clinical outcome suggests that the measurement of plasma HIV RNA level, in addition to the CD4(+) lymphocyte count, has a role in guiding the management of antiretroviral therapy. C1 W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. W HAVEN VET AFFAIRS MED CTR, W HAVEN, CT USA. CEDARS SINAI MED CTR, NEW YORK, NY USA. VET AFFAIRS MED CTR, NEW YORK, NY USA. NYU, SCH MED, NEW YORK, NY USA. DUKE UNIV, MED CTR, DIV INFECT DIS & INT HLTH, DURHAM, NC 27710 USA. VET AFFAIRS MED CTR, DURHAM, NC 27705 USA. RES CTR AIDS & HIV INFECT, DURHAM, NC USA. NR 30 TC 227 Z9 228 U1 0 U2 6 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 JUN 15 PY 1997 VL 126 IS 12 BP 939 EP 945 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XE549 UT WOS:A1997XE54900005 PM 9182470 ER PT J AU Meredith, M Li, GD Metz, SA AF Meredith, M Li, GD Metz, SA TI Inhibition of calcium-induced insulin secretion from intact HIT-T15 or INS-1 beta cells by GTP depletion SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE GTP; insulin secretion; Ca2+; exocytosis; guanine; adenine; mycophenolate ID RAT ISLETS; MYCOPHENOLATE MOFETIL; GUANINE-NUCLEOTIDES; PANCREATIC-ISLETS; B-CELLS; RELEASE; GLUCOSE; ESTABLISHMENT; ACTIVATION; METABOLISM AB Using intact rat islets, we previously observed that GTP depletion (achieved through the use of mycophenolic acid or other synthesis inhibitors) impedes nutrient- but not K+-induced insulin secretion. It was concluded that a proximal nutrient-dependent step in stimulus-secretion coupling (but not the process of Ca2+-induced exocytosis itself) is modulated by ambient GTP levels. To examine Ca2+-dependent steps further in intact beta cells, INS-1 cells (which synthesize GTP and ATP similarly to rat islets) and HIT-T15 cells (whose synthesis of purine nucleotides is different) were studied following cell culture for 1-18 hr in various concentrations of mycophenolic acid (MPA) or mizoribine (MZ). Both agents profoundly reduced GTP content (mean: -78%) and lowered the GTP/GDP ratio by an average of -73%; concomitantly, MPA or MZ reduced insulin secretion induced by 10 mM glucose, 30 or 40 mM KCl, or 100 mu M tolbutamide, independent of any changes in cell viability, insulin content, ATP content, the ATP/ADP ratio, or cytosolic free Ca2+ concentrations. In INS-1 cells (which appear to have normal nucleobase transport and ''salvage'' pathway activities), guanine (but not adenine) restored GTP content, the GTP/GDP ratio, and Ca2+-induced secretion. In HIT cells, the phosphoribosylation of exogenous guanine or hypoxanthine is defective; however, provision of 500 mu M guanosine (but not adenosine) reversed the effects of MPA. We conclude that, at least in certain situations, a requisite role for GTP in the distal step(s) of exocytosis can be demonstrated. (C) 1997 Elsevier Science Inc. C1 UNIV WISCONSIN,ENDOCRINOL SECT,MADISON,WI. UNIV WISCONSIN,DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. FU NIDDK NIH HHS [DK 37312] NR 32 TC 18 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 15 PY 1997 VL 53 IS 12 BP 1873 EP 1882 DI 10.1016/S0006-2952(97)00057-9 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XN780 UT WOS:A1997XN78000012 PM 9256162 ER PT J AU Kyle, RA Anderson, KC AF Kyle, RA Anderson, KC TI A tribute to Jan Gosta Waldenstrom SO BLOOD LA English DT Editorial Material ID X-LINKED AGAMMAGLOBULINEMIA; MACROGLOBULINEMIA; THERAPY; 2-CHLORODEOXYADENOSINE C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Kyle, RA (reprint author), MAYO CLIN & MAYO FDN,SECT PUBLICAT,DIV HEMATOL & INTERNAL MED,200 1ST ST SW,HILTON 920,ROCHESTER,MN 55905, USA. NR 19 TC 5 Z9 6 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 JUN 15 PY 1997 VL 89 IS 12 BP 4245 EP 4247 PG 3 WC Hematology SC Hematology GA XE974 UT WOS:A1997XE97400001 PM 9192746 ER PT J AU Locke, JL AF Locke, JL TI A theory of neurolinguistic development SO BRAIN AND LANGUAGE LA English DT Review ID LANGUAGE-IMPAIRED CHILDREN; TACTILE DISCRIMINATION CAPACITY; MASSIVE CORTICAL REORGANIZATION; PLANUM TEMPORALE ASYMMETRY; EARLY LEXICAL ACQUISITION; TIME-SHARING PARADIGM; SENSORY CORTEX SMI; LEFT-HEMISPHERE; SPEECH-PERCEPTION; YOUNG-CHILDREN AB This article offers a developmental theory of language and the neural systems that lead to and subserve linguistic capabilities. Early perceptual experience and discontinuities in linguistic development suggest that language develops in four phases that occur in a fixed, interdependent sequence. In each phase of language, a unique ontogenetic function is accomplished. These functions have proprietary neural systems that vary in their degree of specialization. Of particular interest is an analytical mechanism that is responsible for linguistic grammar. This mechanism is time-locked and can only be turned on in the third phase. Confirming evidence is provided by children who are delayed in the second phase of the language learning process. These children store insufficient lexical material to activate their analytic mechanism. Inactivation behaves like damage, shifting language functions to homologous mechanisms in the nondominant hemisphere, thereby increasing functional and anatomical symmetry across the hemispheres. This atypical assembly of neurolinguistic resources produces functional but imperfect command of spoken language and may complicate learning of written language. The theory thus offers a different role for genetics and early experience, and a different interpretation of neuroanatomic findings, from those entertained in most other proposals on developmental language disorders. (C) 1997 Academic Press. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA. NR 349 TC 124 Z9 128 U1 6 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD JUN 15 PY 1997 VL 58 IS 2 BP 265 EP 326 DI 10.1006/brln.1997.1791 PG 62 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA XC128 UT WOS:A1997XC12800003 PM 9182750 ER PT J AU Tsao, HS Cosimi, AB Sober, AJ AF Tsao, HS Cosimi, AB Sober, AJ TI Ultra-late recurrence (15 years or longer) of cutaneous melanoma SO CANCER LA English DT Article DE melanoma; ultra-late; delayed; recurrence ID I MALIGNANT-MELANOMA; STAGE-1 MELANOMA; LATE METASTASES; PROGRESSION; MODEL AB BACKGROUND, Melanoma can remain clinically quiescent for decades before regional or distant recurrence appears. This protracted disease free interval challenges the concept of a ''cure'' for melanoma. METHODS, To understand this prolonged dormancy better, the authors retrospectively studied patients who developed recurrent melanoma 15 years or longer after their initial diagnosis (''ultra-late'' recurrence). These cases were identified from 2766 melanoma diagnoses available in the Cancer Registry at the Massachusetts General Hospital (MGH). Histologic features of the primary lesion were also included when possible. RESULTS, Twenty cases were retrieved from the MGH database. There were equal numbers of women and men, although women were younger at the time of initial diagnosis (mean age of women: 29.8 years vs. 43.0 years for men). No patients had more than one primary cutaneous melanoma. The trunk was the most common primary site (35%), although there was no predominant anatomic localization. The average disease free interval was 17.3 years for women, 20.0 years for men, 18.1 years for patients with regional recurrence, and 19.0 years for patients with distant metastases. Distant recurrence was the most common type of recurrence (50% of women and 60% of men). The estimated probability of survival (5 years after recurrence) was 0.8 for regional disease and 0.2 for distant disease. With the available histologic records, it appears that almost all tumors were Clark Level III or IV with thicknesses ranging from 0.8-2.3 mm. In contrast to the published cases, this study did not find that women with lower extremity melanomas were at higher risk for developing ultra-late recurrence. CONCLUSIONS, Ultra-late recurrence of melanoma, although uncommon, can occur in any patient without identifiable risk factors. Because many prognostically favorable melanomas (thin melanomas on extremities) can recur after prolonged disease free intervals, the possibility of delayed recurrence remains and must be kept in mind. (C) 1997 American Cancer Society. C1 HARVARD UNIV,DEPT DERMATOL,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 29 TC 89 Z9 89 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 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 1997 VL 79 IS 12 BP 2361 EP 2370 PG 10 WC Oncology SC Oncology GA XC745 UT WOS:A1997XC74500010 PM 9191524 ER PT J AU Ripple, MO Pickhardt, PA Wilding, G AF Ripple, MO Pickhardt, PA Wilding, G TI Alteration in gamma-glutamyl transpeptidase activity and messenger RNA of human prostate carcinoma cells by androgen SO CANCER RESEARCH LA English DT Article ID TRANSFERASE TRANSPEPTIDASE; EPITHELIAL-CELLS; RAT EPIDIDYMIS; EXPRESSION; GLUTATHIONE; HEPATOCARCINOGENESIS; DIFFERENTIATION; LOCALIZATION; HEPATOMA; KIDNEY AB Concentrations of the synthetic androgen R1881 that correspond to physiologically relevant concentrations of 5 alpha-dihydrotestosterone are capable of altering the activity of gamma-glutamyl transpeptidase (GGT) in human prostate carcinoma cells. GGT activity of the androgen-responsive prostate dancer cell line LNCaP increases >50% above that of the control after a 72-h exposure to 1 nM R1881. This elevation in GGT activity occurs as early as 48 h after treatment and is maintained for at least 96 h. Loss of glutathione (GSH) from media and accumulation of intracellular GSH of cells pretreated with 1 nM R1881 occur at a higher rate than in control cells, suggesting that a greater rate of GSH salvage is associated with the increased GGT activity. Immunohistochemical staining detects an increase in GGT-positive staining in cells treated with 1 nM R1881 for 72 h. Steady-state mRNA levels for GGT are elevated above those of the control 24-72 h after treatment. R1881 has no effect on the GGT activity of the androgen-independent prostate cell line DU145. Growth of LNCaP but not DU145 cells is inhibited by 1 nM R1881 compared to that of the control. Inhibitors of GGT activity, acivicin and serine-borate, are capable of dampening or blocking the effect of R1881 on growth. Growth of LNCaP cells treated with 1 nM R1881 plus 100 mM glycylglycine, a stimulator of GGT activity, is inhibited to a greater extent than the growth of LNCaP cells treated with R1881 alone. These data demonstrate that androgens can elevate GGT activity and increase GGT mRNA and protein levels in human prostate carcinoma cells. In addition, compounds able to alter GGT activity are capable of altering androgen-related growth effects. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT MED,ENVIRONM TOXICOL CTR,MED ONCOL SECT,MADISON,WI 53792. UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53792. FU NIEHS NIH HHS [5-T32-ES07015-18] NR 41 TC 13 Z9 13 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 JUN 15 PY 1997 VL 57 IS 12 BP 2428 EP 2433 PG 6 WC Oncology SC Oncology GA XD800 UT WOS:A1997XD80000023 PM 9192821 ER PT J AU Song, HK Goetinck, PF AF Song, HK Goetinck, PF TI FGF-2 signaling in the early development of cutaneous appendages SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CEN,CUTANEOUS BIO RES,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP B43 EP B43 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400427 ER PT J AU Miller, JB Dunn, JJ Dominov, JA AF Miller, JB Dunn, JJ Dominov, JA TI Muscle stem cells reside in the small subset of myogenic cells that express Bcl-2 and are resistant to apoptosis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 15 PY 1997 VL 186 IS 2 BP S4 EP S4 PG 1 WC Developmental Biology SC Developmental Biology GA XH774 UT WOS:A1997XH77400035 ER PT J AU Sawicki, M Arnold, E Ebrahimi, S Duell, T Jin, S Wood, T Chakrabarti, R Peters, J Wan, Y Samara, G Weier, HUG Udar, N Passaro, E Srivatsan, ES AF Sawicki, M Arnold, E Ebrahimi, S Duell, T Jin, S Wood, T Chakrabarti, R Peters, J Wan, Y Samara, G Weier, HUG Udar, N Passaro, E Srivatsan, ES TI A transcript map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13 SO GENOMICS LA English DT Article ID HUMAN Y-CHROMOSOME; CDNA SELECTION; PARATHYROID TUMORS; LINKAGE ANALYSIS; SMALL REGION; GENE; MARKERS; PROTEIN; DNA; IDENTIFICATION AB A transcription map of a 1200-kb region encompassing the MEN1 locus was constructed by direct cDNA selection and mapping ESTs. A total of 29 genes were mapped. Ten transcripts were identified by cDNA selection of a focused 300-kb genomic region telomeric to the MEN1 consensus region. Since many of the sequences cloned by cDNA selection also identified ESTs from the region, 19 additional RH-mapped ESTs were mapped to the entire contig region by CR amplification of genomic clones. Nine known genes, 2 putative human homologues to mouse genes, and is novel transcripts map to the region. Transcripts that map to the MEN1 interval PYGM-D11S449 include SGC35223, IB1256, AA147620, ZFM1, FAU, and CAPN1. The latter 3 known genes have already been excluded as candidate MEN1 genes. The 2 putative human homologues of mouse genes Ltbp2 and Spa-1 may be candidate tumor suppressor genes, but they map telomeric to D11S449. Although both of these genes map outside the MEN1 consensus region they may play a role in sporadic endocrine tumors independent of the MEN1 gene or in other tumors, such as breast cancer, that have loss of heterozygosity within this region. (C) 1997 Academic Press. C1 UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90073. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV LIFE SCI,BERKELEY,CA 94720. UNIV MUNICH,MED KLIN 3,D-80539 MUNICH,GERMANY. CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90027. HARBOR UCLA MED CTR,DEPT PATHOL,TORRANCE,CA 90509. RP Sawicki, M (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG W112,MOL BIOL CORE UNIT,LOS ANGELES,CA 90073, USA. NR 46 TC 11 Z9 11 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 0888-7543 J9 GENOMICS JI Genomics PD JUN 15 PY 1997 VL 42 IS 3 BP 405 EP 412 DI 10.1006/geno.1997.4773 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XG519 UT WOS:A1997XG51900006 PM 9205112 ER PT J AU Willett, CG Smith, DI Shridhar, V Wang, MH Emanuel, RL Patidar, K Graham, SA Zhang, F Hatch, V Sugarbaker, DJ Sunday, ME AF Willett, CG Smith, DI Shridhar, V Wang, MH Emanuel, RL Patidar, K Graham, SA Zhang, F Hatch, V Sugarbaker, DJ Sunday, ME TI Differential screening of a human chromosome 3 library identifies hepatocyte growth factor-like/macrophage-stimulating protein and its receptor in injured lung - Possible implications for neuroendocrine cell survival SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE tyrosine phosphorylation; apoptosis; cell adhesion; nitrosamines; cell proliferation ID TUMOR-SUPPRESSOR GENE; HAMSTER LUNG; HOMOZYGOUS DELETION; MOLECULAR ANALYSIS; REGION 3P21; CANCER; EXPRESSION; LINES; HYPERPLASIA; APOPTOSIS AB Transient pulmonary neuroendocrine cell hyperplasia and non-neuroendocrine lung tumors develop in nitrosamine-treated hamsters, which we hypothesized might modulate epithelial cell phenotype by expressing gene(s) homologous to human chromosome 3p gene(s) deleted in small cell carcinoma of the lung (SCLC). We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung. HGFL/MSP mRNA is low to undetectable in human SCLC and carcinoid tumors, but the HGFL/MSP tyrosine kinase receptor, RON, is present and functional on many of these neuroendocrine tumors. In H835, a pulmonary carcinoid cell line, and H187, a SCLC cell line, HGFL/MSP induced adhesion/flattening and apoptosis. Using viable cell counts to assess proliferation after 14 d of treatment with HGFL/MSP, there is growth inhibition of H835 but not H187. Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia. These observations suggest that HGFL/MSP might regulate neuroendocrine cell survival during preneoplastic lung injury, which could influence the ultimate tumor cell phenotype. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,DEPT EXPT PATHOL,ROCHESTER,MN 55905. WAYNE STATE UNIV,DEPT INTERNAL MED,DEPT BIOL MOL,DEPT GENET,DETROIT,MI 48201. WAYNE STATE UNIV,DEPT MED,DIV PULM & CRIT CARE MED,DETROIT,MI 48201. CHILDRENS HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 01125. FU NHLBI NIH HHS [HL-44984] NR 54 TC 31 Z9 32 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN 15 PY 1997 VL 99 IS 12 BP 2979 EP 2991 DI 10.1172/JCI119493 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XH277 UT WOS:A1997XH27700024 PM 9185522 ER PT J AU Li, XL Sandoval, D Freeberg, L Carter, RH AF Li, XL Sandoval, D Freeberg, L Carter, RH TI Role of CD19 tyrosine 391 in synergistic activation of B lymphocytes by coligation of CD19 and membrane Ig SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE; T-CELL; MAP KINASE; COMPLEMENT RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; SELECTIVE ACTIVATION; SIGNALING PATHWAY; EXCHANGE ACTIVITY; CROSS-LINKING; MEK KINASE AB CD19 and CD21,which form a complex on B lymphocytes, are required for normal Ab responses to T-dependent Ags, Coligation of the CD21/CD19 complex with membrane IgM (mIgM) powerfully enhances B cell activation in vitro and in vivo, To determine how CD19-mIgM synergy is produced, we examined immediate and downstream signaling events after ligation of either complex alone or after CD19-mIgM coligation in normal and lymphoblastoid B cells, Ligation of mIgM alone is known to result in tyrosine phosphorylation of CD19 and association of CD19 with phosphatidylinositol 3-kinase and Vav, and these events are not enhanced by coligation, In contrast, tyrosine phosphorylation of phosphatidylinositol 3-kinase and Vav is markedly enhanced after CD19-mIgM coligation. Coligation also results in synergistic, prolonged enhancement of mitogen-activated protein kinase activity, relative to ligation of either receptor complex alone, Mutation of CD19 Y391, the site at which Vav binds, but not mutation of CD19 Y482 and Y513, the sites of association with phosphatidylinositol 3-kinase, blocks the enhancement of mitogen-activated protein kinase activation, These findings suggest that the synergistic enhancement of B cell activation following CD19-mIgM coligation results from greater tyrosine phosphorylation of Vav and Vav-dependent enhanced activation of mitogen-activated protein kinases. C1 UNIV ALABAMA,LHRB 409,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL 35294. FU NIAMS NIH HHS [T32 AR07450] NR 50 TC 50 Z9 50 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 JUN 15 PY 1997 VL 158 IS 12 BP 5649 EP 5657 PG 9 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900011 PM 9190913 ER PT J AU Kaul, R Wu, B Goluszko, E Deng, CS Dedhia, V Nabozny, GH David, CS Rimm, IJ Shenoy, M Haqqi, TM Christadoss, P AF Kaul, R Wu, B Goluszko, E Deng, CS Dedhia, V Nabozny, GH David, CS Rimm, IJ Shenoy, M Haqqi, TM Christadoss, P TI Experimental autoimmune myasthenia gravis in B10.BV8S2 transgenic mice - Preferential usage of TCRAV1 gene by lymphocytes responding to acetylcholine receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; V-BETA-GENE; COLLAGEN ARTHRITIS; IMMUNE-RESPONSE; ENCEPHALOMYELITIS; EXPRESSION; ANTIGEN; REPERTOIRE; MEDIATE; MODEL AB Multiple TCRBV genes have been implicated in experimental autoimmune myasthenia gravis (EAMG) pathogenesis in susceptible H-2(b) strains of mice, We studied the contribution of specific TCRBV and AV genes in EAMG pathogenesis using B10.BV8S2 transgenic mice (H-2(b)). The TCR transgenic mice predominantly have TCRBV8S2 transgene, hut can use any of the endogenous AV gene repertoire, The transgenic mice were immunized with acetylcholine receptor (AChR) in CFA and evaluated for EAMG pathogenesis, Although the lymphocyte responses to AChR in B10.BV8S2 transgenic and nontransgenic TCR wild-type mice were equivalent, a marked reduction in lymphocyte response to the dominant AChR alpha chain peptide 146-162 was observed in the TCR transgenic mice, After boosting with AChR in CFA, anti-AChR Abs were detected in the serum, and 14 of 42 (33%) of the TCR transgenic mice developed clinical EAMG. Furthermore, EAMG in TCR transgenic mice was prevented by treatment with mAb to TCRBV8, which depleted BV8-expressing T cells, Cloning and sequencing of TCRAV genes from AChR-reactive T cells from B10.BV8S2 transgenic mice revealed a pattern of restricted TCRAV gene usage, The majority (60%) of the clones sequenced showed a sequence identical with that of the TCRAV1S8 gene, in the normal spleen cells of TCR transgenic mice, AV gene usage was more random, Thus, despite the presence of a complete endogenous TCRAV repertoire in B10.BV8S2 transgenic mice, T cells responding to AChR preferentially used a single endogenous TCRAV gene, thus implicating the involvement of the TCRAV1S8 gene in EAMG pathogenesis. C1 UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555. MAYO CLIN,DEPT IMMUNOL,ROCHESTER,MN 55901. CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CASE WESTERN RESERVE UNIV,DEPT MED RHEUMATOL,CLEVELAND,OH 44106. OI Haqqi, Tariq/0000-0003-3506-6133 NR 31 TC 4 Z9 4 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 JUN 15 PY 1997 VL 158 IS 12 BP 6006 EP 6012 PG 7 WC Immunology SC Immunology GA XE749 UT WOS:A1997XE74900053 PM 9190955 ER PT J AU Kelly, K AF Kelly, K TI The Merck Manual of medical information: Home edition - Berkow,R SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 15 PY 1997 VL 122 IS 11 BP 62 EP 62 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA XE182 UT WOS:A1997XE18200021 ER PT J AU Barlow, C Schroeder, M LekstromHimes, J Kylefjord, H Deng, CX WynshawBoris, A Spiegelman, BM Xanthopoulos, KG AF Barlow, C Schroeder, M LekstromHimes, J Kylefjord, H Deng, CX WynshawBoris, A Spiegelman, BM Xanthopoulos, KG TI Targeted expression of Cre recombinase to adipose tissue of transgenic mice directs adipose-specific excision of loxP-flanked gene segments SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SITE-SPECIFIC RECOMBINATION; DNA RECOMBINATION; BACTERIOPHAGE-P1 AB Functional analysis of mammalian genes relies, in part, on targeted mutations generated by homologous recombination in mice. We have developed a strategy for adipose-specific inactivation of loxP-floxed gene segments. Transgenic mice have been established that express Cre recombinase under the control of the adipose-specific aP2 enhancer/promoter. Crossing of the aP2/Cre mice with any loxP-floxed gene will facilitate its functional analysis in adipose tissue. C1 NATL HUMAN GENOME RES INST,CLIN GENE THERAPY BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL SCI & MOL PHARMACOL,BOSTON,MA 02115. RP Barlow, C (reprint author), NIH,LAB GENET DIS RES,BLDG 10,BETHESDA,MD 20892, USA. RI deng, chuxia/N-6713-2016 NR 14 TC 42 Z9 44 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 15 PY 1997 VL 25 IS 12 BP 2543 EP 2545 DI 10.1093/nar/25.12.2543 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XF705 UT WOS:A1997XF70500045 PM 9171115 ER PT J AU Fairclough, DL AF Fairclough, DL TI Summary measures and statistics for comparison of quality of life in a clinical trial of cancer therapy SO STATISTICS IN MEDICINE LA English DT Article ID OF-LIFE AB Assessment of health related quality of life (QOL) has become an important endpoint in many clinical trials of cancer therapy. Most of these studies entail multiple QOL scales that are assessed repeatedly over time. As a result, the problem of multiple comparisons is a primary analytic challenge with these trials. The use of summary measures and statistics both reduces the number of hypotheses tested and facilitates the interpretation of trial results where the primary question is 'Does the overall QOL differ between treatment arms?' I present two classes of summary measures that are sensitive to consistent trends in the same direction across multiple assessment times or multiple QOL scales. Missing data strongly influences the choice between the two classes, where one class handles missing data on an individual basis, while the other class uses model-based strategies. I present the results from a clinical trial of adjuvant therapy for breast cancer that use summary measures with a focus on the practical issues that affect these analysis strategies, such as missing data and integration of QOL with efficacy endpoints such as survival. (C) 1997 by John Wiley & Sons, Ltd. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP Fairclough, DL (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA23318, CA06516] NR 15 TC 56 Z9 56 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1997 VL 16 IS 11 BP 1197 EP 1209 DI 10.1002/(SICI)1097-0258(19970615)16:11<1197::AID-SIM531>3.0.CO;2-9 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA XD623 UT WOS:A1997XD62300001 PM 9194267 ER PT J AU Emanuel, EJ AF Emanuel, EJ TI Care for dying patients SO LANCET LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Emanuel, EJ (reprint author), DANA FARBER CANC INST,CTR OUTCOMES & POLICY RES,BOSTON,MA 02115, USA. NR 6 TC 14 Z9 15 U1 2 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 14 PY 1997 VL 349 IS 9067 BP 1714 EP 1714 DI 10.1016/S0140-6736(05)62952-2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XE065 UT WOS:A1997XE06500006 PM 9193379 ER PT J AU Erhardt, P Tomaselli, KJ Cooper, GM AF Erhardt, P Tomaselli, KJ Cooper, GM TI Identification of the MDM2 oncoprotein as a substrate for CPP32-like apoptotic proteases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; PROTEIN; GENE AB Programmed cell death is mediated by members of the interleukin 1-beta convertase family of proteases, which are activated in response to diverse cell death stimuli. However, the key substrates of these proteases that are responsible for apoptotic cell death have not been identified. Here we report that the MDM2 oncoprotein is cleaved by members of the CPP32 subfamily of interleukin l-p convertase proteases both in vitro and in vivo, resulting in the disappearance of MDM2 from apoptotic cells. Because MDM2 functions as a negative regulator of the p53 tumor suppressor and because p53 induces apoptosis in response to a variety of stimuli, this cleavage of MDM2 by CPP32-like proteases may result in deregulation of p53 and contribute directly to the process of apoptotic cell death. C1 DANA FARBER CANC INST,DIV MOL GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. IDUN PHARMACEUT INC,LA JOLLA,CA 92037. FU NCI NIH HHS [R01 CA18689] NR 28 TC 80 Z9 81 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 JUN 13 PY 1997 VL 272 IS 24 BP 15049 EP 15052 DI 10.1074/jbc.272.24.15049 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400003 PM 9182520 ER PT J AU Hirai, S Katoh, M Terada, M Kyriakis, JM Zon, LI Rana, A Avruch, J Ohno, S AF Hirai, S Katoh, M Terada, M Kyriakis, JM Zon, LI Rana, A Avruch, J Ohno, S TI MST/MLK2, a member of the mixed lineage kinase family, directly phosphorylates and activates SEK1, an activator of c-Jun N-terminal kinase/stress-activated protein kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; MAMMALIAN-CELLS; IDENTIFICATION; DOMAIN; CLONING; BRAIN; TRANSFORMATION; EXPRESSION; SUBFAMILY; CASCADE AB c-Jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs) are mitogen-activated protein kinase (MAPK)-related protein kinases that are involved in several cellular events, including growth, differentiation, and apoptosis. Mixed lineage kinases (MLKs) form a family of protein kinases sharing two leucine zipper-like motifs and a kinase domain whose primary structure is similar to both the tyrosine-specific and the serine/threonine-specific kinase classes. We have reported that a member of the MLK family, MUK/DLK/ZPK, can activate JNK/SAPK in vivo, and here we show that another member of the MLK family, MST/MLK2, activates JNK/SAPK. Both MUK/DLK/ZPK and MST/MLK2 cause a slight activation of p38/Mpk2 when overexpressed in COS-1 cells, whereas MST/MLK2, but not MCK/DLK/ ZPK, activates extracellular response kinase (ERK) to a certain degree. The activity of SEK1/MKK4/JNKK, a MAPK kinase class protein kinase designated as a direct activator of JNK/SAPK, is also induced by MUK/DLK/ ZPK or MST/MLK2 overexpression. Furthermore, recombinant MST/MLK2 produced in bacteria directly phosphorylates and activates SEK1/MKK4/JNKK in vitro, showing that MST/MLK2 acts like a MAPK kinase kinase. Taken together, these results suggest that MLK family members are MAPK kinase kinases preferentially acting on the JNK/SAPK pathway. C1 NATL CANC CTR,RES INST,DIV GENET,CHUO KU,TOKYO 104,JAPAN. MASSACHUSETTS GEN HOSP E,DIABET UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP E,MED SERV,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. HARVARD UNIV,DANA FARBER CANC INST,SCH MED,BOSTON,MA 02115. RP Hirai, S (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT BIOL MOL,KANAZAWA KU,3-9 FUKUURA,YOKOHAMA,KANAGAWA 236,JAPAN. RI Ohno, Shigeo/B-1768-2010 OI Ohno, Shigeo/0000-0002-1294-5269 NR 38 TC 128 Z9 132 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 JUN 13 PY 1997 VL 272 IS 24 BP 15167 EP 15173 DI 10.1074/jbc.272.24.15167 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE034 UT WOS:A1997XE03400021 PM 9182538 ER PT J AU Posas, F Saito, H AF Posas, F Saito, H TI Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: Scaffold role of Pbs2p MAPKK SO SCIENCE LA English DT Article ID PHEROMONE RESPONSE PATHWAY; SACCHAROMYCES-CEREVISIAE; KINASE CASCADE; SIGNAL TRANSDUCTION; PROTEIN-KINASES; YEAST; STE5; PHOSPHORYLATION; COMPONENTS; MITOGEN AB Exposure of the yeast Saccharomyces cerevisiae to high extracellular osmolarity induces the Sln1p-Ypd1p-Ssk1p two-component osmosensor to activate a mitogen-activated protein (MAP) kinase cascade composed of the Ssk2p and Ssk22p MAP kinase kinase kinases (MAPKKKs), the Pbs2p MAPKK, and the Hog1p MAPK. A second osmosensor, Sho1p, also activated Pbs2p and Hog1p, but did so through the Ste11p MAPKKK. Although Ste11p also participates in the mating pheromone-responsive MAPK cascade, there was no detectable cross talk between these two pathways. The MAPKK Pbs2p bound to the Sho1p osmosensor, the MAPKKK Ste11p, and the MAPK Hog1p. Thus, Pbs2p may serve as a scaffold protein. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [GM50909, GM53415] NR 27 TC 399 Z9 412 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD JUN 13 PY 1997 VL 276 IS 5319 BP 1702 EP 1705 DI 10.1126/science.276.5319.1702 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD947 UT WOS:A1997XD94700044 PM 9180081 ER PT J AU Montminy, M AF Montminy, M TI Transcriptional activation - Something new to hang your HAT on SO NATURE LA English DT Editorial Material ID COACTIVATOR; RECEPTOR; COMMON RP Montminy, M (reprint author), JOSLIN DIABET CTR,MOL BIOL SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 17 TC 48 Z9 48 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 12 PY 1997 VL 387 IS 6634 BP 654 EP 655 DI 10.1038/42594 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD869 UT WOS:A1997XD86900027 PM 9192883 ER PT J AU Seiden, MV Kirby, RE Whitman, GJ AF Seiden, MV Kirby, RE Whitman, GJ TI A 78-year-old man with a sigmoid stricture after radiation treatment for prostatic cancer - Diffuse large-B-cell lymphoma of the colon. Small-B-cell chronic lymphocytic leukemia in lymph nodes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RECTAL ULCER SYNDROME; RICHTERS-SYNDROME; HODGKINS-DISEASE; INJURY; TRANSFORMATION; FEATURES C1 HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA. RP MASSACHUSETTS GEN HOSP, DIV HEMATOL & ONCOL, BOSTON, MA 02114 USA. NR 35 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 12 PY 1997 VL 336 IS 24 BP 1738 EP 1745 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XD543 UT WOS:A1997XD54300008 ER PT J AU Strobel, T Swanson, L Korsmeyer, S Cannistra, SA AF Strobel, T Swanson, L Korsmeyer, S Cannistra, SA TI Radiation-induced apoptosis is not enhanced by expression of either p53 or BAX in SW626 ovarian cancer cells SO ONCOGENE LA English DT Article DE apoptosis; p53; BAX; radiation; ovarian; cancer ID WILD-TYPE P53; TUMOR-SUPPRESSOR P53; DNA-DAMAGE; IN-VIVO; BCL-2; DEATH; GENE; RADIOSENSITIVITY; CHECKPOINT; INDUCTION AB The p53 protein is known to play a central role in mediating G(1) arrest or apoptosis in response to ionizing radiation in some cell types, It has been proposed that the Link between p53 and induction of apoptosis is provided in part by p53-mediated upregulation of BAX. In this study, we used the human SW626 ovarian cancer cell line, which lacks functional p53, to further investigate the relationship between wildtype p53, BAX, and apoptosis, SW626 cells expressing a temperature sensitive (ts) p53 mutant did not undergo G(1) arrest or apoptosis and did not exhibit enhanced sensitivity to radiation at the permissive temperature of 32 degrees C, The tsp53 protein was functional in these cells as evidenced by rapid induction of p21 at 32 degrees C, but not at 37 degrees C, Interestingly, restoration of wildtype p53 function at 32 degrees C was not associated with BAS upregulation. In addition, stable overexpression of BAX in SW626 cells was not capable of enhancing apoptotic cell death in response to radiation, Thus, failure of p53 to upregulate BAS is not the sole reason for its inability to promote radiation-induced apoptosis in SW626 cells, Taken together, our data suggest that neither p53 nor BAX upregulation is sufficient for the induction of apoptosis in response to genotoxic damage in some cell types. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,DIV MOL ONCOL,ST LOUIS,MO. FU NCI NIH HHS [CA 60670] NR 22 TC 23 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 12 PY 1997 VL 14 IS 23 BP 2753 EP 2758 DI 10.1038/sj.onc.1201132 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XD643 UT WOS:A1997XD64300002 PM 9190890 ER PT J AU Wang, MS Liu, YLE Greene, J Sheng, SJ Fuchs, A Rosen, EM Shi, YE AF Wang, MS Liu, YLE Greene, J Sheng, SJ Fuchs, A Rosen, EM Shi, YE TI Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4 SO ONCOGENE LA English DT Article DE TIMP; MMP; mammary carcinoma; nude mice; angiogenesis ID INVASIVE TUMORS; IV COLLAGENASES; MESSENGER-RNAS; STROMAL CELLS; UP-REGULATION; CHICK-EMBRYO; IN-VIVO; EXPRESSION; TIMP-2; ANGIOGENESIS AB We recently identified, cloned, and characterized a novel human tissue inhibitor of metalloproteinases-4, TIMP-4 (Greene et al., 1996), To determine if TIMP-4 can modulate the in vivo growth of human breast cancers, Ne transfected a full-length TIMP-4 cDNA into MDA-MB-435 human breast cancer cells and studied the orthotopic growth of TIMP-4-transfected (TIMP4-435) versus control (neo-435) clones in the mammary fat pad of athymic nude mice, TIMP4-435 clones expressed TIMP-4 mRNA and produced anti-metalloproteinase (MMP) activity, while neo-435 clones did not express TIMP-4 mRNA or produce detectable anti-MMP activity. Overexpression of TIMP-4 inhibited the invasion potential of the cells in the in vitro invasion assay, When injected orthotopically into nude mice, TIMP-4 transfectants were significantly inhibited in tumor growth by 4-10-fold in primary tumor volumes; and in an axillary lymph node and lung metastasis as compared with controls. These results suggest the therapeutic potential of TIMP-4 in treating cancer malignant progression. C1 LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT PEDIAT,NEW HYDE PK,NY 11040. LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT PATHOL,NEW HYDE PK,NY 11040. LONG ISL JEWISH MED CTR,ALBERT EINSTEIN COLL MED,DEPT RADIAT ONCOL,NEW HYDE PK,NY 11040. HUMAN GENOME SCI INC,ROCKVILLE,MD 20850. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA68064-01] NR 47 TC 124 Z9 129 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 12 PY 1997 VL 14 IS 23 BP 2767 EP 2774 DI 10.1038/sj.onc.1201245 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XD643 UT WOS:A1997XD64300004 PM 9190892 ER PT J AU Goldzweig, CL Mittman, BS Carter, GM Donyo, T Brook, RH Lee, P Mangione, CM AF Goldzweig, CL Mittman, BS Carter, GM Donyo, T Brook, RH Lee, P Mangione, CM TI Variations in cataract extraction rates in Medicare prepaid and fee-for-service settings SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-MAINTENANCE ORGANIZATIONS; QUALITY-OF-LIFE; ELDERLY PATIENTS; VISUAL FUNCTION; RISK-FACTORS; SURGERY; VISION; CARE; PHYSICIANS; OUTCOMES AB Objective.-To compare rates of cataract extraction in 2 prepaid health settings and in traditional fee-for-service (FFS) settings. Design.-A cross-sectional analysis using 1993 health maintenance organization (HMO) Medicare claims and encounter files, the Health Care Financing Administration (HCFA) 5% Medicare Part B provider/supplier file, and the HCFA October 1992 100% Medicare population file. Setting.-Southern California Medicare FFS settings and the staff-model and independent practice association (IPA) plans of a large California HMO. Patients.-1993 Medicare beneficiaries aged 65 years and older, The study included 43 387 staff-model HMO enrollees, 19 050 IPA enrollees, and 47 150 FFS beneficiaries (a 5% sample of all Southern California FFS beneficiaries). Main Outcome Measure.-Age and risk-factor adjusted rates of cataract extraction per 1000 beneficiary-years. Results.-After controlling for age, sex, and diabetes mellitus status, FFS beneficiaries were twice as likely to undergo cataract extraction as were prepaid beneficiaries (P<.01). Female FFS beneficiaries were nearly twice as likely to undergo the procedure as were male FFS beneficiaries (P<.001); there were no extraction rate differences by sex in the prepaid settings. Conclusion.-Because of the potential implications for vision care in the elderly, the significantly different rates of cataract extraction in FFS and prepaid settings warrant further clinical investigation to determine whether there is overuse in FFS vs underuse in prepaid settings. Such investigations must assess the appropriateness of cataract surgery by evaluating its use relative to clinical need. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. RAND CORP,SANTA MONICA,CA. UNIV SO CALIF,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90033. RP Goldzweig, CL (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED,11301 WILSHIRE BLVD,111G,LOS ANGELES,CA 90073, USA. OI Lee, Paul/0000-0002-3338-136X FU NIA NIH HHS [K08 AG000605]; OHS HRSA HHS [ST32PE19001] NR 28 TC 60 Z9 60 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 11 PY 1997 VL 277 IS 22 BP 1765 EP 1768 DI 10.1001/jama.277.22.1765 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XC499 UT WOS:A1997XC49900028 PM 9178788 ER PT J AU Yu, JS Burwick, JA Dranoff, G Breakefield, XO AF Yu, JS Burwick, JA Dranoff, G Breakefield, XO TI Gene therapy for metastatic brain tumors by vaccination with granulocyte-macrophage colony-stimulating factor-transduced tumor cells SO HUMAN GENE THERAPY LA English DT Article ID GLIOMA-CELLS; KINASE GENE; RAT-BRAIN; MELANOMA; IMMUNOTHERAPY; INVIVO; IMMUNOBIOLOGY; INTERLEUKIN-2; REGRESSION; VACCINES AB We have developed an ex vivo gene therapy paradigm for the treatment of brain tumors using granulocyte-macrophage colony-stimulating factor (GM-CSF). Murine B16 melanoma cells were infected with MFG recombinant retrovirus containing the mouse GM-CSF cDNA. Subcutaneous vaccination of syngeneic mice with irradiated GM-CSF-secreting B16 melanoma cells was capable of completely protecting animals against subsequent intracranial B16 tumor inoculation, with up to 5 x 10(3) cells. Histologic evaluation revealed the presence of neutrophils, eosinophils, and lymphocytes, including CD4(+), CD8(+), and CD45R(+) cells, in the intracerebral inoculation site, peaking 4 days after intracranial inoculation. In contrast, nonvaccinated animals or animals vaccinated with irradiated, nontransduced B16 cells succumbed to intracranial tumor within 3 weeks after inoculation. Treatment of established intracranial B16 melanoma tumors with subcutaneous injection of irradiated GM-CSF-secreting B16 cells significantly delayed death, as compared to injection of irradiated nontransduced B16 cells or no treatment. In addition, treatment of established intracerebral GL261 gliomas by vaccination with irradiated GM-CSF-secreting B16 cells mixed with irradiated, transduced, or nontransduced GL261 cells also extended survival. These B16/GL261 co-vaccinations also improved outcome and, in some cases, induced immunological memory that protected survivors from subsequent intracranial challenge with GL261 tumor cells. These findings indicate that peripheral vaccination with irradiated tumor cells in the presence of GM-CSF-producing cells can initiate a potent antitumor immune response against intracranial neoplasms. C1 MASSACHUSETTS GEN HOSP E,MOL NEUROGENET UNIT,NEUROSURG SERV,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP E,MOL NEUROGENET UNIT,NEUROL SERV,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02125. DANA FARBER CANC INST,BOSTON,MA 02125. FU NCI NIH HHS [CA69246]; NINDS NIH HHS [NS24279] NR 31 TC 89 Z9 93 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 JUN 10 PY 1997 VL 8 IS 9 BP 1065 EP 1072 DI 10.1089/hum.1997.8.9-1065 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XE655 UT WOS:A1997XE65500005 PM 9189764 ER PT J AU Prasad, KVS Ao, ZH Yoon, Y Wu, MX Rizk, M Jacquot, S Schlossman, SF AF Prasad, KVS Ao, ZH Yoon, Y Wu, MX Rizk, M Jacquot, S Schlossman, SF TI CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL ACTIVATION; TNF RECEPTOR; ANTIGEN CD27; SOLUBLE FORM; DEATH DOMAIN; RING FINGER; FAS-LIGAND; EXPRESSION; CD40; LYMPHOCYTES AB Members of the tumor necrosis factor receptor (TNFR) superfamily are important for cell growth and survival, In addition to providing costimulatory signals for cell proliferation, ligation of both TNFR1 and Fas can result in programmed cell death or apoptosis, The underlying mechanism requires an intact 80-aa stretch present in the cytoplasmic tails of both TNFR1 and Fas, termed the death domain (DD). Here we show that CD27, a member of the TNFR family expressed on discrete subpopulations of T and B cells and known to provide costimulatory signals for T and B cell proliferation and B cell Ig production, can also induce apoptosis. Co-crosslinking of surface Ig receptors along with ligation of CD27 augments CD27-mediated apoptosis. Unlike TNFR1 and Fas, the cytoplasmic tail of CD27 is relatively short and lacks the DD. Using the yeast two-hybrid system, we have cloned a novel protein (Siva) that hinds to the CD27 cytoplasmic tail, It has a DD homology region, a box-B-like ring finger, and a zinc finger-like domain, Overexpression of Siva in various cell lines induces apoptosis, suggesting an important role for Siva in the CD27-transduced apoptotic pathway. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Prasad, KVS (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02120, USA. NR 44 TC 198 Z9 211 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 JUN 10 PY 1997 VL 94 IS 12 BP 6346 EP 6351 DI 10.1073/pnas.94.12.6346 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400069 PM 9177220 ER PT J AU Cheng, LL Ma, MJ Becerra, L Ptak, T Tracey, I Lackner, A Gonzalez, RG AF Cheng, LL Ma, MJ Becerra, L Ptak, T Tracey, I Lackner, A Gonzalez, RG TI Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IN-VIVO; NMR; BRAIN; LOCALIZATION; DISEASE; SOLIDS AB We describe a method that directly relates tissue neuropathological analysis to medical imaging, Presently, only indirect and often tenuous relationships are made between imaging (such as MRI or x-ray computed tomography) and neuropathology. We present a biochemistry-based, quantitative neuropathological method that can help to precisely quantify information provided by in vivo proton magnetic resonance spectroscopy ((HMRS)-H-1), an emerging medical imaging technique, This method, high resolution magic angle spinning (HRMAS) (HMRS)-H-1, is rapid and requires only small amounts of unprocessed samples. Unlike chemical extraction or other forms of tissue processing, this method analyzes tissue directly, thus minimizing artifacts. We demonstrate the utility of this method by assessing neuronal damage using multiple tissue samples from differently affected brain regions in a case of Pick disease, a human neurodegenerative disorder. Among different regions, we found an excellent correlation between neuronal loss shown by traditional neurohistopathology and decrease of the neuronal marker N-acetylaspartate measured by HRMAS (HMRS)-H-1, This result demonstrates for the first time, to our knowledge, a direct, quantitative link between a decrease in N-acetylaspartate and neuronal loss in a human neurodegenerative disease. As a quantitative method, HRMAS (HMRS)-H-1 has potential applications in experimental and clinical neuropathologic investigations. It should also provide a rational basis for the interpretation of in vivo (HMRS)-H-1 studies of human neurological disorders. C1 MASSACHUSETTS GEN HOSP,NMR CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NEURORADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02114. NEW ENGLAND REG PRIMATE RES CTR,DEPT COMPARAT PATHOL,SOUTHBOROUGH,MA 01772. HARVARD UNIV,SCH MED,SOUTHBOROUGH,MA 01772. FU NCRR NIH HHS [P51 RR000168, RR00168, T32 RR007000, K26 RR000168, RR07000]; NINDS NIH HHS [R01 NS034626, NS34626, R01 NS030769] NR 30 TC 265 Z9 273 U1 0 U2 18 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 JUN 10 PY 1997 VL 94 IS 12 BP 6408 EP 6413 DI 10.1073/pnas.94.12.6408 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400080 PM 9177231 ER PT J AU Nau, GJ Guilfoile, P Chupp, GL Berman, JS Kim, SJ Kornfeld, H Young, RA AF Nau, GJ Guilfoile, P Chupp, GL Berman, JS Kim, SJ Kornfeld, H Young, RA TI A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; MYCOBACTERIUM-BOVIS BCG; ATHEROSCLEROTIC PLAQUES; BACTERIAL-INFECTION; MONOCLONAL-ANTIBODY; GENETIC-RESISTANCE; HUMAN MACROPHAGES; OSTEOPONTIN; EXPRESSION; CELLS AB Chronic inflammation and granuloma formation are associated with mononuclear cell infiltrates and are characteristic pathologic responses in tuberculosis, To identify host cell genes involved in tuberculous pathology, we screened macrophage cDNA libraries for genes induced by mycobacterial infection. One gene isolated in this screen, osteopontin (also known as early T lymphocyte activation protein 1 or Eta-1), was of particular interest because it is a cytokine and macrophage chemoattractant. Further study revealed that Mycobacterium tuberculosis infection of primary human alveolar macrophages causes a substantial increase in osteopontin gene expression. Osteopontin protein was identified by immunohistochemistry in macrophages, lymphocytes, and the extracellular matrix of pathologic tissue sections of patients with tuberculosis. Increased osteopontin expression also was found to be associated with silicosis, another granulomatous disease. The association of osteopontin with,granulomatous pathology, together with the known properties of the protein, suggest that osteopontin map participate in granuloma formation, The strategy of identifying host genes whose expression is altered by infection thus can provide valuable clues to disease mechanisms and will be increasingly valuable as additional human genome sequences become available. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02188. VET AFFAIRS MED CTR,BOSTON,MA 02130. OI , /0000-0001-8855-8647; Nau, Gerard/0000-0001-7921-8317 FU NHLBI NIH HHS [HL44846]; NIAID NIH HHS [AI 37869]; NICHD NIH HHS [N01-HD-6-2915] NR 52 TC 140 Z9 141 U1 0 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 JUN 10 PY 1997 VL 94 IS 12 BP 6414 EP 6419 DI 10.1073/pnas.94.12.6414 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400081 PM 9177232 ER PT J AU Shiraki, K Tsuji, N Shioda, T Isselbacher, KJ Takahashi, H AF Shiraki, K Tsuji, N Shioda, T Isselbacher, KJ Takahashi, H TI Expression of Fas ligand in liver metastases of human colonic adenocarcinomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tumor escape; immune surveillance; colonization ID TUMOR-NECROSIS-FACTOR; CANCER METASTASIS; T-LYMPHOCYTES; ANTI-FAS; MEDIATED CYTOTOXICITY; INDUCED APOPTOSIS; IMMUNE PRIVILEGE; DEATH; RECEPTOR; MICE AB Fas ligand (FasL) plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis. Since FasL has been implicated in the existence of immunologically privileged body sites by inducing apoptosis of activated T lymphocytes, wt investigated the expression of FasL in human colon cancers. We found that two out of seven primary tumors and all four hepatic metastatic tumors of surgically obtained colonic adenocarcinoma expressed FasL mRNA and protein, detected by reverse transcription-coupled PCR and by immunohistochemical staining, respectively. Expression of FasL was not detected in normal colonic epithelial cells, FasL mRNA was also expressed in some human colonic adenocarcinoma cell lines including SW480, SW1116, and LS180 cells, Cell-surface-associated FasL was detected in these human colon cancer cells by fluorescence immunocytochemical staining, In addition, the expressed FasL was demonstrated to be functional, since coculture experiments using FasL-expressing SW480 cells resulted in apoptosis of Jurkat T leukemia cells that are sensitive to Fas-mediated apoptosis, and this process was specifically inhibited by the neutralizing anti-human FasL antibody, Thus, our findings and other data suggest an alternative mechanism that enables tumors to evade immune destruction by inducing apoptosis in activated T Iymphocytes. Furthermore, constitutive expression of FasL in hepatic metastatic tumors suggests that FasL may also be important in their colonization in the liver through induction of apoptosis in the surrounding Fas-expressing hepatocytes. C1 HARVARD UNIV,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,TUMOR BIOL LAB,CHARLESTOWN,MA 02129. FU NCI NIH HHS [CA57584]; NIDDK NIH HHS [NIDDK43351] NR 48 TC 248 Z9 267 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 JUN 10 PY 1997 VL 94 IS 12 BP 6420 EP 6425 DI 10.1073/pnas.94.12.6420 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XD844 UT WOS:A1997XD84400082 PM 9177233 ER PT J AU Uddin, S Sher, DA Alsayed, Y Pons, S Colamonici, OR Fish, EN White, MF Platanias, LC AF Uddin, S Sher, DA Alsayed, Y Pons, S Colamonici, OR Fish, EN White, MF Platanias, LC TI Interaction of p59(fyn) with interferon-activated Jak kinases SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DEPENDENT TYROSINE PHOSPHORYLATION; VAV PROTOONCOGENE PRODUCT; SRC FAMILY KINASES; ALPHA-SUBUNIT; SH3 DOMAINS; C-SRC; TRANSCRIPTION FACTOR; RECEPTOR; PROTEIN; CELLS AB During IFN alpha stimulation, p59(fyn) associates with the Type I IFNR-associated Tyk-2 kinase in several human hematopoietic cell lines in vivo. This interaction is direct, and is mediated by the SH2 domain in p59(fyn), as shown by binding studies using glutathione-S-tranferase fusion proteins and far western blots. Furthermore, in response to IFN alpha-treatment of cells, the SH2 domain of Fyn interacts with the Tyk-8-associated c-cbl proto-oncogene product. In a similar manner, during IFN gamma stimulation, p59(fyn) associates via its SH2 domain with the activated form of the IFN gamma-dependent Jak-2 kinase, These data suggest that p59(fyn) is a common element in IFN alpha and IFN gamma signaling, and is selectively engaged by the Type I or II IFN receptors via specific interactions with dis-tinct Jak kinases. (C) 1997 Academic Press. C1 UNIV ILLINOIS,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60607. W SIDE VET AFFAIRS HOSP,CHICAGO,IL 60607. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. UNIV TENNESSEE,DEPT PATHOL,MEMPHIS,TN 38163. UNIV TORONTO,DEPT MED GENET & MICROBIOL,TORONTO,ON M5S 3E2,CANADA. RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 FU NCI NIH HHS [CA73381]; NIDDK NIH HHS [DK43808, DK38712] NR 42 TC 38 Z9 39 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 JUN 9 PY 1997 VL 235 IS 1 BP 83 EP 88 DI 10.1006/bbrc.1997.6741 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XE346 UT WOS:A1997XE34600017 PM 9196040 ER PT J AU Badgett, RG Lucey, CR Mulrow, CD AF Badgett, RG Lucey, CR Mulrow, CD TI Can the clinical examination diagnose left-sided heart failure in adults? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID VENTRICULAR EJECTION FRACTION; ACUTE MYOCARDIAL-INFARCTION; PULMONARY-ARTERY CATHETERIZATION; CRITICALLY ILL PATIENTS; CHEST-X-RAY; RADIONUCLIDE VENTRICULOGRAPHY; DIASTOLIC DYSFUNCTION; SYSTOLIC FUNCTION; ECHOCARDIOGRAPHIC INSIGHTS; VALSALVA MANEUVER AB We systematically reviewed the literature to ascertain how well clinicians determine the probability and type of left-sided heart failure in their patients, Left-sided heart failure is characterized by decreased left ventricular ejection fraction or increased filling pressure. The type of heart failure determines optimal treatment, Systolic dysfunction exists when ejection fraction is reduced, Diastolic dysfunction is presumed to be present when filling pressure is increased with a normal ejection fraction and without another explanatory diagnosis, Many findings are associated with heart failure, and wide variation exists in clinicians' ability to detect these findings. The best findings for detecting increased filling pressure are jugular venous distention and radiographic redistribution, The best findings for detecting systolic dysfunction are abnormal apical impulse, radiographic cardiomegaly, and q waves or left bundle branch block on an electrocardiogram. Diastolic dysfunction is especially difficult to diagnose, but is associated with an elevated blood pressure during heart failure. C1 AUDIE L MURPHY MEM VET ADM MED CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. RP Badgett, RG (reprint author), UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV GEN MED, 4200 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA. OI Badgett, Robert/0000-0003-2888-3303 NR 89 TC 135 Z9 138 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 1997 VL 277 IS 21 BP 1712 EP 1719 DI 10.1001/jama.277.21.1712 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XB088 UT WOS:A1997XB08800034 PM 9169900 ER PT J AU Sandermann, H Addona, GH Miller, KW AF Sandermann, H Addona, GH Miller, KW TI A thermodynamic analysis of the partitioning of cholesterol and related compounds between trioleoylglycerol and egg phosphatidylcholine bilayers SO BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM LA English DT Article DE cholesterol; cholesterol analogue; lipid partitioning; compartmentalization of cholesterol ID EMULSIONS; TRANSPORT; MEMBRANES; BEHAVIOR; TRIOLEIN AB The free energy of transfer of a number of alcohols, including cholesterol, from a bulk isotropic lipid phase. trioleoylglycerol (TG), to an anisotropic lipid phase, egg phosphatidylcholine (PC), was determined. n-Alkane-1-ols partitioned preferentially into the bilayer phase, for example, the free energy of transfer of octanol-1 from TG to PC was about -1.0 kcal/mol. This preference declined with increasing number of carbons at a rate of 40 cal/mol of CH2. Cholesterol had a much stronger preference for the bilayer with a free energy of -1.3 kcal/mol, compared to an extrapolated value of -0.2 kcal/mol for a normal alkane-1-ol with the same number of carbon atoms. Thus, the excess free energy of -1.1 kcal/mol represents the favourable interaction of the cholesterol skeleton with the bilayer phase. This conclusion was confirmed by comparing cholesterol 3-hemisuccinate to oleic acid. Substituting TG for water as the standard state has eliminated the large hydrophobic effect and has permitted us to identify for the first time the subtle binding increment of the steroid ring system. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02114. RP Sandermann, H (reprint author), GSF FORSCHUNGSZENTRUM UMWELT & GESUNDHEIT GMBH,INST BIOCHEM PFLANZENPATHOL,D-85764 OBERSCHLEISSHEIM,GERMANY. FU NIGMS NIH HHS [GM 15904] NR 16 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2760 J9 BBA-LIPID LIPID MET JI Biochim. Biophys. Acta-Lipids Lipid Metab. PD JUN 2 PY 1997 VL 1346 IS 2 BP 158 EP 162 DI 10.1016/S0005-2760(97)00027-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XG918 UT WOS:A1997XG91800006 PM 9219898 ER PT J AU Chueh, H Barnett, GO AF Chueh, H Barnett, GO TI ''Just in time'' clinical information SO ACADEMIC MEDICINE LA English DT Article ID MEDICAL INFORMATION; PHYSICIANS; CARE; QUALITY; NEEDS AB The just-in-time (JIT) model originated in the manufacturing industry as a way to manage parts inventories process so that specific components could be made available at the appropriate times (that is, ''just in time''). This JIT model can be applied to the management of clinical information inventories, so that clinicians can have more immediate access to the most current and relevant information at the time they most need it-when making clinical care decisions. The author discuss traditional modes of managing clinical information, and then describe how a new, JIT model may be developed and implemented, They describe three modes of clinician-information interactions that a JIT model might employ the scope of information that may be made available in a JIT model (global information or local, case-specific information), and the challenges posed by the implementation of such an information-access model, Finally, they discuss how JIT information access may change how physicians practice medicine, various ways JIT information may be delivered, and concerns about the trustworthiness of electronically published and accessed information resources. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Chueh, H (reprint author), MASSACHUSETTS GEN HOSP,COMP SCI LAB,BOSTON,MA 02114, USA. NR 18 TC 63 Z9 63 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1997 VL 72 IS 6 BP 512 EP 517 DI 10.1097/00001888-199706000-00016 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA XE808 UT WOS:A1997XE80800018 PM 9200584 ER PT J AU Rosal, MC Ockene, IS Ockene, JK Barrett, SV Ma, YS Hebert, JR AF Rosal, MC Ockene, IS Ockene, JK Barrett, SV Ma, YS Hebert, JR TI A longitudinal study of students' depression at one medical school SO ACADEMIC MEDICINE LA English DT Article ID GENDER DIFFERENCES; SOCIAL SUPPORT; STRESS; LAW AB Purpose. Using a standardized measure of depression at three assessment points, to examine depression in medical students during their training. Method. Students entering the University of Massachusetts Medical School in the fall in 1987, 1988, and 1989 were mailed a recruitment letter and baseline questionnaire four weeks prior to the start of classes. Subsequent assessments took place in the middles of year 2 and year 4 and included only the students who had participated in the baseline assessment. The baseline assessment included the Center for Epidemiological Studies Depression (CES-D) scale, the Bortner Type A Behavior scale, the Spielberger Trait Anger scale, and the Spielberger Anger Expression scale. In addition, the baseline package included a rating of perceived stress, a demographics questionnaire, and a social-life survey. The follow-up assessments included the CES-D scale, the rating of perceived stress level, and the social-life survey. Analytic methods used were univariate descriptive statistics, correlation, and multiple-linear-regression analyses, two-sample t-tests, analysis of variance, and chi-square tests. Results. Of the initial pool of 300 students, 264 responded at the baseline assessment (88% response rate; 53% men); 171 of these participated in the year-2 assessment (65% response rate; 51% men), and 126 participated in the year-dr assessment (48% response rate; 48% men); a total of 99 students participated in all three assessments. CES-D scares greater than or equal to 80th percentile were obtained for 18% of the entering students. This rose to 39% at year 2 and 31% at year 4 (P = .0001). No gender difference was found at baseline; however, the women experienced higher depression levels than did the men at year 2 (P = .004) and at year 4 (p = .04). Overall, gender and increases in perceived stress (from baseline to year 2) were significant predictors of increased CES-D scores (from baseline to year 2; p = .01 and p = .0001, respectively). For the women, increased perceived stress, anger-in, and frequency of social contacts outside work/school were significant predictors of the magnitude of increases in CES-D scores (baseline to year 2; p = .0001, p = .02, and p = .03, respectively). Conclusion. These preliminary data support the view that, upon entering medical school, students' emotional status resembles that of the general population. However, the rise in depression scores and their persistence over time suggest that emotional distress during medical school is chronic and persistent rather than episodic. Also, the women had more significant increases in depression scores than did the men. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MASSACHUSETTS,SCH MED,PREVENT CARDIOL PROGRAM,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,OFF MED EDUC,WORCESTER,MA 01655. RP Rosal, MC (reprint author), UNIV MASSACHUSETTS,SCH MED,DIV PREVENT & BEHAV MED,55 LAKE AVE N,WORCESTER,MA 01655, USA. OI Ma, Yunsheng/0000-0003-2317-3716 FU NHLBI NIH HHS [1K07 HL01943-01] NR 24 TC 133 Z9 145 U1 3 U2 9 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 1997 VL 72 IS 6 BP 542 EP 546 DI 10.1097/00001888-199706000-00022 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA XE808 UT WOS:A1997XE80800025 PM 9200590 ER PT J AU ArrunateguiCorrea, V Dutt, JE Foster, CS AF ArrunateguiCorrea, V Dutt, JE Foster, CS TI Analysis of T cell receptor V beta gene expression in B cell deficient mice after experimental herpes simplex virus keratitis SO ACTA VIROLOGICA LA English DT Article DE anti-mu antibody; herpes simplex keratitis; T cell receptor; V beta chain ID STROMAL KERATITIS; ANTIGEN RECEPTOR; LYMPHOCYTES; USAGE; RETINITIS AB To examine the importance of B cells in the regulation of the T cell response to herpes simplex virus (HSV) infection, we have analyzed the selection of the T cell receptor (TCR) repertoire in C.B-17 mice that lack B cells (B-mice) compared with age-matched immunocompetent C.B-17 mice, usually resistant to herpes simplex keratitis (HSK). TCR VP transcripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showed that the incidence of HSK was significantly different between untreated (control) and anti-mu antibody (Ab)-treated mice (p <0.0001). Passive transfer of anti-HSV Ab into B-mice, before infection, prevented HSK; transfer of naive B cells allowed HSK to evolve in 50% of these mice. At the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR VP gene expression in eyes, spleen, thymus and lymph nodes (LN) of C.B-17 mice. Preferential utilization of a singleTCR Tb gene was not detected in the course of the disease except in LN, although in resistant mice there were different patterns of mRNA induction in T cells expressing specific TCR Vb elements that were not seen in susceptible mice, namely the lack of expression of V beta 8.1, V beta 8.2 and V beta 8.3 in eyes, the expression of V beta 7 in spleen, and the lack expression of V beta 6 and V beta 13 in thymus. These observations together with previous findings suggest that at the level of protein production, anti-HSV Ab not only can provide protection against HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immune system in B- mice is manifested by dramatic changes in TCR V beta usage at the molecular level. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RHOADS MOL IMMUNOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. NR 20 TC 2 Z9 3 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57, NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0001-723X J9 ACTA VIROL JI Acta Virol. PD JUN PY 1997 VL 41 IS 3 BP 145 EP 152 PG 8 WC Virology SC Virology GA YA570 UT WOS:A1997YA57000004 PM 9385402 ER PT J AU Pontius, AA AF Pontius, AA TI Homicide linked to moderate repetitive stresses kindling limbic seizures in 14 cases of limbic psychotic trigger reaction SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article ID FRONTAL-LOBE; QUESTIONABLE ASPECTS; EPILEPTIC SEIZURES; SYSTEM; NARRATIVES; DISORDER; STIMULI AB Sixteen criteria are discussed regarding a recently proposed new syndrome: Limbic Psychotic Trigger Reaction (LPTR). Included are well-remembered, motiveless, unplanned homicidal acts, committed with flat affect, brief psychosis, and autonomic arousal. LPTR implicates partial limbic seizures, which do not quantitatively impair consciousness and memory. Such seizures are likely ''kindled'' by highly individualized specific trigger stimuli, reviving past repetitive mild to moderate stresses. (C) 1997 Elsevier Science Ltd. RP Pontius, AA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT APS,55 FRUIT ST,BOSTON,MA 02114, USA. NR 63 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD SUM PY 1997 VL 2 IS 2 BP 125 EP 141 DI 10.1016/S1359-1789(96)00002-X PG 17 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA WW154 UT WOS:A1997WW15400002 ER PT J AU Bird, DA Kabakibi, A Laposata, M AF Bird, DA Kabakibi, A Laposata, M TI The distribution of fatty acid ethyl esters among lipoproteins and albumin in human serum SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE lipids; ethanol; fatty acids; FAEE; lipoprotein ID ETHANOL-METABOLISM AB Fatty acid ethyl esters (FAEEs) are nonoxidative products of ethanol metabolism and have been implicated as mediators of ethanol-induced organ damage, Previous studies have demonstrated that FAEEs bind to lipoproteins and albumin in human plasma after ethanol ingestion. Analysis of human serum with varying blood ethanol levels and endogenously formed FAEEs revealed a positive correlation between serum FAEE concentration and the percentage of FAEEs associated with lipoproteins, predominantly very low density and low density lipoprotein. Similar results were obtained when increasing amounts of FAEEs were added to serum with zero blood ethanol. Additional studies indicated that free fatty acids and FAEEs do not compete for binding to albumin or lipoproteins. Data support the conclusion that the distribution of FAEEs among their carriers in the serum is dependent on serum FAEE concentration. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK37454] NR 14 TC 18 Z9 18 U1 0 U2 0 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 JUN PY 1997 VL 21 IS 4 BP 602 EP 605 DI 10.1097/00000374-199706000-00006 PG 4 WC Substance Abuse SC Substance Abuse GA XE768 UT WOS:A1997XE76800006 PM 9194911 ER PT J AU Leonhard, C Gastfriend, DR Tuffy, LJ Neill, J Plough, A AF Leonhard, C Gastfriend, DR Tuffy, LJ Neill, J Plough, A TI The effect of anonymous vs. nonanonymous rating conditions on patient satisfaction and motivation ratings in a population of substance abuse patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE motivation; satisfaction; anonymous; confidential; methodology ID ALCOHOL; PREVENTION; VALIDITY; AIDS AB Patient self-report in evaluations involving alcohol and other drug abuse has generally been found to be reliable and valid. However, little is known about the variables associated with greater or lesser degrees of reliability and validity. This study was conducted to determine how motivation and satisfaction ratings obtained under anonymous conditions would compare with ratings obtained under nonanonymous conditions. Over the course of 12 months, 1397 subjects in the Boston Target Cities Project were assigned to either confidential or fully anonymous data collection procedures in an interrupted time-series design. Anonymity had either no effect on ratings or accounted for <1% of the variance. Satisfaction and motivation ratings obtained under confidential conditions are probably as reliable and valid as ratings obtained under fully anonymous conditions. C1 MASSACHUSETTS GEN HOSP,ADDICT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BOSTON OFF TREATMENT IMPROVEMENT,BOSTON,MA. FU PHS HHS [1-U88-T100022] NR 17 TC 5 Z9 5 U1 2 U2 2 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 JUN PY 1997 VL 21 IS 4 BP 627 EP 630 PG 4 WC Substance Abuse SC Substance Abuse GA XE768 UT WOS:A1997XE76800010 PM 9194915 ER PT J AU Tanaka, S Guth, PH Carryl, OR Kaunitz, JD AF Tanaka, S Guth, PH Carryl, OR Kaunitz, JD TI Cytoprotective effect of bismuth subsalicylate in indomethacin-treated rats is associated with enhanced mucus bismuth concentration SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTRIC-MUCOSAL LESIONS; INTRACELLULAR PH; ALKALINE SECRETION; GEL THICKNESS; IN-VIVO; SUBCITRATE; PATHOGENESIS; PROSTAGLANDIN-E2; STIMULATION; MECHANISM AB Background: Bismuth compounds prevent gastric injury from the short-term administration of nonsteroidal antiinflammatory drugs. We studied the mechanisms underlying the gastroprotective actions of bismuth subsalicylate against indomethacin-induced injury in rats. Methods: An in vivo microscopic technique was used in which acid output, surface cell intracellular pH (pH(i)), gastric mucus gel thickness and mucosaol blood flow were measured simultaneously. Concentrations of bismuth in mucus were measured by atomic absorption. Results: Indomethacin (60 mg/kg) significantly thinned the mucus gel layer and augmented the decrease of pH(i) during luminal acid superfusion, consistent with a weakened gastric mucosal barrier to acid. Bismuth subsalicylate partially reversed this effect of indomethacin on pH(i), consistent with gastroprotection. Neither a prostaglandin-inhibiting but non-injurious dose of indomethacin (5 mg/kg), bismuth subsalicylate, or their combination affected mucus gel thickness or pH(i) homeostasis. In separate experiments, indomethacin (60 mg/kg) significantly increased gastric mucus bismuth concentration in rats given bismuth subsalicylate. Conclusion: Bismuth accumulation in the gastric mucus during the evolution of mucosal injury may play an important role in the gastroprotective effect of bismuth subsalicylate against indomethacin injury. C1 W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. PROCTER & GAMBLE CO,HLTH CARE PROD,CINCINNATI,OH. NR 33 TC 7 Z9 8 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUN PY 1997 VL 11 IS 3 BP 605 EP 612 DI 10.1046/j.1365-2036.1997.00170.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA XF543 UT WOS:A1997XF54300026 PM 9218090 ER PT J AU Rocco, FJ CroninGolomb, A Lai, F AF Rocco, FJ CroninGolomb, A Lai, F TI Alzheimer-like visual deficits in Down syndrome SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT Gatlinburg Conference on Research and Theory in Mental Retardation and Developmental Disabilities CY MAR, 1996 CL GATLINBURG, TN DE Alzheimer disease; Down syndrome; vision ID DOWNS-SYNDROME; CONTRAST SENSITIVITY; DISEASE; DEMENTIA; DYSFUNCTION; NEUROPATHOLOGY; VISION; AGE AB Patients with Alzheimer disease (AD) show visual impairments in color discrimination (blue hues), stereoacuity, and contrast sensitivity. We asked whether the AD-type visual profile occurs in Down syndrome (DS) in light of the fact that AD neuropathology is present in DS by age 40. We tested 22 adults with DS and 18 adults with mental retardation of non-DS etiology (MR). DS subjects made more tritanomalous errors on the test of color vision than predicted by chance (p < 0.05), indicating a deficiency in the discrimination of short wavelengths (blue hues) but not more of other types of hue discrimination errors. DS subjects had higher stereoacuity thresholds than MR subjects (p < 0.01) and reduced contrast sensitivity across the frequency range (p < 0.01). Taken together, the results point to AD-like visual deficits in DS. Like classic AD, DS may be associated with pathological changes in the parastriate and peristriate visual cortex. DS performance was not correlated with age, suggesting that in individual subjects, the AD-like visual deficits may present prior to and independent of age-associated dementia. C1 BOSTON UNIV, DEPT PSYCHOL, BOSTON, MA 02215 USA. CHILDRENS HOSP, DEPT PSYCHIAT, BOSTON, MA 02115 USA. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC, DIV MED GENET, WALTHAM, MA 02154 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. MCLEAN HOSP, LABS MOL NEUROSCI, BELMONT, MA 02178 USA. NR 59 TC 5 Z9 5 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 EI 1546-4156 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUN PY 1997 VL 11 IS 2 BP 88 EP 98 DI 10.1097/00002093-199706000-00005 PG 11 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA XF252 UT WOS:A1997XF25200005 PM 9194955 ER PT J AU Dreicer, R Propert, KJ Kuzel, T Kirkwood, JM ODwyer, PJ Loehrer, PJ AF Dreicer, R Propert, KJ Kuzel, T Kirkwood, JM ODwyer, PJ Loehrer, PJ TI A phase II trial of edatrexate in patients with advanced renal cell carcinoma - An Eastern Cooperative Oncology Group Study SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE edatrexate; renal cell carcinoma ID RECURRENT; TOXICITY AB We performed a Phase II trial of edatrexate in 44 chemotherapy-naive patients with advanced renal cell carcinoma. Prior therapy with one biological-response modifier was permitted. Most patients had multiple sites of metastatic disease and were considered to have a poor prognosis using Eastern Cooperative Oncology Group criteria. Edatrexate was administered intravenously at a dose of 80 mg/m(2) weekly with 5 weeks of therapy considered one cycle. Oral cryotherapy using ice chips was administered before each edatrexate dose. Thirty-seven patients were eligible and evaluable for toxicity and response. Two patients obtained a partial response, for an overall response rate of 5.4% (95% confidence interval of 0.6%, 18.2%); one patient remained in remission at 26+ months. Three treatment-related deaths occurred. Toxicity was severe, with stomatitis, myelosuppression, and other gastrointestinal side effects most prominent. Edatrexate in this dose and schedule has minimal activity in advanced renal cell carcinoma and is toxic. C1 DANA FARBER CANC CTR,BOSTON,MA. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV PITTSBURGH,PITTSBURGH,PA. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. INDIANA UNIV,INDIANAPOLIS,IN 46204. RP Dreicer, R (reprint author), UNIV IOWA,DEPT MED,200 HAWKINS DR,IOWA CITY,IA 52242, USA. FU NCI NIH HHS [CA23318, CA17145, CA18281] NR 10 TC 12 Z9 13 U1 1 U2 1 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 JUN PY 1997 VL 20 IS 3 BP 251 EP 253 DI 10.1097/00000421-199706000-00008 PG 3 WC Oncology SC Oncology GA XA556 UT WOS:A1997XA55600008 PM 9167747 ER PT J AU Writer, JV Kang, H Lee, KL Kelley, PW AF Writer, JV Kang, H Lee, KL Kelley, PW TI Pre-war hospitalization as a risk factor for enrollment on a Persian Gulf Registry. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. US DEPT VET AFFAIRS,WASHINGTON,DC 20036. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 1997 VL 145 IS 11 SU S BP 340 EP 340 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XA896 UT WOS:A1997XA89600338 ER PT J AU Yousfi, MM ElZimaity, HMT Cole, RA Genta, RM Graham, DY AF Yousfi, MM ElZimaity, HMT Cole, RA Genta, RM Graham, DY TI Comparison of agar gel (CLOtest) or reagent strip (PyloriTek) rapid urease tests for detection of Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CAMPYLOBACTER-PYLORI; DIAGNOSTIC-TESTS; COLONIZATION; GASTRITIS; HISTOLOGY; DISEASE; CULTURE AB Objective: Rapid urease tests (RUTs) are used commonly as a convenient method to detect Helicobacter pylori infection, New rapid tests have been commercially available with promotional literature suggesting enhanced utility, We compared CLOtest to a new reagent strip RUT, PyloriTek, Methods: Gastric antral mucosal biopsy specimens were obtained from 102 patients for comparison between CLOtest and PyloriTek (204 specimens), Biopsy specimens obtained from a nearby area were stained using the Genta stain for determination of H. pylori status, The RUT to be used first was selected randomly, Results: Sixty-five of the 102 patients had peptic ulcer disease, two had gastric cancer, and 35 had dyspepsia; 61 patients had active H. pylori infection, There were one false-negative and three false-positive CLOtest results, compared with one false-negative and 13 false-positive PyloriTek results (p < 0.02 for incorrect categorization with PyloriTek), Sensitivity and specificity were 98 and 92% compared with 98 and 68% for CLOtest and PyloriTek, respectively, An erroneous categorization of H. pylori status occurred in 3.9% (95% confidence interval [CI]: 1-9.7%) with CLOtest compared with 13.7% (95% CI: 7.7-22%) with PyloriTek, When the PyloriTek was scored at 1 h (0-1 h) after obtaining the specimen, the accuracy improved; erroneous categorization of H. pylori status occurred in only 2.9% (95% CI: 0.6-8.3%), Conclusion: Used according to manufacturer instructions, the new reagent strip RUT PyloriTek has too many false-positive results for use in a clinical situation, In contrast, when the test was interpreted within 1 h, accuracy was comparable to that of CLOtest. C1 VET AFFAIRS MED CTR 111D,DEPT MED,HOUSTON,TX 77030. VET AFFAIRS MED CTR,DEPT PATHOL,HOUSTON,TX 77030. VET AFFAIRS MED CTR,DIV MOL VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. NR 26 TC 19 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 1997 VL 92 IS 6 BP 997 EP 999 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XC373 UT WOS:A1997XC37300018 PM 9177518 ER PT J AU Small, GW AF Small, GW TI Geriatric psychiatry: Key research topics for clinicians - Murphy,E, Alexopoulos,G SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Book Review C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,GERIATR PSYCHIAT FELLOWSHIP TRAINING PROGRAM,LOS ANGELES,CA 90024. RP Small, GW (reprint author), UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024, 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 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD SUM PY 1997 VL 5 IS 3 BP 271 EP 272 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA XJ829 UT WOS:A1997XJ82900014 ER PT J AU Kriebel, D Sama, SR Woskie, S Christiani, DC Eisen, EA Hammond, SK Milton, DK Smith, M Virji, MA AF Kriebel, D Sama, SR Woskie, S Christiani, DC Eisen, EA Hammond, SK Milton, DK Smith, M Virji, MA TI A field investigation of the acute respiratory effects of metal working fluids .1. Effects of aerosol exposures SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE metal working; spirometry; dust; bronchoconstriction; epidemiology; occupational; exposure; oil mist ID OCCUPATIONAL EPIDEMIOLOGY; AUTOMOBILE WORKERS; SYMPTOMS AB A study of cross-shift change in pulmonary function was conducted among workers exposed to metal working fluids (MWF) in an automobile parts manufacturing company. Three hundred eight-six workers (216 machinists exposed to straight or soluble MWFs, and 170 nonmacinists) were studied for 1 day, performing spirometry at the beginning and end of their shift. Airborne concentrations of inhalable particulate, culturable bacteria, and endotoxin were measured. We observed an approximately threefold increase in the incidence of 5% or greater cross-shift decrement in forced expiratory volume during the first second among those with exposures above about 0.15 mg/m(3), compared to those with exposures below about 0.08 mg/m(3). There was some evidence that chronic respiratory symptoms were more prevalent among machinists than among nonmachinists, notably for chronic cough. Baseline FEB1 was about 3% lower on average among those with soluble MWF exposure compared to nonmachinists. These findings are consistent with earlier studies showing respiratory effects of MWFs. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM CRIT CARE UNIT,BOSTON,MA. UNIV MASSACHUSETTS,MED CTR,DEPT FAMILY & COMMUNITY MED,BOSTON,MA 02125. RP Kriebel, D (reprint author), UNIV LOWELL,DEPT WORK ENVIRONM,1 UNIV AVE,LOWELL,MA 01854, USA. RI Milton, Donald/G-3286-2010 OI Milton, Donald/0000-0002-0550-7834 NR 25 TC 34 Z9 36 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1997 VL 31 IS 6 BP 756 EP 766 DI 10.1002/(SICI)1097-0274(199706)31:6<756::AID-AJIM13>3.0.CO;2-X PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WW145 UT WOS:A1997WW14500013 PM 9131232 ER PT J AU Macones, GA Asch, DA AF Macones, GA Asch, DA TI Costs, true costs, and whose costs in economic analyses in medicine? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID BLOOD ACID-BASE; GAS AB Cost-effectiveness analyses of clinical practices are becoming more common in the development of health policy. However such analyses can be based on misconceptions and flawed assumptions, leading to flawed policies, We argue that such is the case with the recent recommendations for routine measurement of umbilical cord gases at delivery, a policy based on the assumption that this clinical strategy will pay for itself by reduced malpractice awards, As we demonstrate, this argument reflects the physicians' perspective, not that of society or of patients. It also ignores the fact that malpractice awards are largely transfer payments, not costs of healthcare. C1 UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,SCH MED,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. RP Macones, GA (reprint author), UNIV PENN,CTR CLIN EPIDEMIOL & BIOSTAT,ROOM 901,BLOCKLEY HALL,423 GUARDIAN DR,PHILADELPHIA,PA 19104, USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 SN 1088-0224 J9 AM J MANAG C JI Am. J. Manag. Care PD JUN PY 1997 VL 3 IS 6 BP 915 EP 917 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA YB220 UT WOS:A1997YB22000006 PM 10170295 ER PT J AU Bass, EB Fortin, AH Morrison, G Wills, S Mumford, LM Goroll, AH AF Bass, EB Fortin, AH Morrison, G Wills, S Mumford, LM Goroll, AH TI National survey of Clerkship Directors in Internal Medicine on the competencies that should be addressed in the medicine core clerkship SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID EDUCATION; PHYSICIANS AB PURPOSE: TO prioritize competencies that should be addressed in the medicine core clerkship, assess factors influencing this prioritization, and estimate the percentage of clerkship time that should be devoted to inpatient versus outpatient care. METHODS: A national survey of the Clerkship Directors in Internal Medicine (CDIM) was used. Using explicit criteria, respondents assigned priority scores, on a 1 to 5 scale, to 17 general competencies and 60 disease-specific clinical competencies pertinent to care of adult patients in inpatient. ambulatory, intensive care, and emergency settings. RESULTS: Ninety-three (75%) of 124 CDIM members responded. The highest mean priority scores were assigned to 6 general competencies: case presentation skills (4.65), diagnostic decision-making (4.64), history and physical diagnosis (4.61), test interpretation (4.47), communication with patients (4.35), and therapeutic decision-making (4.12). Disease-specific clinical competency areas receiving the highest mean priority scores were: hypertension (4.57), coronary disease (4.53), diabetes mellitus (4.45), heart failure (4.42), pneumonia (4.39), chronic obstructive pulmonary disease (4.26), acid-base/electrolyte disorders (4.19), and acute chest pain (4.08). Priorities for general competencies were moderately correlated with importance to the practice of general internists (mean Spearman rho 0.49) and with importance to students pursuing careers outside internal medicine (mean Spearman rho 0.45), but only weakly correlated with the adequacy with which a competency was addressed in other parts of the curriculum. Respondents' mean recommended allocation of clerkship time was: 52% inpatient, 33% ambulatory care, 8% intensive care, and 7% emergency medicine. This time allocation did not differ by any characteristics of respondents. CONCLUSION: There is consensus among medicine clerkship directors that the medicine core clerkship should emphasize fundamental competencies and devote at least one third of the time to clinical competencies pertinent to ambulatory care. (C) 1997 by Excerpta Medicine, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD 21205. HOSP UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA. NR 31 TC 32 Z9 34 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1997 VL 102 IS 6 BP 564 EP 571 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XG446 UT WOS:A1997XG44600011 PM 9217672 ER PT J AU Fishman, SM Caneris, OA Stojanovic, MP Borsook, D AF Fishman, SM Caneris, OA Stojanovic, MP Borsook, D TI Intravenous lidocaine for treatment-resistant pruritus SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ITCH; HYPERALGESIA; CAPSAICIN RP Fishman, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 18 TC 14 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 1997 VL 102 IS 6 BP 584 EP 585 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XG446 UT WOS:A1997XG44600014 PM 9217675 ER PT J AU Grunwald, JE DuPont, J Dreyer, EB AF Grunwald, JE DuPont, J Dreyer, EB TI Effect of chronic nitrate treatment on retinal vessel caliber in open-angle glaucoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; LASER DOPPLER VELOCIMETRY; BLOOD-FLOW; CIRCULATION; MELLITUS; DIAMETER; TENSION AB PURPOSE: A recent report has suggested that nitrate therapy may delay the progression of glaucomatous damage. To investigate the mechanism that may mediate this effect, we sought to determine whether nitrate therapy is associated with retinal vasodilatation in patients with glaucoma. METHODS: Retinal venous and arterial diameters were determined from color fundus photographs of the optic nerve head obtained during a retrospective study designed to investigate any potential effects of chronic nitrate treatment on the progression of glaucomatous pathology. Fourteen eyes of 14 patients who were receiving chronic nitrate therapy for systemic diseases unrelated to glaucoma were randomly selected, Vascular measurements were compared with those of 15 eyes of 15 control patients with glaucoma who did not receive any nitrate therapy. RESULTS: In comparison with control patients, nitrate treated patients showed significant average vasodilatation of 17% (P = .008) and 13% (P = .01) in the superior and inferior temporal retinal veins, respectively. A 5% increase in average retinal arterial diameter was also detected, but this was not statistically significant. CONCLUSION: Chronic nitrate treatment is associated with retinal venous dilatation in patients with glaucoma. Although not assessed in this study, it is possible that a protective effect of nitrates may be mediated by a vasoactive effect leading to improved perfusion of the retina and perhaps the optic nerve head, in a similar fashion to what has been observed in the circulation of the heart. Additional studies of the effect of nitrates on the ocular circulation are needed, however, to support this speculation. C1 HARVARD UNIV,DEPT OPHTHALMOL,MASSACHUSETTS EYE & EAR INFIRM,GLAUCOMA CONSULTAT SERV,CAMBRIDGE,MA 02138. RP Grunwald, JE (reprint author), UNIV PENN,SCH MED,SCHEIE EYE INST,DEPT OPHTHALMOL,51 N 39TH ST,PHILADELPHIA,PA 19104, USA. FU NEI NIH HHS [R01-EY10009] NR 31 TC 21 Z9 22 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 JUN PY 1997 VL 123 IS 6 BP 753 EP 758 PG 6 WC Ophthalmology SC Ophthalmology GA XC779 UT WOS:A1997XC77900004 PM 9535618 ER PT J AU Kim, RY Hu, LK Flotte, TJ Gragoudas, ES Young, LHY AF Kim, RY Hu, LK Flotte, TJ Gragoudas, ES Young, LHY TI Digital angiography of experimental choroidal melanomas using benzoporphyrin derivative SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MOUSE-TUMOR MODEL; PHOTODYNAMIC THERAPY; BIODISTRIBUTION; PHOTOSENSITIZER; FLUORESCENCE; CANCER; TISSUE; BPD AB PURPOSE: To examine benzoporphyrin derivative angiography as a modality for studying photosensitizer biodistribution in experimental choroidal melanomas. METHODS: A liposomal preparation of benzoporphyrin derivative was used in this study. Digital benzoporphyrin derivative angiograms were performed in 10 rabbits (six for experimental choroidal melanomas, two for normal choroids, and two for irides) using a Topcon ImageNet H1024 digital imaging system, a Kodak Megaplus video camera, and a Topcon TRC-50-VT fundus camera, Only one eye from each rabbit was used. Filters specifically designed for benzoporphyrin derivative (peak absorption at 580 nm and peak emission at 695 nm) were used. Benzoporphyrin derivative (1 mg/kg) was injected into an ear vein while images of tumor, normal choroid, or iris were being obtained. Follow-up images were obtained during the first 3 hours and at 24 hours after injection, Fluorescence microscopy was performed in all 10 rabbits using 1 mg/kg of benzoporphyrin derivative. Tumor-bearing eyes were enucleated at the same time points that angiograms were performed, and the two sets of results were com pared for maximum dye accumulation. RESULTS: Digital angiography demonstrated that maximal benzoporphyrin derivative fluorescence occurred in tumors 15 to 45 minutes after injection. Fluorescence photometry corroborated these results. CONCLUSION: Photosensitizer angiography is a valid modality for determining the optimum treatment time for photodynamic therapy. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. FU NEI NIH HHS [EY10975-01] NR 20 TC 8 Z9 12 U1 0 U2 1 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 JUN PY 1997 VL 123 IS 6 BP 810 EP 816 PG 7 WC Ophthalmology SC Ophthalmology GA XC779 UT WOS:A1997XC77900011 PM 9535625 ER PT J AU Watkins, LM Remulla, HD Rubin, PAD AF Watkins, LM Remulla, HD Rubin, PAD TI Orbital granulocytic sarcoma in an elderly patient SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report a 71-year-old woman with acute myelogenous leukemia in remission who developed orbital granulocytic sarcoma. METHODS: The patient was referred for acute proptosis and decreased vision of the right eye. Computed tomography of the orbits demonstrated a right extraconal mass compressing the optic nerve, A right lateral orbitotomy was performed, and a portion of the mass was excised for diagnostic purposes and orbital decompression. RESULTS: Histopathologic and immunohistochemical evaluation disclosed orbital granulocytic sarcoma, With chemotherapy and radiation, vision remained stable and right proptosis resolved. CONCLUSIONS: Orbital granulocytic sarcoma is usually diagnosed in children with a history of acute myelogenous leukemia, This case demonstrated that this entity may also occur rarely in older patients with a history of acute myelogenous leukemia. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OPHTHALM PLAST & ORBITAL SURG SERV,BOSTON,MA 02114. NR 5 TC 11 Z9 12 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 JUN PY 1997 VL 123 IS 6 BP 854 EP 856 PG 3 WC Ophthalmology SC Ophthalmology GA XC779 UT WOS:A1997XC77900027 PM 9535641 ER PT J AU Shioda, T Munn, LL Fenner, MH Jain, RK Isselbacher, KJ AF Shioda, T Munn, LL Fenner, MH Jain, RK Isselbacher, KJ TI Early events of metastasis in the microcirculation involve changes in gene expression of cancer cells - Tracking mRNA levels of metastasizing cancer cells in the chick embryo chorioallantoic membrane SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MURINE MELANOMA-CELLS; TISSUE INHIBITOR; MESSENGER-RNA; TUMOR-CELLS; HEMATOGENOUS METASTASIS; C-FOS; MICE; ANGIOGENESIS; ACTIVATION AB The early events of metastasis involve multiple interactions between cancer cells and the host microcirculation during cancer cell arrest, adhesion, and extravasation. These interactions may lend to changes in gene expression of the metastasizing cancer cells, althorgh such changes have never been demonstrated directly, To test this hypothesis, B16-F10 murine melanoma cells were injected intravenously into the chick embryo chorioallantoic membrane (CAM), and mRNA levels in the metastasizing cancer cells were evaluated by species-specific reverse transcription polymerase chain reaction. Unlike standard mouse models of experimental metastasis, the CAM model showed successful extravasation of a large number of the arrested cancer cells in the CAM microcirculation without significant cancer cell death, providing a unique opportunity to keep track of mRNA levels in cancer cells during the early phases of metastasis, Using this model, we were able to demonstrate directly the temporal induction of cancer cell genes that potentially affect metastatic efficiency, namely, Fos (5 to 60 minutes after injection), vascular permeability factor (4 to 7 hours), and urokinase plasminogen activator (>9 hours). In conclusion, using the CAM system, we have observed an alteration of gene expression in cancer cells iii the early phases of metastasis, most likely as a consequence of host-cancer cell interactions. These changes may influence the metastatic behavior of cancer cells. C1 MASSACHUSETTS GEN HOSP E,DEPT RADIAT ONCOL,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP E,EDWIN L STEELE LAB,CHARLESTOWN,MA. RP Shioda, T (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,LAB TUMOR BIOL,CHARLESTOWN,MA 02129, USA. RI Fenner, Martin/A-7225-2008; Munn, Lance/L-3950-2016 OI Fenner, Martin/0000-0003-1419-2405; Munn, Lance/0000-0003-0698-7232 NR 59 TC 21 Z9 23 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1997 VL 150 IS 6 BP 2099 EP 2112 PG 14 WC Pathology SC Pathology GA XB700 UT WOS:A1997XB70000021 PM 9176401 ER PT J AU CoupayeGerard, B Zuckerman, JB Duncan, P Bortnik, A Avery, DI Ernst, SA Kleyman, TR AF CoupayeGerard, B Zuckerman, JB Duncan, P Bortnik, A Avery, DI Ernst, SA Kleyman, TR TI Delivery of newly synthesized Na+-K+-ATPase to the plasma membrane of A6 epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE sodium pump; sorting; intracellular trafficking; biotin; sodium-potassium adenosinetriphosphatase ID CELL-SURFACE DELIVERY; INTRACELLULAR-TRANSPORT; BETA-SUBUNITS; ALPHA-SUBUNIT; IMMUNOCYTOCHEMICAL LOCALIZATION; CYTOPLASMIC DOMAIN; KIDNEY-CELLS; MDCK CELLS; NA,K-ATPASE; EXPRESSION AB Na+-K+-ATPase is localized to the basolateral cell surface of most epithelial cells. Conflicting results regarding the intracellular trafficking of Na+-K+- ATPase in Madin-Darby canine kidney cells have been reported, with delivery to both apical and basolateral membranes or exclusively to the basolateral cell surface. We examined the delivery and steady-state distribution of Na+-K+-ATPase in the amphibian epithelial cell line A6 using an antibody raised against Na+-K+-ATPase alpha-subunit and sulfo-N-hydroxysuccinimidobiotin to tag cell surface proteins. The steady-state distribution of the Na+-K+-ATPase was basolateral, as confirmed by immunocytochemistry. Delivery of newly synthesized Na+-K+-ATPase to the cell surface was examined using [S-35]methionine and [S-35]cysteine in a pulse-chase protocol. After a 20-min pulse, the alpha-subunit and core glycosylated beta-subunit were present at both apical and basolateral cell surfaces. The alpha-subunit and core glycosylated beta-subunit delivered to the apical cell surface were degraded within 2 h. Mature alpha/beta-heterodimer was found almost exclusively at the basolateral surface after a 1- to 24-h chase. These data suggest that immature Na+-K+-ATPase alpha-subunit and core glycosylated beta-subunits are not retained in the endoplasmic reticulum of A6 cells and apparently lack sorting signals. Mature Na+-K+-ATPase is targeted to the basolateral surface, suggesting that basolateral targeting of the protein is conformation dependent. C1 VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT PHYSIOL, PHILADELPHIA, PA 19104 USA. UNIV MICHIGAN, DEPT ANAT & CELL BIOL, ANN ARBOR, MI 48109 USA. NR 30 TC 11 Z9 12 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 JUN PY 1997 VL 272 IS 6 BP C1781 EP C1789 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XF782 UT WOS:A1997XF78200004 ER PT J AU Vogt, JA Yarmush, DM Yu, YM Zupke, C Fischman, AJ Tompkins, RG Burke, JF AF Vogt, JA Yarmush, DM Yu, YM Zupke, C Fischman, AJ Tompkins, RG Burke, JF TI TCA cycle flux estimates from NMR- and GC-MS-determined [C-13]glutamate isotopomers in liver SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE carbon-13 nuclear magnetic resonance spectroscopy; mathematical model; tricarboxylic acid cycle ID TRICARBOXYLIC-ACID CYCLE; PERFUSED-RAT-LIVER; GLUCONEOGENESIS; METABOLISM; LACTATE; PLASMA; HUMANS; BRAIN; C-13 AB Infusion of C-13-labeled lactate into rabbits and the subsequent measurement of glutamate isotopomers by C-13 nuclear magnetic resonance (NMR) spectroscopy enables one to calculate relative flow rates associated with the tricarboxylic acid (TCA) cycle, albeit with a lower precision than one would obtain using a perfused organ. Two factors contribute to the lower precision in the determination of relative flow rates for the in vivo system: 1) a poorly defined pyruvate input and 2) low levels of C-13-enriched oxaloacetate and acetyl-CoA isotopomers, which give rise to weaker glutamate isotopomer NMR signals. To help overcome these limitations, we introduce a procedure to 1) include experimental data from gas chromatography-mass spectrometry (GC-MS) and 2) account for the uncertainty in the labeling of the input to pyruvate by treating the labeling as a measurement that is subject to measurement error. The effects of the uncertainties in the input labeling, NMR data, and MS data are evaluated via a Monte Carlo method. The change in the precision of the relative fluxes for the cases of high/low NMR and high/low MS precision is given. An uncertainty in the lactate measurements of up to 10% does not add significantly to the imprecision of the relative flow rates. C1 HARVARD UNIV, TRAUMA SERV,MASSACHUSETTS GEN HOSP,DEPT SURG, MED SCH, BOSTON, MA 02114 USA. UNIV ULM, KLINIKUM ANAESTHESIOGIE, D-89070 ULM, GERMANY. NR 22 TC 14 Z9 14 U1 1 U2 4 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 JUN PY 1997 VL 272 IS 6 BP C2049 EP C2062 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XF782 UT WOS:A1997XF78200033 ER PT J AU Yu, X Alpert, NM Lewandowski, ED AF Yu, X Alpert, NM Lewandowski, ED TI Modeling enrichment kinetics from dynamic C-13-NMR spectra: Theoretical analysis and practical considerations SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE tricarboxylic acid cycle; glutamate; carbon isotope; kinetic analysis; nuclear magnetic resonance spectroscopy ID CITRIC-ACID CYCLE; NUCLEAR-MAGNETIC-RESONANCE; NMR-SPECTROSCOPY; INTACT HEARTS; RAT HEARTS; FLUX; GLUTAMATE; GLYCOLYSIS; MYOCARDIUM; PATHWAYS AB Measurements of oxidative metabolism in the heart from dynamic C-13 nuclear magnetic resonance (NMR) spectroscopy rely on C-13 turnover in the NMR-detectable glutamate pool. A kinetic model was developed for the analysis of isotope turnover to determine tricarboxylic acid cycle flux ((V) over dot(TCA)) and the interconversion rate between alpha-ketoglutarate and glutamate (F-1) by fitting the model to NMR data of glutamate enrichment. The results of data fitting are highly reproducible when the noise level is within 10%, making this model applicable to single or grouped experiments. The values for (V) over dot(TCA) and F-1 were unchanged whether obtained from least-squares fitting of the model to mean experimental enrichment data with standard deviations in the cost function ((V) over dot(TCA)) = 10.52 mu mol.min(-1).g dry wt(-1), F-1 = 10.67 mu mol min(-1).g dry wt(-1)) or to the individual enrichment values for each heart with the NMR noise level in the cost function (V) over dot(TCA) = 10.67 mu mol.min(-1).g dry wt(-1), F-1 = 10.18 mu mol.min(-1).g dry wt(-1)). Computer simulation and theoretical analysis indicate that glutamate enrichment kinetics are insensitive to the fractional enrichment of acetyl-CoA and changes in small intermediate pools (<1 mu mol/g dry wt). Therefore, high-resolution NMR analysis of tissue extracts and biochemical assays for intermediates at low concentrations are unnecessary. However, a high correlation between (V) over dot(TCA) and F-1 exists, as anticipated from competition for alpha-ketoglutarate, which indicates the utility of introducing independent experimental constraints into the data fitting for accurate quantification. C1 MASSACHUSETTS GEN HOSP, NUCL MAGNET RESONANCE CTR, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, POSITRON EMISS TOMOG LAB, DEPT RADIOL, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. NR 27 TC 40 Z9 40 U1 0 U2 0 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 JUN PY 1997 VL 272 IS 6 BP C2037 EP C2048 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA XF782 UT WOS:A1997XF78200032 ER PT J AU Lloyd, KCK Amirmoazzami, S Friedik, F Chew, P Walsh, JH AF Lloyd, KCK Amirmoazzami, S Friedik, F Chew, P Walsh, JH TI Somatostatin inhibits gastrin release and acid secretion by activating sst(2) in dogs SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE somatostatin receptors; stomach; G cells ID FAT-INDUCED INHIBITION; PERFUSED RAT STOMACH; MONOCLONAL-ANTIBODY IMMUNONEUTRALIZATION; ENTEROCHROMAFFIN-LIKE CELLS; HISTAMINE-RELEASE; PRIMARY CULTURE; INTESTINAL FAT; RECEPTOR SUBTYPE; PARIETAL-CELLS; MUCOSAL CELLS AB Somatostatin is a potent inhibitor of gastrin-stimulated acid secretion by activation of somatostatin receptor type 2 (sst(2)) in vivo, probably in part by blocking gastrin-stimulated histamine release from enterochromaffin-like cells expressing sst(2). We propose that activation of sst(2) may also regulate meal-stimulated acid secretion by blocking gastrin release from antral G cells. Using peptide analogs relatively selective for sst(2) (NC-8-12), sst(3) (BIM-23058), and sst(5) (BIM-23052), we tested this hypothesis in two ways: first, in vivo by measuring plasma gastrin release during meal-stimulated acid secretion in dogs, and second, in vitro by measuring bombesin-stimulated gastrin release from an enriched culture of canine antral G cells. In vivo, a low dose (0.05 nmol.kg(-1).h(-1)) of NC-8-12 inhibited acid secretion 56 +/- 16% without blocking gastrin release. A higher dose (1 nmol.kg(-1).h(-1)) of NC-8-12 abolished acid secretion and inhibited gastrin release by 61 +/- 4%, whereas the highest dose (5 nmol.kg(-1).h(-1)) inhibited gastrin release by 84 +/- 3%. Only the highest doses (5 nmol.kg(-1).h(-1)) of BIM-23058 and BIM-23052 significantly inhibited gastrin release and acid secretion. In vitro, NC-8-12 (10(-9) M) reduced bombesin-stimulated gastrin release from antral G cells by 49 +/- 5%, whereas BIM-23058 and BIM-23052 were at least 100-fold less effective. These results indicate that somatostatin activation of sst(2), but not sst(3) Or sst(5), is the major pathway for somatostatin-induced inhibition of meal-stimulated gastrin release and acid secretion. C1 W LOS ANGELES VET AFFAIRS MED CTR, RES SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, CURE, DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90095 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA 90095 USA. NR 55 TC 24 Z9 25 U1 0 U2 0 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 JUN PY 1997 VL 272 IS 6 BP G1481 EP G1488 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XG113 UT WOS:A1997XG11300023 ER PT J AU Tanaka, S Podolsky, DK Engel, E Guth, PH Kaunitz, JD AF Tanaka, S Podolsky, DK Engel, E Guth, PH Kaunitz, JD TI Human spasmolytic polypeptide decreases proton permeation through gastric mucus in vivo and in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intracellular pH; stomach; fluorescein dyes; trefoil peptides; in vivo microscopy ID INTESTINAL TREFOIL FACTOR; HYDROGEN-ION CONCENTRATION; INTRACELLULAR PH; BARRIER FUNCTION; GROWTH-FACTOR; RAT STOMACH; IN-VIVO; CELL; GEL; PEPTIDE AB Exogenously administered trefoil peptides are gastroprotective in rat injury models. We hypothesized that trefoil-associated gastroprotection occurred by decreasing the rate of proton permeation through mucus. Gastric surface cell intracellular pH and mucus gel thickness were measured by in vivo microscopy. Gastric mucosal blood flow was measured by laser-Doppler flowmetry. The effect of human spasmolytic peptide (hSP) on H+ diffusion through 5% purified porcine mucin was measured using an Ussing chamber. Buffering action of mucin was measured by titration. In vivo, gastric mucosal blood flow and mucus gel thickness were not affected by any of the treatments. Topical hSP, but not intravenous hSP, decreased initial acidification rate and elevated the intracellular pH of gastric surface cells during luminal acid challenge. In in vitro studies, hSP dose dependently decreased the diffusion coefficient of H+ through 5% porcine mucin solution. hSP had no significant effect on the buffering action of mucin solutions. These data support our hypothesis that hSP interacts with gastric mucin in a manner that inhibits proton permeation through the mucus gel layer. C1 W LOS ANGELES VET AFFAIRS MED CTR, CURE, DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, MED SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT BIOMATH, LOS ANGELES, CA 90073 USA. MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02115 USA. NR 39 TC 52 Z9 52 U1 0 U2 3 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 JUN PY 1997 VL 272 IS 6 BP G1473 EP G1480 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA XG113 UT WOS:A1997XG11300022 ER PT J AU Schultz, JEJ Yao, ZH Cavero, I Gross, GJ AF Schultz, JEJ Yao, ZH Cavero, I Gross, GJ TI Glibenclamide-induced blockade of ischemic preconditioning is time dependent in intact rat heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardial protection; adenosine 5'-triphosphate-sensitive potassium channels; glibenclamide kinetics; sulfonylurea receptor ID SENSITIVE K+ CHANNEL; MYOCARDIAL INFARCT SIZE; POTASSIUM CHANNELS; SODIUM 5-HYDROXYDECANOATE; VENTRICULAR MYOCYTES; ADENOSINE RELEASE; CARDIAC-MUSCLE; ATP; GLYBURIDE; DOGS AB The ATP-sensitive potassium (K-ATP) channel has been demonstrated to be a potential mediator of ischemic preconditioning (PC) in most species, with the exception of the rat. This conclusion is based on the failure of the K-ATP channel antagonist glibenclamide (Glib) to block PC in this species. However, previous studies did not take into consideration the kinetic properties of Glib binding to its receptor in the rat myocardium. Therefore, the purpose of the present study was to test the hypothesis that ischemic PC is mediated by the myocardial K-ATP channel in the rat and that blockade of PC by Glib is a time-dependent phenomenon. Barbiturate-anesthetized, open-chest male Wistar rats were subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. Infarct size (IS) as a percentage of the area at risk (AAR; IS/AAR) was determined with triphenyltetrazolium staining. PC and the K-ATP channel opener nicorandil (50 mu g.kg(-1).min(-1) iv) resulted in marked reductions in IS/AAR from 53 +/- 3% to 8 +/- 1% and 17 +/- 5%, respectively (P < 0.05). Two doses of Glib (1 or 0.3 mg/kg iv) given 30 min before PC abolished the protective effect of PC; however, Glib (0.3 mg/kg iv) given 5 min before PC failed to block the effect. Glib administered 30 min before the 15-min nicorandil infusion blocked the cardioprotective effect of NC but did not block its transient hypotensive effect. These results demonstrate that the K-ATP channel is involved in ischemic PC in the intact rat heart and that the inhibitory effect of Glib to block PC is time dependent. C1 MED COLL WISCONSIN, DEPT PHARMACOL & TOXICOL, MILWAUKEE, WI 53226 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02114 USA. RHONE POULENC RORER, CTR RECH VITRY ALFORTVILLE, F-94403 VITRY SUR SEINE, FRANCE. NR 44 TC 81 Z9 84 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 JUN PY 1997 VL 272 IS 6 BP H2607 EP H2615 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA XG204 UT WOS:A1997XG20400012 ER PT J AU Ijsselstijn, H Pacheco, BA Albert, A Sluiter, W Donahoe, PK DeJongste, JC Schnitzer, JJ Tibboel, D AF Ijsselstijn, H Pacheco, BA Albert, A Sluiter, W Donahoe, PK DeJongste, JC Schnitzer, JJ Tibboel, D TI Prenatal hormones alter antioxidant enzymes and lung histology in rats with congenital diaphragmatic hernia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE glucocorticosteroids; thyroid-releasing hormone; artificial ventilation; morphometry; newborn animal ID THYROTROPIN-RELEASING-HORMONE; HIGH O-2 EXPOSURE; BIOCHEMICAL IMMATURITY; POSTNATAL-GROWTH; THERAPY IMPROVES; NEWBORN RATS; DEXAMETHASONE; HYPEROXIA; MORPHOMETRY; MATURATION AB Prenatal administration of dexamethasone (Dex) and thyrotropin-releasing hormone (TRH) synergistically enhances lung maturity, but TRH suppresses the antioxidant enzyme activity. Prenatal hormonal therapy improves alveolar surfactant content and lung compliance in rats with congenital diaphragmatic hernia (CDH). In full term neonatal rats with CDH we studied the effects of prenatal Dex or Dex + TRH on antioxidant enzyme activity at birth, on survival, and on lung morphometry after 4 h of ventilation with 100% O-2. CDH was induced by administration of 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) on gestational day 10. Dex + TRH-treated CDH rats had lower activity of glutathione reductase after birth than did sham-treated CDH pups. Dex-treated and sham-treated pups had similar antioxidant enzyme activity. Hormonal treatment did not change survival during ventilation. The average airspace volume increased in Dex-treated CDH pups after ventilation, with a small synergistic effect after addition of TRH. On the basis of our findings, we speculate that prenatal administration of Dex is the best choice to improve lung maturity and airspace volume in CDH patients. C1 ERASMUS UNIV ROTTERDAM HOSP, SOPHIA CHILDRENS HOSP, DEPT PEDIAT SURG, NL-3015 GJ ROTTERDAM, NETHERLANDS. ERASMUS UNIV ROTTERDAM HOSP, SOPHIA CHILDRENS HOSP, DIV PEDIAT RESPIRAT MED, NL-3015 GJ ROTTERDAM, NETHERLANDS. ERASMUS UNIV ROTTERDAM HOSP, SOPHIA CHILDRENS HOSP, DEPT PEDIAT, NL-3015 GJ ROTTERDAM, NETHERLANDS. ERASMUS UNIV ROTTERDAM HOSP, SOPHIA CHILDRENS HOSP, DEPT BIOCHEM, NL-3015 GJ ROTTERDAM, NETHERLANDS. HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP,PEDIATR RES LABS, DEPT PEDIATR SURG, BOSTON, MA 02114 USA. HOSP CLIN ST JOAN DE DEU, DEPT PEDIAT SURG, E-08034 BARCELONA, SPAIN. NR 29 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 1997 VL 272 IS 6 BP L1059 EP L1065 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA XF561 UT WOS:A1997XF56100004 PM 9227504 ER PT J AU Katsura, T Gustafson, CE Ausiello, DA Brown, D AF Katsura, T Gustafson, CE Ausiello, DA Brown, D TI Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE endocytosis; immunofluorescence; water channels ID KIDNEY COLLECTING DUCT; WATER CHANNEL; RAT-KIDNEY; INTRINSIC PROTEIN; EPITHELIAL-CELLS; EXPRESSION; MEMBRANE; LOCALIZATION; PERMEABILITY; IMMUNOLOCALIZATION AB Vasopressin-dependent translocation of aquaporin-2 (AQP2) between intracellular vesicles and the plasma membrane has been demonstrated in vivo and in vitro. Furthermore, the vasopressin-induced increase in apical membrane water permeability of renal principal cells is dependent on a rise in intracellular adenosine 3',5'-cyclic monophosphate and activation of protein kinase A (PKA). To determine whether trafficking of AQP2 is dependent on PKA phosphorylation, we first examined the effect of the PKA-inhibitor N-(2[[3-(4-bromophenyl)-2-propenyl]-amino]-ethyl)- 5-isoquinolinesulfonamide (H-89) on AQP2 translocation in transfected LLC-PK1 cells. Vasopressin-induced membrane insertion of AQP2 was completely inhibited by pretreatment of the cells for 60 min with H-89. This reagent also caused a dense accumulation of AQP2 in the Golgi region. Next, LLC-PK1 cells were stably transfected with AQP2 cDNA in which the PKA phosphorylation site, Ser256, was replaced with alanine (S256A). S256A-AQP2 was not phosphorylated in vitro by PKA, and S256A-AQP2 was mainly localized to intracellular vesicles in the basal condition, similar to wildtype AQP2. However, after stimulation with vasopressin or forskolin, the cellular distribution of S256A-AQP2 remained unchanged. In addition, the usual vasopressin-induced increase in endocytosis seen in AQP2-transfected cells was not observed in S256A-AQP2-transfected cells. These results demonstrate that the Ser256 PKA phosphorylation site is possibly involved in the vasopressin-induced trafficking of AQP2 from intracellular vesicles to the plasma membrane and in the subsequent stimulation of endocytosis. C1 MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. NR 34 TC 55 Z9 55 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 1997 VL 272 IS 6 BP F816 EP F822 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA XG017 UT WOS:A1997XG01700017 ER PT J AU Kraut, JA Hiura, J Besancon, M Smolka, A Sachs, G Scott, D AF Kraut, JA Hiura, J Besancon, M Smolka, A Sachs, G Scott, D TI Effect of hypokalemia on the abundance of HK alpha(1) and HK alpha(2) protein in the rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT XIIIth International Congress of Nephrology CY JUL 02-06, 1995 CL MADRID, SPAIN DE renal hydrogen-potassium-adenosinetriphosphatase; potassium; immunoprecipitation; Western blot analysis ID H-K-ATPASE; GASTRIC H,K-ATPASE; DISTAL COLON; ADENOSINE-TRIPHOSPHATASE; FUNCTIONAL EXPRESSION; COLLECTING DUCT; IMMUNOREACTIVITY; TRANSPORT; TUBULE AB An H+-K+-adenosinetriphosphatase (H+-K+-ATPase) contributes to potassium reabsorption by the collecting ducts of the rat kidney. mRNAs for two isoforms of the H+-K+-ATPase, HK alpha(1) and HK alpha(2), have been found in the rat kidney. To evaluate whether the HK alpha(1) and HK alpha(2) proteins are present in the rat kidney, microsomes enriched in HK alpha(1) or HK alpha(2) were isolated using the MiniMac magnetic separation system with antibodies directed against either HK alpha(1) (HK 12.18) or HK alpha(2) (AS 31.7). Immunoblots of rat kidney microsomal protein isolated with HK 12.18 revealed a band similar to 94 kDa in size that comigrated with the G1 fraction of the stomach. Immunoblots of rat kidney microsomal protein isolated with AS 31.7 revealed a band slightly greater than 94 kDa that comigrated with a band obtained from rat colonic microsomal protein. To examine the effect of perturbations in potassium metabolism, the abundance of the HK alpha(1) and HK alpha(2) isoforms was compared in rats fed a normal or potassium-deficient diet. A low-potassium diet increased the abundance of HK alpha(2), whereas that of HK alpha(1) was not altered. These data suggest that HK alpha(2) might be the isoform responsible for potassium conservation by the kidney. C1 UNIV CALIF LOS ANGELES, SCH MED,W LOS ANGELES VET AFFAIRS MED CTR, MEMBRANE BIOL LAB,RES SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. MED UNIV S CAROLINA, DEPT MED, CHARLESTON, SC 29425 USA. RP Kraut, JA (reprint author), UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VET AFFAIRS MED CTR, DIV NEPHROL 691111L, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-43138] NR 31 TC 41 Z9 42 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 1997 VL 272 IS 6 BP F744 EP F750 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA XG017 UT WOS:A1997XG01700008 PM 9227635 ER PT J AU Green, MF Marshall, BD Wirshing, WC Ames, D Marder, SR McGurk, S Kern, RS Mintz, J AF Green, MF Marshall, BD Wirshing, WC Ames, D Marder, SR McGurk, S Kern, RS Mintz, J TI Does risperidone improve verbal working memory in treatment-resistant schizophrenia? