FN Thomson Reuters Web of Science™ VR 1.0 PT J AU DYER, DG DUNN, JA THORPE, SR BAILIE, KE LYONS, TJ MCCANCE, DR BAYNES, JW AF DYER, DG DUNN, JA THORPE, SR BAILIE, KE LYONS, TJ MCCANCE, DR BAYNES, JW TI ACCUMULATION OF MAILLARD REACTION-PRODUCTS IN SKIN COLLAGEN IN DIABETES AND AGING SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AGING; COLLAGEN; DIABETES; GLYCATION; OXIDATION ID AGE-DEPENDENT ACCUMULATION; OXIDATIVE STRESS; CROSS-LINK; MELLITUS; N-EPSILON-(CARBOXYMETHYL)LYSINE; GLYCATION; PROTEIN; COMPLICATIONS; PENTOSIDINE; PRECURSORS AB To investigate the contribution of glycation and oxidation reactions to the modification of insoluble collagen in aging and diabetes, Maillard reaction products were measured in skin collagen from 39 type 1 diabetic patients and 52 nondiabetic control subjects. Compounds studied included fructoselysine (FL), the initial glycation product, and the glycoxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and pentosidine, formed during later Maillard reactions. Collagen-linked fluorescence was also studied. In nondiabetic subjects, glycation of collagen (FL content) increased only 33% between 20 and 85 yr of age. In contrast, CML, pentosidine and fluorescence increased five-fold, correlating strongly with age. In diabetic patients, collagen FL was increased threefold compared with nondiabetic subjects, correlating strongly with glycated hemoglobin but not with age. Collagen CML, pentosidine and fluorescence were increased up to twofold in diabetic compared with control patients: this could be explained by the increase in glycation alone, without invoking increased oxidative stress. There were strong correlations among CML, pentosidine and fluorescence in both groups, providing evidence for age-dependent chemical modification of collagen via the Maillard reaction, and acceleration of this process in diabetes. These results support the description of diabetes as a disease characterized by accelerated chemical aging of long-lived tissue proteins. C1 MED UNIV S CAROLINA,DEPT CHEM & BIOCHEM,DIV ENDOCRINOL DIABET & METAB,171 ASHLEY AVE,CHARLESTON,SC 29425. UNIV S CAROLINA,DEPT CHEM & BIOCHEM,COLUMBIA,SC 29208. UNIV S CAROLINA,SCH MED,COLUMBIA,SC 29208. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. ALTNAGELVIN HOSP,DEPT MED,LONDONDERRY BT47 1JE,NORTH IRELAND. ROYAL VICTORIA HOSP,SIR GEORGE E CLARK METAB UNIT,BELFAST BT12 6BA,NORTH IRELAND. FU NIDDK NIH HHS [DK-19971] NR 25 TC 482 Z9 491 U1 3 U2 35 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 PY 1993 VL 91 IS 6 BP 2463 EP 2469 DI 10.1172/JCI116481 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LH121 UT WOS:A1993LH12100018 PM 8514858 ER PT J AU MCCANCE, DR DYER, DG DUNN, JA BAILIE, KE THORPE, SR BAYNES, JW LYONS, TJ AF MCCANCE, DR DYER, DG DUNN, JA BAILIE, KE THORPE, SR BAYNES, JW LYONS, TJ TI MAILLARD REACTION-PRODUCTS AND THEIR RELATION TO COMPLICATIONS IN INSULIN-DEPENDENT DIABETES-MELLITUS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE COLLAGEN; COMPLICATIONS OF DIABETES; GLYCATION; OXIDATION; NONENZYMATIC BROWNING ID NON-ENZYMATIC GLYCOSYLATION; HUMAN-SKIN COLLAGEN; LIMITED JOINT MOBILITY; GLYCEMIC CONTROL; LINKED FLUORESCENCE; GLYCATED PROTEINS; CROSS-LINKING; END-PRODUCTS; RETINOPATHY; AGE AB Glycation, oxidation, and browning of proteins have all been implicated in the development of diabetic complications. We measured the initial Amadori adduct, fructoselysine (FL); two Maillard products, N(epsilon)-(carboxymethyl) lysine (CML) and pentosidine; and fluorescence (excitation = 328 nm, emission = 378 nm) in skin collagen from 39 type 1 diabetic patients (aged 41.5 +/- 15.3 117-731 yr; duration of diabetes 17.9 +/- 11.5 10-461 yr, [mean +/- SD, range]). The measurements were related to the presence of background (n = 9) or proliferative (n = 16) retinopathy; early nephropathy (24-h albumin excretion rate [AER24] greater-than-or-equal-to 20 mug/min; n = 9); and limited joint mobility (LJM; n = 20). FL, CML, pentosidine, and fluorescence increased progressively across diabetic retinopathy (P < 0.05, P < 0.001, P < 0.05, P < 0.01, respectively). FL, CML, pentosidine, and fluorescence were also elevated in patients with early nephropathy (P < 0.05, P < 0.001, P < 0.01, P < 0.01, respectively). There was no association with LJM. Controlling for age, sex, and duration of diabetes using logistic regression, FL and CML were independently associated with retinopathy (FL odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.011. 12, P < 0.05; CML OR = 6.77, 95% CI = 1.33-34.56, P < 0.05) and with early nephropathy (FL OR = 1.05, 95% CI = 1.01-1.10, P < 0.05; CML OR = 13.44,95% CI = 2.0093. 30, P < 0.01). The associations between fluorescence and retinopathy and between pentosidine and nephropathy approached significance (P = 0.05). These data show that FL and Maillard products in skin correlate with functional abnormalities in other tissues and suggest that protein glycation and oxidation (glycoxidation) may be implicated in the development of diabetic retinopathy and early nephropathy. C1 MED UNIV S CAROLINA, DIV ENDOCRINOL DIABET & METAB, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. ROYAL VICTORIA HOSP, SIR GEORGE E CLARK METAB UNIT, BELFAST BT12 6BA, NORTH IRELAND. UNIV S CAROLINA, DEPT CHEM & BIOCHEM, COLUMBIA, SC 29208 USA. UNIV S CAROLINA, SCH MED, COLUMBIA, SC 29208 USA. ALTNAGELVIN HOSP, DEPT MED, LONDONDERRY BT47 1JB, NORTH IRELAND. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29401 USA. FU NIDDK NIH HHS [DK-19971] NR 67 TC 338 Z9 343 U1 1 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1993 VL 91 IS 6 BP 2470 EP 2478 DI 10.1172/JCI116482 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LH121 UT WOS:A1993LH12100019 PM 8514859 ER PT J AU TROMP, G WU, YL PROCKOP, DJ MADHATHERI, SL KLEINERT, C EARLEY, JJ ZHUANG, JP NORRGARD, O DARLING, RC ABBOTT, WM COLE, CW JAAKKOLA, P RYYNANEN, M PEARCE, WH YAO, JST MAJAMAA, K SMULLENS, SN GATALICA, Z FERRELL, RE JIMENEZ, SA JACKSON, CE MICHELS, VV KAYE, M KUIVANIEMI, H AF TROMP, G WU, YL PROCKOP, DJ MADHATHERI, SL KLEINERT, C EARLEY, JJ ZHUANG, JP NORRGARD, O DARLING, RC ABBOTT, WM COLE, CW JAAKKOLA, P RYYNANEN, M PEARCE, WH YAO, JST MAJAMAA, K SMULLENS, SN GATALICA, Z FERRELL, RE JIMENEZ, SA JACKSON, CE MICHELS, VV KAYE, M KUIVANIEMI, H TI SEQUENCING OF CDNA FROM 50 UNRELATED PATIENTS REVEALS THAT MUTATIONS IN THE TRIPLE-HELICAL DOMAIN OF TYPE-III PROCOLLAGEN ARE AN INFREQUENT CAUSE OF AORTIC-ANEURYSMS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE FAMILIAL ANEURYSMS; POLYMERASE CHAIN REACTION; POLYMORPHISMS ID EHLERS-DANLOS SYNDROME; SINGLE BASE MUTATION; MARFAN-SYNDROME; COLLAGEN GENES; COL3A1 GENE; I COLLAGEN; FAMILY; CHAIN; POLYMORPHISM; INHERITANCE AB Detailed DNA sequencing of the triple-helical domain of type Ill procollagen was carried out on cDNA prepared from 54 patients with aortic aneurysms. The 43 male and 11 female patients originated from 50 different families and five different nationalities. 43 patients had at least one additional blood relative who had aneurysms. Five overlapping asymmetric PCR products, covering all the coding sequences of the triple-helical domain of type III procollagen, were sequenced with 28 specific sequencing primers. Analysis of the sequencing gels revealed only two nucleotide changes that altered the structure of the protein. One was a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other was a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results indicate that mutations in type III procollagen are the cause of only about 2% of aortic aneurysms. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT SURG,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT MED,DIV RHEUMATOL,PHILADELPHIA,PA 19107. UMEA UNIV,DEPT SURG,S-90185 UMEA,SWEDEN. MASSACHUSETTS GEN HOSP,GEN SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. UNIV OTTAWA,DIV VASC SURG,OTTAWA K1Y 4E9,ONTARIO,CANADA. UNIV KUOPIO,DEPT SURG,SF-70211 KUOPIO,FINLAND. UNIV KUOPIO,DEPT OBSTET & GYNECOL,SF-70211 KUOPIO,FINLAND. NORTHWESTERN UNIV,SCH MED,DIV VASC SURG,CHICAGO,IL 60611. UNIV OULU,DEPT NEUROL,SF-90220 OULU,FINLAND. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA 15261. HENRY FORD HOSP,DIV CLIN & MOLEC GENET,DETROIT,MI 48202. MAYO CLIN & MAYO FDN,DEPT MED GENET,ROCHESTER,MN 55905. MONTREAL GEN HOSP,DIV NEPHROL,MONTREAL H3G 1A4,QUEBEC,CANADA. RI Majamaa, Kari/A-1344-2012; Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NHLBI NIH HHS [HL 45996]; NIAMS NIH HHS [AR 38188] NR 45 TC 90 Z9 92 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 JUN PY 1993 VL 91 IS 6 BP 2539 EP 2545 DI 10.1172/JCI116490 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LH121 UT WOS:A1993LH12100027 PM 8514866 ER PT J AU LANGHOFF, E KALLAND, KH HASELTINE, WA AF LANGHOFF, E KALLAND, KH HASELTINE, WA TI EARLY MOLECULAR REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN CULTURED-BLOOD DERIVED T-HELPER DENDRITIC CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION; INTEGRATION; MONOCYTES; T-CELLS ID LANGERHANS CELLS; HIV-1 INFECTION; GENE; LYMPHOCYTES; EXPRESSION; RETROVIRUS; MONOCYTES; MICE AB The rate and efficiency of key steps in the life cycle of the human immunodeficiency virus type 1 was examined in three primary cell types, T cells, monocytes, and T helper dendritic cells using the same quantity of virus involved and same cell number. The results show that viral DNA synthesis proceeds much more rapidly and efficiently in primary T helper dendritic cell populations than in primary T cell and monocyte populations. The increased rate of virus DNA synthesis is attributable either to an increase in the efficiency and the rate of uptake of the virus particles by the T helper dendritic cells, as compared with that in other cell types, or to an increased efficiency and rate of viral DNA synthesis in the T helper dendritic cells. In the subsequent phase of viral expression the appearance of spliced viral mRNA products also occur more rapidly in cultures of primary-blood-derived T helper dendritic cells than is the case in primary T cells and monocytes. The increased efficiency of the early steps of HIV-1 replication in primary-blood-derived T helper dendritic cells than in other blood-derived mononuclear cells raises the possibility that these cells play a central role in HIV-1 infection and pathogenesis. C1 UNIV BERGEN,HIB,CTR VIROL,N-5020 BERGEN,NORWAY. RP LANGHOFF, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Kalland, Karl-Henning/B-9445-2017 OI Kalland, Karl-Henning/0000-0003-4486-2334 FU NCI NIH HHS [P30CA06516]; PHS HHS [P30A128691] NR 36 TC 31 Z9 31 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 PY 1993 VL 91 IS 6 BP 2721 EP 2726 DI 10.1172/JCI116512 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LH121 UT WOS:A1993LH12100049 PM 8514880 ER PT J AU MELCHER, GP MCGOUGH, DA FOTHERGILL, AW NORRIS, C RINALDI, MG AF MELCHER, GP MCGOUGH, DA FOTHERGILL, AW NORRIS, C RINALDI, MG TI DISSEMINATED HYALOHYPHOMYCOSIS CAUSED BY A NOVEL HUMAN PATHOGEN, FUSARIUM-NAPIFORME SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; FUNGAL INFECTION; LEUKEMIA; PATIENT; SOLANI; HOST AB Fusarium species are saprophytic molds and important plant pathogens, although they are increasingly recognized as agents of human mycosis. Frequently, the infection is superficial. Deep tissue infection may occur as an opportunistic hyalohyphomycosis, and wide dissemination is common in immunocompromised hosts. We describe a novel case of disseminated hyalohyphomycosis caused by F. napiforme in a patient with acute myelogenous leukemia. The clinical manifestations of this infection were similar to those attributed to infection with other species. In vitro susceptibility testing demonstrated resistance to amphotericin B and flucytosine, and progressive infection was documented until recovery of granulocyte function. The distinguishing clinical mycologic characteristics of this opportunistic mold are the unique turnip- or lemon-shaped microconidia. F. napiforme is a new agent of hyalohyphomycosis, further emphasizing the importance of Fusarium species as opportunistic molds. C1 WILFORD HALL USAF MED CTR,DEPT PATHOL,LACKLAND AFB,TX 78236. UNIV TEXAS,HLTH SCI CTR,FUNGUS TESTING LAB,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RP MELCHER, GP (reprint author), WILFORD HALL USAF MED CTR,DEPT INFECT DIS,LACKLAND AFB,TX 78236, USA. NR 34 TC 24 Z9 24 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 1993 VL 31 IS 6 BP 1461 EP 1467 PG 7 WC Microbiology SC Microbiology GA LC728 UT WOS:A1993LC72800012 PM 8314987 ER PT J AU HAMILTON, SR SMITH, CH LESSELL, S AF HAMILTON, SR SMITH, CH LESSELL, S TI IDIOPATHIC HYPERTROPHIC CRANIAL PACHYMENINGITIS SO JOURNAL OF CLINICAL NEURO-OPHTHALMOLOGY LA English DT Article DE PACHYMENINGITIS; DURA; MAGNETIC RESONANCE IMAGING ID INTRACRANIAL EXTENSION; NEUROSARCOIDOSIS; SARCOIDOSIS; PSEUDOTUMOR; BLINDNESS AB We evaluated 3 patients with biopsy-proven hypertrophic cranial pachymeningitis apparently unrelated to any systemic disease. Each patient had chronic headache, cranial neuropathy, an elevated ESR, and a mild CSF pleocytosis. Neuro-ophthalmic findings included bilateral sixth nerve palsies in two patients and the third had bilateral optic neuropathies. MR imaging revealed thickened dura that enhanced with Gd-DTPA administration. Histologic examination showed thickened, fibrotic dura with a sterile, chronic, nongranulomatous inflammation. The response to treatment was variable with corticosteroids, immunosuppressive drugs, or radiation. The distinctive MR appearance should help physicians recognize this rarely reported disease. C1 UNIV WASHINGTON,DEPT MED,DIV NEUROL,SEATTLE,WA 98195. MASSACHUSETTS EYE & EAR INFIRM,NEUROOPHTHAL MOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. NR 23 TC 44 Z9 44 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0272-846X J9 J CLIN NEURO-OPHTHAL PD JUN PY 1993 VL 13 IS 2 BP 127 EP 134 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA LH264 UT WOS:A1993LH26400008 PM 8340479 ER PT J AU HUDSON, MM WEINSTEIN, HJ DONALDSON, SS GREENWALD, C KUN, L TARBELL, NJ HUMPHREY, WA RUPP, C MARINA, NM WILIMAS, J LINK, MP AF HUDSON, MM WEINSTEIN, HJ DONALDSON, SS GREENWALD, C KUN, L TARBELL, NJ HUMPHREY, WA RUPP, C MARINA, NM WILIMAS, J LINK, MP TI ACUTE HYPERSENSITIVITY REACTIONS TO ETOPOSIDE IN A VEPA REGIMEN FOR HODGKINS-DISEASE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TENIPOSIDE; CHILDREN; VM-26 C1 LUCILLE SALTER PACKARD CHILDRENS HOSP, STANFORD, CA USA. ST JUDE CHILDRENS RES HOSP, DEPT RADIAT ONCOL, MEMPHIS, TN 38101 USA. UNIV TENNESSEE, CTR HLTH SCI, COLL MED, DEPT PEDIAT, MEMPHIS, TN 38163 USA. CHILDRENS HOSP MED CTR, JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. STANFORD UNIV, MED CTR, SCH MED, DEPT PEDIAT, STANFORD, CA 94305 USA. STANFORD UNIV, MED CTR, SCH MED, DEPT RADIAT ONCOL, STANFORD, CA 94305 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. RP HUDSON, MM (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, POB 318, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA-34233, CA-21765] NR 21 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1993 VL 11 IS 6 BP 1080 EP 1084 PG 5 WC Oncology SC Oncology GA LF310 UT WOS:A1993LF31000011 PM 8501494 ER PT J AU WHEELER, C STRAWDERMAN, M AYASH, L CHURCHILL, WH BIERER, BE ELIAS, A GILLILAND, DG ANTMAN, K GUINAN, EC EDER, JP WEINSTEIN, H SCHWARTZ, G FERRARA, J MAZANET, R RIMM, IJ TEPLER, I MCCARTHY, P MAUCH, P AULT, K GAYNES, L MCCAULEY, M SCHNIPPER, LE ANTIN, J AF WHEELER, C STRAWDERMAN, M AYASH, L CHURCHILL, WH BIERER, BE ELIAS, A GILLILAND, DG ANTMAN, K GUINAN, EC EDER, JP WEINSTEIN, H SCHWARTZ, G FERRARA, J MAZANET, R RIMM, IJ TEPLER, I MCCARTHY, P MAUCH, P AULT, K GAYNES, L MCCAULEY, M SCHNIPPER, LE ANTIN, J TI PROGNOSTIC FACTORS FOR TREATMENT OUTCOME IN AUTOTRANSPLANTATION OF INTERMEDIATE-GRADE AND HIGH-GRADE NON-HODGKINS-LYMPHOMA WITH CYCLOPHOSPHAMIDE, CARMUSTINE, AND ETOPOSIDE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE THERAPY; CELL LYMPHOMA; DISEASE C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. MAINE MED CTR,DIV HEMATOL & ONCOL,PORTLAND,ME 04102. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. RP WHEELER, C (reprint author), BETH ISRAEL HOSP,330 BROOKLINE AVE,BOSTON,MA 02214, USA. FU NCI NIH HHS [P01CA-38493, P01CA-39542] NR 19 TC 69 Z9 71 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 JUN PY 1993 VL 11 IS 6 BP 1085 EP 1091 PG 7 WC Oncology SC Oncology GA LF310 UT WOS:A1993LF31000012 PM 8099120 ER PT J AU WILLETT, CG FUNG, CY KAUFMAN, DS EFIRD, J SHELLITO, PC AF WILLETT, CG FUNG, CY KAUFMAN, DS EFIRD, J SHELLITO, PC TI POSTOPERATIVE RADIATION-THERAPY FOR HIGH-RISK COLON-CARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT THERAPY; CURATIVE SURGERY; ADENOCARCINOMA; PATTERNS; FAILURE; FLUOROURACIL; LEUCOVORIN; CANCER C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,DEPT MED ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,DEPT SURG,BOSTON,MA 02114. RP WILLETT, CG (reprint author), MASSACHUSETTS GEN HOSP,COX BLDG,3RD FLOOR,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 16 TC 53 Z9 54 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1993 VL 11 IS 6 BP 1112 EP 1117 PG 6 WC Oncology SC Oncology GA LF310 UT WOS:A1993LF31000016 PM 8501497 ER PT J AU SUGARBAKER, DJ STRAUSS, GM LYNCH, TJ RICHARDS, W MENTZER, SJ LEE, TH CORSON, JM ANTMAN, KH AF SUGARBAKER, DJ STRAUSS, GM LYNCH, TJ RICHARDS, W MENTZER, SJ LEE, TH CORSON, JM ANTMAN, KH TI NODE STATUS HAS PROGNOSTIC-SIGNIFICANCE IN THE MULTIMODALITY THERAPY OF DIFFUSE, MALIGNANT MESOTHELIOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ASBESTOS-RELATED DISEASE; PLEURAL MESOTHELIOMA; UNITED-STATES; LUNG-CANCER; EXTRAPLEURAL PNEUMONECTOMY; NATURAL-HISTORY; SOFT-TISSUE; DOXORUBICIN; CHEMOTHERAPY; MANAGEMENT C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SUGARBAKER, DJ (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV THORAC SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 51 TC 146 Z9 150 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 JUN PY 1993 VL 11 IS 6 BP 1172 EP 1178 PG 7 WC Oncology SC Oncology GA LF310 UT WOS:A1993LF31000024 PM 8501504 ER PT J AU BAER, L AF BAER, L TI BEHAVIOR-THERAPY FOR OBSESSIVE-COMPULSIVE DISORDER IN THE OFFICE-BASED PRACTICE SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT SATELLITE SYMP ON DIAGNOSIS AND TREATMENT OF OCD : A CLINICIANS PERSPECTIVE / 145TH ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOC CY MAY 03, 1992 CL WASHINGTON, DC SP AMER PSYCHIAT ASSOC ID CLOMIPRAMINE; EXPOSURE AB The article provides guidance for the clinician in applying scientifically proven behavior therapy techniques for obsessive compulsive disorder. Rationale for considering behavior therapy for all patients with OCD is presented, along with guidelines for determining an adequate trial of this approach and for predicting if a particular patient is likely to benefit. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 17 TC 15 Z9 15 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1993 VL 54 SU S BP 10 EP 15 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA LP324 UT WOS:A1993LP32400003 PM 8331097 ER PT J AU RAPOPORT, JL BAER, L AF RAPOPORT, JL BAER, L TI OBSESSIVE-COMPULSIVE DISORDER IN CHILDREN AND ADOLESCENTS - ISSUES IN MANAGEMENT - DISCUSSION SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Discussion C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RAPOPORT, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1993 VL 54 SU S BP 30 EP 30 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA LP324 UT WOS:A1993LP32400006 ER PT J AU KOSSLYN, SM ALPERT, NM THOMPSON, WL MALJKOVIC, V WEISE, SB CHABRIS, CF HAMILTON, SE RAUCH, SL BUONANNO, FS AF KOSSLYN, SM ALPERT, NM THOMPSON, WL MALJKOVIC, V WEISE, SB CHABRIS, CF HAMILTON, SE RAUCH, SL BUONANNO, FS TI VISUAL MENTAL-IMAGERY ACTIVATES TOPOGRAPHICALLY ORGANIZED VISUAL-CORTEX - PET INVESTIGATIONS SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; GLABELLA-INION LINE; STRIATE CORTEX; CEREBRAL HEMISPHERES; EXTRASTRIATE CORTEX; UNILATERAL NEGLECT; MINDS EYE; BRAIN; GENERATION; ATTENTION AB Cerebral blood flow was measured using positron emission tomography (PET) in three experiments while subjects performed mental imagery or analogous perceptual tasks. In Experiment 1, the subjects either visualized letters in grids and decided whether an X mark would have fallen on each letter if it were actually in the grid, or they saw letters in grids and decided whether an X mark fell on each letter. A region identified as part of area 17 by the Talairach and Tournoux (1988) atlas, in addition to other areas involved in vision, was activated more in the mental imagery task than in the perception task. In Experiment 2, the identical stimuli were presented in imagery and baseline conditions, but subjects were asked to form images only in the imagery condition; the portion of area 17 that was more active in the imagery condition of Experiment 1 was also more activated in imagery than in the baseline condition, as was part of area 18. Subjects also were tested with degraded perceptual stimuli, which caused visual cortex to be activated to the same degree in imagery and perception. In both Experiments 1 and 2, however, imagery selectively activated the extreme anterior part of what was identified as area 17, which is inconsistent with the relatively small size of the imaged stimuli. These results, then, suggest that imagery may have activated another region just anterior to area 17. In Experiment 3, subjects were instructed to close their eyes and evaluate visual mental images of upper case letters that were formed at a small size or large size. The small mental images engendered more activation in the posterior portion of visual cortex, and the large mental images engendered more activation in anterior portions of visual cortex. This finding is strong evidence that imagery activates topographically mapped cortex. The activated regions were also consistent with their being localized in area 17. Finally additional results were consistent with the existence of two types of imagery, one that rests on allocating attention to form a pattern and one that rests on activating stored visual memories. C1 HARVARD UNIV,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Frank, David/E-8213-2012 NR 72 TC 452 Z9 460 U1 1 U2 22 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SUM PY 1993 VL 5 IS 3 BP 263 EP 287 DI 10.1162/jocn.1993.5.3.263 PG 25 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA LM662 UT WOS:A1993LM66200001 PM 23972217 ER PT J AU YEWDELL, JW ESQUIVEL, F ARNOLD, D SPIES, T EISENLOHR, LC BENNINK, JR AF YEWDELL, JW ESQUIVEL, F ARNOLD, D SPIES, T EISENLOHR, LC BENNINK, JR TI PRESENTATION OF NUMEROUS VIRAL PEPTIDES TO MOUSE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-I RESTRICTED T-LYMPHOCYTES IS MEDIATED BY THE HUMAN MHC-ENCODED TRANSPORTER OR BY A HYBRID MOUSE-HUMAN TRANSPORTER SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HLA-B ANTIGENS; INFLUENZA HEMAGGLUTININ; REGION; EXPRESSION; CELLS; RECOGNITION; PROTEINS AB The major histocompatibility complex-encoded transporter associated with antigen processing (TAP) is required for the efficient presentation of cytosolic antigens to class I-restricted T cells. TAP is thought to be formed by the interaction of two gene products, termed TAP1 and TAP2. We find that TAPs consisting either of human subunits, or mouse TAP1 and human TAP2, facilitate the presentation of numerous defined viral peptides to mouse class I-restricted T cells. As human and mouse TAP2 and TAP1 differ in 23 and 28% of their residues, respectively, this indicates that TAP1 and TAP2 can form a functional complex with partners considerably different from those they coevolved with. Moreover, these findings indicate that widely disparate TAPs facilitate delivery of the same peptides to class I molecules. These findings suggest that TAP polymorphism does not greatly influence the types of peptides presented to the immune system. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID NIH HHS [AI-30581] NR 41 TC 30 Z9 30 U1 0 U2 0 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 JUN 1 PY 1993 VL 177 IS 6 BP 1785 EP 1790 DI 10.1084/jem.177.6.1785 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LD660 UT WOS:A1993LD66000029 PM 8496691 ER PT J AU ENGEL, P NOJIMA, Y ROTHSTEIN, D ZHOU, LJ WILSON, GL KEHRL, JH TEDDER, TF AF ENGEL, P NOJIMA, Y ROTHSTEIN, D ZHOU, LJ WILSON, GL KEHRL, JH TEDDER, TF TI THE SAME EPITOPE ON CD22 OF B-LYMPHOCYTES MEDIATES THE ADHESION OF ERYTHROCYTES, T-LYMPHOCYTES AND B-LYMPHOCYTES, NEUTROPHILS, AND MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-SURFACE; CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODY; BINDING-SITES; MOLECULE; IMMUNOGLOBULIN; EXPRESSION; PROTEIN; FAMILY; SIALYLTRANSFERASE AB CD22 is a B lineage-restricted member of the Ig superfamily that serves as an adhesion receptor expressed by mature B lymphocytes. In this study, the ability of different cell types to attach to COS cells transiently transfected with a full-length CD22 cDNA (COS-CD22) was examined to determine the cellular distribution of the ligand for CD22. T and B lymphocytes, monocytes, erythrocytes, and neutrophils formed specific rosettes with COS-CD22 cells at 4-degrees-C. A panel of 33 new mAb directed against CD22 were developed to examine the regions of CD22 that mediate adhesion. Four of these mAb, HB22-7, -22, -23, and -33 (at 1 to 5 mug/ml) specifically blocked adhesion (75 to 95%) of all cell types to COS-CD22 cells. Each of these mAb cross-blocked each other's binding, suggesting that ligand binding occurs through a single region of CD22. These mAb also identify a region of CD22 distinct from those defined by previously described CD22 mAb. CD22-mediated adhesion of cell lines to COS-CD22 cells was independent of CD45RO and CDw75 expression, and it was not inhibited by mAb against known integrins. Although alpha-2,6-linked sialic acid expressed on the surface of COS cells did not serve as a ligand for CD22, the CD22 ligand may contain a critical sialic acid determinant, as neuraminidase treatment of all target cells eliminated CD22-mediated adhesion. CD22-mediated adhesion was Ca2+/Mg2+ independent, again suggesting that integrins were not involved. An inhibitory substance for CD22-mediated adhesion was found to be present in FCS and some ascites fluid. Analysis of CD22 mRNA and protein revealed that although multiple mRNA splice variants of CD22 mRNA can be detected, only a single protein isoform was detected on the cell surface. Therefore, although the identity of the CD22 ligands remains incompletely characterized, it is possible that a single major ligand is expressed by RBC and leukocytes, which binds to a single region of CD22. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-34183, CA-54464]; NIAID NIH HHS [AI-26872] NR 45 TC 153 Z9 156 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1993 VL 150 IS 11 BP 4719 EP 4732 PG 14 WC Immunology SC Immunology GA LD916 UT WOS:A1993LD91600002 PM 7684411 ER PT J AU WAGNER, N ENGEL, P TEDDER, TF AF WAGNER, N ENGEL, P TEDDER, TF TI REGULATION OF THE TYROSINE KINASE-DEPENDENT ADHESION PATHWAY IN HUMAN-LYMPHOCYTES THROUGH CD45 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; ROUS-SARCOMA VIRUS; HUMAN B-CELLS; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; HOMOTYPIC ADHESION; T-CELLS; T200 GLYCOPROTEIN; SURFACE-ANTIGEN; ALTERNATIVE PATHWAY AB Cell-cell adhesive interactions involve numerous receptor/ligand interactions that play a crucial role in the development of immune function. Engagement of multiple cell-surface molecules on B lymphocytes generates intracellular signals through a tyrosine kinase-dependent pathway that activates cell-surface adhesion receptors and thereby induces homotypic cell-cell adhesion. Homotypic adhesion is mediated in part through LFA-1/ICAM-1 and other heretofore unknown adhesion receptors. In this study, evidence of a regulatory role for CD45 in the induction of homotypic adhesion is suggested. A new mAb (HAB-1) was developed that inhibits homotypic adhesion in B cell lines induced through MHC class I and class II, CD19, CD20, CD21, CD40, and Leu-13 cell-surface molecules. Although binding of this mAb strongly inhibited cell-surface Ag-induced homotypic adhesion at mAb concentrations as low as 0.1 mug/ml, it exhibited no effect on homotypic adhesion induced by phorbol esters. Binding of the HAB-1 mAb to lymphocytes altered the pattern of cellular protein tyrosine phosphorylation, but did not have a global inhibitory effect on cell activation because it did not have major effects on the growth of mitogen-activated lymphocytes. Immunoprecipitation studies revealed that the HAB-1 mAb identified an epitope present on all isoforms of CD45. The HAB-1 mAb may identify a unique epitope of CD45 because this mAb had a unique staining pattern when assessed by indirect immunofluorescence staining. The HAB-1 mAb was similar to some other CD45 mAb that have the capacity to amplify CD2-induced proliferation of blood lymphocytes. However, only 1 of 12 other anti-CD45 mAb tested had a similar inhibitory effect on adhesion. Homotypic adhesion of lymphocytes may therefore be governed by a regulatory system of cell-surface molecules that generate positive and negative signals that either trigger adhesion or, like CD45, directly down-regulate adhesion. This highlights the significance of adhesive events that result from surface molecules being engaged by their natural ligands during lymphocyte activation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-34183, CA-54464]; NIAID NIH HHS [AI-26872] NR 76 TC 50 Z9 50 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1993 VL 150 IS 11 BP 4887 EP 4899 PG 13 WC Immunology SC Immunology GA LD916 UT WOS:A1993LD91600017 PM 7684415 ER PT J AU MIROVSKY, P FISHMAN, JA AF MIROVSKY, P FISHMAN, JA TI AN IMPROVED METHOD FOR THE PROLONGED MAINTENANCE OF PNEUMOCYSTIS-CARINII INVITRO SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PROPAGATION AB A culture system for rat-derived Pneumocystis carinii was developed that allows the long-term maintenance of viable organisms in vitro. Organisms were derived from the lungs of immunosuppressed rats infected with P. carinii. P. carinii was maintained in culture with human embryonal lung (HEL) fibroblasts and Eagle MEM for up to 42 days. Passage of organisms was done by reinoculation of infected HEL cells with attached P. carinii onto a fresh monolayer of confluent cells. Rats pretreated with trimethoprim-sulfamethoxazole and inoculated with cultured organisms (up to day 42) developed P. carinii pneumonia by 6 weeks while control animals remained uninfected. P. carinii was able to be harvested from these lungs and reintroduced into tissue culture. Cultures have been maintained for up to 6 weeks without a substantial loss of P. carinii viability. In combination with intratracheal inoculation, this system raises the possibility of maintaining stable laboratory strains of P. carinii. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU FIC NIH HHS [D43 TW 00004]; NHLBI NIH HHS [HL-43510, HL-01916] NR 11 TC 11 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1993 VL 167 IS 6 BP 1470 EP 1473 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LD694 UT WOS:A1993LD69400038 PM 8501343 ER PT J AU KEARSE, LA MARTIN, D MCPECK, K LOPEZBRESNAHAN, M AF KEARSE, LA MARTIN, D MCPECK, K LOPEZBRESNAHAN, M TI COMPUTER-DERIVED DENSITY SPECTRAL ARRAY IN DETECTION OF MILD ANALOG ELECTROENCEPHALOGRAPHIC ISCHEMIC PATTERN CHANGES DURING CAROTID ENDARTERECTOMY SO JOURNAL OF NEUROSURGERY LA English DT Article DE CEREBRAL ISCHEMIA; CAROTID ENDARTERECTOMY; ELECTROENCEPHALOGRAPHY; DENSITY SPECTRAL ARRAY ID CEREBRAL BLOOD-FLOW; LONGITUDINAL DATA-ANALYSIS; APERIODIC ANALYSIS; EEG CHANGES; SURGERY AB The purpose of this prospective study was twofold: 1) to determine the sensitivity and specificity of computer-derived density spectral array in detecting analog electroencephalographic (EEG) ischemic pattern changes during carotid artery cross-clamping in patients undergoing carotid endarterectomy; and 2) to assess the ability of density spectral array to identify such changes in comparison with the degree and type of change seen in the analog EEG ischemic pattern. Sixteen channels of anteroposterior bipolar and two to four channels of referential electroencephalography with four channels of density spectral array were monitored simultaneously during carotid endarterectomy in 103 patients under general anesthesia. Two ''observers'' interpreted the density spectral array and the analog electroencephalograms, one during and immediately after the operations and the other 6 months after completion of all surgery. Analyses were conducted to establish both the number of patients with analog EEG ischemic changes and the number of ischemia events during carotid artery cross-clamping. Observer A indicated that the density spectral array identified analog EEG ischemic changes in 21 of 29 patients, for a sensitivity of 72% (specificity 99%), whereas Observer B's results showed that the density spectral array identified analog EEG ischemic changes in 16 of 27 patients, for a sensitivity of 59% (specificity 96%). Density spectral array detection of analog EEG ischemic changes based on severity classifications were 61% and 18% in the mild group, 70% and 71% in the moderate group, and 95% in the severe group, indicating a relationship between density spectral array sensitivity and severity of analog EEG ischemic change, with p = 0.02 and p = 0.004 for the two observers. The kappa statistics for observer reproducibility were highly significant, with k = 0.95 for analog EEG ischemic changes and 0.85 for density spectral array changes. It is concluded that density spectral array does not reliably detect mild analog EEG pattern changes of cerebral ischemia and is not a reliable substitute for 16-channel analog EEG monitoring of cerebral ischemia during carotid endarterectomy. C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP KEARSE, LA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 22 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 1993 VL 78 IS 6 BP 884 EP 890 DI 10.3171/jns.1993.78.6.0884 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LD500 UT WOS:A1993LD50000005 PM 8487070 ER PT J AU PIERI, P MCKUSICK, KA FISCHMAN, AJ ALPERT, N BOUGAS, C STRAUSS, HW AF PIERI, P MCKUSICK, KA FISCHMAN, AJ ALPERT, N BOUGAS, C STRAUSS, HW TI CHARACTERIZATION OF THE REINJECTION THALLIUM IMAGE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID CORONARY-ARTERY DISEASE; REGIONAL MYOCARDIAL PERFUSION; VIABLE MYOCARDIUM; TL-201; EXERCISE; REDISTRIBUTION; SCINTIGRAPHY; REST; REVASCULARIZATION; DIFFERENTIATION AB The TI-201 image after reinjection was characterized by analysis of stress and reinjection data acquired in 204 consecutive patients undergoing planar Tl-201 cardiac stress tests. In an additional 63 patients, redistribution data were also acquired to determine the effect of washout on the final reinjection image. Maximum count densities for the myocardium, lung and liver were measured, and the ratios between the stress and redistribution and the stress and reinjection sets of data were calculated. In patients with <5% probability of coronary artery disease (CAD) (''normal'' group), the reinjection image was typified by less myocardial activity (initial/reinjection = 1.22), slightly less lung activity (initial/reinjection = 1.05) and greater hepatic activity compared to the initial postexercise image. In male patients with >5% probability of CAD, peak myocardial activity after reinjection was affected by the following variables: the interval between stress and reinjection, the amount of the initial dose and the Tl-201 scan results (normal Tl-201 study: initial/reinjection = 1. 1 6; abnormal = 1.06; p < 0.009). Myocardial activity after reinjection was linearly related to myocardial activity after redistribution (r = 0.82). There was no significant influence by those variables in the 76 women who were studied. In conclusion, myocardial Tl-201 was decreased after reinjection in normal patients. The results indicate that there is an increased likelihood of underlying CAD in male patients undergoing exercise stress tests when Tl-201 myocardial activity on reinjection is greater than on the initial image. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,55 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. NR 30 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 1993 VL 34 IS 6 BP 879 EP 884 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LG085 UT WOS:A1993LG08500011 PM 8509852 ER PT J AU HE, YP CHU, SHW WALKER, WA AF HE, YP CHU, SHW WALKER, WA TI NUCLEOTIDE SUPPLEMENTS ALTER PROLIFERATION AND DIFFERENTIATION OF CULTURED HUMAN (CACO-2) AND RAT (IEC-6) INTESTINAL EPITHELIAL-CELLS SO JOURNAL OF NUTRITION LA English DT Article DE CACO-2 CELLS; IEC-6 CELLS; NUCLEOTIDES; INTESTINAL DEVELOPMENT ID DIETARY NUCLEOTIDES; GLUTAMINE; INFANTS; GROWTH; MILK AB The effect of exogenous nucleotides on the proliferation and differentiation of enterocytes was comparatively studied using a human colon tumor cell line (Caco-2) and a normal rat small intestinal crypt cell line (IEC-6). Caco-2 cells exhibited more active endogenous nucleic acid metabolism than did IEC-6 cells, as evidenced by greater cellular pools of nucleotides and their metabolites. To determine the supplemental nutritional effect of nucleotides, a mixture containing equal amounts (10 mg/L) of AMP, CMP, IMP, GMP and UMP was added to the culture medium. The results showed that a nucleotide supplement under normal culture conditions did not affect proliferation and differentiation of Caco-2 cells. In contrast, nucleotide supplements under normal culture conditions promoted proliferation of IEC6 cells. The addition of nucleotides to the culture medium also enhanced differentiation of IEC-6 cells when grown on an extracellular matrix (Matrigel(TM)). Furthermore, when glutamine levels were less than optimal (nutritional stress conditions), nucleotide supplements enhanced growth and maturation of both cell lines. We conclude that the de novo biosynthesis of nucleotides is sufficient to support proliferation of tumor Caco-2 cells but not of the normal crypt IEC-6 cells. Thus, nucleotide supplements may enhance normal enterocyte growth and maturation as well as spare the need for exogenous glutamine in cell maintenance and development. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,DEV GASTROENTEROL LAB,BOSTON,MA 02115. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK33506] NR 31 TC 65 Z9 73 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUN PY 1993 VL 123 IS 6 BP 1017 EP 1027 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LF086 UT WOS:A1993LF08600006 PM 8505661 ER PT J AU SMITH, DL LUCAS, LM AF SMITH, DL LUCAS, LM TI THE HUMAN SKELETON - AN OVERLOOKED BUT EFFECTIVE VISUAL AID SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 OREGON HLTH SCI UNIV,DIV GEN MED,PORTLAND,OR 97201. PORTLAND VET AFFAIRS MED CTR,GEN MED SECT,PORTLAND,OR 97207. RP SMITH, DL (reprint author), PORTLAND VET AFFAIRS MED CTR,GEN MED RHEUMAT DIS SECT,PORTLAND,OR 97207, USA. NR 2 TC 1 Z9 3 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 1993 VL 20 IS 6 BP 1088 EP 1089 PG 2 WC Rheumatology SC Rheumatology GA LH112 UT WOS:A1993LH11200044 PM 7688813 ER PT J AU MESTER, M TOMPKINS, RG GELFAND, JA DINARELLO, CA BURKE, JF CLARK, BD AF MESTER, M TOMPKINS, RG GELFAND, JA DINARELLO, CA BURKE, JF CLARK, BD TI INTESTINAL PRODUCTION OF INTERLEUKIN-1-ALPHA DURING ENDOTOXEMIA IN THE MOUSE SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE ASSOC-FOR-ACADEMIC-SURGERY CY NOV 18-21, 1992 CL MONTREAL, CANADA SP ASSOC ACAD SURG ID EXPERIMENTAL COLITIS; RECEPTOR ANTAGONIST; EXPRESSION; CYTOKINES; NECROSIS; RATS; GENE C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. TUFTS UNIV NEW ENGLAND MED CTR,DEPT GEOG MED & INFECT DIS,BOSTON,MA 02111. SHRINERS BURNS INST,BOSTON UNIT,BOSTON,MA 02114. TUFTS UNIV,SCH MED,BOSTON,MA 02111. RP MESTER, M (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114, USA. FU PHS HHS [21700-16] NR 28 TC 63 Z9 63 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1993 VL 54 IS 6 BP 584 EP 591 DI 10.1006/jsre.1993.1089 PG 8 WC Surgery SC Surgery GA MA736 UT WOS:A1993MA73600009 PM 8412068 ER PT J AU LEUCHTER, AF DALY, KA ROSENBERGTHOMPSON, S ABRAMS, M AF LEUCHTER, AF DALY, KA ROSENBERGTHOMPSON, S ABRAMS, M TI PREVALENCE AND SIGNIFICANCE OF ELECTROENCEPHALOGRAPHIC ABNORMALITIES IN PATIENTS WITH SUSPECTED ORGANIC MENTAL SYNDROMES SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID DEPRESSED SUBJECTS; EEG; DEMENTIA; AGE AB Objective: To determine the prevalence of electroencephalogram (EEG) abnormalities at different levels of cognitive impairment and to assess the possible diagnostic usefulness of the test. Design: Combined prospective assessment of subjects receiving EEGs and retrospective chart review of symptoms and medications. Setting: Academic geriatric psychiatry service. Patients: 350 adults age 50 and above; 312 were patients being evaluated for possible organic mental syndrome and 38 were normal controls. Measurements: All subjects had EEGs and Mini-Mental State Examinations (MMSE) performed at the time of the EEG. EEGs were rated for the presence and type of abnormality, and subjects were stratified according to the severity of impairment. Charts were reviewed by a person blinded to EEG results to determine clinical diagnosis and medications received. Main Results: Abnormal EEGs were significantly more common among all patients (67%) in the study than among controls (11%), and the prevalence of abnormality increased with increasing impairment. Many demented patients with equivocal impairment (42%), and most with mild-to-moderate impairment (65%) had abnormal EEGs. An abnormal EEG was not indicative of dementia even when clear cognitive impairment was present, since patients with depression frequently also had abnormal EEG results. Conclusions: These findings suggest that the EEG is a moderately sensitive but non-specific indicator of brain dysfunction in the elderly. The significance of abnormalities among patients with equivocal impairment should be more fully assessed by longitudinal follow-up to determine if greater cognitive impairment develops. C1 UNIV CALIF LOS ANGELES, HOSP NEUROPSYCHIAT, QUANTITAT EEG LAB, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, ROBERT WOOD JOHNSON CLIN SCHOLARS PROGRAM, W LOS ANGELES VET ADM MED CTR, VET ADM, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, ROBERT WOOD JOHNSON CLIN SCHOLARS PROGRAM, W LOS ANGELES VET ADM MED CTR, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA USA. RP LEUCHTER, AF (reprint author), UNIV CALIF LOS ANGELES, INST NEUROPSYCHIAT, QUANTITAT EEG LAB, 760 WESTWOOD PLAZA, LOS ANGELES, CA 90024 USA. FU NIA NIH HHS [P30 AG10123]; NIMH NIH HHS [MH 40705, MH 00665] NR 24 TC 17 Z9 19 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 1993 VL 41 IS 6 BP 605 EP 611 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LF776 UT WOS:A1993LF77600002 PM 8505456 ER PT J AU KANTEN, DN MULROW, CD GERETY, MB LICHTENSTEIN, MJ AGUILAR, C CORNELL, JE AF KANTEN, DN MULROW, CD GERETY, MB LICHTENSTEIN, MJ AGUILAR, C CORNELL, JE TI FALLS - AN EXAMINATION OF 3 REPORTING METHODS IN NURSING-HOMES SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article AB Objective: To examine the concordance of various fall reporting methods and to use the results to recommend a preferred method of ascertaining fall frequency for residents of nursing homes, both for research and in the collection of federally mandated nursing home data. Design: A cohort study followed for 858 patient months, with a mean individual follow-up of 6.6 months. Measurements: Falls were independently ascertained monthly by three methods: review of administrative incident reports, nursing home chart abstraction, and structured interview of subjects. Concordance of events was assessed using measures of simple agreement and Kendall's Tau-b. Simple correlation and multiple regression were used to evaluate the relation of age, sex, gender, depression, mental status, and functional status with degree of concordance between self-reported falls and chart-recorded falls. Setting: One academic and six community nursing homes in San Antonio, Texas. Participants: 131 long-stay nursing home residents, greater than 60 years of age, dependent in at least two activities of daily living, and mildly cognitively impaired. Results: Falls were ascertained in 74 of the 131 individuals; 53 subjects fell 124 times by incident report, 58 had 140 falls according to chart review, and 66 subjects self-reported 232 falls. Greatest agreement between reporting methods was shown for incident report and chart review, with a Kendall's Tau-b of 0.88; self-report and chart-review agreement was 0.56; and self-report and incident agreement was 0.53. Estimated total fall events were more often (P = 0.001) identified by chart review (92%) than incident report (82%). Although concordance was higher for non-fallers, no significant relationships were observed between concordance and age, sex, race, depression, mental status, and functional status. Also, there was no systematic relationship between length of follow-up and degree of concordance. Conclusions: Fall frequency varies by ascertainment method, with chart review reflecting a greater number of fall events than the traditionally counted incident reports. C1 UNIV TEXAS,HLTH SCI CTR,DIV GERIATR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV GERONTOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV GEN MED,SAN ANTONIO,TX 78284. RP KANTEN, DN (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [U01AG09117-01] NR 18 TC 54 Z9 55 U1 5 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 1993 VL 41 IS 6 BP 662 EP 666 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LF776 UT WOS:A1993LF77600013 PM 8505465 ER PT J AU MATHIAS, R SALUSKY, I HARMAN, W PAREDES, A EMANS, J SEGRE, G GOODMAN, W AF MATHIAS, R SALUSKY, I HARMAN, W PAREDES, A EMANS, J SEGRE, G GOODMAN, W TI RENAL BONE-DISEASE IN PEDIATRIC AND YOUNG-ADULT PATIENTS ON HEMODIALYSIS IN A CHILDRENS-HOSPITAL SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE RENAL OSTEODYSTROPHY; PARATHYROID HORMONE; BONE BIOPSY; DEFEROXAMINE; BONE FORMATION RATE ID PARATHYROID-HORMONE; DIALYSIS OSTEOMALACIA; CALCIUM-CARBONATE; IRON OVERLOAD; OSTEODYSTROPHY; ALUMINUM; HISTOMORPHOMETRY; ERYTHROPOIETIN; HYPOCALCEMIA; METABOLISM AB Renal bone disease has been well defined in adult patients receiving chronic dialysis and in children on peritoneal dialysis/continuous ambulatory peritoneal dialysis. However, little is known about the histologic features in patients undergoing chronic hemodialysis in a children's hospital center. Twenty one patients, aged 17.5 +/- 1.5 yr, on hemodialysis for 35 +/- 6 months underwent iliac crest bone biopsies and deferoxamine infusion tests. Nineteen of 21 patients were receiving oral calcitriol. The 21 patients were classified by histomorphometry as follows: osteitis fibrosa, 5; mild hyperparathyroidism, 3; normal histology, 3; aplastic, 6; and mixed lesions, 4. Four of 21 patients were surface positive for aluminum, and seven other patients stained positive for iron in bone. Serum parathyroid hormone (PTH) levels correlated directly with the bone formation rate (r = 0.84) and with eroded bone perimeter (r = 0.67). Eight of the nine patients with serum PTH levels above 125 pg/mL had marrow fibrosis. All patients with serum calcium levels <10.0 mg/dL and serum PTH levels >125 pg/mL had either osteitis fibrosa or mixed bone lesions-a group of patients that might benefit from aggressive vitamin D therapy. In contrast, an examination of patients with serum calcium levels >10. mg/dL and serum PTH levels <65 pg/mL correctly identified three out of three patients with aluminum-related bone disease. These findings suggest that measurements of serum intact PTH levels by the immunoradiometric assay method may be valuable in distinguishing high-turnover lesions from normal or low-turnover skeletal lesions in this population. C1 CHILDRENS HOSP MED CTR, DIV NEPHROL, BOSTON, MA 02115 USA. CHILDRENS HOSP MED CTR, DIV ORTHOPED, BOSTON, MA 02115 USA. UNIV CALIF LOS ANGELES, SCH MED, DIV PEDIAT NEPHROL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DIV NEPHROL, LOS ANGELES, CA USA. MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NICHD NIH HHS [T32 HD07268]; NIDDK NIH HHS [DK-35423] NR 36 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 1993 VL 3 IS 12 BP 1938 EP 1946 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA LJ298 UT WOS:A1993LJ29800012 PM 8338926 ER PT J AU GHIKA, J REGLI, F GROWDON, JH AF GHIKA, J REGLI, F GROWDON, JH TI SENSORY SYMPTOMS IN CRANIAL DYSTONIA - A POTENTIAL ROLE IN THE ETIOLOGY SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE MEIGE SYNDROME; SENSORY SYMPTOM; OROMANDIBULAR DYSTONIA ID OROMANDIBULAR DYSTONIA; BRUEGHELS SYNDROME; PERIPHERAL TRAUMA; BLEPHAROSPASM AB Cranial dystonia is normally considered as a pure movement disorder. Sensory symptoms have not received much attention, but we found ill-defined pain, discomfort, distortion of sensory modalities, 'phantom' kinetic or postural sensations in the orofacial areas subsequently involved by the dyskinesia in all of 11 consecutive patients, preceding by weeks or months the motor syndrome. Physicians were often mislead, initially making diagnoses such as trigeminal neuralgia, dental problems, sicca syndrome, chronic conjunctivitis, glossitis or stomatitis. The patients reported that the orofacial movements were at first willingly performed in order to decrease the discomfort which was felt in these facial areas before the movements finally escaped voluntary control and became socially disturbing. We suspect that the sensory symptoms, for which no objective substrate could be found, and which were always reported before and in the exact location of the subsequent dyskinesia, could be the earliest manifestation of an evolving process in cranial and perhaps other focal dystonias. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP GHIKA, J (reprint author), CHU VAUDOIS,SERV NEUROL,BH 13,CH-1011 LAUSANNE,SWITZERLAND. NR 23 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN PY 1993 VL 116 IS 2 BP 142 EP 147 DI 10.1016/0022-510X(93)90318-S PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LF863 UT WOS:A1993LF86300004 PM 8336160 ER PT J AU CAMBRIA, RP YUCEL, EK BREWSTER, DC LITALIEN, G GERTLER, JP LAMURAGLIA, GM KAUFMAN, JA WALTMAN, AC ABBOTT, WM AF CAMBRIA, RP YUCEL, EK BREWSTER, DC LITALIEN, G GERTLER, JP LAMURAGLIA, GM KAUFMAN, JA WALTMAN, AC ABBOTT, WM TI THE POTENTIAL FOR LOWER-EXTREMITY REVASCULARIZATION WITHOUT CONTRAST ARTERIOGRAPHY - EXPERIENCE WITH MAGNETIC-RESONANCE ANGIOGRAPHY SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 19TH ANNUAL MEETING OF THE NEW ENGLAND SOC FOR VASCULAR SURGERY CY SEP 23-25, 1992 CL DIXVILLE NOTCH, NH SP NEW ENGLAND SOC VASC SURG ID MR ANGIOGRAPHY AB Purpose: We report an initial experience with 24 patients studied between March 1990 and April 1992 with magnetic resonance angiography (MRA) for lower extremity occlusive disease. Methods: All patients underwent vascular intervention with either balloon angioplasty or bypass grafting, and in six patients this intervention was based on MRA findings alone. Eighteen patients were studied with both MRA and contrast arteriography, and there was observed agreement between the two studies in 98% of all arterial segments examined. Results: Agreement between MRA and contrast arteriography was uniform for arterial segments below the inguinal ligament. Intraoperative findings and favorable early results of seven bypass grafts performed in six patients after MRA alone suggested this was a valid approach for patients at prohibitive risk of complications from contrast arteriography. Conclusions: Magnetic resonance angiography is accurate in demonstrating relevant anatomy in peripheral arterial occlusive disease and in selected patients may eliminate the need for contrast arteriography before lower extremity revascularization. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV VASC RADIOL,BOSTON,MA 02115. RP CAMBRIA, RP (reprint author), MASSACHUSETTS GEN HOSP,DIV VASC SURG,15 PARKMAN ST,ACC 458,BOSTON,MA 02114, USA. NR 13 TC 58 Z9 58 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1993 VL 17 IS 6 BP 1050 EP 1057 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA LG738 UT WOS:A1993LG73800008 PM 8505783 ER PT J AU LAMURAGLIA, GM BREWSTER, DC MONCURE, AC CAMBRIA, RP GERTLER, JP ABBOTT, WM AF LAMURAGLIA, GM BREWSTER, DC MONCURE, AC CAMBRIA, RP GERTLER, JP ABBOTT, WM TI ANGIOSCOPIC EVALUATION OF UNILATERAL AORTIC GRAFT LIMB THROMBECTOMY - IS IT HELPFUL SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID INTRAOPERATIVE ANGIOSCOPY; THROMBOEMBOLECTOMY; MANAGEMENT; SURGERY AB Purpose: Graft thrombectomy is often an effective method for restoring inflow in an occluded limb of an aortobifemoral graft. A major determinant for its success is the completeness of thrombus removal from the graft, verification of which can be performed by angioscopy. Methods: A retrospective review since january 1989 identified 51 unilateral graft limb thrombectomy operations in 35 patients. At the discretion of the surgeon 20 of these procedures included angioscopic inspection of the graft for significant retained thrombus, which was found and retrieved in 11 (55%). Results: Visualization of the graft limb was very good, but inspection of the graft body was not possible. There were no angioscopy-related complications. Within the first 4 months after graft limb thrombectomy and reconstruction, four of 20 patients in the group inspected by angioscopy and nine of 31 in the conventionally treated group had reocclusion of the treated limb. Conclusions: These results suggest that angioscopy can be a helpful adjunct in the successful inflow management of aortic graft limb thrombectomy to verify the completeness of clot removal. RP LAMURAGLIA, GM (reprint author), MASSACHUSETTS GEN HOSP, DIV GEN SURG, DIV VASC SURG, BOSTON, MA 02114 USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1993 VL 17 IS 6 BP 1069 EP 1076 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA LG738 UT WOS:A1993LG73800010 PM 8505785 ER PT J AU MARTIN, S CASASNOVAS, JM STAUNTON, DE SPRINGER, TA AF MARTIN, S CASASNOVAS, JM STAUNTON, DE SPRINGER, TA TI EFFICIENT NEUTRALIZATION AND DISRUPTION OF RHINOVIRUS BY CHIMERIC ICAM-1/IMMUNOGLOBULIN MOLECULES SO JOURNAL OF VIROLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; COMPLEMENT ACTIVATION; CD4 IMMUNOADHESIN; RECEPTOR; ICAM-1; BINDING; EXPRESSION; REGION; GENE; FLEXIBILITY AB The intercellular adhesion molecule 1 (ICAM-1) is used as a cellular receptor by 90% of human rhinoviruses (HRVs). Chimeric immunoadhesin molecules containing extracellular domains of ICAM-1 and constant regions of immunoglobulins (Igs) were designed in order to determine the effect of increased valency, Ig isotype, and number of ICAM-1 domains on neutralization and disruption of rhinovirus structure. These immunoadhesins include ICAM-1 amino-terminal domains 1 and 2 fused to the hinge and constant domains of the heavy chains of IgA1, IgM, and IgG1 (IC1-2D/IgA, -/IgM, and -/IgG). In addition, all five extracellular domains were fused to IgA1 (IC1-5D/IgA). Immunoadhesins were compared with soluble forms of ICAM-1 containing five and two domains (sICAM-1 and ICI-2D, respectively) in assays of HRV binding, infectivity, and conformation. In prevention of HRV plaque formation, IC1-5D/IgA was 200 times and IC1-2D/IgM and IC1-2D/IgA were 25 and 10 times more effective, respectively, than ICAM-1. The same chimeras were highly effective in inhibiting binding of rhinovirus to cells and disrupting the conformation of the virus capsid, as demonstrated by generation of approximately 65S particles. The results show that the number of ICAM-1 domains and a flexible Ig hinge are important factors contributing to the efficacy of neutralization. The higher efficiency of chimeras that bound bivalently in disrupting HRV was attributed to higher binding avidity. The IC1-5D/IgA immunoadhesin was effective at nanomolar concentrations, making it feasible therapy for rhinovirus infection. C1 CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NIAID NIH HHS [AI31921] NR 41 TC 72 Z9 73 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1993 VL 67 IS 6 BP 3561 EP 3568 PG 8 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400072 PM 8098781 ER PT J AU SULLIVAN, N THALI, M FURMAN, C HO, DD SODROSKI, J AF SULLIVAN, N THALI, M FURMAN, C HO, DD SODROSKI, J TI EFFECT OF AMINO-ACID CHANGES IN THE V1/V2 REGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 GLYCOPROTEIN ON SUBUNIT ASSOCIATION, SYNCYTIUM FORMATION, AND RECOGNITION BY A NEUTRALIZING ANTIBODY SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN MONOCLONAL-ANTIBODY; CD4 RECEPTOR-BINDING; ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; HTLV-III/LAV; GENETIC-VARIATION; FUSION DOMAIN; T4 MOLECULE; AIDS; HIV-1 AB The contributions of the first and second variable regions Of the human immunodeficiency virus type 1 gp120 glycoprotein to envelope glycoprotein structure, function, and recognition by a neutralizing antibody were studied. Several mutants with substitutions in the V2 loop demonstrated complete dissociation of the gp120 and gp41 glycoproteins, suggesting that inappropriate changes in V2 conformation can affect subunit assembly. Some glycoproteins with changes in V1 or V2 were efficiently expressed on the cell surface and were able to bind CD4 but were deficient in syncytium formation and/or virus entry. Recognition of gp120 by the neutralizing monoclonal antibody G3-4 was affected by particular substitutions affecting residues 176 to 184 in the V2 loop. These results suggest that the V1/V2 variable regions of the human immunodeficiency virus type 1 gp120 glycoprotein play a role in postreceptor binding events in the membrane fusion process and can act as a target for neutralizing antibodies. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. FU NIAID NIH HHS [AI24030, AI25541, AI27742] NR 54 TC 159 Z9 161 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 1993 VL 67 IS 6 BP 3674 EP 3679 PG 6 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400093 PM 8497077 ER PT J AU CUNNINGHAM, MJ EAVEY, RD KROUSE, JH KISKADDON, RM AF CUNNINGHAM, MJ EAVEY, RD KROUSE, JH KISKADDON, RM TI TYMPANOSTOMY TUBES - EXPERIENCE WITH REMOVAL SO LARYNGOSCOPE LA English DT Article ID VENTILATION TUBES; COMPLICATIONS AB Whereas the clinical indications for tympanostomy tube placement are well-established, the indications for operative tympanostomy tube removal remain unspecified. A 1-year retrospective review done at the Massachusetts Eye and Ear Infirmary revealed 131 tympanostomy tubes to have been removed under general anesthesia. Chronic otorrhea, granuloma formation, tube nonfunction due to blockage, and migration of the tube into the middle ear constituted the surgical indications in 75 cases. The remaining 56 tubes were removed on the physicians' judgment that artificial ventilation was no longer required. Selected cases are presented. While the vast majority of tubes spontaneously extrude uneventfully, a comparatively small number of patients do require operative tube removal. Practice guidelines for surgical tube removal are suggested. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP CUNNINGHAM, MJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 15 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 1993 VL 103 IS 6 BP 659 EP 662 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA LG818 UT WOS:A1993LG81800014 PM 8502099 ER PT J AU WEISSKOFF, RM COHEN, MS RZEDZIAN, RR AF WEISSKOFF, RM COHEN, MS RZEDZIAN, RR TI NONAXIAL WHOLE-BODY INSTANT IMAGING SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE FAST MRI; ECHO PLANAR; DYNAMIC SCANNING; ARTIFACTS ID MAGNETIC-RESONANCE AB We demonstrate that whole-body, single-shot imaging is practical for imaging out of the central plane, including oblique axes. The technique is illustrated by images of the heart in the cardiac long- and short-axis and by coronal images of the brain. Secondary gradients can produce additional image distortion and ghosting in these images. These artifacts are a direct consequence, predictable by Maxwell's equations, of the large gradients used in echo planar imaging. We show that these effects are, in general, made smaller by working at a high magnetic field. C1 ADV NMR SYST INC,WILMINGTON,MA. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP WEISSKOFF, RM (reprint author), MASSACHUSETTS GEN HOSP,CTR MGH NMR,DEPT RADIOL,2ND FLOOR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NCI NIH HHS [5P01-CA48729, CA54886] NR 22 TC 29 Z9 29 U1 0 U2 0 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 1993 VL 29 IS 6 BP 796 EP 803 DI 10.1002/mrm.1910290612 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LF393 UT WOS:A1993LF39300011 PM 8350723 ER PT J AU GARRIDO, L PFLEIDERER, B PAPISOV, M ACKERMAN, JL AF GARRIDO, L PFLEIDERER, B PAPISOV, M ACKERMAN, JL TI INVIVO DEGRADATION OF SILICONES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE SILICONES; DEGRADATION; NMR ID BREAST IMPLANTS; GEL PROSTHESES; SI-29 NMR; TISSUE; MODEL AB Si-29 nuclear magnetic resonance (NMR) spectroscopy is applied to study the degradation of polysiloxanes (silicones) in vivo. Our results with animal models show that silicone migrates from the implant to the liver (Si-29 resonance at -20 ppm) and new silicon containing compounds form after the silicones are introduced into the rats. The new Si-29 resonances in the chemical shift range of -40 to -85 ppm are related to hydrolyzed silicone, those at -90 to -115 ppm are indicative of the presence of silica (SiO2), and the peaks observed at -120 to -150 are related to high coordinated silicon complexes. These resonances are not present in the Si-29 spectra of the silicones before implantation. Our findings demonstrate that silicones are not metabolically inert. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GARRIDO, L (reprint author), MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,149 13TH ST,BOSTON,MA 02129, USA. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 NR 27 TC 71 Z9 71 U1 2 U2 6 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 1993 VL 29 IS 6 BP 839 EP 843 DI 10.1002/mrm.1910290620 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LF393 UT WOS:A1993LF39300019 PM 8350731 ER PT J AU HAFFNER, SM BAUER, RL AF HAFFNER, SM BAUER, RL TI THE ASSOCIATION OF OBESITY AND GLUCOSE AND INSULIN CONCENTRATIONS WITH BONE-DENSITY IN PREMENOPAUSAL AND POSTMENOPAUSAL WOMEN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID MEXICAN-AMERICANS; DIABETES-MELLITUS; RISK; BODY; MASS C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. FU NHLBI NIH HHS [R01 HL24799, R37 HL36820]; NIAMS NIH HHS [R01 AR39794] NR 24 TC 60 Z9 62 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 1993 VL 42 IS 6 BP 735 EP 738 DI 10.1016/0026-0495(93)90241-F PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LG442 UT WOS:A1993LG44200012 PM 8510518 ER PT J AU TOMERA, JF LILFORD, K AF TOMERA, JF LILFORD, K TI MULTIPLE-REGRESSION OF SKELETAL-MUSCLE TENSION ON INOSITOL PHOSPHATES - CROSS-TALK BETWEEN SIGNAL-TRANSDUCTION MECHANISMS IN BURN TRAUMA SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE BURN TRAUMA; MULTIPLE REGRESSION; POLYINOSITOL PHOSPHATES; PYTHAGOREAN THEOREM; SIGNAL TRANSDUCTION SYSTEMS; SKELETAL MUSCLE; TENSION; VECTORIAL ANALYSIS AB Skeletal muscle weakness associated with burn trauma prolongs the time of rehabilitation of burn patients. Understanding the underlying chemical changes that impact on physiological tension may provide new therapeutic options for the treatment of burn patients. This report demonstrates the novelty of applying 3-dimensional graphic capabilities, involving area and vector changes to understand variations in inositol derivatives and their co-modulating influence on physiological tension in skeletal muscle. This muscle was distant from the primary anatomical burn site. It was subjected to circulatory shock emanating from burn trauma. Burn injury was achieved by scalding of predefined areas (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, tension studies via muscle twitch analyses were performed. Through multiple regression, the dependency of physiologic tension was determined with respect to three polyinositol forms each representing independent parameters simultaneously. The contribution of each of these parameters was assigned to a three-dimensional axis. Relationships of tension on three fixed independent parameters were found only for the 20% and 50% burn groups. Vector analysis on a plane in three-dimensional space determined the relationship of tension to each of the independent parameters in 20% and 50% burn groups. No significant relationship of tension dependency on three fixed polyinositol variables was found in the control group. Such vector analysis, using solid and differential analytical geometry, allowed for a clear visualization of the inter-relationships that existed between secondary messenger systems (viz, IP3) and a resulting physiologic manifestation (viz, tension). This clear visualization allows for a greater understanding of messenger systems that may lead to more effective treatment of skeletal muscle weakness associated with the systemic effects of severe burn trauma. C1 SHRINERS BURN INST, ANESTHESIA SERV, CLIN PHARMACOL LAB, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT ANESTHESIOL, BOSTON, MA 02115 USA. NR 15 TC 14 Z9 14 U1 0 U2 1 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD JUN PY 1993 VL 15 IS 5 BP 255 EP 265 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LQ371 UT WOS:A1993LQ37100001 PM 8412410 ER PT J AU CATLIN, EA MACLAUGHLIN, DT DONAHOE, PK AF CATLIN, EA MACLAUGHLIN, DT DONAHOE, PK TI MULLERIAN-INHIBITING SUBSTANCE - NEW PERSPECTIVES AND FUTURE-DIRECTIONS SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE UNDIFFERENTIATED GONADS; TESTOSTERONE; TESTICULAR INHIBITOR ID GROWTH FACTOR-BETA; OVARIAN FOLLICULAR-FLUID; BOVINE SERTOLI CELLS; FETAL-RAT LUNG; MONOCLONAL-ANTIBODY; TYROSINE KINASE; DUCT REGRESSION; GRANULOSA-CELLS; COLONY GROWTH; ADULT-RAT C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT SURG,PEDIAT SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,PEDIAT SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,PEDIAT SURG RES LAB,BOSTON,MA 02114. FU NCI NIH HHS [CA17393]; NHLBI NIH HHS [R29 HL HD46198-01] NR 79 TC 9 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 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD JUN 1 PY 1993 VL 25 IS 2 BP 121 EP 133 DI 10.1002/jemt.1070250205 PG 13 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA LB607 UT WOS:A1993LB60700004 PM 8518480 ER PT J AU LI, YP STASHENKO, P AF LI, YP STASHENKO, P TI CHARACTERIZATION OF A TUMOR NECROSIS FACTOR-RESPONSIVE ELEMENT WHICH DOWN-REGULATES THE HUMAN OSTEOCALCIN GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; RNA POLYMERASE-II; FACTOR-ALPHA; TRANSCRIPTION FACTOR; BONE-RESORPTION; COLLAGEN GENE; 1ST INTRON; EXPRESSION; ENHANCER; BINDING AB Tumor necrosis factor (TNF) down-regulates the production of bone matrix proteins by osteoblasts, thereby inhibiting bone formation. Osteocalcin, the major noncollagenous protein in bone, is inhibited by TNF at the transcriptional level. Mapping studies were undertaken to characterize the TNF-responsive element (TNFRE) in the osteocalcin promoter. Deletion analysis localized the TNFRE to the -522/-511 region, which contains a 9-bp palindromic motif (AGGCTGCCT). Promoter segments containing this sequence down-regulated a heterologous simian virus 40 promoter. Site-specific mutagenesis of the TNFRE eliminated TNF down-regulation. Mobility shift assays demonstrated that a constitutively expressed nuclear factor bound to the TNFRE; this factor was tentatively identified as the p50 homodimer of NF-kappaB. TNF stimulation induced a second TNFRE-binding protein which displaced the constitutive factor. The TNF-induced protein was not inhibitable by the NF-kappaB consensus sequence and was unreactive with anti-NF-kappaB antiserum. DNase footprinting demonstrated that both factors protected the -522/-501 portion of the promoter, consistent with the results of mapping studies and competitive mobility shift assays. It is hypothesized that the generalized catabolic activities of TNF in infectious and malignant diseases may be regulated via this novel element. C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,140 THE FENWAY,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-07378] NR 48 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3714 EP 3721 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300058 PM 8388544 ER PT J AU SEGARS, JH MARKS, MS HIRSCHFELD, S DRIGGERS, PH MARTINEZ, E GRIPPO, JF BROWN, M WAHLI, W OZATO, K AF SEGARS, JH MARKS, MS HIRSCHFELD, S DRIGGERS, PH MARTINEZ, E GRIPPO, JF BROWN, M WAHLI, W OZATO, K TI INHIBITION OF ESTROGEN-RESPONSIVE GENE ACTIVATION BY THE RETINOID-X RECEPTOR-BETA - EVIDENCE FOR MULTIPLE INHIBITORY PATHWAYS (VOL 13, PG 2258, 1993) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HOFFMANN LA ROCHE INC,DRUG METAB,NUTLEY,NJ 07110. UNIV LAUSANNE,INST BIOL ANIM,CH-1015 LAUSANNE,SWITZERLAND. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3840 EP 3840 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300072 ER PT J AU PENNATHUR, S MADISON, LD KAY, TWH JAMESON, JL AF PENNATHUR, S MADISON, LD KAY, TWH JAMESON, JL TI LOCALIZATION OF PROMOTER SEQUENCES REQUIRED FOR THYROTROPIN-RELEASING-HORMONE AND THYROID-HORMONE RESPONSIVENESS OF THE GLYCOPROTEIN HORMONE ALPHA-GENE IN PRIMARY CULTURES OF RAT PITUITARY-CELLS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SUBUNIT GENE; TRANSCRIPTION FACTOR; EXPRESSION; PLACENTA; RECEPTOR; ELEMENT; INHIBITION; REGIONS; PROTEIN; INVIVO AB The glycoprotein hormone alpha-gene is regulated by multiple hormones in different pituitary and placental cell types. In thyrotropes, the alpha-gene is stimulated by TRH and repressed by thyroid hormone (T3). We used transient expression assays in primary cultures of rat pituitary cells to examine regulation of the alpha-promoter (alphaLuc) by TRH and T3. The -846alpha Luc activity was stimulated 3.4-fold by TRH and repressed 44% by T3. GnRH and cAMP stimulated -846 alphaLuc by 8.3- and 8.6-fold, respectively. T3 blocked TRH stimulation, but it had no effect on stimulation by GnRH or cAMP, suggesting that the T3-mediated effects are thyrotrope specific. TRH and T3 responsiveness was preserved with deletions to -346 basepairs (bp). TRH responsiveness was lost after deletion to -280 bp, whereas T3-mediated repression was eliminated by further deletion to -180 bp. A series of DNA fragments between -420 and -180 was linked to -132 alphaLuc to study TRH and T3 responses in greater detail. Sequences between -346 to -180 bp conferred TRH responsiveness and T3 inhibition. TRH responsiveness was not seen after 3'-deletions of this fragment to -244 or -280 bp. These results together with the 5'-deletions provide evidence for two interdependent TRH regulatory regions: one between -346 to -280 bp and another between -244 to -180 bp. T3-dependent repression only requires sequences between -244 and -180 bp. Site-directed cluster mutations were created in each of these two regulatory domains. A mutation in region 1 (-346 to 7328 bp) eliminated TRH stimulation, but retained basal suppression by T3. A mutation in region 2 (-219 to -197 bp) eliminated TRH and T3 responsiveness. Both mutants still responded to cAMP. We conclude that TRH response elements are distinct from previously defined cAMP regulatory elements and involve two domains in the up-stream region of the alpha-promoter. The region between -219 and -197 bp forms a complex regulatory element that mediates positive regulation by TRH and negative regulation by T3. The sequences required for T3 repression in pituitary cells are distinct from the T3 receptor-binding site identified previously in the a-promoter adjacent to the TATA box, potentially reflecting a locus for thyrotrope-specific factors involved in T3 repression. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, THYROID UNIT, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD-28138]; NIDDK NIH HHS [DK-42144] NR 42 TC 33 Z9 33 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 1993 VL 7 IS 6 BP 797 EP 805 DI 10.1210/me.7.6.797 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL846 UT WOS:A1993LL84600009 PM 7689696 ER PT J AU MCLAUGHLIN, ME SANDBERG, MA BERSON, EL DRYJA, TP AF MCLAUGHLIN, ME SANDBERG, MA BERSON, EL DRYJA, TP TI RECESSIVE MUTATIONS IN THE GENE ENCODING THE BETA-SUBUNIT OF ROD PHOSPHODIESTERASE IN PATIENTS WITH RETINITIS-PIGMENTOSA SO NATURE GENETICS LA English DT Article ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; HUMAN RETINAL DEGENERATION; CGMP-PHOSPHODIESTERASE; PHOTORECEPTOR CELLS; GUANOSINE MONOPHOSPHATE; REVEALS SIMILARITIES; RHODOPSIN MUTATIONS; GMP ACCUMULATION; ALPHA-TRANSDUCIN; GAMMA-SUBUNIT AB We have found four mutations in the human gene encoding the beta-subunit of rod cGMP phosphodiesterase (PDE beta) that cosegregate with autosomal recessive retinitis pigmentosa, a degenerative disease of photoreceptors. In one family two affected siblings both carry allelic nonsense mutations at codons 298 and 531. Affected individuals have abnormal rod and cone electroretinograms. PDE beta is the second member of the phototransduction cascade besides rhodopsin that is absent or altered as a cause of retinitis pigmentosa, suggesting that other members of this pathway may be defective in other forms of this disease. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [EY00169, EY08683] NR 48 TC 393 Z9 401 U1 0 U2 7 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1993 VL 4 IS 2 BP 130 EP 134 DI 10.1038/ng0693-130 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA LF816 UT WOS:A1993LF81600010 PM 8394174 ER PT J AU BLUMENFELD, A SLAUGENHAUPT, SA AXELROD, FB LUCENTE, DE MAAYAN, C LIEBERT, CB OZELIUS, LJ TROFATTER, JA HAINES, JL BREAKEFIELD, XO GUSELLA, JF AF BLUMENFELD, A SLAUGENHAUPT, SA AXELROD, FB LUCENTE, DE MAAYAN, C LIEBERT, CB OZELIUS, LJ TROFATTER, JA HAINES, JL BREAKEFIELD, XO GUSELLA, JF TI LOCALIZATION OF THE GENE FOR FAMILIAL DYSAUTONOMIA ON CHROMOSOME-9 AND DEFINITION OF DNA MARKERS FOR GENETIC DIAGNOSIS SO NATURE GENETICS LA English DT Article ID NERVE GROWTH-FACTOR AB Familial dysautonomia (DYS), the Riley-Day syndrome, is an autosomal recessive disorder characterized by developmental loss of neurons from the sensory and autonomic nervous system. It is limited to the Ashkenazi Jewish population, where the carrier frequency is 1 in 30. We have mapped the DYS gene to chromosome 9q31-q33 by linkage with ten DNA markers in 26 families. The maximum lod score of 21.1 with no recombinants was achieved with D9S58. This marker also showed strong linkage disequilibrium with DYS, with one allele present on 73% of affected chromosomes compared to 5.4% of controls (chi2=3142, 15 d.f. p<0.0001). D9S53 and D9S105 represent the closest flanking markers for the disease gene. This localization will permit prenatal diagnosis of DYS in affected families and aid the isolation of the disease gene. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. HADASSAH UNIV HOSP,DEPT PEDIAT,JERUSALEM,ISRAEL. NYU,SCH MED,DEPT PEDIAT,NEW YORK,NY 10017. RI Haines, Jonathan/C-3374-2012 NR 31 TC 124 Z9 122 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1993 VL 4 IS 2 BP 160 EP 164 DI 10.1038/ng0693-160 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA LF816 UT WOS:A1993LF81600016 PM 8102296 ER PT J AU BAXENDALE, S MACDONALD, ME MOTT, R FRANCIS, F LIN, C KIRBY, SF JAMES, M ZEHETNER, G HUMMERICH, H VALDES, J COLLINS, FS DEAVEN, LJ GUSELLA, JF LEHRACH, H BATES, GP AF BAXENDALE, S MACDONALD, ME MOTT, R FRANCIS, F LIN, C KIRBY, SF JAMES, M ZEHETNER, G HUMMERICH, H VALDES, J COLLINS, FS DEAVEN, LJ GUSELLA, JF LEHRACH, H BATES, GP TI A COSMID CONTIG AND HIGH-RESOLUTION RESTRICTION MAP OF THE 2 MEGABASE REGION CONTAINING THE HUNTINGTONS-DISEASE GENE SO NATURE GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; REFERENCE LIBRARIES; RECOMBINATION; D4S10; LOCALIZATION; CHROMOSOME-4; ASSOCIATION; TELOMERE; SEGMENT; MARKER AB The quest for the mutation responsible for Huntington's disease (HD) has required an exceptionally detailed analysis of a large part of 4p16.3 by molecular genetic techniques, making this stretch of 2.2 megabases one of the best characterized regions of the human genome. Here we describe the construction of a cosmid and Pl clone contig spanning the region containing the HD gene, and the establishment of a detailed, high resolution restriction map. This ordered clone library has allowed the identification of several genes from the region, and has played a vital role in the recent identification of the Huntington's disease gene. The restriction map provides the framework for the detailed analysis of a region extremely rich in coding sequences. This study also exemplifies many of the strategies to be used in the analysis of larger regions of the human genome. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. UNIV MICHIGAN,DEPT INTERNAL MED & HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. RP BAXENDALE, S (reprint author), IMPERIAL CANC RES FUND,GENOME ANAL LAB,44 LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. RI Bates, Gillian/E-1146-2012; Francis, Fiona/B-5854-2016 OI Bates, Gillian/0000-0002-4041-6305; FU NHGRI NIH HHS [HG00169]; NINDS NIH HHS [NS16367] NR 53 TC 73 Z9 73 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1993 VL 4 IS 2 BP 181 EP & DI 10.1038/ng0693-181 PG 0 WC Genetics & Heredity SC Genetics & Heredity GA LF816 UT WOS:A1993LF81600020 PM 8348156 ER PT J AU CHENG, JM HIEMSTRA, JL SCHNEIDER, SS NAUMOVA, A CHEUNG, NKV COHN, SL DILLER, L SAPIENZA, C BRODEUR, GM AF CHENG, JM HIEMSTRA, JL SCHNEIDER, SS NAUMOVA, A CHEUNG, NKV COHN, SL DILLER, L SAPIENZA, C BRODEUR, GM TI PREFERENTIAL AMPLIFICATION OF THE PATERNAL ALLELE OF THE N-MYC GENE IN HUMAN NEUROBLASTOMAS SO NATURE GENETICS LA English DT Article ID HUMAN NEURO-BLASTOMA; RETINOBLASTOMA; METHYLATION; ONCOGENE; DNA; TUMOR AB Genomic imprinting plays a role in influencing the parental origin of genes involved in cancer-specific rearrangements. We have analysed 22 neuroblastomas with N-myc amplification to determine the parental origin of the amplified N-myc allele and the allele that is deleted from chromosome 1 p. We analysed DNA from neuroblastoma patients and their parents, using four polymorphisms for 1 p and three for the N-myc amplicon. We determined that the paternal allele of N-myc was preferentially amplified (1 2 out of 13 cases; P = 0.002). However, the paternal allele was lost from 1 p in six out of ten cases, consistent with a random distribution (P > 0.2). These results suggest that parental imprinting influences which N-myc allele is amplified in neuroblastomas, but it does not appear to affect the 1 p allele that is deleted in the cases that we have examined. C1 LUDWIG INST CANC RES,SAN DIEGO,CA 92093. PEDIAT ONCOL GRP,ST LOUIS,MO 63110. MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,NEW YORK,NY 10021. CHILDRENS MEM HOSP,DEPT PEDIAT,CHICAGO,IL 60614. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. RP CHENG, JM (reprint author), WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110, USA. RI Reiter, Jill/J-3335-2013; OI Reiter, Jill/0000-0001-5460-2355; Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [CA-05887, CA-39771, CA-01027] NR 50 TC 58 Z9 58 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1993 VL 4 IS 2 BP 191 EP 194 DI 10.1038/ng0693-191 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA LF816 UT WOS:A1993LF81600022 PM 8102299 ER PT J AU ZINYK, DL MCGONNIGAL, BG DEAROLF, CR AF ZINYK, DL MCGONNIGAL, BG DEAROLF, CR TI DROSOPHILA AWDK-PN, A HOMOLOG OF THE METASTASIS SUPPRESSOR GENE-NM23, SUPPRESSES THE TUM-I HEMATOPOIETIC ONCOGENE SO NATURE GENETICS LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; GENE; MELANOGASTER; NM23; LETHAL; ASSOCIATION; EXPRESSION; MUTATIONS; PROTEIN; CANCER AB The human nm23-H1 gene is a suppressor of solid tumour metastasis in some types of cancer. It is known that nm23 genes encode nucleoside diphosphate kinase polypeptides, but the regulatory pathways involving Nm23 are unclear. One approach to understanding nm23 function is to identify loci which interact with nm23. The Drosophila awd gene, a homologue of nm23, provides a model system for this genetic analysis. We report that the dominant awd(K-pn) allele suppresses haematopoietic defects associated with the Tum-I oncogene. Premature differentiation and aggregation of Tum-I blood cells is reduced by awd(K-pn), resulting in an increased survival of Tum-I hemizygotes. Tum-I lethality is also suppressed by pn mutations, indicating the existence of a haematopoietic regulatory pathway involving the Tum-I, Awd(K-pn) and Pn proteins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEV GENET FARBER,ROOM JF225,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. NR 42 TC 35 Z9 35 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1993 VL 4 IS 2 BP 195 EP 201 DI 10.1038/ng0693-195 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA LF816 UT WOS:A1993LF81600023 PM 8394175 ER PT J AU MOSKOWITZ, MA AF MOSKOWITZ, MA TI NEUROGENIC INFLAMMATION IN THE PATHOPHYSIOLOGY AND TREATMENT OF MIGRAINE SO NEUROLOGY LA English DT Article ID IMMEDIATE-EARLY GENES; VASCULAR HEAD PAIN; FOS-LIKE PROTEIN; RAT SPINAL-CORD; DURA-MATER; C-FOS; SUBSTANCE-P; PLASMA EXTRAVASATION; BLOOD-VESSELS; ELECTRICAL-STIMULATION AB The trigeminal nerve transmits headache pain from blood vessels of the pia mater and dura mater. Triggers for this pain are not well understood, but probably are multiple and largely chemical and develop within the brain parenchyma, the blood vessel wall, and the blood itself. These unknown triggers stimulate the trigeminovascular axons, causing pain and releasing vasoactive neuropeptides from perivascular axons. Released neuropeptides activate endothelial cells, mast cells, and platelets to then increase extracellular levels of amines, arachidonate metabolites, peptides, and ions. Hyperalgesia and prolongation of pain develop as a consequence, mediated by products from activated cells and injured tissue. Within postsynaptic brain stem neurons of the trigeminal nucleus caudalis, trigeminovascular activation stimulates the expression of an early immediate response gene c-fos. Both neurogenic inflammation and c-fos expression are blocked by sumatriptan and ergot alkaloids via prejunctional mechanisms involving putative 5-HT receptors closely related to the 5-HT1D subtype on trigeminovascular fibers. The mechanisms of action of sumatriptan and ergot alkaloids decribed herein are unrelated to the nature of the migraine trigger or to the contractile state of vascular smooth muscle. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,STROKE RES LAB,BOSTON,MA 02114. RP MOSKOWITZ, MA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,PROGRAM NEUROSURG,STROKE RES LAB,BOSTON,MA 02114, USA. RI Moskowitz, Michael/D-9916-2011 NR 43 TC 127 Z9 130 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 1993 VL 43 IS 6 SU 3 BP 16 EP 20 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA LG858 UT WOS:A1993LG85800004 ER PT J AU LEVIN, JM SCHIFF, D LOEFFLER, JS FINE, HA BLACK, PM WEN, PY AF LEVIN, JM SCHIFF, D LOEFFLER, JS FINE, HA BLACK, PM WEN, PY TI COMPLICATIONS OF THERAPY FOR VENOUS THROMBOEMBOLIC DISEASE IN PATIENTS WITH BRAIN-TUMORS SO NEUROLOGY LA English DT Article ID INFERIOR VENA-CAVA; PULMONARY-EMBOLISM; ANTICOAGULANT-THERAPY; INTRACRANIAL HEMORRHAGE; THROMBOSIS; FILTER; MANAGEMENT; GLIOMAS; RISK AB Venous thromboembolic disease is a frequent complication in patients with intracranial malignancies. Because these patients are often perceived to be at increased risk of intracranial hemorrhage with anticoagulation, inferior vena cava (IVC) filters are frequently used in their treatment. We reviewed the records of 49 patients with intracranial malignancies and venous thromboembolic disease to determine the effectiveness of, and the complications resulting from, treatment. Of the 42 patients receiving IVC filters, a strikingly high percentage (62%) developed complications. Twelve percent developed recurrent pulmonary embolism, while 57% developed either IVC or filter thrombosis, recurrent deep venous thrombosis, or post-phlebitic syndrome. These complications severely reduced the quality of life of the affected patients. Only 15 of our patients were treated with anticoagulation, and seven of these received it because of continued thromboembolic disease. None of these 15 patients had proven hemorrhagic complications. This study suggests that the complication rate of IVC filters in patients with brain tumors is higher than commonly perceived and may outweigh the risk of anticoagulation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP WEN, PY (reprint author), BRIGHAM & WOMENS HOSP,DIV NEUROL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K11 CAO1492] NR 24 TC 93 Z9 97 U1 1 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 1993 VL 43 IS 6 BP 1111 EP 1114 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA LG421 UT WOS:A1993LG42100013 PM 8170553 ER PT J AU CARLISON, S COLES, W COSTIGAN, D CURTIS, L HEDAYA, E KLEMENTS, D MEREDITH, T STERNBERG, P SWORDS, R BELT, J CORNBLATH, D GEORGOPOULIS, A GRIFFIN, J MURPHY, R RYTEL, D SAUDEK, C CARL, J CIATTO, P DATILES, M KUEHL, E KUPFER, C LEE, J ROY, M AIELLO, L BEASER, R BELL, A CAVICCHI, R COOPAN, R DELFS, J DUNN, F MALOBERTI, M RAND, L SHAH, S TARSY, D VIGNATI, L DOBSON, H GARCIA, C JACKSON, J KEICHIAN, A MATHENY, G ORZECK, E ROONGTA, S RUSSELL, S TULLOCH, B BARR, C BROADSTONE, V BROOKS, S CYRUS, J FUQUA, M HECK, M HEINICKE, H MAHL, L MILLERCRAIN, G PFEIFER, M SAMOLS, E WILLHITE, J DAVIS, M EHRLICH, E EICHMAN, P FLAX, M HARRISON, R KNUTSON, G LEWIS, B LYNGAAS, H MYERS, F NEIDER, M QUACKENBOSS, D SOMERS, G WAGE, M ZACKMAN, S COOMBS, G DOELLE, GC GOTTSCHALK, P HAFERMAN, M KARANJIA, P MCKENZIE, A MASON, CM MATTSON, D MILLER, R NIKOLAI, T WEIR, J BAKER, P FRANKLIN, R FRANKLIN, S GARCIA, C MUELLER, T PARKER, T PENNELL, D ROTHSCHILD, H BIESBROECK, R CHENOWETH, R DIEHL, L DREYER, R GRIMM, R HARE, R LINN, M PAGE, O SMITH, B STEPHENS, J WILSON, R CLARKE, D FORD, K NORD, N TOMKY, D WEINRAUCH, S GODDU, K LESKO, V MEHTA, DJ MUNSTER, E MYERS, R PETERSON, M KUPFER, C SEIGEL, D AF CARLISON, S COLES, W COSTIGAN, D CURTIS, L HEDAYA, E KLEMENTS, D MEREDITH, T STERNBERG, P SWORDS, R BELT, J CORNBLATH, D GEORGOPOULIS, A GRIFFIN, J MURPHY, R RYTEL, D SAUDEK, C CARL, J CIATTO, P DATILES, M KUEHL, E KUPFER, C LEE, J ROY, M AIELLO, L BEASER, R BELL, A CAVICCHI, R COOPAN, R DELFS, J DUNN, F MALOBERTI, M RAND, L SHAH, S TARSY, D VIGNATI, L DOBSON, H GARCIA, C JACKSON, J KEICHIAN, A MATHENY, G ORZECK, E ROONGTA, S RUSSELL, S TULLOCH, B BARR, C BROADSTONE, V BROOKS, S CYRUS, J FUQUA, M HECK, M HEINICKE, H MAHL, L MILLERCRAIN, G PFEIFER, M SAMOLS, E WILLHITE, J DAVIS, M EHRLICH, E EICHMAN, P FLAX, M HARRISON, R KNUTSON, G LEWIS, B LYNGAAS, H MYERS, F NEIDER, M QUACKENBOSS, D SOMERS, G WAGE, M ZACKMAN, S COOMBS, G DOELLE, GC GOTTSCHALK, P HAFERMAN, M KARANJIA, P MCKENZIE, A MASON, CM MATTSON, D MILLER, R NIKOLAI, T WEIR, J BAKER, P FRANKLIN, R FRANKLIN, S GARCIA, C MUELLER, T PARKER, T PENNELL, D ROTHSCHILD, H BIESBROECK, R CHENOWETH, R DIEHL, L DREYER, R GRIMM, R HARE, R LINN, M PAGE, O SMITH, B STEPHENS, J WILSON, R CLARKE, D FORD, K NORD, N TOMKY, D WEINRAUCH, S GODDU, K LESKO, V MEHTA, DJ MUNSTER, E MYERS, R PETERSON, M KUPFER, C SEIGEL, D TI THE SORBINIL RETINOPATHY TRIAL - NEUROPATHY RESULTS SO NEUROLOGY LA English DT Article ID PAINFUL DIABETIC NEUROPATHY; ALDOSE REDUCTASE INHIBITOR; NERVE-CONDUCTION; COMPLICATIONS AB We randomized 497 patients, aged 18 to 56 years with insulin-dependent diabetes mellitus for 1 to 15 years' duration, to treatment with sorbinil, an aldose reductase inhibitor, or to a placebo. Nearly 30% of patients showed worsening of clinical measures of distal symmetric polyneuropathy at maximum follow-up, with very little difference in rates in the two groups. We studied nerve conduction in 192 patients. For the median motor, median sensory, and peroneal nerves, there were no benefits in maximum amplitudes over the follow-up period. For the median motor and median sensory nerves, changes in velocities were not significantly different in the two randomized treatment groups. For the peroneal nerve, at the 30-month and maximum follow-up visits, the distribution of changes in nerve conduction velocity showed an overall improvement in the sorbinil group and a decline in the placebo group. The difference in distributions was statistically significant. Overall, we found no evidence that the early clinical signs and symptoms of diabetic neuropathy were altered by sorbinil. C1 NEI,316A10,BETHESDA,MD 20892. EMORY UNIV CLIN,DEPT OPHTHALMOL,ATLANTA,GA 30322. JOHNS HOPKINS UNIV HOSP,WILMER INST,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOSLIN DIABET CTR,WILLIE P BEETHAM EYE UNIT,BOSTON,MA. HERMAN EYE CTR,DIABET UNIT,HOUSTON,TX. VET ADM MED CTR,LOUISVILLE,KY 40202. UNIV WISCONSIN,MADISON,WI 53706. MARSHFIELD CLIN FDN MED RES & EDUC,MARSHFIELD,WI. LOUISIANA STATE UNIV,CTR EYE,NEW ORLEANS,LA. GOOD SAMARITAN HOSP,DEPT OPHTHALMOL,PORTLAND,OR 97210. DIABET HLTH CTR,SALT LAKE CITY,UT. PFIZER INC,CENT RES,GROTON,CT 06340. NR 28 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1993 VL 43 IS 6 BP 1141 EP 1149 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA LG421 UT WOS:A1993LG42100019 ER PT J AU FRIM, DM YEE, WM ISACSON, O AF FRIM, DM YEE, WM ISACSON, O TI NGF REDUCES STRIATAL EXCITOTOXIC NEURONAL LOSS WITHOUT AFFECTING CONCURRENT NEURONAL STRESS SO NEUROREPORT LA English DT Article DE CELLULAR STRESS; EXCITOTOXICITY; GENETICALLY ALTERED CELLS; HEAT SHOCK PROTEIN; IMMUNOCYTOCHEMISTRY; NEUROPROTECTION; NGF; QUINOLINIC ACID; RAT STRIATUM ID NERVE GROWTH-FACTOR; HEAT-SHOCK PROTEIN; EXCITATORY AMINO-ACIDS; BRAIN; RATS AB NERVE growth factor (NGF) has protective effects against striatal excitotoxic injury in the adult brain. To begin to define the mechanism of NGF-mediated sparing, we sought to determine the effects of biologically delivered NGF on the degree of neuronal stress and the development of excitotoxic lesions in the rat striatum. Immortalized fibroblasts genetically altered to secrete NGF (NGF[+]) or control fibroblasts (NGF[-]) were stereotactically implanted near the striatum 7 d before striatal infusion of an NMDA-receptor agonist. Two days after excitotoxin infusion, the volume of neuronal loss was reduced by 34% (p < 0.001) in the NGF[+] group when compared to the NGF[-] group; however, there was no difference in the volume of 72 kD heat shock protein (HSP72) immunoreactivity expressed in the two groups after 2 d. The final volumes of neuronal loss at 10 d were significantly greater than seen at 2 d, with the volume of neuronal loss in the NGF[+] group reduced by 20% (p < 0.004) when compared to the NGF[-] group. Interestingly, the volume of neuronal loss at 10 d in the NGF[-] group, but not the NGF[+] group, closely approximated the HSP72 immunoreactive volumes seen at 2 d. These results suggest that the cell stress marker, HSP72, is predictive of neuronal loss after striatal excitotoxic insult and while NGF treatment does not alter.the overall HSP72 response, it significantly reduces subsequent neuronal loss. We conclude that NGF-mediated neuroprotective mechanisms alter neuronal response to injury without affecting the primary cell stress response to NMDA-receptor activation. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. JOHNS HOPKINS UNIV,PROGRAM NEUROSURG,BALTIMORE,MD 21218. MCLEAN HOSP,NEUROREGENERAT LAB,MRC 119,BELMONT,MA 02178. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. FU NINDS NIH HHS [NINDS 5 T32 NS07340-03, NS 29178, NS 30064] NR 20 TC 35 Z9 35 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN PY 1993 VL 4 IS 6 BP 655 EP 658 DI 10.1097/00001756-199306000-00013 PG 4 WC Neurosciences SC Neurosciences & Neurology GA LH479 UT WOS:A1993LH47900013 PM 7688588 ER PT J AU NISHIZAWA, S PETERSON, JW SHIMOYAMA, I IWASAKI, K UEMURA, K WEIR, BK CHYATTE, D AF NISHIZAWA, S PETERSON, JW SHIMOYAMA, I IWASAKI, K UEMURA, K WEIR, BK CHYATTE, D TI THERAPEUTIC EFFECT OF A NEW IMMUNOSUPPRESSANT, FK-506, ON VASOSPASM AFTER SUBARACHNOID HEMORRHAGE SO NEUROSURGERY LA English DT Article DE IMMUNOLOGICAL REACTION; IMMUNOSUPPRESSANT; SUBARACHNOID HEMORRHAGE; VASOSPASM ID EXPERIMENTAL CEREBRAL VASOSPASM; CANINE LUNG TRANSPLANTATION; BEAGLE DOG; CYCLOSPORINE; FK506; INVITRO; METHYLPREDNISOLONE; INVIVO; MODEL AB WE HYPOTHESIZED THAT the immunological reaction against extravasated blood might play a role in the development of vasospasm after subarachnoid hemorrhage. Under the hypothesis, we had reported significant therapeutic efficacy of cyclosporin A on vasospasm in canine models. We here investigated the efficacy of a new, potent immunosuppressant, FK-506, on vasospasm in animal models. Dogs were randomly classified into sham operated, subarachnoid hemorrhage treated-1 group, (FK-506, 0.3 mg/kg.d, intramuscular injection), and treated-2 group (FK-506, 0.15 mg/kg.d, intramuscular injection). Levels of the third factor of complement (C3) and the activity of serum complement inducing 50% hemolysis of sheep erythrocytes (CH50) in serum were also determined. In the treated groups, the levels of FK-506 in serum were monitored. As for C3 and CH50, there were no statistically significant differences among the groups and there were no changes between Day 1 and Day 7 in any group. Angiographical diameters of a basilar artery on Days 1 and 7 were measured with a computed image analyzer, and the extent of vasospasm was compared among the groups. Statistically significant differences between the sham-operated group and the other three groups were noted. However, under sufficient levels of FK-506 in serum, the extent of vasospasm in either treated group was the same as that in the subarachnoid hemorrhage group. These results indicate a significant discrepancy in the therapeutic mechanism for vasospasm between cyclosporin A and FK-506. They have common aspects in the immunosuppressive mechanism. However, in T-cell suppression, the different mechanism in situ between the two drugs is also postulated. The different pharmacological mechanism would lead to a completely different result. This difference suggests to us that the immunological response suppressed by cyclosporin A might play a pivotal role in the development of vasospasm, although the response suppressed by FK-506 may not. C1 MASSACHUSETTS GEN HOSP, CEREBROVASC BIOPHYS LAB, BOSTON, MA 02114 USA. RP NISHIZAWA, S (reprint author), HAMAMATSU UNIV SCH MED, DEPT NEUROSURG, 3600 HANDACHO, HAMAMATSU, SHIZUOKA 43131, JAPAN. NR 32 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1993 VL 32 IS 6 BP 986 EP 992 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LE907 UT WOS:A1993LE90700018 PM 7687044 ER PT J AU GALL, KP VERHEY, L ALONSO, J CASTRO, J COLLIER, JM CHU, W DAFTARI, I GOITEIN, M KUBO, H LUDEWIGT, B MUNZENRIDER, J PETTI, P RENNER, T ROSENTHAL, S SMITH, A STAPLES, J SUIT, H THORNTON, A AF GALL, KP VERHEY, L ALONSO, J CASTRO, J COLLIER, JM CHU, W DAFTARI, I GOITEIN, M KUBO, H LUDEWIGT, B MUNZENRIDER, J PETTI, P RENNER, T ROSENTHAL, S SMITH, A STAPLES, J SUIT, H THORNTON, A TI STATE-OF-THE-ART - NEW PROTON MEDICAL FACILITIES FOR THE MASSACHUSETTS-GENERAL-HOSPITAL AND THE UNIVERSITY-OF-CALIFORNIA-DAVIS MEDICAL-CENTER SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 12TH INTERNATIONAL CONF ON THE APPLICATION OF ACCELERATORS IN RESEARCH AND INDUSTRY CY NOV 02-05, 1992 CL UNIV N TEXAS, DENTON, TX SP US DOE, NATL SCI FDN, OAK RIDGE ASSOC UNIV, UNIV N TEXAS HO UNIV N TEXAS C1 LAWRENCE BERKELEY LAB,BERKELEY,CA 94720. UNIV CALIF DAVIS,SACRAMENTO MED CTR,MED CTR,DEPT RADIAT ONCOL,SACRAMENTO,CA 95817. UNIV CALIF SAN FRANCISCO,DEPT RADIAT ONCOL,SAN FRANCISCO,CA 94143. RP GALL, KP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD JUN PY 1993 VL 79 IS 1-4 BP 881 EP 884 DI 10.1016/0168-583X(93)95490-V PG 4 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA LH984 UT WOS:A1993LH98400224 ER PT J AU GOFF, BA MUELLER, PR MUNTZ, HG RICE, LW AF GOFF, BA MUELLER, PR MUNTZ, HG RICE, LW TI SMALL CHEST-TUBE DRAINAGE FOLLOWED BY BLEOMYCIN SCLEROSIS FOR MALIGNANT PLEURAL EFFUSIONS SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRACAVITARY BLEOMYCIN; INTRAPLEURAL TETRACYCLINE; CORYNEBACTERIUM-PARVUM; CATHETER DRAINAGE; MANAGEMENT; SPACE AB Objective: To review our experience with bleomycin sclerotherapy as treatment of pleural effusions due to gynecologic malignancies. Methods: Twenty-one women with histologically documented malignant effusions (16 ovarian carcinoma, three uterine sarcoma, and two cervical cancer) were treated with small flexible chest-tube drainage followed by intrapleural bleomycin sclerotherapy (60 units). Results: After placement of the chest tube, suction was required for a median of 5 days (range 3-12) before output was low enough (less than 100 mL/24 hours) to instill bleomycin. Among 24 treated effusions, there was a 71% overall response rate, including ten complete responses (42%) and seven partial responses (29%); seven effusions (29%) did not respond to therapy. Six of the seven patients whose effusions did not respond to bleomycin died of disease within 2 months of attempted sclerotherapy. Fever was the most common side effect, occurring in 13 of 21 patients (62%) following instillation of bleomycin. Pain during sclerosis was reported by only two patients. Conclusion: Bleomycin sclerotherapy after small flexible chest-tube drainage of malignant pleural effusions is an effective technique, with minimal adverse reactions, for controlling effusions that develop in women with gynecologic malignancies. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. RP GOFF, BA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM GYNECOL ONCOL SERV,VINCENT 1,55 FRUIT ST,BOSTON,MA 02114, USA. NR 31 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 1993 VL 81 IS 6 BP 993 EP 996 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LD169 UT WOS:A1993LD16900018 PM 7684517 ER PT J AU TSAI, LH LEES, E FAHA, B HARLOW, E RIABOWOL, K AF TSAI, LH LEES, E FAHA, B HARLOW, E RIABOWOL, K TI THE CDK2 KINASE IS REQUIRED FOR THE G1-TO-S TRANSITION IN MAMMALIAN-CELLS SO ONCOGENE LA English DT Article ID P34CDC2 PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; FISSION YEAST; CYCLIN-A; SCHIZOSACCHAROMYCES-POMBE; PHOSPHORYLATION SITES; CDC28 MUTATION; G1 PHASE; GENE; MITOSIS AB In the cell cycle of fission and budding yeast, the p34cdc2/cDC28 kinase is required for both the G1-to-S and G2-to-M phase transitions. In vertebrates, the homologous p34cdc2 kinase is required for G2-to-M phase transitions but appears to be dispensible for DNA synthesis. We have investigated the function of a related kinase, p33cdk2, using serum-stimulated quiescent human fibroblasts. While the p33cdk2 protein was expressed at constant levels throughout the cell cycle, p33cdk2 kinase activity was first detected a few hours prior to the onset of DNA synthesis. Microinjection of anti-p33cdk2 antibodies blocked cells from entering S phase. Pre-adsorbtion of these antibodies with cdk2 protein abrogated their blocking effect suggesting that the G1 arrest caused by these antibodies is cdk2-specific. These results indicate that p33cdk2 is required for the G1-to-S phase transition in mammalian cells. We also show evidence to suggest that the cyclin E/p33cdk2 complex is likely to be required for entry into S phase since the timing of the cyclin E-associated kinase activity was coincident with that of p33cdk2 and preclearing of either component abolished the majority of the histone H1 kinase activity present in the lysates harvested from the late G1. C1 UNIV CALGARY,SO ALBERTA CANC RES CTR,DEPT MED BIOCHEM,CALGARY T2N 1N4,ALBERTA,CANADA. RP TSAI, LH (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA55339] NR 64 TC 311 Z9 314 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1993 VL 8 IS 6 BP 1593 EP 1602 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LE064 UT WOS:A1993LE06400023 PM 8502482 ER PT J AU FOSTER, CS BARRETT, F AF FOSTER, CS BARRETT, F TI CATARACT DEVELOPMENT AND CATARACT-SURGERY IN PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS-ASSOCIATED IRIDOCYCLITIS SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE AMERICAN ACADEMY OF OPHTHALMOLOGY CY NOV, 1992 CL DALLAS, TX SP AMER ACAD OPHTHALMOL ID ANTERIOR UVEITIS; EXTRACTION AB Purpose: The authors used an aggressive stepladder, steroid-sparing, therapeutic algorithm in the care of patients with iridocyclitis associated with juvenile rheumatoid arthritis (JRA) to preserve vision, limit cataract formation, and improve probability of successful visual rehabilitation when cataract surgery became necessary. Methods: The authors treated 60 patients with JRA-associated iridocyclitis with topical and regional corticosteroids, systemic nonsteroidal anti-inflammatory drugs, systemic steroids, and systemic immunosuppressive chemotherapy to achieve total quiescence of intraocular inflammation. Cataract surgery (phacoemulsification extracapsular cataract extraction) combined with pars plana vitrectomy was performed on those eyes with cataract sufficient to limit visual acuity to 20/200 or less, after maintenance of complete freedom from inflammation for at least 3 months. The incidence of cataract development and the visual outcome of cataract surgery were analyzed in those patients for whom a minimum follow-up of 1 year was available. Results: Eventually, 10 of the 60 patients required systemic immunosuppressive chemotherapy in the stepladder therapeutic approach to achieve complete abolition of all active inflammation. Of 72 phakic eyes without cataract, significant cataract developed in 13 (18%) while under our care. The average postoperative stable visual acuity in this group was 20/40. Sixteen eyes of 12 additional patients had visually significant cataract at the time of our first evaluation of them. The average postoperative stable visual acuity in this group of patients after cataract surgery was 20/40. Conclusions: Iridocyclitis associated with JRA is an insidiously blinding disease, with 12% of individuals affected by this problem eventually blinded by the inflammatory consequences to the eye. A therapeutic philosophy of complete intolerance for active inflammation and limited tolerance for chronic steroid use may offer the most realistic hope for the next step in progress to prevent blindness in this patient population. The results of this study suggest that such a therapeutic attitude results in diminished cataract prevalence and decreased prevalence of vision-limiting retinal pathology, with resultant improved visual outcome of the cataract surgery which is eventually needed in a small proportion of the patients. RP FOSTER, CS (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 42 TC 68 Z9 69 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1993 VL 100 IS 6 BP 809 EP 817 PG 9 WC Ophthalmology SC Ophthalmology GA LF413 UT WOS:A1993LF41300009 PM 8510892 ER PT J AU FRIENDLY, DS PARELHOFF, ES MCKEOWN, CA AF FRIENDLY, DS PARELHOFF, ES MCKEOWN, CA TI EFFECT OF SEVERING THE CHECK LIGAMENTS AND INTERMUSCULAR MEMBRANES ON MEDIAL RECTUS RECESSIONS IN INFANTILE ESOTROPIA SO OPHTHALMOLOGY LA English DT Article ID AXIAL LENGTH AB Background. The effect of severing the check ligaments and intermuscular membranes on the dose-response curve for medial rectus recessions in patients with infantile esotropia has not been previously studied by randomized assignment techniques using contemporary control and experimental groups and masked precautions. Methods: A prospective study of 1 01 patients was performed over an 8-year period. Patients were randomly assigned to either augmented or nonaugmented groups. In the former group, the medial check ligaments and intermuscular membranes were severed; in the latter group, no surgery was performed on the medial check ligaments or intermuscular membranes. Patients were postoperatively evaluated by an observer masked to group assignment. Results: No difference in response to surgery was observed between the two groups at the time of evaluation, which took place, on average, 6 to 7 months after surgery. Conclusion: Severing the check ligaments and intermuscular membranes on patients with infantile esotropia undergoing medial rectus recessions does not appear to affect the dose-response curve. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. RP FRIENDLY, DS (reprint author), CHILDRENS HOSP,NATL MED CTR,DEPT OPHTHALMOL,111 MICHIGAN NW,WASHINGTON,DC 20010, USA. NR 16 TC 2 Z9 2 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 1993 VL 100 IS 6 BP 945 EP 948 PG 4 WC Ophthalmology SC Ophthalmology GA LF413 UT WOS:A1993LF41300030 PM 8510910 ER PT J AU WIDER, TM YAGER, JS RITTENBERG, T HUGO, NE EHRLICH, HP AF WIDER, TM YAGER, JS RITTENBERG, T HUGO, NE EHRLICH, HP TI THE INHIBITION OF FIBROBLAST-POPULATED COLLAGEN LATTICE CONTRACTION BY HUMAN AMNIOTIC-FLUID - A CHRONOLOGICAL EXAMINATION SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SKIN WOUNDS; INVITRO AB The effect of human amniotic fluid on fetal wound healing remains to be fully elucidated and may lead to the isolation of factors that could modulate adult wound healing. This, study uses an in vitro model of wound contraction, the fibroblast-populated collagen lattice, to examine the effects of chronologically sampled human amniotic fluid on contraction of lattices composed of either human adult or fetal fibroblasts. This chronology has not been reported previously. Human amniotic fluid was obtained in a sterile fashion via amniocentesis from 120 different women at different time points in gestation, ranging from 13 to 24 weeks. At each time point of gestation, three to five samples were individually examined in duplicate sets. Only fluid from pregnancies deemed normal by amniocentesis was included. Contaminated specimens were discarded. Using Bell's protocol, lattices were constructed of acid-soluble rat tail collagen, growth medium, and either human adult fibroblasts or human fetal fibroblasts. Lattices contained 20% v/v human amniotic fluid. In the control lattices, phosphate-buffered saline replaced amniotic fluid in equal volumes. Area was measured at 24-hour intervals, and all tests were run in duplicate for each specimen. The mean area at each interval was computed for each gestational week examined. Data were analyzed for significance with ANOVA and Dunnett's t test against control. In the adult fibroblast lattice series, there is a statistically significant inhibition of contraction at endpoint with amniotic fluid from 14 (532 +/- 28 mm2), 20 (539 +/- 20 mm2), 21 (639 +/- 27 mm2), and 22 weeks (554 +/- 36 mm2) in gestation when compared with control (367 +/- 55 mm2)(p < 0.05). In the fetal fibroblast lattice series, there is a significant inhibition of lattice contraction with amniotic fluid from 20 (477 +/- 10 mm2) and 21 weeks (549 +/- 18 mm2) when compared with control (366 +/- 24 mm2)(p < 0.05). In both series, 21-week-old fluid produces the greatest inhibition of contraction, and significant inhibition of lattice contraction is evident by 24 hours. Fetal fibroblasts characteristically show a heightened ability to contract lattices in the presence of amniotic fluid when compared with adult fibroblasts. This study shows that human amniotic fluid of specific gestational age inhibits the ability of fibroblasts to organize a collagen matrix. Such findings corroborate earlier findings in some but not all animal models and demonstrate that human amniotic fluid has the capacity to modulate fetal wound repair. C1 COLUMBIA PRESBYTERIAN MED CTR,SHRINERS BURNS INST,DIV PLAST & RECONSTRUCT SURG,NEW YORK,NY 10032. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 22 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 1993 VL 91 IS 7 BP 1287 EP 1293 DI 10.1097/00006534-199306000-00015 PG 7 WC Surgery SC Surgery GA LF022 UT WOS:A1993LF02200015 PM 8497529 ER PT J AU PAYNE, G SHOELSON, SE GISH, GD PAWSON, T WALSH, CT AF PAYNE, G SHOELSON, SE GISH, GD PAWSON, T WALSH, CT TI KINETICS OF P56(LCK) AND P60(SRC) SRC HOMOLOGY-2 DOMAIN BINDING TO TYROSINE-PHOSPHORYLATED PEPTIDES DETERMINED BY A COMPETITION ASSAY OR SURFACE-PLASMON RESONANCE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOPLASMIC PROTEIN; SIGNAL TRANSDUCTION; KINASE; PP60C-SRC; ACTIVATION; SH2; TRANSFORMATION; PURIFICATION; ELEMENTS; TERMINUS AB Src homology 2 (SH2) domains are phosphotyrosine-binding modules found within various signal-transducing proteins. We have determined hy I-125 competition assay and surface plasmon resonance that the SH2 domains of Src and Lck bind to a variety of phosphopeptides with similar affinity and specificity. Both bound with highest affinity [K(d(app)) almost-equal-to 3.7 nM; k(a) = 2.4 x 10(5) M-1.s-1; k(d) = 1.2 x 10(-3) s-1] a phosphopeptide having a Tyr(P)-Glu-Glu-Ile motif found in the hamster polyomavirus middle-sized tumor antigen. Intermediate affinity (5- to 40-fold lower) was observed with phosphopeptides corresponding to the regulatory domains of Src and Lck, containing Tyr527 and Tyr505, respectively. Lowest affinity (80- to 300-fold lower) was observed with phosphopeptides corresponding to phosphorylated tyrosines of GTPase-activating protein, insulin receptor substrate 1, and SH2 domain-containing protein-tyrosine-phosphatase 1. C1 BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02115 USA. MT SINAI HOSP, SAMUEL LUNENFELD RES INST, TORONTO M5G 1X5, ONTARIO, CANADA. RP PAYNE, G (reprint author), HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RI Pawson, Tony/E-4578-2013; Gish, Gerald/C-7228-2017 NR 48 TC 131 Z9 131 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 4902 EP 4906 DI 10.1073/pnas.90.11.4902 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500027 PM 7685110 ER PT J AU KOVACSOVICSBANKOWSKI, M CLARK, K BENACERRAF, B ROCK, KL AF KOVACSOVICSBANKOWSKI, M CLARK, K BENACERRAF, B ROCK, KL TI EFFICIENT MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PRESENTATION OF EXOGENOUS ANTIGEN UPON PHAGOCYTOSIS BY MACROPHAGES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VACCINE; CYTOTOXIC T-LYMPHOCYTE; VIRAL IMMUNITY; ANTIGEN PRESENTATION ID LYMPHOCYTES-T; SOLUBLE-PROTEIN; SURFACE-ANTIGEN; CELL; RECOGNITION; MOLECULES; PATHWAYS AB Antigens in extracellular fluids can be processed and presented with major histocompatibility complex (MHC) class I molecules by a subset of antigen presenting cells (APCs). Chicken egg ovalbumin (Ova) linked to beads was presented with MHC class I molecules by these cells up to 10(4)-fold more efficiently than soluble Ova. This enhanced presentation was observed with covalently or noncovalently linked Ova and with beads of different compositions. A key parameter in the activity of these conjugates was the size of the beads. The APC that is responsible for this form of presentation is a macrophage. These cells internalize the antigen constructs through phagocytosis, since cytochalasin B inhibited presentation. Processing of the antigen and association with MHC class I molecules appears to occur intracellularly as presentation was observed under conditions where there was no detectable release of peptides into the extracellular fluids. When injected in vivo in C57BL/6 mice, Ova-beads, but not soluble Ova, primed CD4- CD8+ cytotoxic T lymphocytes (CTLs). Similar results were obtained in BALB/c mice immunized with beta-galactosidase-beads. The implications of these findings for development of nonliving vaccines that stimulate CTL immunity are discussed. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP KOVACSOVICSBANKOWSKI, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI31337, AI20248] NR 32 TC 422 Z9 429 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 4942 EP 4946 DI 10.1073/pnas.90.11.4942 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500035 PM 8506338 ER PT J AU KUPRYJANCZYK, J THOR, AD BEAUCHAMP, R MERRITT, V EDGERTON, SM BELL, DA YANDELL, DW AF KUPRYJANCZYK, J THOR, AD BEAUCHAMP, R MERRITT, V EDGERTON, SM BELL, DA YANDELL, DW TI P53 GENE-MUTATIONS AND PROTEIN ACCUMULATION IN HUMAN OVARIAN-CANCER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR SUPPRESSOR GENES; FAMILY SYNDROME; TRANSFORMATION; CARCINOMA; ONCOGENE AB Mutations of the p53 gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. We have analyzed 38 malignant tumors of ovarian or peritoneal mullerian type for evidence of p53 variations at either the DNA or protein levels. Genetic studies were based on single-strand conformation polymorphism analysis and DNA sequencing of exons 2 through 11 of the p53 gene; mutations were detected in 79% of the tumors. These data show a statistically significant association between mutations at C.G pairs and a history of estrogen therapy. Two of 20 patients whose normal tissue could be studied carried germ-line mutations of p53. Immunohistochemical analysis of the p53 protein was carried out using monoclonal antibody PAb180l. Ninety-six percent of the missense mutations were associated with abnormal accumulation of p53 protein, but nonsense mutations, a splicing mutation, and most deletions did not result in p53 protein accumulation. A statistically significant association between p53 protein accumulation in poorly differentiated stage III serous carcinomas and small primary tumor size at diagnosis was found, perhaps suggesting that p53 protein accumulation accelerates the metastatic spread from a primary tumor. Overall, our findings indicate that alterations of p53 play a major role in ovarian cancer, including predisposition to the disease in some patients, and suggest a possible mechanism for somatic mutations leading to this cancer. C1 MASSACHUSETTS EYE & EAR INFIRM,MOLEC GENET RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-44768] NR 42 TC 305 Z9 306 U1 1 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 JUN 1 PY 1993 VL 90 IS 11 BP 4961 EP 4965 DI 10.1073/pnas.90.11.4961 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500039 PM 8506342 ER PT J AU WOOD, KW QI, HQ DARCANGELO, G ARMSTRONG, RC ROBERTS, TM HALEGOUA, S AF WOOD, KW QI, HQ DARCANGELO, G ARMSTRONG, RC ROBERTS, TM HALEGOUA, S TI THE CYTOPLASMIC RAF ONCOGENE INDUCES A NEURONAL PHENOTYPE IN PC12 CELLS - A POTENTIAL ROLE FOR CELLULAR RAF KINASES IN NEURONAL GROWTH-FACTOR SIGNAL-TRANSDUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR-INDUCED DIFFERENTIATION; NEURITE OUTGROWTH; PHEOCHROMOCYTOMA CELLS; B-RAF; PROTEIN; PC12-CELLS; GENE; SRC; MICROINJECTION; EXPRESSION AB The neuron-like differentiation of PC12 cells is induced by nerve growth factor (NGF) through stimulation of a membrane-bound protooncoprotein signaling pathway containing the NGF receptor Trk, the tyrosine kinase Src, and the GTP-binding protein Ras. The Raf-1 and B-raf protooncogenes encode cytoplasmic serine/threonine kinases that are stimulated by NGF in a Ras-dependent manner. To investigate the possible roles of cytoplasmic Raf kinases in eliciting neuronal differentiation, we have expressed the activated Raf-1 oncogene in PC12 cells. Expression of the raf oncogene results in the elaboration of a neuron-like phenotype, including neurite growth and the induction of the NGF-responsive genes NGFI-A and transin. The actions of activated Raf-1 and NGF are not additive. Furthermore, activated Raf-1 oncoprotein can prime cells for transcription-independent neurite growth by NGF and can elicit rapid neurite growth from NGF-primed cells. Our data indicate that the pathways utilized by NGF and activated raf to effect PC12 differentiation overlap and lead to the suggestion that cellular raf kinase activities play significant roles in transducing the differentiating signals of neuronal growth factors. C1 SUNY,DEPT NEUROBIOL & BEHAV,STONY BROOK,NY 11794. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU DS NIH HHS [NINDS 18218]; NCI NIH HHS [CA3803, CA5066] NR 36 TC 168 Z9 169 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5016 EP 5020 DI 10.1073/pnas.90.11.5016 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500050 PM 8389463 ER PT J AU MAHESWARAN, S PARK, S BERNARD, A MORRIS, JF RAUSCHER, FJ HILL, DE HABER, DA AF MAHESWARAN, S PARK, S BERNARD, A MORRIS, JF RAUSCHER, FJ HILL, DE HABER, DA TI PHYSICAL AND FUNCTIONAL INTERACTION BETWEEN WT1 AND P53 PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID WILMS-TUMOR; GENE AB WT1 is a tumor-suppressor gene expressed in the developing kidney, whose inactivation leads to the development of Wilms tumor, a pediatric kidney cancer. WT1 encodes a transcription factor which binds to the EGR1 consensus sequence, mediating transcriptional repression. We now demonstrate that p53, the product of a tumor-suppressor gene with ubiquitous expression, physically associates with WT1 in transfected cells. The interaction between WT1 and p53 modulates their ability to transactivate their respective targets. In the absence of p53, WT1 acts as a potent transcriptional activator of the early growth response gene 1 (EGR1) site, rather than a transcriptional repressor. In contrast, WT1 exerts a cooperative effect on p53, enhancing its ability to transactivate the muscle creatine kinase promoter. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. ONCOGENE SCI INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,BOSTON,MA 02129. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. RI Hill, David/B-6617-2011 FU NCI NIH HHS [CA47983, CA52009, CA58596] NR 21 TC 299 Z9 301 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 JUN 1 PY 1993 VL 90 IS 11 BP 5100 EP 5104 DI 10.1073/pnas.90.11.5100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500068 PM 8389468 ER PT J AU CHUANG, LM MYERS, MG SEIDNER, GA BIRNBAUM, MJ WHITE, MF KAHN, CR AF CHUANG, LM MYERS, MG SEIDNER, GA BIRNBAUM, MJ WHITE, MF KAHN, CR TI INSULIN-RECEPTOR SUBSTRATE-1 MEDIATES INSULIN AND INSULIN-LIKE GROWTH FACTOR-I-STIMULATED MATURATION OF XENOPUS-OOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LAEVIS OOCYTES; CELL-DIVISION; SIGNAL TRANSDUCTION; 3T3-L1 ADIPOCYTES; KINASE-ACTIVITY; IGF-I; PHOSPHORYLATION; IDENTIFICATION; MICROINJECTION AB Insulin and insulin-like growth factor I (IGF-I) initiate cellular functions by activating their homologous tyrosine kinase receptors. In most mammalian cell types, this results in rapid tyrosine phosphorylation of a high-molecular-weight substrate termed insulin receptor substrate 1 (IRS-1). Previous studies suggest that IRS-1 may act as a ''docking'' protein that noncovalently associates with certain signal-transducing molecules containing src homology 2 domains; however, direct evidence for the role of IRS-1 in the final biological actions of these hormones is still lacking. We have developed a reconstitution system to study the role of IRS-1 in insulin and IGF-I signaling, taking advantage of the fact that Xenopus oocytes possess endogenous IGF-I receptors but have little or no IRS-1, as determined by immunoblotting with anti-IRS-1 and antiphosphotyrosine antibodies. After microinjection of IRS-1 protein produced in a baculovirus expression system, tyrosyl phosphorylation of injected IRS-1 is stimulated by both insulin and IGF-I in a concentration-dependent manner, with IGF-I more potent than insulin. Furthermore, after IRS-1 injection, both hormones induce a maturation response that correlates well with the amount of injected IRS-1. By contrast, overexpression of human insulin receptors in the Xenopus oocytes does not enhance either IRS-1 phosphorylation or oocyte maturation response upon insulin stimulation. These results demonstrate that IRS-1 serves a critical role in linking IGF-I and insulin to their final cellular responses. C1 HARVARD UNIV,SCH MED,DEPT MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. OI CHUANG, LEE-MING/0000-0003-0978-2662; Birnbaum, Morris/0000-0001-9972-8680 FU NIDDK NIH HHS [DK33201, DK39519, DK43808] NR 34 TC 90 Z9 91 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 JUN 1 PY 1993 VL 90 IS 11 BP 5172 EP 5175 DI 10.1073/pnas.90.11.5172 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500083 PM 7685118 ER PT J AU WINKLER, DG PARK, I KIM, T PAYNE, NS WALSH, CT STROMINGER, JL SHIN, J AF WINKLER, DG PARK, I KIM, T PAYNE, NS WALSH, CT STROMINGER, JL SHIN, J TI PHOSPHORYLATION OF SER-42 AND SER-59 IN THE N-TERMINAL REGION OF THE TYROSINE KINASE P56(LCK) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SERINE PHOSPHORYLATION; PHORBOL ESTER; MITOGEN-ACTIVATED PROTEIN KINASE; PROTEIN KINASE-C ID PROTEIN-KINASE; CYTOPLASMIC DOMAIN; P56LCK; CD4; SITES; CELLS; ACTIVATION; FEATURES; MITOSIS AB Ser-42 and Ser-59 in the N-terminal region have been identified as the major phorbol ester-induced phosphorylation sites of p56lck. Phosphorylation of Ser-59 results in a gel shift from 56 kDa to 61 kDa. Simultaneous phosphorylation of Ser-42 and Ser-59 results in a further gel shift to 63 kDa. In vitro kinase assays show that Ser-59 can be uniquely phosphorylated by mitogen-activated protein kinase and that Ser-42 can be phosphorylated by either protein kinase A or protein kinase C. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP WINKLER, DG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA47554]; NIAID NIH HHS [AI20182]; NIGMS NIH HHS [GM48961] NR 28 TC 83 Z9 84 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5176 EP 5180 DI 10.1073/pnas.90.11.5176 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500084 PM 8506364 ER PT J AU NITSCH, RM FARBER, SA GROWDON, JH WURTMAN, RJ AF NITSCH, RM FARBER, SA GROWDON, JH WURTMAN, RJ TI RELEASE OF AMYLOID BETA-PROTEIN PRECURSOR DERIVATIVES BY ELECTRICAL DEPOLARIZATION OF RAT HIPPOCAMPAL SLICES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALZHEIMER DISEASE; ELECTRICAL STIMULATION; NEUROTRANSMISSION ID ALZHEIMERS-DISEASE AB Proteolytic processing of the beta-amyloid protein precursor (APP) is regulated by cell-surface receptors. To determine whether neurotransmitter release in response to neuronal activation regulates APP processing in brain, we electrically depolarized superfused rat hippocampal slices and measured soluble APP derivatives released into the superfusate. Electrical depolarization caused a rapid increase in the release of both neurotransmitters and amino-terminal APP cleavage products. These derivatives lacked the APP carboxyl terminus and were similar to those found in both cell culture media and human cerebrospinal fluid. Superfusate proteins including lactate dehydrogenase were not changed by electrical depolarization. The release of amino-terminal APP derivatives increased with increasing stimulation frequencies from 0 to 30 Hz. The increased release was inhibited by the sodium-channel antagonist tetrodotoxin, suggesting that action-potential formation mediates the release of large amino-terminal APP derivatives. These results suggest that neuronal activity regulates APP processing in the mammalian brain. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP NITSCH, RM (reprint author), MIT,DEPT BRAIN & COGNIT SCI,E25-604,CAMBRIDGE,MA 02139, USA. RI Farber, Steven/G-5851-2012 OI Farber, Steven/0000-0002-8037-7312 NR 20 TC 192 Z9 196 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 JUN 1 PY 1993 VL 90 IS 11 BP 5191 EP 5193 DI 10.1073/pnas.90.11.5191 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500087 PM 8506366 ER PT J AU STRITTMATTER, SM CANNON, SC ROSS, EM HIGASHIJIMA, T FISHMAN, MC AF STRITTMATTER, SM CANNON, SC ROSS, EM HIGASHIJIMA, T FISHMAN, MC TI GAP-43 AUGMENTS G-PROTEIN-COUPLED RECEPTOR TRANSDUCTION IN XENOPUS-LAEVIS OOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-ASSOCIATED PROTEIN; CALMODULIN-BINDING DOMAIN; SENSITIVE G-PROTEIN; KINASE-C; PC12 CELLS; SUBCELLULAR FRACTION; NEURITE OUTGROWTH; RAT-BRAIN; CONE; COMPONENT AB The neuronal protein GAP-43 is thought to play a role in determining growth-cone motility, perhaps as an intracellular regulator of signal transduction, but its molecular mechanism of action has remained unclear. We find that GAP-43, when microinjected into Xenopus laevis oocytes, increases the oocyte response to G protein-coupled receptor agonists by 10- to 100-fold. Higher levels of GAP-43 cause a transient current flow, even without receptor stimulation. The GAP-43-induced current, like receptor-stimulated currents, is mediated by a calcium-activated chloride channel and can be desensitized by injection of inositol 1,4,5-trisphosphate. This suggests that neuronal GAP-43 may serve as an intracellular signal to greatly enhance the sensitivity of G protein-coupled receptor transduction. C1 MASSACHUSETTS GEN HOSP,DEV BIOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP E,SCH MED,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,DEPT NEUROL,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. OI Strittmatter, Stephen/0000-0001-8188-3092 NR 50 TC 67 Z9 68 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 1 PY 1993 VL 90 IS 11 BP 5327 EP 5331 DI 10.1073/pnas.90.11.5327 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500115 PM 7685122 ER PT J AU SHELLEY, CS FAROKHZAD, OC ARNAOUT, MA AF SHELLEY, CS FAROKHZAD, OC ARNAOUT, MA TI IDENTIFICATION OF CELL-SPECIFIC AND DEVELOPMENTALLY-REGULATED NUCLEAR FACTORS THAT DIRECT MYELOID AND LYMPHOID EXPRESSION OF THE CD11A GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; MEMBRANE-PROTEINS; BINDING PROTEIN; PROMOTER; SEQUENCE; TRANSCRIPTION; DNA; ADHESION; ENHANCER; ONCOGENE AB Human CD11a/CD18 is a noncovalently associated heterodimeric receptor expressed exclusively on the surface of lymphocytes and myeloid cells. To begin to understand the mechanisms that direct the expression of the genes encoding this receptor, we have cloned and characterized the promoter region of the CD11a gene and localized cis-acting elements involved in its expression in lymphoid and myeloid cells. One such element is the ''LYM'' box, which interacts with two sets of DNA-binding activities, one primarily expressed in lymphocytes and preerythroid cells and the other expressed predominantly in myeloid cells. A second element required for expression of the CD11a gene contains the ''GAGA'' sequence RRRGAGGAAG (R indicates a purine), which interacts with the DNA-binding activities MS-1 and MS-2. MS-1 is expressed exclusively in myeloid cells and probably represents a member of the Ets family of transcription activators. MS-2 is present in epithelial, preerythroid, and lymphoid cells but is only detected in myeloid cells after differentiation. MS-2 also binds to a second element within the CD11a promoter and homologous elements present in the promoter regions of the CD11b and CD43 genes. Since MS-2 interacts with a number of different gene promoters and is developmentally regulated in myeloid cells, it may play a major role in regulating myeloid gene expression. C1 HARVARD UNIV,SCH MED,DEPT MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02115. RP SHELLEY, CS (reprint author), MASSACHUSETTS GEN HOSP,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,149 13TH ST,BOSTON,MA 02129, USA. FU NIAID NIH HHS [P01 AI28465] NR 42 TC 52 Z9 53 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 JUN 1 PY 1993 VL 90 IS 11 BP 5364 EP 5368 DI 10.1073/pnas.90.11.5364 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500123 PM 8099450 ER PT J AU TYAN, ML AF TYAN, ML TI EFFECTS OF H-2 AND DIETARY VITAMIN-A ON THE FREQUENCY OF DORSOVENTRAL VAGINAL SEPTUM SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLEFT-PALATE; MICE; GENE AB The frequency of dorsoventral vaginal septum (DVS) in mice is determined in part by genes associated with the major histocompatibility complex H-2. Data presented here confirm that one locus (DVS-1) maps centromeric to Ealpha and that the second (DVS-2), previously shown to be associated with the S-to-D region, maps to the C4:B144 interval, most likely between Dcp-2 which contributes to glucocorticoid-induced cleft palate susceptibility and Acp which enhances cleft palate susceptibility through the action of vitamin A. Comparisons of data obtained in this laboratory in the periods 1981-1983 and 1985-1990 and observations from the production colony from which many of the strains were purchased revealed minor variations in frequencies of DVS within strains which may be due to differences in ascertainment and/or to environmental factors. The addition of vitamin A to the diet of pregnant mice at a dose that increases the frequency of cleft palate in susceptible strains had no effect on the incidence of DVS. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90073 USA. RP TYAN, ML (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, W 111M, LOS ANGELES, CA 90073 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUN PY 1993 VL 203 IS 2 BP 175 EP 178 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LD339 UT WOS:A1993LD33900007 PM 8502659 ER PT J AU CHO, HJ KRISHNARAJ, R ITOH, M KITAS, E BANNWARTH, W SAITO, H WALSH, CT AF CHO, HJ KRISHNARAJ, R ITOH, M KITAS, E BANNWARTH, W SAITO, H WALSH, CT TI SUBSTRATE SPECIFICITIES OF CATALYTIC FRAGMENTS OF PROTEIN-TYROSINE PHOSPHATASES (HPTP-BETA, LAR, AND CD45) TOWARD PHOSPHOTYROSYLPEPTIDE SUBSTRATES AND THIOPHOSPHOTYROSYLATED PEPTIDES AS INHIBITORS SO PROTEIN SCIENCE LA English DT Article DE CD45; HPTP-BETA; LAR; PHOSPHOTYROSYL PEPTIDE; PTPASE; SUBSTRATE SPECIFICITY; THIOPHOSPHOTYROSYL PEPTIDE ID LEUKOCYTE-COMMON ANTIGEN; SOLID-PHASE SYNTHESIS; RECEPTOR; PURIFICATION; INVITRO; AUTOPHOSPHORYLATION; PHOSPHORYLATION; EXPRESSION; RESIDUES AB The transmembrane PTPase HPTPbeta differs from its related family members in having a single rather than a tandemly duplicated cytosolic catalytic domain. We have expressed the 354-amino acid, 41-kDa human PTPbeta catalytic fragment in Escherichia coli, purified it, and assessed catalytic specificity with a series of pY peptides. HPTPbeta shows distinctions from the related LAR PTPase and T cell CD45 PTPase domains: it recognizes phosphotyrosyl peptides of 9-11 residues from lck, src, and PLCgamma with K(m) values of 2, 4, and 1 muM, some 40-200-fold lower than the other two PTPases. With k(cat) values of 30-205 s-1 , the catalytic efficiency, k(cat)/K(m), of the HPTPbeta 41-kDa catalytic domain is very high, up to 5.7 x 10(7) M-1 s-1. The peptides corresponding to PLCgamma (766-776) and EGFR (1,167-1,177) phosphorylation sites were used for structural variation to assess pY sequence context recognition by HPTPbeta catalytic domain. While exchange of the alanine residue at the +2 position of the PLCgamma (K(m) of 1 muM) peptide to lysine or aspartic acid showed little or no effect on substrate affinity, replacement by arginine increased the K(m) 35-fold. Similarly, the high K(m) value of the EGFR pY peptide (K(m) of 104 muM) derives largely from the arginine residue at the +2 position of the peptide, since arginine to alanine single mutation at the -2 position of the EGFR peptide decreased the K(m) value 34-fold to 3 muM. Three thiophosphotyrosyl peptides have been prepared and act as substrates and competitive inhibitors of these PTPase catalytic domains. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,240 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HOFFMANN LA ROCHE LTD,PHARMA RES NEW TECHNOL,CH-4002 BASEL,SWITZERLAND. NR 37 TC 77 Z9 78 U1 0 U2 1 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 JUN PY 1993 VL 2 IS 6 BP 977 EP 984 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD535 UT WOS:A1993LD53500011 PM 8318901 ER PT J AU STERN, RG KAHN, RS DAVIDSON, M AF STERN, RG KAHN, RS DAVIDSON, M TI PREDICTORS OF RESPONSE TO NEUROLEPTIC TREATMENT IN SCHIZOPHRENIA SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PLASMA HOMOVANILLIC-ACID; LATERAL VENTRICULAR SIZE; SUBJECTIVE RESPONSE; SHORT-TERM; CATECHOLAMINE METABOLITES; ANTIPSYCHOTIC-DRUGS; CLINICAL-RESPONSE; COMPUTERIZED EEG; CT SCANS; HVA C1 BRONX VET AFFAIRS MED CTR,NEW YORK,NY. RP STERN, RG (reprint author), CUNY MT SINAI SCH MED,DEPT PSYCHIAT,BOX 1228,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. NR 58 TC 24 Z9 24 U1 0 U2 1 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 1993 VL 16 IS 2 BP 313 EP 338 PG 26 WC Psychiatry SC Psychiatry GA LG548 UT WOS:A1993LG54800007 PM 8101371 ER PT J AU CAMPBELL, A BALDESSARINI, RJ NEUMEYER, JL AF CAMPBELL, A BALDESSARINI, RJ NEUMEYER, JL TI ALTERED SPONTANEOUS BEHAVIOR AND SENSITIVITY TO APOMORPHINE IN RATS FOLLOWING PRETREATMENT WITH S(+)-APORPHINES OR FLUPHENAZINE SO PSYCHOPHARMACOLOGY LA English DT Article DE ANTIPSYCHOTICS; S(+)APORPHINES; FLUPHENAZINE; DOPAMINE; RECEPTORS; STEREOTYPY; SUPERSENSITIVITY; TARDIVE DYSKINESIA; TOLERANCE ID DOPAMINERGIC SUPER-SENSITIVITY; LIMBIC SYSTEM; RECEPTORS; SUPERSENSITIVITY; INHIBITION; SINGLE; DRUGS; NEUROLEPTICS; HALOPERIDOL; PROPRANOLOL AB Rats were pretreated for 2 weeks with similarly effective doses of the typical neuroleptic fluphenazine (FPZ) or the experimental weak partial D2 agonists S(+)N-n-propylnorapomorphine (NPA) and S(+)11-hydroxy-N-n-propylnoraporphine (11-OH-NPa). Spontaneous and dopamine (DA) agonist (apomorphine; APO) stimulated stereotyped behaviors or locomotion, and interactions with APO were evaluated over the following 2 weeks. While FPZ induced marked supersensitivity in APO stereotypy, (+)NPA showed no significant change, and (+)11-OH-NPa produced only a small, transient increase in response; NPA also lacked a supersensitizing effect on locomotor arousal induced by APO. The time-course of stereotyped responses to APO following pretreatment with FLZ included a marked increase following FPZ that became maximal at day 5 and normalized by day 9; there was a parallel reduction of acute antistereotypy efficacy of FPZ. (+)11-OH-NPa had similar, but much lesser and shorter-lived effects. Spontaneous locomotion was markedly depressed following FPZ, recovered in 1 week, exceeded controls at day 9, and returned to baseline by day 11; (+)11-OH-NPa, again, had similar but smaller effects. Acute effects of FPZ to reduce spontaneous or APO-induced locomotion were greater after FPZ pretreatment and normalized within a week; (+)11-OH-NPa had a similar but smaller effect. Locomotor arousal by APO was altered inconsistently in the week after pretreatment with FPZ or (+)11-OH-NPa. Thus, FPZ appeared to induce tolerance and supersensitivity in central DA systems, most clearly seen following a several-day period to eliminate the drug. In contrast, the S(+)aporphines had negligible, or minor and transient, effects of a similar kind. These findings support proposals of S(+)aporphines or other D2 partial agonists as potential atypical antipsychotic agents with low risk of inducing long-term adaptive changes in DA receptor sensitivity associated with typical neuroleptic agents. C1 MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,115 MILL ST,BELMONT,MA 02178. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. RES BIOCHEM INC,NATICK,MA 01760. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. NORTHEASTERN UNIV,COLL PHARM & ALLIED HLTH PROFESS,MED CHEM SECT,BOSTON,MA 02115. FU NIMH NIH HHS [MH-34006, MH-47370, MH-31154] NR 53 TC 13 Z9 13 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 1993 VL 111 IS 3 BP 351 EP 358 DI 10.1007/BF02244952 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LF209 UT WOS:A1993LF20900013 PM 7870974 ER PT J AU WILLIS, CS AF WILLIS, CS TI WHEN AA DOESNT WORK FOR YOU - RATIONAL STEPS TO QUITTING ALCOHOL - ELLIS,A, VELTEN,E SO PSYCHOTHERAPY LA English DT Book Review RP WILLIS, CS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI PHOENIX PA 3900 E CAMELBACK RD #200, PHOENIX, AZ 85018 SN 0033-3204 J9 PSYCHOTHER JI Psychotherapy PD SUM PY 1993 VL 30 IS 2 BP 373 EP 374 DI 10.1037/h0092288 PG 2 WC Psychology, Clinical SC Psychology GA MT367 UT WOS:A1993MT36700024 ER PT J AU HELD, KD BIAGLOW, JE AF HELD, KD BIAGLOW, JE TI ROLE OF COPPER IN THE OXYGEN RADICAL-MEDIATED TOXICITY OF THE THIOL-CONTAINING RADIOPROTECTOR DITHIOTHREITOL IN MAMMALIAN-CELLS SO RADIATION RESEARCH LA English DT Article ID N-ACETYLCYSTEINE; CYTO-TOXICITY; CYSTEAMINE; HEPATOCYTES; PROTECTION; MECHANISM; OXIDATION; PEROXIDE; IRON; IONS C1 UNIV PENN,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19104. RP HELD, KD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA44982, CA42167] NR 26 TC 21 Z9 21 U1 1 U2 2 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 1993 VL 134 IS 3 BP 375 EP 382 DI 10.2307/3578200 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA LK514 UT WOS:A1993LK51400017 PM 8316632 ER PT J AU HELD, KD TUTTLE, SW BIAGLOW, JE AF HELD, KD TUTTLE, SW BIAGLOW, JE TI ROLE OF THE PENTOSE CYCLE IN OXYGEN RADICAL-MEDIATED TOXICITY OF THE THIOL-CONTAINING RADIOPROTECTOR DITHIOTHREITOL IN MAMMALIAN-CELLS SO RADIATION RESEARCH LA English DT Article ID HAMSTER OVARY CELLS; N-ACETYLCYSTEINE; CYSTEAMINE; COLONIES C1 UNIV PENN,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19104. RP HELD, KD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA42167, CA44982] NR 25 TC 21 Z9 21 U1 0 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 1993 VL 134 IS 3 BP 383 EP 389 DI 10.2307/3578201 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA LK514 UT WOS:A1993LK51400018 PM 8316633 ER PT J AU KOPANS, DB AF KOPANS, DB TI BREAST IMAGING AND THE STANDARD OF CARE FOR THE SYMPTOMATIC PATIENT SO RADIOLOGY LA English DT Editorial Material DE BREAST NEOPLASMS, DIAGNOSIS; BREAST RADIOGRAPHY, UTILIZATION; EDITORIALS; MEDICOLEGAL PROBLEMS ID DETECTION DEMONSTRATION PROJECT; SCREENING MAMMOGRAPHY; CANCER; DIAGNOSIS; DENSITY; US C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP MASSACHUSETTS GEN HOSP, DEPT RADIOL, 32 FRUIT ST, BOSTON, MA 02114 USA. NR 29 TC 17 Z9 17 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 608 EP 611 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200003 PM 8497602 ER PT J AU YUCEL, EK KAUFMAN, JA GELLER, SC WALTMAN, AC AF YUCEL, EK KAUFMAN, JA GELLER, SC WALTMAN, AC TI ATHEROSCLEROTIC OCCLUSIVE DISEASE OF THE LOWER-EXTREMITY - PROSPECTIVE EVALUATION WITH 2-DIMENSIONAL TIME-OF-FLIGHT MR-ANGIOGRAPHY SO RADIOLOGY LA English DT Article DE ANGIOGRAPHY, COMPARATIVE STUDIES; ARTERIES, EXTREMITIES; ARTERIES, STENOSIS OR OBSTRUCTION; MAGNETIC RESONANCE (MR), COMPARATIVE STUDIES; MAGNETIC RESONANCE (MR), VASCULAR STUDIES ID MAGNETIC-RESONANCE; CAROTID BIFURCATION; STENOSIS; DIAGNOSIS AB A prospective, blinded comparison of two-dimensional time-of-flight (TOF) magnetic resonance (MR) angiography and conventional arteriography was performed in 25 patients who underwent routine arteriography for symptomatic atherosclerotic occlusive disease of the lower extremity. MR angiography was performed from the distal abdominal aorta through the popliteal trifurcation. The native arterial tree was divided into nine segments; each segment was assessed for patency (defined as stenosis <50% of arterial diameter), moderate stenosis (50%-69%), severe stenosis (70%-99%), or occlusion (100%). In all 206 segments examined, the sensitivity of MR angiography in diagnosis of occlusion was 100%; the specificity, 98%. All long occlusions were correctly classified. In specific categories of occlusive disease, the sensitivity and specificity were as follows: in all segments with 70% or greater stenosis, including occlusions, 90% and 97%; in all segments with 50% or greater stenosis, including occlusions, 92% and 88%; in femoropopliteal segments with 50% or greater stenosis, 92% and 93%; and in iliac segments, 93% and 83%. Long occlusions were distinguished from short occlusions and stenoses; hence, MR angiography enabled identification of patients with lesions suitable for angioplasty. C1 MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. NR 28 TC 117 Z9 120 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 637 EP 641 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200009 PM 8497608 ER PT J AU LU, DSK MUELLER, PR LEE, MJ DAWSON, SL HAHN, PF BROUNTZOS, E AF LU, DSK MUELLER, PR LEE, MJ DAWSON, SL HAHN, PF BROUNTZOS, E TI GASTROSTOMY CONVERSION TO TRANSGASTRIC JEJUNOSTOMY - TECHNICAL PROBLEMS, CAUSES OF FAILURE, AND PROPOSED SOLUTIONS IN 63 PATIENTS SO RADIOLOGY LA English DT Article DE GASTROSTOMY; JEJUNOSTOMY ID PERCUTANEOUS GASTROSTOMY AB Sixty-three radiologically guided conversions of gastrostomy to transgastric jejunostomy performed over a 4-year period were reviewed. Conversions succeeded in 31 of 38 surgically placed gastrostomies (82%), in 14 of 18 endoscopically placed gastrostomies (78%), and in seven of seven radiologically placed gastrostomies, for an overall success rate of 83%. Almost all failures (10 of 11 gastrostomies) were primarily the result of unfavorable fundal angulation of the surgical or endoscopic tract; unfavorable angulation was also the most common technical problem encountered in the successful conversions. Of the 52 successful conversions, 23 (44%) necessitated tube replacement: eight for spontaneous proximal migration of the tube, 11 for accidental tube dislodgment, and four for tube blockage. While most gastrostomy to transgastric jejunostomy conversions are simple to perform, in many cases the unfavorable angle of the original transcutaneous tract precludes jejunal intubation and may be a cause for early recoil of a successfully placed jejunal catheter back into the stomach. With early recognition of an unfavorable tract, a fresh transgastric jejunostomy through a new, properly angled puncture may be the preferred approach. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV ABDOMINAL IMAGING & INTERVENT,FRUIT ST,BOSTON,MA 02114. NR 11 TC 26 Z9 26 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 679 EP 683 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200016 PM 8497613 ER PT J AU BOGDANOV, AA WEISSLEDER, R FRANK, HW BOGDANOVA, AV NOSSIF, N SCHAFFER, BK TSAI, E PAPISOV, MI BRADY, TJ AF BOGDANOV, AA WEISSLEDER, R FRANK, HW BOGDANOVA, AV NOSSIF, N SCHAFFER, BK TSAI, E PAPISOV, MI BRADY, TJ TI A NEW MACROMOLECULE AS A CONTRAST AGENT FOR MR-ANGIOGRAPHY - PREPARATION, PROPERTIES, AND ANIMAL STUDIES SO RADIOLOGY LA English DT Article DE CONTRAST MEDIA, COMPARATIVE STUDIES; CONTRAST MEDIA, EXPERIMENTAL STUDIES; MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; MAGNETIC RESONANCE (MR), VASCULAR STUDIES, 9-ASTERISK ID MAGNETIC-RESONANCE ANGIOGRAPHY; COVALENT ATTACHMENT; POLYETHYLENE-GLYCOL; CONVENTIONAL ANGIOGRAPHY; GD-DTPA; POLYLYSINE; LIPOSOMES; IMMUNOGENICITY; CIRCULATION; ANTIBODIES AB The authors developed and evaluated a polymer as a contrast agent for magnetic resonance (MR) angiography. The agent consists of a monomethoxy ether of poly(ethylene glycol) covalently attached to poly(L-lysine) (PL), with PL serving as the carrier of gadolinium diethylenetriaminepentaacetic acid (DTPA). Immunogenicity and toxicity studies were performed in mice, and biokinetic and metabolic studies were performed in rats. Dose response studies were performed with a three-dimensional time-of-flight sequence in eight rats. No permanent immune response was elicited against Gd-DTPA or the carrier molecule, and accumulation in organs of the reticuloendothelial system was minimal. The blood half-life of the agent was 14 hours. A dose of 20 mumol of gadolinium per kilogram of body weight was sufficient to increase the vessel-muscle ratio by four- to fivefold. Contrast was substantially improved and remained unchanged 2 hours after contrast medium administration, and good visualization of four orders of vasculature was allowed. C1 MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129. NR 31 TC 158 Z9 164 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 701 EP 706 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200020 PM 8497616 ER PT J AU SILVERMAN, SG MUELLER, PR PINKNEY, LP KOENKER, RM SELTZER, SE AF SILVERMAN, SG MUELLER, PR PINKNEY, LP KOENKER, RM SELTZER, SE TI PREDICTIVE VALUE OF IMAGE-GUIDED ADRENAL BIOPSY - ANALYSIS OF RESULTS OF 101 BIOPSIES SO RADIOLOGY LA English DT Article DE ADRENAL GLAND, BIOPSY; ADRENAL GLAND, NEOPLASMS; BIOPSIES ID CELL LUNG-CARCINOMA; COMPUTED-TOMOGRAPHY; NEEDLE ASPIRATION; MASSES; DIAGNOSIS; TUMORS AB A retrospective study of 97 patients undergoing 101 image-guided adrenal biopsies (IGABs) was performed to analyze the effects of specific pathologic results on test characteristics. Three categories of pathologic results (benign adrenal tissue, malignant tissue, and nondiagnostic) were compared with outcomes. Diagnostic samples were obtained in 86% of cases. Among 72 patients with proved outcomes, IGAB had an accuracy of 96%, a sensitivity of 93%, and a negative predictive value of 91% (92% in patients with bronchogenic carcinoma). In this subset of patients, 33 had biopsy specimens that contained benign adrenal tissue. In these 33 patients, three masses (each smaller than 3 cm) proved malignant. In the 14 patients with nondiagnostic samples, two masses proved malignant. Obtaining benign adrenal tissue was highly predictive of benignity, even in the setting of lung cancer. The authors conclude that IGAB is an accurate procedure in both oncologic and nononcologic patients. However, when the biopsy specimen does not contain benign adrenal tissue or malignant cells, repeat percutaneous biopsy or surgery should be considered. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP SILVERMAN, SG (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 21 TC 120 Z9 123 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 715 EP 718 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200023 PM 8497619 ER PT J AU NIKLASON, LT MARX, MV CHAN, HP AF NIKLASON, LT MARX, MV CHAN, HP TI INTERVENTIONAL RADIOLOGISTS - OCCUPATIONAL RADIATION-DOSES AND RISKS SO RADIOLOGY LA English DT Article DE DOSIMETRY; RADIOLOGY AND RADIOLOGISTS; RADIATIONS, EXPOSURE TO PATIENTS AND PERSONNEL; RADIATIONS, MEASUREMENT ID DIAGNOSTIC-RADIOLOGY; EXPOSURE AB Interventional radiologists receive nonuniform occupational radiation doses, with relatively high doses to the head and extremities and low doses to the trunk, which is protected by a lead apron. Twenty-eight interventional radiologists from 17 institutions wore thermoluminescent dosimeters over their collars and under their aprons for a 2-month period. The estimated annual radiation dose was converted to effective dose as suggested by the International Commission on Radiological Protection. Effective dose is used to relate the risk associated with nonuniform dose to that associated with an equivalent uniform whole-body dose. The mean annual effective dose was 3.16 mSv (316 mrem), with a range of 0.37-10.1 mSv. The mean annual effective dose is approximately equal to the mean natural background dose of 3 mSv per year from radon and other natural sources and is only 6% of the National Council on Radiation Protection and Measurements' recommended effective dose equivalent limit of 50 mSv per year. The annual radiation risk of fatal cancer would be less than one per 10,000 for almost the entire career of an interventional radiologist. C1 UNIV MICHIGAN HOSP,DEPT RADIOL,ANN ARBOR,MI 48109. RP NIKLASON, LT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,55 FRUIT ST,BOSTON,MA 02114, USA. NR 17 TC 73 Z9 75 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 729 EP 733 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200026 PM 8497622 ER PT J AU MOORE, EH AF MOORE, EH TI ATYPICAL MYCOBACTERIAL INFECTION IN THE LUNG - CT APPEARANCE SO RADIOLOGY LA English DT Article DE LUNG, INFECTION; MYCOBACTERIA ID AVIUM COMPLEX; PULMONARY-DISEASE; NONTUBERCULOUS MYCOBACTERIA; DIAGNOSIS; KANSASII; THERAPY AB The author examined computed tomographic (CT) scans of the chest from 40 patients with cultures positive for atypical mycobacteria. Common manifestations included bronchiectasis, air-space disease, nodules, and scarring and/or volume loss. Less commonly observed signs were cavities, lymphadenopathy, and pleural disease. Serial scans were obtained in 10 patients and showed new areas of bronchiectasis and progression of existing bronchiectasis, suggesting that the bronchiectasis was not a preexisting condition but resulted from infection. The anatomic distribution of the above findings was diffuse, not strongly favoring any lung zone. The identification of multifocal coexistent bronchiectasis, air-space disease, and nodules at CT should raise the possibility of atypical mycobacterial lung disease, even in an otherwise healthy patient. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 15 TC 95 Z9 104 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 777 EP 782 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200034 PM 8497629 ER PT J AU SHEPARD, JAO MOORE, EH TEMPLETON, PA MCLOUD, TC AF SHEPARD, JAO MOORE, EH TEMPLETON, PA MCLOUD, TC TI PULMONARY INTRAVASCULAR TUMOR EMBOLI - DILATED AND BEADED PERIPHERAL PULMONARY-ARTERIES AT CT SO RADIOLOGY LA English DT Article DE EMBOLISM, PULMONARY; LUNG, INFARCTION; LUNG NEOPLASMS, SECONDARY ID INFLATION-FIXED LUNGS; RENAL CELL-CARCINOMA; INFARCTION; PROSTATE; PATTERN; SIGN AB The diagnosis of pulmonary intravascular tumor emboli is difficult to establish both clinically and on conventional radiographic studies. Between 1985 and 1991, four cases of pulmonary intravascular metastases were demonstrated on computed tomographic (CT) scans from among 14,000 CT scans of the chest. A retrospective study of these cases was performed, including a review of chest radiographs. All four patients had invasive tumors, including an atrial myxoma, a renal cell carcinoma, an osteosarcoma, and a chondrosarcoma of the pelvis. Three cases had histopathologic documentation of pulmonary artery tumor emboli. At CT, all the patients demonstrated multifocal dilatation and beading of peripheral pulmonary arteries, primarily in a subsegmental distribution involving multiple lobes. Ossification of the pulmonary arteries occurred in one case of metastatic osteosarcoma. In two cases, small, peripheral wedge-shaped opacities distal to some abnormal pulmonary arteries suggested pulmonary infarcts. The finding of dilated and beaded peripheral pulmonary arteries at CT is highly suggestive of metastatic intravascular tumor emboli. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP SHEPARD, JAO (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 31 TC 60 Z9 63 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 797 EP 801 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200038 PM 8497633 ER PT J AU LEE, MJ ROSS, DS MUELLER, PR DANIELS, GH DAWSON, SL SIMEONE, JF AF LEE, MJ ROSS, DS MUELLER, PR DANIELS, GH DAWSON, SL SIMEONE, JF TI FINE-NEEDLE BIOPSY OF CERVICAL LYMPH-NODES IN PATIENTS WITH THYROID-CANCER - A PROSPECTIVE COMPARISON OF CYTOPATHOLOGIC AND TISSUE MARKER ANALYSIS SO RADIOLOGY LA English DT Article DE HORMONES; LYMPHATIC SYSTEM, BIOPSY; LYMPHATIC SYSTEM, NEOPLASMS; THYROID, NEOPLASMS ID FOLLOW-UP; THYROGLOBULIN MEASUREMENT; SERUM THYROGLOBULIN; I-131 THERAPY; BODY SCAN; CARCINOMA; MANAGEMENT; US; SONOGRAPHY; NECK AB Tissue levels of thyroglobulin (Tg) or calcitonin were compared with specimens from neck lymph node biopsy in patients with suspected recurrent differentiated (papillary or follicular) or medullary thyroid cancer. Thirty-six neck lymph node biopsies were performed in 29 patients. Tissue Tg levels were obtained from 31 specimens from patients with differentiated thyroid cancers, and tissue calcitonin levels were obtained from five specimens from patients with medullary cancer. Thirteen nodes were diagnosed as negative for cancer at surgery (n = 3) or follow-up sonography (n = 10). Malignant disease was confirmed at surgery in 23 of the 36 lymph nodes. Cytopathologic examination had a sensitivity of 91% and a specificity of 100%. Tissue Tg levels ranged from 0 to 3.5 ng/mL (mean, 1.5 ng/mL; median, 1.2 ng/mL) in 12 of the 13 benign lymph nodes and from 21 to 247,500 ng/mL (mean, 30,600 ng/mL; median, 2,330 ng/mL) in the 23 malignant nodes. Tissue calcitonin levels were elevated (range, 850-703,125 pg/mL; mean, 184,762 pg/mL; median, 17,538 pg/mL) in four malignant nodes and were normal (3.0 pg/mL) in one benign node. Diagnostic sensitivity of tissue markers was 91%. Specificity was 91%. The combined diagnostic sensitivity and specificity of tissue marker analysis and cytopathologic examination was 100%. C1 MASSACHUSETTS GEN HOSP, DEPT MED, THYROID UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP, DEPT RADIOL, FRUIT ST, BOSTON, MA 02114 USA. NR 15 TC 42 Z9 44 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 851 EP 854 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200050 PM 8497644 ER PT J AU LEE, MJ MUELLER, PR AF LEE, MJ MUELLER, PR TI MEASUREMENT OF TISSUE CARCINOEMBRYONIC ANTIGEN LEVELS - REPLY SO RADIOLOGY LA English DT Letter ID CYTOLOGIC EXAMINATION; CYST CONTENTS; FLUID; EFFUSIONS; LESIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PHARMACOL & CELL BIOPHYS,FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1993 VL 187 IS 3 BP 876 EP 877 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LD192 UT WOS:A1993LD19200060 ER PT J AU MALT, RA AF MALT, RA TI PROS AND CONS OF RESECTING LIVER METASTASES SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP MALT, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1993 VL 10 IS 2 BP 161 EP 161 DI 10.1055/s-2008-1074719 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH939 UT WOS:A1993LH93900013 ER PT J AU GAZELLE, GS BOLAND, G DAWSON, SL MUELLER, PR AF GAZELLE, GS BOLAND, G DAWSON, SL MUELLER, PR TI HEPATIC SEGMENTAL ANATOMY AND ITS RELEVANCE TO THE MANAGEMENT OF PATIENTS WITH HEPATIC MALIGNANCIES SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP GAZELLE, GS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1993 VL 10 IS 2 BP 162 EP 168 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH939 UT WOS:A1993LH93900014 ER PT J AU HOOVER, HC AF HOOVER, HC TI SURGICAL RESECTION OF PRIMARY HEPATOMAS AND HEPATIC METASTASES SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Article RP HOOVER, HC (reprint author), MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1993 VL 10 IS 2 BP 169 EP 174 DI 10.1055/s-2008-1074721 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH939 UT WOS:A1993LH93900015 ER PT J AU MORI, M KAKEJI, Y ADACHI, Y MORIGUCHI, S MAEHARA, Y SUGIMACHI, K JESSUP, JM CHEN, LB STEELE, GD AF MORI, M KAKEJI, Y ADACHI, Y MORIGUCHI, S MAEHARA, Y SUGIMACHI, K JESSUP, JM CHEN, LB STEELE, GD TI THE PROGNOSTIC-SIGNIFICANCE OF PROLIFERATING CELL NUCLEAR ANTIGEN IN CLINICAL GASTRIC-CANCER SO SURGERY LA English DT Article ID MONOCLONAL-ANTIBODY; SACCHAROMYCES-CEREVISIAE; HISTOLOGICAL MATERIAL; FLOW-CYTOMETRY; PHASE FRACTION; CARCINOMA; PCNA; CYCLIN; PROTEIN; BROMODEOXYURIDINE AB Background. Proliferating cell nuclear antigen (PCNA) is an intranuclear protein that is closely linked to the cell cycle. This antigen can be detected in formalin-fixed specimens. We studied the expression of PCNA in primary gastric cancer to identify its significance as a prognostic factor. Methods. The avidin-biotin-peroxidase complex method was used for PCNA staining in sections from 138 patients with primary gastric cancer. All sections were formalin fixed and paraffin embedded. Two different sections were examined in each case. Results. The PCNA labeling index (PCNA-positive cells/1000 cells X 100) varied from 7.0% to 59.7%. There were significant differences in tumor size, morphologic type, depth of tumor invasion, lymphatic permeation, vascular permeation, and lymph node metastasis between the high (greater-than-or-equal-to 33.4) and low (<33.4) PCNA labeling index groups. The 5-year survival rates of the high and low PCNA labeling index groups were 5.8% and 66.2%, respectively, a significant difference (p < 0.001). Multivariate analysis showed that the PCNA labeling index was an independent prognostic factor for gastric cancer. Conclusions. Because PCNA immunostaining can be done in routine formalin-fixed paraffin-embedded sections, this could be a powerful tool for providing information about the prognosis of patients with gastric cancer. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP MORI, M (reprint author), KYUSHU UNIV,FAC MED,DEPT SURG 2,MAIDASHI 3-1-1,HIGASHI KU,FUKUOKA 812,JAPAN. RI Maehara, Yoshihiko/A-4867-2010 NR 39 TC 47 Z9 49 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 1993 VL 113 IS 6 BP 683 EP 690 PG 8 WC Surgery SC Surgery GA LF313 UT WOS:A1993LF31300015 PM 8099452 ER PT J AU MIDHA, KK MARDER, SR JAWORSKI, TJ MCKAY, G HUBBARD, JW HAWES, EM VANPUTTEN, T WIRSHING, WC ARAVAGIRI, M AF MIDHA, KK MARDER, SR JAWORSKI, TJ MCKAY, G HUBBARD, JW HAWES, EM VANPUTTEN, T WIRSHING, WC ARAVAGIRI, M TI CLINICAL PERSPECTIVES OF SOME NEUROLEPTICS THROUGH DEVELOPMENT AND APPLICATION OF THEIR ASSAYS SO THERAPEUTIC DRUG MONITORING LA English DT Article DE FLUPHENAZINE; FLUPHENAZINE DECANOATE; FLUPHENAZINE DIHYDROCHLORIDE; PLASMA LEVEL MONITORING; PHARMACOKINETICS; ASSAY; APPLICATIONS TO CLINICAL STUDIES ID FLUPHENAZINE PLASMA-LEVELS; LIQUID-CHROMATOGRAPHIC METHOD; SCHIZOPHRENIC-PATIENTS; MONOCLONAL-ANTIBODIES; BLOOD-LEVELS; N-OXIDE; DECANOATE; RADIOIMMUNOASSAY; PHARMACOKINETICS; CHLORPROMAZINE AB Attempts to investigate relationships between plasma levels of neuroleptics and therapeutic outcome in schizophrenic patients have been hampered due to such factors as the chemical nature of these drugs, their metabolism, and the very heterogeneous nature of the disease states. Two clinical studies are described that investigate the relationship between plasma levels of fluphenazine (FLU) and its metabolites and therapeutic outcome in schizophrenic patients. In the first of these studies the levels of FLU and fluphenazine sulfoxide (FLUSO) in schizophrenics receiving either 5 or 25 mg of fluphenazine decanoate (FLUD) intramuscularly every 2 weeks were monitored. Patients given 25 mg of FLUD required 3 months to reach plasma level steady state. The results suggest that such patients, when being switched from the oral to the depot formulation of FLU, should continue to receive oral supplementation during the 1st 3 months after conversion. The relationship between log-transformed plasma levels at 26 and 38 weeks with subsequent psychotic exacerbation was investigated with the use of logistic regression and survival analysis. Both demonstrated significant relationships between FLU plasma levels and a risk of psychotic exacerbation at 26 and 38 weeks. The possibility of any correlations between neurological side effects and plasma concentrations were also investigated, with statistically significant correlations between FLU levels and akinesia found at 2 and 26 weeks. In the second of these studies the levels of FLU, FLUSO, 7-hydroxyfluphenazine (7-OHFLU), and fluphenazine N4'-oxide (FLUNO) in schizophrenics receiving 5, 10, or 20 mg of oral fluphenazine dihydrochloride daily for 4 weeks were monitored. The relationships between log-transformed plasma levels, disabling side effects, and global improvement were examined by logistic regression for the 4-week period. The study showed a significant correlation between increases in both plasma levels and disabling side effects such that at a plasma level of 2.7 ng/ml, approximately 90% of acutely ill patients experienced disabling side effects. Conversely, the study also showed that at a plasma level of 0.67 ng/ml, 48% of patients experienced improvement without the development of disabling side effects. When relationships between metabolite levels, disabling side effects, and global improvement were examined by logistic regression, a stronger correlation between disabling side effects and FLUNO levels than between side effects and FLU levels was found. No correlations between disabling side effects and plasma levels of FLUSO or 7-OHFLU were observed. These studies illustrate the usefulness of measuring plasma levels of neuroleptic drugs. C1 UNIV SASKATCHEWAN,COLL MED,SASKATOON S7N 0W0,SASKATCHEWAN,CANADA. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. RP MIDHA, KK (reprint author), UNIV SASKATCHEWAN,COLL PHARM,SASKATOON S7N 0W0,SASKATCHEWAN,CANADA. NR 58 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD JUN PY 1993 VL 15 IS 3 BP 179 EP 189 DI 10.1097/00007691-199306000-00001 PG 11 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA LF859 UT WOS:A1993LF85900001 PM 8101398 ER PT J AU MARK, EJ SHIN, DH AF MARK, EJ SHIN, DH TI DIFFUSE MALIGNANT MESOTHELIOMA OF THE PLEURA - A CLINICOPATHOLOGICAL STUDY OF 6 PATIENTS WITH A PROLONGED SYMPTOM-FREE INTERVAL OR EXTENDED SURVIVAL AFTER BIOPSY AND A REVIEW OF THE LITERATURE OF LONG-TERM SURVIVAL SO VIRCHOWS ARCHIV A-PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY LA English DT Article DE MESOTHELIOMA; PLEURA ID DIFFERENTIATED PAPILLARY MESOTHELIOMA; DIAGNOSIS; PROLIFERATION; HYPERPLASIA; PERITONEUM AB Diffuse malignant mesothelioma of the pleura generally proceeds rapidly with clinical deterioration soon after the initial histopathological diagnosis of the tumor. We encountered six patients in whom the symptom-free interval after biopsy was surprisingly prolonged. Histopathologically, the tumor in each case was epithelioid with prominent myxoid stroma and formation of tubules and micropapillae. Cytologically, the malignant cells had relatively regular nuclei with bland chromatin. As individual findings, these histological and cytological features are common in diffuse malignant mesothelioma. However, the combination of (1) bland cytology of epithelioid cells, (2) formation of tubular and micropapillary patterns, (3) a myxoid stroma and (4) an absence of sclerosing desmoplasia, as observed in these six cases, might indicate indolent disease at the outset in a few patients. It is possible that these features are related to early stage of disease rather than having discriminatory value in their own right. We do not conclude that initially restrained disease necessarily presages a longer mean survival because the follow-up in these patients has not been long enough. We present these observations because, to date, this malignancy has proven so refractory to clinical management. C1 YONSEI UNIV,COLL MED,DEPT PATHOL,SEOUL,SOUTH KOREA. RP MARK, EJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 42 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0174-7398 J9 VIRCHOWS ARCH A JI Virchows Arch. A-Pathol. Anat. Histopathol. PD JUN PY 1993 VL 422 IS 6 BP 445 EP 451 DI 10.1007/BF01606452 PG 7 WC Anatomy & Morphology; Pathology SC Anatomy & Morphology; Pathology GA LN248 UT WOS:A1993LN24800003 PM 8333148 ER PT J AU DEWHIRST, FE PASTER, BJ OLSEN, I FRASER, GJ AF DEWHIRST, FE PASTER, BJ OLSEN, I FRASER, GJ TI PHYLOGENY OF THE PASTEURELLACEAE AS DETERMINED BY COMPARISON OF 16S RIBOSOMAL RIBONUCLEIC-ACID SEQUENCES SO ZENTRALBLATT FUR BAKTERIOLOGIE-INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY VIROLOGY PARASITOLOGY AND INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT SPECIAL SESSION ON TAXONOMY OF THE FAMILY PASTEURELLACEAE, AT THE 3RD INTERNATIONAL CONF ON TAXONOMY AND AUTOMATED IDENTIFICATION OF BACTERIA CY JUL, 1992 CL PRAGUE, CZECHOSLOVAKIA SP INST HYGIENE & EPIDEMOL, CHARLES UNIV, CZECHOSLOVAK SOC MICROBIOL, FEDERAT EUROPEAN MICROBIOL SOC ID DIFFERENT PATHOLOGICAL LESIONS; FAMILY PASTEURELLACEAE; ORAL CAVITY; SENSU-STRICTO; RNA SEQUENCES; SP-NOV; ACTINOBACILLUS; HAEMOLYTICA; STRAINS; HEMOPHILUS AB Previously, virtually complete 16S ribosomal ribonucleic acid sequences were determined for 54 strains of species in the family Pasteurellaceae. The sequences for 16 additional strains have been determined, bringing the total number of strains sequenced to 70. The additional strains include: Actinobacillus hominis, A. muris, A. salpingitidis, Pasteurella bettyae, P. mairii, P. testudinis, and Bisgaard taxa 2, 3, 5, 6, 7, 8, 9, 13, and 14 (2 strains). A phylogenetic tree was constructed based upon sequence similarity using the Neighbor-Joining method. The additional sequence information and phylogenetic analysis generally supported our previously described phylogenetic structure for the family Pasteurellaceae. Cluster 1, containing Haemophilus sensu stricto, was unchanged. P. mairii was closely related to P. aerogenes and Bisgaard taxon 6 was related to H. somnus in Cluster 2. A. salpingitidis and Bisgaard taxa 2, 3, 7, and 13 fell in Cluster 3 which contains Pasteurella sensu stricto. A. hominis was closely related to Actinobacillus sensu stricto species in Cluster 4A. Bisgaard taxa 5, 8, 9 and P. bettyae fell in Cluster 4B. A. muris was related to P. pneumotropica in Cluster 5. Haemophilus parainfluenzae strains branched deeply as a 6th cluster. Bisgaard taxon 14 and P. testudinis formed a 7th cluster which branched deeper than any previously described clusters in the family Pasteurellaceae. The branching was extremely complex and taxonomic division of the family into phylogenetically and phenotypically coherent genera will be difficult. C1 UNIV OSLO,FAC DENT,DEPT MICROBIOL,OSLO 3,NORWAY. UNIV OSLO,DEPT MICROBIOL,OSLO 3,NORWAY. RP DEWHIRST, FE (reprint author), FORSYTH DENT CTR,DEPT PHARMACOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-08303, DE-04881] NR 42 TC 67 Z9 69 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0934-8840 J9 ZBL BAKT-INT J MED M JI Zent.bl. Bakteriol.-Int. J. Med. Microbiol. Virol. Parasitol. Infect. Dis. PD JUN PY 1993 VL 279 IS 1 BP 35 EP 44 PG 10 WC Microbiology; Virology SC Microbiology; Virology GA LN253 UT WOS:A1993LN25300004 PM 7690271 ER PT J AU HAHN, WC MENZIN, E SAITO, T GERMAIN, RN BIERER, BE AF HAHN, WC MENZIN, E SAITO, T GERMAIN, RN BIERER, BE TI THE COMPLETE SEQUENCES OF PLASMIDS PFNEO AND PMH-NEO - CONVENIENT EXPRESSION VECTORS FOR HIGH-LEVEL EXPRESSION OF EUKARYOTIC GENES IN HEMATOPOIETIC-CELL LINES SO GENE LA English DT Note DE RECOMBINANT DNA; HEMATOPOIETIC EXPRESSION; G418 RESISTANCE; T-CELL HYBRIDOMAS ID RECEPTOR AB The eukaryotic expression vector, pFNeo, confers resistance to the antibiotic G418 and directs hematopoietic-specific expression of proteins under the control of the long terminal repeat from the Friend spleen focus-forming virus. Here, we report the entire nucleotide sequence of pFNeo. We have also constructed and sequenced a pFNeo-based expression vector (pMH-Neo) that carries an improved multiple cloning site region for easier subcloning. The utility of both vectors was demonstrated by transfection of murine T-cell hybridomas by electroporation. Transfection with either pFNeo or pMH-Neo yielded a high frequency (1 in 2 x 10(4)) of G418-resistant cell lines. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,DANA 1610B,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHIBA UNIV,SCH MED,CTR NEUROBIOL & MOLEC IMMUNOL,DIV MOLEC GENET,CHIBA,JAPAN. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Saito, Takashi/C-9684-2009 OI Saito, Takashi/0000-0001-9495-3547 FU NIAID NIH HHS [AI28554, AI34565] NR 6 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 30 PY 1993 VL 127 IS 2 BP 267 EP 268 DI 10.1016/0378-1119(93)90731-H PG 2 WC Genetics & Heredity SC Genetics & Heredity GA LF233 UT WOS:A1993LF23300018 PM 8500769 ER PT J AU COLE, BF GELBER, RD GOLDHIRSCH, A AF COLE, BF GELBER, RD GOLDHIRSCH, A TI COX REGRESSION-MODELS FOR QUALITY-ADJUSTED SURVIVAL ANALYSIS SO STATISTICS IN MEDICINE LA English DT Article ID BREAST-CANCER; LARGE SAMPLE AB We develop a method for incorporating covariates as regressors in a quality adjusted survival analysis (Q-TWiST) using Cox's proportional hazards model. The standard Q-TWiST method assumes that patients progress through a series of health states which differ in quality of life. The Kaplan-Meier product limit method is used to estimate the mean duration of each state by estimating the survival curves for the health state transition times. These estimates provide the basis for quality adjusted survival analysis. In this paper, the survival curves are modelled using Cox's proportional hazards regression. Quality adjusted survival is estimated given sets of covariate values, allowing one to profile patients. The results are useful for investigating how prognostic factors affect treatment benefits in terms of quality of life. We give a brief review of the standard Q-TWiST method and illustrate the extended methodology with an example from the International Breast Cancer Study Group Trial V comparing short duration versus long duration chemotherapy in the treatment of node-positive breast cancer. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. OSPED CIVICO, DEPT ONCOL, CH-6900 LUGANO, SWITZERLAND. RP HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. RI Cole, Bernard/I-3775-2012 FU NCI NIH HHS [CA-06516] NR 19 TC 28 Z9 28 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAY 30 PY 1993 VL 12 IS 10 BP 975 EP 987 DI 10.1002/sim.4780121009 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 LF323 UT WOS:A1993LF32300008 PM 8337554 ER PT J AU HALL, JE TAYLOR, AE MARTIN, KA CROWLEY, WF AF HALL, JE TAYLOR, AE MARTIN, KA CROWLEY, WF TI NEW APPROACHES TO THE STUDY OF THE NEUROENDOCRINE ABNORMALITIES OF WOMEN WITH THE POLYCYSTIC OVARIAN SYNDROME SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FREE ALPHA-SUBUNIT; FOLLICLE-STIMULATING-HORMONE; INAPPROPRIATE GONADOTROPIN-SECRETION; HUMAN MENSTRUAL-CYCLE; GNRH-DEFICIENT MEN; LUTEINIZING-HORMONE; PULSE FREQUENCY; DISEASE; SERUM C1 MASSACHUSETTS GEN HOSP, DEPT MED, CTR REPROD ENDOCRINE SCI, BOSTON, MA 02114 USA. RP HALL, JE (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 687 BP 182 EP 192 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK217 UT WOS:A1993LK21700021 ER PT J AU CROWLEY, WF HALL, JE MARTIN, KA ADAMS, J TAYLOR, AE AF CROWLEY, WF HALL, JE MARTIN, KA ADAMS, J TAYLOR, AE TI AN OVERVIEW OF THE DIAGNOSTIC CONSIDERATIONS IN POLYCYSTIC OVARIAN SYNDROME SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 MASSACHUSETTS GEN HOSP, DEPT MED, CTR REPROD ENDOCRINE SCI, BOSTON, MA 02114 USA. RP CROWLEY, WF (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 687 BP 235 EP 241 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK217 UT WOS:A1993LK21700027 ER PT J AU SCHWARTZ, JL ANTONIADES, DZ ZHAO, SC BERTRAM, J PACKER, L AF SCHWARTZ, JL ANTONIADES, DZ ZHAO, SC BERTRAM, J PACKER, L TI MOLECULAR AND BIOCHEMICAL REPROGRAMMING OF ONCOGENESIS THROUGH THE ACTIVITY OF PROOXIDANTS AND ANTIOXIDANTS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID HEAT-SHOCK FACTOR; BETA-CAROTENE; ALPHA-TOCOPHEROL; EXPERIMENTAL CANCER; STRESS PROTEINS; CYCLOSPORINE-A; HUMAN HOMOLOGS; CELL-LINE; P53; PHOSPHORYLATION C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. UNIV HAWAII,HONOLULU,HI 96813. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOPATHOL LAB,BOSTON,MA 02115. ARISTOTLE UNIV THESSALONIKA,SCH DENT MED,DEPT STOMATOL,SALONIKA,GREECE. SUZHOU MED COLL,DEPT RADIOL MED,SUZHOU,PEOPLES R CHINA. RP SCHWARTZ, JL (reprint author), HARVARD UNIV,SCH DENT MED,DEPT ORAL PATHOL & ORAL MED,188 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 77 TC 68 Z9 69 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 686 BP 262 EP 279 DI 10.1111/j.1749-6632.1993.tb39185.x PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG193 UT WOS:A1993LG19300023 PM 8512252 ER PT J AU CADAY, CG SKLAR, RM BERLOVE, DJ KEMMOU, A BROWN, RH FINKLESTEIN, SP AF CADAY, CG SKLAR, RM BERLOVE, DJ KEMMOU, A BROWN, RH FINKLESTEIN, SP TI POLYUBIQUITIN GENE-EXPRESSION FOLLOWING CEREBRAL-ISCHEMIA SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PROGRAMMED CELL-DEATH; DELAYED NEURONAL DEATH; UBIQUITIN-CODING SEQUENCES; HEAT-SHOCK; MESSENGER-RNA; GERBIL HIPPOCAMPUS; TRANSIENT ISCHEMIA; PROTEIN-SYNTHESIS; GLOBAL-ISCHEMIA; BRAIN C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,DAY NEUROMUSCULAR RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CADAY, CG (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,CNS GROWTH FACTOR RES LAB,BOSTON,MA 02114, USA. FU NIA NIH HHS [NIA AG-08207]; NINDS NIH HHS [NINDS NS-10828] NR 61 TC 6 Z9 6 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 679 BP 188 EP 194 DI 10.1111/j.1749-6632.1993.tb18298.x PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800015 PM 8390143 ER PT J AU GABRIEL, SM BIERER, LM HAROTUNIAN, V PUROHIT, DP PERL, DP DAVIS, KL AF GABRIEL, SM BIERER, LM HAROTUNIAN, V PUROHIT, DP PERL, DP DAVIS, KL TI WIDESPREAD DEFICITS IN SOMATOSTATIN BUT NOT NEUROPEPTIDE-Y CONCENTRATIONS IN ALZHEIMERS-DISEASE CEREBRAL-CORTEX SO NEUROSCIENCE LETTERS LA English DT Article DE ALZHEIMERS DISEASE; SOMATOSTATIN; NEUROPEPTIDE-Y; DEMENTIA; NEUROPEPTIDE; NEURODEGENERATION; NITRIC OXIDE SYNTHASE; NADPH-DIAPHORASE ID CHOLINE-ACETYLTRANSFERASE ACTIVITY; SENILE DEMENTIA; NADPH-DIAPHORASE; PARKINSONS-DISEASE; DOWNS-SYNDROME; IMMUNOREACTIVITY; NEURONS; COEXISTENCE; POLYPEPTIDE AB Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in the cerebral cortex of 49 patients with Alzheimer's disease (AD), and 9 elderly controls. Concentrations of SLI were lower in AD patients relative to controls in 9 of 10 cortical regions. In contrast, no significant differences in NPYLI concentrations between the two groups were observed in any of 10 regions. These studies suggest a dissociation between SLI deficits and NPYLI concentrations in the postmortem cerebral cortex of AD patients. The apparent sparing of NPYLI-containing neurons suggests that neuropeptide Y may be located within a separate group of neurons compared to somatostatin. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. RP GABRIEL, SM (reprint author), BRONX VET AFFAIRS MED CTR,DEPT PSYCHIAT,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. FU NIA NIH HHS [NIA AG02219, NIA AG05138, NIA AG00408] NR 33 TC 33 Z9 36 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 28 PY 1993 VL 155 IS 1 BP 116 EP 120 DI 10.1016/0304-3940(93)90686-F PG 5 WC Neurosciences SC Neurosciences & Neurology GA LK125 UT WOS:A1993LK12500027 PM 8103205 ER PT J AU WANG, CY PETRYNIAK, B THOMPSON, CB KAELIN, WG LEIDEN, JM AF WANG, CY PETRYNIAK, B THOMPSON, CB KAELIN, WG LEIDEN, JM TI REGULATION OF THE ETS-RELATED TRANSCRIPTION FACTOR ELF-1 BY BINDING TO THE RETINOBLASTOMA PROTEIN SO SCIENCE LA English DT Article ID LARGE T-ANTIGEN; ADENOVIRUS E1A PROTEINS; LONG TERMINAL REPEAT; GENE-PRODUCT; CELL-CYCLE; SUSCEPTIBILITY GENE; DNA-BINDING; LEUKEMIA-VIRUS; FACTOR E2F; SEQUENCE AB The retinoblastoma gene product (Rb) is a nuclear phosphoprotein that regulates cell cycle progression. Elf-1 is a lymphoid-specific Ets transcription factor that regulates inducible gene expression during T cell activation. In this report, it is demonstrated that Elf-1 contains a sequence motif that is highly related to the Rb binding sites of several viral oncoproteins and binds to the pocket region of Rb both in vitro and in vivo. Elf-1 binds exclusively to the underphosphorylated form of Rb and fails to bind to Rb mutants derived from patients with retinoblastoma. Co-immunoprecipitation experiments demonstrated an association between Elf-1 and Rb in resting normal human T cells. After T cell activation, the phosphorylation of Rb results in the release of Elf-1, which is correlated temporally with the activation of Elf-1-mediated transcription. Overexpression of a phosphorylation-defective form of Rb inhibited Elf-1-dependent transcription during T cell activation. These results demonstrate that Rb interacts specifically with a lineage-restricted Ets transcription factor. This regulated interaction may be important for the coordination of lineage-specific effector functions such as lymphokine production with cell cycle progression in activated T cells. C1 UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. UNIV MICHIGAN,MED CTR,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIAID NIH HHS [R01 AI29673-01] NR 52 TC 196 Z9 200 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 MAY 28 PY 1993 VL 260 IS 5112 BP 1330 EP 1335 DI 10.1126/science.8493578 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LE025 UT WOS:A1993LE02500045 PM 8493578 ER PT J AU HOLTZMAN, EJ HARRIS, HW KOLAKOWSKI, LF GUAYWOODFORD, LM BOTELHO, B AUSIELLO, DA AF HOLTZMAN, EJ HARRIS, HW KOLAKOWSKI, LF GUAYWOODFORD, LM BOTELHO, B AUSIELLO, DA TI A MOLECULAR DEFECT IN THE VASOPRESSIN V2-RECEPTOR GENE CAUSING NEPHROGENIC DIABETES-INSIPIDUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID POINT MUTATION; LINKAGE C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,300 LONGWOOD AVE,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV NEPHROL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-19406, DK-38874] NR 21 TC 65 Z9 66 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 27 PY 1993 VL 328 IS 21 BP 1534 EP 1537 DI 10.1056/NEJM199305273282105 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LC941 UT WOS:A1993LC94100005 PM 8479490 ER PT J AU MERENDINO, JJ SPIEGEL, AM CRAWFORD, JD OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ AF MERENDINO, JJ SPIEGEL, AM CRAWFORD, JD OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ TI A MUTATION IN THE VASOPRESSIN V2-RECEPTOR GENE IN A KINDRED WITH X-LINKED NEPHROGENIC DIABETES-INSIPIDUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID RECEPTORS; DNA C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP MERENDINO, JJ (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,RM 8C-101,BETHESDA,MD 20892, USA. RI Brownstein, Michael/B-8609-2009 NR 26 TC 51 Z9 51 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 27 PY 1993 VL 328 IS 21 BP 1538 EP 1541 DI 10.1056/NEJM199305273282106 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LC941 UT WOS:A1993LC94100006 PM 8479491 ER PT J AU FLEMING, C WASSON, JH ALBERTSEN, PC BARRY, MJ WENNBERG, JE AF FLEMING, C WASSON, JH ALBERTSEN, PC BARRY, MJ WENNBERG, JE TI A DECISION-ANALYSIS OF ALTERNATIVE TREATMENT STRATEGIES FOR CLINICALLY LOCALIZED PROSTATE-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; UNTREATED PATIENTS; TUMOR VOLUME; ADENOCARCINOMA; CARCINOMA; GRADE; THERAPY; DISEASE; BIOPSY AB Objective.-To model the impact of initial therapy on outcomes for men with localized (clinical stage A or B) prostatic carcinoma. Design.-A decision analysis modeling three strategies: radical prostatectomy, external-beam radiation therapy, and watchful waiting, with delayed hormonal therapy if metastatic disease develops. We modeled the main benefit of treatment as a reduction in the chance of death or disutility from metastatic disease. These benefits were offset in the model by the risks of treatment-related morbidity and mortality. The model was used to analyze expected outcomes by tumor grade (well, moderately, and poorly differentiated) for men 60 to 75 years of age. Data.-Probabilities and rates for important clinical events, obtained through review of the literature for prostatic carcinoma and analysis of Medicare claims data. Main Results.