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; ATTENTIONAL PERFORMANCE; PSYCHIATRIC-SYMPTOMS; COGNITIVE FUNCTIONS; CLOZAPINE; MEDICATION AB Objective: Treatment efficacy in schizophrenia is typically defined in terms of symptom reduction. However, new antipsychotic medications could potentially have an impact on aspects of disability, such as neurocognitive deficits. The authors evaluated the effects of risperidone on vel bal working memory, a memory component of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation. Method: Verbal working memory of 59 treatment-resistant schizophrenic patients was assessed as part of a randomized, double-blind comparison of treatment with risperidone and haloperidol. Verbal working memory was measured under both distracting and nondistracting conditions at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy. Results: Risperidone treatment had a greater beneficial effect on verbal working memory than haloperidol treatment across testing conditions (with and without distraction) and study phases (fixed and flexible nose). The treatment effect remained significant after the effects of benztropine cotreatment, change in psychotic symptoms, and change in negative symptoms were controlled. Neither benztropine status nor symptom changes were significantly related to memory Performance. Conclusions: Treatment with risperidone appears to exert a more favorable effect on verbal working memory than treatment with a conventional neuroleptic. The beneficial effect appears to be due, at least partially, to a direct effect of the drug, possibly through antagonism of the 5-HT2A receptor. Results from this study suggest that pharmacotherapeutic efficacy in schizophrenia treatment could be broadened to include impact on neurocognitive abilities. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. CAMARILLO STATE HOSP & DEV CTR,LOS ANGELES,CA. RP Green, MF (reprint author), UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,760 WESTWOOD PLAZA,C9-420,LOS ANGELES,CA 90024, USA. NR 33 TC 344 Z9 350 U1 3 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1997 VL 154 IS 6 BP 799 EP 804 PG 6 WC Psychiatry SC Psychiatry GA XA587 UT WOS:A1997XA58700012 PM 9167507 ER PT J AU Baldessarini, RJ Hegarty, JD Bird, ED Benes, FM AF Baldessarini, RJ Hegarty, JD Bird, ED Benes, FM TI Meta-analysis of postmortem studies of Alzheimer's disease-like neuropathology in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROLEPTICS AB Objective: To evaluate the hypothesis that patients with schizophrenia who have been treated with neuroleptics have a high late of Alzheimer's disease-like neuropathology. Method: Neuropathological studies indicating the presence or absence of Alzheimer's disease-like neuropathology in the postmortem brains of patients with schizophrenia, normal comparison subjects, and comparison subjects who had affective disorder were evaluated with Mantel-Haenszel chi-square and odds ratio analyses. Results: Ten studies with relevant data were reviewed; none of eight with comparisons indicated that Alzheimer's disease-like neuropathology was move likely to be found in the brains of patients with schizophrenia than in the brains of comparison subkects. Conclusions: Suggestions that cerebral plaques and neurofibrillary tangles are more common in schizophrenia in association with neuroleptic treatment were not supported. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT & NEUROL,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA. FU NIMH NIH HHS [MH-31154, MH-47370] NR 18 TC 46 Z9 47 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 1997 VL 154 IS 6 BP 861 EP 863 PG 3 WC Psychiatry SC Psychiatry GA XA587 UT WOS:A1997XA58700024 PM 9167518 ER PT J AU Glassman, PA Jacobson, PD Asch, S AF Glassman, PA Jacobson, PD Asch, S TI Medical necessity and defined coverage benefits in the Oregon Health Plan SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RATIONING PLAN; MANAGED CARE; PHYSICIANS; INSURANCE AB The policy debate in Oregon has primarily focused on the Prioritized List of Services. However, little information is available on how defined coverage benefits and managed care affect the role of medical necessity in determining care for Medicaid patients. This issue is important because medical necessity determinations are currently used by many states to limit extraneous health care costs but require resource-intensive oversight, are open to wide variance, and frequently prompt litigation challenging interpretations of what is necessary and what is not. The qualitative study described here addressed whether medical necessity remains a salient and useful concept in the Oregon Health Plan. Our results indicate that defined coverage benefits, as described by the funded portion of the Prioritized List of Services, supplant medical necessity determinations for coverage, while managed care incentives Limit the need for medical necessity determinations at the provider level. Clinical choices are, for the most part, guided by providers' judgment within the financial constraints of capitation and by targeted use management techniques. The combination of capitated care and Oregon's defined coverage benefits package has marginalized the use of medical necessity, albeit with consequences for state oversight of Medicaid services. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RAND CORP,SANTA MONICA,CA. UNIV MICHIGAN,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,ANN ARBOR,MI 48109. UNIV SO CALIF,LOS ANGELES,CA. RP Glassman, PA (reprint author), UNIV CALIF LOS ANGELES,DIV GEN INTERNAL MED 111G,11301 WILSHIRE AVE,LOS ANGELES,CA 90073, USA. NR 23 TC 3 Z9 3 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC 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 JUN PY 1997 VL 87 IS 6 BP 1053 EP 1058 DI 10.2105/AJPH.87.6.1053 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XJ859 UT WOS:A1997XJ85900039 PM 9224198 ER PT J AU AlOtaibi, L Whitman, GJ Chew, FS AF AlOtaibi, L Whitman, GJ Chew, FS TI Radiologic-Pathologic Conferences of the Massachusetts General Hospital - Fibrous pseudotumor of the epididymis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 6 TC 7 Z9 7 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 JUN PY 1997 VL 168 IS 6 BP 1586 EP 1586 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XA553 UT WOS:A1997XA55300039 PM 9168731 ER PT J AU Eubanks, PJ Sawicki, MP Samara, GJ Wan, YJY Gatti, RA Hurwitz, M Passaro, E AF Eubanks, PJ Sawicki, MP Samara, GJ Wan, YJY Gatti, RA Hurwitz, M Passaro, E TI Pancreatic endocrine tumors with loss of heterozygosity at the multiple endocrine neoplasia type I locus SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID SUPPRESSOR GENE; CHROMOSOME-11 AB BACKGROUND: Loss of heterozygosity (LOH) at chromosome 11q13 has been demonstrated in multiple endocrine neoplasia type I (MEN I) and sporadic parathyroid tumors, pituitary adenomas, and a few types of pancreatic endocrine tumors. Gastrinomas are the most common pancreatic endocrine tumor in MEN I. We hypothesized that all pancreatic endocrine tumors have LOH at 11q13, resulting in inactivation of the previously described tumor suppressor gene in this region. METHODS: We analyzed a sporadic gastrinoma, a MEN I-associated gastrinoma, and a nonfunctional pancreatic endocrine tumor: from a patient with Von Hippel-Lindau (VHL) disease for LOH at seven loci at 11q13: D11S149, PYGM, D11S427, D11S546, SEA, D11S97, and D11S146. RESULTS AND CONCLUSIONS: We found LOH at 11q13 in all three tumors. The MEN I-associated gastrinoma we analyzed is the first tumor of this type to have LOH. This is also the first report of LOH at 11q13 in a pancreatic endocrine tumor from a patient with VHL. These findings suggest that the etiology of pancreatic endocrine tumor formation involves a common genetic pathway for sporadic, MEN I, and VHL tumors. (C) 1997 by Excerpta Medica, Inc. C1 UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PATHOL,TORRANCE,CA 90509. UNIV CALIF LOS ANGELES,SCH MED,DEPT SURG,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Eubanks, PJ (reprint author), UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT SURG,1000 W CARSON ST,BOX 15,TORRANCE,CA 90509, USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUN PY 1997 VL 173 IS 6 BP 518 EP 520 DI 10.1016/S0002-9610(97)00001-9 PG 3 WC Surgery SC Surgery GA XG218 UT WOS:A1997XG21800013 PM 9207166 ER PT J AU Grover, FL Fullerton, DA Zamora, MR Mills, C Ackerman, B Badesch, D Brown, JM Campbell, DN Chetham, P Dhaliwal, A Diercks, M Kinnard, T Niejadlik, K Ochs, M AF Grover, FL Fullerton, DA Zamora, MR Mills, C Ackerman, B Badesch, D Brown, JM Campbell, DN Chetham, P Dhaliwal, A Diercks, M Kinnard, T Niejadlik, K Ochs, M TI The past, present, and future of lung transplantation SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Southwestern Surgical Conference CY APR 23-26, 1995 CL SAN ANTONIO, TX ID OBLITERATIVE BRONCHIOLITIS; LOBAR TRANSPLANTATION; AUTO-TRANSPLANTATION; CYSTIC-FIBROSIS; HEART; METHYLPREDNISOLONE; AZATHIOPRINE; RECIPIENTS; EMPHYSEMA; SURVIVAL AB BACKGROUND: The history of lung transplantation from the first human transplant performed in 1963 to the present is reviewed with particular focus on the added challenges because of the contaminated bronchus, exposure of the graft to airborne organisms, the poor blood supply to the bronchus, and the problem of reperfusion pulmonary edema. METHODS: The technical aspects of single and double sequential lung transplantation are reviewed, as are the current indications for single, double sequential, and heart/lung transplantation. Criteria for lung transplant recipients, in addition to their primary disease are noted, as are absolute and relative contraindications. The standard criteria for donor selection are also reviewed. RESULTS: The results of single, double sequential, and heart-lung transplantation over the past 10 years as reported by the International Society for Heart and Lung Transplantation Database are reviewed. In addition, the statistics of the lung and heart-lung transplantation program at the University of Colorado Health Sciences Center are reviewed, including the current immunosuppressive regimens and early and late monitoring for infection and rejection. This experience includes 3 early deaths in the first 53 patients for an operative mortality of 5.6%, with a 1-year actuarial survival of 90%. CONCLUSIONS: During the past decade remarkable improvement in the result of single and double sequential lung transplantation have occurred. As 1-year, actuarial survival is now approaching 90% at some institutions. Living related lobar transplantation, new antirejection agents, chimerism, and xenograft transplantation are areas for continuing and future investigation. The shortage in donor organ supply continues to be a very significant factor in limiting human lung transplantation. (C) 1997 by Excerpta Medica, Inc. C1 UNIV COLORADO,HLTH SCI CTR,DIV PULM MED,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT ANESTHESIOL,DENVER,CO 80262. DENVER VA MED CTR,DENVER,CO. RP Grover, FL (reprint author), UNIV COLORADO,HLTH SCI CTR,DIV CARDIOTHORAC SURG C310,4200 E 9TH AVE,DENVER,CO 80262, USA. NR 31 TC 22 Z9 22 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUN PY 1997 VL 173 IS 6 BP 523 EP 533 DI 10.1016/S0002-9610(97)00004-4 PG 11 WC Surgery SC Surgery GA XG218 UT WOS:A1997XG21800015 PM 9207168 ER PT J AU Milberger, S Biederman, J Faraone, SV Chen, L Jones, J AF Milberger, S Biederman, J Faraone, SV Chen, L Jones, J TI Further evidence of an association between attention-deficit hyperactivity disorder and cigarette smoking - Findings from a high-risk sample of siblings SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID 15-YEAR FOLLOW-UP; MATERNAL SMOKING; DRUG-USE; PSYCHIATRIC STATUS; NICOTINE EXPOSURE; PRENATAL EXPOSURE; CHILDREN; PREGNANCY; BOYS; FAMILY AB The authors investigated the relationship between attention-deficit/hyperactivity disorder (ADHD) and cigarette smoking in siblings of ADHD and non-ADHD probands. They conducted a 4-year follow-up of siblings from ADHD and control-group families. In the siblings of ADHD probands, ADHD was associated with higher rates and earlier onset of cigarette smoking. There was also a significant positive association between cigarette smoking and conduct disorder, major depression, and drug abuse in the siblings, even after adjusting for confounding variables. Moreover, smoking was found to be familial among ADHD families but not control-group families. Our findings indicate that ADHD is a risk factor for early initiation of cigarette smoking in the high-risk siblings of ADHD probands. C1 MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R0I MH-41314-01A2] NR 85 TC 73 Z9 73 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 1997 VL 6 IS 3 BP 205 EP 217 PG 13 WC Substance Abuse SC Substance Abuse GA XN416 UT WOS:A1997XN41600003 PM 9256986 ER PT J AU Sivarajan, M Wasse, L AF Sivarajan, M Wasse, L TI Perioperative acute renal failure associated with preoperative intake of ibuprofen SO ANESTHESIOLOGY LA English DT Article DE nonsteroidal antiinflammatory drugs; renal dysfunction, perioperative ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; KETOROLAC C1 UNIV WASHINGTON,SCH MED,DEPT ANESTHESIOL,SEATTLE,WA 98195. RP Sivarajan, M (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE DIV,DEPT ANESTHESIOL 112A,ANESTHESIOL SERV,SEATTLE,WA 98108, USA. NR 10 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUN PY 1997 VL 86 IS 6 BP 1390 EP 1392 DI 10.1097/00000542-199706000-00023 PG 3 WC Anesthesiology SC Anesthesiology GA XE806 UT WOS:A1997XE80600023 PM 9197311 ER PT J AU Merkel, PA Polisson, RP Chang, YC Skates, SJ Niles, JL AF Merkel, PA Polisson, RP Chang, YC Skates, SJ Niles, JL TI Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE antibodies, antineutrophil cytoplasmic; connective tissue diseases; Wegener's granulomatosis; vasculitis; enzyme-linked immunosorbent assay; fluorescent antibody technique ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; ANCA; GRANULOMATOSIS; VASCULITIDES; DIAGNOSIS; INFECTION; ANTIGEN; ANTINUCLEAR AB Background: Two types of antineutrophil cytoplasmic antibodies (ANCA), antiproteinase 3 antibodies (anti-PR3) and antimyeloperoxidase antibodies (anti-MPO), are useful in the diagnosis of such types of vasculitis as Wegener granulomatosis and microscopic polyangiitis. Connective tissue diseases frequently appear in the differential diagnosis of this spectrum of vasculitis. Objective: To determine the prevalence of ANCA in patients with connective tissue disease. Design: Blinded, controlled study of a 5-year inception cohort. Setting: Tertiary-care university teaching hospitals. Patients: 70 patients with rheumatoid arthritis, 70 patients with systemic lupus erythematosus, 45 patients with scleroderma, 36 patients with inflammatory myositis, 44 patients with the Sjogren syndrome, 33 patients with the antiphospholipid syndrome, and 165 patients with early undifferentiated connective tissue disease (EUCTD). Serum was taken from 200 blood donors and 52 patients who had known vasculitis and positive results on tests for anti-PR3 or anti-MPO; these patients served as controls. Measurements: The presence of anti-PR3 and anti-MPO was determined by combining the results of indirect immunofluorescence tests for cytoplasmic (C-ANCA) and perinuclear (P-ANCA) patterns with the results of enzyme-linked immunosorbent assays (ELISAs) directed to measure antigen. Results: Cytoplasmic ANCA was not detected in any study or control patient. Perinuclear ANCA was commonly detected among patients with lupus (31%) but was uncommon among patients in other groups (0% to 5%). In all cases, P-ANCA was associated with the presence of antinuclear antibodies. Atypical ANCA immunofluorescence patterns were fairly common in all groups (11% to 39%). Antiproteinase 3 was detected by ELISA in 9 study patients (1 patient with rheumatoid arthritis, 1 with lupus, 1 with polymyositis, and 6 with EUCTD). Antimyeloperoxidase was detected by ELISA in 2 study patients (1 with rheumatoid arthritis and 1 with lupus). None of the patients with positive ELISA results had evidence of renal vasculitis during follow-up. When an ANCA scoring system that combines immunofluorescence and ELISA was used, the test specificity for vasculitis was 99.5% among patients with connective tissue disease. Conclusions: Patients with connective tissue disease are known to develop multiple autoantibodies; positivity for anti-PR3 and anti-MPO ANCA in such patients is rare. Cytoplasmic ANCA immunofluorescence is highly specific for anti-PR3. However, P-ANCA immunofluorescence, which may have positive results because of the presence of antinuclear antibodies, is not a specific marker of anti-MPO. A rigorous ANCA testing system that combines the results of immunofluorescence with those of ELISA is highly specific for Wegener granulomatosis and related vasculitides even in patients with connective tissue disease. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Merkel, PA (reprint author), MASSACHUSETTS GEN HOSP,ARTHRIT UNIT,BULFINCH 165,55 FRUIT ST,BOSTON,MA 02114, USA. NR 34 TC 160 Z9 169 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1997 VL 126 IS 11 BP 866 EP & PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA XA911 UT WOS:A1997XA91100003 PM 9163287 ER PT J AU Badgett, RG OKeefe, M Henderson, MC AF Badgett, RG OKeefe, M Henderson, MC TI Using systematic reviews in clinical education SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MEDICAL LITERATURE; ALCOHOLIC HEPATITIS; INFORMATION NEEDS; METAANALYSIS; PHYSICIANS; KNOWLEDGE; SCIENCE; TRIALS; CARE AB Traditional educational methods change clinical practice only with considerable effort and difficulty. In particular, the teaching of critical appraisal in the setting of journal clubs does not increase the amount of medical research read by trainees. Experiential learning theory, corroborated by the success of problem-based learning, encourages us to link learning to the numerous medical questions that physicians generate while providing patient care. Systematic reviews can link these questions with the results of research that would otherwise be difficult to locate, read, and appraise. Systematic reviews are a uniquely powerful mechanism for teaching, and they offer teachers a new opportunity to model rational and effective use of information. Systematic reviews should be made available at clinical sites for use during ''teachable moments.'' Resistance to the use of systematic reviews can be reduced by using existing journal clubs to teach about the strengths and limitations of these reviews. The point that systematic reviews are meant to assist, not replace, clinical decision making deserves emphasis in such teaching. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Badgett, RG (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. OI Badgett, Robert/0000-0003-2888-3303 NR 46 TC 19 Z9 21 U1 0 U2 1 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 JUN 1 PY 1997 VL 126 IS 11 BP 886 EP 891 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XA911 UT WOS:A1997XA91100006 PM 9163290 ER PT J AU Greenberg, SM Hyman, BT AF Greenberg, SM Hyman, BT TI Cerebral amyloid angiopathy and apolipoprotein E: Bad news for the good allele? SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ONSET ALZHEIMER-DISEASE; DEPOSITION; PROTEIN RP Greenberg, SM (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 16 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1997 VL 41 IS 6 BP 701 EP 702 DI 10.1002/ana.410410604 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XD559 UT WOS:A1997XD55900001 PM 9189029 ER PT J AU GomezIsla, T Wasco, W Pettingell, WP Gurubhagavatula, S Schmidt, SD Jondro, PD McNamara, M Rodes, LA DiBlasi, T Growdon, WB Seubert, P Schenk, D Growdon, JH Hyman, BT Tanzi, RE AF GomezIsla, T Wasco, W Pettingell, WP Gurubhagavatula, S Schmidt, SD Jondro, PD McNamara, M Rodes, LA DiBlasi, T Growdon, WB Seubert, P Schenk, D Growdon, JH Hyman, BT Tanzi, RE TI A novel presenilin-1 mutation: Increased beta-amyloid and neurofibrillary changes SO ANNALS OF NEUROLOGY LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; MISSENSE MUTATIONS; GENE; DIAGNOSIS AB The prevalence of known mutations in presenilin genes (PS1 and PS2) causing early-onset familial Alzheimer's disease (FAD) was assessed in a population of 98 singleton early-onset AD cases, 29 early-onset FAD cases, and 15 late-onset FAD cases. None of the cases tested positive for the eight mutations initially reported, and none of these mutations were observed in 60 age-matched controls. A novel mutation (R269H) in PS1 was found in a single case of early-onset AD but not in any other AD or control case. Thus, the PS mutations tested are quite rare in early-onset AD. Amyloid beta protein (AP) deposition was investigated in the temporal cortex of the R269H mutation case using end-specific monoclonal antibodies to detect the presence of A beta(x-40) and A beta(x-42) subspecies. Stereologically unbiased tangle and neuropil thread counts were obtained from the same region. R269H PS1 mutation was associated with early age of dementia onset, higher amounts of total A beta and A beta(x-42), and increased neuronal cytoskeletal changes. Thus, if the changes observed on this case prove to be typical of PS1 mutations, PS1 mutations may impact both amyloid deposition and neurofibrillary pathology. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,GENET & AGING UNIT,SCH MED,DEPT NEUROL,CHARLESTOWN,MA 01219. ATHENA NEUROSCI INC,S SAN FRANCISCO,CA 94080. RI Schmidt, Stephen/B-5398-2012 FU NIA NIH HHS [AG05134, AG08487]; NINDS NIH HHS [NS30428] NR 20 TC 59 Z9 60 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1997 VL 41 IS 6 BP 809 EP 813 DI 10.1002/ana.410410618 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XD559 UT WOS:A1997XD55900015 PM 9189043 ER PT J AU Rivera, JA FernandezdelCastillo, C Pins, M Compton, CC Lewandrowski, KB Rattner, DW Warshaw, AL AF Rivera, JA FernandezdelCastillo, C Pins, M Compton, CC Lewandrowski, KB Rattner, DW Warshaw, AL TI Pancreatic mucinous ductal ectasia and intraductal papillary neoplasms - A single malignant clinicopathologic entity SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 108th Annual Scientific Session of the Southern-Surgical-Association CY DEC 01-04, 1996 CL PALM BEACH, FL SP So Surg Assoc ID TUMOR; ADENOCARCINOMA; CYSTADENOMA; CARCINOMA AB Objective The purpose of the study is to review a single institutional experience with mucinous ductal ectasia(MDE) and intraductal papillary neoplasms (IPNs) and to compare the clinicopathologic features of the two groups of tumors. Summary Background Data Mucinous ductal ectasia and IPNs represent newly recognized categories of pancreatic exocrine tumors, previously confused with pancreatic cystic neoplasms. The natural history of MDE and IPN is not well understood, and it is unclear whether MDE and IPN represent two distinct tumors or the same clinicopathologic entity. Methods The authors reviewed the clinical presentation, treatment, histopathology, and outcomes of 23 patients diagnosed with MDE or IPN at their institution over the past 6 years. Results The mean age at presentation for the cohort of patients with MDE and IPN was 62.5 years. The prevalence of abdominal pain was 75%, jaundice 25%, weight loss 42%, steatorrhea 37.5%, diabetes 37.5%, and history of pancreatitis 29%. Serum CA 19-9 levels ranged from 0 to 5350 units/mL with high levels reflecting advanced disease. There were no significant differences between MDE and IPN with respect to these parameters. Both MDE and IPN comprised papillary villous epithelial neoplasms involving the main and large pancreatic ducts. The tumors ranged from a few millimeters in size to panductal and were distinguished easily from cystic neoplasms in all cases. Invasive carcinoma was present in 11 (46%) of 24 patients, carcinoma in situ in an additional 10 (42%) of 24 patients, and low grade dysplasia in the remaining 3 (12%) of 24 patients. Mucinous ductal ectasia and IPN differed histopathologically only in degree of mucin secretion and tumor location. Mucinous ductal ectasia, but not IPN, was characteristically mucin-hypersecreting and more frequently involved the head of the gland than did IPN (11/16 vs. 1/8, p < 0.04). All patients were explored surgically and 20 (83%) of 24 of the tumors were resectable with frozen section control of the duct margins (9 pancreatoduodenectomies, 4 distal pancreatectomies, 7 total pancreatectomies). Despite the 88% prevalence of cancer, the overall survival at a mean follow-up of 21 months was 13 (87%) of 15 for MDE and 5 (71%) of 7 for IPN. Conclusions Intraductal papillary neoplasms with or without MDE represent a spectrum of main duct papillary tumors ranging from adenoma to carcinoma with differing amounts of extracellular mucin production. Malignant IPNs with or without MDE typically exhibit extensive intraductal growth but are slow to invade the periductal tissues and slow to metastasize. The majority of patients with these tumors have resectable disease and a favorable prognosis; endoscopic therapy is inappropriate. The encompassing term intraductal papillary-mucinous tumors is appropriate. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 25 TC 108 Z9 110 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 1997 VL 225 IS 6 BP 637 EP 644 DI 10.1097/00000658-199706000-00001 PG 8 WC Surgery SC Surgery GA XL120 UT WOS:A1997XL12000001 PM 9230804 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI The brain uses mostly dissolved oxygen during profoundly hypothermic cardiopulmonary bypass - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP Vlahakes, GJ (reprint author), MASSACHUSETTS GEN HOSP,55 FRUIT ST,EDR105,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1997 VL 63 IS 6 BP 1729 EP 1729 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA XH230 UT WOS:A1997XH23000039 ER PT J AU Mathison, DJ AF Mathison, DJ TI Tracheal stenosis treated with self-expanding nitinol stent - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP Mathison, DJ (reprint author), MASSACHUSETTS GEN HOSP,WARREN 1109,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 1997 VL 63 IS 6 BP 1789 EP 1790 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA XH230 UT WOS:A1997XH23000061 ER PT J AU Held, KD AF Held, KD TI Radiation-induced apoptosis and its relationship to loss of clonogenic survival SO APOPTOSIS LA English DT Review DE apoptosis; cell cycle; clonogenicity; p53; radiation ID MYELOID CELL-LINES; WILD-TYPE P53; IRRADIATED MURINE TUMORS; DIFFERENT DOSE-RATES; IONIZING-RADIATION; IN-VIVO; GAMMA-IRRADIATION; HL-60 CELLS; DNA-DAMAGE; CERVICAL-CARCINOMA AB Ionizing radiation can be an effective inducer of apoptosis and studies of many aspects of the pathways and mechanisms involved in this apoptosis induction have been published. This review stresses two aspects: the relationship between apoptosis and loss of clonogenic ability in irradiated cells and the time course for the appearance of apoptosis after radiation exposure. Although it was initially assumed that apoptosis occurred relatively quickly (within hours) after irradiation, evidence is presented and discussed here showing that apoptosis can occur at long times after irradiation (out to 20 days) in some cell types. This late, or delayed, apoptosis occurs after the cells have divided once or several times. The impact of delayed apoptosis on loss of clonogenicity after irradiation remains unclear. It seems likely that in some cell types, e.g., fibroblasts, the occurrence of late apoptosis is minimal and may have little impact on long term cell survival of the population, but in at least one instance, with a cell line of hematopoietic origin, it appears that late apoptosis can account for all the loss of clonogenicity in irradiated cells. The role of p53 in radiation-induced apoptosis is also discussed, with data presented showing that both p53-dependent and independent pathways for radiation-induced apoptosis exist, depending on the cell type. RP Held, KD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX 302,BOSTON,MA 02114, USA. NR 118 TC 44 Z9 46 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JUN PY 1997 VL 2 IS 3 BP 265 EP 282 DI 10.1023/A:1026485003280 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YD291 UT WOS:A1997YD29100003 PM 14646540 ER PT J AU Small, JG Hirsch, SR Arvanitis, LA Miller, BG Link, CGG Murphy, AL Bowden, CL OBrien, CP Steinbook, RM Wagner, RL Pitts, WM Crabtree, B Corrigan, MHN Lohr, JB Miller, AL Ereshefsky, L Anderson, CB Knesevich, MA Rotrosen, J Owen, RR Karson, CN Lindenmayer, JP Pfefferbaum, A Faustman, WO Keck, PE Patterson, WM Riesenberg, RA Gladson, MB Kolin, IS Barnes, TRE Sensky, T Riccio, M Franks, S Jolley, A Hallstrom, C Bennie, E Darcourt, G Patris, M DeSilva, M Patel, AG Fleischhacker, WW Dietzel, M Seifertova, D Vinar, O Faltus, F Bitter, I Ozsvath, K Shaw, SH Mahapatra, SN Szulecka, TK Sundararajan, K Creaven, F Lynch, J Klieser, E Cooper, SJ Aschauer, H AF Small, JG Hirsch, SR Arvanitis, LA Miller, BG Link, CGG Murphy, AL Bowden, CL OBrien, CP Steinbook, RM Wagner, RL Pitts, WM Crabtree, B Corrigan, MHN Lohr, JB Miller, AL Ereshefsky, L Anderson, CB Knesevich, MA Rotrosen, J Owen, RR Karson, CN Lindenmayer, JP Pfefferbaum, A Faustman, WO Keck, PE Patterson, WM Riesenberg, RA Gladson, MB Kolin, IS Barnes, TRE Sensky, T Riccio, M Franks, S Jolley, A Hallstrom, C Bennie, E Darcourt, G Patris, M DeSilva, M Patel, AG Fleischhacker, WW Dietzel, M Seifertova, D Vinar, O Faltus, F Bitter, I Ozsvath, K Shaw, SH Mahapatra, SN Szulecka, TK Sundararajan, K Creaven, F Lynch, J Klieser, E Cooper, SJ Aschauer, H TI Quetiapine in patients with schizophrenia - A high- and low-dose double-blind comparison with placebo SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID RISPERIDONE AB Background: Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine(2) (5-HT2) receptors than for D-2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d). Methods: In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (less than or equal to 750 mg/d), n = 96; low-dose quetiapine fumarate (less than or equal to 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi(2) tests. Results: Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters. Conclusions: Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d. C1 LARUE D CARTER MEM HOSP, DIV MENTAL HLTH, INDIANAPOLIS, IN USA. CHARING CROSS HOSP, DEPT PSYCHIAT, LONDON, ENGLAND. ZENECA PHARMACEUT, DEPT CLIN & MED AFFAIRS, WILMINGTON, DE USA. ZENECA PHARMACEUT, DEPT MED AFFAIRS, MACCLESFIELD, CHESHIRE, ENGLAND. VET MEM HOSP, SAN ANTONIO, TX USA. VET AFFAIRS MED CTR, PHILADELPHIA, PA USA. UNIV MIAMI, JACKSON MEM MED CTR, MIAMI, FL 33101 USA. INST MENTAL HLTH, CRANSTON, RI USA. UNIV MISSISSIPPI, MED CTR, JACKSON, MS 39216 USA. VET AFFAIRS MED CTR, JACKSON, MS USA. DOROTHEA DIX HOSP, RALEIGH, NC USA. VET AFFAIRS MED CTR, SAN DIEGO, CA 92161 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. SAN ANTONIO STATE HOSP, SAN ANGELO, TX USA. CLIN PHARM PROGRAMS, SAN ANTONIO, TX USA. TERRELL STATE HOSP, TERRELL, TX USA. NEW YORK VET AFFAIRS MED CTR, NEW YORK, NY USA. VET AFFAIRS MED CTR, LITTLE ROCK, AR USA. ARKANSAS STATE HOSP, LITTLE ROCK, AR USA. SCHIZOPHREN RES UNIT, BRONX, NY USA. STANFORD VET AFFAIRS MENT HLTH CLIN RES CTR, PALO ALTO, CA USA. UNIV CINCINNATI, COLL MED, CINCINNATI, OH USA. HILLCREST HOSP, BIRMINGHAM RES GRP, BIRMINGHAM, AL USA. DEKALB MED CTR, DECATUR, GA USA. SAND LAKE HOSP, ORLANDO, FL USA. HORTON HOSP, SURREY, ENGLAND. W MIDDLESEX HOSP, ISLEWORTH, MIDDX, ENGLAND. ST MARY ABBOT HOSP, LONDON, ENGLAND. GORDON HOSP, LONDON, ENGLAND. EALING GEN HOSP, LONDON, MIDDX, ENGLAND. CHARING CROSS HOSP, LONDON, ENGLAND. LEVERNADALE HOSP, GLASGOW, LANARK, SCOTLAND. PASTEUR HOSP, CLIN PSYCHIAT & PSYCOL, NICE, FRANCE. PSYCHIAT CLIN, STRASBOURG, FRANCE. UNIV INNSBRUCK CLIN, INNSBRUCK, AUSTRIA. UNIV VIENNA, PSYCHIAT CLIN, A-1090 VIENNA, AUSTRIA. INST PSYCHIAT RES, PRAGUE, CZECH REPUBLIC. HOSP PSYCHIAT, PRAGUE, CZECH REPUBLIC. CHARLES UNIV, PRAGUE, CZECH REPUBLIC. SEMMELWEIS UNIV MED, H-1085 BUDAPEST, HUNGARY. UNIV PECS, SCH MED, PECS, HUNGARY. GEN HOSP, HARTLEPOOL, ENGLAND. BASSETLAW DISTRICT GEN HOSP, NOTTINGHAM, ENGLAND. HALIFAX GEN HOSP, HALIFAX, W YORKSHIRE, ENGLAND. ST MARYS PSYCHIAT HOSP, CASLEBAR, MAYO, IRELAND. ST LUKES HOSP, CLONMEL, TIPPERARY, IRELAND. PSYCHIAT KLIN, DUSSELDORF, GERMANY. QUEENS UNIV BELFAST, BELFAST, ANTRIM, NORTH IRELAND. UNIV CLIN VIENNA, VIENNA, AUSTRIA. NR 20 TC 430 Z9 455 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1997 VL 54 IS 6 BP 549 EP 557 PG 9 WC Psychiatry SC Psychiatry GA XE945 UT WOS:A1997XE94500007 PM 9193196 ER PT J AU Gabriel, SM Haroutunian, V Powchik, P Honer, WG Davidson, M Davies, P Davis, KL AF Gabriel, SM Haroutunian, V Powchik, P Honer, WG Davidson, M Davies, P Davis, KL TI Increased concentrations of presynaptic proteins in the cingulate cortex of subjects with schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SYNAPTOSOMAL-ASSOCIATED PROTEIN; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; PREFRONTAL CORTEX; SYNAPTIC VESICLES; CEREBRAL-CORTEX; RAT-BRAIN; SYNAPTOPHYSIN; HALOPERIDOL; EXPRESSION AB Background: Cytoarchitectural and neurochemical studies demonstrate disorganization in the cerebral cortex in schizophrenia, which perhaps underlies the severe behavioral disturbances of the disease. This neuronal disarray should be accompanied by synaptic abnormalities. As such, presynaptic proteins have proved valuable indexes of synaptic density and their concentrations have correlated markedly with synaptic loss. Our study sought to determine whether abnormalities exist in the concentrations of presynaptic proteins in the postmortem cerebral cortex of subjects with schizophrenia. Methods: Presynaptic protein immunoreactivities were assessed in 4 different cerebrocortical regions derived from 16 elderly controls, 19 elderly subjects with schizophrenia, and 24 subjects with Alzheimer's disease. Tissues were assayed with the monoclonal antibodies EP10 and SP4, which recognize synaptophysin, and the monoclonal antibodies SP6 and SP14, which detect syntaxin and synaptosomal-associated protein-25-kd immunoreactivities, respectively. Results: In subjects with schizophrenia relative to controls, presynaptic proteins were increased in the cingulate cortex, but were unchanged in the temporal, frontal, and parietal cortices. In contrast, when cases with Alzheimer's disease were compared with controls, pre synaptic proteins were decreased in the frontal, temporal, and parietal samples. Conclusions: These findings reveal changes in the synaptic organization of the cingulate cortex in schizophrenia relative to other areas examined. These changes are distinct from the deficits in presynaptic proteins observed in Alzheimer's disease. C1 BRONX VET AFFAIRS MED CTR, DEPT PSYCHIAT, BRONX, NY 10468 USA. MT SINAI SCH MED, DEPT PSYCHIAT, NEW YORK, NY USA. ALBERT EINSTEIN COLL MED, DEPT PATHOL, BRONX, NY 10467 USA. UNIV BRITISH COLUMBIA, DEPT PSYCHIAT, VANCOUVER, BC, CANADA. FU NIA NIH HHS [AG5138, AG02219]; NIMH NIH HHS [MH46436] NR 52 TC 105 Z9 106 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 1997 VL 54 IS 6 BP 559 EP 566 PG 8 WC Psychiatry SC Psychiatry GA XE945 UT WOS:A1997XE94500008 PM 9193197 ER PT J AU Lu, LY Ding, WZ Fici, D Deulofeut, R Cheng, HH Cheu, CC Sung, PK Schur, PH Fraser, PA AF Lu, LY Ding, WZ Fici, D Deulofeut, R Cheng, HH Cheu, CC Sung, PK Schur, PH Fraser, PA TI Molecular analysis of major histocompatibility complex allelic associations with systemic lupus erythematosus in Taiwan SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; CLASS-II; C2 DEFICIENCY; SOUTHERN CHINESE; PROMOTER REGION; MHC HAPLOTYPES; HLA; POLYMORPHISM; DISEASE; GENES AB Objective. To investigate the association of HLA class II alleles/haplotypes, type I C2 deficiency gene, and tumor necrosis factor alpha gene promoter allele (TNF2) with systemic lupus erythematosus (SLE) in the Chinese population in Taiwan. Methods. The HLA-DRE1 and DQB1 alleles were studied in 105 SLE patients and 115 controls by the polymerase chain reaction (PCR)sequence-specific oligonucleotide probe method, the subtyping of DRB1*15/16 and DRB5 by PCR with sequence-specific primers, type I C2 deficiency gene by PCR, and TNF2 by PCR-Nco I restriction fragment length polymorphism. Results. The frequencies of the HLA class II alleles DRB1*02, DRB1*1502, DRB5*0102, DQB1*0501, and DQB1*0602 and DR2-associated haplotypes DRB1*1501, DRB5*0101, DQB1*0602 and DRB1*1502, DRB5*0102, DQB1*0501 were higher among SLE patients than among controls; however, only DQB1*0501 was statistically significantly associated with SLE, No specific allele/haplotype was significantly associated with lupus nephritis. No subject had type I C2 deficiency, SLE patients had a marginally higher percentage of TNF2, which was in linkage disequilibrium with DR3, Since DR3 was not associated with SLE in this Taiwanese Chinese population, TNF2 might play a role in the immunopathogenesis of SLE. Conclusion. Although no HLA-DRB1 allele was found to be significantly associated with SLE, the associations with DQB1*0501 and TNP2 suggest that DQB1 and tumor necrosis factor alpha mag be important genetic factors in SLE susceptibility in the Chinese population in Taiwan. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. VET GEN HOSP,KAOHSIUNG,TAIWAN. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NIAMS NIH HHS [R01-AR-42459-02] NR 39 TC 44 Z9 49 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1997 VL 40 IS 6 BP 1138 EP 1145 DI 10.1002/art.1780400619 PG 8 WC Rheumatology SC Rheumatology GA XC376 UT WOS:A1997XC37600018 PM 9182925 ER PT J AU McNally, RJ Hornig, CD Otto, MW Pollack, MH AF McNally, RJ Hornig, CD Otto, MW Pollack, MH TI Selective encoding of threat in panic disorder: Application of a dual priming paradigm SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article ID ATTENTIONAL BIAS; ANXIETY; MEMORY AB Patients with panic disorder and psychiatrically healthy control subjects performed a dual priming task whereby they viewed either lexical or non-lexical prime pairs before naming a target that had either threatening (e.g. collapse) or positive (e.g. cheerful) meaning. Lexical prime pairs comprised a threat word and a positive word, and non-lexical prime pairs comprised two rows of asterisks. Suggestive of a bias for encoding threat cues, panic disorder patients (under some conditions) were faster to name lexically primed threat targets than lexically primed positive targets. These data are consistent with the hypothesis that panic disorder is linked to an encoding bias for threatening relative positive information. A cognitive bias for selectively encoding threat cues may figure in the maintenance of anxiety states, such as panic disorder. (C) 1997 Elsevier Science Ltd. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP McNally, RJ (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. FU NIMH NIH HHS [MH51927] NR 13 TC 10 Z9 10 U1 0 U2 1 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 JUN PY 1997 VL 35 IS 6 BP 543 EP 549 DI 10.1016/S0005-7967(96)00125-8 PG 7 WC Psychology, Clinical SC Psychology GA WZ196 UT WOS:A1997WZ19600007 PM 9159978 ER PT J AU Yenush, L White, MF AF Yenush, L White, MF TI The IRS-signalling system during insulin and cytokine action SO BIOESSAYS LA English DT Review ID STIMULATED GLUCOSE-TRANSPORT; NECROSIS-FACTOR-ALPHA; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; SKELETAL-MUSCLE; GROWTH-HORMONE; I RECEPTOR; CHO CELLS AB The discovery of the first intracellular substrate for insulin, IRS-1, redirected the field of diabetes research and has led to many important advances in our understanding of insulin action, Detailed analysis of IRS-I demonstrates structure/function relationships for this modular docking molecule, including mechanisms of substrate recognition and signal propagation. Recent work has also identified other structurally similar molecules, including IRS-2, the Drosophila protein, DOS, and the Grb2-binding protein, Gab1, suggesting that this intracellular signalling strategy is conserved evolutionarily and is utilized by an expanding number of receptor systems. in fact, IRS-1 itself has been shown to be important in other growth factor and cytokine signalling systems, including growth hormone and several interleukins. Analysis of mice lacking IRS-1 confirms an important physiological role for this protein in glucose metabolism and general cell growth in the intact animal. Disregulation of the signalling pathways integrated by the IRS proteins may contribute to the pathophysiology of non-insulin-dependent diabetes mellitus or other diseases. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,GRAD PROGRAM BIOMED & BIOL SCI,BOSTON,MA 02215. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK43808, DK38712] NR 81 TC 227 Z9 231 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JUN PY 1997 VL 19 IS 6 BP 491 EP 500 DI 10.1002/bies.950190608 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA XE970 UT WOS:A1997XE97000007 PM 9204766 ER PT J AU Ibrahim, JG Chen, MH AF Ibrahim, JG Chen, MH TI Predictive variable selection for the multivariate linear model SO BIOMETRICS LA English DT Article DE multivariate regression; posterior distribution; predictive criterion; predictive distribution; replicated experiment ID STANDARDS AB We develop a predictive Bayesian approach to variable selection in the multivariate linear model. A criterion derived from the Bayesian predictive density is proposed and a calibration is provided for it. Reference and informative priors are discussed, and an automated method that focuses on the response variable is proposed for specifying informative priors for the regression parameters. Relationships between the proposed criterion and other several well-known criteria are examined. Illustrative examples involving real data are given to demonstrate the methodology. C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. WORCESTER POLYTECH INST, DEPT MATH SCI, WORCESTER, MA 01609 USA. RP Ibrahim, JG (reprint author), HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA 70101-01] NR 21 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD JUN PY 1997 VL 53 IS 2 BP 465 EP 478 DI 10.2307/2533950 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA XE965 UT WOS:A1997XE96500006 PM 9192446 ER PT J AU Aiba, Y Hirayama, F Ogawa, M AF Aiba, Y Hirayama, F Ogawa, M TI Clonal proliferation and cytokine requirement of murine progenitors for natural killer cells SO BLOOD LA English DT Article ID RECEPTOR-GAMMA-CHAIN; IL-2 RECEPTOR; INTERLEUKIN-2 RECEPTOR; NK CELLS; LYMPHOID DIFFERENTIATION; FUNCTIONAL COMPONENT; MONOCLONAL-ANTIBODY; STAT PROTEINS; BETA-CHAIN; STEM-CELLS AB We have established a clonal cell culture system that supports the proliferation of committed natural killer (NK) cell progenitors of mice to investigate the pathway and cytokine regulation of NK cell development. Day 14 fetal thymocytes cultured in methylcellulose with interleukin-7 (IL-7), IL-15, and steel factor (SF) formed diffuse colonies that could not be classified to known colony types, Single-cell origin of the colonies was established by micromanipulation of the colony-forming cells, Cells in the colonies are very blastic, showing no cytoplasmic differentiation, and express Ly5, Thy-1, and CD25 but not myeloid, B, mature T, or NK cell markers. The cells lack T, B, and myeloid potentials but can differentiate to mature NK cells in fetal thymus organ culture, suggesting that the colonies consist of NK committed progenitors. Examination of the minimal cytokine requirement for the NK colony formation showed that IL-7 and SF are indispensable for the formation of immature NK cell colonies. Both IL-2 and IL-15 increased the frequency of colonies. In contrast to IL-2, IL-7, and IL-15, IL-4 strongly inhibited the formation of the colonies, This quantitative clonal culture will provide a useful means to examine the mechanism of NK cell development. (C) 1997 by The American Society of Hematology. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29401 USA. MED UNIV S CAROLINA, DEPT MED, CHARLESTON, SC 29425 USA. FU NIDDK NIH HHS [DK32294, DK/HL48714] NR 55 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1997 VL 89 IS 11 BP 4005 EP 4012 PG 8 WC Hematology SC Hematology GA XD379 UT WOS:A1997XD37900014 PM 9166839 ER PT J AU Ishimaru, F Mari, B Shipp, MA AF Ishimaru, F Mari, B Shipp, MA TI The type 2 CD10 neutral endopeptidase 24.11 promoter: Functional characterization and tissue-specific regulation by CBF/NF-Y isoforms SO BLOOD LA English DT Article ID CCAAT-BINDING-FACTOR; NF-Y; DNA-BINDING; CLASS-II; B-CELL; HETEROLOGOUS SUBUNITS; HUMAN-NEUTROPHILS; DOWN-REGULATION; IN-VIVO; TRANSCRIPTION AB The cell surface zinc metalloproteinase CD10/neutral endopeptidase 24.11 ([NEP] neprilysin) functions as part of a regulatory loop to control local concentrations of peptide substrates and associated peptide-mediated signal transduction. The physiologic role of the enzyme depends on available substrates in specific organs and cell types, Although CD10/NEP is expressed on a restricted subset of normal and malignant lymphoid progenitors, the enzyme is also expressed by a variety of epithelial cells, To explore the mechanism of tissue-specific expression of this regulatory enzyme, we characterized the major (type 2) CD10/NEP promoter and identified three functionally active transcription factor binding sites (regions I to III). CBF/NF-Y binds to the inverted CCAAT box in region I, whereas a second positive and a third negative factor bind to regions II and III, respectively. Although region I is required for maximal CD10/NEP-driven luciferase activity in the examined epithelial cell lines, this region is not required for maximal activity in the evaluated lymphoid cell lines, The apparent tissue-specific differences in requirements for region I (and CBF/NF-Y) are of particular interest because lymphoid and epithelial cells express alternatively spliced versions of CBF/NF-Y that differ in biologic activity. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015 OI Mari, Bernard/0000-0002-0422-9182 FU NCI NIH HHS [CA-55095] NR 59 TC 33 Z9 33 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 JUN 1 PY 1997 VL 89 IS 11 BP 4136 EP 4145 PG 10 WC Hematology SC Hematology GA XD379 UT WOS:A1997XD37900031 PM 9166856 ER PT J AU Turbay, D Lieberman, J Alper, CA Delgado, JC Corzo, D Yunis, JJ Yunis, EJ AF Turbay, D Lieberman, J Alper, CA Delgado, JC Corzo, D Yunis, JJ Yunis, EJ TI Tumor necrosis factor constellation polymorphism and clozapine-induced agranulocytosis in two different ethnic groups SO BLOOD LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FACTOR-ALPHA; TNF-ALPHA; HLA SYSTEM; COMPLEX; HEMATOPOIESIS; ASSOCIATION; HAPLOTYPES; DISEASE; CELLS AB Genes of the major histocompatibility complex (MHC) are associated with susceptibility to different immune and nonimmune mediated diseases. We had reported that the drug adverse reaction, clozapine-induced agranulocytosis (CA), is associated with different HLA types and HSP70 variants in Ashkenazi Jewish and non-Jewish patients, suggesting that a gene within the MHC region is associated with CA, This study was designed to find common genetic markers for this disorder in both ethnic groups, The tumor necrosis factor (TNF) microsatellites d3 and b4 were found in higher frequencies in both Jewish and nonJewish patients: 51 of 66 (77%) and 48 of 66 (57%), respectively, Comparisons of these frequencies with those of controls, 28 of 66 (42%) and 18 of 66 (27%), were statistically significant (corrected P value = .001 for the d3 allele and .0005 for the b4 allele). On the other hand, the TNF microsatellite b5 was underrepresented in the group of patients, 9 of 66 (14%), when compared with the control subjects, 43 of 66 (65%) (corrected P value = .0005), probably related to protection from CA, Our results show a strong association of some genetic variants of the TNF loci with susceptibility to CA in two different ethnic groups suggesting involvement of TNF and/or associated gene(s) products in the pathogenesis of this hematologic-drug adverse reaction. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV N CAROLINA,DEPT PSYCHIAT,CHAPEL HILL,NC. CTR BLOOD RES,BOSTON,MA 02115. RP Turbay, D (reprint author), DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,44 BINNEY ST,LHRRB 203,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-14157, HL-29583]; NIMH NIH HHS [MH-47029] NR 47 TC 47 Z9 47 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 JUN 1 PY 1997 VL 89 IS 11 BP 4167 EP 4174 PG 8 WC Hematology SC Hematology GA XD379 UT WOS:A1997XD37900035 PM 9166860 ER PT J AU Vogelzang, NJ Herndon, JE Cirrincione, C Harmon, DC Antman, KH Corson, JM Suzuki, Y Citron, ML Green, MR AF Vogelzang, NJ Herndon, JE Cirrincione, C Harmon, DC Antman, KH Corson, JM Suzuki, Y Citron, ML Green, MR TI Dihydro-5-azacytidine in malignant mesothelioma - A Phase II trial demonstrating activity accompanied by cardiac toxicity SO CANCER LA English DT Article DE malignant mesothelioma; chemotherapy; dihydroazacytidine; cardiac toxicity ID LEUKEMIA GROUP-B; PLEURAL MESOTHELIOMA; CANCER; 5,6-DIHYDRO-5-AZACYTIDINE; CARBOPLATIN; MANAGEMENT; DIFFUSE AB BACKGROUND. Malignant mesothelioma is a disease that is refractory to chemotherapy. Therefore, the objective of this multi-institutional, cooperative group Phase II trial was to determine the efficacy of dihydro-5-azacytidine (DHAC), a pyrimidine analogue, in the treatment of malignant mesothelioma. METHODS. Forty-one patients with histologically confirmed malignant mesothelioma received 120-hour continuous infusions of DHAC (1,500 mg/m(2)/day every 21 days) until maximal response, intolerable toxicity, or disease progression. RESULTS. One patient had a complete response, two had objective partial responses,and four had regression of evaluable disease. The overall response rate was 17%. The one complete responder remains without disease progression at 6 years. Chest pain and nausea were the most common toxicities. Supraventricular tachycardia and pericardial effusion occurred in 20% and 15% of patients, respec tively. In most patients, gastrointestinal effects were manageable. There was no significant hematologic toxicity. CONCLUSIONS. In malignant mesothelioma, a disease that is refractory to chemotherapy, dihydro-5-azacytidine has definite antitumor activity. Its modest hematologic toxicity profile favors its use in combination with other agents. Caution regarding cardiac arrhythmias and pericardial effusion is necessary. (C) 1997 American Cancer Society. C1 DUKE UNIV,MED CTR,CANC & LEUKEMIA GRP B STAT OFF,DURHAM,NC. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. COLUMBIA PRESBYTERIAN MED CTR,HERBERT IRVING COMPREHENS CANC CTR,NEW YORK,NY 10032. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. MT SINAI SCH MED,DEPT COMMUNITY MED,NEW YORK,NY. MT SINAI SCH MED,DEPT PATHOL,NEW YORK,NY. LONG ISL JEWISH MED CTR,SECT MED ONCOL,NEW HYDE PK,NY 11042. MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP Vogelzang, NJ (reprint author), UNIV CHICAGO,MED CTR,HEMATOL ONCOL SECT,5841 S MARYLAND AVE,MC 2115,CHICAGO,IL 60637, USA. NR 24 TC 41 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1997 VL 79 IS 11 BP 2237 EP 2242 DI 10.1002/(SICI)1097-0142(19970601)79:11<2237::AID-CNCR23>3.0.CO;2-W PG 6 WC Oncology SC Oncology GA XA433 UT WOS:A1997XA43300023 ER PT J AU Jeffers, L Church, D Basu, H Marton, L Wilding, G AF Jeffers, L Church, D Basu, H Marton, L Wilding, G TI Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the proliferation of three prostate cancer cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE polyamine; prostate carcinoma; nude mouse ID SPERMIDINE SPERMINE N1-ACETYLTRANSFERASE; ALPHA-DIFLUOROMETHYLORNITHINE; ANTITUMOR-ACTIVITY; NECK TUMORS; GROWTH; DNA; CARCINOMA; INVIVO; POTENTIATION; DEPRIVATION AB Purpose: Polyamines are biologic cations necessary for normal cell growth. Polyamine analogues have been shown to be effective inhibitors of tumor growth. We tested the effect of the polyamine analogues 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4), N-1,N-11-bis(ethyl)norspermine (BE-3-3-3) and 1,15-bis(ethylamino)-4,12-diazapentadecane (BE-3-7-3) on the growth of the prostate cancer cell lines DU145, LNCaP and PC-3 in vitro. We also tested the effect of BE-4-4-4-4 on androgen-independent DU145 cells in vivo via a nude mouse xenograft model. Methods: In vitro, cell proliferation was measured using a DNA assay or a colony-formation assay. In vivo, mice were given saline or BE-4-4-4-4 3 mg/kg or 5 mg/kg intraperitoneally twice daily on days 7-10 and 14-17 (cycle 1), days 49-52 and 56-59 (cycle 2) and days 91-94 and 98-101 (cycle 3). Results: The proliferation of DU145, LNCaP and PC-3 prostate cancer cell lines was inhibited in a dose-dependent manner by BE-4-4-4-4. Intracellular putrescine, spermidine and spermine levels in all three cell lines declined after only 24 h exposure to BE-4-4-4-4 in vitro. Animals receiving BE-4-4-4-4 showed inhibition of tumor growth which continued throughout the experiment with 74% (3 mg/kg) and 81% (5 mg/kg) growth inhibition seen on day 101, No overt toxic reactions besides weight loss were observed in BE-4-4-4-4-treated animals. Tumor tissue from animals treated with BE-4-4-4-4 showed a dose-dependent decrease in spermidine and spermine levels but no decline in putrescine levels as compared with control. BE-4-4-4-4 levels were highest in tumors on day 63 with levels reaching 0.33 and 1.45 nmol/mg protein from animals treated at the 3 mg/kg and 5 mg/kg doses, respectively. Conclusion: These results show the polyamine analogues BE-4-4-4-4, BE-3-3-3 and BE-3-7-3 to be effective inhibitors of prostate cancer cell growth in vitro and BE-4-4-4-4 to be an effective inhibitor of DU145 cells in vivo with minimal toxicity. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT MED,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,NJ. UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,DEPT PATHOL & LAB MED,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,MCARDLE LAB CANC RES,DEPT ONCOL,MADISON,WI 53706. NR 38 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1997 VL 40 IS 2 BP 172 EP 179 DI 10.1007/s002800050643 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XB021 UT WOS:A1997XB02100011 PM 9182840 ER PT J AU Elias, A AF Elias, A TI Dose-intensive therapy in lung cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Bristol-Myers-Squibb Nagoya International Cancer Treatment Symposium CY OCT 04-05, 1996 CL NAGOYA, JAPAN SP Bristol Myers Squibb DE small-cell lung cancer; high-dose chemotherapy; minimal residual tumor ID AUTOLOGOUS BONE-MARROW; SMALL-CELL-CARCINOMA; HEMATOPOIETIC PROGENITOR CELLS; COLONY-STIMULATING FACTOR; COMBINED MODALITY THERAPY; METASTATIC BREAST-CANCER; DISEASE-FREE SURVIVAL; PHASE-I; PERIPHERAL-BLOOD; SOLID TUMORS AB Lung cancer is epidemic and lethal throughout the world. Overall survival is estimated to be 13% at 5 years despite treatment. The use of chemotherapy in small-cell lung cancer (SCLC) is established, but it is less active against non-SCLC (NSCLC). Since 98% of SCLC cases are associated with heavy smoking and present at a median age of 60-65 years, the application of dose-intensive therapy to lung cancer patients may be complicated by underlying smoking-related comorbidity and an enhanced risk for secondary smoking-related malignancies. The strategies of intensifying induction therapy, multicycle dose-intensive combination therapies, chest radiotherapy, and stem cell purging for both SCLC and NSCLC are discussed herein. Limited data regarding high-dose therapy for NSCLC have been reported. In SCLC, excellent and immediate palliation is achieved through the use of combination chemotherapy. However, by 2 years, only 20-40% of limited-disease-(LD) and <5% of extensive-disease stage (ED) patients remain alive. Regimens developed using the many established agents produce similar short-and long-term outcomes, an observation that suggests that many of our systemic agents eradicate the same tumor subpopulation but fail to abolish a central core of tumor stem cells, presumably enriched for heterogeneous in vivo resistance mechanisms. The identification of these minimal residual tumor (MRT) cells and systematic evaluation of their biologic characteristics may guide strategies to target these cells specifically; such strategies may include modification of chemotherapy, tumor vaccination, or other forms of biologic therapy, such as replacement of RE, 3p, and/or p53 function; interference with autocrine or paracrine growth loops; or immunologic therapy [interleukin (IL)-2, IL-12, immunotoxins, and tumor vaccines], which would be most effective in the setting of MRT. To this end the detection of heterogeneity and analysis of patterns of coexpression of various markers form the thrust of our MRT detection program. At the Dana-Farber Cancer Institute and Beth Israel Hospital we performed stem-cell autografts in > 40 patients with LD SCLC and >25 patients with ED SCLC who were in first response to conventional-dose therapy comprising highdose combination alkylating agents. Approximately 80% of our patients were in or near complete response after initial chemotherapy. At a minimal follow-up of 23 months (to as long as 10 years) after completion of high-dose chemotherapy in our original trial, 52% of the patients remain disease-free. Of the ED or extrapulmonary patients, approximately 20% remain progression-free at >2 years after high-dose therapy. Local regional recurrence represents about 50% of all relapses. Thus, the roles of thoracic radiation dose intensity and purification of stem-cell autografts are being evaluated in ongoing trials. It is hoped that a cooperative phase III trial testing the concept of dose intensification will begin soon. RP Elias, A (reprint author), HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 13849] NR 78 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1997 VL 40 SU S BP S64 EP S69 DI 10.1007/s002800051064 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA XR329 UT WOS:A1997XR32900013 PM 9272137 ER PT J AU Malach, R Schirman, D Harel, M Tootell, RBH Malonek, D AF Malach, R Schirman, D Harel, M Tootell, RBH Malonek, D TI Organization of intrinsic connections in owl monkey area MT SO CEREBRAL CORTEX LA English DT Article ID TEMPORAL VISUAL AREA; FUNCTIONAL ARCHITECTURE; CORTICAL CONNECTIONS; PREFRONTAL CORTEX; CEREBRAL-CORTEX; STRIATE CORTEX; MACAQUE; FIELD; REPRESENTATION; SPECIFICITY AB Area MT (middle temporal) is a well-defined visual representation common to all primates, which skews a clear selectivity to the analysis of visual motion. In the present study we examined the architecture of the intrinsic connections in area MT in an attempt to reveal its organizing principles and its potential relationship to the functional domains in area MT intrinsic connections were studied by placing small injections of the tracer biocytin in area MT of seven adult owl monkeys (Aotus nancymae). The injections were targeted at well-defined orientation domains revealed using optical imaging of intrinsic signals. The distribution of axons labeled by these injections was related both to the cytochrome oxidase histochemistry and to the layout of functional domains in area MT and surrounding tissue. Tracer injections in the superficial layers of area MT produced a complex network of extrinsic and intrinsic axonal connections. Clear instances of extrinsic connections were observed between area MY proper and the MT crescent situated postero-medially to it. The intrinsic connections were laterally spread and organized in patch-like clusters with an average distance from injection center to the furthest patch of 1.8 +/- 0.55 mm (+/- SD, n = 9). The overall axonal distribution tended to be anisotropic, i.e. the patches were distributed within an elongated ellipse [average anisotropy ratio: 1.86 +/- 0.66 (+/- SC))] and were asymmetrically distributed about either side of the injection site [average asymmetry ratio: 2.3 +/- 0.7 (+/- SD)]. Finally, there was a tendency for the intrinsic connections to connect to functional domains of similar orientation preference in area MT. However, this tendency varied substantially between individual cases. The highly specific nature of MT lateral connections puts clear constraints on models of surround influences in the receptive fields of MT neurons. C1 MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,CHARLESTOWN,MA 02129. RP Malach, R (reprint author), WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. NR 35 TC 36 Z9 36 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUN PY 1997 VL 7 IS 4 BP 386 EP 393 DI 10.1093/cercor/7.4.386 PG 8 WC Neurosciences SC Neurosciences & Neurology GA WX894 UT WOS:A1997WX89400008 PM 9177768 ER PT J AU DeNino, LA Lawrence, VA Averyt, EC Hilsenbeck, SG Dhanda, R Page, CP AF DeNino, LA Lawrence, VA Averyt, EC Hilsenbeck, SG Dhanda, R Page, CP TI Preoperative spirometry and laparotomy - Blowing away dollars SO CHEST LA English DT Article DE economics; preoperative care; pulmonary complications; pulmonary function testing; surgery/operative ID OBSTRUCTIVE PULMONARY-DISEASE; COMPLICATIONS AB Study Objective: Increasing evidence indicates that routine preoperative diagnostic spirometry (pulmonary function tests [PFTs]) before elective abdominal surgery does not predict individual risk of postoperative pulmonary complications and is overutilized, This economic evaluation estimates potential savings from reduced use of preoperative PFTs. Design: Analyses of (1) real costs (resource consumption to perform tests) and (2) reimbursements (expenditures for charges) by third-party payers. Setting: University-affiliated public and Veterans Affairs hospitals. Patients: Adults undergoing elective abdominal operations. Measurements and results: Average real cost of PFTs Was $19.07 (95% confidence interval [CI], $18.53 to $19.61), based on a time and motion study. Average reimbursement expenditure by third-party payers for PFTs was $85 (range, $33 to $150; 95% CI, $68 to $103), based on Medicare payment of $52 and a survey of nine urban US hospitals with a spectrum of bed sizes and teaching status, Estimates from published literature included the following: (1) annual number of major abdominal operations, 3.5 million; and (2) proportion of PFTs not meeting current guidelines, 39% (95% CI, 0.31 to 0.47). Local data were used when estimates were not available in the literature: (1) proportion of laparotomies that are elective, 76% (95% CI, 0.73 to 0.79); and (2) frequency of PFTs before laparotomy, 69% (95% CI, 0.54 to 0.84), Estimated annual national real costs for preoperative PFTs are $25 million to $45 million, If use of PFTs were reduced by our estimate for the proportion of PFTs not meeting current guidelines, potential annual national cost savings would be $7,925,411 to $21,406,707. National reimbursement expenditures by third-party payers range from more than $90 million to more than $235 million. If use were reduced potential annual savings in reimbursements would be $29,084,076 to $111,345,440. Potential savings to Medicare approach $8 million to $20 million annually. Conclusion: Reduced use of PFTs before elective abdominal surgery could generate substantial savings, Current evidence indicates reduced use would not compromise patients' outcomes. C1 S TEXAS VET HEALTHCARE SYST,AUDIE L MURPHY DIV,DIV GEN MED,SAN ANTONIO,TX. S TEXAS VET HEALTHCARE SYST,AUDIE L MURPHY DIV,SURG SERV,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ONCOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG,SAN ANTONIO,TX 78284. RP DeNino, LA (reprint author), S TEXAS VET HEALTHCARE SYST,AUDIE L MURPHY DIV,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX, USA. NR 17 TC 20 Z9 19 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1997 VL 111 IS 6 BP 1536 EP 1541 DI 10.1378/chest.111.6.1536 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XC902 UT WOS:A1997XC90200017 PM 9187170 ER PT J AU Goulet, R Hess, D Kacmarek, RM AF Goulet, R Hess, D Kacmarek, RM TI Pressure vs flow triggering during pressure support ventilation SO CHEST LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-for-Respiratory-Care CY DEC, 1995 CL ORLANDO, FL SP Amer Assoc Resp Care DE flow trigger; mechanical ventilation; pressure support ventilation; pressure trigger ID POSITIVE AIRWAY PRESSURE; INTERMITTENT MANDATORY VENTILATION; INSPIRATORY MUSCLE WORK; DEMAND-FLOW; SYSTEMS AB Background: Adult mechanical ventilators have traditionally been pressure- or time-triggered. More recently, flow triggering has become available and some adult ventilators allow the choice between pressure or flow triggering, Prior studies have supported the superiority of flow triggering during continuous positive airway pressure, but few have compared pressure and flow triggering during pressure support ventilation (PSV). The purpose of this study was to compare pressure and flow triggering during PSV in adult mechanically ventilated patients. Methods: The study population consisted of 10 adult patients ventilated with a mechanical ventilator (Nellcor-Puritan-Bennett 7200ae) in the PSV mode. In random order, we compared pressure triggering of -0.5 H2O, pressure triggering -1 cm H2O, flow triggering of 5/2 L/min, and flow triggering 10/3 L/min. Pressure was measured for 5 min at the proximal endotracheal tube using a data acquisition rate of 100 Hz. From the airway pressure signal, trigger pressure (Delta P) was defined as the difference between positive end-expiratory pressure (PEEP) and the maximum negative deflection prior to onset of the triggered breath. Pressure-time product (PTP) was defined as the area produced by the pressure waveform below PEEP during onset of the triggered breath, Trigger time (Delta T) was defined as the time interval below PEEP during onset of the triggered breath. Results: A pressure trigger of -0.5 cm H2O was significantly more sensitive than the other trigger methods for Delta P, PTP, and Delta T (p<0.001), There was also a significant difference between patients for Delta P, Delta T, and PTP for each trigger method (p<0.001). Conclusions: For this group of patients, flow triggering was not superior to pressure triggering at -0.5 cm H2O during PSV. C1 MASSACHUSETTS GEN HOSP,DEPT RESP CARE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 22 TC 21 Z9 22 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1997 VL 111 IS 6 BP 1649 EP 1653 DI 10.1378/chest.111.6.1649 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XC902 UT WOS:A1997XC90200035 PM 9187188 ER PT J AU Narula, J Petrov, A Pak, KY Ditlow, C Chen, F Khaw, BA AF Narula, J Petrov, A Pak, KY Ditlow, C Chen, F Khaw, BA TI Noninvasive detection of atherosclerotic lesions by Tc-99m-based immunoscintigraphic targeting of proliferating smooth muscle cells SO CHEST LA English DT Article DE antibody; atheroma; radiolabel; radionuclide imaging; smooth muscle cell ID MONOCLONAL-ANTIBODY; LOCALIZATION; FRAGMENTS AB Background: Mouse/human chimeric antibody Z2D3 identifies an antigen produced exclusively by proliferating smooth muscle cells of human atheroma, and also cross reacts with experimentally induced atherosclerotic lesions in rabbits. Fab' fragments of Z2D3 antibody were labeled with Tc-99m using glucaric acid as a weak transchelator. The potential role of Tc-99m-labeled Z2D3 scintigraphy was explored for noninvasive imaging of experimental atherosclerotic lesions. Methods and results: Tc-99m-Z2D3 Fab' was utilized for noninvasive imaging in four rabbits with experimentally induced atherosclerotic lesions and in one control rabbit. In addition, Tc-99m-labeled nonspecific 103D2 Fab' was used for comparison in four other rabbits with atherosclerotic lesions, The atherosclerotic lesions were induced by balloon de-endothelialization of the infradiaphragmatic abdominal aorta and 12 weeks of hyperlipidemic diet, An aliquot of 15 mCi (550 mBq) of Tc-99m pertechnetate was incubated with 6.25 mg of glucaric acid for 30 min followed by incubation of Tc-99m glucarate with 375 mu g of Z2D3 Fab' or 103D2 Fab' for an additional 30 min. Instant thin-layer chromatography demonstrated almost complete radiolabeling. Tc-99m-Z2D3 was administered IV and gamma imaging was pet-formed at the time of injection, 3, 6, 9, and 12 h, followed by ex vivo imaging of the excised aorta, and biodistribution was performed. Unequivocal visualization of atherosclerotic lesions was possible in all four animals at 9 to 12 h with Z2D3 Fab', Quantitative uptake, as represented by mean lesion-to-liver count density ratio, was 0.6+/-0.05. Imaging with nonspecific 103D2 Fab' did not show any localization in the abdominal aorta (lesion-to-liver ratio, 0.45+/-0.02, p=0.02). Ex rico lesion-to-normal aortic segment ratio was 4.3+/-0.9 for Z2D3 and 1.04+/-0.08 for nonspecific 103D2 Fab' (p=0.01). Biodistribution studies demonstrated 0.03+/-0.003% injected Z2D3 dose per gram in the atherosclerotic lesions as compared with 0.01+/-0.003% in the nondenuded thoracic aorta of atherosclerotic rabbits (p=0.008). However, only 0.008+/-0.002% of the mean injected dose per gram was obtained in the atherosclerotic lesions (p=0.001) as compared with 0.005+/-0.003% in the normal aortic segments with 103D2. No Z2D3 uptake in normal rabbits was observed on either the in vivo Or Cr vivo images. Conclusions: The present study demonstrates that Tc-99m-based immunoimaging of the vascular lesions may be feasible by the use of smaller antibody fragments, Earlier visualization is possible at the expense of a lower absolute antibody uptake in the lesions as compared to the use of intact antibody or larger fragments with longer circulating time. C1 SCOTGEN PHARMACEUT INC,MENLO PK,CA. RP Narula, J (reprint author), NORTHEASTERN UNIV,MASSACHUSETTS GEN HOSP,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115, USA. NR 24 TC 11 Z9 11 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1997 VL 111 IS 6 BP 1684 EP 1690 DI 10.1378/chest.111.6.1684 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XC902 UT WOS:A1997XC90200041 PM 9187194 ER PT J AU Susanto, I Peters, JI AF Susanto, I Peters, JI TI Acute lupus pneumonitis with normal chest radiograph SO CHEST LA English DT Article DE corticosteroids; hypoxemia; lupus; pneumonitis ID ERYTHEMATOSUS; DISEASE; HYPOXEMIA; ADHESION AB Patients with acute lupus pneumonitis (ALP) usually have hypoxemia, patchy infiltrates evidenced on a chest x-ray film, and an incomplete response to corticosteroids with high mortality. In contrast, lupus patients with a syndrome of acute reversible hypoxemia (SARH) have hypoxemia with normal chest x-ray films and a rapid response to corticosteroids. We present a case of biopsy-proven ALP with normal initial chest x-ray films, and a normal CT scan. We hypothesize that a continuum of vascular and parenchymal abnormalities may exist in the lungs of lupus patients. This case also illustrates the insensitivity of routine chest radiographs in demonstrating mild or early pneumonitis. C1 AUDIE L MURPHY MEM VET HOSP DIV,S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX. RP Susanto, I (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 9 TC 15 Z9 15 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1997 VL 111 IS 6 BP 1781 EP 1783 DI 10.1378/chest.111.6.1781 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA XC902 UT WOS:A1997XC90200061 PM 9187214 ER PT J AU Ogata, A Chauhan, D Urashima, M Teoh, G Treon, SP Anderson, KC AF Ogata, A Chauhan, D Urashima, M Teoh, G Treon, SP Anderson, KC TI Blockade of mitogen-activated protein kinase cascade signaling in interleukin 6-independent multiple myeloma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR; LINES; DIFFERENTIATION; PHOSPHORYLATION; CYTOKINES; RECEPTOR; P21(RAS); COMPLEX; FAMILY; GP130 AB Interleukin 6 (IL-6) is a growth factor for multiple myeloma (MM) cells, Set not all MM cell lines or patient cells require IL-6 for their growth, It is well known that IL-6 activates the signal transducers and activators of transcription (stat) 1-stat3 heterodimer, stat3 homodimer, and Ras-dependent mitogen-activated protein kinase (MAPK) cascades in multiple cell systems, We have shown previously that the MAPK pathway is an important pathway for IL-6-mediated MM cell growth, In this study, we delineate the pattern of upstream MAPK cascade activation in IL-6-responsive B9 cells and in IL-6-nonresponsive U266, OCI-My5, and RPMI8226 MM cells to define sites of blockade of this pathway associated with loss of responsiveness to IL-6. In B9 cells, IL-6 triggered the following in sequence: gp130 phosphorylation, gp130-to-protein tyrosine phosphatase 1D (PTP1D) binding, PTP1D phosphorylation, PTP1D complex formation with Grb2-Son of sevenless 1 (Sos1), and Sos1 phosphorylation, gp130 phosphorylation, gp130-to-PTP1D binding, PTP1D phosphorylation, and PTP1D-to-Grb2 binding are also induced by IL-6 in all IL-6-independent MM cell lines studied, However, Grb2 is not associated with Sos1, and neither Grb2-to-Sos1 binding nor Sos1 phosphorylation is triggered by IL-6 in OCI-My5 MM cells, On the other hand, Grb2 and Sos1 are associated constitutively in U266 and RPMI8226 MR I cells, but phosphorylation of Sos1 is not induced by IL-6, These data suggest that lack of Sos1 activation is associated with loss of IL-6 responsiveness in MM cell lines that grow independently of IL-6. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NCI NIH HHS [CA 50947] NR 30 TC 48 Z9 49 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1997 VL 3 IS 6 BP 1017 EP 1022 PG 6 WC Oncology SC Oncology GA XC514 UT WOS:A1997XC51400024 PM 9815779 ER PT J AU Dan, L Dhanak, E Lewandrowski, K AF Dan, L Dhanak, E Lewandrowski, K TI Evaluation of the chiron diagnostics ACS:180 CK-MB-II assay and comparison to the stratus CK-MB method. SO CLINICAL CHEMISTRY 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 CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 105 EP 105 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300105 ER PT J AU Anderson, PH Bankson, DD Bock, JL Bodin, SG Eisen, CN Levine, JB Marcus, MN Senior, MB Zhou, Z AF Anderson, PH Bankson, DD Bock, JL Bodin, SG Eisen, CN Levine, JB Marcus, MN Senior, MB Zhou, Z TI Multi-site evaluation of PSA in free and ACT-complexed standard mixtures, CAP certified reference serum, survey samples and human serum. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 ST VINCENTS MED CTR,DEPT PATHOL,PORTLAND,OR. VA PUGET SND HLTH CARE,PATHOL & LAB MED SERV,SEATTLE,WA. SUNY STONY BROOK,MED CTR,STONY BROOK,NY 11794. HUNTSVILLE DIST MEM HOSP,DEPT CHEM,HUNTSVILLE,AL. MEM SLOAN KETTERING CANC CTR,DEPT CLIN CHEM,NEW YORK,NY 10021. BAYER DIAGNOST,CLIN & SCI SVC,TARRYTOWN,NY. HOSP UNIV PENN,SCH MED,DEPT ENDOCRINOL,PHILADELPHIA,PA 19104. BAYER DIAGNOST,ADV TECHNOL,TARRYTOWN,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 140 EP 140 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300140 ER PT J AU Rebeck, GW Yess, JP Jeffries, EP Silberman, SR AF Rebeck, GW Yess, JP Jeffries, EP Silberman, SR TI CSF Apo E levels in Alzheimer's disease. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. PERIMMUNE INC,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1997 VL 43 SU 6 BP 691 EP 691 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XD363 UT WOS:A1997XD36300690 ER PT J AU Johnson, CC Baldessarre, J Levison, ME AF Johnson, CC Baldessarre, J Levison, ME TI Peritonitis: Update on pathophysiology, clinical manifestations, and management SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SPONTANEOUS BACTERIAL PERITONITIS; NECROSIS-FACTOR-ALPHA; INTRAABDOMINAL INFECTION; ASCITIC FLUID; FUNGAL PERITONITIS; TNF-ALPHA; ANTIBIOTIC-THERAPY; MYCOBACTERIAL PERITONITIS; DIFFUSE PERITONITIS; SURGICAL PATIENTS C1 ALLEGHENY UNIV HLTH SCI,MCP,DIV INFECT DIS,PHILADELPHIA,PA 19129. RW JOHNSON PHARMACEUT RES INST,RARITAN,NJ 08869. VET AFFAIRS MED CTR,PHILADELPHIA,PA. NR 98 TC 56 Z9 58 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1997 VL 24 IS 6 BP 1035 EP 1045 DI 10.1086/513658 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XE366 UT WOS:A1997XE36600001 PM 9195055 ER PT J AU Sekeres, MA Abrutyn, E Berlin, JA Kaye, D Kinman, JL Korzeniowski, OM Levison, ME Feldman, RS Strom, BL AF Sekeres, MA Abrutyn, E Berlin, JA Kaye, D Kinman, JL Korzeniowski, OM Levison, ME Feldman, RS Strom, BL TI An assessment of the usefulness of the Duke criteria for diagnosing active infective endocarditis SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB We evaluated the usefulness of the Duke criteria for diagnosing cases of active infective endocarditis (IE). Patients were identified prospectively over a 3-year period at 54 hospitals in the Philadelphia metropolitan area. Three of us independently reviewed abstracted hospital records and classified 410 patients as definite, probable, or possible cases of IE or as probable noncases, We then applied the Duke criteria to this sample to assess the degree of agreement between our diagnoses and the diagnoses based on these new criteria. Agreement was good to excellent, ranging from 72% to 90%, depending on the case definition used, The sensitivity of the Duke criteria was also good to excellent, varying from 71% to 99%, again depending on case definition used. Specificity was lower (0-89%). We conclude that use of the Duke criteria will result in little underdiagnosis of IE but that it may result in overdiagnosis of IE; therefore, these criteria should be applied prospectively to determine their clinical usefulness. C1 UNIV PENN, SCH MED, DEPT BIOSTAT & EPIDEMIOL, CTR CLIN EPIDEMIOL & BIOSTAT, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DEPT MED, DIV GEN INTERNAL MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH DENT MED, PHILADELPHIA, PA 19104 USA. MED COLL PENN & HAHNEMANN UNIV, DIV INFECT DIS, PHILADELPHIA, PA USA. VET AFFAIRS MED CTR, MED SERV, INFECT DIS SECT, PHILADELPHIA, PA USA. VET AFFAIRS MED CTR, DENT SERV, PHILADELPHIA, PA USA. FU NHLBI NIH HHS [R01 HL 39000] NR 23 TC 35 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1997 VL 24 IS 6 BP 1185 EP 1190 DI 10.1086/513657 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XE366 UT WOS:A1997XE36600026 PM 9195080 ER PT J AU Pons, V Greenspan, D LozadaNur, F McPhail, L Gallant, JE Tunkel, A Johnson, CC McCarty, J Panzer, H Levenstein, M Barranco, A Green, S AF Pons, V Greenspan, D LozadaNur, F McPhail, L Gallant, JE Tunkel, A Johnson, CC McCarty, J Panzer, H Levenstein, M Barranco, A Green, S TI Oropharyngeal candidiasis in patients with AIDS: Randomized comparison of fluconazole versus nystatin oral suspensions SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P <.001), Fluconazole eradicated Candida organisms from the oral flora in 60%, vs, a 6% eradication rate with nystatin (P <.001), The fluconazole group had fewer relapses noted on day 28 (18%, vs, 44% in the nystatin group; P <.001), This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse. C1 UNIV CALIF HOSP,DEPT STOMATOL,SAN FRANCISCO,CA 94143. MED COLL PENN & HAHNEMANN UNIV,VET AFFAIRS MED CTR,PHILADELPHIA,PA. CALIF MED RES GRP,FRESNO,CA. PFIZER,US PHARMACEUT GRP,NEW YORK,NY. RP Pons, V (reprint author), UNIV CALIF HOSP,DIV INFECT DIS,521 PARNASSUS AVE,ROOM C-443,SAN FRANCISCO,CA 94143, USA. NR 9 TC 44 Z9 47 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1997 VL 24 IS 6 BP 1204 EP 1207 DI 10.1086/513664 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XE366 UT WOS:A1997XE36600029 PM 9195083 ER PT J AU Mankin, HJ Mankin, CJ Akeson, WH Dick, HM Friedlaender, GE Radin, EL Simon, MA AF Mankin, HJ Mankin, CJ Akeson, WH Dick, HM Friedlaender, GE Radin, EL Simon, MA TI A curriculum for the ideal orthopaedic residency SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID GUIDELINES AB The Academic Orthopaedic Society met in April 1994 to discuss manpower issues in orthopaedics. The members de, eloped an approach using the Delphi system to define and obtain consensus on the characteristics of the ideal residency, Sh categories of educational attributes were included: General; Clinical Management; Skills and Technical Aspects; Rehabilitation; Basic Science and Research: and Educational Environment. The following year a questionnaire was sent to more than 125 programs in an attempt to have residents and staff anonymously self score their residencies according to the standards defined bg the Delphi panels. The results obtained from the 745 responders from 73 programs validate effectively the characteristics of the ideal program and also show the variation among the programs. RP Mankin, HJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,ORTHOPAED GRAY 606,BOSTON,MA 02114, USA. NR 7 TC 9 Z9 9 U1 0 U2 0 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 JUN PY 1997 IS 339 BP 270 EP 281 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XD168 UT WOS:A1997XD16800036 PM 9186229 ER PT J AU Young, AW Rowland, D Calder, AJ Etcoff, NL Seth, A Perrett, DI AF Young, AW Rowland, D Calder, AJ Etcoff, NL Seth, A Perrett, DI TI Facial expression megamix: Tests of dimensional and category accounts of emotion recognition SO COGNITION LA English DT Article ID PERCEPTION; IDENTITY; INFORMATION; UNIVERSALS; CORTEX; FACES AB We report four experiments investigating the perception of photographic quality continua of interpolated ('morphed') facial expressions derived from prototypes of the 6 emotions in the Ekman and Friesen (1976) series (happiness, surprise, fear, sadness, disgust and anger). In Experiment 1, morphed images made from all possible pairwise combinations of expressions were presented in random order; subjects identified these as belonging to distinct expression categories corresponding to the prototypes at each end of the relevant continuum, This result was replicated in Experiment 2, which also included morphs made from a prototype with a neutral expression, and allowed 'neutral' as a response category. These findings are inconsistent with the view that facial expressions are recognised by locating them along two underlying dimensions, since such a View predicts that at least some transitions between categories should involve neutral regions or,identification as a different emotion. Instead, they suggest that facial expressions of basic emotions are recognised by their fit to discrete categories. Experiment 3 used continua involving 6 emotions to demonstrate best discrimination of pairs of stimuli falling across category boundaries; this provides further evidence of categorical perception of facial expressions of emotion. However, in both Experiment 1 and Experiment 2, reaction time data showed that increasing distance from the prototype had a definite cost on ability to identify emotion in the resulting morphed face. Moreover, Experiment 4 showed that subjects had some insight into which emotions were blended to create specific morphed images. Hence, categorical perception effects were found even though subjects were sensitive to physical properties of these morphed facial expressions. We suggest that rapid classification of prototypes and better across boundary discriminability reflect the underlying organisation of human categorisation abilities. C1 UNIV ST ANDREWS,SCH PSYCHOL,ST ANDREWS KY16 9JU,FIFE,SCOTLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,CHARLESTOWN,MA 02129. RP Young, AW (reprint author), MRC,APPL PSYCHOL UNIT,15 CHAUCER RD,CAMBRIDGE CB2 2EF,ENGLAND. RI Young, Andy/G-2189-2011 OI Young, Andy/0000-0002-1202-6297 NR 36 TC 311 Z9 316 U1 2 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD JUN PY 1997 VL 63 IS 3 BP 271 EP 313 DI 10.1016/S0010-0277(97)00003-6 PG 43 WC Psychology, Experimental SC Psychology GA XQ199 UT WOS:A1997XQ19900003 PM 9265872 ER PT J AU Berman, M Gewirtz, H AF Berman, M Gewirtz, H TI Acute effects of 17 beta-estradiol on the coronary microcirculation: observations in sedated, closed-chest domestic swine SO CORONARY ARTERY DISEASE LA English DT Article DE coronary microcirculation; 17 beta-estradiol; sexual dimorphism; diastolic resistance ID NITRIC-OXIDE; POSTMENOPAUSAL WOMEN; RESISTANCE ARTERIES; SMOOTH-MUSCLE; BLOOD-FLOW; ESTROGEN; RESPONSES; VASODILATION; ACETYLCHOLINE; RELAXATION AB Objectives To test the hypotheses: that acute administration of 17 beta-estradiol dilates normal coronary microvessels in vivo; that coronary microvascular responses to acute estrogen stimulation exhibit sexual dimorphism; and that nitric oxide has a role in mediating these effects. Methods Measurements of hemodynamics, coronary flow velocity (Doppler), myocardial blood flow (microspheres) and oxygen consumption were made in closed-chest swine: group 1 consisted of castrated juvenile males, groups 2 and 3 of estrogen pretreated, castrated juvenile males, and group 4 of sexually mature females. 17 beta-Estradiol (2, 20 or 200 ng/kg) was given by intracoronary injection and data obtained 20-30 min later; additional measurements were made 1 h after the 200 ng/kg dose. The effect of L-N-G-monomethylarginine (L-NMMA) on 17 beta-estradiol responses was also tested. Tissue and blood concentrations of 17 beta-estradiol, and concentrations of estrogen receptor in myocardium and coronary vessels were obtained. Results In estrogen-naive castrated males, 17 beta-estradiol had no effect on coronary flow velocity or myocardial blood flow, but 1 h after the 200 ng/kg dose there was an increase in diastolic coronary resistance compared with baseline (48 +/- 20 versus 41 +/- 17 mmHg/mkHz; P< 0.05), Estrogen pretreated castrated males also showed no change in myocardial blood flow after 17 beta-estradiol, but coronary flow velocity decreased (P< 0.05) compared with baseline 1 h after the 200 ng/kg dose (from 1.69 +/- 0.61 to 1.41 +/- 0.42 kHz) and diastolic coronary resistance increased significantly (P < 0.01) compared with control at this time (51 +/- 15 compared with 39 +/- 14 mmHg/mkHz). In sexually mature females, 17 beta-estradiol had no effect on myocardial blood flow but did cause a significant (P< 0.05) decrease in diastolic coronary vascular resistance compared with baseline (51 +/- 9 mmHg/mkHz) at both the 20 ng/kg and the 200 ng/kg doses (both 43 +/- 11 mmHg/mkHz), Coronary flow velocity also increased (P< 0.06) compared with baseline (1.34 +/- 0.26 mmHg/mkHz) after the 200 ng/kg dose (1.69 +/- 0.61 mmHg/mkHz). L-NMMA had no effect on flow responses to 17 beta-estradiol in any group. Classical estrogen receptors were not present in myocardium or coronary arteries from male or female swine. Conclusions These results demonstrate that 17 beta-estradiol exerts a mild constrictor effect on the coronary microvessels of normal castrated, juvenile males whether estrogen-naive or estrogen-pretreated. In contrast, sexually mature normal females exhibit mild dilatation of the coronary microcirculation in response to acute estrogen stimulation. Nitric oxide does not appear to have a role in mediating the dilator response in females, and classical estrogen receptors are not involved. A direct membrane effect of the hormone (perhaps via alteration in potassium conductance) seems likely, and demonstrates sexual dimorphism. (C) Rapid Science Publishers. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT VINCENT BURNHAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. RHODE ISL HOSP,DEPT MED,DIV CARDIOL,PROVIDENCE,RI 02903. NR 42 TC 3 Z9 3 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD JUN PY 1997 VL 8 IS 6 BP 351 EP 361 DI 10.1097/00019501-199706000-00004 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YB562 UT WOS:A1997YB56200004 PM 9347215 ER PT J AU Fishman, MC Chien, KR AF Fishman, MC Chien, KR TI Fashioning the vertebrate heart: Earliest embryonic decisions SO DEVELOPMENT LA English DT Review DE pattern; evolution; polarity; organ; myogenesis; mouse; zebrafish ID LEFT-RIGHT ASYMMETRY; ENDOCARDIAL CUSHION TISSUE; MYOSIN HEAVY-CHAIN; NEURAL CREST; CARDIOVASCULAR DEVELOPMENT; CARDIAC DEVELOPMENT; CONDUCTION SYSTEM; TARGETED DISRUPTION; PRIMITIVE-STREAK; SKELETAL-MUSCLE AB Our goal here is to set out the types of unitary decisions made by heart progenitor cells, from their appearance in the heart field until they form the simple heart tube. This provides a context to evaluate cell fate, lineage and, finally, morphogenetic decisions that configure global heart form and function. Some paradigms for cellular differentiation and for pattern generation may be borrowed from invertebrates, but neither Drosophila nor Caenorhabditis elegans suffice to unravel higher order decisions. Genetic analyses in mouse and zebrafish may provide one entrance to these pathways. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR MOL GENET,LA JOLLA,CA 92093. RP Fishman, MC (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 210 TC 341 Z9 343 U1 4 U2 24 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1997 VL 124 IS 11 BP 2099 EP 2117 PG 19 WC Developmental Biology SC Developmental Biology GA XH383 UT WOS:A1997XH38300001 PM 9187138 ER PT J AU Chin, AJ Chen, JN Weinberg, ES AF Chin, AJ Chen, JN Weinberg, ES TI Bone morphogenetic protein-4 expression characterizes inductive boundaries in organs of developing zebrafish SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE heart; zebrafish; organogenesis; patterning; BMP4 ID EARLY XENOPUS EMBRYO; VENTRALIZING FACTOR; NEURAL INDUCTION; BMP-4; MESODERM; MOUSE; ECTODERM; SIGNALS; GENES; FATE AB We have cloned and examined the expression pattern of zebrafish bone morphogenetic protein-4 (BMP4) as a start to evaluating signals which might participate in the fashioning of organ systems in this genetically tractable species. The predicted sequence of the mature zebrafish protein is more than 75% identical to that of other vertebrates and 66% identical to Drosophila decapentaplegic (Dpp). As in other species, BMP4 is ex pressed ventrally during gastrulation, but the zebrafish is unusual in having an additional dorsal domain of expression. Subsequent BMP4 expression is especially prominent in sensory organs, fm buds, and in the gut, kidney, and heart. In al these sites, it becomes particularly enriched in regions of inductive demarcations. For example, expression initially extends through the entire heart tube but then becomes limited to the boundaries between cardiac chambers (sinus venosus-atrial junction, atrioventricular junction, and aortic root) prior to cushion formation. In early pectoral fin development, BMP4 is at first expressed uniformly but then becomes restricted to the mesenchyme subjacent to the apical ectodermal ridge. This suggests that among its roles in development, BMP4 serves as a signal in primordial outgrowth and also as a signal demarcating the borders within organs or structures where subspecializations occur. C1 CHILDRENS HOSP PHILADELPHIA,DIV CARDIOL,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104. RP Chin, AJ (reprint author), UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104, USA. OI Chen, Jau-Nian/0000-0001-8807-3607; Chin, Alvin/0000-0002-0417-8653 NR 44 TC 44 Z9 45 U1 3 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD JUN PY 1997 VL 207 IS 2 BP 107 EP 114 DI 10.1007/s004270050097 PG 8 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA XL561 UT WOS:A1997XL56100005 PM 27747403 ER PT J AU Zhu, ZM Miller, JB AF Zhu, ZM Miller, JB TI MRF4 can substitute for myogenin during early stages of myogenesis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE MRF4; myogenin; myogenesis; regulatory loops; transgenic mouse ID REGULATORY FACTOR PROTEINS; HEAVY-CHAIN ISOFORMS; SKELETAL-MUSCLE; TRANSCRIPTION FACTORS; MYOD FAMILY; MOUSE EMBRYOGENESIS; CELL LINEAGES; UP-REGULATION; MICE LEADS; EXPRESSION AB MRF4, myogenin, MyoD, and Myf-5 are the four members of the basic helix-loop-helix family of muscle-specific regulatory factors (MRFs), We examined whether MRF4 could substitute for myogenin in vivo by determining if the myofiber- and MRF4-deficient phenotype of myogenin (-/-) mice could be rescued by a myogenin promoter-MRF4 transgene. When the transgene was expressed at a physiological level in myogenin-deficient fetuses, we found that expression of the endogenous MRF4 gene was restored to normal levels, whereas MyoD levels were unchanged. Thus, MRF4 can participate in a positive autoregulatory loop and can substitute for myogenin to activate its own promoter. Myogenin-deficient fetuses that expressed the transgene also had more myosin, more and larger myofibers, and a more normal ribcage morphology than myogenin-deficient littermates without the transgene, The transgene failed, however, to restore normal numbers of myofibers or viability to myogenin-deficient mice, because the similar to 1.6 kb myogenin promoter fragment was not expressed in most late-forming myofibers. These results demonstrate that MRF4 is able to substitute for myogenin to activate MRF4 expression and promote myofiber formation during the early stages of myogenesis. (C) 1997 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. NR 51 TC 32 Z9 38 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 1997 VL 209 IS 2 BP 233 EP 241 DI 10.1002/(SICI)1097-0177(199706)209:2<233::AID-AJA9>3.0.CO;2-J PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA XC555 UT WOS:A1997XC55500009 PM 9186058 ER PT J AU Sigal, RJ ElHashimy, M Martin, BC Soeldner, JS Krolewski, AS Warram, JH AF Sigal, RJ ElHashimy, M Martin, BC Soeldner, JS Krolewski, AS Warram, JH TI Acute postchallenge hyperinsulinemia predicts weight gain - A prospective study SO DIABETES LA English DT Article ID INSULIN RESISTANCE; FOOD-INTAKE; GLUCOSE-TOLERANCE; BODY-WEIGHT; INTRAVENOUS GLUCOSE; OBESITY; SENSITIVITY; SECRETION; INFUSION AB The relationships of insulin secretion and insulin action to body weight are incompletely understood. Obesity is associated with reduced sensitivity to insulin and high fasting and postprandial serum insulin levels. However, it is unknown whether insulin secretion rises to compensate for insulin resistance or high insulin secretion promotes body weight gain and the development of insulin resistance. To shed Light on this question, are examined weight gain over an interval of 16.7 +/- 3.9 years (mean +/- SD) in 107 glucose-tolerant offspring (48 men, 59 women) of two parents with NIDDM. The offspring had a baseline intravenous glucose tolerance test, at which time they were aged 32.9 +/- 9.7 years, and only those who did not develop diabetes during the follow-up period were included. We estimated insulin sensitivity with the insulin sensitivity index from Bergman's minimal model of glucose disposal and acute insulin secretion from the incremental area under the insulin curve in the first 10 min of the intravenous glucose tolerance test. Weight-gain rate (g/year) was defined as the regression slope of each subject's body weight over time. High acute insulin secretion, young age, and low baseline percent ideal body weight (IBW) were each associated with a high rate of weight gain. After adjustment for differences in age and IBW, statistically significant effects of insulin sensitivity (P = 0.05) as well as acute insulin secretion (P = 0.001) were obtained. To estimate the effects of acute insulin secretion and insulin sensitivity on the average rate of weight gain (adjusting for age and IBW), the study group was stratified into four subgroups by dividing it at the medians of these two variables. Among those with low acute insulin secretion, weight-gain rate was the same regardless of whether insulin sensitivity was low or high (176 and 152 g/year, respectively). Among those with high acute insulin secretion, mean weight-gain rate was still rather low in those with low insulin sensitivity (271 g/year), but it was quite high in those with high insulin sensitivity (672 g/year; significantly higher than in all other subgroups). Therefore a high first-phase insulin response to intravenous glucose is a risk factor for long-term weight gain, and this effect is particularly manifested in insulin-sensitive individuals. C1 JOSLIN DIABET CTR, SECT EPIDEMIOL & GENET, BOSTON, MA 02215 USA. UNIV CALIF DAVIS, MED CTR, SACRAMENTO, CA 95817 USA. FU NIDDK NIH HHS [R01-DK-47475] NR 32 TC 94 Z9 97 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 1997 VL 46 IS 6 BP 1025 EP 1029 DI 10.2337/diabetes.46.6.1025 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA240 UT WOS:A1997XA24000015 PM 9166675 ER PT J AU Glucksmann, MA Lehto, M Tayber, O Scotti, S Berkemeier, L Pulido, JC Wu, Y Nir, WJ Fang, L Markel, P Munnelly, KD Goranson, J Orho, M Young, BM Whitacre, JL McMenimen, C Wantman, M Tuomi, T Warram, J Forsblom, CM Carlsson, M Rosenzweig, J Kennedy, G Duyk, GM Krolewski, AS Groop, LC Thomas, JD AF Glucksmann, MA Lehto, M Tayber, O Scotti, S Berkemeier, L Pulido, JC Wu, Y Nir, WJ Fang, L Markel, P Munnelly, KD Goranson, J Orho, M Young, BM Whitacre, JL McMenimen, C Wantman, M Tuomi, T Warram, J Forsblom, CM Carlsson, M Rosenzweig, J Kennedy, G Duyk, GM Krolewski, AS Groop, LC Thomas, JD TI Novel mutations and a mutational hotspot in the MODY3 gene SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GLUCOKINASE GENE; INSULIN; YOUNG; TRANSCRIPTION; HOMEOPROTEIN; SUBTYPE; HNF1 AB Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by mutations in the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1 alpha) located on chromosome 12q. We have identified four novel HNF-1 alpha missense mutations in MODY3 families, In four additional and unrelated families, we observed an identical insertion mutation that had occurred in a polycytidine tract in exon 4. Among those families, one exhibited a de novo mutation at this location. We propose that instability of this sequence represents a general mutational mechanism in MODY3. We observed no HNF-1 alpha mutations among 86 unrelated late-onset diabetic patients with relative insulin deficiency. Hence mutations in this gene appear to be most strongly associated with early-onset diabetes. C1 MILLENNIUM PHARMACEUT INC,CAMBRIDGE,MA 02139. LUND UNIV,MALMO UNIV HOSP,WALLENBERG LAB,DEPT ENDOCRINOL,MALMO,SWEDEN. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,SECT EPIDEMIOL & GENET,BOSTON,MA 02115. UNIV HELSINKI HOSP,DIV INTERNAL MED,HELSINKI,FINLAND. CHIRON CORP,EMERYVILLE,CA 94608. NR 30 TC 76 Z9 83 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1997 VL 46 IS 6 BP 1081 EP 1086 DI 10.2337/diabetes.46.6.1081 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA240 UT WOS:A1997XA24000024 PM 9166684 ER PT J AU Kieffer, TJ Keller, RS Leech, CA Holz, GG Habener, JF AF Kieffer, TJ Keller, RS Leech, CA Holz, GG Habener, JF TI Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta-cells SO DIABETES LA English DT Article ID OBESE GENE-PRODUCT; OB-OB MICE; SULFONYLUREA RECEPTOR; NEUROPEPTIDE-Y; OB/OB MICE; MOUSE; PROTEIN; CLONING; ISLETS AB In the genetic mutant mouse models ob/ob or db/db, leptin deficiency or resistance, respectively, results in severe obesity and the development of a syndrome resembling NIDDM, One of the earliest manifestations in these mutant mice is hyperinsulinemia, suggesting that leptin may normally directly suppress the secretion of insulin. Here, we show that pancreatic islets express a long (signal-transducing) form of leptin-receptor mRNA and that beta-cells bind a fluorescent derivative of leptin (Cy3-leptin). The expression of leptin receptors on insulin-secreting beta-cells was also visualized utilizing antisera generated against an extracellular epitope of the receptor, A functional role for the beta-cell leptin receptor is indicated by our observation that leptin (100 ng/ml) suppressed the secretion of insulin from islets isolated from ob/ob mice, Furthermore, leptin produced a marked lowering of [Ca2+](i) in ob/ob beta-cells, which was accompanied by cellular hyperpolarization and increased membrane conductance. Cell-attached patch measurements of ob/ob beta-cells demonstrated that leptin activated ATP-sensitive potassium channels (K-ATP) by increasing the open channel probability, while exerting no effect on mean open time, These effects were reversed by the sulfonylurea tolbutamide, a specific inhibitor of K-ATP. Taken together, these observations indicate an important physiological role for leptin as an inhibitor of insulin secretion and lead us to propose that the failure of leptin to inhibit insulin secretion from the beta-cells of ob/ob and db/db mice may explain, in part, the development of hyperinsulinemia, insulin resistance, and the progression to NIDDM. C1 MASSACHUSETTS GEN HOSP,MOL ENDOCRINOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [R01 DK045817, R01 DK045817-06A2] NR 40 TC 290 Z9 327 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1997 VL 46 IS 6 BP 1087 EP 1093 DI 10.2337/diabetes.46.6.1087 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA240 UT WOS:A1997XA24000025 PM 9166685 ER PT J AU Kotsanos, JG Vignati, L Huster, W Andrejasich, C Boggs, MB Jacobson, AM Marrero, D Mathias, SD Patrick, SD Zalani, S Anderson, J AF Kotsanos, JG Vignati, L Huster, W Andrejasich, C Boggs, MB Jacobson, AM Marrero, D Mathias, SD Patrick, SD Zalani, S Anderson, J TI Health-related quality-of-life results from multinational clinical trials of insulin lispro - Assessing benefits of a new diabetes therapy SO DIABETES CARE LA English DT Article AB OBJECTIVE - To compare health-related quality of life (HRQOL) in patients with diabetes receiving insulin lispro with patients receiving regular human insulin (Humulin R). RESEARCH DESIGN AND METHODS - We performed two randomized comparative studies over a 6-month period (3 months per treatment). Primary analyses used crossover baseline to 3-month changes in HRQOL scores. Ninety-three principal investigators in Canada, France, Germany, and the U.S. participated in these studies. One HRQOL crossover study included 468 patients with type I diabetes; the other HRQOL crossover study included 474 patients with type II diabetes. In both studies, patients were taking insulin at least 2 months before enrollment. Primary outcomes included two generic HRQOL domains, energy/fatigue and health distress, and two diabetes-specific domains, treatment satisfaction and treatment flexibility. Thirty secondary outcomes included both generic and diabetes-specific measures. Secondary outcome domains were controlled for multiplicity in the analyses. RESULTS - Primary analyses showed that treatment satisfaction scores (P < 0.001) and treatment flexibility scores (P = 0.001) were higher for insulin lispro in type I diabetic patients. No other significant treatment differences were detected using the data from these 6-month crossover studies. CONCLUSIONS - Treatment satisfaction and treatment flexibility were significantly improved in patients with type I diabetes using insulin lispro. Other HRQOL findings were comparable for insulin lispro and regular human insulin. Insulin lispro appears to have a measurable impact on lifestyle benefits in patients with type I diabetes, as demonstrated by increased treatment satisfaction and treatment flexibility. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. REGENSTRIEF INST HLTH CARE,INDIANAPOLIS,IN 46202. TECHNOL ASSESSMENT GRP,SAN FRANCISCO,CA. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. RP Kotsanos, JG (reprint author), ELI LILLY & CO,LILLY CORP CTR,INDIANAPOLIS,IN 46285, USA. NR 19 TC 90 Z9 91 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1997 VL 20 IS 6 BP 948 EP 958 DI 10.2337/diacare.20.6.948 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WZ876 UT WOS:A1997WZ87600008 PM 9167105 ER PT J AU Allan, CJ Argyropoulos, G Bowker, M Zhu, JG Lin, PM Stiver, K Golichowski, A Garvey, WT AF Allan, CJ Argyropoulos, G Bowker, M Zhu, JG Lin, PM Stiver, K Golichowski, A Garvey, WT TI Gestational diabetes mellitus and gene mutations which affect insulin secretion SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE gestational diabetes; gene mutations; impaired insulin secretion; glucokinase; tRNA(leu); mitochondrial DNA ID MITOCHONDRIAL TRNA(LEU(UUR)) GENE; GLUCOKINASE GENE; JAPANESE SUBJECTS; NIDDM; YOUNG; IDENTIFICATION; VARIANTS; MARKER; LOCUS AB We investigated whether genetic mutations known to impair insulin secretion and glucose tolerance are operative in a group of American women with gestational diabetes mellitus. Study groups were comprised of elderly non-diabetic controls (n = 55) with normal glucose tolerance and patients with gestational diabetes (n = 50), together with one family with maturity-onset diabetes of the young (three controls and three affected). No mutations were detected in any exon of the human glucokinase gene or the mitochondrial tRNA(Leu(UUR)) gene by single strand conformational analysis; and direct exon sequencing. Also, X-2 analysis showed no significant association with gestational diabetes for a polymorphism at position -30 (G --> A) of the beta-cell-specific glucokinase gene promoter. We have determined that glucokinase and mitochondrial tRNA(Leu(UUR)) gene mutations, which are known to impair insulin secretion are relatively uncommon and do not constitute a large component of genetic risk for gestational diabetes in the study population. (C) 1997 Elsevier Science Ireland Ltd. C1 MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MED,DIV ENDOCRINOL DIABET & MED GENET,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29425. INDIANA UNIV,SCH MED,DEPT OBSTET & GYNECOL,INDIANAPOLIS,IN 46202. FU NIDDK NIH HHS [DK-47461, DK-38765] NR 24 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD JUN PY 1997 VL 36 IS 3 BP 135 EP 141 DI 10.1016/S0168-8227(97)00042-9 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XK925 UT WOS:A1997XK92500001 PM 9237779 ER PT J AU Seufert, J Lu, M Habener, JF AF Seufert, J Lu, M Habener, JF TI CCAAT/enhancer-binding protein beta (C/EBP beta) is induced by hyperglycemia and inhibits transcription of the rat insulin I gene through interaction with E2A transcription factors SO DIABETOLOGIA LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,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 JUN PY 1997 VL 40 SU 1 BP 97 EP 97 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300097 ER PT J AU Saouaf, R Fielding, RA Donaghue, VM Horton, ES Veves, A AF Saouaf, R Fielding, RA Donaghue, VM Horton, ES Veves, A TI The effect of exercise on the endothelial function of the micro-and macro-circulation in IDDM. SO DIABETOLOGIA LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEACONESS JOSLIN FOOT CTR,BOSTON,MA. BOSTON UNIV,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 JUN PY 1997 VL 40 SU 1 BP 137 EP 137 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300137 ER PT J AU Draznin, B Goalstone, M Leitner, JW AF Draznin, B Goalstone, M Leitner, JW TI Hyperinsulinemia potentiates activation of p21Ras by growth factors. SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. DENVER VAMC,DENVER,CO. 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 JUN PY 1997 VL 40 SU 1 BP 151 EP 151 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300150 ER PT J AU Penfornis, A Ma, L Faustman, D AF Penfornis, A Ma, L Faustman, D TI Examination of human beta 2-microglobulin (beta 2-m) gene as a contributor to defective IDDM antigen presentation. SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV FRANCHE COMTE,F-25030 BESANCON,FRANCE. MASSACHUSETTS GEN HOSP,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 JUN PY 1997 VL 40 SU 1 BP 211 EP 211 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300208 ER PT J AU Suzuki, K BonnerWeir, S Trivedi, N Yoon, KH HollisterLock, J Colton, CK Weir, GC AF Suzuki, K BonnerWeir, S Trivedi, N Yoon, KH HollisterLock, J Colton, CK Weir, GC TI Successful islet transplantation using planar type diffusion membrane devices SO DIABETOLOGIA LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. MIT,CAMBRIDGE,MA 02139. 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 JUN PY 1997 VL 40 SU 1 BP 460 EP 460 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300455 ER PT J AU Weijnen, CF Warram, JH Krolewski, AS AF Weijnen, CF Warram, JH Krolewski, AS TI Maternal and paternal diabetes confer similar risks of Type II diabetes to children SO DIABETOLOGIA LA English DT Meeting Abstract C1 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 JUN PY 1997 VL 40 SU 1 BP 787 EP 787 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300781 ER PT J AU Bajaj, M Kinsley, BT Weinger, K Ley, CJ Waters, M Simonson, DC Cox, D Jacobson, AM AF Bajaj, M Kinsley, BT Weinger, K Ley, CJ Waters, M Simonson, DC Cox, D Jacobson, AM TI Effect of blood glucose awareness training on epinephrine responses to hypoglycemia in intensively treated diabetes SO DIABETOLOGIA LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02115. UNIV VIRGINIA,CHARLOTTESVILLE,VA. 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 JUN PY 1997 VL 40 SU 1 BP 936 EP 936 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12300929 ER PT J AU Smith, F Whitney, C Friedlander, E Mullooly, C Hill, J Bursell, SE King, G AF Smith, F Whitney, C Friedlander, E Mullooly, C Hill, J Bursell, SE King, G TI Prospective exercise and weight loss study in Type II diabetic subjects improved insulin resistance, lipids and leptins SO DIABETOLOGIA LA English DT Meeting Abstract C1 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 JUN PY 1997 VL 40 SU 1 BP 1026 EP 1026 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301019 ER PT J AU delAguila, MA Pugh, J Reiber, GE AF delAguila, MA Pugh, J Reiber, GE TI How does delay in seeking care for a diabetic foot lesion influence outcome? SO DIABETOLOGIA LA English DT Meeting Abstract C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. 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 JUN PY 1997 VL 40 SU 1 BP 1884 EP 1884 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12301873 ER PT J AU Parker, D Kilo, C Baum, J Joynes, J Pistone, B AF Parker, D Kilo, C Baum, J Joynes, J Pistone, B TI Evaluation of an enhanced electrochemical glucose meter system by diabetics and nurses at three clinical sites SO DIABETOLOGIA LA English DT Meeting Abstract C1 W CTY INTERNAL MED,ST LOUIS,MO. ABBOTT NW HOSP,MINNEAPOLIS,MN 55407. DENVER VA MED CTR,DENVER,CO. BAYER CORP,ELKHART,IN. 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 JUN PY 1997 VL 40 SU 1 BP 2514 EP 2514 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG123 UT WOS:A1997XG12302499 ER PT J AU Lembo, T Munakata, J Naliboff, B Fullerton, S Mayer, EA AF Lembo, T Munakata, J Naliboff, B Fullerton, S Mayer, EA TI Sigmoid afferent mechanisms in patients with irritable bowel syndrome SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE sigmoid colon; irritable bowel syndrome ID INTESTINAL MOTILITY; RECTAL DISTENSION; COLON; IBS; DISORDER; BALLOON; TONE AB Up to 60% of patients with IBS have lowered perception thresholds in the rectum to balloon distension. The current study sought to test the hypothesis that IBS patients with normal perception thresholds in the rectum show hypersensitivity of afferent pathways in the sigmoid colon. Eleven healthy normal subjects and eight IBS patients with normal rectal perception thresholds underwent a balloon distension protocol in the sigmoid and rectum. Discomfort thresholds, receptive relaxation, compliance, and referral patterns were measured. Although IBS patients had significantly lower discomfort thresholds in the sigmoid when measured as volume, pressure, and wall tension, thresholds were similar to normals. Receptive relaxation and dynamic compliance were significantly decreased in IBS patients in the sigmoid. Referral patterns were similar during sigmoid distention in IBS patients in comparison to normals. Despite normal perception thresholds in rectum and sigmoid, IBS patients show evidence for alterations in rectosigmoid afferent mechanisms. In the sigmoid, this is seen in the form of reduced reflex relaxation and compliance and in the rectum in the form of altered viscerosomatic referral. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MED,GASTROENTER BIOL CTR,LOS ANGELES,CA 90095. NR 27 TC 48 Z9 48 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 1997 VL 42 IS 6 BP 1112 EP 1120 DI 10.1023/A:1018817132213 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XF479 UT WOS:A1997XF47900002 PM 9201070 ER PT J AU Stoltenberg, RL Madsen, JA Schlack, SC Harms, BA Jacoby, RF AF Stoltenberg, RL Madsen, JA Schlack, SC Harms, BA Jacoby, RF TI Neoplasia in ileal pouch mucosa after total proctocolectomy for juvenile polyposis - Report of a case SO DISEASES OF THE COLON & RECTUM LA English DT Article DE proctocolectomy, restorative; neoplastic syndromes, hereditary; intestinal polyps; colonic polyps; adenomatous polyposis coli; adenomatous polyps ID ILEOANAL ANASTOMOSIS; ULCERATIVE-COLITIS; FAMILIAL POLYPOSIS; TOTAL COLECTOMY; CARCINOMA; PATHOGENESIS; RISK AB PURPOSE: Patients treated with restorative proctocolectomy for familial adenomatous polyposis or ulcerative colitis occasionally develop disease in the ileal pouch similar to that originally present in the colon. We investigated the possibility of analogous involvement in the ileal pouch of juvenile polyposis patients. METHODS: Endoscopic surveillance for neoplasia throughout the gastrointestinal tract was performed, with retrieval of all polypectomy specimens for histologic classification using the criteria of Morson. RESULTS: Multiple large juvenile polyps were found in the ileal pouch of one patient less than 10 years after restorative proctocolectomy for hereditary juvenile polyposis. The pouch was much more severely affected than the proximal ileum, small intestine, or stomach. Although most polyps had a completely benign histologic appearance, three had moderate to severe dysplasia. DISCUSSION: Mucosal changes induced by bacteria or stasis of luminal contents may promote manifestation in the ileal pouch of the disease phenotype usually more evident in the colon. Patients with severe or generalized juvenile polyposis should be considered for periodic endoscopic surveillance of the ileal pouch beginning several years after restorative proctocolectomy. C1 UNIV WISCONSIN,SCH MED,DEPT SURG,MADISON,WI 53792. UNIV WISCONSIN,DEPT PATHOL,MADISON,WI 53792. UNIV WISCONSIN,DEPT MED,GASTROENTEROL SECT,MADISON,WI 53792. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. FU NCI NIH HHS [P30 CA14520, U01 CA59352] NR 27 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JUN PY 1997 VL 40 IS 6 BP 726 EP 730 DI 10.1007/BF02140904 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA XE007 UT WOS:A1997XE00700014 PM 9194469 ER PT J AU Fava, M AF Fava, M TI Anger attacks in unipolar depressive disorders SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Article; Proceedings Paper CT 6th Lilly Symposium of the Central Nervous System CY NOV 22-23, 1996 CL PARIS, FRANCE DE anger attacks; antidepressants; unipolar depressive disorders ID FLUOXETINE TREATMENT; HOSTILITY AB Approximately one third of depressed outpatients present with <>, sudden spells of anger accompanied by symptoms of autonomic activation such as tachycardia, sweating, flushing, and tightness of the chest. These anger attacks are experienced by the patients as uncharacteristic of them and inappropriate to the situations in which they occur. Depressed patients with anger attacks are significantly more anxious and hostile, and they are more likely to meet criteria for borderline, histrionic, narcissistic, and antisocial personality disorders than depressed patients without anger attacks. Treatment studies suggest that antidepressant treatment of anger attacks in depression is helpful and sage. Anger attacks disappear in 53-71 % of depressed outpatients treated with antidepressants such as fluoxetine (Prozac(R)), sertraline and imipramine. In addition, the rate of emergence of anger attacks after treatment with fluoxetine (Prozac(R)) (6-7 %) is no different from the rates observed after treatment with sertraline (8 %) and imipramine (10 %), and lower than the rate with placebo (20 %). Finally, one can hypothesize that antidepressants that affect serotonergic neurotransmission, known to be involved in the modulation of aggressive behavior in animals and humans, should be particularly effective in this population. Larger placebo-controlled studies, comparing selective serotonin reuptake inhibitors such as fluoxetine with relatively noradrenergic tricyclic antidepressants such as desipramine, may help us understand whether depressed patients with anger attacks show a distinctive responsiveness to drug treatment. C1 MASSACHUSETTS GEN HOSP,DEPRESS CLIN & RES PROGRAM,BOSTON,MA 02114. NR 18 TC 6 Z9 6 U1 1 U2 1 PU DOIN EDITEURS PI PARIS PA 47 RUE SAINT-ANDRE-DES-ARTS, F-75006 PARIS, FRANCE SN 0013-7006 J9 ENCEPHALE JI Enceph.-Rev. Psychiatr. Clin. Biol. Ther. PD JUN PY 1997 VL 23 SI 3 BP 39 EP 42 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XK590 UT WOS:A1997XK59000007 PM 9333559 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 ENDOCRINOLOGY LA English DT Article ID HORMONE-BINDING DOMAIN; RETINOID-X-RECEPTOR; 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR; ULTIMOBRANCHIAL GLANDS; CALCIUM-METABOLISM; ACID; SEQUENCE; GENE; EXPRESSION; MUTATIONS AB The Vitamin D receptor (VDR), a member of the nuclear receptor superfamily, mediates the effects of 1,25-dihydroxyvitamin D-3 on mineral ion homeostasis. Although the mammalian and avian VDRs have been extensively studied, little is known about the VDR in lower vertebrate species. To address this, we have isolated the Xenopus laevis VDR (xVDR) complementary DNA. Overall, the xVDR shares 79%, 73%, 73%, and 75% identity at the amino acid level with the chicken, mouse, rat, and human VDRs, respectively. The amino acid residues and subdomains important for DNA binding, hormone binding, dimerization, and transactivation are mostly conserved among all VDR species. The xVDR polypeptide can heterodimerize with the mouse retinoid X receptor alpha, bind to the rat osteocalcin vitamin D response element (VDRE), and induce vitamin D-dependent transactivation in transfected mammalian cells. Northern analysis reveals two xVDR messenger RNA species of 2.2 kb and 1.8 kb in stage 60 Xenopus tissues. In the adult, xVDR expression is detected in many tissues including kidney, intestine, skin, and bone. During Xenopus development, xVDR messenger RNA first appears at developmental stage 13 (preneurulation), increasing to maximum at stages 57-61 (metamorphosis). Our data demonstrate that, in Xenopus, VDR expression is developmentally regulated and that the vitamin D endocrine system is highly conserved during evolution. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. NR 51 TC 40 Z9 42 U1 1 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 JUN PY 1997 VL 138 IS 6 BP 2347 EP 2353 DI 10.1210/en.138.6.2347 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA025 UT WOS:A1997XA02500020 PM 9165021 ER PT J AU Elliott, ME Goodfriend, TL Ball, DL Jefcoate, CR AF Elliott, ME Goodfriend, TL Ball, DL Jefcoate, CR TI Angiotensin-responsive adrenal glomerulosa cell proteins: Characterization by protease mapping, species comparison, and specific angiotensin receptor antagonists SO ENDOCRINOLOGY LA English DT Article ID LEYDIG TUMOR-CELLS; ACUTE REGULATORY PROTEIN; STIMULATED ALDOSTERONE SYNTHESIS; MITOCHONDRIAL PROTEINS; CORPUS-LUTEUM; ADRENOCORTICOTROPIC HORMONE; RAPID ACCUMULATION; FASCICULATA CELLS; STEROID-SYNTHESIS; ZONA-GLOMERULOSA AB Angiotensin II (AngII)-stimulated aldosterone synthesis is mediated by the AngII type 1 (AT(1)) receptor and requires ongoing protein synthesis. Hormonally-stimulated turnover of a family of 28- to 30-kDa proteins (p30, or steroidogenic acute regulatory proteins) has been linked to enhanced steroid synthesis in several tissues. Our previous work showed that AngII, dibutyryl cAMP, potassium, and atrial natriuretic peptide affected labeling of a group of eight proteins (four of 28 kDa and four of 30 kDa) in bovine adrenal glomerulosa cells. This report extends our findings in three ways: I) The eight [S-35]-methionine-labeled p30 proteins in bovine cells were compared with each other by chymotryptic peptide mapping. Similarity in maps indicated that the eight proteins share a common primary structure. 2)Dibutyryl cAMP treatment of rat adrenal glomerulosa cells affected the levels of Four 28-kDa proteins and one 35-kDa protein, whereas AngII affected two of the 28-kDa proteins. There were no responsive 80-kDa proteins in rats comparable with those seen in bovine cells. These results indicate a species difference in the affected proteins. 3) The AT(1) receptor antagonist, losartan, inhibited the effects of AngII on aldosterone synthesis and turnover of the p30 proteins in bovine adrenal glomerulosa cells. PD123319, an antagonist specific for the AngII type 2 receptor, did not block AngII-stimulated aldosterone synthesis and had much less effect on p30 protein labeling than did losartan. These results add to the growing body of evidence that this family of p30 or steroidogenic acute regulatory proteins plays a role in the acute regulation of steroidogenesis by a wide variety of stimulatory hormones in several tissues and species. In addition, Iosartan's inhibition of AngII's effects on the p30 proteins is consistent with a key role for these proteins in processes linking occupation of the AT, receptor to stimulation of aldosterone synthesis. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT PHARMACOL,MADISON,WI 53706. RP Elliott, ME (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,HYPERTENS RES LAB,ROOM C4114,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NIDDK NIH HHS [DK-18585] NR 45 TC 9 Z9 9 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1997 VL 138 IS 6 BP 2530 EP 2536 DI 10.1210/en.138.6.2530 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XA025 UT WOS:A1997XA02500044 PM 9165045 ER PT J AU Robinson, WE Ryan, DK Sullivan, PA Boggs, CC AF Robinson, WE Ryan, DK Sullivan, PA Boggs, CC TI Cadmium binding in the blood plasma of two marine bivalves SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE cadmium; metal transport; blood plasma; mussel; ion-specific electrode ID ION-SELECTIVE ELECTRODES; OYSTER OSTREA-EDULIS; CONTAINING AMEBOCYTES; MYTILUS-EDULIS; NATURAL-WATERS; METAL-IONS; PROTEINS; ZINC; COPPER; METALLOTHIONEIN AB Cadmium transport in the plasma of Mytilus edulis L. displays attributes similar to those previously described for Mercenaria mercenaria (L.). The majority of Cr, Cu, Ni, and Zn is partitioned in the plasma rather than the hemocytes in both species, although differences in Fe and Mn are apparent. Mussels however contain twice the number of circulating hemocytes (2.1 +/- 0.8% of whole blood weight; n = 75 vs 1.2 +/- 0.3%; n = 70 for the quahog) and approximately three times more plasma protein than the quahog. Titration experiments using ion-specific electrode (ISE) measurements and equilibrium dialysis (ED) experiments indicate that both species have a low-affinity, high-capacity system for the internal transport of Cd. At low blood Cd concentrations (<8.9 mu M) and short dialysis times (24 h), approximately 90% of the Cd in mussel plasma is bound to plasma proteins. At higher Cd concentrations and at longer dialysis times, the percentage of free Cd increases substantially. The Cd affinity was slightly lower in mussel plasma compared to the quahog (log(10)K = 2.6-3.9/M vs 3.7-4.3/M), and mussel plasma C-L values were appreciably lower (0.16-1.11 mmol/g protein) than those for the quahog (1.97-2.26 mmol/g protein). Both ISE and ED experiments on quahog plasma yielded similar estimates of K and C-L. C1 UNIV LOWELL,DEPT CHEM,LOWELL,MA 01854. MASSACHUSETTS WATER RESOURCES AUTHOR,CHARLESTOWN NAVY YARD,BOSTON,MA 02152. MASSACHUSETTS GEN HOSP,CHARLESTOWN NAVY YARD,BOSTON,MA 02152. RP Robinson, WE (reprint author), UNIV MASSACHUSETTS,ENVIRONM SCI PROGRAM,BOSTON,MA 02125, USA. NR 40 TC 14 Z9 14 U1 1 U2 6 PU SETAC PRESS PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370 SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JUN PY 1997 VL 16 IS 6 BP 1195 EP 1202 DI 10.1897/1551-5028(1997)016<1195:CBITBP>2.3.CO;2 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA XC442 UT WOS:A1997XC44200014 ER PT J AU Goldmann, WH Tempel, M Sprenger, I Isenberg, G Ezzell, RM AF Goldmann, WH Tempel, M Sprenger, I Isenberg, G Ezzell, RM TI Viscoelasticity of actin-gelsolin networks in the presence of filamin SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE viscoelasticity; actin network; filamin; gelsolin; rheology ID BINDING-PROTEIN; MECHANICAL-PROPERTIES; LIPID-MEMBRANES; ALPHA-ACTININ; F-ACTIN; PURIFICATION; QUANTITATION; FILAMENTS; DYNAMICS; MYOSIN AB Cross-linking of actin filaments by filamin by means of frequency-dependent rheology yields an increase in the filament's elasticity and stiffness. Higher cross-linker (filamin) ratios are required for mean actin-filament lengths of 5-6 mu m than for random-length distribution of actin filaments. The loss modulus (i.e. the viscous portion) in the region of the internal-chain dynamics [G''(omega) approximate to omega(alpha)] is influenced by the cross-linking of filaments, and with an increasing molar ratio of filamin/actin a reduction of a is observed. Rheological measurements reveal that actin networks are already formed at the polymerizing stage at a molar ratio of filamin/actin of less than 1:100, and electron micrographs show phase separation of actin/filament networks of low density and of actin/filament bundles. C1 TECH UNIV MUNICH,D-8046 GARCHING,GERMANY. RP Goldmann, WH (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SURG RES UNIT,SURG RES LABS,BLDG 149,13TH ST,CHARLESTOWN,MA 02139, USA. RI Goldmann, Wolfgang/H-5572-2013 NR 37 TC 22 Z9 22 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUN PY 1997 VL 246 IS 2 BP 373 EP 379 DI 10.1111/j.1432-1033.1997.00373.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XE025 UT WOS:A1997XE02500014 PM 9208927 ER PT J AU Aspnes, LE Lee, CM Weindruch, R Chung, SS Roecker, EB Aiken, JM AF Aspnes, LE Lee, CM Weindruch, R Chung, SS Roecker, EB Aiken, JM TI Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle SO FASEB JOURNAL LA English DT Article DE aging; sarcopenia; mitochondria; skeletal muscle ID CYTOCHROME-C-OXIDASE; ANTIOXIDANT ENZYME-ACTIVITIES; DNA OXIDATIVE DAMAGE; SKELETAL-MUSCLE; DIETARY RESTRICTION; FOOD RESTRICTION; MULTIPLE DELETIONS; RHESUS-MONKEYS; LIFE-SPAN; ATROPHY AB The influence of caloric restriction (CR) initiated at 17 months of age was investigated on selected age-associated measures in skeletal muscle. Tissue from young (3-4 months) ad libitum-fed, old (30-32 months) restricted (35% and 50% CR, designated CR35 and CR50, respectively), and old ad libitum-fed rats (29 months) was studied. CR preserved fiber number and fiber type composition in the vastus lateralis muscle of the CR50 rats. In the old rats from all groups, individual fibers were found with either no detectable cytochrome c oxidase activity (COX-), hyperreactivity for succinate dehydrogenase activity (SDH++; also known as ragged red fibers [RRF]), or both COX- and SDH++. Muscle from the CR50 rats contained significantly fewer COX- and SDH++ fibers than did the muscle from CR35 rats. CR50 rats also had significantly lower numbers of mtDNA deletion products in two (adductor longus and soleus) of the four muscles examined compared to CR35 rats. These data indicate that CR begun in late middle age can retard age-associated fiber loss and fiber type changes, as well as increases in the number of skeletal muscle fibers showing mitochondrial enzyme abnormalities. CR also decreased the accumulation of mtDNA deletions. C1 UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT BIOSTAT,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53706. RP Aspnes, LE (reprint author), UNIV WISCONSIN,DEPT ANIM HLTH & BIOMED SCI,1655 LINDEN DR,MADISON,WI 53706, USA. FU NIA NIH HHS [R01 AG11604, R01 AG10536, P01 AG11915] NR 82 TC 108 Z9 108 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 1997 VL 11 IS 7 BP 573 EP 581 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA XH342 UT WOS:A1997XH34200009 PM 9212081 ER PT J AU Smith, DG Barnes, BC Sands, AK Boyko, EJ Ahroni, JH AF Smith, DG Barnes, BC Sands, AK Boyko, EJ Ahroni, JH TI Prevalence of radiographic foot abnormalities in patients with diabetes SO FOOT & ANKLE INTERNATIONAL LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons CY FEB 22-24, 1996 CL ATLANTA, GA SP Amer Acad Orthopaed Surgeons ID ULCERATION; PRESSURE; JOINT; MANAGEMENT; NEUROPATHY; CALLUS; FEET AB Clinicians are increasingly aware that mechanical aspects of foot deformities, such as Charcot changes, clawtoes, bunion deformities, or cavus or planus foot deformities, might have an impact on the occurrence, potential healing, and recurrence of foot ulcers. We report the prevalence of plain radiographic changes and attempt to rate the severity of those deformities in the feet of 456 diabetic veteran medicine clinic enrollees. All 456 radiographs were reviewed by orthopaedic surgeons to specifically identify Charcot changes, presence of arterial calcification, dislocation of the lesser toe metatarsophalangeal joints, hallux interphalangeal joint dislocation, and radiographic evidence of previous surgery, Radiographs of 428 patients were taken while weightbearing, and these were reviewed to quantify hallux valgus angles, intermetatarsal 1-2 angles, fifth metatarsal-proximal phalangeal angles, second metatarsal lengths, lateral talocalcaneal and talar-first metatarsal angles, and claw toe deformities. The prevalence of Charcot changes was 1.4% (six subjects), and all had radiographic evidence of midfoot Charcot changes. Other deformities, such as clawtoes, hallux valgus, lesser toe joint dislocations, and alterations in arch freight, are more common in veterans with diabetes. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,SURG SERV,SEATTLE,WA. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. VET AFFAIRS PUGET SOUND HLTH CARE SYST,RES & DEV SERV,SEATTLE,WA. RP Smith, DG (reprint author), UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT ORTHOPAED SURG,BOX 359798,325 9TH AVE,SEATTLE,WA 98104, USA. NR 24 TC 30 Z9 32 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JUN PY 1997 VL 18 IS 6 BP 342 EP 346 PG 5 WC Orthopedics SC Orthopedics GA XF355 UT WOS:A1997XF35500006 PM 9208292 ER PT J AU Quirk, DM Barry, MJ AF Quirk, DM Barry, MJ TI Physician specialty and cost-effectiveness of diverticulitis care: A difficult knot to untangle SO GASTROENTEROLOGY LA English DT Editorial Material ID COLONOSCOPY; MANAGEMENT C1 MASSACHUSETTS GEN HOSP,DIV GEN MED,BOSTON,MA 02114. RP Quirk, DM (reprint author), MASSACHUSETTS GEN HOSP,GI UNIT GRJ 724,32 FRUIT ST,BOSTON,MA 02114, USA. NR 18 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1997 VL 112 IS 6 BP 2147 EP 2150 DI 10.1053/gast.1997.v112.agast972147 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA XE188 UT WOS:A1997XE18800052 PM 9178713 ER PT J AU Volker, JL Rameh, LE Zhu, Q DeCaprio, J Hansen, U AF Volker, JL Rameh, LE Zhu, Q DeCaprio, J Hansen, U TI Mitogenic stimulation of resting T cells causes rapid phosphorylation transcription factor LSF and increased DNA-binding activity SO GENES & DEVELOPMENT LA English DT Article DE LSF; MAP kinase; mitogens; phosphorylation; DNA-binding; T lymphocytes ID CASEIN KINASE-II; SERUM RESPONSE FACTOR; MAMMALIAN ORNITHINE DECARBOXYLASE; ACTIVATED PROTEIN-KINASE; NERVE GROWTH-FACTOR; MESSENGER-RNA; GENE; DOMAIN; MECHANISMS; EXPRESSION AB The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters modulated by cell growth signals. We demonstrate here that LSF-DNA-binding activity is strikingly regulated by induction of cell growth in human peripheral T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the electrophoretic mobility of LSF, attributable to phosphorylation, correlated with the increase in DNA-binding activity. pp44 (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in vivo, specifically at amino acid position 291, as indicated by mutant analysis. As direct verification of the causal relationship between phosphorylation and DNA-binding activity, treatment in vitro of LSF with phosphatase both increased the electrophoretic mobility of the protein and decreased LSF-DNA-binding activity. This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. FU NCI NIH HHS [T32-CA09361, CA38038] NR 65 TC 51 Z9 51 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 1997 VL 11 IS 11 BP 1435 EP 1446 DI 10.1101/gad.11.11.1435 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XE403 UT WOS:A1997XE40300007 PM 9192871 ER PT J AU Hurford, RK Cobrinik, D Lee, MH Dyson, N AF Hurford, RK Cobrinik, D Lee, MH Dyson, N TI pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes SO GENES & DEVELOPMENT LA English DT Article DE pRB; p107; p130; E2F; cell cycle regulation ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE REGULATION; HUMAN MYC PROMOTER; RETINOBLASTOMA PROTEIN; GROWTH-REGULATION; IN-VIVO; TRANS-ACTIVATION; MESSENGER-RNA; BINDING-SITE; S-PHASE AB The activity of the E2F transcription factor is controlled by physical association with the retinoblastoma protein (pRB) and two related proteins, p107 and p130. The pRB family members are thought to control different aspects of E2F activity, but it has been unclear what the respective functions of these proteins might be. To dissect the specific functions of pRB, p107, and p130 we have investigated how the expression of E2F-regulated genes is changed in cultures of primary cells lacking each of these family members. Whereas no changes were found in the expression of E2F-target genes in cells lacking either p107 or p130, deregulated expression of E2F targets was seen in cells lacking pRB and in cells lacking both p107 and p130. Surprisingly, the genes that were disregulated in these two settings were completely different. These findings show that PRE and p107/p130 indeed provide different functions in E2F regulation and identify target genes that are dependent on pRB family proteins for their normal expression. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. BOSTON UNIV,SCH MED,DEPT MED,CTR PULM,BOSTON,MA 02118. FU NCI NIH HHS [CA64402] NR 85 TC 357 Z9 361 U1 2 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 1997 VL 11 IS 11 BP 1447 EP 1463 DI 10.1101/gad.11.11.1447 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XE403 UT WOS:A1997XE40300008 PM 9192872 ER PT J AU Dairaku, K Spiro, RG AF Dairaku, K Spiro, RG TI Phylogenetic survey of endomannosidase indicates late evolutionary appearance of this N-linked oligosaccharide processing enzyme SO GLYCOBIOLOGY LA English DT Article DE endomannosidase; processing glycosidases; phylogenetic development; N-linked oligosaccharides; glucosidase II; alpha 1,2-mannosidase ID ALPHA-D-MANNOSIDASE; GLUCOSIDASE-II-DEFICIENT; MOUSE LYMPHOMA-CELLS; RAT-LIVER; GLYCOPROTEIN-BIOSYNTHESIS; ENDOPLASMIC-RETICULUM; TRYPANOSOMA-BRUCEI; SUGAR CHAINS; PATHWAY; EXPRESSION AB Endo-alpha-D-mannosidase is a processing enzyme which in contrast to other glycosidases involved in the trimming of N-linked oligosaccharides of glycoproteins acts at an internal position by cleaving the linkage between the glucosesubstituted mannose and the internal portion of the polymannose unit and thereby provides an alternate deglucosylating pathway, Tn order to evaluate at what stage in evolution this unusual enzyme first emerged, we have carried out a phylogenetic survey of its distribution among a broad group of eukaryotes ranging from unicellular organisms to highly developed animals and plants, all of which are known to have the capacity to N-glycosylate proteins and subsequently trim the nascent glucosylated polymannose oligosaccharides. It became evident from enzyme assays and in vivo studies that endomannosidase is limited in its distribution to members of the chordate phylum, including placental and marsupial mammals, birds, reptiles, amphibians, and fish, with the single except of the Mollusca in which it was detected in three distinct classes, The enzyme's absence in all other invertebrates examined as well as in yeast, various protozoa and higher plants, stands in contrast to gIucosidase II and alpha 1,2-mannosidase which were found to be present in all eukaryotes studied, The observation that endomannosidase activity was not present in insects was confirmed by radiolabeling experiments with Sf9 cells in culture, These cells, which are widely employed for the expression of mammalian genes, were in distinction to mouse cells unable to circumvent a castanospermine (CST)-induced glucosidase blockade, Moreover we observed that Tetrahymenae, which synthesize glycoproteins with truncated N-linked oligosaccharides, could not process these beyond the Glc(3)Man(5)GlcNAc(2) stage in the presence of CST, The late appearance of endomannosidase during evolution suggests a need for an alternate deglucosylation route in higher animals which parallels the development of elaborate complex N-linked oligosaccharides. Such carbohydrate units are believed to carry out vital biological functions and deglucosylation is a prerequisite to the further processing steps required for their formation. C1 JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK 17477] NR 37 TC 38 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD JUN PY 1997 VL 7 IS 4 BP 579 EP 586 DI 10.1093/glycob/7.4.579 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB693 UT WOS:A1997XB69300017 PM 9184840 ER PT J AU LambertMesserlian, GM Steinhoff, M Zheng, W Canick, JA Gajewski, WH Seifer, DB Schneyer, AL AF LambertMesserlian, GM Steinhoff, M Zheng, W Canick, JA Gajewski, WH Seifer, DB Schneyer, AL TI Multiple immunoreactive inhibin proteins in serum from postmenopausal women with epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 10th International Congress of Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA ID LINKED-IMMUNOSORBENT-ASSAY; HUMAN FOLLICULAR-FLUID; ALPHA-INHIBIN; PRECURSOR PROTEINS; MARKER; RADIOIMMUNOASSAY; SUBUNIT; CA-125; BOVINE; TUMORS AB Inhibin is an ovarian protein previously shown, using a nonspecific assay, to be elevated in serum of women with ovarian cancer. However, inhibin is secreted in multiple biochemical forms, including dimeric inhibin A and B and alpha inhibin precursors (pro-alpha C), each of which can now be specifically measured. We have examined the secretion of inhibin B and pro-alpha C inhibin in serum from women with epithelial ovarian cancer (EOC) for the first time, and have compared these analytes to inhibin A and total inhibin (inhibin A + B + pro-alpha C) as potential serum markers for EOC in postmenopausal women. Of all the immunoreactive inhibin proteins studied, the best serum marker was pro-alpha C, with 22% of women with EOC having levels that exceeded the range of values in women without EOC. Since CA 125 and pro-alpha C levels were not significantly correlated, combination of these markers resulted in 87% of EOC cases having elevated preoperative serum levels, a 9% increase over CA 125 alone. These data suggest that alpha inhibin secretion, especially pro-alpha C, may be useful in addition to CA 125 as a serum marker for EOC in postmenopausal women. (C) 1997 Academic Press. C1 BROWN UNIV,WOMEN & INFANTS HOSP,DEPT OBSTET & GYNECOL,PROVIDENCE,RI 02905. OHIO STATE UNIV,MED CTR,DEPT OBSTET & GYNECOL,COLUMBUS,OH 43210. MASSACHUSETTS GEN HOSP,DEPT MED,REPROD ENDOCRINE UNIT,NATL CTR INFERTIL RES,BOSTON,MA 02114. RP LambertMesserlian, GM (reprint author), BROWN UNIV,WOMEN & INFANTS HOSP,DEPT PATHOL & LAB MED,PROVIDENCE,RI 02905, USA. OI Seifer, David/0000-0003-3950-9341; Messerlian, Geralyn/0000-0002-9440-3411 NR 23 TC 37 Z9 37 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 1997 VL 65 IS 3 BP 512 EP 516 DI 10.1006/gyno.1997.4719 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA XE195 UT WOS:A1997XE19500026 PM 9190984 ER PT J AU Beversdorf, D Stommel, E Allen, C Stevens, R Lessell, S AF Beversdorf, D Stommel, E Allen, C Stevens, R Lessell, S TI Recurrent branch retinal infarcts in association with migraine SO HEADACHE LA English DT Article DE migraine; headache; visual loss; branch retinal artery occlusion ID ARTERIAL-OCCLUSION AB Migraine has been blamed for a variety of temporary and permanent visual complications. We describe the case of a young woman with migraine who suffered recurrent episodes of retinal infarction, one of which occurred during an attack of migraine. The infarctions resulted from occlusions of branches of the central retinal artery. Extensive laboratory and radiological investigations failed to establish a nonmigrainous etiology. In some individuals, migraine may cause or promote branch retinal vaso-occlusion and infarction. C1 DARTMOUTH COLL,HITCHCOCK MED CTR,NEUROL SECT,LEBANON,NH 03756. DARTMOUTH COLL,HITCHCOCK MED CTR,SECT OPHTHALMOL,LEBANON,NH 03756. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RI Beversdorf, David/M-2786-2016 OI Beversdorf, David/0000-0002-0298-0634 NR 10 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC STUDY HEADACHE PI WOODBURY PA 875 KINGS HIGHWAY, STE 200, WOODBURY, NJ 08096 SN 0017-8748 J9 HEADACHE JI Headache PD JUN PY 1997 VL 37 IS 6 BP 396 EP 399 DI 10.1046/j.1526-4610.1997.3706396.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA XK542 UT WOS:A1997XK54200009 PM 9237415 ER PT J AU Burgess, BJ Adams, JC Nadol, JB AF Burgess, BJ Adams, JC Nadol, JB TI Morphologic evidence for innervation of Deiters' and Hensen's cells in the guinea pig SO HEARING RESEARCH LA English DT Article DE synaptophysin; neurofilament; acetylcholinesterase; synapse; Deiters' cell; Hensen's cell ID OUTER HAIR-CELLS; IMMUNOELECTRON MICROSCOPY; EFFERENT INNERVATION; SUPPORTING CELLS; ORGAN; CORTI; COCHLEA; LOCALIZATION; SYNAPSES; AFFERENT AB The presence of nerve fibers and terminals among Deiters' and Hensen's cells of the organ of Corti of the adult guinea pig is demonstrated using immunostaining for synaptophysin and neurofilaments, acetylcholinesterase histochemistry, and transmission electron microscopy. These nerve terminals appeared to form chemical synapses with Deiters' and Hensen's cells. Nerve fibers and synapses were more common in the apical as compared to the basal cochlea. The terminals were often present on basal appendages of Hensen's cells, which were rich in mitochondria and often contained a Golgi apparatus and dense core vesicles. Electron microscopy and immunostaining for neurofilaments showed that most Hensen's cells in the apical cochlea received innervation. Few of the nerve fibers and terminals were positive for acetylcholinesterase, which suggests that they were not collaterals of cholinergic olivocochlear fibers. The density of these fibers, as shown by immunohistochemistry for neurofilaments, was far greater than previous reports of GABA-ergic fibers, which suggests that they were not GABA-ergic olivocochlear fibers. The role of such fibers and synapses with supporting cells of the outer hair cell area is unknown. Determination of the origins and functions of these fibers will provide new insights into cochlear structure and function. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 27 TC 42 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUN PY 1997 VL 108 IS 1-2 BP 74 EP 82 DI 10.1016/S0378-5955(97)00040-3 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA XG689 UT WOS:A1997XG68900009 PM 9213124 ER PT J AU Strauss, GM AF Strauss, GM TI Prognostic markers in resectable non-small cell lung cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID INTERNATIONAL STAGING SYSTEM; BLOOD-VESSEL INVASION; DNA CONTENT; SHORTENED SURVIVAL; LYMPH-NODES; MULTIVARIATE-ANALYSIS; POSTSURGICAL STAGE; PROTEIN EXPRESSION; II ADENOCARCINOMA; POOR-PROGNOSIS AB Numerous prognostic factors have been identified in patients with resectable non-small cell lung cancer (NSCLC) which may enable stratification of patients into subsets indicating risk of recurrence following complete resection. Such prognostic markers include a variety of clinico-pathologic factors such as tumor size, nodal status, and histopathologic variables. Several serum tumor markers have also proven useful. Moreover, a wide variety of; molecular markers have been described over the last decade, which can be classified as molecular genetic markers, metastatic propensity markers, differentiation markers, and proliferation markers. This article reviews those prognostic markers most likely to prove clinically useful from the perspective of guiding postresection treatment strategies in early stage NSCLC. C1 DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP Strauss, GM (reprint author), WORCESTER MEM HOSP,DIV HEMATOL ONCOL,119 BELMONT ST,WORCESTER,MA 01605, USA. NR 88 TC 47 Z9 50 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1997 VL 11 IS 3 BP 409 EP & DI 10.1016/S0889-8588(05)70441-X PG 28 WC Oncology; Hematology SC Oncology; Hematology GA XH974 UT WOS:A1997XH97400003 PM 9209903 ER PT J AU Mentzer, SJ AF Mentzer, SJ TI Mediastinoscopy, thoracoscopy, and video-assisted thoracic surgery in the diagnosis and staging of lung cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID LYMPH-NODE METASTASES; BRONCHOGENIC-CARCINOMA; SYSTEM AB The surgical approach to the diagnosis and staging of lung cancer requires the assessment of the lung parenchyma, hilum, pleura, chest wall, and intrathoracic lymph nodes. Chest computerized tomography is sensitive in defining the location of the primary tumor, but is relatively insensitive to invasion. Similarly, radiographic imaging can identify lymph node enlargement, but lymph node enlargement alone is insufficient for accurate staging. To facilitate the tissue biopsies of both the primary tumor and potential sites of metastatic disease, video thoracoscopy has provided a useful complement to traditional bronchoscopy and mediastinoscopy. These instruments provide minimally invasive access to the lung, pleura, and ipsilateral lymph nodes. The combined application of thoracoscopy, bronchoscopy, and mediastinoscopy can provide intrathoracic staging information while minimizing surgical morbidity. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP Mentzer, SJ (reprint author), BRIGHAM & WOMENS HOSP,DIV THORAC SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL47078] NR 21 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1997 VL 11 IS 3 BP 435 EP & DI 10.1016/S0889-8588(05)70442-1 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA XH974 UT WOS:A1997XH97400004 PM 9209904 ER PT J AU Herbst, RS Dang, NH Skarin, AT AF Herbst, RS Dang, NH Skarin, AT TI Chemotherapy for advanced non-small cell lung cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID COOPERATIVE-ONCOLOGY-GROUP; PHASE-II TRIAL; COLONY-STIMULATING FACTOR; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; SUPPORTIVE CARE; MITOMYCIN-C; BRONCHOGENIC-CARCINOMA; STAGE-III; PACLITAXEL TAXOL AB Lung cancer is the most lethal cancer in both men and women. Given that chemotherapy for advanced disease is marginally beneficial and noncurative, its use must be governed judiciously, with each decision being evaluated individually for each patient. Chemotherapy for lung cancer has progressed over the past decade, and with the advent of new agents, its future looks promising. RP Herbst, RS (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,STAMP,44 BINNEY ST,BOSTON,MA 02115, USA. NR 204 TC 15 Z9 17 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1997 VL 11 IS 3 BP 473 EP & DI 10.1016/S0889-8588(05)70445-7 PG 46 WC Oncology; Hematology SC Oncology; Hematology GA XH974 UT WOS:A1997XH97400007 PM 9209907 ER PT J AU Elias, AD AF Elias, AD TI Future directions in lung cancer research and therapeutics SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TUMOR-CELLS; LYMPH-NODES; CARCINOMA AB Lung cancer is preventable, but will remain endemic and lethal so long as tobacco products remain commercially viable. Strategies for chemoprevention and early detection are under development but may overwhelm health care systems unless automated. Therapeutic advances in surgery, radiation oncology, and chemotherapy are incremental at best. Most exciting are the preclinical advances in novel immunologic strategies, particularly vaccine development. Clinical outcomes are not yet available. RP Elias, AD (reprint author), DANA FARBER CANC INST,DEPT MED ONCOL,STAMP,44 BINNEY ST,BOSTON,MA 02115, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1997 VL 11 IS 3 BP 519 EP & DI 10.1016/S0889-8588(05)70446-9 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA XH974 UT WOS:A1997XH97400008 PM 9209908 ER PT J AU Elias, AD AF Elias, AD TI Multidisciplinary care of lung cancer patients .2. Preface SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material RP Elias, AD (reprint author), DANA FARBER CANC INST,44 BINNEY ST,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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1997 VL 11 IS 3 BP R9 EP R11 DI 10.1016/S0889-8588(05)70439-1 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA XH974 UT WOS:A1997XH97400001 ER PT J AU Verchere, CB DAlessio, DA Wang, S Andrikopoulos, S Kahn, SE AF Verchere, CB DAlessio, DA Wang, S Andrikopoulos, S Kahn, SE TI Transgenic overproduction of islet amyloid polypeptide (amylin) is not sufficient for islet amyloid formation SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT 2nd Seattle Islet Symposium on Regulation of Islet Growth CY 1996 CL SEATTLE, WA SP ZymoGenet Inc, Seattle, Univ Washington, Diabet Endocrinol Res Ctr DE transgenic mice; non-insulin-dependent diabetes mellitus; insulin; pancreatic beta cell; hyperglycemia; nicotinic acid ID INDUCED INSULIN RESISTANCE; LONG-TERM EXPOSURE; DIABETES-MELLITUS; PANCREATIC-ISLETS; NICOTINIC-ACID; GROWTH-HORMONE; FATTY-ACIDS; BETA-CELLS; IN-VITRO; MICE AB Islet amyloid polypeptide forms islet amyloid deposits in non-insulin-dependent diabetes mellitus, We have generated transgenic mice which express human islet amyloid polypeptide in their pancreatic beta cells yet do not develop islet amyloid deposits despite producing levels of the amyloidogenic human peptide 2-3 fold higher than the native (mouse) peptide. To determine whether marked overproduction of islet amyloid polypeptide is a potential cause of islet amyloid formation, we increased expression of this transgene by producing homozygous transgenic animals and by making heterozygous mice experimentally insulin resistant with nicotinic acid. Pancreatic content of islet amyloid polypeptide-like immunoreactivity in homozygous and nicotinic acid-treated mice was 2-fold (25 +/- 7 fmol/mu g; n = 6) and 3.5-fold (47 +/- 20 fmol/mu g; n = 3) higher, respectively, than that of untreated heterozygous animals (13 +/- 2 fmol/mu g; n = 11; both p < 0.05). Despite this marked increase in production of islet amyloid polypeptide, neither group of mice developed gross islet amyloid deposits even after 16 months of age. We conclude that overproduction of islet amyloid polypeptide, even as produced by extreme insulin resistance, is not in itself sufficient for islet amyloid formation. C1 UNIV WASHINGTON,SEATTLE,WA 98195. RP Verchere, CB (reprint author), VA PUGET SOUND HLTH CARE SYST,DIV METAB ENDOCRINOL & NUTR,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK-12829, DK-17047] NR 33 TC 18 Z9 18 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 1997 VL 29 IS 6 BP 311 EP 316 DI 10.1055/s-2007-979042 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XH664 UT WOS:A1997XH66400011 PM 9230354 ER PT J AU Walter, UM Ayer, LM Wolitzky, BA Wagner, DD Hynes, RO Manning, AM Issekutz, AC AF Walter, UM Ayer, LM Wolitzky, BA Wagner, DD Hynes, RO Manning, AM Issekutz, AC TI Characterization of a novel adhesion function blocking monoclonal antibody to rat/mouse P-selectin generated in the P-selectin-deficient mouse SO HYBRIDOMA LA English DT Article; Proceedings Paper CT ASBMB / ASIP / AAI Meeting CY JUN 02-06, 1996 CL NEW ORLEANS, LA SP ASBMB, ASIP, AAI ID PLATELET MEMBRANE-PROTEIN; ACTIVATED PLATELETS; ISCHEMIA-REPERFUSION; IN-VIVO; GMP-140; GRANULE; LIGAND; CELLS; GLYCOPROTEIN; ENDOTHELIUM AB P-selectin is an important adhesion molecule involved in leukocyte migration. However, to date, no monoclonal antibodies (MAb) generated against rat P-selectin have been identified which block P-selectin mediated leukocyte adhesion, Most studies in the rat have utilized crossreacting antibodies generated against P-selectin in higher species, In a P-selectin deficient mouse we generated an anti-rat/mouse P-selectin MAb, designated RMP-1, by immunization with activated rat platelets. This IgG2a MAb immunoprecipitates a 140 kDa protein under reducing conditions from rat platelet lysate, By ELISA and immunofluorescence flow cytometry, MAb RMP-1 reacts with thrombin-activated but not unactivated rat platelets, In addition, by ELISA MAb RMP-1 binds to activated mouse platelets and recombinant rat and mouse P-selectin, MAb RMP-1 inhibited adhesion of HL-60 myeloid cells to immobilized mouse P-selectin by 97% and to activated rat and mouse platelets by 100% under static conditions, confirming the adhesion function blocking activity of MAb RMP-1. This novel MAb should be useful for studying P-selectin function in vitro and in vivo in both rat and mouse inflammation models. C1 DALHOUSIE UNIV,DEPT PEDIAT,HALIFAX,NS,CANADA. DALHOUSIE UNIV,DEPT MICROBIOL IMMUNOL,HALIFAX,NS,CANADA. HOFFMANN LA ROCHE INC,INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. CTR BLOOD RES,BOSTON,MA 02115. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA. PHARMACIA & UPJOHN INC,KALAMAZOO,MI 49001. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA. FU NHLBI NIH HHS [P01HL4184] NR 34 TC 68 Z9 68 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1997 VL 16 IS 3 BP 249 EP 257 DI 10.1089/hyb.1997.16.249 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA XJ718 UT WOS:A1997XJ71800005 PM 9219035 ER PT J AU Reed, GL AF Reed, GL TI Functional characterization of monoclonal antibody inhibitors of alpha 2-antiplasmin that accelerate fibrinolysis in different animal plasmas SO HYBRIDOMA LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; ALPHA-2-PLASMIN INHIBITOR; ARTERY AB In humans with acute thrombotic disease, thrombi often appear to resist fibrinolysis induced by plasminogen activators. To examine the potential role of alpha 2-antiplasmin (alpha 2AP) in thrombus resistance in vivo, we generated monoclonal antibody inhibitors of alpha 2AP. In a somatic cell fusion, 99 hybridomas were obtained that produced MAbs that bound to human I-125-alpha 2AP in a capture assay. Screening assays showed that 3 of these MAbs, 49, 70, and 77, neutralized the function of alpha 2AP. Immunoblotting experiments indicated that these MAbs recognized an epitope present in native alpha 2AP that was destroyed by denaturation with SDS. Each of these MAbs fully inhibited the binding of the other MAbs to alpha 2AP, but none of them competed with the binding of another anti-alpha 2AP MAb, RWR. When tested for their binding to nonhuman alpha 2APs in plasmas, all three MAbs were strongly crossreactive with all primate plasmas tested but showed an idiosyncratic pattern of binding to alpha 2AP in other plasmas, suggesting unique fine epitope specificities. In human plasma, all three MAbs amplified the lysis of human plasma clots induced by plasminogen activators, increasing the potency of urokinase by nearly 50- to 100-fold. These MAbs also markedly amplified the lysis of clots from baboon, cynomolgus, african green monkey plasmas, and to a lesser extent, ferret and dog. By virtue of their ability to potently inhibit alpha 2AP in other animal plasmas, these MAbs should be useful for examining the role of alpha 2AP in thrombus resistance to fibrinolysis in vivo. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SCH PUBL HLTH,BOSTON,MA 02115. FU NHLBI NIH HHS [HL02348, HL57314] NR 23 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1997 VL 16 IS 3 BP 281 EP 286 DI 10.1089/hyb.1997.16.281 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA XJ718 UT WOS:A1997XJ71800009 PM 9219039 ER PT J AU Butterton, JR Ryan, ET Acheson, DWK Calderwood, SB AF Butterton, JR Ryan, ET Acheson, DWK Calderwood, SB TI Coexpression of the B subunit of Shiga toxin 1 and EaeA from enterohemorrhagic Escherichia coli in Vibrio cholerae vaccine strains SO INFECTION AND IMMUNITY LA English DT Article ID HEMOLYTIC-UREMIC-SYNDROME; NUCLEOTIDE-SEQUENCE; SYNTHETIC PEPTIDES; SHIGELLA TOXIN; GENETIC-LOCUS; EL-TOR; EXPRESSION; ANTIBODIES; INFECTION; DIARRHEA AB A promoterless gene for the Shiga toxin 1 B subunit (stxB(1)) has been placed under transcriptional control of the Vibrio cholerae heat shock gene htpG. A chromosomal enterohemorrhagic Escherichia coli fragment containing eaeA and 400 bp of upstream DNA was added to the construct, downstream of stxB(1); no transcription terminators were located between the two genes, The plasmid construct was confirmed by DNA sequencing; in vitro transcription-translation studies demonstrated expression of EaeA from the plasmid, The htpGp-->stxB(1), eaeA construct was inserted into lacZ on the chromosome of Peru2, an El Tor V. cholerae strain with both attRSI sequences and the entire cholera toxin genetic element deleted, and into lacZ in JRB10, a PeruZ derivative that has a second copy of htpGp-->stxB(1) also inserted in the V. cholerae virulence gene irgA. Two plasmid constructs, one containing stxB, under the control of the tac promoter and another containing htpGp-->stxB(1),eaeA, were transformed into Peru2, Expression of StxB1 by these constructs,vas quantified by enzyme-linked immunosorbent assay and was highest in the plasmid construct with stxB, under the control of the tac promoter, Localization of EaeA to the outer membrane of the vector strains was demonstrated both by Western blotting and by immunofluorescence with an anti-EaeA antibody, A rabbit model for colonization by V. cholerae was used to compare the immune responses to the two heterologous antigens, StxB1 and EaeA, expressed by these strains, Rabbits immunized with Peru2 transformed with a plasmid carrying tac-->stxB(1) developed neutralizing serum anti-StxB1 immunoglobulin G antibody responses, One of two rabbits immunized with a strain carrying a chromosomal copy of eaeA developed a marked immune response against EaeA, The plasmid construct containing htpGp-->stxB(1),eaeA was unstable, producing low levels of StxB1 in vitro and not evoking anti-EaeA antibody responses in vivo following oral immunization, Chromosomal insertion of eaeA may be preferred for future expression of this antigen in V. cholerae vaccine constructs. C1 TUFTS UNIV NEW ENGLAND MED CTR,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. RP Butterton, JR (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. FU NIAID NIH HHS [K08AI01386, AI40725, T32AI07061-18, R01 AI040725, T32 AI007061] NR 54 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1997 VL 65 IS 6 BP 2127 EP 2135 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XB562 UT WOS:A1997XB56200020 PM 9169742 ER PT J AU Ogata, M Fletcher, MF Kloczewiak, M Loiselle, PM Zanzot, EM Vermeulen, MW Warren, HS AF Ogata, M Fletcher, MF Kloczewiak, M Loiselle, PM Zanzot, EM Vermeulen, MW Warren, HS TI Effect of anticoagulants on binding and neutralization of lipopolysaccharide by the peptide immunoglobulin conjugate CAP18(106-138)-immunoglobulin G in whole blood SO INFECTION AND IMMUNITY LA English DT Article ID PERMEABILITY-INCREASING PROTEIN; TUMOR-NECROSIS-FACTOR; GRAM-NEGATIVE BACTERIA; TERMINAL FRAGMENT; LIPOPROTEIN-BINDING; ESCHERICHIA-COLI; HORSESHOE-CRAB; FACTOR RELEASE; RABBIT SERUM; ALPHA AB The 18-kDa cationic protein CAP18 is an antimicrobial protein isolated from rabbit granulocytes that binds lipopolysaccharide (LPS) and inhibits many of its biological activities. We covalently coupled a synthetic peptide representing amino acids 106 to 138 of CAP18 to human immunoglobulin G (IgG) by using the hetero-bifunctional linker N-succinimidyl-3-(2-pyridyldithio)propionate. The ability of CAP18(106-138)-IgG to bind and neutralize LPS in whole blood in the presence and absence of anticoagulants was studied. Both CAP18(106-138) and CAP18(106-138)-IgG significantly suppressed LPS-induced tumor necrosis factor (TNF) production in whole blood in the absence of anticoagulants. EDTA potentiated the ability of CAP18(106-138) and CAP18(106-138)-IgG to decrease LPS-induced TNF production in a dose-dependent manner. In contrast, heparin inhibited the ability of CAP18(106-138) and CAP18(106-138)-IgG to suppress LPS-induced TNF production, EDTA also enhanced LPS capture in a fluid-phase binding assay that utilizes magnetic anti-IgG beads to capture CAP18(106-138)-IgG (and bound [H-3] LPS) in whole blood, In contrast, heparin inhibited the binding dose dependently. We conclude that CAP18(106-138)-IgG binds to and neutralizes LPS in whole blood in the absence of anticoagulants. Further studies of its protective efficacy in animal models are warranted. Caution should be used in interpreting assays that measure the binding and neutralization of LPS in whole blood in the presence of calcium-binding anticoagulants or heparin. C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,DEPT ANESTHESIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. CREAT BIOMOL,HOPKINTON,MA. FU NHLBI NIH HHS [HL-46966]; NIAID NIH HHS [AI-28943] NR 50 TC 21 Z9 21 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1997 VL 65 IS 6 BP 2160 EP 2167 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XB562 UT WOS:A1997XB56200024 PM 9169746 ER PT J AU Sands, BE AF Sands, BE TI Biologic therapy for inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE biologic therapy; monoclonal antibodies; antisense oligonucleotides; ulcerative colitis; Crohn's disease; cell therapy; gene therapy ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; INTERLEUKIN-1 RECEPTOR ANTAGONIST; INTESTINAL EPITHELIAL-CELLS; CD4(+) T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHIMERIC MONOCLONAL-ANTIBODY; FACTOR-ALPHA PRODUCTION; RABBIT IMMUNE COLITIS; MYELIN BASIC-PROTEIN AB Biologic therapy includes many different categories of agents targeted to diverse mechanisms of disease. Recently, a host of novel biologic therapies have been developed to attack a wide variety of immunologic and inflammatory mechanisms. These include recombinant cytokines and growth factors; monoclonal antibodies against cytokines, accessory molecules, and cellular adhesion molecules; nucleotide based therapies; and cell and gene therapies. Among the biologic agents recently reported to have been prospectively studied in patients with inflammatory bowel disease are monoclonal antibodies against CD4 and tumor necrosis factor, and interleukins 10 and 11. Many other biologics have been examined in other immune-mediated diseases in humans, and in animal models of colitis. This review surveys the rationale and use of biologic therapies in inflammatory bowel disease. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. RP Sands, BE (reprint author), MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT GRJ719, 32 FRUIT ST, BOSTON, MA 02114 USA. NR 194 TC 47 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SUM PY 1997 VL 3 IS 2 BP 95 EP 113 DI 10.1002/ibd.3780030206 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WX205 UT WOS:A1997WX20500005 PM 23282751 ER PT J AU Fiocchi, C Collins, SM James, SP MAyer, L Podolsky, DK Stenson, WF AF Fiocchi, C Collins, SM James, SP MAyer, L Podolsky, DK Stenson, WF TI ''Immune/Non-Immune Cell Interactions in Intestinal Inflammation'' Workshop SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material C1 MCMASTER UNIV,HAMILTON,ON,CANADA. UNIV MARYLAND,BALTIMORE,MD 21201. MT SINAI HOSP,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. RP Fiocchi, C (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,DIV GASTROENTEROL,10900 EUCLID AVE,CLEVELAND,OH 44106, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SUM PY 1997 VL 3 IS 2 BP 133 EP 141 DI 10.1002/ibd.3780030209 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WX205 UT WOS:A1997WX20500008 PM 23282754 ER PT J AU Rennert, P Furlong, K Jellis, C Greenfield, E Freeman, GJ Ueda, Y Levine, B June, CH Gray, GS AF Rennert, P Furlong, K Jellis, C Greenfield, E Freeman, GJ Ueda, Y Levine, B June, CH Gray, GS TI The IgV domain of human B7-2 (CD86) is sufficient to co-stimulate T lymphocytes and induce cytokine secretion SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE B7-1; CD28; CD80; CD86; CTLA-4; cytokine; fusion proteins; IgV; soluble ligand ID ACTIVATION ANTIGEN B7; CELL ACTIVATION; GENOMIC ORGANIZATION; CD28 RECEPTOR; 2ND RECEPTOR; CTLA-4; EXPRESSION; COSTIMULATION; INTERLEUKIN-2; BINDING AB B7-1 (CD80) and B7-2 (CD86) are genetically and structurally related molecules expressed on antigen-presenting cells. Both bind CD28 to co-stimulate T lymphocytes, resulting in proliferation and cytokine production. The extracellular portions of B7-1 and B7-2 which bind to CD28 and CTLA-4 are related to Ig variable (V) and Ig constant (C) domain sequences. Recent reports have described splice variant forms of B7 proteins which occur in vivo and are of unknown function. Here we describe soluble recombinant forms of B7-1 and B7-2 containing either both of the Ig-like extracellular domains or the individual IgV or IgC domains coupled to an Ig Fc tail. Soluble B7-1 and B7-2 bind to CD28 and CTLA-4, and effectively cc-stimulate T lymphocytes resulting in their proliferation and the secretion of cytokines. Furthermore, the IgV domain of B7-2 binds CD28 and CTLA-4, competes with B7-1 and B7-2 for binding to these receptors, and co-stimulates T lymphocytes. Cross-linked soluble B7-2v was the most potent co-stimulatory molecule tested and was active at a concentration similar to 100-fold lower than cross-linked soluble B7-1 or B7-2 proteins. When bound to tosyl-activated beads, B7-2v was capable of sustaining multiple rounds of T cell expansion. These data complement the description of naturally occuring variants to suggest that T cell co-stimulation in vivo may be regulated by soluble or truncated forms of B7 proteins. C1 REPLIGEN CORP,DEPT MOL BIOL,CAMBRIDGE,MA 02139. REPLIGEN CORP,DEPT IMMUNOL,CAMBRIDGE,MA 02139. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 37 TC 35 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1997 VL 9 IS 6 BP 805 EP 813 DI 10.1093/intimm/9.6.805 PG 9 WC Immunology SC Immunology GA XE891 UT WOS:A1997XE89100001 PM 9199963 ER PT J AU Duerinckx, AJ AF Duerinckx, AJ TI MRI of coronary arteries SO INTERNATIONAL JOURNAL OF CARDIAC IMAGING LA English DT Article DE heart; MRI; coronary angiography; MR angiography (MRA); coronary MRA; coronary flow; coronary vessel ID MAGNETIC-RESONANCE ANGIOGRAPHY; CONTRAST AB Magnetic Resonance Angiography (MRA) of the coronary arteries has recently become possible due to the development of a new group of ultrafast imaging sequences. Although the role of coronary MR angiography in screening for coronary artery lesions has not yet been established, coronary MR angiography has been very successful in the detection of coronary artery variants, and the imaging of coronary stents and bypass grafts. Variants of these new MRI techniques can also quantitate velocity in native coronary arteries. Coronary MR angiographic techniques can be subdivided in breath-hold (single or repeated breath-hold) and non-breath-hold techniques. Most of the clinical experience so far has been with a single breath-hold technique, and was limited to cooperative patients. The recent introduction of navigator pulses for real-time respiratory gating or triggering allows non-breath-herd or repeated breath-hold 3-D coronary MR angiography, and will allow a more widespread use of this technique. Notwithstanding the progress being made and the excitement created by the prospect of a noninvasive coronary artery screening tool, several key technical problems remain unresolved and are now being addressed by the scientific and clinical community. This paper reviews ongoing research in coronary MR angiography. C1 UNIV CALIF LOS ANGELES,MED CTR,DEPT RADIOL,LOS ANGELES,CA 90095. RP Duerinckx, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,11301 WILSHIRE BLVD,MRI BLD 507,LOS ANGELES,CA 90073, USA. NR 52 TC 8 Z9 8 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-9899 J9 INT J CARDIAC IMAG JI Int. J. Card. Imaging PD JUN PY 1997 VL 13 IS 3 BP 191 EP 197 DI 10.1023/A:1005791317440 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA XH809 UT WOS:A1997XH80900003 PM 9220281 ER PT J AU Doshi, A Zaheer, H Stiller, MJ AF Doshi, A Zaheer, H Stiller, MJ TI A comparison of current acne grading systems and proposal of a novel system SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Editorial Material C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,DERMATOL CLIN INVEST UNIT,BOSTON,MA 02114. NR 10 TC 136 Z9 155 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD JUN PY 1997 VL 36 IS 6 BP 416 EP 418 DI 10.1046/j.1365-4362.1997.00099.x PG 3 WC Dermatology SC Dermatology GA XK779 UT WOS:A1997XK77900004 PM 9248884 ER PT J AU Teicher, BA Ara, G Northey, D AF Teicher, BA Ara, G Northey, D TI Interaction of interleukin-11 (rhIL-11) with cytotoxic therapies in the human HT-29 colon carcinoma SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE interleukin-11; colon carcinoma ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC RECONSTITUTION; RECOMBINANT INTERLEUKIN-11; CELLS; MICE; RECOVERY; CSF AB The cytokine interleukin-11 (rhIL-11) has been shown to enhance the recovery of bone marrow, oral epithelium and intestinal crypt cells after cytotoxic insult by anticancer drugs or ionizing radiation. 5-Fluorouracil based chemotherapy and radiation therapy are frequently used in the treatment of colon cancer. Simultaneous exposure of human HT-29 colon carcinoma cells in culture to rhIL-11 and 5-fluorouracil for 24 h resulted in enhanced cell killing of the HT-29 cells with lower concentrations (1-10 mu M) of 5-fluorouracil compared with the drug alone. Exposure of HT-29 cells to rhIL-11 prior to, during and after radiation delivery did not alter the killing of normally oxygenated or hypoxic HT-29 cells by the radiation. In vivo treatment of nude mice bearing HT-29 colon tumor xenografts with rhIL-11 prior to and during administration of 5-fluorouracil did not alter the killing of the tumor cells or the killing of the bone marrow CFU-GM by the drug. In the tumor growth delay experiments, administration of rhIL-11 to nude mice bearing HT-29 colon tumor xenografts did not alter the growth of the tumor and did not alter the response of the tumor to 5-fluorouracil. However, administration of rhIL-11 to these animals increased the response of the tumor to fractionated radiation therapy resulting in a radiation dose-modifying factor of 1.5+/-0.2. These results indicate that rhIL-11 may be a selective protector of normal tissues without affecting the response of the tumor to therapy. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Teicher, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 22 TC 0 Z9 0 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 JUN PY 1997 VL 10 IS 6 BP 1081 EP 1085 PG 5 WC Oncology SC Oncology GA XA673 UT WOS:A1997XA67300001 PM 21533487 ER PT J AU August, M Magennis, P Dewitt, D AF August, M Magennis, P Dewitt, D TI Osteogenic sarcoma of the jaws: Factors influencing prognosis SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE osteosarcoma; prognosis; oncology ID ADJUVANT CHEMOTHERAPY; OSTEOSARCOMA; MAXILLA; BONES; EXPERIENCE; SURVIVAL; RELAPSE AB Thirty cases of osteosarcoma of the jaws were reviewed (20 men and 10 women, mean age 34 years). Seventeen lesions occurred in the mandible and 13 in the maxilla. Swelling without pain was the most common presenting symptom. Thirteen lesions were initially misdiagnosed as odontogenic infections. Numbness as a presenting symptom was statistically associated with poor prognosis. Treatment included all combinations of surgery, chemotherapy and radiotherapy. Patients receiving chemotherapy with four or more agents showed a trend toward better survival with 71% alive and disease-free at the time of review. Patients' increasing age was statistically associated with decreased survival. The average age of survivors was 27 years and nonsurvivors, 40 years. Older patients suffered more local recurrences which, in all but one case, resulted in mortality. Expectedly, clear surgical margins correlated statistically with improved survival. With margins of less than 5 mm, 27% of patients were alive and disease-free as compared to 62% with surgical margins greater than 5 mm. The importance of early diagnosis, definitive surgical treatment and aggressive adjuvant chemotherapy is demonstrated. The Proportional Hazards Regression model was employed to evaluate the statistical significance of a variety of factors on disease-free and overall survival. RP August, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,WARREN 1201,32 FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 61 Z9 63 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD JUN PY 1997 VL 26 IS 3 BP 198 EP 204 DI 10.1016/S0901-5027(97)80819-3 PG 7 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA XC391 UT WOS:A1997XC39100007 PM 9180230 ER PT J AU Barlow, JS AF Barlow, JS TI Some aspects of alpha activity in relation to a new generalized model for the EEG SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE extrema-slopes hypothesis; mutual entrainment; 'alpha squeak'; photically-evoked effects; metabolic slowing; dual-modulation oscillator-simulator AB Further explorations with a new type of EEG pattern simulator consisting of an oscillator the extrema and slopes of the waves of which can be independently modulated provide additional support for the 'extrema-slopes' hypothesis as a generalized model for the generation of EEG activity. (C) 1997 Elsevier Science B.V. RP Barlow, JS (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUN PY 1997 VL 26 IS 1-3 BP 341 EP 352 DI 10.1016/S0167-8760(97)00774-5 PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA XF066 UT WOS:A1997XF06600023 PM 9203013 ER PT J AU Barlow, JS AF Barlow, JS TI The early history of EEG data-processing at the Massachusetts Institute of Technology and the Massachusetts General Hospital SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Norbert Wiener; time series analysis; brain potentials; autocorrelation; crosscorrelation; evoked-potential averaging AB The applications to the study of spontaneous and evoked brain potentials in the period from the late 1940's to the early 1060's of Norbert Wiener's World War II work on prediction theory are traced, including the development of an analog correlator system specifically for brain potentials. (C) 1997 Elsevier Science B.V. C1 MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. RP Barlow, JS (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 59 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUN PY 1997 VL 26 IS 1-3 BP 443 EP 454 DI 10.1016/S0167-8760(97)00781-2 PG 12 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA XF066 UT WOS:A1997XF06600030 PM 9203020 ER PT J AU Colvett, KT Hsu, DW Su, M Lingood, RM Pardo, FS AF Colvett, KT Hsu, DW Su, M Lingood, RM Pardo, FS TI High PCNA index in meningiomas resistant to radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 02-06, 1994 CL SAN FRANCISCO, CA SP Amer Soc Therapeut Radiol & Oncol DE meningioma; proliferating cell nuclear antigen; radiation therapy; cell cycle; tumor recurrence; immunocytochemistry ID CELL NUCLEAR ANTIGEN; INTRACRANIAL MENINGIOMAS; DNA-REPLICATION; PROGNOSTIC-SIGNIFICANCE; MONOCLONAL-ANTIBODIES; RESECTED MENINGIOMAS; S-PHASE; RECURRENCE; PROTEIN; CYCLIN AB Purpose: Meningiomas are common intracranial tumors, often well controlled with surgical resection alone, While the efficacy of radiation therapy in improving local control and progression-free survival is well documented, prognostic data substantiate factors that are predictive of poor local control following definitive radiation therapy, PCNA is a DNA polymerase expressed at the highest levels in the S-phase, the most resistant portion of the cell cycle to ionizing radiation iii vitro. We investigated the possible correlation between the levels of PCNA expression and the clinical outcome of patients treated with definitive radiation therapy. Methods and Materials: Archival tissue was collected from 33 cases of meningioma treated at our institution for definitive radiation therapy between 1970 and 1990, Age-matched normal meningeal tissue and asymptomatic meningiomas removed at autopsy served as tissue controls, A standard ABC immunoperoxidase technique employing antibodies to PCNA, PC-10 (Dako, California) was used to stain specimen slides for PCNA. PCNA index was defined as the number of positive nuclei per 10 high-power fields at 400x magnification. Two independent observers scored the slides without prior knowledge of the cases at hand. Results: Patients with high PCNA index were less likely to be controlled by therapeutic radiation (p < 0.001, Kaplan-Meier), All patients with a PCNA index greater that 25 failed radiation therapy. Using multivariate analyses, malignant (but not atypical), histology and PCNA index were significant predictors of progression following radiation therapy (p < 0.05, log rank), Conclusion: PCNA index may be a useful adjunct to more standard histopathologic criteria in the determination of meningioma local control and progression-free survival following therapeutic irradiation, Data on a more expanded population evaluated on a prospective basis will be needed before such criteria are routinely employed in the clinical setting, (C) 1997 Elsevier Science Inc. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,LAB MOL TUMOR BIOL,BOSTON,MA. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,SHIELDS WARREN RADIAT BIOL LABS,BOSTON,MA 02115. NR 39 TC 4 Z9 5 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 JUN 1 PY 1997 VL 38 IS 3 BP 463 EP 468 DI 10.1016/S0360-3016(97)00018-7 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XL056 UT WOS:A1997XL05600002 PM 9231667 ER PT J AU Green, JP Goldberg, RA Shorr, N AF Green, JP Goldberg, RA Shorr, N TI Eyebrow ptosis SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID SURGICAL ANATOMY; FOREHEAD LIFT; FACIAL-NERVE; RELEVANCE; SCALP; SMAS RP Green, JP (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 30 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1997 VL 37 IS 3 BP 97 EP 122 DI 10.1097/00004397-199703730-00008 PG 26 WC Ophthalmology SC Ophthalmology GA XR840 UT WOS:A1997XR84000007 PM 9279645 ER PT J AU Gill, TJ Micheli, LJ Gebhard, F Binder, C AF Gill, TJ Micheli, LJ Gebhard, F Binder, C TI Bankart repair for anterior instability of the shoulder - Long-term outcomes SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PUTTI-PLATT; DISLOCATION AB Anterior instability of the shoulder is a commonly encountered entity in orthopaedic practice, The Bankart procedure is considered by many surgeons to be the treatment of choice for this condition, Despite its widespread popularity, there have been no studies on the long-term outcome of the Bankart procedure as far as we know, Sixty shoulders (fifty-six patients) that had been followed for a minimum of eight years after a Bankart procedure were evaluated for range of motion, stability and strength according to the data form of the American Shoulder and Elbow Surgeons for examination of the shoulder, The results for the involved shoulder were compared with the findings for the contralateral, normal shoulder, All patients completed a questionnaire regarding the history of the instability of the shoulder, the level of participation in sports before and after the operation, the preoperative and postoperative level of pain, and whether the patient had ever sustained a dislocation that needed reduction by a physician, Information about the current ability of the patient to function at home, at work, and during sports also was requested, In addition, the patients were asked to rate the results of the operation and to indicate whether they would have the same procedure again for the same problem, At a mean of 11.9 years after the operation, the mean loss of external rotation was 12 degrees (range, 0 to 30 degrees) (p < 0.0001), There were no significant differences in forward elevation, abduction, or internal rotation between the involved shoulder and the contralateral, normal shoulder. One patient had crepitus on glenohumeral motion, Fifty-five of the fifty-six patients returned to the occupation that they had had preoperatively, without having to alter their activities, Twenty-eight patients had mild pain with strenuous activity and one patient had pain at rest, Three patients had a dislocation of the involved shoulder because of a new traumatic event more than three years postoperatively Fifty-two patients rated the result as good or excellent; three, as fair; and one, as poor, Fifty-four patients said that they would have a Bankart procedure performed again for the same problem, We present a new system for rating the shoulder that emphasizes function and is based specifically on the goals stated by the patients to be most important with regard to the shoulder, Using this system, we found that the Bankart procedure offers an excellent objective long-term outcome with a high degree of patient satisfaction. C1 CHILDRENS HOSP,DEPT ORTHOPED SURG,DIV SPORTS MED,BOSTON,MA 02115. RP Gill, TJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,32 FRUIT ST,BOSTON,MA 02114, USA. NR 21 TC 131 Z9 134 U1 0 U2 6 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 JUN PY 1997 VL 79A IS 6 BP 850 EP 857 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XF138 UT WOS:A1997XF13800008 PM 9199382 ER PT J AU Lazor, MA Pierce, ET Stanley, GD Cass, JL Halpern, EF Bode, RH AF Lazor, MA Pierce, ET Stanley, GD Cass, JL Halpern, EF Bode, RH TI Evaluation of the accuracy and response time of STAT-mode continuous cardiac output SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Cardiovascular-Anesthesiologists CY MAY 04-08, 1996 CL SALT LAKE CITY, UT SP Soc Cardiovasc Anesthesiologists DE cardiac output; continuous thermodilution; monitoring; pulmonary artery catheter; mixed venous oximetry ID THERMODILUTION; CATHETER; AGREEMENT; FLOW AB Objectives: This study was conducted to compare continuous cardiac output (CCO) with bolus thermodilution cardiac output (BTD) at steady state, and to compare the response time of STAT CCO with that of trend CCO, mean arterial pressure, and mixed venous oxygen saturation (SvO(2)) during an acute hemodynamic change. Design: Prospective study. Setting: University hospital. Participants: Twenty-nine patients undergoing cardiac surgery or liver transplantation. Interventions: STAT and trend CCO were compared with BTD cardiac output during steady state intraoperatively and postoperatively in the intensive care unit. Ten patients, who required epicardial pacing after cardiac surgery, were studied to compare the response time of STAT CCO with that of trend CCO, mean arterial pressure, and SvO(2) after a 10% to 20% increase in pacing rate. Measurements and Main Results: A total of 108 cardiac output data sets were analyzed at steady state. Steady state was defined as stable heart rate and mean arterial pressure (+/-5%) and stable central venous pressure (+/-2 mmHg) measured immediately before and after each data set. Cardiac output ranged from 2.3 to 8.5 L/min. The correlation between STAT CCO and BID was r = 0.94, and for trend CCO and BTD was r = 0.94. The bias and precision for STAT CCO versus BTD were 0.06 L/min (Cl 95%: -0.06 to 0.18) and 0.61 L/min. The bias and precision for trend CCO versus BTD were 0.06 L/min (Cl 95%: -0.04 to 0.16) and 0.49 L/min. Eleven data sets were analyzed to study response time of STAT CCO, which was defined as the first time the percent change of the mean of each variable was significantly increased from baseline. Significant increases in mean arterial pressure and SvO(2) were detected after 30 seconds (2.5%, p = 0.01) and 90 seconds (2.0%, p = 0.04), respectively. A significant increase in STAT CCO was reached at 270 seconds (4.4%, p = 0.006), Trend CCO tended to increase but did not reach statistical significance within 6 minutes. Conclusions: STAT and trend CCO are accurate and precise and show close agreement with BTD cardiac output at steady state. The faster algorithm of STAT CCO offers some advantage over trend CCO during an acute hemodynamic change. However, because of the averaging process for determining CCO, the response time of STAT CCO is slower than that of mean arterial pressure and SvO(2). Copyright (C) 1997 by W.B. Saunders Company. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. RP Lazor, MA (reprint author), HARVARD UNIV,SCH MED,BETH ISREAL DEACONESS MED CTR,DEPT ANESTHESIA & CRIT CARE,WEST CAMPUS,BOSTON,MA 02215, USA. NR 22 TC 31 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD JUN PY 1997 VL 11 IS 4 BP 432 EP 436 DI 10.1016/S1053-0770(97)90050-1 PG 5 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA XD294 UT WOS:A1997XD29400006 PM 9187990 ER PT J AU delaMonte, SM Garner, W Wands, JR AF delaMonte, SM Garner, W Wands, JR TI Neuronal thread protein gene modulation with cerebral infarction SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral infarction; stroke; neuronal thread protein; gene expression; neuropathology; Alzheimer's disease; AD7c-NTP ID NITRIC-OXIDE SYNTHASE; SYNAPTOSOMAL-ASSOCIATED PROTEIN; KROX TRANSCRIPTION FACTORS; GROWTH-ASSOCIATED PROTEIN; ALZHEIMERS-DISEASE; RAT-BRAIN; SECRETORY PROTEIN; ARTERY OCCLUSION; APOLIPOPROTEIN-E; MESSENGER-RNAS AB Neuronal thread proteins (NTP) are a family of phosphoproteins expressed during neuritic sprouting. The 15 to 18 kD NTP cluster is associated with development and neuronal differentiation, whereas the 21 kD and 39 to 42 kD species are overexpressed in Alzheimer's disease, correlating with neurodegenerative sprouting and synaptic disconnection. Empirical observations suggested that NTP might also be modulated with central nervous system injury and stroke. In this study of both human and experimental (rat) focal cerebral infarcts, in situ hybridization and immunocytochemical staining revealed NTP gene expression up-regulated in perifocal neurons. These findings were confirmed by quantitative Northern and Western blot analyses. Moreover, Western blot analysis demonstrated selectively increased expression of the 15 to 18 kD NTP species during the acute, subacute, and healing phases of cerebral infarction in both humans and experimental animals, cone spending with the expected period of neuronal repair. These results suggest an additional role for the 15 to 18 kD NTP species in neuritic sprouting required for neuronal regeneration after injury in the mature central nervous system. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ALZHEIMERS DIS RES CTR,DIV NEUROPATHOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169]; NINDS NIH HHS [NS-29793] NR 55 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 1997 VL 17 IS 6 BP 623 EP 635 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XL368 UT WOS:A1997XL36800004 PM 9236719 ER PT J AU Biller, BMK Swearingen, B Zervas, NT Klibanski, A AF Biller, BMK Swearingen, B Zervas, NT Klibanski, A TI Profiles of the endocrine clinic - A decade of the Massachusetts General Hospital Neuroendocrine Clinical Center SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article C1 MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. RP Biller, BMK (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED,NEUROENDOCRINE CLIN CTR, NEUROENDOCRINE UNIT,BUL457B, 55 FRUIT ST, BOSTON, MA 02114 USA. NR 0 TC 5 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1997 VL 82 IS 6 BP 1668 EP 1674 DI 10.1210/jc.82.6.1668 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC080 UT WOS:A1997XC08000004 PM 9177360 ER PT J AU Boyko, EJ Ahroni, JH Davignon, D Stensel, V Prigeon, RL Smith, DG AF Boyko, EJ Ahroni, JH Davignon, D Stensel, V Prigeon, RL Smith, DG TI Diagnostic utility of the history and physical examination for peripheral vascular disease among patients with diabetes mellitus SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article ID ARTERIAL-DISEASE; LIKELIHOOD RATIOS; BLOOD-PRESSURE; FOOT; AMPUTATION; MORTALITY; LEVEL AB Background: We assessed the value of the medical history and physical examination in the diagnosis of peripheral vascular disease in diabetic subjects. Methods: We performed a cross-sectional study in 631 diabetic veteran enrollees of a general internal medicine clinic that compared data obtained from a history and clinical evaluation with the presence of severe peripheral vascular disease defined as an ankle-arm index (AAI) less than or equal to 0.5 derived from Doppler blood pressure measurement. Results: We identified 90 limbs with an AAI less than or equal to 0.5. Results presented below apply to the right leg, but do not differ from the left. Diminished or absent foot peripheral pulses (sensitivity 65%, specificity 78%), venous filling time > 20 sec (sensitivity 22%, specificity 93.9%), age > 65 years (sensitivity 83%, specificity 54%), claudication symptoms in < 1 block (sensitivity 50%, specificity 87%), and patient reported history of physician diagnosed peripheral vascular disease (PVD) (sensitivity 80%, specificity 70%) had the largest positive (or smallest negative) likelihood ratios. Capillary refill time > 5 sec or foot characteristics (absent hair, blue/purple color, skin coolness, or atrophy) conveyed little diagnostic information. Individual factors did not change disease probability to a clinically important degree. A stepwise logistic regression model identified four factors significantly (P < 0.05) associated with low AAI: absent or diminished peripheral pulses, patient reported history of PVD, age, and venous filling time. Substitution of < 1 block claudication for PVD history in this model resulted in a small reduction in model accuracy. Conclusions: Many purportedly useful historical and exam findings need not be elicited in diabetic patients suspected of having severe peripheral vascular disease, since most information related to probability of this disorder may be obtained from patient age, self-reported history of physician diagnosed PVD (or < 1 block claudication), peripheral pulse palpation, and venous filling time. (C) 1997 Elsevier Science Inc. C1 UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98108. VA PUGET SOUND HLTH CARE SYST,DEPT ORTHOPED,SEATTLE,WA 98108. UNIV WASHINGTON,DEPT ORTHOPED,SEATTLE,WA 98108. RP Boyko, EJ (reprint author), VA PUGET SOUND HLTH CARE SYST,MED SERV,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 32 TC 43 Z9 43 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 1997 VL 50 IS 6 BP 659 EP 668 DI 10.1016/S0895-4356(97)00005-X PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XH671 UT WOS:A1997XH67100006 PM 9250264 ER PT J AU Taylor, AE Khoury, RH AF Taylor, AE Khoury, RH TI Interferences in immunometric assays for gonadotropins SO JOURNAL OF CLINICAL LIGAND ASSAY LA English DT Article DE gonadotropins; LH; FSH; heterologous antibodies; hook effect ID FOLLICLE-STIMULATING-HORMONE; FREE ALPHA-SUBUNIT; PITUITARY GLYCOPROTEIN HORMONES; ASPARAGINE-LINKED OLIGOSACCHARIDES; HUMAN CHORIO-GONADOTROPIN; LUTEINIZING-HORMONE; BETA-SUBUNIT; SIALYLATED OLIGOSACCHARIDES; NORMAL WOMEN; SECRETION AB In spite of advances in immunoassay technology, the measurement of the human pituitary gonadotropin hormones, luteinizing hormone (LH) and follicle stimulating hormone (FSH), remains complicated by the heterogeneity of the gonadotropin hormones, resulting in persistent significant variability between assays, Potential interfering factors in gonadotropin assays include biologic factors such as the gonadotropin subunits, heterogeneous forms of the gonadotropins, and heterologous antibodies in serum, immunologic factors such as variability in antibody specificity for gonadotropin forms, and design factors that may result in underestimation of large gonadotropin quantities, This review focuses on the biochemical features of gonadotropins that are critical for the optimization and interpretation of LH and FSH measurements, with an emphasis on their clinical consequences. RP Taylor, AE (reprint author), MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114, USA. NR 32 TC 1 Z9 1 U1 0 U2 0 PU CLINICAL LIGAND ASSAY SOC PI WAYNE PA 3139 S WAYNE RD, WAYNE, MI 48184 SN 1081-1672 J9 J CLIN LIGAND ASSAY JI J. Clin. Ligand Assay PD SUM PY 1997 VL 20 IS 2 BP 190 EP 199 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA XW446 UT WOS:A1997XW44600004 ER PT J AU Pegues, DA Pegues, CF Hibberd, PL Ford, DS Hooper, DC AF Pegues, DA Pegues, CF Hibberd, PL Ford, DS Hooper, DC TI Emergence and dissemination of a highly vancomycin-resistant vanA strain of Enterococcus faecium at a large teaching hospital SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFECTION; FAECALIS; STATES; GENES AB We prospectively identified patients at the Massachusetts General Hospital from whom vancomycin-resistant enterococci (VRE) were isolated from a clinical specimen from 1 January 1991 through 31 December 1995. VRE strains were available from 139 (82%) of the 169 patients with clinical cases. Of these, 39 (28%) were identical or closely related by pulsed-field gel electrophoresis (i.e., VRE type A strain), including 38 (43%) of 89 VRE strains in 1995. By multivariate analysis, acquisition of the VRE type A strain was associated with receipt of clindamycin (odds ratio [OR] = 10.5), 15 or more days of hospitalization before the first isolation of VRE (OR = 2.9), and residence on one of the general medical floors (OR = 7.8). The VRE type A strain was a vanA strain of Enterococcus faecium and was highly resistant to all antimicrobial agents tested except chloramphenicol. These findings document the rapid dissemination of a highly resistant strain of E. faecium among patients and among other extant VRE strains at the Massachusetts General Hospital in 1995. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT CONTROL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 24 TC 60 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1997 VL 35 IS 6 BP 1565 EP 1570 PG 6 WC Microbiology SC Microbiology GA XA755 UT WOS:A1997XA75500052 PM 9163483 ER PT J AU Guadagnoli, E Shapiro, C Gurwitz, JH Silliman, RA Weeks, JC Barbos, C Soumerai, SB AF Guadagnoli, E Shapiro, C Gurwitz, JH Silliman, RA Weeks, JC Barbos, C Soumerai, SB TI Age-related patterns of care: Evidence against ageism in the treatment of early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; CHEMOTHERAPY; THERAPY; HIGHLIGHTS; PATIENT; CHOICE; TRIAL AB Purpose: To assess whether the use of adjuvant systemic therapy in postmenopausal women with early-stage breast cancer is influenced by patient age. Methods: A retrospective cohort study based on data collected from medical records and from patients and their surgeons was performed among 746 postmenopausal patients diagnosed with early-stage breast cancer at 30 hospitals located throughout Minnesota, The adjusted odds of receiving hormonal therapy, chemotherapy, and both hormonal therapy and chemotherapy as a function of age was determined. Results: Among women with negative lymph nodes, 62% received some form of adjuvant drug therapy. For these women, the likelihood of receiving hormonal therapy or both hormonal therapy and chemotherapy did not vary with patient age and the likelihood of receiving chemotherapy declined with age, Among women with positive lymph nodes, 92% received some form of adiuvant therapy, For these women, the likelihood of receiving hormonal therapy increased with age and the likelihood of receiving chemotherapy declined with age, as did the likelihood of receiving both hormonal therapy and chemotherapy. Conclusion: The observed associations between age and the use of adjuvant systemic therapy appear to reflect, in general, available information about treatment efficacy and do not suggest underuse among elderly women with early-stage breast cancer. The use of adjuvant therapy depends on clinical factors that predict the increased risk of metastases or the increased likelihood of response to treatment, rather than other sociodemographic factors, Our results also suggest that younger postmenopausal women with positive lymph nodes compared with older women may be undertreated with respect to tamoxifen because of the substitution of chemotherapy for hormonal therapy. (C) 1997 by American Society of Clinical Oncology. C1 HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV GERONTOL,BOSTON,MA 02115. HARVARD PILGRIM HLTH PLAN,BOSTON,MA. BOSTON UNIV,SCH MED,BOSTON,MA 02118. HEALTHCARE EDUC & RES FDN INC,ST PAUL,MN. RP Guadagnoli, E (reprint author), HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,DEPT MED,25 SHATTUCK ST,PARCEL B 1ST FLOOR,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA57755, CA59408]; NIA NIH HHS [KO8 AG00510] NR 27 TC 55 Z9 56 U1 1 U2 1 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 JUN PY 1997 VL 15 IS 6 BP 2338 EP 2344 PG 7 WC Oncology SC Oncology GA XD977 UT WOS:A1997XD97700021 PM 9196148 ER PT J AU Sporn, J Sachs, G AF Sporn, J Sachs, G TI The anticonvulsant lamotrigine in treatment-resistant manic-depressive illness SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ASPARTATE RECEPTOR COMPLEX; ANTIEPILEPTIC DRUGS; PARTIAL SEIZURES; PARTIAL EPILEPSY; DOUBLE-BLIND; ANTIDEPRESSANT; ANTAGONISTS; CARBAMAZEPINE; ADAPTATION; SAFETY AB Anticonvulsants are used extensively in the treatment of bipolar disorder. Treating depression in bipolar disorder can be difficult because of the Limited antidepressant effects of the standard mood stabilizers and the tendency of antidepressants to induce mania or decrease cycle length. Lamotrigine is a new anticonvulsant with few side effects that may have mood-stabilizing and elevating effects. Its mechanism of action probably involves the inhibition of excessive release of excitatory amino acids such as glutamate. Antiglutamatergic agents may be antidepressant and mood stabilizing. A case series of 16 patients treated with lamotrigine (dose range 50 mg to 250 mg, mean dose of responders = 141 mg) is presented along with two case reports. All patients were considered treatment-resistant bipolar type I or II. Patients were rated on average 5 weeks after starting lamotrigine using a semistructured follow-up form that included symptom rating, Clinical Global Impressions (CGI), and Global Assessment of Functioning (GAF) scores. Eight of 16 patients were rated as ''responders'' (CGI less than or equal to 2) and had a mean increase of 16 in their GAF scores. Lamotrigine seems to have antidepressant and mood-stabilizing effects, but this requires confirmation in randomized, controlled trials. RP Sporn, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 31 TC 121 Z9 122 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1997 VL 17 IS 3 BP 185 EP 189 DI 10.1097/00004714-199706000-00008 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA XA697 UT WOS:A1997XA69700008 PM 9169963 ER PT J AU Jellinek, MS AF Jellinek, MS TI DSM-PC: Bridging pediatric primary care and mental health services SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material RP Jellinek, MS (reprint author), MASSACHUSETTS GEN HOSP,DEPT CHILD PSYCHIAT,55 FRUIT ST,BULFINCH ROOM 351,BOSTON,MA 02114, USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 1997 VL 18 IS 3 BP 173 EP 174 DI 10.1097/00004703-199706000-00007 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA XG168 UT WOS:A1997XG16800007 PM 9213234 ER PT J AU Bortolami, SB Riley, PO Krebs, DE AF Bortolami, SB Riley, PO Krebs, DE TI Numerical differentiation of tracking data of human motion: The virtual accelerometer SO JOURNAL OF DYNAMIC SYSTEMS MEASUREMENT AND CONTROL-TRANSACTIONS OF THE ASME LA English DT Article ID POSITION AB A method based on the Kalman Filter for deriving whole-body segment accelerations from position tracking data is described. Such a procedure is experimentally calibrated and qualified as a Virtual Accelerometer supplying a resolution of 0.2 m/s(2) and a relative accuracy of better than 10 percent rms within 0-8 Hz bandwidth. Results are finally compared to accelerometer performances reported by previous investigators. C1 MGH,INST HLTH & PROFESS,BOSTON,MA. RP Bortolami, SB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BIOMOT LAB,BOSTON,MA 02114, USA. RI Riley, Patrick/B-3053-2009 NR 16 TC 0 Z9 0 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0022-0434 J9 J DYN SYST-T ASME JI J. Dyn. Syst. Meas. Control-Trans. ASME PD JUN PY 1997 VL 119 IS 2 BP 355 EP 358 DI 10.1115/1.2801265 PG 4 WC Automation & Control Systems; Instruments & Instrumentation SC Automation & Control Systems; Instruments & Instrumentation GA XE290 UT WOS:A1997XE29000041 ER PT J AU Bortolami, SB Riley, PO Krebs, DE AF Bortolami, SB Riley, PO Krebs, DE TI Modeling the systematic uncertainty of photogrammetric tracking of human motion SO JOURNAL OF DYNAMIC SYSTEMS MEASUREMENT AND CONTROL-TRANSACTIONS OF THE ASME LA English DT Article AB We address bias errors of photogrammetric tracking of four SELSPOT-II(R) cameras using active marker photogrammetry in a 2 m x 2 m x 2 m viewing volume for human locomotion measurements. We present uncertainty modeling regarding the first stage of equipment set tip, which provides the camera frame to global frame rotation matrices and the distances among cameras. We also characterize the uncertainty due to the camera distortions of the bare system as compared to published performances achieved with a camera correction procedure. The particular approach is to qualify performances of photogrammetric tracking during routine operation and to identify the nature and magnitude of the uncertainty due to equipment set tip and camera distortions as part of the total uncertainty in a self-consistent manner. We found that uncertainty of the camera frame to global frame rotation matrices produced rotation of the image and uncorrected camera hardware uncertainty produced dilatation or compression of the image twice the magnitude of that seen with camera correction. However, camera resolution remains as an equally important factor limiting the accuracy of photogrammetric tracking that can not be easily reduced numerically. In conclusion, the analysis elucidates how uncertainty propagates to numerical derivatives of the tracking data and prepares the groundwork for future development. C1 MGH,INST HLTH & PROFESS,BOSTON,MA. RP Bortolami, SB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BIOMOT LAB,BOSTON,MA 02114, USA. RI Riley, Patrick/B-3053-2009 NR 7 TC 0 Z9 0 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0022-0434 J9 J DYN SYST-T ASME JI J. Dyn. Syst. Meas. Control-Trans. ASME PD JUN PY 1997 VL 119 IS 2 BP 358 EP 361 DI 10.1115/1.2801266 PG 4 WC Automation & Control Systems; Instruments & Instrumentation SC Automation & Control Systems; Instruments & Instrumentation GA XE290 UT WOS:A1997XE29000042 ER PT J AU Nakabayashi, T Letterio, JJ Geiser, AG Kong, LP Ogawa, N Zhao, WG Koike, T Fernandes, G Dang, H Talal, N AF Nakabayashi, T Letterio, JJ Geiser, AG Kong, LP Ogawa, N Zhao, WG Koike, T Fernandes, G Dang, H Talal, N TI Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-beta 1 knockout mice - MHC class II is a factor in the pathogenesis of TGF-beta 1 knockout mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SJOGRENS-SYNDROME; HUMAN-LYMPHOCYTES; INTERFERON-GAMMA; DEFICIENT MICE; TGF-BETA; EXPRESSION; MOUSE; ICAM-1; DEATH AB Mice homozygous for a disrupted TGF-beta 1 allele develop multiple lymphoproliferative disorders similar to those seen in the pseudolymphoma of Sjogren's syndrome. At 2 wk of age, these TGF-beta 1 mutant mice begin to develop wasting syndrome and die at around 4 to 5 wk of age, We studied salivary glands from symptomatic mutant mice >14 days of age, Reverse transcriptase-PCR analysis showed up-regulation of proinflammatory cytokine genes such as IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, and IFN-gamma in these mutant mice. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining, To elucidate the role of MHC class II, salivary glands from TGF-beta 1/MHC class II double knockout mice were used to investigate the expression of adhesion molecules and MHC class II, In spite of the existence of basal intercellular adhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands, These results suggest that MHC class II plays a significant role in the pathogenesis of TGF-beta 1 mutant mice, Although the mechanism that initiates multiple inflammatory diseases in these mice remains unclear, the context reported here would provide insight into the immunopathology of Sjogren's syndrome. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. HOKKAIDO UNIV,SCH MED,SAPPORO,HOKKAIDO 060,JAPAN. FU NIDCR NIH HHS [DE 09311, DE 10863] NR 41 TC 34 Z9 34 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 JUN 1 PY 1997 VL 158 IS 11 BP 5527 EP 5535 PG 9 WC Immunology SC Immunology GA XA063 UT WOS:A1997XA06300061 PM 9164977 ER PT J AU Stern, RS Vakeva, LH Bauer, E Koo, J Epstein, JH Wolf, J Nigra, TP Anderson, TF Prystowsky, J McEvoy, M Taylor, JR Zaias, N Urbach, F Arndt, KA Baughman, RD Braverman, IM Murray, J Werth, V Fitzpatrick, TB Parrish, J Sober, A AF Stern, RS Vakeva, LH Bauer, E Koo, J Epstein, JH Wolf, J Nigra, TP Anderson, TF Prystowsky, J McEvoy, M Taylor, JR Zaias, N Urbach, F Arndt, KA Baughman, RD Braverman, IM Murray, J Werth, V Fitzpatrick, TB Parrish, J Sober, A TI Noncutaneous malignant tumors in the PUVA follow-up study: 1975-1996 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE noncutaneous cancer; psoralens; ultraviolet A; cohort study ID A RADIATION PUVA; PSORIASIS; CANCER; RISK; 8-METHOXYPSORALEN; METHOTREXATE; DISEASE AB There is concern about possible association between PUVA treatment and an increased risk of noncutaneous cancer. An alteration in the risk of cancer among persons with psoriasis has also been postulated. To test this hypothesis, for nearly two decades we have prospectively followed 1380 patients who first began PUVA treatment for psoriasis in 1975-1976. We compare the risk of noncutaneous cancer in our cohort with that expected based on general population incidence rates. The overall risk of noncutaneous cancer was nearly identical to that expected in general population. For three separate sites, we noted significant increases: thyroid cancer (RR = 3.57, 95% CI = 1.16-8.34), breast cancer (RR = 1.81, 95% CI = 1.19-2.64), and central nervous system neoplasms (RR = 2.80, 95% CI = 1.13-5.57). Since 1987, however, the risk of central nervous system neoplasms has not been elevated (RR = 0.00, 95% CI = 0.00-3.35) and the relative risk of breast cancer was lower than in the prior decade and not statistically significant. There was no association between higher levels of exposure to PUVA and the risk of any of these cancers. We did not detect any significant increase in the risk of lymphoma or leukemia. Our study does not support the hypothesis that long-term PUVA treatment increases the risk of noncutaneous cancer. C1 STANFORD UNIV,SCH MED,STANFORD,CA 94305. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. BAYLOR COLL MED,HOUSTON,TX 77030. WASHINGTON HOSP CTR,WASHINGTON,DC 20010. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55901. UNIV MIAMI,MIAMI,FL 33152. MT SINAI MED CTR,MIAMI,FL. TEMPLE UNIV,SCH MED,PHILADELPHIA,PA 19122. BETH ISRAEL HOSP,BOSTON,MA 02215. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756. YALE UNIV MED,NEW HAVEN,CT. DUKE UNIV,MED CTR,DURHAM,NC. HOSP UNIV PENN,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Stern, RS (reprint author), HARVARD UNIV,SCH MED,BETH ISRAEL DEACONESS MED CTR,DEPT DERMATOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAMS NIH HHS [N01-AR-4-2214] NR 28 TC 42 Z9 42 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1997 VL 108 IS 6 BP 897 EP 900 DI 10.1111/1523-1747.ep12292698 PG 4 WC Dermatology SC Dermatology GA XB836 UT WOS:A1997XB83600012 PM 9182818 ER PT J AU Muntz, KH Ishikawa, Y Wagner, T Homcy, CJ Vatner, SF Vatner, DE AF Muntz, KH Ishikawa, Y Wagner, T Homcy, CJ Vatner, SF Vatner, DE TI Localisation of cardiac G(S alpha) in transgenic mice overexpressing G(S alpha) SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE immunofluorescence; confocal imaging; T-tubule; intercalated disk ID G-PROTEINS; CAVEOLAE AB The biochemical and physiological effects of G(S alpha) activation are well known; however, little is known about the anatomical localisation of G(S alpha) in the myocardium. Knowledge of the localisation might yield insights into G protein function in heart. The utility of immunocytochemistry using immunofluorescent methods is limited in normal hearts because of the low expression of G(S alpha). In order to magnify the G(S alpha) signal, we studied transgenic mice overexpressing myocardial G(S alpha). Immunofluorescent techniques with confocal imaging using rabbit antiserum specific for G(S alpha) were studied in frozen sections of mouse left ventricle. G(S alpha) labeling appeared to be localised to the T-tubules and intercalated disks in the G(S alpha) overexpressing mouse hearts, whereas the control mice showed background fluorescence with diffuse faint labeling. The localisation of G(S alpha) to structures involved in calcium handling and membrane conductance places G(S alpha) at a focal point in the regulation of these key functions. (C) 1997 Academic Press Limited. C1 ALLEGHENY UNIV HLTH SCI, CARDIOVASC & PULM RES INST, PITTSBURGH, PA 15212 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02115 USA. NEW ENGLAND REG PRIMATE RES CTR, SOUTHBOROUGH, MA 01722 USA. MASSACHUSETTS GEN HOSP, DEPT PEDIAT, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL33107, HL38070, HL37404] NR 19 TC 4 Z9 4 U1 0 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 JUN PY 1997 VL 29 IS 6 BP 1649 EP 1653 DI 10.1006/jmcc.1997.0400 PG 5 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA XG425 UT WOS:A1997XG42500014 PM 9220350 ER PT J AU Blais, MA AF Blais, MA TI Clinician ratings of the five-factor model of personality and the DSM-IV personality disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID III-R; 5-FACTOR MODEL AB This study explored the associations among the domains of the five-factor model (FFM) of personality (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and the DSM-IV personality disorders (PDs). Clinician ratings were obtained for both the DSM-IV PDs and the FFM on a sample of 100 PD patients. The correlational data showed that the DSM PDs were most strongly associated with the FFM domains of neuroticism, extraversion, and agreeableness. Factor analysis revealed four underlying factors that provided insights into qualities shared by subgroups of the DSM-IV PDs. The domain of neuroticism was associated with the borderline, avoidant, and dependent PDs (factor 1). The paranoid, avoidant, schizoid, and schizotypal PDs were negatively associated with the domain of agreeableness (factor 2). The domain of extraversion was positively associated with the narcissistic and histrionic PDs and negatively with schizoid PD (factor 3). The FFM conscientiousness and openness domains loaded onto a single factor and were positively associated with the obsessive-compulsive PD and negatively associated with the antisocial and borderline PDs. Exploring the relationships between these two personality systems will improve our conceptualization and understanding of the DSM PDs. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Blais, MA (reprint author), INPATIENT PSYCHIAT SERV,BLAKE 11,MGH,55 FRUIT ST,BOSTON,MA 02114, USA. NR 27 TC 84 Z9 84 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUN PY 1997 VL 185 IS 6 BP 388 EP 393 DI 10.1097/00005053-199706000-00005 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XE747 UT WOS:A1997XE74700005 PM 9205425 ER PT J AU Dangond, F Windhagen, A Groves, CJ Hafler, DA AF Dangond, F Windhagen, A Groves, CJ Hafler, DA TI Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE costimulation; glia; immunity ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; T-CELLS; MULTIPLE-SCLEROSIS; LYMPHOCYTES-T; B7-2; CD86; CD28; ANTIGEN; B7/BB1 AB Human microglia constitute the primary residential antigen presenting cells (APCs) in the central nervous system (CNS) and have the capacity of activating myelin reactive T-cells. T-cell activation requires two signals: first is the interaction of the T-cell receptor with the MHC-antigen complex and, secondly, contact of the CD28/CTLA4 T-cell surface molecules with the B7 family of costimulatory molecules on the APCs. We have previously shown high expression of B7.1 in early multiple sclerosis (MS) plaques, suggesting that acute T-cell-mediated CNS inflammation may require local B7.1 upregulation. We have now examined the expression of B7.1 and B7.2 costimulatory molecules on resting ex-vivo human microglia isolated directly from biopsy specimens. We found constitutive expression of B7.2 but not B7.1 on resting microglia, suggesting that B7.2 expression may lead to downregulation of pro-inflammatory Th1 T-cell responses in the normal brain. C1 BRIGHAM & WOMENS HOSP,LAB MOL IMMUNOL,CTR NEUROL DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,FLOW CYTOMETRY LAB,TUMOR IMMUNOL DIV,BOSTON,MA 02115. NR 26 TC 41 Z9 41 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUN PY 1997 VL 76 IS 1-2 BP 132 EP 138 DI 10.1016/S0165-5728(97)00043-X PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XC997 UT WOS:A1997XC99700016 PM 9184642 ER PT J AU Aquino, DA Capello, E Weisstein, J Sanders, V Lopez, C Tourtellotte, WW Brosnan, CF Raine, CS Norton, WT AF Aquino, DA Capello, E Weisstein, J Sanders, V Lopez, C Tourtellotte, WW Brosnan, CF Raine, CS Norton, WT TI Multiple sclerosis: Altered expression of 70- and 27-kDa heat shock proteins in lesions and myelin SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BASIC-PROTEIN; T-CELLS; MONOCLONAL-ANTIBODIES; CANDIDATE AUTOANTIGEN; ACTIN POLYMERIZATION; CEREBROSPINAL-FLUID; GENE REARRANGEMENTS; PROTEOLIPID PROTEIN; INCREASED FREQUENCY AB Recent studies have implicated heat shock proteins (HSP) in the pathogenesis of the multiple sclerosis (MS) lesion. Expression of the 73 kDa constitutive HSP (HSC70), the 72 kDa stress-inducible HSP (HSP70), and the 27 kDa small HSP (HSP27) was analyzed in white matter and myelin from central nervous system (CNS) tissue of MS and normal subjects using a combination of immunocytochemistry and quantitative immunoblotting. Plaques of all types were sharply defined by reduced immunostaining for HSC70, and shown by immunoblotting to contain 30 to 50% less HSC70 than surrounding white matter or normal tissue. Ln contrast, HSP27 was markedly enhanced 2.5- to 4-fold in plaque regions, especially in fibrous astrocytes and in hyperplastic interfascicular oligodendrocytes at the lesion edge. HSP70 was less abundant than HSC70, and no significant differences in HSP70 levels were noted between MS and normal white matter. Myelin isolated from active plaques contained 3- to 4-fold more HSC70 than normal myelin. Pronounced expression of HSP70 and HSP27 was also found in MS myelin, although neither protein was detected in normal myelin. Thus, white matter undergoing immune-mediated destruction in MS was associated with altered distribution and expression of HSC70 and HSP27. These changes may initially serve to protect myelin from further destruction and facilitate repair; however, enhanced expression of HSC70, HSP70, and HSP27 in myelin may subsequently present as additional immune targets involved in the progression of disease. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90024. 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. RP Aquino, DA (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,1300 MORRIS PK AVE,F-140,BRONX,NY 10461, USA. FU NINDS NIH HHS [NS-23705, NS-30319]; PHS HHS [MS-08952] NR 46 TC 62 Z9 64 U1 1 U2 3 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 JUN PY 1997 VL 56 IS 6 BP 664 EP 672 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XD281 UT WOS:A1997XD28100004 PM 9184657 ER PT J AU StemmerRachamimov, AO GonzalezAgosti, C Xu, L Burwick, JA Beauchamp, R Pinney, D Louis, DN Ramesh, V AF StemmerRachamimov, AO GonzalezAgosti, C Xu, L Burwick, JA Beauchamp, R Pinney, D Louis, DN Ramesh, V TI Expression of NF2-encoded merlin and related ERM family proteins in the human central nervous system SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ezrin; glia; merlin; moesin; neurofibromatosis 2; NF2; radixin ID NEUROFIBROMATOSIS TYPE-2 GENE; BILATERAL ACOUSTIC NEUROFIBROMATOSIS; EPIDERMAL GROWTH-FACTOR; EZRIN; CYTOSKELETON; RADIXIN; MOESIN; MUTATIONS; CELLS; LOCALIZATION AB Germline mutations of the neurofibromatosis 2 (NF2) gene are associated with an increased incidence of gliomas and glial hamartoma, suggesting a role for the NF2-encoded protein, merlin, in glial growth control. Using monoclonal and polyclonal anti-merlin antibodies for Western blotting and immunohistochemistry, we evaluated the cellular pattern of merlin expression in the normal human central nervous system (CNS), reactive gliosis, and NF2-associated glial hamartomas. In the normal CNS, merlin is widely expressed in coarse cytoplasmic granules in both glia and neurons, with less pronounced expression in other cells. Merlin is also expressed in reactive astrocytes and in the astrocytes of NF2-associated glial hamartomas. In reactive astrocytes, however, merlin is also present at the cell membrane and in cellular processes, suggesting redistribution of the protein in activated cells. Merlin is structurally related to ezrin, radixin and moesin, which are also expressed in the CNS, as demonstrated by Western blotting. The pattern of merlin expression, however, is distinct from that of ezrin, which has been previously described, and that of moesin, in which immunohistochemistry with an anti-moesin antibody showed expression in endothelial cells, glia and neurons in a membranous or diffuse cytoplasmic pattern. These findings imply that merlin has widespread and specific functions in the human central nervous system. C1 MASSACHUSETTS GEN HOSP, MOL NEUROONCOL LAB, DEPT PATHOL NEUROPATHOL, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, NEUROSURG SERV, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, MOL NEUROGENET UNIT, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. FU NINDS NIH HHS [NS24279] NR 32 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 1997 VL 56 IS 6 BP 735 EP 742 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XD281 UT WOS:A1997XD28100011 PM 9184664 ER PT J AU Trimble, MR Mendez, MF Cummings, JL AF Trimble, MR Mendez, MF Cummings, JL TI Neuropsychiatric symptoms from the temporolimbic lobes SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID INTERICTAL BEHAVIOR; EMISSION TOMOGRAPHY; TEMPORAL LOBES; MOOD DISORDERS; EPILEPSY; SCHIZOPHRENIA; HYPERGRAPHIA; DEPRESSION; PSYCHOSIS; ANXIETY AB Neuropsychiatric symptoms are common manifestations of temporolimbic. lesions. These neuropsychiatric symptoms result from disturbances of specific temporolimbic networks, including medial limbic circuits, lateral limbic circuits, and the ''extended'' amygdala. Moreover, temporolimbic networks interface with multiple cortical and subcortical circuits that modulate emotional behavior and affect. This article not only reviews these behaviorally relevant aspects of temporolimbic neuroanatomy, but also describes positive, productive symptoms from the temporal lobes. The Kluver-Bucy syndrome, the Gastaut-Geschwind syndrome, emotional or mood disorders, delusions, anxiety and associative disorders, and neurovegetative symptoms are discussed, as well as amnesia, the signature temporolimbic disturbance of cognition. The temporolimbic lobe is a classic example of a widely distributed circuit within the brain that has behaviorally relevant manifestations. C1 UNIV CALIF LOS ANGELES,SCH MED,REED NEUROL RES CTR,DEPT NEUROL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90095. INST NEUROL,LONDON WC1N 3BG,ENGLAND. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,NEUROBEHAV & NEUROPSYCHIAT PROGRAM,LOS ANGELES,CA 90073. FU NIA NIH HHS [AG10123] NR 86 TC 42 Z9 42 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1997 VL 9 IS 3 BP 429 EP 438 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XR782 UT WOS:A1997XR78200009 PM 9276844 ER PT J AU Kanwisher, N McDermott, J Chun, MM AF Kanwisher, N McDermott, J Chun, MM TI The fusiform face area: A module in human extrastriate cortex specialized for face perception SO JOURNAL OF NEUROSCIENCE LA English DT Article DE extrastriate cortex face perception; functional MRI; fusiform gyrus; ventral visual pathway; object recognition ID TEMPORAL CORTEX; RECOGNITION; OBJECT; DISSOCIATION; AGNOSIA; PROSOPAGNOSIA; NEURONS; MACAQUE; CELLS AB Using functional magnetic resonance imaging (fMRI), we found an area in the fusiform gyrus in 12 of the 15 subjects tested that was significantly more active when the subjects viewed faces than when they viewed assorted common objects. This face activation was used to define a specific region of interest individually for each subject, within which several new tests of face specificity were run. In each of five subjects tested, the predefined candidate ''face area'' also responded significantly more strongly to passive viewing of (1) intact than scrambled two-tone faces, (2) full front-view face photos than front-view photos of houses, and (in a different set of five subjects) (3) three-quarter-view face photos (with hair concealed) than photos of human hands; it also responded more strongly during (4) a consecutive matching task performed on three-quarter-view faces versus hands. Our technique of running multiple tests applied to the same region defined functionally within individual subjects provides a solution to two common problems in functional imaging: (1) the requirement to correct for multiple statistical comparisons and (2) the inevitable ambiguity in the interpretation of any study in which only two or three conditions are compared. Our data allow us to reject alternative accounts of the function of the fusiform face area (area ''FF'') that appeal to visual attention, subordinate-level classification, or general processing of any animate or human forms, demonstrating that this region is selectively involved in the perception of faces. C1 MASSACHUSETTS GEN HOSP, NMR CTR, CHARLESTOWN, MA 02129 USA. YALE UNIV, DEPT PSYCHOL, NEW HAVEN, CT 06520 USA. RP Kanwisher, N (reprint author), HARVARD UNIV, DEPT PSYCHOL, 33 KIRKLAND ST, CAMBRIDGE, MA 02138 USA. RI Li, Chong/F-4265-2015; OI Chun, Marvin/0000-0003-1070-7993 NR 41 TC 3799 Z9 3847 U1 76 U2 461 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 1997 VL 17 IS 11 BP 4302 EP 4311 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XA056 UT WOS:A1997XA05600034 PM 9151747 ER PT J AU Bartold, SP Donohoe, KJ Fletcher, JW Haynie, TP Henkin, RE Silberstein, EB Royal, HD VandenAbbeele, A AF Bartold, SP Donohoe, KJ Fletcher, JW Haynie, TP Henkin, RE Silberstein, EB Royal, HD VandenAbbeele, A TI Procedure guideline for gallium scintigraphy in the evaluation of malignant disease SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE practice guidelines; gallium-67; malignant disease ID NON-HODGKINS-LYMPHOMA; GA-67 SCINTIGRAPHY; CELL LYMPHOMA; CHEMOTHERAPY; SPECT; MANAGEMENT; RECURRENCE; CHILDREN; CITRATE; SCANS C1 TEXAS TECH UNIV,ODESSA,TX. BETH ISRAEL HOSP,BOSTON,MA 02215. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. MALLINCKRODT INST RADIOL,ST LOUIS,MO. DANA FARBER CANC INST,BOSTON,MA 02115. NR 36 TC 53 Z9 54 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 1997 VL 38 IS 6 BP 990 EP 994 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XD639 UT WOS:A1997XD63900041 PM 9189158 ER PT J AU Sorensen, G Glasgow, RE Topor, M Corbett, K AF Sorensen, G Glasgow, RE Topor, M Corbett, K TI Worksite characteristics and changes in worksite tobacco-control initiatives - Results from the COMMIT study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SMOKING CONTROL ACTIVITIES AB Few studies have prospectively examined the characteristics associated with worksite adoption of tobacco-control initiatives, Data were collected as part of the Community Intervention Trial (COMMIT) for Smoking Cessation, which conducted interventions in II communities, This smoking cessation intervention was based on community organization principles and delivered through multiple community channels, including worksites, health care providers, the media, and cessation resources. This article reports results from telephone interviews of intervention community worksites having TO or more employees, conducted at baseline and the end of the intervention period. Among worksites that responded to both baseline and final surveys; 83 % had not adopted a smoke-free policy at baseline, and 61 % did not offer any cessation aid or quitting resources at baseline. By the final survey 34% of those with no smoking ban at baseline had become smoke-free, and 36 % of those offering no cessation assistance at baseline were offering cessation resources at the follow-up. The prevalence of policy adoption was higher among worksites employing more female employees and offering other health-promotion activities; manufacturing businesses were significantly less likely; than businesses other than service and wholesale/retail businesses to adopt policies. Adoption of cessation programs was significantly more likely among worksites employing 100 to 249 workers, compared with those employing 50 to 99 workers; those predominantly employing men; those offering other types of health-promotion activities; and those with a higher rate of turnover. These results provide important information about the characteristics of worksites likely to engage in tobacco-control efforts, Health educators and others may choose to target those worksites most ready for adoption of tobacco control policies and programs, as indicated by these findings. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. OREGON RES INST,EUGENE,OR 97403. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. UNIV COLORADO,DEPT ANTHROPOL,DENVER,CO 80202. RP Sorensen, G (reprint author), DANA FARBER CANC INST,CTR COMMUNITY BASED RES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CN55513-38] NR 21 TC 9 Z9 9 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUN PY 1997 VL 39 IS 6 BP 520 EP 526 DI 10.1097/00043764-199706000-00006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XH197 UT WOS:A1997XH19700005 PM 9211209 ER PT J AU Todd, R Donoff, RB Wong, DTW AF Todd, R Donoff, RB Wong, DTW TI The molecular biology of oral carcinogenesis: Toward a tumor progression model SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR-ALPHA; NECROSIS FACTOR-ALPHA; NECK-CANCER; GENE-THERAPY; SUPPRESSOR GENES; FACTOR RECEPTOR; CYCLE CONTROL; HEAD; ONCOGENES AB Purpose: An understanding of the molecular basis of oval carcinogenesis will alter our clinical approach to oral cancer, The nomenclature and major themes of molecular oral tumor biology are reviewed, beginning with the regulation events governing normal cellular physiology, In carcinogenesis, chromosomal or cytogenetic alterations lead to deregulation of tightly controlled stimulatory and inhibitory pathways, growth-promoting proto-oncogenes are mutated into overactive oncogenes, and growth-suppressing or tumor suppressor genes are inactivated. Recent advances in defining these fundamental mechanisms of tumor biology may allow prevention, diagnosis, and treatment of oral cancer to be approached at the molecular level. C1 MASSACHUSETTS GEN HOSP, DEPT ORAL & MAXILLOFACIAL SURG, BOSTON, MA 02114 USA. RP Todd, R (reprint author), HARVARD UNIV, SCH DENT MED, LAB MOL PATHOL, 188 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NIDCR NIH HHS [DE-08680, DE-10208, DE-00275] NR 96 TC 53 Z9 53 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 1997 VL 55 IS 6 BP 613 EP 623 DI 10.1016/S0278-2391(97)90495-X PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XD372 UT WOS:A1997XD37200019 PM 9191644 ER PT J AU Li, KK Meara, JG Joseph, MP AF Li, KK Meara, JG Joseph, MP TI Reversal of blindness after facial fracture repair by prompt optic nerve decompression SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID NEUROPATHY; RETINA; INJURY; TRAUMA C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA 02114. NR 24 TC 18 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 1997 VL 55 IS 6 BP 648 EP 650 DI 10.1016/S0278-2391(97)90503-6 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XD372 UT WOS:A1997XD37200027 PM 9191650 ER PT J AU Frueh, BC Gold, PB deArellano, MA Brady, KL AF Frueh, BC Gold, PB deArellano, MA Brady, KL TI A racial comparison of combat veterans evaluated for PTSD SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; SCALE; BLACK; RELIABILITY; ETHNICITY; VALIDITY; IMPACT; WHITE AB This study attempted to replicate the work of Frueh, Smith, and Libet (1996), which showed racial differences on psychological measures of dissociation/thought disturbance and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) F-K index in combat veterans evaluated for posttraumatic stress disorder (PTSD). Veterans completed the Beck Depression Inventory, Mississippi Scale for Combat-Related PTSD, a fixed-response format version of the Dissociative Experiences Scale (DES-FRF), and MMPI-2. prior to treatment at a Veterans affairs hospital outpatient PTSD clinic, Contrary to expectation, significant racial differences on the DES-FRF, MMPI-2 validity scales, and MMPI-2 Scales 6 and 8 were not found. Consistent with the previous study, no racial differences on measures of anxiety, depression, or PTSD symptomatology were found; nor were there racial differences on clinician ratings of global assessment of functioning or on most categories of psychiatric diagnoses. This suggests that Black and White combat veterans evaluated for PTSD do not differ with regard to reported manifestation or severity of psychopathology. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,NATL CRIME VICTIM RES & TREATMENT CTR,CHARLESTON,SC 29425. RP Frueh, BC (reprint author), RALPH H JOHNSON VA MED CTR,MENTAL HLTH SERV 116,109 BEE ST,CHARLESTON,SC 29401, USA. NR 32 TC 18 Z9 18 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JUN PY 1997 VL 68 IS 3 BP 692 EP 702 DI 10.1207/s15327752jpa6803_14 PG 11 WC Psychology, Clinical; Psychology, Social SC Psychology GA WZ566 UT WOS:A1997WZ56600014 PM 9170304 ER PT J AU Strack, S Lorr, M AF Strack, S Lorr, M TI Invited essay: The challenge of differentiating normal and disordered personality SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID TAXONOMY; NUMBER AB By separating personality disorders from other psychiatric conditions and requiring mental health professionals to assess the personalities of all their patients, DSM-III Axis II created an explosion of ideas and research on the nature and structure of personality, Since 1980, theorists and researchers from previously segregated camps have come together to address a number of important taxonomic issues, including the relationship between normal and disordered character, In this article, we place the challenge of differentiating normal and abnormal personality in historical perspective. and outline major theories, models, and methods that inform personologists in their quest. The complexity of personality, and the differences in the way people view the subject matter, ensure that there will be several research lines in the next generation, Progress in the field can be quickened by refinements in theory, the development of more assessment instruments that tap both normal and abnormal traits, and empirical studies that follow well-match groups of normals and patients over significant time periods. C1 CATHOLIC UNIV AMER,INST LIFE CYCLE,WASHINGTON,DC 20064. RP Strack, S (reprint author), US DEPT VET AFFAIRS,OUTPATIENT CLIN,PSYCHOL SERV 116B,351 E TEMPLE ST,LOS ANGELES,CA 90012, USA. NR 88 TC 12 Z9 12 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SUM PY 1997 VL 11 IS 2 BP 105 EP 122 PG 18 WC Psychiatry SC Psychiatry GA XF773 UT WOS:A1997XF77300001 PM 9203106 ER PT J AU Bernstein, DP Kasapis, C Bergman, A Weld, E Mitropoulou, V Horvath, T Klar, HM Silverman, J Siever, LJ AF Bernstein, DP Kasapis, C Bergman, A Weld, E Mitropoulou, V Horvath, T Klar, HM Silverman, J Siever, LJ TI Assessing axis II disorders by informant interview SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID DIAGNOSING PERSONALITY-DISORDERS; DSM-III AB Although much of personality disorder research depends on diagnostic data obtained directly from patients, this approach has rarely been compared to interviews with knowledgeable informants. The purpose of this study was to determine the diagnostic agreement between these two assessment methods, as well as their relative contribution to the formulation of consensus diagnoses, Sixty-two psychiatric patients were assessed directly with the Structured Interview for DSM-III Personality Disorders (SIDP), and were asked to nominate an informant - either a family member or friend - to provide information about the patient in an interview with the same instrument, Informant interviews were conducted blind to patient-based information whenever feasible, and diagnostic consensus was achieved by an independent review of all available data by a senior clinician, Diagnostic agreement between patient-based and informant-based personality disorder interview was poor, confirming the findings of two previous studies, Information obtained from patients tended to be given greater weight in formulating consensus diagnoses than information provided by informants. However, about one quarter of diagnostic disagreements were resolved in favor of informant-based information. in contrast to a previous study, the inclusion of informant information did not appear to reveal greater psychopathology in patients. We conclude that supplementing direct patient interview with data provided by a knowledgeable informant appears to enhance the resolution of some personality disorder diagnoses. The utility of informant Interviews may depend on an analysis of the costs and benefits of this additional degree of descriptive refinement. C1 COLUMBIA UNIV,NEW YORK,NY. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. NORTHPORT VET AFFAIRS MED CTR,NORTHPORT,NY. RP Bernstein, DP (reprint author), BRONX VET ADM MED CTR,PSYCHIAT SERV 116A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. FU NIMH NIH HHS [MH42827-07] NR 18 TC 25 Z9 25 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SUM PY 1997 VL 11 IS 2 BP 158 EP 167 PG 10 WC Psychiatry SC Psychiatry GA XF773 UT WOS:A1997XF77300005 PM 9203110 ER PT J AU Blais, MA Norman, DK AF Blais, MA Norman, DK TI A psychometric evaluation of the DSM-IV personality disorder criteria SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID PSYCHIATRIC CLASSIFICATION; III-R; ISSUES AB In this study, we examined the psychometric quality of the recently revised DSM-IV Personality Disorders (PCI). A nationally drawn sample of mental health professionals rated 280 patients known to them, using a symptom checklist containing all the DSM-IV PD criteria. From this symptom level data we determined internal consistency, convergent validity, and discriminant validity for each DSM-HV PD criteria. Overall, the findings were encouraging. The internal consistency - a measure of reliability - of the PD criteria sets appears to be substantially improved. The median coefficient alpha for the DSM-TV PDs was .73. Convergent validity was generally adequate for the DSM-IV PD criteria sets. However, discriminant validity, a measure of the specificity of a criterion's relationship to its parent scale, continues to be a problem of the PDs. The findings suggest that the DSM-IV PDs may have better reliability than did their DSM-III-R predecessors. However, the weak discriminant validity found for the DSM-IV PD criteria sets indicates that the Axis II system will continue to show high levels of comorbidity. The usefulness of psychometric procedures in the development and refinement of the DSM PDs is also highlighted. C1 HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA. RP Blais, MA (reprint author), MASSACHUSETTS GEN HOSP, INPATIENT PSYCHIAT SERV, DEPT PSYCHIAT, BLAKE 11, 55 FRUIT ST, BOSTON, MA 02114 USA. NR 24 TC 93 Z9 93 U1 0 U2 2 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SUM PY 1997 VL 11 IS 2 BP 168 EP 176 PG 9 WC Psychiatry SC Psychiatry GA XF773 UT WOS:A1997XF77300006 PM 9203111 ER PT J AU Blais, MA McCann, JT Benedict, KB Norman, DK AF Blais, MA McCann, JT Benedict, KB Norman, DK TI Toward an empirical/theoretical grouping of the DSM-III-R personality disorders SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID CLUSTERS AB Despite some recent favorable findings, there has not been strong empirical support for the validity of DSM-III-R - and now DSM-IV - personality disorder (PD) clusters. III this study, Axis II symptom ratings on 320 personality disordered patients were used to obtain dimensional scores for the 11 DSM-III-R PDs, The dimensional scores for the DSM PDs were subjected to a principal component analysis with orthoginal rotation. Three factors emerged having eigenvalues greater than or equal to than I, The pattern of factor loadings for the individual PDs were not consistent with the DSM Cluster, Rather, the factor loadings were quite consistent with Millon's theory of personality. These results are discussed in Light of the clinical benefits provided by employing empirically determined and theoretically anchored model for organizing the Axis II disorders. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Blais, MA (reprint author), MASSACHUSETTS GEN HOSP,INPATIENT PSYCHIAT SERV,PSY D,BLAKE 11,BOSTON,MA 02114, USA. NR 21 TC 18 Z9 18 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD SUM PY 1997 VL 11 IS 2 BP 191 EP 198 PG 8 WC Psychiatry SC Psychiatry GA XF773 UT WOS:A1997XF77300008 PM 9203113 ER PT J AU Petrecca, K Amellal, F Laird, DW Cohen, SA Shrier, A AF Petrecca, K Amellal, F Laird, DW Cohen, SA Shrier, A TI Sodium channel distribution within the rabbit atrioventricular node as analysed by confocal microscopy SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID JUNCTION PROTEIN PHENOTYPES; CONDUCTION SYSTEM; RAT-HEART; PURKINJE-FIBERS; GAP-JUNCTIONS; PATTERNS; MUSCLE; CONNEXIN43; TISSUES AB 1. Paired 20 mu m thick sections of fresh frozen tissue taken from the frontal plane of the rabbit atrioventricular (AV) nodal region were processed for histology and immunohistochemistry. Confocal microscopy was used to image the distribution of sodium channels using IgG (R12) developed against a highly conserved sequence in the interdomain 3-4 region of cloned sodium channels. 2. In ventricular and atrial cells, sodium channel immunofluorescence was localized to lateral membranes and T-tubules. In the open AV node, levels of sodium channel immunofluorescence in the transitional cell zone and in the lower nodal cell tract were comparable to that found in the atrial and ventricular myocardium. 3. In the enclosed AV node a gradation of sodium channel immunofluorescence is present such that peripherally located circumferential transitional cells display high levels of immunofluorescence, comparable to that of atrial and ventricular myocardium, while centrally located midnodal cells display decreased levels of or no immunofluorescence. 4. In order to correlate the distribution of sodium channels with the distribution of gap junctions, we used IgG directed against the carboxyl terminus of connexin43 (CT-360). Ventricular cell immunofluorescence was localized primarily to the intercalated disk region, while in the AV node, the pattern of distribution was found to be similar to that of sodium channels. 5. The reduced levels of and/or absence of immunofluorescence in the midnodal cell region indicates a paucity of sodium channel and connexin43 protein expression in this region of the AV node that would favour slow impulse conduction. C1 MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT ANAT & CELL BIOL,MONTREAL,PQ,CANADA. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. RI Laird, Dale /E-4176-2015 NR 33 TC 35 Z9 35 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN 1 PY 1997 VL 501 IS 2 BP 263 EP 274 DI 10.1111/j.1469-7793.1997.263bn.x PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XF545 UT WOS:A1997XF54500002 PM 9192299 ER PT J AU Richey, GK Gorp, WG AF Richey, GK Gorp, WG TI The impact of psychosocial variables on immune system functioning in a sample of HIV-positive males SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Meeting Abstract C1 PLYMOUTH STATE COLL,PLYMOUTH,DEVON,ENGLAND. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 1997 VL 19 IS 2 BP 179 EP 180 PG 2 WC Psychology, Clinical SC Psychology GA YL136 UT WOS:A1997YL13600015 ER PT J AU Moore, CA Fishman, IJ Hirshkowitz, M AF Moore, CA Fishman, IJ Hirshkowitz, M TI Evaluation of erectile dysfunction and sleep-related erections SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Review DE sleep; impotence; erections; erectile dysfunction; nocturnal penile tumescence ID NOCTURNAL PENILE TUMESCENCE; SMOOTH-MUSCLE CELLS; CORPUS CAVERNOSUM; NITRIC-OXIDE; MEN; TESTOSTERONE; RELAXATION; PREVALENCE; IMPOTENCE; DOGS AB Significant advances in this past decade have improved our understanding of erectile physiology. A variety of tests are available for diagnosing impotence, SRE testing provides objective physiological information that is useful for indexing erectile capability and formulating a rational treatment plan. As such, SRE testing is a powerful noninvasive tool for assessing dysfunction. Nonetheless, in making a final diagnosis, the skillful clinician relies on more than one assessment parameter and on clinical acumen. (C) 1997 Elsevier Science Inc. C1 BAYLOR COLL MED,HOUSTON,TX 77030. RP Moore, CA (reprint author), DEPT VET AFFAIRS MED CTR,SLEEP CTR 116A,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 33 TC 7 Z9 9 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 1997 VL 42 IS 6 BP 531 EP 539 DI 10.1016/S0022-3999(97)00014-7 PG 9 WC Psychiatry SC Psychiatry GA XE719 UT WOS:A1997XE71900004 PM 9226600 ER PT J AU Hirshkowitz, M Moore, CA OConnor, S Bellamy, M Cunningham, GR AF Hirshkowitz, M Moore, CA OConnor, S Bellamy, M Cunningham, GR TI Androgen and sleep-related erections SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE testosterone; sleep; erections ID NOCTURNAL PENILE TUMESCENCE; HYPOGONADAL MEN; PLASMA TESTOSTERONE; SERUM TESTOSTERONE; MEDROXYPROGESTERONE ACETATE; CIRCADIAN-RHYTHM; REPLACEMENT; BEHAVIOR; GONADOTROPIN; PROLACTIN AB Sleep-related penile erections provide a unique opportunity to objectively study erectile physiology in man. Testosterone is one of several factors involved in normal sexual function and testosterone reduction can be achieved by administering luteinizing-hormone releasing-hormone agonists (LHRH-A). In this study, ten healthy, young adult males were administered LHRH-A or placebo for a 12-week period. Subjects taking LHRH-A had a marginally significant decline in sleep-related erection duration at week 4 and significant reductions at weeks 8 and 12. By contrast, no statistically reliable change was found for the number of erections over the course of study. Maximum circumference increase during sleep erections showed mixed results. These results indicate that, whereas androgen reduction adversely affects sleep-related erections, it does not eliminate them over a 12-week trial in healthy young adult men. Further study in a larger sample is needed. Nonetheless, these preliminary findings support androgen having an important role in sleep-related erections. (C) 1997 Elsevier Science Inc. C1 BAYLOR COLL MED,HOUSTON,TX 77030. RP Hirshkowitz, M (reprint author), DEPT VET AFFAIRS MED CTR,SLEEP CTR 116A,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 20 TC 27 Z9 29 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 1997 VL 42 IS 6 BP 541 EP 546 DI 10.1016/S0022-3999(97)00006-8 PG 6 WC Psychiatry SC Psychiatry GA XE719 UT WOS:A1997XE71900005 PM 9226601 ER PT J AU Ellabban, A Schumacher, HR AF Ellabban, A Schumacher, HR TI Erythema elevatum diutinum with extensive acro-osteolysis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE erythema elevatum diutinum; acro-osteolysis; leukocytoclastic vasculitis ID PATIENT AB Erythema elevatum diutinum (EED) is a rare chronic skin disease with cutaneous vasculitis, characterized by the absence of systemic vasculopathy, We describe a 79-year-old white woman who has been followed with the diagnosis of EED for 27 years, Our patient has a previously unreported combination of EED and acro-osteolysis. After reviewing possible reasons for the association, her vasculitis seems the most likely factor. C1 DEPT VET AFFAIRS MED CTR,ARTHRIT IMMUNOL CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DIV RHEUMATOL,PHILADELPHIA,PA 19104. NR 9 TC 5 Z9 5 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 1997 VL 24 IS 6 BP 1203 EP 1205 PG 3 WC Rheumatology SC Rheumatology GA XD791 UT WOS:A1997XD79100033 PM 9195535 ER PT J AU Silverman, SL Cranney, A AF Silverman, SL Cranney, A TI Quality of life measurement in osteoporosis SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Conference on the Outcome Measures in Arthritis Clinical Trials (OMERACT III) CY APR 16-19, 1996 CL CAIRNS, AUSTRALIA DE osteoporosis; quality of life ID VERTEBRAL COMPRESSION FRACTURES; HEALTH-STATUS; OF-LIFE; FUNCTIONAL STATUS; QUESTIONNAIRE; INSTRUMENT; COMPLAINTS; ARTHRITIS; WOMEN AB Quality of life measurement may be helpful in randomized clinical trials in osteoporosis to assess therapeutic tradeoffs and compare effects of different interventions. Quality of life measures include generic measures, disease targeted measures, and performance based measures. Disease targeted measures increase the coverage of domains that are of particular importance to the patient with established osteoporosis. Several disease targeted measures are currently available. These measures show discriminant validity, but data on longitudinal responsiveness and validity in randomized clinical trials are not yet available. C1 OTTAWA GEN HOSP,OTTAWA,ON K1H 8L6,CANADA. RP Silverman, SL (reprint author), UNIV CALIF LOS ANGELES,DIV RHEUMATOL 111J,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073, USA. NR 29 TC 27 Z9 28 U1 2 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 1997 VL 24 IS 6 BP 1218 EP 1221 PG 4 WC Rheumatology SC Rheumatology GA XD791 UT WOS:A1997XD79100038 PM 9195540 ER PT J AU Caplan, D Waters, GS Hildebrandt, N AF Caplan, D Waters, GS Hildebrandt, N TI Determinants of sentence comprehension in aphasic patients in sentence-picture matching tasks SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE aphasia; syntactic comprehension; sentence-picture matching ID SYNTACTIC COMPREHENSION; ALZHEIMERS-DISEASE; WORKING-MEMORY; AGRAMMATIC COMPREHENSION; CAPACITY; DISORDERS; LANGUAGE; RECOVERY; BROCA AB The results of two studies of sentence comprehension in aphasic patients using sentence-picture matching tests are presented. In the first study, 52 aphasic patients were tested on 10 sentence types. Analysis of the number of correct responses per sentence type showed effects of syntactic complexity and number of propositions. Factor analysis yielded first factors that accounted For two-thirds of the variance in performance to which all sentence types contributed. Clustering analysis yielded groups of patients whose performances progressively deteriorated and in which performance was more affected by sentence types that were harder for the group overall. These results were very similar to those previously obtained using an enactment task. In the second study, 17 aphasic patients were tested on the some 10 sentence types using both sentence-picture matching and enactment tasks. Correlational analyses showed that performance on the two tests was significantly correlated across both subjects and sentences. The results provide data relevant to the determinants of the complexity of a sentence in auditory comprehension. C1 MCGILL UNIV,SCH COMMUN SCI & DISORDERS,MONTREAL,PQ,CANADA. RP Caplan, D (reprint author), MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,VINCENT BURNHAM 827,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00942] NR 48 TC 37 Z9 37 U1 2 U2 3 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD JUN PY 1997 VL 40 IS 3 BP 542 EP 555 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA XG790 UT WOS:A1997XG79000007 PM 9210113 ER PT J AU Shekelle, PG Coulter, I AF Shekelle, PG Coulter, I TI Cervical spine manipulation: Summary report of a systematic review of the literature and a multidisciplinary expert panel SO JOURNAL OF SPINAL DISORDERS LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; LOW-BACK-PAIN; NECK COMPLAINTS; MANUAL THERAPY; PHYSIOTHERAPY C1 W LOS ANGELES VET AFFAIRS MED CTR,SANTA MONICA,CA. NR 21 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0895-0385 J9 J SPINAL DISORD JI J. Spinal Disord. PD JUN PY 1997 VL 10 IS 3 BP 223 EP 228 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA XG955 UT WOS:A1997XG95500007 PM 9213278 ER PT J AU Pincus, D AF Pincus, D TI The dense linear ordering principle SO JOURNAL OF SYMBOLIC LOGIC LA English DT Article AB Let DO denote the principle: Every infinite set has a dense linear ordering. DO is compared to other ordering principles such as O, the Linear Ordering principle, KW, the Kinna-Wagner Principle, and PI, the Prime Ideal Theorem, in ZF, Zermelo-Fraenkel set theory without AC, the Axiom of Choice. The main result is: THEOREM. AC double right arrow KW double right arrow DO double right arrow O, and none of the implications is reversible in ZF + PI. The first and third implications and their irreversibilities were known. The middle one is new. Along the way other results of interest am established. O, while not quite implying DO, does imply that every set differs finitely from a densely ordered set. The independence result for ZF is reduced to one for Fraenkel-Mostowski models by showing that DO fails into two of the known classes of statements automatically transferable from Fraenkel-Mostowski to ZF models. Finally, rite proof of PI in the Fraenkel-Mostowski model leads naturally to versions of the Ramsey and Ehrenfeucht-Mostowski theorems involving sets that are both ordered and colored. RP Pincus, D (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CAMBRIDGE HOSP,SCH MED,DEPT ANESTHESIA,1493 CAMBRIDGE ST,CAMBRIDGE,MA 02139, USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU ASSN SYMBOLIC LOGIC INC PI CHAMPAIGN PA 1325 SOUTH OAK ST, CHAMPAIGN, IL 61820 SN 0022-4812 J9 J SYMBOLIC LOGIC JI J. Symb. Log. PD JUN PY 1997 VL 62 IS 2 BP 438 EP 456 DI 10.2307/2275540 PG 19 WC Mathematics; Logic SC Mathematics; Science & Technology - Other Topics GA XN940 UT WOS:A1997XN94000005 ER PT J AU Morrison, DA Sacks, J Barbiere, CC Sethi, G AF Morrison, DA Sacks, J Barbiere, CC Sethi, G TI PTCA comes to the bifurcations in the road: What the VA has to offer SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID TRANSLUMINAL CORONARY ANGIOPLASTY; ASSOCIATION TASK-FORCE; UNSTABLE ANGINA; BYPASS-SURGERY; FOLLOW-UP; HIGH-RISK; CARDIOLOGY; REVASCULARIZATION; GUIDELINES; SURVIVAL C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,COOPERAT STUDIES PROGRAM COORDINATING CTR,HINES,IL 60141. VET AFFAIRS MED CTR,TUCSON,AZ. RP Morrison, DA (reprint author), DENVER VET AFFAIRS MED CTR,CARDIOL SECT,1055 CLERMONT ST 111-B,DENVER,CO 80220, USA. NR 24 TC 3 Z9 3 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 JUN PY 1997 VL 29 IS 7 BP 1512 EP 1514 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XB643 UT WOS:A1997XB64300016 PM 9180112 ER PT J AU Flynn, MA Herbert, V Nolph, GB Krause, G AF Flynn, MA Herbert, V Nolph, GB Krause, G TI Atherogenesis and the homocysteine-folate-cobalamin triad: Do we need standardized analyses? SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE homocysteine; cobalamin; holotranscobalamin; folate; methionine ID CORONARY-ARTERY DISEASE; HOLO-TRANSCOBALAMIN-II; HOLOTRANSCOBALAMIN-II; PLASMA HOMOCYST(E)INE; ELDERLY POPULATION; ATROPHIC GASTRITIS; HEALTHY-SUBJECTS; SERUM; DEFICIENCY; VITAMIN-B-12 AB Background: Bioscientists, physicians and nutritionists are newly interested in the homocysteine-folate cobalamin triad, in part because homocysteine may be important both in atherogenesis and thrombogenesis. Homocysteine imbalance may be an early marker for cobalamin disorders because cobalamin is a cofactor in remethylation of homocysteine to methionine. Methods: In 139 men and 32 women of similar mean age of 65 years, we measured markers which have been cited as risk for atherosclerosis: serum homocysteine, folate, total cobalamin, holotranscobalamin I and II, (TCI and TCII), total serum cholesterol (SCHOL), high density lipoprotein cholesterol (HDLC), triglycerides (STG) as well as red blood cell (RBC) folate, food records and body composition by whole body counting of potassium-forty (K-40). Results: Statistical relationships among the data showed healthy women had lower mean serum homocysteine and their mean RBC folate and TCI and TCII were higher than men. Eighty-three subjects had TCII much lower than 60 pg/ml (subnormal), yet only 11 of these men and two women had total cobalamin <200 pg/ml (abnormal). Fifty-two subjects with serum homocysteine greater than 17.5 nmol/ml had TCII less than 60 pg/ml, suggesting serum homocysteine may be a marker for early cobalamin negative balance. None of the subjects in the study had serum folate below abnormal values, i.e., less than 1.6 mg/ml, All subjects had RBC folate within normal range. Serum homocysteine showed inverse relationship with RBC folate and serum total cobalamin, TCI and TCII. Conclusions: 1) importance of using serum holotranscobalamin TCI and TCII as markers of cobalamin deficiency, 2) necessity to use documented quantitative components of dietary intake if strong comparisons are to be made among quantitative values of serum or plasma homocysteine, folate, cobalamin, and nutrients in food intake. C1 MT SINAI VET AFFAIRS MED CTR,NEW YORK,NY. BRONX VET AFFAIRS MED CTR,NEW YORK,NY. RP Flynn, MA (reprint author), UNIV MISSOURI,HLTH SCI CTR,DEPT FAMILY & COMMUNITY MED,DEPT STAT,1 HOSP DR M221,COLUMBIA,MO 65212, USA. NR 54 TC 20 Z9 21 U1 0 U2 1 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 1997 VL 16 IS 3 BP 258 EP 267 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XB707 UT WOS:A1997XB70700012 PM 9176833 ER PT J AU Felsenfeld, AJ AF Felsenfeld, AJ TI Considerations for the treatment of secondary hyperparathyroidism in renal failure SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DIALYSATE CALCIUM-CONCENTRATION; PARATHYROID-HORMONE; INTRAVENOUS CALCITRIOL; HEMODIALYSIS-PATIENTS; UREMIC PATIENTS; BONE-DISEASE; PROSPECTIVE TRIAL; IONIZED CALCIUM; INTERMITTENT; HYPERPLASIA C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP Felsenfeld, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEPHROL SECT 111L,DEPT MED,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 48 TC 46 Z9 48 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 1997 VL 8 IS 6 BP 993 EP 1004 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA XD569 UT WOS:A1997XD56900018 PM 9189868 ER PT J AU Shah, A Laird, N Schoenfeld, D AF Shah, A Laird, N Schoenfeld, D TI A random-effects model for multiple characteristics with possibly missing data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE bivariate response; EM algorithm; longitudinal data; Mycobacterium Avium complex; random effects; restricted maximum likelihood estimates ID LONGITUDINAL DATA AB The use of random-effects models for the analysis of longitudinal data with missing responses has bean discussed by several authors. This article extends the random-effects model for a single characteristic to the case of multiple characteristics, allowing for arbitrary patterns of observed data. Two different structures for the covariance matrix of measurement error are considered: uncorrelated error between responses and correlation of error terms at the same measurement times. Parameters for this model are estimated via the EM algorithm. The set of equations for this estimation procedure is derived; these equations are appropriately modified to deal with missing data. The methodology is illustrated with an example from clinical trials. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Shah, A (reprint author), CLEVELAND CLIN FDN,DEPT BIOSTAT,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 10 TC 86 Z9 87 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 1997 VL 92 IS 438 BP 775 EP 779 DI 10.2307/2965726 PG 5 WC Statistics & Probability SC Mathematics GA XE296 UT WOS:A1997XE29600043 ER PT J AU Mahmood, Z Khan, AH Kasi, MM Mehmood, K Khan, AA Hoessli, DC RunggerBraendle, E Jeanloz, RW NasirudDin AF Mahmood, Z Khan, AH Kasi, MM Mehmood, K Khan, AA Hoessli, DC RunggerBraendle, E Jeanloz, RW NasirudDin TI Structural studies on sialylated oligosaccharides of bonnet monkey (Macaca radiata) luteal phase cervical mucus glycoprotein. SO JOURNAL OF THE CHEMICAL SOCIETY OF PAKISTAN LA English DT Article ID SECRETION; GEL AB Mucin glycoproteins were purified and fractionated from cervical epithelial secretion in luteal phase of the bonnet monkey (Macaca radiata). Polyclonal antibody against the purified luteal phase glycoprotein ness reacted with crude luteal phase mucus as well as weakly with ovulatory phase mucus and purified midcycle glycoproteins, thus suggesting some common epitopes in the ovulatory and luteal phase glycoproteins. Alkaline borohydride cleavage of a purified glycoprotein resulted in a mixture of acidic and neutral oligosaccharide alditols. Utilizing high performance chromatography, six oligosaccharide fractions (b-1 to b-6) have been purified from the sialylated oligosaccharide fraction b. Based on the results of enzymic and chemical studies, following structures are proposed for these oligosaccharides that bear similarities with those of the midcycle oligosaccharide structures. C1 UNIV BALUCHISTAN,INST BIOCHEM,QUETTA,PAKISTAN. UNIV GENEVA,CTR MED,DEPT PATHOL,CH-1211 GENEVA,SWITZERLAND. MASSACHUSETTS GEN HOSP,LAB CARBOHYDRATE RES,BOSTON,MA 02114. GOVT SCI COLL,QUETTA,PAKISTAN. NR 30 TC 0 Z9 0 U1 0 U2 0 PU CHEM SOC PAKISTAN PI KARACHI PA HEJ RES INST CHEM UNIV KARACHI, 75270 KARACHI, PAKISTAN SN 0253-5106 J9 J CHEM SOC PAKISTAN JI J. Chem. Soc. Pak. PD JUN PY 1997 VL 19 IS 2 BP 162 EP 171 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA YE190 UT WOS:A1997YE19000016 ER PT J AU Clark, DE Ryan, LM AF Clark, DE Ryan, LM TI Modeling injury outcomes using time-to-event methods SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE trauma; length of stay; proportional hazards model; outcome prediction ID TRAUMA PATIENTS; HEAD-INJURY; LENGTH; STAY; SEVERITY; SCORE; COMA; RISK AB Background: Mortality is an important measurement of injury outcomes, but measurements reflecting disability or cost also important, Hospital length of stay (LOS) has been used as an outcome variable, but reduced LOS could be achieved either by improved care or by increased mortality, A solution to this statistical problem of ''competing risks'' would enable injury outcomes based on LOS to be modeled using time-to-event methods, Methods: Time-to-event methodology was applied to 2,106 cases with complete data from the 1991-1994 registry of a regional trauma center. LOS was used as the outcome variable, modified by assigning an arbitrarily long LOS to any fatal case, A combination of proportional hazards and logistic regression models was used to explore the effects of potential predictive variables, including Trauma Score (TS), Injury Severity Score (ISS), components of TS or ISS, age, sex, alcohol use, and whether a patient was transferred. Results: The ''TRISS'' combination of TS, ISS, and age previously shown to predict mortality also predicted ''modified LOS'' (Wald p value less than 0.001 for each variable). Models using only age and certain components of ISS or TS fit our data even better, with fewer parameters, Other variables were not predictive, Modified Kapian-Meier plots provided easily interpreted graphical results, combining both mortality and LOS information. Conclusions: With a simple modification to allow for competing risks, time-to-event methods enable more informative modeling of injury outcomes than binary (lived/died) methods alone, Such models may be useful for describing and comparing groups of hospitalized trauma patients. C1 MAINE MED CTR,DEPT SURG,PORTLAND,ME 04102. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 27 TC 9 Z9 9 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 JUN PY 1997 VL 42 IS 6 BP 1129 EP 1134 DI 10.1097/00005373-199706000-00025 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA XH700 UT WOS:A1997XH70000032 PM 9210554 ER PT J AU Barry, MJ AF Barry, MJ TI The American Urological Association symptom index for benign prostatic hyperplasia as a function of age, volume and ultrasonic appearance of the prostate - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material RP Barry, MJ (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1997 VL 157 IS 6 BP 2165 EP 2165 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA WY050 UT WOS:A1997WY05000036 ER PT J AU Stampfer, DS AF Stampfer, DS TI Free intraperitoneal rupture of hydronephrotic kidney SO JOURNAL OF UROLOGY LA English DT Article DE hydronephrosis; kidney; wounds and injuries; rupture RP Stampfer, DS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1997 VL 157 IS 6 BP 2242 EP 2243 DI 10.1016/S0022-5347(01)64731-1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA WY050 UT WOS:A1997WY05000064 PM 9146628 ER PT J AU vanEps, RGS LaMuraglia, GM AF vanEps, RGS LaMuraglia, GM TI Photodynamic therapy inhibits transforming growth factor beta activity associated with vascular smooth muscle cell injury SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 26-27, 1996 CL DIXVILLE NOTCH, NH SP New England Soc Vasc Surg ID EXPERIMENTAL INTIMAL HYPERPLASIA; ENDOTHELIAL-CELLS; RAT MODEL; FACTOR-BETA-1; PROLIFERATION; ARTERIES; GENE; EXPRESSION; DISEASE; REPAIR AB Purpose: The multifunctional cytokine, transforming growth factor beta 1 (TGF-beta), plays an important role in the development of injury-associated intimal hyperplasia (IH). Strategies to suppress local TGF-beta activity may have a clinical potential to prevent restenosis caused by IH. Photodynamic therapy (PDT) involves the local generation of cytotoxic free radicals by light activation of photosensitizer dyes and has been shown to inhibit experimental IH. This study investigated whether PDT-generated free radicals can affect TGF-beta activity in a biologic system using vascular smooth muscle cells (SMCs). Methods: The release and activation of TGF-beta by injured SMCs in culture was compared between mechanical injury and PDT. Mechanical injury was induced with a rubber policeman, and PDT was performed with the photosensitizer chloroaluminum sulfonated phthalocyanine (5 mu g/ml) and 675 nm laser light at subtherapeutic 10 J/cm(2) and the in vivo therapeutic dose of 100 J/cm(2). Cell viability was assessed by the tetrazolium salt conversion assay, and active and total (active + latent) TGP-beta was determined by enzyme-linked immunosorbent assay in the conditioned media of SMCs 24 hours after treatment. Functional TGF-beta activity was assessed by inhibition of endothelial cell mitogenesis. Results: Both forms of injury severely reduced (p < 0.0005) SMC viability to less than 15%. In untreated SMC conditioned media, only 14.5% of the total TGF-beta was active (27.7 +/- 8.7 pg per 1 x 10(5) cells). However, after mechanical injury and PDT with 10 J/cm(2), there was a significant increase (p < 0.02) in active TGF-beta (60.1 +/- 10.1 pg and 48.6 +/- 21.0 pg, respectively), despite a total reduction of approximately 50%. In contrast to this result, PDT with 100 J/cm(2) did not result in increased levels of active TGF-beta (8.1 +/- 3.5 pg), despite having similar levels of total TGF-beta. Consequently, the conditioned media of SMCs that had 100 J/cm(2) PDT did not inhibit endothelial cell mitogenesis as compared with the conditioned media of SMCs with mechanical injury and 10 J/cm(2) PDT (p < 0.0002). Conclusions: This report describes two novel findings: (1) injury to SMCs in vitro induces the conversion of biologically latent TGF-beta to active TGF-beta; and (2) the therapeutic PDT dose interferes with this injury activation process. This study substantiates the concept of local cytokine inhibition by PDT in a biologic system and provides new insights into the mechanisms of PDT-mediated inhibition of experimental IH. C1 HARVARD UNIV,DIV VASC SURG,GEN SURG SERV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,WELLMAN LABS PHOTOMED,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 40 TC 20 Z9 20 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1997 VL 25 IS 6 BP 1044 EP 1053 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA XG440 UT WOS:A1997XG44000010 ER PT J AU Karlsson, GB Halloran, M Li, J Park, IW Gomila, R Reimann, KA Axthelm, MK Iliff, SA Letvin, NL Sodroski, J AF Karlsson, GB Halloran, M Li, J Park, IW Gomila, R Reimann, KA Axthelm, MK Iliff, SA Letvin, NL Sodroski, J TI Characterization of molecularly cloned simian human immunodeficiency viruses causing rapid CD4(+) lymphocyte depletion in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL; PERSISTENT INFECTION; ENVELOPE GLYCOPROTEINS; MACAQUE MONKEYS; TYPE-1; MACROPHAGE; HIV-1 AB In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV-89.6) expressing the human immunodeficiency virus type 1 (HIV-1) tat, rev, vpu, and env genes generated pathogenic viruses (SHIV-89.6P) inducing rapid CD4(+) lymphocyte depletion and AIDS-like illness in rhesus monkeys iii, Reimann, J. T. Li, R. Veazey, M. Halloran, L.-W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin, J. Virol, 70:6922-6928, 1996). To characterize the molecular changes responsible for this increase in virulence, infectious proviral clones of SHIV-89.6P isolates were derived. Viruses generated from some of these clones caused a rapid and profound decline of CD4(+) lymphocytes in a high percentage of inoculated monkeys. Nucleotide changes potentially responsible for the increased virulence of SHIV-89.6P were limited to the env, tat, or long terminal repeat sequences, with most of the observed changes in env. Nucleotide changes in env altered 12 amino acids in the gp120 and gp41 exterior domains, and a 140-bp deletion in env resulted in the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for that of the HIV-1 gp41 glycoprotein. The availability of pathogenic proviral clones should facilitate dissection of the molecular determinants of SHIV-89.6P virulence. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BETH ISRAEL DEACONESS MED CTR,DIV VIRAL PATHOGENESIS,BOSTON,MA 02215. OREGON REG PRIMATE RES CTR,BEAVERTON,OR 97006. FU NCI NIH HHS [CA-50139]; NIAID NIH HHS [AI-20729, AI-33832] NR 21 TC 169 Z9 169 U1 1 U2 7 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 JUN PY 1997 VL 71 IS 6 BP 4218 EP 4225 PG 8 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100005 PM 9151808 ER PT J AU Rizzuto, CD Sodroski, JG AF Rizzuto, CD Sodroski, JG TI Contribution of virion ICAM-1 to human immunodeficiency virus infectivity and sensitivity to neutralization SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 ENVELOPE GLYCOPROTEIN; MATRIX PROTEIN; SYNCYTIUM FORMATION; ADHESION MOLECULES; MEMBRANE-PROTEINS; RECEPTOR; HIV-1; CELLS; LFA-1; ASSOCIATION AB Incorporation of the intercellular adhesion molecule ICAM-1 into human immunodeficiency virus type 1 (HIV-1) particles increased virus infectivity on peripheral blood mononuclear cells (PBMCs) by two- to sevenfold. The degree of ICAM-1-mediated enhancement was greater for viruses bearing envelope glycoproteins derived from primary HIV-1 isolates than for those bearing envelope glycoproteins from laboratory adapted strains. Treatment of target PBMCs with an antibody against LFA-1, a principal ICAM-1 receptor, was able to nullify the ICAM-1-mediated enhancement. The incorporation of ICAM-1 rendered HIV-1 virions less susceptible to neutralization by a monoclonal antibody directed against the viral envelope glycoproteins. Surprisingly, an antibody against ICAM-1 completely neutralized infection by ICAM-1-containing viruses, reducing the efficiency of virus entry by almost 100-fold. Thus, HIV-1 neutralization by an ICAM-1-directed antibody involves more than an inhibition of the contribution of ICAM-1 to virus entry. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 01225. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 06516]; NIAID NIH HHS [AI 24755] NR 49 TC 109 Z9 109 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 JUN PY 1997 VL 71 IS 6 BP 4847 EP 4851 PG 5 WC Virology SC Virology GA WZ571 UT WOS:A1997WZ57100081 PM 9151884 ER PT J AU Geissler, M Wands, G Gesien, A delaMonte, S Bellet, D Wands, JR AF Geissler, M Wands, G Gesien, A delaMonte, S Bellet, D Wands, JR TI Genetic immunization with the free human chorionic gonadotropin beta subunit elicits cytotoxic T lymphocyte responses and protects against tumor formation in mice SO LABORATORY INVESTIGATION LA English DT Article ID IMMUNE-RESPONSE; IN-VIVO; EXPRESSION; CANCER; CELLS; HCG; ANTIGEN; SECRETION; PEPTIDE; SELF AB The free beta subunit of human chorionic gonadotropin (hCG beta) is produced and secreted by human lung, bladder, and pancreatic tumors. We attempted to generate cytotoxic T lymphocytes (CTL) with activity against free hCG beta-producing tumors by genetic immunization using a construct containing a beta subunit expressing cDNA. To assess CTL activity in vivo, a cloned syngeneic SP2/O myeloma cell line was established that constitutively expresses the free hCG beta protein. Inoculation of this cell line into BALB/c mice produced large tumors within 2 weeks. However, mice immunized with the free hCG beta expression construct demonstrated a marked reduction of tumor size and weight compared with animals immunized with mock DNA (''empty'' plasmid). Indeed, 30% of immunized mice were tumor-free after 3 months and thus considered long-term survivors. Inhibition of tumor growth was strongly associated with the level of CTL activity present in CD8(+) cells derived from the spleen. In addition, immunized mice developed high titer anti-hCG beta antibodies that neutralized the biologic effects of the intact hCG glycoprotein hormone on its cellular receptor as well. These results illustrate that substantial cellular and humoral immune responses to the free hCG beta subunit may be generated by DNA immunization. This study thus presents a potential approach to inhibiting growth of human tumor cells that produce and secrete the free hCG beta protein. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOL HEPATOL LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,CHARLESTOWN,MA. ARES ADV TECHNOL INC,RANDOLPH,MA. FAC SCI PHARMACEUT & BIOL PARIS,LAB IMMUNOL TUMEURS,URA,PARIS,FRANCE. INST GUSTAVE ROUSSY,SERV BIOL ONCOL,VILLEJUIF,FRANCE. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 43 TC 33 Z9 36 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 JUN PY 1997 VL 76 IS 6 BP 859 EP 871 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA XE883 UT WOS:A1997XE88300011 PM 9194861 ER PT J AU Kelly, K AF Kelly, K TI Lost futures: Our forgotten children - Grossfeld,S SO LIBRARY JOURNAL LA English DT Book Review RP Kelly, K (reprint author), MASSACHUSETTS GEN HOSP,TREADWELL LIB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 1 PY 1997 VL 122 IS 10 BP 122 EP 122 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA XC735 UT WOS:A1997XC73500137 ER PT J AU Perry, MC Deslauriers, J Albain, KS Choi, NC Depierre, A Johnston, MR Lacquet, LK Payne, DG Putnam, JB Sculier, JP Shepherd, FA AF Perry, MC Deslauriers, J Albain, KS Choi, NC Depierre, A Johnston, MR Lacquet, LK Payne, DG Putnam, JB Sculier, JP Shepherd, FA TI Induction treatment for resectable non-small-cell lung cancer SO LUNG CANCER LA English DT Article; Proceedings Paper CT 4th IASLC Workshop on Controversies in Staging and Combined Treatment Modalities in Lung Cancer CY JUN 23-27, 1996 CL BRUGGE, BELGIUM SP Int Assoc Study Lung Canc ID RANDOMIZED TRIAL; CHEMOTHERAPY; SURGERY C1 HOP LAVAL,QUEBEC CITY,PQ,CANADA. LOYALA UNIV,CTR MED,MAYWOOD,IL. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CHR BESANCON,BESANCON,FRANCE. MT SINAI HOSP,TORONTO,ON M5G 1X5,CANADA. UNIV NIJMEGEN ST RADBOUD HOSP,NL-6500 HB NIJMEGEN,NETHERLANDS. ONTARIO CANC INST,TORONTO,ON M4X 1K9,CANADA. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. INST JULES BORDET,B-1000 BRUSSELS,BELGIUM. TORONTO GEN HOSP,TORONTO,ON,CANADA. RP Perry, MC (reprint author), UNIV MISSOURI ELLIS FISCHEL,COLUMBIA,MO, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUN PY 1997 VL 17 SU 1 BP S15 EP S18 DI 10.1016/S0169-5002(97)00038-X PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA XG146 UT WOS:A1997XG14600004 PM 9213297 ER PT J AU Mandeville, JB Moore, J Chesler, DA Garrido, L Weissleder, R Weisskoff, RM AF Mandeville, JB Moore, J Chesler, DA Garrido, L Weissleder, R Weisskoff, RM TI Dynamic liver imaging with iron oxide agents: Effects of size and biodistribution on contrast SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; contrast agents; iron oxide; liver ID TRANSVERSE RELAXATION; NANOPARTICLES; HEPATOCYTES; PARTICLES; MION; MRI; RAT AB In vivo effective relaxation rates in normal rat liver were evaluated for four dextran coated iron oxide agents: monocrystalline iron oxide nanocolloid (MION) with a mean particle diameter of 3.9 nm, a polycrystalline agent (PION) with a larger mean diameter of 12 nm, and these two agents labeled with the asialofetuin (ASF) protein for high hepatocytic receptor binding affinity (MION-ASF and PION-ASF), Using echo planar imaging at 2 Tesla, dose response was measured with high temporal resolution for 3 h after injection of agent, and by comparing with relaxivities in vitro and in brain, dominant in vivo contrast phenomena were elucidated, While transverse relaxivity for PION-ASF exceeded that for MION-ASF by almost a factor of 2 in solution, relaxation rates in vivo became equivalent. Liver relaxation using non-ASF agents was consistent with rapid water exchange between vascular and extravascular compartments, which dominated relaxation as a result of agent accumulation in Kupffer cells. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR MOL IMAGING RES,BOSTON,MA 02114. RP Mandeville, JB (reprint author), MASSACHUSETTS GEN HOSP,NMR CTR,BLDG 149,ROOM 2301,13TH ST,CHARLESTOWN,MA 02129, USA. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 FU NCI NIH HHS [P01 CA48729, 2T32CA09362-14, SR01 CA59648-04] NR 26 TC 39 Z9 40 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1997 VL 37 IS 6 BP 885 EP 890 DI 10.1002/mrm.1910370613 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XB900 UT WOS:A1997XB90000012 PM 9178240 ER PT J AU Barnett, PG AF Barnett, PG TI Research without billing data - Econometric estimation of patient-specific costs SO MEDICAL CARE LA English DT Article DE hospital cost; long-term care cost; psychiatric care cost; ambulatory care cost; US Department of Veterans Affairs ID HOSPITAL COST AB OBJECTIVES. This article describes a method for computing the cost of care provided to individual patients in health care systems that do not routinely generate billing data, but gather information on patient utilization and total facility costs. METHODS. Aggregate data on cost and utilization were used to estimate how costs vary with characteristics of patients and facilities of the US Department of Veterans Affairs. A set of cost functions was estimated, taking advantage of the department-level organization of the data. Casemix measures were used to determine the costs of acute hospital and long-term care. RESULTS. Hospitalization for medical conditions cost an average of $5,642 per US Health Care Financing Administration diagnosis-related group weight; surgical hospitalizations cost $11,836. Nursing home care cost $197.33 per day, intermediate care cost $280.66 per day, psychiatric care cost $307.33 per day, and domiciliary care cost $111.84 per day. Outpatient visits cost an average of $90.36. These estimates include the cost of physician services. CONCLUSIONS. The econometric method presented here accounts for variation in resource use caused by casemix that is not reflected in length of stay and for the effects of medical education, research, facility size, and wage rates. Data on non-Veteran's Affairs hospital stays suggest that the method accounts for 40% of the variation in acute hospital care costs and is superior to cost estimates based on length of stay or diagnosis-related group weight alone. C1 US DEPT VET AFFAIRS,CTR COOPERAT STUDIES HLTH SERV,MENLO PK,CA. US DEPT VET AFFAIRS,HLTH SERV RES & DEV FIELD PROGRAM,MENLO PK,CA. STANFORD UNIV,DEPT HLTH RES & POLICY,STANFORD,CA 94305. NR 6 TC 18 Z9 18 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 JUN PY 1997 VL 35 IS 6 BP 553 EP 563 DI 10.1097/00005650-199706000-00002 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XD644 UT WOS:A1997XD64400002 PM 9191701 ER PT J AU Geraci, JM Ashton, CM Kuykendall, DH Johnson, ML Wu, L AF Geraci, JM Ashton, CM Kuykendall, DH Johnson, ML Wu, L TI International Classification of Diseases, 9th Revision, Clinical Modification codes in discharge abstracts are poor measures of complication occurrence in medical inpatients SO MEDICAL CARE LA English DT Article DE ICD-9-CM; administrative data bases; adverse events; complications ID ADMINISTRATIVE DATA; IDENTIFYING COMPLICATIONS; NOSOCOMIAL INFECTIONS; QUALITY ASSESSMENT; OUTCOMES RESEARCH; CARE; HOSPITALS; CLAIMS; SYSTEM; REIMBURSEMENT AB OBJECTIVES. The authors tested the ability of international Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes in discharge abstracts to identify medical inpatients who experienced an in-hospital complication, using complications identified through chart review as the gold standard. METHODS. TWO sets of ICD-9-CM codes were used: an inclusive set including many medical diagnoses that may also be coexistent complicating conditions on admission rather than complications and an exclusive set consisting primarily of ICD-9-CM-specified complication and adverse drug event codes. RESULTS. Neither set performed well as a diagnostic test for complication occurrence according to receiver operating characteristic analysis (ROC areas were 0.61 for the inclusive set and 0.55 for the exclusive set). Sensitivities of the ICD-9-CM codes for complications were 0.34 for the inclusive set and 0.14 for the exclusive set. Corresponding positive predictive values were 0.32 and 0.37, respectively. Sensitivities of code definitions for individual complications were generally poor, less than 0.5 in most cases. CONCLUSIONS. The authors conclude that ICD-9-CM codes in discharge abstracts are poor measures of complication occurrence. RP Geraci, JM (reprint author), BAYLOR COLL MED,DEPT MED,HOUSTON VET AFFAIRS MED CTR,MED SERV 3C,HOUSTON,TX 77030, USA. NR 28 TC 54 Z9 56 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 1997 VL 35 IS 6 BP 589 EP 602 DI 10.1097/00005650-199706000-00005 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XD644 UT WOS:A1997XD64400005 PM 9191704 ER PT J AU Lane, AM Egan, KM Yang, J Saornil, MA Alroy, J Albert, D Gragoudas, ES AF Lane, AM Egan, KM Yang, J Saornil, MA Alroy, J Albert, D Gragoudas, ES TI An evaluation of tumour vascularity as a prognostic indicator in uveal melanoma SO MELANOMA RESEARCH LA English DT Article DE neoplasm metastasis; neovascularization; uveal neoplasms ID INVASIVE BREAST-CARCINOMA; CUTANEOUS MELANOMA; MALIGNANT MELANOMAS; MELANOCYTIC NEVI; ANGIOGENESIS; MM; PROGRESSION; METASTASIS; THICKNESS; VESSELS AB Experimental and clinical evidence suggests that tumour angiogenesis plays a role in the tendency for certain neoplasms, including cutaneous melanomas, to metastasize. We evaluated whether tumour vasculature is associated with the rate of metastases in patients with melanoma of the choroid or ciliary body. The study was based on a group of 63 patients enucleated between 1976 and 1984 with paraffin-embedded tissue blocks available for sectioning and with known survival status as of December 1988. Vessel endothelial cells were highlighted with Ulex europaeus agglutinin I (UEA-I) conjugated with peroxidase. UEA-I-stained microvessels were counted at varying levels in the tumour (apex, centre and base) without knowledge of patient outcome. Patients with (n = 30) and without (n = 33) metastases had similar total vessel counts (P = 0.31). There was no evidence of greater vessel density in tumours that had metastasized, by level within the tumour. Similar results were obtained in multivariate analyses. Findings of this study suggest that tumour microvessel density is unrelated to patient survival in uveal melanoma. C1 MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OCULAR IMMUNOL,BOSTON,MA 02114. UNIV VALLADOLID,DEPT OPHTHALMOL,VALLADOLID,SPAIN. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED & VET MED,DEPT PATHOL,BOSTON,MA 02111. UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,MADISON,WI. FU NEI NIH HHS [EY01917] NR 23 TC 25 Z9 25 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD JUN PY 1997 VL 7 IS 3 BP 237 EP 242 DI 10.1097/00008390-199706000-00008 PG 6 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA XE086 UT WOS:A1997XE08600008 PM 9195563 ER PT J AU Qu, ZS Chow, JC Ling, PR Ziegler, TR Bistrian, BR Smith, RJ AF Qu, ZS Chow, JC Ling, PR Ziegler, TR Bistrian, BR Smith, RJ TI Tissue-specific effects of chronic dietary protein restriction and gastrostomy on the insulin-like growth factor-I pathway in the liver and colon of adult rats SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID IGF-BINDING-PROTEINS; GENERAL MEDICAL PATIENTS; DIFFERENTIAL REGULATION; SOMATOMEDIN ACTIVITY; NUTRITIONAL SUPPORT; BIOLOGICAL ACTIONS; SERUM; MALNUTRITION; RECEPTORS; HORMONE AB Dietary protein restriction decreases plasma concentrations of insulin-like growth factor-I (IGF-I) and reduces IGF-I mRNA levels in the liver, In addition to the actions of systemic IGF-I, locally produced IGF-I is thought to mediate autocrine and paracrine growth effects in the colon, The objectives of the present study were to investigate the IGF-I pathway in the colon and liver of adult rats under conditions of dietary protein restriction, surgical stress, and dietary protein repletion. Two groups of rats were placed on either a 20% or 2% casein diet for 19 days, Two additional groups of rats underwent gastrostomy after a 2% casein diet for 2 weeks, and then were either kept on the 2% casein diet or changed to a 20% casein diet until day 19. Dietary protein restriction reduced plasma concentrations of IGF-I and IGF-binding proteins (IGFBPs) and hepatic IGF-I mRNA content, while increasing colonic IGF-I receptor mRNA, Gastrostomy in protein-depleted animals had no effect on hepatic IGF-I mRNA, but led to a marked increase in colonic IGF-I mRNA levels. Dietary protein repletion resulted in a decrease in colonic IGF-I receptor mRNA. The distinct effects of dietary protein depletion and operative stress on the IGF pathway in the colon as compared with the liver may serve to maintain the level of IGF-I signaling in the colon by autocrine or paracrine mechanisms under these conditions. Copyright (C) 1997 by W.B. Saunders Company. C1 JOSLIN DIABET CTR,METAB SECT,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,SCH MED,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL MED CTR,DEPT MED,SCH MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK48503, DK45750, DK31933] NR 51 TC 5 Z9 5 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 JUN PY 1997 VL 46 IS 6 BP 691 EP 697 DI 10.1016/S0026-0495(97)90015-9 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XC873 UT WOS:A1997XC87300016 PM 9186307 ER PT J AU Corbett, AH Silver, PA AF Corbett, AH Silver, PA TI Nucleocytoplasmic transport of macromolecules SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID NUCLEAR-PORE COMPLEX; GUANINE-NUCLEOTIDE EXCHANGE; MESSENGER-RNA TRANSPORT; GTPASE-ACTIVATING PROTEIN; AMINO-ACID MOTIF; SACCHAROMYCES-CEREVISIAE; BINDING-PROTEIN; HIV-1 REV; POLY(A)(+) RNA; CHROMOSOME CONDENSATION AB Nucleocytoplasmic transport is a complex process that consists of the movement of numerous macromolecules back and forth across the nuclear envelope. All macromolecules that move in and out of the nucleus do so via nuclear pore complexes that fern? large proteinaceous channels in the nuclear envelope. In addition to nuclear-pores, nuclear transport of macromolecules requires a number of soluble factors that are found both in the cytoplasm and in the nucleus. A combination of biochemical, genetic, and cell biological approaches have been used to identify and characterize the various components of the nuclear transport machinery. Recent studies have shown that both import to and export from the nucleus are mediated by signals found within the transport substrates. Several studies have demonstrated that these signals are recognized by soluble factors that target these substrates to the nuclear pore. Once substrates have been directed to the pore, most transport events depend on a cycle of GTP hydrolysis mediated by the small Ras-like GTPase, Ran as well as other proteins that regulate the guanine nucleotide-bound state of Ran. Many of the essential factors have been identified, and the challenge that remains is to determine the exact mechanism by which transport occurs. This review attempts to present an integrated view of our current understanding of nuclear transport while highlighting the contributions that have been made through studies with genetic organisms such as the budding yeast, Saccharomyces cerevisiae. 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 281 TC 165 Z9 167 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD JUN PY 1997 VL 61 IS 2 BP 193 EP & PG 20 WC Microbiology SC Microbiology GA XN207 UT WOS:A1997XN20700004 PM 9184010 ER PT J AU Ruffolo, EF Koerner, FC Maluf, HM AF Ruffolo, EF Koerner, FC Maluf, HM TI Metaplastic carcinoma of the breast with melanocytic differentiation SO MODERN PATHOLOGY LA English DT Article DE breast; melanocytic differentiation; melanoma; metaplastic carcinoma ID MALIGNANT-MELANOMA AB We report the clinical and pathologic findings of a metaplastic carcinoma of the breast that exhibited melanocytic differentiation, The tumor possessed both in situ and invasive components. Lower grade regions of the infiltrating carcinoma had features of tubular, mucinous, and matrix-producing carcinomas. In the higher grade areas, conventional poorly differentiated ductal carcinoma merged with an anaplastic neoplasm that looked like malignant melanoma The nonpigmented cells stained for keratin but lacked HMB-45 and S-100 proteins, whereas the cells containing melanin showed the opposite characteristics. Electron microscopic examination disclosed melanosomes in the neoplastic cells. We believe that these observations convincingly establish both the origin of the tumor from the mammary epithelium and the synthesis of melanin by the tumor cells. We propose the diagnosis of metaplastic carcinoma with melanocytic differentiation for this neoplasm and suggest that the phenomenon of melanocytic metaplasia might underlie the formation of primary melanomas of the breast. C1 VET ADM MED CTR,DEPT PATHOL,MEMPHIS,TN 38104. RP Ruffolo, EF (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 24 Z9 24 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 JUN PY 1997 VL 10 IS 6 BP 592 EP 596 PG 5 WC Pathology SC Pathology GA XE334 UT WOS:A1997XE33400012 PM 9195577 ER PT J AU Jaster, R Zhu, Y Pless, M Bhattacharya, S MatheyPrevot, B DAndrea, AD AF Jaster, R Zhu, Y Pless, M Bhattacharya, S MatheyPrevot, B DAndrea, AD TI JAK2 is required for induction of the murine DUB-1 gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; ERYTHROPOIETIN RECEPTOR; BETA-SUBUNIT; ACTIVATION; KINASE; INTERLEUKIN-3; EXPRESSION; UBIQUITIN; PROTEIN; GROWTH AB Cytokine receptors activate multiple signal transduction pathways, resulting in the induction of specific target genes. We have recently identified a hematopoietic cell-specific immediate-early gene, DUE-I, that encodes a growth-regulatory deubiquitinating enzyme. The DUE-I gene contains: a 112-bp enhancer element that is specifically induced by the beta c subunit of the interleukin-3 (IL-3) receptor. To investigate the mechanism of DUE-I induction, we examined the effects of dominant-negative forms of JAK kinases, STAT transcription factors, and Raf-l in transient transfection assays. In Ba/F3 cells, IL-3 induced a dose-dependent activation of DUB-I-luciferase (luc) and GAS-luc reporter constructs. A dominant-negative form of JAK2 (truncated at amino acid 829) inhibited the induction of DUB-1-luc and GAS-luc by IL-3. A dominant-negative form of STAT5 (truncated at amino acid 650) inhibited the induction of GAS-luc but not DUB-1-luc. A dominant-negative form of Raf-l inhibited the induction of DUB-1-luc but had no effect on the induction of GAS-luc by IL-3. The requirement for JAK2 in the stimulation of the DUE-I enhancer was further supported by the suppression of DUB-1 induction in Ba/F3 cells stably expressing the dominant-negative JAK2 polypeptide. We hypothesize that IL-3 activates a JAK2/Raf-1 signaling pathway that is required for DUE-I induction and is independent of STAT5. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. RI Bhattacharya, Shoumo/F-4127-2010 FU NIDDK NIH HHS [R01 DK 43889-01] NR 56 TC 36 Z9 36 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 JUN PY 1997 VL 17 IS 6 BP 3364 EP 3372 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WZ637 UT WOS:A1997WZ63700041 PM 9154835 ER PT J AU Passani, LA Vonsattel, JPG Carter, RE Coyle, JT AF Passani, LA Vonsattel, JPG Carter, RE Coyle, JT TI N-acetylaspartylglutamate, N-acetylaspartate, and N-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer diseases SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE Alzheimer disease; Huntington disease; N-acetylaspartylglutamate; N-acetylaspartate; N-acetylated alpha-linked acidic dipeptidase; amino acids; striatum; amygdala; hippocampus; glia ID NUCLEAR-MAGNETIC-RESONANCE; ASPARTYL-L-GLUTAMATE; RAT-BRAIN; PYRAMIDAL NEURONS; NEUROFIBRILLARY TANGLES; RETINAL NEURONS; AMINO-ACIDS; SPINAL-CORD; RELEASE; CORTEX AB There is mounting evidence, primarily from research in experimental animals, that the dipeptide N-acetylaspartylglutamate (NAAG) and its catabolic enzyme, N-acetylated alpha-linked acid dipeptidase (NAALADase), are involved in glutamatergic neurotransmission. Previous studies in neuropsychiatric disorders associated with the dysregulation of glutamatergic neurotransmission, such as schizophrenia, seizure disorders, and amyotrophic lateral sclerosis (ALS), have revealed. region-specific alterations in the levels of NAAG and in the activity of NAALADase. To establish better the cellular localization of these and related parameters in human brain, we have examined their alterations in two well-characterized selective neurodegenerative disorders, Huntington Disease (HD) and Alzheimer Disease (AD). Brain regions from postmortem controls and HD-or AD-affected individuals were assayed to determine the activity of NAALADase as well as the levels of NAAG, N-acetylaspartate (NAA), and several amino acids. The relationships between changes in these neurochemical parameters and changes in neuronal and glial cell density were determined. The present report demonstrates that the decreases in the levels of NAAG and NAA and in the activity of NAALADase in AD and HD brain correlate primarily with neuronal loss. BY inference, the results suggest that NAAG and NAA have primarily a neuronal localization in human brain and that there is a close relationship between NAAG and the dipeptidase NAALADase in populations of affected neurons. C1 MASSACHUSETTS GEN HOSP,LAB MOL & DEV NEUROSCI,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,LAB MOL NEUROPATHOL,CHARLESTOWN,MA. HARVARD UNIV,MCLEAN HOSP,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BELMONT,MA 02178. FU NIMH NIH HHS [MH/NS 31862, MH-572901] NR 67 TC 47 Z9 48 U1 2 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD JUN PY 1997 VL 31 IS 2 BP 97 EP 118 DI 10.1007/BF02815236 PG 22 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XT683 UT WOS:A1997XT68300001 PM 9376025 ER PT J AU Nagy, AK Walton, NY Treiman, DM AF Nagy, AK Walton, NY Treiman, DM TI Reduced cortical ecto-ATPase activity in rat brains during prolonged status epilepticus induced by sequential administration of lithium and pilocarpine SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE ecto-ATPase; synaptosomes; rat; lithium/pilecarpine; status epilepticus; subcellular brain fractions; Mg2+-dependent ATPase; Ca2+-dependent ATPase ID CENTRAL-NERVOUS-SYSTEM; ADENOSINE-TRIPHOSPHATASE-ACTIVITY; SYNAPTIC PLASMA-MEMBRANES; TORPEDO ELECTRIC ORGAN; SEIZURE-PRONE MICE; EXTRACELLULAR ATP; FOCAL EPILEPSY; SYNAPTOSOMES; RELEASE; DIPHOSPHOHYDROLASE AB Considerable evidence indicates that ATP, acting intracellularly or as a neurotransmitter, can influence nerve cell physiology in a variety of ways. Defects in the functioning of ATP-metabolizing enzymes could therefore lead to disturbances in neurotransmission and creation of sustained neuronal discharges characteristic of status epilepticus. in this study we investigated synaptosomal ATPase changes in rat brains during lithium/pilocarpine-induced status epilepticus. After 2 h of continuous electroencephalographic spiking, both Mg2+- and Ca2+-dependent ecto-ATPases were significantly decreased in freshly prepared synaptosomal preparations from the status rats. The intracellulary acting Ca2+M2+-ATPase (Ca-pump) was also decreased, but no changes occurred in synaptosomal Na+K+-ATPase activity. The difference between ecto-ATPase activities of the control and status rat brains was not affected by repeated freezing-thawing and lengthy storage. Possible involvement of reduced synaptosomal divalent cation-dependent ATPases in the pathophysiology of status epilepticus is discussed. C1 W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90095 USA. RP Nagy, AK (reprint author), UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, 10833 LE CONTE AVE, LOS ANGELES, CA 90095 USA. NR 52 TC 21 Z9 21 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD JUN PY 1997 VL 31 IS 2 BP 135 EP 147 DI 10.1007/BF02815238 PG 13 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA XT683 UT WOS:A1997XT68300003 PM 9376020 ER PT J AU Haroutunian, V Greig, N Pei, XF Utsuki, T Gluck, R Acevedo, LD Davis, KL Wallace, WC AF Haroutunian, V Greig, N Pei, XF Utsuki, T Gluck, R Acevedo, LD Davis, KL Wallace, WC TI Pharmacological modulation of Alzheimer's beta-amyloid precursor protein levels in the CSF of rats with forebrain cholinergic system lesions SO MOLECULAR BRAIN RESEARCH LA English DT Article DE amyloid beta-protein; amyloid beta-protein, precursor; rat; Alzheimer's disease; cerebrospinal fluid; cerebral cortex; basal nucleus of Meynert; acetylcholine; acetylcholinesterase; acetylcholinesterase inhibitor; butyrylcholinesterase; receptor, muscarinic; DFP; phenserine; in vivo ID INDUCED LEARNING IMPAIRMENT; 14-UNIT T-MAZE; ORAL PHYSOSTIGMINE; SENILE DEMENTIA; NUCLEUS BASALIS; CEREBRAL-CORTEX; AGED RATS; DISEASE; MEMORY; CHOLINESTERASE AB Abnormal deposition and accumulation of Alzheimer's amyloid beta-protein (A beta) and degeneration of forebrain cholinergic neurons are among the principal features of Alzheimer's disease. Studies in rat model systems have shown that forebrain cholinergic deficits are accompanied by induction of cortical beta-amyloid precursor protein (beta-APP) mRNAs and increased levels of secreted beta-APP in the CSF. The studies reported here determined whether the CSF levels of secreted beta-APP could be altered pharmacologically. In different experiments, rats with lesions of the forebrain cholinergic system received injections of vehicle, a muscarinic receptor antagonist scopolamine, or one of two cholinesterase inhibitors - diisopropyl phosphorofluoridate (DFP) or phenserine. Scopolamine was administered to determine whether the levels of beta-APP in the CSF could be increased by anticholinergic agents. The cholinesterase inhibitors were administered to determine whether the forebrain cholinergic system lesion-induced increases in CSF beta-APP could be reduced by cholinergic augmentation. Scopolamine administration led to a significant increase in the CSF levels of secreted beta-APP in sham-lesioned rats. Phenserine, a novel, reversible acetyl-selective cholinesterase inhibitor, significantly decreased the levels of secreted beta-APP in the CSF of forebrain cholinergic system-lesioned rats whereas DFP, a relatively non-specific cholinesterase inhibitor, failed to affect CSF levels of secreted beta-APP. These results suggest that the levels of secreted beta-APP in the CSF can be pharmacologically modulated but that this modulation is dependent upon the status of the forebrain cholinergic system and the pharmacological properties of the drugs used to influence it. C1 BRONX VET ADM MED CTR,NEW YORK,NY. MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY. NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIA,MOL & CELLULAR BIOL PROGRAM,MOL PHYSIOL & GENET SECT,BETHESDA,MD 20892. NR 59 TC 60 Z9 60 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN PY 1997 VL 46 IS 1-2 BP 161 EP 168 DI 10.1016/S0169-328X(96)00297-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XA506 UT WOS:A1997XA50600019 ER PT J AU Schipani, E Jensen, GS Pincus, J Nissenson, RA Gardella, TJ Juppner, H AF Schipani, E Jensen, GS Pincus, J Nissenson, RA Gardella, TJ Juppner, H TI Constitutive activation of the cyclic adenosine 3',5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BETA(2)-ADRENERGIC RECEPTOR; EXPRESSION CLONING; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; MUTATIONS; GENE; PITUITARY; CYCLASE; REGION AB Two different activating PTH/PTH-related peptide (PTHrP) receptor mutations, H223R and T410P, were recently identified as the most likely cause of Jansen's metaphyseal chondrodysplasia. To assess the functional importance of either amino acid position in the human PTH/PTHrP receptor, H223 and T410 were individually replaced by all other amino acids. At position 223, only arginine and lysine led to agonist-independent cAMP accumulation; all other amino acid substitutions resulted in receptor mutants that lacked constitutive activity or were uninformative due to poor cell surface expression. In contrast, most amino acid substitutions at position 410 conferred constitutive cAMP accumulation and affected PTH/PTHrP receptor expression not at all or only mildly. Mutations corresponding to the H223R or T410P exchange in the human PTH/PTHrP receptor also led to constitutive activity when introduced into the opossum receptor homolog, but showed little or no change in basal cAMP accumulation when introduced into the rat PTH/PTHrP receptor. The PTH/PTHrP receptor residues mutated in Jansen's disease are conserved in all mammalian members of this family of G protein-coupled receptors. However, when the equivalent of either the H223R or the T410P mutation was introduced into several other related receptors, including the PTH2 receptor and the receptors for calcitonin, secretin, GH-releasing hormone, glucagon-like peptide I, and CRH, the resulting mutants failed to induce constitutive activity. These studies suggest that two residues in the human PTH/PTHrP receptor, 223 and 410, have critical roles in signal transduction, but with different sequence constrains. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED & CHILDRENS SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. VET AFFAIRS MED CTR, SAN FRANCISCO, CA 94121 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94121 USA. FU NIDDK NIH HHS [DK-50708-01] NR 37 TC 55 Z9 56 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1997 VL 11 IS 7 BP 851 EP 858 DI 10.1210/me.11.7.851 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XB329 UT WOS:A1997XB32900002 PM 9178745 ER PT J AU Wyngaarden, J Potts, J Cotter, F Martin, RR Mehta, V Eckstein, F Levin, A Weiss, B Black, L Cole, R Crooke, S Kreig, A Diasio, R AF Wyngaarden, J Potts, J Cotter, F Martin, RR Mehta, V Eckstein, F Levin, A Weiss, B Black, L Cole, R Crooke, S Kreig, A Diasio, R TI Antisense '97: A roundtable on the state of the industry SO NATURE BIOTECHNOLOGY LA English DT Editorial Material AB The following article is excerpted from the transcript of a one-hour roundtable discussion that concluded Nature Biotechnology's conference ''Antisense 97: Targeting the Molecular Basis of Disease,'' May 1-2, 1997 in Cambridge, MA. The purpose of the roundtable was to allow both speakers and conference attendees to address what they saw as the critical issues that had arisen during the two-day meeting. The transcript has been edited to address the major themes emerging from that discussion: the impact of first-generation vs. second-generation antisense drugs, the need to encourage dissemination of high-quality data, the reasons for the lack of reproducibility of certain data, whether genotoxicity should be a more closely studied issue, and what future directions may be for the field. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. INST CHILD HLTH, MOL HEMATOL UNIT, LONDON, ENGLAND. MAX PLANCK INST EXPT MED, D-37075 GOTTINGEN, GERMANY. ISIS PHARMACEUT, CARLSBAD, CA 92008 USA. ALLEGHENY UNIV HLTH SCI, PHILADELPHIA, PA 19102 USA. US FDA, CTR BIOL, ROCKVILLE, MD 20857 USA. UNIV N CAROLINA, CTR COMPREHENS CANC, CHAPEL HILL, NC USA. UNIV IOWA, DEPT INTERNAL MED, IOWA CITY, IA 52242 USA. UNIV ALABAMA, DEPT PHARMACOL, DIV CLIN PHARMACOL, BIRMINGHAM, AL 35294 USA. MRC, MOL BIOL LAB, CAMBRIDGE CB2 2QH, ENGLAND. MEHTA & ISALY, NEW YORK, NY USA. RP Wyngaarden, J (reprint author), HYBRIDON INC, CAMBRIDGE, MA USA. NR 0 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 1997 VL 15 IS 6 BP 519 EP 524 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XC772 UT WOS:A1997XC77200025 ER PT J AU Yarmush, ML Berthiaume, F AF Yarmush, ML Berthiaume, F TI Metabolic engineering and human disease SO NATURE BIOTECHNOLOGY LA English DT Article ID TRICARBOXYLIC-ACID CYCLE; RAT-LIVER CELLS; C-13 NMR; SUBSTRATE SELECTION; PERFUSED LIVER; UNTREATED RATS; GLUCONEOGENESIS; FLUX; PYRUVATE; GLUCOSE C1 SHRINERS BURN INST,BOSTON,MA 02114. RP Yarmush, ML (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR ENGN MED,55 FRUIT ST,BIGELOW 1401,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [5P50 GM-21700-21] NR 32 TC 21 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 1997 VL 15 IS 6 BP 525 EP 528 DI 10.1038/nbt0697-525 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA XC772 UT WOS:A1997XC77200026 PM 9181573 ER PT J AU Morris, JC Ernesto, C Schafer, K Coats, M Leon, S Sano, M Thal, LJ AF Morris, JC Ernesto, C Schafer, K Coats, M Leon, S Sano, M Thal, LJ TI Clinical Dementia Rating training and reliability in multicenter studies: The Alzheimer's Disease Cooperative Study experience SO NEUROLOGY LA English DT Article ID SCALE AB Global ratings of dementia severity are used increasingly in clinical trials of antidementia compounds. Such ratings are clinically relevant, but their reliability in multicenter settings has not been determined. To evaluate the reliability of one global scale, the Clinical Dementia Rating (CDR), 82 investigators of the multicenter Alzheimer's Disease Cooperative Study participated in a training and relibility protocol using videotaped assessments of subjects in various stages of Alzheimer's disease, Following training, overall agreement of the investigators with ''gold standard'' CDR scores was 83%, These results indicate that the training protocol is useful for establishing good levels of agreement in staging dementia severity and that the CDR can be standardized as a clinical global scale for multicenter studies of Alzheimer's disease. C1 UNIV CALIF SAN DIEGO,DEPT NEUROSCI,SAN DIEGO,CA 92103. COLUMBIA UNIV,NEUROL INST,NEW YORK,NY. SO ILLINOIS UNIV,SPRINGFIELD,IL. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. BURKE REHABIL CTR,WHITE PLAINS,NY. UNIV PENN,PHILADELPHIA,PA 19104. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. MT SINAI SCH MED,NEW YORK,NY. UNIV PITTSBURGH,PITTSBURGH,PA 15260. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV MASSACHUSETTS,WORCESTER,MA 01605. NYU,NEW YORK,NY. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. EMORY UNIV,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV ALABAMA,BIRMINGHAM,AL. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV MIAMI,MIAMI BEACH,FL. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV S FLORIDA,TAMPA,FL. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV KENTUCKY,LEXINGTON,KY 40506. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV ROCHESTER,ROCHESTER,NY 14627. UNIV TEXAS,DALLAS,TX 75230. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. RP Morris, JC (reprint author), WASHINGTON UNIV,SCH MED,DEPT NEUROL,BOX 8111,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. RI Morris, John/A-1686-2012 FU NIA NIH HHS [AG-03991, AG-05681, AG-10483, U19 AG010483] NR 9 TC 172 Z9 175 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1997 VL 48 IS 6 BP 1508 EP 1510 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA XE091 UT WOS:A1997XE09100006 PM 9191756 ER PT J AU Bressman, SB deLeon, D Raymond, D Greene, PE Brin, MF Fahn, S Ozelius, LJ Breakefield, XO Kramer, PL Risch, NJ AF Bressman, SB deLeon, D Raymond, D Greene, PE Brin, MF Fahn, S Ozelius, LJ Breakefield, XO Kramer, PL Risch, NJ TI Secondary dystonia and the DYTI gene SO NEUROLOGY LA English DT Article ID IDIOPATHIC TORSION DYSTONIA; DELAYED-ONSET DYSTONIA; NON-JEWISH FAMILY; ASHKENAZI JEWS; INHERITANCE; POPULATION; EXCLUSION; 9Q34; MAP AB Early-onset (<28 years) primary dystonia in most Ashkenazi Jews is due to a single founder mutation in the DYT1 gene on chromosome 9q34, as determined by very strong linkage disequilibrium with a haplotype of 9q34 alleles at surrounding marker loci. The role of this mutation in individuals with secondary causes for dystonia has never been tested, although environmental insults, such as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in 40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms, including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of the 25 patients with early onset, 9 were considered phenocopies of DYT1 having normal examinations except for dystonia, normal radiographic and other laboratory studies, and onset in a limb or the neck. Only one individual whose dystonia developed in the setting of a measles infection carried the associated haplotype. Our findings indicate that clinical diagnostic criteria that include historical information to detect tardive dystonia and perinatal asphyxia discriminate primary dystonia due to the DYT1 founder mutation. We found no evidence that the DYT1 founder mutation contributes to secondary dystonia. C1 MT SINAI MED CTR,DEPT NEUROL,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. STANFORD UNIV,DEPT GENET,STANFORD,CA 94305. RP Bressman, SB (reprint author), COLUMBIA PRESBYTERIAN MED CTR,INST NEUROL,DEPT NEUROL,710 W 168TH ST,NEW YORK,NY 10032, USA. FU NINDS NIH HHS [NS28384, NS26656] NR 28 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1997 VL 48 IS 6 BP 1571 EP 1577 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA XE091 UT WOS:A1997XE09100018 PM 9191768 ER PT J AU Cannon, SC AF Cannon, SC TI From mutation to myotonia in sodium channel disorders SO NEUROMUSCULAR DISORDERS LA English DT Article; Proceedings Paper CT 1st International Congress of the World-Muscle-Society CY SEP 25-27, 1996 CL LONDON, ENGLAND SP World Muscle Soc DE periodic paralysis; SkM1; skeletal muscle ID HYPERKALEMIC PERIODIC PARALYSIS; ADYNAMIA EPISODICA HEREDITARIA; NA+-CHANNEL; PARAMYOTONIA-CONGENITA; FUNCTIONAL EXPRESSION; MUSCLE; INACTIVATION; MEMBRANE; POTASSIUM; FLUCTUANS AB Hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium-aggravated myotonias are all caused by point mutations in the alpha-subunit of a sodium channel expressed selectively in skeletal muscle. This review updates the growing list of genotype-phenotype correlations for these mutations and summarizes the alterations in channel function they produce. A toxin-based in vitro model demonstrates that subtle defects in sodium channel inactivation are sufficient to cause myotonia and computer modeling suggests that specific types of inactivation defect may predispose to paralysis or myotonia. (C) 1997 Elsevier Science B.V. RP Cannon, SC (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR42703] NR 44 TC 58 Z9 58 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD JUN PY 1997 VL 7 IS 4 BP 241 EP 249 DI 10.1016/S0960-8966(97)00430-6 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XE579 UT WOS:A1997XE57900006 PM 9196906 ER PT J AU Carter, BS Ogilvy, CS Candia, GJ Rosas, HD Buonanno, F AF Carter, BS Ogilvy, CS Candia, GJ Rosas, HD Buonanno, F TI One-year outcome after decompressive surgery for massive nondominant hemispheric infarction SO NEUROSURGERY LA English DT Article DE cerebral infarction; embolus; hemicraniectomy; intracranial hypertension ID CEREBRAL INFARCTION; STROKE; HEMICRANIECTOMY; INDEX AB OBJECTIVE: Massive cerebral infarction is often accompanied by early death secondary to transtentorial herniation. We have tested the hypothesis that decompressive hemicraniectomy for massive nondominant cerebral infarction is lifesaving in a series of 14 patients presenting with right hemispheric infarction and clinical signs of uncal herniation and impending death. We have further analyzed, in prospective follow-up examinations, the levels of physical, psychiatric, and social disabilities in these patients. METHODS: The methods used included retrospective analysis to determine rates of immediate mortality and morbidity after surgical intervention. Prospective follow-up data were obtained to determine the level of recovery in surviving patients after 1 year. Standardized measures of outcome to assess physical, psychiatric, and social recovery included the Barthel Index, Zung Depression Scale, and Reintegration to Normal Living Index. RESULTS: With decompressive hemicraniectomy, we were able to prevent death secondary to transtentorial herniation in all cases; 11 patients experienced long-term survival after the procedure, and three deaths were related to non-neurological causes. We observed that 8 of the 11 surviving patients were at home, were functioning with minimal to moderate assistance, and had Barthel scores greater than 60. The remaining three patients were severely disabled. Seven of the 11 survivors were able to walk at 1 year after undergoing the procedure. Depression and failure to reintegrate socially were experienced by most patients. CONCLUSION: This series confirms the lifesaving nature of hemicraniectomy in patients deteriorating because of cerebral edema after infarction. In patients younger than 50 years, recovery to a state of near-independence is possible. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. ST ELIZABETHS MED CTR,BRIGHTON,MA. NR 20 TC 187 Z9 197 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1997 VL 40 IS 6 BP 1168 EP 1175 DI 10.1097/00006123-199706000-00010 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XC450 UT WOS:A1997XC45000024 PM 9179889 ER PT J AU Nakajima, S Atsumi, H Kikinis, R Moriarty, TM Metcalf, DC Jolesz, FA Black, PM AF Nakajima, S Atsumi, H Kikinis, R Moriarty, TM Metcalf, DC Jolesz, FA Black, PM TI Use of cortical surface vessel registration for image-guided neurosurgery SO NEUROSURGERY LA English DT Article DE central nervous system neoplasm; cortical vessel; image-guided neurosurgery; video registration ID MR IMAGES AB OBJECTIVE: We have treated patients with brain surface tumors by using video registration of a three-dimensional image to the surgical field, to identify eloquent cortices, localize the lesions, and define the tumor margins. ''Skin-to-skin'' registration using the skin surface to produce alignment was performed earlier but was difficult in areas with few prominent registration landmarks. For this reason, ''vessel-to-vessel'' registration using the cortical vessels as fiducials was applied to 17 cases, to improve accuracy. This article presents the advantages and limitations of vessel-to-vessel registration, as determined from the data for these cases. The accuracy is also estimated. METHODS: A three-dimensional model was reconstructed from magnetic resonance imaging data, and a two-dimensional projection was superimposed on the video image of the actual surgical field. The tumor was resected with guidance from the registered video image. The two-dimensional projection accuracy of vessel-to-vessel registration was compared with that of skin-to-skin registration by using a phantom study. RESULTS: All 17 tumors underwent gross total resection, and the patients experienced no major permanent neurological deficits. In the phantom study, the two-dimensional, projected, target registration error of a tumor with skin-to-skin registration was estimated as 8.9 +/- 5.3 mm and that with vessel-to-vessel registration was 1.3 +/- 1.4 mm (99th percentile confidence intervals, 24.8 and 5.5 mm, respectively). CONCLUSION: Video registration using cortical surface vessels is practical and improves two-dimensional projection accuracy significantly, compared with skin registration. C1 BRIGHAM & WOMENS HOSP, DIV NEUROSURG, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, CHILDRENS HOSP, DANA FARBER CANC INST, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT SURG, BOSTON, MA 02115 USA. RP BRIGHAM & WOMENS HOSP, DEPT RADIOL, SURG PLANNING LAB, 75 FRANCIS ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [P01-CA67165-02] NR 16 TC 45 Z9 46 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1997 VL 40 IS 6 BP 1201 EP 1208 DI 10.1097/00006123-199706000-00018 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XC450 UT WOS:A1997XC45000041 PM 9179893 ER PT J AU Ogilvy, CS AF Ogilvy, CS TI Repair of an arterial perforation of the internal carotid artery using hemashield wrapping with aneurysm clip reinforcement: Technical note SO NEUROSURGERY LA English DT Article DE aneurysm; arterial perforation; clip; wrapping AB OBJECTIVE: To review a technique used to repair a hole in the carotid artery encountered during the dissection and clipping of a giant paraclinoid aneurysm. METHODS: The technique of repair involves wrapping the artery using a woven double velour material impregnated with bovine collagen (Hemashield; Meadox, Oakland, NI) and securing the material around the carotid artery with an aneurysm clip. The intravascular pressure of the carotid artery provides the counterforce necessary to seal the hole. RESULTS: The carotid artery was slightly narrowed after the treatment. The patient made an excellent recovery from surgery. CONCLUSION: This technique provides an alternative means of repairing a defect in the walls of intracranial arteries. RP Ogilvy, CS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT CEREBROVASC SURG,VBK710,32 FRUIT ST,BOSTON,MA 02114, USA. NR 6 TC 10 Z9 10 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 JUN PY 1997 VL 40 IS 6 BP 1312 EP 1314 DI 10.1097/00006123-199706000-00041 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XC450 UT WOS:A1997XC45000107 PM 9179909 ER PT J AU Kwong, K AF Kwong, K TI Current issues in functional MRI SO NMR IN BIOMEDICINE LA English DT Editorial Material ID CEREBRAL BLOOD-FLOW; SENSORY STIMULATION; BRAIN; ACTIVATION; PERFUSION; SPECTROSCOPY; INVERSION RP MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NR 33 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD JUN-AUG PY 1997 VL 10 IS 4-5 BP 157 EP 159 DI 10.1002/(SICI)1099-1492(199706/08)10:4/5<157::AID-NBM492>3.0.CO;2-4 PG 3 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA YJ807 UT WOS:A1997YJ80700001 PM 9430341 ER PT J AU Pessina, MA Ellis, SM AF Pessina, MA Ellis, SM TI Rehabilitation SO NURSING CLINICS OF NORTH AMERICA LA English DT Article AB Rehabilitation of a patient with a burn injury requires multidisciplinary collaboration, especially between the burn therapist and the burn rehabilitation nurse. Each discipline brings unique educational backgrounds and skills to promote the rehabilitation process throughout all phases of burn recovery. This article highlights major aspects of burn rehabilitation and emphasizes the collaboration between the burn therapist and the rehabilitation nurse. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,ACUTE CARE UNIT,BOSTON,MA 02114. SHRINERS BURNS INST,DEPT REHABIL,BOSTON,MA 02114. NR 14 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 1997 VL 32 IS 2 BP 365 EP & PG 11 WC Nursing SC Nursing GA XA072 UT WOS:A1997XA07200010 PM 9115482 ER PT J AU AlRajhi, AA Wagoner, MD AF AlRajhi, AA Wagoner, MD TI Penetrating keratoplasty in congenital hereditary endothelial dystrophy SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of American-Academy-of-Ophthalmology CY OCT 29-NOV 02, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID PEDIATRIC KERATOPLASTY; DONOR AGE; CELL LOSS; GLAUCOMA; MANAGEMENT AB Purpose: The purpose of the study is to determine the outcome of penetrating keratoplasty in congenital hereditary endothelia[ dystrophy. Methods: Records of 40 patients (13 males, 27 females) who underwent penetrating keratoplasty (56 eyes) were reviewed. The mean age at surgery was 11.8 years (range, 2 months-35 years). The mean follow-up was 37 months (range, 6-136 months). Results: In 35 (62.5%) of 56 eyes that underwent primary penetrating keratoplasty, the grafts survived, Graft survival analysis showed the probability of obtaining a clear graft is 92% at 1 year, 72% at 2 years, and 56.5% at 5 years. Graft survival was statistically better in eyes where onset of the disease is delayed (P = 0.02), if the graft donor age is between 5 and 30 years versus older than 30 years (P = 0.02), and for patients who kept follow-up appointments Versus those who were delinquent (P < 0.03), Visual acuity was 20/40 in 1.9%, 20/50 to 20/80 in 18.9%, 20/100 to 20/300 in 49%, and less than 20/400 in 30.2%. The main causes of graft failure were graft rejection (six eyes) and bacterial keratitis (four eyes). Conclusions: Penetrating keratoplasty in congenital hereditary endothelia[ dystrophy is moderately successful, and graft survival is better in cases of delayed onset compared with that of congenital onset. Early surgical intervention is recommended to prevent development or progression of amblyopia. C1 MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RP AlRajhi, AA (reprint author), KING KHALID EYE SPECIALIST HOSP,MED LIB,ANTERIOR SEGMENT DIV,POB 7191,RIYADH 11462,SAUDI ARABIA. NR 29 TC 19 Z9 21 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 JUN PY 1997 VL 104 IS 6 BP 956 EP 961 PG 6 WC Ophthalmology SC Ophthalmology GA XD424 UT WOS:A1997XD42400027 PM 9186436 ER PT J AU Ciulla, TA Beck, AD Topping, TM Baker, AS AF Ciulla, TA Beck, AD Topping, TM Baker, AS TI Blebitis, early endophthalmitis, and late endophthalmitis after glaucoma-filtering surgery SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of American-Academy-of-Ophthalmology CY OCT 29-NOV 02, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID INFECTIOUS ENDOPHTHALMITIS; BACTERIAL ENDOPHTHALMITIS; BLEBS; TRABECULECTOMY AB Purpose: The differentiating characteristics in blebitis and early and late endophthalmitis after glaucoma filtration surgery are reviewed. Methods: All admission records and operative reports, as well as available office notes, on patients with blebitis or bleb-associated endophthalmitis admitted to a large referral eye center from 1985 to 1995 were reviewed retrospectively. Results: Ten cases of blebitis and 33 cases of bleb-associated endophthalmitis were identified, One patient with blebitis progressed to culture-positive endophthalmitis. Of the 33 cases of bleb-associated endophthalmitis, there were 6 cases of early endophthalmitis (before postoperative week 6) and 27 cases of late endophthalmitis. In early endophthalmitis, Staphylococcus epidermidis was isolated on vitreous culture in 4 (67%) of 6 cases, whereas in late endophthalmitis, this organism was isolated in only 1 (4%) of 27 cases. in the 27 late cases, Streptococcus species and gram-negative organisms comprised 48% of isolates; of 33 cases of endophthalmitis, 15 (45%) demonstrated no growth on vitreous culture. Patients with endophthalmitis fared more poorly than those with blebitis in terms of visual outcome. Conclusions: Because blebitis may be prodromal to endophthalmitis, aggressive antimicrobial therapy, perhaps with oral quinolones, is warranted, In addition, patients with blebitis should be observed closely to identify extension into the vitreous cavity so that intravitreous antibiotics can be administered in a timely fashion. Finally, clinicians should not extrapolate the results of the Endophthalmitis Vitrectomy Study to the postfiltration surgery endophthalmitis given the differing pathogenesis and unique spectrum of organisms. C1 EMORY UNIV,SCH MED,DEPT OPHTHALMOL,ATLANTA,GA. OPHTHALM CONSULTANTS BOSTON,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,CAMBRIDGE,MA 02138. TUFTS SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV MED,BOSTON,MA. RP Ciulla, TA (reprint author), INDIANA UNIV,SCH MED,DEPT OPHTHALMOL,RETINA SECT,702 ROTARY CIRCLE,INDIANAPOLIS,IN 46202, USA. NR 27 TC 82 Z9 90 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 JUN PY 1997 VL 104 IS 6 BP 986 EP 995 PG 10 WC Ophthalmology SC Ophthalmology GA XD424 UT WOS:A1997XD42400031 PM 9186440 ER PT J AU Mandal, AK Walton, DS John, T Jayagandan, A AF Mandal, AK Walton, DS John, T Jayagandan, A TI Mitomycin C-augmented trabeculectomy in refractory congenital glaucoma SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of American-Academy-of-Ophthalmology CY OCT 29-NOV 02, 1995 CL ATLANTA, GA SP Amer Acad Ophthalmol ID FILTERING SURGERY; 5-FLUOROURACIL AB Objective: The purpose of the study is to determine the safety and efficacy of mitomycin C-augmented trabeculectomy in children with developmental glaucoma treated previously by conventional procedures. Design: Retrospective review of all cases of developmental glaucoma with previously failed conventional procedures that underwent mitomycin C-augmented trabeculectomy between January 1992 and December 1994. Participants: A total of 19 eyes of 13 patients were included in the study. Nineteen eyes included primary congenital glaucoma (15 eyes) with documented failure of primary trabeculotomy, Axenfeld-Reiger syndrome (2 eyes) and aniridia (2 eyes). Intervention: Mitomycin C-augmented (0.4 mg/ml for 3 minutes) trabeculectomy was the chosen intervention. Main outcome measures: Preoperative and postoperative intraocular pressures (IOPs), visual acuities, success rate, bleb characteristics, time of surgical failure, and complications were the main outcome measures. Results: The mean IOP was reduced from a preoperative level of 33.74 +/- 10.70 mmHg to 11.89 +/- 1.33 mmHg (P < 0.0001) with the percentage reduction in IOP being 64.75. The mean follow-up was 19.52 +/- 2.65 months. Visual acuity was maintained in all the cases after surgery. Complete success as defined in the authors' study was achieved in 18 eyes (94.74%). Only one patient was classified as a qualified success. The bleb was characterized by its large elevated, avascular, transparent appearance in all the eyes. The only significant complication was retinal detachment in an eye with buphthalmos, aphakia, and large axial length. However, the retina was reattached successfully by retinal reattachment surgery, and visual acuity improved to the preoperative level of 20/200. It was not possible to determine the cause of retinal detachment or to assess the possible role of mitomycin C in this complication. Conclusions: Mitomycin C-augmented trabeculectomy is a viable option in eyes with failed conventional trabeculotomy surgery. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. RP Mandal, AK (reprint author), VST,CTR GLAUCOMA CARE,LV PRASAD EYE INST,RD 2,BANJARA HILLS,HYDERABAD 500034,ANDHRA PRADESH,INDIA. OI Freedman, Sharon/0000-0003-3615-3511 NR 18 TC 72 Z9 75 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 JUN PY 1997 VL 104 IS 6 BP 996 EP 1001 PG 6 WC Ophthalmology SC Ophthalmology GA XD424 UT WOS:A1997XD42400032 PM 9186441 ER PT J AU Seymour, GJ Taubman, MA Eastcott, JW Gemmell, E Smith, DJ AF Seymour, GJ Taubman, MA Eastcott, JW Gemmell, E Smith, DJ TI CD29 expression on CD4(+) gingival lymphocytes supports migration of activated memory T lymphocytes to diseased periodontal tissue SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE periodontal disease; T lymphocyte; CD4(+)CD29(+)CD45RA(+); memory T lymphocyte; migration ID ANTIGEN-FREE DIET; BONE LOSS; IMMUNOHISTOLOGICAL ANALYSIS; ADOPTIVE TRANSFER; HELPER CELLS; RATS; POPULATIONS; SUBSETS; UCHL1; IDENTIFICATION AB The cell surface phenotypes of CD4(+) cells extracted from inflammatory periodontal disease tissues were analyzed using two- and three-color immunofluorescence and flow cytometry. Cells extracted from both adult periodontal and localized juvenile periodontilis lesions showed a depressed CD4/CD8 ratio (1.0+/-0.1 adult periodontitis and 1.1+/-0.1 localized juvenile periodontitis) compared with cells recovered from normal/marginal gingivitis tissue (1.8+/-0.2) or with normal peripheral blood cells (2.1+/-0.1) or periodontal disease blood cells (2.1+/-0.1 and 1.7+/-0.1 for adult periodontitis and juvenile periodontitis, respectively). The monoclonal antibodies anti-2H4 and anti-4B4 were used to identify the CD45RA and CD29 antigens respectively on CD4(+) T cells from the periodontal disease lesions. In peripheral blood, CD29(+) cells accounted for 66-77% of the CD4(+) population, and CD45RA(+) cells accounted for 22-27% of the CD4(+) subset. No differences in expression were found between peripheral blood lymphocytes from normal subjects and from periodontal disease patients. Two-color analyses of lymphocytes from periodontal diseased tissues showed that 87-89% of the CD4(+) population were CD29(+) and that 70-79% of the CD4(+) cells were CD45RA(+). Normal tissues contained significantly fewer CD4(+)CD29(+) cells (56+/-4%) and CD4(+)CD45RA(+) cells (40+/-4%) on average, and few, if any double-labelled cells could be accounted for. These data implied that a significant percentage of the CD4(+) cells from the diseased tissues were both CD29(+) and CD45RA(+) and that these populations are found in quite different proportions in diseased periodontal tissue than in peripheral blood or nondiseased tissue. In further analyses using three-color cytometry the mean percentage of CD4(+)CD29(+)CD45RA(+) lymphocytes extracted from periodontal disease lesions was 43+/-9% of the CD4(+) population. These results suggest that CD4(+) T lymphocytes in periodontal disease not only demonstrate varying levels of maturity but also that the accumulation of CD4(+) T cells within the periodontal tissues may be a result of increased adhesion and transendothelial migration. C1 FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115. UNIV QUEENSLAND,DEPT DENT,IMMUNOPATHOL LAB,ST LUCIA,QLD 4067,AUSTRALIA. OI Seymour, Gregory/0000-0001-7595-5651 FU NIDCR NIH HHS [DE-03420, DE-04881] NR 31 TC 16 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 1997 VL 12 IS 3 BP 129 EP 134 DI 10.1111/j.1399-302X.1997.tb00368.x PG 6 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA XC449 UT WOS:A1997XC44900001 PM 9467397 ER PT J AU Alora, MBT Taylor, CR AF Alora, MBT Taylor, CR TI Narrow-band (311 nm) UVB phototherapy: an audit of the first year's experience at the Massachusetts General Hospital SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article; Proceedings Paper CT Photomedicine Workshop at the Annual Meeting of the Photomedicine-Society CY MAR 20, 1997 CL SAN FRANCISCO, CA SP Photomed Soc DE narrow-band UVB ID PSORIASIS C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,PHOTOTHERAPY UNIT,BOSTON,MA 02114. NR 6 TC 16 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD JUN PY 1997 VL 13 IS 3 BP 82 EP 84 PG 3 WC Dermatology SC Dermatology GA YB849 UT WOS:A1997YB84900005 PM 9372520 ER PT J AU Fava, M AF Fava, M TI Psychopharmacologic treatment of pathologic aggression SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; MENTALLY-HANDICAPPED PATIENTS; SEROTONIN REUPTAKE INHIBITOR; PLACEBO-CONTROLLED TRIAL; BRAIN-INJURED PATIENTS; DOUBLE-BLIND TRIAL; PREMENSTRUAL-SYNDROME; CONDUCT DISORDER; PSYCHIATRIC-INPATIENTS AB The article reviews the drug treatment of pathologic aggressive behavior, a heterogeneous phenomenon found In a wide range of psychiatric and neurological disorders. It appears that several drugs are effective and superior to placebo in treating pathologic aggression. Traditional antipsychotics and benzodiazepines can reduce agitation and aggression, but they fan also induce behavioral disinhibition and their effects appear to be modest. Atypical antipsychotics ate promising agents in the management of aggressive patients. Psychostimulants seem to be effective in reducing aggressiveness primarily in brain-injured patients as well as in violent adolescents with attention deficit disorder and/or conduct disorder. Finally, antidepressants, particularly those with relative selective serotonin reuptake blocking action, are the treatment of choice for aggressiveness and hostility among patients with unipolar depression and may be effective in reducing irritability and aggression in other psychiatric conditions as well. Further studies are necessary to evaluate the efficacy of these drugs in the treatment of pathologic aggressive behavior across different neuropsychiatric conditions. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS CLIN & RES PROGRAM,ACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 179 TC 136 Z9 138 U1 4 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1997 VL 20 IS 2 BP 427 EP & DI 10.1016/S0193-953X(05)70321-X PG 26 WC Psychiatry SC Psychiatry GA XF243 UT WOS:A1997XF24300011 PM 9196923 ER PT J AU Alpert, JE Spillmann, MK AF Alpert, JE Spillmann, MK TI Psychotherapeutic approaches to aggressive and violent patients SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID COGNITIVE-BEHAVIORAL TREATMENT; SELF-CONTROL; SYSTEMATIC-DESENSITIZATION; DISRUPTIVE BEHAVIOR; TREATMENT PROGRAM; YOUNG-CHILDREN; ANGER CONTROL; THERAPY; MODEL; HYPERTENSION AB A broad range of psychotherapeutic approaches have been marshalled alone and together with pharmacotherapies in the treatment of aggression and violence, although the research and clinical literature is characterized by marked heterogeneity of patient populations, treatment settings, and outcome measures. This article presents general principles that underlie most forms of psychotherapy with aggressive and violent individuals. Representative approaches are described including behavioral and cognitive behavioral therapies, group, couples, and family therapies, and therapeutic communities. The ongoing needs for standardized, controlled research designs for the study of efficacy and effectiveness, greater focus on specific mediating and moderating variables relevant to treatment success, development of algorithms for combined modality treatment, and application of psychotherapeutic strategies for primary prevention are highlighted. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHOL,BOSTON,MA 02115. RP Alpert, JE (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS CLIN & RES PROGRAM,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 125 TC 18 Z9 18 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1997 VL 20 IS 2 BP 453 EP & DI 10.1016/S0193-953X(05)70322-1 PG 21 WC Psychiatry SC Psychiatry GA XF243 UT WOS:A1997XF24300012 PM 9196924 ER PT J AU Fava, M AF Fava, M TI Anger, aggression, and violence - Preface SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material RP Fava, M (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS CLIN & RES PROGRAM,15 PARKMAN ST,WAC 815,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1997 VL 20 IS 2 BP R11 EP R12 DI 10.1016/S0193-953X(05)70311-7 PG 2 WC Psychiatry SC Psychiatry GA XF243 UT WOS:A1997XF24300001 ER PT J AU Shaner, A Roberts, LJ Eckman, TA Tucker, DE Tsuang, JW Wilkins, JN Mintz, J AF Shaner, A Roberts, LJ Eckman, TA Tucker, DE Tsuang, JW Wilkins, JN Mintz, J TI Monetary reinforcement of abstinence from cocaine among mentally ill patients with cocaine dependence SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 22-27, 1996 CL SAN JUAN, PR SP Coll Problems Drug Dependence ID ABUSERS AB Objective: The study investigated whether contingency management could reduce cocaine use by patients with schizophrenia. Methods: An A-B-A research design, with two-month baseline, intervention, and follow-up phases, was used to study two homeless, treatment-resistant male outpatients with DSM-III-R diagnoses of schizophrenia and cocaine dependence. During the intervention phase, subjects provided daily urine specimens for testing for the cocaine metabolite benzoylecgonine (BE) and received $25 for each negative test. Concentrations of BE and metabolites of other illicit drugs were assayed twice a week to determine the amount of drug use in addition to frequency. Analysis of variance was used to compare drug use during the three study phases. Results: During the intervention, the proportion of tests positive for cocaine was lower for both subjects. Mean urinary concentrations of BE were significantly lower during the intervention than during the baseline. Conclusions: These results suggest that modest monetary reinforcement of abstinence may decrease cocaine use among cocaine-dependent patients with schizophrenia. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA 90024 USA. RP W LOS ANGELES VET AFFAIRS MED CTR, 11301 WILSHIRE BLVD OOMH, LOS ANGELES, CA 90073 USA. FU NIMH NIH HHS [MH 30911] NR 13 TC 62 Z9 62 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 1997 VL 48 IS 6 BP 807 EP 810 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA XB452 UT WOS:A1997XB45200011 PM 9175190 ER PT J AU Hagan, MP Hopcia, KL Sylvester, FC Held, KD AF Hagan, MP Hopcia, KL Sylvester, FC Held, KD TI Caffeine-induced apoptosis reveals a persistent lesion after treatment with bromodeoxyuridine and ultraviolet-B light SO RADIATION RESEARCH LA English DT Article ID ATAXIA-TELANGIECTASIA; CELL-LINES; 5-BROMODEOXYURIDINE; RADIOSENSITIZATION; ENDONUCLEASE; RADIATION; DELAY AB Ultraviolet-B (UVB) light treatment of synchronized V79 Chinese hamster cells after pulse-labeling with bromodeoxyuridine (BrdUrd) reveals a marked age response for cell killing. Incubation after treatment in growth medium containing caffeine increases cell killing during the resistant portions of the cell cycle, resulting in a much less marked age response to UVB irradiation. Examination of the split-dose survival curves for BrdUrd and UVB light in the presence or absence of caffeine indicates that sensitization by caffeine is completely independent of the sparing effect of dose fractionation. Further, sensitization by caffeine is nearly complete after the first mitosis after the UVB exposure. With delayed addition of caffeine, however, nearly full sensitization can be elicited as late as two cell cycles after the treatment with BrdUrd and UVB light. Also, synchronized cells exposed to caffeine after treatment with BrdUrd and UVB in the S phase cease to incorporate radiolabeled thymidine and undergo apoptosis after the second mitosis. Thus exposure to caffeine reveals a persistent sensitivity lasting for at least two cell cycles after the injury induced by treatment with BrdUrd and UVB. (C) 1997 by Radiation Research Society. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP Hagan, MP (reprint author), UNIV FLORIDA,SHANDS CANC CTR,DEPT RADIAT ONCOL,GAINESVILLE,FL 32610, USA. NR 19 TC 9 Z9 9 U1 1 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 1997 VL 147 IS 6 BP 674 EP 679 DI 10.2307/3579479 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA XC885 UT WOS:A1997XC88500003 PM 9189164 ER PT J AU Rao, PM Rhea, JT Novelline, RA AF Rao, PM Rhea, JT Novelline, RA TI CT diagnosis of acute abdominal trauma SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review ID BLUNT TRAUMA; COMPUTED-TOMOGRAPHY; PERITONEAL-LAVAGE; CONTRAST MATERIAL; AORTIC RUPTURE; RENAL TRAUMA; CHILDREN; INJURY; BOWEL; MESENTERY AB This article outlines the indications and methodology as well as the potential findings of abdominal CT examinations in patients who undergo different types of trauma. Injuries to the spleen, liver, gallbladder, pancreas, adrenal glands, kidneys, bowel, mesentery, bladder, and vascular structures are reviewed. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1997 VL 14 IS 2 BP 111 EP 123 DI 10.1055/s-2008-1057078 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RK UT WOS:000078937900002 ER PT J AU Harari, D Sarkarati, M Gurwitz, JH McGlincheyBerroth, G Minaker, KL AF Harari, D Sarkarati, M Gurwitz, JH McGlincheyBerroth, G Minaker, KL TI Constipation-related symptoms and bowel program concerning individuals with spinal cord injury SO SPINAL CORD LA English DT Article DE spinal cord injury; constipation; bowel program; cathartics; tetraplegia ID GASTROINTESTINAL-TRACT; COLONIC TRANSIT; PATIENT; HOME; AGE; DYSFUNCTION; MANAGEMENT; LACTULOSE; MOTILITY; DISEASE AB Purpose. To determine the prevalence of constipation-related symptoms in individuals with chronic spinal cord injury (SCI), to describe the bowel program as reported by patients and including use of bowel medications and evacuation techniques, and to examine the clinical, functional and pharmacological risks of difficulty with evacuation. Patients and Methods. This is a cross-sectional study of all in-patients at least 3 months beyond acute injury, on the West Roxbury/Brockton VAMC SCI Service, during a 10 month period (n = 197). Clinical, functional and medication data were abstracted from medical and nursing records. Individual interviews were conducted with all available participants (n = 161, 82%) regarding bowel-related symptoms and treatment over the previous 1 month period. The study definition of difficulty with evacuation was spending more than 1 h per episode of bowel evacuation. Results. Forty-one percent of the 161 interview responders spent more than 1 h on bowel evacuation, 50% reported abdominal distension and 38% reported abdominal pain, 27% reported headaches or sweats relieved by having a bowel movement, and 33% reported fecal incontinence at least once a month. The bisacodyl suppository was the most commonly used laxative agent, while docusate was the most popular oral agent. Subjects with difficulty with evacuation (n = 66) were compared with those who spent less than 1 h on evacuation (n = 95). Factors associated with difficulty with evacuation were tetraplegia, Frankel grade A/B, laxative use, polypharmacy, previous urinary outlet surgery, and symptoms of abdominal pain and distension. Conclusion. Constipation-related symptoms are highly prevalent in individuals with spinal cord injury, despite considerable laxative use. Our findings suggest that difficulty with evacuation can be predicted on the basis of a patient's clinical profile. C1 HARVARD UNIV,SCH MED,DIV AGING,BROCKTON,MA 02401. MASSACHUSETTS GEN HOSP,BEACON HILL GERIATR MED UNIT,BROCKTON,MA 02401. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,GEN MED UNIT,BROCKTON,MA 02401. VET ADM MED CTR,SPINAL CORD INJURY SERV,BROCKTON,MA 02401. BRIGHAM & WOMENS HOSP,PROGRAM ANAL CLIN STRATEGIES,GERONTOL DIV,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. FU NIA NIH HHS [AG00599, AG04390, AG08812-05] NR 61 TC 49 Z9 51 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD JUN PY 1997 VL 35 IS 6 BP 394 EP 401 DI 10.1038/sj.sc.3100417 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA XE173 UT WOS:A1997XE17300011 PM 9194264 ER PT J AU Grabowski, EF Boor, SE Laposata, M Johnson, SM Furman, MI Benoit, SE Michelson, AD Li, CY Roth, G AF Grabowski, EF Boor, SE Laposata, M Johnson, SM Furman, MI Benoit, SE Michelson, AD Li, CY Roth, G TI Platelet hyperaggregability and aspirin resistance in two brothers with syndrome X: A non-cyclo-oxygenase-dependent platelet defect SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. VET AFFAIRS MED CTR,SEATTLE,WA 98108. NR 0 TC 0 Z9 0 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 JUN PY 1997 SU S BP PS288 EP PS288 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89800287 ER PT J AU Pannell, R Gurewich, V AF Pannell, R Gurewich, V TI The relative and variable stabilities of glycosylated and non-glycosylated pro-urokinases in plasma SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEACONESS MED CTR,BI,VASC RES LAB,BOSTON,MA. NR 0 TC 0 Z9 0 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 JUN PY 1997 SU S BP P2063 EP P2063 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89802062 ER PT J AU Denis, C Rayburn, H Hynes, RO Wagner, DD AF Denis, C Rayburn, H Hynes, RO Wagner, DD TI Generation of von Willebrand factor-deficient mice SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 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 JUN PY 1997 SU S BP S1532 EP S1532 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XE898 UT WOS:A1997XE89801531 ER PT J AU Russotti, G Campbell, J Toner, M Yarmush, ML AF Russotti, G Campbell, J Toner, M Yarmush, ML TI Studies of heat and PGA(1)-induced cold tolerance show that HSP27 may help preserve actin morphology during hypothermia SO TISSUE ENGINEERING LA English DT Article ID TRANSCRIPTION FACTOR; GENE-EXPRESSION; PROSTAGLANDIN-A; HUMAN-CELLS; INDUCTION; PROTEIN; THERMOTOLERANCE; PHOSPHORYLATION; FIBROBLASTS; ORGANIZATION AB Preservation of organs and tissue prior to transplantation is highly limited by hypothermic storage times. One potential method to increase preservation times is to condition tissue and/or cells for hypothermia by administering prior physiological stress. In a prior study, we have demonstrated that mammalian cells ire culture can be conditioned to better withstand 4 degrees C hypothermia if they are exposed to prior 42.5 degrees C heat shock. However, the mechanisms by which heat confers tolerance to hypothermia are not known. Since it is likely that heat shock proteins (HSPs) are playing a role in this phenomenon, and since antiproliferative prostaglandins (PGs) often induce a different spectrum of HSPs than induced by heat shock, the effect of prostaglandin A(1) (PGA(1)) on HSP synthesis and induction of cold tolerance in IMR-90 human diploid fibroblasts was examined and compared to the effect of heat shock. Both heat shock and PGA(1) induced the same concentration of HSP70, but only heat induced HSP27 above basal levels. Furthermore, the degree of cold tolerance conferred by PGA(1) with respect to cell membrane integrity, cell morphology, and actin structure was suboptimal as compared to the degree of cold tolerance conferred by heat shock. One mechanism by which heat may induce a greater degree of cold tolerance than does PGA(1) is through the induction of HSP27, a known stabilizer of actin. An additive effect of sub-optimal heat shock, which induces the maximum level of HSP27, and PGA(1) exposure supports this finding since this combination gives better cold tolerance than either treatment alone. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR ENGN MED,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,BOSTON,MA 02114. NR 25 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SUM PY 1997 VL 3 IS 2 BP 135 EP 147 DI 10.1089/ten.1997.3.135 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA XZ367 UT WOS:A1997XZ36700002 ER PT J AU Vamvakas, EC Moore, SB AF Vamvakas, EC Moore, SB TI Length of survival after perioperative transfusion SO TRANSFUSION MEDICINE LA English DT Article DE cost-effectiveness; epidemiology; mortality; population statistics; survival; transfusion ID IMMUNE-DEFICIENCY SYNDROME; BLOOD-TRANSFUSION; AUTOLOGOUS BLOOD; COST-EFFECTIVENESS; COLORECTAL-CANCER; TOTAL HIP; SURGERY; EPIDEMIOLOGY; POPULATION; MORTALITY AB To describe the post-transfusion survival of an entire, geographically defined population, we observed all residents of a US county who underwent perioperative transfusion before and after the introduction of a large autologous transfusion programme. We enrolled 444 and 1540 county residents, transfused in 1981 and in 1986-88, respectively. Complete follow-up (until death or for 5 years) was available on 1960 patients (98.8%). Of patients transfused in 1986-88, 67.6% were alive at 5 years, having survived for a mean (+/-SE) period of 46.15 (+/-0.575) months. The survival statistics were 66.2% and 46.09 (+/-1.047) months, respectively, for patients transfused in 1981 (P = 0.8424). Transfusion in 1986-88 vs. 1981 (with 615 [40%] vs. six [1.3%] patients receiving some autologous blood) did not have an effect on survival (P = 0.3892), following adjustment for age, gender, transfusion dose, receipt of a single-unit transfusion and transfusing surgical service. We conclude that the survival of an entire, geographically defined transfused population is substantially longer than that reported previously for patients referred to tertiary-care medical centres. The aggregate 5-year survival of patients transfused in 1981 and in 1986-88 does not differ, despite differences in patient case-mix and in perioperative transfusion practice, particularly as it relates to autologous blood usage. C1 MAYO CLIN & MAYO FDN,DIV TRANSFUS MED,ROCHESTER,MN 55905. RP Vamvakas, EC (reprint author), MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,GRJ-224,BOSTON,MA 02114, USA. NR 26 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD JUN PY 1997 VL 7 IS 2 BP 115 EP 121 DI 10.1046/j.1365-3148.1997.d01-13.x PG 7 WC Hematology SC Hematology GA XC803 UT WOS:A1997XC80300007 PM 9195697 ER PT J AU Arita, S Thompson, K Stein, E Matsuda, N Cochrum, K Jemtrud, S Une, S Kawahara, T Shevlin, L Trieu, C Mullen, Y AF Arita, S Thompson, K Stein, E Matsuda, N Cochrum, K Jemtrud, S Une, S Kawahara, T Shevlin, L Trieu, C Mullen, Y TI In vitro activation of human lymphocytes by crude and purified alginates SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Congress of the Transplant-Society CY SEP 29-OCT 02, 1996 CL MIAMI BEACH, FL SP Transplantat Soc C1 UNIV CALIF LOS ANGELES,DEPT SURG,HUMAN ISLET PROGRAM,LOS ANGELES,CA 90024. RP Arita, S (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,HUMAN ISLET PROGRAM,11301 WILSHIRE BLVD,BLDG 304,LOS ANGELES,CA 90073, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1997 VL 29 IS 4 BP 2125 EP 2125 DI 10.1016/S0041-1345(97)00258-3 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XE833 UT WOS:A1997XE83300098 PM 9193553 ER PT J AU Trivedi, N Suzuki, K BonnerWeir, S HollisterLock, J Weir, GC AF Trivedi, N Suzuki, K BonnerWeir, S HollisterLock, J Weir, GC TI Islet number in an immunobarrier device required to treat diabetes in mice SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Congress of the Transplant-Society CY SEP 29-OCT 02, 1996 CL MIAMI BEACH, FL SP Transplantat Soc ID TRANSPLANTATION C1 JOSLIN DIABET CTR,DEPT ISLET TRANSPLANTAT & CELL BIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [R01 DK-50657, DK-36836, R01 DK-35449] NR 4 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1997 VL 29 IS 4 BP 2142 EP 2143 DI 10.1016/S0041-1345(97)00265-0 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA XE833 UT WOS:A1997XE83300106 PM 9193561 ER PT J AU Corbett, AH AF Corbett, AH TI Nuclear moguls meet SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material RP Corbett, AH (reprint author), DANA FARBER CANC INST,DIV CELL & MOL BIOL,BOSTON,MA 02115, USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUN PY 1997 VL 7 IS 6 BP 252 EP 253 DI 10.1016/S0962-8924(97)01064-7 PG 2 WC Cell Biology SC Cell Biology GA XC716 UT WOS:A1997XC71600009 PM 17708955 ER PT J AU Jang, JC Sheen, J AF Jang, JC Sheen, J TI Sugar sensing in higher plants SO TRENDS IN PLANT SCIENCE LA English DT Review ID CARBON CATABOLITE REPRESSION; INDUCIBLE GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; GLUCOSE REPRESSION; HEXOKINASE-PII; YEAST; PHOSPHORYLATION; CELLS; SNF1 AB Sugars are capable of acting as regulatory signals that affect gene expression, growth and development in all organisms. Although fundamental, the mechanisms that multicellular eukaryotes use to perceive and transduce these signals are not fully understood. Recent studies in plants have shed light on a conserved sugar signaling pathway that uses hexokinase as a sensor. C1 MASSACHUSETTS GEN HOSP, DEPT MOL BIOL, BOSTON, MA 02114 USA. RP Jang, JC (reprint author), HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. NR 53 TC 250 Z9 260 U1 1 U2 24 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1360-1385 J9 TRENDS PLANT SCI JI Trends Plant Sci. PD JUN PY 1997 VL 2 IS 6 BP 208 EP 214 DI 10.1016/S1360-1385(97)01043-1 PG 7 WC Plant Sciences SC Plant Sciences GA XD663 UT WOS:A1997XD66300003 ER PT J AU Gahn, G Ackerman, RH Candia, MR AF Gahn, G Ackerman, RH Candia, MR TI Neurovascular applications of ultrasound contrast agents SO ULTRASCHALL IN DER MEDIZIN LA German DT Review DE colour coded duplex sonography; ultrasound contrast agent; transcranial colour coded duplex sonography; carotid disease ID REAL-TIME SONOGRAPHY; PHASE-2; SYSTEM AB Ultrasound is widely used in the assessment of neurovascular diseases. In spite of its effectiveness there are considerable limitations such as low flow detection in carotid disease or limited bony windows in transcranial Doppler. One approach to overcome these limitations is the use of ultrasound contrast enhancing agents. The usefulness of ultrasound contrast enhancing agents Levovist(R), EchoGen(R) and BY 963 in neurovascular applications has been evaluated. Contrast enhanced colourflow Doppler for the diagnosis of carotid disease has been investigated in three small trials and might be effective for improving the diagnostic yield in severe disease. Contrast enhanced transcranial colourflow Doppler has been relatively more widely explored also with promising results. Based on the combined findings out of these preliminary investigational trials, it appears to be reasonable to undertake larger trials for assessment of usefulness of ultrasound contrast agents for a variety of neurovascular applications. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RADIOL DEPT,NEUROVASC LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0172-4614 J9 ULTRASCHALL MED JI Ultraschall Med. PD JUN PY 1997 VL 18 IS 3 BP 101 EP 104 DI 10.1055/s-2007-1000403 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA XM119 UT WOS:A1997XM11900002 PM 9340734 ER PT J AU Brufsky, A FontaineRothe, P Berlane, K Rieker, P Jiroutek, M Kaplan, I Kaufman, D Kantoff, P AF Brufsky, A FontaineRothe, P Berlane, K Rieker, P Jiroutek, M Kaplan, I Kaufman, D Kantoff, P TI Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate SO UROLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 1996 CL PHILADELPHIA, PA SP Amer Soc Clin Oncol ID CONTROLLED TRIAL; CANCER; CARCINOMA; COMBINATION; DIHYDROTESTOSTERONE; 5-ALPHA-REDUCTASE; BICALUTAMIDE; ORCHIECTOMY; MONOTHERAPY; EXPERIENCE AB Objectives. Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide. Methods. Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values. Results. The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 5 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). Conclusions. Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed. (C) 1997, Elsevier Science Inc. C1 DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NCI NIH HHS [K08-CA67993-01] NR 28 TC 60 Z9 61 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 1997 VL 49 IS 6 BP 913 EP 920 DI 10.1016/S0090-4295(97)00091-5 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA XC721 UT WOS:A1997XC72100021 PM 9187700 ER PT J AU Teichman, JMH Rogenes, VJ Barber, DB AF Teichman, JMH Rogenes, VJ Barber, DB TI The Malone antegrade continence enema combined with urinary diversion in adult neurogenic patients: Early results SO UROLOGY LA English DT Article ID SPINAL-CORD INJURY; FECAL INCONTINENCE; CONSTIPATION AB Objectives. Patients with neurogenic voiding dysfunction often have coexisting neurogenic bowel problems. Impaired bowel evacuation is a cause of major morbidity and impaired lifestyle for these patients. The Malone antegrade continence enema (ACE) performed synchronously with a urinary continence procedure has been successful in pediatric patients. We report early experience combining the ACE with a urinary continence procedure in adult neurogenic patients. Methods. Adult patients with neurogenic voiding dysfunction and impaired bowel evacuation refractory to conservative management underwent a urinary continence procedure synchronously with an ACE. Results. Two patients have undergone the procedure. One patient chose a continent catheterizable supravesical bladder augmentation, whereas the other patient chose an ileal conduit. Both patients had a separate appendiceal stoma for their ACE. Both patients are continent of stool at their appendiceal stoma and per rectum. Both patients have stabilized their urinary tracts. Complications were minimal. Conclusions. The ACE may benefit adult patients with impaired bowel evacuation and may be combined with a urinary continence procedure. Further study of the ACE is warranted. (C) 1997, Elsevier Science Inc. C1 UNIV TEXAS,HLTH SCI CTR,SPINAL CORD INJURY SERV,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Teichman, JMH (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT REHABIL MED,DIV UROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 1997 VL 49 IS 6 BP 963 EP 967 DI 10.1016/S0090-4295(97)00087-3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA XC721 UT WOS:A1997XC72100034 PM 9187713 ER PT J AU McGough, P Back, AL Colley, J AF McGough, P Back, AL Colley, J TI Physician-assisted suicide - Finding common ground SO WESTERN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Comprehensive Care of the Terminally Ill: The Northern California Consensus Development Conference for Guidelines on Aid-in-Dying CY SEP, 1996 CL STANFORD UNIV CTR BIOMED ETH, STANNFORD, CA SP Stanford Univ, Ctr Biomed Eth HO STANFORD UNIV CTR BIOMED ETH ID PATIENT REQUESTS; EUTHANASIA; DEATH; MANAGEMENT AB In Washington state, practicing physicians have been forced to confront the emotional, complex issue of physician-assisted suicide sooner than physicians elsewhere in the US.(1-12) The Washington State Medical Association has struggled at length with the issue and ultimately delineated a policy on safeguards for physician-assisted suicide. The Washington experience may prove instructive to other professional physician organizations even before the US Supreme Court rules on the issue. C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV WASHINGTON,SEATTLE,WA 98195. RP McGough, P (reprint author), WASHINGTON STATE MED ASSOC END LIFE TASK FORCE,2033 6TH AVE,SUITE 1100,SEATTLE,WA 98121, USA. NR 26 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 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUN PY 1997 VL 166 IS 6 BP 394 EP 397 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XG751 UT WOS:A1997XG75100005 PM 9217451 ER PT J AU Lancaster, T Mant, J Singer, DE AF Lancaster, T Mant, J Singer, DE TI Stroke prevention in atrial fibrillation - Warfarin is most effective when the INR lies between 2.0 and 4.0 SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID RISK-FACTORS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. RP Lancaster, T (reprint author), RADCLIFFE INFIRM,DIV PUBL HLTH & PRIMARY CARE,OXFORD OX2 6HE,ENGLAND. NR 15 TC 10 Z9 10 U1 0 U2 0 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 MAY 31 PY 1997 VL 314 IS 7094 BP 1563 EP 1564 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XC500 UT WOS:A1997XC50000002 PM 9186155 ER PT J AU Sayin, U Rutecki, PA AF Sayin, U Rutecki, PA TI Effects of pilocarpine on paired pulse inhibition in the CA3 region of the rat hippocampus SO BRAIN RESEARCH LA English DT Article DE alveus; Str radiatum; epilepsy; muscarinic receptor; gamma-aminobutyric acid (GABA); inhibition; status epilepticus ID SPONTANEOUS RECURRENT SEIZURES; GABA-MEDIATED INHIBITION; DENTATE GYRUS; GABAERGIC INTERNEURONS; SYNAPTIC TRANSMISSION; EXPERIMENTAL-MODEL; PERFORANT PATH; FASCIA-DENTATA; EPILEPSY; DEPRESSION AB Pilocarpine (PILO), a muscarinic agonist, produces status epilepticus when administered to rats in vivo and induces interictal or ictal patterns of epileptiform activity in rat hippocampal slices. We investigated the effects of PILO (10 mu M) on paired pulse inhibition (PPI) in the CA3 region of rat hippocampal slices. PPI was assessed by stimulating either the alveus or str. radiatum and recording the extracellular response from str. pyramidale of CA3. The evoked population spike following the second stimulus was compared to the first. PILO was bath applied for 1 h and then washed out to assess acute and long lasting effects. PILO decreased the amplitude of evoked population spikes measured in CA3. PPI following alveus stimulation was not affected by PILO; however, a significant loss of PPI at 15 and 30 ms interpulse intervals occurred following str. radiatum stimulation in the presence of PILO and 5 mM [K+](0) artificial cerebrospinal fluid (ACSF). The decrease in PPI at the 15 ms interval persisted following wash-out of PILO. PILO in 7.5 mM [K+](0) ACSF produced epileptiform activity and a resultant long lasting loss of PPI that followed str. radiatum stimulation. This effect was not observed following epileptiform activity produced by 7.5 mM [K+](0) alone, suggesting that the loss of PPI was due to PILO. Because str. radiatum-evoked PPI was selectively impaired, PILO appears to preferentially decreased feed-forward inhibition. The more dramatic loss of PPI following exposure to PILO and high [K+](0) may represent the first steps in the development of chronic seizures that results from PILO-induced status epilepticus in rats. C1 UNIV WISCONSIN,DEPT NEUROSURG,MADISON,WI 53706. UNIV WISCONSIN,NEUROSCI TRAINING PROGRAM,MADISON,WI 53706. RP Sayin, U (reprint author), UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,DEPT NEUROL,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NINDS NIH HHS [NS 28580] NR 42 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 30 PY 1997 VL 758 IS 1-2 BP 136 EP 142 DI 10.1016/S0006-8993(97)00198-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA XE606 UT WOS:A1997XE60600017 PM 9203542 ER PT J AU Yu, CL Burakoff, SJ AF Yu, CL Burakoff, SJ TI Involvement of proteasomes in regulating Jak-STAT pathways upon interleukin-2 stimulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; PROTEIN-TYROSINE KINASES; RECEPTOR-BETA CHAIN; CYTOKINE RECEPTORS; IN-VIVO; KAPPA-B; C-FOS; PHOSPHORYLATION; ACTIVATION; GENE AB Interleukin-2 (IL-2) activates the receptor-associated Janus family tyrosine kinases, Jak1 and Jak3, which in turn phosphorylate and activate specific STAT proteins (signal transducers and activators of transcription), such as STATE. Activation of Jak and STAT proteins by IL-2 is transient and the mechanism for the subsequent down-regulation of their activity is largely unknown. We report here that IL-2-induced DNA-binding activity and tyrosine phosphorylation of STATE are stabilized by a proteasome inhibitor MG132; however, no detectable ubiquitination of the STAT proteins is observed. This sustained STATE activation can be blocked by protein kinase inhibitors, which is consistent with the ability of the proteasome inhibitor to stabilize IL-2-induced tyrosine phosphorylation of Jak1 and Jak3. These results suggest that proteasome-mediated protein degradation modulates protein-tyrosine phosphatase activity that negatively regulates the Jak-STAT signaling pathways. C1 DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 FU NIAID NIH HHS [AI-17258] NR 35 TC 98 Z9 100 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14017 EP 14020 DI 10.1074/jbc.272.22.14017 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200006 PM 9162019 ER PT J AU Sattler, M Salgia, R Shrikhande, G Verma, S Uemura, P Law, SF Golemis, EA Griffin, JD AF Sattler, M Salgia, R Shrikhande, G Verma, S Uemura, P Law, SF Golemis, EA Griffin, JD TI Differential signaling after beta 1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-CBL PROTOONCOGENE; ABL TYROSINE KINASE; PROTEIN PRODUCT; SH3 DOMAIN; JURKAT CELLS; FACTOR C3G; V-CBL; RECEPTOR; PHOSPHORYLATION; IDENTIFICATION AB CRKL is an SH2-SH3-SH3 adapter protein that is a major substrate of the BCR/ABL oncogene, The function of CRKL in normal cells is unknown, In cells transformed by BCR/ABL we have previously shown that CRKL is associated with two focal adhesion proteins, tensin and paxillin, suggesting that CRKL, could be involved in integrin signaling, In two hematopoietic cell lines, MO7e and H9, we found that CRKL rapidly associates with tyrosine-phosphorylated proteins after cross-linking of beta 1 integrins with fibronectin or anti-beta 1 integrin monoclonal antibodies, The major tyrosine-phosphorylated CRKL-binding protein in the megakaryocytic MO7e cells was identified as p120(CBL), the cellular homolog of the v-Cbl oncoprotein, However in the lymphoid He cell line, the major tyrosine-phosphorylated CRKL-binding protein was p110(HEF1), In both cases, this binding was mediated by the CRKL SH2 domain, Interestingly, although both MO7e and H9 cells express p120(CBL) and p110(HEF1), beta 1 integrin cross-linking induces tyrosine phosphorylation of p120(CBL) (but not p110(HEF1)) in MO7e cells and of p110(HEF1) (but not p120(CBL)) in H9 cells, In both cell types, CRKL is constitutively complexed to C3G, SOS, and c-ABL through its SH3 domains, and the stoichiometry of these complexes does not change upon integrin ligation, Thus, in different cell types CRKL and its SH3-associated proteins may form different multimeric complexes depending on whether p120(CBL) or p110(HEF1) is tyrosine-phosphorylated after integrin ligation, The shift in association of CRKL and its SH3-associated proteins from p120(CBL) to p110(HEF1) could contribute to different functional outcomes of ''outside-in'' integrin signaling in different cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. FU NCI NIH HHS [CA60821, R29-CA63366] NR 52 TC 72 Z9 73 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 30 PY 1997 VL 272 IS 22 BP 14320 EP 14326 DI 10.1074/jbc.272.22.14320 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB492 UT WOS:A1997XB49200054 PM 9162067 ER PT J AU Carter, EA Tompkins, RG Hsu, HB Christian, B Alpert, NM Weise, S Fischman, AJ AF Carter, EA Tompkins, RG Hsu, HB Christian, B Alpert, NM Weise, S Fischman, AJ TI Metabolic alterations in muscle of thermally injured rabbits, measured by positron emission tomography SO LIFE SCIENCES LA English DT Article DE positron emission tomography; skeletal muscle; metabolism ID TUMOR-NECROSIS-FACTOR; OXYGEN-METABOLISM; INSULIN; INFECTION; BRAIN; O-15 AB The hypermetabolic inflammatory state that occurs after major trauma has been extensively studied at the whole body level, however, there is only limited information on metabolic changes in individual tissues. In this study, the effect of thermal injury on metabolic function of uninjured hind limb muscle of rabbits was measured noninvasively by positron emission tomography (PET). Rabbits were subjected to full thickness burn on 25% of their body surface area. Two to three weeks after injury, PET and arterial blood sampling was performed during inhalation of O-15(2), (CO2)-O-15 and (CO)-C-11 and after injection of (18)FDG. The tissue and blood data were analyzed by standard kinetic models for blood flow, oxygen extraction fraction (OEF), oxygen utilization and glucose metabolism. A total of seven injured and five sham animals were studied. Total body oxygen consumption was measured by indirect calorimetry and plasma concentrations of glucose, insulin and IGF-I were measured with standard assays. Compared to sham rabbits, blood flow to muscle of injured animals was unchanged. However, OEF, oxygen utilization and glucose metabolism were significantly reduced (p<0.01) in uninjured muscle of burned rabbits. These data demonstrate that thermal injury is associated with alterations in muscle metabolism, which are not related to change in blood flow. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RP Carter, EA (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT GASTROINTESTINAL UNIT,DEPT SURG,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [P50-GM21700] NR 23 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAY 30 PY 1997 VL 61 IS 1 BP 39 EP 44 DI 10.1016/S0024-3205(97)00355-X PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA XC738 UT WOS:A1997XC73800005 PM 9200667 ER PT J AU Belisle, JT Vissa, VD Sievert, T Takayama, K Brennan, PJ Besra, GS AF Belisle, JT Vissa, VD Sievert, T Takayama, K Brennan, PJ Besra, GS TI Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis SO SCIENCE LA English DT Article ID CYCLOPROPANATED MYCOLIC ACIDS; PROTEINS; IDENTIFICATION; BIOSYNTHESIS; ETHAMBUTOL; SEQUENCE; COMPLEX; TARGET AB The dominant exported proteins and protective antigens of Mycobacterium tuberculosis are a triad of related gene products called the antigen 85 (Ag85) complex. Each has also been implicated in disease pathogenesis through its fibronectin-binding capacities, A carboxylesterase domain was found within the amino acid sequences of Ag85A, B, and C, and each protein acted as a mycolyltransferase involved in the final stages of mycobacterial cell wall assembly, as shown by direct enzyme assay and site-directed mutagenesis. Furthermore, the use of an antagonist (6-azido-6-deoxy-alpha,alpha'-trehalose) of this activity demonstrates that these proteins are essential and potential targets for new antimycobacterial drugs. C1 UNIV WISCONSIN, WILLIAM S MIDDLETON MEM VET HOSP, MYCOBACTERIOL RES LAB, MADISON, WI 53705 USA. RP COLORADO STATE UNIV, DEPT MICROBIOL, FT COLLINS, CO 80523 USA. RI Belisle, John/B-8944-2017; OI Belisle, John/0000-0002-2539-2798; Besra, Gurdyal/0000-0002-5605-0395 FU NIAID NIH HHS [AI-18357, AI-35220, AI-38087] NR 32 TC 427 Z9 463 U1 6 U2 39 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAY 30 PY 1997 VL 276 IS 5317 BP 1420 EP 1422 DI 10.1126/science.276.5317.1420 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB533 UT WOS:A1997XB53300051 PM 9162010 ER PT J AU Jeltsch, M Kaipainen, A Joukov, V Meng, XJ Lakso, M Rauvala, H Swartz, M Fukumura, D Jain, RK Alitalo, K AF Jeltsch, M Kaipainen, A Joukov, V Meng, XJ Lakso, M Rauvala, H Swartz, M Fukumura, D Jain, RK Alitalo, K TI Hyperplasia of lymphatic vessels in VEGF-C transgenic mice SO SCIENCE LA English DT Article ID RECEPTOR TYROSINE KINASE; GROWTH-FACTOR; ENDOTHELIAL-CELLS; EXPRESSION; GENE; FLT4; ANGIOGENESIS; FLK-1; TIE AB No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia of the lymphatic vasculature, which is involved in the draining of interstitial fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play a role in disorders involving the lymphatic system and may be of potential use in therapeutic lymphangiogenesis. C1 UNIV HELSINKI, HAARTMAN INST, MOL CANC BIOL LAB, SF-00014 HELSINKI, FINLAND. UNIV HELSINKI, INST BIOTECHNOL, HELSINKI 00014, FINLAND. MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Swartz, Melody/F-9563-2011; Jeltsch, Michael/I-5340-2012; Alitalo, Kari/J-5013-2014 OI Jeltsch, Michael/0000-0003-2890-7790; Alitalo, Kari/0000-0002-7331-0902 NR 30 TC 861 Z9 929 U1 2 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 30 PY 1997 VL 276 IS 5317 BP 1423 EP 1425 DI 10.1126/science.276.5317.1423 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB533 UT WOS:A1997XB53300052 PM 9162011 ER PT J AU Kim, SJ Kahn, CR AF Kim, SJ Kahn, CR TI Insulin stimulates p70 S6 kinase in the nucleus of cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; 2 ISOFORMS; ACTIVATION; RAPAMYCIN; PHOSPHORYLATION; LOCALIZATION; WORTMANNIN; P70(S6K); P85(S6K) AB Insulin action on both cytoplasmic and nuclear processes is dependent on activation of p70 S6 kinase (p70(S6K)). In CHO cells expressing human insulin receptors, Western blotting revealed the presence of p70(S6K) in the cell. nucleus at a level of about 32 % of that in the cytoplasm. Following insulin treatment, there was a retardation in mobility nuclear p70(S6K) in SDS-PAGE indicative of a change in phosphorylation of the enzyme, but no change in the amount of enzyme, Stimulation was maximal after 10 min of insulin treatment and decreased gradually at 30 min, There was also a rapid doubling of nuclear p70(S6K) activity in immunocomplex assays followed by a return to baseline by 30 min. Simultaneously, insulin stimulated cytoplasmic p70(S6K) by almost 10-fold at 10 min, and activity remained high up to 30 min. Tetradecanoylphorbol acetate (TPA) and fetal calf serum also stimulated nuclear p70(S6K) as judged by gel mobility shift, TPA also promoted a decrease in cytosolic p70(S6K) and an increase in nuclear enzyme suggestive of translocation of the enzyme, Rapamycin, a selective inhibitor of p70(S6K), an the casein kinase II inhibitor DRB blocked insulin-stimulated nuclear and cytosolic p70(S6K). Thus, nuclear p70(S6K) is regulated by insulin, serum and TPA. The insulin effect is downstream of rapamycin and DRB-sensitive targets and occurs without translocation of the enzyme. (C) 1997 Academic Press. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIDDK NIH HHS [DK 33201, P30 DK36836] NR 29 TC 38 Z9 38 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 MAY 29 PY 1997 VL 234 IS 3 BP 681 EP 685 DI 10.1006/bbrc.1997.6699 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XC939 UT WOS:A1997XC93900029 PM 9175775 ER PT J AU Shafman, T Khanna, KK Kedar, P Spring, K Kozlov, S Yen, T Hobson, K Gatei, M Zhang, N Watters, D Egerton, M Shiloh, Y Kharbanda, S Kufe, D Lavin, MF AF Shafman, T Khanna, KK Kedar, P Spring, K Kozlov, S Yen, T Hobson, K Gatei, M Zhang, N Watters, D Egerton, M Shiloh, Y Kharbanda, S Kufe, D Lavin, MF TI Interaction between ATM protein and c-Abl in response to DNA damage SO NATURE LA English DT Article ID ATAXIA-TELANGIECTASIA CELLS; IONIZING-RADIATION; TYROSINE KINASE; RADIOSENSITIVITY; INDUCTION; GENE; P53 AB The gene mutated in the autosomal recessive disorder ataxia telangiectasia (AT), designated ATM (for 'AT mutated'), is a member of a family of phosphatidylinositol-3-kinase-like enzymes that are involved in cell-cycle control, meiotic recombination, telomere length monitoring and DNA-damage response(1-4). Previous results have demonstrated that AT cells are hypersensitive to ionizing radiation(5-7) and are defective at the G1/S checkpoint after radiation damage(8-10). Because cells lacking the protein tyrosine kinase c-Abl are also defective in radiation-induced G1 arrest(11), we investigated the possibility that ATM might interact with c-Abl in response to radiation damage. Here we show that ATM binds c-Abl constitutively in control cells but not in AT cells. Our results demonstrate that the SH3 domain of c-Abl interacts with a DPAPNPPHFP motif (residues 1,373-1,382) of ATM. The results also reveal that radiation-induction of c-Abl tyrosine kinase activity is diminished in AT cells. These findings indicate that ATM is involved in the activation of c-Abl by DNA damage and this interaction may in part mediate radiation-induced G1 arrest. C1 QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. UNIV QUEENSLAND,ROYAL BRISBANE HOSP,DEPT SURG,BRISBANE,QLD 4029,AUSTRALIA. DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 RAMAT AVIV,ISRAEL. RI Watters, Dianne/E-6007-2010; Lavin, Martin/F-5961-2014; Kozlov, Sergei/M-2067-2014; OI Watters, Dianne/0000-0002-2555-5825; Lavin, Martin/0000-0002-5940-4769; Kozlov, Sergei/0000-0001-6183-7339; Yen, Tim/0000-0003-2159-0997 NR 26 TC 365 Z9 372 U1 1 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 29 PY 1997 VL 387 IS 6632 BP 520 EP 523 DI 10.1038/387520a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB479 UT WOS:A1997XB47900053 PM 9168117 ER PT J AU Hiyama, H Iavarone, A LaBaer, J Reeves, SA AF Hiyama, H Iavarone, A LaBaer, J Reeves, SA TI Regulated ectopic expression of cyclin D1 induces transcriptional activation of the cdk inhibitor p21 gene without altering cell cycle progression SO ONCOGENE LA English DT Article DE cyclin D1; p21; E2F; cell cycle; transcription; tetracycline ID HUMAN BREAST-CARCINOMA; WILD-TYPE P53; RETINOBLASTOMA PROTEIN; KINASE-ACTIVITY; DEPENDENT KINASES; MAMMALIAN-CELLS; GROWTH ARREST; IN-VIVO; G(1); E2F AB Cyclin D1 plays a key regulatory role during the G(1) phase of the cell cycle and its gene is amplified and overexpressed in many cancers. To address the relationship between cyclin D1 and other cell cycle regulatory proteins, we established human glioma and rodent fibroblast cell lines in which cyclin D1 expression could be regulated ectopically with tetracycline. In both of these cell lines, we found that ectopic expression of cyclin D1 in asynchronously growing cells was accompanied by increased levels of the p53 tumor suppressor protein and the cyclin/cdk inhibitor p21. Despite the induction of these cell cycle inhibitory proteins, cyclin D1-associated cdk kinase remained activated and the cells grew essentially like that of the parent cells. Although growth parameters were unchanged in these cells, morphological changes were clearly identifiable and anchorage independent growth was observed in NIH3T3 cells. In a first step toward elaborating the mechanism for cyclin D1-mediated induction of p21 gene expression we show that co-expression of E2F-1 and DP-1 can specifically transactivate the p21 promoter. In support of these findings and a direct effect of E2F on induction of p21 gene expression a putative E2F binding site was identified within the p21 promoter. In summary, our results demonstrate that ectopic expression of cyclin D1 can induce gene expression of the cdk inhibitor p21 through an E2F mechanism the consequences of which are not to growth arrest tells but possibly to stabilize cyclin D1/cdk function. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,NEUROSURG SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NR 69 TC 84 Z9 84 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 29 PY 1997 VL 14 IS 21 BP 2533 EP 2542 DI 10.1038/sj.onc.1201080 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XA949 UT WOS:A1997XA94900005 PM 9191053 ER PT J AU Wong, H Yang, D Hill, JS Davis, RC Nikazy, J Schotz, MC AF Wong, H Yang, D Hill, JS Davis, RC Nikazy, J Schotz, MC TI A molecular biology-based approach to resolve the subunit orientation of lipoprotein lipase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR-RELATED PROTEIN; HEPATIC LIPASE; TERMINAL DOMAIN; HEPARIN-BINDING; ENZYME-ACTIVITY; MUTAGENESIS; IDENTIFICATION; INACTIVATION; CATABOLISM; RESIDUES AB The subunit orientation of a dimeric enzyme influences the mechanism of action and function, To determine the subunit arrangement of lipoprotein lipase (LPL), a molecular biology-based approach was initiated, An eight amino acid linker region was engineered between two LPL monomers and expressed in COS-7 cells, The resultant tandem-repeat molecule (LPLTR) was lipolytically active and had kinetic parameters, salt inhibition, cofactor-dependent activity, heparin-binding characteristics, and a functional unit size very similar to the expressed native human enzyme, By these criteria, LPLTR was the functional equivalent of native LPL. Considering the length of the linker peptide (no more than 24 Angstrom), monomers in the tethered molecule were restricted to a head-to-tail subunit arrangement, Since LPLTR demonstrated native enzyme-like properties while constrained to this subunit arrangement, these results provide the first compelling evidence that native LPL monomers are arranged in a head-to-tail subunit orientation within the active dimer, Thus, LPL function in physiology, lipolysis, and binding to cell-surface components must now be addressed with this subunit orientation in mind, The utility of the tandem-repeat approach to resolve the subunit arrangement of an obligate dimer has been demonstrated with LPL and could be generalized for use with other oligomeric enzymes. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. RP Wong, H (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,BLDG 113,ROOM 312,LOS ANGELES,CA 90073, USA. FU NHLBI NIH HHS [P01 HL028481, HL28481] NR 33 TC 48 Z9 50 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 1997 VL 94 IS 11 BP 5594 EP 5598 DI 10.1073/pnas.94.11.5594 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB711 UT WOS:A1997XB71100022 PM 9159117 ER PT J AU Scully, R Anderson, SF Chao, DM Wei, WJ Ye, LY Young, RA Livingston, DM Parvin, JD AF Scully, R Anderson, SF Chao, DM Wei, WJ Ye, LY Young, RA Livingston, DM Parvin, JD TI BRCA1 is a component of the RNA polymerase II holoenzyme SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OVARIAN-CANCER; BINDING PROTEIN; TRANSCRIPTION; BREAST; ACTIVATION; INVITRO; YY1 AB The familial breast-ovarian tumor suppressor gene product BRCA1 was found to be a component of the RNA polymerase II holoenzyme by several criteria, BRCA1 was found to copurify with the holoenzyme over multiple chromatographic steps. Other tested transcription activators that could potentially contact the holoenzyme were not stably associated with the holoenzyme as determined by copurification. Antibody specific for the holoenzyme component hSRB7 specifically purifies BRCA1, Immunopurification of BRCA1 complexes also specifically purifies transcriptionally active RNA polymerase II and transcription factors TFIIF, TFIIE, and TFIIH. Moreover, a BRCA1 domain, which is deleted in about 90% of clinically relevant mutations, participates in binding to the holoenzyme complex in cells. These data are consistent with recent data identifying transcription activation domains in the BRCA1 protein and link the BRCA1 tumor suppressor protein with the transcription process as a holoenzyme-bound protein. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV MOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MIT,WHITEHEAD INST BIOL RES,CAMBRIDGE,MA 02142. RI Parvin, Jeffrey/C-8955-2009; Young, Richard/F-6495-2012; Scully, Ralph/F-5008-2013 OI Young, Richard/0000-0001-8855-8647; FU NIGMS NIH HHS [GM-53504, R01 GM053504] NR 32 TC 355 Z9 362 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 1997 VL 94 IS 11 BP 5605 EP 5610 DI 10.1073/pnas.94.11.5605 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB711 UT WOS:A1997XB71100024 PM 9159119 ER PT J AU Zhang, M Magit, D Sager, R AF Zhang, M Magit, D Sager, R TI Expression of maspin in prostate cells is regulated by a positive Ets element and a negative hormonal responsive element site recognized by androgen receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAMMARY EPITHELIAL-CELLS; ALLELIC LOSS; GENE; CANCER; PEA3; AP-1; TRANSCRIPTION; CARCINOMA; DELETION AB Prostate cancer is the most common cancer in men. The molecular mechanisms leading to its development are poorly understood. Maspin is a tumor-suppressing serpin expressed in normal breast and prostate epithelium. We have found that expression of maspin in normal and carcinoma derived prostate epithelial cells is differentially regulated at the transcriptional level. We have identified two different kinds of cis elements, Ets and hormonal responsive element (HRE), in the maspin promoter. The Ets element is active in regulating maspin expression in normal prostate epithelial cells but inactive in tumor cells. The HRE site is a negative element that is active in both cell types. This negative DNA sequence can repress a heterologous promoter recognized by the androgen receptor. We conclude that expression of maspin is under the influence of both a positive Ets and a negative HRE element. Loss of maspin expression during tumor progression apparently results from both the absence of transactivation through the Ets element and the presence of transcription repression through the negative HRE element recognized by androgen receptor. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 61253, 5-T32-CA09361, T32 CA009361] NR 30 TC 113 Z9 119 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 1997 VL 94 IS 11 BP 5673 EP 5678 DI 10.1073/pnas.94.11.5673 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XB711 UT WOS:A1997XB71100036 PM 9159131 ER PT J AU Ren, JM Finklestein, SP AF Ren, JM Finklestein, SP TI Time window of infarct reduction by intravenous basic fibroblast growth factor in focal cerebral ischemia SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE bFGF (basic fibroblast growth factor); cerebral ischemia, focal ID HIPPOCAMPAL-NEURONS; BLOOD-FLOW; SIZE; GLUTAMATE; STROKE; SYSTEM; MODEL; ROLES; RATS AB Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide with potent trophic and protective effects on brain neurons, glia and endothelia. In previous studies, we showed that intravenously administered bFGF reduced the volume of cerebral infarcts following permanent occlusion of the middle cerebral artery in rats. In the current study, we examined the time dependence of bFGF infusion on infarct reduction, and the effect of co-infusion of bFGF with heparin. We found a significant reduction in infarct volume when the bFGF infusion (50 mu g/kg per h for 3 h) was begun up to 3 h, but not 4 h after the onset of ischemia. The infarct reducing effects of bFGF were not altered by co-infusion of heparin. These results are potentially important in light of the ongoing clinical trials of intravenous bFGF in acute stroke. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,CNS,GROWTH FACTOR RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NINDS NIH HHS [NS-10828] NR 25 TC 55 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 26 PY 1997 VL 327 IS 1 BP 11 EP 16 DI 10.1016/S0014-2999(97)89672-0 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XC564 UT WOS:A1997XC56400002 PM 9185830 ER PT J AU Zhang, LX Wang, HN Liu, D Liddington, R Fu, HA AF Zhang, LX Wang, HN Liu, D Liddington, R Fu, HA TI Raf-1 kinase and exoenzyme S interact with 14-3-3 zeta through a common site involving lysine 49 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; PSEUDOMONAS-AERUGINOSA; IN-VITRO; 14-3-3-PROTEINS; ACTIVATION; ASSOCIATION; BRAIN; IDENTIFICATION; PURIFICATION AB 14-3-3 proteins are a family of conserved dimeric molecules that bind to a range of cellular proteins involved in signal transduction and oncogenesis. Our solution of the crystal structure of 14-3-3 zeta revealed a conserved amphipathic groove that may allow the association of 14-3-3 with diverse ligands (Liu, D., Bienkowska, J., Petosa, C., Collier, R. J., Fu, H., and Liddington, R. (1995) Nature 376, 191-194). Here, the contributions of three positively charged residues (Lys-49, Arg-56, and Arg-60) that lie in this Raf-binding groove were investigated. Two of the charge-reversal mutations greatly (K49E) or partially (R56E) decreased the interaction of 14-3-3 zeta with Raf-1 kinase, whereas R60E showed only subtle effects on the binding. Interestingly, these mutations exhibited similar effects on the functional interaction of 14-3-3 zeta with another target protein, exoenzyme S (ExoS), an ADP-ribosyltransferase from Pseudomonas aeruginosa. The EC50 values of 14-3-3 zeta required for ExoS activation increased by similar to 110-, 5-, and 2-fold for the K49E, R56E, and R60E mutants, respectively. The drastic reduction of 14-3-3 zeta ligand affinity by the K49E mutation is due to a local electrostatic effect, rather than the result of a gross structural alteration, as evidenced by partial proteoIysis and circular dichroism analysis. This work identifies the first point mutation (K49E) that dramatically disrupts 14-3-5 zeta ligand interactions. The parallel effects of this single point mutation on both Raf-1 binding and ExoS activation strongly suggest that diverse associated proteins share a common structural binding determinant on 14-3-3 zeta. C1 EMORY UNIV,SCH MED,DEPT PHARMACOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,GRAD PROGRAM CELL & DEV BIOL,ATLANTA,GA 30322. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV LEICESTER,DEPT BIOCHEM,LEICESTER LE1 7RH,LEICS,ENGLAND. FU NIGMS NIH HHS [GM53165] NR 53 TC 114 Z9 116 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 1997 VL 272 IS 21 BP 13717 EP 13724 DI 10.1074/jbc.272.21.13717 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200039 PM 9153224 ER PT J AU Bickel, PE Scherer, PE Schnitzer, JE Oh, P Lisanti, MP Lodish, HF AF Bickel, PE Scherer, PE Schnitzer, JE Oh, P Lisanti, MP Lodish, HF TI Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GPI-ANCHORED PROTEINS; MOLECULAR-CLONING; LINKED PROTEIN; CELL-SURFACE; TRANSPORT; ADIPOCYTES; SUBDOMAINS; VESICLES; RECEPTOR; DOMAINS AB Caveolae are plasmalemmal microdomains that are involved in vesicular trafficking and signal transduction. We have sought to identify novel integral membrane proteins of caveolae. Here we describe the identification and molecular cloning of flotillin. By several independent methods, flotillin behaves as a resident integral membrane protein component of caveolae. Furthermore, we have identified epidermal surface antigen both as a flotillin homologue and as a resident caveolar protein. Significantly, flotillin is a marker for the Triton-insoluble, buoyant membrane fraction in brain, where to date mRNA species for known caveolin gene family members have not been detected. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,DEPT MED,DIABET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02215. BETH ISRAEL HOSP,BOSTON,MA 02215. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. RI Lisanti, Michael/C-6866-2013 FU NHLBI NIH HHS [HL43278]; NIDDK NIH HHS [DK02219, DK47618] NR 43 TC 416 Z9 429 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 MAY 23 PY 1997 VL 272 IS 21 BP 13793 EP 13802 DI 10.1074/jbc.272.21.13793 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XA062 UT WOS:A1997XA06200050 PM 9153235 ER PT J AU Lee, MM Donahoe, PK Silverman, BL Hasegawa, T Hasegawa, Y Gustafson, ML Chang, YC MacLaughlin, DT AF Lee, MM Donahoe, PK Silverman, BL Hasegawa, T Hasegawa, Y Gustafson, ML Chang, YC MacLaughlin, DT TI Measurements of serum Mullerian inhibiting substance in the evaluation of children with nonpalpable gonads SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 1996 Annual Meeting of the Pediatric-Academic-Societies CY MAY 05-10, 1996 CL WASHINGTON, D.C. SP Pediat Acad Soc ID HCG STIMULATION; HORMONE; CRYPTORCHIDISM; TESTOSTERONE; IMMUNOASSAY; BOYS; DIAGNOSIS; ANORCHISM; INTERSEX; INFANTS AB Background Mullerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the mullerian ducts during normal male sexual differentiation. In children with virilization and nonpalpable gonads, only those with testicular tissue should have detectable serum concentrations of mullerian inhibiting substance. Methods We measured serum mullerian inhibiting substance in 65 children with virilization at birth and nonpalpable gonads (age at diagnosis, 2 days to 11 years) and serum testosterone in 54 of them either after the administration of human chorionic gonadotropin or during the physiologic rise in testosterone that occurs in normal infants. Results The mean (+/-SD) serum mullerian inhibiting substance concentration in the 17 children with no testicular tissue was 0.7+/-0.5 ng per milliliter, as compared with 37.5+/-39.6 ng per milliliter in the 48 children with testes (P < 0.001). In the latter group, the mean values in the 14 children with abnormal testes and the 34 with normal testes were 11.5+/-11.8 and 48.2+/-42.1 ng per milliliter, respectively (P < 0.001). The sensitivity and specificity of the serum mullerian inhibiting substance assay for detecting the absence of testicular tissue were 92 percent and 98 percent, respectively, as compared with 69 percent and 83 percent for the measurement of serum testosterone. Furthermore, measurement of serum mullerian inhibiting substance was more sensitive than serum testosterone measurement for the identification of children with abnormal testes (67 percent vs. 25 percent), whereas the specificity of the two tests was similar. Conclusions Measurements of serum mullerian inhibiting substance can be used to determine testicular status in prepubertal children with nonpalpable gonads, thus differentiating anorchia from undescended testes in boys with bilateral cryptorchidism and serving as a measure of testicular integrity in children with intersexual anomalies. (C) 1997, Massachusetts Medical Society. C1 MASSACHUSETTS GEN HOSP, MED PRACTICES EVALUAT CTR, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, PEDIAT SURG RES LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. CHILDRENS MEM HOSP, DEPT PEDIAT ENDOCRINOL & DIABET, CHICAGO, IL 60614 USA. NW MED SCH, CHICAGO, IL USA. TOKYO METROPOLITAN KIYOSE CHILDRENS HOSP, DIV ENDOCRINOL & METAB, TOKYO, JAPAN. RP Lee, MM (reprint author), MASSACHUSETTS GEN HOSP, PEDIAT ENDOCRINE UNIT, ACC 709, BOSTON, MA 02114 USA. RI Hasegawa, Tomonobu/L-3331-2013 FU NCI NIH HHS [CA 17393]; NICHD NIH HHS [2F32HD07435]; NIDDK NIH HHS [DK-02129] NR 33 TC 89 Z9 96 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 22 PY 1997 VL 336 IS 21 BP 1480 EP 1486 DI 10.1056/NEJM199705223362102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WZ767 UT WOS:A1997WZ76700002 PM 9154766 ER PT J AU Li, A Baba, TW Sodroski, J ZollaPazner, S Gorny, MK Robinson, J Posner, MR Katinger, H Barbas, CF Burton, DR Chou, TC Ruprecht, RM AF Li, A Baba, TW Sodroski, J ZollaPazner, S Gorny, MK Robinson, J Posner, MR Katinger, H Barbas, CF Burton, DR Chou, TC Ruprecht, RM TI Synergistic neutralization of a chimeric SIV/HIV type 1 virus with combinations of human Anti-HIV type 1 envelope monoclonal antibodies or hyperimmune globulins SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 BINDING-SITE; CD4-BINDING SITE; RHESUS-MONKEYS; V3 DOMAIN; GP120; INFECTION; SEQUENCE; VARIANTS; MACAQUES AB A panel of 14 human IgG monoclonal antibodies (MAbs) specific for envelope antigens of the human immunodeficiency virus type 1 (HIV-1), 2 high-titer human anti-HIV-1 immunoglobulin (HIVIG) preparations, and 15 combinations of MAbs or MAb/HIVIG were tested for their ability to neutralize infection of cultured human T cells (MT-2) with a chimeric simian immunodeficiency virus (SHIV-vpu(+)), which expressed HIV-1 IIIB envelope antigens, Eleven MAbs and both HIVIGs were neutralizing, When used alone, the anti-CD4-binding site MAb b12, the anti-gp41 MAb 2F5, and the anti-gp120 MAb 2G12 were the most potent, When combination regimens involving two MAbs targeting different epitopes were tested, synergy was seen in all paired MAbs, except for one combination that revealed additive effects, The lowest effective antibody concentration for 50% viral neutralization (EC50) and EC90 were achieved with combinations of MAbs b12, 2F5, 2G12, and the anti-V3 MAb 694/98D, Depending on the combination regimen, the concentration of MAbs required to reach 90% virus neutralization was reduced approximately 2- to 25-fold as compared to the dose requirement of individual MAbs to produce the same effect, Synergy of the combination regimens implies that combinations of antibodies may have a role in passive immunoprophylaxis against HIV-1, The ability of SHIV to replicate in rhesus macaques will allow us to test such approaches in vivo. C1 DANA FARBER CANC INST, LAB VIRAL PATHOGENESIS, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. TUFTS UNIV, SCH MED, DEPT PEDIAT, DIV NEWBORN MED, BOSTON, MA 02111 USA. DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. VET AFFAIRS MED CTR, RES CTR AIDS & HIV INFECT, NEW YORK, NY 10010 USA. NYU, MED CTR, DEPT PATHOL, NEW YORK, NY 10016 USA. TULANE UNIV, MED CTR, DEPT PEDIAT, NEW ORLEANS, LA 70112 USA. HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, DIV HEMATOL, BOSTON, MA 02215 USA. HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, DEPT MED, BOSTON, MA 02215 USA. UNIV AGR VIENNA, INST APPL MICROBIOL, A-1190 VIENNA, AUSTRIA. Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. Scripps Res Inst, DEPT MOL BIOL, LA JOLLA, CA 92037 USA. MEM SLOAN KETTERING CANC CTR, BIOCHEM PHARMACOL LAB, NEW YORK, NY 10021 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NIAID NIH HHS [1R01 AI34266, 1R01 AI33832, 1R01 AI35478] NR 40 TC 51 Z9 51 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 20 PY 1997 VL 13 IS 8 BP 647 EP 656 DI 10.1089/aid.1997.13.647 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WZ648 UT WOS:A1997WZ64800002 PM 9168233 ER PT J AU Narula, J DiSalvo, TG Williams, W Kaufman, J Dec, GW Semigran, M AF Narula, J DiSalvo, TG Williams, W Kaufman, J Dec, GW Semigran, M TI An 'ACE' of a test SO CIRCULATION LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 20 PY 1997 VL 95 IS 10 BP 2456 EP 2457 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WZ212 UT WOS:A1997WZ21200023 PM 9170411 ER PT J AU Muruve, DA Nicolson, AG Manfro, RC Strom, TB Sukhatme, VP Libermann, TA AF Muruve, DA Nicolson, AG Manfro, RC Strom, TB Sukhatme, VP Libermann, TA TI Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after systemic administration and apoptosis of ex vivo-infected pancreatic islet allografts and isografts SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT ADENOVIRUS; CD95 LIGAND; ANTIGEN; MICE; REJECTION; DISEASE; DNA AB Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expressed on a limited number of tissues, predominantly activated T lymphocytes, We describe the construction and biological activity of a replication-deficient type-5 adenovirus encoding murine Fast under the control of the cytomegalovirus (CMV) promoter (adCMV-FasL). In vitro, Jurkat cells undergo apoptosis when co-incubated with adCMV-FasL-infected COS cells, Systemic administration of adCMV-FasL to Wistar rats or DBA/2J mice results in widespread hepatic apoptosis and death in a dose-dependent manner within 72 hr, an effect not seen in lpr mice, or animals administered equivalent doses of adCMV-beta gal. Murine pancreatic islets also undergo apoptosis when infected ex vivo with adCMV-FasL, resulting in uniform primary nonfunction when transplanted into syngeneic or allogeneic diabetic recipients, These results indicate that adCMV-FasL is a potentially useful tool to study Fas/FasL biology. C1 BETH ISRAEL DEACONNESS MED CTR,DIV IMMUNOL,BOSTON,MA 02215. BETH ISRAEL DEACONNESS MED CTR,DIV NEPHROL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RI Libermann, Towia/F-9866-2010; Manfro, Roberto/M-8250-2014 FU NIDDK NIH HHS [DK51060] NR 27 TC 68 Z9 71 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY 20 PY 1997 VL 8 IS 8 BP 955 EP 963 DI 10.1089/hum.1997.8.8-955 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XC072 UT WOS:A1997XC07200008 PM 9195218 ER PT J AU Niemz, MH Lin, CP Pitsillides, C Cui, J Doukas, AG Deutsch, TF AF Niemz, MH Lin, CP Pitsillides, C Cui, J Doukas, AG Deutsch, TF TI Laser-induced generation of pure tensile stresses SO APPLIED PHYSICS LETTERS LA English DT Article ID ABLATION; SOLIDS; SPALL AB While short compressive stresses can readily be produced by laser ablation, the generation of pure tensile stresses is more difficult. We demonstrate that a 90 degrees prism made of polyethylene can serve to produce short and pure tensile stresses. A compressive wave is generated by ablating a thin layer of strongly absorbing ink on one surface of the prism with a e-switched frequency-doubled Nd:YAG laser. The compressive wave driven into the prism is reflected as a tensile were by the polyethylene-air interface at its long surface. The low acoustic impedance of polyethylene makes it ideal for coupling tensile stresses into liquids, In water, tensile stresses up to -200 bars with a rise time of the order of 20 ns and a duration of 100 ns are achieved. The tensile strength of water is determined for pure tensile stresses lasting for 100 ns only. The technique has potential application in studying the initiation of cavitation in liquids and in comparing the effect of compressive and tensile stress transients on biological media. (C) 1997 American Institute of Physics. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 18 TC 1 Z9 1 U1 1 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD MAY 19 PY 1997 VL 70 IS 20 BP 2676 EP 2678 DI 10.1063/1.118991 PG 3 WC Physics, Applied SC Physics GA WZ348 UT WOS:A1997WZ34800013 ER PT J AU Reppert, SM Weaver, DR AF Reppert, SM Weaver, DR TI Forward genetic approach strikes gold: Cloning of a mammalian Clock gene SO CELL LA English DT Review ID BEHAVIOR; MOUSE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Reppert, SM (reprint author), MASSACHUSETTS GEN HOSP,LAB DEV CHRONOBIOL,BOSTON,MA 02114, USA. OI Weaver, David/0000-0001-7941-6719 NR 17 TC 41 Z9 42 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 16 PY 1997 VL 89 IS 4 BP 487 EP 490 DI 10.1016/S0092-8674(00)80229-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WZ323 UT WOS:A1997WZ32300001 PM 9160739 ER PT J AU Lopes, UG Erhardt, P Yao, RJ Cooper, GM AF Lopes, UG Erhardt, P Yao, RJ Cooper, GM TI p53-dependent induction of apoptosis by proteasome inhibitors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; PROTEIN-DEGRADATION; CELL-DEATH; ACTIVATION; UBIQUITIN; P53; PATHWAY; COMPLEX; ALPHA AB Proteolysis by the ubiquitin/proteasome pathway controls the intracellular levels of a number of proteins that regulate cell proliferation and cell cycle progression, To determine whether this pathway of protein turnover was also linked to apoptosis, we treated Rat-1 and PC12 cells with specific proteasome inhibitors. The peptide aldehydes PSI and MG115, which specifically inhibit the chymotrypsin-like activity of the proteasome, induced apoptosis of both cell types, In contrast, apoptosis was not induced by inhibitors of lysosomal proteases or by an alcohol analog of PSI. The tumor suppressor p53 rapidly accumulated in cells treated with proteasome inhibitors, as did the p53-inducible gene products p21 and Mdm-2. In addition, apoptosis induced by proteasome inhibitors was inhibited by expression of dominant-negative p53, whereas overexpression of wild-type p53 was sufficient to induce apoptosis of Rat-1 cells in transient transfection assays. Although other molecules may also be involved, these results suggest that stabilization and accumulation of p53 plays a key role in apoptosis induced by proteasome inhibitors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Lopes, Ulisses/N-4416-2013 FU NCI NIH HHS [CA18689] NR 25 TC 405 Z9 410 U1 0 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 MAY 16 PY 1997 VL 272 IS 20 BP 12893 EP 12896 DI 10.1074/jbc.272.20.12893 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400004 PM 9148891 ER PT J AU Kho, CJ Huggins, GS Endege, WO Patterson, C Jain, MK Lee, ME Haber, E AF Kho, CJ Huggins, GS Endege, WO Patterson, C Jain, MK Lee, ME Haber, E TI The polymyositis-scleroderma autoantigen interacts with the helix-loop-helix proteins E12 and E47 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-STEP PURIFICATION; B-CELL DEVELOPMENT; NUCLEAR MATRIX; DNA-BINDING; MOLECULAR-CLONING; OVERLAP SYNDROMES; G(1) PROGRESSION; ESCHERICHIA-COLI; HOMEOBOX GENE; EXPRESSION AB The basic helix-loop-helix (bHLH) transcription factors E12 and E47 regulate cellular differentiation and proliferation in diverse cell types, While looking for proteins that bind to E12 and E47 by the yeast interaction trap, we isolated the rat (r) homologue of the human ih) polymyositis-scleroderma autoantigen (PM-Scl), which has been localized to the granular layer of the nucleolus and to distinct nucleocytoplasmic foci. The rPM-Scl and hPM-Scl homologues are 96% similar and 91% identical, We found that rPM-Scl mRNA expression was regulated by growth factor stimulation in cultured rat aortic smooth muscle cells, rPM-Scl bound to E12 and E47 but not to Id3, Gax, Myb, OCT-1, or Max. The C terminus of rPM-Scl (amino acids 283-353) interacted specifically with a 54-amino acid domain in E12 that is distinct from the bHLH domain, Finally, cotransfection of rPM-Scl and E47 specifically increased the promoter activity of a luciferase reporter construct containing an E box and did not affect the basal activity of the reporter construct, rPM-Scl appears to be a novel non-HLH-interacting partner of E12/E47 that regulates E2A protein transcription. C1 HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. FU NIGMS NIH HHS [R01GM 53249] NR 49 TC 12 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 16 PY 1997 VL 272 IS 20 BP 13426 EP 13431 DI 10.1074/jbc.272.20.13426 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400080 PM 9148967 ER PT J AU Craiu, A Gaczynska, M Akopian, T Gramm, CF Fenteany, G Goldberg, AL Rock, KL AF Craiu, A Gaczynska, M Akopian, T Gramm, CF Fenteany, G Goldberg, AL Rock, KL TI Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-ACTIVATING ENZYME; CELL-LINE; THERMOPLASMA-ACIDOPHILUM; PROTEOLYTIC PATHWAY; LYMPHOCYTES-T; EXPRESSION; PEPTIDES; GENES; GENERATION; MOLECULES AB The antibiotic lactacystin was reported to covalently modify beta-subunit X of the mammalian 20 S proteasome and inhibit several of its peptidase activities, However, we demonstrate that [H-3]lactacystin treatment modifies all the proteasome's catalytic beta-subunits. Lactacystin and its more potent derivative beta-lactone irreversibly inhibit protein breakdown and the chymotryptic, tryptic, and peptidylglutamyl activities of purified 20 S and 26 S particles, although at different rates, Exposure to these agents for 1 to 2 h reduced the degradation of short- and long-lived proteins in four different mammalian cell lines, Unlike peptide aldehyde inhibitors, lactacystin and the beta-lactone do not inhibit lysosomal degradation of an endocytosed protein, These agents block class I antigen presentation of a model protein, ovalbumin (synthesized endogenously or loaded exogenously), but do not affect presentation of the peptide epitope SIINFEKL, which does not require proteolysis for presentation. Generation of most peptides required for formation of stable class I heterodimers is also inhibited, Because these agents inhibited protein breakdown and antigen presentation similarly in interferon-gamma-treated cells (where proteasomes contain LMP2 and LMP7 subunits in place of X and Y), all beta-subunits must be affected similarly, These findings confirm our prior conclusions that proteasomes catalyze the bulk of protein breakdown in mammalian cells and generate the majority of class I-bound epitopes for immune recognition. C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,DEPT CHEM & BIOL CHEM,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 53 TC 326 Z9 331 U1 1 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 MAY 16 PY 1997 VL 272 IS 20 BP 13437 EP 13445 DI 10.1074/jbc.272.20.13437 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ384 UT WOS:A1997WZ38400082 PM 9148969 ER PT J AU Tsai, FY Orkin, SH AF Tsai, FY Orkin, SH TI Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation SO BLOOD LA English DT Article ID STEM-CELLS; P53; EXPRESSION; APOPTOSIS; GENE; MICE; CANCER; REGULATORS; SPECTRUM; SURVIVAL AB The zinc-finger transcription factor GATA-2 plays a critical role in maintaining the pool of early hematopoietic cells. To define its specific functions in the proliferation, survival, and differentiation of hematopoietic cells, we analyzed the hematopoietic potential of GATA-2(-/-) cells in in vitro culture systems for proliferation and maintenance of uncommitted progenitors or differentiation of specific lineages. From a two-step in vitro differentiation assay of embryonic stem cells and in vitro culture of yolk sac cells, we demonstrate that GATA-2 is required for the expansion of multipotential hematopoietic progenitors and the formation of mast cells, but dispensable for the terminal differentiation of erythroid cells and macrophages. The rare GATA-2(-/-) multipotential progenitors that survive proliferate poorly and generate small colonies with extensive cell death, implying that GATA-2 may play a role in both the proliferation and survival of early hematopoietic cells. To explore possible mechanisms resulting in the hematopoietic defects of GATA-2(-/-) cells, we interbred mutant mouse strains to assess the effects of p53 loss on the behavior of GATA-2(-/-) hematopoietic cells, Analysis of GATA-2(-/-)/p53(-/-) compound-mutant embryos shows that the absence of p53 partially restores the number of total GATA-2(-/-) hematopoietic cells, and therefore suggests a potential link between GATA-2 and p53 pathways. (C) 1997 by The American Society of Hematology. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. NR 36 TC 362 Z9 373 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1997 VL 89 IS 10 BP 3636 EP 3643 PG 8 WC Hematology SC Hematology GA XD976 UT WOS:A1997XD97600016 PM 9160668 ER PT J AU Hurwitz, SJ Terashima, M Mizunuma, N Slapak, CA AF Hurwitz, SJ Terashima, M Mizunuma, N Slapak, CA TI Vesicular anthracycline accumulation in Doxorubicin-selected U-937 cells: Participation of lysosomes SO BLOOD LA English DT Article ID RESISTANCE-ASSOCIATED PROTEIN; CONFERS MULTIDRUG-RESISTANCE; RED-BLOOD-CELLS; P-GLYCOPROTEIN; SUBCELLULAR-LOCALIZATION; MEMBRANE-GLYCOPROTEINS; MONOCLONAL-ANTIBODIES; DRUG RESISTANCE; LEUKEMIA-CELLS; CYTO-TOXICITY AB The U-A10 cell line, a doxorubicin-selected variant of human U-937 myeloid leukemia cells, exhibits a redistribution of anthracyclines into a expanded vesicular compartment. The acidic nature of this compartment was confirmed by vital staining with a pH sensitive dye, LysoSensor yellow/blue DND-160. Identification of the vesicular compartment was performed by immunofluorescence analysis. Staining for the LAMP-1 and LAMP-2 antigens showed that the vesicles are enlarged lysosomes that are eccentrically placed near the nucleus of U-A10 cells. By contrast, the expression of the multidrug resistance-associated protein and the P-glycoprotein wits observed predominately on the plasma membrane of the drug-resistant cells. The accumulation of daunorubicin into cellular compartments was quantified using radiolabeled drug. Exposing cells to (3)[H]-daunorubicin and then isolating intact nuclei showed that nuclei from U-A10 cells accumulated twofold to threefold less anthracycline than nuclei from U-937 cells, However, when nuclei were isolated first and then exposed to (3)[H]-daunorubicin, little difference in net nuclear drug accumulation was detected. Cytoplasts prepared from U-A10 and U-937 cells were exposed to (3)[H]daunorubicin to measure cytoplasmic drug accumulation. C1 DANA FARBER CANC INST, DIV CANC PHARMACOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 42 TC 89 Z9 93 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1997 VL 89 IS 10 BP 3745 EP 3754 PG 10 WC Hematology SC Hematology GA XD976 UT WOS:A1997XD97600028 PM 9160680 ER PT J AU Schultze, JL Seamon, MJ Michalak, S Gribben, JG Nadler, LM AF Schultze, JL Seamon, MJ Michalak, S Gribben, JG Nadler, LM TI Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMAS; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; B-CELLS; DENDRITIC CELLS; LYMPHOCYTES-T; CD28 RECEPTOR; BEARING MICE; IN-VITRO; NK CELLS AB Follicular lymphomas (FLs) rarely induce clinically significant T-cell-mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-gamma, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL-specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Schultze, JL (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,D742,BOSTON,MA 02115, USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 44 TC 77 Z9 79 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1997 VL 89 IS 10 BP 3806 EP 3816 PG 11 WC Hematology SC Hematology GA XD976 UT WOS:A1997XD97600036 PM 9160688 ER PT J AU Huff, V Amos, CI Douglass, EC Fisher, R Geiser, CF Krill, CE Li, FP Strong, LC McDonald, JM AF Huff, V Amos, CI Douglass, EC Fisher, R Geiser, CF Krill, CE Li, FP Strong, LC McDonald, JM TI Evidence for genetic heterogeneity in familial Wilms' tumor SO CANCER RESEARCH LA English DT Article ID DELETION; PREDISPOSITION; CHROMOSOME-11; ABNORMALITIES; LINKAGE; 11P13 AB Wilms' tumor (WT), a childhood kidney cancer, occurs both sporadically and, less frequently, in a familial context, Genetic linkage studies of several large WT families have excluded the one cloned WT gene, WT1, as the locus responsible for familial predisposition, These data demonstrate the existence of a familial predisposition gene distinct from WT1 and, more broadly, imply that the genetic etiology of WT is heterogenous, However, it has been unknown whether the predisposition observed in large WT families is also heterogenous or perhaps is due to mutations at a single locus. Recently, examination of a large French-Canadian WT family has demonstrated genetic linkage to 17q12-q21. We report here the results from a genetic linkage study of sis WT pedigrees. Analyses of genotype data from eight loci within the 17q12-q21 region in these families resulted in cumulative lod scores of <--4,0 through the region, thereby excluding linkage. The ability to rule out the 17q region as the site of a predisposition gene in several of these pedigrees individually demonstrates the existence of more than one gene that predisposes to WT in large pedigrees and again emphasizes that the etiology of WT is genetically heterogenous. C1 UNIV TEXAS, MD ANDERSON CANCER CTR, DEPT EPIDEMIOL, HOUSTON, TX 77030 USA. TEMPLE UNIV, ST CHRISTOPHERS HOSP CHILDREN, SCH MED, DEPT PEDIAT, PHILADELPHIA, PA 19134 USA. ST JUDE CHILDRENS RES HOSP, DEPT PATHOL & TUMOR CELL BIOL, MEMPHIS, TN 38101 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PEDIAT, SAN ANTONIO, TX 78284 USA. CHILDRENS HOSP, MED CTR, AKRON, OH 44308 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. RP Huff, V (reprint author), UNIV TEXAS, MD ANDERSON CANCER CTR, DEPT EXPT PEDIAT GENET, BOX 88, 1515 HOLCOMBE BLVD, HOUSTON, TX 77030 USA. FU NCI NIH HHS [CA60114, CA34936] NR 25 TC 24 Z9 24 U1 0 U2 1 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 MAY 15 PY 1997 VL 57 IS 10 BP 1859 EP 1862 PG 4 WC Oncology SC Oncology GA WZ216 UT WOS:A1997WZ21600009 PM 9157975 ER PT J AU Meroni, G Reymond, A Alcalay, M Borsani, G Tanigami, A Tonlorenzi, R LoNigro, C Messali, S Zollo, M Ledbetter, DH Brent, R Ballabio, A Carrozzo, R AF Meroni, G Reymond, A Alcalay, M Borsani, G Tanigami, A Tonlorenzi, R LoNigro, C Messali, S Zollo, M Ledbetter, DH Brent, R Ballabio, A Carrozzo, R TI Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor SO EMBO JOURNAL LA English DT Article DE bHLHZip proteins; Max-interacting proteins; Myc; sin3; transcriptional repressor ID HUMAN C-MYC; LOOP-HELIX PROTEIN; TUMOR-SUPPRESSOR GENE; CASEIN KINASE-II; DNA-BINDING; ACTIVATES TRANSCRIPTION; N-MYC; NEOPLASTIC TRANSFORMATION; TUMORIGENIC CONVERSION; NUCLEAR-LOCALIZATION AB Proteins of the Myc and Mad family are involved in transcriptional regulation and mediate cell differentiation and proliferation, These molecules share a basic-helix-loop-helix leucine zipper domain (bHLHZip) and bind DNA at the E box (CANNTG) consensus by forming heterodimers with Max, We report the isolation, characterization and mapping of a human gene and its mouse homolog encoding a new member of this family of proteins, named Pox, Through interaction mating and immunoprecipitation techniques, we demonstrate that Rox heterodimerizes with Max and weakly homodimerizes, Interestingly, bandshift assays demonstrate that the Fox-Max heterodimer shows a novel DNA binding specificity, having a higher affinity for the CACGCG site compared with the canonical E box CACGTG site, Transcriptional studies indicate that Fox represses transcription in both human HEK293 cells and yeast. We demonstrate that repression in yeast is through interaction between the N-terminus of the protein and the Sin3 co-repressor, as previously shown for the other Mad family members, ROX is highly expressed in quiescent fibroblasts and expression markedly decreases when cells enter the cell cycle. Moreover, ROX expression appears to be induced in U937 myeloid leukemia cells stimulated to differentiate with 12-O-tetradecanoylphorbol-13-acetate, The identification of a novel Max-interacting protein adds an important piece to the puzzle of Myc/Max/Mad coordinated action and function in normal and pathological situations. Furthermore, mapping of the human gene to chromosome 17p13.3 in a region that frequently undergoes loss of heterozygosity in a number of malignancies, together with the biochemical and expression features, suggest involvement of ROX in human neoplasia. C1 TELETHON INST GENET & MED,MILAN,ITALY. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MOL BIOL,BOSTON,MA. IST EUROPEO ONCOL,MILAN,ITALY. NATL CANC CTR,RES INST,TOKYO 104,JAPAN. UNIV CHICAGO,CTR GENET MED,CHICAGO,IL 60637. HOSP SAN RAFFAELE,SERV GENET MED,I-20132 MILAN,ITALY. RI Borsani, Giuseppe/B-1709-2010; Alcalay, Myriam/B-3182-2016; OI Borsani, Giuseppe/0000-0003-0110-1148; Alcalay, Myriam/0000-0002-5558-4272; BALLABIO, Andrea/0000-0003-1381-4604 FU Telethon [TGM06S01, TGM94000, TGM97000] NR 93 TC 111 Z9 115 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 1997 VL 16 IS 10 BP 2892 EP 2906 DI 10.1093/emboj/16.10.2892 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC307 UT WOS:A1997XC30700032 PM 9184233 ER PT J AU McClatchey, AI Saotome, I Ramesh, V Gusella, JF Jacks, T AF McClatchey, AI Saotome, I Ramesh, V Gusella, JF Jacks, T TI The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation SO GENES & DEVELOPMENT LA English DT Article DE merlin; neurofibromatosis type II; tumor suppressor gene; extraembryonic ectoderm; gastrulation; ERM ID ALBINO-DELETION COMPLEX; EMBRYONIC STEM-CELLS; MOUSE EMBRYOS; NEUROFIBROMATOSIS TYPE-2; EXPRESSION; MEMBRANE; EZRIN; MICE; CHROMOSOME-22; HYALURONAN AB The neurofibromatosis type II (NF2) tumor suppressor encodes a putative cytoskeletal associated protein, the loss of which leads to the development of Schwann cell tumors associated with NF2 in humans. The NF2 protein merlin belongs to the band 4.1 family of proteins that link membrane proteins to the cytoskeleton and are thought to be involved in dynamic cytoskeletal reorganization. Beyond its membership in this family, however, the function of merlin remains poorly understood. In order to analyze the function of merlin during embryogenesis and to develop a system to study merlin function in detail, we have disrupted the mouse Nf2 gene by homologous recombination in embryonic stem cells. Most embryos homozygous for a mutation at the Nf2 locus fail between embryonic days 6.5 and 7.0, exhibiting a collapsed extraembryonic region and the absence of organized extraembryonic ectoderm. The embryo proper continues to develop, but fails to initiate gastrulation. These observations are supported by the expression patterns of markers of the extraembryonic lineage and the lack of expression of mesodermal markers in the mutant embryos. Mosaic studies demonstrate that merlin function is not required cell autonomously in mesoderm, and support the proposition that merlin function is essential for the development of extraembryonic structures during early mouse development. C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. FU NINDS NIH HHS [NS24279] NR 47 TC 119 Z9 121 U1 2 U2 8 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1997 VL 11 IS 10 BP 1253 EP 1265 DI 10.1101/gad.11.10.1253 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XB687 UT WOS:A1997XB68700004 PM 9171370 ER PT J AU Thomas, BJ Zavitz, KH Dong, XZ Lane, ME Weigmann, K Finley, RL Brent, R Lehner, CF Zipursky, SL AF Thomas, BJ Zavitz, KH Dong, XZ Lane, ME Weigmann, K Finley, RL Brent, R Lehner, CF Zipursky, SL TI roughex down-regulates G(2) cyclins in G(1) SO GENES & DEVELOPMENT LA English DT Article DE cell cycle; cyclin A; eye development; G(I); Drosophila; protein stability ID DEVELOPING DROSOPHILA EYE; CELL-CYCLE; S-PHASE; PATTERN-FORMATION; MAMMALIAN FIBROBLASTS; DNA-REPLICATION; PROTEIN-KINASE; EXPRESSION; TRANSITION; PROGRESSION AB Cell cycle arrest in G(1) at the onset of patterning in the Drosophila eye is mediated by rougher. In rougher mutants, cells accumulate Cyclin A protein in early G(1) and progress into S phase precociously. When Rougher is overexpressed in S/G(2) cells, Cyclin A is mislocalized to the nucleus and degraded, preventing mitosis. Whereas Rougher inhibits Cyclin A accumulation, Cyclin E down-regulates Rougher protein in vivo. Rougher binds to Cyclin E and is a substrate for a Cyclin E-Cdk complex in vitro. These data argue that Rougher inhibits Cyclin A accumulation in early G(1) by targeting Cyclin A for destruction. In late G(1), Rougher is destabilized in a Cyclin E-dependent process, releasing Cyclin A for its role in S/G(2). C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOL CHEM,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST MOL BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,HOWARD HUGHES MED INST,LOS ANGELES,CA 90095. WAYNE STATE UNIV,SCH MED,CTR MOL MED & GENET,DETROIT,MI. MASSACHUSETTS GEN HOSP,DEPT BIOL MOL,BOSTON,MA 02114. UNIV BAYREUTH,DEPT GENET,D-95440 BAYREUTH,GERMANY. RP Thomas, BJ (reprint author), NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM07185] NR 49 TC 59 Z9 59 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1997 VL 11 IS 10 BP 1289 EP 1298 DI 10.1101/gad.11.10.1289 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XB687 UT WOS:A1997XB68700007 PM 9171373 ER PT J AU Byrd, TF AF Byrd, TF TI Tumor necrosis factor alpha (TNF alpha) promotes growth of virulent Mycobacterium tuberculosis in human monocytes - Iron-mediated growth suppression is correlated with decreased release of TNF alpha from iron-treated infected monocytes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 06-10, 1994 CL ORLANDO, FL SP Infect Dis Soc Amer DE transferrin; lactoferrin; polymorphonuclear leukocyte; interferon gamma; calcitriol ID ACTIVATED HUMAN-MONOCYTES; TRANSFERRIN RECEPTOR EXPRESSION; INTERFERON-GAMMA; INTRACELLULAR MULTIPLICATION; LEGIONELLA-PNEUMOPHILA; HUMAN MACROPHAGES; POLYMORPHONUCLEAR LEUKOCYTES; MONONUCLEAR PHAGOCYTES; SCHISTOSOMA-MANSONI; IFN-GAMMA AB The human immune response to Mycobacterium tuberculosis is not well characterized, To better understand the cellular immune response to tuberculosis, a human mononuclear phagocyte culture system using a low-infecting inoculum of M. tuberculosis to mimic in vivo conditions was developed, Using this system, monocytes treated with IFN gamma/TNF alpha/calcitriol (CytD) were permissive for the growth of virulent M. tuberculosis. In the presence of iron, however, these monocytes suppressed the growth of M. tuberculosis, The enhanced permissiveness of CytD-preincubated monocytes was found to be due to TNF alpha, however, the ability of iron to suppress M. tuberculosis growth also required preincubation with TNF alpha Iron-mediated growth suppression was correlated with selective suppression of TNF alpha release from infected monocytes, In addition, removal of TNF alpha from CytD-treated monocytes 2 d after infection mimicked the suppressive effect of iron, suggesting that iron may also be decreasing monocyte sensitivity to exogenously added TNF alpha. In the absence of iron, permissive, CytD-treated monocytes formed large infected cellular aggregates, With iron treatment, aggregation was suppressed, suggesting that the iron-suppressive effect on M. tuberculosis growth may be related to suppression of monocyte aggregation and diminished cell-to-cell spread of M. tuberculosis, The results of this study indicate that TNF alpha preincubation is required for human monocytes to exert an iron-mediated suppressive effect on M. tuberculosis growth. In the absence of iron, however, the continued presence of TNF alpha has a growth-promoting effect on M. tuberculosis in human monocytes. Iron may be an important early modulator of M. tuberculosis growth via its effects on TNF alpha. C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,DIV INFECT DIS,LOS ANGELES,CA 90073. FU NIAID NIH HHS [AI-93-03] NR 66 TC 69 Z9 70 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1997 VL 99 IS 10 BP 2518 EP 2529 DI 10.1172/JCI119436 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XB226 UT WOS:A1997XB22600032 PM 9153296 ER PT J AU She, J Simpson, SJ Gupta, A Hollander, G Levelt, C Liu, CP Allen, D vanHouten, N Wang, BP Terhorst, C AF She, J Simpson, SJ Gupta, A Hollander, G Levelt, C Liu, CP Allen, D vanHouten, N Wang, BP Terhorst, C TI CD16-expressing CD8 alpha alpha(+) T lymphocytes in the intestinal epithelium - Possible precursors of Fc gamma R(-)CD8 alpha alpha(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-GAMMA CHAIN; FC-RECEPTORS; INTRAEPITHELIAL LYMPHOCYTES; THYMOCYTE DEVELOPMENT; MUTANT MICE; EXPRESSION; MOUSE; CD3; CD3-EPSILON; SELECTION AB T lymphocytes normally express their Ag receptors in association with the CD3 proteins, which include CD3 zeta. In CD3 zeta(eta)(null) mice thymic and peripheral T lymphocytes do not express the TCR/CD3 complex on their surface due to retention in the endoplasmic reticulum of the remaining polypeptide chains, However, intestinal intraepithelial lymphocytes (iIEL) of CD3 zeta eta(null) mice do express surface TCR, because the Fc epsilon RI gamma chain replaced the CD3 zeta chain in the TCR/CD3 complex, Here we report that in a subset of CD8 alpha alpha(+) ilEL the presence of the Fc epsilon RI gamma chain could be accounted for by the surface expression of the Fc gamma RIII(CD16) complex, Because in wild-type (wt) mice only CD16(+) iIEL coexpressed Fc epsilon RI gamma and CD3 zeta, we concluded that the presence of Fc epsilon RI gamma was dictated by its required participation of CD16 complex, CD8 alpha alpha(+) ilEL bearing CD16 and B220 were also detected in the intestinal mucosa of RAG-2(null) mice from 12 days after birth onward, Two independent experimental settings were used in an attempt to demonstrate that CD16(+) iIEL matured into CD16(-) T cells. First, in the RAG-2(null) mice, ilEL responded to in vivo administration of an anti-CD3 epsilon mAb by progression to a more mature stage of development, characterized by a loss of CD16 and B220, Secondly, a conversion to CD16(-) iIEL occurred upon transfer of wt CD16(+) ilEL into RAG-2(null) mice, We conclude from these experiments that in both RAG-2(null) and wt mice, a precursor/progeny relationship may exists between CD16(+)B220(+)CD8 alpha alpha(+) and CD16(-)B220(-)CD8 alpha alpha(+) iIEL. C1 BETH ISRAEL HOSP,DIV IMMUNOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. UNIV TEXAS,DEPT PEDIAT,GALVESTON,TX 77555. FU NIAID NIH HHS [AI-35714] NR 36 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1997 VL 158 IS 10 BP 4678 EP 4687 PG 10 WC Immunology SC Immunology GA WX987 UT WOS:A1997WX98700020 PM 9144480 ER PT J AU Schwarzschild, MA Cole, RL Hyman, SE AF Schwarzschild, MA Cole, RL Hyman, SE TI Glutamate, but not dopamine, stimulates stress-activated protein kinase and AP-1-mediated transcription in striatal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate; NMDA; SAPK; JNK; c-fos; c-jun; AP-1; transcription; striatum; cell culture ID MESSENGER-RNA EXPRESSION; MULTIPLE SEQUENCE ELEMENTS; RECEPTOR GENE-EXPRESSION; D-ASPARTATE RECEPTORS; C-FOS TRANSCRIPTION; RAT STRIATUM; BASAL GANGLIA; DIFFERENTIAL EXPRESSION; HIPPOCAMPAL-NEURONS; SIGNALING PATHWAYS AB Drugs that stimulate dopamine and glutamate receptors have been shown to induce the expression of AP-1 proteins (such as c-Fos and c-Jun) in the striatum and to induce binding of these proteins to AP-1 sites on DNA, leading to the hypothesis that AP-1-mediated transcription contributes to the long-term effects of these drugs. To examine this hypothesis, we compared the regulation of AP-1-mediated transcription to the inductions of AP-1-binding activity and genes encoding AP-1 proteins in primary cultures of striatal neurons. Although glutamate, dopamine, and forskolin (an activator of adenylate cyclase) all induce c-fos mRNA and AP-1 binding, we found, surprisingly, that only glutamate induces transcription of a transfected AP-1-driven fusion gene. To explore the basis for this discrepancy, we investigated the possibility that the phosphorylation of c-Jun may also be required for AP-1-mediated transcription in striatal neurons. Glutamate, but neither dopamine nor forskolin, raises the levels of phosphorylated c-Jun as well as the activity of a Jun kinase (SAPK/JNK) in striatal cultures. Both the glutamatergic induction of AP-1-mediated transcription and activation of SAPK/JNK appear to be mediated, at least in part, via NMDA receptors. In striatal neurons, the phosphorylation of AP-1 proteins produced by glutamate may be required to convert AP-1 protein expression and binding to transcriptional activation. C1 MASSACHUSETTS GEN HOSP,LAB MOL & DEV NEUROSCI,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NIDA NIH HHS [DA00257, DA07134]; NINDS NIH HHS [NS01729] NR 84 TC 132 Z9 134 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 1997 VL 17 IS 10 BP 3455 EP 3466 PG 12 WC Neurosciences SC Neurosciences & Neurology GA WX661 UT WOS:A1997WX66100008 PM 9133371 ER PT J AU Peng, L MartinVasallo, P Sweadner, KJ AF Peng, L MartinVasallo, P Sweadner, KJ TI Isoforms of Na,K-ATPase alpha and beta subunits in the rat cerebellum and in granule cell cultures SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Na,K-ATPase; cerebellum; isoform localization; ion transport; granule cell; astrocyte; Purkinje cell; basket cell ID CENTRAL-NERVOUS-SYSTEM; NEURON-SPECIFIC GLYCOPROTEIN; TISSUE-SPECIFIC EXPRESSION; ADHESION MOLECULE; CATALYTIC SUBUNIT; MESSENGER-RNA; FUNCTIONAL-CHARACTERIZATION; MONOCLONAL-ANTIBODY; MURINE NA,K-ATPASE; GLIA AMOG/BETA-2 AB There are multiple isoforms of the Na,K-ATPase in the nervous system, three isoforms of the alpha subunit, and at least two of the beta subunit. The alpha subunit is the catalytic subunit. The beta subunit has several roles. It is required for enzyme assembly, it has been implicated in neuron-glia adhesion, and the experimental exchange of beta subunit isoforms modifies enzyme kinetics, implying that it affects functional properties. Here we describe the specificities of antibodies against the Na,K-ATPase beta subunit isoforms beta 1 and beta 2. These antibodies, along with antibodies against the alpha subunit isoforms, were used to stain sections of the rat cerebellum and cultures of cerebellar granule cells to ascertain expression and subcellular distribution in identifiable cells. Comparison of alpha and beta isoform distribution with double-label staining demonstrated that there was no preferential association of particular alpha subunits with particular beta subunits, nor was there an association with excitatory or inhibitory neurotransmission modes. Isoform composition differences were seen when Purkinje, basket, and granule cells were compared. Whether beta 1 and beta 2 are specific for neurons and glia, respectively, has been controversial, but expression of both beta subunit types was seen here in granule cells. In rat cerebellar astrocytes, in sections and in culture, alpha 2 expression was prominent, yet the expression of either beta subunit was low in comparison. The complexity of Na,K-ATPase isoform distribution underscores the subtlety of its regulation and physiological role in excitable cells. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,LAB MEMBRANE BIOL,CHARLESTOWN,MA 02129. UNIV LA LAGUNA,DEPT BIOQUIM & BIOL MOL,LAB BIOL DESARROLLO,E-38207 LA LAGUNA,SPAIN. FU NINDS NIH HHS [NS 27653] NR 56 TC 103 Z9 105 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 1997 VL 17 IS 10 BP 3488 EP 3502 PG 15 WC Neurosciences SC Neurosciences & Neurology GA WX661 UT WOS:A1997WX66100011 PM 9133374 ER PT J AU Casasnovas, JM Springer, TA Liu, JH Harrison, SC Wang, JH AF Casasnovas, JM Springer, TA Liu, JH Harrison, SC Wang, JH TI Crystals structure of ICAM-2 reveals a distinctive integrin recognition surface SO NATURE LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; CELL-ADHESION; PLASMODIUM-FALCIPARUM; BINDING-SITE; IMMUNOGLOBULIN SUPERFAMILY; HUMAN RHINOVIRUS; LFA-1; RECEPTOR; FRAGMENT; DOMAIN-1 AB Recognition by integrin proteins on the cell surface regulates the adhesive interactions between cells and their surroundings(1,2). The structure of the 'I' domain that is found in some but not all integrins, has been determined(3,4). However, the only integrin ligands for which structures are known, namely fibronectin and VCAM-1 (refs 5-7), are recognized by integrins that lack I domains. The intercellular adhesion molecules ICAM-1, 2 and 3 are, like VCAM-1, members of the immunoglobulin superfamily (IgSF), but they are recognized by an I domain-containing integrin, lymphocyte-function-associated antigen 1 (LFA-1, or CD11a/CD18). Here we present the crystal structure of the extracellular region of ICAM-2. The glutamic acid residue at position 37 is critical for LFA-1 binding and is proposed to coordinate the Mg2+ ion in the I domain; this Glu 37 is surrounded by a relatively flat recognition surface and lies in a beta-strand, whereas the critical aspartic acid residue in VCAM-1 and fibronectin lie in protruding loops. This finding suggests that there are differences in the architecture of recognition sites between integrins that contain or lack I domains. A bend between domains 1 and 2 of ICAM-2 and a tripod-like arrangement of N-linked glycans in the membrane-proximal region of domain 2 may be important for presenting the recognition surface to LFA-1. A model of ICAM-1 based on the ICAM-2 structure provides a framework for understanding its recognition by pathogens. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,DEPT CELLULAR & MOL BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 NR 31 TC 90 Z9 91 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 15 PY 1997 VL 387 IS 6630 BP 312 EP 315 DI 10.1038/387312a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ167 UT WOS:A1997WZ16700060 PM 9153399 ER PT J AU Couch, FJ DeShano, ML Blackwood, MA Calzone, K Stopfer, J Campeau, L Ganguly, A Rebbeck, T Weber, BL Jablon, L Cobleigh, MA Hoskins, K Garber, JE AF Couch, FJ DeShano, ML Blackwood, MA Calzone, K Stopfer, J Campeau, L Ganguly, A Rebbeck, T Weber, BL Jablon, L Cobleigh, MA Hoskins, K Garber, JE TI BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OVARIAN-CANCER; SUSCEPTIBILITY GENE; FAMILY HISTORY; CARRIERS; KINDREDS AB Background To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. Methods Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. Results BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian an cancer in a family. Conclusions Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative. (C) 1997, Massachusetts Medical Society. C1 UNIV PENN,DEPT MED,STELLAR CHANCE LABS 1009,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. UNIV PENN,DEPT BIOSTAT & EPIDEMIOL,PHILADELPHIA,PA 19104. ALBERT EINSTEIN MED CTR,PHILADELPHIA,PA 19141. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. ROCKFORD MEM HOSP,ROCKFORD,IL. DANA FARBER CANC INST,BOSTON,MA 02115. NR 28 TC 502 Z9 510 U1 1 U2 10 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 15 PY 1997 VL 336 IS 20 BP 1409 EP 1415 DI 10.1056/NEJM199705153362002 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WY577 UT WOS:A1997WY57700002 PM 9145677 ER PT J AU Krainer, M SilvaArrieta, S FitzGerald, MG Shimada, A Ishioka, C Kanamaru, R MacDonald, DJ Unsal, H Finkelstein, DM Bowcock, A Isselbacher, KJ Haber, DA AF Krainer, M SilvaArrieta, S FitzGerald, MG Shimada, A Ishioka, C Kanamaru, R MacDonald, DJ Unsal, H Finkelstein, DM Bowcock, A Isselbacher, KJ Haber, DA TI Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OVARIAN-CANCER; SUSCEPTIBILITY GENE; FAMILIAL BREAST; MUTATIONS; LINKAGE AB Background Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. Methods Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein-truncation assay, followed by automated nucleotide sequencing, In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. Results Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P = 0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. Conclusions Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer. (C) 1997, Massachusetts Medical Society. C1 MASSACHUSETTS GEN HOSP,CTR CANC,GENET MOL LAB,CHARLESTOWN,MA 02129. CTR CANC RISK ANAL,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,DIV BIOSTAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. TOHOKU UNIV,DEPT CLIN ONCOL,SENDAI,MIYAGI 980,JAPAN. UNIV TEXAS,SW MED CTR,DIV PEDIAT HEMATOL ONCOL,DALLAS,TX. FU NCI NIH HHS [CA60650] NR 28 TC 155 Z9 157 U1 0 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 15 PY 1997 VL 336 IS 20 BP 1416 EP 1421 DI 10.1056/NEJM199705153362003 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WY577 UT WOS:A1997WY57700003 PM 9145678 ER PT J AU Schrag, D Kuntz, KM Garber, JE Weeks, JC AF Schrag, D Kuntz, KM Garber, JE Weeks, JC TI Decision analysis - Effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FAMILIAL-OVARIAN-CANCER; PRIMARY BREAST-CANCER; COST-EFFECTIVENESS; FOLLOW-UP; SUBCUTANEOUS MASTECTOMY; ADJUVANT THERAPY; CARRIERS; EFFICACY; TRIAL; RISK AB Background Women with BRCA1 or BRCA2 mutations have an increased risk of breast cancer and ovarian cancer. Prophylactic mastectomy and oophorectomy are often considered as ways of reducing these risks, but the effect of the procedures on life expectancy has not been established. Methods In a decision analysis, we compared prophylactic mastectomy and prophylactic oophorectomy with no prophylactic surgery among women who carry mutations in the BRCA1 or BRCA2 gene. We used available data about the incidence of cancer, the prognosis for women with cancer, and the efficacy of prophylactic mastectomy and oophorectomy in preventing breast and ovarian cancer to estimate the effects of these interventions on life expectancy among women with different levels of risk of cancer. Results We calculated that, on average, 30-year-old women who carry BRCA1 or BRCA2 mutations gain from 2.9 to 5.3 years of life expectancy from prophylactic mastectomy and from 0.3 to 1.7 years of life expectancy from prophylactic oophorectomy, depending on their cumulative risk of cancer. Gains in life expectancy decline with age at the time of prophylactic surgery and are minimal for 60-year-old women. Among 30-year-old women, oophorectomy may be delayed 10 years with little loss of life expectancy. Conclusions On the basis of a range of estimates of the incidence of cancer, prognosis, and efficacy of prophylactic surgery, our model suggests that prophylactic mastectomy provides substantial gains in life expectancy and prophylactic oophorectomy more limited gains for young women with BRCA1 or BRCA2 mutations. (C) 1997, Massachusetts Medical Society. C1 DANA FARBER CANC INST,CTR OUTCOMES & POLICY RES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,CLIN EPIDEMIOL SECT,BOSTON,MA 02115. NR 43 TC 281 Z9 284 U1 2 U2 15 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 15 PY 1997 VL 336 IS 20 BP 1465 EP 1471 DI 10.1056/NEJM199705153362022 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WY577 UT WOS:A1997WY57700032 PM 9148160 ER PT J AU Soucek, T Pusch, O HengstschlagerOttnad, E Adams, PD Hengstschlager, M AF Soucek, T Pusch, O HengstschlagerOttnad, E Adams, PD Hengstschlager, M TI Deregulated expression of E2F-1 induces cyclin A- and E-associated kinase activities independently from cell cycle position SO ONCOGENE LA English DT Article DE E2F; cyclin E; cyclin A; CDK; centrifugal elutriation ID TUMOR-SUPPRESSOR PROTEIN; S-PHASE ENTRY; TRANSCRIPTION FACTOR; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; DNA-SYNTHESIS; G(1); FIBROBLASTS; APOPTOSIS; GENES AB The transcription factor E2F activates genes required for S phase, such as cyclin E and cyclin A, We show that, contrary to long term effects of E2F-1 overexpression, short ectopic overexpression of this transcription factor in logarithmically growing cells does neither affect the cell cycle distribution nor the cell size, but heavily induces cyclin E and A expression as well as cyclin E- and A-dependent kinase activities, We further separated logarithmically growing E2F-1-overexpressing cells according to their different cell cycle phases by centrifugal elutriation, These experiments revealed that deregulated E2F-1 expression triggers high levels of cyclin E and A expression and kinase activities in small early G(1) cells, normally not exhibiting these activities, These effects on the regulation of cyclin E- and A-associated kinases are not accompanied by any detectable alteration in the rate of progression through the cell cycle, suggesting that these changes are independent of any mitogenic properties of E2F-1. C1 UNIV VIENNA,DEPT PRENATAL DIAGNOSIS & THERAPY,A-1090 VIENNA,AUSTRIA. UNIV VIENNA,INST MOL GENET,A-1030 VIENNA,AUSTRIA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. NR 44 TC 31 Z9 31 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 15 PY 1997 VL 14 IS 19 BP 2251 EP 2257 DI 10.1038/sj.onc.1201061 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WY883 UT WOS:A1997WY88300001 PM 9178900 ER PT J AU Yu, EY Siegal, JA Meyer, GE Ji, XR Ni, XZ Brawer, MK AF Yu, EY Siegal, JA Meyer, GE Ji, XR Ni, XZ Brawer, MK TI Histologic differences in benign prostrate hyperplasia between Chinese and American men SO PROSTATE LA English DT Article DE morphometry; Chinese; American; BPH ID PROSTATIC HYPERPLASIA; CANCER AB BACKGROUND. This investigation sought to determine morphologic differences between Chinese and Americans with symptomatic benign prostatic hyperplasia (BPH), in an admixture of stroma, epithelium, and luminal spaces. METHODS. Adjacent sections of simple prostatectomy specimens from China and the U.S. were stained to highlight the stroma and epithelium. Image analysis was performed on random fields. RESULTS. Chinese tissue had higher glandular densities (mean = 12.5 acini/mm(2) vs. 6.2 acini/mm(2); P < 0.0001), while American samples had higher percent stroma (mean = 66% vs. 51%; P = 0.0003). Mean luminal cell heights in the Chinese and American prostate acini were 11.7 and 19.0 microns, respectively (P < 0.0001). CONCLUSIONS. These data indicate significant histologic variation in BPH between Chinese and American men undergoing simple prostatectomy. These differences may provide a focus for investigating the epidemiological variation in clinical BPH and carcinoma between our two countries, and could have applications in clinical management of symptomatic BPH. (C) 1997 Wiley-Liss, Inc. C1 VA PUGET SOUND HLTH CARE SYST,UROL SECT,SEATTLE,WA 98108. AFFILIATED HOSP,QUINGDAO MED COLL,DEPT UROL,QINGDAO,PEOPLES R CHINA. UNIV WASHINGTON,DEPT UROL,SEATTLE,WA 98195. FU NIDDK NIH HHS [DK45761-01] NR 12 TC 8 Z9 9 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 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 1997 VL 31 IS 3 BP 175 EP 179 PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA XA510 UT WOS:A1997XA51000005 PM 9167769 ER PT J AU Delmonico, FL Cosimi, AB Colvin, R Farrell, ML Thistlethwaite, R Spargo, B OLaughlin, R Matas, AJ Burke, B McHugh, L Lindblad, AS Stablein, DM CarterCampbell, S Salomon, DR Quinn, S Haverty, T Knowles, R Kale, R AF Delmonico, FL Cosimi, AB Colvin, R Farrell, ML Thistlethwaite, R Spargo, B OLaughlin, R Matas, AJ Burke, B McHugh, L Lindblad, AS Stablein, DM CarterCampbell, S Salomon, DR Quinn, S Haverty, T Knowles, R Kale, R TI Murine OKT4A immunosuppression in cadaver donor renal allograft recipients - A cooperative clinical trials in transplantation pilot study SO TRANSPLANTATION LA English DT Article ID ANTI-CD4 MONOCLONAL-ANTIBODY; HUMAN ORGAN-TRANSPLANTATION; TOLERANCE; REJECTION; SURVIVAL; MICE; CD4 AB Background. A phase I study of anti-CD4 immunosuppression of cadaver donor renal allograft recipients was conducted by the NIH Cooperative Clinical Trials in Transplantation to assess safety, tolerability, immunoactivity, and pharmacokinetics of multiple infusions of murine anti-human CD4 monoclonal antibody OKT4A. Methods. Thirty patients were enrolled (from August 1992 to October 1993) and received OKT4A at doses of 0.5 mg/kg (24 patients), 1.0 mg/kg (three patients), and 2.0 mg/kg (three patients) beginning and continuing for 12 consecutive days with a standard regimen of cyclosporine, azathioprine, and prednisone. OKT4A treatment was continued postoperatively if serum creatinine 24 hr after transplantation was <85% of pre-transplantation baseline creatinine. Results. Ninety-three percent of patients treated at 0.5 mg/kg OKT4A and all patients at higher doses had mean peak CD4 saturations in excess of 90%. A human antimouse antibody response of more than three times pretreatment levels was observed in 84% of patients. There was no evidence of CD4 T-cell depletion. OKT4A was well tolerated without first-dose side effects. For the 19 eligible patients treated with 0.5 mg/kg OKT4A with initial graft function, the 3-month treated rejection rate was 37%. The 2-year graft survival rate for all 30 patients enrolled was 83%, and for the 19 eligible patients it was 95%. Conclusions. The high percentage of CD4 saturation, minimal side effects, the observation of a low 3-month rejection rate, and an excellent 2-year graft survival rate in patients treated with 0.5 mg/kg OKT4A support the continued investigation of an anti-CD4 approach to immunosuppressive therapy. C1 UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. UNIV MINNESOTA,MINNEAPOLIS,MN. CLIN COORDINATING CTR,POTOMAC,MD. RP Delmonico, FL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,32 FRUIT ST,BOSTON,MA 02114, USA. RI Salomon, Daniel/E-9380-2012 NR 25 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1997 VL 63 IS 9 BP 1243 EP 1251 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WZ231 UT WOS:A1997WZ23100009 ER PT J AU Sawada, T DellaPelle, PA Seebach, JD Sachs, DH Colvin, RB Iacomini, J AF Sawada, T DellaPelle, PA Seebach, JD Sachs, DH Colvin, RB Iacomini, J TI Human cell-mediated rejection of porcine xenografts in an immunodeficient mouse model SO TRANSPLANTATION LA English DT Article ID HUMAN T-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN NATURAL ANTIBODIES; SKIN-GRAFT REJECTION; ENDOTHELIAL-CELLS; HYPERACUTE REJECTION; V(D)J RECOMBINATION; MINIATURE SWINE; SCID MUTATION; DISCORDANT XENOGRAFT AB Background. In this study, we describe the development of a novel experimental system in which rejection of porcine skin grafts by human peripheral blood cells can be studied directly in vivo in immunodeficient mice. Methods. To construct a small animal model of discordant xenograft rejection, recombinase-activating gene-deficient mice (R-) lacking both mature B and T cells were grafted with porcine skin grafts and administered, by adoptive cell transfer, human cells stimulated in vitro with irradiated porcine peripheral blood cells to create Hu-R- mice. Results. R- mice accepted porcine skin grafts indefinitely without the need for immunosuppression. In contrast, Hu-R- mice were able to reject porcine skin grafts. Immunohistochemical analysis of rejecting skin grafts revealed the accumulation of human T cells around dermal porcine vessels and focally in the epidermis. Graft rejection was manifested by vascular endothelial cell proliferation, edema at the dermal-epidermal border, and perivascular hemorrhage. The tissue damage observed in the rejecting grafts was similar to that observed in delayed primate anti-porcine cell-mediated rejection of vascularized organ xenografts. Conclusions. The development and characterization of a small animal model, to study cellular immune responses of human cells to discordant xenografts in vivo, should provide a convenient means for asking mechanistic questions related to discordant xenotransplantation, and may also provide a practical system for testing new approaches designed to prevent xenograft rejection. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, TRANSPLANTAT BIOL RES CTR, BOSTON, MA 02129 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02129 USA. NR 61 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1997 VL 63 IS 9 BP 1331 EP 1338 DI 10.1097/00007890-199705150-00022 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WZ231 UT WOS:A1997WZ23100022 PM 9158029 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Oncology ASAP - Where to find reliable cancer information on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BLDG 49,4B56,BETHESDA,MD 20892, USA. NR 2 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1431 EP 1432 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200012 PM 9145704 ER PT J AU Geller, G Botkin, JR Green, MJ Press, N Biesecker, B Wilfond, B Grana, G Daly, MB Schneider, K Kahn, MJE AF Geller, G Botkin, JR Green, MJ Press, N Biesecker, B Wilfond, B Grana, G Daly, MB Schneider, K Kahn, MJE TI Genetic testing for susceptibility to adult-onset cancer - The process and content of informed consent SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID COMPUTER-ASSISTED-INSTRUCTION; LINE P53 MUTATIONS; OVARIAN-CANCER; PATIENT EDUCATION; BREAST-CANCER; HUNTINGTON DISEASE; COLON-CANCER; KNOWLEDGE; DISCRIMINATION; UNDERSTAND AB Objective.-To provide guidance on informed consent to clinicians offering cancer susceptibility testing. Participants.-The Task Force on Informed Consent is part of the Cancer Genetics Studies Consortium (CGSC), whose members were recipients of National Institutes of Health grants to assess the implications of cancer susceptibility testing. The 10 task force members represent a range of relevant backgrounds, including various medical specialties, social science, genetic counseling, and consumer advocacy. Evidence.-The CGSC held 3 public meetings from 1994 to 1996. At its first meeting, the task force jointly established a list of topics. The cochairs (G.G. and J.R.B) then developed an outline and assigned each topic to an appropriate writer and reviewer, Writers summarized the literature on their topics and drafted recommendations, which were then revised by the reviewers. The cochairs compiled and edited the entire manuscript. All members were involved in writing this report. Consensus Process.-The first draft was distributed to task force members, after which a meeting was held to discuss its content and organization. Consensus was reached by voting. A subsequent draft was presented to the entire CGSC at its third meeting, and comments were incorporated. Conclusions.-The task force recommends that informed consent for cancer susceptibility testing be an ongoing process of education and counseling in which (1) providers elicit participant, family, and community values and disclose their own, (2) decision making is shared, (3) the style of information disclosure is individualized, and (4) specific content areas are discussed. C1 UNIV UTAH,ECCLES INST HUMAN GENET,UTAH CTR HUMAN GENOME RES,SALT LAKE CITY,UT. MILTON S HERSHEY MED CTR,DEPT HUMANITIES,HERSHEY,PA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. NATL HUMAN GENOME RES INST,MED GENET BRANCH,BETHESDA,MD. UNIV ARIZONA,DEPT PEDIAT,TUCSON,AZ 85721. CANC CTR SO NEW JERSEY,CAMDEN,NJ. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,BOSTON,MA 02115. NATL BREAST CANC COALIT,RICHMOND,VA. RP Geller, G (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,550 N BROADWAY,SUITE 511,BALTIMORE,MD 21205, USA. NR 119 TC 143 Z9 145 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1467 EP 1474 DI 10.1001/jama.277.18.1467 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200032 PM 9145720 ER PT J AU Chabner, BA Haluska, FG Talcott, JA AF Chabner, BA Haluska, FG Talcott, JA TI Screening strategies for cancer - Implications and results SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 DANA FARBER PARTNERS CANCERCARE,BOSTON,MA. RP Chabner, BA (reprint author), MASSACHUSETTS GEN HOSP,DEPT HEMATOL ONCOL,100 BLOSSOM ST,COX 640,BOSTON,MA 02114, USA. NR 9 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1475 EP 1476 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200033 PM 9145721 ER PT J AU Livingston, DM AF Livingston, DM TI Genetics is coming to oncology SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Livingston, DM (reprint author), DANA FARBER CANC INST,DIV SOLID TUMORS,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 14 PY 1997 VL 277 IS 18 BP 1476 EP 1477 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WX852 UT WOS:A1997WX85200034 PM 9145722 ER PT J AU Bosch, I DunussiJoannopoulos, K Wu, RL Furlong, ST Croop, J AF Bosch, I DunussiJoannopoulos, K Wu, RL Furlong, ST Croop, J TI Phosphatidylcholine and phosphatidylethanolamine behave as substrates of the human MDR1 P-glycoprotein SO BIOCHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANT CELLS; FUNCTIONAL EXPRESSION; MONOCLONAL-ANTIBODY; TRANSPORT PROTEINS; LIPID-COMPOSITION; PLASMA-MEMBRANE; TRANSGENIC MICE; GENE; ATPASE; LINES AB The multidrug resistant cell line CEM/VBL300 and the parental CEM T-lymphoblastic cell line from which it was derived were used to study the accumulation of fluorescent phospholipid analogs of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS). The fluorescent analogs NBD-PC, NBD-PE, and NBD-PS and [H-3]PC were delivered in liposomes prepared by ethanol injection. Fluorescence microscopy demonstrated decreased accumulation of the NBD-PC analog in the multidrug resistant cell line compared to the parental cell line. Verapamil enhanced NBD-PC accumulation in the resistant eels. Similar results were obtained with insect cells expressing high levels of recombinant human MDR1. Elimination of NBD fluorescence on the outer leaflet of the plasma membrane with dithionite permitted quantification of the internal cellular fluorescence by FAGS analysis. The drug resistant CEM/VBL300 cells accumulated approximately 10% the amount of NBD-PE and 20% the amount of NBD-PC compared to CEM drug sensitive cells. No difference in internal accumulation of NBD-PS was found between the drug resistant and drug sensitive cell lines. The internal accumulation of NBD-PE and NBD-PC was enhanced by the MDR reversal agents verapamil, cyclosporin A, and SDZ PSC 833 in the CEM/VBL300 cells but not in the CEM cells. The increased accumulation was dose dependent, and the relative potency of the reversal agents paralleled their ability to circumvent multidrug resistance. In addition, the monoclonal antibody UIC2 directed against the P-glycoprotein produced similar results. The evidence presented here suggests that PC and PE but not PS behave as substrates for human MDR1 P-glycoprotein. C1 DANA FARBER CANC INST, DIV PEDIAT HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT MED, BOSTON, MA 02115 USA. FU NIAID NIH HHS [AI24570] NR 54 TC 121 Z9 122 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 13 PY 1997 VL 36 IS 19 BP 5685 EP 5694 DI 10.1021/bi962728r PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY820 UT WOS:A1997WY82000009 PM 9153408 ER PT J AU vonAndrian, UH AF vonAndrian, UH TI A massage for the journey: Keeping leukocytes soft and silent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AGGREGATION; ELEMENT C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP vonAndrian, UH (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL048675, HL48675, HL54936, HL56949, P01 HL056949, R01 HL054936] NR 22 TC 5 Z9 5 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 1997 VL 94 IS 10 BP 4825 EP 4827 DI 10.1073/pnas.94.10.4825 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700004 PM 9144149 ER PT J AU Seeger, M Nordstedt, C Petanceska, S Kovacs, DM Gouras, GK Hahne, S Fraser, P Levesque, L Czernik, AJ StGeorgeHyslop, P Sisodia, SS Thinakaran, G Tanzi, RE Greengard, P Gandy, S AF Seeger, M Nordstedt, C Petanceska, S Kovacs, DM Gouras, GK Hahne, S Fraser, P Levesque, L Czernik, AJ StGeorgeHyslop, P Sisodia, SS Thinakaran, G Tanzi, RE Greengard, P Gandy, S TI Evidence for phosphorylation and oligomeric assembly of presenilin 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; MISSENSE MUTATIONS; GENE; CHROMOSOME-1; LOCUS AB Pathogenic mutations in presenilin 1 (PS1) are associated with approximate to 50% of early-onset familial Alzheimer disease, PS1 is endoproteolytically cleaved to yield a 30-kDa N-terminal fragment (NTF) and an 18-kDa C-terminal fragment (CTF), Using COS7 cells transfected with human PS1, we have found that phorbol 12,13-dibutyrate and forskolin increase the state of phosphorylation of serine residues of the human CTF, Phosphorylation of the human CTP resulted in a shift in electrophoretic mobility from a single major species of 18 kDa to a doubler of 20-23 kDa, This mobility shift was also observed with human PS1 that had been transfected into mouse neuroblastoma (N2a) cells, Treatment of the phosphorylated CTF doublet with phage lambda protein phosphatase eliminated the 20- to 23-kDa doubler while enhancing the 18-kDa species, consistent with the interpretation that the electrophoretic mobility shift was due to the addition of phosphate to the 18-kDa species, The NTF and CTF eluted from a gel filtration column at an estimated mass of over 100 kDa, suggesting that these fragments exist as an oligomerized species, Upon phosphorylation of the PS1 CTF, the apparent mass of the NTF- or CTF-containing oligomers was unchanged, Thus, the association of PS1 fragments may be maintained during cycles of phosphorylation/dephosphorylation of the PS1 CTF. C1 CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,ALZHEIMERS RES LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,MOL & CELLULAR NEUROSCI LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,FISHER CTR RES ALZHEIMER DIS,NEW YORK,NY 10021. KAROLINSKA INST,LAB BIOCHEM & MOL PHARMACOL,SECT EXPT ALCOHOL & DRUG ADDICT RES,S-17177 STOCKHOLM,SWEDEN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,GENET & AGING UNIT,CHARLESTOWN,MA 02129. UNIV TORONTO,CTR RES NEURODEGENERAT DIS,TORONTO,ON M5S 1A8,CANADA. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. RI Gouras, Gunnar/B-3021-2010 OI Gouras, Gunnar/0000-0002-5500-6325 FU NIA NIH HHS [AG09464, P01 AG009464, AG11508, F32 AG005689, AG13780] NR 35 TC 135 Z9 136 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 1997 VL 94 IS 10 BP 5090 EP 5094 DI 10.1073/pnas.94.10.5090 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700050 PM 9144195 ER PT J AU Lindeman, GJ Gaubatz, S Livingston, DM Ginsberg, D AF Lindeman, GJ Gaubatz, S Livingston, DM Ginsberg, D TI The subcellular localization of E2F-4 is cell-cycle dependent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F-1; DNA-BINDING ACTIVITY; S-PHASE ENTRY; IN-VIVO; GROWTH SUPPRESSION; FAMILY MEMBERS; PROTEIN; EXPRESSION; LEADS AB The E2F family of transcription factors plays a crucial role in cell cycle progression, E2F activity is tightly regulated by a number of mechanisms, which include the timely synthesis and degradation of E2F, interaction with retinoblastoma protein family members (''pocket proteins''), association with DP heterodimeric partner proteins, and phosphorylation of the E2F/DP complex, Here we report that another mechanism, subcellular localization, is important for the regulation of E2F activity. Unlike E2F-1, -2, or -3, which are constitutively nuclear, ectopic E2F-4 and -5 were predominantly cytoplasmic, Cotransfection of expression vectors encoding p107, p130, or DP-2, but not DP-1, resulted in the nuclear localization of E2F-4 and -5. Moreover, the transcriptional activity of E2F-4 was markedly enhanced when it was invariably nuclear, Conversely, it was reduced when the protein was excluded from the nucleus, implying that E2F-4 transcription function depends upon its cytological location, In keeping with this, the nuclear/cytoplasmic ratios of endogenous E2F-4 changed as cells exited G(0), with high ratios in G(0) and early G(1) and a progressive increase in cytoplasmic E2F-4 as cells approached S phase, Thus, the subcellular location of E2F-4 is regulated in a cell cycle-dependent manner, providing another potential mechanism for its functional regulation. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 38 TC 148 Z9 150 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 1997 VL 94 IS 10 BP 5095 EP 5100 DI 10.1073/pnas.94.10.5095 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700051 PM 9144196 ER PT J AU Yan, SD Zhu, HJ Fu, J Yan, SF Roher, A Tourtellotte, WW Rajavashisth, T Chen, X Godman, GC Stern, D Schmidt, AM AF Yan, SD Zhu, HJ Fu, J Yan, SF Roher, A Tourtellotte, WW Rajavashisth, T Chen, X Godman, GC Stern, D Schmidt, AM TI Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: A proinflammatory pathway in Alzheimer disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microglia; neurons; cerebrospinal fluid ID ADHESION MOLECULE-1 VCAM-1; HUMAN ENDOTHELIAL-CELLS; FACTOR-KAPPA-B; MICROGLIAL CELLS; NEURITE OUTGROWTH; PROTEIN TOXICITY; OXIDANT STRESS; IMMUNE-SYSTEM; END-PRODUCTS; ACTIVATION AB In Alzheimer disease (AD), neurons are thought to be subjected to the deleterious cytotoxic effects of activated microglia, We demonstrate that binding of amyloid-beta peptide (A beta) to neuronal Receptor for Advanced Glycation Endproduct (RAGE), a cell surface receptor for A beta, induces macrophage-colony stimulating factor (M-CSF) by an oxidant sensitive, nuclear factor kappa B-dependent pathway, AD brain shows increased neuronal expression of M-CSF in proximity to A beta deposits, and in cerebrospinal fluid from AD patients there was approximate to 5-fold increased M-CSF antigen (P < 0.01), compared with age-matched controls, M-CSF released by A beta-stimulated neurons interacts with its cognate receptor, c-fms, on microglia, thereby triggering chemotaxis, cell proliferation, increased expression of the macrophage scavenger receptor and apolipoprotein E, and enhanced survival of microglia exposed to A beta, consistent with pathologic findings in AD, These data delineate an inflammatory pathway triggered by engagement of A beta on neuronal RAGE, We suggest that M-CSF, thus generated, contributes to the pathogenesis of AD, and that M-CSF in cerebrospinal fluid might provide a means for monitoring neuronal perturbation at an early stage in AD. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT SURG,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PHYSIOL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. SUN HLTH RES INST,HALDEMAN LAB ALZHEIMERS DIS RES,SUN CITY,AZ 85372. W LOS ANGELES VET AFFAIRS MED CTR,NATL NEUROL RES SPECIMEN BANK,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,SCH MED,TORRANCE,CA 90502. RP Yan, SD (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032, USA. RI Fu, Jin/A-3510-2012 NR 53 TC 144 Z9 149 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 13 PY 1997 VL 94 IS 10 BP 5296 EP 5301 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WZ257 UT WOS:A1997WZ25700086 ER PT J AU Shaker, JL Brickner, RC Findling, JW Kelly, TM Rapp, R Rizk, G Haddad, JG Schalch, DS Shenker, Y AF Shaker, JL Brickner, RC Findling, JW Kelly, TM Rapp, R Rizk, G Haddad, JG Schalch, DS Shenker, Y TI Hypocalcemia and skeletal disease as presenting features of celiac disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the Endocrine-Society CY JUN 14-17, 1995 CL WASHINGTON, DC SP Endocrine Soc, Minist Educ, Sci & Culture Japan, Dtsch ForschGemeinsch ID BONE-MINERAL DENSITY; VITAMIN-D DEFICIENCY; GLUTEN-FREE DIET; DIABETES-MELLITUS; OSTEOMALACIA; ENTEROPATHY; MECHANISM AB Objective: To describe 15 patients examined for hypo calcemia, skeletal disease, or both in whom the diagnosis of celiac disease was subsequently made. Design: Observational case series. Patients: Fifteen patients (7 women and 8 men) were examined for hypocalcemia (n=11), skeletal disease (n=3), or both (n=1). The diagnosis of celiac disease was subsequently made. The mean age of the patients was 62 years, and 11 patients were 60 years of age or older. Results: Four patients had no gastrointestinal symptoms, 7 patients had mild or intermittent gastrointestinal symptoms, and 4 patients had persistent diarrhea. Ten patients had experienced weight loss. The serum total alkaline phosphatase level was elevated in 10 of 15 patients, the parathyroid hormone level was elevated in all patients, and the urinary calcium level was low in all 6 of the patients tested. The level of 25-hydroxyvitamin D was frankly low in 4 patients, marginal in 8 patients, and normal in 3 patients. Bone mineral density was reduced in all 8 patients in whom it was measured. Conclusions: Celiac disease should be considered in patients with unexplained metabolic bone disease or hypocalcemia, especially because gastrointestinal symptoms may be absent or mild. Advanced age does not exclude the diagnosis of celiac disease. C1 ST JOSEPHS HOSP,DEPT MED,MILWAUKEE,WI. ST MARYS HOSP,DEPT MED,RACINE,WI. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,MADISON,WI. RP Shaker, JL (reprint author), ST LUKES HOSP,DEPT MED,2901 W KINNICKINN RIVER PKWY,SUITE 503,MILWAUKEE,WI 53215, USA. NR 25 TC 26 Z9 26 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 12 PY 1997 VL 157 IS 9 BP 1013 EP 1016 DI 10.1001/archinte.157.9.1013 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WX439 UT WOS:A1997WX43900010 PM 9140273 ER PT J AU Calderwood, DA Tuckwell, DS Eble, J Kuhn, K Humphries, MJ AF Calderwood, DA Tuckwell, DS Eble, J Kuhn, K Humphries, MJ TI The integrin alpha 1 A-domain is a ligand binding site for collagens and laminin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I-DOMAIN; CR3 CD11B/CD18; ALPHA-2-BETA-1 VLA-2; ADHESION MOLECULE-1; CRYSTAL-STRUCTURE; RECOGNITION SITE; CELL-ADHESION; SUBUNIT; IDENTIFICATION; RECEPTOR AB The integrin alpha 1 beta 1 is a cell surface receptor for collagens and laminin. The alpha 1 subunit contains an A-domain, and the A-domains of other integrins are known to mediate ligand binding. To determine the role of the alpha 1 A-domain in ligand binding and the extent to which it reproduced the ligand binding activity and specificity of the parent molecule, we produced recombinant alpha 1 A-domain and tested its ability to bind collagens and laminin. In solid phase assays, the A-domain from alpha 1 was found to bind to collagen I, collagen IV, and laminin in a largely cation-dependent manner. The alpha 2 A-domain, from the alpha 2 beta 1 integrin, also bound to these ligands, but the binding hierarchy differed from that seen for alpha 1. This is the first demonstration of laminin binding by A-domains. Specificity of A-domain-ligand binding was further investigated using the triple-helical proteolytic fragment of collagen IV, CB3, and its subfragments, F1 and F4. alpha 1 A-domain bound to all three fragments, while the alpha 2 A-domain bound CB3 less well and exhibited little binding to F1 and no binding to F4. These differences mirror previous reports of distinct integrin binding sites in collagen IV and for the first time identify a limited proteolytic fragment of a ligand that contains integrin A-domain binding activity. To gain insight into the contribution that the A-domain makes to ligand binding within the whole integrin heterodimer, we measured binding constants for A-domain-collagen interactions using surface plasmon resonance biosensor technology. The values obtained were similar to those reported for intact integrin binding, suggesting that the A-domain is the major collagen binding site in the alpha 1 beta 1 and alpha 2 beta 1 integrins. C1 UNIV MANCHESTER,SCH BIOL SCI,WELLCOME TRUST CTR CELL MATRIX RES,MANCHESTER M13 9PT,LANCS,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. FU Wellcome Trust NR 35 TC 108 Z9 108 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 9 PY 1997 VL 272 IS 19 BP 12311 EP 12317 DI 10.1074/jbc.272.19.12311 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY829 UT WOS:A1997WY82900012 PM 9139675 ER PT J AU Yamamoto, M Bharti, A Li, YQ Kufe, D AF Yamamoto, M Bharti, A Li, YQ Kufe, D TI Interaction of the DF3/MUC1 breast carcinoma-associated antigen and beta-catenin in cell adhesion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID E-CADHERIN; CYTOPLASMIC DOMAIN; DROSOPHILA HOMOLOG; ARMADILLO PROTEIN; ALPHA-CATENIN; PLAKOGLOBIN; REGION; GENE; EPISIALIN; COMPLEX AB The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast carcinomas. The functional role of DF3 is unknown. The present studies demonstrate that DF3 associates with beta-catenin. Similar findings have been obtained for gamma-catenin but not alpha-catenin. DF3, like E-cadherin and the adenomatous polyposis coli gene product, contains an SXXXXXSSL site that is responsible for direct binding to beta-catenin. The results further demonstrate that interaction of DF3 and beta-catenin is dependent on cell adhesion. These findings and the role of beta-catenin in cell signaling support a role for DF3 in the adhesion of epithelial cells. RP Yamamoto, M (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CANC PHARMACOL, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 29 TC 250 Z9 255 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 MAY 9 PY 1997 VL 272 IS 19 BP 12492 EP 12494 DI 10.1074/jbc.272.19.12492 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WY829 UT WOS:A1997WY82900035 PM 9139698 ER PT J AU Meydani, SN Meydani, M Blumberg, JB Leka, LS Siber, G Loszewski, R Thompson, C Pedrosa, MC Diamond, RD Stollar, BD AF Meydani, SN Meydani, M Blumberg, JB Leka, LS Siber, G Loszewski, R Thompson, C Pedrosa, MC Diamond, RD Stollar, BD TI Vitamin E supplementation and in vivo immune response in healthy elderly subjects - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CELL-MEDIATED-IMMUNITY; DELAYED-HYPERSENSITIVITY; PNEUMOCOCCAL VACCINE; NURSING-HOME; MORTALITY; ANTIBODY; MICE; CANCER; POPULATION; EXPRESSION AB Objective.-To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects. Design.-Randomized, double-blind, placebo-controlled intervention study. Setting and Participants.-A total of 88 free-living, healthy subjects at least 65 years of age. Intervention.-Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days. Main Outcome Measures.-Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation. Results.-Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and S-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum a-tocopherol (vitamin E) concentration (>48.4 mu mol/l [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed. Conclusions.-Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation. C1 TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,VASC BIOL LAB,BOSTON,MA 02111. TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,ANTIOXIDANTS RES LAB,BOSTON,MA 02111. DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. VET AFFAIRS MED CTR,DEPT GASTROENTEROL,BOSTON,MA. BOSTON UNIV HOSP,DIS PROGRAM,BOSTON,MA. TUFTS UNIV,DEPT BIOCHEM,BOSTON,MA 02111. RP Meydani, SN (reprint author), TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,NUTR IMMUNOL LAB,711 WASHINGTON ST,BOSTON,MA 02111, USA. NR 46 TC 341 Z9 349 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 7 PY 1997 VL 277 IS 17 BP 1380 EP 1386 DI 10.1001/jama.277.17.1380 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WW261 UT WOS:A1997WW26100028 PM 9134944 ER PT J AU Carabello, BA AF Carabello, BA TI Timing of valve replacement in aortic stenosis - Moving closer to perfection SO CIRCULATION LA English DT Editorial Material DE valves; editorials; aorta; stenosis ID SYMPTOMATIC PATIENTS; ASYMPTOMATIC PATIENTS; NATURAL-HISTORY; REGURGITATION C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS,CHARLESTON,SC. RP Carabello, BA (reprint author), MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 14 TC 49 Z9 50 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 6 PY 1997 VL 95 IS 9 BP 2241 EP 2243 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WW865 UT WOS:A1997WW86500001 PM 9141998 ER PT J AU Clark, RA Erickson, HP Springer, TA AF Clark, RA Erickson, HP Springer, TA TI Tenascin supports lymphocyte rolling SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEIN; FIBRINOGEN-LIKE DOMAIN; ENDOTHELIAL-CELLS; PHYSIOLOGICAL FLOW; ADHESION MOLECULE; COUNTER-RECEPTOR; IV-COLLAGEN; L-SELECTIN; FIBRONECTIN; BINDING AB Tenascin is a large extracellular matrix molecule expressed at specific sites in the adult, including immune system tissues such as the bone marrow, thymus, spleen, and T cell areas of lymph nodes. Tenascin has been reported to have both adhesive and anti-adhesive effects in static assays. We report here that tenascin supports the tethering and rolling of lymphocytes and lymphoblastic cell lines under flow conditions. Binding was calcium dependent and was not inhibited by treatment of lymphocytes with O-glycoprotease or a panel of glycosidases including neuraminidase and heparitinase but was inhibited by treatment of cells with proteinase K. Binding was to the fibrinogen-like terminal domain of tenascin as determined by antibody blocking studies and binding to recombinant tenascin proteins. When compared to rolling of the same cell type on E-selectin, rolling on tenascin was found to be smoother at all shear stresses tested, suggesting that cells formed a larger number of bonds on the tenascin substrate than on the E-selectin substrate. When protein plating densities were adjusted to give similar profiles of cell detachment under increasing shears, the density of tenascin was 8.5-fold greater than that of E-selectin. Binding to tenascin was not dependent on any molecules previously identified as tenascin receptors and is likely to involve a novel tenascin receptor on lymphocytes. We postulate that the ability of tenascin to support lymphocyte rolling may reflect its ability to support cell migration and that this interaction may be used by lymphocytes migrating through secondary lymphoid organs. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. FU NCI NIH HHS [R01 CA047056, R37 CA047056, CA47056, CA31798, R01 CA031798, R37 CA031798] NR 67 TC 53 Z9 55 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 5 PY 1997 VL 137 IS 3 BP 755 EP 765 DI 10.1083/jcb.137.3.755 PG 11 WC Cell Biology SC Cell Biology GA WY019 UT WOS:A1997WY01900018 PM 9151679 ER PT J AU Tsuji, J Liberman, MC AF Tsuji, J Liberman, MC TI Intracellular labeling of auditory nerve fibers in guinea pig: Central and peripheral projections SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cochlea; cochlear nucleus; spontaneous rate; sensory systems ID ANTEROVENTRAL COCHLEAR NUCLEUS; DIFFERING SPONTANEOUS RATE; SPIRAL GANGLION; CHARACTERISTIC FREQUENCY; HORSERADISH-PEROXIDASE; BASILAR-MEMBRANE; SINGLE UNITS; CAT COCHLEA; AFFERENT; NEURONS AB Auditory-nerve fibers (ANFs) in the cat have been subdivided according to spontaneous rate (SR), with high-SR fibers showing the lowest thresholds. Cochlear terminals of the three SR groups differ in caliber and synaptic position around the inner hair cell(liberman [1982b] Science 216:1239-1241); central terminals differ in degree of branching and in which subregions of the cochlear nucleus (CN) are targeted (Liberman [1991] J. Comp. Neurol. 313:240-258). The present study investigates whether these SR-bascd differences in ANF connections are unique to the cat. Thirty ANFs from 15 guinea pigs were intracellularly labeled after measuring characteristic frequency, threshold, and SR. Labeled cochlear projections showed significant SR-based differences in axonal caliber, with low and medium-SR fibers 20-40% thinner than those of high-SR fibers for both peripheral and central (modiolar) axons. Spatial segregation in the inner hair cell area could not be assessed; however, the peripheral axons in the osseous spiral lamina showed the same SR-based organization reported for the cat (Kawase and Liberman [1992] J. Comp. Neurol. 319:312-318). Labeled central projections also showed significant SR-based differences. Low: and medium-SR fibers: 1) were more highly branched, 2) sent significantly more terminals to the small-cell cap region of the CN, and 3) produced endbulb terminals (on spherical cells) that were significantly more complex than high-SR fibers. All of these SR-based trends for both central and peripheral projections are analogous to those reported in the cat, and, thus, may represent a fundamental organizational principle of the mammalian ear. (C) 1997 Wiley-Liss, Inc. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. KYOTO UNIV,DEPT OTOLARYNGOL,KYOTO 606,JAPAN. MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. FU NIDCD NIH HHS [R01 DC00188] NR 47 TC 114 Z9 118 U1 1 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 5 PY 1997 VL 381 IS 2 BP 188 EP 202 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA WW326 UT WOS:A1997WW32600006 PM 9130668 ER PT J AU Adler, H Beland, JL DelPan, NC Kobzik, L Brewer, JP Martin, TR Rimm, IJ AF Adler, H Beland, JL DelPan, NC Kobzik, L Brewer, JP Martin, TR Rimm, IJ TI Suppression of Herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article; Proceedings Paper CT AAAAI / AAI / CIS Joint Meeting CY FEB 21-26, 1997 CL SAN FRANCISCO, CA SP AAAAI, AAI, CIS ID INTERSTITIAL PNEUMONITIS; VIRAL PNEUMONITIS; LUNG INFECTION; REPLICATION; CELLS; INFLAMMATION; RESPONSES; MOUSE; EXPRESSION; DISEASE AB Intranasal Herpes simplex virus type 1 (HSV-1) infection of mice caused pneumonia. Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival. Immunohistochemical staining demonstrated iNOS induction and the nitrotyrosine antigen in the lungs of infected, but not uninfected mice, suggesting that nitric oxide contributes to the development of pneumonia. To elucidate the role of nitric oxide in the pathogenesis of HSV-1 pneumonia, infected mice were treated either with the inhibitor of nitric oxide synthase activity, N-G-monomethyl-L-arginine (L-NMMA), or, as a control, with PBS or D-NMMA. L-NMMA treatment decreased the histological evidence of pneumonia and reduced the bronchoalveolar lavage lymphocyte number to one-quarter of the total measured in control-treated mice. L-NMMA treatment significantly improved survival and pulmonary compliance of HSV-l-infected mice. Strikingly, the L-NMMA-mediated suppression of pneumonia occurred despite the presence of a 17-fold higher pulmonary viral titer. Taken together, these data demonstrated a previously unrecognized role of nitric oxide in HSV-l-induced pneumonia. Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects. C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV PEDIAT HEMATOL ONCOL,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,PHYSIOL PROGRAM,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV PULM,BOSTON,MA 02115. NR 51 TC 99 Z9 103 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 5 PY 1997 VL 185 IS 9 BP 1533 EP 1540 DI 10.1084/jem.185.9.1533 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WY117 UT WOS:A1997WY11700002 PM 9151890 ER PT J AU Wu, LJ Paxton, WA Kassam, N Ruffing, N Rottman, JB Sullivan, N Choe, H Sodroski, J Newman, W Koup, RA Mackay, CR AF Wu, LJ Paxton, WA Kassam, N Ruffing, N Rottman, JB Sullivan, N Choe, H Sodroski, J Newman, W Koup, RA Mackay, CR TI CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL LINE; CHEMOTACTIC CYTOKINES; HUMAN MONOCYTES; LYMPHOCYTES-T; LEUKOCYTE; INFECTION; MEMORY; CHEMOATTRACTANT; NEUTRALIZATION AB Chemokine receptors serve as coreceptors for HIV entry into CD4(+) cells. Their expression is thought to determine the tropism of viral strains for different cell types, and also to influence susceptibility to infection and rates of disease progression. Of the chemokine receptors, CCR5 is the most important for viral transmission, since CCR5 is the principal receptor for primary, macrophage-tropic viruses, and individuals homozygous for a defective CCR5 allele (Delta 32/Delta 32) are highly resistant to infection with HIV-1. In this study, CCR5-specific mAbs were generated using transfectants expressing high levels of CCR5. The specificity of these mAbs was confirmed using a broad panel of chemokine receptor transfectants, and by their non-reactivity with T cells from Delta 32/Delta 32 individuals. CCR5 showed a distinct pattern of expression, being abundant on long-term activated, IL-2-stimulated T cells, on a subset of effector/memory T cells in blood, and on tissue macrophages. A comparison of normal and CCR5 Delta 32 heterozygotes revealed markedly reduced expression of CCR5 on T cells from the heterozygotes. There was considerable individual to individual variability in the expression of CCR5 on blood T cells, that related to factors other than CCR5 genotype. Low expression of CCR5 correlated with the reduced infectability of T cells with macrophage-tropic HIV-1, in vitro. Anti-CCR5 mAbs inhibited the infection of PBMC by macrophage-tropic HIV-1 in vitro, but did not inhibit infection by T cell-tropic virus. Anti-CCR5 mAbs were poor inhibitors of chemokine binding, indicating that HIV-1 and ligands bind to separate, but overlapping regions of CCR5. These results illustrate many of the important biological features of CCR5, and demonstrate the feasibility of blocking macrophage-tropic HIV-1 entry into cells with an anti-CCR5 reagent. C1 ROCKEFELLER UNIV,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. HARVARD UNIV,SCH MED,DEPT PATHOL,DANA FABER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RP Wu, LJ (reprint author), LEUKOSITE INC,215 1ST ST,CAMBRIDGE,MA 01242, USA. RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NIAID NIH HHS [AI-35522, AI-41384, AI-45218, R01 AI035522, R37 AI024755, R37 AI035522] NR 70 TC 573 Z9 583 U1 1 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 5 PY 1997 VL 185 IS 9 BP 1681 EP 1691 DI 10.1084/jem.185.9.1681 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WY117 UT WOS:A1997WY11700017 PM 9151905 ER PT J AU Allen, DN Gilbertson, MW vanKammen, DP Kelley, ME Gurklis, JA Barry, EJ AF Allen, DN Gilbertson, MW vanKammen, DP Kelley, ME Gurklis, JA Barry, EJ TI Chronic haloperidol treatment does not affect structure of attention in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE attention; haloperidol; schizophrenia ID DISORDERS AB Results of a number of investigations indicate attention is a multifactorial construct composed of four distinct cognitive factors including focus-execute, sustain, encode and shift abilities. While investigators have partially or fully replicated this attentional structure in a number of clinical and nonclinical populations, no study has adequately examined the structure of attention in patients with schizophrenia who are not treated with antipsychotics. In this study, we examined the four-factor theory of attention in patients with schizophrenia while they were stabilized on haloperidol(with no adjunctive antiparkinsonian/anticholinergic medications) and again when they were approximately 3 weeks drug free. Standard neuropsychological measures were used to assess attentional functions. Principal components analyses (varimax rotation) of neuropsychological test scores in medicated and drug-free conditions indicated that four factors accounted for 84.2 and 91.8 of total variance in medicated and unmedicated conditions, respectively. Based on these results, it appears that: (1) haloperidol does not appreciably affect structure of the attentional system in patients with schizophrenia; (2) unmedicated patients with schizophrenia exhibit a similar structure of attention as both medicated patients and controls, suggesting that attentional structure is 'normal' in schizophrenia: and (3) the four-factor attention theory is a useful and valid paradigm for evaluating attention in patients with schizophrenia, regardless of medication status. C1 VET ADM MED CTR,MANCHESTER,NH 03104. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA 15213. RP Allen, DN (reprint author), VA PITTSBURGH HLTH CARE SYST,HIGH DR DIV,7180 HIGHLAND DR,PITTSBURGH,PA 15206, USA. FU NIMH NIH HHS [R01 MH44-841] NR 25 TC 16 Z9 16 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 MAY 3 PY 1997 VL 25 IS 1 BP 53 EP 61 DI 10.1016/S0920-9964(97)00006-6 PG 9 WC Psychiatry SC Psychiatry GA WZ796 UT WOS:A1997WZ79600006 PM 9176927 ER PT J AU Moyers, JS Bilan, PJ Zhu, JH Kahn, CR AF Moyers, JS Bilan, PJ Zhu, JH Kahn, CR TI Rad and Rad-related GTPases interact with calmodulin and calmodulin-dependent protein kinase II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING PROTEIN; ACTIVATION; IDENTIFICATION; ADIPOCYTES; INSULIN; FAMILY; MUSCLE AB Members of the Rad family of GTPases (including Rad, Gem, and Kir) possess several unique features of unknown function in comparison to other Ras like proteins, with major N terminal and C-terminal extensions, a lack of typical prenylation motifs, and several nonconservative changes in the sequence of the GTP binding domain. Here we show that Rad and Gem bind to calmodulin (CaM)-Sepharose in vitro in a calcium-dependent manner and that Rad can be co-immunoprecipitated with CaM in C2C12 cells. The interaction is influenced by the guanine nucleotide binding state of Rad with the GDP-bound form exhibiting 5-fold better binding to CaM than the GTP-bound protein. In addition, the dominant negative mutant of Rad (S105N) which binds GDP, but not GTP, exhibits enhanced binding to CaM in vivo when expressed in C2C12 cells. Peptide competition studies and expression of deletion mutants of Rad localize the binding site for CaM to residues 278-297 at the C terminus of Rad. This domain contains a motif characteristic of a calmodulin-binding region, consisting of numerous basic and hydrophobic residues. In addition, we have identified a second potential regulatory domain in the extended N terminus of Rad which, when removed, decreases Rad protein expression but increases the binding of Rad to CaM. The ability of Rad mutants to bind CaM correlates with their localization in cytoskeletal fractions of C2C12 cells. Immunoprecipitates of calmodulin-dependent protein kinase II, the cellular effector of Ca2+-calmodulin, also contain Rad, and in vitro both Rad and Gem can serve as substrates for this kinase. Thus, the Rad family of GTP-binding proteins possess unique characteristics of binding CaM and calmodulin-dependent protein kinase II, suggesting a role for Rad-like GTPases in calcium activation of serine/threonine kinase cascades. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 45935, DK 07260, P30DK36836] NR 26 TC 73 Z9 75 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 2 PY 1997 VL 272 IS 18 BP 11832 EP 11839 DI 10.1074/jbc.272.18.11832 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX569 UT WOS:A1997WX56900029 PM 9115241 ER PT J AU The, I Hannigan, GE Cowley, GS Reginald, S Zhong, Y Gusella, JF Hariharan, IK Bernards, A AF The, I Hannigan, GE Cowley, GS Reginald, S Zhong, Y Gusella, JF Hariharan, IK Bernards, A TI Rescue of a Drosophila NF1 mutant phenotype by protein kinase A SO SCIENCE LA English DT Article ID GTPASE-ACTIVATING PROTEIN; RECEPTOR TYROSINE KINASE; NEUROFIBROMATOSIS TYPE-1; SEVENLESS PROTEIN; DEVELOPMENTAL ABNORMALITIES; GENE ENCODES; EGF RECEPTOR; CELL FATE; RAS; EXPRESSION AB The neurofibromatosis type 1 (NF1) tumor suppressor protein is thought to restrict cell proliferation by functioning as a Ras-specific guanosine triphosphatase-activating protein. However, Drosophila homozygous for null mutations of an NF1 homolog showed no obvious signs of perturbed Ras1-mediated signaling, Loss of NF1 resulted in a reduction in size of larvae, pupae, and adults. This size defect was not modified by manipulating Ras1 signaling but was restored by expression of activated adenosine 3',5'-monophosphate-dependent protein kinase (PKA). Thus, NF1 and PKA appear to interact in a pathway that controls the overall growth of Drosophila. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. RI The, Inge/B-8884-2011; Hannigan, Greg/A-5092-2009; OI Zhong, Yi/0000-0001-7810-9899 FU NINDS NIH HHS [NS22229, NS36084, NS34779] NR 45 TC 164 Z9 168 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 2 PY 1997 VL 276 IS 5313 BP 791 EP 794 DI 10.1126/science.276.5313.791 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW900 UT WOS:A1997WW90000057 PM 9115203 ER PT J AU Haimovici, JBA TrotmanDickenson, B Halpern, EF Dec, GW Ginns, LC Shepard, JAO McLoud, TC AF Haimovici, JBA TrotmanDickenson, B Halpern, EF Dec, GW Ginns, LC Shepard, JAO McLoud, TC TI Relationship between pulmonary artery diameter at computed tomography and pulmonary artery pressures at right-sided heart catheterization SO ACADEMIC RADIOLOGY LA English DT Article DE heart, interventional procedure; heart, transplantation; hypertension, pulmonary; lung, transplantation; pulmonary arteries; CT ID HYPERTENSION; DISEASE AB Rationale and Objectives. The purpose of the study was to determine the relationship between pulmonary artery (PA) size at computed tomography (CT) and PA pressures, to develop a noninvasive CT method of PA pressure measurement, and to determine a PA diameter that can enable differentiation of normal subjects from those with pulmonary hypertension. Methods. PA vessel diameters in 55 candidates for lung and heart-lung transplantation were measured at CT and correlated with PA pressures with both linear and stepwise multiple regression. The multiple regression equations were then tested prospectively in 35 pretransplantation patients. Results. Combined main and left main PA cross-sectional area corrected for body surface area showed the best correlation with mean PA pressure (r = .87), The multiple regression equations helped predict mean PA pressure within 5 mm Hg in 50% of patients with chronic lung disease and in only 8% of patients with pulmonary vascular disease. Conclusion. There was a very good correlation between main and left main PA size and mean PA pressure. At present, however, CT has not demonstrated sufficient accuracy to be used clinically. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV CARDIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV PULM & CRIT CARE MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,LUNG TRANSPLANTAT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 18 TC 60 Z9 61 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 1997 VL 4 IS 5 BP 327 EP 334 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WY035 UT WOS:A1997WY03500001 PM 9156228 ER PT J AU OSullivan, RL Fava, M Agustin, C Baer, L Rosenbaum, JF AF OSullivan, RL Fava, M Agustin, C Baer, L Rosenbaum, JF TI Sensitivity of the six-item Hamilton depression rating scale SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE six-item Hamilton depression rating scale; sensitivity; depression; atypical depression AB We studied the sensitivity in detecting changes of the 6-item version of the original 17-item Hamilton Depression Rating Scale (HAM-D) and compared it with the more widely used versions among 164 depressed outpatients with and without atypical features before and after treatment with fluoxetine. The 6-item HAM-D was shown to be as sensitive as the 17-, 21- and 24-item versions of this scale. In addition, the different versions of the HAM-D were strongly correlated with each other at baseline and at the endpoint. It appears that the 6-item version of the HAM-D allows the assessment of severity of depression with comparable sensitivity to the standard and more elaborate versions of the same scale. C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP OSullivan, RL (reprint author), OBSESS COMPULS DISORDERS CLIN & RES UNIT,PSYCHIAT NEUROSCI PROGRAM,MGH E,CNY-9,BLDG 149,13TH ST,CHARLESTOWN,MA 02129, USA. NR 12 TC 82 Z9 82 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAY PY 1997 VL 95 IS 5 BP 379 EP 384 DI 10.1111/j.1600-0447.1997.tb09649.x PG 6 WC Psychiatry SC Psychiatry GA XB101 UT WOS:A1997XB10100004 PM 9197901 ER PT J AU Steiner, J Kirsteins, L LaPaglia, N Lawrence, A Williams, D Emanuele, N Emanuele, M AF Steiner, J Kirsteins, L LaPaglia, N Lawrence, A Williams, D Emanuele, N Emanuele, M TI The effect of acute ethanol (EtOH) exposure on protein kinase C (PKC) activity in anterior pituitary SO ALCOHOL LA English DT Article DE ethanol (EtOH); protein kinase C (PKC); anterior pituitary ID GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RNA LEVELS; FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; SECRETION; RAT; CELLS; EXPRESSION; CALCIUM; ACTIVATORS AB Alterations in the protein kinase C (PKC) pathway may interupt anterior pituitary luteinizing hormone (LH) synthesis and/or secretion, which may impair normal reproductive function. Work by our laboratory and others has shown that EtOH has profound deleterious effects on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. The present study focuses on PKC translocation from the cytosol to the membrane of anterior pituitary after acute EtOH exposure. Serum levels of LH were measured at three time points (15, 30, and 90 min) after an TP injection of either saline or 3 g/kg EtOH in adult castrated male rats. LH levels dropped significantly (p < 0.03) in EtOH-injected compared to saline-injected control animals. In the same animals, EtOH significantly suppressed PKC localization at its active site at the pituitary cell membrane (p < 0.05). These findings suggest that the mechanism of EtOH's suppression of LH is mediated, at least in part, through a decrease in PKC translocation to the anterior pituitary cell membrane. (C) 1997 Elsevier Science Inc. C1 LOYOLA UNIV,STRITCH SCH MED,DIV RES DRUGS ABUSE,MAYWOOD,IL 60153. LOYOLA UNIV,STRITCH SCH MED,DEPT MED,MAYWOOD,IL 60153. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,RES & MED SERV,HINES,IL 60141. RP Steiner, J (reprint author), LOYOLA UNIV,STRITCH SCH MED,DEPT MOL & CELLULAR BIOCHEM,PROGRAM MOL BIOL,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. NR 23 TC 10 Z9 10 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAY-JUN PY 1997 VL 14 IS 3 BP 209 EP 211 DI 10.1016/S0741-8329(96)00113-9 PG 3 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA WZ025 UT WOS:A1997WZ02500002 PM 9160797 ER PT J AU Harris, RA Mihic, SJ Brozowski, S Hadingham, K Whiting, PJ AF Harris, RA Mihic, SJ Brozowski, S Hadingham, K Whiting, PJ TI Ethanol, flunitrazepam, and pentobarbital modulation of GABA(A) receptors expressed in mammalian cells and Xenopus oocytes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE GABA; receptors; ethanol; oocytes; benzodiazepine ID GAMMA-AMINOBUTYRIC-ACID; PROTEIN-KINASE-C; A RECEPTORS; SUBUNIT; PHOSPHORYLATION; PHARMACOLOGY; CURRENTS; DESENSITIZATION; POTENTIATION; RESPONSES AB GABA(A) receptors composed of human alpha 1 beta 2 gamma 2L, alpha 1 beta 2 gamma 2S, alpha 1 beta 3 gamma 2S, alpha 6 beta 3 gamma 2S, and alpha 5 beta 3 gamma 3 subunits as well as bovine alpha 1 beta 1 gamma 2L and alpha 1 beta 1 subunits were stably expressed in mammalian L(tk(-)) cells and transiently expressed in Xenopus oocytes, Effects of muscimol, ethanol, flunitrazepam, and pentobarbital on receptor function were compared for the two expression systems using a Cl-36(-) flux assay for cells and an electrophysiological assay for oocytes. Muscimol activated all receptors in both expression systems but was more potent for L(tk(-)) cells than oocytes; this difference ranged from 2.6- to 26-fold, depending upon subunit composition, The most pronounced differences between receptors and expression systems were found for ethanol. In L(tk(-)) cells, low (5-50 mM) concentrations of ethanol potentiated muscimol responses only with receptors containing the gamma 2L subunit, In oocytes, concentrations of 30-100 mM produced small enhancements for most subunit combinations, Flunitrazepam enhanced muscimol responses for all receptors except alpha 6 beta 3 gamma 2S and alpha 1 beta 1, and this enhancement was similar for both expression systems, Pentobarbital also enhanced muscimol responses for all receptors, and this enhancement was similar for L(tk(-)) cells and oocytes, except for alpha 6 beta 3 gamma 2S where the pentobarbital enhancement was much greater in oocytes than cells, The alpha 6 beta 3 gamma 2S receptors were also distinct in that pentobarbital produced direct activation of chloride channels in both expression systems. Thus, the type of expression/assay system markedly affects the actions of ethanol on GABA(A) receptors and also influences the actions of muscimol and pentobarbital on this receptor, Differences between these expression systems may reflect posttranslational modifications of receptor subunits. C1 DENVER VET AFFAIRS MED CTR,DENVER,CO. MERCK SHARP & DOHME RES LABS,HARLOW,ESSEX,ENGLAND. RP Harris, RA (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL C236,SCH MED,4200 E 9TH AVE,DENVER,CO 80262, USA. FU NIAAA NIH HHS [AA06399, AA03527] NR 41 TC 61 Z9 61 U1 0 U2 1 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 MAY PY 1997 VL 21 IS 3 BP 444 EP 451 PG 8 WC Substance Abuse SC Substance Abuse GA WZ645 UT WOS:A1997WZ64500011 PM 9161604 ER PT J AU Wolfsdorf, JI Crigler, JF AF Wolfsdorf, JI Crigler, JF TI Cornstarch regimens for nocturnal treatment of young adults with type I glycogen storage disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the Society-for-Pediatric-Research CY MAY 02-10, 1996 CL WASHINGTON, DC SP Soc Pediat Res DE type I glycogen storage disease; GSD-I; glucose treatment; uncooked cornstarch; metabolic control; young adults; hypoglycemia; metabolism at night ID UNCOOKED CORNSTARCH; PHYSICAL GROWTH; HYPOGLYCEMIA; DEXTROSE; CHILDREN; GLUCOSE; THERAPY AB The goal of treatment of type I glycogen storage disease (CSD-I) is to prevent hypoglycemia and its biochemical consequences. In seven patients with GSD-I with a mean age of 19.5 y (range: 18.8-21.7 y), we compared the biochemical effects of isoenergetic amounts of uncooked cornstarch (UCS; 1.76 +/- 0.41 g/kg) given in random order on consecutive nights either as a single dose at 2100 (time 0) or as equally divided doses at 2100 and 0200. Over the 10-h period of observation there were significant regimen-by-time interactions for plasma glucose, serum insulin, and blood lactate concentrations. Mean time-averaged plasma glucose (5.8 +/- 0.5 compared with 4.9 +/- 0.9 mmol/L) and serum insulin (244 +/- 93 compared with 151 +/- 57 pmol/L) concentrations from 0 to 360 min were significantly higher after the single dose; blood lactate and serum fatty acid concentrations were not significantly different. At 360 min, mean plasma glucose (4.8 +/- 1.2 compared with 4.7 +/- 1.6 mmol/L) and serum insulin (138 +/- 76 compared with 136 +/- 116 pmol/L) concentrations were virtually identical. After a single dose, plasma glucose concentrations were greater than or equal to 3.9 mmol/L for 7 h in five of seven subjects; three subjects were treated for hypoglycemia after 7-9.5 h. With divided doses, plasma glucose concentrations were greater than or equal to 3.9 mmol/L for 9 h in six of seven subjects; hypoglycemia occurred at 6 h in one subject. A single dose (1.76 +/- 0.41 g/kg) of UCS at bedtime maintains plasma glucose concentrations greater than or equal to 3.9 mmol/L for greater than or equal to 7 h in most young adults with GSD-I. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,JOSLIN DIABET CTR,BOSTON,MA 02115. RP Wolfsdorf, JI (reprint author), HARVARD UNIV,DIV ENDOCRINOL,DEPT MED,CHILDRENS HOSP,SCH MED,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCRR NIH HHS [M01 RR02172] NR 21 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1997 VL 65 IS 5 BP 1507 EP 1511 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WW078 UT WOS:A1997WW07800021 PM 9129484 ER PT J AU Akerman, BR Natowicz, MR Kaback, MM Loyer, M Campeau, E Gravel, RA AF Akerman, BR Natowicz, MR Kaback, MM Loyer, M Campeau, E Gravel, RA TI Novel mutations and DNA-based screening in non-Jewish carriers of Tay-Sachs disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BETA-HEXOSAMINIDASE-A; ALPHA-SUBUNIT; HEXA-GENE; ASHKENAZI JEWS; FRENCH-CANADIANS; CYSTIC-FIBROSIS; SPLICE-SITE; IDENTIFICATION; FREQUENCY; PSEUDODEFICIENCY AB We have evaluated the feasibility of using PCR-based mutation screening for non-Jewish enzyme-defined carriers identified through Tay-Sachs disease-prevention programs. Although Tay-Sachs mutations are rare in the general population, non-Jewish individuals may be screened as spouses of Jewish carriers or as relatives of probands. In order to define a panel of alleles that might account for the majority of mutations in non-Jewish carriers, we investigated 26 independent alleles from 20 obligate carriers and 3 affected individuals. Eighteen alleles were represented by 12 previously identified mutations, 7 that were newly identified, and 1 that remains unidentified. We then investigated 46 enzyme-defined carrier alleles: 19 were pseudodeficiency alleles, and five mutations accounted for 15 other alleles. An eighth new mutation was detected among enzyme-defined carriers. Eleven alleles remain unidentified, despite the testing for 23 alleles. Some may represent false positives for the enzyme test. Our results indicate that predominant mutations, other than the two pseudodeficiency alleles (739C-->T and 745C-->T) and one disease allele (IVS9+1G-->A), do not occur in the general population. This suggests that it is not possible to define a collection of mutations that could identify an overwhelming majority of the alleles in non-Jews who may require Tay-Sachs carrier screening. We conclude that determination of carrier status by DNA analysis alone is inefficient because of the large proportion of rare alleles. Notwithstanding the possibility of false positives inherent to enzyme screening, this method remains an essential component of carrier screening in non-Jews. DNA screening can be best used as an adjunct to enzyme testing to exclude known HEXA pseudodeficiency alleles, the IVS9+1G-->A disease allele, and other mutations relevant to the subject's genetic heritage. C1 MCGILL UNIV,MONTREAL CHILDRENS HOSP,RES INST,MONTREAL,PQ H3Z 2Z3,CANADA. MCGILL UNIV,DEPT BIOL,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT PEDIAT,MONTREAL,PQ H3A 2T5,CANADA. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02154. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV CALIF SAN DIEGO,DEPT PEDIAT,SAN DIEGO,CA 92103. UNIV CALIF SAN DIEGO,DEPT REPROD MED,SAN DIEGO,CA 92103. NR 46 TC 9 Z9 11 U1 0 U2 6 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 MAY PY 1997 VL 60 IS 5 BP 1099 EP 1106 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WX760 UT WOS:A1997WX76000010 PM 9150157 ER PT J AU Hutchinson, FN Jones, WJ AF Hutchinson, FN Jones, WJ TI A cost-effectiveness analysis of anemia screening before erythropoietin in patients with end-stage renal disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE anemia; erythropoietin; end-stage renal disease; cost-effectiveness ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; BIRTH-WEIGHT INFANTS; PARATHYROID-HORMONE; HEMODIALYSIS-PATIENTS; EARLY PREDICTION; SERUM; IRON; FAILURE; TRANSFUSION; RESISTANCE AB The treatment efficacy of erythropoietin (EPO) in end-stage renal disease (ESRD) can be limited by deficiencies of iron, folate, or vitamin B-12, by hyperparathyroidism, or by aluminum intoxication. Since EPO costs are significant, this study attempted to determine the cost-effectiveness of performing a panel of screening tests for anemia before starting EPO. Anemia screening was performed prospectively in 48 new-onset ESRD patients at the Ralph H. Johnson Veterans Affairs Medical Center before EPO treatment was started. Serum iron, transferrin, folate, vitamin B-12, parathyroid hormone, and aluminum levels were determined, and transferrin saturation (Tfsat) was calculated at the first dialysis session. At presentation for dialysis, the mean hematocrit was 0.264 +/- 0.036 and the mean blood urea nitrogen was 32 +/- 2 mmol/L. Eighteen patients (37.5%) had a serum iron level tower than 7 mu mol/L, suggesting iron deficiency. Twenty-five patients (52%) had Tfsat less than 0.20, consistent with overt iron deficiency. No patient was found to be vitamin B-12 deficient, to be aluminum intoxicated, or to have significant hyperparathyroidism. One patient had folate deficiency. A cost-effectiveness analysis was performed assuming that (1) EPO would be given at an average starting dose of 6,000 U/wk at a cost of $14/2,000 U of EPO; (2) that without screening 1 month would elapse before a poor response was identified; and (3) that the failure to treat aluminum intoxication and hyperparathyroidism or to replete iron, vitamin B-12, or folate deficiency would significantly impair the response to EPO. The Tfsat screen had a cost-effectiveness ratio of 0.2019, saving approximately $5.00 in EPO use for each dollar of test administration. All other screens had cost-effectiveness ratios greater than 1.0, indicating that their testing costs exceeded dollar savings in EPO use. In conclusion, iron deficiency is common in anemic patients starting dialysis, but other causes of anemia are not. It is imperative that current clinical practices be influenced by cost-effectiveness considerations. Given the cost of laboratory screens, and the relative ineffectiveness of the other screens examined here to identify factors known to impair the response to EPO, anemia screening before initiating EPC therapy should be limited to tests to identify iron deficiency. (C) 1997 by the National Kidney Foundation, Inc. C1 MED UNIV S CAROLINA,DEPT HLTH POLICY & ADM,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. RP Hutchinson, FN (reprint author), MED UNIV S CAROLINA,DEPT MED,DIV NEPHROL,171 ASHLEY MED,CHARLESTON,SC 29425, USA. NR 25 TC 29 Z9 32 U1 1 U2 3 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 MAY PY 1997 VL 29 IS 5 BP 651 EP 657 DI 10.1016/S0272-6386(97)90116-5 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA WZ641 UT WOS:A1997WZ64100002 PM 9159297 ER PT J AU Nussenblatt, RB Gery, I Weiner, HL Ferris, FL Shiloach, J Remaley, N Perry, C Caspi, RR Hafler, DA Foster, CS Whitcup, SM AF Nussenblatt, RB Gery, I Weiner, HL Ferris, FL Shiloach, J Remaley, N Perry, C Caspi, RR Hafler, DA Foster, CS Whitcup, SM TI Treatment of uveitis by oral administration of retinal antigens: Results of a phase I/II randomized masked trial SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; COLLAGEN-INDUCED ARTHRITIS; II COLLAGEN; S-ANTIGEN; SUPPRESSION; TOLERANCE; DISEASE; UVEORETINITIS; INDUCTION AB PURPOSE: To evaluate the effect and safety of the oral administration of retinal antigens as a treatment of ocular inflammation. METHODS: In a phase I/II randomized masked trial, patients with endogenous uveitis who were dependent on immunosuppressive agents were randomly assigned to receive either retinal S antigen alone (10 patients), retinal S antigen and a mixture of soluble retinal antigens (10 patients), a mixture of soluble retinal antigens alone (10 patients), or placebo (15 patients). An attempt was then made to taper patients completely off their standard immunosuppressive therapy over an 8-week period. The primary study endpoint was time to ocular inflammatory attack. The secondary study endpoint was the ability to taper patients completely off their immunosuppressive or cytotoxic medication within 8 weeks. RESULTS: Time to development of the main study endpoint was not statistically significantly different for any of the four treatment groups. However, the group receiving the purified S antigen alone appeared to be tapered off their immuno suppressive medication more successfully compared with patients given placebo (P = .08), whereas all the other groups appeared to do worse than did those receiving placebo. No toxic effects attributable to any treatment were observed. CONCLUSIONS: This phase I/II study is the first to test the use of orally administered S antigen in the treatment of uveitis. Although not statistically significant, patients given S antigen were more likely to be tapered off their chronically administered systemic immunosuppressive therapy than were the other groups tested. C1 NEI,BIOMETRY & EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,BIOTECHNOL UNIT,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. RP Nussenblatt, RB (reprint author), NEI,IMMUNOL LAB,NIH,BLDG 10,ROOM 10N-202,10 CTR DR,BETHESDA,MD 20892, USA. NR 35 TC 105 Z9 112 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 MAY PY 1997 VL 123 IS 5 BP 583 EP 592 PG 10 WC Ophthalmology SC Ophthalmology GA WX869 UT WOS:A1997WX86900001 PM 9152063 ER PT J AU Bhattacharyya, N Wenokur, RK Rubin, PAD AF Bhattacharyya, N Wenokur, RK Rubin, PAD TI Metastasis of squamous cell carcinoma of the conjunctiva: Case report and review of the literature SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Review RP Bhattacharyya, N (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD MAY-JUN PY 1997 VL 18 IS 3 BP 217 EP 219 DI 10.1016/S0196-0709(97)90087-9 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA WZ351 UT WOS:A1997WZ35100012 PM 9164628 ER PT J AU McCue, MP Guinan, JJ AF McCue, MP Guinan, JJ TI Sound-evoked activity in primary afferent neurons of a mammalian vestibular system SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE auditory system; efferents; otoliths; saccule ID ACOUSTIC RESPONSES; SQUIRREL-MONKEY; BRAIN-STEM; GUINEA-PIG; CAT; NERVE; PROJECTIONS; POTENTIALS; INJECTION; SACCULUS AB Hypothesis: Some primary vestibular afferents in the cat respond to sound at moderately intense sound levels. Background: In fish and amphibians, parts of the vestibular apparatus are involved in audition. The possibility was explored that the vestibular system in mammals is also acoustically responsive. Methods: Microelectrodes were used to record from single afferent fibers in the inferior vestibular nerve of the cat; some acoustically responsive fibers were labeled intracellularly with biocytin. Results: Vestibular afferents with regular spontaneous activity were unresponsive to sound, whereas a sizable fraction of vestibular afferents with irregular activity were acoustically responsive. Labeling experiments demonstrated that acoustically responsive afferents innervate the saccule, have cell bodies in Scarpa's ganglion, and project to central regions both inside and outside the traditional boundaries of the vestibular nuclei. Acoustically responsive vestibular afferents responded to sound with shorter latencies than cochlear afferents but had higher thresholds (>90 dB sound pressure level) and responded only in the range 0.1-3.0 kHz. In contrast to cochlear afferents, efferent stimulation excited background activity and proportionately increased sound-evoked responses in these vestibular afferents, that is, there was centrally mediated enhancement of gain (gain = spike-rate/motion). Conclusions: The evolutionary conservation of a saccular auditory pathway in mammals suggests that it confers survival advantages. Recent evidence suggests that acoustically responsive saccular afferents trigger acoustic reflexes of the sternocleidomastoid muscle, and hence measurement of such reflexes may provide a relatively simple test for saccular dysfunction. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB,BOSTON,MA 02114. UNIV MINNESOTA,DEPT NEUROSURG,MINNEAPOLIS,MN 55455. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. FU NIDCD NIH HHS [5 RO1 DC00235, 8T32DC000006] NR 38 TC 81 Z9 87 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 1997 VL 18 IS 3 BP 355 EP 360 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA WX858 UT WOS:A1997WX85800016 PM 9149831 ER PT J AU Qiao, JH Tripathi, J Mishra, NK Cai, Y Tripathi, S Wang, XP Imes, S Fishbein, MC Clinton, SK Libby, P Lusis, AJ Rajavashisth, TB AF Qiao, JH Tripathi, J Mishra, NK Cai, Y Tripathi, S Wang, XP Imes, S Fishbein, MC Clinton, SK Libby, P Lusis, AJ Rajavashisth, TB TI Role of macrophage colony-stimulating factor in atherosclerosis - Studies of osteopetrotic mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LOW-DENSITY LIPOPROTEINS; FACTOR MESSENGER-RNA; GROWTH-FACTOR; APOLIPOPROTEIN-E; GENETIC DETERMINATION; CELL-PROLIFERATION; PLASMA-CHOLESTEROL; FACTOR CSF-1; C-FMS; RECEPTOR AB Previous in vitro and in vivo studies have suggested that macrophage colony-stimulating factor (M-CSF) plays a role in atherogenesis. To examine this hypothesis, we have studied atherogenesis in osteopetrotic (op/op) mice, which lack M-CSF due to a structural gene mutation. Atherogenesis was induced either by feeding the mice a high fat, high cholesterol diet or by crossing op mice with apolipoprotein E (apo E) knockout mice to generate mice lacking both M-CSF and apo E. In both the dietary and apo E knockout models, M-CSF deficiency resulted in significantly reduced atherogenesis. For example, in the apo E knockout model, homozygosity for the op mutation totally abolished aortic atherogenesis in male mice and reduced the size of the lesions approximately 97% in female mice. Mice heterozygous for the op mutation also exhibited a significant decrease in lesion size. Among apo E knockout mice, the frequency of atherosclerosis in aortic arch was 0/6 (op/op), 1/15 (op/+), and 12/16 (+/+). The effect of the M-CSF on atherosclerosis did not appear to be mediated by changes in plasma lipoproteins, as the op mice exhibited higher levels of atherogenic lipoprotein particles. The effects of the op mutation on atherogenesis may have resulted from decreased circulating monocytes, reduced tissue macrophages, or diminished arterial M-CSF. C1 UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DIV ENDOCRINOL,DEPT MED,TORRANCE,CA 90502. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT MICROBIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT MOL GENET,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90024. CEDARS SINAI MED CTR,DEPT PATHOL,LOS ANGELES,CA 90048. CEDARS SINAI MED CTR,DEPT LAB MED,LOS ANGELES,CA 90048. DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,VASC MED & ATHEROSCLEROSIS UNIT,BOSTON,MA 02115. FU NHLBI NIH HHS [HL34636, HL51980, HL30568] NR 49 TC 203 Z9 217 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1997 VL 150 IS 5 BP 1687 EP 1699 PG 13 WC Pathology SC Pathology GA WX141 UT WOS:A1997WX14100017 PM 9137093 ER PT J AU Subramaniam, M Saffaripour, S VanDeWater, L Frenette, PS Mayadas, TN Hynes, RO Wagner, DD AF Subramaniam, M Saffaripour, S VanDeWater, L Frenette, PS Mayadas, TN Hynes, RO Wagner, DD TI Role of endothelial selectins in wound repair SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GRANULE MEMBRANE-PROTEIN; WEIBEL-PALADE BODIES; P-SELECTIN; DEFICIENT MICE; PLASMINOGEN-ACTIVATOR; PLASMA-MEMBRANE; LEUKOCYTE; ALPHA; CELLS; MACROPHAGES AB P- and E-selectins are adhesion molecules expressed on activated endothelium and platelets at sites of vascular injury and inflammation. The selectins are important for leukocyte recruitment. Because little is known about the role of selectins in wound healing, we studied cutaneous wound repair of full-thickness excisional skin wounds in mice lacking P-selectin, E-selectin, or both of these selectins. The absence of either selectin alone had no notable effect on healing, and the only deficit observed was a delay in early neutrophil extravasation in the P-selectin-deficient mice. Mice deficient in both P- and E-selectins had markedly reduced recruitment of inflammatory cells and impaired closure of the wounds. Wound sections, studied up to 3 days after wounding, showed significant impairment of neutrophil influx. Macrophage numbers were also reduced in the double mutants at 3 and 7 days after wounding as compared with wild-type mice. Additionally, a wider epithelial gap in the wounds of the P- and E-selectin-double-deficient mice 3 days after wounding indicated delayed keratinocyte migration. These results demonstrate an important combined role for P- and E-selectins in processes leading to wound healing. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,SHRINERS BURNS INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. RI Frenette, Paul/J-8272-2012 FU NHLBI NIH HHS [HL41484, HL53756, R01 HL065095] NR 42 TC 74 Z9 75 U1 1 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 MAY PY 1997 VL 150 IS 5 BP 1701 EP 1709 PG 9 WC Pathology SC Pathology GA WX141 UT WOS:A1997WX14100018 PM 9137094 ER PT J AU Kradin, R MacLean, J Duckett, S Schneeberger, EE Waeber, C Pinto, C AF Kradin, R MacLean, J Duckett, S Schneeberger, EE Waeber, C Pinto, C TI Pulmonary response to inhaled antigen - Neuroimmune interactions promote the recruitment of dendritic cells to the lung and the cellular immune response to inhaled antigen SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; SUBSTANCE-P; RESPIRATORY-TRACT; LANGERHANS CELLS; ACCESSORY CELLS; NERVES; CAPSAICIN; AIRWAYS; NEUROENDOCRINE; IDENTIFICATION AB Dendritic cells (DCs) play a critical role in capturing and presenting inhaled antigens to T lymphocytes. We report that pulmonary DCs in the Lewis rat are normally located in the lung in immediate proximity to nerve fibers that contain immunoreactive substance P (SP). Functionally, pulmonary DCs bound I-125-SP and displayed increased motility in vitro in response to graded concentrations of SP. However, SP had no effect on the accessory cell activities of DCs. To examine the role of neural influences on the pulmonary immune response to inhaled antigen, Lewis rats were pretreated with capsaicin (CAP), which damages small nerves and depletes neuropeptide stores, and then challenged intratracheally (i.t.) with hen egg lysozyme (HEL). The number and antigen-presenting cell activities of pulmonary DCs in the CAP-treated rats were comparable to those of controls up to day 14. T lymphocytes harvested from the regional lymph nodes draining the lung were effectively sensitized to HEL in both groups. However, when CAP-treated rats sensitized to HEL i.t. at day 0 were rechallenged with HEL i.t. at day 14, the lungs showed decreased numbers of OX-6(+) DCs and diminished pulmonary lymphoid infiltrates compared with controls. We suggest that CAP interferes with a neural-mediated response that contributes to the accumulation of inflammatory cells during the efferent limb of the pulmonary-cell-mediated immune response in vivo. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,GEN MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. RP Kradin, R (reprint author), MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,DEPT PATHOL,100 BLOSSOM ST,COX 5,BOSTON,MA 02114, USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NHLBI NIH HHS [HL48385, HL36781] NR 30 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1997 VL 150 IS 5 BP 1735 EP 1743 PG 9 WC Pathology SC Pathology GA WX141 UT WOS:A1997WX14100021 PM 9137097 ER PT J AU Coito, AJ Brown, LF Peters, JH KupiecWeglinski, JW VanDeWater, L AF Coito, AJ Brown, LF Peters, JH KupiecWeglinski, JW VanDeWater, L TI Expression of fibronectin splicing variants in organ transplantation - A differential pattern between rat cardiac allografts and isografts SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HYPERSENSITIVITY SKIN REACTIONS; MESSENGER-RNA PRECURSORS; SMOOTH-MUSCLE CELLS; GROWTH FACTOR-BETA; CD4+ T-CELLS; EXTRACELLULAR-MATRIX; PROLIFERATIVE GLOMERULONEPHRITIS; EMBRYONIC FIBRONECTINS; CORONARY ARTERIOPATHY; CELLULAR FIBRONECTIN AB Allograft rejection is associated with infiltration of inflammatory cells and deposition of extracellular matrix proteins. The extent to which diversity in the extracellular matrix regulates inflammatory cell function in transplants remains unclear. One group of extracellular matrix proteins, termed fibronectins (FNs), exhibits inherent diversity as a consequence of alternative splicing in three segments: EIIIA, EIIIB, or V. Although the EIIIA segment has documented functions in mesenchymal cell differentiation, neither this segment nor the EIIIB segment have been tested for effects specific to leukocyte functions. By contrast, the V region can include the CS-1 segment to which leukocytes may adhere through alpha(4) beta(1) integrins. In this study, we demonstrate that EIIIA(+), EIIIB+, and V+ FN variants are synthesized, primarily by macrophages in distinct temporal and spatial patterns in two rat cardiac transplant models: either with antigenic challenge, allografts, or without challenge, isografts. The ratio of EIIIA inclusion into FN increases by day 1 in allografts and isografts and remains high until allografts are rejected (similar to 7 days) but falls to normal levels in tolerated isografts (day 6). EIIIB+ FN ratios in allografts peak later than do EIIIA(+) FNs (day 4). EIIIB+ FN ratios remain relatively low in isografts. Interestingly, EIIIA(+) and EIIIB+ FNs are deposited prominently in the myocardium of rejecting allografts in close association with infiltrating leukocytes, and FN expression and deposition are prominent at sites of infarction. By contrast, these FNs are largely restricted to the epicardium and to a lesser degree in the immediately adjacent myocardium in isografts. CS-1(+) FNs increase in allografts and isografts at 3 hours after transplantation but are particularly prominent in allografts 1 to 3 days before rejection. Our data suggest that FN splicing variants have a differential role in the effector functions of leukocytes in allografts and isografts and provide a foundation for testing their function on leukocytes and a rationale for FN-based therapeutics to modulate allograft rejection in transplant recipients. C1 BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,SURG RES LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. CEDARS SINAI MED CTR,DIV PULM MED,LOS ANGELES,CA 90048. FU NIAID NIH HHS [R01 AI23847]; NIGMS NIH HHS [GM-36812] NR 62 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1997 VL 150 IS 5 BP 1757 EP 1772 PG 16 WC Pathology SC Pathology GA WX141 UT WOS:A1997WX14100023 PM 9137099 ER PT J AU Aurang, K Spraggs, CF Jordan, C Lloyd, KCK AF Aurang, K Spraggs, CF Jordan, C Lloyd, KCK TI Role of gastrin/CCK-B receptors in meal-stimulated acid secretion in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE stomach; histamine; somatostatin; receptor antagonists ID HISTAMINE-RELEASE; CHOLECYSTOKININ RECEPTORS; SOMATOSTATIN SECRETION; STOMACH; ANTAGONISTS; PEPTONE; NEURONS; CCK; ACETYLCHOLINE; PENTAGASTRIN AB Gastrin is the principal hormonal mediator of gastric acid secretion. Using an in vivo, intact, anesthetized rat model, we studied the role of gastrin/cholecystokinin (CCK)-B receptors in regulating the release of histamine and somatostatin during intragastric stimulation of acid secretion during a peptone meal. In pylorus-ligated, adult male rats (each implanted with a gastric cannula and portal venous and splenic artery catheters), after a 30-min basal period, gastric acid secretion was stimulated for 90 min either by an intravenous infusion of gastrin-17 (15 mu g.kg(-1).h(-1)) or by extragastric titration of 5 mi 8% peptone meal at pH 5.5. Basal and stimulated acid outputs and portal venous plasma gastrin, histamine, and somatostatin concentrations were measured before and after close-arterial injection of a new, relatively selective, gastrin/CCK-B receptor antagonist GR143330X. GR143330X reduced basal acid output by 50% but not basal plasma gastrin, histamine, or somatostatin concentrations. GR143330X reduced gastrin-stimulated acid output by 80%, plasma histamine by 70%, and plasma somatostatin by 34%. During intragastric peptone meal stimulation GR143330X reduced the acid response by 42% during the 30- to 60-min period but not during the 60- to 90-min period. GR143330X reduced the plasma histamine response by 72 and 68%, and the plasma somatostatin response by 32 and 54% during the 30- to 60- and 60- to 90-min periods, respectively. GR143330X did not block the gastrin response to peptone at any time. These results indicate that GR143330X is an effective agent for blocking gastrin-stimulated acid secretion and histamine and somatostatin release in rats. Furthermore, we show for the first time in an intact, in vivo, anesthetized rat model that meal-stimulated activation of gastrin/CCK-B receptors stimulates acid secretion in part by regulating the release of histamine and somatostatin. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, RES SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, MED SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, CTR ULCER RES & EDUC, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, GASTROENTER BIOL CTR, LOS ANGELES, CA 90073 USA. GLAXO GRP RES LTD, RES & DEV, WARE SG12 0DP, HERTS, ENGLAND. NR 34 TC 10 Z9 10 U1 0 U2 0 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 MAY PY 1997 VL 272 IS 5 BP G1243 EP G1248 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WZ327 UT WOS:A1997WZ32700038 ER PT J AU Lloyd, KCK Amirmoazzami, S Friedik, F Heynio, A Solomon, TE Walsh, JH AF Lloyd, KCK Amirmoazzami, S Friedik, F Heynio, A Solomon, TE Walsh, JH TI Candidate canine enterogastrones: acid inhibition before and after vagotomy SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE peptide YY; cholecystokinin; secretin; neurotensin; glucagon-like peptide-1; oxyntomodulin; somatostatin; gastric inhibitory peptide; gastric acid secretion ID STIMULATED GASTRIC-ACID; DUODENAL-ULCER PATIENTS; PEPTIDE-YY; OLEIC-ACID; SOMATOSTATIN RELEASE; TRUNCAL VAGOTOMY; FAT INHIBITION; INTESTINAL FAT; SECRETION; DOGS AB The relative contributions of several gut-derived peptides as enterogastrones known to be released in response to a fatty meal and to inhibit acid secretion have not previously been compared directly. We determined the acid-inhibitory activities of increasing intravenous doses of several peptides before and after highly selective vagotomy (HSV) during intragastric titration of a peptone meal in dogs. Before HSV, threshold inhibitory doses of peptide YY (PYY), cholecystokinin (CCK), and secretin were 5, 7, and 10 pmol.kg(-1).h(-1), respectively, whereas neurotensin, glucagonlike peptide-1 (GLP-1), and oxyntomodulin failed to inhibit acid secretion at doses up to 1,000 pmol.kg(-1).h(-1). The calculated dose producing 50% acid inhibition (ID50) Of secretin (62 pmol.kg(-1).h(-1)) was one-half that of PW (128 pmol.kg(-1).h(-1)). Maximal (90%) acid inhibition was produced by 100 pmol.kg(-1).h(-1) secretin and 500 pmol.kg(-1).h(-1) PYY. The highest dose of CCK that did not cause vomiting (100 pmol.kg(-1).h(-1)) inhibited peptone-stimulated acid output by only 60%. After HSV, 500 pmol.kg(-1).h(-1) PYY and 200 pmol.kg(-1).h(-1) CCK failed to inhibit acid output by more than 50%. Threshold doses for inhibition by PW and CCK were 200 and 100 pmol.kg(-1).h(-1), respectively. Secretin remained a potent inhibitor after HSV, with an ID50 Of 80 pmol.kg(-1).h(-1) and a threshold dose of 10 pmol.kg(-1).h(-1). HSV also failed to affect inhibition caused by somatostatin. This study has shown that PYY and secretin are somewhat more potent and efficacious inhibitors of acid secretion than CCK but that all three peptides are far more active than GLP-1, neurotensin, and oxyntomodulin. PW and CCK inhibit acid secretion in large part through vagal innervation of the gastric fundus, but the inhibitory effects of secretin are independent of fundic vagal innervation. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, RES SERV, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, MED SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. RP Lloyd, KCK (reprint author), UNIV CALIF LOS ANGELES, CURE VA WADSWORTH MED CTR, DIGEST DIS CORE CTR, BLDG 115, RM 115, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-45752] NR 53 TC 9 Z9 9 U1 0 U2 0 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 MAY PY 1997 VL 272 IS 5 BP G1236 EP G1242 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WZ327 UT WOS:A1997WZ32700037 PM 9176235 ER PT J AU Menconi, MJ Salzman, AL Unno, N Ezzell, RM Casey, DM Brown, DA Tsuji, Y Fink, MP AF Menconi, MJ Salzman, AL Unno, N Ezzell, RM Casey, DM Brown, DA Tsuji, Y Fink, MP TI Acidosis induces hyperpermeability in Caco-2BBe cultured intestinal epithelial monolayers SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intestine; tight junction; ATP; hypercarbia; epithelium; dextran ID TIGHT JUNCTION PERMEABILITY; CELL MONOLAYERS; PARACELLULAR PERMEABILITY; MUCOSAL HYPERPERMEABILITY; BARRIER FUNCTION; CYTOPLASMIC PH; MDCK CELLS; TRANSPORT; INCREASES; PIGS AB We previously demonstrated that ileal mucosal acidosis in pigs reversibly increases intestinal permeability to hydrophilic macromolecules, even in the absence of tissue hypoxia [A. L. Salzman, H. Wang, P. S. Wollert, T. J. Vandermeer, C. C. Compton, A. G. Denenberg, and M. P. Fink. Am. J. Physiol. 266 (Gastrointest. Liver Physiol. 29): G633-G646, 1994]. In an effort to further explore the mechanism(s) underlying this phenomenon, we examined the effect of acidic pH on the permeability characteristics of cultured Caco-2BBe (human intestinal epithelial) cells grown as monolayers on permeable supports. Permeability was determined by measuring the mucosal-to-basolateral flux of fluorescein disulfonic acid (FS; mol wt 478 Da), fluorescein isothiocyanate-labeled dextran (FD4; average mol wt 4 kDa), or [H-3]mannitol. Incubation of monolayers under hypercarbic conditions or with acidified bicarbonate-free medium significantly increased permeability to FS, FD4, and mannitol in a manner dependent on both time and pH. Incubation in medium at pH 5.43 for 24 h increased the release of lactate dehydrogenase and decreased the intensity of staining with calcein-acetoxymethyl ester, findings that are indicative of plasma membrane injury; nevertheless, the percentage of nonviable cells did not increase. Ultrastructural analyses revealed evidence of increased paracellular trafficking of horseradish peroxidase after incubation of monolayers under acidic conditions. Fluorescence confocal microscopy and temperature studies demonstrated that incubation at pH 5.43 induced an increase in both the intracellular uptake of FD4 and the activation energy for FS permeation across Caco-2BBe monolayers, respectively, suggesting increased transcellular permeation. Exposure to acidic conditions also decreased cellular levels of ATP. We conclude that acidosis increases both paracellular and transcellular permeability to hydrophilic macromolecules and leads to depletion of ATP. C1 BETH ISRAEL DEACONESS MED CTR, DEPT SURG, BOSTON, MA 02215 USA. BETH ISRAEL DEACONESS MED CTR, DEPT ANESTHESIOL, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02215 USA. NR 39 TC 51 Z9 53 U1 0 U2 1 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 MAY PY 1997 VL 272 IS 5 BP G1007 EP G1021 PG 15 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WZ327 UT WOS:A1997WZ32700011 ER PT J AU Graf, O Boland, GW Kaufman, JA Warshaw, AL delCastillo, CF Mueller, PR AF Graf, O Boland, GW Kaufman, JA Warshaw, AL delCastillo, CF Mueller, PR TI Anatomic variants of mesenteric veins: Depiction with helical CT venography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SPIRAL CT; ANGIOGRAPHY; VASCULATURE; APPEARANCE AB OBJECTIVE, The purpose of this study was to describe the variable anatomy of mesenteric veins on axial CT Images and on volume-rendered CT venograins that use maximum intensity projection and shaded-surface display. SUBJECTS AND METHODS, Fifty-seven patients undergoing helical CT of the pancreas were included in the study. The mesenteric venous system was analyzed in 54 patients. Three patients were excluded because the helical CT data were unsatisfactory. RESULTS. On helical CT with maximum intensity projection and shaded-surface display, the superior mesenteric vein (SMV) was seen as a single trunk of variable length in 40 patients, In seven other patients, two mesenteric trunks merged separately with the splenic vein. In the remaining seven patients, the SMV was occluded by tumor. The inferior mesenteric vein drained into the splenic vein in 28 patients (56%), into the SMV in 14 patients (26%), and into the splenomesenteric angle in nine patients (18%). CONCLUSION, Both axial and volume-rendered CT venograms accurately reveal the variable mesenteric venous anatomy, CT venograms may replace conventional angiography in presurgical planning. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 24 TC 28 Z9 33 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1997 VL 168 IS 5 BP 1209 EP 1213 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV568 UT WOS:A1997WV56800013 PM 9129413 ER PT J AU Hunter, JC Escobedo, EM Wilson, AJ Hanel, DP ZinkBrody, GC Mann, FA AF Hunter, JC Escobedo, EM Wilson, AJ Hanel, DP ZinkBrody, GC Mann, FA TI MR imaging of clinically suspected scaphoid fractures SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 05-10, 1996 CL SAN DIEGO, CA SP Amer Roentgen Ray Soc ID OCCULT FRACTURES; BONE; CT; SCINTIGRAPHY AB OBJECTIVE. The purpose of this study was to evaluate the usefulness of MR imaging in revealing occult fractures in patients with clinically suspected acute scaphoid fractures who have normal or equivocal findings on radiographs. SUBJECTS AND METHODS. Thirty-six patients underwent MR imaging within 7 days of wrist injury. All had physical findings suggestive of scaphoid fracture. Coronal T1-weighted, short inversion time inversion recovery, and either T2-weighted or proton density-weighted fast spin-echo sequences with fat suppression were used. Follow-up radiographs were obtained at least 2 weeks after MR imaging whenever possible. All imaging studies were reviewed by two musculoskeletal radiologists. RESULTS. MR imaging revealed 22 occult fractures in 20 patients. Thirteen of these 22 fractures were in the scaphoid bone, and nine were in the distal radius. On MR images, 18 patients had no evidence of fracture. Follow-up radiographs were available in 14 of the 20 patients who had occult fracture revealed by MR imaging. Eleven of the 13 occult fractures of the scaphoid bone were followed up (two were lost to follow-up), and 10 of the 11 showed signs of healing. Five of the nine lesions of the distal radius were followed up, and three of these showed evidence of healing fracture. Three patients without MR evidence of a fracture had follow-up radiographs that showed no fracture. Three patients had findings consistent with bone contusion on MR images; in two patients, the contusion was associated with other fractures, and in one patient, the contusion was isolated. CONCLUSION. MR imaging can reveal occult wrist fractures when findings on radiographs are normal or equivocal. C1 UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT ORTHOPAED SURG,SEATTLE,WA 98104. UNIV WASHINGTON,VET AFFAIRS PUGET SOUND HLTH CARE SYST,DEPT RADIOL,SEATTLE,WA 98108. UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT ORTHOPAED SURG,SEATTLE,WA 98104. KAISER PERMANENTE HOSP,DEPT RADIOL,HAYWARD,CA 94545. RP Hunter, JC (reprint author), UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT RADIOL,325 9TH AVE,BOC 359728,SEATTLE,WA 98104, USA. NR 33 TC 86 Z9 87 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1997 VL 168 IS 5 BP 1287 EP 1293 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV568 UT WOS:A1997WV56800032 PM 9129428 ER PT J AU Mehta, A Teoh, SK Schaefer, PW Chew, FS AF Mehta, A Teoh, SK Schaefer, PW Chew, FS TI Radiologic-pathologic conferences of the Massachusetts general hospital - Cerebral schistosomiasis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Mehta, A (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 9 Z9 11 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1997 VL 168 IS 5 BP 1322 EP 1322 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV568 UT WOS:A1997WV56800039 PM 9129435 ER PT J AU Duerinckx, AJ Hayrapetian, A Melany, M Valentino, DJ Rahbar, D Kiszonas, M Franco, R Narin, SL Ragavendra, N Grant, EG AF Duerinckx, AJ Hayrapetian, A Melany, M Valentino, DJ Rahbar, D Kiszonas, M Franco, R Narin, SL Ragavendra, N Grant, EG TI Real-time sonographic video transfer using asynchronous transfer mode technology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID NETWORK C1 UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT RADIOL,LOS ANGELES,CA 90095. GTE TEL OPERAT,THOUSAND OAKS,CA 91362. RP Duerinckx, AJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,SERV RADIOL,11301 WILSHIRE BLVD,MAIL ROUTE W114,MRI,BLDG 506,LOS ANGELES,CA 90073, USA. NR 9 TC 7 Z9 7 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1997 VL 168 IS 5 BP 1353 EP 1355 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV568 UT WOS:A1997WV56800047 PM 9129443 ER PT J AU Weir, MM Bell, DA Young, RH AF Weir, MM Bell, DA Young, RH TI Transitional cell metaplasia of the uterine cervix and vagina: An underrecognized lesion that may be confused with high-grade dysplasia - A report of 59 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE transitional cell metaplasia; Walthard's nest; cervix; vagina ID ENDOCRINE-CELLS AB Sixty-three examples of transitional cell metaplasia of the cervix or vagina from patients 50 to 84 (average 67.6) years of age are described. Fifty-seven of the 59 patients were postmenopausal and two perimenopausal. Only four patients were documented to have received hormonal therapy. The lesion was an incidental microscopic finding in all patients and was found in 29 hysterectomy specimens, 18 endocervical or endometrial curettage specimens, 11 cervical biopsy or cone biopsy specimens, and five vaginal biopsy specimens. The sites involved by transitional cell metaplasia were the exocervix (n = 14), transformation zone (n = 33), vagina (n = 10), or a combination (n = 4). The cervical and vaginal specimens most commonly showed involvement of the surface epithelium by transitional cell metaplasia. Other transitional cell patterns were isolated stromal nests (n = 9) and invagination of surface epithelium into the underlying stroma (n = 2). The typical appearance of transitional cell metaplasia was a hyperplastic epithelium with lack of maturation, consisting of spindled nuclei with tapered ends and frequent longitudinal nuclear grooves. The nuclei were typically oriented vertically in the deeper layers, and horizontally with a streaming pattern superficially. The cells had low nuclear to cytoplasmic ratios, perinuclear halos, and absent to rare mitotic figures. Mild to moderate atypia was seen in only two cases. Many of the cases could have been confused with squamous dysplasia due to the lack of apparent maturation. However, in most cases, attention to cytologic detail disclosed the typical features of transitional cell metaplasia. This process, usually seen in older women, has not been emphasized and can be overdiagnosed as dysplasia, leading to unnecessary treatment. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. NR 12 TC 25 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1997 VL 21 IS 5 BP 510 EP 517 DI 10.1097/00000478-199705000-00002 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA WZ255 UT WOS:A1997WZ25500002 PM 9158674 ER PT J AU Keel, SB Bhan, AK Liebsch, NJ Rosenberg, AE AF Keel, SB Bhan, AK Liebsch, NJ Rosenberg, AE TI Chondromyxoid fibroma of the skull base: A tumor which may be confused with chordoma and chondrosarcoma: A report of three cases and review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE chondromyxoid fibroma; skull base; clivus; chordoma; chondrosarcoma ID OCCIPITAL BONE; S-100 PROTEIN; CHONDROBLASTOMA AB Three cases of chondromyxoid fibroma arising in the skull base are reported. The tumors arose in females 34, 65, and 66 (median 55) years of age. Two women presented with headaches, and one with nasal obstruction. Radiographic studies revealed that all three lesions were expansile soft tissue masses centered in the clivus, at least 4 cm in greatest diameter. One lesion involved primarily the clivus, the others extended from the clivus into the sphenoid and ethmoid sinuses. Two of the three cases were initially misdiagnosed as chordoma or chondrosarcoma. The initial treatment was curettage of gross disease in all three cases. One patient also received radiation therapy. One patient had local progression of disease, which was treated with surgery and radiation therapy. All patients are clinically free of disease 11 to 26 months following the most recent treatment. Chondromyxoid fibroma can and should be distinguished from chondrosarcoma and chordoma, two tumors which more commonly arise in the skull base and which have the potential to metastasize. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. NR 25 TC 38 Z9 40 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1997 VL 21 IS 5 BP 577 EP 582 DI 10.1097/00000478-199705000-00011 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA WZ255 UT WOS:A1997WZ25500011 PM 9158683 ER PT J AU Ferry, JA Young, RH Scully, RE AF Ferry, JA Young, RH Scully, RE TI Testicular and epididymal plasmacytoma: A report of 7 cases, including three that were the initial manifestation of plasma cell myeloma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testis; epididymis; plasmacytoma; plasma cell; myeloma; immunoperoxidase ID TESTIS; LYMPHOMA AB We report the cases of six men, 40 to 89 years of age, with testicular (6 cases) or epididymal (1 case) plasmacytoma. Patients presented with a mass in five cases. One tumor was found during evaluation of progressive myeloma. In the final case, the testicular lesion was identified when the patient presented with pathologic fractures. Gross inspection revealed discrete or, less often, ill-defined lesions. Microscopic examination disclosed masses of atypical plasma cells, including binucleated and multinucleated cells and, occasionally, anaplastic cells that obliterated the underlying parenchyma or invaded between seminiferous or epididymal tubules. Immunohistochemical stains on paraffin sections in five cases showed tumor cell expression of monotypic cytoplasmic immunoglobulin. The cells were positive for the leukocyte common antigen (CD45) in three of five cases. All four cases tested were negative for B (CD20) and T (CD3) cell specific antigens and for CD30 and placental alkaline phosphatase. Expression of CD43, CD45RO, and epithelial membrane antigen was found in three, two, and one of four cases respectively. All the patients also had plasma cell neoplasia distant from the testis, identified before (3 cases), concurrent with (3 cases) or after (1 case) the testicular or epididymal plasmacytoma. In one patient a plasmacytoma developed in the contralateral testis three years later; he was alive with plasma cell myeloma 51 months after diagnosis. Another had a plasmacytoma in the contralateral epididymis 8 years later; he also had a nasal cavity plasmacytoma and multiple subcutaneous plasmacytomas, and was alive and well after 26 years. One additional patient was alive with myeloma 6 months later, and four final patients died between 2 months and 3 years after orchiectomy. Three of the four consultation cases in this series were submitted with diagnoses of spermatocytic seminoma, anaplastic seminoma and lymphoma. The diagnosis of plasmacytoma should be borne in mind when examining testicular or paratesticular tumors with a diffuse pattern without glandular differentiation, particularly in men 40 years of age or older. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 35 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1997 VL 21 IS 5 BP 590 EP 598 DI 10.1097/00000478-199705000-00013 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA WZ255 UT WOS:A1997WZ25500013 PM 9158685 ER PT J AU Zupke, C Tompkins, R Yarmush, D Yarmush, M AF Zupke, C Tompkins, R Yarmush, D Yarmush, M TI Numerical isotopomer analysis: Estimation of metabolic activity SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID CITRIC-ACID CYCLE; FLUXES; C-13; LIVER AB The use of stable isotopes to analyze intracellular metabolism is a powerful technique because of the wealth of information contained in the distribution of isotopes in key metabolites. We present a new numerical method of using measurements of isotope isomer (isotopomer) distributions to calculate the fluxes through a biochemical reaction network. Nuclear magnetic resonance (NMR) and/or mass spectroscopy can quantify the isotopomers which result from the metabolism of an isotopically enriched substrate. These data can be analyzed via a numerical model of the metabolic network which uses atom-mapping matrices to simplify model construction. The atom-mapping matrices describe the transfer of atoms from reactant to product and the resulting isotopomer balance equations are compact and intuitive. These equations are solved iteratively to determine the unknown intracellular fluxes. Results from the numerical method agreed with an analytical solution developed for the analysis of the tricarboxylic acid cycle in perfused hearts. (C) 1997 Academic Press. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. NR 16 TC 17 Z9 19 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 1 PY 1997 VL 247 IS 2 BP 287 EP 293 DI 10.1006/abio.1997.2076 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WZ661 UT WOS:A1997WZ66100015 PM 9177690 ER PT J AU Povey, S Attwood, J Chadwick, B Frezal, J Haines, JL Knowles, M Kwiatkowski, DJ Olopade, OI Slaugenhaupt, S Spurr, NK Smith, M Steel, K White, JA PericakVance, MA AF Povey, S Attwood, J Chadwick, B Frezal, J Haines, JL Knowles, M Kwiatkowski, DJ Olopade, OI Slaugenhaupt, S Spurr, NK Smith, M Steel, K White, JA PericakVance, MA TI REPORT on the Fifth International Workshop on Chromosome 9 held at Eynsham, Oxfordshire, UK, September 4-6, 1996 SO ANNALS OF HUMAN GENETICS LA English DT Editorial Material ID LINKAGE; APRIL; GENE; LOCI AB The Fifth International workshop on chromosome 9 comprised a gathering of 36 scientists from seven countries and included a fairly even distribution of interests along chromosome 9 as well as a strong input from more global activities and from comparative mapping. At least eight groups had participated in the goal set at the previous workshop which was to improve the fine genetic mapping in different regions of chromosome 9 by meiotic breakpoint mapping in allocated regions and this has resulted in some greatly improved order information. Excellent computing facilities were available and all contributed maps were entered not only into SIGMA (and thence submitted to GDB) but also into a dedicated version of ACEDB which can be accessed on the Web in the form of one of 28 slices into which the chromosome has been arbitrarily divided. It was generally agreed that the amount of data is now overwhelming and that the integration and validation of all data is not only unrealistic in a short meeting but probably impossible until the whole chromosome has been sequenced and fully annotated. Sequence-ready contigs presented at the meeting totalled about 3 MB which is about one fiftieth of the estimated length. The single biggest barrier to integration of maps is the problem of non-standard nomenclature of loci. In the past 2 workshops efforts have been made to compare traditional 'consensus' maps made by human insight (still probably best for small specific regions) with those generated with some computer assistance (such as SIGMA) and those generated objectively by defined computer algorithms such as ldb. Since no single form of map or representation is entirely satisfactory for all purposes the maps reproduced in the published version of the report are confined to one of the genetic maps, in which Genethon and older markers have been incorporated, a Sigma map of the genes as symbols together with a listing of known 'disease' genes on chromosome 9, and, a revised assessment of the mouse map together with a list of mouse loci predicted to be on human chromosome 9. One of the 28 ACEDB slices is also shown to illustrate strengths and weaknesses of this approach. Workshop files include not. only all maps available at the time but also details of loci and details of the meiotic breakpoints in the CEPH families (http://www.gene.ucl.ac.uk/scw9db.shtml). This report and other information on chromosome 9 can be found on the chromosome 9 homepage at the URL:http://www.gene.ucl.ac.uk/chr9/. C1 IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. HOP NECKER ENFANTS MALAD,SERV GENET MED,GENATLAS,F-75743 PARIS 15,FRANCE. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. MARIE CURIE RES INST,OXTED RH8 0TL,SURREY,ENGLAND. BRIGHAM & WOMENS HOSP,DIV EXPT MED,BOSTON,MA 02115. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. SMITHKLINE BEECHAM PHARMACEUT,HARLOW CM19 5AW,ESSEX,ENGLAND. JOHNS HOPKINS UNIV HOSP,CTR MED GENET,BALTIMORE,MD 21287. MRC,INST HEARING RES,NOTTINGHAM NG7 2RD,ENGLAND. DUKE UNIV,MED CTR,DIV NEUROL,DURHAM,NC 27710. RP Povey, S (reprint author), UNIV LONDON UNIV COLL,GALTON LAB,MRC,HUMAN BIOCHEM GENET UNIT,WOLFSON HOUSE,4 STEPHENSON WAY,LONDON NW1 2HE,ENGLAND. RI Haines, Jonathan/C-3374-2012 NR 49 TC 24 Z9 24 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 183 EP 206 DI 10.1046/j.1469-1809.1997.6130183.x PN 3 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500001 PM 9250350 ER PT J AU Haines, JL Burgess, K Terwedow, H AF Haines, JL Burgess, K Terwedow, H TI A meiotic breakpoint map near the FRDA region of chromosome 9. SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 213 EP 213 PN 3 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500013 ER PT J AU Kwiatkowski, DJ Humphrey, D VanSlegtenhorst, M Attwood, J Haines, JL Burley, MW Hornigold, N Smith, M Nahmias, J Faure, S Povey, S AF Kwiatkowski, DJ Humphrey, D VanSlegtenhorst, M Attwood, J Haines, JL Burley, MW Hornigold, N Smith, M Nahmias, J Faure, S Povey, S TI A dense STR map of 1.5 Mb of 9q34: Small reduction in the TSC1 critical region. SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,DEPT CLIN GENET,NL-3000 DR ROTTERDAM,NETHERLANDS. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. UNIV LONDON UNIV COLL,GALTON LAB,LONDON,ENGLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. UNIV CALIF IRVINE,DEPT PEDIAT,IRVINE,CA 92717. GENETHON,EVRY,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 214 EP 215 PN 3 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500016 ER PT J AU McIntosh, I Clough, MV Schaffer, AA Francomano, CA McCormick, MK AF McIntosh, I Clough, MV Schaffer, AA Francomano, CA McCormick, MK TI Fine mapping of the nail-patella syndrome locus and integration of new markers into the 9q34 map. SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21287. NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. RI Schaffer, Alejandro/F-2902-2012 NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 216 EP 217 PN 3 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500019 ER PT J AU Ozelius, L Attwood, J Rebello, M Povey, S Breakefield, X AF Ozelius, L Attwood, J Rebello, M Povey, S Breakefield, X TI Use of meiotic breakpoint panel to map markers into the interval between D9S60 and ABL. SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET LAB,CHARLESTOWN,MA 02129. UCL,MRC,HUMAN BIOCHEM GENET UNIT,LONDON NW1 2HE,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 219 EP 220 PN 3 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500023 ER PT J AU Slaughenhaupt, SA Moody, D Liebert, CB Povey, S Rebello, M Attwood, J Gusella, JF AF Slaughenhaupt, SA Moody, D Liebert, CB Povey, S Rebello, M Attwood, J Gusella, JF TI Saturation of the genetic map and expansion of the physical map surrounding the familial dysautonomia gene on human chromosome 9. SO ANNALS OF HUMAN GENETICS LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. UNIV LONDON UNIV COLL,MRC,HUMAN BIOCHEM GENET UNIT,LONDON NW1 2HE,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAY PY 1997 VL 61 BP 223 EP 223 PN 3 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA XM185 UT WOS:A1997XM18500029 ER PT J AU Koroshetz, WJ Gonzalez, G AF Koroshetz, WJ Gonzalez, G TI Diffusion-weighted MRI: An ECG for ''brain attack'' SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID ACUTE HUMAN STROKE; CEREBRAL-ISCHEMIA; RESONANCE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEURORADIOL,BOSTON,MA. RP Koroshetz, WJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114, USA. NR 9 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1997 VL 41 IS 5 BP 565 EP 566 DI 10.1002/ana.410410502 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ809 UT WOS:A1997WZ80900001 PM 9153515 ER PT J AU Stern, Y Brandt, J Albert, M Jacobs, DM Liu, XH Bell, K Marder, K Sano, M Albert, S Castenada, CD Bylsma, F Tycko, B Mayeux, R AF Stern, Y Brandt, J Albert, M Jacobs, DM Liu, XH Bell, K Marder, K Sano, M Albert, S Castenada, CD Bylsma, F Tycko, B Mayeux, R TI The absence of an apolipoprotein epsilon 4 allele is associated with a more aggressive form of Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID PROBABLE ALZHEIMERS-DISEASE; EXTRAPYRAMIDAL SIGNS; ELDERLY INDIVIDUALS; DEMENTIA; PROGRESSION; PREDICTORS; RISKS; SURVIVAL AB We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon 4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon 4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon 4 allele, the risk of mortality was also decreased in patients with at least one epsilon 4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon 4 is associated with a less aggressive form of AD. C1 COLUMBIA UNIV COLL PHYS & SURG, DEPT NEUROL, NEW YORK, NY 10032 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT PSYCHIAT, NEW YORK, NY 10032 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT PATHOL, NEW YORK, NY 10032 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21205 USA. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA USA. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA USA. RP Stern, Y (reprint author), COLUMBIA UNIV COLL PHYS & SURG, GERTRUDE H SERGIEVSKY CTR, 630 W 168TH ST, NEW YORK, NY 10032 USA. FU NIA NIH HHS [AG07370, AG080702, AG10963] NR 32 TC 104 Z9 105 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1997 VL 41 IS 5 BP 615 EP 620 DI 10.1002/ana.410410510 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ809 UT WOS:A1997WZ80900009 PM 9153523 ER PT J AU Browne, SE Bowling, AC MacGarvey, U Baik, MJ Berger, SC Muqit, MMK Bird, ED Beal, MF AF Browne, SE Bowling, AC MacGarvey, U Baik, MJ Berger, SC Muqit, MMK Bird, ED Beal, MF TI Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia SO ANNALS OF NEUROLOGY LA English DT Article ID D-ASPARTATE RECEPTOR; GLUCOSE CONSUMPTION; BRAIN; GENE; EXCITOTOXICITY; DEHYDROGENASE; IMPAIRMENT; EXPRESSION; INHIBITION; MUTATION AB The etiology of the selective neuronal death that occurs in Huntington's disease (HD) is unknown. Several lines of evidence implicate the involvement of energetic defects and oxidative damage in the disease process, including a recent study that demonstrated an interaction between huntingtin protein and the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Using spectrophotometric assays in postmortem brain tissue, we found evidence of impaired oxidative phosphorylation enzyme activities restricted to the basal ganglia in HD brain, while enzyme activities were unaltered in three regions relatively spared by HD pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase-corrected complex II-III activity was markedly reduced in both I-ID caudate (-29%) and putamen (-67%), and complex IV activity was reduced in HD putamen (-62%). Complex I and GAPDH activities were unaltered in all regions examined. We also measured levels of the oxidative damage product 8-hydroxydeoxyguanosine (OH(8)dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH(8)dG levels were significantly increased in HD caudate. Cytosolic SOD activity was slightly reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity was unaltered in these regions. These results further support a role for metabolic dysfunction and oxidative damage in the pathogenesis of HD. C1 MASSACHUSETTS GEN HOSP, NEUROCHEM LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. MCLEAN HOSP, DEPT NEUROPATHOL, BELMONT, MA 02178 USA. MCLEAN HOSP, BRAIN TISSUE RESOURCE CTR, BELMONT, MA 02178 USA. OI Muqit, Miratul/0000-0001-9733-2404 NR 38 TC 540 Z9 544 U1 1 U2 19 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1997 VL 41 IS 5 BP 646 EP 653 DI 10.1002/ana.410410514 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ809 UT WOS:A1997WZ80900013 PM 9153527 ER PT J AU Penney, JB Vonsattel, JP MacDonald, ME Gusella, JF Myers, RH AF Penney, JB Vonsattel, JP MacDonald, ME Gusella, JF Myers, RH TI CAG repeat number governs the development rate of pathology in Huntington's disease SO ANNALS OF NEUROLOGY LA English DT Article ID TRINUCLEOTIDE REPEAT; PROGRESSION; LENGTH AB We compared the number of CAG repeats, the age at death, and the severity of neuropathology in 89 Huntington's disease brains. We found a linear correlation between the CAG repeat number and the quotient of the degree of atrophy in the striatum (the brain region most severely affected in Huntingon's disease) divided by age at death, with an intercept at 35.5 repeats. The largest CAG repeat length, therefore, at which no pathology is expected to develop is 35.5. These results imply that striatal damage in Huntington's disease is almost entirely a linear function of the length of the polyglutamine stretch beyond 35.5 glutamines multiplied by the age of the patient. Thus, it is predicted that the pathological process develops linearly from birth. Analysis of other measures of striatal function could test this hypothesis and might determine when treatment for CAG repeat diseases should start. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROPATHOL SERV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROGENET UNIT,BOSTON,MA. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. RP Penney, JB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,WARREN 408,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD16367]; NINDS NIH HHS [NS31579, NS31862] NR 23 TC 298 Z9 299 U1 0 U2 17 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1997 VL 41 IS 5 BP 689 EP 692 DI 10.1002/ana.410410521 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ809 UT WOS:A1997WZ80900020 PM 9153534 ER PT J AU Tseng, JF Tanabe, KK Gadd, MA Cosimi, AB Malt, RA Haluska, FG Mihm, MC Sober, AJ Souba, WW AF Tseng, JF Tanabe, KK Gadd, MA Cosimi, AB Malt, RA Haluska, FG Mihm, MC Sober, AJ Souba, WW TI Surgical management of primary cutaneous melanomas of the hands and feet SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 108th Annual Meeting of the Southern-Surgical-Association CY DEC 01-04, 1996 CL PALM BEACH, FL SP So Surg Assoc ID MALIGNANT-MELANOMA; MARGINS; FOOT AB Objective The purpose of the study was to investigate the surgical management of cutaneous melanomas of the hands and feet. Summary Background Data Prior studies suggest that patients with melanomas >1-mm thick should be treated with excision with a 2-cm margin and undergo elective lymphadenectomy in selected circumstances. These recommendations are based primarily on data from melanomas of the trunk and extremities. Melanomas of the hands and feet are less common and less well studied. They pose a surgical challenge because primary wound closure often is difficult, and the incidence and management of regional node metastases are unclear. Methods Charts of patients with melanomas of the hands or feet treated at the Massachusetts General Hospital between 1980 and 1994 were reviewed retrospectively. Local recurrence rates and the incidence of regional node metastases were analyzed as a function of histology, margin of excision, and microscopic thickness of the melanoma. Results Data from 116 patients (39 men, 77-women) with melanomas of the hands (n = 26) and feet (n = 90) were evaluated. Pathologic diagnoses were: acral lentiginous melanoma (48 patients); subungual melanoma (13 patients), and skin of dorsum of the hand or foot (n = 55). Digital amputation was required in all 13 patients with subungual melanoma to maintain local control; still, nodal metastases developed in 46% of patients within 1 year. Seventy-one percent of patients with acral lentiginous melanoma presented with lesions greater than or equal to 1.5 mm, and nodes or systemic disease or both developed in 56% of patients. Acral lentiginous melanoma lesions <1.5-mm thick were treated principally by excision with a 1cm margin; a local recurrence or metastases did not develop in any of the patients. None of the patients with melanomas on the dorsum of the hand or foot <1.5-mm thick had a local recurrence, but regional or systemic disease developed in >50%. Local control in patients with lesions >1.5-mm thick frequently required skin grafting or amputation. The majority of patients with melanomas>1.5 mm in thickness undergoing elective lymph node dissection had histologically positive nodes for melanoma. Conclusions Melanomas of the hands and feet <1.5-mm thick have a low incidence of nodal metastases and are treated effectively with wide excision of the primary with a I-cm margin. Thicker melanomas are associated with a >50% rate of regional or systemic failure. In the absence of metastatic disease, these individuals should undergo local excision with a 2-cm margin and intraoperative lymphatic mapping followed by lymphadenectomy if the sentinel node is positive. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02144. MASSACHUSETTS GEN HOSP,DEPT MED ONCOL,BOSTON,MA 02144. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02144. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02144. HARVARD UNIV,SCH MED,BOSTON,MA. NR 15 TC 28 Z9 31 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 1997 VL 225 IS 5 BP 544 EP 550 DI 10.1097/00000658-199705000-00011 PG 7 WC Surgery SC Surgery GA XE063 UT WOS:A1997XE06300044 PM 9193182 ER PT J AU Lahorra, JA Torchiana, DF Tolis, G Bashour, CA Hahn, C Titus, JS Geffin, GA Daggett, WM AF Lahorra, JA Torchiana, DF Tolis, G Bashour, CA Hahn, C Titus, JS Geffin, GA Daggett, WM TI Rapid cooling contracture with cold cardioplegia SO ANNALS OF THORACIC SURGERY LA English DT Article ID VENTRICULAR MUSCLE; SARCOPLASMIC-RETICULUM; GUINEA-PIG; BLOOD CARDIOPLEGIA; CALCIUM; TEMPERATURE; MYOCARDIUM; TRANSIENTS; ACTIVATION; RABBIT AB Background. Cold cardioplegia can induce rapid cooling contracture. The relations of cardioplegia-induced cooling contracture to myocardial temperature or myocyte calcium are unknown. Methods. Twelve crystalloid-perfused isovolumic rat hearts received three 2-minute cardioplegic infusions (1 mmol/L calcium) at 4 degrees, 20 degrees, and 37 degrees C in random order, each followed by 10 minutes of beating at 37 degrees C. Finally, warm induction of arrest by a 1-minute cardioplegic infusion at 37 degrees C was followed by a 1-minute infusion at 4 degrees C Indo-1 was used to measure the intracellular Ca2+ concentration in 6 of these hearts. Additional hearts received hypoxic, glucose-free cardioplegia at 4 degrees or 37 degrees C. Results. After 1 minute of cardioplegia at 4 degrees, 20 degrees, and 37 degrees C, left ventricular developed pressure rose rapidly to 54% +/- 3%, 43% +/- 3%, and 18% +/- 1% of its prearrest value, whereas the intracellular Ca2+ concentration reached 166% +/- 23%, 94% +/- 4%, and 37% +/- 10% of its prearrest transient. Coronary flow was 5.7 +/- 0.2, 8.7 +/- 0.3, and 12.6 +/- 0.6 mL/min, respectively. Warm cardioplegia induction at 37 degrees C reduced left ventricular developed pressure and [Ca2+](i) during subsequent 4 degrees C cardioplegia by 16% (p = 0.001) and 34% (p = 0.03), respectively. Adenosine triphosphate and phosphocreatine contents were lower after 4 degrees C than after 37 degrees C hypoxic, glucose-free cardioplegia. Conclusions. Rapid cooling during cardioplegia increases left ventricular pressure, [Ca2+](i), and coronary resistance, and is energy consuming. The absence of rapid cooling contracture may be a benefit of warm heart operations and warm induction of cardioplegic arrest. (C) 1997 by The Society of Thoracic Surgeons. C1 MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL12322, HL12777] NR 25 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 1997 VL 63 IS 5 BP 1353 EP 1360 DI 10.1016/S0003-4975(97)00087-8 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA WY309 UT WOS:A1997WY30900028 PM 9146327 ER PT J AU Bisognano, C Vaudaux, PE Lew, DP Ng, EYW Hooper, DC AF Bisognano, C Vaudaux, PE Lew, DP Ng, EYW Hooper, DC TI Increased expression of fibronectin-binding proteins by fluoroquinolone-resistant Staphylococcus aureus exposed to subinhibitory levels of ciprofloxacin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID QUINOLONE RESISTANCE; COLLAGEN ADHESIN; MOLECULAR CHARACTERIZATION; BACTERIAL ADHESION; IN-VITRO; ADHERENCE; ANTIBIOTICS; VIRULENCE; FIBRINOGEN; MUTANTS AB Bacterial adhesion, which plays an important role in Staphylococcus aureus colonization and infection, may be altered by the presence of antibiotics or/and antibiotic resistance determinants. This study evaluated the effect of fluoroquinolone resistance determinants on S. aureus adhesion to solid-phase fibronectin, which is specifically mediated by two surface-located fibronectin-binding proteins. Five isogenic mutants, derived from strain NCTC 8325 and expressing various levels of quinolone resistance, were tested in an in vitro bacterial adhesion assay with polymethylmethacrylate coverslips coated with increasing amounts of fibronectin. These strains contained single or combined mutations in the three major loci contributing to fluoroquinolone resistance, namely, grlA, gyrA, and flqB, which code for altered topoisomerase IV, DNA gyrase, and increased norA-mediated efflux of fluoroquinolones, respectively. Adhesion characteristics of the different quinolone-resistant mutants grown in the absence of fluoroquinolone shelved only minor differences from those of parental strains. However, more important changes in adhesion were exhibited by mutants highly resistant to quinolones following their exponential growth in the presence of one-quarter MIC of ciprofloxacin. Increased bacterial adhesion of the highly quinolone-resistant mutants, which contained combined mutations in grlA and gyrA, was associated with and explained by the overexpression of their fibronectin-binding proteins as assessed by Western ligand affinity blotting. These findings contradict the notion that subinhibitory concentrations of antibiotics generally decrease the expression of virulence factors by S. aureus. Perhaps the increased adhesion of S. aureus strains highly resistant to fluoroquinolones contributes in part to that emergence in clinical settings. C1 UNIV HOSP,DIV INFECT DIS,CH-1211 GENEVA 14,SWITZERLAND. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. FU NIAID NIH HHS [AI23988] NR 62 TC 77 Z9 78 U1 0 U2 2 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 MAY PY 1997 VL 41 IS 5 BP 906 EP 913 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WX583 UT WOS:A1997WX58300005 PM 9145842 ER PT J AU Zhang, JL Sharma, PL Li, CJ Dezube, BJ Pardee, AB Crumpacker, CS AF Zhang, JL Sharma, PL Li, CJ Dezube, BJ Pardee, AB Crumpacker, CS TI Topotecan inhibits human immunodeficiency virus type 1 infection through a topoisomerase-independent mechanism in a cell line with altered topoisomerase I SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LONG TERMINAL REPEAT; REVERSE-TRANSCRIPTASE; CYTO-TOXICITY; CAMPTOTHECIN; REPLICATION; IDENTIFICATION; RESISTANCE; EXPRESSION; CLEAVAGE; BINDING AB Topotecan (TPT), a known inhibitor of topoisomerase I, has previously been shown to inhibit the replication of several viruses. The mechanism of inhibition was proposed to be the inhibition of topoisomerase I. We report that TPT decreased replication of human immunodeficiency virus type I (HIV-I) in CPT-KS, a cell line with a topoisomerase I mutation, TPT inhibited production of HIV-1 RNA end p24 in CPT-K5 and wild-type cells equally effectively, The antiviral effects of TPT were observed not only in the topoisomerase-mutated CPT-K5 line but also in peripheral blood mononuclear cells (PBMC) acutely infected with clinical isolates and in OM10.1 cells latently infected with HIV and activated by tumor necrosis factor alpha, Little toxicity from TPT was noted in HIV-1-infected PBMC and in CPT-BS and OM10.1 cells as measured by cell growth and proliferation assays. These observations suggest that TPT targets factors in virus replication other than cellular topoisomerase I and inhibits cytokine-mediated activation in latently infected cells by means other than cytotoxicity, These results suggest a potential for TPT and for other camptothecins in anti-HIV therapy alone and in combination with other antiretroviral drugs. C1 BETH ISRAEL DEACONESS MED CTR,CHARLES A DANA RES INST,DIV HEMATOL ONCOL,BOSTON,MA 02215. DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. RP Zhang, JL (reprint author), BETH ISRAEL DEACONESS MED CTR,CHARLES A DANA RES INST,DIV INFECT DIS,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI27659, AI29173-04]; PHPPO CDC HHS [NIH PHS 2271] NR 28 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1997 VL 41 IS 5 BP 977 EP 981 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WX583 UT WOS:A1997WX58300018 PM 9145855 ER PT J AU Nguyen, MH Najvar, LK Yu, CY Graybill, JR AF Nguyen, MH Najvar, LK Yu, CY Graybill, JR TI Combination therapy with fluconazole and flucytosine in the murine model of Cryptococcal meningitis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; AIDS AB This study elucidates the role of combined fluconazole and flucytosine as therapy for cryptacorcosis in the murine model of meningitis, Three strains of Cryptococus neoformans for which the range of fluconazole MICs was wide-2 mu g/ml (susceptible strain), 8 mu g/ml (moderately susceptible strain), and 32 mu g/ml (resistant strain ere used for infection, One day postinfection, the mice were randomized into eight treatment groups: placebo; flucytosine (40 mg/kg of body weight/day); fluconazole at 3 mg/kg/day (low dosage), 10 mg/kg/day !moderate dosage), or 10 mg/kg/day (high dosage); and combined flucytosine and fluconazole at low, moderate, or high doses of fluconazole. Three major findings were demonstrated: (i) correlation between the MICs for the isolates and the in vivo effectiveness of fluconazole as assessed by the reduction in cryptococcal brain burden, (iii a dose-response curve (a higher dose of fluconazole was significantly more efficacious than a lower dose [P < 0.001]), and (iii) synergism between fluconazole and flucytosine (therapy with a combination of fluconazole and flucytosine was superior to therapy with either agent alone [P < 0.01]). C1 VET ADM MED CTR,GAINESVILLE,FL 32602. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Nguyen, MH (reprint author), UNIV FLORIDA,COLL MED,J HILLIS MILLER HLTH CTR,DEPT MED,DIV INFECT DIS,POB 100277,GAINESVILLE,FL 32610, USA. NR 11 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1997 VL 41 IS 5 BP 1120 EP 1123 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WX583 UT WOS:A1997WX58300042 PM 9145879 ER PT J AU Barsky, AJ Ahern, DK Delamater, BA Clancy, SA Bailey, ED AF Barsky, AJ Ahern, DK Delamater, BA Clancy, SA Bailey, ED TI Differential diagnosis of palpitations - Preliminary development of a screening instrument SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID MEDICAL OUTPATIENTS; SOMATOSENSORY AMPLIFICATION; CARDIAC-ARRHYTHMIAS; HYPOCHONDRIASIS; DISORDERS; CARE AB Objective: To develop a self-report screening instrument to assist in the differential diagnosis of medical outpatients complaining of palpitations. Design: Patients completed self-report questionnaires assessing somatization, cardiac symptoms, and hypochondriacal concerns about health. Principal components analysis was performed to identify a subset of questions that could be used to distinguish patients with palpitations who have panic disorder from those with palpitations who do not have panic disorder. Patients: Sixty-seven medical outpatients referred for Holter monitoring because of a complaint of palpitations. Main Outcome Measures: Patients with Palpitations were classified into 2 groups, those with and those without current panic disorder (established with a structured, diagnostic interview). The sensitivity, specificity, and posttest probability of the screening instrument were determined. Results: A reliable, stable, 10-item instrument was derived. It seems to tap diffuse, vague, or generalized somatic complaints and worry about physical illness. With the use of a criterion cutoff score of 21, this instrument had a sensitivity of 0.81, a specificity of 0.80, and a posttest probability of .57 in detecting current panic disorder in patients with palpitations. Conclusion: A psychometrically sound and brief self-report instrument was developed to assist in the differential diagnosis of palpitations. It can be used to identify patients whose symptoms are more likely to result from panic disorder and in whom ambulatory monitoring might be deferred. C1 BRIGHAM & WOMENS HOSP, DIV PSYCHIAT, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, PSYCHIAT SERV, BOSTON, MA 02114 USA. RP Barsky, AJ (reprint author), HARVARD UNIV, SCH MED, DEPT PSYCHIAT, 75 FRANCIS ST, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL43216] NR 31 TC 7 Z9 7 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD MAY-JUN PY 1997 VL 6 IS 3 BP 241 EP 245 DI 10.1001/archfami.6.3.241 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XD349 UT WOS:A1997XD34900007 PM 9161349 ER PT J AU Reite, M Sheeder, J Teale, P Adams, M Richardson, D Simon, J Jones, RH Rojas, DC AF Reite, M Sheeder, J Teale, P Adams, M Richardson, D Simon, J Jones, RH Rojas, DC TI Magnetic source imaging evidence of sex differences in cerebral lateralization in schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HUMAN AUDITORY-CORTEX; GENDER DIFFERENCES; FIRST-EPISODE; TEMPORAL-LOBE; TONOTOPIC ORGANIZATION; PLANUM TEMPORALE; BRAIN MORPHOLOGY; SOURCE LOCATION; ABNORMALITIES; ASYMMETRIES AB Background: It has been postulated that schizophrenia represents a disorder of anomalous cerebral lateralization. This study is a replication of earlier preliminary findings using a multichannel neuromagnetometer, suggesting altered lateralization in schizophrenia in male subjects, with an extension of the findings to female subjects. Methods: We used magnetoencephalography-based magnetic source imaging to estimate the intracranial location of the 100-millisecond latency auditory-evoked field component (M100) in both left and right hemispheres of 20 patients with paranoid schizophrenia and 20 controls without schizophrenia. Neuroanatomical data were obtained by means of magnetic resonance imaging, from which we segmented and computed volumes of both total brain and left and right superior temporal gyri. Results: Locations of M100 source were compatible with neuronal generators located in the transverse gyri of Heschl on the superior temporal gyri in both study groups; M100 sources were asymmetric in all the control subjects. The male patient subgroup exhibited significantly less asymmetry than the control group, while the female patient subgroup actually showed significantly more asymmetry. The male patient subgroup generally had smaller superior temporal gyri than the control group. No evidence of total brain volume differences was observed. Conclusions: Our findings support previous magnetoencephalography-based studies suggesting anomalous cerebral lateralization in schizophrenia. Further, in extending our studies to female patients, our data suggest that the nature of this anomaly is sex specific, a finding that, to our knowledge, has not previously been reported. C1 UNIV COLORADO, HLTH SCI CTR, DEPT RADIOL, DENVER, CO 80262 USA. UNIV COLORADO, HLTH SCI CTR, DEPT PREVENT MED & BIOMETR, DENVER, CO 80262 USA. DENVER VET AFFAIRS MED CTR, PSYCHIAT SERV, DENVER, CO USA. RP Reite, M (reprint author), UNIV COLORADO, HLTH SCI CTR, DEPT PSYCHIAT, BOX C268-68, 4200 E 9TH AVE, DENVER, CO 80262 USA. RI Rojas, Don/F-4296-2012; OI Rojas, Don/0000-0001-6560-9616; Sheeder, Jeanelle/0000-0002-4463-3569 FU NIMH NIH HHS [MH46335, MH47476] NR 76 TC 84 Z9 85 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1997 VL 54 IS 5 BP 433 EP 440 PG 8 WC Psychiatry SC Psychiatry GA WY633 UT WOS:A1997WY63300006 PM 9152097 ER PT J AU Green, MF Nuechterlein, KH Breitmeyer, B AF Green, MF Nuechterlein, KH Breitmeyer, B TI Backward masking performance in unaffected siblings of schizophrenic patients - Evidence for a vulnerability indicator SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID VISUAL MASKING; DISORDERS; DEFICITS; CHANNELS; SYMPTOM; MANIA AB Background: Visual masking is a procedure that is used to assess the earliest components of visual processing. In backward masking, the identification of an initial stimulus (the target) is disrupted by a later stimulus (the mask). The masking function can be divided into an early component (eg, up to about 60 ms) that reflects the involvement of sensory-perceptual processes, and a later component that reflects susceptibility to attentional disengagement as the mask diverts processing away from the representation of the target. Schizophrenic patients show anomalies on both masking components. It is not known whether backward masking deficits reflect enduring genetic vulnerability to schizophrenia. Methods: We assessed 32 unaffected siblings of schizophrenic patients and 52 normal control subjects on the early and late components of 4 masking conditions. The conditions differentially involved the sustained and transient visual pathways. Results: The unaffected siblings showed poorer overall performance than control subjects on the masking procedures. More specifically, siblings showed anomalies on the early, sensory-perceptual component, but not on the later, attentional disengagement component. Conclusions: The backward masking performance deficits that have been observed in schizophrenic patients appear to reflect enduring vulnerability to the disorder rather than only the symptoms of the illness. This vulnerability appears to be associated with early, sensory-perceptual processes. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. UNIV HOUSTON,DEPT PSYCHOL,HOUSTON,TX. RP Green, MF (reprint author), UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,DEPT PSYCHIAT & BIOBEHAV SCI,760 WESTWOOD PLAZA,C9-420,LOS ANGELES,CA 90024, USA. FU NIMH NIH HHS [MH-43292] NR 38 TC 103 Z9 105 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1997 VL 54 IS 5 BP 465 EP 472 PG 8 WC Psychiatry SC Psychiatry GA WY633 UT WOS:A1997WY63300009 PM 9152100 ER PT J AU Foster, BS March, GA Lucarelli, MJ Samiy, N Lessell, S AF Foster, BS March, GA Lucarelli, MJ Samiy, N Lessell, S TI Optic nerve avulsion SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EVULSION; GLOBE; ORBIT AB Objective: To characterize the presentation, role of diagnostic imaging, and course in patients with optic nerve avulsion. Methods: A retrospective review of medical records of all 6 patients with optic nerve avulsion who were seen at the Massachusetts Eye and Ear Infirmary, Boston, from January 1, 1991, to July 31, 1995. Results: The initial visual acuity ranged from 20/100 to no light perception, All 6 patients underwent neuroimaging, including computed tomography, magnetic resonance imaging, or both. B-scan ultrasonography was performed on 4 patients, and the condition of 1 patient was evaluated with color Doppler ultrasonography to assess the optic nerve vasculature. In 1 patient, a computed tomographic scan was suggestive of an optic nerve avulsion. Neuroimaging in the other 5 patients, including 2 patients who underwent magnetic resonance imaging, failed to demonstrate an avulsion. During a follow-up period of up to 25 months, 4 patients showed no improvement in visual acuity, 1 patient improved from no light perception to bare light perception, and 1 patient improved from 20/100 to 20/25. Conclusions: These data suggest that final visual outcome was dependent on initial postinjury visual acuity. Neuroimaging, B-scans, and Doppler ultrasonography were usually not helpful in establishing the presence of optic nerve avulsion, although they may be useful in evaluating comorbid conditions. RP Foster, BS (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114, USA. NR 33 TC 24 Z9 30 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 MAY PY 1997 VL 115 IS 5 BP 623 EP 630 PG 8 WC Ophthalmology SC Ophthalmology GA WY804 UT WOS:A1997WY80400008 PM 9152130 ER PT J AU Marcus, DM Rustgi, AK Defoe, D Brooks, SE McCormick, RS Thompson, TP Edelmann, W Kucherlapati, R Smith, S AF Marcus, DM Rustgi, AK Defoe, D Brooks, SE McCormick, RS Thompson, TP Edelmann, W Kucherlapati, R Smith, S TI Retinal pigment epithelium abnormalities in mice with adenomatous polyposis coli gene disruption SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CONGENITAL HYPERTROPHY; FUNDUS LESIONS; APC MUTATIONS; TUMORS; MOUSE AB Objective: To examine eyes from mice with targeted adenomatous polyposis coli (APC) gene disruption to determine if retinal pigment epithelium (RPE) abnormalities replicate the human counterpart. Methods: Thirty-two eyes from 16 mice heterozygous for APC gene disruption (chain-termination mutation in codon 1638 of exon 15) and 12 control eyes were examined by light microscopy. Results: Fifteen of 32 eyes from 12 of 16 APC-disrupted mice demonstrated abnormalities of the RPE and retina. The RPE abnormalities included RPE coloboma, unifocal and multifocal RPE hypertrophy, RPE hyperplasia, and RPE duplication with invasion in the areas of outer and inner segments. Retinal abnormalities included outer nuclear layer duplication and outer nuclear layer atrophy. There were no RPE and retinal abnormalities seen in the control eyes. Conclusions: This study is consistent with the hypothesis that the APC gene is critical in the regulation of RPE proliferation and development. These findings also demonstrate that mutation of the APC gene in codon 1638, a location beyond the previously described critical region for human RPE abnormalities, leads to perturbation in the mouse RPE and retina. Further study of this murine model and the APC/RPE relationship may provide insight into regulatory mechanisms for RPE proliferation. C1 MED COLL GEORGIA,DEPT CELL BIOL & ANAT,AUGUSTA,GA 30912. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. E TENNESSEE STATE UNIV,COLL MED,DEPT ANAT & CELL BIOL,JOHNSON CITY,TN. ALBERT EINSTEIN COLL MED,DEPT MOL GENET,BRONX,NY 10467. RP Marcus, DM (reprint author), MED COLL GEORGIA,DEPT OPHTHALMOL,AUGUSTA,GA 30912, USA. FU NEI NIH HHS [EY07036, EY09682] NR 18 TC 27 Z9 27 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 MAY PY 1997 VL 115 IS 5 BP 645 EP 650 PG 6 WC Ophthalmology SC Ophthalmology GA WY804 UT WOS:A1997WY80400013 PM 9152133 ER PT J AU McLendon, RE Bentley, RC Parisi, JE Tien, RD Harrison, JC Tarbell, NJ Billitt, AL Gualtieri, RJ Friedman, HS AF McLendon, RE Bentley, RC Parisi, JE Tien, RD Harrison, JC Tarbell, NJ Billitt, AL Gualtieri, RJ Friedman, HS TI Malignant supratentorial glial-neuronal neoplasms - Report of two cases and review of the literature SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT US/Canada-Academy-of-Pathology CY MAR 16, 1994 CL SAN FRANCISCO, CA SP US Canada Acad Pathol ID PRIMITIVE NEUROECTODERMAL TUMORS; CHILDHOOD BRAIN-TUMORS; CENTRAL-NERVOUS-SYSTEM; HEALTH-ORGANIZATION CLASSIFICATION; NEUROEPITHELIAL TUMOR; SYNAPTOPHYSIN EXPRESSION; MEDULLOBLASTOMA; DIFFERENTIATION; BLASTOMA; MARKER AB Objective.-Malignant neoplasms exhibiting mixed populations of neuronal and glial cells occurring in the cerebral hemispheres of young adults and children are well recognized, but rare. A confusing array of diagnostic terms has arisen. We describe two patients with such tumors and review the literature concerning these interesting cases. Patients.-A 21-year-old man and a 5-year-old girl presented with large, cystic, intracerebral lesions on magnetic resonance images, which proved to be composite neoplasms exhibiting malignant neurons and astrocytes. Results.-The 21-year-old man had a frontal lobe mass with enhancing and nonenhancing regions, which corresponded to cerebral neuroblastoma and anaplastic astrocytoma, respectively. The presence of occasional microtubules and rare primitive presynaptic processes, accompanied by antisynaptophysin immunoreactivity, established the neuronal nature of the cells in the enhancing region. The nonenhancing region was composed of a moderately cellular neoplasm of fibrillar astrocytes that were mitotically active. The 5-year-old girl presented with a left parietal lobe neoplasm, which histologically was composed of lobular proliferations of neuroblasts and glia. The neuroblastic populations exhibited evidence of maturation with small anaplastic cells, spindle-shaped cells, and large dysmorphic ganglion cells. The glial tumor showed both well-differentiated fibrillary astrocytes with microcysts and anaplastic populations with central necrosis and pseudopalisading. Conclusions.-Present classification systems devised to describe mixed neuronal and glial tumors do not adequately encompass the diversity of morphologies presented by these two cases. We conclude that the terms cerebral neuroblastoma-anaplastic astrocytoma for case 1 and cerebral ganglioneuroblastoma-glioblastoma for case 2 are preferred because they convey useful clinical information by reflecting concepts already encompassed by the World Health Organization's classification system of tumors of the central nervous system. C1 DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. MAYO CLIN,DEPT LAB MED,ROCHESTER,MN. MAYO CLIN,DEPT PATHOL,ROCHESTER,MN. MAYO CLIN,DEPT NEUROL,ROCHESTER,MN. HUNTSVILLE DIST MEM HOSP,DEPT PATHOL,HUNTSVILLE,AL. HUNTSVILLE DIST MEM HOSP,DEPT MED ONCOL,HUNTSVILLE,AL. HUNTSVILLE DIST MEM HOSP,CTR COMPREHENS CANC,HUNTSVILLE,AL. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. RP McLendon, RE (reprint author), DUKE UNIV,MED CTR,DEPT PATHOL,BOX 3712,DURHAM,NC 27710, USA. NR 45 TC 17 Z9 18 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 1997 VL 121 IS 5 BP 485 EP 492 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA WZ640 UT WOS:A1997WZ64000004 PM 9167602 ER PT J AU Brun, RP Spiegelman, BM AF Brun, RP Spiegelman, BM TI PPAR gamma and the molecular regulation of adipocyte differentiation SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 1997 VL 130 SU S BP 66 EP 66 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XB823 UT WOS:A1997XB82300065 ER PT J AU Kim, SJ Kahn, CR AF Kim, SJ Kahn, CR TI Insulin regulation of mitogen-activated protein kinase kinase (MEK), mitogen-activated protein kinase and casein kinase in the cell nucleus: A possible role in the regulation of gene expression SO BIOCHEMICAL JOURNAL LA English DT Article ID TRANSCRIPTION FACTOR; DNA-BINDING; MAP KINASES; C-JUN; PHOSPHORYLATION; LOCALIZATION; TRANSLOCATION; GROWTH; RAF; FIBROBLASTS AB After insulin receptor activation, many cytoplasmic enzymes, including mitogen-activated protein (MAP) kinase, MAP kinase kinase (MEK) and casein kinase II (CKII) are activated, but exactly how insulin signalling progresses to the nucleus remains poorly understood. In Chinese hamster ovary cells overexpressing human insulin receptors [CHO(Hirc)], MEK, CKII and the MAP kinases ERK I and ERK II can be detected by immunoblotting in the nucleus, as well as in the cytoplasm, in the unstimulated state. Nuclear localization of MAP kinase is also observed in 3T3-F442A adipocytes, NIH-3T3 cells and Fao hepatoma cells, whereas MEK is found in the nucleus only in Fao and CHO cells. Insulin treatment for 5-30 min induces a translocation of MEK from the cytoplasm to the nucleus, whereas the MAP kinases and CKII are not translocated into the nucleus in response to insulin during this period. However, nuclear MAP kinase and CKII activities increase by 2-3-fold within 1-10 min after stimulation with insulin. By using gel-shift assays, it has been shown that insulin also stimulates nuclear protein binding to an AP-1 site with kinetics similar to MEK translocation and MAP kinase and CKII activation. Treatment of the extracts in vitro with protein phosphatase 2A or treatment of the intact cells with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a cell-permeable inhibitor of CKII, almost completely blocks the insulin-induced DNA-binding activity, whereas incubation of cells with a MEK inhibitor produces only a slight decrease. These results suggest that insulin signalling results in the activation of serine kinases in the nucleus via two pathways: (1) insulin stimulates the nuclear translocation of some kinases, such as MEK, which might directly phosphorylate nuclear protein substrates or activate other nuclear kinases, and (2) insulin activates nuclear kinases without translocation. The latter is true of CKII, which seems to regulate the binding of nuclear proteins to the AP-1 site, possibly by phosphorylation of AP-1 transcription factors. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DERC P30 DK 36836, DK 33201] NR 48 TC 64 Z9 65 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1997 VL 323 BP 621 EP 627 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ258 UT WOS:A1997WZ25800006 PM 9169593 ER PT J AU daSilva, AJ Raab, M Li, Z Rudd, CE AF daSilva, AJ Raab, M Li, Z Rudd, CE TI TcR zeta/CD3 signal transduction in T-cells: Downstream signalling via ZAP-7O, SLP-76 and FYB SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 660th Meeting Biochemical-Society / British-Society-Immunology CY DEC 10-13, 1996 CL HARROGATE, ENGLAND SP Biochem Soc, Brit Soc Immunol ID ANTIGEN RECEPTOR; TYROSINE KINASES; PROTEIN; VAV; PROTOONCOGENE; ACTIVATION; PRODUCT; TCR; KD C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP daSilva, AJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 19 TC 12 Z9 12 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD MAY PY 1997 VL 25 IS 2 BP 361 EP 366 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB637 UT WOS:A1997XB63700004 PM 9191118 ER PT J AU Simister, NE Israel, EJ Ahouse, JC Story, CM AF Simister, NE Israel, EJ Ahouse, JC Story, CM TI New functions of the MHC class I-related Fc receptor, FcRn SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 660th Meeting Biochemical-Society / British-Society-Immunology CY DEC 10-13, 1996 CL HARROGATE, ENGLAND SP Biochem Soc, Brit Soc Immunol ID PLACENTAL ALKALINE-PHOSPHATASE; HUMAN IMMUNOGLOBULIN-G; MYOTONIC-DYSTROPHY; GAMMA-RECEPTORS; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; NEONATAL RAT; IGG; BETA-2-MICROGLOBULIN; TRANSPORT C1 BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,COMBINED PROGRAM PEDIAT GASTROENTEROL,BOSTON,MA 02114. RP Simister, NE (reprint author), BRANDEIS UNIV,WM KECK INST CELLULAR VISUALIZAT,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254, USA. FU NICHD NIH HHS [HD12437, HD27691, HD00938] NR 70 TC 35 Z9 35 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD MAY PY 1997 VL 25 IS 2 BP 481 EP 486 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XB637 UT WOS:A1997XB63700026 PM 9191140 ER PT J AU Edery, P Eng, C Munnich, A Lyonnet, S AF Edery, P Eng, C Munnich, A Lyonnet, S TI RET in human development and oncogenesis SO BIOESSAYS LA English DT Review ID MULTIPLE ENDOCRINE NEOPLASIA; MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; ENDOTHELIN-B RECEPTOR; HIRSCHSPRUNG-DISEASE; TRANSFORMING GENE; MOLECULAR CHARACTERIZATION; MISSENSE MUTATION; PROTO-ONCOGENE; LONG ARM AB Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction, The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto-oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and whose ligand, glial-cell-line-derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation, Thus, the two 'faces' of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect. C1 HOP NECKER ENFANTS MALAD,SERV GENET MED,INSERM U393,F-75743 PARIS 15,FRANCE. HOP NECKER ENFANTS MALAD,UNITE RECH HANDICAPS GENET ENFANT,INSERM U393,F-75743 PARIS 15,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. UNIV CAMBRIDGE,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. OI Eng, Charis/0000-0002-3693-5145 NR 76 TC 60 Z9 60 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAY PY 1997 VL 19 IS 5 BP 389 EP 395 DI 10.1002/bies.950190506 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA WZ256 UT WOS:A1997WZ25600006 PM 9174404 ER PT J AU Forman, SA AF Forman, SA TI Homologous mutations on different subunits cause unequal but additive effects on n-alcohol block in the nicotinic receptor pore SO BIOPHYSICAL JOURNAL LA English DT Article ID AFFINITY BINDING-SITE; ACETYLCHOLINE-RECEPTOR; ION CHANNEL; H-3 CHLORPROMAZINE; ALPHA-SUBUNIT; DELTA-SUBUNIT; AMINO-ACIDS; NONCOMPETITIVE ANTAGONIST; GAMMA-SUBUNIT; M2 DOMAIN AB Hydrophobic antagonists of the nicotinic acetylcholine receptor inhibit channel activity by binding within the transmembrane pore formed by the second of four transmembrane domains (M2) on each of the receptor's subunits. Hydrophobic mutagenesis near the middle (10 ' locus) of the alpha-subunit M2 domain results in channels that are much more sensitive to block by long-chain alcohols and general anesthetics, indicating that the inhibitory site on wild-type receptors is nearby. To determine whether other receptor subunits also contribute to the blocker site, the hydrophobic mutagenesis strategy was extended to all four subunits at 10 ' loci. alpha S10 ' l causes the largest increase in apparent hexanol binding (4.3-fold compared to wild type), approximately twice the size of the change caused by beta T10 ' l (2.2-fold). gamma A10 ' l and delta A10 ' l mutations cause much smaller changes in apparent hexanol binding affinity (about 1.2-fold each), even when corrected for their smaller degree of side-chain hydrophobicity changes. When 10 ' l mutant subunits are coexpressed, the change from wild type in apparent hexanol binding energy (Delta Delta G(mixture)) is roughly equal to the sum of hexanol binding energy changes for the constituent mutant subunits (Sigma Delta Delta G(subunits)). The simplest model consistent with these results is one in which hydrophobic blockers make simultaneous contact with all five M2 10 ' residues, but the extent of contact is much greater for the alpha and beta than for gamma and delta side chains. RP Forman, SA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CLN-3,BOSTON,MA 02114, USA. FU NIAAA NIH HHS [1-K21-AA00206-01] NR 43 TC 35 Z9 35 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 1997 VL 72 IS 5 BP 2170 EP 2179 PG 10 WC Biophysics SC Biophysics GA WV984 UT WOS:A1997WV98400024 PM 9129819 ER PT J AU Barber, DL Mason, JM Fukazawa, T Reedquist, KA Druker, BJ Band, H DAndrea, AD AF Barber, DL Mason, JM Fukazawa, T Reedquist, KA Druker, BJ Band, H DAndrea, AD TI Erythropoietin and interleukin-3 activate tyrosine phosphorylation of CBL and association with CRK adaptor proteins SO BLOOD LA English DT Article ID PHOSPHOTYROSINE PHOSPHATASE SYP; MYELOGENOUS LEUKEMIA-CELLS; COLONY-STIMULATING FACTOR; PRODUCT C-CBL; PROTOONCOGENE PRODUCT; EGF RECEPTOR; SH3 DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS AB Transformation of hematopoietic cells by the Bcr-abl oncoprotein reads to constitutive tyrosine phosphorylation of a number of cellular polypeptides that function in normal growth factor-dependent cell proliferation. Recent studies have shown that the CrkL adaptor protein and the Cbl protooncoprotein are constitutively tyrosine phosphorylated and form a preformed complex in cells expressing Bcr-abl. In the current study, we have examined cytokine-dependent tyrosine phosphorylation of Cbl and its association with Crk proteins. Erythropoietin (EPO) and interleukin-3 induced a dose and time-dependent tyrosine phosphorylation of Cbl in both EPO-dependent Ba/F3 and DA-3 transfectants, and the erythroid cell line HCD-57. Furthermore, once phosphorylated, Cbl associated with Crk adaptor proteins. of the three Crk isoforms expressed in hematopoietic cells (CrkL, CrkII, and CrkI), tyrosine phosphorylated Cbl binds preferentially to CrkL and CrkII. The amount of Cbl associated with CrkL and CrkII exceeded the fraction of Cbl associated with Grb2 indicating that unlike other receptor systems, the Cbl-Crk association represents the dominant complex of Cbl in growth factor-stimulated hematopoietic cells. In factor-dependent hematopoietic cell lines, CrkL constitutively associated with the guanine nucleotide release factor, C3G, which is known to interact via Crk src-homology 3 (SH3) domains, Our data suggest that the inducible CbI-Crk association is a proximal component: of a signaling pathway downstream of multiple cytokine receptors. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. ONTARIO CANC INST,DIV CELLULAR & MOL BIOL,TORONTO,ON M4X 1K9,CANADA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. FU NIAMS NIH HHS [AR6308]; NIDDK NIH HHS [R01 DK 43889-01] NR 74 TC 93 Z9 94 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1997 VL 89 IS 9 BP 3166 EP 3174 PG 9 WC Hematology SC Hematology GA WX542 UT WOS:A1997WX54200011 PM 9129019 ER PT J AU Pless, M Norga, K Carroll, M Heim, MH DAndrea, AD MatheyPrevot, B AF Pless, M Norga, K Carroll, M Heim, MH DAndrea, AD MatheyPrevot, B TI Receptors that induce erythroid differentiation of Ba/F3 cells: Structural requirements and effect on STAT5 binding SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; MURINE ERYTHROPOIETIN RECEPTOR; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAIN; HEMATOPOIETIC PROGENITORS; SIGNAL-TRANSDUCTION; LYMPHOID-CELLS; INTERLEUKIN-3; ACTIVATION; PROLIFERATION AB Ectopic expression of the erythropoietin receptor (EpoR) in the interleukin-3 (IL-3)-dependent cell line Ba/F3 results in growth and partial erythroid differentiation in Epo. In contrast, introduction and activation of the interleukin-5 receptor (IL-5R) or of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) results in proliferation only, As this effect is specific to the EpoR, the role of its extracellular or cytoplasmic domain in differentiation was tested after construction of two chimeric receptors. One receptor contained the extracellular domain of EpoR fused to the endodomain of IL-3R beta-chain (E/beta), while the other contained the EpoR cytoplasmic region fused to the extracellular domain of GM-CSFR alpha-chain (GMER), Surprisingly, both receptors induced differentiation ruling out a strict specificity of the extracellular or cytoplasmic region of EpoR in this process. Instead the ability to signal differentiation correlated with structural features shared by the EpoR, GMER, and E/beta receptors. Dimerization of all three receptors results in the pairing of two signal transducing chains in the cytoplasm, in contrast to the mitogenic receptors IL-3R, IL-5R, GM-CSFR, which assemble as alpha beta heterodimers, Two new chimeric receptors that fulfilled the structural requirement exemplified by EpoR, but lacked any part of EpoR, were designed to consolidate this model. They consisted of the ectodomains of the GMR-alpha and IL-5R alpha, respectively, fused to the endodomain of IL-3R beta-chain. Both receptors were as effective as EpoR in signaling differentiation in response to their cognate ligand. Another property of receptors fulfilling these structural requirements is that they cause a marked delay in signal transducers and activators of transcription 5 (STAT5) activation on ligand stimulation. Taken together our studies show that structural assembly of receptors dictates their potential to signal erythroid differentiation in Ba/F3 cells, that differentiation can take place in the absence of Epo and that a delay in STATS activation is highly predictive of this process. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL & HEMATOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. KANTONSSPITAL BASEL,DEPT INTERNAL MED,BASEL,SWITZERLAND. RP Pless, M (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. OI Heim, Markus/0000-0002-7523-4894 FU NHLBI NIH HHS [2P01 HL32262] NR 47 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1997 VL 89 IS 9 BP 3175 EP 3185 PG 11 WC Hematology SC Hematology GA WX542 UT WOS:A1997WX54200012 PM 9129020 ER PT J AU Leonard, CL Waters, GS Caplan, D AF Leonard, CL Waters, GS Caplan, D TI The use of contextual information by right brain-damaged individuals in the resolution of ambiguous pronouns SO BRAIN AND LANGUAGE LA English DT Article ID RIGHT-HEMISPHERE DAMAGE; RIGHT-HANDERS; SYNTACTIC COMPREHENSION; APHASIA; APPRECIATION; ADULTS; LANGUAGE; ORGANIZATION; SENSITIVITY; PARAGRAPHS AB Two experiments were conducted with the primary purpose of investigating the ability of right brain-damaged (RED) individuals to use contextual information-at the level of the single sentence, in terms of the integration of information between clauses, and at the level of a minimal discourse (i.e., two sentences)-in the resolution of ambiguous pronouns. The investigation was extended to a group of left brain-damaged (LED) and non-brain-damaged (NBD) individuals. Contrary to the prevailing view that RED patients have difficulty in the use of contextual information to process language, both experiments were consistent in demonstrating that the RED group was influenced by contextual information in a manner similar to that demonstrated by both the LED and NBD groups. (C) 1997 Academic Press. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. RP Leonard, CL (reprint author), MCGILL UNIV,SCH COMMUN SCI & DISORDERS,1266 PINE AVE W,MONTREAL,PQ H3G 1A8,CANADA. FU NIDCD NIH HHS [DC00942] NR 70 TC 23 Z9 23 U1 2 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 1997 VL 57 IS 3 BP 309 EP 342 DI 10.1006/brln.1997.1743 PG 34 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA WT602 UT WOS:A1997WT60200002 PM 9126419 ER PT J AU Leonard, CL Waters, GS Caplan, D AF Leonard, CL Waters, GS Caplan, D TI The use of contextual information related to general world knowledge by right brain-damaged individuals in pronoun resolution SO BRAIN AND LANGUAGE LA English DT Article ID RIGHT-HEMISPHERE DAMAGE; RIGHT-HANDERS; COMPREHENSION; APPRECIATION; APHASIA; LANGUAGE; ADULTS; ORGANIZATION; SENSITIVITY; METAPHOR AB This study investigated the ability of right brain-damaged individuals (RBD) to use contextual information to resolve ambiguous pronouns. Subjects were presented with sentence pairs and required to resolve the ambiguous pronoun in the second sentence. Contrary to the prevailing view that RED patients have difficulty using contextual information to integrate language, the RED group demonstrated a normal pattern of response, demonstrating a sensitivity to the pragmatic information contained in the leading sentence. They responded more quickly to sentences with a pragmatically constrained preferred referent than to those sentences for which there was no preferred referent. As well, they chose the preferred referent significantly more often than the non-preferred referent. These results suggest that RED patients can use contextual information at the level of a minimal discourse (i.e., two sentences). (C) 1997 Academic Press. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. RP Leonard, CL (reprint author), MCGILL UNIV,SCH COMMUN SCI & DISORDERS,1266 PINE AVE W,MONTREAL,PQ H3G 1A8,CANADA. FU NIDCD NIH HHS [DC00942] NR 51 TC 17 Z9 17 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 1997 VL 57 IS 3 BP 343 EP 359 DI 10.1006/brln.1997.1744 PG 17 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA WT602 UT WOS:A1997WT60200003 PM 9126420 ER PT J AU Tedesco, AC Martinez, L Gonzalez, S AF Tedesco, AC Martinez, L Gonzalez, S TI Photochemistry and photobiology of actinic erythema: Defensive and reparative cutaneous mechanisms SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Review DE sunburn; antioxidant; DNA photodamage; reactive oxygen species; UV radiation ID LEUKOCYTE ADHESION MOLECULE-1; NORMAL HUMAN-SKIN; SINGLET OXYGEN PRODUCTION; DIRECT EXPRESSION CLONING; LEVEL CHEMI-LUMINESCENCE; ABSORBING AMINO-ACIDS; ULTRAVIOLET-RADIATION; ARACHIDONIC-ACID; PROSTAGLANDIN SYNTHESIS; HUMAN KERATINOCYTES AB Sunlight is part of our everyday life and most people accept it as beneficial to our health. With the advance of our knowledge in cutaneous photochemistry, photobiology and photomedicine over the past four decades, the terrestrial solar radiation has become a concern of dermatologists and is considered to be a major damaging environmental factor for our skin. Most photobiological effects (e.g., sunburn, suntanning, local and systemic immunosuppression, photoaging or dermatoheliosis, skin cancer and precancer, etc.) are attributed to ultraviolet radiation (UVR) and more particularly to UVB radiation (290-320 nm). UVA radiation (320-400 nm) also plays an important role in the induction of erythema by the photosensitized generation of reactive oxygen species (singlet oxygen (O-1(2)), superoxide (O-2(.-)) and hydroxyl radicals ((OH)-O-.)) that damage DNA and cellular membranes, and promote carcinogenesis and the changes associated with photoaging. Therefore, research efforts have been directed at a better photochemical and photobiological understanding of the so-called sunburn reaction, actinic or solar erythema. To survive the insults of actinic damage, the skin appears to have different intrinsic defensive mechanisms, among which antioxidants (enzymatic and non-enzymatic systems) play a pivotal role. In this paper, we will review the basic aspects of the action of UVR on the skin: a) photochemical reactions resulting from photon absorption by endogenous chromophores; b) the lipid peroxidation phenomenon, and c) intrinsic defensive cutaneous mechanisms (antioxidant systems). The last section will cover the inflammatory response including mediator release after cutaneous UVR exposure and adhesion molecule expression. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA 02114. RP Tedesco, AC (reprint author), USP,FAC FILOSOFIA CIENCIAS & LETRAS RIBEIRAO PRET,DEPT QUIM,AV BANDEIRANTES 3900,BR-14040901 RIBEIRAO PRET,SP,BRAZIL. RI Tedesco, Antonio/B-7584-2012 OI Tedesco, Antonio/0000-0003-4198-9321 NR 113 TC 14 Z9 14 U1 0 U2 4 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD MAY PY 1997 VL 30 IS 5 BP 561 EP 575 PG 15 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA WZ102 UT WOS:A1997WZ10200002 PM 9283623 ER PT J AU Weeks, JC AF Weeks, JC TI A guide for the guideline reader SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Editorial Material DE treatment guidelines RP Weeks, JC (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,CTR OUTCOMES & POLICY RES,44 BINNEY ST,BOSTON,MA 02115, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAY PY 1997 VL 43 IS 3 BP 277 EP 278 DI 10.1023/A:1005753215941 PG 2 WC Oncology SC Oncology GA WX772 UT WOS:A1997WX77200009 PM 9150906 ER PT J AU Wang, DK Freeman, GJ Levine, H Ritz, J Robertson, MJ AF Wang, DK Freeman, GJ Levine, H Ritz, J Robertson, MJ TI Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD40; CD95; APO-1; Fas; apoptosis ID CHRONIC LYMPHOCYTIC-LEUKEMIA; FAS ANTIGEN; MEDIATED APOPTOSIS; BCL-2 EXPRESSION; FAS/APO-1 CD95; MYELOMA CELLS; DEATH DOMAIN; PROTEIN; LYMPHOMAS; LIGATION AB Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus participate in the pathogenesis of lymphoid malignancies. The expression and function of CD40 and CD95 on neoplastic B cells from patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non-Hodgkin's lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells in most cases. Furthermore, CD40 activation led to up-regulation of the CD95 antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL cases. The degree of apoptosis induced by CD95 triggering was greater for NHL cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL cells was not significantly changed. However, there was no correlation between the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus, factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL and CLL cells to CD95 triggering may facilitate the development of novel therapeutic approaches to these diseases as well. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA01730, CA66996] NR 58 TC 93 Z9 94 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 1997 VL 97 IS 2 BP 409 EP 417 DI 10.1046/j.1365-2141.1997.422688.x PG 9 WC Hematology SC Hematology GA WZ562 UT WOS:A1997WZ56200026 PM 9163608 ER PT J AU Moulton, PJ Hiran, TS Goldring, MB Hancock, JT AF Moulton, PJ Hiran, TS Goldring, MB Hancock, JT TI Detection of protein and mRNA of various components of the NADPH oxidase complex in an immortalized human chondrocyte line SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Article DE cytokines; human chondrocyte; NADPH oxidase; superoxide ID CHRONIC GRANULOMATOUS-DISEASE; NECROSIS-FACTOR-ALPHA; RESPIRATORY BURST OXIDASE; HYDROGEN-PEROXIDE; ARTICULAR-CARTILAGE; PROTEOGLYCAN SYNTHESIS; CYTOSOLIC COMPONENT; FREE-RADICALS; DEPENDENT CHEMILUMINESCENCE; SUPEROXIDE PRODUCTION AB The immortalized human chondrocyte cell line C-20/A4 has the ability to produce superoxide constitutively at low levels of 5.4 x 10(-2) nmol/min/10(6) cells (S.E.M. = +/-0.5, n = 30) and at raised levels upon stimulation with ionomycin and phorbol 12-myristate 13-acetate. Priming and anti-priming effects of interleukin (IL)-1 beta and IL-4, respectively, are also demonstrated. Reverse transcriptase polymerase chain reaction (RT-PCR) amplification using oligonucleotide primers to components of the NADPH oxidase enzyme complex showed mRNA expression of p22-phox, p40-phox, p47-phox and p67-phox. Western blot analysis using polyclonal antisera indicated the presence of the p47-phox and p67-phox polypeptide components. These results show that the C-20/A4 cells contain an NADPH oxidase-like complex, similar to that found in other cell types, which produces superoxide anions. C1 UNIV W ENGLAND,FAC SCI APPL,BRISTOL BS16 1QY,AVON,ENGLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,E CHARLESTOWN,MA. NR 60 TC 37 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PD MAY PY 1997 VL 36 IS 5 BP 522 EP 529 PG 8 WC Rheumatology SC Rheumatology GA XD164 UT WOS:A1997XD16400004 PM 9189052 ER PT J AU Anderson, K Catterson, A Gaudet, M Gautam, M Kerr, PJ Pecher, M Waiser, D Kaji, J Fava, M AF Anderson, K Catterson, A Gaudet, M Gautam, M Kerr, PJ Pecher, M Waiser, D Kaji, J Fava, M TI A cross-sectional study of private psychiatric practices under a single-payer health care system SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE survey; psychiatric practice; single payer; health care system AB Objectives: To examine current concerns that in the Canadian single-payer mental health care system, the ''rich worried well'' (that is, wealthy individuals who are worried yet mentally well) may overuse psychiatric services, while low-income, uninsured mentally ill individuals may remain undertreated. The current study focuses on the mental health care in the Canadian region of Ottawa-Carleton, where a single-payer system provides universal access to mental health services, to assess how psychiatric services are provided by psychiatrists in private practice. Method: One hundred and seven private psychiatrists working in the region of Ottawa-Carleton completed a questionnaire which contained questions about the sociodemographic characteristics and background of the psychiatrists themselves and which asked the psychiatrists specific questions about the sociodemographic status, diagnosis, and treatment of each patient seen on November 10, 1994. Results: Approximately 93% of the patients seen met criteria for one or more Axis I disorders, of which mood and anxiety disorders were the most common. Wealthier patients were relatively underrepresented among the patients treated by the private psychiatrists. In addition, we found no significant differences in the distribution of Axis I, Axis II, and Axis III disorders between patients earning below $30 000 per year compared with patients earning above $60 000 per year. Conclusions: Our results suggest that outpatient psychiatric care delivered by private psychiatrists in a Canadian single-payer system targets primarily individuals with major psychiatric disorders and does not seem to favour ''the worried well.'' Larger epidemiological studies with independent assessments of psychiatric populations are necessary to confirm our findings. C1 MASSACHUSETTS GEN HOSP,DEPRESS CLIN & RES PROGRAM,BOSTON,MA 02114. UNIV OTTAWA,OTTAWA,ON,CANADA. COMM PRIVATE PSYCHIATRISTS,OTTAWA,ON,CANADA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD MAY PY 1997 VL 42 IS 4 BP 395 EP 401 PG 7 WC Psychiatry SC Psychiatry GA XA799 UT WOS:A1997XA79900006 PM 9161764 ER PT J AU Holden, SA Emi, Y Kakeji, Y Northey, D Teicher, BA AF Holden, SA Emi, Y Kakeji, Y Northey, D Teicher, BA TI Host distribution and response to antitumor alkylating agents of EMT-6 tumor cells from subcutaneous tumor implants SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE detection of micrometastases; metastatic disease response; tumor tissue distribution; tumor/host interaction ID MARROW AUTO-TRANSPLANTATION; SITE-DEPENDENT DIFFERENCES; COLON-CARCINOMA CELLS; HIGH-DOSE MELPHALAN; ORTHOTOPIC TRANSPLANTATION; CANCER-CHEMOTHERAPY; NUDE-MOUSE; SENSITIVITY; DOXORUBICIN; INVIVO AB Purpose: Minimal residual tumor or minimal residual metastatic disease is a major clinical problem for detection and treatment. The purpose of the study was to develop a model system to detect the occurrence and response to therapy of minimal residual tumor in distant organs. Methods: Animals bearing subcutaneously growing established (day 8) murine EMT-6 mammary carcinoma tumors were treated with single doses of the antitumor alkylating agents, cyclophosphamide, melphalan, cis-diamminedichloroplatinum(II) (CDDP) or thiotepa. Tumors, livers, lungs, brain, spleen, blood and bone marrow were collected from the animals 24 h later and single-cell suspensions of these tissues were plated and cultured under conditions suitable for tumor cell colony growth. Results: Tumor cell colonies grew from each of the tissues with varying frequency ranging from about 6 x 10(3) tumor cell colonies per 10(6) cells plated from the liver, to about 2 tumor cell colonies per 10(6) cells plated from the brain. There was a wide range of sensitivity, spanning 2- to 3-log of the tumor cells, to the antitumor alkylating agents depending upon the tissue in which the tumor cells were located. Tumor cells in the circulating blood were most sensitive to the antitumor alkylating agents with no colony growth after treatment of the animals with any of the four drugs tested. The primary tumor growing subcutaneously in the upper hindleg of the animals was also relatively sensitive to each of the four antitumor alkylating agents tested. EMT-6 tumor cells in the spleen were very sensitive to cyclophosphamide, moderately sensitive to melphalan, less sensitive to CDDP and least sensitive to thiotepa. EMT-6 tumor cells in the bone marrow were moderately sensitive to cyclophosphamide, melphalan and thiotepa but less sensitive to CDDP. EMT-6 tumor cells in the lungs were relatively sensitive to thiotepa, moderately sensitive to cyclophosphamide and CDDP and least sensitive to melphalan. EMT-6 tumor cells in the liver or brain were least responsive to treatment of the host with any of the four antitumor alkylating agents tested. Conclusions: Treatment of the tumor-bearing animals with the antiangiogenic combination, TNP-470/minocycline, markedly increased EMT-6 tumor cell killing by cyclophosphamide in the liver, lungs and bone marrow. These results indicate that location within the host is an important determinant in the response of tumor cells to therapy. C1 DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [5 P01-CA38493-09, 5 R01-CA50174-05] NR 37 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1997 VL 40 IS 1 BP 87 EP 93 DI 10.1007/s002800050631 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA WW321 UT WOS:A1997WW32100015 PM 9137536 ER PT J AU Eng, C Schneider, K Fraumeni, JF Li, FP AF Eng, C Schneider, K Fraumeni, JF Li, FP TI Third international workshop on collaborative interdisciplinary studies of p53 and other predisposing genes in Li-Fraumeni syndrome SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID SPONTANEOUS TUMORIGENESIS; MUTATIONS; MICE; TUMORS C1 DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD 20893. OI Eng, Charis/0000-0002-3693-5145 NR 17 TC 25 Z9 25 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1997 VL 6 IS 5 BP 379 EP 383 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WZ603 UT WOS:A1997WZ60300013 PM 9149899 ER PT J AU Frei, E AF Frei, E TI Clinical trials of antitumor agents: Experimental design and timeline considerations SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Article ID PHASE-I TRIALS; CANCER-CHEMOTHERAPY; TOXICOLOGY; ESCALATION; PRECISION; TOXICITY; QUALITY RP Frei, E (reprint author), DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 62 TC 6 Z9 6 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD MAY-JUN PY 1997 VL 3 IS 3 BP 127 EP 136 PG 10 WC Oncology SC Oncology GA XC487 UT WOS:A1997XC48700001 PM 9161775 ER PT J AU Westphal, CH Schmaltz, C Rowan, S Elson, A Fisher, DE Leder, P AF Westphal, CH Schmaltz, C Rowan, S Elson, A Fisher, DE Leder, P TI Genetic interactions between atm and p53 influence cellular proliferation and irradiation-induced cell cycle checkpoints SO CANCER RESEARCH LA English DT Article ID ATAXIA-TELANGIECTASIA; DNA-DAMAGE; MICE; RESPONSES; APOPTOSIS; PATHWAY AB Ataxia-telangiectasia and Li-Fraumeni syndrome, pleiotropic disorders caused by mutations in the genes atm and p53, share a marked increase in cancer rates. A number of studies have argued for an interaction between these two genes (for comprehensive reviews, see M. S. Meyn, Cancer Res., 55: 5991-6001, 1995, and M. F. Lavin and Y. Shiloh, Annu. Rev., Immunol., 15: 177-202, 1996). Specifically, atm is placed upstream of p53 in mediating G(1)-S tell cycle checkpoint control, and both afm and p53 are believed to influence cellular proliferation. To analyze the genetic interactions of atm and p53, mouse embryonic fibroblasts (MEFs) homozygously deficient for both atm and p53 were used to assess cell cycle and growth control. These double-null fibroblasts proliferate rapidly and fail to exhibit the premature growth arrest seen with atm-null MEFs. MEFs null for both atm and p53 do not express any p21(cipl/wafl), showing that p53 is required for p21(cipl/wafl) expression in an atm-null background. By contrast, homozygous loss of either atm, p53, or both results in similar abnormalities of the irradiation-induced G(1)-S cell cycle checkpoint. Our results suggest two separate pathways of interaction between atm and p53, one linear, involving G(1)-S cell cycle control, and another more complex, involving aspects of growth regulation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. WEIZMANN INST SCI,DEPT MOL GENET,IL-76100 REHOVOT,ISRAEL. FU NCI NIH HHS [CA69531]; NIAMS NIH HHS [AR43369] NR 18 TC 68 Z9 71 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 MAY 1 PY 1997 VL 57 IS 9 BP 1664 EP 1667 PG 4 WC Oncology SC Oncology GA WW569 UT WOS:A1997WW56900010 PM 9135004 ER PT J AU Augenlicht, LH Wadler, S Corner, G Richards, C Ryan, L Multani, AS Pathak, S Benson, A Haller, D Heerdt, BG AF Augenlicht, LH Wadler, S Corner, G Richards, C Ryan, L Multani, AS Pathak, S Benson, A Haller, D Heerdt, BG TI Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: A frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DNA-SEQUENCE AMPLIFICATION; P53 GENE-MUTATIONS; WILD-TYPE P53; COLORECTAL CARCINOMAS; THYMIDYLATE SYNTHASE; CHROMOSOME MICRODISSECTION; MYELOCYTOMATOSIS VIRUS; TRANSFORMING GENE; CYCLE CHECKPOINT AB Human colonic cancer is associated with multiple genetic deletions, mutations, and alterations in gene expression; in contrast, gene amplification has not been recognized as a prominent characteristic of human colonic tumors. Although the c-myc gene is overexpressed in approximately 70% of human colonic cancers, previous studies have not detected frequent gene amplification or rearrangement of c-myc in these tumors, although such amplification has been reported in chemically induced rodent colon cancer and quantitative analysis of gene copy number has shown the gene to be amplified at a low level in mucinous and poorly differentiated human colon carcinomas. Using rigorously controlled blot methodology, we have established that the c-myc gene, Located at 8q21, exhibited amplification of 87% to 35-fold in 7 of 10 human colonic carcinoma cell lines. This was highly significant even at a low level of amplification in HT29 cells (P < 0.0001). Cytogenetic analysis by G-banding did not detect aneuploidy involving chromsome 8q, suggesting that the amplification for the c-myc gene on 8q was relatively specific, and this was consistent with a lack of amplification detected for the c-mos gene on 8q24, which was assayed similarly. The same methodology then revealed amplification of c-myc from 1.5-fold to 5-fold in 32% of tumors from 149 patients entered into a multi-institutional Phase III study of adjuvant therapy for colon cancer. c-myc status was not related to time to recurrence or death, but low levels of c-myc amplification identified a subset of patients who showed a statistically significant increase in disease-free survival, and a corresponding trend to longer overall survival, in response to adjuvant therapy with 5-fluorouracil plus levamisole. Presence of c-myc amplification was not related to incidence of p53 mutations. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX 77030. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. RP Augenlicht, LH (reprint author), ALBERT EINSTEIN CANC CTR,DEPT ONCOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [P30-CA13330, CA53446, CA57694] NR 47 TC 88 Z9 91 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1997 VL 57 IS 9 BP 1769 EP 1775 PG 7 WC Oncology SC Oncology GA WW569 UT WOS:A1997WW56900027 PM 9135021 ER PT J AU Weller, EA Ryan, LP Spiegelman, D Smith, T AF Weller, EA Ryan, LP Spiegelman, D Smith, T TI Statistical issues in assessing human population exposures SO CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS LA English DT Article; Proceedings Paper CT 3rd International Conference on Environmetrics and Chemometrics CY SEP 11-13, 1995 CL LAS VEGAS, NV SP US EPA, NISS, NIST, Elsevier Sci Publ, Gulf Coast Hazardous Subst Res Ctr, Monsanto Chem Co, Texas A&M Univ DE exposure; dose; model; measurement error ID COVARIATE MEASUREMENT ERROR; COST-EFFICIENT; DESIGNS AB Relating an exposure level to a particular outcome in occupational and environmental epidemiology studies may be challenging. In these studies, researchers are interested in the health effects from exposure. Two factors that complicate this process are the measurement error that is usually present in exposure assessment and the complex nature of the exposure-dose relationship. Statistical aspects of the measurement error problem has been the focus of many researchers in the past few years. However, less attention has been given to the second issue of incorporating the relationship between exposure and dose and directly modeling the dose-response relationship, when this is of primary scientific interest. For complex exposure-dose relationships, a direct application of statistical methods to relate exposure to the health outcome may lead to bias and loss of efficiency in estimates of the dose-response relationship. In this paper, we present some of the statistical issues that arise using a study of the health effects of arc welding fumes as an illustration. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Weller, EA (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 10 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-7439 J9 CHEMOMETR INTELL LAB JI Chemometrics Intell. Lab. Syst. PD MAY PY 1997 VL 37 IS 1 BP 189 EP 195 DI 10.1016/S0169-7439(97)00003-8 PG 7 WC Automation & Control Systems; Chemistry, Analytical; Computer Science, Artificial Intelligence; Instruments & Instrumentation; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Automation & Control Systems; Chemistry; Computer Science; Instruments & Instrumentation; Mathematics GA XB913 UT WOS:A1997XB91300019 ER PT J AU Chandrasekar, B Colston, JT Freeman, GL AF Chandrasekar, B Colston, JT Freeman, GL TI Induction of proinflammatory cytokine and antioxidant enzyme gene expression following brief myocardial ischaemia SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE reperfusion injury; ischaemia; proinflammatory cytokines; antioxidant enzymes; gene expression ID TUMOR-NECROSIS-FACTOR; MANGANESE SUPEROXIDE-DISMUTASE; NF-KAPPA-B; HEAT-SHOCK PROTEIN; FACTOR-ALPHA; STUNNED MYOCARDIUM; IONIZING-RADIATION; MESSENGER-RNA; INTERLEUKIN-1; ISCHEMIA AB The purpose of this study was to determine if proinflammatory cytokines are up-regulated during reperfusion following sublethal ischaemia, and whether concurrent up-regulation of antioxidant enzymes occurs. Open-chest rats were subjected to 15 min of ischaemia followed by 1 or 3 h reperfusion (R). Myocardium from the ischaemic zone showed a significantly higher (P < 0.01) generation of thiobarbituric acid-reactive substances at Ih and 3 h R. Northern blots showed a weak signal in controls for IL-6 mRNA (0.13 +/- 0.01); this was elevated to 0.68 +/- 0.12 at 1 h and 0.69 +/- 0.10 at 3 h R. Neither IL-1 beta nor tumour necrosis factor-alpha (TNF-alpha) were detectable in controls. IL-1 beta rose to 0.78 +/- 0.07 at 1 h and 0.51 +/- 0.08 at 3 h R, and TNF-alpha rose to 0.69 +/- 0.10 at 1 h and 0.38 +/- 0.15 at 3 h R. Western blotting showed no signals in the control, but readily detectable signals at 1 h R; these remained high (IL-6) or decreased (IL-1 beta and TNF-alpha) at 3 h R. mRNA analysis for antioxidant enzymes revealed a weak signal in controls for catalase (CAT; 0.16 +/- 0.08), glutathione peroxidase (GSH-Px; 0.15 +/- 0.06) and superoxide dismutase (SOD; 0.21 +/- 0.05). After 1 h R, levels increased significantly for CAT (0.46 +/- 0.10; P < 0.025) and GSH-Px (0.51 +/- 0.13; P < 0.01), but remained similar to controls for SOD (0.26 +/- 0.15). At 3 h R the mRNA levels were significantly elevated for the three enzymes (CAT 0.48 +/- 0.13; GSH-Px 0.47 +/- 0.10; SOD 0.54 +/- 0.08). We conclude that mRNA for proinflammatory cytokines is expressed early in reperfusion, and that the proteins are present in heart tissue. Also, reperfusion is associated with rapid expression of genes for antioxidant enzymes, which may enhance reactive oxygen intermediate (ROI) scavenging. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CARDIOVASC,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 38 TC 49 Z9 50 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 1997 VL 108 IS 2 BP 346 EP 351 DI 10.1046/j.1365-2249.1997.d01-1017.x PG 6 WC Immunology SC Immunology GA WY467 UT WOS:A1997WY46700026 PM 9158109 ER PT J AU Pfaller, MA Rex, JH Rinaldi, MG AF Pfaller, MA Rex, JH Rinaldi, MG TI Antifungal susceptibility testing: Technical advances and potential clinical applications SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IN-VITRO SUSCEPTIBILITY; FLUCONAZOLE-RESISTANT CANDIDA; HUMAN-IMMUNODEFICIENCY-VIRUS; BROTH MICRODILUTION METHOD; AMPHOTERICIN-B; COLLABORATIVE EVALUATION; MULTICENTER EVALUATION; MACRODILUTION METHOD; TORULOPSIS-GLABRATA; NATIONAL-COMMITTEE AB The clinical application of in vitro antifungal susceptibility testing has been limited by a lack of reproducibility and uncertain clinical relevance. As a result of several collaborative studies, the National Committee for Clinical Laboratory Standards (NCCLS) has proposed a standardized antifungal susceptibility test method, NCCLS M27-T. More convenient, user-friendly methods (microdilution broth and stable gradient technology) have been evaluated, and the potential for a similar process with a disk diffusion method is apparent, Adaptation of the standard method for susceptibility testing of filamentous fungi appears promising, The existence of a standardized method facilitates meaningful analysis of studies addressing the issue of clinical relevance of antifungal susceptibility testing, Correlation of MICs with clinical response to therapy is beginning to emerge, most notably in relation to fluconazole and itraconazole therapy for oropharyngeal candidiasis associated with infection with the human immunodeficiency virus. This accumulated experience with antifungal susceptibility testing allows us to provide several specific recommendations for antifungal susceptibility testing in the clinical laboratory, Application of this developing technology to new antifungal agents and other disease states will enhance our ability to effectively deal with the emerging problem of fungal infection. C1 UNIV TEXAS, SCH MED,CTR STUDY EMERGING & REEMERGING PATHOGENS, DEPT INTERNAL MED,DIV INFECT DIS, HOUSTON, TX USA. UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, AUDIE L MURPHY MEM VET HOSP, SAN ANTONIO, TX 78284 USA. RP Pfaller, MA (reprint author), UNIV IOWA, COLL MED, DEPT PATHOL, 273 MRC, IOWA CITY, IA 52242 USA. NR 75 TC 83 Z9 87 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1997 VL 24 IS 5 BP 776 EP 784 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WX257 UT WOS:A1997WX25700004 PM 9142769 ER PT J AU Ali, MZ Goetz, MB AF Ali, MZ Goetz, MB TI A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE INFECTIONS; FEBRILE NEUTROPENIC PATIENTS; DAILY NETILMICIN REGIMENS; URINARY-TRACT INFECTION; SERIOUS INFECTIONS; COMPARATIVE TRIAL; GENTAMICIN-NEPHROTOXICITY; PSEUDOMONAS-AERUGINOSA; CONVENTIONAL SCHEDULES; CORTICAL ACCUMULATION AB We performed a meta-analysis of the efficacy and toxicity of single daily dosing (SDD) vs. multiple daily dosing of aminoglycosides and summarized the results of the four previously published meta-analyses on this subject. Our analysis showed that the overall clinical response rate favored SDD therapy (mean difference, + 3.06%; 95% confidence limit [CL], + 0.17% to + 5.95%; P = .04). However, we found no significant difference in the overall microbiological response rates (mean difference. + 1.25%; 95% CL, - 0.40% to + 2.89%) or in the clinical response rates (mean difference, + 0.62%; 95% CL, - 2.48% to + 3.7%) when patients who received adjunctive antimicrobial therapy were excluded from the analysis. No significant differences were found in the incidences of nephrotoxicity, ototoxicity, or vestibular toxicity; the summary differences in the rates of these toxicities were - 0.18% (95% CL, - 2.17% to + 1.81%), + 1.38% (95% CL, - 0.99% to + 3.75%), and - 3.05% (95% CL, - 10.69% to + 4.59%), respectively. These results are similar to those of the previously published meta-analyses. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. WILKES BARRE VET AFFAIRS MED CTR,DEPT MED,WILKES BARRE,PA. OI Goetz, Matthew/0000-0003-4542-992X NR 88 TC 154 Z9 163 U1 2 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1997 VL 24 IS 5 BP 796 EP 809 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA WX257 UT WOS:A1997WX25700007 PM 9142772 ER PT J AU Krosnick, A AF Krosnick, A TI Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, 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 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAY-JUN PY 1997 VL 19 IS 3 BP 367 EP 368 DI 10.1016/S0149-2918(97)80123-3 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XJ311 UT WOS:A1997XJ31100001 ER PT J AU Rumelt, S Remulla, H Rubin, PAD AF Rumelt, S Remulla, H Rubin, PAD TI Silicone punctal plug migration resulting in dacryocystitis and canaliculitis SO CORNEA LA English DT Article DE dry eyes; silicone punctal plugs; complications; dacryocystitis; canaliculitis ID DRY EYE; COMPLICATIONS AB Purpose. One of the modalities of treating dry eyes is punctal plugs. They are usually used for temporary occlusion of the lacrimal drainage system. Among the complications associated with silicone punctal plugs are extrusion, downward migration, irritation, and epiphora. To our knowledge, this is the first report of dacryocystitis and canaliculitis as a result of spontaneous migration of punctal plugs into the lacrimal drainage system. Methods, We describe the sequelae of spontaneous migration of silicone punctal plugs into the lacrimal drainage system in two patients with dry eyes. Results, In two patients, spontaneous migration of silicone punctal plugs into the canaliculus or the lacrimal sac, respectively, resulted in canaliculitis or dacryocystitis. Conclusion, Smaller sized newer generation punctal plugs were designed to facilitate insertion; however, this design also increases the likelihood of proximal migration within the lacrimal drainage system. The importance of monitoring patients after punctal-plug placement cannot be overemphasized. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,SCH MED,EYE PLAST & ORBIT SERV,BOSTON,MA 02114. NR 13 TC 43 Z9 48 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD MAY PY 1997 VL 16 IS 3 BP 377 EP 379 DI 10.1097/00003226-199705000-00022 PG 3 WC Ophthalmology SC Ophthalmology GA WW875 UT WOS:A1997WW87500021 PM 9143816 ER PT J AU Cheek, RF Olszak, I Madoff, S Preffer, FI AF Cheek, RF Olszak, I Madoff, S Preffer, FI TI In vitro detection of Mycoplasma fermentans binding to B-lymphocytes in fresh peripheral blood using flow cytometry SO CYTOMETRY LA English DT Article DE Mycoplasma fermentans binding; B cells; T cells; B cells in HIV+ peripheral blood; infectious disease; B cell hematopoietic malignancy; flow cytometry ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIFFERENTIATION; INCOGNITUS; INFECTIONS; CULTURE AB Previous reports have shown, using fluorescent probes conjugated to the organism, that Mycoplasma fermentans fuses with about 12% of peripheral blood lymphocytes, However, no lymphocyte subset was specified. To elucidate the specific subset of lymphocytes involved, we developed a three-color flow cytometric assay to detect M. fermentans binding to fresh peripheral blood cells, In our assay, two strains of M. fermentans were grown in SP4 glucose broth, mixed with fresh whole blood samples (n > 20), and incubated at 37 degrees C. The blood samples were then stained with a polyclonal antibody to M. fermentans, a monoclonal antibody to B-lymphocytes (CD19), and a monoclonal antibody to T-lymphocytes (CD3), Using three-color now cytometry, we obtained data confirming binding of M. fermentans to 10%-15% of peripheral blood lymphocytes with minimal granulocyte or monocyte staining detected, Flow cytometric analysis showed that early binding appears predominantly directed towards B-lymphocytes (86.7 +/- 9.0%), and that this binding could not be blocked by antibodies directed towards common B lymphocyte cell. surface antigens, M. fermentans binding to B-lymphocytes occurred within 5 min of in vitro inoculation, reached a maximum within 30-60 min (94-97%), and thereafter plateaued, The binding was concentration dependent over a three log dilution using 10(3) color changing units as standard. Binding to T-lymphocytes was minimal (< 5% positive), B lineage tumor cells or peripheral blood B cells obtained from HIV infected individuals demonstrated reduced binding of M. fermentans. This assay provides a good method to study the cellular interactions of mycoplasma and may help to elucidate pathogenic mechanisms of mycoplasma infections. (C) 1997 WLley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MICROBIOL,BOSTON,MA 02114. NR 14 TC 11 Z9 12 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 0196-4763 J9 CYTOMETRY JI Cytometry PD MAY 1 PY 1997 VL 28 IS 1 BP 90 EP 95 DI 10.1002/(SICI)1097-0320(19970501)28:1<90::AID-CYTO11>3.0.CO;2-M PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WW924 UT WOS:A1997WW92400011 PM 9136760 ER PT J AU Grevelink, JM Gonzalez, S Bonoan, R Vibhagool, C Gonzalez, E AF Grevelink, JM Gonzalez, S Bonoan, R Vibhagool, C Gonzalez, E TI Treatment of nevus spilus with the Q-switched ruby laser SO DERMATOLOGIC SURGERY LA English DT Article ID CUTANEOUS MELANOMA AB BACKGROUND. Q-switched lasers have shown to be effective in the removal of unwanted cutaneous pigmentation. Benign cutaneous pigmented lesions represent a heterogeneous group. Nevus spilus is a relatively uncommon pigmented lesion characterized by dark, hyperpigmented clots scattered over a tan-colored macule. OBJECTIVE. A cohort of patients with nevus spilus was studied to determine the effects of R-switched ruby and R-switched Nd:YAG laser treatment an clearance of pigment and to evaluate potential side effects. METHODS. Six patients with nevus spilus were treated with the Q-switched ruby laser (QSR). In addition, three lesions received a test treatment with the Q-switched Nd:YAG (QSYAG) laser at 532 or 1064 nm. The results of treatment were documented during follow up visits. RESULTS. Most lesions showed a near-complete or complete response to laser treatment. In one case partial hyperpigmentation occurred after treatment and in one case no follow-up could be obtained. In the three cases that received both QSR and QSYAG laser treatment, the QSR laser was shown to be the most effective in removing pigment. CONCLUSION. Nevus spilus can be treated effectively with the Q-switched ruby laser. (C) 1997 by the American Society for Dermatologic Surgery, Inc. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DERMATOL LASER CTR, PROFESS OFF BLDG, SUITE 503, BOSTON, MA 02114 USA. NR 22 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 1997 VL 23 IS 5 BP 365 EP 369 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA XC349 UT WOS:A1997XC34900003 PM 9179247 ER PT J AU Desai, CJ Krueger, NX Saito, H Zinn, K AF Desai, CJ Krueger, NX Saito, H Zinn, K TI Competition and cooperation among receptor tyrosine phosphatases control motoneuron growth cone guidance in Drosophila SO DEVELOPMENT LA English DT Article DE receptor tyrosine phosphatase; growth cone; Drosophila; neuromuscular system; neural development; neurogenetics ID NEURITE OUTGROWTH; EXPRESSION; MOLECULE; NEURONS AB The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved in motor axon guidance in the Drosophila embryo, Here we analyze the requirements for these three phosphatases in growth cone guidance decisions along the ISN and SNb motor pathways, Any one of the three suffices for the progression of ISN pioneer growth cones beyond their first intermediate target in the dorsal muscle field, DLAR or DPTP69D can facilitate outgrowth beyond a second intermediate target, and DLAR is uniquely required for formation of a normal terminal arbor, A different pattern of partial redundancy among the three phosphatases is observed for the SNb pathway, Any one of the three suffices to allow SNb axons to leave the common ISN pathway at the exit junction, When DLAR is not expressed, however, SNb axons sometimes bypass their ventrolateral muscle targets after leaving the common pathway, instead growing out as a separate bundle adjacent to the ISN, This abnormal guidance decision can be completely suppressed by also removing DPTP99A, suggesting that DLAR turns off or counteracts a DPTP99A signal that favors the bypass axon trajectory, Our results show that the relationships among the tyrosine phosphatases are complex and dependent on cellular context, At growth cone choice points along one nerve, two phosphatases cooperate, while along another nerve these same phosphatases can act in opposition to one another. C1 CALTECH,DIV BIOL,PASADENA,CA 91125. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM-53415]; NINDS NIH HHS [NS28182] NR 27 TC 119 Z9 120 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1997 VL 124 IS 10 BP 1941 EP 1952 PG 12 WC Developmental Biology SC Developmental Biology GA XD825 UT WOS:A1997XD82500010 PM 9169841 ER PT J AU Arora, S Simeone, L Smakowski, P Habershaw, G Freeman, R Frykberg, R Veves, A AF Arora, S Simeone, L Smakowski, P Habershaw, G Freeman, R Frykberg, R Veves, A TI Microcirculation in the foot and forearm is equally impaired in diabetic neuropathy SO DIABETES LA English DT Meeting Abstract C1 DEACONESS HOSP,JOSLIN FOOT CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 44 EP 44 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38000044 ER PT J AU Veves, A Primavera, J Akbari, C Donaghue, V Zacharoulis, D Chrzan, J Degirolami, U Logerfo, F Freeman, R AF Veves, A Primavera, J Akbari, C Donaghue, V Zacharoulis, D Chrzan, J Degirolami, U Logerfo, F Freeman, R TI Expression of endothelial nitric oxide synthetase (eNOS) in diabetic neuropathy. SO DIABETES LA English DT Meeting Abstract C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,JOSLIN FOOT CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 124 EP 124 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38000124 ER PT J AU Saouaf, R Fielding, R Donaghue, V Giurini, J Horton, E Veves, A AF Saouaf, R Fielding, R Donaghue, V Giurini, J Horton, E Veves, A TI The effect of exercise on the endothelial function of the micro- and macro-circulation in IDDM. SO DIABETES LA English DT Meeting Abstract C1 BOSTON UNIV,DEACONESS JOSLIN FOOT CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 430 EP 430 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38000429 ER PT J AU Akbari, C Saouaf, R Barnhill, D Newman, P Logerfo, F AF Akbari, C Saouaf, R Barnhill, D Newman, P Logerfo, F TI Endothelium-dependent vasodilatation is impaired during acute hyperglycemia. SO DIABETES LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEACONESS JOSLIN FOOT CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 445 EP 445 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38000444 ER PT J AU Heller, RS Kieffer, TJ Habener, JF AF Heller, RS Kieffer, TJ Habener, JF TI Insulinotropic glucagon-like peptide I receptor expression in glucagon-producing alpha-cells of the rat endocrine pancreas SO DIABETES LA English DT Article ID GENE-EXPRESSION; SOMATOSTATIN; RELEASE; GLUCOSE; LINE; POLYPEPTIDE; IMMUNOREACTIVITY; PEPTIDE-I(7-37); INTESTINE; HORMONES AB Glucagon-like peptide I (GLP-I), an intestine-derived incretin hormone, is a potent stimulator of insulin and somatostatin secretion. In some studies, GLP-I is an inhibitor of glucagon secretion. It remains uncertain, however, whether the effect of GLP-I on the inhibition of glucagon secretion is direct, owing to interactions with GLP-I receptors on alpha-cells, or indirect, via paracrine suppression by insulin or somatostatin. The localization of the GLP-I receptor on insulin and somatostatin-producing cells in the islets is well established. Whether the GLP-I receptor also resides on the glucagon-producing alpha-cells remains controversial and is reported to be absent on rat alpha-cells. To investigate the distribution of the GLP-I receptor on islet cells, we examined the expression of GLP-I receptor mRNA in phenotypically distinct islet cell Lines and islets, and the presence of immunoreactive GLP-I receptor in dispersed rat islet cells using a specific antiserum. GLP-I receptor mRNA was readily detected by reverse transcription-polymerase chain reaction (RT-PCR) in both rat islets and in established islet cell lines representing distinct alpha-, beta-, and delta-cell phenotypes. In addition, GLP-I receptor expression was detected in single rat alpha-cells by single-cell RT-PCR. In dispersed rat islet cells analyzed by double immunofluorescent staining, 90% of the insulin, 76% of the somatostatin, and 20% of the glucagon positive cells colocalized with the GLP-I receptor immnnoreactivity. Thus, a substantial population of glucagon immunoreactive alpha-cells express the GLP-I receptor. These findings imply that GLP-I may have a direct receptor-mediated action in the regulation of the physiological functions on a substantial subpopulation of alpha-cells. We suggest that a possible role for GLP-I receptors on alpha-cells may be to provide positive autocrine feedback control on glucagon secretion during fasting and/or to dampen the potent paracrine suppression of glucagon secretion by insulin during feeding. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,LAB MOL ENDOCRINOL,BOSTON,MA 02114. RI Heller, R.Scott/A-7279-2008 FU NIDDK NIH HHS [DK-30834] NR 39 TC 113 Z9 114 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 IS 5 BP 785 EP 791 DI 10.2337/diabetes.46.5.785 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW792 UT WOS:A1997WW79200008 PM 9133545 ER PT J AU Ji, LN Malecki, M Warram, JH Yang, YD Rich, SS Krolewski, AS AF Ji, LN Malecki, M Warram, JH Yang, YD Rich, SS Krolewski, AS TI New susceptibility locus for NIDDM is localized to human chromosome 20q SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; YOUNG MODY; INSULIN-RESISTANCE; LINKAGE ANALYSIS; FAMILIAL NIDDM; GENE; GLUCOKINASE; GLUCOSE; 12Q AB To test the hypothesis that a gene (or genes) in the ''MODY1 region'' of the long arm of chromosome 20 contributes to the development of NIDDM, we conducted linkage studies in 29 extended Caucasian families in which many members were affected with NIDDM. A total of 498 individuals, including 159 NIDDM patients with an average age at diagnosis of 47 years, were genotyped for eight highly polymorphic microsatellite markers spanning a 31-cM region on chromosome 20q12-13.1. Using affected sib-pair analysis, we obtained evidence suggesting linkage between NIDDM and markers D20S119, D20S178, and D20S197 (allele sharing identical-by-descent [IBD], 0.56 for all three; P = 0.005, P = 0.009, and P = 0.004, respectively). Multipoint nonparametric linkage (NPL) analysis also showed evidence for linkage of NIDDM with the same three markers. The evidence for linkage was much stronger (allele sharing IBD by affected sibpairs, 0.64 [P < 0.0001]; maximum NPL score, 3.3 [P = 0.009]) in the 14 families whose average age at diagnosis of NIDDM was above the median (47 years) for all families. In these 14 families, one particular allele of the microsatellite D20S197 was transmitted from heterozygous parents to NIDDM offspring more frequently than expected (P < 0.01). This indicates that the marker allele and the disease allele are in linkage disequilibrium, implying that they are in close proximity. Consequently, the recently identified MODY1 gene (hepatocyte nuclear factor 4) is an unlikely candidate gene for NIDDM in our families, since it is located about 8 cM centromeric of D20S197. In conclusion, we have identified a new region on chromosome 20q that contains one or more NIDDM genes distinct from the recently identified MODY1 gene. 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. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. FU NIDDK NIH HHS [DK-36836, DK-47475] NR 32 TC 135 Z9 141 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 IS 5 BP 876 EP 881 DI 10.2337/diabetes.46.5.876 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW792 UT WOS:A1997WW79200021 PM 9133558 ER PT J AU Pasquarello, C Fanizzi, PM Laffel, L AF Pasquarello, C Fanizzi, PM Laffel, L TI Evaluation of a short insulin syringe needle (30 gauge, 8 mm) in children with IDDM. SO DIABETES LA English DT Meeting Abstract C1 JOSLIN CLIN,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1997 VL 46 SU 1 BP 1278 EP 1278 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX380 UT WOS:A1997WX38001272 ER PT J AU Welch, GW Jacobson, AM Polonsky, WH AF Welch, GW Jacobson, AM Polonsky, WH TI The Problem Areas in Diabetes Scale - An evaluation of its clinical utility SO DIABETES CARE LA English DT Article ID HEALTH BELIEF MODEL; MELLITUS AB OBJECTIVE - To evaluate the reliability and concurrent and discriminant validity of the Problem Areas in Diabetes (PAID) scale, a new measure of emotional functioning in diabetes. RESEARCH DESIGN AND METHODS - A battery of questionnaires, including the PAID, was completed by 256 volunteer diabetic outpatients. In our analyses, we examined the PAID's internal structure and compared mean IDDM and NIDDM treatment group scores in regression analyses to explore its discriminant validity. We also evaluated concurrent validity from the correlations between the PAID and diabetes-specific measures of coping and health attitudes and HbA(1c). RESULTS - Principal component analyses identified a large emotional adjustment factor, supporting the use of the total score. Significant sizable correlations were found between the PAID and a range of selected health attitudinal measures. There were significant differences (with small-to-moderate effect sizes) in PAID scores between IDDM and NIDDM patients and between IDDM and NIDDM insulin- and tablet-treated subgroups; no differences were found between NIDDM insulin- and tablet-treated subgroups. CONCLUSIONS - The study findings provided support for the construct validity of the PAID, including evidence for discriminant validity from its ability to detect differences between IDDM and NIDDM treatment groups expected to differ in the emotional impact of life with diabetes. Future studies should explore the PAID's performance in nonspecialist treatment settings as well as its responsiveness to clinical change. C1 BALBOA MED CTR,HLTH PSYCHOL DIV,SAN DIEGO,CA. RP Welch, GW (reprint author), JOSLIN DIABET CTR,MENTAL HLTH UNIT,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-42315, DK-27845] NR 27 TC 247 Z9 256 U1 2 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1997 VL 20 IS 5 BP 760 EP 766 DI 10.2337/diacare.20.5.760 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW589 UT WOS:A1997WW58900014 PM 9135939 ER PT J AU Jacobson, AM Hauser, ST Willett, JB Wolfsdorf, JI Dvorak, R Herman, L deGroot, M AF Jacobson, AM Hauser, ST Willett, JB Wolfsdorf, JI Dvorak, R Herman, L deGroot, M TI Psychological adjustment to IDDM: 10-year follow-up of an onset cohort of child and adolescent patients SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; YOUNG-ADULTS; EGO DEVELOPMENT; SELF-ESTEEM; EMPLOYMENT; EDUCATION; YOUTH; RISK AB OBJECTIVE - To evaluate the psychological adjustment of young adults with IDDM in comparison with similarly aged individuals without chronic illness. RESEARCH DESIGN AND METHODS - An onset cohort of young adults (n = 57), ages 19-26 years, who have been followed over a 10-year period since diagnosis, was compared with a similarly aged group of young adults identified at the time of a moderately severe, acute illness (n = 54) and followed over the same 10-year period. The groups were assessed at 10-year follow-up in terms of 1) sociodemographic indices (e.g., schooling, employment, delinquent activities, drug use), 2) psychiatric symptoms, and 3) perceived competence. In addition, IDDM patients were examined for longitudinal change in adjustment to diabetes. RESULTS - The groups differed only minimally in terms of sociodemographic indices, with similar rates of high school graduation, post-high school education, employment, and drug use. The IDDM group reported fewer criminal convictions and fewer non-diabetes-related illness episodes than the comparison group. There were no differences in psychiatric symptoms. However, IDDM patients reported lower perceived competence, with specific differences found on the global self-worth, sociability, physical appearance, being an adequate provider, and humor subscales. The IDDM patients reported improving adjustment to their diabetes over the course of the 10-year follow-up. CONCLUSIONS - Overall, the young adults with IDDM appeared to be as psychologically well adjusted as the young adults without a chronic illness. There were, however, indications of lower self-esteem in the IDDM patients that could either portend or predispose them to risk for future depression or other difficulties in adaptation. C1 JOSLIN DIABET CTR,DEPT PEDIAT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. JUDGE BAKER CHILDRENS CTR,BOSTON,MA. HARVARD UNIV,GRAD SCH EDUC,BOSTON,MA 02115. RP Jacobson, AM (reprint author), JOSLIN DIABET CTR,DEPT PSYCHIAT,1 JOSLIN PL,BOSTON,MA 02215, USA. OI Willett, John/0000-0001-7183-350X FU NIDDK NIH HHS [DK-27845] NR 37 TC 80 Z9 80 U1 1 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1997 VL 20 IS 5 BP 811 EP 818 DI 10.2337/diacare.20.5.811 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW589 UT WOS:A1997WW58900022 PM 9135947 ER PT J AU Barnes, CJ Hardman, WE Cameron, IL Lee, M AF Barnes, CJ Hardman, WE Cameron, IL Lee, M TI Aspirin, but not sodium salicylate, indomethacin, or nabumetone, reversibly suppresses 1,2-dimethylhydrazine-induced colonic aberrant crypt foci in rats SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE aspirin; sodium salicylate; indomethacin; nabumetone; prostaglandin E-2; aberrant crypt foci; colon; rat; carcinogenesis ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DIFFERENTIAL INHIBITION; CARCINOGENESIS; CYCLOOXYGENASE-2; SYNTHASE-2; CANCER; TUMORS; MICE AB The aim of this study was to determine if selective inhibition of cyclooxygenase isozymes affects the initiation of carcinogen-induced colon cancer using aberrant crypt foci (ACF) as a surrogate biomarker, Male Sprague-Dawley rats (18 per group) were given single subcutaneous injections of saline (4 ml/kg), aspirin (50 mg/kg body wt) sodium salicylate (50 mg/kg), indomethacin (4 mg/kg), nabumetone (100 mg/kg), or 16,16-dimethyl-prostaglandin E-2 (50 mg/kg) for three days. On day 4, 12 rats per group were given a subcutaneous injection of 1,2-dimethylhydrazine (12 mg base/kg body wt) and six rats per group received vehicle alone (4 ml/kg) every week for eight weeks, after which drug treatment ceased. Control and six carcinogen-treated rats per group were killed at this time and the remaining six rats per group killed 22 weeks later. Colons were scored for ACF number and size. Only aspirin caused a significant reduction in total ACF and ACF formation at the early time point, but at the later time, there were no significant differences between groups, ACF from all treatment groups increased in size at similar rates at both time points, Thus, only aspirin demonstrated a significant, although reversible, suppression of carcinogen-induced ACF. Possible mechanisms of action and the clinical implications of aspirin chemoprevention are discussed. C1 UNIV TEXAS,HLTH SCI CTR,DIV GASTROENTEROL & NUTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. VET AFFAIRS MED CTR,SAN ANTONIO,TX 78284. NR 33 TC 17 Z9 18 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 1997 VL 42 IS 5 BP 920 EP 926 DI 10.1023/A:1018812430512 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WY084 UT WOS:A1997WY08400008 PM 9149043 ER PT J AU Martin, MG Wu, SV Walsh, JH AF Martin, MG Wu, SV Walsh, JH TI Ontogenetic development and distribution of antibody transport and Fc receptor mRNA expression in rat intestine SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE absorption; lactation; immunity ID CLASS-I ANTIGENS; SUCKLING RATS; NEONATAL RAT; IMMUNOGLOBULIN TRANSFER; EPITHELIAL-CELLS; IGG; FETAL; MICE; MHC; TRANSMISSION AB The intestine of the suckling rat has the unique capacity of absorbing immunoglobulins from maternal milk. We investigated intestinal Fc receptor mRNA expression and the absorption of orally administered antibodies to delineate the ontogeny and tissue specificity of this transport system, Duodenal expression of Fc receptor mRNA was at maximum levels between 1 and 19 days of age, but was not detectable during fetal life and in animals after weaning. Along the horizontal axis of the intestine, FcRn mRNA expression was maximum in the proximal duodenum and declined gradually in distal bowel. Similarly, absorption of orally administered antibody was low shortly after birth, but reached maximum levels at 14 days of age, By the time of weaning, antibody uptake had almost completely ceased, These data further delineate the temporal and spatial nature of the intestinal immunoglobulin transport system, and represent additional examples of how the intestinal Fc receptor is transcriptionally regulated. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, DIV GASTROENTEROL, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, CURE, DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. RP UNIV CALIF LOS ANGELES, SCH MED, DEPT PEDIAT, DIV GASTROENTEROL, LOS ANGELES, CA 90095 USA. FU NICHD NIH HHS [HD-22297]; NIDCR NIH HHS [DE-10054]; NIDDK NIH HHS [DK-07180] NR 45 TC 59 Z9 66 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 1997 VL 42 IS 5 BP 1062 EP 1069 DI 10.1023/A:1018853506830 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WY084 UT WOS:A1997WY08400028 PM 9149063 ER PT J AU Rapoport, I Miyazaki, M Boll, W Duckworth, B Cantley, LC Shoelson, S Kirchhausen, T AF Rapoport, I Miyazaki, M Boll, W Duckworth, B Cantley, LC Shoelson, S Kirchhausen, T TI Regulatory interactions in the recognition of endocytic sorting signals by AP-2 complexes SO EMBO JOURNAL LA English DT Article DE adaptors; clathrin; coated pits; membrane traffic; protein sorting ID ASSEMBLY PROTEIN AP-2; EPIDERMAL GROWTH-FACTOR; TRANS-GOLGI NETWORK; CLATHRIN-ASSOCIATED PROTEINS; COATED VESICLE ADAPTERS; FACTOR-II RECEPTOR; PLASMA-MEMBRANE; CYTOPLASMIC DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; BINDING SUBUNIT AB Many plasma membrane proteins destined for endocytosis are concentrated into clathrin-coated pits through the recognition of a tyrosine-based moth in their cytosolic domains by an adaptor (AP-2) complex. The mu 2 subunit of isolated AP-2 complexes binds specifically, but rather weakly, to proteins bearing the tyrosine-based signal. We now demonstrate, using peptides with a photoreactive probe, that this binding is strengthened significantly when the AP-2 complex is present in clathrin coats, indicating that there is cooperativity between receptor-AP-2 interactions and coat formation. Phosphoinositides with a phosphate at the D-3 position of the inositol ring, but not other isomers, also increase the affinity of the AP-2 complex for the tyrosine-based moth. AP-2 is the first protein known (in any context) to interact with phosphatidyl-inositol 3-phosphate. Our findings indicate that receptor recruitment can be coupled to clathrin coat assembly and suggest a mechanism for regulation of membrane traffic by lipid products of phosphoinositide 3-kinases. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02115. RI Miyazaki, Masaya/F-8520-2012; Cantley, Lewis/D-1800-2014 OI Miyazaki, Masaya/0000-0003-4031-7224; Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [GM 41890, R01 GM056203] NR 77 TC 172 Z9 173 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 1997 VL 16 IS 9 BP 2240 EP 2250 DI 10.1093/emboj/16.9.2240 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WY677 UT WOS:A1997WY67700008 PM 9171339 ER PT J AU Clayton, LK Ghendler, Y Mizoguchi, E Patch, RJ Ocain, TD Orth, K Bhan, AK Dixit, VM Reinherz, EL AF Clayton, LK Ghendler, Y Mizoguchi, E Patch, RJ Ocain, TD Orth, K Bhan, AK Dixit, VM Reinherz, EL TI T-cell receptor ligation by peptide/MHC induces activation of a caspase in immature thymocytes: The molecular basis of negative selection SO EMBO JOURNAL LA English DT Article DE apoptosis; caspase; negative selection; thymus ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; TRANSGENIC MICE; LYMPHOCYTES-T; (ACYLOXY)METHYL KETONES; SUBSTRATE-SPECIFICITY; MONOCLONAL-ANTIBODY; CYSTEINE PROTEASE; INDUCED APOPTOSIS; GRANZYME-B; DEATH AB T-cell receptors (TCRs) are created by a stochastic gene rearrangement process during thymocyte development, generating thymocytes bearing useful, as well as unwanted, specificities, Within the latter group, autoreactive thymocytes arise which are subsequently eliminated via a thymocyte-specific apoptotic mechanism, termed negative selection, The molecular basis of this deletion is unknown. Here, we show that TCR triggering by peptide/MHC ligands activates a caspase in double-positive (DP) CD4(+)CD8(+) thymocytes, resulting in their death, Inhibition of this enzymatic activity prevents antigen-induced death of DP thymocytes in fetal thymic organ culture (FTOC) from TCR transgenic mice as well as apoptosis induced by anti-CD3 epsilon monoclonal antibody and corticosteroids in FTOC of normal C57BL/6 mice, Hence, a common caspase mediates immature thymocyte susceptibility to cell death. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. PROCEPT INC,DEPT MED CHEM,CAMBRIDGE,MA 02139. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. RP Clayton, LK (reprint author), DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115, USA. RI dixit, vishva/A-4496-2012 OI dixit, vishva/0000-0001-6983-0326 FU NIAID NIH HHS [AI19807]; NIDDK NIH HHS [DK43551, DK47677] NR 89 TC 85 Z9 85 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 1997 VL 16 IS 9 BP 2282 EP 2293 DI 10.1093/emboj/16.9.2282 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WY677 UT WOS:A1997WY67700012 PM 9171343 ER PT J AU Kimura, RS Hutta, J AF Kimura, RS Hutta, J TI Inhibition of experimentally induced endolymphatic hydrops by middle ear ventilation SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE tympanic membrane; endolymphatic hydrops; Meniere's disease; tympanostomy ID GUINEA-PIGS; PRESSURE; PERILYMPH AB The tympanic membrane was perforated (n = 19) or a tube was inserted into the middle ear through the wall of the tympanic bulla (n = 6) immediately after blockage of the endolymphatic duct in guinea pigs. Total cochlear endolymph volume and volumes in each cochlear turn were determined from serial sections of the temporal bones and volume changes were analyzed statistically by comparison with hydropic controls without treatment (n = 12). Results showed that both middle ear ventilation procedures significantly reduced the subsequent development of endolymphatic hydrops. This inhibition of hydrops was presumed to be due to pressure release into the middle ear and/or improved oxygenation of the middle and inner ears. Findings suggest the possible merit of a tympanostomy as a treatment for Meniere's disease in carefully selected patients refractory to medical management. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Kimura, RS (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 35 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD MAY PY 1997 VL 254 IS 5 BP 213 EP 218 DI 10.1007/BF00874091 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA XB619 UT WOS:A1997XB61900001 PM 9195144 ER PT J AU Hussain, MA AF Hussain, MA TI Transcription factors in the pathophysiology of diabetes mellitus SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Editorial Material ID INSULIN GENE; EXPRESSION; CELLS RP Hussain, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,LAB MOL ENDOCRINOL,BOSTON,MA 02114, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAY PY 1997 VL 136 IS 5 BP 469 EP 470 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XD408 UT WOS:A1997XD40800005 PM 9186265 ER PT J AU Babich, JW Graham, W Fischman, AJ AF Babich, JW Graham, W Fischman, AJ TI Effect of adrenergic receptor ligands on metaiodobenzylguanidine uptake and storage in neuroblastoma cells SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE adrenergic receptor ligands; metaiodobenzylguanidine uptake; storage; neuroblastoma cells ID HUMAN NEURO-BLASTOMA; SK-N-SH; RADIOIODINATED METAIODOBENZYLGUANIDINE; ADRENAL-MEDULLA; I-131 MIBG; CONCISE COMMUNICATION; NORADRENALINE RELEASE; BLOCKING-AGENTS; PHEOCHROMOCYTOMA; IODOBENZYLGUANIDINE AB The effects of adrenergic receptor ligands on uptake and storage of the radiopharmaceutical [I-125]metaiodobenzylguanidine (MIBG) were studied in the human neuroblastoma cell line SK-N-SH. For uptake studies, cells were incubated for 15 min with varying concentrations of alpha-agonist (clonidine, methoxamine, and xylazine), alpha-antagonist (phentolamine, tolazoline, phenoxybenzamine, yohimbine, and prazosin), beta-antagonist (propranolol, atenolol), beta-agonist (isoprenaline and salbutamol), mixed alpha/beta antagonist (labetalol), or the neuronal blocking agent guanethidine, prior to the addition of [I-125]MIBG (0.1 mu M). The incubation was continued for 2 h and specific cell-associated radioactivity was measured. For the storage studies, cells were incubated with [I-125]MIBG for 2 h, followed by replacement with fresh medium with or without drug (MIBG, clonidine, or yohimbine). Cell-associated radioactivity was measured at various times over the next 20 h. Propanolol reduced [I-125]MIBG uptake by approximately 30% (P<0.01) at all concentrations tested, most likely due to nonspecific membrane changes. However, incubation with the other beta-agonists or antagonists failed to elicit significant reductions in uptake. In contrast, all of the alpha-agonists significantly inhibited uptake (P<0.05); guanethidine>xylazine>clonidine=methoxamine. The alpha-antagonists demonstrated a broad range of inhibition (phenoxybenzamine>>phentolamine>prazosin>>yohimbine=tolazoline) (P<0.05). The mixed ligand, labetolol, inhibited MIBG uptake in a dose-dependent manner with an apparent IC50 of 0.65 mu M. The retention studies demonstrated that unlabeled MIBG caused profound self-inhibition (P<0.01). Clonidine produced a modest inhibition of retention and yohimbine had no effect. Labetalol, phenoxybenzamine, guanethidine, and propranolol reduced uptake of [I-125]MIBG by neuroblastoma cells in culture. Although only labetalol has been reported to cause false-negative MIBG scans, our results suggest that these other drugs have the potential to interfere with MIBG imaging and therapy, particularly at high doses. Adrenergic drugs did not alter cytoplasmic retention of [I-125]MIBG in neuroblastoma cells but may have potential in tumors such as phenochromocytoma, where granular storage of MIBG has been observed. Inhibition of [I-125]MIBG retention by unlabeled MIBG supports the use of high specific activity radioiodinated MIBG for both diagnosis and therapy. C1 HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA 02115 USA. RP Babich, JW (reprint author), MASSACHUSETTS GEN HOSP, DEPT RADIOL, DIV NUCL MED, 55 FRUIT ST, BOSTON, MA 02114 USA. NR 49 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD MAY PY 1997 VL 24 IS 5 BP 538 EP 543 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XA985 UT WOS:A1997XA98500011 PM 9142735 ER PT J AU Reimer, P Bader, A Weissleder, R AF Reimer, P Bader, A Weissleder, R TI Application of a stable cell culture assay for the functional assessment of novel MR contrast agents SO EUROPEAN RADIOLOGY LA English DT Article DE cell culture; hepatocytes; MR receptor agents ID ASIALOGLYCOPROTEIN RECEPTOR; LIVER; HEPATOCYTES; CIRRHOSIS; MODEL; DTPA; MION; RAT AB The purpose of this study was to apply a new cell culture assay that preserves hepatocyte orientation and differentiation for screening of MR contrast agents with hepatocyte specificity. Cultured hepatocytes were sandwiched between two layers of collagen, preserving both hepatocyte function and morphology over a prolonged period of time. Plain and rhodaminated monocrystalline iron-oxide particles (MION and MION-rh) and asialoglycoprotein receptor-specific rhodaminated asialofetuin coupled to MION (MION-ASF-rh) were prepared. Dose-dependent competition experiments of these agents were performed with D(+)-galactose to determine the specificity of galactose-mediated cell uptake. To assess the impact of cell integrity on cell uptake dose-dependent functional experiments with two hepatotoxins (ethanol and CCl4) were performed. Normal cell cultures showed significantly higher fluorescent-light emission after incubation with hepatocyte-directed ASF-MION-rh than after incubation with MION-rh. Competition experiments of ASF-MION with galactose showed a dose-dependent decrease in calibrated fluorescent-light emission. Cell cultures treated with hepatotoxins demonstrated a dose-dependent reduction in calibrated fluorescent-light emission following incubation with ASF-MION-rh. The validated assay system allows assessment not only of hepatocyte specificity, but also of hepatocyte damage. Because the assay can be applied to cells from any species (rat, pig, human), it may represent an ideal test system prior to clinical trials of new hepatocyte-directed MR contrast agents. C1 HANNOVER MED SCH,INST ALLGEMEINE PHARMAKOL & TOXIKOL,HANNOVER,GERMANY. MASSACHUSETTS GEN HOSP,CTR MOL IMAGING RES,DEPT RADIOL,CHARLESTOWN,MA. RP Reimer, P (reprint author), UNIV MUNSTER,INST CLIN RADIOL,ALBERT SCHWEITZER STR 33,D-48129 MUNSTER,GERMANY. FU NCI NIH HHS [R0I CA 59649-04] NR 23 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD MAY PY 1997 VL 7 IS 4 BP 527 EP 531 DI 10.1007/s003300050197 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XA177 UT WOS:A1997XA17700015 PM 9204333 ER PT J AU Thiel, M Zourelidis, C Chambers, JD vonAndrian, UH Arfors, KE Messmer, K Peter, K AF Thiel, M Zourelidis, C Chambers, JD vonAndrian, UH Arfors, KE Messmer, K Peter, K TI Expression of beta(2)-integrins and L-selectin on polymorphonuclear leukocytes in septic patients SO EUROPEAN SURGICAL RESEARCH LA English DT Article DE adhesion molecules; integrins; selectin; CD18; CD62L; sepsis ID RESPIRATORY-DISTRESS SYNDROME; ENDOTHELIAL CELL RECOGNITION; MONOCLONAL-ANTIBODY; NEUTROPHIL; SEPSIS; ADHESION; INVIVO; ADHERENCE; MAC-1; IDENTIFICATION AB Adhesion molecules on polymorphonuclear leukocytes (PMNL) play an important role in nonspecific defense mechanisms directed at invading microorganisms. When local infection, however, cannot be controlled, a systemic inflammatory response syndrome (SIRS) ensues which may progress to septic shock and multiple organ failure, these being major determinants of the patient's outcome, In the present study, the expression of beta(2)-integrins and L-selectin on blood PMNL was measured on subsequent clays in patients with sepsis (n = 17) and in healthy volunteers (n = 15). beta(2)-Integrins and L-selectin molecules were detected by flow cytometry, using the monoclonal antibodies IB4 (anti-CD18) and Dreg200 (anti-CD62L), respectively. Adhesion molecules were determined at baseline immediately after blood collection and also 45 min after incubation of cells in vitro at body temperature to allow for spontaneous regulation, In addition, PMNL were activated by receptor-dependent and receptor-independent stimuli to characterize stimulus-specific adhesion molecule expression. In parallel with the measurement of adhesion molecules, severity of sepsis was assessed by the Elebute score, The results demonstrate significant differences in the basal, spontaneous and stimulus-induced expression of adhesion molecules between healthy volunteers, survivors (n = 11) and nonsurvivors (n = 6), Moreover, when survivors and nonsurvivors with severe sepsis (Elebute score >12) were compared, basal expressions of both beta(2)-integrins and L-selectin were significantly lower in patients who did not survive. Thus, measurement of adhesion molecules on circulating PMNL may be useful to identify septic patients at high risk for lethal outcome. C1 UNIV MUNICH,INST SURG RES,D-81377 MUNICH,GERMANY. UNIV MUNICH,DEPT ANAESTHESIOL,D-81377 MUNICH,GERMANY. SAN DIEGO REG CANC CTR,SAN DIEGO,CA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. EXPT MED INC,PRINCETON,NJ. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL-46022] NR 38 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-312X J9 EUR SURG RES JI Eur. Surg. Res. PD MAY-JUN PY 1997 VL 29 IS 3 BP 160 EP 175 DI 10.1159/000129521 PG 16 WC Surgery SC Surgery GA WY439 UT WOS:A1997WY43900002 PM 9161833 ER PT J AU Ehrman, RN Robbins, SJ Cornish, JW AF Ehrman, RN Robbins, SJ Cornish, JW TI Comparing self-reported cocaine use with repeated urine tests in outpatient cocaine abusers SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ADDICTION SEVERITY INDEX; DRUG-USE; HEROIN USE; VALIDITY; RELIABILITY; HAIR AB Sixty-one participants in outpatient therapy for cocaine dependence provided urine samples and self-reports of cocaine use 3 times a week for 4 weeks. Participants later gave a retrospective self-report of cocaine use for the month on the Addiction Severity Index (ASI). Comparisons with urine test values revealed substantial underreporting of cocaine use on both measures, and results from the 2 forms of self-report were only imperfectly correlated, More participants admitted to at least I cocaine use episode on The ASI than on the repeated self-reports, but the repeated reports provided a more accurate index of the relative frequency of cocaine use during the month, Self-reports can enhance cocaine Use detection when urines are infrequently collected and can help determine whether consecutive positive urine samples represent elevated metabolite levels from a single drug use episode. However, self-reports cannot substitute for regular urine sampling. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,PHILADELPHIA,PA. RP Ehrman, RN (reprint author), UNIV PENN,TREATMENT RES CTR,3900 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA03008] NR 15 TC 28 Z9 28 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD MAY PY 1997 VL 5 IS 2 BP 150 EP 156 DI 10.1037/1064-1297.5.2.150 PG 7 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA WY838 UT WOS:A1997WY83800009 PM 9234052 ER PT J AU Campbell, KS Mullane, KP Aksoy, IA Stubdal, H Zalvide, J Pipas, JM Silver, PA Roberts, TM Schaffhausen, BS DeCaprio, JA AF Campbell, KS Mullane, KP Aksoy, IA Stubdal, H Zalvide, J Pipas, JM Silver, PA Roberts, TM Schaffhausen, BS DeCaprio, JA TI DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication SO GENES & DEVELOPMENT LA English DT Article DE SV40 virus; large T antigen; DnaJ Hsc70; chaperone; J-domain ID LARGE TUMOR-ANTIGEN; HEAT-SHOCK PROTEINS; TRANSFORMATION-GOVERNING SEQUENCE; POLYMERASE-ALPHA-PRIMASE; SIMIAN VIRUS-40; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; ATPASE ACTIVITY; BINDING DOMAIN AB The amino-terminal domain of SV40 large tumor antigen (TAg) is required for efficient viral DNA replication. However, the biochemical activity associated with this domain has remained obscure. We show here that the amino-terminal domain of TAg shares functional homology with the J-domain of DnaJ/hsp40 molecular chaperones. DnaJ proteins function as cofactors by regulating the activity of a member of the 70-kD heat shock protein family. Genetic analyses demonstrated that amino-terminal sequences of TAg comprise a novel T-domain that mediates a specific interaction with the constitutively expressed hsc70 and show that the T-domain is also required for efficient viral DNA replication in vivo. Furthermore, we demonstrated that the T-domain of two human DnaJ homologs, HSJ1 or DNAJ2, could substitute functionally for the amino-terminus of TAg in promoting viral DNA replication. Together, our findings suggest that TAg uses its T-domain to support SV40 DNA replication in a manner that is strikingly similar to the use of Escherichia coli DnaJ by bacteriophage lambda in DNA replication. However, TAg has evolved a more efficient strategy of DNA replication through an intrinsic T-domain to associate directly with a partner chaperone protein. Our observations provide evidence of a role for chaperone proteins in the process of eukaryotic DNA replication. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260. NR 83 TC 160 Z9 165 U1 1 U2 9 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1997 VL 11 IS 9 BP 1098 EP 1110 DI 10.1101/gad.11.9.1098 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XA029 UT WOS:A1997XA02900002 PM 9159391 ER PT J AU Glazebrook, J Zook, M Mert, F Kagan, I Rogers, EE Crute, IR Holub, EB Hammerschmidt, R Ausubel, FM AF Glazebrook, J Zook, M Mert, F Kagan, I Rogers, EE Crute, IR Holub, EB Hammerschmidt, R Ausubel, FM TI Phytoalexin-deficient mutants of Arabidopsis reveal that PAD4 encodes a regulatory factor and that four PAD genes contribute to downy mildew resistance SO GENETICS LA English DT Article ID CAMPESTRIS PV CAMPESTRIS; DISEASE RESISTANCE; PERONOSPORA-PARASITICA; ANTIFUNGAL PROTEINS; TRANSGENIC TOBACCO; THALIANA; PLANT; PATHOGENS; SYRINGAE; LEAVES AB We are working to determine the role of the Arabidopsis phytoalexin, camalexin, in protecting the plant from pathogen attack by isolating phytoalexin-deficient (pad) mutants in the accession Columbia (Col-0) and examining their response to pathogens. Mutations in PAD1, PAD2, and PAD4 caused enhanced susceptibility to the bacterial pathogen Pseudomonas syringae pv. maculicola strain ES4326 (PsmES4326), while mutations in PAD3 or PAD5 did not. Camalexin was not detected in any of the double mutants pad1-1 pad2-1, pad1-1 pad3-1 or pad2-1 pad3-1. Growth of PsmES4326 in pad1-1 pad2-1 was greater than that in pad1-1 or pad2-1 plants, while growth in pad1-1 pad3-1 and pad2-1 pad3-1 plants was similar to that in pad1-1 and pad2-1 plants, respectively. The pad4-1 mutation caused reduced camalexin synthesis in response to PsmES4326 infection, but not in response to Cochliobolus carbonum infection, indicating that PAD4 has a regulatory function. PAD1, PAD2, PAD3 and PAD4 are all required for resistance to the eukaryotic biotroph Peronospora parasitica. The pad4-1 mutation caused the most dramatic change, exhibiting full susceptibility to four of six Col-incompatible parasite isolates. Interestingly, each combination of double mutants between pad1-1, pad2-1 and pad3-1 exhibited additive shifts to moderate or full susceptibility to most of the isolates. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. MICHIGAN STATE UNIV,DEPT BOT & PLANT PATHOL,E LANSING,MI 48824. HORT RES INT,DEPT PLANT PATHOL WEED SCI,WELLESBOURNE CV35 9EF,WARWICK,ENGLAND. RP Glazebrook, J (reprint author), UNIV MARYLAND,CTR AGR BIOTECHNOL,INST BIOTECHNOL,5128 PLANT SCI BLDG,COLLEGE PK,MD 20742, USA. RI Rogers, Elizabeth/D-2087-2009; allasia, valerie/B-4214-2009; OI Rogers, Elizabeth/0000-0002-0545-4744; Glazebrook, Jane/0000-0001-5167-736X NR 52 TC 224 Z9 233 U1 3 U2 9 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1997 VL 146 IS 1 BP 381 EP 392 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA WW880 UT WOS:A1997WW88000031 PM 9136026 ER PT J AU Ozelius, LJ Hewett, J Kramer, P Bressman, SB Shalish, C deLeon, D Rutter, M Risch, N Brin, MF Markova, ED Limborska, SA IvanovaSmolenskaya, IA McCormick, MK Fahn, S Buckler, AJ Gusella, JF Breakefield, XO AF Ozelius, LJ Hewett, J Kramer, P Bressman, SB Shalish, C deLeon, D Rutter, M Risch, N Brin, MF Markova, ED Limborska, SA IvanovaSmolenskaya, IA McCormick, MK Fahn, S Buckler, AJ Gusella, JF Breakefield, XO TI Fine localization of the torsion dystonia gene (DYT1) on human chromosome 9q34: YAC map and linkage disequilibrium SO GENOME RESEARCH LA English DT Article ID AUTOSOMAL DOMINANT INHERITANCE; ASHKENAZI JEWS; HUMAN GENOME; CONSTRUCTION; FAMILY; YEAST; POPULATION; REGION AB The DYT1 gene, which maps to chromosome 9q34, appears to be responsible For most cases of early-onset torsion dystonia in both Ashkenazic Jewish (AJ) and non-Jewish families. This disease is inherited in an autosomal dominant mode with reduced penetrance (30%-40%). The abnormal involuntary movements associated with this disease are believed to be caused by unbalanced neural transmission in the basal ganglia. Previous linkage disequilibrium studies in the Al population placed the DY71 gene in a 2-cM region between the loci D9S62a and ASS. A YAC contig has now been created spanning 600 kb of this region including D9S62a. The location of the DYT1 gene has been refined within this contig using several new polymorphic loci to expand the linkage disequilibrium analysis of the AJ founder mutation. The most likely location of the DYT1 gene is within a 150 kb region between the loci D9S2161 and DPS63. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, MOL NEUROGENET UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. COLUMBIA PRESBYTERIAN MED CTR, DEPT SURG, DYSTONIA CLIN RES CTR, NEW YORK, NY 10032 USA. STANFORD UNIV, DEPT GENET, STANFORD, CA 94305 USA. OREGON HLTH SCI UNIV, DEPT NEUROL, PORTLAND, OR 97201 USA. INST NEUROL, MOSCOW 123367, RUSSIA. INST GENET MOL, MOSCOW 123367, RUSSIA. MT SINAI HOSP, DEPT NEUROL, MOVEMENT DISORDERS CTR, NEW YORK, NY 10029 USA. RI Ivanova-Smolenskaya, Irina/C-9041-2012 FU NINDS NIH HHS [NS24279, NS26656, NS28384] NR 44 TC 56 Z9 57 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 1997 VL 7 IS 5 BP 483 EP 494 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WX931 UT WOS:A1997WX93100009 PM 9149944 ER PT J AU Baer, L Elford, DR Cukor, P AF Baer, L Elford, DR Cukor, P TI Telepsychiatry at forty: What have we learned? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID TELEMEDICINE; COST; SYSTEM AB We examined all articles describing video applications of telemedicine for psychiatry (i.e., ''telepsychiatry'') that have been published in peer-reviewed journals. We found three reports of video application to continuing education, eight uncontrolled studies or anecdotal clinical reports of video application to assessment or consultation, five clinical investigations including a control group or control condition, three studies evaluating the reliability of administering psychological rating scales by video, and two studies of the cost-effectiveness of telepsychiatry. Although the conclusions of all studies reviewed recommend the use of telepsychiatry, evidence currently available is insufficient to suggest its widespread implementation. Additional studies are needed to determine when and for what age groups and conditions telepsychiatry is an effective way to deliver psychiatric services, and whether it is cost-effective. We recommend that telepsychiatry be employed on a limited basis and be restricted to research settings and underserved communities (where it may be the only option) until further evidence is available. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MEM UNIV NEWFOUNDLAND,TELEMED CTR,ST JOHNS,NF,CANADA. NR 25 TC 63 Z9 63 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1997 VL 5 IS 1 BP 7 EP 17 DI 10.3109/10673229709034720 PG 11 WC Psychiatry SC Psychiatry GA XD209 UT WOS:A1997XD20900002 PM 9385015 ER PT J AU Candilis, PJ Pollack, MH AF Candilis, PJ Pollack, MH TI The hidden costs of untreated anxiety disorders SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID EPIDEMIOLOGIC CATCHMENT-AREA; PSYCHIATRIC-DISORDER; PANIC DISORDER; HEALTH; CARE; ATTACKS; QUALITY; LIFE C1 MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS PROGRAM,BOSTON,MA 02114. NR 18 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1997 VL 5 IS 1 BP 40 EP 42 DI 10.3109/10673229709034724 PG 3 WC Psychiatry SC Psychiatry GA XD209 UT WOS:A1997XD20900006 PM 9385019 ER PT J AU Gopen, Q Rosowski, JJ Merchant, SN AF Gopen, Q Rosowski, JJ Merchant, SN TI Anatomy of the normal human cochlear aqueduct with functional implications SO HEARING RESEARCH LA English DT Article DE temporal bone; histologic section; quantitative model analysis ID HUMAN MIDDLE-EAR; PRESSURE; PATENCY; MODEL AB There is great variation in published descriptions of the shape, size, and patency of the human cochlear aqueduct. The first part of this paper describes the anatomy of the normal human cochlear aqueduct as determined from a study of 101 temporal bones. Nineteen bones aged 0-1 years and approximately 10 bones per decade of life until age 100 years were examined. The aqueduct was found to have a funnel shaped aperture at the cranial end with a dural sheath extending into it for a varying distance. The rest of the aqueduct was filled with a meshwork of loose connective tissue, often with a central lumen within it. Four types of patencies were noted: central lumen patent throughout length of aqueduct (34%), lumen filled with loose connective tissue (59%), lumen occluded by bone (4%), and obliteration of the aqueduct (3%). The mean value (+/-SD) of the narrowest portion was 138 (+/-58) mu m which occurred 200-300 mu m from the cochlear end of the aqueduct. There was no correlation between age and narrowest diameter, or between age and category of patency. In the second part of this paper, we propose quantitative models of aqueduct function, based on measurements of ductal dimensions and known acoustical properties of the inner ear. Our model analyses suggest that in normal ears, the aqueduct (1) cannot support fluid flows large enough to explain stapedectomy gushers, (2) does filter out cardiac- and respiration-induced pulses in CSF and prevents them from affecting cochlear function, and (3) has little effect on normal ossicular transmission of sound for frequencies above 20 Hz. In pathological ears, such as those with ossicular disruption or after a type IV tympanoplasty, a patent aqueduct might affect hearing for frequencies below 150 Hz. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,SPEECH & HEARING SCI PROGRAM,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [P01 DC00119, K08 DC00088, T32 DC00038] NR 30 TC 90 Z9 93 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1997 VL 107 IS 1-2 BP 9 EP 22 DI 10.1016/S0378-5955(97)00017-8 PG 14 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA WZ418 UT WOS:A1997WZ41800002 PM 9165342 ER PT J AU Brezinski, ME Tearney, GJ Weissman, NJ Boppart, SA Bouma, BE Hee, MR Weyman, AE Swanson, EA Southern, JF Fujimoto, JG AF Brezinski, ME Tearney, GJ Weissman, NJ Boppart, SA Bouma, BE Hee, MR Weyman, AE Swanson, EA Southern, JF Fujimoto, JG TI Assessing atherosclerotic plaque morphology: Comparison of optical coherence tomography and high frequency intravascular ultrasound SO HEART LA English DT Article DE atherosclerosis; plaque morphology; infrared light; intravascular ultrasound; optical coherence tomography ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; BIOLOGICAL TISSUES; REFLECTOMETRY; GUIDANCE; CATHETER; INVITRO AB Background-OCT can image plaque microstructure at a level of resolution not previously demonstrated with other imaging techniques because it uses infrared light rather than acoustic waves. Objectives-To compare optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of in vitro atherosclerotic plaques. Methods-Segments of abdominal aorta were obtained immediately before postmortem examination. Images of 20 sites from five patients were acquired with OCT (operating at an optical wavelength of 1300 nm which was delivered to the sample through an optical fibre) and a 30 MHz ultrasonic transducer. After imaging, the microstructure of the tissue was assessed by routine histological processing. Results-OCT yielded superior structural information in all plaques examined. The mean (SEM) axial resolution of OCT and IVUS imaging was 16 (1) and 110 (7), respectively, as determined by the point spread function from a mirror. Furthermore, the dynamic range of OCT was 109 dB compared with 43 dB for IVUS imaging. Conclusions-OCT represents a promising new technology for intracoronary imaging because of its high resolution, broad dynamic range, and ability to be delivered through intravascular catheters. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MIT,DEPT ELECT ENGN & COMP SCI,ELECT RES LAB,CAMBRIDGE,MA 02139. MIT,LINCOLN LAB,LEXINGTON,MA 02173. RP Brezinski, ME (reprint author), MIT,DEPT PATHOL,BLDG 36-357,CAMBRIDGE,MA 02139, USA. RI Boppart, Stephen/C-7338-2009 FU NEI NIH HHS [9-RO1-EY11289-10]; NHLBI NIH HHS [R29-HL55686-01A1]; NIGMS NIH HHS [5-RO1-GM35459-09] NR 34 TC 162 Z9 165 U1 1 U2 8 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1355-6037 J9 HEART JI Heart PD MAY PY 1997 VL 77 IS 5 BP 397 EP 403 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA XA371 UT WOS:A1997XA37100003 PM 9196405 ER PT J AU McNeil, SM Novelletto, A Srinidhi, J Barnes, G Kornbluth, I Altherr, MR Wasmuth, JJ Gusella, JF MacDonald, ME Myers, RH AF McNeil, SM Novelletto, A Srinidhi, J Barnes, G Kornbluth, I Altherr, MR Wasmuth, JJ Gusella, JF MacDonald, ME Myers, RH TI Reduced penetrance of the Huntington's disease mutation SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRINUCLEOTIDE REPEAT EXPANSION; POLYMERASE CHAIN-REACTION; (CAG)(N) REPEAT; INTERMEDIATE ALLELES; INSTABILITY; FAMILIES; LENGTH; ONSET; AGE; POLYMORPHISM AB Controversy persists concerning the significance of Huntington disease (HD) alleles in the 36-39 repeat range, Although some clinically affected persons have been documented with repeats in this range, elderly unaffected individuals have also been reported, We examined 10 paternal transmissions of HD alleles of 37-39 repeats in collateral branches of families with de novo HD. All 10 descendants, including many who are elderly, are without symptoms of HD, Forty percent of the transmissions were unstable, although none varied by more than one repeat. The observation that individuals with alleles of 37-39 repeats may survive unaffected beyond common life expectancy supports the presence of reduced penetrance for HD among some persons with repeat sizes which overlap the clinical range, Non-penetrance may be increased in the collateral branches of de novo mutation families when compared to penetrance estimates from patient series, There was no CAA-->CAG mutation for the penultimate glutamine in either a de novo expanded 42 repeat allele or the corresponding non-penetrant 38 repeat allele in a family with fresh mutation to HD. C1 BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. UNIV ROMA TOR VERGATA,DEPT BIOL,I-00173 ROME,ITALY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOL NEUROGENET UNIT,BOSTON,MA 02114. LOS ALAMOS NATL LAB,HLTH RES LAB,LOS ALAMOS,NM 87545. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. OI Novelletto, Andrea/0000-0002-1146-7680 FU NINDS NIH HHS [NS16367]; Telethon [E.0087] NR 31 TC 82 Z9 83 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1997 VL 6 IS 5 BP 775 EP 779 DI 10.1093/hmg/6.5.775 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA WX608 UT WOS:A1997WX60800016 PM 9158152 ER PT J AU Yoon, DW Lee, H Seol, W DeMaria, M Rosenzweig, M Jung, JU AF Yoon, DW Lee, H Seol, W DeMaria, M Rosenzweig, M Jung, JU TI Tap: A novel cellular protein that interacts with Tip of herpesvirus saimiri and induces lymphocyte aggregation SO IMMUNITY LA English DT Article ID INVITRO IMMORTALIZATION; GROWTH TRANSFORMATION; SIGNAL-TRANSDUCTION; RECEPTOR FAMILY; IDENTIFICATION; INFECTION; CELLS; TRANSMEMBRANE; PHENOTYPE; TERMINUS AB Tip of herpesvirus saimiri associates with Lck and down-regulates Lck-mediated activation. We identified a novel cellular Tip-associated protein (Tap) by a yeast two-hybrid screen. Tap associated with Tip following transient expression in COS-1 cells and stable expression in human Jurkat-T cells. Expression of Tip and Tap in Jurkat-T cells induced dramatic cell aggregation. Aggregation was likely caused by the upregulated surface expression of adhesion molecules including integrin alpha, L-selectin, ICAM-3, and H-CAM. Furthermore, NF-kappa B transcriptional factor of aggregated cells had approximately 40-fold higher activity than that of parental cells. Thus, Tap is likely to be an important cellular mediator of Tip function in T cell transformation by herpesvirus saimiri. C1 HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,DEPT IMMUNOL,SOUTHBOROUGH,MA 01772. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT BIOL MOL,BOSTON,MA 02114. RP Yoon, DW (reprint author), HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,DEPT MOL GENET & MICROBIOL,SOUTHBOROUGH,MA 01772, USA. FU NCI NIH HHS [CA31363]; NCRR NIH HHS [RR00168] NR 47 TC 57 Z9 61 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1997 VL 6 IS 5 BP 571 EP 582 DI 10.1016/S1074-7613(00)80345-3 PG 12 WC Immunology SC Immunology GA XB819 UT WOS:A1997XB81900008 PM 9175835 ER PT J AU Jarvis, BW Qureshi, N AF Jarvis, BW Qureshi, N TI Inhibition of lipopolysaccharide-induced transcription factor Sp1 binding by spectrally pure diphosphoryl lipid A from Rhodobacter sphaeroides, protein kinase inhibitor H-8, and dexamethasone SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; CELLS; CD14; IMMUNOSUPPRESSION; GLUCOCORTICOIDS; ACTIVATION; ATCC-17023; INDUCTION; ENDOTOXIN; RECEPTORS AB The transcription factor Sp1 plays a crucial role in the monocyte-specific expression of CD14, a binding site (or putative receptor) for lipopolysaccharide (LPS) complexes with LPS-binding protein (LBP). By using RAW 264.7 macrophages treated with spectrally pure deep-rough-chemotype hexa-acyl LPS from Escherichia coli D31m4, three inhibitors were found to block the binding activity of transcription factor Sp1, as measured by electrophoretic mobility shift assays. These inhibitors were diphosphoryl lipid A from Rhodobacter sphaeroides (10 u mu g/ml); the isoquinoline-sulfonamide H-8 (10 and 100 mu M), which is through to be a cGMP-dependent protein kinase inhibitor; and the anti-inflammatory agent dexamethasone (10 mu M). C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL LAB,MADISON,WI 53705. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53705. FU NIGMS NIH HHS [GM-50870] NR 28 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1997 VL 65 IS 5 BP 1640 EP 1643 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA WW398 UT WOS:A1997WW39800010 PM 9125541 ER PT J AU Doshi, A Zaheer, A Stiller, MJ AF Doshi, A Zaheer, A Stiller, MJ TI Methods for assessing erythema: A critique of parametric and nonparametric techniques SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID SKIN; QUANTIFICATION; INFLAMMATION; DERMATITIS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DERMATOL CLIN INVEST UNIT,DEPT DERMATOL,BOSTON,MA 02114. NR 17 TC 6 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAY PY 1997 VL 36 IS 5 BP 334 EP 337 DI 10.1046/j.1365-4362.1997.00110.x PG 4 WC Dermatology SC Dermatology GA XE893 UT WOS:A1997XE89300003 PM 9199978 ER PT J AU Glosser, G McManus, P Munzenrider, J AustinSeymour, M Fullerton, B Adams, J Urie, MM AF Glosser, G McManus, P Munzenrider, J AustinSeymour, M Fullerton, B Adams, J Urie, MM TI Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE high dose fractionated radiation; neuropsychological function; skull base tumors ID CENTRAL-NERVOUS-SYSTEM; CELL LUNG-CANCER; LONG-TERM SURVIVORS; PROPHYLACTIC CRANIAL IRRADIATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; CHILDHOOD LEUKEMIA; FOLLOW-UP; CHILDREN; MEMORY AB Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment, None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation, Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment, A mild decline in psychomotor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures. (C) 1997 Elsevier Science Inc. C1 UNIV PENN,GRAD HOSP,DEPT NEUROL,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV WASHINGTON,DEPT RADIAT ONCOL,SEATTLE,WA 98195. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT RADIAT ONCOL,WORCESTER,MA 01655. RP Glosser, G (reprint author), UNIV PENN,SCH MED,MED CTR,DEPT NEUROL GATES 3W,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA 21239] NR 61 TC 43 Z9 44 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1997 VL 38 IS 2 BP 231 EP 239 DI 10.1016/S0360-3016(97)00099-0 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA XJ938 UT WOS:A1997XJ93800002 PM 9226308 ER PT J AU DelaPaz, MA PericakVance, MA Lennon, F Haines, JL Seddon, JM AF DelaPaz, MA PericakVance, MA Lennon, F Haines, JL Seddon, JM TI Exclusion of TIMP3 as a candidate locus in age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE age-related macular degeneration; Sorsby's fundus dystrophy; tissue inhibitor of metalloproteinases-3 ID GENETICALLY COMPLEX TRAITS; SORSBY FUNDUS DYSTROPHY; LINKAGE STRATEGIES; PAIRS AB Purpose. Age-related macular degeneration (AMD) is a genetically complex disorder. Tissue inhibitor of metalloproteinases-3 (TIMP3) on chromosome 22 has been identified as a gene that is mutated in Sorsby's fundus dystrophy, an autosomal-dominant macular dystrophy that phenotypically resembles AMD. The purpose of this study iras to determine whether TIMP3 is a major susceptibility gene for the AMD phenotype. Methods. Thirty-eight multiplex families with AMD were identified in Massachusetts and North Carolina. The macular findings were graded according to a modification of the grading system used in the Age-Related Eye Disease Study, and persons with extensive intermediate drusen, any large drusen, geographic atrophy, or evidence of exudative maculopathy were coded as affected for the purpose of the analysis. Linkage analysis was performed using both model-dependent (led score) and model-independent (sibpair) methods. For the lod score analysis, both autosomaldominant as well as recessive low penetrance ''affecteds only'' analyses were examined. Three markers, D22S280, D22S529, and D22568, linked tightly and flanking the TIMP3 locus, were chosen for the analysis. Association studies were performed by examining one randomly chosen affected person per family and comparing the patients with AMD with a series of age, gender, and ethnically matched control subjects with no known history of AMD. Results. Lod score analysis excluded linkage in these data for an approximately 10-cm interval surrounding the TIMP3 gene for all models tested. In addition, no significant findings were observed with either the sibpair or the association study. Conclusions. No evidence of linkage or association or both was found between AMD and TIMP3 in these 38 families. These data suggest that although clinically similar, the genetic defect in Sorsby's fundus dystrophy is of a different cause than the majority of the genetic causes of AMD. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,EPIDEMIOL UNIT,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,RETINA SERV,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP DelaPaz, MA (reprint author), DUKE UNIV,CTR EYE,MED CTR,DEPT OPHTHALMOL,BOX 3802,DURHAM,NC 27710, USA. RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [EY08541]; NINDS NIH HHS [NS26630] NR 22 TC 68 Z9 70 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1997 VL 38 IS 6 BP 1060 EP 1065 PG 6 WC Ophthalmology SC Ophthalmology GA WY217 UT WOS:A1997WY21700005 PM 9152225 ER PT J AU Lev, MH Kulke, SF Sorensen, AG Boxerman, JL Brady, TJ Rosen, BR Buchbinder, BR Weisskoff, RM AF Lev, MH Kulke, SF Sorensen, AG Boxerman, JL Brady, TJ Rosen, BR Buchbinder, BR Weisskoff, RM TI Contrast-to-noise ratio in functional MRI of relative cerebral blood volume with sprodiamide injection SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE brain, blood flow; magnetic resonance, vascular studies; magnetic resonance, echo planar; magnetic resonance, volume measurement ID MAGNETIC-SUSCEPTIBILITY; FLOW; DYSPROSIUM; ISCHEMIA; AGENTS AB The purpose of this study was to investigate the dependence of contrast-to-noise ratio (CNR) on the dose and rate of sprodiamide injection in magnetic resonance relative cerebral blood volume [rCBV] imaging, rCBV maps for 35 normal volunteers were constructed from dynamic MR image sets acquired with echo-planar spin-echo imaging after intravenous injection of sprodiamide, Doses of .1, .2, and .3 mmol/kg, at rates of 2 ml/second and 5 ml/second, were tested, CNRs and blood/volume ratios of gray to white matter were computed, CNR depended on dose [P <.0001] but was independent of injection rate [P <.69). rCBV ratios of gray to white matter were dose independent (P <.38) and rate independent (P <.97), The dependence of CNR on dose, but not injection rate, has practical implications in optimal protocol design, The independence of gray/white ratios supports the theory underlying the generation of rCBV maps. RP Lev, MH (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NEURORADIOL,BOSTON,MA 02114, USA. NR 24 TC 26 Z9 27 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAY-JUN PY 1997 VL 7 IS 3 BP 523 EP 527 DI 10.1002/jmri.1880070312 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XA923 UT WOS:A1997XA92300012 PM 9170037 ER PT J AU Boxerman, JL Rosen, BR Weisskoff, RM AF Boxerman, JL Rosen, BR Weisskoff, RM TI Signal-to-noise analysis of cerebral blood volume maps from dynamic NMR imaging studies SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE cerebral blood volume mapping; signal-to-noise ratio; Monte Carlo modeling; Optimization of imagine parameters ID CONTRAST; BRAIN AB The use of cerebral blood volume (CBV) maps generated from dynamic MRI studies tracking the bolus passage of paramagnetic contrast agents strongly depends on the signal-to-noise ratio (SNR) of the maps, The authors present a semianalytic model for the noise in CBV maps and introduce analytic and Monte Carlo techniques for determining the effect of experimental parameters and processing strategies upon CBV-SNR, CBV-SNR increases as more points are used to estimate the baseline signal level, For typical injections, maps made with 10 baseline points have 34% more noise than those made with 50 baseline points, For a given peak percentage signal drop, an optimum TE can be chosen that, In general, is less than the baseline T2. However, because CBV-SNR is relatively insensitive to TE around this optimum value, choosing TE approximate to T2 does not sacrifice much SNR for typical doses of contrast agent. The TR that maximizes spin-echo CBV-SNR satisfies TR/T1 approximate to 1.26, whereas as short a TR as possible should be used to maximize gradient-echo CBV-SNR. In general, CBV-SNR is maximized for a given dose of contrast agent by selecting as short an input bolus duration as possible, For image SNR exceeding 20-30, the Gamma-fitting procedure adds little extra noise compared with simple numeric integration, However, for noisier input images, as can be the case for high resolution echo-planar images, the covarying parameters of the Gamma-variate fit broaden the distribution of the CBV estimate and thereby decrease CBV-SNR, The authors compared the analytic noise predicted by their model with that of actual patient data and found that the analytic model accounts for roughly 70% of the measured variability of CBV within white matter regions of interest. C1 MASSACHUSETTS GEN HOSP,MGH NMR CTR,DEPT RADIOL,CHARLESTOWN,MA 02129. FU NHLBI NIH HHS [R01-HL39810]; PHS HHS [P01-48729] NR 22 TC 57 Z9 57 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD MAY-JUN PY 1997 VL 7 IS 3 BP 528 EP 537 DI 10.1002/jmri.1880070313 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XA923 UT WOS:A1997XA92300013 PM 9170038 ER PT J AU Tracey, I Lane, J Chang, I Navia, B Lackner, A Gonzalez, RG AF Tracey, I Lane, J Chang, I Navia, B Lackner, A Gonzalez, RG TI H-1 magnetic resonance spectroscopy reveals neuronal injury in a simian immunodeficiency virus macaque model SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE simian immunodeficiency virus; AIDS model; AIDS dementia complex; rhesus macaque; magnetic resonance spectroscopy ID AIDS DEMENTIA COMPLEX; PROTON MR SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; RHESUS-MONKEYS; HIV-INFECTION; NEOCORTICAL DAMAGE; MULTIPLE-SCLEROSIS; MOLECULAR CLONES; RAT-BRAIN; ENCEPHALITIS AB Infection with human immunodeficiency virus (HIV) commonly results in neurologic disease called the AIDS dementia complex. Neuronal loss and injury have been found in the HIV brain, but the underlying mechanisms are not understood. The simian immunodeficiency virus (SIV)-infected macaque is an excellent animal model for HIV infection, but neuronal loss has not been demonstrated. To determine whether neuronal damage occurs in the SIV brain, we quantified the neuronal marker N-acetylaspartate (NAA) using proton magnetic resonance spectroscopy (H-1-MRS) in brain extracts of control and SIV-infected macaques and correlated these findings with histologic analyses. We found reduced NAA in the SIV-infected animals compared with controls (2.94 +/- 1.37 versus 6.21 +/- 1.73 mu mol/g of wet weight; p = 0.004). A significant decrease in NAA was also found in SIV-infected animals sacrificed in the acute stages of infection 9 or 10 days after inoculation with SIVmacYnef. We conclude that SIV infection of rhesus macaques results in neuronal damage that is demonstrable shortly after infection and that H-1-MRS may be used to measure such injury. The results further support the SIV macaque as a useful model to study the mechanisms of neuropathogenesis by HIV. C1 HARVARD MED SCH,MASSACHUSETTS GEN HOSP,NMR CTR,CHARLESTOWN,MA 02129. HARVARD MED SCH,MASSACHUSETTS GEN HOSP,NEURORADIOL DIV,CHARLESTOWN,MA 02129. HARVARD MED SCH,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA. FU NCRR NIH HHS [RR07000, RR00168]; NINDS NIH HHS [NS34626] NR 65 TC 30 Z9 31 U1 1 U2 1 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 MAY 1 PY 1997 VL 15 IS 1 BP 21 EP 27 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XH946 UT WOS:A1997XH94600004 PM 9215650 ER PT J AU Levin, RM Hypolite, JA Broderick, GA AF Levin, RM Hypolite, JA Broderick, GA TI Evidence for a role of intracellular-calcium release in nitric oxide-stimulated relaxation of the rabbit corpus cavernosum SO JOURNAL OF ANDROLOGY LA English DT Article DE calcium; erection; thapsigargin; ryanodine ID SMOOTH-MUSCLE; SARCOPLASMIC-RETICULUM; CONTRACTILE RESPONSE; FIELD STIMULATION; PENILE ERECTION; THAPSIGARGIN; RYANODINE; NEUROTRANSMISSION; MODULATION; MEMBRANES AB Erection is mediated by relaxation of the smooth muscle elements within the sinusoids of the corpus cavernosum. Although cavernosal relaxation can be mediated by a variety of mechanisms including purinergic stimulation, prostoglandins, and beta-adrenergic stimulation the major mechanism involves the stimulated release-of nitric oxide (NO) and subsequent relaxation of the corporal smooth muscle. Experimentally, NO can be released both by direct stimulation of NO-containing nerves (using field stimulation) and indirectly via cholinergic stimulation of NO release from the endothelium (using bethanechol). Preliminary studies have indicated that NO release and/or NO-stimulated relaxation of corporal smooth muscle is an active process involving both an increase in cytosolic calcium and an increase in metabolic energy utilization. Ryanodine is a pharmacological agent that can inhibit calcium-stimulated calcium release from the sarcoplasmic reticulum. The results of the current study demonstrated that ryanodine inhibited both field-stimulated relaxation and bethanechol-stimulated relaxation but did not affect relaxation induced by adenosine triphosphate (ATP) or nitroprusside. These studies strongly support the hypothesis that NO-stimulated relaxation is mediated, in part, by calcium release from the sarcoplasmic reticulum through ryanodine-sensitive channels. C1 STRATTON VET AFFAIRS MED CTR, ALBANY, NY USA. UNIV PENN, SCH MED, DIV UROL, PHILADELPHIA, PA 19104 USA. VET AFFAIRS MED CTR, PHILADELPHIA, PA USA. RP Levin, RM (reprint author), ALBANY COLL PHARM, DEPT BIOL SCI, 106 NEW SCOTLAND AVE, ALBANY, NY 12208 USA. FU NIDDK NIH HHS [1RO1 DK 33559]; PHS HHS [R0-3 46162] NR 27 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAY-JUN PY 1997 VL 18 IS 3 BP 246 EP 249 PG 4 WC Andrology SC Endocrinology & Metabolism GA XF813 UT WOS:A1997XF81300004 PM 9203051 ER PT J AU Hales, CA Elsasser, TH Ocampo, P Efimova, O AF Hales, CA Elsasser, TH Ocampo, P Efimova, O TI TNF-alpha in smoke inhalation lung injury SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE lung lymph; acute lung injury; sheep; tumor necrosis factor-alpha ID TUMOR-NECROSIS-FACTOR; RESPIRATORY-DISTRESS-SYNDROME; PULMONARY-EDEMA; SHEEP; PENTOXIFYLLINE; PLASMA; MORTALITY; ACROLEIN; GENE AB Adult respiratory distress syndrome is a major cause of morbidity in fire victims. Tumor necrosis factor-alpha (TNF-alpha) is edematogenic and has been associated with the etiology of other forms of adult respiratory distress syndrome. In the sheep lymph fistula model, we measured TNF-alpha after 48 (n = 7) or 128 (n = 3) breaths of cotton smoke and compared this with sham controls (n = 5) or controls in which left atrial pressure was elevated to 20 mmHg (n = 5) to increase lymph flow in the absence of inflammation. Smoke induced a rise in lymph flow and pulmonary arterial pressure with either no fall in lymph-to-plasma protein ratio (128 breaths) or a modest fall in lymph-to-plasma protein ratio (48 breaths), consistent with a change in microvascular permeability as well as a rise in microvascular pressure. Lymph concentration of TNF-alpha fell in both groups, although lymph flux (concentration x flow) transiently rose in both. In neither case did TNF-alpha. flux exceed that induced by left atrial pressure elevation. TNF-alpha was detectable in only one out of five sheep in alveolar lavage. Thus, by utilizing a sensitive and specific radioimmunoassay, we were unable to demonstrate a role for TNF-alpha in smoke-induced microvascular lung injury in sheep. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. USDA,GROWTH BIOL LAB,LIVESTOCK & POULTRY INST,BELTSVILLE,MD 20705. RP Hales, CA (reprint author), MASSACHUSETTS GEN HOSP,PULM CRIT CARE UNIT,DEPT MED,SHRINERS BURNS INST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-36829] NR 25 TC 21 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1997 VL 82 IS 5 BP 1433 EP 1437 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA WX868 UT WOS:A1997WX86800008 PM 9134889 ER PT J AU Jasty, M Bragdon, C Burke, D OConnor, D Lowenstein, J Harris, WH AF Jasty, M Bragdon, C Burke, D OConnor, D Lowenstein, J Harris, WH TI In vivo skeletal responses to porous-surfaced implants subjected to small induced motions SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BONE INGROWTH AB Cylindrical porous-coated implants were placed in the distal femoral metaphyses of twenty dogs and were subjected to zero, twenty, forty, or 150 micrometers of oscillatory motion for eight hours each day for six weeks with use of a specially designed loading apparatus, The in vivo skeletal responses to the different magnitudes of relative motion were evaluated, Histological analysis demonstrated growth of bone into the porous coatings of all of the implants, including those that had been subjected to 150 micrometers of motion, However, the ingrown bone was in continuity with the surrounding bone only in the groups of implants that had not been subjected to motion or that had been subjected to twenty micrometers of motion; in contrast, the implants that had been subjected to forty micrometers of motion were surrounded in part by trabecular bone but also in part by fibrocartilage and fibrous tissue, and those that had been subjected to 150 micrometers of motion were surrounded by dense fibrous tissue, Trabecular microfractures were identified around three of the five implants that had been subjected to forty micrometers of motion and around four of the five that had been subjected to 150 micrometers of motion, suggesting that the ingrown bone had failed at the interface because of the large movements. The architecture of the surrounding trabecular bone also was altered by the micromotion of the implant. The implants that had stable ingrowth of bone were surrounded by a zone of trabecular atrophy, whereas those that had unstable ingrowth of bone were surrounded by a zone of trabecular hypertrophy, The trabeculae surrounding the fibrocartilage or fibrous tissue that had formed around the implants that had been subjected to forty or 150 micrometers of motion had been organized into a shell of dense bone tangen-tial to the implant (that is, a neocortex outside the non-osseous tissue). CLINICAL RELEVANCE: The findings of the present study quantitate the in vivo patterns of bone in-growth and remodeling that occur in association with different magnitudes of micromovement of porous-coated implants. Small movements (zero and twenty micrometers) are compatible with stable ingrowth of bone and atrophy of the surrounding trabecular bone, whereas larger movements (forty and 150 micrometers) result in less stable or unstable ingrowth of bone, the formation of fibrocartilage or fibrous tissue around the implant, and hypertrophy of the surrounding trabecular bone, This study not only quantified the magnitudes of relative micromotion that cause these different skeletal responses but also may help in the interpretation of radiographs of patients who have a porous-coated prosthesis. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Jasty, M (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114, USA. NR 15 TC 184 Z9 199 U1 1 U2 6 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 1997 VL 79A IS 5 BP 707 EP 714 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XA213 UT WOS:A1997XA21300009 PM 9160943 ER PT J AU Hara, H Ayata, C Huang, PL Waeber, C Ayata, G Fujii, M Moskowitz, MA AF Hara, H Ayata, C Huang, PL Waeber, C Ayata, G Fujii, M Moskowitz, MA TI [H-3]L-N-G-nitroarginine binding after transient focal ischemia and NMDA-induced excitotoxicity in type I and type III nitric oxide synthase null mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE autoradiography; excitotoxicity; ischemia; N-methyl-D-aspartate; mutant mouse; nitric oxide synthase ID CEREBRAL-ISCHEMIA; MESSENGER-RNA; RAT-BRAIN; NADPH-DIAPHORASE; NERVOUS-SYSTEM; INDUCTION; ARGININE; AUTORADIOGRAPHY; NEURONS; ENZYME AB We investigated the density and distribution of nitric oxide synthase (NOS) binding by quantitative autoradiography using [H-3]L-N-G-nitroarginine ([H-3]L-NNA) after transient focal ischemia or intrastriatal injection of N-methyl-D-aspartate (NMDA) in wild-type (SV-129 and C57black/6) and type I (neuronal) and type III (endothelial) NOS-deficient mice. The middle cerebral artery (MCA) was occluded by an intraluminal filament for 3 h followed by 10 min to 7 days of reperfusion. Specific [H-3]L-NNA binding, observed in the wild-type and type III mutant mouse at baseline, increased by 50-250% in the MCA territory during ischemia and the first 3 h of reperfusion. The density of binding sites (B-max), but not the dissociation constant (K-d), increased significantly during the ischemic period as did type I NOS mRNA as detected by quantitative reverse transcription polymerase chain reaction. [H-3]L-NNA binding after intrastriatal NMDA injection also increased by 20-230%. In the type I NOS-deficient mouse, [H-3]L-NNA binding was low and only a very small increase was observed after ischemia or excitotoxicity. Under conditions of this study, [3H]L-NNA did not bind to type II NOS as there was no difference in the distribution or density of [H-3]L-NNA binding in the rat spleen obtained after lipopolysaccharide treatment despite induction of NOS type II catalytic activity. Our data suggest that an ischemic/excitotoxic insult up-regulates type I NOS gene expression and [H-3]L-NNA binding and that this up-regulation may play a pivotal role in the pathogenesis of ischemic/excitotoxic diseases. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG & NEUROL,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS10828, NS2683, NS33335] NR 36 TC 37 Z9 39 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1997 VL 17 IS 5 BP 515 EP 526 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA XC697 UT WOS:A1997XC69700005 PM 9183289 ER PT J AU Grinspoon, S Corcoran, C Miller, K Biller, BMK Askari, H Wang, E Hubbard, J Anderson, EJ Basgoz, N Heller, HM Klibanski, A AF Grinspoon, S Corcoran, C Miller, K Biller, BMK Askari, H Wang, E Hubbard, J Anderson, EJ Basgoz, N Heller, HM Klibanski, A TI Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE SECRETION; VIRUS INFECTION; GH SECRETION; FACTOR-I; AIDS; PROTEIN; SEX; TESTOSTERONE; HUMANS; MEN AB The acquired immunodeficiency syndrome (AIDS) wasting syndrome is a devastating complication of human immunodeficiency virus (HIV) infection characterized by progressive weight loss and severe inanition. In men, the wasting syndrome is characterized by a disproportionate decrease in lean body mass and relative fat sparing. In contrast, relatively little is known about the gender-specific changes in body composition that characterize AIDS wasting in women. Three groups of women were studied to determine body composition and hormonal changes with respect to stage of wasting [non-wasting (NN; weight >90% ideal body weight; weight loss <10% of preillness maximum; n = 12), early wasting (EW; weight >90% ideal body weight; weight loss >10% of preillness maximum; n = 10), and late wasting (LW; weight <90%; n = 9)] and compared with a control group of 12, healthy, age-matched women. Weight loss averaged 6 +/- 6% (NW), 15 +/- 6% (EW), and 20 +/- 8% (LW) in the three groups. Lean, fat, and muscle masses were determined by dual energy x-ray absorptiometry and urinary creatinine excretion. Subjects were 36 +/- 5 yr of age (mean +/- so) with a CDS cell count of 379 +/- 239 cells/mm(3). The body mass index was 24.4 +/- 2.6 kg/m(2) (NW), 22.2 +/- 1.2 kg/m(2) (EW), 18.2 +/- 2.0 kg/m(2) (LW), and 24.3 +/- 2.6 kg/m(2) (controls; P < 0.01, NW vs. EW; P < 0.0001, NW as. LW). Lean body mass indexed for height was 15.7 +/- 2.4 kg/m(2) (NW), 14.8 +/- 2.0 kg/m(2) (EW), and 13.7 +/- 1.2 kg/m(2) (LW) and was decreased significantly only in the LW group (P < 0.05 vs. NW). Muscle mass was 96% (NW), 94% (EW), and 78% (LW) of that predicted for height (P < 0.05, NW vs. LW). In contrast, fat mass indexed for height was decreased significantly among patients in both the EW and LW groups [8.7 +/- 1.9 kg/m(2) (NW), 6.5 +/- 1.9 kg/m(2) (EW), and 3.7 +/- 1.4 kg/m(2) (LW); P < 0.05, NW as. EW; P < 0.001, NW vs. LW). Expressed as a percentage of the value In nonwasting HIV-positive controls (NW), the relative loss of fat was greater than the loss of lean mass with progressive degrees of wasting [EW, 25% vs. 6% (fat vs. lean); LW, 58% vs. 13%]. The prevalence of amenorrhea was 20% among study subjects [17% (NW), 10% (EW), and 38% (LW)]. The percent predicted muscle mass was significantly lower in subjects with amenorrhea (74 +/- 8%) compared to that in eumenorrheic HIV-positive subjects (94 +/- 4%; P < 0.05). Estradiol levels were lower among subjects with amenorrhea (17.6 +/- 21.8 pg/mL) compared to eumenorrheic HIV-positive (48.9 +/- 33.6 pg/mL) and control (68.3 +/- 47.6 pg/mL) subjects and did not correlate with body composition. Mean free testosterone, but not total testosterone, levels were decreased in subjects with EW and LW compared to those in age-matched healthy controls, but not compared with those in NW [0.9 +/- 0.6 ng/dL (NW), 0.7 +/- 0.4 ng/dL (EW), 0.6 +/- 0.3 ng/dL (LW), and 2.0 +/- 2.4 ng/dL (controls); P < 0.05, EW us. controls and LN vs. controls] and correlated with muscle mass (r = 0.37; P < 0.05). The percentages of women with free testosterone levels below the age-adjusted normal range were 33% (NW), 50% (EW), and 66% (LW). Dehydroepiandrosterone sulfate levels were also low in the subjects with LW compared to those in the control group [98 +/- 85 mu g/dL (NW), 102 +/- 53 mu g/dL (EW), 55 +/- 46 mu g/dL (LW), and 132 +/- 68 mu g/dL (controls); P < 0.05 LW vs. controls] and were correlated highly with free testosterone levels (r = 0.73; P < 0.00001) and also with muscle mass (r = 0.48; P < 0.01). These data demonstrate that women lose significant lean body and muscle mass in the late stages of wasting. However, in contrast to men, women exhibit a progressive and disproportionate decrease in body fat relative to lean body mass at all stages of wasting, consistent with gender-specific effects in body composition in AIDS wasting. In addition, these data demonstrate that androgen deficiency is common in women with AIDS wasting and may contribute to decreased muscle mass in this population. C1 MASSACHUSETTS GEN HOSP, DEPT INFECT DIS, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, GEN CLIN RES CTR, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Grinspoon, S (reprint author), MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, NEUROENDOCRINE DEPT, BULFINCH 457B, BOSTON, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [P32-DK-07028, R01-DK-49302] NR 36 TC 161 Z9 162 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1997 VL 82 IS 5 BP 1332 EP 1337 DI 10.1210/jc.82.5.1332 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WX551 UT WOS:A1997WX55100005 PM 9141512 ER PT J AU Dong, RP Umezawa, Y Ikushima, H Munakata, Y Schlossman, SF Morimoto, C AF Dong, RP Umezawa, Y Ikushima, H Munakata, Y Schlossman, SF Morimoto, C TI Different regulatory effects of pentoxifylline on human T cell activation pathways SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE pentoxifylline; CD3; CD26; CD28; cytokine ID NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD; RECEPTOR; MICE; INTERLEUKIN-2; EXPRESSION; RESPONSES; INCREMENT; ANTIGEN; CD2 AB Pentoxifylline (PTX), a methylxanthine derivative, was examined for its effects on T cell proliferation and cytokine production stimulated by cross-linking anti-CD3 alone, anti-CD3 with PMA, anti-CD3 with anti-CD26, or anti-CDS with anti-CD28 mAb, respectively. PTX at a 3.5 x 10(-5) M concentration significantly inhibited T cell proliferation and the production of tumor necrosis factor-alpha, interleukin-2, and interleukin-4. Moreover, this effect was selective for stimulation by cross-linking anti-CD3 with PMA, or anti-CD3 with anti-CD26, but not by cross-linking anti-CDS with anti-CD28. These results suggest that the inhibitory effect of PTX on T cell activation involves the CD3 and CD26, but not the CD28 signal pathway. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. JUNTENDO UNIV,SCH MED,DEPT PATHOL 2,TOKYO 113,JAPAN. NR 31 TC 14 Z9 14 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1997 VL 17 IS 3 BP 247 EP 252 DI 10.1023/A:1027362629161 PG 6 WC Immunology SC Immunology GA XA037 UT WOS:A1997XA03700007 PM 9168405 ER PT J AU Slack, JL Arthur, DC Lawrence, D Mrozek, K Mayer, RJ Davey, FR Tantravahi, R Pettenati, MJ Bigner, S Carroll, AJ Rao, KW Schiffer, CA Bloomfield, CD AF Slack, JL Arthur, DC Lawrence, D Mrozek, K Mayer, RJ Davey, FR Tantravahi, R Pettenati, MJ Bigner, S Carroll, AJ Rao, KW Schiffer, CA Bloomfield, CD TI Secondary cytogenetic changes in acute promyelocytic leukemia - Prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: A cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Association-for-Cancer-Research CY APR 20-24, 1996 CL WASHINGTON, DC SP Amer Assoc Canc Res ID POLYMERASE CHAIN-REACTION; ACUTE MYELOID-LEUKEMIA; TRANS-RETINOIC ACID; ACUTE MYELOGENOUS LEUKEMIA; MINIMAL RESIDUAL DISEASE; CHROMOSOMAL-ABNORMALITIES; ALPHA ISOFORMS; CELL-CYCLE; TRANSCRIPTS; DIAGNOSIS AB Purpose: To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) mRNA types, Patients and Methods: One hundred sixty-one patients with t(15;17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied, Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML-RAR alpha mRNA type wets determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients, Results: The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28), In a separate group of 56 patients with both cytogenetic and molecular date, 32 had the type L PML-RAR alpha transcript (intron 6 PML breakpoint). OF these 32 patients, four (12.5%) had chromosome changes in addition to t(15; 17), whereas 12 of 20 patients (60%) with the type S PML-RAR alpha transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P < .001), Conclusion: (1) secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RAR alpha S isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL. (C) 1997 by American Society of Clinical Oncology. C1 SUNY HLTH SCI CTR,SYRACUSE,NY 13210. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. DANA FARBER CANC INST,BOSTON,MA 02115. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV N CAROLINA,CHAPEL HILL,NC 27515. UNIV ALABAMA,BIRMINGHAM,AL. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. RP Slack, JL (reprint author), ROSWELL PK CANC INST,DIV MED,BUFFALO,NY 14263, USA. RI Mrozek, Krzysztof/A-3142-2008 FU NCI NIH HHS [CA16450, CA37027, CA59518] NR 52 TC 71 Z9 72 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 1786 EP 1795 PG 10 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400012 PM 9164186 ER PT J AU Sparano, JA Neuberg, D Glick, JH Robert, NJ Goldstein, LJ Sledge, GW Wood, W AF Sparano, JA Neuberg, D Glick, JH Robert, NJ Goldstein, LJ Sledge, GW Wood, W TI Phase II trial of biweekly paclitaxel and cisplatin in advanced breast carcinoma: An eastern cooperative oncology group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 1996 CL PHILADELPHIA, PA SP Amer Soc Clin Oncol ID CRITERIA; TOXICITY AB Purpose: To determine the efficacy of ct biweekly paclitaxel and cisplatin regimen in patients with advanced breast carcinoma, which has previously been reported to produce on 85% response rate in such patients. Patients and Methods: Sixteen patients with metastatic breast carcinoma who had relapsed after prior doxorubicin-containing adjuvant chemotherapy were treated with paclitaxel (90 mg/m(2)) by intravenous (IV) infusion over 3 hours followed by cisplatin (60 mg/m(2)) given by IV infusion over 1 hour on an outpatient basis. Treatment was repeated every 2 weeks if the absolute neutrophil count was greater than or equal to 750/mu L and platelet count greater than or equal to 75,000/mu L. After a maximum of eight cycles of paclitaxel/cisplatin, patients received biweekly paclitaxel alone (90 mg/m(2) with dose escalation). Thirteen patients were assessable for response and all for toxicity, Nine of 13 patients assessable for response (69%) had at least three sites of metastases and 10 patients (77%) had visceral-dominant disease. Results: Partial response occurred in three of 13 assessable patients (23%; 90% confidence interval, 7% to 49%). All responders had two or fewer sites of metastases, The median time to progression was 4.3 months and the median survival duration was 11.4 months. Patients received a median of seven cycles of therapy (range, two to 21), Severe and/or life-threatening toxicity occurred in 50% and 38%, respectively, and consisted primarily of granulocytopenia, anemia, and neuropathy. The trial was terminated after the first interim analysis as per its two-stage design, since it was unlikely that the response rate would exceed 70%. Conclusion: Biweekly paclitaxel/cisplatin is not likely to produce a response rate greater than 70% in patients with metastatic breast cancer who have relapsed after prior doxorubicin-containing adjuvant chemotherapy and who have multiple sites of metastases and/or visceral-dominant disease, (C) 1991 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. UNIV PENN,PHILADELPHIA,PA 19104. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. FAIRFAX HOSP,ANNANDALE,VA. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. EMORY UNIV,ATLANTA,GA 30322. RP Sparano, JA (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [CA14958, CA23318, CA21076] NR 11 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 1880 EP 1884 PG 5 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400024 PM 9164198 ER PT J AU Hahn, WC Jones, D Leavitt, P Garber, J Stone, R Skarin, AT AF Hahn, WC Jones, D Leavitt, P Garber, J Stone, R Skarin, AT TI Leukemia cutis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Hahn, WC (reprint author), BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1997 VL 15 IS 5 BP 2170 EP 2171 PG 2 WC Oncology SC Oncology GA WZ564 UT WOS:A1997WZ56400058 PM 9164232 ER PT J AU Haffajee, AD Cugini, MA Dibart, S Smith, C Kent, RL Socransky, SS AF Haffajee, AD Cugini, MA Dibart, S Smith, C Kent, RL Socransky, SS TI The effect of SRP on the clinical and microbiological parameters of periodontal diseases SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases; periodontitis; treatment; SRP; microbiology ID RELEASE TETRACYCLINE FIBERS; NON-SURGICAL TREATMENT; ADULT PERIODONTITIS; SUBGINGIVAL MICROFLORA; THERAPY; METRONIDAZOLE; CHLORHEXIDINE; MINOCYCLINE; MULTICENTER; MICROBIOTA AB The purpose of the present investigation was to examine the effect of SRP on clinical and microbiological parameters in 57 subjects with adult periodontitis (mean age 47+/-11 years). Subjects were monitored clinically and microbiologically prior to and 3, 6 and 9 months after full-mouth SRP under local anaesthesia. Clinical assessments of plaque, redness, suppuration, BOP, pocket depth and attachment level were made at 6 sites per tooth. The means of duplicate attachment level measurements taken at each visit were used to assess change between visits. Clinical data were averaged within each subject and then averaged across subjects for each visit. Subgingival plaque samples were taken from the mesial aspect of each tooth and the presence and levels of 40 subgingival taxa were determined using whole genomic DNA probes and checkerboard DNA-DNA hybridization. The mean levels and % of sites colonized by each species (prevalence) was computed for each subject at each visit. Differences in clinical and microbiological parameters before and after SRP were sought using the Wilcoxon signed ranks test or the Quade test for more than 2 visits. Overall, there was a mean gain in attachment level of 0.11+/-0.23 mm (range -0.53 to 0.64 mm) 3 months post-therapy. There was a significant decrease in the % of sites exhibiting gingival redness (68 to 57%) and BOP (58 to 52%) as well as a mean (+/-SEM) pocket depth (3.3+/-0.06 to 3.1+/-0.05 mm). Sites with pre-therapy pocket depths of <4 mm showed a non-significant increase in pocket depth and attachment level, 4-6 mm pockets showed a significant decrease in pocket depth and a non-significant gain in attachment post-therapy, while >6 mm pockets showed a significant decrease in pocket depth and attachment level measurements posttherapy. Significant clinical improvements were seen in subjects who had never smoked or were past smokers but not in current smokers. Mean prevalences and levels of P. gingivalis, T. denticola and B. forsythus were significantly reduced after SRP, while A. viscosus showed a significant increase in mean levels. The mean decrease in prevalence of P. gingivalis was similar at all pocket depth categories, while B. forsythus decreased more at shallow and intermediate pockets and A. viscosus increased most at deep sites. P. gingivalis, B. forsythus and T. denticola were equally prevalent among current, past and never smokers pretherapy, decreased significantly post-SRP in never and past smokers but increased in current smokers. Clinical improvement post-SRP was accompanied by a modest change in the subgingival microbiota, primarily a reduction in P. gingivalis, B. forsythus and T. denticola, suggesting potential targets for therapy and indicating that radical alterations in the subgingival microbiota may not be necessary or desirable in many patients. C1 FORSYTH DENT CTR,DEPT BIOSTAT,BOSTON,MA 02115. RP Haffajee, AD (reprint author), FORSYTH DENT CTR,DEPT PERIODONTOL,140 FENWAY,BOSTON,MA 02115, USA. RI de la Flor, Maria/B-9212-2015 FU NIDCR NIH HHS [DE-04881] NR 50 TC 264 Z9 284 U1 1 U2 20 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 MAY PY 1997 VL 24 IS 5 BP 324 EP 334 DI 10.1111/j.1600-051X.1997.tb00765.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW578 UT WOS:A1997WW57800006 PM 9178112 ER PT J AU McDowell, RK Gazelle, GS Murphy, BL Boland, GW MayoSmith, WW Warshaw, AL Mueller, PR AF McDowell, RK Gazelle, GS Murphy, BL Boland, GW MayoSmith, WW Warshaw, AL Mueller, PR TI Mucinous ductal ectasia of the pancreas SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pancreas, abnormalities; computed tomography; pancreatography ID CYST FLUID ANALYSIS; HYPERSECRETING NEOPLASMS; TUMORS; LESIONS; ENTITY; CT AB Purpose: Pancreatic mucinous ductal ectasia (MDE) is a recently described and poorly understood disorder, with few cases reported in the imaging literature. We undertook this study to describe the spectrum of CT and pancreatographic findings of MDE and to investigate the incidence of associated pancreatic malignancy. Method: The medical records, CT scans, and pancreatograms of 12 consecutive patients with pathologically proven MDE were retrospectively reviewed. There were nine men and three women, ranging in age from 37 to 72 years (mean 59 years). Results: Focal lesions involved primarily the uncinate (two patients) and head (eight patients) by CT imaging. The entire gland was involved in two patients. CT findings were variable and included focal pancreatic enlargement, a low attenuation or cystic mass, low attenuation of the entire gland, or marked ductal dilatation. Pancreatographic findings were more consistent, showing ductal dilatation with or without intraluminal filling defects, obstruction, or displacement. In all cases, findings at enodscopy were felt to be characteristic, with ductal dilatation, filling defects, or abundant mucus seen upon cannulation of the pancreatic duct. Carcinoma-in-situ was present in six cases, cellular atypia without malignancy in two, and in three cases the lesions were histologically benign. One case demonstrated invasive adenocarcinoma. No finding or group of findings on CT or pancreatography permitted differentiation between benign and malignant lesions. Conclusion: MDE can present with a variety of appearances on CT, none of which is diagnostic. Pancreatography can be diagnostic if dilatation and intraluminal filling defects are seen. Carcinoma-in-situ, invasive adenocarcinoma, or cellular atypia is present in similar to 75%, but cannot be accurately diagnosed prospectively. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. BROWN UNIV,RHODE ISL HOSP,DEPT RADIOL,PROVIDENCE,RI 02903. RADIOL ASSOCIATES CLEARWATER,CLEARWATER,FL. NR 16 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 1997 VL 21 IS 3 BP 383 EP 388 DI 10.1097/00004728-199705000-00008 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WV864 UT WOS:A1997WV86400008 PM 9135644 ER PT J AU Quinn, TR Young, RH AF Quinn, TR Young, RH TI Smooth-muscle hamartoma of the tunica dartos of the scrotum: Report of a case SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MELANOSIS AB Hamartomatous proliferations of genital smooth muscle are uncommon and may be easily overlooked if the normal microscopic appearance of the scrotal dartos is unfamiliar to the pathologist. We describe a hamartomatous proliferation of the scrotum in a 60-year-old patient in which incomplete knowledge of the regional histology caused initial problems in diagnosis. On histologic examination, the lesion consisted of an expansile, unencapsulated, relatively circumscribed proliferation of smooth muscle accompanied by muscular arterioles and prominent nerve branches embedded in a densely collagenized stroma. These features are dissimilar both clinically and histologically from all previous reported lesions at this site. We highlight the histologic differences between our case and genital leiomyomas, and the spectrum of hamartomatous smooth-muscle proliferations associated with a Becker nevus, and congenital and acquired smooth muscle hamartomas. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Quinn, TR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 12 Z9 12 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 MAY PY 1997 VL 24 IS 5 BP 322 EP 326 DI 10.1111/j.1600-0560.1997.tb00799.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA XB681 UT WOS:A1997XB68100010 PM 9194587 ER PT J AU Adriaens, PA Goodson, JM Encarnacion, M AF Adriaens, PA Goodson, JM Encarnacion, M TI One-year follow-up after tetracycline fiber therapy of non-responding localized periodontal defects. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV BRUSSELS,BRUSSELS,BELGIUM. ICPOI,BRUSSELS,BELGIUM. FORSYTH DENT CTR,BOSTON,MA 02115. ALZA CORP,PALO ALTO,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1997 VL 76 IS 5 BP 1122 EP 1122 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW075 UT WOS:A1997WW07501339 ER PT J AU Silva, JA Leong, GB Rhodes, LJ Weinstock, R AF Silva, JA Leong, GB Rhodes, LJ Weinstock, R TI A new variant of ''subjective'' delusional misidentification associated with aggression SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; forensic psychiatry; delusional misidentification; aggression; violence; psychosis; visual perception; chromosomal abnormalities ID POSITRON EMISSION TOMOGRAPHY; FACE-PROCESSING IMPAIRMENTS; CAPGRAS SYNDROME; GLUCOSE-METABOLISM; SCHIZOPHRENIA; SUBSTITUTION; PERSPECTIVE; DIAGNOSIS; ATROPHY; SELF AB Delusional misidentification syndromes are psychotic conditions in which the affected individual experiences delusions of radical change concerning the identity of others and/or of the self. These syndromes may lead to aggression including serious violence toward others. In this article, we describe and analyze in derail an aggressive individual who suffered from a delusion that physical and psychological replicas of himself existed. We specifically analyze the link between the patient's subjective misidentification delusion and his resulting aggression. Both the roles of phenomenology and biology of delusional misidentification are evaluated as potential contributors of aggression. C1 UNIV MISSOURI,SCH MED,COLUMBIA,MO. HARRY S TRUMAN MEM VET HOSP,COLUMBIA,MO 65201. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Silva, JA (reprint author), S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 63 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAY PY 1997 VL 42 IS 3 BP 406 EP 410 PG 5 WC Medicine, Legal SC Legal Medicine GA WX108 UT WOS:A1997WX10800011 PM 9144929 ER PT J AU Holmgren, M Smith, PL Yellen, G AF Holmgren, M Smith, PL Yellen, G TI Trapping of organic blockers by closing of voltage-dependent K+ channels - Evidence for a trap door mechanism of activation gating SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE potassium channels; tetraethylammonium compounds; ion channel gating; open channel blockade; use-dependent blockade ID SHAKER POTASSIUM CHANNELS; MOLECULAR DETERMINANTS; LOCAL-ANESTHETICS; HIGH-CONDUCTANCE; RECEPTOR-SITE; GIANT-AXONS; BARIUM IONS; NA+ CHANNEL; SQUID AXON; INACTIVATION AB Small organic molecules, like quaternary ammonium compounds, have long been used to probe both the permeation and gating of voltage-dependent K+ channels. For most K+ channels, intracellularly applied quaternary ammonium (OA) compounds such as tetraethylammonium (TEA) and decyltriethylammonium (C-10) behave primarily as open channel blockers: they can enter the channel only when it is open, and they must dissociate before the channel can close. In some cases, it is possible to force the channel to close with a QA blocker still bound, with the result that the blocker is ''trapped.'' Armstrong (J. Gen. Physiol. 58:413-437) found that at very negative voltages, squid axon K+ channels exhibited a slow phase: of recovery from QA blockade consistent with such trapping. In our studies on the cloned Shaker channel, we find that wild-type channels can trap neither TEA nor C-10, but channels with a point mutation in S6 can trap either compound very efficiently. The trapping occurs with very little change in the energetics of channel gating, suggesting that in these channels the gate may function as a trap door or hinged lid that occludes access from the intracellular solution to the blocker site and to the narrow ion-selective pore. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [R01 NS029693, NS29693] NR 35 TC 170 Z9 171 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAY PY 1997 VL 109 IS 5 BP 527 EP 535 DI 10.1085/jgp.109.5.527 PG 9 WC Physiology SC Physiology GA WY012 UT WOS:A1997WY01200003 PM 9154902 ER PT J AU Leaf, DA Kobashigawa, J Gleeson, M Laks, H AF Leaf, DA Kobashigawa, J Gleeson, M Laks, H TI Defining obesity in patients undergoing orthotopic heart transplantation: Body mass index versus percent body fat SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID HYPERLIPIDEMIA; PREDICTORS AB We examined body mass index (BMI) as a proxy for percent body fat among 26 men and women successfully undergoing orthotopic heart transplantation. Percent body fat was determined by use of bioelectrical impedance techniques. We found that, although BMI was well correlated with percent body fat (r = 0.58, p < 0.01), use of a BMI of greater than 27 kg/m(2) to define obesity potentially misclassified patients when compared with defining obesity as a percentage of body fat as both greater than 30% (BMI = 9 of 26 patients vs percent body fat = 6 of 26 patients) and greater than 40% (BMI = 9 of 26 versus percent body fat = 1 of 9). We conclude that percent body fat measurements are more methodologically appropriate means for defining obesity among these patients. RP Leaf, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED 691 111G,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAY PY 1997 VL 16 IS 5 BP 563 EP 565 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA XB106 UT WOS:A1997XB10600013 PM 9171276 ER PT J AU RemoldODonnell, E Cooley, J Shcherbina, A Hagemann, TL Kwan, SP Kenney, DM Rosen, FS AF RemoldODonnell, E Cooley, J Shcherbina, A Hagemann, TL Kwan, SP Kenney, DM Rosen, FS TI Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED THROMBOCYTOPENIA; MUTATIONS; GENE; IDENTIFICATION; LYMPHOCYTES; GTPASES; CDC42; RAC AB The Wiskott-Aldrich syndrome (WAS) arises from defects of the X-chromosome gene WASP. Severe platelet defects, thrombocytopenia with small platelets, are a hallmark of the disease, but clinical immunodeficiency based in lymphocyte dysfunction varies from negligible to life threatening among WAS patients. To address the connection between WASP mutations and clinical outcomes, we generated and characterized a panel of patient B cell lines. Three cell lines from patients with exon 2 missense mutations and mild immune dysfunction were found to express substantial levels of WASP mRNA and protein. On the other hand, 8 of 10 cell lines from patients with moderate or severe immune dysfunction lack detectable WASP protein. The findings suggest that the clinical variability of the WAS can partially be explained by the level of WASP protein in the patient's cells. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RUSH UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,CHICAGO,IL 60612. RP RemoldODonnell, E (reprint author), CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCRR NIH HHS [RR02172]; NIAID NIH HHS [AI31587, AI39574] NR 37 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1997 VL 158 IS 9 BP 4021 EP 4025 PG 5 WC Immunology SC Immunology GA WV761 UT WOS:A1997WV76100001 PM 9126958 ER PT J AU Fricchione, G Bush, G Fozdar, M Francis, A Fink, M AF Fricchione, G Bush, G Fozdar, M Francis, A Fink, M TI Recognition and treatment of the catatonic syndrome SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Review ID NEUROLEPTIC MALIGNANT SYNDROME; BRAIN BENZODIAZEPINE RECEPTORS; LETHAL CATATONIA; ELECTROCONVULSIVE-THERAPY; PSYCHOGENIC CATATONIA; SUDDEN-DEATH; PREFRONTAL CORTEX; BASAL GANGLIA; LORAZEPAM; METABOLISM AB We define the catatonic syndrome and review the history of the concept of catatonia, including its recent acceptance as a syndrome. Diagnosis of the catatonic syndrome, with its associated extensive differential diagnoses related to systemic and mental disorders, is addressed. Catatonia is related to variants of the syndrome, such as lethal (malignant) catatonia and the neuroleptic malignant syndrome (NMS). Medical sequelae of these conditions are outlined. The Literature on the treatment of the catatonic syndrome is reviewed, and a suggested approach to treatment and management of catatonic patients in the intensive care unit is provided. An hypothesis regarding the neuropathophysiological basis for the syndrome is also offered. C1 SUNY STONY BROOK,DEPT PSYCHIAT & BEHAV SCI,STONY BROOK,NY 11794. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP Fricchione, G (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 117 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD MAY-JUN PY 1997 VL 12 IS 3 BP 135 EP 147 PG 13 WC Critical Care Medicine SC General & Internal Medicine GA XF257 UT WOS:A1997XF25700004 ER PT J AU Bagot, M Hall, K Freeman, GJ Boumsell, L Bensussan, A AF Bagot, M Hall, K Freeman, GJ Boumsell, L Bensussan, A TI CD101, a major antigen for the activation of T lymphocytes by skin dendritic cells, is identical to the V.7 antigen. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 HOP HENRI MONDOR,INSERM,U448,F-94010 CRETEIL,FRANCE. DANA FARBER CANC INST,BOSTON,MA 02115. RI Bensussan, Armand/E-5434-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1997 VL 108 IS 5 BP C3 EP C3 PG 1 WC Dermatology SC Dermatology GA WV133 UT WOS:A1997WV13300030 ER PT J AU Hardin, TC Najvar, LK Rizzo, J Fothergill, AW Rinaldi, MG Graybill, JR AF Hardin, TC Najvar, LK Rizzo, J Fothergill, AW Rinaldi, MG Graybill, JR TI Discrepancy between in vitro and in vivo antifungal activity of albendazole SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article; Proceedings Paper CT 35th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 17-22, 1995 CL SAN FRANCISCO, CA SP Amer Soc Microbiol DE antifungal; albendazole; Candida albicans; Cryptococcus neoformans ID BENZIMIDAZOLES AB Albendazole has in vitro activity against Cryptococcus neoformans and reduced in vitro activity for albendazole when compared with Candida albicans. The major metabolite of albendazole, albendazole sulphoxide showed no in vitro activity against isolates of either fungus. Immunocompetent mice infected intravenously (IV) with C. albicans were treated with albendazole doses of 20-600 mg kg(-1) per day in noble agar or sesame oil for per oral (PO) administration, or 80 mg kg(-1) per day in DMSO for intraperitoneal (IP) and IV administration for 10 days, and were observed for survival. Mice infected with C. neoformans intracranially received albendazole in daily doses of 600 mg kg(-1) prepared in DMSO (IF) or peanut butter/rat chow (PO) for 10 days and were observed for survival. Mortality was not different between the treated and control animals in any study. Plasma samples from uninfected mice dosed with similar formulations and doses of albendazole were analysed by HPLC for albendazole and albendazole sulphoxide. No albendazole could be detected in any sample, while concentrations of albendazole sulphoxide (286-8697 ng ml(-1)) were observed in all samples. These data suggest that the absence of in vivo activity for albendazole is due to rapid conversion to the inactive albendazole sulphoxide metabolite. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX 78284. RP Hardin, TC (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU PHS HHS [N0 1-A1-25141] NR 8 TC 4 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD MAY-JUN PY 1997 VL 35 IS 3 BP 153 EP 158 PG 6 WC Mycology SC Mycology GA XG192 UT WOS:A1997XG19200001 PM 9229330 ER EF