-Several patterns emerged within the range of uncertainty about the risks and benefits of treatment for prostatic carcinoma. In patients with well-differentiated tumor grades, based on clinical staging, treatment at best offers limited benefit in terms of quality-adjusted life expectancy and may result in harm to the patient. Among patients with moderately or poorly differentiated tumors, if we use the most optimistic assumptions about treatment efficacy, then patients aged 60 to 65 years would benefit from either radical prostatectomy or external-beam radiation therapy, compared with watchful waiting. However, in most other cases, treatment offers less than a 1-year improvement in quality-adjusted life expectancy or decreases the quality-adjusted life expectancy compared with watchful waiting. Invasive treatment generally appears to be harmful for patients older than 70 years. Conclusions.-Radical prostatectomy and radiation therapy may benefit selected groups of patients with localized prostate cancer, particularly younger patients with higher-grade tumors. However, our model shows that in most cases the potential benefits of therapy are small enough that the choice of therapy is sensitive to the patient's preferences for various outcomes and discounting. The choice of watchful waiting is a reasonable alternative to invasive treatment for many men with localized prostatic carcinoma. C1 OREGON HLTH SCI UNIV,CTR BIOMED INFORMAT COMMUN,PORTLAND,OR 97201. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT COMMUNITY & FAMILY MED,HANOVER,NH 03756. UNIV CONNECTICUT,CTR HLTH,DIV UROL,FARMINGTON,CT 06032. MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. FU PHS HHS [H506336-03] NR 42 TC 364 Z9 364 U1 0 U2 2 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 26 PY 1993 VL 269 IS 20 BP 2650 EP 2658 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA LC865 UT WOS:A1993LC86500030 PM 8487449 ER PT J AU KHARBANDA, S HUBERMAN, E KUFE, D AF KHARBANDA, S HUBERMAN, E KUFE, D TI ACTIVATION OF THE JUN-D GENE DURING TREATMENT OF HUMAN MYELOID-LEUKEMIA CELLS WITH 1-BETA-D-ARABINOFURANOSYLCYTOSINE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID PROTEIN-KINASE-C; TRANSCRIPTION FACTOR AP-1; DNA-BINDING PROTEIN; CYCLIC-AMP; MONOCYTIC DIFFERENTIATION; B GENE; ARA-C; EXPRESSION; ONCOGENE; FOS AB The jun-D gene is a member of the c-jun family of early response genes that code for DNA binding proteins. The present studies demonstrate that 1-beta-D-arabinofuranosylcytosine (ara-C) increases jun-D expression in HL-525 myeloid leukemia cells. This induction by ara-C was maximal at 6 hr and transient. In contrast, ara-C had no detectable effect on the gene coding for the cAMP-responsive element binding protein 1. Nuclear run-on assays demonstrated that ara-C treatment is associated with an increased rate of jun-D transcription. The results also show that jun-D transcripts are stabilized at a posttranscriptional level in ara-C-treated cells. Taken together, these results demonstrate that ara-C induces expression of the jun-D gene and that this effect is regulated by transcriptional and posttranscriptional mechanisms. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. ARGONNE NATL LAB,DIV BIOL & MED RES,ARGONNE,IL 60347. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. FU NCI NIH HHS [CA29431, CA42802] NR 42 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 25 PY 1993 VL 45 IS 10 BP 2055 EP 2061 DI 10.1016/0006-2952(93)90016-P PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LF228 UT WOS:A1993LF22800016 PM 8512587 ER PT J AU BAENZIGER, JE MILLER, KW ROTHSCHILD, KJ AF BAENZIGER, JE MILLER, KW ROTHSCHILD, KJ TI FOURIER-TRANSFORM INFRARED DIFFERENCE SPECTROSCOPY OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR - EVIDENCE FOR SPECIFIC PROTEIN STRUCTURAL-CHANGES UPON DESENSITIZATION SO BIOCHEMISTRY LA English DT Article ID CONFORMATIONAL-CHANGES; TORPEDO-CALIFORNICA; PROTONATION CHANGES; BACTERIORHODOPSIN; BINDING; MEMBRANE; AGONIST; TRANSITIONS; CHROMOPHORE; TRANSPORT AB We have previously reported a new method based on Fourier transform infrared spectroscopy for probing conformational changes that occur upon the binding of ligands to the nicotinic acetylcholine receptor (nAChR) [Baenziger, J. E., Miller, K. W., & Rothschild, K. J. (1992) Biophys. J. 61, 983-992; Baenziger, J. E., Miller, K. W., McCarthy, M. P., & Rothschild, K. J. (I 992) Biophys. J. 62, 64-66]. Spectra are recorded using attenuated total reflection both in the presence and absence of agonists. The resulting nAChR ''resting-to-desensitized'' difference spectra reveal small highly reproducible infrared bands which can arise from vibrations of the agonist and structural changes in the nAChR membrane during the conversion of the receptor from the resting to desensitized state. In this work we have used a combination of different agonists and an antagonist along with isotopic labeling to assign bands in these spectra. nAChR membranes pretreated with the competitive antagonist alpha-bungarotoxin exhibit no bands above the noise level (approximately 10(-5) au) demonstrating that vibrations of the unbound agonist do not contribute to the normal difference spectrum. In contrast, bands in the resting-to-desensitized difference spectra are identified which can be assigned to the bound agonist, providing a means to probe its interaction and orientation in the binding site. Additional difference bands are due to secondary structural changes of the protein, perturbation of tyrosine(s), and changes in carboxyl groups possibly from Asp and/or Glu residues. Remarkably, some of these spectral changes are similar to those detected during the bleaching of the photoreceptor membrane protein rhodopsin. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. BOSTON UNIV,DEPT PHYSIOL,BOSTON,MA 02215. BOSTON UNIV,PROGRAM CELLULAR BIOPHYS,BOSTON,MA 02215. FU NEI NIH HHS [EY05499]; NIGMS NIH HHS [NIGMS GM-15904] NR 40 TC 52 Z9 52 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 25 PY 1993 VL 32 IS 20 BP 5448 EP 5454 DI 10.1021/bi00071a022 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD661 UT WOS:A1993LD66100022 PM 8499448 ER PT J AU MOTOKURA, T ARNOLD, A AF MOTOKURA, T ARNOLD, A TI CYCLINS AND ONCOGENESIS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; MATURATION-PROMOTING FACTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; E2F TRANSCRIPTION FACTOR; ADENOVIRUS E1A PROTEINS; T(11-14) CHROMOSOME-TRANSLOCATION; PARATHYROID-HORMONE GENE; SQUAMOUS-CELL CARCINOMAS; HUMAN-BREAST TUMORS; SEA-URCHIN EGGS C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,WELLMAN 503,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MGH,CTR CANC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 55909]; NIDDK NIH HHS [DK11794] NR 234 TC 212 Z9 216 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD MAY 25 PY 1993 VL 1155 IS 1 BP 63 EP 78 DI 10.1016/0304-419X(93)90022-5 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LF800 UT WOS:A1993LF80000004 PM 8504131 ER PT J AU FEENER, EP BACKER, JM KING, GL WILDEN, PA SUN, XJ KAHN, CR WHITE, MF AF FEENER, EP BACKER, JM KING, GL WILDEN, PA SUN, XJ KAHN, CR WHITE, MF TI INSULIN STIMULATES SERINE AND TYROSINE PHOSPHORYLATION IN THE JUXTAMEMBRANE REGION OF THE INSULIN-RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE ACTIVITY; BETA-SUBUNIT; THREONINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; HEPATOMA-CELLS; AMINO-ACIDS; AUTOPHOSPHORYLATION; IDENTIFICATION; RESIDUES; DOMAIN AB Insulin-stimulated autophosphorylation of the cytoplasmic juxtamembrane region of the human insulin receptor was examined by Tricine/SDS-PAGE. Various mutant receptor molecules were used to identify two tryptic phosphopeptides associated with the juxtamembrane region which accounts for 15% of the autophosphorylation of partially purified insulin receptor. These phosphopeptides were immunoprecipitated with an antipeptide antibody against the juxtamembrane sequence and were phosphorylated exclusively on tyrosine. Substitution of both Tyr960 and Tyr953 with alanine eliminated insulin-stimulated phosphorylation of the juxtamembrane region without affecting tyrosine autophosphorylation in the C terminus or regulatory regions. Monosubstitution of Tyr960 with phenylalanine or alanine reduced phosphorylation in the juxtamembrane region by more than 50%, and manual Edman degradation indicated that Tyr960 was phosphorylated in wild-type receptor. In vivo, phosphorylation of the juxtamembrane region accounts for one-third of the insulin receptor phosphorylation and contains both phosphoserine and phosphotyrosine. Deletion of Tyr960 and 11 adjacent amino acids eliminated insulin-stimulated phosphorylation of the juxtamembrane region. Substitution of Tyr960 reduced this phosphorylation by more than 50%. The insulin receptor also undergoes serine phosphorylation outside of the juxtamembrane region which depends on the presence of Tyr1151. Together with our previous studies, this report suggests that phosphorylation of Tyr960 may play an important role in signal transduction by the insulin receptor. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP FEENER, EP (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK 36433, P30 DK036836, DK 33201, DK 38712] NR 41 TC 88 Z9 88 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 25 PY 1993 VL 268 IS 15 BP 11256 EP 11264 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600079 PM 8496180 ER PT J AU FUKUOKA, SI ZHANG, DE TANIGUCHI, Y SCHEELE, GA AF FUKUOKA, SI ZHANG, DE TANIGUCHI, Y SCHEELE, GA TI STRUCTURE OF THE CANINE PANCREATIC COLIPASE GENE INCLUDES 2 PROTEIN-BINDING SITES IN THE PROMOTER REGION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; EXOCRINE PANCREAS; SECRETORY PROTEINS; CDNA SEQUENCE; MESSENGER-RNA; DIABETIC RATS; DNA; ENHANCER; PORCINE; TRANSCRIPTION AB Characterization of a lambda phage genomic clone, CL5A, which encodes the canine pancreatic colipase gene, revealed the primary structure of 987 nucleotides (nt) of 5'-flanking sequence, 2066 nt defining the primary transcriptional unit, which is organized into three exon sequences, and 130 nt of 3'-flanking sequence. Exon 1 encodes the amino-terminal signal peptide, the propeptide (Val1-Pro-Asp-Pro-Arg), and the hydrophobic lipid-binding region (Gly6-Ile-Ile-Ile) at the amino terminus of the mature coenzyme. Exon 2 encodes carboxylate residues (Glu12 and Glu15) likely to be involved in binding of pancreatic lipase to colipase at the aqueous-lipid interface. Exon 3 encodes the hydrophobic sequence (Leu54-Tyr-Gly-Tyr-Tyr) that is essential for binding the central tightly structured disulfide-bonded region of the coenzyme to lipid. Southern blot analysis was consistent with the presence of a single-copy colipase gene and a potential colipase gene homologue. Among 16 tissues examined by Northern blot analysis, colipase expression was detected only in pancreas. Proteins contained in nuclear extracts prepared from dog pancreas conferred two regions of DNase I protection coincident for both coding and noncoding strands (positions -62 to -44 (CL-I site) and -128 to -106 (CL-II site) in the coding strand). Competition gel mobility shift experiments indicated that protein-DNA interactions that occur at colipase sites I and II are sequence- and protein-specific and unrelated to the PAN-binding sequence described in the 5'-enhancer region of the rat chymotrypsin B gene (Nelson, C., Shen, L.P., Meister, A., Fodor, E., and Rutter, W. J. (1990) Genes & Dev. 4, 1035-1043). Nuclear extracts from pancreas and brain, but not liver, contain similar CL-I and CL-II-binding proteins. CL-I and CL-II represent protein-binding elements that may participate as additional promoter regions in regulated expression of the colipase gene. CL-I contains a central homopolymeric d(G) sequence. CL-II shows a GC-rich region on the noncoding strand (5' GGGGGCGTGT 3') that is similar (8/9 match) to the Sp1-binding sequence. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,THORNDIKE LAB,CELL & MOLEC BIOL LAB,DA-554,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. KYOTO UNIV,FOOD SCI RES INST,UJI,KYOTO 611,JAPAN. FU NIDDK NIH HHS [DDK-18532] NR 59 TC 6 Z9 7 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 25 PY 1993 VL 268 IS 15 BP 11312 EP 11320 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600087 PM 7684378 ER PT J AU FUJIMOTO, T STROUD, E WHATLEY, RE PRESCOTT, SM MUSZBEK, L LAPOSATA, M MCEVER, RP AF FUJIMOTO, T STROUD, E WHATLEY, RE PRESCOTT, SM MUSZBEK, L LAPOSATA, M MCEVER, RP TI P-SELECTIN IS ACYLATED WITH PALMITIC ACID AND STEARIC-ACID AT CYSTEINE-766 THROUGH A THIOESTER LINKAGE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRANULE MEMBRANE-PROTEIN; WEIBEL-PALADE BODIES; PLASMA-MEMBRANE; COVALENT MODIFICATION; MONOCLONAL-ANTIBODY; VIRAL GLYCOPROTEIN; ENDOTHELIAL-CELLS; CELLULAR PROTEINS; GMP-140; ACTIVATION AB We report that the adhesion receptor P-selectin can be metabolically labeled with [H-3]palmitic acid in human platelets. Analysis of alkaline methanolysis products from labeled protein demonstrated that the radioactivity associated with P-selectin was covalently bound palmitic acid. [H-3]Palmitic acid was cleaved by hydroxylamine treatment at neutral pH and by reducing agents, indicating that acylation occurred through a thioester linkage. Both stearic acid and palmitic acid were detected by gas chromatography-mass spectrometry analysis of alkaline hydrolysates of purified P-selectin. Deletion or mutation of Cys766 eliminated [H-3] palmitic acid labeling of P-selectin in transfected COS-7 cells. We conclude that the cytoplasmic domain of P-selectin is acylated at Cys766 through a thioester bond. Fatty acid acylation may regulate intracellular trafficking or other functions of P-selectin. C1 UNIV OKLAHOMA HLTH SCI CTR,WK WARREN MED RES INST,DEPT MED,825 NE 13TH ST,OKLAHOMA CITY,OK 73104. VET AFFAIRS MED CTR,SALT LAKE CITY,UT 84112. UNIV UTAH,SCH MED,DEPT BIOCHEM,SALT LAKE CITY,UT 84112. UNIV UTAH,SCH MED,DEPT MED,NORA ECCLE HARRISON CARDIOVASC RES & TRAINING INST,SALT LAKE CITY,UT 84112. UNIV SCH MED DEBRECEN,DEPT CLIN CHEM,H-4012 DEBRECEN,HUNGARY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. UNIV OKLAHOMA HLTH SCI CTR,WK WARREN MED RES INST,DEPT BIOCHEM,OKLAHOMA CITY,OK 73104. OKLAHOMA MED RES FDN,CARDIOVASC BIOL RES PROGRAM,OKLAHOMA CITY,OK 73104. FU NHLBI NIH HHS [HL 34127, HL 34363, HL 45510] NR 44 TC 47 Z9 48 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 25 PY 1993 VL 268 IS 15 BP 11394 EP 11400 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600098 PM 7684381 ER PT J AU STRASSMAN, AM VOS, BP AF STRASSMAN, AM VOS, BP TI SOMATOTOPIC AND LAMINAR ORGANIZATION OF FOS-LIKE IMMUNOREACTIVITY IN THE MEDULLARY AND UPPER CERVICAL DORSAL HORN INDUCED BY NOXIOUS FACIAL STIMULATION IN THE RAT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE TRIGEMINAL NUCLEUS CAUDALIS; CORNEA; NOCICEPTION; BRAIN-STEM; OROFACIAL PAIN ID TRIGEMINAL SUBNUCLEUS CAUDALIS; PRIMARY AFFERENT NEURONS; LUMBAR SPINAL-CORD; BRAIN-STEM; HORSERADISH-PEROXIDASE; CENTRAL PROJECTIONS; EXPRESSION; PROTEIN; CAT; REPRESENTATION AB The distribution of fos-like-immunoreactivity (fos-LI) in the medullary and upper cervical dorsal horn was examined following noxious facial stimulation, in order to evaluate the use of fos as a marker for neuronal activation in trigeminal nociceptive pathways. Control animals that received urethane anesthesia and no facial stimulation showed substantial bilateral labeling in the trigeminal complex that was restricted to one rostrocaudal level, at the transition between the medullary dorsal horn (nucleus caudalis) and nucleus interpolaris. Noxious mechanical stimulation (pinch) of different facial sites produced labeling in the ipsilateral dorsal horn whose distribution varied predictably with the rostrocaudal and dorsoventral position of the facial stimulation site, such that rostral facial sites were represented rostrally in the dorsal horn and dorsal sites were represented ventrolaterally. The cornea was exceptional among the facial stimulation sites in that it had a specific representation at two distinct rostrocaudal levels, in C1 and the interpolaris-caudalis transition region; the position of the rostral peak was somatotopically inappropriate, based on the representation of other facial sites. The proportion of labelling in laminae III-IV relative to laminae I-II was higher with noxious mechanical stimulation than with noxious thermal (55-degrees-C) or chemical (subcutaneous injection of capsaicin) stimulation. The proportion of labelling in laminae III-IV produced by electrical stimulation of the infraorbital nerve was no greater than that produced by pinch. The results suggest that fos-LI mapping can be a useful method for the investigation of somatotopy but is subject to serious limitations when used for the investigation of laminar organization. The results also suggest that the interpolaris-caudalis transition region may have properties that are distinct from those of the rest of the trigeminal complex, possibly related to an involvement in autonomic function. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP STRASSMAN, AM (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02129, USA. FU NINDS NIH HHS [NS24594] NR 66 TC 193 Z9 195 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 22 PY 1993 VL 331 IS 4 BP 495 EP 516 DI 10.1002/cne.903310406 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA LA020 UT WOS:A1993LA02000005 PM 8509507 ER PT J AU WANG, PH LAU, J CHALMERS, TC AF WANG, PH LAU, J CHALMERS, TC TI METAANALYSIS OF EFFECTS OF INTENSIVE BLOOD-GLUCOSE CONTROL ON LATE COMPLICATIONS OF TYPE-I DIABETES SO LANCET LA English DT Article ID SUBCUTANEOUS INSULIN INFUSION; CLINICAL-TRIALS; RETINOPATHY; PROGRESSION; EXPERIENCE; MELLITUS; THERAPY; IDDM AB Tight blood glucose control has been speculated to reduce late complications in insulin-dependent diabetics but results from individual studies have been inconsistent. We have done a meta-analysis of sixteen randomised trials of intensive therapy to estimate its impact on the progression of diabetic retinopathy and nephropathy and the risks of severe side-effects. In the intensive therapy group, the risk of retinopathy progression was insignificantly higher after 6.12 months of intensive control (odds ratio [OR] 2.11). After more than two years of intensive therapy the risk of retinopathy progression was lower (OR 0.49 [95% confidence interval 0.28-0.85], p = 0.011). The risk of nephropathy progression was also decreased significantly (OR 0.34 [0.20-0.58], p<0.001). The incidence of severe hypoglycaemia increased by 9.1 episodes per 100 person-years (95% CI -1.4 to +19.6) in the intensively treated patients. The incidence of diabetic ketoacidosis increased by 12.6 episodes per 100 person-years (95% CI, 8.7-16.5) in the patients on continuous subcutaneous insulin infusion. Long-term intensive blood glucose control significantly reduces the risk of diabetic retinopathy and nephropathy progression but long-term continuous subcutaneous insulin infusion was associated with an increased incidence of diabetic ketoacidosis, and intensive therapy may cause more severe hypoglycaemic reactions. C1 BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NEW ENGLAND MED CTR, CTR CARDIOVASC HLTH RES SERV, BOSTON, MA 02111 USA. TECHNOL ASSESSMENT GRP, BOSTON, MA USA. RP WANG, PH (reprint author), JOSLIN DIABET CTR, 1 JOSLIN PL, BOSTON, MA 02115 USA. FU AHRQ HHS [R01 HS-05936] NR 26 TC 348 Z9 353 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAY 22 PY 1993 VL 341 IS 8856 BP 1306 EP 1309 DI 10.1016/0140-6736(93)90816-Y PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LD253 UT WOS:A1993LD25300004 PM 8098449 ER PT J AU KLAFFKE, W WARREN, CD JEANLOZ, RW AF KLAFFKE, W WARREN, CD JEANLOZ, RW TI SYNTHESIS OF OLIGOSACCHARIDES HAVING THE BETA-D-GLCPNAC-(1-]4)-D-GLC STRUCTURE SO CARBOHYDRATE RESEARCH LA English DT Note ID N-PENTENYL GLYCOSIDES; CARBOHYDRATE-CHEMISTRY C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM,CARBOHYDRATE UNIT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 40930] NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 21 PY 1993 VL 244 IS 1 BP 171 EP 179 DI 10.1016/0008-6215(93)80013-5 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LG458 UT WOS:A1993LG45800013 PM 8339300 ER PT J AU SPIEGELMAN, BM HOTAMISLIGIL, GS AF SPIEGELMAN, BM HOTAMISLIGIL, GS TI THROUGH THICK AND THIN - WASTING, OBESITY, AND TNF-ALPHA SO CELL LA English DT Review ID TUMOR-NECROSIS-FACTOR; INSULIN RESISTANCE; CACHECTIN; MICE; ENDOTOXIN; CACHEXIA; EXPRESSION; RECEPTORS C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP SPIEGELMAN, BM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 30 TC 172 Z9 176 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 21 PY 1993 VL 73 IS 4 BP 625 EP 627 DI 10.1016/0092-8674(93)90243-J PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD830 UT WOS:A1993LD83000002 PM 8500160 ER PT J AU COLONNA, M BROOKS, EG FALCO, M FERRARA, GB STROMINGER, JL AF COLONNA, M BROOKS, EG FALCO, M FERRARA, GB STROMINGER, JL TI GENERATION OF ALLOSPECIFIC NATURAL-KILLER-CELLS BY STIMULATION ACROSS A POLYMORPHISM OF HLA-C SO SCIENCE LA English DT Article ID PARENTAL LYMPHOCYTES; EXPRESSION; NK; RECOGNITION; RESISTANCE; MOLECULES; ANTIGENS; GENE AB The cytotoxicity of human natural killer (NK) cells is modulated by the major histocompatibility complex human leukocyte antigen (HLA)-C molecules on the surface of the target cell. Alloreactive NK cells specific for the NK-1 alloantigen could be reproducibly generated from individuals that were homozygous for HLA-C with asparagine at residue 77 and lysine at residue 80 [HLA-C(Asn77, Lys80] by stimulation with target cells that were homozygous for HLA-C(Ser77, Asn80); the reciprocal stimulation yielded NK cells specific for the NK-2 alloantigen. However, neither homozygous target cell stimulated the generation of alloreactive NK cells from heterozygous individuals. Thus, these data reveal an unanticipated difference between human NK alloreactivity defined by this system and murine ''hybrid resistance.'' C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. CTR RIC AVIS,BERGAMO,ITALY. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. RP COLONNA, M (reprint author), IST NAZL RIC CANC,IMMUNOGENET LAB,I-16132 GENOA,ITALY. RI Falco, Michela/K-1574-2016; OI Colonna, Marco/0000-0001-5222-4987 FU NCI NIH HHS [CA 47554]; NIAID NIH HHS [KO8 AI01064] NR 23 TC 206 Z9 220 U1 0 U2 1 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 21 PY 1993 VL 260 IS 5111 BP 1121 EP 1124 DI 10.1126/science.8493555 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC942 UT WOS:A1993LC94200028 PM 8493555 ER PT J AU DONOFF, RB WEBER, AR SCULLY, RE COLIN, WB ROSENBERG, AE AF DONOFF, RB WEBER, AR SCULLY, RE COLIN, WB ROSENBERG, AE TI A 23-YEAR-OLD WOMAN WITH A RAPIDLY ENLARGING INTRAORAL MASS AFTER A TOOTH EXTRACTION - CENTRAL GIANT-CELL REPARATIVE GRANULOMA OF MANDIBLE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion C1 HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,CAMBRIDGE,MA 02138. RP DONOFF, RB (reprint author), MASSACHUSETTS GEN HOSP,ORAL & MAXILLOFACIAL SURG SERV,BOSTON,MA 02114, USA. NR 16 TC 1 Z9 1 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 20 PY 1993 VL 328 IS 20 BP 1478 EP 1483 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA LB783 UT WOS:A1993LB78300009 ER PT J AU LONDON, SJ SACKS, FM STAMPFER, MJ HENDERSON, IC MACLURE, M TOMITA, A WOOD, WC REMINE, S ROBERT, NJ DMOCHOWSKI, JR WILLETT, WC AF LONDON, SJ SACKS, FM STAMPFER, MJ HENDERSON, IC MACLURE, M TOMITA, A WOOD, WC REMINE, S ROBERT, NJ DMOCHOWSKI, JR WILLETT, WC TI FATTY-ACID COMPOSITION OF THE SUBCUTANEOUS ADIPOSE-TISSUE AND RISK OF PROLIFERATIVE BENIGN BREAST DISEASE AND BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIETARY-FAT; MAMMARY CARCINOGENESIS; WOMEN; QUESTIONNAIRE; COMPONENTS; VALIDITY; HEALTH; FOODS AB Background. Studies in animals and geographic correlations across populations suggest that fatty acid intake may have a positive relationship with breast cancer risk, but analytic epidemiologic studies of fat intake have been less supportive. Adipose tissue analysis provides a more objective assessment of intakes of fatty acids that are not endogenously synthesized than do the questionnaire survey methods used in many epidemiologic studies. Purpose: This case-control study of postmenopausal women was designed to examine the relationship between fatty acid composition of subcutaneous adipose tissue and risk of breast cancer and proliferative benign breast disease. In addition, we examined specific hypotheses that breast cancer risk is negatively associated with long-chain N-3 fatty acid intake, positively associated with trans fatty acid intake, and positively associated with increased intake of polyunsaturated fat together with low intake of antioxidants. Methods: Aspirates of subcutaneous fat from the buttocks were obtained from 380 women with newly diagnosed stage I or II breast cancer and 176 with proliferative benign breast disease. A total of 397 women who were evaluated for breast abnormalities at the same institutions but did not require breast biopsy or whose biopsy revealed nonproliferative benign breast disease served as the control group. We examined associations between saturated, monounsaturated, polyunsaturated, trans, or long-chain N-3 fatty acids and breast cancer, atypical hyperplasia, or proliferative benign breast disease without atypia. Results: We observed no consistent patterns of association between breast cancer risk and any of the categories of fatty acids or the individual constituent fatty acids in the adipose tissue. Saturated fatty acids were inversely associated with risk of proliferative benign breast disease without atypia but not with atypical hyperplasia or breast cancer. This association was not observed, however, when total fat intake was taken into account. Women with high levels of polyunsaturated fatty acids in adipose tissue and low serum or dietary levels of antioxidants were not observed to be at higher risk of breast cancer. Conclusions: Using an objective measure of intake, we observed no major associations between polyunsaturated fatty acids, including long-chain N-3 fatty acids and trans fatty acids, and risk of breast cancer or proliferative benign breast disease. Implications: These data do not support the hypothesis that intake of specific fatty acids, particularly polyunsaturated and trans fatty acids, is an important risk factor for malignant or benign breast disease. C1 HARVARD UNIV,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. DANA FARBER CANC CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. LAHEY CLIN FDN,DEPT SURG,BURLINGTON,MA. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. RP LONDON, SJ (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,PMB B306,1420 SAN PABLO ST,LOS ANGELES,CA 90033, USA. OI London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [CA-09001, CA-40429] NR 40 TC 97 Z9 98 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 19 PY 1993 VL 85 IS 10 BP 785 EP 793 DI 10.1093/jnci/85.10.785 PG 9 WC Oncology SC Oncology GA LE267 UT WOS:A1993LE26700011 PM 8487323 ER PT J AU SHAPIRO, CL GELMAN, RS HAYES, DF OSTEEN, R OBANDO, A CANELLOS, GP FREI, E HENDERSON, IC AF SHAPIRO, CL GELMAN, RS HAYES, DF OSTEEN, R OBANDO, A CANELLOS, GP FREI, E HENDERSON, IC TI COMPARISON OF ADJUVANT CHEMOTHERAPY WITH METHOTREXATE AND FLUOROURACIL WITH AND WITHOUT CYCLOPHOSPHAMIDE IN BREAST-CANCER PATIENTS WITH ONE TO 3 POSITIVE AXILLARY LYMPH-NODES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LEUKEMIA FOLLOWING CHEMOTHERAPY; TRIAL; CMF; EXPERIENCE; RADIATION; MELPHALAN; THERAPY AB Background: Alkylating agents administered as single agents or in combination with antimetabolites or anthracyclines delay the appearance of metastases and prolong the survival of breast cancer patients after surgery. Purpose: This phase III clinical trial was designed to evaluate the therapeutic efficacy and toxicity of the alkylating agent cyclophosphamide in combination with the antimetabolites methotrexate and fluorouracil adjuvant to breast cancer surgery. Methods: This study consisted of 255 breast cancer patients (a) with one to three histologically positive axillary lymph nodes and either no detectable primary tumor or operable primary tumors 5 cm or less (T0-T2) (95% of the patients) or (b) with tumors larger than 5 cm (T3) and with negative axillary nodes. Patients were randomly allocated to receive either methotrexate (60 mg/m2) and fluorouracil (600 mg/m2) (MF) intravenously on days 1 and 8 every 28 days for eight cycles or cyclophosphamide (100 mg/m2) orally on days 1-14 plus MF (CMF) every 28 days for the same duration. Median follow-up was 7.8 years, and maximum follow-up was 13 years. Results: There were no statistically significant differences in time to treatment failure or overall survival for patients treated with MF or CMF. At 8 years after completion of treatment, time to treatment failure was 55% (95% confidence interval [CI] = 50%-60%) and 59% (95% CI = 54%-64%) and overall survival was 69% (95% CI = 65%-73%) and 67% (95% CI = 62%-72%) for MF- and CMF-treated patients, respectively. The hazard ratios (MF to CMF) for time to treatment failure and for survival, estimated with a proportional hazards model, were 1.02 (95% CI = 0.69-1.50) and 0.87 (95% CI = 0.56-1.34), respectively. Myelosuppression was significantly greater (P<.0001) in CMF-treated patients during cycles 1-6. Median white blood cell count nadirs were between 4.4 X 10(3)/muL and 3.5 X 10(3)/muL in patients receiving MF and between 3.0 X 10(3)/muL and 2.4 X 10(3)/muL in those receiving CMF. Dose reductions were more frequent in CMF-treated patients, which led to statistically significant differences (P<.0001) in amounts of methotrexate and fluorouracil administered. Primary cancers at other sites occurred in 14 patients (5.5%)-six treated with MF and eight treated with CMF. Conclusions: Our findings suggest that the addition of cyclophosphamide to adjuvant chemotherapy with MF offers no therapeutic advantage but results in increased myelosuppression. Implications: Future trials will define the possible advantages of antimetabolites in adjuvant therapy. Further information will also become available when results of the ongoing National Surgical Adjuvant Breast and Bowel Project trial comparing adjuvant MF to CMF in node-negative breast cancer patients are presented. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,DIV CLIN ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP SHAPIRO, CL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BREAST EVALUAT,DANA 1508,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-09172-16, CA-06516] NR 23 TC 8 Z9 8 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 19 PY 1993 VL 85 IS 10 BP 812 EP 817 DI 10.1093/jnci/85.10.812 PG 6 WC Oncology SC Oncology GA LE267 UT WOS:A1993LE26700015 PM 8487326 ER PT J AU MILLER, JA NARHI, LO HUA, QX ROSENFELD, R ARAKAWA, T ROHDE, M PRESTRELSKI, S LAUREN, S STONEY, KS TSAI, L WEISS, MA AF MILLER, JA NARHI, LO HUA, QX ROSENFELD, R ARAKAWA, T ROHDE, M PRESTRELSKI, S LAUREN, S STONEY, KS TSAI, L WEISS, MA TI OXIDATIVE REFOLDING OF INSULIN-LIKE GROWTH FACTOR-I YIELDS 2 PRODUCTS OF SIMILAR THERMODYNAMIC STABILITY - A BIFURCATING PROTEIN-FOLDING PATHWAY SO BIOCHEMISTRY LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; NUCLEAR-MAGNETIC-RESONANCE; MOLTEN GLOBULE STATE; FACTOR-I; SECONDARY STRUCTURE; RECEPTOR-BINDING; PHOTO-CIDNP; NMR; INTERMEDIATE; MUTANT AB Can one protein sequence encode two structures? Oxidative folding of human insulin-like growth factor 1 (IGF-1), a globular protein of 70 residues, is shown to yield two products of similar thermodynamic stability. This observation is of particular interest in light of the recent demonstration that two of the three disulfide bonds in native IGF-1 rearrange in the presence of dithiothreitol [Hober, S., et al. (1992) Biochemistry 31, 1749-1756]. Kinetics of the IGF-1 folding pathway were monitored by high-performance liquid chromatography (rp-HPLC). Disulfide-pairing schemes of intermediates and products were established by peptide mapping. Two disulfide isomers were obtained as products: one with native insulin-like pairing [6-48; 18-61; 47-52] (designated native IGF-1; 60% yield) and the other with alternative pairing [6-47; 18-61; 48-52] (designated IGF-swap; 40% yield). The predominant early intermediate contains the single disulfide 18-61, which is shared in common by the two products. Relative yields of native IGF-1 and IGF-swap are independent of protein concentration under dilute conditions. In the absence of an added thiol reagent, each isomer is stable indefinitely at neutral pH; in the presence of an added thiol reagent, the two isomers interconvert with an Arrhenius activation barrier of 12 kcal/mol. Interconversion does not require complete reduction and yields the same ratio of products as initial folding, demonstrating thermodynamic control. Spectroscopic studies using circular dichroism (CD), infrared spectroscopy (FTIR), two-dimensional H-1-NMR (2D-NMR), and photochemical dynamic nuclear polarization (photo-CIDNP) suggest that IGF-1 and IGF-swap adopt similar secondary structures but distinct tertiary folds. Implications of these observations for understanding the topology of protein-folding pathways are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP MILLER, JA (reprint author), AMGEN INC,AMGEN CTR,THOUSAND OAKS,CA 91320, USA. FU NIDDK NIH HHS [DK-40949] NR 69 TC 96 Z9 101 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 18 PY 1993 VL 32 IS 19 BP 5203 EP 5213 DI 10.1021/bi00070a032 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LC721 UT WOS:A1993LC72100032 PM 8494897 ER PT J AU NARHI, LO HUA, QX ARAKAWA, T FOX, GM TSAI, L ROSENFELD, R HOLST, P MILLER, JA WEISS, MA AF NARHI, LO HUA, QX ARAKAWA, T FOX, GM TSAI, L ROSENFELD, R HOLST, P MILLER, JA WEISS, MA TI ROLE OF NATIVE DISULFIDE BONDS IN THE STRUCTURE AND ACTIVITY OF INSULIN-LIKE GROWTH FACTOR-I - GENETIC MODELS OF PROTEIN-FOLDING INTERMEDIATES SO BIOCHEMISTRY LA English DT Article ID PANCREATIC TRYPSIN-INHIBITOR; NUCLEAR-MAGNETIC-RESONANCE; FACTOR-I; ALPHA-LACTALBUMIN; RECEPTOR; SEQUENCE; NMR; DETERMINANTS; MOLECULE; LOCATION AB Insulin and insulin-related proteins contain three motif-specific disulfide bonds. Here we examine the role of these disulfide bonds in the folding and function of one family member, human insulin-like growth factor 1 (IGF-1). Analogues containing pairwise Cys-->Ser or Cys-->Ala substitutions were expressed in Escherichia coli, purified, and analyzed with respect to receptor-binding, solution structure, and thermodynamic stability. An analogue lacking all three disulfide bonds (designated des-Cys-IGF-1) is inactive and unfolded. Introduction of the [18-61] disulfide bond, previously shown to occur in an early intermediate in oxidative refolding [Miller, J. A., Owers-Narhi, L., Hua, Q. X., Rosenfeld, R., Arakawa, T., Rohde, M., Prestrelski, S., Lauren, S., S. Stoney, K. S., Tsai, L., & Weiss, M. A. (1993) Biochemistry (preceding paper in this issue)], results in a compact partially folded state with low but significant biological activity. Additional but incomplete structural organization and biological activity are observed following introduction of either the [6-48] or the [47-52] disulfide bonds. Native function, structure, and stability require the presence of all three disulfide bonds. These analogues provide genetic models of IGF-1 protein-folding intermediates. Their characterization suggests that bifurcation of the IGF-1 folding pathway reflects alternative late steps in the folding of a molten-globule intermediate. C1 AMGEN INC,AMGEN CTR,THOUSAND OAKS,CA 91320. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NR 57 TC 57 Z9 59 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 18 PY 1993 VL 32 IS 19 BP 5214 EP 5221 DI 10.1021/bi00070a033 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LC721 UT WOS:A1993LC72100033 PM 8494898 ER PT J AU NETLAND, PA CHATURVEDI, N DREYER, EB AF NETLAND, PA CHATURVEDI, N DREYER, EB TI CALCIUM-CHANNEL BLOCKERS IN THE MANAGEMENT OF LOW-TENSION AND OPEN-ANGLE GLAUCOMA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-PRESSURE; NIFEDIPINE AB Fifty-six patients with either open-angle or low-tension glaucoma who were concurrently taking calcium channel blockers were compared to similar groups not taking such medications for a mean follow-up period of 3.4 years. Serial stereoscopic optic nerve photographs and visual fields of all patients were evaluated for evidence of glaucomatous progression. In patients with low-tension glaucoma, there was a significant difference in the progression of visual field defects, with only two of 18 eyes (11%) of patients taking calcium channel blockers, compared to ten of 18 eyes (56%) of controls showing new visual field defects. Similarly, low-tension glaucoma patients taking calcium channel blocker therapy demonstrated no evidence of progressive optic nerve damage, compared to eight of 18 control eyes (44%). In contrast, patients with open-angle glaucoma taking calcium channel blockers showed no marked difference in the progression of glaucoma, compared to controls. These findings suggest that calcium channel blockers may be useful in the management of low-tension glaucoma. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,GLAUCOMA CONSULTAT SERV,243 CHARLES ST,BOSTON,MA 02114. NR 22 TC 160 Z9 168 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 15 PY 1993 VL 115 IS 5 BP 608 EP 613 PG 6 WC Ophthalmology SC Ophthalmology GA LA791 UT WOS:A1993LA79100008 PM 8488913 ER PT J AU GARNICK, MB AF GARNICK, MB TI PROSTATE-CANCER - SCREENING, DIAGNOSIS, AND MANAGEMENT SO ANNALS OF INTERNAL MEDICINE LA English DT Review DE PROSTATIC NEOPLASMS; PROSTATE-SPECIFIC ANTIGEN; NEOPLASM STAGING; HORMONES; NEOPLASM METASTASIS ID DIGITAL RECTAL EXAMINATION; POST-IRRADIATION BIOPSY; FINE NEEDLE ASPIRATION; RADICAL PROSTATECTOMY; RADIATION-THERAPY; TREATED PATIENTS; PROGNOSTIC-SIGNIFICANCE; PELVIC LYMPHADENECTOMY; LYMPHATIC METASTASES; COMPUTED-TOMOGRAPHY AB Objective: To provide physicians with a review of diagnosis, screening, staging evaluation, treatment options, prognosis, psychosocial issues, economic considerations, and future research directions in the management of patients with all stages of prostate cancer. Data Sources:A MEDLINE search of articles relating to the diagnosis, staging, screening, surgery, radiation therapy, medical management, and research in prostate cancer. Emphasis on information reported from government- and nongovernment-sponsored large cooperative trials, consensus development conferences, and proceedings of prostate cancer organ site workshops. Study Selection: Results of randomized treatment trials and consensus summary statements are reported where long-term results (> 5 years follow-up) are available for localized prostate cancer treatment and where survival outcomes are available for metastatic disease treatment. Data Synthesis: Both qualitative and quantitative data are reported. Information on staging, management, and prognosis of localized prostate cancer is based on studies that are predominantly nonrandomized, include heterogeneous patient groups, and often use differing outcome measures. Information on management of metastatic prostate cancer is more quantitative and includes side effects of treatment and survival results obtained from randomized, prospective, multi-institutional studies. Conclusions: Despite the increase in prostate cancer incidence and detection, substantial controversy still exists about the advisability and effectiveness of screening programs, the most appropriate staging evaluation, and the optimal management of patients with all stages of prostate cancer, Although randomized, prospective studies attempt to address some of these issues, physicians must appreciate inherent ambiguities involved in recommending staging and treatment choices. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP GARNICK, MB (reprint author), GENET INST INC,87 CAMBRIDGE PK DR,CAMBRIDGE,MA 02140, USA. NR 138 TC 137 Z9 143 U1 2 U2 10 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1993 VL 118 IS 10 BP 804 EP 818 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA LB649 UT WOS:A1993LB64900008 PM 7682387 ER PT J AU GOFF, DC RENSHAW, PF SARIDSEGAL, O DREYFUSS, DA AMICO, ET CIRAULO, DA AF GOFF, DC RENSHAW, PF SARIDSEGAL, O DREYFUSS, DA AMICO, ET CIRAULO, DA TI A PLACEBO-CONTROLLED TRIAL OF SELEGILINE (L-DEPRENYL) IN THE TREATMENT OF TARDIVE-DYSKINESIA SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SELEGILINE; TARDIVE DYSKINESIA; FREE RADICALS; ANTIOXIDANT; MONOAMINE OXIDASE INHIBITOR ID CHRONIC-SCHIZOPHRENIC PATIENTS; GLUTATHIONE-PEROXIDASE; FREE-RADICALS; PLASMA PHENYLETHYLAMINE; SUPEROXIDE-DISMUTASE; MOVEMENT-DISORDERS; VITAMIN-E; AMPHETAMINE; DISEASE; METHAMPHETAMINE AB The goal of this study was to determine whether selegiline (L-deprenyl), a selective monoamine oxidase B inhibitor and antioxidant, would improve neuroleptic-induced tardive dyskinesia (TD). Thirty-three patients with TD were randomly assigned to selegiline 10 mg/day or placebo for 6 weeks and were assessed at baseline and at weeks 1, 2, 4, and 6 for TD, parkinsonism, akathisia, depression, and positive and negative symptoms. Examinations for TD were videotaped and scored by a rater unaware of the temporal sequence of examination. Twenty-eight subjects completed at least 1 week of treatment; all five dropouts were receiving selegiline. When baseline score and gender were controlled, the group receiving selegiline displayed significantly less improvement of TD compared with the placebo group. The two treatment groups did not differ in any other outcome measure. Selegiline was less effective than placebo in reducing symptoms of TD over a 6-week trial. This may be the result of the dopamine agonist effects associated with selegiline. C1 BOSTON VA OUTPATIENT CLIN, BOSTON, MA USA. TUFTS UNIV, SCH MED, BOSTON, MA 02111 USA. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ERICH LINDEMANN MENTAL HLTH CTR, FREEDOM TRAIL CLIN, BOSTON, MA 02114 USA. FU NIMH NIH HHS [MH-19053] NR 65 TC 26 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 1993 VL 33 IS 10 BP 700 EP 706 DI 10.1016/0006-3223(93)90119-X PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LJ396 UT WOS:A1993LJ39600003 PM 8102552 ER PT J AU ABBOUD, SL AF ABBOUD, SL TI A BONE-MARROW STROMAL CELL-LINE IS A SOURCE AND TARGET FOR PLATELET-DERIVED GROWTH-FACTOR SO BLOOD LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; FACTOR-LIKE PROTEIN; FACTOR-BETA; C-SIS; MESSENGER-RNA; FACTOR PDGF; A-CHAIN; B-CHAIN; PROGENITOR CELLS; EXPRESSION C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP ABBOUD, SL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 47 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1993 VL 81 IS 10 BP 2547 EP 2553 PG 7 WC Hematology SC Hematology GA LC496 UT WOS:A1993LC49600011 PM 7683921 ER PT J AU LYNCH, TJ KASS, F KALISH, LA ELIAS, AD STRAUSS, G SHULMAN, LN SUGARBAKER, DJ SKARIN, A FREI, E AF LYNCH, TJ KASS, F KALISH, LA ELIAS, AD STRAUSS, G SHULMAN, LN SUGARBAKER, DJ SKARIN, A FREI, E TI CISPLATIN, 5-FLUOROURACIL, AND ETOPOSIDE FOR ADVANCED NONSMALL CELL LUNG-CANCER SO CANCER LA English DT Article DE NONSMALL CELL LUNG CANCER; CISPLATIN; 5-FLUOROURACIL; CLINICAL TRIAL; HUMAN SUBJECTS ID COMBINATION CHEMOTHERAPY; BREAST-CANCER; MANAGEMENT; CARCINOMA; REGIMENS; TRIAL; BOLUS AB Background. Cisplatin and etoposide combination chemotherapy is the most commonly used regimen for advanced non-small cell lung cancer (NSCLC). 5-Fluorouracil (5-FU) is an agent with little intrinsic activity against NSCLC. However, there is increasing evidence that 5-FU is synergistic with cisplatin and vice versa. In an effort to improve on the traditional chemotherapeutic approach to NSCLC, a treatment regimen consisting of cisplatin, 5-FU, and etoposide (PFE) was developed. Methods. Thirty-five patients with advanced NSCLC were treated with the PFE regimen (cisplatin 25/Mg/M2/etoposide d and 5-FU 1000 mg/m2/d by continuous infusion and 60 mg/m2/d, each for 4 days). The cycles were repeated every 28 days. Results. The patients received a mean of 2.8 cycles of PFE. Ten patients had a partial response to chemotherapy for an overall response rate of 28.6%. The median survival was 7.0 months. Toxicities included myocardial infarction (2 of 35), congestive heart failure (2 of 35), fatal pulmonary embolus (1 of 35), and a cerebrovascular accident (1 of 35). The incidence of Grade 4 neutropenia (5.7%) and thrombocytopenia (8.5%) was acceptable. Conclusions. The response rate, duration of response, and survival in this group of 35 patients treated with PFE was similar to that reported for cisplatin and etoposide. The increased cardiovascular toxicity may be the result of the infused 5-FU. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CLIN ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED,DANA FARBER CANC INST,SCH MED, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DIV THORAC SURG, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA 19589, CA 06516] NR 24 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 BP 2953 EP 2957 DI 10.1002/1097-0142(19930515)71:10<2953::AID-CNCR2820711011>3.0.CO;2-J PG 5 WC Oncology SC Oncology GA LD041 UT WOS:A1993LD04100010 PM 8387871 ER PT J AU RYAN, L KRAMAR, A BORDEN, E AF RYAN, L KRAMAR, A BORDEN, E TI PROGNOSTIC FACTORS IN METASTATIC MELANOMA SO CANCER LA English DT Article DE RESPONSE; SURVIVAL; CUTANEOUS MELANOMA ID MALIGNANT-MELANOMA; PHASE-II AB Background. Each year, 6000 people die in the United States from metastatic melanoma. Further study of factors affecting the prognosis of patients with this disease is needed. Methods. The authors analyzed response and survival data from 635 patients who had entered three Eastern Cooperative Oncology Group trials for metastatic melanoma. Results. Factors associated with poorer survival after study entry included poor performance status and the presence of symptoms, such as reduced appetite, fever, or nausea/vomiting. Male patients had poor survival, as did patients entering the study less than 1 year after a documented recurrence to study entry. As expected, characteristics of the initial primary disease (treatment and symptoms) had little association with survival after entering the advanced disease protocol. Two summary measures of the extent of metastatic involvement had a strong influence on survival. These were the number of nonbone metastases and the clinician's assessment as to the most significant metastatic site. Patients with the liver as their clinically most significant metastatic site had a poorer prognosis than those otherwise classified, including those with central nervous system metastases. The prognosis also worsened with an increasing number of sites of nonbone metastases, including skin and soft tissue. Tumor response occurred in only 11% of the patients. Patients with poor performance status and those with lung involvement had a significantly lower response rate than did others. Although the frequency of response was low, patients with objective responses survived significantly longer than did the nonresponders (based on an analysis appropriately adjusted for the time of response using a time-dependent proportional-hazards model). Conclusions. These results provide useful guidelines for the design and analysis of clinical trials in metastatic melanoma. C1 INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53706. RP RYAN, L (reprint author), HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA 21115] NR 13 TC 72 Z9 73 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 MAY 15 PY 1993 VL 71 IS 10 BP 2995 EP 3005 DI 10.1002/1097-0142(19930515)71:10<2995::AID-CNCR2820711018>3.0.CO;2-P PG 11 WC Oncology SC Oncology GA LD041 UT WOS:A1993LD04100017 PM 8490827 ER PT J AU FISHER, DE SCHNITT, SJ CHRISTIAN, R HARRIS, JR HENDERSON, IC AF FISHER, DE SCHNITT, SJ CHRISTIAN, R HARRIS, JR HENDERSON, IC TI CHEST-WALL RECURRENCE OF DUCTAL CARCINOMA INSITU OF THE BREAST AFTER MASTECTOMY SO CANCER LA English DT Article DE BREAST CANCER; DUCTAL CARCINOMA INSITU; MASTECTOMY; CHEST WALL RECURRENCE; LOCAL CONTROL ID INTRADUCTAL CARCINOMA; FOLLOW-UP; FREQUENCY; DISEASE; CANCER AB Background. Optimal management of ductal carcinoma in situ (DCIS) of the breast is a problem that is occurring with greater frequency, mostly because of the increasing use of mammographic screening. The traditional role of mastectomy for DCIS has been challenged by breast-conserving procedures. Regardless of the method of treatment used, local control with complete tumor eradication is the major goal in the management of DCIS. Methods and Results. A patient is reported in whom DCIS recurred in residual breast tissue in the chest wall several years after mastectomy. Conclusions. Chest wall recurrence of DCIS within residual breast tissue probably is caused by failure of tumor excision, new primary tumor, or both. This observation underscores that (1) mastectomy may not result in complete removal of breast tissue, and (2) this residual breast tissue may be the substrate for ''chest wall recurrences'' in some patients with breast cancer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP FISHER, DE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 20 TC 16 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 BP 3025 EP 3028 DI 10.1002/1097-0142(19930515)71:10<3025::AID-CNCR2820711023>3.0.CO;2-Z PG 4 WC Oncology SC Oncology GA LD041 UT WOS:A1993LD04100022 PM 8387874 ER PT J AU GLASS, J HOCHBERG, FH MILLER, DC AF GLASS, J HOCHBERG, FH MILLER, DC TI INTRAVASCULAR LYMPHOMATOSIS - A SYSTEMIC-DISEASE WITH NEUROLOGIC MANIFESTATIONS SO CANCER LA English DT Article DE LYMPHOMA; INTRAVASCULAR LYMPHOMATOSIS; ANGIOENDOTHELIOMATOSIS; ANGIOENDOTHELIOSIS; BRAIN; SPINAL CORD; PERIPHERAL NERVE ID LARGE-CELL LYMPHOMA; CENTRAL NERVOUS-SYSTEM; MALIGNANT ANGIOENDOTHELIOMATOSIS PROLIFERANS; NEOPLASTIC ANGIOENDOTHELIOSIS; ANGIOTROPIC-LYMPHOMA; CEREBRAL ANGIOENDOTHELIOMATOSIS; SPINAL-CORD; HISTIOCYTIC LYMPHOMA; B MARKERS; ORIGIN AB Background. Intravascular lymphomatosis (IL) is a systemic neoplasm that often involves the nervous system, inducing progressive neurologic deficits in the setting of undiagnosed or quiescent extranodal non-Hodgkin lymphoma. Methods. The clinical and pathologic files of the Massachusetts General Hospital and New York University Medical Center and the English language literature were reviewed to identify all reports of intravascular lymphomatosis (angioendotheliomatosis) or other examples of a diffuse proliferation of neoplastic cells filling capillaries, arterioles, and venules. Results. The authors report seven patients with IL and note 114 patients reported in the literature. Almost two-thirds (63%) of patients had neurologic manifestations, without abnormalities on bone marrow biopsy, chest and abdominal tomographic examinations for adenopathy, and cerebrospinal fluid (CSF) analysis. All patients had one or more of four syndromes, each reflecting a vascular occlusive process: progressive, multifocal cerebrovascular events; paraparesis, pain, and incontinence; a subacute encephalopathy; and peripheral or cranial neuropathies. Conclusions. The unexplained presence of any one or more of these neurologic syndromes should alert the physician to the possible presence of this disease. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. NYU, SCH MED, DEPT PATHOL, NEW YORK, NY 10003 USA. RP GLASS, J (reprint author), TEMPLE UNIV, HLTH SCI CTR, DEPT NEUROL, 3401 N BROAD ST, PHILADELPHIA, PA 19140 USA. NR 97 TC 175 Z9 181 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 BP 3156 EP 3164 DI 10.1002/1097-0142(19930515)71:10<3156::AID-CNCR2820711043>3.0.CO;2-O PG 9 WC Oncology SC Oncology GA LD041 UT WOS:A1993LD04100042 PM 8490846 ER PT J AU AMATRUDA, TT GERARD, NP GERARD, C SIMON, MI AF AMATRUDA, TT GERARD, NP GERARD, C SIMON, MI TI SPECIFIC INTERACTIONS OF CHEMOATTRACTANT FACTOR RECEPTORS WITH G-PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; NUCLEOTIDE REGULATORY PROTEIN; PLATELET-ACTIVATING FACTOR; PERTUSSIS TOXIN; HL-60 CELLS; SIGNAL-TRANSDUCTION; PHOSPHOLIPASE-C; C5A RECEPTOR; INOSITOL TRISPHOSPHATE; HUMAN-NEUTROPHILS AB Stimulation of leukocytes with chemoattractant ligands activates phospholipid turnover and calcium release, ultimately leading to chemotaxis, degranulation, and the inflammatory response. The leukocyte response to these ligands is transduced by the interaction of transmembrane receptors with GTP-binding regulatory proteins (G-proteins). To examine the mechanisms of signal transduction by these receptors, we transfected cDNA clones encoding the receptors for the active cleavage product of the fifth component of complement (C5a) and platelet-activating factor (PAF) into COS-7 cells, then measured the production of inositol phosphates (IP) in response to stimulation with these chemoattractant ligands. Cells transfected with the C5a receptor showed no increase in IP production when stimulated with ligand (5-120 nm). However, in cells co-transfected with these receptors and with the cDNA for Galpha16, a G-protein alpha subunit that is specific to cells of hematopoietic lineage, addition of ligand caused up to a 5-fold increase in IP production. This interaction was specific, as co-transfection of receptors with the G-proteins Galpha(q), or Galpha11 did not allow ligand-dependent increase in IP production. In contrast, ligand-dependent activation of IP production was seen in COS cells transfected solely with the PAF receptor. These results indicate that the C5a receptor utilizes signaling pathways distinct from the PAF receptor and suggest that a pertussis toxin-resistant G-protein, Galpha16, may play a role in the leukocyte response to inflammatory ligands. C1 CALTECH,DIV BIOL,PASADENA,CA 91125. CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,INA SUE PERLMUTTER LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,THORNDIKE LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36162]; NIGMS NIH HHS [GM34236] NR 46 TC 192 Z9 193 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 15 PY 1993 VL 268 IS 14 BP 10139 EP 10144 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000032 PM 8486684 ER PT J AU KIRCHHAUSEN, T TOYODA, T AF KIRCHHAUSEN, T TOYODA, T TI IMMUNOELECTRON MICROSCOPIC EVIDENCE FOR THE EXTENDED CONFORMATION OF LIGHT-CHAINS IN CLATHRIN TRIMERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN COMPLEX AP-2; HEAVY-CHAIN; ELECTRON-MICROSCOPY; UNCOATING ATPASE; BINDING; DOMAINS; INTERMEDIATE; SEQUENCES; COATS AB Clathrin is a major component of the basket-like network of hexagons and pentagons that forms the ''coat'' on the cytoplasmic face of the plasma membrane and the trans Golgi network during the invagination of coated pits. Soluble clathrin is a three-legged structure (triskelion) comprising three identical heavy chains and three different light chains located toward the center of the triskelion on the proximal segment of the leg. All mammalian light chains contain a central domain of 10 heptad repeats, which is necessary for the interaction with heavy chain. Because the repeats are characteristic of alpha helical coiled coils, we proposed that the central domain had an extended conformation (Kirchhausen, T., Scarmato, P., and Harrison, S. C. et al. (1987) Science 236, 320-324). However, an alternative model has recently been proposed (Nathke, I. S., Heuser, J., Lupas, A., Stock, J., Turck, C. W., and Brodsky, F. M. (1992) Cell 68, 899-910). Here, we use single-molecule electron microscopy of clathrin decorated with monoclonal antibodies directed against different epitopes on light chains to show that the light chain central domain has an extended conformation and reaches along most of the proximal segment of the heavy chain leg. C1 HARVARD UNIV,SCH MED,DEPT ANAT & CELL BIOL,BOSTON,MA 02115. RP KIRCHHAUSEN, T (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 26 TC 30 Z9 30 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 15 PY 1993 VL 268 IS 14 BP 10268 EP 10273 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000048 PM 7683673 ER PT J AU DANG, LH LIEN, LL BENACERRAF, B ROCK, KL AF DANG, LH LIEN, LL BENACERRAF, B ROCK, KL TI A MUTANT ANTIGEN-PRESENTING CELL DEFECTIVE IN ANTIGEN PRESENTATION EXPRESSES CLASS-II MHC MOLECULES WITH AN ALTERED CONFORMATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-CONTROLLED POLYMERS; LYMPHOCYTE-T ACTIVATION; INVARIANT CHAIN; MONOCLONAL-ANTIBODIES; IA ANTIGENS; B-CELL; ACCESSORY CELLS; ASSOCIATION; HYBRIDOMAS; LINES AB Ag presentation by APC to class II MHC-restricted T cells involves a sequence of events: 1) intracellular processing of protein Ag into immunogenic peptides, 2) specific binding of peptides to class II MHC molecules, and then 3) transport of the MHC-peptide complexes to the plasma membrane. The critical event in the activation of T cells by APC is the recognition of MHC-associated antigenic determinants by the TCR/CD3 complex. In this report we describe the isolation and characterization of a mutant APC with a defect in an intracellular process that results in its inability to form MHC-peptide complexes for recognition by T cells. The mutant APC cannot present many different protein Ag with both I-A and I-E molecules but is able to present processing-independent peptides. The functional defect in the mutant APC is not caused by either a decrease in expression or a structural mutation in class II MHC molecules. Further, there is no mutation in the invariant chain (li) and it displays a normal kinetics of association and dissociation from the class II MHC molecules during biosynthesis. Although the mutation is not in the genes encoding for the class II MHC molecules or li, the mutant APC expresses class II MHC molecules with distinct serological epitopes suggestive of an altered conformation. Pulse-chase experiments suggest that a conformational difference between I-A(d) molecules of wild-type and mutant cells occurs after the class II molecules exit from the endoplasmic reticulum but while they are still associated with li. The mutant cell produces few compact (SDS-resistant) class II heterodimers. This mutant APC provides a tool for studying the cell biology of Ag processing and presentation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NIAID NIH HHS [AI20248] NR 48 TC 20 Z9 20 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 1993 VL 150 IS 10 BP 4206 EP 4217 PG 12 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000002 PM 8482833 ER PT J AU PERKINS, DL WANG, YS HO, SS WIENS, GR SEIDMAN, JG RIMM, IJ AF PERKINS, DL WANG, YS HO, SS WIENS, GR SEIDMAN, JG RIMM, IJ TI SUPERANTIGEN-INDUCED PERIPHERAL TOLERANCE INHIBITS T-CELL RESPONSES TO IMMUNOGENIC PEPTIDES IN TCR (BETA-CHAIN) TRANSGENIC MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; CONVENTIONAL ANTIGEN; MONOCLONAL-ANTIBODY; CLONAL DELETION; RECEPTOR; ANERGY; ACTIVATION; STIMULATION; INDUCTION; MLS-1A AB TCR (beta-chain) transgenic mice were tolerized with the superantigen staphylococcal enterotoxin B (SEB). Three to 28 days after tolerization with SEB, flow cytometry of peripheral T cells showed the persistence of SEB-unresponsive T cells that did not express reduced levels of the TCR (beta-chain) transgene. Stimulation of the tolerized T cells with a panel of superantigens (SEC1), mitogens (Con A, PHA, and pertussis toxin) and mAb (anti-CD3epsilon) did not induce T cell proliferation. In contrast to other models, exogenous rIL-2 did not reverse unresponsiveness and induce proliferation. In addition, lymphokines rIL-4 and rIL-6 also did not induce proliferation. However, the unresponsive T cells did respond to the combination of PMA plus ionomycin, but not to PMA or ionomycin alone. Thus, the block in signal transduction in the.anergic state occurs between the stimulation of cell surface receptors and the activation of protein kinase C and the increase in intracellular calcium. In addition, these results show that mature T cells tolerized with the superantigen SEB are unresponsive to a wide array of T cell stimuli, indicating a block in a common signal transduction pathway. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP PERKINS, DL (reprint author), BRIGHAM & WOMENS HOSP,IMMUNOGENET & TRANSPLANTAT LAB,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-31517] NR 37 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1993 VL 150 IS 10 BP 4284 EP 4291 PG 8 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000011 PM 8097752 ER PT J AU REED, GL KUSSIE, P PARHAMISEREN, B AF REED, GL KUSSIE, P PARHAMISEREN, B TI A FUNCTIONAL-ANALYSIS OF THE ANTIGENICITY OF STREPTOKINASE USING MONOCLONAL-ANTIBODY MAPPING AND RECOMBINANT STREPTOKINASE FRAGMENTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SERUM-SICKNESS; PLASMINOGEN; THERAPY; ACTIVATION; PROTEINS; SEQUENCE; PLASMA AB Streptokinase (SK), a bacterial product of pathogenic Streptococcus species, is now widely used as an effective therapy for the treatment of heart attacks. Because naturally occurring antibody to SK is ubiquitous, serious allergic reactions to SK therapy are common. To begin to identify regions of the molecule that are important for the antigenicity of SK we performed studies using a panel of 51 hybridomas producing anti-SK antibodies, recombinant SK fragments, and assays of SK activity. Antibodies generated from mice hyperimmunized with wild-type SK were shown to fall into six distinct complementation groups by competitive binding studies. Recombinant SK fragments were used to determine the peptide regions recognized by these complementation groups. Correlation of the effects of the mAb on SK function, with knowledge of their SK fragment-binding pattern, suggested regions of the SK molecule that are important for the construction and the catalytic function of the SK-plasminogen activator complex. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. FU NCI NIH HHS [R01 CA24432]; NHLBI NIH HHS [HL02348] NR 25 TC 33 Z9 35 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1993 VL 150 IS 10 BP 4407 EP 4415 PG 9 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000024 PM 8482842 ER PT J AU PAINE, R ROLFE, MW STANDIFORD, TJ BURDICK, MD ROLLINS, BJ STRIETER, RM AF PAINE, R ROLFE, MW STANDIFORD, TJ BURDICK, MD ROLLINS, BJ STRIETER, RM TI MCP-1 EXPRESSION BY RAT TYPE-II ALVEOLAR EPITHELIAL-CELLS IN PRIMARY CULTURE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; BLOOD MONONUCLEAR LEUKOCYTES; AMINO-ACID ANALYSIS; GENE-EXPRESSION; HUMAN-FIBROBLASTS; MACROPHAGES; CLONING; LUNG; PURIFICATION; ACTIVATION AB Recruitment and activation of mononuclear phagocytes are potentially critical regulatory events for control of pulmonary inflammation. Located at the boundary between the alveolar airspace and the interstitium, alveolar epithelial cells are ideally situated to regulate the recruitment and activation of mononuclear phagocytes through the production of cytokines in response to inflammatory stimulation from the alveolar space. To test this hypothesis, we investigated the production of monocyte chemotactic polypeptide-1 (MCP-1), a protein that is chemotactic for and that activates monocytes, by rat type II alveolar epithelial cells in primary culture. Immunocytochemical staining using anti-murine JE, an antibody recognizing rat MCP-1, demonstrated cell-associated MCP-1 Ag throughout the monolayer. The intensity of staining was increased in response to IL-1 beta. When type II epithelial cells formed a tight monolayer on a filter support, there was polar secretion of MCP-1 Ag into the apical compartment by both control and IL-1-stimulated cells as measured by specific MCP-1 ELISA. Northern blot analysis revealed that IL-1 and TNF-alpha stimulated MCP-1 mRNA expression in a dose-dependent manner, whereas dexamethasone blocked MCP-1 expression by cells stimulated with IL-1. In contrast to previous results using transformed epithelial cell lines, MCP-1 mRNA was induced in these primary cultures directly by stimulation with LPS. These data suggest that alveolar epithelial cells may have an important and previously unrecognized role in the initiation and maintenance of inflammatory processes in the lung by recruiting and activating circulating monocytes through the production of MCP-1. C1 HARVARD UNIV,DANA FARBER CANC INST,CAMBRIDGE,MA 02138. RP PAINE, R (reprint author), UNIV MICHIGAN,DEPT INTERNAL MED,DIV PULM & CRIT CARE MED,3916 TAUBMAN CTR,BOX 0360,ANN ARBOR,MI 48109, USA. FU NHLBI NIH HHS [HL02401, HL02415, 1P50HL46487] NR 37 TC 145 Z9 145 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 1993 VL 150 IS 10 BP 4561 EP 4570 PG 10 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000040 PM 8482848 ER PT J AU CHEN, JZ LANSFORD, R STEWART, V YOUNG, F ALT, FW AF CHEN, JZ LANSFORD, R STEWART, V YOUNG, F ALT, FW TI RAG-2-DEFICIENT BLASTOCYST COMPLEMENTATION - AN ASSAY OF GENE-FUNCTION IN LYMPHOCYTE DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECOMBINATION-ACTIVATING GENE; EMBRYONIC STEM CELLS; TARGETED MUTATION; SOMATIC CHIMERAS; LYMPHOCYTE DIFFERENTIATION ID VARIABLE REGION; REARRANGEMENT; MICE; DISRUPTION; MUTATION AB We describe a system to evaluate the function of lymphocyte-specific and generally expressed genes in the differentiation and/or function of lymphocytes. RAG-2 (recombination-activating gene 2)-deficient mice have no mature B and T lymphocytes due to the inability to initiate VDJ recombination. Blastocysts from RAG-2-deficient mice generate animals with no mature B and T cells following implantation into foster mothers. However, injection of normal ES cells into RAG-2-deficient blastocysts leads to the generation of somatic chimeras with mature B and T cells all of which derive from the injected ES cells (referred to as RAG-2-deficient blastocyst complementation). Complementation of RAG-2-deficient blastocysts with mutant ES cells heterozygous for a targeted mutation that deletes all immunoglobulin heavy-chain joining (J(H)) gene segments (J(H)+/-) also leads to generation of chimeras with normal B and T cells. However, complementation with ES cells homozygous for the JH mutation (J(H)-/-) generates animals with normal T cells but no B cells, due to a block in B-cell development at a very early stage. Transfection of a functionally assembled mu heavy-chain gene into the J(H)-/- ES cells prior to blastocyst injection rescues the J(H)-/- mutation and allows the generation of both mature T and mature B cells. The rescued B cells express IgM but not IgD and respond normally to bacterial lipopolysaccharide stimulation by proliferating and by secreting IgM. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,300 LONGWOOD AVE,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. RI Lansford, Rusty/C-6956-2014 FU NIAID NIH HHS [AI20047, U01AI31541] NR 29 TC 246 Z9 249 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 MAY 15 PY 1993 VL 90 IS 10 BP 4528 EP 4532 DI 10.1073/pnas.90.10.4528 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000044 PM 8506294 ER PT J AU TANAKA, T KAMEOKA, J YARON, A SCHLOSSMAN, SF MORIMOTO, C AF TANAKA, T KAMEOKA, J YARON, A SCHLOSSMAN, SF MORIMOTO, C TI THE COSTIMULATORY ACTIVITY OF THE CD26 ANTIGEN REQUIRES DIPEPTIDYL PEPTIDASE-IV ENZYMATIC-ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL ACTIVATION; HUMAN LYMPHOCYTE-T; SITE-SPECIFIC MUTAGENESIS; PHENOTYPIC SELECTION; MONOCLONAL-ANTIBODY; SURFACE; AMINOPEPTIDASE; TA1; EXPRESSION; INHIBITION AB T cells have been shown to express CD26, a known ectoenzyme with dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) activity in its extracellular domain. CD26 can also deliver a second costimulatory signal and contribute to T-cell activation. In an earlier study, we established CD26-transfected Jurkat T-cell lines and demonstrated that monoclonal antibody-mediated crosslinking of CD26 and CD3 induced interleukin 2 (IL-2) production. To determine the contribution of DPPIV enzymatic activity to the costimulatory activity of CD26, human CD26 cDNA was mutated so that active-site serine was replaced by alanine. The mutant CD26 antigen lacked DPPIV enzyme activity but still retained reactivity with three anti-CD26 monoclonal antibodies directed against distinct epitopes of CD26. After stimulation with a combination of anti-CD26 and anti-CD3 antibodies, wild-type CD26 (DPPIV+)-transfected Jurkat cells produced substantially more IL-2 than did mutant CD26 (DPPIV-) or CD26-control transfectants. Nevertheless, the mutant CD26-transfected cells still produced significantly more IL-2 than did CD26- control transfectants. These results suggest that DPPIV activity plays an important but not absolute role in the costimulatory activity of CD26 in this system. We also found that wild-type CD26 (DPPIV+) transfectants produced more IL-2 than mutant CD26 (DPPIV-)-transfected cells or CD26- control transfectants when triggered by stimuli not involving CD26, such as anti-CD3 and phorbol ester. These results suggest that the DPPIV activity of CD26 functions to augment the cellular responses of CD26-transfected Jurkat cells to external stimuli mediated by CD26 and/or the CD3/T-cell receptor complex, thus enhancing IL-2 production. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI12069, AI29530]; NIAMS NIH HHS [AR33713] NR 29 TC 172 Z9 174 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 MAY 15 PY 1993 VL 90 IS 10 BP 4586 EP 4590 DI 10.1073/pnas.90.10.4586 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000056 PM 7685106 ER PT J AU VALLEJO, M RON, D MILLER, CP HABENER, JF AF VALLEJO, M RON, D MILLER, CP HABENER, JF TI C/ATF, A MEMBER OF THE ACTIVATING TRANSCRIPTION FACTOR FAMILY OF DNA-BINDING PROTEINS, DIMERIZES WITH CAAT ENHANCER-BINDING PROTEINS AND DIRECTS THEIR BINDING TO CAMP RESPONSE ELEMENTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID REGULATORY ELEMENTS; CYCLIC-AMP; GENE; EXPRESSION; CDNA; JUN AB Members of the C/EBP family of basic-leucine zipper (bZip) transcription factors form heterodimers and bind to the CAAT box and other sequence-related enhancer motifs. Using a P-32-labeled protein probe consisting of the bZip domain of C/EBPbeta, we isolated a clone encoding C/EBP-related ATF (C/ATF), a bZip protein that heterodimerizes with C/EBP-like proteins but belongs to the CREB/ATF family. C/ATF homodimers do not bind to typical C/EBP DNA sites. Instead they bind to palindromic cAMP response elements such as that of the somatostatin gene. In addition, C/ATF-C/EBPbeta heterodimers bind to a subclass of asymmetric cAMP response elements exemplified by those in the phosphoenolpyruvate carboxykinase and proenkephalin genes. Transient transfection studies indicate that interactions between C/ATF and C/EBPbeta are the basis for a functional cross talk between these two families of transcription factors that may be important for the integration of hormonal and developmental stimuli that determine the expression of subsets of genes in specific cellular phenotypes. RP VALLEJO, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK30457] NR 25 TC 201 Z9 207 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4679 EP 4683 DI 10.1073/pnas.90.10.4679 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000075 PM 8506317 ER PT J AU LIN, DY FISCHL, MA SCHOENFELD, DA AF LIN, DY FISCHL, MA SCHOENFELD, DA TI EVALUATING THE ROLE OF CD4-LYMPHOCYTE COUNTS AS SURROGATE END-POINTS IN HUMAN-IMMUNODEFICIENCY-VIRUS CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; DOUBLE-BLIND; AZIDOTHYMIDINE AZT; REGRESSION-MODEL; HIV INFECTION; EFFICACY; CANCER AB In human immunodeficiency virus clinical trials, the CD4-lymphocyte count has been regarded as a promising surrogate endpoint for clinical efficacy measures such as time to opportunistic infection and survival time. In the present paper, we test this hypothesis according to a criterion proposed by Prentice. This criterion requires the surrogate variable to capture the entire effect of treatment on the clinical endpoint, and it is satisfied if the hazard rate of the clinical endpoint is not affected by treatment among patients with the same preceding history of the surrogate variable. We analyse data from two completed zidovudine trials using the Cox regression model with the CD4-lymphocyte count as a time-varying covariate. The results indicate that the CD4-lymphocyte count captures part of the relationship between zidovudine and time to a first critical event but does not fulfil the Prentice criterion. C1 UNIV MIAMI,SCH MED,DEPT MED,MIAMI,FL 33101. MASSACHUSETTS GEN HOSP,CTR BIOSTAT,BOSTON,MA 02114. RP LIN, DY (reprint author), UNIV WASHINGTON,DEPT BIOSTAT,SC-32,SEATTLE,WA 98195, USA. FU NIAID NIH HHS [R01-AI-24643, U01-AI-27675, R01-AI-29168] NR 16 TC 60 Z9 61 U1 0 U2 0 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 MAY 15 PY 1993 VL 12 IS 9 BP 835 EP 842 DI 10.1002/sim.4780120904 PG 8 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 LD776 UT WOS:A1993LD77600003 PM 8101011 ER PT J AU GUT, IG HEFETZ, Y KOCHEVAR, IE HILLENKAMP, F AF GUT, IG HEFETZ, Y KOCHEVAR, IE HILLENKAMP, F TI 2-PHOTON ABSORPTION CROSS-SECTIONS OF GUANOSINE 5'-MONOPHOSPHATE AND URIDINE 5'-MONOPHOSPHATE AT 532-NM SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID STRAND BREAK FORMATION; LASER-INDUCED PHOTOIONIZATION; NUCLEIC-ACID COMPONENTS; AQUEOUS-SOLUTION; HIGH-INTENSITY; HUMAN-CELLS; SINGLE-STRAND; DNA; PICOSECOND; RADIATION AB The two-photon absorption cross sections, sigma2, for guanosine 5'-monophosphate (GMP) and uridine 5'-monophosphate (UMP) were measured at 532 nm by optoacoustic calorimetry and, for UMP, by direct absorption. The values of sigma2 obtained were 5.1 x 10(-51) cm4.s for UMP and 7.0 x 10(-51) cm4.s for GMP. These values are about 2 orders of magnitude greater than the values we previously reported for double-stranded DNA.27 In that study the number of photons absorbed was deduced from the yield of cyclobutylpyrimidine dimers, the literature value for the, dimer quantum yield, PHI(D), and the assumption that PHI(D) was the same for absorption of one UV photon or two 532-nm photons. A possible explanation for this discrepancy is that the excited state populated in DNA by two-photon absorption was depleted by further absorption to a non-dimer-forming state. This explanation was not supported since exciting DNA with low-intensity 266-nm ps pulses in the presence and absence of high-intensity (4 GW.cm2) 532-nm pulses did not substantially reduce the dimer yield. The quantum yield for cyclobutylpyrimidine dimers in double-stranded DNA was measured to be 1.8 X 10(-3) Using low-intensity 266-nm radiation. This value is about 10 times lower than that used in previous studies and yields a value of sigma2 for DNA of 6 x 10(-52) cm4.s. The 10-fold difference between this value and the values we measured for nucleotides by physical techniques may reflect a difference in the PHI(D) formed from states populated by one- and two-photon excitation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. UNIV MUNSTER,INST MED PHYS & BIOPHYS,W-4400 MUNSTER,GERMANY. NR 37 TC 12 Z9 13 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD MAY 13 PY 1993 VL 97 IS 19 BP 5171 EP 5176 DI 10.1021/j100121a053 PG 6 WC Chemistry, Physical SC Chemistry GA LB803 UT WOS:A1993LB80300053 ER PT J AU KRAMER, R WEBER, TK ARCECI, R MORSE, B SIMPSON, H STEELE, GD SUMMERHAYES, IC AF KRAMER, R WEBER, TK ARCECI, R MORSE, B SIMPSON, H STEELE, GD SUMMERHAYES, IC TI MODULATION OF MDR-1 EXPRESSION BY A H-RAS ONCOGENE IN A HUMAN COLON-CARCINOMA CELL-LINE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN; INDUCED DIFFERENTIATION; SENSITIVITY; CANCER; ACID AB In an established colon differentiation model, introduction of a c-H-ras-I oncogene into a poorly differentiated human colon carcinoma cell line (Clone A) results in changes associated with the acquisition of a more differentiated phenotype. Down-regulation of mdr-1 mRNA was shown to accompany ras-related differentiation events resulting in decreased Pgp synthesis and a significant reduction in membrane Pgp as detected by immunoprecipitation, Western-blot and FACS analysis. Consistent with these observations was a reduction in Pgp-mediated drug resistance associated with Clone-A ras transfectants, with no alteration in drug sensitivity being observed with non-MDR drugs in these cells. An alternative differentiation model involves exposure of Clone-A cells to sodium butyrate. Under these conditions, differentiation-related changes resulted in up-regulation of mdr-1 mRNA and Pgp synthesis, although no alteration in drug sensitivity was recorded. In agreement with this observation, the levels of membrane-associated Pgp remained unchanged throughout the period of exposure to sodium butyrate. This study shows that modulation of Pgp expression in colon differentiation is dependent upon the differentiation induction agent used. C1 NEW ENGLAND DEACONESS HOSP,CANC BIOL LAB,50 BINNEY ST,BOSTON,MA 02215. AMER CYANAMID CO,LEDERLE LABS,PEARL RIVER,NY 10965. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NCI NIH HHS [CA42944, CA44704, CA50473] NR 24 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 8 PY 1993 VL 54 IS 2 BP 275 EP 281 DI 10.1002/ijc.2910540219 PG 7 WC Oncology SC Oncology GA LB688 UT WOS:A1993LB68800018 PM 8098015 ER PT J AU EWEN, ME SLUSS, HK SHERR, CJ MATSUSHIME, H KATO, JY LIVINGSTON, DM AF EWEN, ME SLUSS, HK SHERR, CJ MATSUSHIME, H KATO, JY LIVINGSTON, DM TI FUNCTIONAL INTERACTIONS OF THE RETINOBLASTOMA PROTEIN WITH MAMMALIAN D-TYPE CYCLINS SO CELL LA English DT Article ID SV40 LARGE-T; ADENOVIRUS E1A PROTEINS; GENE-PRODUCT; CELL-CYCLE; SUSCEPTIBILITY GENE; RB PROTEIN; G1 PHASE; PHOSPHORYLATION; BINDING; ONCOGENE AB The retinoblastoma gene product (Rb) can interact efficiently with two of three D-type G1 cyclins (D2 and D3) in vitro. Binding depended upon the minimal regions of Rb necessary for its growth-suppressive activity, as well as upon the D-type cyclin sequence motif shared with Rb-binding DNA tumor virus oncoproteins. Coexpression of the three D-type cyclins with the cyclin-dependent kinase (cdk4) in insect cells generated Rb kinase activity. By contrast, cyclins D2 and D3, but not D1, activated another such kinase, cdk2. Introduction of cyclin D2 and Rb into the Rb-deficient cell line SAOS-2 led to overt Rb hyperphosphorylation, whereas Rb, expressed alone or together with cyclin D1, remained unphosphorylated. Cyclin D2-dependent phosphorylation inhibited its binding to the transcription factor E2F and reversed the Rb G1 exit block in the cell cycle. Thus, all D-type cyclins do not function equivalently, and one of them plays a major role in reversing the cycle-blocking function of a known tumor suppressor. C1 HOWARD HUGHES MED INST, MEMPHIS, TN 38105 USA. ST JUDE CHILDRENS RES HOSP, DEPT TUMOR CELL BIOL, MEMPHIS, TN 38101 USA. RP EWEN, ME (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA-47064] NR 61 TC 999 Z9 1006 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAY 7 PY 1993 VL 73 IS 3 BP 487 EP 497 DI 10.1016/0092-8674(93)90136-E PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LA743 UT WOS:A1993LA74300010 PM 8343202 ER PT J AU DOWDY, SF HINDS, PW LOUIE, K REED, SI ARNOLD, A WEINBERG, RA AF DOWDY, SF HINDS, PW LOUIE, K REED, SI ARNOLD, A WEINBERG, RA TI PHYSICAL INTERACTION OF THE RETINOBLASTOMA PROTEIN WITH HUMAN D-CYCLINS SO CELL LA English DT Article ID LARGE-T-ANTIGEN; ADENOVIRUS E1A PROTEINS; VIRUS-40 LARGE-T; GENE-PRODUCT; CELL-CYCLE; SUSCEPTIBILITY GENE; TRANSCRIPTION FACTOR; CANDIDATE ONCOGENE; G1 CYCLIN; BINDING AB The retinoblastoma protein (pRb) functions as a regulator of cell proliferation and in turn is regulated by cyclin-dependent kinases. Cyclins D1 and D3 can form complexes with pRb that resemble those formed by several viral oncoproteins and are disrupted by the adenovirus E1A oncoprotein and derived peptides. These cyclins contain a sequence motif similar to the pRb-binding conserved region II motif of the viral oncoproteins. Alteration of this motif in cyclin Dl prevents formation of cyclin D1-pRb complexes while enhancing the biological activity of cyclin D1 assayed in vivo. We conclude that cyclins D1 and D3 interact with pRb in a fashion distinct from cyclins A and E, which can induce pRb hyperphosphorylation, and that cyclin D1 activity may be regulated by its association with pRb. C1 MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. MASSACHUSETTS GEN HOSP, CTR CANC, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP DOWDY, SF (reprint author), WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. OI Louie, Kenway/0000-0002-9665-5436 FU NCI NIH HHS [CA55909]; NIGMS NIH HHS [GM38328, GM46006] NR 96 TC 755 Z9 760 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 7 PY 1993 VL 73 IS 3 BP 499 EP 511 DI 10.1016/0092-8674(93)90137-F PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LA743 UT WOS:A1993LA74300011 PM 8490963 ER PT J AU GREVELINK, JM WALTMAN, AC SCULLY, RE LYON, NB SPRINGFIELD, D ROSENBERG, AE DOW, EC AF GREVELINK, JM WALTMAN, AC SCULLY, RE LYON, NB SPRINGFIELD, D ROSENBERG, AE DOW, EC TI A 57-YEAR-OLD MAN WITH CHRONIC LYMPHEDEMA AND ENLARGING PURPLE CUTANEOUS NODULES OF THE LEG - ANGIOSARCOMA ARISING IN CHRONIC LYMPHEDEMA (STEWART-TREVES SYNDROME) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID ACQUIRED IMMUNODEFICIENCY SYNDROME; KAPOSIS-SARCOMA; MALIGNANT ANGIOENDOTHELIOMATOSIS; POSTMASTECTOMY LYMPHEDEMA; LYMPHANGIOSARCOMA; EXTREMITIES; SKIN C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GREVELINK, JM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 38 TC 8 Z9 8 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 6 PY 1993 VL 328 IS 18 BP 1337 EP 1343 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KZ640 UT WOS:A1993KZ64000010 ER PT J AU CARPENTER, CL AUGER, KR CHANUDHURI, M YOAKIM, M SCHAFFHAUSEN, B SHOELSON, S CANTLEY, LC AF CARPENTER, CL AUGER, KR CHANUDHURI, M YOAKIM, M SCHAFFHAUSEN, B SHOELSON, S CANTLEY, LC TI PHOSPHOINOSITIDE 3-KINASE IS ACTIVATED BY PHOSPHOPEPTIDES THAT BIND TO THE SH2 DOMAINS OF THE 85-KDA SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MIDDLE-T-ANTIGEN; PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; RECEPTOR TYROSINE KINASES; FACTOR-I RECEPTOR; SIGNAL TRANSDUCTION; PDGF RECEPTOR; PHOSPHORYLATION; POLYOMAVIRUS; TRANSFORMATION; PROTEIN AB Tyrosine-phosphorylated peptides based on the regions of polyoma virus middle t antigen and the platelet-derived growth factor receptor that bind phosphoinositide 3-kinase are shown to activate this enzyme 2-3-fold in vitro. The concentrations of the peptides required to activate the enzyme are at least 10-1000-fold higher than the dissociation constants of these peptides for the individual SH2 domains of the 85-kDa subunit (K(D) < 100 nM). Doubly phosphorylated peptides are more effective than singly phosphorylated peptides. The results suggest that a fraction of the cellular phosphoinositide 3-kinase has SH2 domains with relatively low affinity for phosphopeptides and that binding of phosphopeptides to these enzymes causes activation. Thus, SH2 domains may be involved not only in recruiting the enzyme but also in regulating activity. C1 BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02115. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA 34722]; NIGMS NIH HHS [GM 36624, GM 41890, R01 GM041890] NR 51 TC 307 Z9 312 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 5 PY 1993 VL 268 IS 13 BP 9478 EP 9483 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900051 PM 7683653 ER PT J AU BIRKENMEIER, CS WHITE, RA PETERS, LL HALL, EJ LUX, SE BARKER, JE AF BIRKENMEIER, CS WHITE, RA PETERS, LL HALL, EJ LUX, SE BARKER, JE TI COMPLEX PATTERNS OF SEQUENCE VARIATION AND MULTIPLE 5' AND 3' ENDS ARE FOUND AMONG TRANSCRIPTS OF THE ERYTHROID ANKYRIN GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLOBIN MESSENGER-RNA; CYTOPLASMIC DOMAIN; MEMBRANE SKELETON; BRAIN ANKYRIN; CDNA SEQUENCE; SPECTRIN; PROTEIN; PURIFICATION; CELLS; DNA AB The structural protein ankyrin functions in red blood cells to link the spectrin-based membrane skeleton to the plasma membrane. Ankyrin proteins are now known to occur in most cell types, and two distinct ankyrin genes have been identified (erythroid (Ank-1) and brain (Ank-2)). We have characterized transcripts of the mouse erythroid ankyrin gene by cDNA cloning and DNA sequencing. Ank-1 transcripts of 7.5 and 9.0 kilobases are found in erythroid tissues, and a 9.0-kilobase transcript is found in cerebellum. RNA hybridization blot analysis of 13 additional mouse tissues has detected four novel Ank-1 transcripts (5.0, 3.5, 2.0, and 1.6 kilobases in size). Sequencing of Ank-1 cDNA clones isolated from mouse reticulocyte, spleen, and cerebellar libraries has identified (i) multiple 5' ends that indicate possible multiple promoters; (ii) alternative polyadenylation sites that probably account for the 7.5- and 9.0-kilobase size difference; (iii) a variety of small insertions and deletions that could produce transcripts (and ultimately proteins) of nearly identical size, but different functions; and (iv) clones with large deletions of coding sequence that account for the smaller transcripts seen in spleen, skeletal muscle, and heart. C1 CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP BIRKENMEIER, CS (reprint author), JACKSON LAB,BAR HARBOR,ME 04609, USA. FU NHLBI NIH HHS [HL29305, HL15157]; NIDDK NIH HHS [DK27726] NR 47 TC 54 Z9 56 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 5 PY 1993 VL 268 IS 13 BP 9533 EP 9540 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900060 PM 8486643 ER PT J AU HUSTEN, EJ TAUSK, FA KEUTMANN, HT EIPPER, BA AF HUSTEN, EJ TAUSK, FA KEUTMANN, HT EIPPER, BA TI USE OF ENDOPROTEASES TO IDENTIFY CATALYTIC DOMAINS, LINKER REGIONS, AND FUNCTIONAL INTERACTIONS IN SOLUBLE PEPTIDYLGLYCINE ALPHA-AMIDATING MONOOXYGENASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PEPTIDE AMIDATION; MESSENGER-RNA; ENZYME; CELLS; PURIFICATION; EXPRESSION; PITUITARY; SEQUENCE; INTERMEDIATE; BIOSYNTHESIS AB The production of alpha-amidated peptides is accomplished through the sequential action of two enzymes, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), that are contained within the bifunctional peptidylglycine alpha-amidating monooxygenase (PAM) protein. Tissue-specific alternative splicing and endoproteolysis are known to generate both soluble and integral membrane mono- and bifunctional PAM proteins. In order to investigate the functional consequences of these differences we purified PAM-3, a soluble 95-kDa bifunctional form of the enzyme, from the spent medium of stably transfected hEK-293 cells. Using NH2-terminal sequence analysis of products of limited endoproteolysis and antibody cross-reactivity we identified protease-sensitive regions at the NH2 terminus, between the 35-kDa PHM and 42-kDa PAL domains and at the COOH terminus of the protein. Endoproteolytic removal of the COOH-terminal region from the bifunctional PAM-3 protein shifted the pH optimum of PHM to a more alkaline pH, increased the turnover number (k(cat)) of PHM and decreased its K(M) for alpha-N-acetyl-Tyr-Val-Gly; the catalytic properties of PAL were not altered. Since peptide amidation can be a rate-limiting step in the biosynthesis of neuropeptides, similar increases in PHM activity in vivo may play an important role in regulating the extent of peptide alpha-amidation. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,WOOD BASIC SCI BLDG,RM 907,725 N WOLFE ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT DERMATOL,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. FU NIDA NIH HHS [DA 00098]; NIDDK NIH HHS [DK 32949, DK 08504] NR 38 TC 46 Z9 46 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 5 PY 1993 VL 268 IS 13 BP 9709 EP 9717 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900082 PM 8486658 ER PT J AU CSERMELY, P SCHNAIDER, T CHEATHAM, B OLSON, MOJ KAHN, CR AF CSERMELY, P SCHNAIDER, T CHEATHAM, B OLSON, MOJ KAHN, CR TI INSULIN INDUCES THE PHOSPHORYLATION OF NUCLEOLIN - A POSSIBLE MECHANISM OF INSULIN-INDUCED RNA EFFLUX FROM NUCLEI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CASEIN KINASE-II; EPIDERMAL GROWTH-FACTOR; PROTEIN-KINASE; MESSENGER-RNA; RAT-LIVER; NUCLEOSIDE TRIPHOSPHATASE; 3T3-L1 ADIPOCYTES; RIBOSOMAL-RNA; CELLS; TRANSPORT AB Insulin induces the serine phosphorylation of the nucleolar protein nucleolin at subnanomolar concentrations in differentiated 3T3-442A cells. The stimulation is biphasic with phosphorylation reaching a maximum at 10 pM insulin and then declining to only 40% of basal levels at insulin concentrations of 1 muM. These changes are rapid, reaching half-maximal after 4 min and maximal after 15 min of incubation. The cell-permeable casein kinase II inhibitor 5,6-dichlorobenzimidazole-riboside prevents the insulin-stimulated phosphorylation of nucleolin suggesting that casein kinase II may mediate this effect of the hormone. Insulin-like growth factor 1 mimics the action of insulin on dephosphorylation of nucleolin at nanomolar concentrations suggesting that the latter effect may be mediated by insulin-like growth factor 1 receptors. Insulin treatment of 3T3-442A cells also results in a stimulation of RNA efflux from isolated, intact cell nuclei. The dose dependence of insulin-induced nucleolin phosphorylation and insulin-stimulated RNA efflux from intact cell nuclei are almost identical. Insulin induces an increase in the RNA efflux at subnanomolar concentrations in 3T3-442A adipocytes, while high (micromolar) concentrations of insulin inhibited the efflux of RNA. These data indicate that insulin regulates the phosphorylation/dephosphorylation of nucleolin, possibly via stimulation of casein kinase II, and this may play a role in regulation of the RNA efflux from nuclei. C1 JOSLIN DIABET CTR,DIV RES,ONE JOSLIN PL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MISSISSIPPI,MED CTR,JACKSON,MS 39216. FU FIC NIH HHS [1F05 TW04319-01 B1-5]; NIDDK NIH HHS [DK 36836, DK 33201] NR 51 TC 41 Z9 41 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 5 PY 1993 VL 268 IS 13 BP 9747 EP 9752 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900087 PM 7683660 ER PT J AU HIRAIZUMI, S SPOHR, U SPIRO, RG AF HIRAIZUMI, S SPOHR, U SPIRO, RG TI CHARACTERIZATION OF ENDOMANNOSIDASE INHIBITORS AND EVALUATION OF THEIR EFFECT ON N-LINKED OLIGOSACCHARIDE PROCESSING DURING GLYCOPROTEIN-BIOSYNTHESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-D-MANNOSIDASE; RAT-LIVER; ENDOPLASMIC-RETICULUM; SYNCYTIUM FORMATION; GLUCOSE REMOVAL; CELL-LINE; 1-DEOXYNOJIRIMYCIN; CASTANOSPERMINE; SECRETION; COMPLEX AB Endo-alpha-D-mannosidase is a Golgi-located processing enzyme that achieves deglucosylation of N-linked carbohydrate units through its unique property of cleaving the oligosaccharide chain internally with the release of glucose-substituted mannose (Glc1-3Man). By chemically modifying the characteristic disaccharide product, Glcalpha1-->3Man, a number of potent inhibitors of the endomannosidase were obtained, foremost among which were Glcalpha1-->3(1-deoxy)mannojirimycin (Glcalpha1-->3DMJ) and Glcalpha1-->3(1,2-dideoxy)mannose (IC50 = 1.7 and 3.8 muM, respectively), which, while blocking the in vitro action of the enzyme, had negligible effect on other endoplasmic reticulum- and Golgi-processing glycosidases. Although preparation of a large number of Glcalpha1-->3DMJ derivatives did not yield a more effective endomannosidase inhibitor it provided valuable information relating to the structural requirements for the enzyme-substrate interaction. Glcalpha1-->3DMJ was found to be active not only on rat liver endomannosidase but also on the enzyme from a number of other sources including mouse lymphoma (BW5147.3), HepG2, baby hamster kidney, and Madin-Darby canine kidney cell lines. When tested in vivo in lymphoma and Madin-Darby canine kidney cells during a castanospermine-imposed glucosidase blockade, Glcalpha1-->3DMJ interrupted the endomannosidase processing pathway as evident from a concomitant inhibition of complex oligosaccharide formation and Glc3Man release; similarly the capacity of the glucosidase II-deficient mouse lymphoma cell line (PHA(R)2.7) to synthesize complex oligosaccharides was blocked by Glcalpha1-->3DMJ. Endomannosidase could not be detected in Chinese hamster ovary cells by in vitro assay and consistent with this these cells produced only glucosylated polymannose N-linked oligosaccharides during glucosidase blockade. It would appear that by acting in conjunction with a glucosidase inhibitor, Glcalpha1--> 3DMJ and related endomannosidase-blocking agents could have the potential of influencing the exit of glycoproteins from the endoplasmic reticulum and interfering with viral replication. C1 JOSLIN DIABET CTR,ELLIOTT P JOSLIN RES LAB,ONE JOSLIN PL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHEM BIOMED LTD,EDMONTON T6G 2G2,AB,CANADA. UNIV ALBERTA,DEPT CHEM,EDMONTON T6G 2G2,ALBERTA,CANADA. FU NIDDK NIH HHS [DK 17477] NR 47 TC 54 Z9 54 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 5 PY 1993 VL 268 IS 13 BP 9927 EP 9935 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900109 PM 8486671 ER PT J AU LOVE, RR CARBONE, PP VERMA, AK GILMORE, D CAREY, P TUTSCH, KD POMPLUN, M WILDING, G AF LOVE, RR CARBONE, PP VERMA, AK GILMORE, D CAREY, P TUTSCH, KD POMPLUN, M WILDING, G TI RANDOMIZED PHASE-I CHEMOPREVENTION DOSE-SEEKING STUDY OF ALPHA-DIFLUOROMETHYLORNITHINE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ORNITHINE DECARBOXYLASE; POLYAMINE BIOSYNTHESIS; INHIBITOR AB Background: Alpha-difluoromethylornithine (DFMO) is an irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in mammalian polyamine biosynthesis. Levels of ODC are closely related to tumor promotion, and inhibition of ODC is associated with suppression of tumor development in laboratory animals. DFMO has shown a dose-response effect in tumor inhibition in mice. Purpose: A randomized phase I study of DFMO was conducted to determine the lowest daily oral dose that can achieve at least 50% inhibition of ODC activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human skin, with minimal clinical toxicity (grade 1 or lower; Eastern Cooperative Oncology Group [ECOG]). Methods: Cancer patients entered in steps 1 and 2 of the study had been treated and had no clinical evidence of cancer. In step 1, 13 patients received 0.125, 0.25, 0.5, or 0.75 g/m2 DFMO four times a day. In step 2, 13 patients received 0.125 or 0.25 g/m2 four times a day or 0.5 or 1.0 g/m2 every day. The 26 patients treated in steps 1 and 2 (range, <1-6 months) had colon, prostate, or bladder cancer. In step 3, six cancer-free subjects at risk for colorectal cancer received 0.5 g/m2 every day for 5-12 months. To evaluate the effectiveness of DFMO in reducing TPA-induced ODC activity, we calculated the percent change from pretreatment ODC levels in skin biopsy specimens and the percentage of subjects with at least a 50% reduction in ODC levels. Results: In step 1 of the study, treatment-limiting audiotoxicity was observed at the three highest doses. Because the only dose with no major toxic effects in step 2 was 0.5 g/m2 every day, that dose was administered in step 3, with no major toxic effects. Seven subjects treated with 0.5 g/m2 every day had pretreatment ODC levels in the normal range; five averaged a reduction in ODC activity of at least 50%. DFMO had linear pharmacokinetics over the entire dose range. When 0.5 g/m2 was given every day, the peak plasma concentration was 47.1 +/- 5.1 muM at 3-4 hours (monthly mean +/- SE, 14.5 +/- 5.2 muM); half-life was 3.5 hours; and area under the curve for plasma concentration X time for a single dose of DFMO was 311 +/- 39 muM X hour. Conclusions: These data support phase II chemoprevention studies with DFMO given at a dose of 0.5 g/m2 every day. Implications: Studies investigating prevention of cancers with DFMO are under consideration. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP LOVE, RR (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53792, USA. FU NCI NIH HHS [N01-CN-85109] NR 13 TC 95 Z9 95 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 5 PY 1993 VL 85 IS 9 BP 732 EP 737 DI 10.1093/jnci/85.9.732 PG 6 WC Oncology SC Oncology GA LA672 UT WOS:A1993LA67200014 PM 8478959 ER PT J AU DIN, ZZ MUKERJEE, P KASTOWSKY, M TAKAYAMA, K AF DIN, ZZ MUKERJEE, P KASTOWSKY, M TAKAYAMA, K TI EFFECT OF PH ON SOLUBILITY AND IONIC STATE OF LIPOPOLYSACCHARIDE OBTAINED FROM THE DEEP ROUGH MUTANT OF ESCHERICHIA-COLI SO BIOCHEMISTRY LA English DT Article ID DIPHOSPHORYL-LIPID-A; PHOTOAFFINITY CROSS-LINKING; RHODOPSEUDOMONAS-SPHAEROIDES; BINDING-SITES; STRUCTURAL CHARACTERISTICS; 70Z/3 CELLS; FATTY-ACIDS; LYMPHOCYTES; MACROPHAGES; INDUCTION AB The dissociation of the highly aggregated form of lipopolysaccharide (LPS) from Gram-negative bacteria to the monomeric (or soluble) form is though to be the initial step in the activation of responding cells (macrophages, B-cells, neutrophils, monocytes, and endothelial cells) by LPS. This process is presently not adequately understood. Using the equilibrium dialysis apparatus and a highly purified and well-characterized radiolabeled deep rough chemotype LPS ([C-14]ReLPS) from Escherichia coli D31m4, we have examined the effect of pH on its solubility (CT) and ionic states in aqueous media. The solubility range of [C-14]ReLPS suspended in 50 mM Tris-HCl-100 mM KCl buffer (or 50 mM MES-100 mM KCl buffer at pH 6.5) was determined to be from (2.91 +/- 0.01) X 10-8 to (4.55 +/- 0.07) X 10(-8) M over a pH range of 6.50-8.20, respectively. These experimental data satisfactorily fitted the curve generated by the solubility equation C(T)=S0(1+K5/[H+])/([H+]/K4'+1), where S0 is the concentration of the tetraanionic ReLPS, K5 is the dissociation constant of the tetraanionic ReLPS in solution, and K4' is the dissociation constant of the trianionic ReLPS at the surface of the solid particles in suspension. The increase in solubility of ReLPS with increase in pH from 7.00 to 8.20 is primarily caused by the formation of the pentaanionic form from the tetraanions. The pK5 (primarily the second dissociation of the l-phosphate) of ReLPS was determined to be 8.58 from experimental data. Theoretical arguments were presented to show that this value is higher than that for simple model compounds (monosaccharide monophosphates where pK = 6.1 for the second dissociation) because of electrostatic effects caused by the other phosphate and carboxylate groups of two 2-keto-3-deoxyoctonate (Kdo) moieties of ReLPS. Using the same theoretical arguments, pK6 was calculated to be much higher, 10.8. In the absence of Kdo groups, as is the case of 1,4'-diphosphoryl lipid A, the same theoretical approach showed that the pK values of the second dissociations of the two phosphate groups are lower and are separated by smaller numbers, giving calculated pK values of 6.9 and 7.8. The presence of nearby Kdo units in ReLPS gives the molecule fewer negative charges on the phosphate groups compared to lipid A. This may contribute to better binding of ReLPS to the LPS receptors and may explain its higher biological activity when compared to lipid A. From these results, we can now provide the monomeric concentrations, pK values, ionic states, and charge distribution of a model, toxic LPS dissolved in aqueous media. Such information is necessary to understand the molecular basis for the biological activities of LPS. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,2500 OVERLOOK TERRACE,MADISON,WI 53705. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. UNIV WISCONSIN,SCH PHARM,MADISON,WI 53706. FREE UNIV BERLIN,INST KRISTALLOG,W-1000 BERLIN 33,GERMANY. FU NIGMS NIH HHS [GM-36054] NR 49 TC 41 Z9 42 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 4 PY 1993 VL 32 IS 17 BP 4579 EP 4586 DI 10.1021/bi00068a014 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA560 UT WOS:A1993LA56000014 PM 8485134 ER PT J AU NADOL, JB CHO, YB BURGESS, BJ ADAMS, JC AF NADOL, JB CHO, YB BURGESS, BJ ADAMS, JC TI THE LOCALIZATION OF SYNAPTOPHYSIN IN THE ORGAN OF CORTI OF THE HUMAN AS SHOWN BY IMMUNOELECTRON MICROSCOPY SO ACTA OTO-LARYNGOLOGICA LA English DT Article; Proceedings Paper CT 1992 SCIENTIFIC CONGRESS OF THE COLLEGIUM-OTO-RHINO-LARYNGOLOGICUM - AMICTAE-SACRUM ( CORLAS ) CY NOV 01-04, 1992 CL CAIRO, EGYPT SP COLLEGIUM OTO RHINO LARYNGOL DE SYNAPTOPHYSIN; HUMAN ORGAN OF CORTI; SYNAPTIC VESICLES; IMMUNOHISTOCHEMISTRY; EFFERENT ENDINGS ID NEURO-ENDOCRINE CELLS; GUINEA-PIG ORGAN; SYNAPSIN-I; SYNAPTIC VESICLES; EFFERENT SYNAPSES; PROTEIN; MEMBRANE; NEOPLASMS; IMMUNOCYTOCHEMISTRY; EXPRESSION AB Synaptophysin, or p38, a polypeptide of molecular weight 38 kD, is a calcium-binding membrane protein found in synaptic vesicles of neurons and smooth surfaced vesicles of neuroendocrine cells. Six human neonatal and infant temporal bones were fixed in paraformaldehyde and glutaraldehyde, decalcified in EDTA and were then immunoreacted for synaptophysin (ICN Biomedicals) using the avidin-biotin reaction (ABC kit, Vector Labs). The tissue was then prepared for light microscopic surface preparation, radial sections of 5 microns, and serial section electron microscopy. At a light microscopic level, the inner spiral bundle, tunnel spiral bundle, upper tunnel crossing fibers and the base of outer hair cells were stained. At the base of outer hair cells, the immunoreactivity was seen to decrease from the base to the apex and from the first to third outer hair cells. At an electron microscopic level, immunoreactivity at the base of outer hair cells was limited to vesiculated efferent fibers. The degree of immunoreactivity between adjacent efferent fibers varied significantly. Immunoreactive vesiculated endings were also found in the supranuclear region of outer hair cells. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. CHONNAM NATL UNIV,SCH MED,DEPT OTOLARYNGOL,KWANGJU,SOUTH KOREA. RP NADOL, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01 DC00152] NR 25 TC 15 Z9 15 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD MAY PY 1993 VL 113 IS 3 BP 312 EP 317 DI 10.3109/00016489309135815 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA LB217 UT WOS:A1993LB21700019 PM 8517133 ER PT J AU WORTH, JL SAVAGE, CR BAER, L ESTY, EK NAVIA, BA AF WORTH, JL SAVAGE, CR BAER, L ESTY, EK NAVIA, BA TI COMPUTER-BASED NEUROPSYCHOLOGICAL SCREENING FOR AIDS DEMENTIA COMPLEX SO AIDS LA English DT Note DE HIV-1; AIDS DEMENTIA; COMPUTER-BASED; SCREENING; REACTION TIME; NEUROPSYCHOLOGY ID IMMUNODEFICIENCY-VIRUS INFECTION; HIV-INFECTION; HOMOSEXUAL MEN; BRAINS AB Objective: To test the efficacy of reaction time (RT) measures as a screening test for AIDS dementia complex (ADC). Design and methods: Forty-two patients with mild-to-moderate ADC and 33 healthy HIV-1-seronegative control subjects took a computer-administered battery of four RT measures: simple RT, choice RT, and two types of sequential RT (1 and 2). Results: The performance of the ADC group was significantly worse than that of the control group on all four RT measures, but not all tasks were equally sensitive. The two tests of sequential RT were found to be the best discriminators, and receiver operating characteristic curves analyses indicated that the optimal cut-off z score was 1.0 for both tests. Conclusions: These preliminary results suggest that computer-based RT, using these two measures of sequential RT, may provide a sensitive method of detecting HIV-1-associated cognitive deficits. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP WORTH, JL (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,ROBERT B ANDREWS UNIT,FRUIT ST,WANG 812,BOSTON,MA 02114, USA. NR 31 TC 24 Z9 24 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD MAY PY 1993 VL 7 IS 5 BP 677 EP 681 DI 10.1097/00002030-199305000-00011 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LD156 UT WOS:A1993LD15600011 PM 8318175 ER PT J AU MORGAN, MB CINTRON, G BALIS, JU AF MORGAN, MB CINTRON, G BALIS, JU TI INFECTIVE MYCOTIC AORTIC ROOT ANEURYSM FOLLOWING CORONARY-ARTERY BYPASS-GRAFTING SO AMERICAN JOURNAL OF MEDICINE LA English DT Note C1 US DEPT VET AFFAIRS,JAMES A HALEY VET HOSP,TAMPA,FL. RP MORGAN, MB (reprint author), UNIV S FLORIDA,COLL MED,TAMPA,FL 33612, USA. NR 6 TC 4 Z9 4 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 MAY PY 1993 VL 94 IS 5 BP 550 EP 552 DI 10.1016/0002-9343(93)90096-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA LC874 UT WOS:A1993LC87400020 PM 8498404 ER PT J AU HOWIESON, J KAYE, JA HOLM, L HOWIESON, D AF HOWIESON, J KAYE, JA HOLM, L HOWIESON, D TI INTERUNCAL DISTANCE - MARKER OF AGING AND ALZHEIMER-DISEASE SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE DEMENTIA; BRAIN, MEASUREMENTS; BRAIN, MAGNETIC RESONANCE; AGE AND AGING; DEGENERATIVE BRAIN DISEASE ID DEMENTIA AB PURPOSE: To evaluate the utility of a recently reported simple measure of brain atrophy on MR imaging, the interuncal distance (IUD). METHODS: Measurements of the IUD were made over a 12-month interval in 10 patients with probable early Alzheimer disease and in a comparison group of age-matched healthy control subjects. The measurements were made in both the transaxial and coronal planes. RESULTS: Significant group differences for the coronal measurement of IUD were found in both the absolute value of the measurement and the IUD corrected for head size. There was overlap in IUD between the disease and the control groups. These differences were not found for the transaxial IUD. Significant positive correlations of the IUD with Mini-Mental State Examination score and Clinical Dementia Rating Scale stage were observed. Over the age range tested, age was not significantly correlated with IUD in the sample. CONCLUSIONS: The interuncal distance IUD is not a useful screening measurement for Alzheimer disease. C1 OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR. RP HOWIESON, J (reprint author), OREGON HLTH SCI UNIV,DEPT DIAGNOST RADIOL,L340,3181 SAM JACKSON PK RD,PORTLAND,OR 97201, USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG 08017] NR 11 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY-JUN PY 1993 VL 14 IS 3 BP 647 EP 650 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA LC082 UT WOS:A1993LC08200023 PM 8517353 ER PT J AU ZHOU, WG LEVINE, BA OLSON, MS AF ZHOU, WG LEVINE, BA OLSON, MS TI PLATELET-ACTIVATING-FACTOR - A MEDIATOR OF PANCREATIC INFLAMMATION DURING CERULEIN HYPERSTIMULATION SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CALCIUM MOBILIZATION; RECEPTOR OCCUPATION; ENZYME-SECRETION; RAT; BN-52021; ACINI; AGGREGATION; NEUTROPHILS; ANTAGONIST; INCREASES AB Hyperstimulation of the exocrine pancreas with cerulein causes acute pancreatitis, characterized by intensive interstitial edema, acinar vacuolization, leukocytic infiltration, and hyperamylasemia Whereas the pathogenesis of cerulein-induced pancreatitis is not well-defined, a local inflammatory response may contribute to the full expression of acute pancreatitis. Platelet-activating factor (PAF) seems to be an important mediator of the inflammatory response. The present evidence includes: 1) pancreatic PAF levels increased in rats in which cerulein-induced pancreatitis was initiated, concomitant with an increase in calcium concentrations in the pancreatic tissue, 2) treatment of rats exposed to cerulein with WEB2170, a PAF receptor antagonist, was shown to reduce inflammatory injury, as demonstrated by decreases in pancreatic weight, Evan's blue extravasation, and myeloperoxidase activity and an improvement in pancreatic histology. In an idealized in vitro experiment mimicking cerulein-induced acute pancreatitis, in which pancreatic acini were employed, cerulein induced amylase release, an increase in [Ca2+]i, and an increase in PAF synthesis. Whereas amylase release was induced by low concentrations of cerulein (10(-11) mol/L), relatively high concentrations of cerulein (10(-9) mol/L) were required for the observed increases in PAF synthesis and the [Ca2+]i, indicating that these two responses may not occur under physiological conditions. The present study suggests that the pancreatic accumulation of PAF coupled with Ca2+ overload are important biochemical components of the pathophysiology of cerulein-induced acute pancreatitis. In fact, PAF production may serve as a primary mediator of inflammation observed during pancreatic hyperstimulation. This is an important observation that will allow a more detailed characterization of the molecular basis of cerulein-induced acute pancreatitis. C1 UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM-19473] NR 38 TC 49 Z9 52 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1993 VL 142 IS 5 BP 1504 EP 1512 PG 9 WC Pathology SC Pathology GA LC123 UT WOS:A1993LC12300020 PM 8494049 ER PT J AU BILLETT, AL SALLAN, SE AF BILLETT, AL SALLAN, SE TI AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN CHILDHOOD ACUTE LYMPHOID LEUKEMIA WITH USE OF PURGING SO AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE AUTOLOGOUS BONE MARROW TRANSPLANT; CONDITIONING REGIMEN; MONOCLONAL ANTIBODIES ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; 2ND REMISSION; SUBSEQUENT REMISSION; TUMOR-CELLS; CHEMOTHERAPY; CHILDREN; 4-HYDROPEROXYCYCLOPHOSPHAMIDE; RELAPSE; DONORS AB Introduction: Chemotherapy alone is rarely curative for children with recurrent acute lymphoid leukemia (ALL). Although allogeneic bone marrow transplantation has been reported to provide disease-free survival rates of from 40 to 70%, its application is severely limited by the lack of sibling donors. The use of autologous bone marrow transplantation (ABMT) allows the application of therapy of comparable intensity to a larger number of patients. A potential problem associated with transplanting autologous marrow, the reinfusion of residual leukemic cells in the harvested marrow, can be addressed through purging. The most widely used purging techniques involve either immunologic or pharmacologic techniques. Patients and Methods: Since 1980, the Dana-Farber Cancer Institute has had an active autologous bone marrow transplantation program for children with recurrent ALL. Sixty-six children underwent autologous marrow transplants with a conditioning regimen consisting of teniposide, cytarabine, cyclophosphamide, and total body irradiation. This was followed by infusion of autologous marrow purged with two monoclonal antibodies directed against CD9 and CD10 and complement. Results: Twelve patients died of acute complications, 26 experienced relapse of ALL, one patient had acute myeloid leukemia 6 years after marrow transplant, and 27 remain in continuous complete remission. The event-free survival rate was 47% for patients with a first remission of at least 2 years, as compared with a rate of 10% for those with a shorter first remission. Since 1989, we have used a new conditioning regimen consisting of fractionated total body irradiation followed by high-dose etoposide and cyclophosphamide for patients with a short first remission. For the first 11 patients, the event-free survival rate is 61%. Literature Review: We reviewed reports of 552 patients with ALL who underwent ABMT at 17 centers. To our knowledge, only four series, including our own, were limited to pediatric patients. Some form of purging was used in 483 (87%) patients. Although conditioning regimens varied greatly, more than 80% of patients received at least total body irradiation and cyclophosphamide. Failure of engraftment was reported in only three patients. The rates of disease-free survival in these series clustered between 25-35%. The most common cause of treatment failure after ABMT was relapse, which occurred in 40-85% of patients. Early deaths from toxicity occurred in 5-21% of patients. Two studies attempted to compare the results of allogeneic and autologous bone marrow transplantation by using the same conditioning regimen for all. Neither series reported significant differences in overall survival. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP BILLETT, AL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 48 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-8562 J9 AM J PEDIAT HEMATOL PD MAY PY 1993 VL 15 IS 2 BP 162 EP 168 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA KX827 UT WOS:A1993KX82700003 PM 8498641 ER PT J AU FILOCOMA, D NEEDLEMAN, HL ARCECI, R GELBER, RD DONNELLY, M AF FILOCOMA, D NEEDLEMAN, HL ARCECI, R GELBER, RD DONNELLY, M TI PEDIATRIC HISTIOCYTOSIS - CHARACTERIZATION, PROGNOSIS, AND ORAL INVOLVEMENT SO AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE HISTIOCYTOSIS; PEDIATRIC PATIENTS; ORAL INVOLVEMENT AB Purpose: Forty-five children with histiocytosis were reviewed to characterize such a group and to establish the prevalence of oral involvement. In addition, patients with and without oral disease were compared for severity of disease, response to treatment, and incidence of recurrent disease. Patients and Methods: There were more boys (62.2%) than girls (37.8%) among the patients studied. About half (53.3%) were <2 years of age. Approximately half of all patients had two or fewer affected organ systems at diagnosis. The average length of treatment was 46 weeks. Results: A total 75.6% of patients were alive without disease at the completion of data collection, 15.6% died from the disease, 4.4% were alive with active disease, and 4.4% were alive with unknown status. Of the patients, 55.6% had long-term sequelae, and oral sequelae were present in 22.2% of the sample. In all, 28.8% of the patients exhibited oral symptoms at diagnosis, while 44.4% had oral involvement at some point during the course of the disease. Patients with oral symptoms were treated significantly longer and had more systemic therapy when compared with those without oral disease. C1 HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP FILOCOMA, D (reprint author), CHILDRENS HOSP MED CTR,DEPT DENT,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 16 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-8562 J9 AM J PEDIAT HEMATOL PD MAY PY 1993 VL 15 IS 2 BP 226 EP 230 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA KX827 UT WOS:A1993KX82700011 PM 8498646 ER PT J AU DONOVAN, DS SOLOMON, CG SEELY, EW WILLIAMS, GH SIMONSON, DC AF DONOVAN, DS SOLOMON, CG SEELY, EW WILLIAMS, GH SIMONSON, DC TI EFFECT OF SODIUM-INTAKE ON INSULIN SENSITIVITY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BLOOD PRESSURE; INSULIN RESISTANCE; INSULIN CLAMP; FREE FATTY ACIDS ID DEPENDENT DIABETES-MELLITUS; GLUCOSE-INTOLERANCE; NORMOTENSIVE SUBJECTS; IMPAIRED SUPPRESSION; THIAZIDE DIURETICS; SALT-SENSITIVITY; ORAL GLUCOSE; FATTY-ACIDS; RESISTANCE; HYPERTENSION AB To examine the effects of sodium intake on insulin sensitivity, we performed euglycemic insulin clamp studies (40 mU.m-2.min-1) in eight healthy normotensive nondiabetic white males (age = 36 +/- 5 yr; wt = 66 +/- 3 kg) after 5 days on high (200 meq/day)- and low (10 meq/day)-sodium diets administered in random order. High sodium intake was associated with significantly greater urinary sodium excretion (160 +/- 7 vs. 8 +/- 2 meq/day; P < 0.0001), suppression of plasma aldosterone (7 +/- 3 vs. 38 +/- 6 ng/dl; P < 0.001) and renin (1.5 +/- 0.2 vs. 6.0 +/- 0.9 ng.ml-1.h-1; P < 0.005) levels, but no change in blood pressure (116 +/- 3/63 +/- 2 vs. 114 +/- 3/64 +/- 2 mmHg; P = not significant). The rate of glucose infusion during the clamp was significantly reduced during the high- vs. low-sodium diet (279 +/- 19 vs. 334 +/- 24 mg.m-2.min-1; P < 0.01). This impairment in insulin sensitivity was not related to changes in serum potassium, epinephrine, norepinephrine, cortisol, or growth hormone but was highly correlated with an increment in circulating free fatty acid levels during high sodium intake (r = 0.82, P < 0.05). These data suggest that 1) high sodium intake may exacerbate insulin resistance by increasing circulating free fatty acids, and 2) differences in sodium intake may influence measures of insulin sensitivity in other disease states. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP SIMONSON, DC (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DIV ENDOCRINE HYPERTENS,DIABET & METAB SECT,BOSTON,MA 02115, USA. FU NCRR NIH HHS [RR-02635]; NICHD NIH HHS [HD-24499]; NIDDK NIH HHS [DK-43505] NR 34 TC 94 Z9 94 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1993 VL 264 IS 5 BP E730 EP E734 PN 1 PG 5 WC Physiology SC Physiology GA LD346 UT WOS:A1993LD34600042 PM 8498495 ER PT J AU HWANG, SJ HARRIS, HW OTUECHERE, G YALLA, S SULLIVAN, MR KASHGARIAN, M BENOS, DJ KLEYMAN, TR ZEIDEL, ML AF HWANG, SJ HARRIS, HW OTUECHERE, G YALLA, S SULLIVAN, MR KASHGARIAN, M BENOS, DJ KLEYMAN, TR ZEIDEL, ML TI TRANSPORT DEFECTS OF RABBIT INNER MEDULLARY COLLECTING DUCT CELLS IN OBSTRUCTIVE NEPHROPATHY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE URETERAL OBSTRUCTION; SODIUM CHANNEL; SODIUM-POTASSIUM ADENOSINE-TRIPHOSPHATASE; KIDNEY MEDULLA ID NA-K-ATPASE; EPITHELIAL SODIUM-CHANNEL; IMMUNOCYTOCHEMICAL LOCALIZATION; POSTOBSTRUCTIVE DIURESIS; URETERAL OBSTRUCTION; RAT; TUBULE; MINERALOCORTICOIDS; MICROPUNCTURE; NA,K-ATPASE AB Urinary obstruction markedly reduces collecting duct Na+ reabsorption. To define the cellular mechanisms of this derangement in Na+ reabsorption in inner medullary collecting duct (IMCD) of obstructed kidneys, suspensions of intact IMCD cells and inner medulla plasma membranes (IMPM) were prepared from 24 h obstructed and untreated control kidneys. Oxygen consumption (QO2) studies revealed marked reductions in both amiloride-sensitive and ouabain-sensitive QO2 but not ouabain-insensitive QO2 in intact IMCD cells from obstructed, compared with control animals, indicating a reduction in oxygen-dependent transport activities of both the Na+ channel and the Na+-K+-adenosinetriphosphatase (ATPase). Amiloride-sensitive conductive Na-22+ uptake in intact IMCD cells from obstructed kidneys was significantly decreased by 45% at 10 s, 30 s, and 1-5 min (10 s: 2.42 +/- 0.63 vs. 4.49 +/- 0.64 nmol Na+ flux/mg protein, n = 7, P < 0.05; 1 min: 4.65 +/- 0.7 vs. 8.27 +/- 0.98 nmol Na+ flux/mg protein, n = 7, P < 0.05), indicating decreased activity of amiloride-sensitive Na+ channels in these cells. However, immunoblots of IMPM with antibodies to Na+ channel proteins did not show significant differences in content of Na+ channel proteins between membranes from obstructed and control groups. Ouabain-sensitive Na+-K+-ATPase activity in IMPM of obstructed kidneys was also reduced (61.1 +/- 18.1 vs. 152.6 +/- 25.8 nmol ATP degradation . min-1.mg protein-1, n = 6, P < 0.02), and immunoblots with monoclonal antibodies against the alpha1- and beta-subunits of rabbit Na+-K+-ATPase showed a 51 +/- 7% reduction of both subunits in IMPM from obstructed kidneys (n = 4). In summary, ureteral obstruction reduces the activities of apical Na+ channel and basolateral Na+-K+ATPase of the IMCD, probably contributing to the salt wasting that characterizes obstructive nephropathy. However, the lack of change in the amount of Na+ channel protein in contrast to the decreased numbers of Na+-K+-ATPase subunits suggests distinct regulatory mechanisms for these two transporters in obstructed kidneys. C1 W ROXBURY DEPT VET AFFAIRS MED CTR,RES SERV,BOSTON,MA 02132. KAOHSIUNG MED COLL,DEPT INTERNAL MED,KAOHSIUNG,TAIWAN. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. RI Hwang, Shang-Jyh /C-7270-2009 FU NIDDK NIH HHS [DK-17433, DK-38774, DK-43955] NR 46 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1993 VL 264 IS 5 BP F808 EP F815 PN 2 PG 8 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700091 PM 8388652 ER PT J AU MOLITORIS, BA MEYER, C DAHL, R GEERDES, A AF MOLITORIS, BA MEYER, C DAHL, R GEERDES, A TI MECHANISM OF ISCHEMIA-ENHANCED AMINOGLYCOSIDE BINDING AND UPTAKE BY PROXIMAL TUBULE CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GENTAMICIN; PHOSPHOLIPIDS; PHOSPHATIDYLINOSITOL; IMMUNOCYTOCHEMICAL TECHNIQUES; IMMUNOGOLD LABELING; ENDOCYTOSIS ID BORDER MEMBRANE-VESICLES; BRUSH-BORDER; GENTAMICIN-NEPHROTOXICITY; EPITHELIAL POLARITY; TEMPORARY ISCHEMIA; CELLULAR RECOVERY; RENAL-FAILURE; RAT-KIDNEY; INHIBITION; DYSFUNCTION AB Preceding ischemia or concurrent hypotension is known to enhance aminoglycoside nephrotoxicity; however, the underlying mechanisms responsible have not been determined. To investigate the effect of preceding mild ischemia on cellular gentamicin handling, brush-border membrane vesicle binding and in vivo cellular gentamicin uptake were quantified using [H-3]gentamicin as a tracer. Fifteen minutes of ischemia resulted in a marked increase in apical membrane gentamicin binding (2.8 +/- 0.4 vs. 4.9 +/- 0.8 nmol/mg protein, P < 0.01). This increase was associated with an increased number of binding sites (3.7 +/- 0.3 vs. 9.1 +/- 2.3 nmol/mg protein, P < 0.0 1) and a reduced binding affinity (11.8 +/- 2.2 vs. 27.7 +/- 10.4 muM, P < 0.01). This increase in gentamicin binding was accompanied by alterations in apical membrane phospholipids including a doubling of phosphatidylinositol ( PI) levels (13.8 +/- 0.4 vs. 27.5 +/- 3.1 nmol/mg protein, P < 0.01). Furthermore, treatment of apical membrane vesicles with PI-specific phospholipase C markedly reduced the difference in gentamicin binding between paired control and ischemic membrane fractions. Increased gentamicin binding was associated with increased in vivo uptake of gentamicin by SI/S2 and S3 cells. Outer cortical uptake of gentamicin increased from 2.18 +/- 0.39 to 2.68 +/- 0.27 nmol/mg protein (P < 0.01) after 15 min of ischemia and 4 h of reperfusion. Juxtamedullary uptake also increased from 1.39 +/- 0.31 to 1.75 +/- 0.12 nmol/mg protein (P < 0.01). Immunocytochemical techniques, utilizing immunogold labeling, showed gentamicin was taken up via the receptor-mediated endocytic pathway by S1/S2 and S3 cells. After ischemic injury gentamicin was localized in abnormal intracellular accumulations in S3 but not S1 or S2 cells. Taken together, these data indicate ischemia results in a marked increase in apical gentamicin binding due to increases in apical PI content. This is associated with increased internalization by S1/S2 and S3 cells and abnormal intracellular compartmentalization of gentamicin within S3 cells. C1 UNIV COLORADO,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80262. RP MOLITORIS, BA (reprint author), DENVER VET AFFAIRS MED CTR,111C,1055 CLERMONT ST,DENVER,CO 80220, USA. FU NIDDK NIH HHS [DK-41126] NR 37 TC 23 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1993 VL 264 IS 5 BP F907 EP F916 PN 2 PG 10 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700105 PM 8498544 ER PT J AU GOLDBERG, MA HAHN, PF SAINI, S COHEN, MS REIMER, P BRADY, TJ MUELLER, PR AF GOLDBERG, MA HAHN, PF SAINI, S COHEN, MS REIMER, P BRADY, TJ MUELLER, PR TI VALUE OF T1-RELAXATION AND T2-RELAXATION TIMES FROM ECHOPLANAR MR IMAGING IN THE CHARACTERIZATION OF FOCAL HEPATIC-LESIONS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CAVERNOUS HEMANGIOMA; MAGNETIC-RESONANCE; HEPATOCELLULAR-CARCINOMA; RELAXATION-TIME; T2 VALUES; DIFFERENTIATION; TUMORS; METASTASES; LIVER; CONTRAST AB OBJECTIVE. The purpose of this study was to determine the value of echoplanar imaging in characterizing focal hepatic lesions on the basis of image-derived T1 and T2 relaxation times. SUBJECTS AND METHODS. Forty-six proven hepatic lesions were analyzed: 24 solid (21 metastases, three primary liver tumors) and 22 nonsolid (11 hemangiomas and 11 cysts). Mean lesion size (maximal length) was 4.0 (+/- 3.2) cm, and 16 of 46 lesions were less than 2.0 cm. A commercially available 1.5-T echoplanar-equipped MR scanner was used to obtain fat-suppressed, single-excitation (TR essentially infinite) axial images with a slice thickness of 10 mm. T1-weighted inversion recovery images (TE = 25 msec; TI = 100, 380, 600, or 800 msec) were acquired for 28 of 46 lesions, and T2-weighted spin-echo images (TE = 25, 50,100, 75 or 150 msec) were acquired for 45 of 46 lesions. For each acquisition (i.e., each different TI or TE), the entire liver was imaged in a single breath-hold of 12 sec or less. RESULTS. The mean T1 was 1004 (+/- 234) msec for solid lesions, 1337 (+/- 216) msec for hemangiomas, and 3143 (+/- 1392) msec for cysts. Although the mean T1 of solid and nonsolid lesions differed (p < .004), overlap precluded the use of T1 as a discriminatory index. Mean T2 times were 80 (+/- 18) msec for solid lesions, 178 (+/- 40) msec for hemangiomas, and 517 (+/- 429) msec for cysts. The mean T2 for hemangiomas is the longest reported to date. A T2 cutoff of 116 msec was 100% accurate for classifying lesions as solid or nonsolid and 93% accurate for characterizing them as benign or malignant. CONCLUSION. Our study suggests that echoplanar-derived T2 times (but not T1 times) are useful for characterizing focal hepatic lesions. An important use may be to characterize small lesions measuring less than 2.0 cm. The main advantages of echoplanar imaging are the absence of motion-induced volume averaging and phase artifacts, the ability to acquire purely T2-weighted images, and the use of multiple data points to calculate relaxation times. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GOLDBERG, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 NR 35 TC 75 Z9 77 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1993 VL 160 IS 5 BP 1011 EP 1017 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KY249 UT WOS:A1993KY24900014 PM 8470568 ER PT J AU MCGINNIS, HD CHEW, FS AF MCGINNIS, HD CHEW, FS TI MUCIN-PRODUCING ADENOMA OF THE APPENDIX SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID MUCOCELE C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 4 TC 4 Z9 4 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 1993 VL 160 IS 5 BP 1046 EP 1046 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KY249 UT WOS:A1993KY24900020 PM 8470572 ER PT J AU WYMAN, SM AF WYMAN, SM TI DEPARTMENT OF RADIOLOGY, MASSACHUSETTS-GENERAL-HOSPITAL - A BRIEF-HISTORY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material RP WYMAN, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1993 VL 160 IS 5 BP 1141 EP 1144 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KY249 UT WOS:A1993KY24900045 PM 8470596 ER PT J AU WHITING, J AF WHITING, J TI NOMINAL DYSPHASIA REDUX SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter RP WHITING, J (reprint author), PORTLAND VET AFFAIRS MED CTR,PORTLAND,OR 97207, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1993 VL 160 IS 5 BP 1146 EP 1146 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KY249 UT WOS:A1993KY24900048 PM 8470597 ER PT J AU RAINES, DE KORTEN, SE HILL, WAG MILLER, KW AF RAINES, DE KORTEN, SE HILL, WAG MILLER, KW TI ANESTHETIC CUTOFF IN CYCLOALKANEMETHANOLS - A TEST OF CURRENT THEORIES SO ANESTHESIOLOGY LA English DT Article DE ANESTHETICS, ALCOHOLS, CYCLOALKANEMETHANOL; POTENCY, CUTOFF; LIPID ORDER PARAMETER ID GENERAL-ANESTHETICS; LIPID BILAYERS; MOLECULAR DIMENSIONS; NORMAL-ALCOHOLS; MEMBRANES; FLUIDITY; LIPOSOMES; POTENCIES; ALKANOLS; PROTON AB Background. N-alkanols containing up to 12 carbons are anesthetic; however, those with more than 12 carbons are not. This phenomenon has been termed cutoff. Lipid disordering theories of anesthesia suggest that cutoff occurs because the alkyl chains of long-chain alcohols approach the length and shape of the lipids of neuronal membranes and, therefore, intercalate into membranes without perturbing them. Protein theories suggest that cutoff occurs because the size of long-chain alcohols exceeds that of a protein binding site having finite dimensions. These theories were tested with a new series of alcohols, the cycloalkanemethanols, c(CnH2n-1) . CH2 . OH. Methods. Anesthetic potency was measured in Rana pipiens tadpoles using the reversible loss of righting reflexes as the endpoint. The change in order parameter induced by cycloalkanemethanols and n-alkanols in lipid bilayers made of egg phosphatidylcholine and cholesterol was measured with electron paramagnetic resonance spectroscopy. Results: On ascending the series from cyclopropanemethanol (EC50 = 54 +/- 3.2 mM) to cycloundecanemethanol (EC50 = 7.0 +/- 0.12 muM) anesthetic potencies first increased exponentially but then decreased sharply at cyclododecanemethanol (EC50 = 13 +/- 0.2 muM). Cyclotetradecanemethanol was found not to cause anesthesia in tadpoles, even after 48 h of exposure, although saturated solutions shifted the dose-response curve of octanol from 66 +/- 2.6 to 47 +/- 2.8 muM. A linear loss in the ability to disorder lipid bilayers was observed on ascending both alcohol series such that cyclotetradecanemethanol and n-tridecanol actually increased bilayer order. Conclusions. Molecular length does not correlate with anesthetic cutoff in these two alcohol series. Cutoff is predicted by the ability of both series of alcohols to disorder lipid bilayers and correlates with their molecular volume. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT BIOL CHEM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC PHARMACOL,BOSTON,MA 02114. RP RAINES, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [GM07592, GM15904] NR 29 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 1993 VL 78 IS 5 BP 918 EP 927 DI 10.1097/00000542-199305000-00017 PG 10 WC Anesthesiology SC Anesthesiology GA LA777 UT WOS:A1993LA77700016 PM 8489064 ER PT J AU HUANG, D CHANG, TR AGGARWAL, A LEE, RC EHRLICH, HP AF HUANG, D CHANG, TR AGGARWAL, A LEE, RC EHRLICH, HP TI MECHANISMS AND DYNAMICS OF MECHANICAL STRENGTHENING IN LIGAMENT-EQUIVALENT FIBROBLAST-POPULATED COLLAGEN MATRICES SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE COLLAGEN; FIBROBLASTS; LIGAMENT; STIFFNESS; CROSS-LINK; COLLAGEN GEL; BREAKING STRENGTH ID HUMAN-SKIN FIBROBLASTS; PERIODONTAL-LIGAMENT; GROWTH-FACTOR; CELLS; CONTRACTION; GELS; INVITRO; LATTICES; GLYCOSAMINOGLYCANS; REORGANIZATION AB We have measured the dynamics of extracellular matrix consolidation and strengthening by human dermal fibroblasts in hydrated collagen gels. Constraining matrix consolidation between two porous polyethylene posts held rigidly apart set up the mechanical stress which led to the formation of uniaxially oriented fibroblast-populated collagen matrices with a histology resembling a ligament. We measured the mechanical stiffness and tensile strength of these ligament equivalents (LEs) as a function of age at biweekly intervals up to 12 weeks in culture using a mechanical spectrometer customized for performing experiments under physiologic conditions. The LE load-strain curve changed as a function of LE age, increasing in stiffness and exhibiting less plastic-like behavior. At 12 weeks, LEs had acquired up to 30 times the breaking strength of 1-week-old LEs. Matrix strengthening occurred primarily through the formation of BAPN-sensitive, lysyl oxidase catalyzed crosslinks. Sulfated glycosaminoglycan (GAG) content increased monotonically with LE age, reaching levels that are characteristic of ligaments. Cells in the LEs actively incorporated [H-3]proline and [S-35]sulfate into the extracellular matrix. Over the first three weeks, DNA content increased rapidly but thereafter remained constant. This data represent the first documentation of strengthening kinetics for cell-assembled biopolymer gels and the results suggest that this LE tissue may be a valuable model for studying the cellular processes responsible for tissue growth, repair, and remodeling. C1 HARVARD UNIV,MIT DIV HLTH SCI & TECHNOL,ELECTROMAGNET & ELECTR SYST LAB,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT SURG,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,SHRINERS BURN INST,BOSTON,MA 02114. NR 51 TC 144 Z9 148 U1 0 U2 13 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD MAY-JUN PY 1993 VL 21 IS 3 BP 289 EP 305 DI 10.1007/BF02368184 PG 17 WC Engineering, Biomedical SC Engineering GA LE086 UT WOS:A1993LE08600009 PM 8328728 ER PT J AU KOPANS, DB AF KOPANS, DB TI THE BREAST-CANCER SCREENING CONTROVERSY CONTINUES SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1993 VL 118 IS 9 BP 746 EP 746 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KY502 UT WOS:A1993KY50200015 PM 8460864 ER PT J AU WEBER, AL LOEWENHEIM, HM AF WEBER, AL LOEWENHEIM, HM TI OSTEOMA ARISING FROM THE STYLOHYOID CHAIN AND MANIFESTING AS A NECK AND OROPHARYNGEAL MASS SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID STYLOID PROCESS; OSSIFICATION; ETIOLOGY C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP WEBER, AL (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 1993 VL 102 IS 5 BP 399 EP 401 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA LB519 UT WOS:A1993LB51900014 PM 8489172 ER PT J AU YAREMCHUK, MJ DELVECCHIO, DA FIALA, TGS LEE, WPA AF YAREMCHUK, MJ DELVECCHIO, DA FIALA, TGS LEE, WPA TI MICROFIXATION OF ACUTE ORBITAL FRACTURES SO ANNALS OF PLASTIC SURGERY LA English DT Article ID INTERNAL-FIXATION; RIGID FIXATION; CRANIOMAXILLOFACIAL SURGERY; PLATE OSTEOSYNTHESIS; FACIAL OSTEOTOMIES; MIDFACE FRACTURES; TRAUMA; RECONSTRUCTION; CLASSIFICATION; ADVANCEMENT AB Microfixation techniques were used as an adjunct to the use of miniplates and screws in the acute treatment of fractures involving the orbit in 42 patients over a 2-year period. Miniplates were used in all fractures at the Le Fort I level and at the zygomatic-frontal suture in high-energy injuries. Microfixation was used to stabilize all other fractures of the zygomatic, nasoethmoid, and frontal areas. Problems with plate visibility and objectionable palpability through thin periorbital skin were eliminated. The use of microplates allowed more precise positioning of small fragments than possible with miniplates or interfragmentary wires. Fracture reduction remained clinically stable in the frontal and nasoethmoid areas. Microplates were inadequate to resist soft tissue deforming forces along the infraorbital rim and the zygomatic arch in high-energy injuries. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP YAREMCHUK, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,DIV PLAST SURG,WACC 453,BOSTON,MA 02114, USA. NR 42 TC 5 Z9 7 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 1993 VL 30 IS 5 BP 385 EP 397 DI 10.1097/00000637-199305000-00001 PG 13 WC Surgery SC Surgery GA LB864 UT WOS:A1993LB86400001 PM 8342922 ER PT J AU ELMALEH, DR KIZUKA, H HANSON, RN JONES, GS HERMAN, LW STRAUSS, HW AF ELMALEH, DR KIZUKA, H HANSON, RN JONES, GS HERMAN, LW STRAUSS, HW TI STRUCTURE-LOCALIZATION RELATIONSHIPS OF C-11 LABELED PHENTERMINE DERIVATIVES - EFFECT OF AROMATIC-SUBSTITUTION SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID CEREBRAL BLOOD-FLOW; EMISSION COMPUTED-TOMOGRAPHY; BRAIN; PERFUSION; MICROSPHERES; STROKE; I-123; IODOAMPHETAMINE; INHALATION; METABOLISM AB A series of phentermine analogs, including the unsubstituted, the para-F, -Cl, -Br and -1, and the meta-CF3 derivatives, were labeled by [C-11]methylation and evaluated in rats to determine the structure-localization relationships for this class of regional cerebral blood flow imaging agents. All the phentermines were well-localized in the brain; however, only the para-substituted agents were well-retained. Localization in the nontarget tissue was affected by the lipophilicity of the substituent. Comparison with the radioiodinated analogs showed virtually identical results, which suggests that the compounds were not significantly metabolized. The agent with the best biodistribution characteristics was the N-[C-11]methyl-p-iodophentermine, with the p-bromo analog almost equivalent. C1 NORTHEASTERN UNIV,COLL PHARM & ALLIED HLTH PROFESS,DEPT MED CHEM,BOSTON,MA 02115. RP ELMALEH, DR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV RADIOL SCI & TECHNOL,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [1 R01 HL24666] NR 44 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD MAY PY 1993 VL 44 IS 5 BP 821 EP 829 DI 10.1016/0969-8043(93)90023-4 PG 9 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA KY859 UT WOS:A1993KY85900005 PM 8485509 ER PT J AU WEINER, NC NEWMAN, NJ LESSELL, S JOHNS, DR LOTT, MT WALLACE, DC AF WEINER, NC NEWMAN, NJ LESSELL, S JOHNS, DR LOTT, MT WALLACE, DC TI ATYPICAL LEBERS HEREDITARY OPTIC NEUROPATHY WITH MOLECULAR CONFIRMATION SO ARCHIVES OF NEUROLOGY LA English DT Article ID MITOCHONDRIAL-DNA MUTATION; GENETIC-HETEROGENEITY; FUNDUS FINDINGS; NEURORETINOPATHY; PEDIGREES; ATROPHY; DIAGNOSIS; MEMBERS; DISEASE; FAMILY AB Objective.-Leber's hereditary optic neuropathy (LHON) is typically a familial disease of primarily young, male adults. Analysis of mitochondrial DNA has identified point mutations associated with LHON and allowed us to identify cases of LHON not consistent with traditional descriptions of the disease. Data Sources.-The collective experience of three tertiary referral centers contributed to this report. Study Selection.-Patients with bilateral optic neuropathies who were positive for the 11 778 LHON mutation were included in this study if they were female and there was no family history of visual loss. Data Extraction.-Six case histories are presented. Data Synthesis.-The diagnosis of LHON remained unknown in six female patients with bilateral optic neuropathies until molecular analysis revealed the 11778 mitochondrial DNA mutation. None of the patients had a family history of visual loss, and five were initially diagnosed as having factitious visual loss. Other individual features atypical for LHON included lack of the characteristic LHON funduscopic appearance, bitemporal hemianopia, optic disc cupping and premonitory episodes of transient visual loss. In one patient the correct diagnosis was delayed 17 years. Conclusions.-The diagnosis of LHON should be considered in all cases of unexplained optic neuropathy, including those with negative family history, late or early age at onset, female gender, or normal funduscopic appearance. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. EMORY UNIV,SCH MED,DEPT OPHTHALMOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,ATLANTA,GA 30322. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. FU NINDS NIH HHS [NS21328] NR 37 TC 40 Z9 42 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 1993 VL 50 IS 5 BP 470 EP 473 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA LB393 UT WOS:A1993LB39300004 PM 8489402 ER PT J AU HARDIMAN, O HALPERIN, JJ FARRELL, MA SHAPIRO, BE WRAY, SH BROWN, RH AF HARDIMAN, O HALPERIN, JJ FARRELL, MA SHAPIRO, BE WRAY, SH BROWN, RH TI NEUROPATHIC FINDINGS IN OCULOPHARYNGEAL MUSCULAR-DYSTROPHY - A REPORT OF 7 CASES AND A REVIEW OF THE LITERATURE SO ARCHIVES OF NEUROLOGY LA English DT Review ID NUCLEAR INCLUSIONS; DISTAL SPREAD AB We describe seven patients with clinical evidence of oculopharyngeal muscular dystrophy. Four of these patients were members of the same Italian-American family. The age at onset was after the fourth decade in all patients. All seven patients had extraocular muscle involvement, and six of the seven patients had clinical, electrophysiological, and/or pathological evidence of neuropathy in addition to features that were suggestive of myopathy. An autopsy was performed on one patient. We discuss the significance of the concurrence of neuropathic features with oculopharyngeal muscular dystrophy in relation to these patients and previously reported cases. C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR RES & NEUROL SERV,BLDG 149,6TH FLOOR,NAVY YARD,13TH ST,BOSTON,MA 02114. BETH ISRAEL HOSP,HARVARD LONGWOOD AREA NEUROL TRAINING PROGRAM,BOSTON,MA 02215. BEAUMONT HOSP,RICHMOND INST NEUROL & NEUROSURG,DUBLIN,IRELAND. SUNY,SCH MED,STONY BROOK,NY 11794. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. NR 53 TC 20 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 1993 VL 50 IS 5 BP 481 EP 488 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA LB393 UT WOS:A1993LB39300006 PM 8387769 ER PT J AU JESSUP, JM STEELE, G MAYER, RJ POSNER, M BUSSE, P CADY, B STONE, M JENKINS, R OSTEEN, R COLACCHIO, TA WARSHAW, AL AF JESSUP, JM STEELE, G MAYER, RJ POSNER, M BUSSE, P CADY, B STONE, M JENKINS, R OSTEEN, R COLACCHIO, TA WARSHAW, AL TI NEOADJUVANT THERAPY FOR UNRESECTABLE PANCREATIC ADENOCARCINOMA SO ARCHIVES OF SURGERY LA English DT Article ID REGIONAL PANCREATECTOMY; PERIAMPULLARY CARCINOMA; CANCER; EXPERIENCE; PANCREATODUODENECTOMY; SURVIVAL; PANCREATICODUODENECTOMY; 5-FLUOROURACIL; RESECTABILITY; MORBIDITY AB The purposes of this study were to determine whether continuous infusion of fluorouracil combined with external-beam radiation therapy improved the resectability and survival of patients with pancreatic carcinoma. Sixteen patients with unresectable disease confined to the pancreas and celiac nodes were treated, and their outcome was compared with that of 24 patients with potentially resectable disease who were treated concurrently. The neoadjuvant therapy was completed with acceptably few toxic effects but with only a minor decrease in tumor size. Two patients underwent resection and remained free of disease 20 and 22.5 months later. However, the median survival of the entire neoadjuvant group was 8 months. All 24 patients with potentially resectable carcinoma underwent surgical exploration. Fifteen of the 24 patients underwent resection and survived a median of 12.5 months. Neoadjuvant chemoradiation may have improved outcome and resectability for two (12.5%) of 16 patients with unresectable pancreatic carcinoma, but more effective therapy options must be developed to improve outcome. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,DEPT TECH PHYS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. FU NCI NIH HHS [CA 42857, CA 47041] NR 27 TC 127 Z9 129 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 1993 VL 128 IS 5 BP 559 EP 564 PG 6 WC Surgery SC Surgery GA LB406 UT WOS:A1993LB40600013 PM 8098206 ER PT J AU RATTNER, DW ELLMAN, L WARSHAW, AL FOSTER, JH MCDERMOTT, WV JENKINS, RL FRIEDMANN, P SHOEMAKER, CP BUTSCH, DW HENDREN, WH AF RATTNER, DW ELLMAN, L WARSHAW, AL FOSTER, JH MCDERMOTT, WV JENKINS, RL FRIEDMANN, P SHOEMAKER, CP BUTSCH, DW HENDREN, WH TI PORTAL-VEIN THROMBOSIS AFTER ELECTIVE SPLENECTOMY - AN UNDERAPPRECIATED, POTENTIALLY LETHAL SYNDROME SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 73RD ANNUAL MEETING OF THE NEW ENGLAND SURGICAL SOC CY SEP 26, 1992 CL DIXVILLE NOTCH, NH SP NEW ENGLAND SUR SOC ID POSTSPLENECTOMY THROMBOCYTOSIS; MYELOPROLIFERATIVE DISORDERS; VENOUS THROMBOSIS AB We describe seven cases of thrombosis of the portal and splenic vein after elective splenectomy. The diagnosis was initially unrecognized in all patients and was confused with biliary sepsis (three cases), postoperative pancreatitis (three cases), or pulmonary emboli (one case). Two patients in whom the diagnosis of portal vein thrombosis was not made within 3 days of disease onset died. In the five survivors, the diagnosis was based on clinical suspicion, confirmed with color flow Doppler ultrasonography or computed tomography with intravenous contrast material, and treated with thrombolytic agents, anticoagulants, and antibiotics. In two patients, splenic vein thrombus was visualized on initial postoperative imaging studies and the thrombus subsequently extended into the portal vein. Portal vein thrombosis should be considered in patients with fever and abdominal complaints after splenectomy. Urgent treatment with thrombolysis and anticoagulants may preserve bowel integrity and be lifesaving. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RATTNER, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 15 TC 96 Z9 105 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 1993 VL 128 IS 5 BP 565 EP 570 PG 6 WC Surgery SC Surgery GA LB406 UT WOS:A1993LB40600014 PM 8489390 ER PT J AU YASUDA, T GOLD, HK KOHMURA, C GUERRERO, L YAOITA, H FALLON, JT BUNTING, S COLLEN, D AF YASUDA, T GOLD, HK KOHMURA, C GUERRERO, L YAOITA, H FALLON, JT BUNTING, S COLLEN, D TI INTRAVENOUS AND ENDOBRONCHIAL ADMINISTRATION OF G4120, A CYCLIC ARG-GLY-ASP-CONTAINING PLATELET GPIIB/IIIA RECEPTOR BLOCKING PENTAPEPTIDE, ENHANCES AND SUSTAINS CORONARY ARTERIAL THROMBOLYSIS WITH RT-PA IN A CANINE PREPARATION SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE ACUTE MYOCARDIAL INFARCTION; THROMBOLYTIC THERAPY; ARTERIAL REOCCLUSION; TEMPLATE BLEEDING TIME; GLYCOPROTEIN-IIB/IIIA RECEPTOR ID ACTIVATOR-INDUCED THROMBOLYSIS; ACUTE MYOCARDIAL-INFARCTION; IIB-IIIA ANTAGONIST; PLASMINOGEN-ACTIVATOR; AGGREGATION INHIBITOR; THROMBIN INHIBITION; CONTAINING PEPTIDE; REOCCLUSION; PREVENTION; MODEL AB G4120, L-cysteine, N-(mercaptoacetyl)-D-tyrosyl-L-arginylglycyl-L-alpha-aspartyl-cyclic(1-->5)-sulfide, 5-oxide, a synthetic cyclic Arg-Gly-Asp-containing pentapeptide, has a high affinity (dissociation constant of 4 nM) for the platelet glycoprotein (GP) IIb/IIIa receptor. The effects of its intravenous or endobronchial administration on thrombolysis, reocclusion, and bleeding time prolongation induced with 0.45 mg/kg bolus injections of recombinant tissue-type plasminogen activator in combination with intravenous heparin (4,000-unit bolus and 1,000 units each hour) were studied in a canine model consisting of an erythrocyte-rich blood clot in the left anterior descending coronary artery. Coronary patency was monitored for 3 hours both by ultrasonic How probe and by repeat coronary angiography. Four groups of six to 10 dogs were studied with intravenous infusions of 0, 0.1, 0.2, or 0.3 mg/kg G4120 over 60 minutes. G4120 at a dose of 0.3 mg/kg reduced the time to reflow from a mean control value of 45 to 8 minutes (p=0.036) and delayed reocclusion (p=0.001). Four groups of five or six dogs were studied with endobronchial instillation of G4120 in a randomized, blinded study design using 0, 0.13, 0.25, or 0.5 mg/kg G4120. Endobronchial G4120 at a dose of 0.5 mg/kg reduced the time to reflow from a mean control value of 52 to 7 minutes (p=0.039) and abolished cyclic reocclusion and reflow (p=0.008). G4120 induced a dose-related transient prolongation of the template bleeding time and inhibition of ADP-induced platelet aggregation. G4120, a synthetic low-molecular-weight GPIIb/IIIa inhibitor that may be produced by chemical synthesis, may be of clinical value as a conjunctive agent for thrombolysis in patients with ischemic coronary syndromes. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,ACC 4,ROOM 480,15 PARKMAN ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. GENENTECH INC,S SAN FRANCISCO,CA. NR 30 TC 21 Z9 21 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD MAY PY 1993 VL 13 IS 5 BP 738 EP 747 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LB036 UT WOS:A1993LB03600015 PM 8485125 ER PT J AU WEINBLATT, ME POLISSON, R BLOTNER, SD SOSMAN, JL ALIABADI, P BAKER, N WEISSMAN, BN AF WEINBLATT, ME POLISSON, R BLOTNER, SD SOSMAN, JL ALIABADI, P BAKER, N WEISSMAN, BN TI THE EFFECTS OF DRUG-THERAPY ON RADIOGRAPHIC PROGRESSION OF RHEUMATOID-ARTHRITIS - RESULTS OF A 36-WEEK RANDOMIZED TRIAL COMPARING METHOTREXATE AND AURANOFIN SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOW-DOSE METHOTREXATE; CONTROLLED CLINICAL-TRIAL; DOUBLE-BLIND TRIAL; RADIOLOGIC PROGRESSION; PULSE METHOTREXATE; INTRAMUSCULAR METHOTREXATE; AZATHIOPRINE; EFFICACY AB Objective. To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA). Methods. We conducted a 9-month randomized, multicenter, double-blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation. Results. Two hundred eighty-one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean +/- SEM change of 1.67 +/- 0.4) compared with the change in the MTX group (0.60 +/- 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 +/- 0.3 versus 0.42 +/- 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation. Conclusion. The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36-week period. C1 AMER CYANAMID CO,DEPT CLIN STAT,DIV MED RES,PEARL RIVER,NY. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV RHEUMATOL,BOSTON,MA 02114. RP WEINBLATT, ME (reprint author), BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 28 TC 109 Z9 110 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 MAY PY 1993 VL 36 IS 5 BP 613 EP 619 DI 10.1002/art.1780360507 PG 7 WC Rheumatology SC Rheumatology GA LD137 UT WOS:A1993LD13700007 PM 8489539 ER PT J AU BLACKBURN, WD CHATHAM, WW AF BLACKBURN, WD CHATHAM, WW TI NEUTROPHIL HYPOCHLOROUS ACID (HOCL) PRODUCTION IN RESPONSE TO SURFACE-ASSOCIATED IGG (SAIGG) IS DEPENDENT UPON BOTH FC-GAMMA-R-II AND FC-GAMMA-R-III AND THE INFLUX OF EXTRACELLULAR CALCIUM SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US DEPT VET AFFAIRS,BIRMINGHAM,AL. UNIV ALABAMA,BIRMINGHAM,AL 35294. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R25 EP R25 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900113 ER PT J AU CHATHAM, WW BLACKBURN, WD AF CHATHAM, WW BLACKBURN, WD TI LIGATION OF CR-1 ON NEUTROPHILS ATTENUATES SURFACE-ASSOCIATED IGG-INDUCED HOCL GENERATION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. US DEPT VET AFFAIRS,RES SERV,BIRMINGHAM,AL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R25 EP R25 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900114 ER PT J AU CHATHAM, WW BLACKBURN, WD AF CHATHAM, WW BLACKBURN, WD TI SOLID-PHASE IGA INDUCES NEUTROPHIL DEGRANULATION AND OXIDANT GENERATION THROUGH A PERTUSSIS TOXIN-INSENSITIVE PATHWAY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US DEPT VET AFFAIRS,RES SERV,BIRMINGHAM,AL. UNIV ALABAMA,UNIVERSITY,AL 35486. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R18 EP R18 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900069 ER PT J AU MOK, SCH LO, KW TSAO, SW AF MOK, SCH LO, KW TSAO, SW TI DIRECT CYCLE SEQUENCING OF MUTATED ALLELES DETECTED BY PCR SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSIS SO BIOTECHNIQUES LA English DT Note ID POLYMERASE CHAIN-REACTION; P53 GENE; DNA AB A rapid protocol for direct sequencing of a mutated allele, detected by combining polymerase chain reaction with single-strand conformation polymorphism (PCR-SSCP) analysis and cycle sequencing using a thermal cycler, is described. End-labeled radioactive primers were used both for PCR-SSCP analysis for the detection of p53 gene mutation and for cycle sequencing using DELTATaq(TM) Version 2.0 DNA Polymerase. The point mutations along the various exons of the p53 gene can be rapidly determined by this sequencing method. This protocol requires only a small amount of DNA template (0.1 mug) and produces sequencing images with low backgrounds and very uniform band intensity. It has also been used successfully in the study of other gene mutations including ras and NF-1 (neurofibromatosis 1) genes. C1 BRIGHAM & WOMENS HOSP, GYNECOL ONCOL LAB, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT OBSTET GYNECOL & REPROD BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV GYNECOL ONCOL, BOSTON, MA 02115 USA. CHINESE UNIV HONG KONG, DEPT ANAT & CELLULAR PATHOL, SHA TIN, HONG KONG. NR 9 TC 18 Z9 18 U1 0 U2 0 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 EI 1940-9818 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1993 VL 14 IS 5 BP 790 EP + PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA812 UT WOS:A1993LA81200029 PM 8512704 ER PT J AU ARCECI, RJ AF ARCECI, RJ TI CLINICAL-SIGNIFICANCE OF P-GLYCOPROTEIN IN MULTIDRUG RESISTANCE MALIGNANCIES SO BLOOD LA English DT Editorial Material ID MDR1 GENE-EXPRESSION; CLASS-II REGION; BACTERIAL TRANSPORT PROTEINS; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; DRUG-RESISTANCE; DOXORUBICIN RESISTANCE; MONOCLONAL-ANTIBODIES; CELL-LINES; IMMUNOHISTOCHEMICAL DETECTION RP ARCECI, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA48162] NR 148 TC 232 Z9 240 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 1993 VL 81 IS 9 BP 2215 EP 2222 PG 8 WC Hematology SC Hematology GA KZ991 UT WOS:A1993KZ99100001 PM 8097632 ER PT J AU GROSSBARD, ML GRIBBEN, JG FREEDMAN, AS LAMBERT, JM KINSELLA, J RABINOWE, SN ELISEO, L TAYLOR, JA BLATTLER, WA EPSTEIN, CL NADLER, LM AF GROSSBARD, ML GRIBBEN, JG FREEDMAN, AS LAMBERT, JM KINSELLA, J RABINOWE, SN ELISEO, L TAYLOR, JA BLATTLER, WA EPSTEIN, CL NADLER, LM TI ADJUVANT IMMUNOTOXIN THERAPY WITH ANTI-B4-BLOCKED RICIN AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR PATIENTS WITH B-CELL NON-HODGKINS-LYMPHOMA SO BLOOD LA English DT Article ID BREAKPOINT-CLUSTER REGION; MONOCLONAL-ANTIBODY; PHASE-I; HEMATOLOGIC MALIGNANCIES; CHAIN IMMUNOTOXIN; TOXICITY; INTERLEUKIN-2; RELAPSE; ADULTS; GRADE C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. IMMUNOGEN INC,CAMBRIDGE,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [1K12CA01730, CA34183, CA55207] NR 30 TC 101 Z9 101 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 1993 VL 81 IS 9 BP 2263 EP 2271 PG 9 WC Hematology SC Hematology GA KZ991 UT WOS:A1993KZ99100006 PM 8481509 ER PT J AU EMERY, DW SHAFER, GE KARSON, EM SACHS, DH LEGUERN, C AF EMERY, DW SHAFER, GE KARSON, EM SACHS, DH LEGUERN, C TI RETROVIRUS-MEDIATED TRANSFER AND EXPRESSION OF AN ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II DRB CDNA IN SWINE BONE-MARROW CULTURES SO BLOOD LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; LONG-TERM CULTURES; MINIATURE SWINE; GENE-TRANSFER; TRANSPLANTATION TOLERANCE; STEM-CELLS; HLA-DR; VECTOR; IDENTIFICATION; RECOMBINATION C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL46532]; NIAID NIH HHS [AI33053] NR 35 TC 24 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1993 VL 81 IS 9 BP 2460 EP 2465 PG 6 WC Hematology SC Hematology GA KZ991 UT WOS:A1993KZ99100031 PM 8386951 ER PT J AU LEE, K DEEDS, JD BOND, AT JUPPNER, H ABOUSAMRA, AB SEGRE, GV AF LEE, K DEEDS, JD BOND, AT JUPPNER, H ABOUSAMRA, AB SEGRE, GV TI INSITU LOCALIZATION OF PTH/PTHRP RECEPTOR MESSENGER-RNA IN THE BONE OF FETAL AND YOUNG-RATS SO BONE LA English DT Article; Proceedings Paper CT 6TH INTERNATIONAL MEETING ON BONE MORPHOMETRY CY OCT 04-09, 1992 CL LEXINGTON, KY SP ABBOTT LABS, BOEHRINGER MANNHEIM, CHUGAI PHARM, CIBA GEIGY, DIALYSIS CLIN, INTERMED ORTHOPED, RHONE POULENC RORER, SANDOZ PHARM, STRAUMANN, DEPUY AB We characterized cells that express parathyroid hormone/ parathyroid hormone related peptide (PTH/PTHrP) receptor mRNA in bones of fetal and postnatal rats by in situ hybridization. During endochondral development of fetal bones, PTH/PTHrP receptor transcripts were highly expressed both in maturing chondrocytes and in osteoblasts in the periosteum and ossification center, but not in fully hypertrophic chondrocytes. Similar to the localization in the fetal bones, PTH/PTHrP receptor mRNA expression was highly localized to maturing chondrocytes in the articular cartilage and growth plate, and to osteoblasts in the femur of young rats. In both young and fetal rats, transcripts for Type X collagen were localized to hypertrophic chondrocytes, mostly between chondrocytes and bone cells both of which express PTH/PTHrP receptor mRNA. Transcripts for PTH/PTHrP receptors and alkaline phosphatase co-localized in the bone of young rats, but they did not co-localize in fetal bones at the early stages of endochondral ossification. These results show that PTH/PTHrP receptor mRNA is expressed in a cell-type and stage-specific manner during skeletal development. RP LEE, K (reprint author), MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,FRUIT ST,BOSTON,MA 02114, USA. NR 3 TC 81 Z9 81 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD MAY-JUN PY 1993 VL 14 IS 3 BP 341 EP 345 DI 10.1016/8756-3282(93)90162-4 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LD833 UT WOS:A1993LD83300025 PM 8395866 ER PT J AU KRAMER, R WEBER, TK MORSE, B ARCECI, R STANIUNAS, R STEELE, G SUMMERHAYES, IC AF KRAMER, R WEBER, TK MORSE, B ARCECI, R STANIUNAS, R STEELE, G SUMMERHAYES, IC TI CONSTITUTIVE EXPRESSION OF MULTIDRUG-RESISTANCE IN HUMAN COLORECTAL TUMORS AND CELL-LINES SO BRITISH JOURNAL OF CANCER LA English DT Article ID HUMAN-COLON-CARCINOMA; PRODUCT P-GLYCOPROTEIN; INTRINSIC DRUG-RESISTANCE; MDR1 GENE; HUMAN CANCERS; KB CELLS; TISSUES; TRANSPORT; TUMORS AB In this study we report detection of mdr1 gene expression in the liver metastases of 7/11 patients with colon carcinoma and characterise the MDR phenotype associated with a panel of 19 human colon carcinoma cell lines. Within this panel, mdr1 mRNA biosynthesis and surface localisation of Pgp were assessed with respect to MDR functionality where the cell lines are representative of different clinical stages of tumour progression, metastatic potential and differentiation. The data indicates that constitutive levels of mdr1 mRNA/Pgp expression may not necessarily result in the functional expression of the MDR phenotype. While low levels of mdr1 mRNA/Pgp were detected in 5/8 well differentiated colon cell lines, only 2/8 were functionally MDR. In contrast, 10/11 moderate and poorly differentiated lines expressed mdr1 mRNA/Pgp and of these, 9/11 were functionally MDR. The phosphorylation status of the mature 170 kD P-glycoprotein and the surface localisation of this glycoprotein showed the strongest correlation with functionality. Analysis of cell lines for cross-resistance and chemosensitivity profiles against a battery of chemotherapeutic drugs suggests multiple mechanisms, in addition to Pgp, contribute to the overall resistance of colorectal cancer. C1 NEW ENGLAND DEACONESS HOSP,DEPT SURG,CANC BIOL LAB,50 BINNEY ST,BOSTON,MA 02215. AMER CYANAMID CO,LEDERLE LABS,ONCOL RES SECT,PEARL RIVER,NY 10965. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. FU NCI NIH HHS [CA42944, CA50473, CA44704] NR 41 TC 40 Z9 40 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1993 VL 67 IS 5 BP 959 EP 968 DI 10.1038/bjc.1993.177 PG 10 WC Oncology SC Oncology GA LA813 UT WOS:A1993LA81300014 PM 8098614 ER PT J AU RUSSELL, RGG KRANE, SM AF RUSSELL, RGG KRANE, SM TI GLUCOCORTICOIDS AND BONE - PROCEEDINGS OF A SYMPOSIUM HELD IN VIENNA, AUSTRIA, 12 MARCH 1991 SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID RHEUMATOID-ARTHRITIS; MINERAL METABOLISM; IMMUNOSUPPRESSIVE POTENCY; INDUCED OSTEOPOROSIS; DEFLAZACORT; PREDNISONE; PATHOGENESIS; THERAPY; MASS; RAT C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRIT UNIT,BOSTON,MA 02114. RP RUSSELL, RGG (reprint author), MED SCH SHEFFIELD,DEPT HUMAN METAB & CLIN BIOCHEM,BEECH HILL RD,SHEFFIELD S10 2RX,ENGLAND. NR 55 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PD MAY PY 1993 VL 32 SU 2 BP 1 EP 2 PG 2 WC Rheumatology SC Rheumatology GA LD797 UT WOS:A1993LD79700001 ER PT J AU KRANE, SM AF KRANE, SM TI SOME MOLECULAR MECHANISMS OF GLUCOCORTICOID ACTION SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT SYMP ON GLUCOCORTICOIDS AND BONE, AT THE 14TH EUROPEAN SYMP ON CALCIFIED TISSUES CY MAR 12, 1991 CL VIENNA, AUSTRIA SP MARION MERRELL DOW DE GENE; TRANSCRIPTION; TRANSACTIVATION; TRANSREPRESSION; AP-1; PROCOLLAGENASE ID C-JUN; RECEPTOR; COLLAGENASE; GENE RP KRANE, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 9 TC 20 Z9 20 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PD MAY PY 1993 VL 32 SU 2 BP 3 EP 5 PG 3 WC Rheumatology SC Rheumatology GA LD797 UT WOS:A1993LD79700002 PM 8495278 ER PT J AU AVIOLI, LV RUSSELL, RGG KRANE, SM OLGAARD, K GENNARI, C REEVE, J BENSO TANNER AF AVIOLI, LV RUSSELL, RGG KRANE, SM OLGAARD, K GENNARI, C REEVE, J BENSO TANNER TI GLUCOCORTICOIDS AND BONE - PROCEEDINGS OF A SYMPOSIUM HELD IN VIENNA, AUSTRIA, 12 MARCH 1991 - DISCUSSION SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Discussion CT SYMP ON GLUCOCORTICOIDS AND BONE, AT THE 14TH EUROPEAN SYMP ON CALCIFIED TISSUES CY MAR 12, 1991 CL VIENNA, AUSTRIA SP MARION MERRELL DOW C1 IST GIANNINI GASLINI,IST PUERICULTURA & MED NEONATELE,I-16147 GENOVA QUARTO,ITALY. UNIV SIENA,INST MED PATHOL,I-53100 SIENA,ITALY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ARTHRIT UNIT,BOSTON,MA 02114. RIGSHOSP,DIV NEPHROL,MED DEPT P2132,DK-2100 COPENHAGEN,DENMARK. NORTHWICK PK HOSP & CLIN RES CTR,HARROW HA1 3UJ,MIDDX,ENGLAND. MRC,CLIN RES CTR,HARROW HA1 3UJ,MIDDX,ENGLAND. MED SCH SHEFFIELD,DEPT HUMAN METAB & CLIN BIOCHEM,SHEFFIELD S10 2RX,ENGLAND. RP AVIOLI, LV (reprint author), JEWISH HOSP ST LOUIS,DIV ENDOCRINOL,216 S KINGSHIGHWAY BLVD,ST LOUIS,MO 63110, USA. RI Reeve, Jonathan/C-7551-2012 OI Reeve, Jonathan/0000-0002-4364-2682 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PD MAY PY 1993 VL 32 SU 2 BP 45 EP 46 PG 2 WC Rheumatology SC Rheumatology GA LD797 UT WOS:A1993LD79700010 ER PT J AU SILVA, JA LEONG, GB WINE, DB AF SILVA, JA LEONG, GB WINE, DB TI MISIDENTIFICATION DELUSIONS, FACIAL MISRECOGNITION, AND RIGHT BRAIN INJURY SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Note ID CAPGRAS SYNDROME; INTERMETAMORPHOSIS; PROSOPAGNOSIA AB Individuals suffering from misidentification syndromes may present with right hemispheric pathology and deficits in facial recognition. In addition, misidentification delusions have been associated with aggressive behaviour. The possible linkage between misidentification phenomena,facial recognition, and aggression is discussed, illustrated by the case of a patient suffering from an organic delusional disorder. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 23 TC 19 Z9 19 U1 0 U2 1 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 1993 VL 38 IS 4 BP 239 EP 241 PG 3 WC Psychiatry SC Psychiatry GA LF032 UT WOS:A1993LF03200001 PM 8518973 ER PT J AU SPIRO, IJ WANG, CC MONTGOMERY, WW AF SPIRO, IJ WANG, CC MONTGOMERY, WW TI CARCINOMA OF THE PAROTID-GLAND - ANALYSIS OF TREATMENT RESULTS AND PATTERNS OF FAILURE AFTER COMBINED SURGERY AND RADIATION-THERAPY SO CANCER LA English DT Article DE PAROTID; RADIATION ONCOLOGY; SURGERY; MAJOR SALIVARY GLAND ID MALIGNANT EPITHELIAL TUMORS; SALIVARY-GLANDS; IRRADIATION; RADIOTHERAPY AB Background. The authors retrospectively studied 62 patients with malignant parotid tumors, treated by combined surgery and radiation therapy between 1975 and 1989. No patients were lost to follow-up, and all living patients were interviewed. The median follow-up time was 66 months. Results. Among the 62 patients, there were five isolated local failures. Distant failure was observed in 11 patients. Neck failure was uncommon except in patients with advanced neck disease on presentation. The actuarial 5-year and 10-year local control rates were 95% and 84%, respectively. The corresponding actuarial disease-free survival (DFS) rates were 77% and 65%, respectively. Patients with larger tumors, recurrent disease, or involvement of the facial nerve tended to have lower DFS rates. No statistically significant differences were observed for patients treated with once-daily versus twice-daily radiation therapy fractionation schemes. Conclusions. Treatment was well tolerated, and severe treatment sequelae were uncommon. In summary, surgery in combination with radiation therapy is highly efficacious in controlling malignant tumors of the parotid gland. C1 MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 14 TC 43 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1993 VL 71 IS 9 BP 2699 EP 2705 DI 10.1002/1097-0142(19930501)71:9<2699::AID-CNCR2820710902>3.0.CO;2-T PG 7 WC Oncology SC Oncology GA KY918 UT WOS:A1993KY91800001 PM 8467451 ER PT J AU HEMLER, M MIHICH, E AF HEMLER, M MIHICH, E TI 4TH ANNUAL PEZCOLLER SYMPOSIUM - ADHESION MOLECULES - CELLULAR RECOGNITION MECHANISMS SO CANCER RESEARCH LA English DT Editorial Material C1 ROSWELL PK CANC INST,BUFFALO,NY 14263. RP HEMLER, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 0 TC 1 Z9 1 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 MAY 1 PY 1993 VL 53 IS 9 BP 2192 EP 2194 PG 3 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100041 PM 8481924 ER PT J AU SCHUNKERT, H TANG, SS LITWIN, SE DIAMANT, D RIEGGER, G DZAU, VJ INGELFINGER, JR AF SCHUNKERT, H TANG, SS LITWIN, SE DIAMANT, D RIEGGER, G DZAU, VJ INGELFINGER, JR TI REGULATION OF INTRARENAL AND CIRCULATING RENIN-ANGIOTENSIN SYSTEMS IN SEVERE HEART-FAILURE IN THE RAT SO CARDIOVASCULAR RESEARCH LA English DT Article DE RENIN; ANGIOTENSINOGEN; ANGIOTENSIN-II; GENE EXPRESSION; KIDNEY; HEART FAILURE; RAT ID CONVERTING-ENZYME-INHIBITION; MESSENGER-RNA EXPRESSION; MYOCARDIAL-INFARCTION; ALDOSTERONE SYSTEM; SODIUM-EXCRETION; RENAL-FUNCTION; MECHANISMS; CAPTOPRIL; SURVIVAL; RELEASE AB Objective: Activation of the intrarenal renin-angiotensin system may contribute to the pathophysiology of heart failure by accelerating the generation of angiotensin II at local sites within the kidneys. Activation of the local intrarenal renin-angiotensin system occurs in rats and with mild heart failure. The aim of the present study was to examine components of the circulating as well as the intrarenal renin-angiotensin system in rats with severe heart failure. Methods: Six weeks after experimental myocardial infarction (heart failure, HF; n=8) or sham operation (control, C; n=6), haemodynamics and the circulating and intrarenal components of the renin-angiotensin system were studied. Results: HF rats were characterised by large infarctions (scar tissue >40% of the left ventricular circumference). In comparison to sham operated controls, large myocardial infarctions resulted in severe heart failure with decreased systolic [108(SEM 3) mm Hg v 132(3) in C; p<0.001] and diastolic arterial blood pressure [83(3) mm Hg v 95(2) in C; p<0.05], decreased left ventricular systolic pressure [109(3) mm Hg v 132(3) in C; p<0.0051 and increased left ventricular end diastolic pressure [27(2) mm Hg v 5(1) in C; p<0.0001]. In rats with severe heart failure, the circulating renin-angiotensin system was activated, with an increase in plasma renin activity (3.5-fold, p<0.05) and plasma angiotensin II concentration (threefold, p<0.01). In parallel, the intrarenal renin-angiotensin system was activated in severe heart failure. Increases occurred in renal renin mRNA level (1.7-fold, p<0.01), renal angiotensinogen mRNA level (1.8-fold, p<0.05), and renal angiotensin II concentration (twofold, p<0.05) compared to C. Intrarenal angiotensin II concentrations exceeded plasma levels by a factor of 50 and were positively correlated with renal angiotensinogen mRNA levels (r=0.874, p<0.001), suggesting that local synthesis is the major source of angiotensin II found in the kidney. Conclusions: The intrarenal renin-angiotensin system may be selectively activated in mild heart failure, while both circulating and intrarenal renin-angiotensin systems are induced as the extent of left ventricular function worsens. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV PEDIAT NEPHROL,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV CARDIOVASC,BOSTON,MA 02215. STANFORD UNIV,MED CTR,SCH MED,CARDIOVASC RES CTR,STANFORD,CA 94305. STANFORD UNIV,MED CTR,SCH MED,DIV CARDIOVASC MED,STANFORD,CA 94305. RP SCHUNKERT, H (reprint author), UNIV REGENSBURG,DEPT INTERNAL MED 2,FRANZ JOSEPH STRAUSS STR,W-8400 REGENSBURG,GERMANY. FU NHLBI NIH HHS [HL 19259, HL 35792, HL 35810] NR 38 TC 47 Z9 47 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY PY 1993 VL 27 IS 5 BP 731 EP 735 DI 10.1093/cvr/27.5.731 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LD417 UT WOS:A1993LD41700006 PM 8348571 ER PT J AU GUDAS, JM FRIDOVICHKEIL, JL PARDEE, AB AF GUDAS, JM FRIDOVICHKEIL, JL PARDEE, AB TI POSTTRANSCRIPTIONAL CONTROL OF THYMIDINE KINASE MESSENGER-RNA ACCUMULATION IN CELLS RELEASED FROM G0-G1 PHASE BLOCKS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HETEROGENEOUS NUCLEAR-RNA; SERUM-STIMULATED CELLS; C-FOS GENE; S-PHASE; GROWTH-FACTOR; DNA-SYNTHESIS; 3T3 CELLS; TRANSCRIPTIONAL REGULATION; DIHYDROFOLATE-REDUCTASE; MOUSE FIBROBLASTS AB In this study, we have utilized thymidine kinase (TK) mRNA induction as a model for investigating regulatory events at the G1-S boundary of the cell cycle. Using three independent methods for synchronizing diploid, nontumorigenic CHEF/18 cells, we found that the mechanism(s) underlying TK mRNA accumulation varied with the method of cell synchrony used. When cells were arrested by serum deprivation, both transcriptional and posttranscriptional controls contributed to the observed accumulation of TK mRNA at the G1-S boundary. When synchronized by isoleucine deprivation, mature TK mRNA and TK pre-mRNAs increased significantly at the G1-S boundary of the cell cycle with no detectable change in the rate of TK gene transcription. Following lovastatin treatment, which appears to arrest cells at a point very early in G1, posttranscriptional mechanisms were solely responsible for the subsequent accumulation of TK mRNA observed upon mevalonate repletion. We confirmed that transcriptional mechanisms were involved in TK mRNA regulation only when cells progressed from G0 into S phase using reporter genes transcribed from the heterologous human TK promoter. Taken together, these results indicate that posttranscriptional mechanism(s) are primarily responsible for regulating the abundance of TK mRNA during the cell cycle in CHEF/18 cells and further suggest uncoupling of transcriptional and posttranscriptional controls following different physiological conditions of cell cycle arrest. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. FU NCI NIH HHS [CA08317-03, T32CA09361]; NIGMS NIH HHS [GM 24571] NR 70 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1993 VL 4 IS 5 BP 421 EP 430 PG 10 WC Cell Biology SC Cell Biology GA LA841 UT WOS:A1993LA84100009 PM 8518235 ER PT J AU WANG, LT WILKINS, EW BODE, HH AF WANG, LT WILKINS, EW BODE, HH TI BRONCHIAL CARCINOID-TUMORS IN PEDIATRIC-PATIENTS SO CHEST LA English DT Article ID CHILDHOOD AB Bronchial carcinoid tumors (BCT) are the most frequent primary pulmonary neoplasms of childhood. Seventeen of 208 patients diagnosed as having BCT at the Massachusetts General Hospital were between 10 and 21 years of age. We reviewed our records of the 17 patients and 8 other pediatric cases and compared their findings with those of seven large series of adults. Distribution was equal between the sexes. The average age at diagnosis was 17 years; 4 patients were less-than-or-equal-to 15 years old. The duration of symptoms prior to diagnosis varied from 2 weeks to 2.6 years, with a median duration of 8.5 months. In contrast to adults, no child was asymptomatic. The majority of children presented with wheezing and atelectasis in addition to the characteristic adult triad of cough, hemoptysis, and pneumonitis. Five patients presented with weight loss and one patient presented with hoarseness. One of the 17 pediatric patients presented with Cushing's syndrome and a functional BCT. Twelve of 14 patients were disease free for 9 months to 34 years after surgical resection. We conclude that BCT should be suspected in children with pneumonitis resistant to therapy, atelectasis, wheezing, and hemoptysis. Surgical resection will result in symptom-free recovery in the majority of cases in spite of low-grade malignancy. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP WANG, LT (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS & SURG SERV,ELLISON 1,BOSTON,MA 02114, USA. NR 17 TC 43 Z9 45 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 MAY PY 1993 VL 103 IS 5 BP 1426 EP 1428 DI 10.1378/chest.103.5.1426 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA LB235 UT WOS:A1993LB23500025 PM 8387419 ER PT J AU SALZMAN, A WOLLERT, PS WANG, HL MENCONI, MJ YOUSSEF, ME COMPTON, CC FINK, MP AF SALZMAN, A WOLLERT, PS WANG, HL MENCONI, MJ YOUSSEF, ME COMPTON, CC FINK, MP TI INTRALUMINAL OXYGENATION AMELIORATES ISCHEMIA REPERFUSION-INDUCED GUT MUCOSAL HYPERPERMEABILITY IN PIGS SO CIRCULATORY SHOCK LA English DT Article DE ATP; FLUORESCEIN; PERFUSION; OXYGEN; MUCOSA; PERMEABILITY ID SMALL-INTESTINAL ISCHEMIA; LOW-FLOW; INJURY; LESIONS; SHOCK; MODEL AB We tested the hypothesis that intraluminal oxygenation can prevent increased gut mucosal permeability to a hydrophilic solute caused by mesenteric ischemia/reperfusion (I/R). Studies were performed using pentobarbital-anesthetized immature pigs. Paired 20 cm segments of ileum were perfused intraluminally at 200 ml/hr with either nitrogenated or oxygenated 37-degrees-C Ringer's lactate. Beginning at T = -90 min, fluorescein disodium acetate was infused intravenously (12.5 mg/kg bolus, then 12.5 mg/kg/hr). Permeability was assessed by calculating the plasma-to-lumen clearance of fluorescein. Five pigs were subjected to complete mesenteric ischemia (T = 0-120 min) followed by reperfusion (T = 120-270 min). In nitrogenated segments, I/R resulted in a 1015 +/- 195% increase in fluorescein clearance (P < 0.01 vs baseline). In contrast, the increase in fluorescein clearance induced by I/R in oxygenated segments was only 264 t 63% (P < 0.01 vs baseline). Intraluminal oxygenation afforded significant (P < .01) protection against I/R-induced mucosal hyperpermeability at all time points from T = 150-270 min. Histologic sections revealed complete villous epithelial denudation in nitrogenated segments, whereas the mucosal epithelium was largely intact in oxygenated segments. After reperfusion, mucosal ATP levels normalized in oxygenated segments, but there was only partial recovery of ATP levels in nitrogenated segments. These data indicate that intraluminal oxygenation ameliorates mucosal hyperpermeability induced by I/R. C1 UNIV MASSACHUSETTS,MED CTR,DEPT SURG,WORCESTER,MA 01605. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NIGMS NIH HHS [5T32GM07035, 2 RO1 GM37631-07] NR 35 TC 19 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0092-6213 J9 CIRC SHOCK JI Circ. Shock PD MAY PY 1993 VL 40 IS 1 BP 37 EP 46 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LB560 UT WOS:A1993LB56000006 PM 8324888 ER PT J AU CRIJNS, MB BERGMAN, W BERGER, MJ HERMANS, J SOBER, AJ AF CRIJNS, MB BERGMAN, W BERGER, MJ HERMANS, J SOBER, AJ TI ON NEVI AND MELANOMAS IN DYSPLASTIC NEVUS SYNDROME PATIENTS SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; NEVUS SYNDROME; PIGMENTED MOLES; NEVOCYTIC NEVI; SUN EXPOSURE; RISK; POPULATION; FREQUENCY; FAMILIES; NUMBER AB Cutaneous melanoma may occur as isolated, so-called 'sporadic' cases or in association with multiple atyical naevi and in familial clusters, in which case it is referred to as the familial dysplastic naevus syndrome (DNS). In this retrospective study (a) the number and body distribution of naevocytic naevi and (b) the body distribution of malignant melanoma (MM) in individuals with familial DNS were compared in order to study their association. In 45 patients with familial DNS aged 20-39 years naevus counts on trunk and lower extremities were compared with melanoma data and distributions from a second group of 43 patients from the same DNS families aged 12-66 years. Men had significantly more naevi of a size greater-than-or-equal-to 2 mm or greater-than-or-equal-to 5 mm on the back than women (P=0.02). Women showed a tendency towards a greater number of naevi on the lower extremities than men, but in women no significant difference in naevi between the lower extremities and the back was found. The total number of naevi on the trunk and lower extremities in familial DNS patients was higher than that in the general population. In conclusion, it was found that predilection sites for melanoma in familial DNS patients of both sexes correspond with the distribution of naevi; in males naevi and melanoma counts and percentage distributions were higher on the back, in females both the back and the lower extremities were affected. These findings strongly suggest an association between naevus distribution and melanoma occurrence and site in familial DNS, analogous to earlier reports on sporadic melanoma.1,2 C1 UNIV HOSP LEIDEN,DEPT DERMATOL,POSTBOX 9600,2300 RC LEIDEN,NETHERLANDS. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. UNIV ROTTERDAM,CTR CLIN DECIS MAKING,ROTTERDAM,NETHERLANDS. LEIDEN UNIV,DEPT MED STAT,2300 RA LEIDEN,NETHERLANDS. NR 21 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD MAY PY 1993 VL 18 IS 3 BP 248 EP 252 DI 10.1111/j.1365-2230.1993.tb02179.x PG 5 WC Dermatology SC Dermatology GA LD748 UT WOS:A1993LD74800009 PM 8348718 ER PT J AU HASNAIN, Q MACDONALD, G HAUPERT, GT AF HASNAIN, Q MACDONALD, G HAUPERT, GT TI METABOLISM OF URIDINE IN EXPANDED EXTRACELLULAR VOLUME STATES SO CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY LA English DT Note DE HEMODIALYSIS; NA+; K+-ATPASE INHIBITOR; ONE-KIDNEY; ONE-CLIP; 2-KIDNEY; ONE-CLIP; ULTRAFILTRATION; URIDINE NUCLEOTIDES ID HYPERTENSION; NUCLEOTIDES; TRANSPORT; INHIBITOR; RECEPTOR; DISTINCT; ARTERY AB 1. Uridine and uridine monophosphate (UMP) are natriuretic and a vasopressor in intact rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats metabolic clearance rate (MCR) of uridine is raised and basal plasma uridine diminished, suggesting that metabolism of uridine is linked to changes in extracellular space. 2. Plasma uridine concentration was raised in 38 patients with chronic renal failure compared with age- and sex-matched healthy controls (8.49 mumol/L, 4.37-13.74 mumol/L median, interquartile range, and 2.64 mumol/L 2.51-2.74 mumol/L, respectively, P<0.001). Plasma uridine was significantly diminished after isotonic fluid removal by ultrafiltration (UF) from 7.25 mumol/L (3.7-11.08) to 5.07 mumol/L (3.3-8.3), P<0.001, whereas concentration of marker solutes urea and creatinine remained unchanged. During haemodialysis (HD), plasma uridine fell significantly from its pre-HD level. 3. In an animal model of expanded extracellular space the one-kidney, one-clip rat, plasma uridine was significantly higher (20.56 +/- 1.19 mumol/L, P<0.01) and MCR diminished (34.93 +/- 3.44 mL/kg per min, P<0.01) compared with sham-operated animals (plasma uridine 12.14 +/- 1.07 and MCR 53.59 +/- 4.11 mL/kg per min). Uridine or UMP did not inhibit Na+, K+-ATPase in either of the two assay systems. 4. It was concluded that catabolism of uridine is reduced by extracellular expansion and probably increased by volume reduction by UF. Such a function may be due to the presence of a hypertensive natriuretic factor postulated by Dahl and de Wardener (1980), but would not be consistent with the ouabain-like factor postulated by other workers in this situation because it has no inhibitory effect on Na+, K+-ATPase. C1 UNIV NEW S WALES,SCH MED,SYDNEY,NSW,AUSTRALIA. PRINCE HENRY HOSP,DEPT NEPHROL,SYDNEY,NSW,AUSTRALIA. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. NR 14 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0305-1870 J9 CLIN EXP PHARMACOL P JI Clin. Exp. Pharmacol. Physiol. PD MAY PY 1993 VL 20 IS 5 BP 313 EP 316 DI 10.1111/j.1440-1681.1993.tb01692.x PG 4 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA LB246 UT WOS:A1993LB24600011 PM 8391945 ER PT J AU MORIMOTO, C SCHLOSSMAN, SF AF MORIMOTO, C SCHLOSSMAN, SF TI HUMAN NAIVE AND MEMORY T-CELLS REVISITED - NEW MARKERS (CD31 AND CD27) THAT HELP DEFINE CD4+ T-CELL SUBSETS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE HUMAN NAIVE T-CELLS; HUMAN MEMORY T-CELLS; CD45RA; CD45RO; CD29 VLA; CD4 T-CELL SUBSETS; CD31; CD27 ID LEUKOCYTE-COMMON ANTIGEN; LUPUS-ERYTHEMATOSUS PATIENTS; MIXED LYMPHOCYTE-REACTION; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; ADHESION MOLECULES; ACTIVATION ANTIGEN; INDUCER CELLS; 2H4 MOLECULE; PROLIFERATION AB The human CD4 population can be divided into functionally distinct and largely reciprocal subsets based on their differential expression of CD45 isoforms (CD45RA, CD45RO) and the CD29/VLA beta chain. CD4+CD45RO+ CD29high ''memory '' (helper inducer) cells respond maximally to recall antigens and provide help for B cell IgG synthesis. In contrast, the CD4+CD45RA+CD29low ''naive '' (suppressor inducer) population responds poorly to recall Ag, lacks helper function for B cells, but can both induce CD8 cells to suppress B cell IgG synthesis and proliferate preferentially in an autologous mixed lymphocyte response (AMLR). The phenotypic ''conversion '' after activation and the preferential responsiveness of CD45RA-CD45RO+ CD29high cells to recall antigen led to the view that CD45RA + cells are ''naive '' and immature and convert to CD45RA-CD45RO+ ''memory '' cells after activation. This conversion was believed by many to be unidirectional and irreversible. It has become increasingly clear that the naive-memory concept outlined above is far from settled and that naive CD4+CD45RA+ T cells retain their unique functional program after activation and are distinct from the freshly isolated CD4+CD45RO+ subset. Moreover, CD45 RA is not irreversibly lost following activation, but in fact recycles on the cell surface. Given the problems with CD45 isoform expression as a definition of maturational state, we have investigated the possibility that more reliable cell surface molecules are needed which could delineate between the functions of activated CD45RA+ and CD45RA- CD45RO+ cells. We could show that CD31 and CD27 are preferentially expressed on the CD4+CD45RA+ subset of cells and their expressions are stably maintained on these cells. These findings suggest that the CD4 population remains phenotypically and functionally heterogeneous following activation and further implies the existence of a commitment to distinct functional lineages. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. FU NIAID NIH HHS [AI12069, AI29530]; NIAMS NIH HHS [AR33713] NR 57 TC 28 Z9 28 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAY-JUN PY 1993 VL 11 IS 3 BP 241 EP 247 PG 7 WC Rheumatology SC Rheumatology GA LJ435 UT WOS:A1993LJ43500001 PM 8394793 ER PT J AU JELLINEK, MS TODRES, ID CATLIN, EA CASSEM, EH SALZMAN, A AF JELLINEK, MS TODRES, ID CATLIN, EA CASSEM, EH SALZMAN, A TI PEDIATRIC INTENSIVE-CARE TRAINING - CONFRONTING THE DARK SIDE SO CRITICAL CARE MEDICINE LA English DT Article DE TRAINING PROGRAMS; ANGER; FRUSTRATION; MENTORSHIP; INTENSIVE CARE UNIT; PEDIATRIC; PHYSICIAN-PATIENT RELATIONS; MEDICAL EDUCATION; RESIDENCY TRAINING; FAMILY RELATIONSHIP; CRITICAL CARE; MENTAL HEALTH, PHYSICIAN AB Purpose: To describe the dark side of pediatric intensive care fellowship training and offer educational approaches for understanding feelings of fallibility, anger, frustration, and loss. Data Sources: Listening and observing fellows in the courses of their pediatric intensive care training and later careers. Study Selection: Studies that discussed pediatric residency and fellowship training, especially in the context of intensive care. Data Extraction: From group meetings, unit conferences, rounds, individual discussions, and child psychiatric consultations. Results of Data Synthesis. Pediatric intensive care unit (ICU) fellows gain a sense of mastery from the nature of their work: complex, technological, and frequently lifesaving. They face the usual personal stresses of extended training, including long work hours, limited financial resources, and relative isolation from family and friends. Pediatric ICU fellows confront deeper, ''dark'' feelings regarding their own high expectations, fallibility, anger, sense of loss, frustration, limited control, and the need to work closely with tense, grieving families. If the dark side is not acknowledged, fellows, team members, and faculty are likely to experience anger, detachment, and depression that may extend beyond work into their personal lives. Conclusions. Since the dark side is expected, normal, and inevitable, fellowship training programs should help fellows cope with and understand these feelings. Such understanding requires a sense of trust among intensive care staff and can be gained through group discussions, mentorship, specific team conferences, and child psychiatric consultation. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NEONATAL & PEDIAT INTENS CARE,BOSTON,MA 02114. NR 9 TC 29 Z9 29 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1993 VL 21 IS 5 BP 775 EP 779 DI 10.1097/00003246-199305000-00023 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA LA847 UT WOS:A1993LA84700023 PM 8482100 ER PT J AU KAPLAN, JM AF KAPLAN, JM TI NEURODEGENERATION - GREAT MINDS THINK ALIKE SO CURRENT BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; SODIUM-CHANNEL; NEURONS; PROTEIN C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GENET,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 12 TC 0 Z9 7 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY PY 1993 VL 3 IS 5 BP 285 EP 287 DI 10.1016/0960-9822(93)90180-V PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LL957 UT WOS:A1993LL95700007 PM 15335750 ER PT J AU ROSEN, FS AF ROSEN, FS TI X-LINKED IMMUNODEFICIENCY - B-CELL DISEASES SO CURRENT BIOLOGY LA English DT Article ID T-CELLS; CD40; AGAMMAGLOBULINEMIA; EXPRESSION; PROTEIN; DEFECT; LIGAND; FORM C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 17 TC 2 Z9 2 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY PY 1993 VL 3 IS 5 BP 312 EP 314 DI 10.1016/0960-9822(93)90189-U PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LL957 UT WOS:A1993LL95700016 PM 15335759 ER PT J AU MYERS, MG WHITE, MF AF MYERS, MG WHITE, MF TI THE NEW ELEMENTS OF INSULIN SIGNALING - INSULIN-RECEPTOR SUBSTRATE-1 AND PROTEINS WITH SH2 DOMAINS SO DIABETES LA English DT Article ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; PHOSPHOLIPASE-C-GAMMA; STIMULATES TYROSINE PHOSPHORYLATION; DEPENDENT DIABETES-MELLITUS; MATURATION-PROMOTING FACTOR; PDGF BETA-RECEPTOR; JUXTAMEMBRANE REGION; BINDING SITE; CELL-CYCLE; SUBUNIT AB Since the discovery of insulin and its receptor, the downstream elements responsible for the pleiotropic insulin signal have been difficult to define. The recently discovered insulin receptor substrate, IRS-1, provides an innovative and simple way to think about this problem: IRS-1 may mediate the control of various cellular processes by insulin. Overexpression of IRS-1 enhances insulin-stimulated DNA synthesis in Chinese hamster ovary cells, and microinjection of IRS-1 protein potentiates the maturation of Xenopus oocytes. We suspect that insulin signals are enabled when the activated insulin receptor kinase phosphorylates specific tyrosine residues in IRS-1. These phosphorylated sites associate with high affinity to cellular proteins that contain SH2 (src homology-2) domains. This association is specific and depends on the amino acid sequence surrounding the phosphotyrosine residue and the isoform of the SH2 domain. A growing number of SH2 domain-containing proteins have been identified, and we suspect that IRS-1 has the potential to simultaneously regulate many of them. We have only begun to identify the specific proteins that associate with phosphorylated IRS-1. One of them, the phosphatidylinositol 3'-kinase, is activated when the SH2 domains in its 85,000-M(r) regulatory subunit bind to phosphorylated IRS-1. IRS-1 also interacts with other proteins such as SHPTP2, a novel SH2 domain-containing Tyr phosphatase, and GRB-2/sem-5, a protein that is implicated in p21ras signaling. The interaction between phosphorylated IRS-1 and multiple SH2 domain-containing proteins may ultimately explain the pleiotropic effects of insulin. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CELL & DEV BIOL PROGRAM,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-43808, DK-38712] NR 84 TC 229 Z9 231 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1993 VL 42 IS 5 BP 643 EP 650 DI 10.2337/diabetes.42.5.643 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ308 UT WOS:A1993KZ30800002 PM 8387037 ER PT J AU BONORA, E BONADONNA, RC DELPRATO, S GULLI, G SOLINI, A MATSUDA, M DEFRONZO, RA AF BONORA, E BONADONNA, RC DELPRATO, S GULLI, G SOLINI, A MATSUDA, M DEFRONZO, RA TI INVIVO GLUCOSE-METABOLISM IN OBESE AND TYPE-II DIABETIC SUBJECTS WITH OR WITHOUT HYPERTENSION SO DIABETES LA English DT Article ID INSULIN RESISTANCE; ANTIHYPERTENSIVE DRUGS; LIPOPROTEIN METABOLISM; LIPID-METABOLISM; BODY-COMPOSITION; BLOOD-PRESSURE; DOUBLE-BLIND; MELLITUS; HYPERINSULINEMIA; MUSCLE AB This study examined whether the presence of hypertension, an insulin-resistant condition, exacerbates the defect in insulin action observed in obesity and type II diabetes mellitus. Glucose metabolism in the basal state and in response to insulin was quantitated by using the euglycemic insulin (20 mU . min-1 . m-2) clamp in combination with 3-[H-3]glucose infusion and indirect calorimetry in 20 obese nondiabetic subjects (10 hypertensive and 10 normotensive), 26 type II diabetic subjects (13 hypertensive and 13 normotensive), and 11 normal nondiabetic subjects. The two groups of obese subjects and the two groups of diabetic subjects were matched for sex, age, race, body mass index, and fat distribution. Both in the basal state and during insulin infusion, glucose disposal rates (total, oxidative, and nonoxidative) were similar in obese subjects with or without hypertension. Compared with control subjects, both groups of obese subjects were markedly insulin resistant. Similarly, type II diabetic individuals, whether normotensive or hypertensive, were equally insulin resistant. The severity of insulin resistance was nearly identical in obese and diabetic groups. In diabetic subjects, the inhibitory effect of insulin on hepatic glucose output, lipolysis, and lipid oxidation was blunted compared with normal subjects. In obese subjects the ability of insulin to inhibit lipolysis and lipid oxidation was impaired. However, hypertension did not alter the suppressive effects of insulin on hepatic glucose production, plasma free fatty acid levels, or lipid oxidation in either obese or type II diabetic subjects. These results indicate that hypertension does not confer a greater severity of insulin resistance than that already is present in obesity and type II diabetes mellitus. C1 UNIV TEXAS,HLTH SCI CTR,DEPT INTERNAL MED,DIV DIABET,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RI Del Prato, Stefano/K-3405-2016; Solini, Anna/K-4666-2016; OI Del Prato, Stefano/0000-0002-5388-0270; Solini, Anna/0000-0002-7855-8253; BONORA, Enzo/0000-0003-1074-5164; Matsuda, Masafumi/0000-0001-8543-1616 FU NCRR NIH HHS [M01-RR-01346]; NIDDK NIH HHS [DK-24092] NR 53 TC 40 Z9 40 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 MAY PY 1993 VL 42 IS 5 BP 764 EP 772 DI 10.2337/diabetes.42.5.764 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ308 UT WOS:A1993KZ30800018 PM 8482434 ER PT J AU PUGLIESE, A MOROMISATO, R GIANANI, R AWDEH, Z ALPER, C JACKSON, R ERLICH, H EISENBARTH, GS AF PUGLIESE, A MOROMISATO, R GIANANI, R AWDEH, Z ALPER, C JACKSON, R ERLICH, H EISENBARTH, GS TI 2 SUBTYPES OF DQA1 SEQUENCES (EF VS GL) CORRELATE WITH DIFFERENT LEVELS OF INSULIN AUTOANTIBODIES IN 1ST DEGREE RELATIVES SO DIABETES LA English DT Meeting Abstract C1 BARBARA DAVIS CTR,DENVER,CO. CTR BLOOD RES,BOSTON,MA. JOSLIN DIABET CTR,BOSTON,MA. ROCHE MOLEC SYST,ALAMEDA,CA. 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 1993 VL 42 SU 1 BP A63 EP A63 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ626 UT WOS:A1993KZ62600198 ER PT J AU BERRY, J VANGORP, WG HERZBERG, DS HINKIN, C BOONE, K STEINMAN, L WILKINS, JN AF BERRY, J VANGORP, WG HERZBERG, DS HINKIN, C BOONE, K STEINMAN, L WILKINS, JN TI NEUROPSYCHOLOGICAL DEFICITS IN ABSTINENT COCAINE ABUSERS - PRELIMINARY FINDINGS AFTER 2 WEEKS OF ABSTINENCE SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE NEUROPSYCHOLOGY; COCAINE ABUSE; COGNITION ID ADDICTION AB Sixteen subjects hospitalized for treatment of cocaine dependence were administered a battery of neuropsychological tests within 72 h of last cocaine use and again approximately 2 weeks later. Twenty-one non-cocaine using control subjects, matched for age, gender, ethnicity and education, also received neuropsychological testing. Abstinence from mood altering substances during the 2-week study period was verified for both groups on three occasions using quantitative urine analysis. The results suggest that recent cocaine use is associated with impairment in memory, visuospatial abilities, and concentration during the acute phase of withdrawal, independent of withdrawal-related depression. Furthermore, many of these deficits appear to persist at least 2 weeks beyond cessation of cocaine use. C1 W LOS ANGELES VA MED CTR,DIV BRENTWOOD,ALCOHOL & DRUG TREATMENT PROGRAM,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073. NR 20 TC 107 Z9 108 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAY PY 1993 VL 32 IS 3 BP 231 EP 237 DI 10.1016/0376-8716(93)90087-7 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA LK717 UT WOS:A1993LK71700004 PM 8394237 ER PT J AU SKOLNIK, EY LEE, CH BATZER, A VICENTINI, LM ZHOU, M DALY, R MYERS, MJ BACKER, JM ULLRICH, A WHITE, MF SCHLESSINGER, J AF SKOLNIK, EY LEE, CH BATZER, A VICENTINI, LM ZHOU, M DALY, R MYERS, MJ BACKER, JM ULLRICH, A WHITE, MF SCHLESSINGER, J TI THE SH2 SH3 DOMAIN-CONTAINING PROTEIN GRB2 INTERACTS WITH TYROSINE-PHOSPHORYLATED IRS1 AND SHC - IMPLICATIONS FOR INSULIN CONTROL OF RAS SIGNALING SO EMBO JOURNAL LA English DT Article DE GRB2; RAS SIGNALING; SH2; SH3; TYROSINE PHOSPHORYLATION ID KINASE-ACTIVITY; VIRAL ONCOGENE; PC12 CELLS; RECEPTOR; GROWTH; TRANSDUCTION; DIFFERENTIATION; TRANSFORMATION; REQUIREMENT; PI3-KINASE AB GRB2, a small protein comprising one SH2 domain and two SH3 domains, represents the human homologue of the Caenorhabditis elegans protein, sem-5. Both GRB2 and sem-5 have been implicated in a highly conserved mechanism that regulates p21ras signalling by receptor tyrosine kinases. In this report we show that in response to insulin, GRB2 forms a stable complex with two tyrosine-phosphorylated proteins. One protein is the major insulin receptor substrate IRS-1 and the second is the SH2 domain-containing oncogenic protein, Shc. The interactions between GRB2 and these two proteins require ligand activation of the insulin receptor and are mediated by the binding of the SH2 domain of GRB2 to phosphotyrosines on both IRS-1 and Shc. Although GRB2 associates with IRS-1 and Shc, it is not tyrosine-phosphorylated after insulin stimulation, implying that GRB2 is not a substrate for the insulin receptor. Furthermore, we have identified a short sequence motif (YV/IN) present in IRS-1, EGFR and Shc, which specifically binds the SH2 domain of GRB2 with high affinity. Interestingly, both GRB2 and phosphatidylinositol-3 (PI-3) kinase can simultaneously bind distinct tyrosine phosphorylated regions on the same IRS-1 molecule, suggesting a mechanism whereby IRS-1 could provide the core for a large signalling complex. We propose a model whereby insulin stimulation leads to formation of multiple protein-protein interactions between GRB2 and the two targets IRS-1 and Shc. These interactions may play a crucial role in activation of p21ras and the control of downstream effector molecules. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY. RP SKOLNIK, EY (reprint author), NYU MED CTR,DEPT PHARMACOL,550 1ST AVE,NEW YORK,NY 10016, USA. RI Daly, Roger/C-8179-2009; Lee, Chi-Hon/G-9190-2012 FU NIDDK NIH HHS [DK01927, DK438080] NR 42 TC 656 Z9 660 U1 0 U2 10 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY PY 1993 VL 12 IS 5 BP 1929 EP 1936 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LC948 UT WOS:A1993LC94800022 PM 8491186 ER PT J AU PEEPER, DS PARKER, LL EWEN, ME TOEBES, M HALL, FL XU, M ZANTEMA, A VANDEREB, AJ PIWNICAWORMS, H AF PEEPER, DS PARKER, LL EWEN, ME TOEBES, M HALL, FL XU, M ZANTEMA, A VANDEREB, AJ PIWNICAWORMS, H TI A-TYPE AND B-TYPE CYCLINS DIFFERENTIALLY MODULATE SUBSTRATE-SPECIFICITY OF CYCLIN CDK COMPLEXES SO EMBO JOURNAL LA English DT Article DE CELL CYCLE; CYCLIN-DEPENDENT KINASES; P107; PHOSPHORYLATION; SUBSTRATE TARGETING ID RETINOBLASTOMA GENE-PRODUCT; CDC2 PROTEIN-KINASE; BACULOVIRUS EXPRESSION VECTORS; SEA-URCHIN EGGS; CELL-CYCLE; M-PHASE; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTOR; MOLECULAR-CLONING; P34CDC2 KINASE AB Both cyclins A and B associate with and thereby activate cyclin-dependent protein kinases (cdks). We have investigated which component in the cyclin-cdk complex determines its substrate specificity. The A- and B-type cyclin-cdk complexes phosphorylated histone H1 and their cyclin subunits in an indistinguishable manner, irrespective of the catalytic subunit, p33cdk2 or p34cdc2. In contrast, only the cyclin A-cdk complexes phosphorylated the Rb-related p107 protein in vitro. Likewise, binding studies revealed that cyclin A-cdk complexes bound stably to p107 in vitro, whereas cyclin B-cdk complexes did not detectably associate with p107, under identical assay conditions. Binding to p107 required both cyclin A and a cdk as neither subunit alone bound to p107. These results demonstrate that although the kinase subunit provides a necessary component for binding, it is the cyclin subunit that plays the critical role in targeting the complex to p107. Finally, we show that the cyclin A-p33cdk2 complex phosphorylated, p107 in vitro at most of its sites that are also phosphorylated in human cells, suggesting that the cyclin A-p33cdk2 complex is a major kinase for p107 in vivo. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. USC,CHILDRENS HOSP LOS ANGELES,SCH MED,ORTHOPAED SURG RES LAB,LOS ANGELES,CA 90054. USC,SCH PHARM,LOS ANGELES,CA 90054. RP PEEPER, DS (reprint author), LEIDEN UNIV,DEPT MOLEC CARCINOGENESIS,SYLVIUS LAB,WASSENAARSEWEG 72,2333 AL LEIDEN,NETHERLANDS. RI Piwnica-Worms, Helen/C-5214-2012 FU NCI NIH HHS [CA 08894-01A1]; NIGMS NIH HHS [GM47017] NR 59 TC 159 Z9 160 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY PY 1993 VL 12 IS 5 BP 1947 EP 1954 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LC948 UT WOS:A1993LC94800024 PM 8491188 ER PT J AU GARDELLA, TJ WILSON, AK KEUTMANN, HT OBERSTEIN, R POTTS, JT KRONENBERG, HM NUSSBAUM, SR AF GARDELLA, TJ WILSON, AK KEUTMANN, HT OBERSTEIN, R POTTS, JT KRONENBERG, HM NUSSBAUM, SR TI ANALYSIS OF PARATHYROID HORMONES PRINCIPAL RECEPTOR-BINDING REGION BY SITE-DIRECTED MUTAGENESIS AND ANALOG DESIGN SO ENDOCRINOLOGY LA English DT Article ID HUMORAL HYPERCALCEMIA; PROTEIN; PEPTIDE; MALIGNANCY; FRAGMENT; CELLS; ACTIVATION; EXPRESSION; SEQUENCES; MEMBRANE AB Previous deletion studies established that the 25-34 region of PTH is important for receptor binding. We used oligonucleotide-directed mutagenesis to generate 47 different mutations in this region of human (h) PTH-(1-84) and evaluated cAMP-stimulating activity in ROS 17/2.8 cells. The hydrophobic residues Leu24 and Leu28 stood out as mutationally intolerant sites, while neighboring polar residues were comparatively tolerant. A series of synthetic PTH analogs was designed to test these residues further. The affinity of [Tyr34]hPTH-(1-34)NH2 for ROS 17/2.8 cells [dissociation constant (K(d)), approximately 5 nm)] was dramatically reduced by the substitution of either Leu24 or Leu28 with Glu (K(d), approximately 20,000 and 8,000 nm, respectively). The Val31-->Glu substitution also sharply reduced affinity (K(d), approximately 200 nm). In contrast, the nearby charge-reversing change of Asp30-->Lys had no effect on binding affinity (K(d), approximately 5 nm). Similar effects were observed in the opossum kidney cell line. The binding of [Tyr34]hPTH-(15-34)NH2 to ROS 17/2.8 and opossum kidney cells (K(d), approximately 10 muM) was abolished by Glu substitutions at position 24, 28, or 31; the Lys30 change was without effect. These results suggest that the adverse effects of the Glu substitutions on receptor binding are not due purely to the disruption of tertiary interactions with the 1-14 region. Circular dichroism spectroscopy indicated that the substitutions do not affect local helical structure. The data suggest that Leu24, Leu28, and Val31 contribute important receptor-binding interactions and are consistent with the hypothesis that an amphipathic a-helix in the carboxy-terminal region of PTH-(1-34) is involved in receptor binding. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GARDELLA, TJ (reprint author), MASSACHUSETTS GEN HOSP,COUNSELING UNIT,BOSTON,MA 02114, USA. NR 40 TC 70 Z9 70 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1993 VL 132 IS 5 BP 2024 EP 2030 DI 10.1210/en.132.5.2024 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ699 UT WOS:A1993KZ69900020 PM 8386605 ER PT J AU BRINGHURST, FR JUPPNER, H GUO, J URENA, P POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV AF BRINGHURST, FR JUPPNER, H GUO, J URENA, P POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV TI CLONED, STABLY EXPRESSED PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTORS ACTIVATE MULTIPLE MESSENGER SIGNALS AND BIOLOGICAL RESPONSES IN LLC-PK1 KIDNEY-CELLS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; OSTEO-SARCOMA CELLS; CYCLIC-AMP; PHOSPHATE-TRANSPORT; ADENYLATE-CYCLASE; RAT OSTEOBLASTS; MEMBRANE; LINE; HYPERCALCEMIA; OSTEOSARCOMA AB PTH elicits multiple second messenger signals in target cells. This signaling diversity may reflect coupling of a single species of PTH receptors to multiple effectors, the action of different subtypes of PTH receptors, or both. We recently reported the expression cloning, from rat and opossum cells, of closely related cDNAs encoding receptors for PTH [and PTH-related peptide (PTHRP)]. To determine if these cloned PTH/PTHRP receptors can activate multiple intracellular effectors when present at near-physiological levels in intact target cells, we have stably expressed the rat and opossum PTH/PTHRP receptor cDNAs in LLC-PK, porcine renal epithelial cells. These cells lack endogenous PTH/PTHRP receptors, but do express abundant calcitonin receptors and many features of a proximal tubular phenotype. Subclones of transfected LLC-PK1 cells exhibited high affinity binding (K(d), 1-5 nm) of [Nle8,18,Tyr34]bovine PTH-(1-34)amide (PTH) and dose-dependent activation by PTH of both cAMP accumulation (EC50, 1 nm) and increased release of cytosolic free calcium from intracellular stores (EC50, greater-than-or-equal-to 20-50 nm) across a wide range of receptor expression. Expressed rat and opossum receptors exhibited similar properties, except for a 5-fold lower binding affinity of the rat receptor for PTH-(7-34). Stimulation by PTH of both cAMP accumulation and elevated cytosolic free calcium was augmented in cells expressing higher numbers of PTH/PTHRP receptors. Like calcitonin, PTH (1-100 nm) reduced the rate of cell proliferation and augmented the rate of inorganic phosphate transport after 24 and 5 h of preincubation, respectively. The growth effect was mimicked by cAMP analogs, forskolin, phorbol esters, and calcium ionophores. Regulation of phosphate transport, however, was mimicked by phorbols, but not by cAMP analogs or forskolin. We conclude that LLC-PK1 cells provide a useful model in which to study the function of cloned PTH/PTHRP receptors. In these cells, a single species of cloned PTH/PTHRP receptors, stably expressed at near-physiological numbers, activates multiple second messenger responses and regulates subsequent biological responses, including at least one (phosphate transport) that is mediated by mechanisms independent of cAMP. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. RP BRINGHURST, FR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114, USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIADDK NIH HHS [AM-11794] NR 43 TC 199 Z9 201 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1993 VL 132 IS 5 BP 2090 EP 2098 DI 10.1210/en.132.5.2090 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ699 UT WOS:A1993KZ69900028 PM 8386606 ER PT J AU SCHIPANI, E KARGA, H KARAPLIS, AC POTTS, JT KRONENBERG, HM SEGRE, GV ABOUSAMRA, AB JUPPNER, H AF SCHIPANI, E KARGA, H KARAPLIS, AC POTTS, JT KRONENBERG, HM SEGRE, GV ABOUSAMRA, AB JUPPNER, H TI IDENTICAL COMPLEMENTARY DEOXYRIBONUCLEIC ACIDS ENCODE A HUMAN RENAL AND BONE PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR SO ENDOCRINOLOGY LA English DT Article ID OSTEO-SARCOMA CELLS; HUMORAL HYPERCALCEMIA; ADENYLATE-CYCLASE; BINDING DOMAINS; INTRONLESS GENE; PROTEIN; RAT; EXPRESSION; MALIGNANCY; FRAGMENT AB Identical complementary DNAs (cDNAs) that encode a 593-amino acid human PTH (PTH)/PTH-related peptide (PTHrP) receptor were isolated by hybridization techniques from two cDNA libraries which had been constructed from human kidney and human osteoblast-like osteosarcoma cells (SaOS-2). Northern blot analysis of total RNA from human bone- and kidney-derived tissue revealed one single major messenger RNA species of about 2.5 kilobases in both tissues. The human PTH/PTHrP receptor has 91 % and 81 % identity, respectively, with the previously cloned rat and opossum receptors, indicating a high degree of conservation among mammals. Despite this striking degree of amino-acid conservation, the human PTH/PTHrP receptor has several unique biological properties when transiently expressed in COS-7 cells. The apparent dissociation constants for [Nle8,18,Tyr34] bovine PTH(I-34) amide [bPTH(1-34)] are similar for the human and the rat receptor (approximately 8 vs. approximately 15 nm) whereas [Tyr36]PTHrP(1-36) amide has a slightly lower affinity for the human (15-40 nm) than for the rat receptor (approximately 15 nm). Both ligands stimulate efficiently and with similar efficacy the accumulation of intracellular cAMP. The affinities for the antagonists [Nle8,18,Tyr34] bPTH(3-34) amide [bPTH(3-34)] and in particular for [Nle8,18,Tyr34] bPTH(7-34) amide [bPTH(7-34)] are considerably higher for the human receptor, e.g. approximately 8 nm us. 30 nm for bPTH(3-34) and approximately 100 nm vs. 5000 nm for bPTH(7-34), respectively. Similar biological findings were previously attributed to differences in species- and/or organ-specific PTH/PTHrP receptors. The expression of the recombinant, highly homologous rat and human receptors in a uniform environment indicate that the moderate differences in the primary receptor structure have profound consequences for the receptor binding affinity of amino-terminally truncated PTH analogs. Furthermore, the molecular cloning of identical cDNAs encoding a human PTH/PTHrP receptor from the two major target organs for PTH, bone and kidney, provides strong evidence for one single PTH/PTHrP receptor in both organs, although additional and/or alternatively spliced receptors cannot be excluded. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. RP SCHIPANI, E (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114, USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-11794] NR 48 TC 196 Z9 199 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1993 VL 132 IS 5 BP 2157 EP 2165 DI 10.1210/en.132.5.2157 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ699 UT WOS:A1993KZ69900037 PM 8386612 ER PT J AU GUINAN, EC GILLO, AP AF GUINAN, EC GILLO, AP TI CYTOKINE THERAPY OF FANCONI-ANEMIA (FA) SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,NEW YORK,NY 10021. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1993 VL 21 IS 5 BP 714 EP 715 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW610 UT WOS:A1993MW61000038 ER PT J AU CHUNG, RT SCHAPIRO, RH WARSHAW, AL AF CHUNG, RT SCHAPIRO, RH WARSHAW, AL TI INTRALUMINAL PANCREATIC CANDIDIASIS PRESENTING AS RECURRENT PANCREATITIS SO GASTROENTEROLOGY LA English DT Article ID ABSCESS C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP CHUNG, RT (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 7,BOSTON,MA 02114, USA. NR 9 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1993 VL 104 IS 5 BP 1532 EP 1534 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KZ487 UT WOS:A1993KZ48700038 PM 8482466 ER PT J AU STEEL, DM SELLAR, GC UHLAR, CM SIMON, S DEBEER, FC WHITEHEAD, AS AF STEEL, DM SELLAR, GC UHLAR, CM SIMON, S DEBEER, FC WHITEHEAD, AS TI A CONSTITUTIVELY EXPRESSED SERUM AMYLOID-A PROTEIN GENE (SAA4) IS CLOSELY LINKED TO, AND SHARES STRUCTURAL SIMILARITIES WITH, AN ACUTE-PHASE SERUM AMYLOID-A PROTEIN GENE (SAA2) SO GENOMICS LA English DT Article ID MESSENGER-RNAS; NUCLEAR FACTOR; DNA; INTERLEUKIN-6; FAMILY; SEQUENCE; CELLS; MODULATION; VARIANTS; MOUSE C1 UNIV DUBLIN TRINITY COLL,DEPT GENET,LINCOLN PL GATE,DUBLIN 2,IRELAND. CTR BLOOD RES,BOSTON,MA. VET ADM MED CTR,LEXINGTON,KY. UNIV KENTUCKY,MED CTR,DEPT MED,LEXINGTON,KY 40506. FU Wellcome Trust NR 35 TC 38 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1993 VL 16 IS 2 BP 447 EP 454 DI 10.1006/geno.1993.1209 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LB928 UT WOS:A1993LB92800021 PM 7686132 ER PT J AU LEV, AA ROSEN, DR KOS, C CLIFFORD, E LANDES, G HAUSER, SL BROWN, RH AF LEV, AA ROSEN, DR KOS, C CLIFFORD, E LANDES, G HAUSER, SL BROWN, RH TI HUMAN CILIARY NEUROTROPHIC FACTOR - LOCALIZATION TO THE PROXIMAL REGION OF THE LONG ARM OF CHROMOSOME-11 AND ASSOCIATION WITH CA/GT DINUCLEOTIDE REPEAT SO GENOMICS LA English DT Note ID INSITU HYBRIDIZATION; SYMPATHETIC NEURONS; RECOMBINANT HUMAN; DIFFERENTIATION; CULTURE C1 MASSACHUSETTS GEN HOSP,NEUROIMMUNOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. IG LABS INC,FRAMINGHAM,MA. FU NIAMS NIH HHS [R01-AR41025-01] NR 14 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1993 VL 16 IS 2 BP 539 EP 541 DI 10.1006/geno.1993.1226 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LB928 UT WOS:A1993LB92800038 PM 8314594 ER PT J AU KRISTAL, BS CONRAD, CC RICHARDSON, A YU, BP AF KRISTAL, BS CONRAD, CC RICHARDSON, A YU, BP TI IS POLY(A) TAIL LENGTH ALTERED BY AGING OR DIETARY RESTRICTION SO GERONTOLOGY LA English DT Article DE POLYADENYLATION; DIETARY RESTRICTION; POLY(A) TAIL LENGTH ID AGE-RELATED-CHANGES; MESSENGER-RNA; RIBONUCLEIC-ACID; GENE-EXPRESSION; RATS; TRANSCRIPTION; SEQUENCES; LONGEVITY; LEVEL AB We examined age- and diet-related alterations in RNA poly(A) tail length using high-resolution gel electrophoresis followed by Northern hybridization. The results demonstrate conclusively that there is no age-related decrease in the size of the Poly(A) tail of RNA isolated from the male Fischer 344 rat. In contrast, our results suggest that there is actually a slight age-related increase in the length of the poly(A) tail isolated from the liver and hypothalamus of these rats. Dietary restriction did not affect either poly(A) tail length or its age-related increase. These data demonstrate conclusively that oligo(dT) probes can be used to standardize RNA hybridization experiments between animals of different ages and dietary groups. In addition, these data provide further evidence that the ratio between RNA polymerase I and RNA polymerase II activity does not change with age. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR CLIN & EDUC,SAN ANTONIO,TX. FU NIA NIH HHS [AG01048, AG01188, NIA T32 AG00205] NR 25 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PD MAY-JUN PY 1993 VL 39 IS 3 BP 152 EP 162 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LU211 UT WOS:A1993LU21100005 PM 7691690 ER PT J AU ROSENBAUM, JF BIEDERMAN, J BOLDUCMURPHY, EA FARAONE, SV CHALOFF, J HIRSHFELD, DR KAGAN, J AF ROSENBAUM, JF BIEDERMAN, J BOLDUCMURPHY, EA FARAONE, SV CHALOFF, J HIRSHFELD, DR KAGAN, J TI BEHAVIORAL-INHIBITION IN CHILDHOOD - A RISK FACTOR FOR ANXIETY DISORDERS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID PANIC DISORDER; TEMPERAMENTAL CHARACTERISTICS; PSYCHIATRIC-DISORDERS; EXTREME TEMPERAMENT; MULTIPLE THRESHOLDS; SEPARATION ANXIETY; YOUNG-CHILDREN; SOCIAL PHOBIA; HEART-RATE; AGORAPHOBIA AB Childhood antecedents of anxiety disorders in adulthood remain poorly understood. We have, therefore, examined from longitudinal and familial perspectives the relationship between behavioral inhibition in children and anxiety disorders. We review a series of studies describing the association between behavioral inhibition and anxiety disorders in two independently ascertained and previously described samples of children. One sample was cross-sectional and clinically derived (Massachusetts General Hospital at-risk sample), and the other was epidemiologically derived and longitudinal (Kagan et al. longitudinal cohort). Our studies have found that (1) children of parents with panic disorder with agoraphobia, either alone or comorbid with major depressive disorder, are at increased risk for behavioral inhibition; (2) children identified as having behavioral inhibition have high rates of childhood-onset anxiety disorders themselves; (3) behavioral inhibition is associated with familial risk for anxiety disorders; (4) children with behavioral inhibition and anxiety disorders have greater familial loading of anxiety disorders; (5) children who remain inhibited over time are at highest risk for anxiety disorders in themselves and their families; and (6) these differences between inhibited children and not-inhibited controls become more robust at 3-year follow-up. Our research strongly indicates that behavioral inhibition is an identifiable early childhood predictor of later anxiety disorders. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BEHAV THERAPY UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BROCKTON W ROXBURY VET ADM MED CTR,PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02115. MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,BOSTON,MA 02115. BOSTON UNIV,DOCTOR PROGRAM CLIN PSYCHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PSYCHOL & SOCIAL RELAT,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 NR 66 TC 174 Z9 174 U1 1 U2 26 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 1993 VL 1 IS 1 BP 2 EP 16 DI 10.3109/10673229309017052 PG 15 WC Psychiatry SC Psychiatry GA MU379 UT WOS:A1993MU37900002 PM 9384823 ER PT J AU JENIKE, MA AF JENIKE, MA TI AUGMENTATION STRATEGIES FOR TREATMENT-RESISTANT OBSESSIVE-COMPULSIVE DISORDER SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID CLOMIPRAMINE-TREATED PATIENTS; FENFLURAMINE AUGMENTATION; BUSPIRONE AUGMENTATION; LITHIUM AUGMENTATION; FLUOXETINE; CARBONATE; CLONIDINE; EFFICACY AB This review discusses augmentation strategies for patients with obsessive-compulsive disorder who fail to respond to treatment. A patient's failure to respond to treatment may be due to any of a number of factors, such as noncompliance with a behavioral program, concurrent severe depression or personality disorder, certain ritualistic behaviors, inaccurate diagnosis, and inadequate treatment. It is particularly important that comorbid psychiatric disorders be diagnosed and treated. A review of the literature and my experience with the use of augmenting agents such as lithium, buspirone, clonidine, fenfluramine, antidepressants, anxiolytic agents, and neuroleptics in treatment-resistant obsessive-compulsive disorder are presented. Existing evidence suggests that some of these approaches are useful for some patients. However, many questions remain, and much research remains to be done on this topic. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 49 TC 9 Z9 10 U1 0 U2 1 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 1993 VL 1 IS 1 BP 17 EP 26 DI 10.3109/10673229309017053 PG 10 WC Psychiatry SC Psychiatry GA MU379 UT WOS:A1993MU37900003 PM 9384824 ER PT J AU SCHOUTEN, R AF SCHOUTEN, R TI PITFALLS OF CLINICAL-PRACTICE - THE TREATING CLINICIAN AS EXPERT WITNESS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article RP SCHOUTEN, R (reprint author), MASSACHUSETTS GEN HOSP,LAW & PSYCHIAT SERV,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 11 Z9 11 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1993 VL 1 IS 1 BP 64 EP 65 DI 10.3109/10673229309017058 PG 2 WC Psychiatry SC Psychiatry GA MU379 UT WOS:A1993MU37900008 PM 9384829 ER PT J AU HYMAN, SE AF HYMAN, SE TI NEW INSIGHTS INTO HOW ANTIPSYCHOTIC-DRUGS MIGHT WORK SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article C1 MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 3 TC 3 Z9 3 U1 0 U2 1 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 1993 VL 1 IS 1 BP 68 EP 69 DI 10.3109/10673229309017060 PG 2 WC Psychiatry SC Psychiatry GA MU379 UT WOS:A1993MU37900010 PM 9384831 ER PT J AU ZAPPIA, JJ CARROLL, WR WOLF, GT THORNTON, AF HO, L KRAUSE, CJ AF ZAPPIA, JJ CARROLL, WR WOLF, GT THORNTON, AF HO, L KRAUSE, CJ TI OLFACTORY NEUROBLASTOMA - THE RESULTS OF MODERN TREATMENT APPROACHES AT THE UNIVERSITY-OF-MICHIGAN SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article ID ESTHESIONEUROBLASTOMA AB A retrospective study was undertaken to review patterns of treatment and survival for patients with olfactory neuroblastomas at the University of Michigan since the introduction of craniofacial resection in the late 1970s. Recent results were compared to previous reports. Disease-free and overall survival for patients with Kadish stage B tumors were unchanged from prior years. Improvement in both disease-free intervals and overall survival was evident for patients with stage C tumors. Interestingly, in two patients with ''unresectable'' local disease, complete responses to induction chemotherapy followed by radiotherapy were noted. C1 MICHIGAN EAR INST,FARMINGTON HILLS,MI. UNIV MICHIGAN,DEPT OTOLARYNGOL HEAD & NECK SURG,ANN ARBOR,MI 48109. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. ST JOSEPH MERCY HOSP,DEPT SURG,ANN ARBOR,MI 48104. NR 15 TC 40 Z9 41 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAY-JUN PY 1993 VL 15 IS 3 BP 190 EP 196 DI 10.1002/hed.2880150303 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA KY607 UT WOS:A1993KY60700002 PM 8491582 ER PT J AU CHIONG, CM BURGESS, BJ NADOL, JB AF CHIONG, CM BURGESS, BJ NADOL, JB TI POSTNATAL MATURATION OF HUMAN SPIRAL GANGLION-CELLS - LIGHT AND ELECTRON-MICROSCOPIC OBSERVATIONS SO HEARING RESEARCH LA English DT Article DE SPIRAL GANGLION; MORPHOMETRY; NEONATE; HUMAN ID ADULT CATS; INNERVATION; AFFERENT; COCHLEAE; NEURONS; FIBERS; COUNTS; RAT AB The presence of two types of ganglion cells, based on cell size and other morphologic parameters, is well established in the adult mammalian and human spiral ganglion. On the other hand, there is little data concerning cell morphology in the neonatal spiral ganglion. The present study was undertaken to evaluate the differences in the morphometry and distribution of cell types in the spiral ganglion of the human neonate as compared to the adult. A total of five human temporal bones from two neonates and three infants were included in this study. Light microscopic analysis of all specimens was performed, and electron microscopic evaluation of a 14 day old neonatal spiral ganglion was accomplished. The segmental density of spiral ganglion cells was higher in the neonate than in the adult. The prevalence of type II spiral ganglion cells was higher in the neonate than has been reported in the adult, particularly in the middle and apical turns where type II cells constituted 24% and 26% of all ganglion cells, respectively. The prevalence of type II ganglion cells decreased with age, particularly in the middle and apical turns. In the neonate, the maximal cross sectional area of type I neurons increased from the base to the apex and seemed to increase with age especially in the basal turn. The present study strongly supports a clear differentiation of type I and type Il ganglion cells in the human neonate and that the prevalence of type II cells is greater in the neonate than the adult. This finding is discussed with reference to postnatal development of the spiral ganglion. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114. SUNNYBROOK HLTH SCI CTR,DEPT OTOLARYNGOL,TORONTO,ON,CANADA. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01 DC00152] NR 40 TC 13 Z9 14 U1 0 U2 0 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 1993 VL 67 IS 1-2 BP 211 EP 219 DI 10.1016/0378-5955(93)90249-Z PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA LH027 UT WOS:A1993LH02700024 PM 8340274 ER PT J AU SCULLY, RE AF SCULLY, RE TI BENIGN TO MALIGNANT TRANSFORMATION IN EPITHELIAL OVARIAN-TUMORS - REPLY SO HUMAN PATHOLOGY LA English DT Letter RP SCULLY, RE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1993 VL 24 IS 5 BP 562 EP 563 DI 10.1016/0046-8177(93)90173-E PG 2 WC Pathology SC Pathology GA LB934 UT WOS:A1993LB93400019 ER PT J AU USUKU, K JOSHI, N HATEM, CJ ALPER, CA SCHOENFELD, DA HAUSER, SL AF USUKU, K JOSHI, N HATEM, CJ ALPER, CA SCHOENFELD, DA HAUSER, SL TI THE HUMAN T-CELL RECEPTOR BETA-CHAIN REPERTOIRE - LONGITUDINAL FLUCTUATIONS AND ASSESSMENT IN MHC MATCHED POPULATIONS SO IMMUNOGENETICS LA English DT Article ID VARIABLE REGION; EXPRESSION; SELECTION; COMPLEX; SUPERANTIGENS; CD4+ AB The influence of the environment and of the major histocompatibility complex (MHC) in shaping the human T-cell receptor beta-chain variable region (TCRBV) repertoire has not been systematically studied. Here, expression of TCRBV gene families was estimated by a sensitive polymerase chain reaction (PCR)-based method. Serial studies of peripheral blood, performed at 2-week intervals over a 3-month period, revealed that fluctuation in the expression of many TCRBV genes occurred in healthy individuals and in the absence of clinically evident infections. Fluctuation of TCRBV4, TCRBV5.2, TCRBV9, and TCRBV13.1 genes were present in all subjects. Additional TCRBV genes fluctuated in some but not in other individuals. Comparison of the TCRBV repertoire between these unrelated individuals indicated differences in the mean expression of TCRBV5.1, TCRBV9, TCRBV11, TCRBV1.5, TCRBV17, and TCRBV20 genes. For any TCRBV gene, intersubject differences were generally of a magnitude of twofold or less. Larger differences characterized the TCRBV repertoire of CD4 compared to CD8 cells. Some differences, for example over-representation of TCRBV2 and TCRBV5.1 on CD4, and TCRBV10, TCRBV14, and TCRBV16 on CD8 cells, were present in most subjects. Individuals homozygous for DR2- or DR3-bearing extended MHC haplotypes displayed similar individual variability of TCRBV expression. These data indicate that the circulating TCRBV repertoire in humans is both dynamic and diverse. Both environment and MHC effects contribute to the diversity of TCRBV expression. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT MED,BOSTON,MA 02114. CTR BLOOD RES,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-29583]; NICHD NIH HHS [HD 17461]; NIDDK NIH HHS [DK 26844] NR 26 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY PY 1993 VL 38 IS 3 BP 193 EP 198 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA LD695 UT WOS:A1993LD69500003 PM 8099343 ER PT J AU ISRAEL, EJ SIMISTER, N FREIBERG, E CAPLAN, A WALKER, WA AF ISRAEL, EJ SIMISTER, N FREIBERG, E CAPLAN, A WALKER, WA TI IMMUNOGLOBULIN-G BINDING-SITES ON THE HUMAN FETAL INTESTINE - A POSSIBLE MECHANISM FOR THE PASSIVE TRANSFER OF IMMUNITY FROM MOTHER TO INFANT SO IMMUNOLOGY LA English DT Article ID RAT SMALL-INTESTINE; NEONATAL RAT; BRUSH-BORDERS; HUMAN FETUS; RECEPTOR; IGG; TRANSPORT; SYSTEMS AB In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for IgG on the placenta. However, amniotic fluid contains IgG of maternal origin, and transfer of swallowed IgG into the circulation from the foetal intestine represents another potential pathway of passive immunization. In this study we assayed for a foetal intestinal IgG receptor to support the hypothesis of this alternate pathway of antibody transfer. Microvillous membrane (MVM) from small bowel of aborted foetuses (18 weeks gestation) were probed with [I-125]IgG to detect specific IgG binding sites. Binding was pH dependent and was maximal at pH 6. Competitive inhibition of the binding of [I-125]IgG was noted with the addition of increasing amounts of unlabelled IgG. Scatchard analysis showed one binding site with a dissociation constant of 1.58 x 10(-7), similar to that of the IgG receptor described on the suckling rat intestine. The binding of labelled IgG to the human MVM receptor was Fc mediated. These observations provide evidence for an Fc receptor on the human foetal intestine. C1 ROSENSTIEL CTR BASIC MED SCI,DEPT BIOL,WALTHAM,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP ISRAEL, EJ (reprint author), MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD00438, HD12437]; NIDDK NIH HHS [DK33506] NR 25 TC 47 Z9 47 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAY PY 1993 VL 79 IS 1 BP 77 EP 81 PG 5 WC Immunology SC Immunology GA KZ918 UT WOS:A1993KZ91800011 PM 8509144 ER PT J AU CEPEDA, MS LIPKOWSKI, AW LANGLADE, A OSGOOD, PF EHRLICH, HP HARGREAVES, K SZYFELBEIN, SK CARR, DB AF CEPEDA, MS LIPKOWSKI, AW LANGLADE, A OSGOOD, PF EHRLICH, HP HARGREAVES, K SZYFELBEIN, SK CARR, DB TI LOCAL INCREASES OF SUBCUTANEOUS BETA-ENDORPHIN IMMUNOACTIVITY AT THE SITE OF THERMAL-INJURY SO IMMUNOPHARMACOLOGY LA English DT Article DE OPIOID; ENDORPHIN; TRAUMA; BURN; STRESS RESPONSE ID OPIOID RECEPTORS; BURN INJURY; IMMUNE; INFLAMMATION; STRESS; PEPTIDES; MORPHINE; RELEASE; CORTICOTROPIN; INVOLVEMENT AB To examine interactions between exogenous opioid analgesia and endogenous opioid generation at a site of burn-induced tissue injury, we measured beta-endorphin (BE) and corticosterone (C) in aliquots of plasma and wound fluid withdrawn from subcutaneous wire mesh chambers beneath the site of a 3-5% surface area burn. After brief inhalational anesthesia at the time of thermal injury, rats received morphine (4 mg/kg, single dose), fentanyl (0.02 mg/kg hourly for 4 h), or no opioid. Systemic hormone responses and behavioral changes were minimal as expected for the minimal percentage burn. In all three groups intrachamber BE and C rose above baseline at 1, 2 and 4 h postburn, then returned to baseline at 24 h. Systemic opioid treatment produced analgesia (by tail flick latency testing) but did not reduce intrachamber hormone responses. Thus local BE and C responses at the site of thermal injury are regulated differently from systemic pituitary-adrenal responses. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA, ANALGES PEPTIDE RES UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, ANALGES PEPTIDE RES UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT SURG, BOSTON, MA 02114 USA. HOP LARIBOISIERE, DEPT ANESTHESIE REANIMAT, CTR TRAITEMENT DOULEUR, F-75475 PARIS 10, FRANCE. UNIV MINNESOTA, DIV ENDODONT, MINNEAPOLIS, MN 55455 USA. RI Hargreaves, Kenneth/F-5308-2010 NR 35 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD MAY-JUN PY 1993 VL 25 IS 3 BP 205 EP 213 DI 10.1016/0162-3109(93)90049-V PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA LL076 UT WOS:A1993LL07600002 PM 8102620 ER PT J AU DUNCAN, MJ NAKAO, S SKOBE, Z XIE, H AF DUNCAN, MJ NAKAO, S SKOBE, Z XIE, H TI INTERACTIONS OF PORPHYROMONAS-GINGIVALIS WITH EPITHELIAL-CELLS SO INFECTION AND IMMUNITY LA English DT Article ID BACTEROIDES-GINGIVALIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; YERSINIA-PSEUDOTUBERCULOSIS; ESCHERICHIA-COLI; ENTEROCOLITICA; ADHERENCE; INVASION AB The invasion of gingival epithelial cells by certain pathogenic periodontal bacteria may account for their presence within diseased gingival tissue. To dissect the initial steps of a potential invasion pathway for the periodontal pathogen Porphyromonas gingivalis, laboratory and clinical bacterial isolates were tested for their interactions with a human oral epithelial cell line (KB). Several P. gingivalis strains immobilized on filters could bind oral epithelial cells. Quantitative adherence assays supported these results. The invasion of epithelial cells by P. gingivalis 33277 was measured by assay and confirmed by transmission electron microscopy. These preliminary results demonstrate that certain P. gingivalis strains are capable of internalization by human oral epithelial cells in vitro. RP DUNCAN, MJ (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-02847] NR 17 TC 145 Z9 149 U1 0 U2 4 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 1993 VL 61 IS 5 BP 2260 EP 2265 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700097 PM 8386706 ER PT J AU NG, SF WAXMAN, DJ AF NG, SF WAXMAN, DJ TI ACTIVATION OF THIO-TEPA CYTOTOXICITY TOWARD HUMAN BREAST-CANCER CELLS BY HEPATIC CYTOCHROME-P450 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE THIO-TEPA; TEPA; CYTOCHROME-P450; GLUTATHIONE; LIVER METABOLISM ID HIGH-DOSE THIOTEPA; PHASE-I; PLASMA PHARMACOKINETICS; N,N',N''-TRIETHYLENETHIOPHOSPHORAMIDE; CYCLOPHOSPHAMIDE; N,N',N''-TRIETHYLENEPHOSPHORAMIDE; MONOOXYGENASE; CHEMOTHERAPY; COMBINATION; MODULATION AB The anti-tumor alkylating agent thio-TEPA is metabolized by hepatic cytochrome P450 to yield an oxo derivative. TEPA, plus one or more reactive metabolites. The contribution of this metabolism to the parent drug's cytotoxicity was evaluated in cell culture using the human breast carcinoma cell line MCF-7 as a model. Incubation of thio-TEPA in the presence of NADPH + an Aroclor 1254-induced rat liver 9000. x - supernatant fraction (S9 fraction) resulted in a dramatic increase in drug cytotoxicity, as measured using a clonogenic assay for cell survival. This increase in cytotoxicity was not evident when thio-TEPA was incubated with an uninduced rat liver homogenate, indicating that one or more Aroclor-inducible liver enzymes contribute to drug activation in this system. Metyrapone, a selective inhibitor of the Aroclor-inducible cytochrome P450 2B1, completely blocked liver S9-dependent cytotoxicity, as did an inhibitory antibody directed against P450 2B1, demonstrating that P450 2B1 is the S9 catalyst of thio-TEPA activation. Although TEPA is the major thio-TEPA metabolite formed by P450 2B 1, neither TEPA nor a TEPA metabolite is the cytotoxic species generated by the liver S9 fraction, as evidenced by the moderate cytotoxicity of TEPA in this cellular system, by the failure of S9 to activate TEPA appreciably, and by the lack of synergism between TEPA and thio-TEPA. While glutathione had little or no effect on the cytotoxicity of thio-TEPA or TEPA, low levels of extracellular glutathione (0.25-0.5 mM) fully blocked S9-dependent thio-TEPA activation, suggesting a cell surface site of action of the S9-generated cytotoxic metabolites. These metabolites may also act intracellulary, since depletion of intracellular glutathione by treatment with buthionine sulfoximine enhanced the cytotoxicity of thio-TEPA to a V79 cell transformant that stably expresses P450 2B1, but not to the parental V79 line or to MCF-7 cells. These studies establish a role for cytochrome P450 2B1 in the activation of thio-TEPA to cytotoxic metabolites that are distinct from TEPA, and furthermore suggest a mechanism of action that includes the cell surface as a novel target of this cancer chemotherapeutic agent. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ROOM JF-525,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 31 TC 7 Z9 7 U1 0 U2 1 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 MAY PY 1993 VL 2 IS 5 BP 731 EP 738 PG 8 WC Oncology SC Oncology GA KY165 UT WOS:A1993KY16500003 PM 21573617 ER PT J AU CASTRESANA, JS RUBIO, MP KUNIMI, K BARRIOS, C KREICBERGS, A AF CASTRESANA, JS RUBIO, MP KUNIMI, K BARRIOS, C KREICBERGS, A TI LACK OF MUTATION AT CODON 12 OF THE C-H-RAS ONCOGENE IN 51 HUMAN SARCOMAS ASSESSED BY PCR-RFLP SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE SARCOMA; POINT MUTATION; C-H-RAS ID POINT MUTATIONS; GASTRIC-CANCER; ACTIVATION; GENES; TUMORIGENESIS; CARCINOMAS; FREQUENCY; DNAS AB Mutations of the ras genes in codons 12, 13 or 61 make them oncogenic. There are several methods to determine the point mutations in the ras family. In an attempt to do so in a sensitive and time saving manner we have checked a total of 51 sarcomas (14 bone tumors and 37 soft tissue tumors) for mutations in codon 12 of the c-H-ras oncogene. First we amplified a 100 bp fragment covering this codon and then performed RFLP analysis after digestion with restriction endonuclease Msp I. We did not find mutations in any of the tumors. Our results, may reinforce previous data on the fact that ras genes do not play an important role in tumorigenesis of sarcomas. C1 KAROLINSKA HOSP & INST,DEPT TUMOR PATHOL,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP & INST,LUDWIG INST CANC RES,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP & INST,DEPT ORTHOPED,S-10401 STOCKHOLM,SWEDEN. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RI Rubio, Mari-Paz/K-4364-2014; OI Rubio, Mari-Paz/0000-0003-3963-5903; Castresana, Javier S./0000-0002-2373-482X NR 23 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 MAY PY 1993 VL 2 IS 5 BP 823 EP 825 PG 3 WC Oncology SC Oncology GA KY165 UT WOS:A1993KY16500019 PM 21573633 ER PT J AU KOLODNY, NH KOHLER, SJ RETTIG, ES BOTTI, PA DAMICO, DJ GRAGOUDAS, ES AF KOLODNY, NH KOHLER, SJ RETTIG, ES BOTTI, PA DAMICO, DJ GRAGOUDAS, ES TI A FEASIBILITY STUDY OF NA-23 MAGNETIC-RESONANCE-IMAGING OF HUMAN AND RABBIT VITREAL DISORDERS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE MRI; SODIUM; VITREOUS; HEMORRHAGE; MELANOMA ID BODY AB Purpose. To assess the clinical feasibility of sodium magnetic resonance imaging for the visualization and characterization of intraocular tissues. Methods. Na-23 magnetic resonance images were obtained of enucleated human eyes and of rabbit eyes in vivo. The magnetic resonance imaging technique used in this study provided slices of <2 mm thickness and in-plane resolution of <2 X 2 mm. From each of these slices local values of spin-spin relaxation time (T2*) were calculated from pixel intensities in each of the eight echoes. Results. The images clearly display normal anatomic details of the lens and vitreous humor, and important pathologic details such as intravitreal and subretinal hemorrhages, ocular melanoma, and retinal detachments. Intraocular tissue identifications based on relative spin-spin relaxation time values and pixel intensities correlate with those made by standard diagnostic techniques. Conclusions. Na-23 magnetic resonance imaging may be used for the visualization and characterization of intraocular tissues. Differentiation among vitreous humor, lens, aqueous humor, subretinal fluid, or hemorrhage and tumor may be based on image intensity and/or spin-spin relaxation times. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,MUS EDUC SERV,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,NMR LAB,BOSTON,MA 02115. MIT,MAGNET RESONANCE IMAGING FACIL,CAMBRIDGE,MA 02139. WELLESLEY COLL,DEPT CHEM,WELLESLEY,MA 02181. FU NCRR NIH HHS [RR00995]; NEI NIH HHS [1 R15 EY08548-01] NR 5 TC 5 Z9 5 U1 0 U2 0 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 1993 VL 34 IS 6 BP 1917 EP 1922 PG 6 WC Ophthalmology SC Ophthalmology GA LB755 UT WOS:A1993LB75500004 PM 8491544 ER PT J AU WEBSTER, EW AF WEBSTER, EW TI HORMESIS AND RADIATION PROTECTION SO INVESTIGATIVE RADIOLOGY LA English DT Article ID ADAPTIVE RESPONSE; HUMAN-LYMPHOCYTES; IRRADIATION; MORTALITY; CANCER; TUBERCULOSIS; MICE RP WEBSTER, EW (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD MAY PY 1993 VL 28 IS 5 BP 451 EP 453 DI 10.1097/00004424-199305000-00016 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LA271 UT WOS:A1993LA27100012 PM 8496041 ER PT J AU KELLER, MB LAVORI, PW GOLDENBERG, IM BAKER, LA POLLACK, MH SACHS, GS ROSENBAUM, JF DELTITO, JA LEON, A SHEAR, K KLERMAN, GL AF KELLER, MB LAVORI, PW GOLDENBERG, IM BAKER, LA POLLACK, MH SACHS, GS ROSENBAUM, JF DELTITO, JA LEON, A SHEAR, K KLERMAN, GL TI INFLUENCE OF DEPRESSION ON THE TREATMENT OF PANIC DISORDER WITH IMIPRAMINE, ALPRAZOLAM AND PLACEBO SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE DEPRESSION; PANIC DISORDER; IMIPRAMINE; ALPRAZOLAM; PLACEBO ID MAJOR DEPRESSION; AGORAPHOBIA; ANXIETY; AMITRIPTYLINE; ANTIDEPRESSANT; DESIPRAMINE; OUTPATIENTS; COMORBIDITY; EFFICACY AB This paper presents findings from a multisite study of 126 subjects meeting DSM-III-R criteria for Panic Disorder who also met criteria for a concurrent Major Depressive Episode, Dysthymia, or Depressive Disorder NOS. The study's primary aim was to discern the influence of varying degrees of depression on the comparative efficacy of alprazolam, imipramine and placebo on anxiety outcomes. A placebo-controlled, double-blind, parallel random assignment design was utilized over a total of 16 weeks. There was no medication effect on panic outcomes. At endpoint, percent of anticipatory anxiety (i.e., time spent worrying about having an anxiety attack) was significantly lower in the patients taking active medications vs. placebo. Phobic measures were significantly improved by alprazolam, vs. both imipramine and placebo early in the study; however, by week 8 both active medications were equally superior to placebo in the reduction of phobic symptoms. In addition, both active medications were significantly more effective than placebo in reducing depression. The same efficacy pattern (i.e., active medications superior to placebo) was observed on measures of general functioning. Importantly, there were no significant interactions observed between medication and presence of major depression on the depression measures, indicating that both alprazolam and imipramine were equally efficacious in treating the depression in patients with panic disorder and major depression. Since the patients enrolled in this study suffered from major depressive disorder in the mild to moderate severity range, these results may not be transferrable to patients with panic disorder and severe major depression. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NEW ENGLAND BIOMED RES FDN,BROOKLINE,MA. CORNELL UNIV,NEW YORK HOSP WESTCHESTER DIV,COLL MED,ITHACA,NY 14853. CORNELL UNIV,MED CTR,COLL MED,DEPT PSYCHIAT,NEW YORK,NY 10021. RP KELLER, MB (reprint author), BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02906, USA. FU NIMH NIH HHS [R01 MH025478] NR 32 TC 42 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 1993 VL 28 IS 1 BP 27 EP 38 DI 10.1016/0165-0327(93)90074-T PG 12 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LD295 UT WOS:A1993LD29500004 PM 8326078 ER PT J AU CRAIG, WA AF CRAIG, WA TI POSTANTIBIOTIC EFFECTS IN EXPERIMENTAL-INFECTION MODELS - RELATIONSHIP TO INVITRO PHENOMENA AND TO TREATMENT OF INFECTIONS IN MAN SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT SYMP ON BACTERIAL INFECTION MODELS IN ANTIMICROBIAL CHEMOTHERAPY CY OCT 26-28, 1992 CL HELSINORE, DENMARK SP BRIT SOC ANTIMICROBIAL CHEMOTHERAPY, COMMISS EUROPEAN COMMUNITIES, EUROPEAN SOC CLIN MICROBIAL & INFECTIOUS DIS, DANISH SOC CLIN MICROBIOL, STATENS SERUMINISTUT, DANISH RESEARCH COUNCIL ID EXPERIMENTAL PSEUDOMONAS ENDOCARDITIS; STREPTOCOCCUS-PNEUMONIAE; EXPERIMENTAL MENINGITIS; AMIKACIN INVITRO; THIGH-INFECTION; INVIVO; EFFICACY; THERAPY; AMINOGLYCOSIDE; GENTAMICIN C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. RP CRAIG, WA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 36 TC 91 Z9 92 U1 0 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 1993 VL 31 SU D BP 149 EP 158 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA LF614 UT WOS:A1993LF61400014 PM 8335516 ER PT J AU GUDMUNDSSON, S EINARSSON, S ERLENDSDOTTIR, H MOFFAT, J BAYER, W CRAIG, WA AF GUDMUNDSSON, S EINARSSON, S ERLENDSDOTTIR, H MOFFAT, J BAYER, W CRAIG, WA TI THE POSTANTIBIOTIC EFFECT OF ANTIMICROBIAL COMBINATIONS IN A NEUTROPENIC MURINE THIGH INFECTION MODEL SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; ENTEROCOCCUS-FAECALIS; IMIPENEM; INVIVO; INVITRO; GENTAMICIN; RIFAMPIN C1 BORGARSPITALINN, DEPT MED, REYKJAVIK, ICELAND. UNIV WISCONSIN, DEPT MED, MADISON, WI 53706 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MED SERV, MADISON, WI 53705 USA. BORGARSPITALINN, CLIN MICROBIOL LAB, REYKJAVIK, ICELAND. UNIV ICELAND, SCH MED, REYKJAVIK, ICELAND. NR 31 TC 23 Z9 23 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 1993 VL 31 SU D BP 177 EP 191 PG 15 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA LF614 UT WOS:A1993LF61400017 PM 8335520 ER PT J AU VENEGAS, JG TSUZAKI, K FOX, BJ SIMON, BA HALES, CA AF VENEGAS, JG TSUZAKI, K FOX, BJ SIMON, BA HALES, CA TI REGIONAL COUPLING BETWEEN CHEST-WALL AND LUNG EXPANSION DURING HFV - A POSITRON IMAGING STUDY SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE REGIONAL IMPEDANCE MODEL; REGIONAL LUNG-CHEST WALL COUPLING ID HIGH-FREQUENCY VENTILATION; GAS-TRANSPORT; ALVEOLAR PRESSURE; PERIODIC-FLOW; DOGS; OSCILLATION; MOTION AB Apparently conflicting differences between the regional chest wall motion and gas transport have been observed during high-frequency ventilation (HFV). To elucidate the mechanism responsible for such differences, a positron imaging technique capable of assessing dynamic chest wall volumetric expansion, regional lung volume, and regional gas transport was developed. Anesthetized supine dogs were studied at ventilatory frequencies (f) ranging from 1 to 15 Hz and eucapnic tidal volumes. The regional distribution of mean lung volume was found to be independent of f, but the apex-to-base ratio of regional chest wall expansion favored the lung bases at low f and became more homogeneous at higher f. Regional gas transport per unit of lung volume, assessed from washout maneuvers, was homogeneous at 1 Hz, favored the bases progressively as f increased to 9 Hz, and returned to homogeneity at 15 Hz. Interregional asynchrony (pendelluft) and right-to-left differences were small at this large regional scale. Analysis of the data at a higher spatial resolution showed that the motion of the diaphragm relative to the excursions of the rib cage decreased as f increased. These differences from apex to base in regional chest wall expansion and gas transport were consistent with a simple model including lung, rib cage, and diaphragm regional impedances and a viscous coupling between lungs and chest wall caused by the relative sliding between pleural surfaces. To further test this model, we studied five additional animals under open chest conditions. These studies resulted in a homogeneous and f-independent regional gas transport. We conclude that the apex-to-base distribution-of gas transport observed during HFV is not caused by intrinsic lung heterogeneity but rather is a result of chest wall expansion dynamics and its coupling to the lung. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP VENEGAS, JG (reprint author), MASSACHUSETTS GEN HOSP,DEPT BIOMED ENGN,CLIN 2,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-38267] NR 25 TC 15 Z9 15 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 1993 VL 74 IS 5 BP 2242 EP 2252 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LD699 UT WOS:A1993LD69900029 PM 8335554 ER PT J AU TONER, M CRAVALHO, EG KAREL, M AF TONER, M CRAVALHO, EG KAREL, M TI CELLULAR-RESPONSE OF MOUSE OOCYTES TO FREEZING STRESS - PREDICTION OF INTRACELLULAR ICE FORMATION SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID CRYOMICROSCOPIC ANALYSIS; ISOLATED PROTOPLASTS; COLD-ACCLIMATION; NUCLEATION; CELLS; WATER; THERMODYNAMICS; GRANULOCYTES; KINETICS; EMBRYOS AB Successful protocols for cryopreservation of living cells can be designed if the physicochemical conditions to preclude intracellular ice formation (IIF) can be defined. Unfortunately, all attempts to predict the probability of IIF have met with very limited success. In this study, an analytical model is developed to predict ice formation inside mouse oocytes subjected to a freezing stress. According to the model, IIF is catalyzed heterogeneously by the plasma membrane (i.e., surface catalyzed nucleation, SCN). A local site on the plasma membrane is assumed to become an ice nucleator in the presence of the extracellular ice via its effects on the membrane. This interaction is characterized by the contact angle between the plasma membrane and the ice cluster. In addition, IIF is assumed to be catalyzed at temperatures below -30-degrees-C by intracellular particles distributed throughout the cell volume (i.e., volume catalyzed nucleation, VCN). In the present study, these two distinctly coupled modes of IIF, especially SCN, are applied to various experimental protocols from mouse oocytes. Excellent agreement between predictions and observations suggests that the proposed model of IIF is adequate. C1 HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02138. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. RP TONER, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG RES LAB,BOSTON,MA 02114, USA. NR 36 TC 51 Z9 57 U1 1 U2 4 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAY PY 1993 VL 115 IS 2 BP 169 EP 174 DI 10.1115/1.2894117 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA LE604 UT WOS:A1993LE60400006 PM 8326722 ER PT J AU JASTY, M BRAGDON, CR HAIRE, T MULROY, RD HARRIS, WH AF JASTY, M BRAGDON, CR HAIRE, T MULROY, RD HARRIS, WH TI COMPARISON OF BONE INGROWTH INTO COBALT CHROME SPHERE AND TITANIUM FIBER MESH POROUS COATED CEMENTLESS CANINE ACETABULAR COMPONENTS SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article AB Bone ingrowth into uncemented hemispherical canine acetabular components porous-coated with cobalt chrome spheres was compared to those porous-coated with titanium fiber mesh. While good bone ingrowth was noted in both types of porous coatings at 6 weeks after surgery with no difference in the histologic quality of the ingrown bone, quantitation of bone ingrowth showed that significantly more bone grew into titanium fiber mesh porous-coated components. The mean amount of bone ingrowth measured 10.5% of the area of the porous coating with fiber mesh coatings and only 5.5% of the area of the porous coating with spherical coatings (significant difference at P < .0005). The mean area density of the ingrown bone inside the pores measured 21.5% of the pore area with fiber mesh coatings, also significantly greater than 13.4% of the pore area with sphere coatings (P < .025). The ingrown bone penetrated a mean 66% of the depth of the porous layer with fiber mesh coatings compared to 32% of the depth of the porous layer with spherical coating (significant difference at P < .0005). The mean extent of the periphery of the porous layer with bone ingrowth was 88% for the mesh coatings and 55% for the spherical coatings (also a significant difference at P < .01). RP JASTY, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114, USA. NR 16 TC 42 Z9 43 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD MAY PY 1993 VL 27 IS 5 BP 639 EP 644 DI 10.1002/jbm.820270511 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA KX333 UT WOS:A1993KX33300010 PM 8314816 ER PT J AU VILLARREAL, FR ALFONSO, EC ALBERT, DM FORSTER, RK AF VILLARREAL, FR ALFONSO, EC ALBERT, DM FORSTER, RK TI DEFECTS IN AN INJECTION-MOLDED INTRAOCULAR-LENS SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article DE CATARACT SURGERY; INJECTION MOLDED; INTRAOCULAR LENS; POSTMORTEM EXAMINATION; TRIPLE PROCEDURE AB Injection-molded intraocular lenses may undergo structural changes when exposed to solvents and fixatives during post-mortem examination. We report a case in which this phenomenon was seen in an injection-molded lens. We were able to duplicate these changes by immersing injection-molded lenses in 60% alcohol for 48 hours. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,HOWE LAB OPHTHALMOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CATARACT REFRACTIVE SURGERY PI FAIRFAX PA 4000 LEGATO RD, SUITE 850, FAIRFAX, VA 22030 SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAY PY 1993 VL 19 IS 3 BP 417 EP 419 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA LA290 UT WOS:A1993LA29000019 PM 8501642 ER PT J AU SAMUELS, M EZZELL, RM CARDOZO, TJ CRITCHLEY, DR COLL, JL ADAMSON, ED AF SAMUELS, M EZZELL, RM CARDOZO, TJ CRITCHLEY, DR COLL, JL ADAMSON, ED TI EXPRESSION OF CHICKEN VINCULIN COMPLEMENTS THE ADHESION-DEFECTIVE PHENOTYPE OF A MUTANT MOUSE-F9 EMBRYONAL CARCINOMA CELL SO JOURNAL OF CELL BIOLOGY LA English DT Article ID UVOMORULIN-CATENIN COMPLEX; CYTOPLASMIC DOMAIN; MICROFILAMENT BUNDLES; CULTURED FIBROBLASTS; MOLECULE UVOMORULIN; GENE-EXPRESSION; FOCAL ADHESIONS; BINDING PROTEIN; ACTIN; LOCALIZATION AB A mutant cell line, derived from the mouse embryonal carcinoma cell line F9, is defective in cell-cell adhesion (compaction) and in cell-substrate adhesion. We have previously shown that neither uvomorulin (E-cadherin) nor integrins are responsible for the mutant phenotype (Calogero, A., M. Samuels, T. Darland, S. A. Edwards, R. Kemler, and E. D. Adamson. 1991. Dev. Biol. 146:499-508). Several cytoskeleton proteins were assayed and only vinculin was found to be absent in mutant (5.51) cells. A chicken vinculin expression vector was transfected into the 5.51 cells together with a neomycin-resistance vector. Clones that were adherent to the substrate were selected in medium containing G418. Two clones, 5.51Vin3 and Vin4, were analyzed by Nomarski differential interference contrast and laser confocal microscopy as well as by biochemical and molecular biological techniques. Both clones adhered well to substrates and both exhibited F-actin stress fibers with vinculin localized at stress fiber tips in focal contacts. This was in marked contrast to 5.51 parental cells, which had no stress fibers and no vinculin. The mutant and complemented F9 cell lines will be useful models for examining the complex interactions between cytoskeletal and cell adhesion proteins. C1 LA JOLLA CANC RES FDN,10901 N TORREY PINES RD,LA JOLLA,CA 92037. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAT & CELLULAR BIOL,SURG RES LAB,BOSTON,MA 02129. UNIV LEICESTER,DEPT BIOCHEM,LEICESTER LE1 7RH,ENGLAND. RI Coll, Jean-Luc/G-2520-2013 OI Coll, Jean-Luc/0000-0002-2453-3552 FU NCI NIH HHS [CA 54233]; NIDDK NIH HHS [DK 43351] NR 68 TC 48 Z9 48 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 PY 1993 VL 121 IS 4 BP 909 EP 921 DI 10.1083/jcb.121.4.909 PG 13 WC Cell Biology SC Cell Biology GA LB638 UT WOS:A1993LB63800018 PM 8491782 ER PT J AU PASQUALINI, R BODOROVA, J YE, S HEMLER, ME AF PASQUALINI, R BODOROVA, J YE, S HEMLER, ME TI A STUDY OF THE STRUCTURE, FUNCTION AND DISTRIBUTION OF BETA-5 INTEGRINS USING NOVEL ANTI-BETA-5 MONOCLONAL-ANTIBODIES SO JOURNAL OF CELL SCIENCE LA English DT Article DE BETA-5 INTEGRIN; ANTI-BETA-5 MONOCLONAL ANTIBODIES; CELL ADHESION ID AMINO-ACID-SEQUENCE; ADHESION RECEPTOR; CELL-SURFACE; VITRONECTIN RECEPTOR; GLYCOPROTEIN-IIIA; GPIIB-IIIA; SUBUNIT; CLONING; CDNA; INTEGRIN-ALPHA-V-BETA-5 AB Here, we have utilized six new anti-human beta5 monoclonal antibodies to perform a detailed investigation of the structure, function and distribution Of beta5 integrins. Monoclonal anti-beta5 specificity was confirmed by reactivity with beta5-transfected CHO cells, by direct binding to the beta5 subunit (immunoblotting), and by immunodepletion experiments using polyclonal anti-beta5 serum. The beta5 subunit was predominantly associated with the alpha(v) subunit, although on some cell lines, the level of beta5; exceeded that of alpha(v) for unknown reasons. Cell adhesion studies showed that the adhesive function of beta5 could be stimulated, inhibited or unaltered by different anti-beta5 monoclonal antibodies. The beta5 subunit was involved in adhesion to both vitronectin and fibronectin and, at least for K562 cells, fibronectin appeared to be the preferred ligand. Flow-cytometry studies showed that the beta5 subunit was expressed at moderate to high levels on all adherent cell lines examined, was absent from all lymphoid cell lines, and was only weakly expressed on myeloid cell lines. Staining of thymic sections showed the distribution of beta5 on blood vessels, Hassal's corpuscles, cortical and medullary stromal cells, and basement membranes. Skin sections showed beta5 on the basal layer of the epidermis and on some dermal blood vessel walls, and kidney sections showed staining of glomerular regions, juxta glomerular apparatus, proximal convoluted tubules and collecting tubules, and at least one anti-beta5 antibody also stained epithelial cells of proximal tubules. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,ROOM M613,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [CA42368]; NIAID NIH HHS [AI15669] NR 38 TC 94 Z9 94 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1993 VL 105 BP 101 EP 111 PN 1 PG 11 WC Cell Biology SC Cell Biology GA LE940 UT WOS:A1993LE94000011 PM 7689573 ER PT J AU CALDERWOOD, SK STEVENSON, MA AF CALDERWOOD, SK STEVENSON, MA TI INDUCERS OF THE HEAT-SHOCK RESPONSE STIMULATE PHOSPHOLIPASE-C AND PHOSPHOLIPASE-A2 ACTIVITY IN MAMMALIAN-CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INOSITOL PHOSPHATE FORMATION; PERTUSSIS TOXIN; ARACHIDONIC-ACID; BINDING PROTEINS; CALCIUM; TRISPHOSPHATE; HYPERTHERMIA; FIBROBLASTS; ACTIVATION; CALMODULIN AB Although the mammalian heat shock response has been well characterized, the processes that mediate the induction of the response and the regulation of heat shock protein function are not completely understood. We have investigated the potential role in heat-shocked cells of phosphoinositide-specific phospholipase C (PLC), a membrane enzyme activity involved in transmembrane signal transduction. Our studies indicate that heat shock activates PLC in each of seven cell lines, including cells of human, rat, mouse, and hamster origin. Heat shock produced increases in inositol phosphate concentrations comparable in magnitude to those achieved after simulation with growth factors, indicating that heat shock might initiate transmembrane signaling cascades of potential importance in cellular regulation. Common cellular responses to heat and growth factors also included feedback modulation of PLC by its products and the parallel stimulation of phospholipase A, activity. In addition to heat shock, other agents that induce the stress response stimulated PLC activity. The data indicate a close correlation between expression of the mammalian heat shock response and stimulation of PLC activity and indicate a possible role for this enzyme activity in the regulation of some aspects of the stress response. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP CALDERWOOD, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,STRESS PROT GRP,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-47407-01, CA44940-01] NR 50 TC 33 Z9 33 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1993 VL 155 IS 2 BP 248 EP 256 DI 10.1002/jcp.1041550205 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA KZ501 UT WOS:A1993KZ50100004 PM 8482717 ER PT J AU BOUSSIOTIS, VA PANGALIS, GA AF BOUSSIOTIS, VA PANGALIS, GA TI MALIGNANT-LYMPHOMAS IN IMMUNOCOMPROMISED HOSTS SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 8th Mediterranean Congress of Chemotherapy CY MAY 24-29, 1992 CL ATHENS, GREECE C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD MAY PY 1993 VL 5 SU 1 BP 652 EP 653 PG 2 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA MN665 UT WOS:A1993MN66500380 ER PT J AU BOUSSIOTIS, VA PANGALIS, GA AF BOUSSIOTIS, VA PANGALIS, GA TI MEDIASTINAL LYMPHOMAS SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 8th Mediterranean Congress of Chemotherapy CY MAY 24-29, 1992 CL ATHENS, GREECE C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD MAY PY 1993 VL 5 SU 1 BP 654 EP 655 PG 2 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA MN665 UT WOS:A1993MN66500381 ER PT J AU BALLANTYNE, JC CARR, DB CHALMERS, TC DEAR, KBG ANGELILLO, IF MOSTELLER, F AF BALLANTYNE, JC CARR, DB CHALMERS, TC DEAR, KBG ANGELILLO, IF MOSTELLER, F TI POSTOPERATIVE PATIENT-CONTROLLED ANALGESIA - METAANALYSES OF INITIAL RANDOMIZED CONTROL TRIALS SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE ANALGESIA; METAANALYSIS; OPIOID; PAIN, PATIENT-CONTROLLED ANALGESIA AB Study Objective: To compare outcomes during conventional analgesia (as-needed intramuscular dosing) and patient-controlled analgesia (PCA) in postoperative patients by analyzing data from published comparative trials. Design: Meta-analyses of 15 randomized control trials. Patients: Seven hundred eighty-seven adult patients (aged 16 to 65) undergoing various operative procedures. Interventions: Either PCA or conventional analgesia for postoperative pain control Measurements and Main Results: Data were extracted on analgesic efficacy, analgesic use, patient satisfaction, length of hospital stay, and side effects. Meta-analyses of the data showed the following: (1) greater analgesic efficacy when PCA was used, with a mean additional benefit of 5.6 on a scale of 0 to 100 (SED, 2.2; p = 0.006); (2) a nonsignificant trend toward reduced analgesic use in PCA patients, based on a count of trials finding in one direction or the other (p = 0. 092); (3) a 42 % difference in the proportion of patients expressing satisfaction over dissatisfaction (SED, 20%; p = 0.02), with PCA being preferred; (4) a nonsignificant trend toward shortening of length of hospital stay with PCA use (mean, 0.15 days, SED, 0.13; p = 0.24); (5) no significant differences in the occurrence of any side effect. Conclusions: Patient preference strongly favors PCA over conventional analgesia. Patients using PCA also obtain better pain relief than those using conventional analgesia, without an increase in side effects. Favorable effects of PCA upon analgesic usage and length of hospital stay did not in the initial trials attain statistical significance. Nonetheless, the favorable trends in the mean effect sizes for both outcomes argue that further studies of both outcomes should be performed to determine whether the favorable impact of PCA upon either may become statistically significant if larger numbers of patients are enrolled. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114. OI Angelillo, Italo F/0000-0003-1213-6602 NR 0 TC 201 Z9 203 U1 0 U2 7 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAY-JUN PY 1993 VL 5 IS 3 BP 182 EP 193 DI 10.1016/0952-8180(93)90013-5 PG 12 WC Anesthesiology SC Anesthesiology GA LF822 UT WOS:A1993LF82200002 PM 8318237 ER PT J AU KATZNELSON, L ALEXANDER, JM KLIBANSKI, A AF KATZNELSON, L ALEXANDER, JM KLIBANSKI, A TI CLINICAL REVIEW 45 - CLINICALLY NONFUNCTIONING PITUITARY-ADENOMAS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMORS C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT, JACKSON 10,32 FRUIT ST, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NIDDK NIH HHS [DK08738, DK40947] NR 8 TC 79 Z9 83 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1993 VL 76 IS 5 BP 1089 EP 1093 DI 10.1210/jc.76.5.1089 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LD045 UT WOS:A1993LD04500001 PM 8496297 ER PT J AU KING, KA HUA, J TORDAY, JS DRAZEN, JM GRAHAM, SA SHIPP, MA SUNDAY, ME AF KING, KA HUA, J TORDAY, JS DRAZEN, JM GRAHAM, SA SHIPP, MA SUNDAY, ME TI CD10/NEUTRAL ENDOPEPTIDASE 24 11 REGULATES FETAL LUNG GROWTH AND MATURATION INUTERO BY POTENTIATING ENDOGENOUS BOMBESIN-LIKE PEPTIDES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE METALLOENDOPEPTIDASE; AUTOCRINE GROWTH FACTORS; FETAL LUNG DEVELOPMENT; CELL SURFACE ENZYME; COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN ID GASTRIN-RELEASING PEPTIDE; LEUKEMIA ANTIGEN CALLA; NEUTRAL ENDOPEPTIDASE; PULMONARY SURFACTANT; 24.11 ENKEPHALINASE; MOLECULAR-CLONING; SUBSTANCE-P; PROTEIN; CELLS; EXPRESSION AB Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [H-3]thymidine incorporation into nuclear DNA; and (b) maturation using: [H-3]choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [H-3]thymidine incorporation into DNA (70% above baseline' P < 0.005), [H-3]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED,BOSTON,MA 02115. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. FU NHLBI NIH HHS [R01-HL44984] NR 34 TC 65 Z9 66 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 PY 1993 VL 91 IS 5 BP 1969 EP 1973 DI 10.1172/JCI116417 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600019 PM 8486767 ER PT J AU GIORGINO, F ALMAHFOUZ, A GOODYEAR, LJ SMITH, RJ AF GIORGINO, F ALMAHFOUZ, A GOODYEAR, LJ SMITH, RJ TI GLUCOCORTICOID REGULATION OF INSULIN-RECEPTOR AND SUBSTRATE IRS-1 TYROSINE PHOSPHORYLATION IN RAT SKELETAL-MUSCLE INVIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AUTOPHOSPHORYLATION; CORTISONE; INSULIN RECEPTOR SUBSTRATE-1; INSULIN RESISTANCE; TYROSINE KINASE ACTIVITY ID GROWTH FACTOR-I; KINASE-ACTIVITY; PROTEIN-KINASE; DIABETIC RATS; INTACT-CELLS; INVITRO; ADIPOCYTES; AUTOPHOSPHORYLATION; PHOSPHOTYROSINE; HEPATOCYTES AB To test the hypothesis that glucocorticoid-induced insulin resistance might originate from abnormalities in insulin receptor signaling, we investigated the effects of glucocorticoids on in vivo tyrosine phosphorylation of the insulin receptor and the insulin receptor substrate IRS-1 in rat skeletal muscle. Male Sprague-Dawley rats were treated with cortisone (100 mg/kg for 5 d) and compared to pair-fed controls. Cortisone treatment of rats resulted in both hyperglycemia and hyperinsulinemia. Anesthetized animals were injected with 10 U/kg insulin via cardiac puncture and, after 2 min, hindlimb muscles were removed, snap-frozen, and homogenized in SDS. Protein tyrosine phosphorylation was studied by immunoblotting with phosphotyrosine antibody. Insulin receptors and substrate IRS-1 were identified and quantified with specific antibodies. Cortisone treatment increased the amount of insulin receptor protein by 36%, but decreased the total level of receptor tyrosine phosphorylation (69+/-4% of control, P < 0.05). The decreased level of receptor phosphorylation was explained by a reduced number of receptors containing phosphorylated tyrosine residues (64.6+/-5% of control, P< 0.05). Glucocorticoid excess decreased skeletal muscle IRS-1 content by 50%, but did not significantly alter the total level of IRS-1 tyrosine phosphorylation. The apparent M(r) of IRS-1 was reduced by approximately 10 kD. Treatment with protein phosphatase-2A reduced IRS-1 M(r) in control but not in glucocorticoid-treated muscle indicating that the lower M(r) likely results from lower phosphoserine and/or phosphothreonine content. To investigate the role of hyperinsulinemia in the glucocorticoid response, rats were made insulin-deficient with streptozotocin (100 mg / kg, i.p.). Subsequent treatment with cortisone for 5 d had no effects on insulin levels, tyrosine phosphorylation of insulin receptors or IRS-1, or the M(r) of IRS-1. In conclusion, glucocorticoid-treated skeletal muscle is characterized by: (a) decreased total tyrosine phosphorylation of insulin receptors as a result of a reduction in the pool of receptors undergoing tyrosine phosphorylation; (b) decreased IRS-1 content and reduced serine and/or threonine phosphorylation of IRS-1. Glucocorticoid-induced hyperinsulinemia appears to be essential for the development of these alterations. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 FU NIDDK NIH HHS [DK36836, DK07260]; NIGMS NIH HHS [GM36428] NR 50 TC 132 Z9 135 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 2020 EP 2030 DI 10.1172/JCI116424 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600026 PM 7683695 ER PT J AU FU, YE NATHAN, DM LI, FQ LI, XP FAUSTMAN, DL AF FU, YE NATHAN, DM LI, FQ LI, XP FAUSTMAN, DL TI DEFECTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION ON LYMPHOID-CELLS IN AUTOIMMUNITY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE MAJOR HISTOCOMPATIBILITY COMPLEX-CLASS-I; INSULIN-DEPENDENT DIABETES-MELLITUS; GRAVES DISEASE; HASHIMOTO THYROIDITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; RHEUMATOID ARTHRITIS ID DEPENDENT DIABETES-MELLITUS; T-CELLS; VIRAL PEPTIDES; MURINE MHC; GENE; SUSCEPTIBILITY; HLA; DISEASE; REGION AB Lymphocytes from patients with insulin-dependent diabetes mellitus (IDDM), a chronic autoimmune disease, have recently been shown to have decreased surface expression of MHC class I antigens. Since IDDM and other autoimmune diseases share a strong genetic association with MHC class II genes, which may in turn be linked to genes that affect MHC class I expression, we studied other autoimmune diseases to determine whether MHC class I expression is abnormal. Fresh PBLs were isolated from patients with IDDM, Hashimoto's thyroiditis, Graves' disease, systemic lupus erythematosis, rheumatoid arthritis, and Sjogren's syndrome. Nondiabetic and non-insulin-dependent diabetes mellitus patients served as controls. MHC class I expression was measured with a conformationally dependent monoclonal antibody, W6/32. Freshly prepared PBLs from the autoimmune diseases studied and the corresponding fresh EBV-transformed B cell lines had decreased MHC class I expression compared with PBLs from normal volunteers and non-insulin-dependent (nonautoimmune) diabetic patients. Only 3 of more than 180 donors without IDDM or other clinically recognized autoimmune disease had persistently decreased MHC class I expression; one patient was treated with immunosuppressive drugs, and subsequent screening of the other two patients revealed high titers of autoantibodies, revealing clinically occult autoimmunity. Patients with nonautoimmune inflammation (osteomyelitis or tuberculosis) had normal MHC class I expression. Autoimmune diseases are characterized by decreased expression of MHC class I on lymphocytes. MHC class I expression may be necessary for self-tolerance, and abnormalities in such expression may lead to autoimmunity. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIABET UNIT,IMMUNOBIOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. NR 22 TC 44 Z9 44 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 2301 EP 2307 DI 10.1172/JCI116459 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600061 PM 8486790 ER PT J AU FREEDMAN, AS TAKVORIAN, T NEUBERG, D MAUCH, P RABINOWE, SN ANDERSON, KC SOIFFER, RJ SPECTOR, N GROSSBARD, M ROBERTSON, MJ BLAKE, K CORAL, F CANELLOS, GP RITZ, J NADLER, LM AF FREEDMAN, AS TAKVORIAN, T NEUBERG, D MAUCH, P RABINOWE, SN ANDERSON, KC SOIFFER, RJ SPECTOR, N GROSSBARD, M ROBERTSON, MJ BLAKE, K CORAL, F CANELLOS, GP RITZ, J NADLER, LM TI AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN POOR-PROGNOSIS INTERMEDIATE-GRADE AND HIGH-GRADE B-CELL NON-HODGKINS-LYMPHOMA IN 1ST REMISSION - A PILOT-STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; COMBINATION CHEMOTHERAPY; LYMPHOCYTIC LYMPHOMA; MALIGNANT-LYMPHOMA; LONG-TERM; SURVIVAL; DISEASE; MODEL C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. RP FREEDMAN, AS (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55207, CA50947, CA34183] NR 34 TC 98 Z9 99 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 1993 VL 11 IS 5 BP 931 EP 936 PG 6 WC Oncology SC Oncology GA LA026 UT WOS:A1993LA02600019 PM 8487057 ER PT J AU SHULMAN, LN FRISARD, B ANTIN, JH WHEELER, C PINKUS, G MAGAURAN, N MAUCH, P NOBLES, E MASHAL, R CANELLOS, G TUNG, N KADIN, M AF SHULMAN, LN FRISARD, B ANTIN, JH WHEELER, C PINKUS, G MAGAURAN, N MAUCH, P NOBLES, E MASHAL, R CANELLOS, G TUNG, N KADIN, M TI PRIMARY KI-1 ANAPLASTIC LARGE-CELL LYMPHOMA IN ADULTS - CLINICAL CHARACTERISTICS AND THERAPEUTIC OUTCOME SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; BONE-MARROW TRANSPLANTATION; DISEASE; EXPRESSION; FEATURES C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD LONGWOOD ONCOL GRP,BOSTON,MA. BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. JOINT CTR RADIAT ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP SHULMAN, LN (reprint author), BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA39542] NR 21 TC 75 Z9 77 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 1993 VL 11 IS 5 BP 937 EP 942 PG 6 WC Oncology SC Oncology GA LA026 UT WOS:A1993LA02600020 PM 8387578 ER PT J AU LINDHE, J ROSLING, B SOCRANSKY, SS VOLPE, AR AF LINDHE, J ROSLING, B SOCRANSKY, SS VOLPE, AR TI THE EFFECT OF A TRICLOSAN-CONTAINING DENTIFRICE ON ESTABLISHED PLAQUE AND GINGIVITIS SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE ANTIMICROBIAL; CLINICAL TRIAL; GINGIVITIS; PLAQUE; TRICLOSAN ID FLUORIDE TOOTHPASTE; CHLORHEXIDINE AB The aim of the present clinical trial was to study the effect on existing plaque and gingivitis of an oral hygiene regimen which utilized a dentifrice which contained triclosan. 120 subjects were recruited for the trial. They were examined for plaque and gingivitis using the criteria of (i) the Turesky modification of the Quigley & Hein plaque index and (ii) the Loe & Silness gingival index. Plaque and gingivitis were assessed in all parts of the dentition and at 6 location points around each tooth. Following a baseline examination, the subjects were stratified in 2 balanced groups based on age, plaque and gingivitis scores. The subjects were randomly assigned to the following treatment: 1 test group used a dentifrice containing triclosan/copolymer/fluoride and 1 control group used a traditional fluoride containing dentifrice. The participants were given the assigned dentifrice and a soft-bristled toothbrush for home use. They were instructed to brush their teeth in the morning and in the evening for one minute each time. They were re-examined 6 weeks, 3 and 6 months after the baseline examination. The findings from the re-examinations revealed that an oral hygiene regimen which utilized a dentifrice which contained triclosan/copolymer significantly reduced pre-existing plaque and gingivitis above what was accomplished by a traditional fluoride containing dentifrice. The improvement of the gingival conditions occurred in all parts of the dentition and at all tooth surfaces and units. In addition, the present data support the hypothesis that triclosan may induce alterations in the quality of existing plaque. C1 FORSYTH DENT CTR,DEPT PERIODONTOL,BOSTON,MA 02115. COLGATE PALMOLIVE CO,CTR TECHNOL,PISCATAWAY,NJ 08854. RP LINDHE, J (reprint author), UNIV GOTHENBURG,FAC ODONTOL,DEPT PERIODONTOL,MEDICINAREGATAN 12,S-41390 GOTHENBURG,SWEDEN. NR 24 TC 63 Z9 66 U1 0 U2 5 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 1993 VL 20 IS 5 BP 327 EP 334 DI 10.1111/j.1600-051X.1993.tb00368.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LB037 UT WOS:A1993LB03700004 PM 8501272 ER PT J AU TORCHILIN, VP TRUBETSKOY, VS NARULA, J KHAW, BA KLIBANOV, AL SLINKIN, MA AF TORCHILIN, VP TRUBETSKOY, VS NARULA, J KHAW, BA KLIBANOV, AL SLINKIN, MA TI CHELATING POLYMER-MODIFIED MONOCLONAL-ANTIBODIES FOR RADIOIMMUNODIAGNOSTICS AND RADIOIMMUNOTHERAPY SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 2ND EUROPEAN SYMP ON CONTROLLED DRUG DELIVERY CY APR 01-03, 1992 CL NOORDWIJK AAN ZEE, NETHERLANDS SP DUTCH EXECUT AGCY TECHNOL POLICY, ORGANON INT, SANDOZ PHARMA, DUPHAR, SCHWARZ PHARMA, THERATECH, HOFFMANN LA ROCHE, MEDISOB TECHNOL, THREE M MEDICA DE CHELATING POLYMER; MONOCLONAL ANTIBODY; RADIOIMMUNODIAGNOSIS; RADIOIMMUNOTHERAPY ID EXPERIMENTAL MYOCARDIAL-INFARCTION; CONJUGATION AB Polylysine (PL) was used to prepare derivatives with chelating properties. For this purpose PL was modified with cyclic or mixed anhydride of diethylene triamine pentaacetic acid (DTPA) or with deferoxamine (DFA). The modification permits to introduce into single polylysine molecule up to 100 DTPA residues (for 55 kDa polylysine), capable of firm binding metals like In or Gd, which are widely used in radioscintigraphy and NMR-tomography. To make polymeric chelates specific towards target areas, they were conjugated with specific monoclonal antibodies. Special technique of antibody modification with chelating polymer has been developed, permitting to bind whole antibody or its Fab with the polymer via minimal number of chemical bonds and with minimal loss in immunoreactivity. Very high specific radioactivity was achieved for antibodies labeled with In-111: ca. 100 muCi per 1 mug of protein. In vivo studies were performed in rabbits with experimental myocardial infarction, utilizing monoclonal antibodies against cardiac myosin, labeled with In-111 via DTPA-containing PL-based chelating polymers. Good accumulation of antibody-polymer conjugates in infarcted areas was demonstrated (target-to-normal ratio can reach several dozens). C1 UNIV PITTSBURGH,DEPT PHARMACOL,PITTSBURGH,PA 15260. INSERM,U211,NANTES,FRANCE. RP TORCHILIN, VP (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,149 13TH ST,BOSTON,MA 02129, USA. NR 15 TC 12 Z9 12 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAY 1 PY 1993 VL 24 IS 1-3 BP 111 EP 118 DI 10.1016/0168-3659(93)90171-Z PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA LF865 UT WOS:A1993LF86500009 ER PT J AU ARULANANDAM, ARN MOINGEON, P CONCINO, MF RECNY, MA KATO, K YAGITA, H KOYASU, S REINHERZ, EL AF ARULANANDAM, ARN MOINGEON, P CONCINO, MF RECNY, MA KATO, K YAGITA, H KOYASU, S REINHERZ, EL TI A SOLUBLE MULTIMERIC RECOMBINANT CD2 PROTEIN IDENTIFIES CD48 AS A LOW AFFINITY LIGAND FOR HUMAN CD2 - DIVERGENCE OF CD2 LIGANDS DURING THE EVOLUTION OF HUMANS AND MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL ACTIVATION; FUNCTION-ASSOCIATED ANTIGEN-3; ADHESION MOLECULE-1 ICAM-1; LYMPHOCYTE-T; ALTERNATIVE PATHWAY; MOUSE CHROMOSOME-1; LFA-3 MOLECULES; SURFACE LIGAND; RECEPTOR CD2; B-CELLS AB To search for possible ligands of CD2 distinct from CD58 (lymphocyte function-associated antigen 3), we have produced a soluble pentameric CD2-immunoglobulin (Ig) fusion protein (spCD2) linking the 182-amino acid human CD2 extracellular segment with CH2-CH3-CH4 domains of human IgM heavy chain, thus enhancing the micromolar affinity of the CD2 monomer through multimeric interaction. Using quantitative immunofluorescence and standard stringency wash conditions, we observed that the binding of spCD2 to human B lymphoblastoid JY cells and red blood cells is virtually inhibited by anti-CD58 TS2/9 monoclonal antibody, even though these cells express levels of CD48 and CD59 comparable to CD58. Consistent with these results, spCD2 did not show any binding to Chinese hamster ovary (CHO) cells transfected with human CD48 or CD59. However, binding studies on CD48-, CD58-, or CD59-transfected CHO cells with spCD2 under low stringency wash conditions revealed that human CD48 is a low affinity ligand of human CD2 compared with CD58 (K(d) approximately 10(-4) VS. approximately 10(-6) M, respectively). The findings are noteworthy given that in the murine system CD48 is the major ligand for CD2. No detectable binding was observed to CD59-transfected CHO cells despite a report suggesting that CD59 may bind to the human CD2 adhesion domain. Importantly, in cell-cell adhesion assays between CD2+ Jurkat T cells and CD48- or CD59-transfected CHO cells, there was no conjugate formation, whereas binding of Jurkat T cells to CD58-transfected CHO cells was readily detected. Collectively, our findings provide evidence for a conservation of the CD2-CD48 interaction in the human species that may be of limited, if any, functional significance. Given the importance of the CD2-CD48 interaction in the murine system and CD2-CD58 interaction in humans, it would appear that there has been a divergence of functional CD2 ligands during the evolution of humans and mice. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. PROCEPT INC,CAMBRIDGE,MA 02139. JUNTENDO UNIV,DEPT IMMUNOL,TOKYO 113,JAPAN. RP ARULANANDAM, ARN (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI-21226] NR 56 TC 121 Z9 121 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1993 VL 177 IS 5 BP 1439 EP 1450 DI 10.1084/jem.177.5.1439 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KY849 UT WOS:A1993KY84900021 PM 7683037 ER PT J AU NALEFSKI, EA RAO, A AF NALEFSKI, EA RAO, A TI NATURE OF THE LIGAND RECOGNIZED BY A HAPTEN-SPECIFIC AND CARRIER-SPECIFIC, MHC-RESTRICTED T-CELL RECEPTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; ANTIGEN RECOGNITION; MONOCLONAL-ANTIBODIES; POLYMORPHIC RESIDUES; SURFACE EXPRESSION; OVALBUMIN PEPTIDE; IA; BINDING; ALPHA; HYBRIDOMAS AB The hapten- and carrier-specific T lymphocyte clone D5 and a T hybridoma (D5h) derived from D5 cells recognize several different protein Ag conjugated with p-azobenzenearsonate (arsonate) presented by the class II MHC protein I-A(d). We show here that the ligand recognized by the D5 TCR is a complex of a haptenated peptide bound to I-A(d). We have identified a peptide fragment generated by enzymatic cleavage of arsonate-conjugated OVA (Ars-OVA), which stimulates D5 cells when presented by I-A(d)-bearing APC. A synthetic peptide corresponding to this fragment, OVA(36-50), forms a ligand for D5h cells when it is conjugated with arsonate and presented by cells bearing I-A(d). Paraformaldehyde-fixed, I-A(d)-bearing cel s present Ar -OVA(36-50), or the longer stimulatory peptide Ars-OVA(33-49), to D5h cells, demonstrating that haptenated synthetic peptides can substitute for naturally pro-cessed antigenic peptides. The peptide Ars-OVA(33-49) binds to the major peptide-binding site of I-A(d) because it competitively inhibited presentation of the peptide OVA(323-339), previously demonstrated to bind to I-A(d) directly in vitro, to the OVA/1-A(d)-specific T cell hybridoma 3DO-54.8. The unconjugated OVA(33-49) peptide failed to inhibit the presentation of OVA(323-339), demonstrating that the hapten facilitates binding of the peptide to I-A(d). Conversely, the peptide OVA(323-339) competitively inhibited the presentation of Ars-OVA(33-49) to D5h cells, indicating that the two peptides Ars-OVA(33-49) and OVA(323-339) bind to overlapping sites on I-A(d). Amino acid substitutions introduced into the beta1 domain of I-A(d) that affected recognition of OVA(323-339) by 3DO-54.8 cells also affected recognition of Ars-OVA(33-50) by D5h cells, demonstrating that similar regions on I-A(d) are required for TCR recognition of conventional as well as haptenated peptides. These results represent the first demonstration that the ligand recognized by a hapten- and carrier-specific T cell clone restricted to an MHC class II protein is a haptenated peptide Ag bound to the MHC molecule. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-22900]; NIGMS NIH HHS [5 T32 GM07226] NR 44 TC 51 Z9 51 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 1993 VL 150 IS 9 BP 3806 EP 3816 PG 11 WC Immunology SC Immunology GA KY452 UT WOS:A1993KY45200015 PM 7682584 ER PT J AU MARUIWA, M MIZOGUCHI, A RUSSELL, GJ NARULA, N STRONSKA, M MIZOGUCHI, E RABB, H ARNAOUT, MA BHAN, AK AF MARUIWA, M MIZOGUCHI, A RUSSELL, GJ NARULA, N STRONSKA, M MIZOGUCHI, E RABB, H ARNAOUT, MA BHAN, AK TI ANTI-KCA-3, A MONOCLONAL-ANTIBODY REACTIVE WITH A RAT COMPLEMENT C3 RECEPTOR, DISTINGUISHES KUPFFER CELLS FROM OTHER MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEMBRANE GLYCOPROTEIN; ANTIGEN PRESENTATION; C-3 RECEPTORS; LIVER; HETEROGENEITY; INVIVO; CR-1; IDENTIFICATION; LOCALIZATION; HEPATOCYTES AB A new mAb, designated anti-KCA-3, was developed against rat Kupffer cells. The reactivity of anti-KCA-3 was restricted to macrophages with preferential binding to Kupffer cells; only a few macrophages in the spleen, lymph nodes, lungs, and intestine stained with the antibody. A very small number of peritoneal resident and exudate macrophages reacted with the antibody and no reactivity was seen within the thymus, skin, heart, kidneys, brain, peripheral blood, and bone marrow. KCA-3 was expressed predominantly by the Kupffer cells in the periportal region rather than in the centrilobular region of the hepatic lobules. The cells in the portal tract did not stain with the antibody. The staining of the cytosmears and FACS analysis of the Kupffer cell fraction isolated from hepatic sinusoidal cells by centrifugal elutriation revealed that as many as 62% and 49% of the cells were stained with anti-KCA-3, respectively. Immunoelectron microscopic study of the liver indicated that expression of KCA-3 on Kupffer cells was limited to the plasma membrane facing the sinusoid rather than the space of Disse. Immunoprecipitation and SDS-PAGE analysis demonstrated KCA-3 to have a m.w. of approximately 50 kDa under both reducing and nonreducing conditions. After treatment of KCA-3 with N-glycanase, there was no significant change in the m.w., indicating KCA-3 was not highly glycosylated. C3b- and iC3b-mediated rosette formation between Kupffer cells and sensitized SRBC was inhibited by the antibody, implying that KCA-3 functioned as a complement C3 receptor or complement receptor-associated molecule. Furthermore, KCA-3 was eluted from C3b-Sepharose but not HSA-Sepharose after incubation with Kupffer cell lysate, indicating that KCA-3 directly binds C3b. The cell distribution, ligand-binding specificity, and biochemical properties of the protein were found to be different from the complement C3 receptors previously described. Because OX42 (antibody reactive with the rat CR3 receptor) inhibited complement C3-mediated rosette formation with peritoneal resident macrophages but not with Kupffer cells, the findings suggest that C3-mediated binding to Kupffer cells and to peritoneal macrophages is mediated by two different receptors. We conclude that anti-KCA-3 recognizes a novel type of complement C3 receptor preferentially expressed on Kupffer cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,IMMUNOPATHOL UNIT,COX 5,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. FU NIAID NIH HHS [AI21964]; NIDDK NIH HHS [DK43351, DK33506] NR 44 TC 10 Z9 10 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 1993 VL 150 IS 9 BP 4019 EP 4030 PG 12 WC Immunology SC Immunology GA KY452 UT WOS:A1993KY45200037 PM 8473747 ER PT J AU BELL, RB LINDSEY, JW SOBEL, RA HODGKINSON, S STEINMAN, L AF BELL, RB LINDSEY, JW SOBEL, RA HODGKINSON, S STEINMAN, L TI DIVERSE T-CELL RECEPTOR V-BETA GENE USAGE IN THE CENTRAL-NERVOUS-SYSTEM IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; AUTOIMMUNE ENCEPHALOMYELITIS; MONOCLONAL-ANTIBODY; LYMPHOCYTE-T; REGION GENES; IDENTIFICATION; EXPRESSION; REPERTOIRE; ANTIGENS AB The repertoire of TCR Vbeta genes transcribed and expressed within the central nervous system was determined in mice with experimental allergic encephalomyelitis. Disease was induced in (PL/J x SJL/J)F1 mice by immunizing with myelin basic protein-acetylated peptide 1-11, and mice were sacrificed at intervals from day 3 postimmunization to 3 wk after recovery from disease. Transcription of Vbeta genes was determined by reverse transcriptase polymerase chain reaction on RNA extracted from spinal cord, and expression of the Vbeta gene products was detected by immunohistochemistry with mAb specific for various Vbeta proteins. Multiple Vbeta genes were found to be transcribed and expressed in the central nervous system starting 7 days after immunization, and continuing up to 3 wk after clinical recovery. Preferential utilization of a single TCR Vbeta gene was not detected in the central nervous system at any time in the course of disease. C1 STANFORD UNIV,DEPT NEUROL,ROOM H3160,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. OI Hodgkinson, Suzanne/0000-0002-9029-6663 FU NINDS NIH HHS [NS-18235, NS-26773] NR 45 TC 71 Z9 71 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 1993 VL 150 IS 9 BP 4085 EP 4092 PG 8 WC Immunology SC Immunology GA KY452 UT WOS:A1993KY45200043 PM 8473751 ER PT J AU ALLENDOERFER, R MAGEE, DM SMITH, JG BONEWALD, L GRAYBILL, JR AF ALLENDOERFER, R MAGEE, DM SMITH, JG BONEWALD, L GRAYBILL, JR TI INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN MURINE CANDIDA-ALBICANS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LISTERIA-MONOCYTOGENES INFECTION; CACHECTIN; MICE; ENDOTOXIN; SHOCK; TNF AB Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis. Tumor necrosis factor-alpha (TNFalpha) has been implicated as a mediator in the endotoxic shock syndrome. The possible role of TNFalpha causing early deaths was explored in a murine model of acute infection with Candida albicans. In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained. Peritoneal macrophages from all three strains produced TNFalpha in vitro when stimulated with C albicans. After intravenous infection with 10(8) cfu of C. albicans, mice died within 12 h. TNF concentrations in sera from these mice were significantly greater than in controls. Pretreatment of BALB/c mice with anti-murine TNFalpha did not alter mortality of C. albicans-infected mice, but pretreatment with murine TNFalpha reduced mortality. Therefore, in contrast to what was anticipated, TNFalpha may serve a protective role in murine candidiasis. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX 78284. RP ALLENDOERFER, R (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 21 TC 48 Z9 48 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1993 VL 167 IS 5 BP 1168 EP 1172 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA KZ499 UT WOS:A1993KZ49900026 PM 8486950 ER PT J AU ETOH, T THOMAS, L PASTELLEVY, C COLVIN, RB MIHM, MC BYERS, HR AF ETOH, T THOMAS, L PASTELLEVY, C COLVIN, RB MIHM, MC BYERS, HR TI ROLE OF INTEGRIN ALPHA-2-BETA (VLA-2) IN THE MIGRATION OF HUMAN-MELANOMA CELLS ON LAMININ AND TYPE-IV COLLAGEN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; TUMOR PROGRESSION; EXTRACELLULAR-MATRIX; METASTATIC MELANOMA; ALPHA-ACTININ; ADHESION; RECEPTOR; FIBRONECTIN; EXPRESSION; MOTILITY AB The random cell migration of four human melanoma cell lines on laminin and type IV collagen - coated substrates was studied by video time-lapse image analysis and compared to the expression of a number of beta1 integrins including alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1 using flow cytometry. These integrins were heterogeneously expressed in the four cell lines tested with three of four lines expressing alpha2beta1. The melanoma cell line that did not express alpha2beta1, exhibited weak attachment and low cell migration rate on both laminin and type IV collagen, whereas the other melanoma cell lines showed an increase in attachment and mean cell migration rate in a dose-dependent manner on the matrix molecules (p < 0.001). The enhanced migration seen in the three cell lines could be specifically inhibited by function blocking anti-beta1 and anti-2 monoclonal antibodies (p < 0.001) but not by function blocking anti-alpha3 and anti-alpha6 monoclonal antibodies. Image analysis of the cells before and after treatment with anti-beta1 and anti-alpha2 MoAb indicated that the inhibition of migration did not result in detectable cell detachment, retraction of cell processes, or other significant cell-shape change. Taken together, the findings suggest that the observable enhanced migration on laminin and type IV collagen of a number of human melanoma cell lines is largely mediated by integrin alpha2beta1. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA 02114. FU NCI NIH HHS [CA-45587, T32-CA-09216] NR 44 TC 38 Z9 39 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1993 VL 100 IS 5 BP 640 EP 647 DI 10.1111/1523-1747.ep12472299 PG 8 WC Dermatology SC Dermatology GA LA730 UT WOS:A1993LA73000006 PM 8491987 ER PT J AU LIANG, TJ RUSTGI, V GALUN, E BLUM, HE AF LIANG, TJ RUSTGI, V GALUN, E BLUM, HE TI HCV RNA IN PATIENTS WITH CHRONIC HEPATITIS-C TREATED WITH INTERFERON-ALPHA SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE RT-PCR NON-A; NON-B HEPATITIS RIBA ID NON-B-HEPATITIS; NON-A; CONTROLLED TRIAL; VIRUS-INFECTION; VIRAL-RNA; SERUM; THERAPY; DISEASE; LIVER; ASSAY AB In order to assess the efficacy of interferon-alpha on hepatitis C viral RNA in patients with chronic hepatitis C, we analyzed the levels of HCV RNA in sera and liver tissues of 16 patients pre- and posttreatment using a semiquantitative polymerase chain reaction method. Fifteen of 16 patients were positive for anti-HCV antibodies by four-antigen recombinant immunoblot assay (4RIBA). Only two patients demonstrated normalization of ALT in response to interferon; three patients showed a partial response. Only one patient from the partial responder group displayed a significant reduction of HCV RNA level posttreatment. In the nonresponder group, several patients, although their ALTs remained elevated, demonstrated significant decreases in HCV RNA levels in either serum or liver in response to interferon. Our data suggest that interferon treatment of chronic hepatitis C may not be effective in eradicating HCV infection and a reduction in ALT is infrequently associated with a decrease in HCV RNA level in either serum or liver. Cessation of treatment is frequently associated with the recrudescence of HCV replication and disease. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. INOVA INST,OFF MED RES,FALLS CHURCH,VA. MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02114. RP LIANG, TJ (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,GASTROENTEROL UNIT,JACKSON 7,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA54524]; NIDDK NIH HHS [DK01952] NR 25 TC 11 Z9 12 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 1993 VL 40 IS 1 BP 69 EP 75 DI 10.1002/jmv.1890400114 PG 7 WC Virology SC Virology GA KZ695 UT WOS:A1993KZ69500013 PM 8390560 ER PT J AU BOWLING, AC MUTISYA, EM WALKER, LC PRICE, DL CORK, LC BEAL, MF AF BOWLING, AC MUTISYA, EM WALKER, LC PRICE, DL CORK, LC BEAL, MF TI AGE-DEPENDENT IMPAIRMENT OF MITOCHONDRIAL-FUNCTION IN PRIMATE BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE ELECTRON TRANSPORT CHAIN; COMPLEX-I; CYTOCHROME OXIDASE; NEURODEGENERATION; MITOCHONDRIA ID CARDIOLIPIN REQUIREMENT; RESPIRATORY-CHAIN; COMPLEX-I; DNA; MUTATION; MONKEYS; OXIDASE; DECLINE AB It has been hypothesized that some of the functional impairments associated with aging are the result of increasing oxidative damage to mitochondrial DNA that produces defects in oxidative phosphorylation. To test this hypothesis, we examined the enzymes that catalyze oxidative phosphorylation in crude mitochondrial preparations from frontoparietal cortex of 20 rhesus monkeys (5-34 years old). Samples were assayed for complex I, complex II-III, complex IV, complex V, and citrate synthase activities. When enzyme activities were corrected for citrate synthase activities (to account for variable degrees of mitochondrial enrichment), linear regression analysis demonstrated a significant negative correlation of the activities of complex I (p < 0.002) and complex IV (p < 0.03) with age but no significant change in complex II-III or complex V activities. Relative to animals 6.9 +/- 0.9 years old (n = 7), the citrate synthase-corrected activity of complex I was reduced by 17% in animals 22.5 +/- 0.9 years old (n = 6) (p < 0.05) and by 22% in animals 30.7 +/- 0.9 years old (n = 7) (p < 0.01). Similar age-related reductions in the activities of complexes I and IV were obtained when enzyme activities were corrected for complex II-III activity. These findings show an age-associated progressive impairment of mitochondrial complex I and complex IV activities in cerebral cortices of primates. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DIV COMPARAT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,NEUROPATHOL LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RI Walker, L/J-6541-2015 OI Walker, L/0000-0001-9166-3261 FU DS NIH HHS [NINDS 16367]; NIA NIH HHS [AG05134]; NINDS NIH HHS [NS 20471] NR 28 TC 207 Z9 213 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1993 VL 60 IS 5 BP 1964 EP 1967 DI 10.1111/j.1471-4159.1993.tb13430.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KY255 UT WOS:A1993KY25500050 PM 8473911 ER PT J AU BEERS, DR HENKEL, JS SCHAEFER, DC ROSE, JW STROOP, WG AF BEERS, DR HENKEL, JS SCHAEFER, DC ROSE, JW STROOP, WG TI NEUROPATHOLOGY OF HERPES-SIMPLEX VIRUS ENCEPHALITIS IN A RAT SEIZURE MODEL SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE ENCEPHALITIS; HERPES SIMPLEX VIRUS; HISTOPATHOLOGY; HSV-1; NEUROANATOMY; RAT; SEIZURES ID CENTRAL-NERVOUS-SYSTEM; INFLUENCE VIRAL NEUROTROPISM; TYPE-1 STRAINS; INFECTIONS; SPREAD; BRAIN; MICE; REACTIVATION; ANTIBODY; HOST AB Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by HSV-1 central nervous system (CNS) infection. Following intranasal inoculation of Lewis rats with a neurovirulent strain of HSV-1, animals shed virus in both ocular and nasal secretions and developed clinical signs of infection, including partial complex motor seizures that eventually generalized. Homogenization assays demonstrated infectious virus in the trigeminal ganglia, olfactory bulbs, and the piriform and entorhinal cortices. Histopathological assessment revealed inflammatory and hemorrhagic lesions in the trigeminal ganglia, olfactory bulbs, amygdala, hippocampus, the piriform and entorhinal cortices, and the spinal trigeminal nuclei. Viral antigens and nucleic acids were also detected within these structures by immunofluorescence microscopy and in situ hybridization, respectively. Viral-induced astrocytic hypertrophy in the CNS was demonstrated by glial fibrillary acidic protein immunoreactivity. Together, these results indicate that HSV-1 has the ability to invade, replicate, and induce site-specific CNS damage in the Lewis rat. C1 DEPT VET AFFAIRS MED CTR,HOUSTON,TX. DEPT VET AFFAIRS MED CTR,SALT LAKE CITY,UT. UNIV UTAH,PROGRAM NEUROSCI,SALT LAKE CITY,UT 84112. UNIV UTAH,DEPT NEUROL,SALT LAKE CITY,UT 84112. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. CONNAUGHT LABS INC,DEPT RES,SWIFTWATER,PA. RP BEERS, DR (reprint author), BAYLOR COLL MED,CULLEN EYE INST,6501 FANNIN NC-200,HOUSTON,TX 77030, USA. FU NEI NIH HHS [F32 EY07001]; NIDCD NIH HHS [1RO1 DC1706]; NIMH NIH HHS [1 F31 MH10094-01A1] NR 56 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 241 EP 252 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500008 PM 8388040 ER PT J AU HYMAN, BT MARZLOFF, K ARRIAGADA, PV AF HYMAN, BT MARZLOFF, K ARRIAGADA, PV TI LACK OF ACCUMULATION OF SENILE PLAQUES OR AMYLOID BURDEN IN AGING, ALZHEIMERS-DISEASE AND DOWN-SYNDROME SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CATHOLIC UNIV CHILE,SANTIAGO,CHILE. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 264 EP 264 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500013 ER PT J AU DELAMONTE, SM WANDS, JR AF DELAMONTE, SM WANDS, JR TI ISOLATION OF A NEURONAL THREAD PROTEIN CDNA, AND CHARACTERIZATION OF THE MESSENGER-RNAS EXPRESSED IN NEUROECTODERMAL TUMOR-CELLS AND ALZHEIMERS-DISEASE BRAINS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 265 EP 265 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500019 ER PT J AU LOUIS, DN RUBIO, MP CORREA, K VONDEIMLING, A GUSELLA, JF AF LOUIS, DN RUBIO, MP CORREA, K VONDEIMLING, A GUSELLA, JF TI MOLECULAR-GENETIC ALTERATIONS IN PEDIATRIC BRAIN-STEM GLIOMAS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 267 EP 267 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500027 ER PT J AU HSU, DW EFIRD, JT PARDO, FS LINGGOOD, RM HEDLEYWHYTE, ET AF HSU, DW EFIRD, JT PARDO, FS LINGGOOD, RM HEDLEYWHYTE, ET TI PROGNOSTIC-SIGNIFICANCE OF PROLIFERATIVE INDEXES IN MENINGIOMAS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 268 EP 268 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500031 ER PT J AU GOLDEN, JA HYMAN, BT AF GOLDEN, JA HYMAN, BT TI NEOCORTICAL DEVELOPMENT IN TRISOMY-21 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 285 EP 285 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500100 ER PT J AU XU, YY WANDS, JR DELAMONTE, S AF XU, YY WANDS, JR DELAMONTE, S TI THREAD PROTEIN EXPRESSION IN NEUROECTODERMAL TUMOR-CELL LINES OF CENTRAL-NERVOUS-SYSTEM ORIGIN SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 291 EP 291 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500122 ER PT J AU MCKEE, AC COLE, DG LEE, JM KOWALL, NW GROWDON, JH AF MCKEE, AC COLE, DG LEE, JM KOWALL, NW GROWDON, JH TI DISTINCTIVE CORTICAL NEURONAL DEGENERATION IN PROGRESSIVE SUPRANUCLEAR PALSY SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 292 EP 292 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500126 ER PT J AU GE, P AIZAWA, H BIRD, ED HEDLEYWHYTE, ET DIFIGLIA, M VONSATTEL, JP AF GE, P AIZAWA, H BIRD, ED HEDLEYWHYTE, ET DIFIGLIA, M VONSATTEL, JP TI THE EFFECTS OF POSTMORTEM INTERVAL AND DURATION OF STORAGE AT -80-DEGREES-C OF HUMAN BRAIN-TISSUE ON MESSENGER-RNA LEVELS DETECTED BY INSITU HYBRIDIZATION SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 294 EP 294 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500135 ER PT J AU SIMONIAN, NA ELVHAGE, TI HYMAN, BT AF SIMONIAN, NA ELVHAGE, TI HYMAN, BT TI CALCIUM CALMODULIN KINASE-II IS COLOCALIZED WITH PAIRED HELICAL FILAMENTS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 304 EP 304 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500175 ER PT J AU RUBIO, MP LOUIS, DN AF RUBIO, MP LOUIS, DN TI ACCUMULATION OF WILD-TYPE P53 PROTEIN IN ASTROCYTOMAS IS NOT MEDIATED BY MDM2 GENE AMPLIFICATION SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 323 EP 323 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500250 ER PT J AU GILLES, FH SOBEL, E TAVARE, CJ HEDLEYWHYTE, ET AF GILLES, FH SOBEL, E TAVARE, CJ HEDLEYWHYTE, ET TI THE HISTOLOGIC EXPRESSION OF FACTORS UNDERLYING CHILDHOOD INFRATENTORIAL GLIAL TUMORS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV SO CALIF,CHILDRENS HOSP LOS ANGELES,SCH MED,LOS ANGELES,CA 90033. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1993 VL 52 IS 3 BP 327 EP 327 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA LB785 UT WOS:A1993LB78500264 ER PT J AU HSU, DW HAKIM, F BILLER, BMK DELAMONTE, S ZERVAS, NT KLIBANSKI, A HEDLEYWHYTE, ET AF HSU, DW HAKIM, F BILLER, BMK DELAMONTE, S ZERVAS, NT KLIBANSKI, A HEDLEYWHYTE, ET TI SIGNIFICANCE OF PROLIFERATING CELL NUCLEAR ANTIGEN INDEX IN PREDICTING PITUITARY-ADENOMA RECURRENCE SO JOURNAL OF NEUROSURGERY LA English DT Article DE PROLIFERATING CELL NUCLEAR ANTIGEN; PITUITARY ADENOMA; TUMOR RECURRENCE; IMMUNOCYTOCHEMISTRY ID DNA-POLYMERASE-DELTA; HUMAN-BRAIN TUMORS; S-PHASE CELLS; AUXILIARY PROTEIN; CYCLIN PCNA; MONOCLONAL-ANTIBODIES; RESECTED MENINGIOMAS; RADIATION-THERAPY; LABELING INDEX; GROWTH-RATE AB The recurrence rate of pituitary adenomas has been reported to be as high as 10% to 35% despite their generally benign nature. A monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) was used to investigate whether the proliferative index might help to predict adenoma recurrence. This antigen is a nuclear protein identified as the auxiliary protein of deoxyribonucleic acid polymerase delta, and its gene expression correlates with cell proliferation. The authors studied 30 patients with recurrent pituitary adenomas, 32 with nonrecurrent adenomas, and seven normal pituitary tissue samples. The mean interval to recurrence (+/- standard error of the mean) was 5.3 +/- 0.7 years. The age- and sex-matched nonrecurrent group had a mean follow-up period of 6.6 +/- 0.3 years without clinical recurrence. Mean percentages of PCNA-positive tumor nuclei in both the initial and the second surgical specimens of the recurrent adenomas (13.45% +/- 3.02% and 19.56% +/- 3.66%, respectively) were significantly higher than that of the nonrecurrent group (2.49% +/- 1.21%). In addition, recurrent tumors had a higher PCNA index than the initial tumors in the same patients. Normal anterior pituitary gland tissue had a significantly lower mean PCNA index (0.12% +/- 0.11%) than either patient group. Stepwise multivariate regression analysis indicated that factors which collectively cor-related significantly with recurrence were: high PCNA index, large tumor size, extrasellar extension, and incomplete surgical excision. The PCNA nuclear count was not associated with age, sex, or hormone hypersecretion, but was higher in macro- than in microadenomas, in tumors with extrasellar extension, and in those incompletely excised. A higher PCNA index also correlated with a shorter disease-free interval. The authors conclude that evaluation of the PCNA index assists in predicting the likelihood of pituitary adenoma recurrence. C1 MASSACHUSETTS GEN HOSP,DIV NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NEUROSURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NEUROENDOCRINE,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-40947] NR 37 TC 123 Z9 132 U1 1 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1993 VL 78 IS 5 BP 753 EP 761 DI 10.3171/jns.1993.78.5.0753 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA KY468 UT WOS:A1993KY46800011 PM 8096873 ER PT J AU GEWIRTZ, H AF GEWIRTZ, H TI PARAMETRIC IMAGES FOR QUANTITATIVE MEASUREMENTS OF REGIONAL MYOCARDIAL BLOOD-FLOW IN HUMANS - A STEP IN THE RIGHT DIRECTION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; GRAPHICAL EVALUATION; STENOSIS; DISTAL RP GEWIRTZ, H (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 BP 862 EP 864 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LA579 UT WOS:A1993LA57900035 PM 8478726 ER PT J AU ALPERT, NM BERDICHEVSKY, D WEISE, S TANG, J RAUCH, SL AF ALPERT, NM BERDICHEVSKY, D WEISE, S TANG, J RAUCH, SL TI STEREOTAXIC TRANSFORMATION OF PET SCANS BY DEFORMATION OF A STANDARD BRAIN ATLAS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P71 EP P71 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800279 ER PT J AU ALPERT, NM RABITO, C BERDICHEVSKY, D CORREIA, JA BABICH, JW LORING, NA WEISE, S HUNTER, GJ LITTMAN, B RUBIN, NT RUBIN, RH FISCHMAN, AJ AF ALPERT, NM RABITO, C BERDICHEVSKY, D CORREIA, JA BABICH, JW LORING, NA WEISE, S HUNTER, GJ LITTMAN, B RUBIN, NT RUBIN, RH FISCHMAN, AJ TI MAPPING OF LOCAL RENAL BLOOD-FLOW WITH PET AND O-15 WATER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. PFIZER INC,GROTON,CT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P51 EP P51 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800196 ER PT J AU ARONEN, HJ GOLDBERG, IE PARDO, FS KENNEDY, DN HOCHBERG, FH BRADY, TJ ROSEN, BR FISCHMAN, AJ AF ARONEN, HJ GOLDBERG, IE PARDO, FS KENNEDY, DN HOCHBERG, FH BRADY, TJ ROSEN, BR FISCHMAN, AJ TI MULTISLICE MRI CBV MAPPING OF BRAIN-TUMORS - A COMPARISON WITH PET STUDIES USING FDG AND CO SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Kennedy, David/H-3627-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P208 EP P209 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800844 ER PT J AU BABICH, JW SOLOMON, H PIKE, MC KROON, D GRAHAM, W ABRAMS, MJ RUBIN, RH FISCHMAN, AJ AF BABICH, JW SOLOMON, H PIKE, MC KROON, D GRAHAM, W ABRAMS, MJ RUBIN, RH FISCHMAN, AJ TI TC99M-LABELED HYDRAZINO NICOTINAMIDE DERIVATIZED CHEMOTACTIC PEPTIDE ANALOGS FOR IMAGING FOCAL SITES OF BACTERIAL-INFECTION IN RABBITS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 RW JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA. JOHNSON MATTHEY,W CHESTER,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P173 EP P173 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800695 ER PT J AU BABICH, JW GRAHAM, W BARROW, S DRAGOTAKES, S FISCHMAN, AJ AF BABICH, JW GRAHAM, W BARROW, S DRAGOTAKES, S FISCHMAN, AJ TI TC-99M-LABELED CHEMOTACTIC PEPTIDES FOR INFECTION IMAGING - COMPARISON WITH INDIUM-111-LABELED LEUKOCYTES IN INFECTED-RABBITS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P172 EP P172 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800693 ER PT J AU BECKER, JA JOHNSON, KA ZIMMERMAN, RE GARADA, B HOLMAN, BL AF BECKER, JA JOHNSON, KA ZIMMERMAN, RE GARADA, B HOLMAN, BL TI A UNIFIED PROCESSING ENVIRONMENT FOR IMAGE FUSION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P179 EP P180 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800722 ER PT J AU BROWNELL, AL SHOUP, T WULLNER, U ELMALEH, D PAKZABAN, P FRIM, DM BROWNELL, G ISACSON, O AF BROWNELL, AL SHOUP, T WULLNER, U ELMALEH, D PAKZABAN, P FRIM, DM BROWNELL, G ISACSON, O TI INVIVO VISUALIZATION OF STRIATAL TRANSPLANTS IN A PRIMATE MODEL OF HUNTINGTONS-DISEASE (HD) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P202 EP P203 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800819 ER PT J AU CALLAHAN, BJ KILLIUS, DR MOORE, H BABICH, JW CORREIA, JA AF CALLAHAN, BJ KILLIUS, DR MOORE, H BABICH, JW CORREIA, JA TI IDENTIFICATION OF METALLIC SILVER CRYSTALS IN A WATER TARGET USED FOR THE ROUTINE PRODUCTION OF F-18 FLUORIDE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. IEA INC,N BILLERICA,MA. DUPONT MERCH PHARMA,N BILLERICA,MA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P69 EP P69 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800273 ER PT J AU CALLAHAN, RJ JACKSON, LR MARINI, RP JYAWOOK, S ESTEVES, MI WILKINSON, RA STRAUSS, HW FOX, JG AF CALLAHAN, RJ JACKSON, LR MARINI, RP JYAWOOK, S ESTEVES, MI WILKINSON, RA STRAUSS, HW FOX, JG TI ISOFLURANE INDUCED CHANGES IN TC-99M RED-BLOOD-CELL DISTRIBUTION IN THE FERRET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MIT,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P171 EP P171 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800689 ER PT J AU CALLAHAN, RJ BOGDANOV, AA WEISSLEDER, R WILKINSON, RA FISCHMAN, AJ BRADY, TJ AF CALLAHAN, RJ BOGDANOV, AA WEISSLEDER, R WILKINSON, RA FISCHMAN, AJ BRADY, TJ TI DEVELOPMENT OF A SYNTHETIC-POLYMER BASED BLOOD POOL IMAGING AGENT LABELED WITH TC-99M SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P39 EP P39 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800149 ER PT J AU ELMALEH, DR METLEV, V MENG, XJ RAPAPORT, E BABICH, JW HANSON, RH FISCHMAN, AJ ZEMACNIK, PC AF ELMALEH, DR METLEV, V MENG, XJ RAPAPORT, E BABICH, JW HANSON, RH FISCHMAN, AJ ZEMACNIK, PC TI ANTISENSE OLIGONUCLEOTIDES AS RADIOTRACERS FOR DIAGNOSTIC NUCLEAR-MEDICINE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P232 EP P232 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800942 ER PT J AU ELMALEH, DR MENG, XJ SHOUP, TM BROWNELL, AL FISCHMAN, AJ AF ELMALEH, DR MENG, XJ SHOUP, TM BROWNELL, AL FISCHMAN, AJ TI THE INVIVO BEHAVIOR OF D AND L [C-11] N-METHYLNORFENFLURAMINE AS SEROTONIN REUPTAKE LIGANDS IN RATS AND MONKEYS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P25 EP P25 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800090 ER PT J AU FISCHMAN, AJ SOLOMON, HF BABICH, JW ABRAMS, MJ CALLAHAN, RJ STRAUSS, HW RUBIN, RH AF FISCHMAN, AJ SOLOMON, HF BABICH, JW ABRAMS, MJ CALLAHAN, RJ STRAUSS, HW RUBIN, RH TI IMAGING OF FOCAL SITES OF INFLAMMATION IN NONHUMAN-PRIMATES WITH TC-99M-LABELED HUMAN POLYCLONAL IGG SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 ROBERT WOOD JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA. JOHNSON MATTHEY,W CHESTER,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P172 EP P172 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800692 ER PT J AU FISCHMAN, AJ RAUH, D SOLOMON, HF ABRAMS, MJ BABICH, JW KROON, D STRAUSS, HW RUBIN, RH AF FISCHMAN, AJ RAUH, D SOLOMON, HF ABRAMS, MJ BABICH, JW KROON, D STRAUSS, HW RUBIN, RH TI IMAGING OF FOCAL SITES OF INFLAMMATION IN NONHUMAN-PRIMATES WITH A TC99M-LABELED CHEMOTACTIC PEPTIDE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ROBERT WOOD JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA. JOHNSON MATTHEY,W CHESTER,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P104 EP P104 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800415 ER PT J AU GEWIRTZ, H FISCHMAN, AJ STRAUSS, H GILSON, M ALPERT, NM AF GEWIRTZ, H FISCHMAN, AJ STRAUSS, H GILSON, M ALPERT, NM TI PET MEASUREMENT OF REGIONAL MYOCARDIAL BLOOD-FLOW PERMITS RECOGNITION OF VIABLE AND NONVIABLE MYOCARDIUM IN HUMANS WITH CHRONIC MYOCARDIAL-INFARCTION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 RHODE ISL HOSP,PROVIDENCE,RI 02902. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P24 EP P24 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800087 ER PT J AU HAMBERG, LM HUNTER, GJ ALPERT, NM CHOI, NC CORREIA, JA BABICH, JW LORING, NA WHITE, SB FISCHMAN, AJ AF HAMBERG, LM HUNTER, GJ ALPERT, NM CHOI, NC CORREIA, JA BABICH, JW LORING, NA WHITE, SB FISCHMAN, AJ TI THE DOSE UPTAKE RATIO - USEFUL PARAMETER OR POTENTIALLY MISLEADING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P73 EP P73 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800286 ER PT J AU HENDEL, RC EAGLE, K CHEN, M LITALIAN, G NEWELL, J LEPPO, J AF HENDEL, RC EAGLE, K CHEN, M LITALIAN, G NEWELL, J LEPPO, J TI GENDER DIFFERENCES FOR LONG-TERM, CARDIAC EVENT-FREE SURVIVAL IN VASCULAR-SURGERY PATIENTS - AN ANALYSIS OF CLINICAL AND DIPYRIDAMOLE THALLIUM SCAN VARIABLES SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,CHICAGO,IL 60611. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01605. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P149 EP P149 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800597 ER PT J AU JACOBSON, AF SHAPIRO, CL KAPLAN, WD AF JACOBSON, AF SHAPIRO, CL KAPLAN, WD TI BONE METASTASES IN PATIENTS WITH BREAST-CANCER - SIGNIFICANCE OF SCINTIGRAPHIC PATTERNS AT PRESENTATION AND FOLLOW-UP SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. DVA MED CTR,SEATTLE,WA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P74 EP P74 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800291 ER PT J AU JOHNSON, KA BECKER, JA ZIMMERMAN, RE GARADA, B NAVIA, B WORTH, JL HOLMAN, BL AF JOHNSON, KA BECKER, JA ZIMMERMAN, RE GARADA, B NAVIA, B WORTH, JL HOLMAN, BL TI SPECT MR BRAIN IMAGE FUSION IN AIDS DEMENTIA COMPLEX (ADC) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P212 EP P212 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800858 ER PT J AU JOHNSON, KA KIJEWSKI, MF BECKER, JA GARADA, B SATLIN, A HOLMAN, BL AF JOHNSON, KA KIJEWSKI, MF BECKER, JA GARADA, B SATLIN, A HOLMAN, BL TI QUANTITATIVE BRAIN SPECT DISCRIMINATES ALZHEIMERS-DISEASE (AD) FROM NORMAL AGING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MCLEAN HOSP,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P208 EP P208 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800841 ER PT J AU JOHNSON, KA KIJEWSKI, MF BECKER, JA ZIMMERMAN, RE GARADA, B NAVIA, B WORTH, JL HOLMAN, BL AF JOHNSON, KA KIJEWSKI, MF BECKER, JA ZIMMERMAN, RE GARADA, B NAVIA, B WORTH, JL HOLMAN, BL TI CLASSIFICATION OF AIDS DEMENTIA COMPLEX BRAIN PERFUSION PATTERN BY QUALITATIVE AND QUANTITATIVE SPECT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P203 EP P204 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800823 ER PT J AU LIVNI, E BABICH, JW ROBEY, RL WHEELER, WJ OBANNON, DD SATTERLY, W FISCHMAN, AJ AF LIVNI, E BABICH, JW ROBEY, RL WHEELER, WJ OBANNON, DD SATTERLY, W FISCHMAN, AJ TI [C-11] DAPOXETINE (2) - A POTENTIAL AGENT FOR PET STUDIES OF SEROTONIN REUPTAKE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P240 EP P240 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800975 ER PT J AU MELDER, RJ BROWNELL, AL SHOUP, TM ELMALEH, DR BROWNELL, GL JAIN, RK AF MELDER, RJ BROWNELL, AL SHOUP, TM ELMALEH, DR BROWNELL, GL JAIN, RK TI TUMOR-LOCALIZATION AND SYSTEMIC DISTRIBUTION OF EFFECTOR-CELLS MONITORED BY POSITRON EMISSION TOMOGRAPHY (PET) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P73 EP P74 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800289 ER PT J AU MENG, XJ ELMALEH, DR FISCHMAN, AJ AF MENG, XJ ELMALEH, DR FISCHMAN, AJ TI [1-125]-N-(E)-3-IODO-ALLYL-D(L) NORFENFLURAMINE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P236 EP P236 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800958 ER PT J AU MOLEA, N WILKINSON, RA JYAWOOK, S CALLAHAN, RJ SOLOMON, HF RUBIN, RH FISCHMAN, AJ STRAUSS, HW AF MOLEA, N WILKINSON, RA JYAWOOK, S CALLAHAN, RJ SOLOMON, HF RUBIN, RH FISCHMAN, AJ STRAUSS, HW TI COMPARISON OF IN-111 IGG, TC-99M HMPAO WBCS AND TC-99M MDP IMAGING AND CONVENTIONAL X-RAY IN A RABBIT MODEL OF ACUTE AND CHRONIC OSTEOMYELITIS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RW JOHNSON RES INST,SPRING HOUSE,PA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P83 EP P83 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800328 ER PT J AU ODRISCOLL, GA STRAKOWSKI, S ALPERT, NM RAUCH, SL ELLIOTT, D LEVY, D MATTHYSSE, S HOLZMAN, PS AF ODRISCOLL, GA STRAKOWSKI, S ALPERT, NM RAUCH, SL ELLIOTT, D LEVY, D MATTHYSSE, S HOLZMAN, PS TI EXAMINATION OF THE NEURAL CONTROL OF EYE-MOVEMENTS WITH PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MCLEAN HOSP,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P203 EP P203 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800822 ER PT J AU ODRISCOLL, GA STRAKOWSKI, S ALPERT, NM RAUCH, SL ELLIOTT, D LEVY, D MATTHYSSE, S HOLZMAN, PS AF ODRISCOLL, GA STRAKOWSKI, S ALPERT, NM RAUCH, SL ELLIOTT, D LEVY, D MATTHYSSE, S HOLZMAN, PS TI EXAMINATION OF THE NEURAL CONTROL OF EYE-MOVEMENTS WITH PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MCLEAN HOSP,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P196 EP P196 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800791 ER PT J AU PARDO, FS EFFIRD, J ARONEN, H LINGGOOD, RM GRUBER, M HOCHBERG, FH ROSEN, BR OKUNIEFF, PG SCHMIDT, EV FISCHMAN, AJ AF PARDO, FS EFFIRD, J ARONEN, H LINGGOOD, RM GRUBER, M HOCHBERG, FH ROSEN, BR OKUNIEFF, PG SCHMIDT, EV FISCHMAN, AJ TI FUNCTIONAL IMAGING CORRELATES OF GLIOMA PROGNOSIS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P206 EP P206 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800834 ER PT J AU RABITO, CA PANICO, FG RUBIN, RH TOLKOFFRUBIN, N TEPLICK, RS AF RABITO, CA PANICO, FG RUBIN, RH TOLKOFFRUBIN, N TEPLICK, RS TI NONINVASIVE REAL-TIME MEASUREMENT OF RENAL-FUNCTION IN THE ACUTE CARE OF PATIENTS AT RISK OF ACUTE-RENAL-FAILURE (ARF) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P250 EP P250 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13801019 ER PT J AU RABITO, CA ALPERT, NM CHEN, Y BERDICHEVSKY, D CORREIA, JA BABICH, JW LORING, NA WISE, S HUNTER, GJ LITTMAN, B RUBIN, RH FISCHMAN, AJ AF RABITO, CA ALPERT, NM CHEN, Y BERDICHEVSKY, D CORREIA, JA BABICH, JW LORING, NA WISE, S HUNTER, GJ LITTMAN, B RUBIN, RH FISCHMAN, AJ TI RAPID MEASUREMENT OF TOTAL AND REGIONAL RENAL BLOOD-FLOW WITH POSITRON EMISSION TOMOGRAPHY AND O-15 WATER IN PATIENTS WITH DIFFERENT DEGREE OF RENAL-FAILURE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. PFIZER INC,GROTON,CT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P88 EP P88 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800349 ER PT J AU RAUCH, SL JENIKE, MA ALPERT, NM BAER, L BREITER, HCR FISCHMAN, AJ AF RAUCH, SL JENIKE, MA ALPERT, NM BAER, L BREITER, HCR FISCHMAN, AJ TI REGIONAL CEREBRAL BLOOD-FLOW MEASURED DURING BEHAVIORAL CHALLENGE IN OBSESSIVE-COMPULSIVE DISORDER - AN O-15 PET STUDY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P47 EP P47 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800180 ER PT J AU SCHAEFER, C MACHAC, J KEILP, J WAKEMAN, J DORFMAN, D BRICHTSWEIN, K CHAYES, Z STRITZKE, P INTRATOR, J AF SCHAEFER, C MACHAC, J KEILP, J WAKEMAN, J DORFMAN, D BRICHTSWEIN, K CHAYES, Z STRITZKE, P INTRATOR, J TI CEREBRAL ACTIVATION OF LEXICAL DECISION IN PSYCHOPATHS USING SINGLE-PHOTON EMISSION TOMOGRAPHY (SPECT) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,BRONX,NY. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P77 EP P78 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800306 ER PT J AU STROMSWOLD, K CAPLAN, D ALPERT, NM RAUCH, SL AF STROMSWOLD, K CAPLAN, D ALPERT, NM RAUCH, SL TI INVESTIGATING THE FUNCTIONAL NEUROANATOMY OF SYNTACTIC PROCESSING AND SENTENCE COMPREHENSION USING PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P57 EP P57 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800222 ER PT J AU WAKASUGI, S BABICH, JW FISCHMAN, AJ CALLAHAN, RJ STRAUSS, HW AF WAKASUGI, S BABICH, JW FISCHMAN, AJ CALLAHAN, RJ STRAUSS, HW TI MYOCARDIAL SUBSTRATE UTILIZATION AND LEFT-VENTRICULAR FUNCTION IN ADRIAMYCIN CARDIOMYOPATHY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 CTR ADULT DIS,OSAKA 537,JAPAN. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1993 VL 34 IS 5 SU S BP P15 EP P16 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LB138 UT WOS:A1993LB13800052 ER PT J AU KELLY, JP AF KELLY, JP TI EXPANDING THE SPECIALTY - A SURVEY OF ORAL AND MAXILLOFACIAL SURGERY RESIDENCIES IN THE UNITED-STATES - DISCUSSION SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Discussion RP KELLY, JP (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 1993 VL 51 IS 5 BP 562 EP 563 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LA573 UT WOS:A1993LA57300015 ER PT J AU GREENBERG, DB GRAY, JL MANNIX, CM EISENTHAL, S CAREY, M AF GREENBERG, DB GRAY, JL MANNIX, CM EISENTHAL, S CAREY, M TI TREATMENT-RELATED FATIGUE AND SERUM INTERLEUKIN-1 LEVELS IN PATIENTS DURING EXTERNAL BEAM IRRADIATION FOR PROSTATE-CANCER SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE FATIGUE; RADIATION TREATMENT; PROSTATE CANCER; INTERLEUKIN-1 AB To define changes in sleep and subjective fatigue associated with localized radiation treatment, and to determine their relationship to interleukin-1B (IL-1), we prospectively followed 15 men, none of whom were depressed during 8 wk of radiation treatment for localized prostate cancer. Each patient rated fatigue daily on a visual analogue scale, recorded hours slept, and completed the Beck Depression Inventory weekly. Serum IL-1, taken at baseline and Fridays, was measured by quantitative enzyme immunoassay. Ranked weekly mean fatigue scores for each subject increased at week 4 (mean, 17 fractions, 1.8 Gy) then plateaued and rose in weeks 6 and 7. In week 6, the last week of full volume radiation, subjects slept most compared to all other weeks including week 7 when treatment was coned down. Ranked serum IL-1 tended to rise between weeks 1 and 4, as fatigue scores rose. These data suggest that localized radiation treatment is associated with increased fatigue and sleep requirement independent of depressive symptoms. Relative serum IL-1 changes may be one signal for the systemic reaction and subjective fatigue associated with the acute effects of radiation. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,DEPT PSYCHIAT,COX 2,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 0 TC 104 Z9 105 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 1993 VL 8 IS 4 BP 196 EP 200 DI 10.1016/0885-3924(93)90127-H PG 5 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA LC735 UT WOS:A1993LC73500003 PM 7963760 ER PT J AU SINGER, M NOONAN, KR AF SINGER, M NOONAN, KR TI CONTINUOUS INTRAVENOUS-INFUSION OF FENTANYL - CASE-REPORTS OF USE IN PATIENTS WITH ADVANCED CANCER AND INTRACTABLE PAIN SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Note DE ADVANCED CANCER; CANCER PAIN; CONTINUOUS INTRAVENOUS OPIOIDS; FENTANYL; HIGH-DOSE OPIOIDS AB The use of continuous intravenous infusion of opioids may be efficacious in managing pain related to advanced cancer. Short-acting opioids, such as morphine and hydromorphone, are commonly used. We describe the use of a fentanyl infusion in four cases. This experience suggests that fentanyl may be considered an alternative drug for infusion in the treatment of refractory cancer pain. RP SINGER, M (reprint author), DANA FARBER CANC INST D15,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 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 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 1993 VL 8 IS 4 BP 215 EP 220 DI 10.1016/0885-3924(93)90130-N PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA LC735 UT WOS:A1993LC73500006 PM 7963762 ER PT J AU EISENBERG, JM GLICK, HA BUZBY, GP KINOSIAN, B WILLIFORD, WO AF EISENBERG, JM GLICK, HA BUZBY, GP KINOSIAN, B WILLIFORD, WO TI DOES PERIOPERATIVE TOTAL PARENTERAL-NUTRITION REDUCE MEDICAL-CARE COSTS SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID GASTROINTESTINAL SURGERY; SUPPORT AB An economic analysis accompanied a multicenter Department of Veterans Affairs randomized, controlled trial of perioperative total parenteral nutrition (TPN). The cost of providing TPN for an average of 16.15 days before and after surgery was $2405, more than half of which ($1025) included costs of purchasing, preparing, and delivering the TPN solution itself; lipid solutions accounted for another $181, additional nursing care for $843, and miscellaneous costs for $356. Prolonged hospital stay added another $764 per patient to the $2405 cost of providing TPN, bringing the total to $3169. The incremental costs attributed to perioperative TPN were highest ($3921) for the patients least likely to benefit, that is, those who were less malnourished and at low risk of nutrition-related complications. Incremental costs were lowest ($3071) for high-risk patients. On the basis of the hospital-based method of administering TPN that was used in the clinical trial, perioperative TPN did not result in decreased costs for any subgroup of patients. C1 UNIV PENN, LEONARD DAVIS INST HLTH ECON, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT MED, DEPT SURG, GEN INTERNAL MED SECT, PHILADELPHIA, PA 19104 USA. PHILADELPHIA DEPT VET AFFAIRS MED CTR, PHILADELPHIA, PA USA. DEPT VET AFFAIRS MED RES SERV, DEPT COOPERAT STUDIES PROGRAM, PERRY POINT, MD USA. GEORGETOWN UNIV, MED CTR, DEPT MED, 3800 RESERVOIR RD, WASHINGTON, DC 20007 USA. NR 20 TC 25 Z9 27 U1 0 U2 1 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD MAY-JUN PY 1993 VL 17 IS 3 BP 201 EP 209 DI 10.1177/0148607193017003201 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LA456 UT WOS:A1993LA45600002 PM 8505824 ER PT J AU HILLMAN, JD MAIDEN, MFJ PFALLER, SP MARTIN, L DUNCAN, MJ SOCRANSKY, SS AF HILLMAN, JD MAIDEN, MFJ PFALLER, SP MARTIN, L DUNCAN, MJ SOCRANSKY, SS TI CHARACTERIZATION OF HEMOLYTIC BACTERIA IN SUBGINGIVAL PLAQUE SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE HEMOLYSINS; PERIODONTAL BACTERIA; IDENTIFICATION; CHARACTERIZATION ID ESCHERICHIA-COLI; PORPHYROMONAS-GINGIVALIS; LISTERIA-MONOCYTOGENES; ALPHA-HEMOLYSIN; VIRULENCE; GENE; BACTEROIDES; EXPRESSION; CLONING AB Three-quarters of the patients with periodontal diseases surveyed in this study had one or more distinct types of hemolytic bacteria in their subgingival plaque. Twelve different species of bacteria were identified, belonging to five genera (Actinomyces, Streptococcus, Staphylococcus, Prevotella, and Actinobacillus). Nine hemolytic isolates, consisting of four Prevotella denticola strains, two Actinomyces naeslundii genospecies 2 strains, and one each of P. melaninogenica, Streptococcus constellatus, and A. naeslundii genospecies 1 strains were characterized. Incorporation of pronase into blood agar medium inhibited hemolysis by all of the isolates, suggesting a proteinaceous component for each of their hemolysins. With one exception, hemolysin production appeared to be regulated by the concentration of environmental iron: exogenous hemin was found to inhibit hemolysin production, and the iron scavenging compound, 2,2'-dipyridyl, was found to promote hemolysin production by all of the strains except for the S. constellatus isolate. Genomic libraries of each of the hemolytic plaque isolates were prepared in Escherichia coli using pBR322. Hemolytic clones were isolated on blood agar medium containing ampicillin at frequencies ranging from 1-6.7 x 10(-4). Extensive restriction mapping revealed regions of homology in the case of clones derived from three P denticola strains isolated from the same subject. Two of the P denticola-derived clones were virtually identical throughout the entirety of their > 5 Kb inserts. The clone derived from the third strain showed good homology to the other two within a 1.3 Kb region, but the flanking DNA showed no homology even though all three P denticola isolates were shown to be clonally related by ribotyping. The results indicate that hemolytic bacteria are frequently recovered from active disease sites of subjects with periodontal diseases. The hemolytic phenotype appears to be restricted to a small proportion of the total number of species normally resident in subgingival plaque. Restriction mapping suggested that a variety of hemolysin genes may be involved and that, at least in certain cases, they may be on mobile genetic elements. C1 FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. UNIV FLORIDA,SCH DENT,DEPT ORAL BIOL,GAINESVILLE,FL 32610. FU NIDCR NIH HHS [DE-04881, DE-02487] NR 27 TC 24 Z9 24 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD MAY PY 1993 VL 28 IS 3 BP 173 EP 179 DI 10.1111/j.1600-0765.1993.tb01066.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LB648 UT WOS:A1993LB64800003 PM 8496781 ER PT J AU NATHANSON, JA AF NATHANSON, JA TI IDENTIFICATION OF OCTOPAMINERGIC AGONISTS WITH SELECTIVITY FOR OCTOPAMINE RECEPTOR SUBTYPES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SENSITIVE ADENYLATE-CYCLASE; PERIPLANETA-AMERICANA L; LOCUSTA-MIGRATORIA; BINDING PROTEIN; CYCLIC-AMP; POTENT; INSECTS; MUSCLE; TISSUE; FLASH AB Previous studies utilizing relatively nonselective octopamine (OA) agonists have suggested that differences may exist between the pharmacological responses of G(s)-linked OA receptors found in various insect tissues and species. The present experiments identify and characterize two structurally related phenyl(imino)imidazolidine (PII) derivatives that demonstrate a significant degree of OA receptor subtype selectivity and, when used in concert, are able to distinguish tissue- and/or species-related differences in OA receptor response. In membrane preparations, 2,4,6-triethyl-PII (TEP) showed > 60-fold selectivity for activating adenylate cyclase in the firefly light organ vs. that in Manduca sexta nerve cord, whereas 2,4,6-trimethyl-PII (TMP) showed > 2-fold selectivity for activating adenylate cyclase in Manduca nerve cord vs. that in the light organ. Within the same tissue, the potency ratio for TEP/TMP was 29 in the light organ and 0.2 in the nerve cord, a degree of selectivity much greater than that of other PII analogs examined. Corresponding physiological measurements of octopaminergic response correlated well with biochemical measurements. TEP was 24-fold more potent than TMP for OA-mediated light emission in intact firefly light organs, whereas TMP was more than 3-fold more potent than TEP as an antifeeding agent in Manduca. These results indicate that the PII analogs, TEP and TMP, should prove quite useful for characterizing and differentiating OA receptor subtypes in various tissues and species. In addition, these findings provide further evidence that light emission in fireflies and disruption of feeding in Manduca involve G(s)-linked OA receptors, subtypes of which are distributed differently in the end organs of these two species. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP NATHANSON, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPHARMACOL RES LAB,CNY-6,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI29533] NR 35 TC 9 Z9 9 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1993 VL 265 IS 2 BP 509 EP 515 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LD060 UT WOS:A1993LD06000004 PM 8496802 ER PT J AU SHAPIRO, BH PAMPORI, NA RAM, PA WAXMAN, DJ AF SHAPIRO, BH PAMPORI, NA RAM, PA WAXMAN, DJ TI IRREVERSIBLE SUPPRESSION OF GROWTH HORMONE-DEPENDENT CYTOCHROME-P450 2C11 IN ADULT-RATS NEONATALLY TREATED WITH MONOSODIUM GLUTAMATE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID REGULATING EXPRESSION; PITUITARY REGULATION; ULTRADIAN RHYTHM; FOOD-ADDITIVES; FEMALE RATS; SECRETION; MICE; HEPATOCYTES; DEPLETION; LESIONS AB Neonatal exposure to monosodium glutamate (MSG) permanently blocks growth hormone (GH) secretion, which results in the development of a well-defined syndrome characterized by stunted body growth, obesity and impaired drug metabolism. We have found that restoration of the normal masculine circulating profile of GH (i.e., six daily pulses) by use of an external pumping apparatus is ineffective in restoring the normal expression of hepatic cytochrome P450 2C11, a major GH-dependent drug and steroid metabolizing enzyme that is eliminated by MSG treatment, Moreover, administering GH at two, four or seven plasma pulses per day with amplitudes ranging from physiologic to 7 times normal were similarly ineffective in restoring the expression (at both an activity and mRNA level) of the cytochrome. Additionally, multicytochrome P450-dependent hexobarbital hydroxylase was also unresponsive to GH administration in the MSG-treated rats. Because GH replacement was unable to correct the enzyme defects, our results suggest that the developmental abnormalities produced by neonatal MSG are not simply a result of a GH deficiency per se, but are due to an irreversible insensitivity of the target cell to GH. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP SHAPIRO, BH (reprint author), UNIV PENN,SCH VET MED,BIOCHEM LAB,3800 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NICHD NIH HHS [HD-16358]; NIDDK NIH HHS [DK-33765]; NIGMS NIH HHS [GM-45758] NR 31 TC 27 Z9 29 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1993 VL 265 IS 2 BP 979 EP 984 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LD060 UT WOS:A1993LD06000066 PM 8496838 ER PT J AU LITTMAN, AB FAVA, M HALPERIN, P LAMONFAVA, S DREWS, FR OLESHANSKY, MA BIELENDA, CC MACLAUGHLIN, RA AF LITTMAN, AB FAVA, M HALPERIN, P LAMONFAVA, S DREWS, FR OLESHANSKY, MA BIELENDA, CC MACLAUGHLIN, RA TI PHYSIOLOGICAL BENEFITS OF A STRESS REDUCTION PROGRAM FOR HEALTHY MIDDLE-AGED ARMY OFFICERS SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article ID CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; A BEHAVIOR PATTERN; DEHYDROEPIANDROSTERONE SULFATE; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PLASMA-LIPIDS; FOLLOW-UP; MEN; RISK AB Stress reduction programs (SRPs) can reduce morbidity and mortality in patients with coronary artery disease (CAD), This study evaluated the effect of an SRP on metabolic and hormonal risk factors for CAD. Twenty army officers participating in an SRP, Group I, and a comparison group of seventeen SRP nonparticipants, Group C, volunteered to undergo measurement of dehydroepiandrosterone-sulfate (DHEA-S), cortisol, DHEA-S/cortisol ratio, testosterone, apolipoprotein-A1, apolipoprotein-B, triglycerides, cholesterol, fibrinogen, and leukocyte count both before and after the SRP period. No differences in the changes in biochemical risk factors for CAD were found between participant and nonparticipant except for DHEA-S. While Group C had a marked reduction in DHEA-S levels, Group I had a small increase. Previous studies indicate DHEA-S is inversely associated with extent of CAD and age-adjusted DHEA-S levels below 3.78 mumol/l confer an increased risk for CAD mortality. SRP participation appears to effect DHEA-S levels, possibly partially accounting for the benefits observed in SRPs among CAD patients. C1 TUFTS UNIV, USDA, HUMAN NUTR CTR AGING, LIPID METAB LAB, MEDFORD, MA 02155 USA. USA, WAR COLL, CARLISLE, PA 17013 USA. MASSACHUSETTS GEN HOSP, ENDOCRINE STEROID LAB, BOSTON, MA 02114 USA. WALTER REED ARMY INST RES, WASHINGTON, DC 20307 USA. RP LITTMAN, AB (reprint author), MASSACHUSETTS GEN HOSP, CTR CARDIOVASC HLTH, BEHAV MED CLIN, DEPT PSYCHIAT, DIV BEHAV MED, BOSTON, MA 02114 USA. NR 49 TC 15 Z9 15 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD MAY PY 1993 VL 37 IS 4 BP 345 EP 354 DI 10.1016/0022-3999(93)90136-4 PG 10 WC Psychiatry SC Psychiatry GA LB664 UT WOS:A1993LB66400004 PM 8510060 ER PT J AU SCHUMACHER, HR HUDSON, AP BARDIN, T AF SCHUMACHER, HR HUDSON, AP BARDIN, T TI SHOULD WE TREAT POSTVENEREAL REITERS-SYNDROME BY ANTIBIOTICS - REPLY SO JOURNAL OF RHEUMATOLOGY LA English DT Letter C1 HOP LARIBOISIERE,RHUMATOL CLIN,F-75475 PARIS 10,FRANCE. RP SCHUMACHER, HR (reprint author), UNIV PENN,SCH MED,VET AFFAIRS MED CTR,CTR ARTHRITIS IMMUNOL,PHILADELPHIA,PA 19104, USA. NR 15 TC 2 Z9 2 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 MAY PY 1993 VL 20 IS 5 BP 907 EP 908 PG 2 WC Rheumatology SC Rheumatology GA LC727 UT WOS:A1993LC72700032 ER PT J AU MCLELLAN, AT GRISSOM, GR BRILL, P DURELL, J METZGER, DS OBRIEN, CP AF MCLELLAN, AT GRISSOM, GR BRILL, P DURELL, J METZGER, DS OBRIEN, CP TI PRIVATE SUBSTANCE-ABUSE TREATMENTS - ARE SOME PROGRAMS MORE EFFECTIVE THAN OTHERS SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE SUBSTANCE ABUSE; TREATMENT; OUTCOME; EFFICACY ID ALCOHOLISM AB There have been few studies of treatments for substance dependence among private programs. The present study compared the patient populations, treatment services provided and six-month outcomes of employed, insured patients referred by an employee assistance program to four private treatment programs (two inpatient and two outpatient). Subjects were alcohol and/or cocaine dependent males referred from a single employer. Ninety-four percent were successfully contacted at six-month follow-up, with confirmatory urinalysis and breathalyzer samples taken. Three results were obtained. First, there were significant and pervasive improvements shown in the total sample at follow-up. Fifty-nine percent were completely abstinent, 82% were working and only 8% required re-treatment. Second, there were significant differences among the programs in levels of improvement and six-month outcomes. Finally, the differences in efficacy were related to the differences in the nature and amount of treatment services provided. C1 INTEGRA INC,RADNOR,PA. RP MCLELLAN, AT (reprint author), VET AFFAIRS MED CTR,DEPT PSYCHIAT,CTR STUDIES ADDICT,BLD 7,UNIV AVE,PHILADELPHIA,PA 19104, USA. RI Metzger, David/D-9499-2012 NR 22 TC 80 Z9 80 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAY-JUN PY 1993 VL 10 IS 3 BP 243 EP 254 DI 10.1016/0740-5472(93)90071-9 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA LE199 UT WOS:A1993LE19900001 PM 8391086 ER PT J AU LANCIANO, RM CALKINS, AR WOLKOV, HB BUZYDLOWSKI, J NOYES, RD SAUSE, W NELSON, D WILLETT, C OWENS, JC HANKS, GM AF LANCIANO, RM CALKINS, AR WOLKOV, HB BUZYDLOWSKI, J NOYES, RD SAUSE, W NELSON, D WILLETT, C OWENS, JC HANKS, GM TI A PHASE-I/II STUDY OF INTRAOPERATIVE RADIOTHERAPY IN ADVANCED UNRESECTABLE OR RECURRENT CARCINOMA OF THE RECTUM - A RADIATION-THERAPY ONCOLOGY GROUP (RTOG) STUDY SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE INTRAOPERATIVE RADIOTHERAPY; RECTAL CARCINOMA ID PREOPERATIVE IRRADIATION; CANCER AB The Radiation Therapy Oncology Group (RTOG) initiated a phase I/II study of intraoperative radiotherapy (IORT) in advanced or recurrent rectal cancer to assess therapeutic efficacy, toxicity, and establish quality control guidelines prior to beginning a phase III trial. From October 1985 through December 1989, 87 patients with histologically proven adenocarcinoma of the rectum or rectosigmoid with recurrent/persistent disease after surgery or those primarily inoperable were entered by 14 institutions. Of 86 evaluable patients, 42 patients received IORT either alone (n = 15) or in combination with external beam (n = 27). Local control was dependent on the amount of residual disease prior to IORT, with 2-year actuarial local control of 77% if no gross residual disease remained vs. 10% with gross residual disease (P = 0.0001). For the recurrent/residual group (n = 33), this observation was also significant with a 2-year actuarial local control rate of 64% if no gross residual remained vs. 10% with gross residual disease (P = 0.004). Local control translated into an improved survival for all patients and the recuffent/residual group with 2-year actuarial survival of 88% and 89% if no gross residual disease remained vs. 48% and 45% with gross residual disease, respectively (P = .0005, 0.006). Six patients (14.6%) experienced four grade 3 and three grade 4 complications as a possible result of IORT during follow-up with a 2-year actuarial risk of major complications of 16%. We conclude that IORT is feasible within a cooperative group and can be performed with acceptable complication rates. A phase III trial to demonstrate a therapeutic advantage for IORT over external beam alone is currently in progress. C1 FOX CHASE CANC CTR,DEPT RADIAT ONCOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111. AMER COLL RADIOL,DEPT STAT,PHILADELPHIA,PA. JOHNS HOPKINS UNIV HOSP,DEPT RADIAT ONCOL,BALTIMORE,MD 21205. SUTTER COMMUNITY HOSP,CTR RADIAT ONCOL,DEPT RADIAT ONCOL,SACRAMENTO,CA. LDS HOSP,DEPT RADIAT ONCOL,SALT LAKE CITY,UT. HIGHLAND HOSP,DEPT RADIAT ONCOL,ROCHESTER,NY 14620. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP LANCIANO, RM (reprint author), FOX CHASE CANC CTR,DEPT RADIAT ONCOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. NR 13 TC 30 Z9 30 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAY PY 1993 VL 53 IS 1 BP 20 EP 29 DI 10.1002/jso.2930530108 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA LA010 UT WOS:A1993LA01000005 PM 8479193 ER PT J AU MENTZER, SJ ANTMAN, KH ATTINGER, C SHEMIN, R CORSON, JM SUGARBAKER, DJ AF MENTZER, SJ ANTMAN, KH ATTINGER, C SHEMIN, R CORSON, JM SUGARBAKER, DJ TI SELECTED BENEFITS OF THORACOTOMY AND CHEMOTHERAPY FOR SARCOMA METASTATIC TO THE LUNG SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE PULMONARY METASTASES; DOXORUBICIN; SURGERY; LONG-TERM SURVIVAL ID SOFT-TISSUE SARCOMA; PULMONARY METASTASES; OSTEOGENIC-SARCOMA; MEDIAN STERNOTOMY; ADJUVANT CHEMOTHERAPY; SURGICAL RESECTION; SURVIVAL; DOXORUBICIN; IFOSFAMIDE; NEOPLASMS AB To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy. Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. BOSTON UNIV HOSP,SCH MED,DEPT CARDIOTHORAC SURG,BOSTON,MA 02218. GEORGETOWN UNIV,MED CTR,SCH MED,DEPT PLAST SURG,WASHINGTON,DC 20007. RP MENTZER, SJ (reprint author), BRIGHAM & WOMENS HOSP,DEPT SURG,DIV THORAC SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 52 TC 15 Z9 16 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAY PY 1993 VL 53 IS 1 BP 54 EP 59 DI 10.1002/jso.2930530114 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA LA010 UT WOS:A1993LA01000010 PM 8479198 ER PT J AU FISHER, PW SHAFFER, D PIACENTINI, JC LAPKIN, J KAFANTARIS, V LEONARD, H HERZOG, DB AF FISHER, PW SHAFFER, D PIACENTINI, JC LAPKIN, J KAFANTARIS, V LEONARD, H HERZOG, DB TI SENSITIVITY OF THE DIAGNOSTIC INTERVIEW SCHEDULE FOR CHILDREN, 2ND EDITION (DISC-2.1) FOR SPECIFIC DIAGNOSES OF CHILDREN AND ADOLESCENTS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DIAGNOSTIC INTERVIEW; SENSITIVITY; MEASUREMENT ID SCHOOL-AGE-CHILDREN; AFFECTIVE-DISORDERS; PSYCHIATRIC INTERVIEW; K-SADS; RELIABILITY; VALIDITY; SCHIZOPHRENIA; AGREEMENT; PARENT; POPULATION AB Objective: The sensitivity of the Diagnostic Interview Schedule for Children, second edition (DISC-2.1) was examined for certain ''rare'' disorders: eating disorders, major depressive episode, obsessive compulsive disorder, psychosis, tic disorders, and substance use disorders. Method: Subjects recruited from specialized centers were interviewed with the DISC-2.1; the centers' diagnoses served as the criterion measure. Results: Overall the DISC showed good to excellent sensitivity (range = 0.73 to 1.0). Used alone, the DISC-P (parent interview) was generally more sensitive than the DISC-C (child interview). Areas for additional instrument revision were identified. Recommendations about informant choice by diagnosis are offered. Conclusions: The strategy used in this study was useful for assessing the DISC's sensitivity for these disorders. Additional work examining specificity of the DISC remains to be done. The DISC should prove a useful adjunct in clinical settings given the ease and relatively low cost of administration. C1 SCHNEIDER CHILDRENS HOSP,LONG ISL JEWISH MED CTR,DEPT PSYCHIAT,NEW HYDE PK,NY. COLUMBIA UNIV,DIV CHILD & ADOLESCENT PSYCHIAT,NEW YORK,NY 10027. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP FISHER, PW (reprint author), NYSPI,UNIT 78,722 W 168TH ST,NEW YORK,NY 10032, USA. RI Piacentini, John/C-4645-2011 FU NIMH NIH HHS [MH-36971, MH-16434, MHCRC-30906] NR 30 TC 178 Z9 180 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1993 VL 32 IS 3 BP 666 EP 673 DI 10.1097/00004583-199305000-00026 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA KY441 UT WOS:A1993KY44100026 PM 8496131 ER PT J AU MANGIONE, CM SEDDON, JM COOK, EF KRUG, JH SAHAGIAN, CR CAMPION, EW GLYNN, RJ AF MANGIONE, CM SEDDON, JM COOK, EF KRUG, JH SAHAGIAN, CR CAMPION, EW GLYNN, RJ TI CORRELATES OF COGNITIVE FUNCTION SCORES IN ELDERLY OUTPATIENTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID MINI-MENTAL STATE; STATUS QUESTIONNAIRE; ALZHEIMERS-DISEASE; SCREENING-TEST; IMPAIRMENT; DEMENTIA AB Objective: To determine medical, ophthalmologic, and demographic predictors of cognitive function scores as measured by the Telephone Interview for Cognitive Status (TICS), an adaptation of the Folstein Mini-Mental Status Exam. A secondary objective was to perform an item-by-item analysis of the TICS scores to determine which items correlated most highly with the overall scores. Design: Cross-sectional cohort study. Setting: The Glaucoma Consultation Service of the Massachusetts Eve and Ear Infirmary. Subjects: 472 of 565 consecutive patients age 65 and older who were seen at the Glaucoma Consultation Service between November 1, 1987 and October 31, 1988. Measurements: Each subject had a standard visual examination and review of medical history at entry, followed by a telephone interview that collected information on demographic characteristics, cognitive status, health status, accidents, falls, symptoms of depression, and alcohol intake. Results: A multivariate linear regression model of correlates of TICS score found the strongest correlates to be education, age, occupation, and the presence of depressive symptoms. The only significant ocular condition that correlated with lower TICS score was the presence of surgical aphakia (model R2 = .46). Forty-six percent (216/472) of patients fell below the established definition of normal on the mental status scale. In a logistic regression analysis, the strongest correlates of an abnormal cognitive function score were age, diabetes, educational status, and occupational status. An item analysis using step-wise linear regression showed that 85 percent of the variance in the TICS score was explained by the ability to perform serial sevens and to repeat 10 items immediately after hearing them. Educational status correlated most highly with both of these items (Kendall Tau R = .43 and Kendall Tau R = .30, respectively). Conclusion: Education, occupation, depression, and age were the strongest correlates of the score on this new screening test for assessing cognitive status. These factors were stronger correlates of the TICS score than chronic medical conditions, visual loss, or medications. The Telephone Interview for Cognitive Status is a useful instrument, but it may overestimate the prevalence of dementia in studies with a high prevalence of persons with less than a high school education. C1 MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,GLAUCOMA SERV,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV AGING,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. NR 24 TC 47 Z9 48 U1 3 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1993 VL 41 IS 5 BP 491 EP 497 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LA893 UT WOS:A1993LA89300003 PM 8486880 ER PT J AU ROYALL, DR MAHURIN, RK GRAY, KF AF ROYALL, DR MAHURIN, RK GRAY, KF TI EXECUTIVE COGNITIVE IMPAIRMENT - REPLY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP ROYALL, DR (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1993 VL 41 IS 5 BP 577 EP 578 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LA893 UT WOS:A1993LA89300022 ER PT J AU SHIPLEY, WU AF SHIPLEY, WU TI RADICAL RETROPUBIC PROSTATECTOMY AND POSTOPERATIVE ADJUVANT RADIATION FOR PATHOLOGICAL STAGE-C (PCN0) PROSTATE-CANCER FROM 1976 TO 1989 - INTERMEDIATE FINDINGS - COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material RP SHIPLEY, WU (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1993 VL 149 IS 5 BP 1034 EP 1034 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA LA464 UT WOS:A1993LA46400022 ER PT J AU FAHA, B HARLOW, E LEES, E AF FAHA, B HARLOW, E LEES, E TI THE ADENOVIRUS E1A-ASSOCIATED KINASE CONSISTS OF CYCLIN E-P33CDK2 AND CYCLIN A-P33CDK2 SO JOURNAL OF VIROLOGY LA English DT Review ID RETINOBLASTOMA SUSCEPTIBILITY GENE; E2F TRANSCRIPTION FACTOR; CELLULAR DNA-SYNTHESIS; CDC2 PROTEIN-KINASE; REGION 1A PROTEINS; E1A PROTEINS; FISSION YEAST; RAT-CELLS; SCHIZOSACCHAROMYCES-POMBE; MESSENGER-RNA AB The adenovirus EIA oncoproteins form stable complexes with several cellular proteins. Association of E1A with these proteins has been shown to be important for the oncogenic potential of E1A. Several of these proteins have been identified and include the product of the retinoblastoma gene and a key cell cycle regulatory protein, cyclin A. E1A also associates with a potent histone H1 kinase. The two major components of this activity are the cyclin E-p33cdks and cyclin A-p33cdk2 complexes. Both the cyclin E-p33cdk2 and cyclin A-p33cdk2 complexes have been implicated in regulatory events controlling entry into or passage through DNA synthesis. Although the architecture of such interactions remains unclear. it is likely that by targeting such complexes, adenovirus is affecting some aspect of cell cycle control. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. FU NCI NIH HHS [CA55339] NR 115 TC 73 Z9 73 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 MAY PY 1993 VL 67 IS 5 BP 2456 EP 2465 PG 10 WC Virology SC Virology GA KX335 UT WOS:A1993KX33500005 PM 8386263 ER PT J AU CAO, J BERGERON, L HELSETH, E THALI, M REPKE, H SODROSKI, J AF CAO, J BERGERON, L HELSETH, E THALI, M REPKE, H SODROSKI, J TI EFFECTS OF AMINO-ACID CHANGES IN THE EXTRACELLULAR DOMAIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP41 ENVELOPE GLYCOPROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID SOLUBLE CD4 BINDING; HTLV-III/LAV; MONOCLONAL-ANTIBODY; RECEPTOR-BINDING; MEMBRANE-FUSION; T4 MOLECULE; TRANSMEMBRANE PROTEIN; OLIGOMERIC STRUCTURE; AIDS PATIENTS; GP120 AB Changes were introduced into conserved amino acids within the ectodomain of the human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope glycoprotein. The effect of these changes on the structure and function of the HIV-1 envelope glycoproteins was examined. The gp41 glycoprotein contains an amino-terminal fusion peptide (residues 512 to 527) and a disulfide loop near the middle of the extracellular domain (residues 598 to 604). Mutations affecting the hydrophobic sequences between these two regions resulted in two phenotypes. Some changes in amino acids 528 to 562 resulted in a loss of the noncovalent association between gp41 and the gp120 exterior glycoprotein. Amino acid changes in other parts of the gp41 glycoprotein (residues 608 and 628) also resulted in subunit dissociation. Some changes affecting amino acids 568 to 596 resulted in envelope glycoproteins partially or completely defective in mediating membrane fusion. Syncytium formation was more sensitive than virus entry to these changes. Changes in several amino acids from 647 to 675 resulted in higher-than-wild-type syncytium-forming ability. One of these amino acid changes affecting tryptophan 666 resulted in escape from neutralization by an anti-gp41 human monoclonal antibody, 2F5. These results contribute to an understanding of the functional regions of the HTV-1 gp41 ectodomain. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI24755] NR 86 TC 223 Z9 224 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1993 VL 67 IS 5 BP 2747 EP 2755 PG 9 WC Virology SC Virology GA KX335 UT WOS:A1993KX33500039 PM 8474172 ER PT J AU JASSOY, C HARRER, T ROSENTHAL, T NAVIA, BA WORTH, J JOHNSON, RP WALKER, BD AF JASSOY, C HARRER, T ROSENTHAL, T NAVIA, BA WORTH, J JOHNSON, RP WALKER, BD TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES RELEASE GAMMA-INTERFERON, TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA), AND TNF-BETA WHEN THEY ENCOUNTER THEIR TARGET ANTIGENS SO JOURNAL OF VIROLOGY LA English DT Article ID AIDS DEMENTIA COMPLEX; CEREBROSPINAL-FLUID; HIV-1 INFECTION; CELL CLONES; SYNTHETIC PEPTIDES; IMMUNE INTERFERON; FINE SPECIFICITY; INDIVIDUALS; EXPRESSION; NEOPTERIN AB Human immunodeficiency virus type 1 (HIV-1) infection is associated with elevated levels of inflammatory cytokines in the serum and cerebrospinal fluid of infected persons, but the sources of these proteins as well as the specific stimuli which trigger their production and release have not been fully defined. In this study, we evaluated the ability of HIV-1-specific cytotoxic T-lymphocyte (CTL) clones derived from seropositive persons to release gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and TNF-beta upon contact with target cells presenting viral antigen. Peripheral blood- and cerebrospinal fluid-derived HIV-1-specific CD3+ CD4- CD8+ CTL clones as well as freshly isolated peripheral blood mononuclear cells from infected persons were tested in parallel for HIV-1-specific cytotoxicity and cytokine release. Target cells consisted of autologous and allogeneic B-lymphoblastoid cell lines sensitized with synthetic HIV-1 peptides containing the epitopes recognized by these CTL. Cytokine production was measured by specific enzyme-linked immunosorbent assay of culture supernatant fluid. HIV-1-specific CTL clones directed at envelope, Gag, reverse transcriptase, and Nef epitopes specifically released IFN-gamma, TNF-alpha, and TNF-beta upon contact with their relevant target epitopes but not following contact with irrelevant epitopes. These cytokines were released in an HLA class I-restricted fashion, and release was detectable as early as 4 to 6 h of incubation and remained elevated at 48 h. Fresh peripheral blood mononuclear cells from a seropositive person likewise released IFN-gamma in an antigen-specific and HLA class I-restricted manner when incubated with target cells presenting a peptide containing a CTL epitope, paralleling the HIV-specific cytolytic activity of these cells. These studies indicate that in addition to mediating direct cytotoxicity, HIV-1-specific CTL may affect other immune responses by releasing IFN-gamma, TNF-alpha, and TNF-beta. Elevated levels of these cytokines which have been detected in serum and cerebrospinal fluid of infected persons may be due at least in part to the persistent HIV-1-specific CTL response. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,FRUIT ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. FU NIAID NIH HHS [AI 30914, AI 26463, AI 28568] NR 62 TC 110 Z9 110 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1993 VL 67 IS 5 BP 2844 EP 2852 PG 9 WC Virology SC Virology GA KX335 UT WOS:A1993KX33500050 PM 7682629 ER PT J AU BONVENTRE, JV AF BONVENTRE, JV TI MECHANISMS OF ISCHEMIC ACUTE-RENAL-FAILURE SO KIDNEY INTERNATIONAL LA English DT Review ID CYTOSOLIC FREE CALCIUM; ACUTE TUBULAR-NECROSIS; DIFFERENTIAL GENE-EXPRESSION; GLOMERULAR MESANGIAL CELLS; OXYGEN FREE-RADICALS; HEAT-SHOCK RESPONSE; RAT-KIDNEY; SUPEROXIDE-DISMUTASE; EPITHELIAL POLARITY; PROXIMAL TUBULES C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-38452, DK-39773]; NINDS NIH HHS [NS-10828] NR 191 TC 382 Z9 390 U1 0 U2 5 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1993 VL 43 IS 5 BP 1160 EP 1178 DI 10.1038/ki.1993.163 PG 19 WC Urology & Nephrology SC Urology & Nephrology GA KX289 UT WOS:A1993KX28900024 PM 8510397 ER PT J AU ROBERTS, DJ HABER, D SKLAR, J CRUM, CP AF ROBERTS, DJ HABER, D SKLAR, J CRUM, CP TI EXTRARENAL WILMS-TUMORS - A STUDY OF THEIR RELATIONSHIP WITH CLASSICAL RENAL WILMS-TUMOR USING EXPRESSION OF WT1 AS A MOLECULAR MARKER SO LABORATORY INVESTIGATION LA English DT Article DE DEVELOPMENT; GYNECOLOGIC MALIGNANCIES; GENITOURINARY DEVELOPMENT; GENITAL DISEASE ID MESSENGER-RNAS; GENE WT1; PROGNOSIS; DELETION AB BACKGROUND: Wilms' tumors (WT) are renal malignancies typically of childhood with classic histopathologic features. A candidate WT gene (WT1) has been described, expression of which is largely restricted to the developing genitourinary system. WT1 is highly expressed in most sporadic childhood renal WT, and inactivating mutations have been described, consistent with its role as a tumor suppressor gene. WT1, therefore, may be used as a molecular marker for renal WT in most cases. Rarely, do tumors, that histologically resemble WT, develop in adult kidneys or exceptionally at nonrenal sites. This study addresses the question, are extrarenal tumors that have the morphology of renal WT really a type of WT? We investigated this question by using WT1 expression as a molecular marker for WT. EXPERIMENTAL DESIGN: We studied WT1 expression in eight well-documented cases of extra-renal WT by RNA-RNA in situ hybridization using an S-35-labeled probe derived from a cloned WT1 gene sequence. RESULTS: WT1 mRNA expression was detected in 5 of 5 childhood cases of sporadic childhood renal WT and 2 of 8 extrarenal WT. Both WT1-positive extrarenal WT were endometrial primaries. The WT1-negative extrarenal WT included retroperitoneal (3), pararenal or paravesical (2), and paraspinal (1) primaries. The seven non-WT uterine malignancies (carcinomas and sarcomas) studied were WT1-negative. CONCLUSIONS: These findings suggest that some cases of extrarenal WT are related to classical renal WT by more than mere morphologic resemblance, as indicated by the detection of WT1 mRNA expression in at least a subset of these rare tumors. Furthermore, the results suggest different pathogeneses of subsets of extrarenal WT. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV MOLEC ONCOL,BOSTON,MA 02115. RP ROBERTS, DJ (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV WOMENS & PERINATAL PATHOL,BOSTON,MA 02115, USA. FU PHS HHS [R01-47676] NR 26 TC 23 Z9 23 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 MAY PY 1993 VL 68 IS 5 BP 528 EP 536 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA LD864 UT WOS:A1993LD86400005 PM 8388523 ER PT J AU SILVERMAN, LR HOLLAND, JF WEINBERG, RS ALTER, BP DAVIS, RB ELLISON, RR DEMAKOS, EP CORNELL, CJ CAREY, RW SCHIFFER, C ILL, EF MCINTYRE, OR AF SILVERMAN, LR HOLLAND, JF WEINBERG, RS ALTER, BP DAVIS, RB ELLISON, RR DEMAKOS, EP CORNELL, CJ CAREY, RW SCHIFFER, C ILL, EF MCINTYRE, OR TI EFFECTS OF TREATMENT WITH 5-AZACYTIDINE ON THE INVIVO AND INVITRO HEMATOPOIESIS IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES SO LEUKEMIA LA English DT Article; Proceedings Paper CT WORKSHOP ON 5-AZA-2 - DEOXYCYTIDINE AND DNA METHYLTRANSFERASE INHIBITORS, AT THE 5TH INTERNATIONAL SYMP ON THERAPY OF ACUTE LEUKEMIAS CY NOV 03, 1991 CL ROME, ITALY ID COLONY-STIMULATING FACTOR; RECOMBINANT-HUMAN-ERYTHROPOIETIN; FRIEND-ERYTHROLEUKEMIA CELLS; FETAL HEMOGLOBIN PRODUCTION; ERYTHROID PROGENITOR CELLS; DOSE CYTOSINE-ARABINOSIDE; 13-CIS RETINOIC ACID; MARROW STROMAL CELLS; PHASE-I-II; BONE-MARROW AB The myelodysplastic syndrome (MDS) comprises a group of clonal hematopoietic disorders derived from an abnormality affecting a multipotent hematopoietic stem cell. Despite trials testing numerous agents in patients with MDS, no single drug has yet emerged as the accepted standard of treatment. Observation and supportive care with blood products and antibiotics, when necessary, continue to be the mainstays of therapy. We administered 5-azacytidine, a cell-cycle specific ring analog of the pyrimidine nucleoside cytosine, as a continuous intravenous infusion, 75 mg/m2 per day for 7 days every 4 weeks. Patients had refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T). Responses were seen in 21 (49%) of 43 evaluable patients: five (1 2 %) in complete remission (CR, complete normalization of bone marrow and peripheral blood counts); 11 (25%) in partial remission (PR, greater-than-or-equal-to 50% restoration of the deficit from normal of all three peripheral blood cell lines, elimination of transfusion requirements, and a decrease in percentage bone marrow blasts by greater-than-or-equal-to 50% from prestudy values); five (12%) improved (greater-than-or-equal-to 50% restoration in the deficit from normal of one or more peripheral blood cell lines and/or a greater-than-or-equal-to 50% decrease in transfusion requirements). A trilineage improvement (CR and PR) occurred in 37% of the patients. The median survival for all patients was 13.3 months and the median duration of remission for those with CR and PR was 14.7 months. Mild to moderate nausea and/or vomiting was the most common side effect (63%). Myelosuppression, either bone marrow hypoplasia or drug related cytopenias requiring a reduction in the dose of azacitidine, occurred in only 33% of the patients. Prior to treatment, bone marrow erythroid progenitor cells were assayed in vitro. Colonies derived from erythroid burst-forming units (BFU-e) were undetectable in one patient and reduced in two. The number of colonies derived from erythroid colony-forming units (CFU-e)) were also reduced in two of the three patients. In the two patients with detectable colony growth prior to treatment, colony number decreased by day 8 of the first cycle, followed by a subsequent increase. Continued treatment with azacitidine led to normalization of the number of CFU-e derived colonies as well as an increase in the number of BFU-e derived colonies. This improvement in erythroid colony number correlated with the spontaneous rise in hemoglobin levels and red cell transfusion independence. Subsequent decrease in colony number (CFU-e, BFU-e) preceded a progressive fall in hemoglobin levels by 2 to 4 months. Azacitidine is an effective agent for the treatment of patients with RAEB and RAEB-T. The trilineage response rate is higher than those reported with the hematopoietic growth factors erythropoietin, interleukin-3, granulocyte-macrophage or granulocyte colony-stimulating factors (GM-CSF or G-CSF). Further trials testing azacitidine in a regimen administered in an ambulatory setting have been initiated. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,NORRIS COTTON CANC CTR,HANOVER,NH 03756. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. COLUMBIA UNIV,NEW YORK,NY 10027. RP SILVERMAN, LR (reprint author), MT SINAI MED CTR,DEPT NEOPLAST DIS,BOX 1129,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. FU NCI NIH HHS [CA-04326, CA-04457, CA 31946] NR 62 TC 154 Z9 162 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1993 VL 7 SU 1 BP 21 EP 29 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA LE632 UT WOS:A1993LE63200006 PM 7683352 ER PT J AU PICHERT, G RITZ, J AF PICHERT, G RITZ, J TI CLINICAL-SIGNIFICANCE OF BCR-ABL GENE REARRANGEMENT DETECTED BY THE POLYMERASE CHAIN-REACTION AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION IN CHRONIC MYELOGENOUS LEUKEMIA SO LEUKEMIA & LYMPHOMA LA English DT Article DE BCR-ABL; GENE REARRANGEMENT; PCR; ALLOGENEIC BONE MARROW TRANSPLANTATION; CML; CHRONIC MYELOGENOUS LEUKEMIA AB Although serial detection of bcr-abl positive cells by PCR appears able to identify distinct patient groups with different risks of relapse following BMT, there remain many unanswered questions regarding the clinical utility and biological significance of PCR detectable cells in this disease. Many of the studies summarized have conflicting results and the influence of various clinical parameters which are known to affect the fisk of relapse post-BMT has not yet been consistently associated with the ability to detect bcr-abl positive cells by PCR. These clinical parameters include GVHD, T-cell depletion and intensity of immunosuppression following BMT. Prospective studies with larger patient numbers will be necessary to define the impact of these factors in PCR status and relapse. The answers to all these questions will increase our understanding of the biology of chronic myelogenous leukemia and help provide more effective therapies for the future. RP PICHERT, G (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI 29530] NR 0 TC 9 Z9 9 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAY PY 1993 VL 10 IS 1-2 BP 1 EP 8 DI 10.3109/10428199309147350 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA LN720 UT WOS:A1993LN72000001 PM 8374516 ER PT J AU SHEN, T WEISSLEDER, R PAPISOV, M BOGDANOV, A BRADY, TJ AF SHEN, T WEISSLEDER, R PAPISOV, M BOGDANOV, A BRADY, TJ TI MONOCRYSTALLINE IRON-OXIDE NANOCOMPOUNDS (MION) - PHYSICOCHEMICAL PROPERTIES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE PHARMACEUTICALS; IRON OXIDE; CONTRAST AGENTS; MAGNETISM AB We have previously described a novel monocrystalline iron oxide nanocompound (MION), a stable colloid that enables target specific MR imaging. In this study, the physicochemical properties of MION are reported using a variety of analytical techniques. High resolution electron microscopy indicates that a MION consists of hexagonal shaped electron-dense cores of 4.6 +/- 1.2 nm in diameter. This iron oxide core has an inverse spinel crystal structure which was confirmed by x-ray powder diffraction. Chemical analysis showed that each core has 25 +/- 6 dextran molecules (10 kD) attached, resulting in a unimodal hydrodynamic radius of 20 nm by laser light scattering. Because of the flexibility of the dextran layer, the radius is only 8 nm in nonaqueous reverse micelles. At room temperature, MION exhibit superparamagnetic behavior with an induced magnetization of 68 emu/g Fe at 1.5 T. Mossbauer studies show that the saturation internal magnetic field is 505 KOe, and blocking temperature is at 100 K. The R1 relaxivity of MION is 16.5 (mM.sec)-1 and the R2 relaxivity is 34.8 (mM.sec)-1 in aqueous solution at 37-degrees-C and 0.47 T in vitro phantom studies show that the detectability of MION in liver tissue is less than 50 nmol Fe/g tissue using gradient echo imaging techniques. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA. FU NCI NIH HHS [1RO1 CA54886-01] NR 13 TC 405 Z9 414 U1 1 U2 48 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 MAY PY 1993 VL 29 IS 5 BP 599 EP 604 DI 10.1002/mrm.1910290504 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KZ525 UT WOS:A1993KZ52500003 PM 8505895 ER PT J AU PFLEIDERER, B ACKERMAN, JL GARRIDO, L AF PFLEIDERER, B ACKERMAN, JL GARRIDO, L TI INVIVO H-1 CHEMICAL-SHIFT IMAGING OF SILICONE IMPLANTS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE SILICONE; CHEMICAL SHIFT IMAGING; MIGRATION ID STIMULATED ECHOES; GEL PROSTHESES; BREAST AB In order to study the aging process (i.e., silicone migration, fat infiltration) of silicone (polydimethylsiloxane, PDMS) based biomaterials in living subjects by NMR imaging, a hybrid H-1 selective excitation and saturation chemical shift imaging technique (IR/CHESS-CSSE) has been developed. This sequence allows selective mapping of the distribution of silicone protons in vivo, while suppressing the contributions of fat and water. Our results indicate that a combined inversion recovery and CHESS pulse, followed by a spoiler gradient, must be applied to suppress all contributions of fat protons to the NMR signal. The sensitivity of our experiments allows the detection of a chemically unchanged silicone concentration of 5% in a voxel of 0.9 mm3 at a signaL/noise ratio of 2. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NMR,BLDG 149,13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 NR 25 TC 20 Z9 20 U1 1 U2 1 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 MAY PY 1993 VL 29 IS 5 BP 656 EP 659 DI 10.1002/mrm.1910290512 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KZ525 UT WOS:A1993KZ52500011 PM 8505902 ER PT J AU HASTY, KA WU, H BYRNE, M GOLDRING, MB SEYER, JM JAENISCH, R KRANE, SM MAINARDI, CL AF HASTY, KA WU, H BYRNE, M GOLDRING, MB SEYER, JM JAENISCH, R KRANE, SM MAINARDI, CL TI SUSCEPTIBILITY OF TYPE-I COLLAGEN CONTAINING MUTATED ALPHA-1(1) CHAINS TO CLEAVAGE BY HUMAN NEUTROPHIL COLLAGENASE SO MATRIX LA English DT Article DE FIBROBLAST COLLAGENASE; METALLOPROTEINASE; NEUTROPHIL COLLAGENASE; SITE-DIRECTED MUTAGENESIS; TYPE-I COLLAGEN ID EMBRYONIC LETHAL MUTATION; FIBROBLAST COLLAGENASE; SECRETED FORMS; GENE; SPECIFICITY; HOMOLOGY; DEATH; SITE AB Two members of the matrix metalloproteinase family which can cleave native types I, II and III triple helical collagens are collagenases from fibroblasts and neutrophils. These enzymes are the products of different genes which share structural motifs but are only 57% identical. In this study, we determined the site of cleavage in the alpha1 (I) chains and showed that the neutrophil collagenase acted at the same site as the fibroblast collagenase. We also used collagens as substrates which were generated by site-directed mutagenesis of the murine Colla 1 gene and found that the pattern of susceptibility to cleavage by purified neutrophil collagenase was indistinguishable from that previously described for the fibroblast collagenase. Collagens containing substitutions of Pro for Ile-776 (P1) were not cleaved; whereas those containing substitutions of Met for Ile-776 were cleaved. Type I collagen which contained alpha1(I) chains in which there were double substitutions of Pro for Gln-774 (P2) and Ala-777 (P2') were also not cleaved. These type I collagens contained wild type alpha2(I) chains as well as mutant alpha1(I) chains in the mixed helical trimers; the alpha2(I) chain in the trimers containing the resistant alpha1(I) chains were also not cleaved by the neutrophil collagenase. C1 UNIV TENNESSEE CTR HLTH SCI,DEPT MED,MEMPHIS,TN 38104. UNIV TENNESSEE CTR HLTH SCI,DEPT BIOCHEM,MEMPHIS,TN 38104. WHITEHEAD INST BIOMED RES,DEPT BIOL,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP HASTY, KA (reprint author), UNIV TENNESSEE CTR HLTH SCI,DEPT ANAT & NEUROBIOL,MEMPHIS,TN 38104, USA. FU NCI NIH HHS [5R35CA443339]; NIAMS NIH HHS [AR-39166, AR-39472] NR 20 TC 19 Z9 19 U1 1 U2 3 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0934-8832 J9 MATRIX JI Matrix PD MAY PY 1993 VL 13 IS 3 BP 181 EP 186 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KZ774 UT WOS:A1993KZ77400001 PM 8326908 ER PT J AU YUAN, F LEUNIG, M BERK, DA JAIN, RK AF YUAN, F LEUNIG, M BERK, DA JAIN, RK TI MICROVASCULAR PERMEABILITY OF ALBUMIN, VASCULAR SURFACE-AREA, AND VASCULAR VOLUME MEASURED IN HUMAN ADENOCARCINOMA LS174T USING DORSAL CHAMBER IN SCID MICE SO MICROVASCULAR RESEARCH LA English DT Article ID NEOPLASTIC TISSUES; INTERSTITIAL DIFFUSION; BLOOD-FLOW; TRANSPORT; TUMORS; MACROMOLECULES; FLUORESCENCE; CONVECTION; MOLECULES RP YUAN, F (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [CA-36902, CA-49792] NR 28 TC 157 Z9 159 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAY PY 1993 VL 45 IS 3 BP 269 EP 289 DI 10.1006/mvre.1993.1024 PG 21 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LC382 UT WOS:A1993LC38200005 PM 8321142 ER PT J AU HUTCHISON, FN AF HUTCHISON, FN TI PROTEINURIA, HYPERLIPIDEMIA, AND THE KIDNEY SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Review DE ALBUMIN SYNTHESIS; ANALBUMINEMIA; CHOLESTEROL; CHRONIC RENAL FAILURE; DIETARY PROTEIN; LIPOPROTEIN; NEPHROTIC SYNDROME; ONCOTIC PRESSURE; PROTEINURIA; TRIGLYCERIDE ID CHRONIC AMINONUCLEOSIDE NEPHROSIS; HIGH-DENSITY LIPOPROTEINS; APOLIPOPROTEIN-A-I; PERFUSED-RAT-LIVER; ANALBUMINEMIC RATS; ALBUMIN SYNTHESIS; FOCAL GLOMERULOSCLEROSIS; GLOMERULAR LIPIDOSIS; RENAL-DISEASE; METABOLISM AB Hyperlipidemia in the nephrotic syndrome is the result of abnormalities in both synthesis and catabolism of lipids and lipoproteins. The etiology of nephrotic hyperlipidemia has not been established, but both abnormal glomerular permeability to plasma proteins and reduced serum oncotic pressure may contribute. Although standard hypolipemic drugs are effective in nephrotic patients, therapies such as dietary protein restriction and angiotensin-converting enzyme inhibitors which reduce proteinuria and increase serum oncotic pressure ameliorate hyperlipidemia as well. Hyperlipidemia may also induce proteinuric renal disease in normal animals and worsen renal injury in a variety of animal models of kidney disease. Conversely, treatment of hyperlipidemia prevents renal injury and lessens proteinuria. Potential mechanisms by which hyperlipidemia may cause renal injury include inflammatory and immunologically mediated injury and alteration of glomerular paracrine function. C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP HUTCHISON, FN (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,DIALYSIS UNIT,109 BEE ST,CHARLESTON,SC 29401, USA. NR 105 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD MAY-JUN PY 1993 VL 19 IS 3 BP 127 EP 136 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MB319 UT WOS:A1993MB31900003 PM 8232099 ER PT J AU HEYDARI, AR WU, B TAKAHASHI, R STRONG, R RICHARDSON, A AF HEYDARI, AR WU, B TAKAHASHI, R STRONG, R RICHARDSON, A TI EXPRESSION OF HEAT-SHOCK PROTEIN 70 IS ALTERED BY AGE AND DIET AT THE LEVEL OF TRANSCRIPTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SEQUENCE-SPECIFIC BINDING; HUMAN-DIPLOID FIBROBLASTS; MESSENGER-RNA; GENE-EXPRESSION; DNA-BINDING; CELLS; PROMOTER; HSP70; RESTRICTION; ACTIVATION AB Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of physiological stresses, it was of interest to determine what effect age and caloric restriction have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionarily conserved of the heat shock proteins. Caloric restriction is the only experimental manipulation known to retard aging and increase survival of mammals. The ability of hepatocytes isolated from young/adult (4- to 7-month-old) and old (22- to 28-month-old) male Fischer F344 rats fed ad libitum or a caloric restriction diet (60% of the content of the ad libitum diet) to express hsp70 was determined after a mild heat shock (42.5-degrees-C for 30 min). We found that the induction of hsp70 synthesis and mRNA levels by heat shock was 40 to 50% lower in hepatocytes isolated from old rats than in hepatocytes isolated from young rats. Using in situ hybridization, we found that essentially all hepatocytes from the young/adult and old rats expressed hsp70 in response to heat shock, therefore, the age-related decrease in the induction of hsp70 expression was not due to an age-related accumulation of cells that do not respond to heat shock. Measurements of bsp70 mRNA stability and hsp70 transcription demonstrated that the age-related decline in hsp70 expression arose from a decline in hsp70 transcription. Interestingly, the age-related decline in the induction of hsp70 expression was reversed by caloric restriction; e.g., the induction of hsp70 synthesis, mRNA levels, and nuclear transcription were significantly higher in hepatocytes isolated from old rats fed the caloric restricted diet than in hepatocytes isolated from old rats fed ad libitum. The levels of the heat shock transcription factor in nuclear extracts isolated from heat-shocked hepatocytes were measured in a gel shift assay. Binding of the heat shock transcription factor to the heat shock element decreased with age and was significantly higher in hepatocyte extracts isolated from old rats fed the caloric restriction diet than in those from old rats fed ad libitum. Thus, our study demonstrates that the ability of hepatocytes to respond to hyperthermia and express hsp70 decreases significantly with age and that this decrease occurs at the transcriptional level. In addition, caloric restriction, which retards aging, reversed the age-related decline in the induction of hsp70 transcription in hepatocytes. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. FU NIA NIH HHS [AG01548, AG09557] NR 55 TC 227 Z9 235 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1993 VL 13 IS 5 BP 2909 EP 2918 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KY632 UT WOS:A1993KY63200026 PM 7682654 ER PT J AU GALSON, DL HENSOLD, JO BISHOP, TR SCHALLING, M DANDREA, AD JONES, C AURON, PE HOUSMAN, DE AF GALSON, DL HENSOLD, JO BISHOP, TR SCHALLING, M DANDREA, AD JONES, C AURON, PE HOUSMAN, DE TI MOUSE BETA-GLOBIN DNA-BINDING PROTEIN B1 IS IDENTICAL TO A PROTOONCOGENE, THE TRANSCRIPTION FACTOR SPI-1/PU.1, AND IS RESTRICTED IN EXPRESSION TO HEMATOPOIETIC-CELLS AND THE TESTIS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE ERYTHROLEUKEMIA-CELLS; PROVIRAL INTEGRATION SITE; WILMS-TUMOR GENE; PUTATIVE ONCOGENE; CRYSTAL-STRUCTURE; LEUKEMIA-VIRUS; LYMPHOCYTES-T; MAST-CELLS; BFU-E; DIFFERENTIATION AB The hematopoietic-specific DNA-binding protein B1 binds to the DNA consensus sequence AAAGRGGAARYG located twice in intervening sequence 2 of both of the mouse beta-globin genes (D. L. Galson and D. E. Housman, Mol. Cell. Biol. 8:381-392, 1988). B1 was cloned by expression of a murine erythroleukemia (MEL) cell cDNA library in transfected COS cells and screening by electrophoretic mobility shift analysis. B1 is identical to the proto-oncogene Spi-1/PU.1 (Spi-1), an ets family member. Protein-DNA contacts are shown to resemble those of the helix-turn-helix homeodomain proteins. By Northern (RNA) analysis, we found that Spi-1 mRNA is present at low levels during murine CFU-E maturation and is at least 20-fold higher in uninduced MEL, a transformed proerythroblast-like cell line which contains an activating/transforming insertion of spleen focus-forming virus at the Spi-1 locus. Dimethyl sulfoxide-induced MEL cell differentiation decreases Spi-1 mRNA to approximately 20% of the uninduced level before commitment occurs. In addition to erythroid cells, Spi-1 mRNA is present in B cells, myelomonocytes, and mast cells but not in T cells and nonhematopoietic cell types. In situ hybridization demonstrated Spi-1 mRNA expression in bone marrow, spleen, interstitial nonhepatocytes of the liver, and interstitial nontubular cells of the testis. The Spi-1 locus was mapped on human chromosome 11 to the same interval as ACP2 (lysosomal acid phosphatase), between the anonymous DNA markers D11S33 and D11S14. This region has not yet been found to be associated with a human malignancy. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. CASE WESTERN RESERVE UNIV,SCH MED,IRELAND CANC CTR,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MED,CLEVELAND,OH 44106. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,DIV PEDIAT ONCOL,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,CTR DENT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV COLORADO,HLTH SCI CTR,DEPT BIOCHEM,DENVER,CO 80262. ELANOR ROOSVELT INST CANC RES,DEPT BIOCHEM,DENVER,CO 80262. RP GALSON, DL (reprint author), MIT,CTR CANC RES,CAMBRIDGE,MA 02139, USA. RI Schalling, Martin/F-1518-2015; Galson, Deborah/E-9370-2010 OI Schalling, Martin/0000-0001-5011-2922; Galson, Deborah/0000-0002-2045-8807 FU NCI NIH HHS [CA-18724, P30-CA-43703]; NIDDK NIH HHS [DK-39888] NR 89 TC 156 Z9 157 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 MAY PY 1993 VL 13 IS 5 BP 2929 EP 2941 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KY632 UT WOS:A1993KY63200028 PM 8474451 ER PT J AU TANZI, RE WENNIGER, JJ HYMAN, BT AF TANZI, RE WENNIGER, JJ HYMAN, BT TI CELLULAR SPECIFICITY AND REGIONAL DISTRIBUTION OF AMYLOID BETA-PROTEIN PRECURSOR ALTERNATIVE TRANSCRIPTS ARE UNALTERED IN ALZHEIMER HIPPOCAMPAL-FORMATION SO MOLECULAR BRAIN RESEARCH LA English DT Article DE AMYLOID BETA-PROTEIN PRECURSOR; MESSENGER RNA; INSITU HYBRIDIZATION; HIPPOCAMPAL FORMATION; ALTERNATIVE SPLICING ID MESSENGER-RNA; HUMAN-BRAIN; DISEASE; EXPRESSION; LOCALIZATION; DOMAIN; GENE; CDNA AB Studies comparing the expression of the amyloid beta protein precursor (APP) gene in brains of patients with Alzheimer's disease (AD) and control individuals have resulted in contradictory findings indicative of selective reductions and relative increases of APP alternative transcripts in AD brain. It has been suggested that changes in APP expression in relation to AD neuropathology may represent highly specific and localized events involving only select populations of cells in particular brain regions. For example, reported AD-related alterations in ratios of APP alternative transcripts could be attributed to changes in expression of APP in specific neuronal subpopulations, and/or reactive astrocytes and/or microglia. To address this question, we have employed in situ hybridization using biotinylated oligonucleotide probes designed to localize specific APP mRNA transcripts in the hippocampal formation of AD patients and age-matched controls since this method allows a clear distinction of the classes of neurons and glia containing a particular message. Our findings can be summarized as follows: (1) APP695 and APP751 mRNAs are made primarily by pyramidal neurons in both AD and age-matched control hippocampal sections, (2) the cellular specificity and regional distribution of these messages are extremely similar not only with respect to each other, but also in AD and control hippocampal formation, (3) glial cells appear to contain only small or negligible amounts of APP message, and even in affected regions of AD brain displaying marked gliosis, reactive astrocytes do not contain increased amounts of APP RNA, and (4) APP695 and APP751 mRNAs were localized to both the soma and neuronal processes of neurons but dendritic staining for both messages appeared to be less pronounced in the AD cases. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. NR 32 TC 36 Z9 36 U1 0 U2 0 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 MAY PY 1993 VL 18 IS 3 BP 246 EP 252 DI 10.1016/0169-328X(93)90196-V PG 7 WC Neurosciences SC Neurosciences & Neurology GA KY616 UT WOS:A1993KY61600008 ER PT J AU HYMAN, BT WENNIGER, JJ TANZI, RE AF HYMAN, BT WENNIGER, JJ TANZI, RE TI NONISOTOPIC INSITU HYBRIDIZATION OF AMYLOID BETA-PROTEIN PRECURSOR IN ALZHEIMERS-DISEASE - EXPRESSION IN NEUROFIBRILLARY TANGLE BEARING NEURONS AND IN THE MICROENVIRONMENT SURROUNDING SENILE PLAQUES SO MOLECULAR BRAIN RESEARCH LA English DT Article DE AMYLOID BETA-PROTEIN PRECURSOR; MESSENGER RNA; INSITU HYBRIDIZATION; NEUROFIBRILLARY TANGLE; SENILE PLAQUE; HIPPOCAMPAL FORMATION ID MESSENGER-RNA; DIFFERENTIAL EXPRESSION; HUMAN-BRAIN; GENE; CDNA; LOCALIZATION; CORTEX AB We have used nonisotopic in situ hybridization techniques with biotinylated junctional oligonucleotide probes to study expression of amyloid precursor protein (APP) 695 and 751 mRNA in the hippocampal formation of Alzheimer's disease. Both mRNAs are strongly expressed in neurons of the hippocampal formation, particularly in the dentate gyrus granule cells and the pyramidal neurons of CA3. The patterns of expression of neither APP695 nor APP751 mRNA correlate well with the stereotyped topography of neurofibrillary tangles or senile plaques, which occur primarily in CA1 and subiculum. We double-labeled in situ sections with immunohistochemical reagents for neurofibrillary tangles or senile plaques. Neurons that contain neurofibrillary tangles continue to express APP mRNA. The level of APP695 and APP751 was measured semiquantitatively by optical density measurements in neurons that were close to (within 25 mum) or farther from a senile plaque (more than 100 mum). There was no increase in expression in neurons in the immediate microenvironment of senile plaques. Our results suggest that no major change in distribution or type of APP mRNA accompanies neurofibrillary tangle or senile plaque development. RP HYMAN, BT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,WARREN 4,BOSTON,MA 02114, USA. NR 32 TC 23 Z9 23 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 MAY PY 1993 VL 18 IS 3 BP 253 EP 258 DI 10.1016/0169-328X(93)90197-W PG 6 WC Neurosciences SC Neurosciences & Neurology GA KY616 UT WOS:A1993KY61600009 ER PT J AU PAL, SK CROWELL, R KIESSLING, AA COOPER, GM AF PAL, SK CROWELL, R KIESSLING, AA COOPER, GM TI EXPRESSION OF PROTOONCOGENES IN MOUSE EGGS AND PREIMPLANTATION EMBRYOS SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE REVERSE TRANSCRIPTION; OOCYTES; TRANSCRIPTION; POLYMERASE CHAIN REACTION ID LEUKEMIA INHIBITORY FACTOR; HA-RAS MUTATION; GROWTH-FACTORS; MORPHOLOGICAL DEVELOPMENT; SIGNAL TRANSDUCTION; INSULIN INCREASES; MESSENGER-RNA; DNA-BINDING; PC12 CELLS; W-LOCUS AB The expression of several protooncogenes has been investigated in mouse eggs and preimplantation embryos using reverse transcription coupled to amplification of cDNAs by the polymerase chain reaction (RT-PCR). The genes chosen for analysis included both cytoplasmic (c-raf-1, rasH, rasK, and rasN) and nuclear (c-fos and c-myc) proto-oncogenes encoding proteins involved in the transduction of signals from protein-tyrosine kinase growth factor receptors. Transcripts of the cytoplasmic proto-oncogenes were detected both as maternal and embryonic mRNAs at levels (ca. 1,000 copies per egg or embryo) approximately comparable to their levels of transcription in somatic cells. Transcripts of c-fos and c-myc were also detected in both eggs and embryos, although at more variable levels: Maternal transcripts were present at very low levels (ca. 1-10 copies per egg) in growing oocytes and ovulated eggs; embryonic transcription of c-myc increased, reaching mRNA levels of approximately 100-1,000 copies per embryo in four-cell embryos, morula, and blastocysts; in contrast the transcription of c-fos remained at low, barely detectable levels throughout preimplantation development. Although the significance of the low levels of c-fos mRNA is unclear, these results indicate that preimplantation embryos possess the basic intracellular signaling apparatus required to respond to polypeptide growth factors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FAULKNER HOSP,FAULKNER CTR REPROD MED,BOSTON,MA. FU NCI NIH HHS [T32 CA09031]; NICHD NIH HHS [R01 HD26594] NR 63 TC 32 Z9 35 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD MAY PY 1993 VL 35 IS 1 BP 8 EP 15 DI 10.1002/mrd.1080350103 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA LA775 UT WOS:A1993LA77500002 PM 8507485 ER PT J AU HELD, KD HOPCIA, KL AF HELD, KD HOPCIA, KL TI ROLE OF PROTEIN THIOLS IN INTRINSIC RADIATION PROTECTION OF DNA AND CELLS SO MUTATION RESEARCH LA English DT Article DE DNA DAMAGE; THIOL DEPLETION; PROTEIN THIOLS; RADIATION SENSITIZATION ID DOUBLE-STRAND BREAKS; RAY-SENSITIVE MUTANTS; HAMSTER OVARY CELLS; CO-ION DEPLETION; MAMMALIAN-CELLS; COUNTERION CONDENSATION; CHROMATIN STRUCTURE; IONIZING-RADIATION; DIMETHYL FUMARATE; FILTER ELUTION AB Previous data have been consistent with the hypothesis that the thiol depleter dimethyl fumarate (DMF) increases radiation sensitivity of hypoxic mammalian cells by a combination of two actions: depletion of glutathione (GSH) which interferes with the chemical competition between damage fixation and repair and depletion of protein thiol (PSH) which causes inhibition of enzymatic repair processes. However, one cannot rule out the possibility that PSH also acts in the chemical competition to restitute damaged DNA. The studies presented here have addressed this question by studying the effects of ionizing radiation on isolated nuclei which contain very low levels of GSH, but substantial amounts of PSH, compared to intact cells. The results show that DNA damage, measured using the non-denaturing filter elution assay, is increased about 1.6-fold in isolated nuclei irradiated in air, compared to whole cells, and about 4.3-fold in nuclei irradiated in N2. Thus, the OER for DNA damage decreases from about 3 in whole cells to 1 in isolated nuclei. Also, although DMF increases radiation-induced DNA damage in whole cells irradiated in hypoxia about 2-fold, it does not increase DNA damage in isolated nuclei irradiated in hypoxia. These data do not support the idea that PSH can act in the chemical competition reaction to chemically repair radiation-induced DNA radicals. The data are discussed in relation to the effect that various procedures for nuclei isolation can have on radiation sensitivity of DNA and on the OER. We also address the question of whether radiation-induced DNA damage measured by non-denaturing elution correlates with cell killing. RP HELD, KD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA18614, CA42167] NR 30 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD MAY PY 1993 VL 299 IS 3-4 BP 261 EP 269 DI 10.1016/0165-1218(93)90102-J PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA KZ113 UT WOS:A1993KZ11300014 PM 7683093 ER PT J AU WEINER, HL MACKIN, GA ORAV, EJ HAFLER, DA DAWSON, DM LAPIERRE, Y HERNDON, R LEHRICH, JR HAUSER, SL TUREL, A FISHER, M BIRNBAUM, G MCARTHUR, J BUTLER, R MOORE, M SIGSBEE, B SAFRAN, A AF WEINER, HL MACKIN, GA ORAV, EJ HAFLER, DA DAWSON, DM LAPIERRE, Y HERNDON, R LEHRICH, JR HAUSER, SL TUREL, A FISHER, M BIRNBAUM, G MCARTHUR, J BUTLER, R MOORE, M SIGSBEE, B SAFRAN, A TI INTERMITTENT CYCLOPHOSPHAMIDE PULSE THERAPY IN PROGRESSIVE MULTIPLE-SCLEROSIS - FINAL REPORT OF THE NORTHEAST-COOPERATIVE-MULTIPLE-SCLEROSIS-TREATMENT-GROUP SO NEUROLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Academy-of-Neurology CY MAY, 1992 CL SAN DIEGO, CA SP AMER ACAD NEUROL ID INTENSIVE IMMUNOSUPPRESSION; PLASMA-EXCHANGE; DISEASE; ACTH; FOLLOW AB Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primarily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97. In addition, patients with primary progressive MS had a poorer prognosis at 12 months than patients with secondarily progressive MS (p = 0.04). Our findings (1) support a role for immunosuppression in the treatment of MS, (2) begin to identify variables that may explain differences between studies of immunosuppression with cyclophosphamide in progressive MS, and (3) suggest that intermittent pulse therapy is an important method for the treatment of progressive MS and perhaps for earlier stages of MS as well. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV NEUROL,CTR NEUROL DIS,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. MONTREAL NEUROL HOSP & INST,MONTREAL H3A 2B4,QUEBEC,CANADA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. STRONG MEM HOSP,ROCHESTER,NY 14642. GEISINGER MED CTR,DANVILLE,PA 17822. UNIV MINNESOTA HOSP & CLIN,MINNEAPOLIS,MN 55455. WORCESTER MEM HOSP,WORCESTER,MA. JOHNS HOPKINS UNIV,MED CTR,BALTIMORE,MD 21218. EASTERN MAINE MED CTR,BANGOR,ME 04401. FRAMINGHAM UNION HOSP,FRAMINGHAM,MA 01701. EMERSEN HOSP,CONCORD,MA. BOSTON UNIV,SCH MED,CONCORD,MA. RI Hauser, Stephen/J-2978-2016 NR 27 TC 195 Z9 197 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1993 VL 43 IS 5 BP 910 EP 918 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA LC363 UT WOS:A1993LC36300014 PM 8388090 ER PT J AU ELMALEH, DR PADMANABHAN, S HASSAN, MA CORREIA, JA HERMAN, LW HANSON, RN STRAUSS, HW AF ELMALEH, DR PADMANABHAN, S HASSAN, MA CORREIA, JA HERMAN, LW HANSON, RN STRAUSS, HW TI SYNTHESIS AND EVALUATION OF 1-[C-11]METHYL-4-ARYL-PIPERAZINIUM SALTS AS MYOCARDIAL IMAGING AGENTS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID RADIOIODINATED 1-SUBSTITUTED-4-PHENYLPIPERAZINES; INITIAL EXPERIENCE; PERFUSION; COMPLEXES; TL-201; RADIOPHARMACEUTICALS; DERIVATIVES; TOMOGRAPHY; ANALOGS; CATIONS AB Our previous study with radioiodinated 1-methyl-1-(2-hydroxyethyl)-4-phenylpiperazinium derivatives indicated that these compounds localize selectively in the rat myocardium. Based upon these results, 1-[C-11]methyl-1-alkyl-4-phenylpiperazinium cations were synthesized and evaluated for their potential as myocardial imaging agents. Biodistribution studies were performed in rats and imaging studies in normal dogs. The results indicate high concentrations of 3-4% ID/g in the rat heart at 5 min, comparable to those obtained with the radioiodinated analogs. Sequential imaging of the canine heart showed a similar pattern of uptake. The level of activity reached at 20 min was maintained over the 1-h time period. These results suggest that the phenylpiperazinium agents may have potential application as myocardial imaging agents. C1 NORTHEASTERN UNIV,COLL PHARM & ALLIED HLTH PROFESS,DEPT MEDICINAL CHEM,BOSTON,MA 02115. RP ELMALEH, DR (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV RADIOL SCI,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [1 RO1 HL 24666] NR 31 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1993 VL 20 IS 4 BP 427 EP 433 DI 10.1016/0969-8051(93)90073-4 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LA491 UT WOS:A1993LA49100007 PM 8504285 ER PT J AU SLINKIN, MA CURTET, C FAIVRECHAUVET, A SAIMAUREL, C GESTIN, JF TORCHILIN, VP CHATAL, JF AF SLINKIN, MA CURTET, C FAIVRECHAUVET, A SAIMAUREL, C GESTIN, JF TORCHILIN, VP CHATAL, JF TI BIODISTRIBUTION OF ANTI-CEA F(AB')2 FRAGMENTS CONJUGATED WITH CHELATING POLYMERS - INFLUENCE OF CONJUGATE ELECTRON CHARGE ON TUMOR UPTAKE AND BLOOD CLEARANCE SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; CARCINOEMBRYONIC ANTIGEN; COVALENT ATTACHMENT; POLYETHYLENE-GLYCOL; IN-111 DTPA; PERMEABILITY; PEROXIDASE; CARCINOMA; AGENTS; SIZE AB F(ab')2 fragments of anti-carcinoembryonic antigen (CEA) monoclonal antibody (mAb) were modified with three chain-terminal polylysine-based chelating polymers so as to carry different electron charges. Immunoreactive conjugates labeled with In-111 up to a specific radioactivity of 120-140 muCi/mug were injected into nude mice bearing human colorectal carcinoma, and the biodistribution patterns were compared with each other and with that of an anti-CEA F(ab')2-DTPA control. Immunoconjugate modified with positively-charged polymer produced the highest tumor uptake [up to 20% injected dose per gram (ID/g)], with very significant non-specific radioactivity in normal organs (particularly kidneys). When modified with a polymer carrying only a slight negative charge, the immunoconjugate also produced fairly high tumor uptake (up to 18% ID/g), with much lower non-specific radioactivity in normal organs. Highly negatively-charged conjugate produced the lowest tumor uptake (up to 8% ID/g), whereas blood and whole-body clearances were the fastest but slower than those of conventionally labeled F(ab')2 mAb. The possible mechanisms for the effects described are discussed. C1 CHR,BIOPHYS CANCEROL LAB,INSERM,U211,PLATEAU TECH,QUAI MONCOUSU,F-44035 NANTES 1,FRANCE. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129. RI GESTIN, Jean-Francois/M-1505-2015; Faivre-Chauvet, Alain/L-9923-2015 OI Faivre-Chauvet, Alain/0000-0003-3849-0087 NR 33 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1993 VL 20 IS 4 BP 443 EP 452 DI 10.1016/0969-8051(93)90075-6 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LA491 UT WOS:A1993LA49100009 PM 8504286 ER PT J AU ORMEROD, LD HO, DD BECKER, LE CRUISE, RJ GROHAR, HI PATON, BG FREDERICK, AR TOPPING, TM WEITER, JJ BUZNEY, SM LING, RA BAKER, AS AF ORMEROD, LD HO, DD BECKER, LE CRUISE, RJ GROHAR, HI PATON, BG FREDERICK, AR TOPPING, TM WEITER, JJ BUZNEY, SM LING, RA BAKER, AS TI ENDOPHTHALMITIS CAUSED BY THE COAGULASE-NEGATIVE STAPHYLOCOCCI .1. DISEASE SPECTRUM AND OUTCOME SO OPHTHALMOLOGY LA English DT Article ID ANAEROBIC BACTERIAL ENDOPHTHALMITIS; POSTOPERATIVE ENDOPHTHALMITIS; PSEUDOPHAKIC ENDOPHTHALMITIS; EPIDERMIDIS ENDOPHTHALMITIS; CATARACT-EXTRACTION; LENS IMPLANTATION; ANTIBIOTICS; DIAGNOSIS; SURGERY AB Purpose: The coagulase-negative staphylococci are the most common causes of postoperative endophthalmitis. This study investigates the variability in the disease spectrum and visual outcome of coagulase-negative staphylococcal endophthalmitis in a large, single-center series. Methods: Ninety consecutive cases of coagulase-negative staphylococcal endophthalmitis were investigated retrospectively from two time periods, 1978 to 1982 and 1985 to 1987, separated by a transitional period in cataract surgery technique. Using a detailed protocol, inpatient, outpatient, and microbiologic records were analyzed. Six-month visual acuity results were obtained. Results: Diagnosis frequently was delayed, often suspected only after hypopyon development. Thirty-seven percent of patients presented more than 1 week after the inoculating event, and 13% presented after more than 1 month. Variable asymptomatic intervals and gradually worsening inflammatory prodromes are noted. Painless endophthalmitis occurred in 16%. Non-epidermidis infections comprised 28%. With vitrectomy/intraocular antibiotic management, 38% and 68% achieved visual acuities of 20/50 and 20/400, respectively. Overall, 10% of patients developed late retinal detachments. This occurred in only 4% of patients, with endophthalmitis occurring after cataract surgery. Conclusion: Ophthalmologists should become familiar with the emerging concepts of delayed-onset, chronic, and often painless endophthalmitis in which the coagulase-negative staphylococci play a prominent role. C1 MASSACHUSETTS EYE & EAR INFIRM,INFECT DIS SERV,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02115. LOMA LINDA UNIV,DEPT OPHTHALMOL,LOMA LINDA,CA 92350. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114. LOMA LINDA UNIV,SCH PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,LOMA LINDA,CA 92350. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,PORTER BACTERIOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. CTR EYE RES,BOSTON,MA. RETINA ASSOCIATES,BOSTON,MA. NR 44 TC 42 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1993 VL 100 IS 5 BP 715 EP 723 PG 9 WC Ophthalmology SC Ophthalmology GA LB970 UT WOS:A1993LB97000028 PM 8493015 ER PT J AU ORMEROD, LD BECKER, LE CRUISE, RJ GROHAR, HI PATON, BG FREDERICK, AR TOPPING, TM WEITER, JJ BUZNEY, SM BAKER, AS AF ORMEROD, LD BECKER, LE CRUISE, RJ GROHAR, HI PATON, BG FREDERICK, AR TOPPING, TM WEITER, JJ BUZNEY, SM BAKER, AS TI ENDOPHTHALMITIS CAUSED BY THE COAGULASE-NEGATIVE STAPHYLOCOCCI .2. FACTORS INFLUENCING PRESENTATION AFTER CATARACT-SURGERY SO OPHTHALMOLOGY LA English DT Article ID PSEUDOPHAKIC ENDOPHTHALMITIS; BACTERIAL ENDOPHTHALMITIS; EPIDERMIDIS; ADHERENCE AB Purpose: This study, comprising 60 patients with coagulase-negative staphylococcal endophthalmitis which occurred after cataract surgery, was designed to define the variation in disease presentation and visual outcome and to evaluate statistically the role of the primary surgery and its management. Methods: An intensive evaluation of microbiological, inpatient, outpatient, and cataract surgery charts was made retrospectively using a standardized protocol. The predictive value of surgical, iatrogenic, and clinical factors was analyzed for their influence on defined aspects of the disease pattern and of the visual results using multiple regression models, via a stepwise technique. Results: There was commonly a significant asymptomatic latent period after cataract surgery. The median diagnostic delay was 7 days; 22% of patients presented after 2 weeks and 12% after 1 month. Symptoms progressed longer than 3 days in 25% of patients. Ten percent had no pain. Clinical variation proved largely unrelated to cataract surgery events and postoperative management; bacterial factors were implicated. Good visual outcome was associated statistically with intensive topical corticosteroid in the symptomatic period, but was negatively associated with operative subconjunctival corticosteroid. Conclusions: The clinical variation in cases of postoperative coagulase-negative staphylococcal endophthalmitis poses particular problems for diagnosis in the outpatient setting. Surgical and perioperative events (except corticosteroid use) probably can be disregarded in studies of endophthalmitis management. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,INFECT DIS SERV,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02115. LOMA LINDA UNIV,DEPT OPHTHALMOL,LOMA LINDA,CA 92350. LOMA LINDA UNIV,SCH PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,LOMA LINDA,CA 92350. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,PORTER BACTERIOL LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. OPHTHALM CONSULTANTS BOSTON,BOSTON,MA. CTR EYE RES,BOSTON,MA. RETINA ASSOCIATES,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114. NR 25 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1993 VL 100 IS 5 BP 724 EP 729 PG 6 WC Ophthalmology SC Ophthalmology GA LB970 UT WOS:A1993LB97000029 PM 8493016 ER PT J AU ADAMS, JC AF ADAMS, JC TI PROSPECTS FOR IMMUNOCYTOCHEMICAL STUDIES OF THE LABYRINTH SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article DE IMMUNOCYTOCHEMISTRY; COCHLEAR EFFERENTS AB Immunocytochemistry, when used with traditional and other modem techniques, offers great promise as a tool for cytochemically characterizing cells and their processes in the normal and pathological labyrinth. The strength of assertions regarding results of such studies is proportional to the degree to which antibodies are characterized, a limitation that has often been neglected in studies of the labyrinth. Examples are given to demonstrate the degree of species variability of cytochemically distinct efferent fibers in the cochlea, and to demonstrate how readily new information can be obtained when appropriate antibodies are available. RP ADAMS, JC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOL & LARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00269] NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PD MAY-JUN PY 1993 VL 55 IS 3 BP 164 EP 166 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA LB577 UT WOS:A1993LB57700009 PM 8321549 ER PT J AU YOON, KL ERNST, SG RASMUSSEN, C DOOLING, EC APRILLE, JR AF YOON, KL ERNST, SG RASMUSSEN, C DOOLING, EC APRILLE, JR TI MITOCHONDRIAL DISORDER ASSOCIATED WITH NEWBORN CARDIOPULMONARY ARREST SO PEDIATRIC RESEARCH LA English DT Article ID CYTOCHROME-C-OXIDASE; LACTIC-ACIDOSIS; DEFICIENCY; MYOPATHY; MUTATION; DNA; ORGANIZATION; EXPRESSION; DISEASES; SEQUENCE AB A female infant who died 2.5 d after birth with hypoglycemia, lactic acidosis, and sudden multisystem failure was studied. Biochemical studies showed complex III and IV deficiency in liver, kidney, and muscle, with muscle most severely affected. Southern blot analysis of the patient's mitochondrial DNA did not reveal any deletions. Denaturing gradient gel analysis, which detects single base changes by differences in melting behavior, showed an extra band that was not seen in mitochondrial DNA from the mother, the mother's identical twin sister, or an unrelated normal subject. This extra band indicated heteroplasmy for a restriction fragment containing the apocytochrome b and transfer RNA(thr) genes. Sequencing revealed an A to G mutation at nucleotide 15923, the last base of the anticodon loop of the transfer RNA(thr) gene. The mutation lengthens the anticodon stem by added pairing and reduces the anticodon loop size from 7 to 5 nucleotides, potentially compromising transfer RNA(thr) function in translation and/or in processing the polycistronic RNA transcript. The patient's mother previously had a male infant who also died at 1.5 d postnatal, and both the mother and her twin have had multiple miscarriages. Amniocentesis for a genetic screen was performed on the mother's twin sister during a recent pregnancy; some of the cultured cells were made available for this study. The mutation was not found in the amniocytes or in umbilical cord blood obtained at birth; the baby was normal at birth and remains healthy. It is concluded that the mutation at nucleotide 15923 was most likely the cause of the fatal disease in the index case. The timing of the illness was consistent with postnatal depletion of glycogen reserves. The findings suggest that a mitochondrial disorder should be considered for infants who experience sudden cardiopulmonary arrest within the first few days of life. C1 TUFTS UNIV,DEPT BIOL,MITOCHONDRIAL PHYSIOL UNIT,MEDFORD,MA 02155. MASSACHUSETTS GEN HOSP,PEDIAT NEUROL UNIT,BOSTON,MA 02114. FU NICHD NIH HHS [HD16936] NR 30 TC 24 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1993 VL 33 IS 5 BP 433 EP 440 DI 10.1203/00006450-199305000-00002 PG 8 WC Pediatrics SC Pediatrics GA LA512 UT WOS:A1993LA51200002 PM 8511015 ER PT J AU LAZAR, G HONG, Z GOODMAN, HM AF LAZAR, G HONG, Z GOODMAN, HM TI THE ORIGIN OF THE BIFUNCTIONAL DIHYDROFOLATE-REDUCTASE THYMIDYLATE SYNTHASE ISOGENES OF ARABIDOPSIS-THALIANA SO PLANT JOURNAL LA English DT Article ID LEISHMANIA-TROPICA; SEQUENCE-ANALYSIS; ENZYME COMPLEX; GENE; DNA; INTRONS; CELLS; PURIFICATION; POLYPEPTIDE; PHAGE-T4 AB In most prokaryotic and eukaryotic organisms dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are encoded by independent genes. Evidence is presented here that the higher plant Arabidopsis thaliana has two bifunctional DHFR-TS genes. The structure of the genes, DHFR at the amino terminus and TS at the carboxy terminus, is identical to their organization in protozoa, the only other known organisms with bifunctional genes. Sequence alignments suggest that the bifunctional genes from protozoa and higher plants may have different evolutionary origins. The positions of the introns support the complementary hypothesis that the DHFR domain of the bifunctional plant genes and the monofunctional DHFR gene of vertebrates derive from a common, intron-containing progenitor, although the structure (bifunctional or monofunctional) of the ancestral gene remains indeterminate. Comparison of the two bifunctional genes of Arabidopsis indicates that the DHFR and TS domains evolved at different rates; each following the evolutionary history of their monofunctional counterparts. In contrast to the DHFR domain, the evolution of the TS domain shows a higher level of nucleotide and amino acid sequence conservation, but a remarkable variability in the intron positions. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 40 TC 37 Z9 39 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7412 J9 PLANT J JI Plant J. PD MAY PY 1993 VL 3 IS 5 BP 657 EP 668 PG 12 WC Plant Sciences SC Plant Sciences GA LC758 UT WOS:A1993LC75800004 PM 8374616 ER PT J AU HAUGE, BM HANLEY, SM CARTINHOUR, S CHERRY, JM GOODMAN, HM KOORNNEEF, M STAM, P CHANG, C KEMPIN, S MEDRANO, L MEYEROWITZ, EM AF HAUGE, BM HANLEY, SM CARTINHOUR, S CHERRY, JM GOODMAN, HM KOORNNEEF, M STAM, P CHANG, C KEMPIN, S MEDRANO, L MEYEROWITZ, EM TI AN INTEGRATED GENETIC RFLP MAP OF THE ARABIDOPSIS-THALIANA GENOME SO PLANT JOURNAL LA English DT Article ID ARTIFICIAL CHROMOSOME LIBRARY; POLYMORPHISM LINKAGE MAP; MOLECULAR-CLONING; MUTANTS; DNA; EXPRESSION; PROTEIN; CONSTRUCTION; CHLOROPLAST; SEQUENCE AB We have assembled an integrated genetic/restriction fragment length polymorphism (RFLP) linkage map of the nuclear genome of the flowering plant Arabidopsis thaliana. The map is based on two independent sets of RFLP data, RFLP data for 123 new markers, and pairwise segregation data of 125 classical genetic markers. Mathematical integration of the independent data sets was performed using the JOINMAP computer package. Sixty-two markers common to two or more data sets were exploited to facilitate integration of the individual maps. The current map, which encompasses a total genetic distance of 520 cM, contains 125 classical genetic markers and 306 RFLP markers. Comparison of the integrated consensus map with the individual maps demonstrates that the overall linear order of the integrated map is in good agreement with the component maps. It must be emphasized, however, that the integrated map represents the 'best fit' which is clearly subject to the statistical limitations of the available data. We present several examples where local differences in map order are observed between the integrated and component maps. It is likely, given the problems associated with statistical integration of mapping data from different populations, that the integrated map will contain additional local inconsistencies and problematic regions. None the less, the unified map provides a framework for building an increasingly accurate and useful map. Subsequent refinements of the map will be available electronically and researchers are invited to submit revised map data to the corresponding author for inclusion in future updates (see Appendix 1). C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,WELLMAN 11,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. WAGENINGEN UNIV AGR,DEPT GENET,6703 HA WAGENINGEN,NETHERLANDS. CPRO,DLO,CTR PLANT BREEDING & REPROD RES,6700 AA WAGENINGEN,NETHERLANDS. CALTECH,DIV BIOL,PASADENA,CA 91125. RI Meyerowitz, Elliot/A-7118-2009; OI Koornneef, Maarten/0000-0002-7759-4869 NR 65 TC 152 Z9 154 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7412 J9 PLANT J JI Plant J. PD MAY PY 1993 VL 3 IS 5 BP 745 EP 754 DI 10.1111/j.1365-313X.1993.00745.x PG 10 WC Plant Sciences SC Plant Sciences GA LC758 UT WOS:A1993LC75800013 ER PT J AU BORODIC, GE PEARCE, LB CHENEY, M METSON, R BROWNSTONE, D TOWNSEND, D MCKENNA, M AF BORODIC, GE PEARCE, LB CHENEY, M METSON, R BROWNSTONE, D TOWNSEND, D MCKENNA, M TI BOTULINUM-A TOXIN FOR TREATMENT OF ABERRANT FACIAL-NERVE REGENERATION SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HEMIFACIAL SPASM; BLEPHAROSPASM; HYPERKINESIAS; ANASTOMOSIS AB Twelve patients with involuntary synkinetic eyelid closure were given 40 injections of botulinum A toxin. Temporary improvement in involuntary eyelid closure was observed in all 12 patients. Eleven of the 12 patients desired repeated injections. Dose requirements for this indication were compared with doses used in 697 injections in 1 12 patients with essential blepharospasm and Meige syndrome. Additionally, dose comparisons were made with 269 injections in 71 patients with hemifacial spasm. Dose requirements needed to treat aberrant regeneration of the facial nerve were substantially less than needed to treat blepharospasm and Meige syndrome. The dose requirement was similar to that in hemifacial spasm treatment. The reason for the differences probably relates to existing muscular denervation associated with hemifacial spasm and aberrant facial nerve regeneration. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL & OTOLARYNGOL,FACIAL NERVE CLIN,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT OPHTHALMOL & PHARMACOL,BOSTON,MA 02118. NR 15 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 1993 VL 91 IS 6 BP 1042 EP 1045 DI 10.1097/00006534-199305000-00011 PG 4 WC Surgery SC Surgery GA KZ624 UT WOS:A1993KZ62400011 PM 8479969 ER PT J AU GLANZ, K KRISTAL, AR SORENSEN, G PALOMBO, R HEIMENDINGER, J PROBART, C AF GLANZ, K KRISTAL, AR SORENSEN, G PALOMBO, R HEIMENDINGER, J PROBART, C TI DEVELOPMENT AND VALIDATION OF MEASURES OF PSYCHOSOCIAL FACTORS INFLUENCING FAT-RELATED AND FIBER-RELATED DIETARY BEHAVIOR SO PREVENTIVE MEDICINE LA English DT Article ID MODEL; RISK C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MASSACHUSETTS DEPT HLTH,BOSTON,MA. NCI,BETHESDA,MD 20892. UNIV FLORIDA,GAINESVILLE,FL 32611. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP GLANZ, K (reprint author), TEMPLE UNIV,DEPT HLTH EDUC,304 SELTZER HALL,PHILADELPHIA,PA 19122, USA. RI Kristal, Alan/A-8779-2008 FU NCI NIH HHS [U01 CA51687, U01 CA51686, U01 CA51671] NR 28 TC 93 Z9 93 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 1993 VL 22 IS 3 BP 373 EP 387 DI 10.1006/pmed.1993.1031 PG 15 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA LC523 UT WOS:A1993LC52300008 PM 8392175 ER PT J AU UMEZU, K CHI, NW KOLODNER, RD AF UMEZU, K CHI, NW KOLODNER, RD TI BIOCHEMICAL INTERACTION OF THE ESCHERICHIA-COLI RECF, RECO, AND RECR PROTEINS WITH RECA PROTEIN AND SINGLE-STRANDED-DNA BINDING-PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENETIC RECOMBINATION; RECF PATHWAY; STRAND TRANSFER; DNA REPAIR ID HOMOLOGOUS RECOMBINATION; GENETIC-RECOMBINATION; SSB PROTEIN; PURIFICATION; EXCHANGE; MUTANT; COMPLEXES; PATHWAY AB The Escherichia coli RecF, RecO, and RecR proteins were analyzed for their effect on RecA-mediated pairing of single-stranded circular DNA and homologous linear duplex DNA substrates. As shown by other workers, joint molecule formation by RecA was inhibited by E. coli single-stranded DNA binding protein (SSB) when it was added to single-stranded DNA before RecA. This inhibitory effect was overcome by the addition of RecO and RecR or RecF, RecO, and RecR. Both the rate and extent of joint molecule formation were restored to the maximal level observed when SSB was added after RecA. RecF, RecO, and RecR proteins had no effect on the conversion of joint molecules to final products and only appeared to stimulate an early step in the pairing reaction. The stimulatory effect of RecF, RecO, and RecR was not seen without SSB or when SSB was added after RecA. RecF protein by itself inhibited reactions in mixtures containing RecA and SSB, and this inhibition was overcome by the addition of RecO and RecR. These data suggest that RecO and RecR, and possibly RecF, help RecA overcome inhibition by SSB and utilize SSB-single-stranded-DNA complexes as substrates. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM26017] NR 36 TC 188 Z9 191 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1993 VL 90 IS 9 BP 3875 EP 3879 DI 10.1073/pnas.90.9.3875 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LA430 UT WOS:A1993LA43000022 PM 8483906 ER PT J AU GRUSBY, MJ AUCHINCLOSS, H LEE, R JOHNSON, RS SPENCER, JP ZIJLSTRA, M JAENISCH, R PAPAIOANNOU, VE GLIMCHER, LH AF GRUSBY, MJ AUCHINCLOSS, H LEE, R JOHNSON, RS SPENCER, JP ZIJLSTRA, M JAENISCH, R PAPAIOANNOU, VE GLIMCHER, LH TI MICE LACKING MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II MOLECULES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CD8+ T-CELLS; DEFICIENT MICE; BONE-MARROW; BETA-2-MICROGLOBULIN; REJECTION AB Mice lacking major histocompatibility complex (MHC) antigens were generated by mating beta2-microglobulin-deficient, and therefore class I-deficient, animals with MHC class II-deficient animals. When housed under sterile conditions, the resulting MHC-deficient mice appear healthy, survive for many months, and breed successfully. Phenotypically, MHC-deficient mice are depleted of CD4+ and CD8+ T cells in peripheral lymphoid organs due to a lack of appropriate restricting elements. In contrast, the B-cell compartment of these animals appears intact, and MHC-deficient mice can mount specific antibody responses when challenged with a T-independent antigen. Spleen cells from MHC-deficient animals are poor stimulators and responders in a mixed lymphocyte reaction. Despite their relatively weak cellular immune responses in vitro, MHC-deficient mice reject allogeneic skin grafts with little delay, and grafts from MHC-deficient animals are rapidly rejected by normal allogeneic recipients. Taken together, these results emphasize the plasticity of the immune system and suggest that MHC-deficient mice may be useful for examining compensatory mechanisms in severely immunocompromised animals. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG & PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED & VET MED,DEPT PATHOL,BOSTON,MA 02111. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. OI Johnson, Randall/0000-0002-4084-6639 FU NHLBI NIH HHS [HL18646, HL36372]; NIAID NIH HHS [AI21569] NR 21 TC 214 Z9 218 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 1 PY 1993 VL 90 IS 9 BP 3913 EP 3917 DI 10.1073/pnas.90.9.3913 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LA430 UT WOS:A1993LA43000030 PM 8483910 ER PT J AU WANG, LM KEEGAN, AD LI, WQ LIENHARD, GE PACINI, S GUTKIND, JS MYERS, MG SUN, XJ WHITE, MF AARONSON, SA PAUL, WE PIERCE, JH AF WANG, LM KEEGAN, AD LI, WQ LIENHARD, GE PACINI, S GUTKIND, JS MYERS, MG SUN, XJ WHITE, MF AARONSON, SA PAUL, WE PIERCE, JH TI COMMON ELEMENTS IN INTERLEUKIN-4 AND INSULIN SIGNALING PATHWAYS IN FACTOR-DEPENDENT HEMATOPOIETIC-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INSULIN RECEPTOR SUBSTRATE-1; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION ID STIMULATES TYROSINE PHOSPHORYLATION; INTACT-CELLS; ENDOGENOUS SUBSTRATE; JUXTAMEMBRANE REGION; MOLECULAR-CLONING; KINASE-ACTIVITY; RECEPTOR; PROTEIN; TRANSDUCTION; GROWTH AB Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. UNIV FLORENCE,INST GEN PATHOL,I-50121 FLORENCE,ITALY. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. HARVARD UNIV,JOSLIN DIABET CTR,SCH MED,DEPT MED,BOSTON,MA 02215. RI Gutkind, J. Silvio/A-1053-2009 NR 45 TC 175 Z9 175 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1993 VL 90 IS 9 BP 4032 EP 4036 DI 10.1073/pnas.90.9.4032 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LA430 UT WOS:A1993LA43000054 PM 7683417 ER PT J AU ZIEGLER, A LEFFELL, DJ KUNALA, S SHARMA, HW GAILANI, M SIMON, JA HALPERIN, AJ BADEN, HP SHAPIRO, PE BALE, AE BRASH, DE AF ZIEGLER, A LEFFELL, DJ KUNALA, S SHARMA, HW GAILANI, M SIMON, JA HALPERIN, AJ BADEN, HP SHAPIRO, PE BALE, AE BRASH, DE TI MUTATION HOTSPOTS DUE TO SUNLIGHT IN THE P53 GENE OF NONMELANOMA SKIN CANCERS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE UV LIGHT; DNA PHOTOPRODUCTS; MULTISTAGE CARCINOGENESIS ID BASAL-CELL CARCINOMA; BREAST-CANCER; DNA; ONCOGENESIS; BIOLOGY; RAS AB To identify the sites in the p53 tumor suppressor gene most susceptible to carcinogenic mutation by sunlight, the entire coding region of 27 basal cell carcinomas (BCCs) of the skin was sequenced. Fifty-six percent of tumors contained mutations, and these were UV-like: primarily CC --> TT or C --> T changes at dipyrimidine sites. Such mutations can alter more than half of the 393 amino acids in p53, but two-thirds occurred at nine sites at which mutations were seen more than once in BCC or in 27 previously studied squamous cell carcinomas of the skin. Seven of these mutation hotspots were specific to skin cancers. Internal-cancer hotspots not located at dipyrimidine sites were not mutated in skin cancers; moreover, UV photoproducts were absent at these nucleotides. The existence of hotspots altered the process of inactivating p53 in BCC compared to other cancers: allelic loss was rare, but 45% of the point mutations were accompanied by a second point mutation on the other allele. At least one of each pair was located at a hotspot. Sunlight, acting at mutation hotspots, appears to cause mutations so frequently that it is often responsible for two genetic events in BCC development. C1 YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. DERMATOPATHOL ASSOCIATES NEW YORK,NEW ROCHELLE,NY 10805. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. FU NCI NIH HHS [CA55737, T32CA09259] NR 41 TC 573 Z9 585 U1 2 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1993 VL 90 IS 9 BP 4216 EP 4220 DI 10.1073/pnas.90.9.4216 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LA430 UT WOS:A1993LA43000091 PM 8483937 ER PT J AU HANDELSMAN, L SONG, IS LOSONCZY, M PARK, S JACOBSON, J WIENER, J ARONSON, M AF HANDELSMAN, L SONG, IS LOSONCZY, M PARK, S JACOBSON, J WIENER, J ARONSON, M TI MAGNETIC-RESONANCE ABNORMALITIES IN HIV-INFECTION - A STUDY IN THE DRUG-USER RISK GROUP SO PSYCHIATRY RESEARCH LA English DT Article DE MAGNETIC RESONANCE IMAGING; HUMAN IMMUNODEFICIENCY VIRUS; COGNITIVE IMPAIRMENT; ACQUIRED IMMUNE DEFICIENCY SYNDROME ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; BASE-LINE ASSESSMENT; HOMOSEXUAL MEN; CT; NEUROPATHOLOGY AB Cognitive impairment is a frequent complication of advanced human immunodeficiency virus-1 (HIV-1) infection. However, structural imaging of the brain has not revealed abnormalities that precede the onset of clinical abnormalities. Cranial magnetic resonance (MR) studies were performed in 28 male subjects with intravenous drug use histories; nine were HIV-1 seronegative, 11 were HIV-1 seropositive but asymptomatic, and eight were seropositive and met symptomatic criteria for acquired immune deficiency syndrome (AIDS). Cortical atrophy, but not the degree of ventricular enlargement or signal abnormalities, was increased in the seropositive group compared with the seronegative group and also differed between asymptomatic seropositive and seronegative patients. An increased level of cortical atrophy may reflect the early impact of HIV-1 infection on the brain. C1 BRONX VET AFFAIRS MED CTR,RADIOL SERV,BRONX,NY 10468. BRONX VET AFFAIRS MED CTR,NEUROL SERV,BRONX,NY 10468. BRONX VET AFFAIRS MED CTR,INFECT DIS SERV,BRONX,NY 10468. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. RP HANDELSMAN, L (reprint author), BRONX VET AFFAIRS MED CTR,PSYCHIAT SERV,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 31 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY PY 1993 VL 47 IS 2 BP 175 EP 186 DI 10.1016/0165-1781(93)90047-K PG 12 WC Psychiatry SC Psychiatry GA LG163 UT WOS:A1993LG16300007 PM 8341770 ER PT J AU SILVA, JA LEONG, GB WEINSTOCK, R AF SILVA, JA LEONG, GB WEINSTOCK, R TI DELUSIONS OF TRANSFORMATION OF THE SELF SO PSYCHOPATHOLOGY LA English DT Article ID CAPGRAS SYNDROME; LYCANTHROPY; SYSTEM AB A series of 20 patients suffering from delusions of physical and psychological transformation of the self is studied. Nosological, psychosocial, and biological aspects are discussed. Two cases are presented in detail. C1 W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 40 TC 13 Z9 13 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PD MAY-AUG PY 1993 VL 26 IS 3-4 BP 181 EP 188 PG 8 WC Psychiatry SC Psychiatry GA LW106 UT WOS:A1993LW10600011 PM 8234633 ER PT J AU GREEN, AI AUSTIN, CP AF GREEN, AI AUSTIN, CP TI PSYCHOPATHOLOGY OF PANCREATIC-CANCER - A PSYCHOBIOLOGIC PROBE SO PSYCHOSOMATICS LA English DT Review ID SODIUM LACTATE INFUSION; PANIC ATTACKS; HUMORAL HYPERCALCEMIA; LIMBIC ENCEPHALITIS; CUSHINGS-SYNDROME; ENDOCRINE TUMORS; DEPRESSION; CARCINOMA; SECRETION; DIAGNOSIS AB Reports of characteristic psychiatric symptoms occurring in patients with pancreatic cancer appear regularly in the literature. A review of this literature reveals that symptoms of depression and/or anxiety may appear in approximately 50% of patients with pancreatic cancer before the diagnosis is made. This review proposes that the psychopathology of pancreatic tumors may be linked to tumor-induced changes in neuroendocrine or acid-base systems. Although confirmatory data are lacking, informed speculation centers on the potential role of adrenocorticotropic hormone, parathyroid hormone, thyrotropin-releasing hormone, glucagon, serotonin, insulin, and bicarbonate in the production of depression an&or anxiety in this disease. Elucidation of the pathophysiology of the psychiatric symptoms in patients with pancreatic cancer may provide a marker for early diagnosis of pancreatic neoplasia as well as a probe into the biologic bases of depression and anxiety. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP GREEN, AI (reprint author), MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHOL,COMMONWEALTH RES CTR,74 FENWOOD RD,BOSTON,MA 02115, USA. NR 106 TC 58 Z9 59 U1 3 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1993 VL 34 IS 3 BP 208 EP 221 PG 14 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LA089 UT WOS:A1993LA08900003 PM 8493302 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI BUSPIRONE FOR MYOCLONUS, OBSESSIVE FEARS, AND CONFUSION SO PSYCHOSOMATICS LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,DIV HEMATOL ONCOL,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1993 VL 34 IS 3 BP 270 EP 272 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LA089 UT WOS:A1993LA08900012 PM 8493311 ER PT J AU SICHEL, DA COHEN, LS ROSENBAUM, JF DRISCOLL, J AF SICHEL, DA COHEN, LS ROSENBAUM, JF DRISCOLL, J TI POSTPARTUM ONSET OF OBSESSIVE-COMPULSIVE DISORDER SO PSYCHOSOMATICS LA English DT Article ID SOCIAL SUPPORT; LIFE EVENTS; DEPRESSION; PREGNANCY; CHILDBEARING; WOMEN RP SICHEL, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,PSYCHOPHARMACOL UNIT,WACC 815,FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 35 Z9 35 U1 4 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1993 VL 34 IS 3 BP 277 EP 279 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LA089 UT WOS:A1993LA08900014 PM 8493313 ER PT J AU SIBERSKI, JR AF SIBERSKI, JR TI CLINICAL GERIATRIC PSYCHOPHARMACOLOGY, 2ND EDITION - SALZMAN,C SO PSYCHOSOMATICS LA English DT Book Review RP SIBERSKI, JR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1993 VL 34 IS 3 BP 280 EP 281 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LA089 UT WOS:A1993LA08900015 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI PSYCHOIMMUNOLOGY UPDATE - GORMAN,JM, KERTZNER,RM SO PSYCHOSOMATICS LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GREENBERG, DB (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1993 VL 34 IS 3 BP 281 EP 282 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LA089 UT WOS:A1993LA08900016 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI TARDIVE-DYSKINESIA - A TASK-FORCE REPORT OF THE AMERICAN-PSYCHIATRIC-ASSOCIATION - KANE,JM, JESTE,DV SO PSYCHOSOMATICS LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GREENBERG, DB (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1993 VL 34 IS 3 BP 282 EP 283 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA LA089 UT WOS:A1993LA08900017 ER PT J AU DISLER, DG ALEXANDER, AA MANKIN, HJ OCONNELL, JX ROSENBERG, AE ROSENTHAL, DI AF DISLER, DG ALEXANDER, AA MANKIN, HJ OCONNELL, JX ROSENBERG, AE ROSENTHAL, DI TI MULTICENTRIC FIBROMATOSIS WITH METAPHYSEAL DYSPLASIA SO RADIOLOGY LA English DT Article DE BONES, METAPHYSES; BONES, OSTEOCHONDRODYSPLASIAS; DESMOID; FIBROMA; MUSCLES, NEOPLASMS ID AGGRESSIVE FIBROMATOSIS; DESMOID TUMORS; BONE AB A new association between multicentric fibromatosis and a bone dysplasia is reported. Three patients are described, each of whom had multicentric fibromatosis of the lower extremity and a skeletal dysplasia. One of the patients had dysplastic changes restricted to the involved extremity. The other two had dysplastic changes of all the long bones. The dysplasia consisted predominantly of undertubulation reminiscent of the findings seen in Pyle disease. No clinical or radiographic abnormalities of the marrow were found in any of these patients. It is believed that this association represents mesenchyme that is predisposed to develop both dysplastic bone changes and tumor. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,STE 515,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 19 TC 17 Z9 18 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1993 VL 187 IS 2 BP 489 EP 492 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KY907 UT WOS:A1993KY90700040 PM 8475296 ER PT J AU SCHENKER, S HALFF, GA AF SCHENKER, S HALFF, GA TI NUTRITIONAL THERAPY IN ALCOHOLIC LIVER-DISEASE SO SEMINARS IN LIVER DISEASE LA English DT Review ID PROTEIN-CALORIE MALNUTRITION; RANDOMIZED CONTROLLED TRIAL; AMINO-ACID SUPPLEMENTATION; PARENTERAL-NUTRITION; SHORT-TERM; CIRRHOTIC-PATIENTS; CLINICAL-TRIAL; PYRIDOXAL 5'-PHOSPHATE; ABDOMINAL OPERATIONS; HEPATIC CIRRHOSIS C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED GASTROENTEROL & NUTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG LIVER TRANSPLANTAT,SAN ANTONIO,TX 78284. RP SCHENKER, S (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIAAA NIH HHS [R01 AA07514] NR 114 TC 17 Z9 19 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 1993 VL 13 IS 2 BP 196 EP 209 DI 10.1055/s-2007-1007349 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LL293 UT WOS:A1993LL29300008 PM 8337604 ER PT J AU WONG, TY DUNCAN, LM MIHM, MC AF WONG, TY DUNCAN, LM MIHM, MC TI MELANOMA MIMICKING DERMAL AND SPITZS NEVUS (NEVOID MELANOMA) SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4TH ANNUAL MELANOMA CONF : ADVANCES IN MELANOMA TREATMENT AND RESEARCH CY SEP 03-06, 1992 CL UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST, TAMPA, FL SP UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST HO UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST DE MELANOCYTIC NEVUS; MATURATION; SKIN AB We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as ''nevoid'' melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma. RP WONG, TY (reprint author), MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114, USA. RI Duncan, Lyn/E-9878-2013 NR 0 TC 24 Z9 24 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD MAY-JUN PY 1993 VL 9 IS 3 BP 188 EP 193 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA LC811 UT WOS:A1993LC81100005 PM 8516601 ER PT J AU SOBER, AJ AF SOBER, AJ TI DIAGNOSIS AND MANAGEMENT OF EARLY MELANOMA - A CONSENSUS VIEW SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4TH ANNUAL MELANOMA CONF : ADVANCES IN MELANOMA TREATMENT AND RESEARCH CY SEP 03-06, 1992 CL UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST, TAMPA, FL SP UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST HO UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST DE DYSPLASTIC NEVUS; ATYPICAL MOLE; MULTIPLE PRIMARIES; SCREENING AB The inefficacy of treatments for advanced melanoma have shifted the focus toward the recognition of early melanoma which is associated with a much more favorable outcome. In January 1992 the National Institutes of Health (NIH) held a Consensus Conference to establish definitions and therapeutic recommendations for the management of early melanoma. Early melanoma was defined as either in situ or invasive melanoma < 1 mm in depth. Surgical margins of 0.5 cm for in situ melanoma, and 1 cm for invasive melanoma less-than-or-equal-to 1 mm thick were recommended. The pathology reports should include as a minimum the diagnosis of melanoma, the maximum tumor thickness, and the status of the margins. Elective nodal dissection as well as high-tech radiologic procedures were not recommended. Follow-up of patients for the development of second primaries and of family members who may be at increased risk for Melanoma was also recommended. Public education programs were suggested to inform the public of the increasing melanoma risk and improved survival through early detection. RP SOBER, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BARTLETT 410,BOSTON,MA 02114, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD MAY-JUN PY 1993 VL 9 IS 3 BP 194 EP 197 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA LC811 UT WOS:A1993LC81100006 PM 8516602 ER PT J AU SOBER, AJ AF SOBER, AJ TI DIGITAL EPILUMINESCENCE MICROSCOPY IN THE EVALUATION OF PIGMENTED LESIONS - A BRIEF REVIEW SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4TH ANNUAL MELANOMA CONF : ADVANCES IN MELANOMA TREATMENT AND RESEARCH CY SEP 03-06, 1992 CL UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST, TAMPA, FL SP UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST HO UNIV S FLORIDA, H LEE MOFFITT CANC CTR & RES INST DE MELANOMA; COMPUTER DIAGNOSIS; MELANOMA PRECURSORS; NEVI AB Epiluminescence microscopy (ELM) is the application of oil followed by compression by a transparent material and examination under tangential illumination with magnification. This technique reduces the reflected light from the irregular surface of the stratum corneum and makes the epidermis more transparent so that structures at the dermal epidermal junction and upper dermis may be visualized. Digital ELM is the capture of ELM images by a television camera attached to a computer. The ELM approach results in improved diagnostic accuracy for pigmented lesions in the order of 20%. Advantages of digital ELM over standard ELM are the ability to capture images in an almost endless array of colors and hues, permanence of recording without degradation over time, the ability to transmit information electronically over long distances, and the ability to enhance certain features through electronic manipulation. Among the potential applications of digital ELM are assistance in establishing the diagnosis of melanoma during screening, maintenance and retrieval of images in patients who are being followed clinically with pigmented lesions, and better understanding of clinical histopathologic correlations. RP SOBER, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BARTLETT 410,BOSTON,MA 02114, USA. NR 0 TC 26 Z9 26 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD MAY-JUN PY 1993 VL 9 IS 3 BP 198 EP 201 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA LC811 UT WOS:A1993LC81100007 PM 8516603 ER PT J AU RAMESH, N RAMESH, V GUSELLA, JF GEHA, R AF RAMESH, N RAMESH, V GUSELLA, JF GEHA, R TI CHROMOSOMAL LOCALIZATION OF THE GENE FOR HUMAN B-CELL ANTIGEN-CD40 SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Note ID LYMPHOCYTES-B; GROWTH-FACTOR; RECEPTOR; CD40; INTERLEUKIN-4; ACTIVATION; ASSIGNMENT; APOPTOSIS; ANTIBODY; PROTEIN AB CD40 is a surface glycoprotein expressed on all human B lymphocytes and plays an important role in B-cell development, growth, and differentiation. Anti-CD40 monoclonal antibodies cause isotype switching in B cells treated with IL-4. CD40 is a member of a family of proteins that include low-affinity nerve growth factor receptor, TNF receptor, and the antigen Fas. The ligand for CD40 had been recently identified and has been assigned to the X chromosome. Using a panel of human-rodent somatic cell hybrids, we now show that CD40 maps to human chromosome 20. C1 MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP RAMESH, N (reprint author), CHILDRENS HOSP MED CTR,DIV IMMUNOL,BOSTON,MA 02115, USA. FU NCRR NIH HHS [RR-02172]; NIAID NIH HHS [AI31541, AI31136] NR 27 TC 20 Z9 21 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAY PY 1993 VL 19 IS 3 BP 295 EP 298 DI 10.1007/BF01233077 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA LP141 UT WOS:A1993LP14100009 PM 7687385 ER PT J AU MENTZER, SJ REILLY, JJ SKARIN, AT SUGARBAKER, DJ AF MENTZER, SJ REILLY, JJ SKARIN, AT SUGARBAKER, DJ TI PATTERNS OF LUNG INVOLVEMENT BY MALIGNANT-LYMPHOMA SO SURGERY LA English DT Article ID NON-HODGKINS LYMPHOMA; PULMONARY LYMPHOMAS; BRONCHOALVEOLAR LAVAGE; DISEASE; BIOPSY; DIAGNOSIS; LEUKEMIA; LESIONS; TISSUE; LFA-1 AB Background. Recent evidence has suggested that the anatomic distribution of malignant lymphomas may reflect important differences in biologic behavior. To determine if the anatomic distribution of malignant lymphomas in the lung correlated with the disease course, we examined the pattern of lung involvement in patients with Hodgkin's and non-Hodgkin's lymphomas. Methods. We reviewed the medical records of 651 patients with a diagnosis of malignant lymphoma and identified 54 patients with histologically documented lung involvement. Based on radiologic and surgical findings, these patients had lung involvement characterized as either (1) bronchovascular-lymphangitic, (2) nodular, or (3) alveolar. The pattern of lung involvement was correlated with clinical manifestations and disease course. Results. Distinct clinical courses were associated with these three patterns Of lung involvement. In contrast, traditional histopathologic classification did not correlate with the pattern of lung involvement or the disease course in these 54 patients. An alveolar pattern of lung involvement was a poor prognostic factor and was associated with a median survival of 12 1/2 months. Pleural effusions eventually developed in 24 patients and were associated with a median survival of only 3 months. Conclusions. These findings suggest that the anatomic pattern of lung involvement is a measure of biologic behavior and may be a useful variable in the staging of patients with malignant lymphoma. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV PULM MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MENTZER, SJ (reprint author), BRIGHAM & WOMENS HOSP,DEPT SURG,DIV THORAC SURG,BOSTON,MA 02115, USA. FU PHS HHS [09280] NR 36 TC 17 Z9 17 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 1993 VL 113 IS 5 BP 507 EP 514 PG 8 WC Surgery SC Surgery GA LB132 UT WOS:A1993LB13200005 PM 8488467 ER PT J AU CARLSON, JA DICKERSIN, GR AF CARLSON, JA DICKERSIN, GR TI MELANOTIC PARAGANGLIOID CARCINOID-TUMOR - A CASE-REPORT AND REVIEW OF THE LITERATURE SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE HMB-45; MELANIN; MULTIDIRECTIONAL DIFFERENTIATION; NEUROENDOCRINE NEOPLASMS; PARAGANGLIOID CARCINOID; S-100 PROTEIN; SUSTENTACULAR CELLS ID NERVE SHEATH TUMOR; SUSTENTACULAR CELLS; MELANIN PRODUCTION; LUNG; PHEOCHROMOCYTOMAS; DIFFERENTIATION; NEOPLASMS; PEPTIDES; UTERUS; THYMUS AB An unusual case of peripheral melanotic paraganglioid carcinoid tumor of the lung is described. By light microscopic, immunohistochemical, and electron microscopic examination, melanocytic, schwannian, and neuroepithelial lines of differentiation were evident. This case may represent another example of neoplastic multidirectional differentiation and highlights the close relationship among the genes represented in these three cell lines. In addition, these findings support the concept of a neoplastic origin for the sustentacular cells found in some bronchial carcinoid tumors. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA 02114. OI Carlson, John Andrew/0000-0002-6866-6314 NR 39 TC 13 Z9 13 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-AUG PY 1993 VL 17 IS 3-4 BP 353 EP 372 PG 20 WC Microscopy; Pathology SC Microscopy; Pathology GA LZ586 UT WOS:A1993LZ58600016 PM 8266598 ER PT J AU DICKERSIN, GR AF DICKERSIN, GR TI INTRODUCTION - ELECTRON-MICROSCOPY OF TUMORS OF THE GENITAL SYSTEMS SO ULTRASTRUCTURAL PATHOLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA 02114. RP DICKERSIN, GR (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-AUG PY 1993 VL 17 IS 3-4 BP 375 EP 375 PG 1 WC Microscopy; Pathology SC Microscopy; Pathology GA LZ586 UT WOS:A1993LZ58600017 ER PT J AU DICKERSIN, GR SCULLY, RE AF DICKERSIN, GR SCULLY, RE TI ROLE OF ELECTRON-MICROSCOPY IN METASTATIC ENDOMETRIAL STROMAL TUMORS SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE ELECTRON MICROSCOPY, ENDOMETRIAL STROMAL NODULES; ENDOMETRIAL STROMAL SARCOMA, ENDOMETRIAL STROMAL TUMORS, ULTRASTRUCTURE ID MIXED MULLERIAN TUMORS; FLOW CYTOMETRIC ANALYSIS; CLINICOPATHOLOGIC ANALYSIS; HISTOGENETIC CONSIDERATIONS; CLINICAL CORRELATION; UTERUS; SARCOMA; NEOPLASMS; ADENOSARCOMA; IMMUNOHISTOCHEMISTRY AB Endometrial stromal tumors may pose a problem in diagnosis when they appear as metastatic lesions without a known primary tumor. To determine the usefulness of electron microscopy in identifying them in these situations, optimally fixed low-grade stromal sarcomas (five), normal endometrial specimens (six), and malignant mesodermal mixed tumors (four) were studied. The endometrial stromal sarcomas had a general resemblance to normal proliferative endometrial stroma, being composed of undifferentiated cells, fibroblasts, and myofibroblasts. One stromal tumor showed evidence of partial epithelial differentiation. One of the four malignant mesodermal mixed tumors had a fibrosarcomalike component, but there was insufficient resemblance to normal endometrial stroma to indicate a relationship between the two. Together with a review of the literature, this study indicates that electron microscopy is useful in the diagnosis of low-grade endometrial stromal tumors by demonstrating characteristic cellular findings as well as a lack of features specific for other round cell and spindle cell neoplasms. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA 02114. RP DICKERSIN, GR (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114, USA. NR 56 TC 9 Z9 9 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-AUG PY 1993 VL 17 IS 3-4 BP 377 EP 403 PG 27 WC Microscopy; Pathology SC Microscopy; Pathology GA LZ586 UT WOS:A1993LZ58600018 PM 8266599 ER PT J AU DICKERSIN, GR SCULLY, RE AF DICKERSIN, GR SCULLY, RE TI AN UPDATE ON THE ELECTRON-MICROSCOPY OF SMALL-CELL CARCINOMA OF THE OVARY WITH HYPERCALCEMIA SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article AB Since the first description of small cell carcinoma of the ovary with hypercalcemia in 1982, similar tumors have been reported, and more than 150 additional cases have been seen in consultation. This tumor is the most common form of undifferentiated carcinoma of the ovary in women younger than 40 years and has a poor prognosis. It is now recognized to have a large cell component in 40% of cases, and large cells occasionally predominate. The tumors are also unaccompanied by hypercalcemia in about one third of the cases. Microscopically, the most common pattern is diffuse sheets of compact cells, but clusters, cords, and folliclelike structures are also usually present as well. Mitoses are numerous. Immunostaining is almost always positive for keratin, often for vimentin, and occasionally for epithelial membrane antigen. Electron microscopy (19 cases) has revealed oval, polygonal, and occasionally elongated cells that are poorly differentiated but usually contain a moderate to large amount of dilated rough endoplasmic reticulum as their most constant cytologic feature. Junctions, including desmosomes and in some cases tight junctions, mark the cells as epithelial. The histogenesis of small cell carcinoma of the ovary is still not known, but it is usually possible to distinguish it from other small cell tumors of the ovary. Neuroendocrine cells and germ cells have been suggested as possible lineages, but the clinical and morphologic evidence is against those interpretations. C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA 02114. RP DICKERSIN, GR (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114, USA. NR 12 TC 16 Z9 16 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-AUG PY 1993 VL 17 IS 3-4 BP 411 EP 422 PG 12 WC Microscopy; Pathology SC Microscopy; Pathology GA LZ586 UT WOS:A1993LZ58600020 PM 8266601 ER PT J AU DICKERSIN, GR AF DICKERSIN, GR TI ULTRAPATH-VI - SCIENCE AND CAMARADERIE SO ULTRASTRUCTURAL PATHOLOGY LA English DT Editorial Material RP DICKERSIN, GR (reprint author), MASSACHUSETTS GEN HOSP,LOCAL ORGANIZING COMM ULTRAPATH VI,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-AUG PY 1993 VL 17 IS 3-4 BP R5 EP R7 PG 3 WC Microscopy; Pathology SC Microscopy; Pathology GA LZ586 UT WOS:A1993LZ58600001 ER PT J AU LI, XQ HOM, DL BLACK, J STEVENSON, S AF LI, XQ HOM, DL BLACK, J STEVENSON, S TI RELATIONSHIP BETWEEN METALLIC IMPLANTS AND CANCER - A CASE-CONTROL STUDY IN A CANINE POPULATION SO VETERINARY AND COMPARATIVE ORTHOPAEDICS AND TRAUMATOLOGY LA English DT Article DE FRACTURE; METALLIC IMPLANTS; CANCER; CASE-CONTROL STUDY; LOCAL AND SYSTEMIC EFFECTS AB To assess the possible role of metallic implants in the development of local, systemic and remote site cancer, a case-controlled study was conducted in a canine population. The cases consisted of 222 dogs with tumours of any kind, preceded by a fracture and fixation between January 1979 and December 1990. The controls consisted of 1635 dogs who had fracture and fixation for fracture without a later development of tumour during the same time period, randomly selected from the same database. Age was found to be a strong positive predictor for the development of tumours. A significant protective effect on tumours other than bone and soft tissue tumour development was seen associated with internal fixation (P < 0.05). There was not a significant increase of risk associated with metal materials for the development of bone and soft tissue tumours. Further study is needed to address the local effect of metallic implants on the development of bone and soft tissue tumours. RP LI, XQ (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED SERV,JACKSON 11,BOSTON,MA 02114, USA. NR 0 TC 15 Z9 15 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 0932-0814 J9 VET COMP ORTHOPAED JI Vet. Comp. Orthop. Traumatol. PD MAY PY 1993 VL 6 IS 2 BP 70 EP 74 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA LC138 UT WOS:A1993LC13800001 ER PT J AU ZAZOPOULOS, E HASELTINE, WA AF ZAZOPOULOS, E HASELTINE, WA TI EFFECT OF NEF ALLELES ON REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO VIROLOGY LA English DT Article ID OPEN READING FRAME; NUCLEOTIDE-SEQUENCE; MUTATIONAL ANALYSIS; AIDS VIRUS; HTLV-III; PROTEIN; GENE; EFFICIENT; INVIVO; REGION C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, U01 AI24845] NR 30 TC 50 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 1993 VL 194 IS 1 BP 20 EP 27 DI 10.1006/viro.1993.1230 PG 8 WC Virology SC Virology GA KY344 UT WOS:A1993KY34400003 PM 7683154 ER PT J AU DELOS, SE MONTROSS, L MORELAND, RB GARCEA, RL AF DELOS, SE MONTROSS, L MORELAND, RB GARCEA, RL TI EXPRESSION OF THE POLYOMAVIRUS VP2 AND VP3 PROTEINS IN INSECT CELLS - COEXPRESSION WITH THE MAJOR CAPSID PROTEIN VP1 ALTERS VP2/VP3 SUBCELLULAR-LOCALIZATION SO VIROLOGY LA English DT Note ID VIRUS-LIKE PARTICLES; NUCLEAR LOCATION SIGNAL; HIGH-LEVEL EXPRESSION; SIMIAN VIRUS-40; RECOMBINANT BACULOVIRUS; BLUETONGUE VIRUS; STRUCTURAL PROTEINS; AMINO-ACIDS; SV40 VP3; INVITRO C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. FU NCI NIH HHS [CA37667, R01 CA037667] NR 38 TC 48 Z9 49 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 1993 VL 194 IS 1 BP 393 EP 398 DI 10.1006/viro.1993.1274 PG 6 WC Virology SC Virology GA KY344 UT WOS:A1993KY34400047 PM 8386884 ER PT J AU STRUBEL, NA NGUYEN, M KANSAS, GS TEDDER, TF BISCHOFF, J AF STRUBEL, NA NGUYEN, M KANSAS, GS TEDDER, TF BISCHOFF, J TI ISOLATION AND CHARACTERIZATION OF A BOVINE CDNA-ENCODING A FUNCTIONAL HOMOLOG OF HUMAN P-SELECTIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GRANULE MEMBRANE-PROTEIN; LEUKOCYTE ADHESION; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; PLASMA-MEMBRANE; GMP-140; RECEPTOR; ACTIVATION; EXPRESSION; LECTINS C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,SURG RES LAB,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. OI Strubel, Naomi/0000-0002-4394-2108 FU NCI NIH HHS [5 T32CA 09535-06] NR 19 TC 28 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 30 PY 1993 VL 192 IS 2 BP 338 EP 344 DI 10.1006/bbrc.1993.1420 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LA360 UT WOS:A1993LA36000003 PM 7683458 ER PT J AU HUG, EB WANG, CC MONTGOMERY, WW GOODMAN, ML AF HUG, EB WANG, CC MONTGOMERY, WW GOODMAN, ML TI MANAGEMENT OF INVERTED PAPILLOMA OF THE NASAL CAVITY AND PARANASAL SINUSES - IMPORTANCE OF RADIATION-THERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE INVERTED PAPILLOMA; NASAL CAVITY; PARANASAL SINUSES; RADIATION THERAPY ID NOSE AB Purpose: Locally advanced inverted papilloma and inverted papilloma associated with squamous cell carcinoma are at high risk of local failure due to limitations of surgical resection resulting in repeat surgical procedures. The role of adjuvant radiation therapy is poorly defined. This study reviews a single institution experience of radiation therapy in the management of this disease. Methods and Material: Between 1977 and 1990 25 patients were treated at the Massachusetts General Hospital and the Massachusetts Eye and Ear Infirmary with radiation therapy for inverted papilloma (seven patients) and inverted papilloma associated with squamous cell carcinoma (18 patients) of the nasal cavity and paranasal sinuses. All patients presented with locally advanced invasive tumors; 5 of 7 with inverted papilloma had previous resections and 4 of 18 with associated squamous cell carcinoma had history of prior surgical excisions of inverted papilloma only (three patients) or inverted papilloma with squamous cell carcinoma in situ (one patient). Sixteen patients underwent radiation treatment following gross total resection, eight patients after subtotal tumor resection and one patient was inoperable by local invasion and received radiation therapy alone. Results: Local control was achieved in 6 of 7 patients with inverted papilloma only and one patient required additional resection for persistent disease. Of 18 patients with associated squamous cell carcinoma, 17 were locally controlled after radiation therapy and one had persistent tumor. One patient failed locally 3 years after treatment. With a mean observation time of 4.8 years (range: 0.5-12.9 years) all seven (100%) patients with inverted papilloma only and 15 of 18 (83%) patients with associated invasive carcinoma are alive and without evidence of disease. Three patients with inverted papilloma associated with squamous cell carcinoma died, two patients as a result of their disease (one patient with persistent disease, one patient after local failure) and one patient of intercurrent disease. No failure in either regional lymph nodes or at distant sites was recorded. In the majority of cases radiation therapy was well-tolerated. Conclusions: Combined radiation therapy and surgery can offer excellent long-term local control and should be considered in patients with history of recurrent disease, in the presence of suspected residual disease, after incomplete resection or for unresectable lesions. Patients with associated squamous cell carcinoma have a more aggressive course, however radiation therapy still has the prospect of permanent disease-free survival in patients who achieve local control. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. RP HUG, EB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 26 TC 22 Z9 22 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 APR 30 PY 1993 VL 26 IS 1 BP 67 EP 72 DI 10.1016/0360-3016(93)90174-T PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LC327 UT WOS:A1993LC32700008 PM 8482632 ER PT J AU TEICHER, BA HOLDEN, SA NORTHEY, D DEWHIRST, MW HERMAN, TS AF TEICHER, BA HOLDEN, SA NORTHEY, D DEWHIRST, MW HERMAN, TS TI THERAPEUTIC EFFECT OF INFUSED FLUOSOL-DA CARBOGEN WITH EPHEDRINE, FLUNARIZINE, OR NITROPRUSSIDE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE RADIOSENSITIZATION; FLUOSOL-DA; FLUNARIZINE; NITROPRUSSIDE; TUMOR PERFUSION ID TUMOR CYTO-TOXICITY; ENERGY-METABOLISM; BEARING RATS; BLOOD-FLOW; HYDRALAZINE; RADIATION; MELPHALAN; CHEMOTHERAPY; POTENTIATION; HYPERTHERMIA AB The perfluorochemical emulsion Fluosol-DA plus carbogen breathing has been shown to increase the effectiveness of radiation therapy in preclinical solid tumors when the emulsion was administered by i.v. bolus injection. Much of the enhancement in tumor radiation response was lost when the emulsion was administered slowly. Purpose: We hypothesized that an increase in tumor perfusion resulted when Fluosol-DA was administered rapidly. Methods and Materials: In the present study, the alpha/beta agonist ephedrine, the Ca2+ channel blocker flunarizine and the nitric oxide producing vasodilating drug nitroprusside have been tested. Results: Ephedrine administration resulted in a decrease in the radiation plus Fluosol-DA +/- carbogen antitumor effects in both the Lewis lung carcinoma and FSaIIC tumor systems. In contrast, flunarizine administration resulted in an increase in the efficacy of the radiation plus carbogen and the radiation plus Fluosol-DA/carbogen in both tumor systems. Even with flunarizine administration Fluosol-DA delivered slowly was less effective than when the emulsion was given rapidly. Flunarizine with Fluosol-DA infused i.v. over 30 min followed by carbogen breathing prior to and during radiation therapy resulted in a 1.7-1.6-fold increase in response compared with 2.4-2.2-fold with Fluosol-DA administered by injection i.v. and carbogen breathing prior to and during radiation therapy using growth delay of the Lewis lung carcinoma. The effects of nitroprusside were complex. This drug had considerably more effect at 10 Gy than at higher radiation doses. Conclusion: These studies suggest that Fluosol-DA given by i.v. injection may increase tumor perfusion and that a drug like flunarizine may be beneficial if the Fluosol-DA is administered slowly followed by carbogen breathing and radiation therapy. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,DURHAM,NC 27710. RP TEICHER, BA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [5R01-CA40355, P01-CA19589] NR 45 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1993 VL 26 IS 1 BP 103 EP 109 DI 10.1016/0360-3016(93)90179-Y PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LC327 UT WOS:A1993LC32700013 PM 8482616 ER PT J AU HARRIS, JR RECHT, A AF HARRIS, JR RECHT, A TI SEQUENCING ADJUVANT CHEMOTHERAPY AND RADIOTHERAPY IN BREAST-CANCER PATIENTS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID RANDOMIZED TRIAL C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT RADIAT ONCOL,BOSTON,MA 02115. RP HARRIS, JR (reprint author), BETH ISRAEL HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02215, USA. NR 15 TC 12 Z9 12 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 APR 30 PY 1993 VL 26 IS 1 BP 183 EP 185 DI 10.1016/0360-3016(93)90191-W PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LC327 UT WOS:A1993LC32700025 PM 8482626 ER PT J AU WANG, CC AF WANG, CC TI RADIATION-THERAPY FOR INVERTED PAPILLOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter RP WANG, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 30 PY 1993 VL 26 IS 1 BP 189 EP 189 DI 10.1016/0360-3016(93)90194-Z PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LC327 UT WOS:A1993LC32700028 ER PT J AU OLINER, JD PIETENPOL, JA THIAGALINGAM, S GVURIS, J KINZLER, KW VOGELSTEIN, B AF OLINER, JD PIETENPOL, JA THIAGALINGAM, S GVURIS, J KINZLER, KW VOGELSTEIN, B TI ONCOPROTEIN MDM2 CONCEALS THE ACTIVATION DOMAIN OF TUMOR SUPPRESSOR-P53 SO NATURE LA English DT Article ID P53 PROTEIN; WILD-TYPE; SEQUENCES; GENE AB THE tumour-suppressor gene p53 is inactivated in most human malignancies1 either by missense mutations1 or by binding to oncogenic proteins2-4. In human soft tissue sarcomas, inactivation apparently results from MDM2 gene amplification4. MDM2 is an oncogene product5,6 that may function by binding to p53 and inhibiting its ability to activate transcription3 . Here we show that, when expressed in Saccharomyces cerevisiae, human MDM2 inhibits human p53's ability to stimulate transcription by binding to a region that nearly coincides with the p53 acidic activation domain. The isolated p53 activation domain fused to another DNA-binding protein is also inactivated by MDM2, confirming that MDM2 can inhibit p53 function by concealing the activation domain of p53 from the cellular transcription machinery. C1 JOHNS HOPKINS ONCOL CTR,424 N BOND ST,BALTIMORE,MD 21231. JOHNS HOPKINS UNIV,SCH MED,PROGRAM HUMAN GENET,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 27 TC 1146 Z9 1158 U1 5 U2 24 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 29 PY 1993 VL 362 IS 6423 BP 857 EP 860 DI 10.1038/362857a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KZ563 UT WOS:A1993KZ56300063 PM 8479525 ER PT J AU GROWDON, JH YOUNG, TI RICHARDSON, EP VONSATTEL, JP MARGOLIN, DH AF GROWDON, JH YOUNG, TI RICHARDSON, EP VONSATTEL, JP MARGOLIN, DH TI A 53-YEAR-OLD WOMAN WHO DIED AFTER SEVERAL YEARS OF A DEMENTING ILLNESS WITH INTERMITTENT GENERALIZED SEIZURES AND ABNORMAL MOVEMENTS OF THE EXTREMITIES AND HEAD - SPONGIFORM ENCEPHALOPATHY (CREUTZFELDT-JAKOB DISEASE), WITH AMYLOID (KURU) PLAQUES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID JAKOB DISEASE; ALZHEIMERS-DISEASE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GROWDON, JH (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 29 PY 1993 VL 328 IS 17 BP 1259 EP 1266 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA KZ061 UT WOS:A1993KZ06100009 ER PT J AU LAVIE, CJ MILANI, RV AF LAVIE, CJ MILANI, RV TI FACTORS PREDICTING IMPROVEMENTS IN LIPID VALUES FOLLOWING CARDIAC REHABILITATION AND EXERCISE TRAINING SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; HEART-DISEASE; SECONDARY PREVENTION; BYPASS-SURGERY; OVERWEIGHT MEN; RISK-FACTORS; OBESITY; MORTALITY AB Background: Cardiac rehabilitation and exercise training improve prognosis following major cardiac events, partly by improving coronary risk factors, including plasma lipids. Only limited data are available to define predictors of lipid improvements following aggressive non-pharmacologic therapy with cardiac rehabilitation. Methods: We studied 237 consecutive patients from two institutions who were enrolled in outpatient phase 2 cardiac rehabilitation and exercise programs. By univariable and multivariable analyses, we assessed the impact of numerous clinical variables, including indexes of obesity, age, gender, lipid concentrations, exercise capacity, and psychological factors, on improvements in plasma lipid values with cardiac rehabilitation. Results: Coronary risk factors improved following cardiac rehabilitation, including levels of low-density lipoprotein cholesterol (-4%; P<.05), high-density lipoprotein cholesterol (7%; P<.0001), and triglycerides (-13%; P<.0001), body mass index (-2%; P<.0001); percentage of body fat (-5%; P<.0001); and exercise capacity (26%; P<.0001). By both univariable and multivariable analyses, corresponding dyslipidemic baseline values were the strongest predictors of improvements in levels of low-density lipoprotein cholesterol (univariable: r=.5 1, P<.0001; multivariable: t=8.5, p<.0001), high-density lipoprotein cholesterol (univariable: r=.37, P<.0001; multivariable: t=6.6, P<.0001), and triglycerides (univariable: r=.36, P<.0001; multivariable: t=6.8, P<.0001). By multivariable analyses, reductions in body mass index (t=4.6, P<.0001) and older age (t=4.0, P<.0001) were strong independent predictors of reduction in triglyceride values following cardiac rehabilitation. However, low baseline triglyceride values were independently associated with improvements in both low-density and high-density lipoprotein cholesterol levels. Using a model incorporating 13 clinical variables, improvements in lipid values with cardiac rehabilitation were only modestly predictable with the variables assessed, accounting for only 30% to 40% of the improvements in lipid values. Conclusion: (1) Coronary risk factors markedly improved following cardiac rehabilitation and exercise training. (2) Improvements in lipid values are modestly predictable. (3) Those patients with the worst baseline lipid values had the most improvements in lipid values following cardiac rehabilitation. However, patients with combined hyplerlipidemia and low levels of high-density lipoprotein cholesterol are likely to require drug treatment. C1 ALTON OCHSNER MED FDN & OCHSNER CLIN,CTR CARDIOVASC HLTH,DEPT INTERNAL MED,CARDIOL SECT,NEW ORLEANS,LA 70121. MASSACHUSETTS GEN HOSP,CTR CARDIOVASC HLTH,DEPT PREVENT MED,BOSTON,MA 02114. RI Lavie, Carl/A-6014-2011; Milani, Richard/A-6045-2011; Gomez Gonzalez, Adela/D-2863-2012 NR 43 TC 31 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 26 PY 1993 VL 153 IS 8 BP 982 EP 988 DI 10.1001/archinte.153.8.982 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KZ436 UT WOS:A1993KZ43600007 PM 8481069 ER PT J AU HUSAIN, SS AF HUSAIN, SS TI FIBRIN AFFINITY OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR - EVIDENCE THAT ZN2+ MEDIATES STRONG AND SPECIFIC INTERACTION OF SINGLE-CHAIN UROKINASE WITH FIBRIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-ENDOTHELIAL CELLS; AMINO-ACID-SEQUENCE; PRO-UROKINASE; HUMAN-URINE; PROTEOLYTIC CLEAVAGE; ESCHERICHIA-COLI; U937 MONOCYTES; TISSUE; BINDING; PURIFICATION AB Interactions of components of the fibrinolytic system with fibrin play a key role in localization and regulation of plasminogen activation at the clot surface. Although interaction of tissue plasminogen activator (tPA) with fibrin is well established, the prevailing view is that urokinase-type plasminogen activator (uPA) does not bind to fibrin. In this report, I show that although there is little or no interaction of single-chain urokinase (Sc-uPA), two-chain urokinase (Tc-uPA), or low molecular weight urokinase (LMW-uPA) with fibrin in the absence of divalent metal cations, Sc-uPA is effectively bound to fibrin in the presence of Zn2+. By comparison, Tc-uPA is poorly bound and LMW-uPA is not bound to fibrin in the presence of the metal ion. The Zn2+-mediated fibrin binding of Sc-uPA is reversible, specific, and saturable. The interaction involves a single class of binding site with dissociation constant of 0.3 muM and stoichiometry of 2.7. Lacking apparent affinity for fibrin, uPA has not been considered to play a role in physiological fibrinolysis. The present study conclusively shows that Sc-uPA possesses a latent affinity for fibrin that is expressed in the presence of Zn2+. These findings raise the possibility that Zn2+ plays a regulatory role in uPA-mediated fibrinolysis by promoting effective localization of Sc-uPA at the clot surface. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP HUSAIN, SS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL38178] NR 58 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 25 PY 1993 VL 268 IS 12 BP 8574 EP 8579 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KX811 UT WOS:A1993KX81100033 PM 8473303 ER PT J AU WEITZMAN, JB PASQUALINI, R TAKADA, Y HEMLER, ME AF WEITZMAN, JB PASQUALINI, R TAKADA, Y HEMLER, ME TI THE FUNCTION AND DISTINCTIVE REGULATION OF THE INTEGRIN VLA-3 IN CELL-ADHESION, SPREADING, AND HOMOTYPIC CELL-AGGREGATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; MEMBRANE GLYCOPROTEIN; T-CELLS; ONCOGENIC TRANSFORMATION; FIBRONECTIN RECEPTOR; COLLAGEN RECEPTOR; DIVALENT-CATIONS; LAMININ RECEPTOR; BINDING-SITE; ALPHA-3-BETA-1 AB To assess directly the functional role of the integrin VLA-3 (alpha3beta1), we transfected human alpha3 cDNA into erythroleukemia (K562) cells and rhabdomyosarcoma (RD) cells. The resulting transfectants (KA3 and RA3) expressed alpha3beta1 on the cell surface as confirmed using a panel of nine anti-alpha3 monoclonal antibodies. Neither of the transfected cells exhibited increased adhesion to the extracellular matrix proteins fibronectin, laminin, and collagen. However, the KA3 transfectants did bind strongly to the extracellular matrix deposited by epidermal and carcinoma cell lines, allowing the cells to attach and spread. Binding to this cell-deposited ligand, probably containing epiligrin/kalinin, was specific to VLA-3 and could be inhibited by anti-alpha3 antibodies and by EDTA, but not by RGD peptides. In marked contrast to other integrins (VLA-2 and VLA-4), VLA-3 showed high constitutive activity in K562 cells, but was minimally active in RD cells. Also contrasting with other beta1 integrins, VLA-3 was minimally stimulated by the anti-beta1 monoclonal antibody TS/216 under normal conditions. VLA-3-mediated adhesive function was well supported by either Mg2+ or Mn2+, but was almost completely abolished by the presence of 1 mM Ca2+. Surprisingly, this negative Ca2+ effect was completely overcome by the addition of the stimulatory anti-beta1 monoclonal antibody TS2/16. Together, these results point to markedly distinct regulation for VLA-3 function compared to other beta1 integrins. Also, all anti-VLA-3 antibodies were able to induce temperature-dependent homotypic cell aggregation of KA3 cells, but not K562 cells. However, this aggregation did not appear to be directly mediated by VLA-3 since it was not inhibited by EDTA. In addition, no enhancement of heterotypic cell-cell adhesion was observed in alpha3-transfected cells. C1 Scripps Res Inst, RES INST, COMM VASC BIOL, LA JOLLA, CA 92037 USA. RP WEITZMAN, JB (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. OI Weitzman, Jonathan/0000-0001-8445-0102; takada, yoshikazu/0000-0001-5481-9589 FU NIGMS NIH HHS [GM47157, GM38903, GM46526] NR 62 TC 155 Z9 155 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 25 PY 1993 VL 268 IS 12 BP 8651 EP 8657 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KX811 UT WOS:A1993KX81100043 PM 8473308 ER PT J AU LI, FP GARBER, JE AF LI, FP GARBER, JE TI CANCER GENETICS - GENE FOR FAMILIAL BREAST AND OVARIAN-CANCER SO LANCET LA English DT Editorial Material RP LI, FP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115, USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 24 PY 1993 VL 341 IS 8852 BP 1060 EP 1061 DI 10.1016/0140-6736(93)92416-Q PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KZ018 UT WOS:A1993KZ01800009 PM 8096963 ER PT J AU MANOME, Y DATTA, R FINE, HA AF MANOME, Y DATTA, R FINE, HA TI EARLY RESPONSE GENE INDUCTION FOLLOWING DNA DAMAGE IN ASTROCYTOMA CELL-LINES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID MYELOID-LEUKEMIA CELLS; IMMEDIATE EARLY GENES; C-JUN PROTOONCOGENE; NERVE GROWTH-FACTOR; PROTO-ONCOGENE; TRANSCRIPTIONAL REGULATION; BINDING PROTEINS; LEUCINE ZIPPER; PC12 CELLS; FOS AB Early response genes (ERGs) are a group of genes with low or absent expression in quiescent cells that can be induced rapidly by a variety of proliferation and differentiation stimuli. c-jun and c-fos are prototypes for this group of genes. Recent evidence suggests that DNA damaging agents such as cytotoxic drugs and ionizing radiation can elicit strong ERG induction, suggesting that these genes may be involved in DNA damage repair and/or cell death. Paralleling this interest in drug-induced ERG expression is a growing body of evidence implicating ERG expression as important to the intrinsic function of the central nervous system. We therefore set out to explore the pattern of chemotherapeutic drug- and radiation-induced c-jun and c-fos expression in neuroectodermally (astrocytic) derived cell lines. We have demonstrated that various chemotherapeutic agents and ionizing radiation can induce c-jun in a time- and concentration-dependent manner. Furthermore, this induction can be prevented by pretreatment of the cells with agents that protect against DNA damage. Finally, we have demonstrated that c-fos and c-jun expression and induction are discoordinately regulated, reflecting a difference in astrocytic cell lines compared to hemapoietic cell lines. The possible relevance of these observations to the clinical resistance of astrocytic tumors to standard chemotherapy and radiation is discussed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN PHARMACOL,44 BINNEY ST,BOSTON,MA 02115. NR 49 TC 28 Z9 28 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 APR 22 PY 1993 VL 45 IS 8 BP 1677 EP 1684 DI 10.1016/0006-2952(93)90309-K PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LA820 UT WOS:A1993LA82000016 PM 8484806 ER PT J AU WEBER, GF WAXMAN, DJ AF WEBER, GF WAXMAN, DJ TI ACTIVATION OF THE ANTICANCER DRUG IFOSPHAMIDE BY RAT-LIVER MICROSOMAL P450 ENZYMES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ISOPHOSPHAMIDE NSC-109724; HORMONAL-REGULATION; STEROID-METABOLISM; CYTOCHROME-P-450; CYCLOPHOSPHAMIDE; IDENTIFICATION; EXPRESSION; PHARMACOKINETICS; PURIFICATION; IFOSFAMIDE AB The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide. Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes. Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes. Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates. Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies. Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s. These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JF-525,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-49248] NR 39 TC 66 Z9 66 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 22 PY 1993 VL 45 IS 8 BP 1685 EP 1694 DI 10.1016/0006-2952(93)90310-S PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LA820 UT WOS:A1993LA82000017 PM 8484807 ER PT J AU ANDREWS, NC ERDJUMENTBROMAGE, H DAVIDSON, MB TEMPST, P ORKIN, SH AF ANDREWS, NC ERDJUMENTBROMAGE, H DAVIDSON, MB TEMPST, P ORKIN, SH TI ERYTHROID TRANSCRIPTION FACTOR NF-E2 IS A HEMATOPOIETIC-SPECIFIC BASIC LEUCINE ZIPPER PROTEIN SO NATURE LA English DT Article ID BETA-GLOBIN GENE; DOMINANT CONTROL REGION; DNA-BINDING PROTEIN; PORPHOBILINOGEN DEAMINASE GENE; LOCUS-CONTROL REGION; AMINO-ACID-SEQUENCE; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; FUNCTIONAL-PROPERTIES; MAMMALIAN-CELLS AB Expression of globin genes in developing erythroid cells is controlled by upstream locus control regions. Activity of these regions in vivo requires an erythroid-specific nuclear factor (NF-E2) that binds AP-1-like recognition sites. Its tissue-specific component (p45 NF-E2) has been characterized by complementary DNA cloning as a new basic region-leucine zipper protein which dimerizes with a ubiquitous partner to form native NF-E2. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,MOLEC BIOL PROGRAM,NEW YORK,NY 10021. HOWARD HUGHES MED INST,BOSTON,MA 02115. OI Andrews, Nancy/0000-0003-0243-4462 NR 56 TC 543 Z9 546 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 1993 VL 362 IS 6422 BP 722 EP 728 DI 10.1038/362722a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KY450 UT WOS:A1993KY45000046 PM 8469283 ER PT J AU PETERS, LL ANDREWS, NC EICHER, EM DAVIDSON, MB ORKIN, SH LUX, SE AF PETERS, LL ANDREWS, NC EICHER, EM DAVIDSON, MB ORKIN, SH LUX, SE TI MOUSE MICROCYTIC ANEMIA CAUSED BY A DEFECT IN THE GENE ENCODING THE GLOBIN ENHANCER-BINDING PROTEIN NF-E2 SO NATURE LA English DT Article ID DOMINANT CONTROL REGION; MESSENGER-RNA; ALPHA-GLOBIN; CELLS; IRON AB THE nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha and beta-globin locus control regions1-4 and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase)1,5 The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors6. This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages6. The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk). Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption. Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles. The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein. Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta-thalassaemic (Hbb(d-th3)/Hbb(d-th3)) mice. We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly. C1 CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. JACKSON LAB,BAR HARBOR,ME 04609. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 23 TC 59 Z9 58 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 22 PY 1993 VL 362 IS 6422 BP 768 EP 770 DI 10.1038/362768a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KY450 UT WOS:A1993KY45000062 PM 8469289 ER PT J AU MCLELLAN, AT ARNDT, IO METZGER, DS WOODY, GE OBRIEN, CP AF MCLELLAN, AT ARNDT, IO METZGER, DS WOODY, GE OBRIEN, CP TI THE EFFECTS OF PSYCHOSOCIAL SERVICES IN SUBSTANCE-ABUSE TREATMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID METHADONE-MAINTENANCE; DRUG-ABUSE; SEVERITY; PSYCHOTHERAPY; SUCCESS AB Objective.-To examine whether the addition of counseling, medical care, and psychosocial services improves the efficacy of methadone hydrochloride therapy in the rehabilitation of opiate-dependent patients. Design.-Random assignment to one of three treatment groups for a 6-month clinical trial: (1) minimum methadone services (MMS)-methadone alone (a minimum of 60 mg/d) with no other services; (2) standard methadone services (SMS) -same dose of methadone plus counseling; or (3) enhanced methadone services (EMS)-same dose of methadone plus counseling and on-site medical/psychiatric, employment, and family therapy. Setting.-The methadone maintenance program of the Philadelphia (Pa) Veterans Affairs Medical Center. Subjects.-Ninety-two male intravenous opiate users in methadone maintenance treatment. Results.-While methadone treatment alone (MMS) was associated with reductions in opiate use, 69% of these subjects had to be ''protectively transferred'' from the trial because of unremitting use of opiates or cocaine, or medical/psychiatric emergencies. This was significantly different from the 41% of SMS subjects and 19% of EMS subjects who met the criteria. End-of-treatment data (at 24 weeks) showed minimal improvements among the 10 MMS patients who completed the trial. The SMS group showed significantly more and larger improvements than did the MMS group; and the EMS group showed significantly better outcomes than did the SMS group. Minimum methadone services subjects who had been ''protectively transferred'' to standard care showed significant reductions in opiate and cocaine use within 4 weeks. Conclusions.-Methadone alone (even in substantial doses) may only be effective for a minority of eligible patients. The addition of basic counseling was associated with major increases in efficacy; and the addition of on-site professional services was even more effective. C1 UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. RP MCLELLAN, AT (reprint author), PHILADELPHIA VET AFFAIRS MED CTR,PENN VA CTR STUDIES ADDICT,DEPT PSYCHIAT,UNIV AVE,BLDG 7,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA05634] NR 19 TC 567 Z9 572 U1 3 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 1993 VL 269 IS 15 BP 1953 EP 1959 DI 10.1001/jama.269.15.1953 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KX215 UT WOS:A1993KX21500024 PM 8385230 ER PT J AU BIESECKER, BB BOEHNKE, M CALZONE, K MARKEL, DS GARBER, JE COLLINS, FS WEBER, BL AF BIESECKER, BB BOEHNKE, M CALZONE, K MARKEL, DS GARBER, JE COLLINS, FS WEBER, BL TI GENETIC-COUNSELING FOR FAMILIES WITH INHERITED SUSCEPTIBILITY TO BREAST AND OVARIAN-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUNTINGTON DISEASE; LINKAGE AB Efforts are under way to isolate a gene (BRCA1) on chromosome 17q12-21. Mutations in this gene predispose women to breast and ovarian cancer. Women with germline mutations in BRCA1 are estimated to have an 85% lifetime risk of developing breast cancer and an increased but as yet undetermined risk of ovarian cancer. It is estimated that one in 200 to 400 American women may be carriers of BRCA1 mutations. We have identified several families that show linkage between breast and/or ovarian cancer and genetic markers that flank BRCA1. It is now possible, within these linked families, to prospectively identify family members likely to be carrying BRCA1 mutations. Because of profound and immediate clinical ramifications, we offered to provide this information to one such extended family. To provide information to this family, we developed a protocol to address the many issues that arise in the delivery of these services. Although testing for BRCA1 mutation carriers is currently limited to very rare families being analyzed for research purposes, this experience presages the complexities of the much larger scale availability of population screening for BRCA1 mutations, which is likely to become a reality in the next few years. C1 UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,DIV HEMATOL ONCOL,ROOM 5510,MSRB 1,1150 W MED CTR DR,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. HOWARD HUGHES MED INST,ANN ARBOR,MI. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA57601]; NHGRI NIH HHS [HG00209] NR 28 TC 244 Z9 244 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 21 PY 1993 VL 269 IS 15 BP 1970 EP 1974 DI 10.1001/jama.269.15.1970 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA KX215 UT WOS:A1993KX21500028 PM 8352830 ER PT J AU ANTONIADES, HN AF ANTONIADES, HN TI CELLULAR INJURY AND PROLIFERATIVE DISORDERS SO FASEB JOURNAL LA English DT Meeting Abstract C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 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 APR 20 PY 1993 VL 7 IS 7 BP A1293 EP A1293 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84801483 ER PT J AU BACHINSKY, D ZHENG, G ANDRES, G BROWN, D MCCLUSKEY, RT AF BACHINSKY, D ZHENG, G ANDRES, G BROWN, D MCCLUSKEY, RT TI EVIDENCE FOR INVIVO INTERACTIONS OF GP330, A MEMBER OF THE LDL RECEPTOR GENE FAMILY, AND APOLIPOPROTEIN-E AND AIV IN KIDNEY PROXIMAL TUBULES SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1244 EP A1244 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84801198 ER PT J AU BIERER, BE AF BIERER, BE TI MOLECULAR MECHANISMS OF IMMUNOSUPPRESSANT ACTION SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 APR 20 PY 1993 VL 7 IS 7 BP A1053 EP A1053 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800083 ER PT J AU CLAIRMONT, KB KIRCHHAUSEN, T AF CLAIRMONT, KB KIRCHHAUSEN, T TI STABLE EXPRESSION OF THE CLATHRIN ASSOCIATED BETA-CHAIN AND BETA'-CHAIN IN CHINESE-HAMSTER OVARY CELLS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1249 EP A1249 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84801226 ER PT J AU KAMITANI, T CHANG, HM ROLLINS, C WANECK, G YEH, ETH AF KAMITANI, T CHANG, HM ROLLINS, C WANECK, G YEH, ETH TI CORRECTION OF A DEFECT IN GPI ANCHOR BIOSYNTHESIS IN LTK- CELLS BY A CLONED HUMAN CDNA SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TEXAS,HOUSTON MED CTR,DEPT MED,HOUSTON,TX 77030. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 20 PY 1993 VL 7 IS 7 BP A1050 EP A1050 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800070 ER PT J AU KOLAKOWSKI, LF HOLTZMAN, EJ AUSIELLO, DA AF KOLAKOWSKI, LF HOLTZMAN, EJ AUSIELLO, DA TI MOLECULAR DEFECT IN THE VASOPRESSIN V2 RECEPTOR GENE CAUSING NEPHROGENIC DIABETES-INSIPIDUS SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,RENAL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1114 EP A1114 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800440 ER PT J AU LAUHON, C SZOSTAK, J AF LAUHON, C SZOSTAK, J TI INVITRO SELECTION OF RNA MOLECULES THAT SPECIFICALLY BIND RIBOFLAVIN SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 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 APR 20 PY 1993 VL 7 IS 7 BP A1087 EP A1087 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800285 ER PT J AU RAO, A MCCAFFREY, PG JAIN, J MINER, Z LAMBERT, J VERDINE, GL KERPPOLA, TK CURRAN, T AF RAO, A MCCAFFREY, PG JAIN, J MINER, Z LAMBERT, J VERDINE, GL KERPPOLA, TK CURRAN, T TI NUCLEAR FACTOR OF ACTIVATED T-CELLS (NF-AT) - INTERACTION WITH CALCINEURIN AND FOS JUN PROTEINS SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. ROCHE INST MOLEC BIOL,DEPT MOLEC ONCOL & VIROL,NUTLEY,NJ 07110. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOUR VIROL,BOSTON,MA 02115. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011 OI Curran, Tom/0000-0003-1444-7551; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1053 EP A1053 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800085 ER PT J AU WANECK, GL ROLLINS, C BROWN, D FLAVELL, RA FLYER, DC AF WANECK, GL ROLLINS, C BROWN, D FLAVELL, RA FLYER, DC TI INABILITY OF GPI-ANCHORED MHC CLASS-I (H-2) MOLECULES TO PRESENT VIRAL-ANTIGEN CORRELATES WITH THEIR DIFFERENCES IN INTRACELLULAR TRAFFICKING SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,HERSHEY,PA 17033. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1045 EP A1045 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800040 ER PT J AU HEBERT, LE SCHERR, PA BECKETT, LA ALBERT, MS ROSNER, B TAYLOR, JO EVANS, DA AF HEBERT, LE SCHERR, PA BECKETT, LA ALBERT, MS ROSNER, B TAYLOR, JO EVANS, DA TI RELATION OF SMOKING AND LOW-TO-MODERATE ALCOHOL-CONSUMPTION TO CHANGE IN COGNITIVE FUNCTION - A LONGITUDINAL-STUDY IN A DEFINED COMMUNITY OF OLDER PERSONS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE AGING; ALCOHOL DRINKING; ALZHEIMERS DISEASE; COGNITION; PROSPECTIVE STUDIES; LONGITUDINAL STUDIES; RISK FACTORS; SMOKING ID ALZHEIMERS-DISEASE; MEN; DRINKING AB To determine whether smoking habits and alcohol consumption are related to changes in cognitive function, the authors conducted a prospective, community-based study of persons aged 65 years and over in East Boston, Massachusetts. In 1982 and again in 1985, the subjects were given three brief tests of cognitive function: immediate memory, digit span, and a mental status questionnaire, which primarily assessed orientation. The 1,201 individuals who performed well in 1982 were included in linear regression analyses of 3-year change in performance, adjusted for age, sex, education, and income. Relative to nonsmoking, current smoking, past smoking, and pack-years were not significantly related to change in immediate memory. None was significantly related to change in orientation. Only pack-years was significantly related to normal change score in digit span (normal change score change per unit of predictor = 0.001, 95% confidence interval 0.0003-0.002). Low-to-moderate alcohol consumption during the month preceding baseline testing was not significantly related to a subsequent 3-year change in performance in two of the three tests. However, people who consumed a very small amount of alcohol had a normal change score that was 0.088 (95% confidence interval 0.015-0.160) better for digit span than did nondrinkers. This study provides evidence that the reported levels of smoking and alcohol use among older persons are not consistent or substantial predictors of the longitudinal change in cognitive function observed in a community. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP HEBERT, LE (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,CTR RES HLTH & AGING,1653 CONGRESS PKWY,CHICAGO,IL 60612, USA. NR 17 TC 54 Z9 54 U1 1 U2 4 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 1993 VL 137 IS 8 BP 881 EP 891 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LC830 UT WOS:A1993LC83000007 ER PT J AU NEUMANN, R DUTT, CJ FOSTER, CS AF NEUMANN, R DUTT, CJ FOSTER, CS TI IMMUNOHISTOPATHOLOGIC FEATURES AND THERAPY OF CONJUNCTIVAL LICHEN-PLANUS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TOPICAL CYCLOSPORINE; KERATOCONJUNCTIVITIS; IMMUNOPATHOLOGY; CHEMOTHERAPY; CELLS AB Lichen planus is an autoimmune disease that typically involves skin and the mucosa of the genitalia and mouth. Conjunctival involvement is rare, and the microscopic abnormalities of affected conjunctivae are not well characterized. We treated two patients with cicatrizing conjunctivitis and extraocular conjunctival lichen planus confirmed by biopsy. We found irregular, thickened basement membrane with reduplications similar to the findings in oral mucosa affected by lichen planus. The absence of basement membrane immunoreactants excluded ocular cicatricial pemphigoid. Results of laboratory tests for collagen vascular diseases including sarcoidosis and lupus were also negative. Treatment with 2% cyclosporine eyedrops controlled inflammation and stopped cicatrization in one patient who was followed up for 12 months. The other patient, in whom lichen planus was recently diagnosed, responded favorably to topical cyclosporine. Lichen planus should be included in the differential diagnosis of cicatrizing conjunctivitis and its immunohistopathologic features should be studied in conjunctival biopsies. Topical cyclosporine may be used successfully for conjunctival lichen planus. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,IMMUNOL SERV,BOSTON,MA 02114. NR 21 TC 34 Z9 35 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR 15 PY 1993 VL 115 IS 4 BP 494 EP 500 PG 7 WC Ophthalmology SC Ophthalmology GA KW262 UT WOS:A1993KW26200012 PM 8470722 ER PT J AU KYLSTRA, JA LAMKIN, JC RUNYAN, DK AF KYLSTRA, JA LAMKIN, JC RUNYAN, DK TI CLINICAL PREDICTORS OF SCLERAL RUPTURE AFTER BLUNT OCULAR TRAUMA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GLOBE AB We conducted a two-part study to define better the clinical predictors of scleral rupture after blunt trauma. In part 1 we ascertained the prevalence of scleral rupture among a population of patients examined in an ophthalmic emergency room with severe blunt ocular trauma over a six-month period. Scleral rupture was diagnosed in ten of 283 patients (3.5%). In part 2 we compared the clinical findings in 29 patients with scleral rupture to those of 273 patients with no scleral rupture after blunt trauma. We noted that eyes with visual acuity of light perception or less, an intraocular pressure of 5 mm Hg or less, an abnormally deep or shallow anterior chamber, or a media opacity preventing a view of fundus details by indirect ophthalmoscopy, should be considered ruptured when severe intra- or periocular hemorrhage is present. This diagnostic algorithm had a sensitivity of 100.0% (98.7% to 100.0%), specificity of 98.5% (97.1% to 99.9%), and a positive predictive value of 71.4% (66.3% to 76.5%). C1 UNIV N CAROLINA,SCH MED,DEPT SOCIAL MED,CHAPEL HILL,NC 27514. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC 27514. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. RP KYLSTRA, JA (reprint author), UNIV N CAROLINA,SCH MED,DEPT OPHTHALMOL,617 CLIN SCI BLDG,CB 7040,CHAPEL HILL,NC 27599, USA. NR 10 TC 13 Z9 13 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 APR 15 PY 1993 VL 115 IS 4 BP 530 EP 535 PG 6 WC Ophthalmology SC Ophthalmology GA KW262 UT WOS:A1993KW26200018 PM 8470728 ER PT J AU WHEAT, J HAFNER, R WULFSOHN, M SPENCER, P SQUIRES, K POWDERLY, W WONG, B RINALDI, M SAAG, M HAMILL, R MURPHY, R CONNOLLYSTRINGFIELD, P BRIGGS, N OWENS, S AF WHEAT, J HAFNER, R WULFSOHN, M SPENCER, P SQUIRES, K POWDERLY, W WONG, B RINALDI, M SAAG, M HAMILL, R MURPHY, R CONNOLLYSTRINGFIELD, P BRIGGS, N OWENS, S TI PREVENTION OF RELAPSE OF HISTOPLASMOSIS WITH ITRACONAZOLE IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; HISTOPLASMOSIS; ASTERISK-ITRACONAZOLE; AMPHOTERICIN-B; HUMAN IMMUNODEFICIENCY VIRUS INFECTIONS ID CAPSULATUM ANTIGEN; AMPHOTERICIN-B; AIDS; DIAGNOSIS; FLUCONAZOLE; THERAPY AB Objective: To assess the efficacy and safety of itraconazole in preventing relapse of histoplasmosis after induction therapy with amphotericin B in patients with the acquired immunodeficiency syndrome (AIDS) and disseminated histoplasmosis. Design: A prospective, multicenter, open-label clinical trial, with follow-up for at least 52 weeks. Setting: Tertiary care hospitals participating in a clinical investigation sponsored by the National Institutes of Allergy and Infectious Diseases (AIDS Clinical Trial Group and Mycoses Study Group). Patients: Forty-two patients with AIDS who had successfully completed induction therapy for disseminated histoplasmosis amphotericin B, at least 15 mg/kg body weight given over 4 to 12 weeks. Interventions: Itraconazole, 200 mg given orally twice daily. Main Outcome Measures: Response to therapy, specifically prevention of histoplasmosis relapse, was the main outcome measure. Secondary end points were survival and the effect of therapy on Histoplasma capsulatum variety capsulatum antigen levels in urine and serum. Plasma itraconazole concentrations were measured to document drug absorption and compliance with therapy. Results: The median follow-up was 109 weeks, and median survival was 98 weeks. Two relapses occurred (5%; 95% CI, 0.5% to 16%), one in a patient withdrawn from the study 18 weeks earlier and one in a patient who did not comply with the study therapy. Patients with elevated antigen levels at study entry showed clearance of antigen from urine and serum; urine specimens became negative in 43% of patients (CI, 26% to 59%), and serum specimens became negative in 75% of patients (CI, 56% to 94%). Only one patient discontinued treatment because of itraconazole toxicity (hypokalemia). Conclusions: Itraconazole, 200 mg twice daily, is safe and effective in preventing relapse of disseminated histoplasmosis in patients with AIDS. Antigen clearance from blood and urine correlates with clinical efficacy. C1 UNIV CINCINNATI,COLL MED,DEPT INTERNAL MED,CINCINNATI,OH 45221. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RICHARD L ROUDEBUSH VET AFFAIRS HOSP,INDIANAPOLIS,IN. DEPT VET AFFAIRS MED CTR,BIRMINGHAM,AL 35233. DEPT VET AFFAIRS MED CTR,DIV INFECT DIS 111G,HOUSTON,TX 77030. FRONTIER SCI & TECH RES FDN,AMHERST,NY 14226. WASHINGTON UNIV,CLIN TRIALS UNIT,ST LOUIS,MO 63130. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. INDIANA UNIV,SCH MED,IDRC,INDIANAPOLIS,IN 46202. CORNELL UNIV,ITHACA,NY 14853. RICHARD L ROUDEBUSH VET ADM MED CTR,INDIANAPOLIS,IN 46202. NIH,DIV AIDS,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. OI Murphy, Robert/0000-0003-3936-2052 FU NIAID NIH HHS [1-AI-15082] NR 19 TC 150 Z9 153 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 APR 15 PY 1993 VL 118 IS 8 BP 610 EP 616 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KW470 UT WOS:A1993KW47000006 PM 8383934 ER PT J AU CHANG, TKH TEIXEIRA, J GIL, G WAXMAN, DJ AF CHANG, TKH TEIXEIRA, J GIL, G WAXMAN, DJ TI THE LITHOCHOLIC ACID 6-BETA-HYDROXYLASE CYTOCHROME-P-450, CYP 3A10, IS AN ACTIVE CATALYST OF STEROID-HORMONE 6-BETA-HYDROXYLATION SO BIOCHEMICAL JOURNAL LA English DT Article ID RAT-LIVER MICROSOMES; AGE-DEPENDENT EXPRESSION; HEPATIC CYTOCHROME-P-450; SEXUAL-DIFFERENTIATION; BILE-ACIDS; METABOLISM; TESTOSTERONE; ENZYMES; FORMS; 5-ALPHA-REDUCTASE AB CYP 3A10 is a hamster liver cytochrome P-450 (P450) that encodes lithocholic acid 6beta-hydroxylase, an enzyme that plays an important role in the detoxification of the cholestatic secondary bile acid lithocholate. Western-blot analysis revealed that the expression of CYP 3A10 protein is male-specific in hamster liver microsomes, a finding that is consistent with earlier analysis of CYP 3A10 mRNA. Since it has not been established whether the specificities of bile acid hydroxylase P450s, such as CYP 3A10, are restricted to their anionic bile acid substrates, we investigated the role of CYP 3A10 in the metabolism of a series of neutral steroid hormones using cDNA directed-expression in COS cells. The steroid hormones examined, testosterone, androstenedione and progesterone, were each metabolized by the expressed CYP 3A10, with 6beta-hydroxylation corresponding to a major activity in all three instances. CYP3A10-dependent steroid hydroxylation was increased substantially when the microsomes were prepared from COS cells co-transfected with NADPH:P450 reductase cDNA. In this case, the expressed P450 actively catalysed the 6beta-hydroxylation of testosterone (288 +/- 23 pmol of product formed/min per mg of COS-cell microsomal protein), androstenedione (107 +/- 19 pmol/min per mg) and progesterone (150 +/- 7 pmol/min per mg). Other major CYP 3A10-mediated steroid hydroxylase activities included androstenedione 16alpha-hydroxylation, progesterone 16alpha- and 21-hydroxylation, and the formation of several unidentified products. CYP 3A10 exhibited similar V(max) values for the 6beta-hydroxylation of androstenedione and lithocholic acid (132 and 164 pmol/min per mg respectively), but metabolized the bile acid with a 3-fold lower K(m) (25 muM, as against 75 muM for androstenedione). Together, these studies establish that the substrate specificity of the bile acid hydroxylase CYP 3A10 is not restricted to bile acids, and further suggest that CYP 3A10 can play a physiologically important role in the metabolism of two classes of endogenous P450 substrates: steroid hormones and bile acids. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,RM JF-525,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WORCESTER,MA 01655. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK33765] NR 40 TC 24 Z9 25 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1993 VL 291 BP 429 EP 434 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KZ698 UT WOS:A1993KZ69800015 PM 8484723 ER PT J AU FINE, HA DEAR, KBG LOEFFLER, JS BLACK, PM CANELLOS, GP AF FINE, HA DEAR, KBG LOEFFLER, JS BLACK, PM CANELLOS, GP TI METAANALYSIS OF RADIATION-THERAPY WITH AND WITHOUT ADJUVANT CHEMOTHERAPY FOR MALIGNANT GLIOMAS IN ADULTS SO CANCER LA English DT Article DE METAANALYSIS; MALIGNANT GLIOMAS; ASTROCYTOMA; GLIOBLASTOMA; CHEMOTHERAPY; ADJUVANT; BRAIN TUMORS ID COMBINED MODALITY THERAPY; BRAIN-TUMORS; CCNU-CHEMOTHERAPY; CLINICAL-TRIALS; METHYL-CCNU; POSTOPERATIVE RADIOTHERAPY; MYOCARDIAL-INFARCTION; ANAPLASTIC GLIOMAS; RANDOMIZED TRIALS; ONCOLOGY-GROUP AB Background. The value of chemotherapy after standard postoperative external beam radiation in the treatment of malignant gliomas remains controversial. Despite recent recommendations from the Brain Tumor Cooperative Group that chemotherapy should be considered part of the standard treatment of patients with high-grade astrocytomas, several recent trials have questioned the efficacy of this approach. Methods. Using results from 16 randomized clinical trials involving more than 3000 patients, the authors compared the survival rates of patients who received radiation alone or radiation with chemotherapy. The combined data were analyzed using the statistical method of meta-analysis as described by DerSimonian and Laird. Results. The estimated increase in survival for patients treated with combination radiation and chemotherapy was 10.1% at 1 year (95% confidence interval, 6.8, 13.3%) and 8.6% at 2 years (5.2, 12.0%). These absolute increases in survival (treated-control [TC]) in patients treated with chemotherapy represent relative increases (T-C)/C of 23.4% at 1 year (15.8, 30.9%) and 52.4% at 2 years (31.7, 73.2%). This survival advantage is conferred by several different chemotherapeutic agents. When the prognostic variables of age and histology are factored into the analysis, however, the data suggest that the survival benefit from chemotherapy occurs earlier in patients with anaplastic astrocytoma (AA) than in patients with glioblastoma. Conclusions. The authors concluded that chemotherapy is advantageous for patients with malignant gliomas and should be considered part of the standard therapeutic regimen. Additional randomized trials using optimal radiation and chemotherapy may still be needed to precisely define which subgroups of patients, based on prognostic variables, will benefit most from chemotherapy after radiation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BRAIN TUMOR,BOSTON,MA 02115. RP FINE, HA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K11 CA-O1467-01A1, CA-06516] NR 54 TC 676 Z9 687 U1 3 U2 14 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1993 VL 71 IS 8 BP 2585 EP 2597 DI 10.1002/1097-0142(19930415)71:8<2585::AID-CNCR2820710825>3.0.CO;2-S PG 13 WC Oncology SC Oncology GA KW562 UT WOS:A1993KW56200024 PM 8453582 ER PT J AU HEALEY, EA TARBELL, NJ KALISH, LA SILVER, B ROSENTHAL, DS MARCUS, K SHULMAN, LN COLEMAN, CN CANELLOS, G WEINSTEIN, H MAUCH, P AF HEALEY, EA TARBELL, NJ KALISH, LA SILVER, B ROSENTHAL, DS MARCUS, K SHULMAN, LN COLEMAN, CN CANELLOS, G WEINSTEIN, H MAUCH, P TI PROGNOSTIC FACTORS FOR PATIENTS WITH HODGKIN DISEASE IN 1ST RELAPSE SO CANCER LA English DT Article DE HODGKIN DISEASE; RELAPSE; SALVAGE; PROGNOSTIC FACTORS; RADIATION THERAPY; CHEMOTHERAPY; HISTOLOGY ID COMBINATION CHEMOTHERAPY; PATHOLOGIC STAGE; INITIAL RELAPSES; RADIOTHERAPY; RADIATION; THERAPY; MANTLE; TABLES AB Background, This study aims to identify factors that predict outcome after salvage therapy for patients with Hodgkin disease (HD) in first relapse. Methods. Between 1969 and 1985, 627 patients with Pathologic Stage IA-IIIB HD were treated at the joint Center for Radiation Therapy. With a median follow-up time for survivors of 135 months, 138 patients (22%) have experienced relapse. One hundred twenty-seven of these were retreated with curative intent and form the basis of this report. Results. The complete response (CR) rate after retreatment was 79%. The 10-year actuarial freedom from second relapse (FSR) was 53%, and the 10-year survival rate from the time of first relapse was 57%. For patients experiencing relapse after initial radiation therapy (RT) alone (n = 110), the 10-year FSR and overall survival rates were 58% and 62%, respectively. Histologic type was the single most important prognostic factor for second CR rate, FSR, and survival. Patients with nodular sclerosis or lymphocyte predominant (NS/LP) histologic type had a 91% second CR rate, 67% 10-year FSR rate, and 75% 10-year survival rate, compared with 66%, 44%, and 43%, respectively, for patients with mixed cellularity or lymphocyte depleted (MC/LD) histologic type. For patients who experienced relapse after initial combined modality therapy (CMT; n = 17), the 10-year FSR and overall survival rates were 13% and 24%, respectively. Conclusion. This study demonstrates that patients who experience relapse after RT alone can be effectively salvaged with combination chemotherapy. The implications of these results for clinical decision making are discussed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOSP PEDIAT,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP HEALEY, EA (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,JOINT CTR RADIAT THERAPY,50 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516, 2T32CA09001] NR 25 TC 47 Z9 47 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1993 VL 71 IS 8 BP 2613 EP 2630 DI 10.1002/1097-0142(19930415)71:8<2613::AID-CNCR2820710828>3.0.CO;2-T PG 18 WC Oncology SC Oncology GA KW562 UT WOS:A1993KW56200027 PM 8453585 ER PT J AU WONG, JM MAFUNE, K YOW, H RIVERS, EN RAVIKUMAR, TS STEELE, GD CHEN, LB AF WONG, JM MAFUNE, K YOW, H RIVERS, EN RAVIKUMAR, TS STEELE, GD CHEN, LB TI UBIQUITIN-RIBOSOMAL PROTEIN-S27A GENE OVEREXPRESSED IN HUMAN COLORECTAL-CARCINOMA IS AN EARLY GROWTH-RESPONSE GENE SO CANCER RESEARCH LA English DT Article ID MESSENGER-RNA CONTENT; SEQUENCE ANALYSIS; ESCHERICHIA-COLI; 3T3 CELLS; EXPRESSION; CDNA; MECHANISMS; CLONING; FUSION; FAMILY AB One of the extension proteins on the carboxy terminus of ubiquitin was reported as the ribosomal protein S27a. We have cloned a gene which encodes this ubiquitin hybrid protein from a complementary DNA library of a human colon carcinoma cell line. Northern blot analysis of surgical specimens from colon cancer patients showed that these messenger RNA levels were higher in tumor tissue than in adjacent normal mucosa. Furthermore, to investigate the role of this novel ubiquitin hybrid gene in cellular growth control, the responsiveness of this gene to serum growth factors was examined. Within 30 min after serum or 12-O-tetradecanoylphorbol-13-acetate stimulation, its messenger RNA expression in rat fibroblast cells (Rat 1) was increased. Nuclear runoff transcription studies showed that the kinetics of induction of this gene is almost identical to that of protooncogene c-jun or c-fos, the known early growth response genes. Thus, this ubiquitin hybrid gene appears to be a novel early growth response gene overexpressed in human colon cancer and warrants further studies in the pathogenesis of colorectal carcinoma. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. FU NCI NIH HHS [P01-CA44704-02] NR 33 TC 50 Z9 56 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 APR 15 PY 1993 VL 53 IS 8 BP 1916 EP 1920 PG 5 WC Oncology SC Oncology GA KY096 UT WOS:A1993KY09600036 PM 8385574 ER PT J AU LEE, YM BEINBORN, M MCBRIDE, EW LU, M KOLAKOWSKI, LF KOPIN, AS AF LEE, YM BEINBORN, M MCBRIDE, EW LU, M KOLAKOWSKI, LF KOPIN, AS TI THE HUMAN BRAIN CHOLECYSTOKININ-B GASTRIN RECEPTOR - CLONING AND CHARACTERIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE-ANALYSIS; ANTAGONIST; CELLS; CCK; L-365,260; POTENT; ANALGESIA; PEPTIDES; PANCREAS; ANXIETY AB The predominant brain cholecystokinin receptor (CCK-B/gastrin) has been implicated in mediating many of the central effects of cholecystokinin, including anxiety, panic attacks, satiety, and analgesia, suggesting it is an important pharmacologic target. We now report the cloning and characterization of the cDNA encoding the human brain CCK-B/gastrin receptor. The cDNA was isolated from a human brain library by low stringency screening using the canine ''gastrin'' receptor cDNA as a hybridization probe. Nucleotide sequence analysis revealed an open reading frame encoding a 447-amino-acid protein with seven putative hydrophobic transmembrane domains and significant homology with other known members of the gastrin/cholecystokinin receptor family. Agonist and antagonist affinities of the recombinant human brain receptor expressed in COS-7 cells are consistent with a classical ''CCK-B'' receptor as defined by the literature. In COS-7 cells expressing the cloned receptor, CCK-8-stimulated phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization suggesting second messenger signaling through phospholipase C. CCK-B/gastrin receptor transcripts were identified in human brain, stomach, and pancreas using high stringency Northern blot analysis. Southern blot hybridization analysis of human genomic DNA indicates that a single gene encodes both the brain and the stomach CCK-B/gastrin receptors. Our data suggest that the CCK-B and gastrin receptors are identical and that the long standing distinction between them may no longer apply. C1 TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DIV GASTROENTEROL,BOSTON,MA 02111. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,GRASP DIGEST DIS CTR,BOSTON,MA 02111. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77035. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MED SCH HANNOVER,DEPT GEN PHARMACOL,W-3000 HANNOVER 61,GERMANY. FU NIDDK NIH HHS [DK01934, DK46767, P30-DK34928] NR 38 TC 238 Z9 243 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1993 VL 268 IS 11 BP 8164 EP 8169 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KW979 UT WOS:A1993KW97900083 PM 7681836 ER PT J AU BACKER, JM MYERS, MG SUN, XJ CHIN, DJ SHOELSON, SE MIRALPEIX, M WHITE, MF AF BACKER, JM MYERS, MG SUN, XJ CHIN, DJ SHOELSON, SE MIRALPEIX, M WHITE, MF TI ASSOCIATION OF IRS-1 WITH THE INSULIN-RECEPTOR AND THE PHOSPHATIDYLINOSITOL 3'-KINASE - FORMATION OF BINARY AND TERNARY SIGNALING COMPLEXES IN INTACT-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; PDGF RECEPTOR; BINDING SITE; BETA-SUBUNIT; PROTEIN; PHOSPHORYLATION; PURIFICATION; SUBSTRATE; 3-KINASE; TRANSDUCTION AB Insulin stimulates the formation of binary and ternary signaling complexes between the phosphatidylinositol (PtdIns) 3'-kinase, IRS-1, and the insulin receptor in vivo. Binary complex formation between IRS-1 and the PtdIns 3'-kinase occurs in intact cells and requires the tyrosyl phosphorylation IRS-1, as mutant insulin receptors which weakly phosphorylate IRS-1 in vivo do not mediate formation of IRS-1/PtdIns 3'-kinase complexes in transfected CHO cells. Association with IRS-1 involves as much as 70% of total cellular PtdIns 3'-kinase activity. Insulin also stimulates the formation of ternary signaling complexes, as both IRS-1 and the PtdIns 3'-kinase are present in anti-insulin receptor immunoprecipitates from insulin-stimulated cells. Overexpression of IRS-1 in CHO cells increases the amount of PtdIns 3'-kinase activity in alphaIR immunoprecipitates, and IRS-1 markedly increases the in vitro binding of p85alpha and PtdIns 3-kinase activity to anti-receptor immunoprecipitates. The mechanism for this association is unknown, but appears to involve the binding of IRS-1/PtdIns 3'-kinase complexes to the insulin receptor. The formation of binary and ternary complexes between the insulin receptor, IRS-1 and the PtdIns 3'-kinase may play a critical role in transmission of the insulin signal. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,SCH MED,DEPT MED,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-43808, DK 36836, DK-38712] NR 40 TC 156 Z9 156 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1993 VL 268 IS 11 BP 8204 EP 8212 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KW979 UT WOS:A1993KW97900090 PM 8385139 ER PT J AU MUSZBEK, L LAPOSATA, M AF MUSZBEK, L LAPOSATA, M TI MYRISTOYLATION OF PROTEINS IN PLATELETS OCCURS PREDOMINANTLY THROUGH THIOESTER LINKAGES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FATTY-ACID ACYLATION; N-MYRISTOYLTRANSFERASE; COVALENT MODIFICATION; EUKARYOTIC PROTEINS; CELLULAR PROTEINS; PLASMA-MEMBRANE; COA; SPECIFICITY; RECEPTOR; PEPTIDE AB We have demonstrated by several lines of evidence that in platelets myristate is linked to proteins predominantly via thioester bonds as is palmitate, and the covalent binding of the two long chain saturated fatty acids to proteins involves the same mechanisms. The first piece of evidence to support the thioester linkage between myristate and proteins is that [H-3]myristate could be removed from proteins via alkaline methanolysis, which disrupts ester bonds but not amide bonds. The second piece of evidence is that unlabeled palmitate, which can form only thioester bonds in physiologic concentrations, competitively inhibits the formation of alkaline methanolysis-sensitive covalent bonds between [H-3]myristate and proteins. Third, by SDS-polyacrylamide gel electrophoresis and fluorography, the patterns of labeled proteins from [H-3]myristate- and [H-3]palmitate-labeled platelets are identical. Fourth, [H-3]myristate-labeled proteins, like [H-3]palmitate-labeled proteins, both release their fatty acid moieties when exposed to hydroxylamine at neutral pH, which disrupts thioester but not hydroxyester bonds. These findings indicate that although the covalent binding of palmitate to proteins was found to occur at a faster rate than that of myristate, protein S fatty acid acylation that occurs posttranslationally is not specific for palmitate. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,CLIN LABS,RM 249,GRAY BLDG,BOSTON,MA 02114. DEBRECEN UNIV MED,SCH MED,DEPT CLIN CHEM,H-4012 DEBRECEN,HUNGARY. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK43159] NR 32 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1993 VL 268 IS 11 BP 8251 EP 8255 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KW979 UT WOS:A1993KW97900096 PM 8463334 ER PT J AU MASCHEK, BJ ZHANG, W ROSOFF, PM REISER, H AF MASCHEK, BJ ZHANG, W ROSOFF, PM REISER, H TI MODULATION OF THE INTRACELLULAR CA2+ AND INOSITOL TRISPHOSPHATE CONCENTRATIONS IN MURINE-T LYMPHOCYTES BY THE GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED PROTEIN SGP-60 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE-C; SURFACE MOLECULES; CALCIUM; ACTIVATION; COMPLEX; PHOSPHATIDYLINOSITOL; STIMULATION AB Stimulation of T lymphocytes via the TCR/CD3 complex initiates a series of intracellular biochemical events. Among the earliest cellular responses are the stimulation of the turnover of phosphatidylinositol and an increase in the intracellular Ca2+ concentration. The significance of these second messengers for distal cellular responses such as lymphokine production or cell proliferation is not understood. We have previously shown that a hamster mAb to the murine glycosylphosphatidylinositol-anchored protein sgp-60 can inhibit IL-2 production, IL-2R expression, and cell proliferation, events normally observed after stimulation of T cells with an antibody to the TCR/CD3 complex or with the lectin Con A. We now show that the anti-sgp-60 mAb inhibits the activation-induced increase in intracellular Ca2+ concentration. Additional analysis demonstrates that the mAb interferes with the release of Ca2+ from intracellular stores and with the generation of inositol 1,4,5-trisphosphate. Our findings suggest a role for this glycosylphosphatidylinositol-anchored protein in the generation of second messengers in signal transduction through the TCR/CD3 complex in murine T lymphocytes. 3198. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 43 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP 3198 EP 3206 PN 1 PG 9 WC Immunology SC Immunology GA KX321 UT WOS:A1993KX32100010 PM 8468465 ER PT J AU ARULANANDAM, ARN MOINGEON, P CONCINO, M RECNY, MA KATO, K YAGITA, H KOYASU, S REINHERZ, EL AF ARULANANDAM, ARN MOINGEON, P CONCINO, M RECNY, MA KATO, K YAGITA, H KOYASU, S REINHERZ, EL TI A SOLUBLE MULTIMERIC RECOMBINANT CD2 PROTEIN IDENTIFIES CD48 AS A LOW AFFINITY LIGAND FOR HUMAN CD2 - DIVERGENCE OF CD2 LIGANDS DURING THE EVOLUTION OF MAN AND MOUSE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. PROCEPT INC,CAMBRIDGE,MA 02139. JUNTENDO UNIV,SCH MED,TOKYO 113,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A187 EP A187 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601073 ER PT J AU BRAESCHANDERSEN, S STAMENKOVIC, I AF BRAESCHANDERSEN, S STAMENKOVIC, I TI CD22 MEDIATED ADHESION IS NEGATIVELY REGULATED BY A GANGLIOSIDE PRESENT IN SERUM SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A99 EP A99 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600564 ER PT J AU BROOKS, E BALK, S AUPEIX, K COLONNA, M STROMINGER, JL GROHSPIES, V AF BROOKS, E BALK, S AUPEIX, K COLONNA, M STROMINGER, JL GROHSPIES, V TI HUMAN TCR ALPHA-BETA+ CD4- CD8- T-CELLS EXPRESS AN OLIGOCLONAL V-BETA-GENE REPERTOIRE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A104 EP A104 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600593 ER PT J AU EASTCOTT, JW TAUBMAN, MA SMITH, DJ AF EASTCOTT, JW TAUBMAN, MA SMITH, DJ TI AGE-RELATED DEVELOPMENT AND ACTIVITIES OF T-CELLS IN NUDE RATS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 FORSYTH DENT CTR,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A108 EP A108 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600616 ER PT J AU FERRARA, JLM SILVERSTEIN, M SHANLEY, JD AF FERRARA, JLM SILVERSTEIN, M SHANLEY, JD TI INTERSTITIAL PNEUMONITIS (IP) DURING MURINE CYTOMEGALOVIRUS (CMV) INFECTION AND GRAFT-VERSUS-HOST REACTION (GVHR) IS MEDIATED BY IL-1 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A293 EP A293 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601685 ER PT J AU HOLLANDER, GA BURAKOFF, SJ AF HOLLANDER, GA BURAKOFF, SJ TI LOSS OF PROPER THYMIC DEVELOPMENT AND REPERTOIRE SELECTION IN CHRONIC GRAFT-VERSUS-HOST DISEASE (GVHD) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A319 EP A319 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601841 ER PT J AU KANDIL, O FISHMAN, JA KOZIEL, H PINKSTON, P ROSE, RM REMOLD, HG AF KANDIL, O FISHMAN, JA KOZIEL, H PINKSTON, P ROSE, RM REMOLD, HG TI DIFFERENTIAL REGULATION OF TNF-ALPHA, IL-1-BETA, AND IL-6 PRODUCTION BY HIV-INFECTED HUMAN MACROPHAGES EXPOSED TO PNEUMOCYSTIS-CARINII SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 NE DEACONESS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A229 EP A229 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601318 ER PT J AU KUCHROO, VK ALSABBAGH, A SOBEL, RA RIMM, IJ AF KUCHROO, VK ALSABBAGH, A SOBEL, RA RIMM, IJ TI SUSCEPTIBILITY OF T-CELL RECEPTOR (TCR) V-BETA-8.2 TRANSGENIC (TG) MICE TO EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS (EAE) INDUCED BY MYELIN PROTEINS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR NEUROL DIS,BOSTON,MA 02115. STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,STANFORD,CA 94305. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A80 EP A80 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600455 ER PT J AU KUMAGAI, M BOYLE, L KUMICK, JT AF KUMAGAI, M BOYLE, L KUMICK, JT TI T-CELL RECEPTOR USAGE BY HUMAN ALLOGRAFT-DERIVED LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY 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 IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A27 EP A27 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600149 ER PT J AU LEE, LA GRITSCH, HA ARN, JS EMERY, DW GLASER, RM SABLINSKI, T SACHS, DH SYKES, M AF LEE, LA GRITSCH, HA ARN, JS EMERY, DW GLASER, RM SABLINSKI, T SACHS, DH SYKES, M TI MURINE T-CELL MATURATION IN DISCORDANT XENOGENEIC FETAL THYMUS GRAFTS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A321 EP A321 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601854 ER PT J AU MACLEAN, JA SU, Z COLVIN, RB WONG, JT AF MACLEAN, JA SU, Z COLVIN, RB WONG, JT TI ANTI-CD3 - ANTI-IL-2 RECEPTOR (CD3,25) BISPECIFIC MONOCLONAL-ANTIBODY (BSMAB) - T-CELL IMMUNOMODULATION WITH REDUCED ACTIVATION AND TOXICITY THAN ANTI-CD3 MAB INVIVO SO JOURNAL OF IMMUNOLOGY 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 IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A189 EP A189 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601085 ER PT J AU MELDER, RJ BROWNELL, AL BROWNELL, GL JAIN, RK AF MELDER, RJ BROWNELL, AL BROWNELL, GL JAIN, RK TI POSITRON EMISSION TOMOGRAPHY (PET) MONITORED TUMOR-LOCALIZATION AND SYSTEMIC DISTRIBUTION OF EFFECTOR-CELLS SO JOURNAL OF IMMUNOLOGY 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 IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A97 EP A97 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600548 ER PT J AU MICHALEK, MT GRANT, EP GRAMM, C GOLDBERG, AL ANDERSON, RW YEWDELL, JW BENNINK, JR ROCK, KL AF MICHALEK, MT GRANT, EP GRAMM, C GOLDBERG, AL ANDERSON, RW YEWDELL, JW BENNINK, JR ROCK, KL TI A ROLE FOR THE UBIQUITIN-DEPENDENT PROTEOLYTIC PATHWAY IN MHC CLASS-I-RESTRICTED ANTIGEN PRESENTATION SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIAID,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A91 EP A91 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600518 ER PT J AU PAHLAVANI, MA RICHARDSON, A AF PAHLAVANI, MA RICHARDSON, A TI AGE-RELATED-CHANGES IN HEAT-SHOCK GENE-EXPRESSION IN RAT LYMPHOCYTES (NIA AG-00165 AND AG-01548) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELL & STR BIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,GRECC,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A22 EP A22 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600117 ER PT J AU PALLISER, D LACY, E MCGREW, J ROCK, KL BAMEZAI, A AF PALLISER, D LACY, E MCGREW, J ROCK, KL BAMEZAI, A TI T-CELL DEVELOPMENT IN LY6A.2 (TAP) TRANSGENIC MICE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A32 EP A32 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600176 ER PT J AU PARHAMISEREN, B MARGOLIES, MN AF PARHAMISEREN, B MARGOLIES, MN TI STRUCTURAL BASIS FOR THE EXPRESSION OF MAJOR IDIOTYPIC DETERMINANTS BY P-AZOPHENYLARSONATE SPECIFIC ANTIBODIES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A7 EP A7 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600038 ER PT J AU PERVAIZ, S IHARA, A BOYLE, L PANDOLFI, F KURNICK, JT AF PERVAIZ, S IHARA, A BOYLE, L PANDOLFI, F KURNICK, JT TI TCR IN MELANOMA TIL SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Pervaiz, Shazib/C-4188-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A94 EP A94 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600531 ER PT J AU RASMUSSEN, R COUNTS, S AF RASMUSSEN, R COUNTS, S TI ISOLATION AND CHARACTERIZATION OF CD6- T-CELLS FROM PERIPHERAL-BLOOD SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A21 EP A21 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600114 ER PT J AU RAVICHANDRAN, KS HOLLANDER, GA BURAKOFF, SJ AF RAVICHANDRAN, KS HOLLANDER, GA BURAKOFF, SJ TI DIFFERENTIAL SIGNALING VIA CD4 AND CD8 MOLECULES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A265 EP A265 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601526 ER PT J AU REID, RR PEMBERTON, P ROSEN, FS CARROLL, MC AF REID, RR PEMBERTON, P ROSEN, FS CARROLL, MC TI BINDING OF COMPLEMENT-C3 TO THE HEAVY-CHAIN OF ANTITETANUS TOXOID ANTIBODY SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A226 EP A226 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601301 ER PT J AU RIMM, IJ FRUMAN, D SEIDMAN, JG FERRARA, JLM AF RIMM, IJ FRUMAN, D SEIDMAN, JG FERRARA, JLM TI TCR-BETA TRANSGENIC MICE HAVE SELECTIVE DEFICITS IN GAMMA-DELTA- T-CELL SUBPOPULATIONS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A30 EP A30 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600164 ER PT J AU RODBERG, G PINTO, C SURMAN, O KRADIN, R AF RODBERG, G PINTO, C SURMAN, O KRADIN, R TI EPINEPHRINE AUGMENTS T-CELL IMMUNITY IN LOW RESPONDER MICE SO JOURNAL OF IMMUNOLOGY 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 IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A279 EP A279 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601608 ER PT J AU ROSENSTEIN, Y LEE, K IGRAS, V BURAKOFF, SJ AF ROSENSTEIN, Y LEE, K IGRAS, V BURAKOFF, SJ TI CD43 AS A CORECEPTOR IN T-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A268 EP A268 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601544 ER PT J AU RUDD, CE JANSSEN, O RAAB, M TELFER, J PRASAD, KVS AF RUDD, CE JANSSEN, O RAAB, M TELFER, J PRASAD, KVS TI REGULATION OF THE CD4-P56(LCK) COMPLEX AND ASSOCIATED PHOSPHATIDYLINOSITOL 3-KINASE IN T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RI Janssen, Ottmar/E-9735-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A251 EP A251 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601444 ER PT J AU SANDERSON, IR OUELLETTE, AJ WALKER, WA CARTER, EA HARMATZ, PJ AF SANDERSON, IR OUELLETTE, AJ WALKER, WA CARTER, EA HARMATZ, PJ TI EXPRESSION OF INVARIANT CHAIN (II) IN MOUSE INTESTINAL EPITHELIUM IS INDEPENDENT OF TNF-ALPHA AND IFN-GAMMA RESPONSE ELEMENTS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A36 EP A36 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600202 ER PT J AU SMITH, D KING, W IMELMANN, C TAUBMAN, M AF SMITH, D KING, W IMELMANN, C TAUBMAN, M TI FUNCTIONAL INHIBITION OF GLUCOSYLTRANSFERASE BY ANTIBODY TO SYNTHETIC PEPTIDES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 FORSYTH DENT CTR,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A34 EP A34 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600189 ER PT J AU SYKES, M HARTY, MW KARLHOFER, FM PEARSON, DA SZOT, G YOKOYAMA, WM AF SYKES, M HARTY, MW KARLHOFER, FM PEARSON, DA SZOT, G YOKOYAMA, WM TI HEMATOPOIETIC-CELLS AND RADIORESISTANT HOST ELEMENTS DETERMINE THE NATURAL-KILLER-CELL REPERTOIRE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A256 EP A256 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601475 ER PT J AU TAUBMAN, MA SHIMAUCHI, H EASTCOTT, JW SMITH, DJ AF TAUBMAN, MA SHIMAUCHI, H EASTCOTT, JW SMITH, DJ TI MIGRATION OF TH1 AND TH2 CLONES INTO TISSUES OF INFECTED AND NONINFECTED RATS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 FORSYTH DENT CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A270 EP A270 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601553 ER PT J AU TODD, WM WEISZCARRINGTON, P RYPINS, E CARTER, E AF TODD, WM WEISZCARRINGTON, P RYPINS, E CARTER, E TI IGA IN NORMAL AND CIRRHOTIC HUMAN LIVER SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MCGUIRE VET AFFAIRS MED CTR,DEPT PATHOL,RICHMOND,VA 23249. MASSACHUSETTS GEN HOSP,DEPT PEDIAT GI MASS,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A116 EP A116 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600663 ER PT J AU VERMEULEN, MW BERKOVITS, HJ AURON, PE SILVEY, K AF VERMEULEN, MW BERKOVITS, HJ AURON, PE SILVEY, K TI TUMOR-NECROSIS-FACTOR - SECONDARY STRUCTURE OF REGULATORY 3'-UNTRANSLATED REGION MESSENGER-RNA SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A295 EP A295 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601695 ER PT J AU VIRELLA, G LOPESVIRELLA, MF AF VIRELLA, G LOPESVIRELLA, MF TI AUTOIMMUNITY AND ATHEROSCLEROSIS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC 29425. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A238 EP A238 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601370 ER PT J AU WAGNER, N ENGEL, P TEDDER, TF AF WAGNER, N ENGEL, P TEDDER, TF TI THE CD45 TYROSINE PHOSPHATASE DOWN-REGULATES HOMOTYPIC ADHESION IN HUMAN-LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A254 EP A254 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601460 ER PT J AU WARD, PA HEMLER, ME AF WARD, PA HEMLER, ME TI MOLECULAR, BIOLOGIC, AND THERAPEUTIC ROLES OF ADHESION MOLECULES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A2 EP A2 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600007 ER PT J AU WONG, JT WECHER, H MACLEAN, JA SU, Z COLVIN, RB AUCHINCLOSS, H AF WONG, JT WECHER, H MACLEAN, JA SU, Z COLVIN, RB AUCHINCLOSS, H TI ANTI-CD3-ANTI-IL2 RECEPTOR (CD3,25) BISPECIFIC MONOCLONAL-ANTIBODY (BSMAB) - PROLONGATION OF CARDIAC ALLOGRAFT SURVIVAL WITH LOWER TOXICITY THAN ANTI-CD3 MAB SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02090. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A249 EP A249 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601435 ER PT J AU ZHOU, LJ SMITH, H TEDDER, TF AF ZHOU, LJ SMITH, H TEDDER, TF TI EXPRESSION OF THE HUMAN CD19 GENE IN TRANSGENIC MICE ALTERS B-LYMPHOCYTE DEVELOPMENT SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1993 VL 150 IS 8 BP A14 EP A14 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600075 ER PT J AU WALSH, C CEPKO, CL AF WALSH, C CEPKO, CL TI CLONAL DISPERSION IN PROLIFERATIVE LAYERS OF DEVELOPING CEREBRAL-CORTEX SO NATURE LA English DT Article ID MIGRATION PATTERNS AB IN the adult cerebral cortex, many retrovirally labelled clones are widely dispersed1, though the mechanisms of this dispersion are not well understood. Here we investigate the temporal sequence of clonal dispersion after labelling progenitors of rat cortical cells with replication-incompetent retroviruses at early stages of cortical neurogenesis, 14-15 days after conception (E14/15). The location of labelled daughter cells was determined 3, 6 or 10 days later. Labelled sibling cells were radially arrayed three days after infection (E18). In contrast, by six days after infection (E20/21), 43% of cortical clones were dispersed non-radially by at least 500 mum. Four of these widespread clones were dispersed longitudinally by greater-than-or-equal-to 2 mm, implying sustained rates of dispersion of > 15 mum per hour. Dispersed sibling cells occurred within proliferative zones of the forebrain in 35% of widely dispersed clones, suggesting that some dispersion reflects movement of dividing cells. Some clones dispersed beyond the neocortex into the olfactory bulb. Progenitor cell dispersion represents a previously unrecognized mode of migration by which sibling cells become widely dispersed in the developing forebrain. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 17 TC 180 Z9 181 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 15 PY 1993 VL 362 IS 6421 BP 632 EP 635 DI 10.1038/362632a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KX438 UT WOS:A1993KX43800048 PM 8464513 ER PT J AU BUNKER, CJ YUCEL, EK PODOLSKY, DK SCULLY, RE RICHTER, JM GIRADET, C AF BUNKER, CJ YUCEL, EK PODOLSKY, DK SCULLY, RE RICHTER, JM GIRADET, C TI A 58-YEAR-OLD MAN WITH RECURRENT LOWER GASTROINTESTINAL-BLEEDING FOR OVER 2 YEARS - STROMAL TUMOR OF LOW-GRADE MALIGNANCY, OF SMALL-INTESTINE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID SMOOTH-MUSCLE TUMORS; SMALL-BOWEL; MECKELS-DIVERTICULUM; EXPERIENCE; TRACT; LEIOMYOSARCOMA C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BUNKER, CJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 36 TC 5 Z9 5 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 1993 VL 328 IS 15 BP 1107 EP 1114 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA KX178 UT WOS:A1993KX17800008 ER PT J AU MARTIN, KA FREEMAN, MW AF MARTIN, KA FREEMAN, MW TI POSTMENOPAUSAL HORMONE-REPLACEMENT THERAPY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ESTROGEN; LIPOPROTEIN(A); PROGESTERONE; RISK RP MARTIN, KA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 13 TC 38 Z9 38 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 1993 VL 328 IS 15 BP 1115 EP 1117 DI 10.1056/NEJM199304153281509 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA KX178 UT WOS:A1993KX17800009 PM 8455670 ER PT J AU AGNELLO, V CHUNG, RT KAPLAN, LM AF AGNELLO, V CHUNG, RT KAPLAN, LM TI HEPATITIS-C VIRUS AND CRYOGLOBULINEMIA - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP AGNELLO, V (reprint author), LAHEY CLIN FDN,MED CTR,BURLINGTON,MA 01805, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 15 PY 1993 VL 328 IS 15 BP 1123 EP 1124 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KX178 UT WOS:A1993KX17800016 ER PT J AU KOBAYASHI, H MAN, S GRAHAM, CH KAPITAIN, SJ TEICHER, BA KERBEL, RS AF KOBAYASHI, H MAN, S GRAHAM, CH KAPITAIN, SJ TEICHER, BA KERBEL, RS TI ACQUIRED MULTICELLULAR-MEDIATED RESISTANCE TO ALKYLATING-AGENTS IN CANCER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DRUG RESISTANCE; CHEMOTHERAPEUTIC DRUGS; TUMOR SPHEROIDS ID THERAPEUTIC AGENTS; CYTO-TOXICITY; SPHEROIDS; CELLS; XENOGRAFTS; DELIVERY; ADRIAMYCIN; MECHANISM; BARRIERS; CULTURES AB EMT-6 murine mammary tumor sublines highly resistant to cyclophosphamide, cis-diamminedichloro-platinum(II), or N,N',N''-triethylenethiophosphoramide were generated in vivo by sequential treatment of tumor-bearing mice with the respective drugs. Previous studies demonstrated the drug-resistant phenotypes of the sublines were not expressed in vitro when the cells were grown as monolayer cultures. We now show that expression of drug resistance- including patterns of cross-drug resistance observed in vivo- can be fully recapitulated in vitro when the cells are grown under in vivo-like, three-dimensional conditions-namely, as multicellular tumor spheroids. Moreover, the spheroids generated from all of the drug-resistant sublines manifested a much more compact structure. Immediate drug-sensitivity testing of single cells released by trypsin treatment from compact drug-resistant spheroids revealed that such cells lost much of their drug-resistant properties. The results suggest a possible mechanism of acquired drug resistance in tumors based on the response of a cell population (i.e., multicellular or tissue resistance) as opposed to classic (uni)cellular resistance mechanisms. C1 SUNNYBROOK MED CTR,DIV CANC RES,REICHMANN RES BLDG,S-218,2075 BAYVIEW AVE,TORONTO M4N 3M5,ONTARIO,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO M5S 1A8,ONTARIO,CANADA. UNIV TORONTO,DEPT MED GENET,TORONTO M5S 1A8,ONTARIO,CANADA. FU NCI NIH HHS [P01-CA38497] NR 24 TC 223 Z9 231 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1993 VL 90 IS 8 BP 3294 EP 3298 DI 10.1073/pnas.90.8.3294 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KX816 UT WOS:A1993KX81600038 PM 8475071 ER PT J AU AUCHINCLOSS, H LEE, R SHEA, S MARKOWITZ, JS GRUSBY, MJ GLIMCHER, LH AF AUCHINCLOSS, H LEE, R SHEA, S MARKOWITZ, JS GRUSBY, MJ GLIMCHER, LH TI THE ROLE OF INDIRECT RECOGNITION IN INITIATING REJECTION OF SKIN-GRAFTS FROM MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-DEFICIENT MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOXIC LYMPHOCYTES-T; MINOR H-ANTIGENS; MONOCLONAL-ANTIBODY; CELL SUBSETS; ALLOGRAFT-REJECTION; CROSS-REACT; INVIVO; MHC; SURVIVAL; DETERMINANTS AB In vitro studies have revealed several pathways by which T cells can respond to alloantigens, including CD4+ direct responses to allogeneic class II antigens, CD8+ direct responses to allogeneic class I antigens, and CD4+ ''indirect'' responses to peptides of alloantigens presented in association with responder class II molecules. In vivo studies of skin graft rejection, however, have so far provided clear evidence for the contribution of only the two direct pathways and not for indirect recognition. We have used major histocompatibility complex class II-deficient mice as donors to test the role of indirect recognition in rejection of skin grafts. Class II-deficient skin was always rejected without delay by normal recipients. Removal of recipient CD8+ cells (to leave the animals dependent on CD4+ function) or depletion of recipient CD4+ cells revealed that CD4+ cells were usually involved and sometimes absolutely required in this rapid rejection. Since the donor grafts lacked class II antigens, the CD4+ cells must have recognized donor antigens presented in association with recipient class II molecules. These results therefore indicate that indirect recognition can initiate rapid skin graft rejection. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP AUCHINCLOSS, H (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NHLBI NIH HHS [HL18646, HL36372]; NIAID NIH HHS [AI21569] NR 44 TC 273 Z9 277 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 APR 15 PY 1993 VL 90 IS 8 BP 3373 EP 3377 DI 10.1073/pnas.90.8.3373 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KX816 UT WOS:A1993KX81600054 PM 8475083 ER PT J AU CABRERO, JG FREEMAN, GJ LANE, WS REISER, H AF CABRERO, JG FREEMAN, GJ LANE, WS REISER, H TI IDENTIFICATION, BY PROTEIN SEQUENCING AND GENE TRANSFECTION, OF SGP-60 AS THE MURINE HOMOLOG OF CD48 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMINO-ACID-SEQUENCE; MRC OX-45 ANTIGEN; POLYACRYLAMIDE GELS; NITROCELLULOSE; EXPRESSION; MEMBRANE; CELLS; CD2; ELECTROPHORESIS; IMMUNOGLOBULIN AB We have recently described a murine lymphocyte protein, provisionally termed sgp-60, which is expressed on virtually all lymphocytes of both T- and B-cell origin. A hamster monoclonal antibody to sgp-60 can inhibit interleukin-2 (IL-2) production, IL-2-receptor expression, and T-cell proliferation, events normally observed after stimulation of T cells with an antibody to the T-cell receptor/CD3 complex or with the lectin concanavalin A. Our previous studies did not reveal the molecular nature of the sgp-60 antigen. Purification of sgp-60 and protein sequencing demonstrate that sgp-60 is identical to the CD48 antigen, a ligand for the CD2 antigen, which is also called Blast-1 in humans, BCM1 in mice, and OX-45 in rats. The identity of sgp-60 and CD48 was independently confirmed in gene transfection experiments. The anti-sgp-60 monoclonal antibody was selectively reactive with COS-7 cells transfected with a BCM1 cDNA clone but not with K(b)-transfected controls. The results of the present report, together with our previous functional studies, may have implications for the role of CD2 and CD48 in murine T-cell activation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BIOL LABS,MICROCHEM FACIL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-30169] NR 29 TC 15 Z9 16 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1993 VL 90 IS 8 BP 3418 EP 3422 DI 10.1073/pnas.90.8.3418 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KX816 UT WOS:A1993KX81600063 PM 8475091 ER PT J AU DRANOFF, G JAFFEE, E LAZENBY, A GOLUMBEK, P LEVITSKY, H BROSE, K JACKSON, V HAMADA, H PARDOLL, D MULLIGAN, RC AF DRANOFF, G JAFFEE, E LAZENBY, A GOLUMBEK, P LEVITSKY, H BROSE, K JACKSON, V HAMADA, H PARDOLL, D MULLIGAN, RC TI VACCINATION WITH IRRADIATED TUMOR-CELLS ENGINEERED TO SECRETE MURINE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR STIMULATES POTENT, SPECIFIC, AND LONG-LASTING ANTITUMOR IMMUNITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TUMOR IMMUNOLOGY; GENE TRANSFER ID NECROSIS-FACTOR-ALPHA; GENE-TRANSFER; MOLECULAR-CLONING; MONOCLONAL-ANTIBODY; CDNA CLONE; EXPRESSION; MOUSE; INVIVO; TUMORIGENICITY; DIFFERENTIATION AB To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4+ and CD8+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines. C1 MIT, WHITEHEAD INST BIOMED RES, 9 CAMBRIDGE CTR, CAMBRIDGE, MA 02142 USA. MASSACHUSETTS GEN HOSP, DEPT CHEM, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CLIN ONCOL, BOSTON, MA 02115 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT ONCOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA. NR 39 TC 2319 Z9 2361 U1 8 U2 72 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1993 VL 90 IS 8 BP 3539 EP 3543 DI 10.1073/pnas.90.8.3539 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KX816 UT WOS:A1993KX81600088 PM 8097319 ER PT J AU BECK, WS AF BECK, WS TI TONGUE LESIONS IN TREATED PERNICIOUS-ANEMIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP BECK, WS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1993 VL 269 IS 14 BP 1785 EP 1785 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KW250 UT WOS:A1993KW25000014 ER PT J AU KELLER, RJ EISENBARTH, GS JACKSON, RA AF KELLER, RJ EISENBARTH, GS JACKSON, RA TI INSULIN PROPHYLAXIS IN INDIVIDUALS AT HIGH-RISK OF TYPE-I DIABETES SO LANCET LA English DT Note ID CELL ACTIVITY AB Prevention of type I diabetes is now a practical goal thanks to the ability to define confidently a high-risk group and the success of preventive strategies in animal models. We describe here a pilot trial of low-dose insulin to prevent diabetes in relatives of patients with type I diabetes. C1 JOSLIN DIABET CTR,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO. RP KELLER, RJ (reprint author), CHILDRENS HOSP MED CTR,DIV ENDOCRINOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 9 TC 292 Z9 297 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 10 PY 1993 VL 341 IS 8850 BP 927 EP 928 DI 10.1016/0140-6736(93)91215-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KW981 UT WOS:A1993KW98100007 PM 8096268 ER PT J AU KOPANS, DB AF KOPANS, DB TI MAMMOGRAPHY SO LANCET LA English DT Letter RP KOPANS, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 4 TC 3 Z9 3 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 10 PY 1993 VL 341 IS 8850 BP 957 EP 957 DI 10.1016/0140-6736(93)91246-I PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KW981 UT WOS:A1993KW98100033 PM 8096288 ER PT J AU ROCA, AL WEAVER, DR REPPERT, SM AF ROCA, AL WEAVER, DR REPPERT, SM TI SEROTONIN RECEPTOR GENE-EXPRESSION IN THE RAT SUPRACHIASMATIC NUCLEI SO BRAIN RESEARCH LA English DT Article DE SUPRACHIASMATIC NUCLEUS; SEROTONIN RECEPTOR; NUCLEIC ACID HYBRIDIZATION ID INSITU HYBRIDIZATION HISTOCHEMISTRY; MESSENGER-RNA; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; CIRCADIAN-RHYTHMS; 5-HT1C RECEPTOR; H-3 QUIPAZINE; RODENT BRAIN; 1C RECEPTOR; LOCALIZATION AB Serotonin (5HT) is thought to reset the biological clock in the suprachiasmatic nuclei (SCN) in vitro through a postsynaptic 5HT-1a receptor. Thus we examined 5HT receptor gene expression in the SCN by in situ hybridization. On film autoradiograms, 5HT-1c receptor mRNA showed intense SCN hybridization, while 5HT-1b receptor mRNA displayed a weaker signal. Emulsion autoradiograms additionally revealed expression of 5HT-1a and 5HT-2 receptor mRNAs by a few scattered SCN cells. 5HT-3 receptor mRNA was not detected in the SCN, although the transcript was detected elsewhere in the brain. 5HT-1d and -1e receptor mRNAs were not detected in the SCN or elsewhere in brain within the sections examined. The results do not support a major role for postsynaptic 5HT-1a receptors in resetting SCN rhythms. C1 MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,CHILDRENS SERV 1226,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [HD 14427] NR 35 TC 74 Z9 75 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 9 PY 1993 VL 608 IS 1 BP 159 EP 165 DI 10.1016/0006-8993(93)90789-P PG 7 WC Neurosciences SC Neurosciences & Neurology GA KW778 UT WOS:A1993KW77800025 PM 8495340 ER PT J AU ABADJI, VC RAINES, DE WATTS, A MILLER, KW AF ABADJI, VC RAINES, DE WATTS, A MILLER, KW TI THE EFFECT OF GENERAL-ANESTHETICS ON THE DYNAMICS OF PHOSPHATIDYLCHOLINE-ACETYLCHOLINE RECEPTOR INTERACTIONS IN RECONSTITUTED VESICLES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE GENERAL ANESTHETIC; ANESTHETIC; LIPID PROTEIN INTERACTION; ACETYLCHOLINE RECEPTOR; RECONSTITUTION; SPIN LABEL ID LIPID-PROTEIN INTERACTIONS; TORPEDO-MARMORATA; RICH MEMBRANES; ROTATIONAL-DYNAMICS; DIETHYL-ETHER; FATTY-ACIDS; PHOSPHOLIPIDS; BINDING AB The interaction of general anesthetics at the lipid/protein interface of the nicotinic acetylcholine receptor reconstituted in dioleoylphosphatidylcholine bilayers at various lipid/protein ratios has been studied using the electron spin resonance spectra of phosphatidylcholine spin-labeled at the fourteenth acyl carbon (14-PCSL). In addition to the bilayer spectrum, the spin label reported a more motionally restricted environment whose contribution increased with increasing protein/lipid ratio. Exchange between thses two environments occurred at a rate of approx. 6 . 10(7) s-1. The motionally restricted, protein-associated 14-PCSL had a rotational correlation time of about 10-20 ns, an order of magnitude slower than when in the bilayer. Addition of 1-hexanol (up to 16 mM) to the reconstituted receptor perturbed the acyl chains of the bulk lipid phase, but the motional properties of the lipid acyl chains at the protein/lipid interface near the membrane center were not significantly perturbed on the EPR motional time-scale. Similarly, anesthetics that were less effective at perturbing the bilayer, such as pentobarbital (up to 2 mM) and isoflurane (7 mM), did not perturb the lipid/protein interface on the conventional EPR motional time scale. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV OXFORD,DEPT BIOCHEM,OXFORD,ENGLAND. FU NIAAA NIH HHS [AA-07040]; NIGMS NIH HHS [GM07592-14, GM15904] NR 34 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD APR 8 PY 1993 VL 1147 IS 1 BP 143 EP 153 DI 10.1016/0005-2736(93)90325-T PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KX463 UT WOS:A1993KX46300018 PM 8466926 ER PT J AU AISENBERG, AC AF AISENBERG, AC TI MOPP, ABVD, OR BOTH TO TREAT HODGKINS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP AISENBERG, AC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 TC 2 Z9 2 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 APR 8 PY 1993 VL 328 IS 14 BP 1045 EP 1045 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KW282 UT WOS:A1993KW28200030 PM 7680765 ER PT J AU CANELLOS, GP AF CANELLOS, GP TI MOPP, ABVD, OR BOTH TO TREAT HODGKINS-DISEASE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP CANELLOS, GP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 1993 VL 328 IS 14 BP 1045 EP 1046 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KW282 UT WOS:A1993KW28200032 ER PT J AU ELIAS, AD AYASH, L FREI, E SKARIN, AT HUNT, M WHEELER, C SCHWARTZ, G MAZANET, R TEPLER, I EDER, JP MCCAULEY, M HERMAN, T SCHNIPPER, L ANTMAN, KH AF ELIAS, AD AYASH, L FREI, E SKARIN, AT HUNT, M WHEELER, C SCHWARTZ, G MAZANET, R TEPLER, I EDER, JP MCCAULEY, M HERMAN, T SCHNIPPER, L ANTMAN, KH TI INTENSIVE COMBINED MODALITY THERAPY FOR LIMITED-STAGE SMALL-CELL LUNG-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID AUTOLOGOUS BONE-MARROW; HIGH-DOSE CYCLOPHOSPHAMIDE; BRONCHOGENIC-CARCINOMA; INTENSIFICATION THERAPY; ALKYLATING-AGENTS; RADIATION-THERAPY; CHEMOTHERAPY; TRANSPLANTATION; RADIOTHERAPY; INDUCTION AB Background: Conventional-dose chemotherapy for small-cell lung cancer has resulted in high response rates but rarely in a cure. The addition of thoracic radiotherapy (chemoradiotherapy) has improved survival for patients having limited disease, resulting in a median survival of 14-18 months. Previous trials evaluating high-dose chemotherapy and autologous bone marrow transplantation have demonstrated enhanced complete response rates without documenting overall survival benefit. Purpose: The purpose of this phase II trial was to determine the disease-free and overall survival, toxic effects, and relapse patterns in patients with limited small-cell lung cancer who were in partial or complete response to first-line conventional-dose chemotherapy and then received intensive systemic combined modality therapy. Methods: Adults with stage III small-cell lung cancer who had achieved at least a partial response to conventional-dose induction chemotherapy were treated with high-dose cyclophosphamide, cisplatin, and carmustine combined with autologous bone marrow transplantation. Cumulative doses of the three drugs were 5625, 165, and 480 mg/m2, respectively. After recovery, patients received thoracic radiotherapy (50-60 Gy in 25-30 fractions over 5-6 weeks) and cranial radiotherapy (30 Gy in 15 fractions during 3 weeks). Results: Of 19 patients in the study, six had achieved complete response, eight had a greater than 90% reduction in tumor size, and five had a 50%-90% reduction in tumor size. After high-dose therapy, 15 of the 19 were in complete response. Overall, median time to treatment failure after high-dose therapy was 12 months. Overall survival was 73% (95% confidence interval [CI] = 42%-89%) at 1 year and 53% (95% CI = 22%-77%) at 2 years. Of the 14 patients in or near complete response before high-dose therapy, 10 remain disease free with no further chemotherapy a median of 15 (4-69+) months after therapy. Actuarial 2-year disease-free survival is 57% (95% CI = 20%-82%). One patient died of Candida sepsis. Morbidity was low, and most patients returned to full-time work. With the exception of herpes zoster, there were no complications more than 3 months after high-dose therapy. Conclusions: The majority of the patients in this study are experiencing prolonged and unmaintained disease-free survival. Our findings suggest that patients in or near complete response before high-dose therapy have the most favorable prognosis. Implications: A randomized comparison between this approach and conventional-dose therapy is planned to define the utility of dose intensification with autologous bone marrow transplantation in the treatment of patients with limited-stage small-cell lung cancer who are in or near complete response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215. RP ELIAS, AD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-13849] NR 45 TC 63 Z9 64 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 1993 VL 85 IS 7 BP 559 EP 566 DI 10.1093/jnci/85.7.559 PG 8 WC Oncology SC Oncology GA KV467 UT WOS:A1993KV46700012 PM 8384264 ER PT J AU KRANER, JC LASKER, JM CORCORAN, GB RAY, SD RAUCY, JL AF KRANER, JC LASKER, JM CORCORAN, GB RAY, SD RAUCY, JL TI INDUCTION OF P4502E1 BY ACETONE IN ISOLATED RABBIT HEPATOCYTES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; ETHANOL-INDUCIBLE CYTOCHROME-P-450; LIVER-MICROSOMES; TREATED RABBITS; DIABETIC RAT; EXPRESSION; P450IIE1; STABILIZATION; MAINTENANCE; ACTIVATION AB The molecular mechanism(s) underlying induction of the hepatic microsomal cytochrome P4502E1 (2E1) by xenobiotics (e.g. ethanol and acetone) is controversial. Proposed mechanisms include increased rates of enzyme synthesis due to elevated 2E1 mRNA levels, enhanced translation of pre-existing mRNA, or stabilization of 2E1 protein. To further assess which, if any, of these events predominates during the initial stages of 2E1 protein induction, we investigated the effects of acetone treatment on 2E1 content in cultured rabbit hepatocytes, an in vitro system that allows for precise control of the cellular mileau. Hepatocytes harvested from female rabbits and plated on plastic dishes with serum-supplemented medium were 90-100% viable for at least 48 hr in culture. Analysis of immunoreactive 2E1 content and aniline hydroxylase activity in microsomes isolated from hepatocytes cultured for up to 24 hr revealed that 2E1 expression was equal to that of microsomes from unplated cells and by 48 hr of culture, 2E1 levels decreased by only 35%. Moreover, microsomes isolated from cells exposed to 17 mM acetone for 24 hr exhibited a 53 and 62% increase in aniline hydroxylase activity and 2E1 content, respectively, compared to untreated cells. To explain these increases, the rate of 2E1 protein synthesis was determined in untreated cells or in cells treated with 17 mM acetone by first exposing hepatocytes to medium supplemented with S-35-labeled methionine and cysteine ([S-35]Met/Cys) and subsequently assessing radiolabel incorporation into 2E1 protein. While no difference was found between untreated and acetone-treated cells in the incorporation of [S-35]Met/Cys into trichloroacetic acid-precipitable microsomal proteins, immunoaffinity purification of 2E1 revealed that incorporation of S-35-labeled amino acids specifically into 2E1 was elevated by acetone to 200% of control values. Treatment of hepatocytes with the transcriptional inhibitor, alpha-amanitin, markedly inhibited this acetone-mediated increase in [S-35]Met/Cys incorporation into 2E1. Analysis of hepatocyte RNA revealed that acetone increased 2E1 mRNA to 130 and 160% of control levels at 6 and 24 hr, respectively, and that these increases were prevented by pretreatment with alpha-amanitin. Our results indicate that acetone increases 2E1 protein levels in cultured rabbit hepatocytes by stimulating its rate of de novo synthesis. Since this increase in 2E1 synthesis stems, at least in part, from the acetone-mediated enhancement of hepatocyte 2E1 mRNA content and is inhibitable by alpha-amanitin, transcriptional activation of the rabbit CYP2E1 gene is apparently involved in the induction of 2E1 protein by acetone. C1 UNIV NEW MEXICO,COLL PHARM,TOXICOL PROGRAM,ALBUQUERQUE,NM 87131. BRONX VET ADM MED CTR,CTR ALCOHOL RES & TREATMENT,NEW YORK,NY 10468. MT SINAI SCH MED,NEW YORK,NY 10468. FU NIAAA NIH HHS [AA-07842, AA-08139]; NIGMS NIH HHS [GM-41564] NR 42 TC 35 Z9 35 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 APR 6 PY 1993 VL 45 IS 7 BP 1483 EP 1492 DI 10.1016/0006-2952(93)90049-3 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KX573 UT WOS:A1993KX57300015 PM 8471070 ER PT J AU PICCIONE, E CASE, RD DOMCHEK, SM HU, P CHAUDHURI, M BACKER, JM SCHLESSINGER, J SHOELSON, SE AF PICCIONE, E CASE, RD DOMCHEK, SM HU, P CHAUDHURI, M BACKER, JM SCHLESSINGER, J SHOELSON, SE TI PHOSPHATIDYLINOSITOL 3-KINASE P85 SH2 DOMAIN SPECIFICITY DEFINED BY DIRECT PHOSPHOPEPTIDE SH2 DOMAIN BINDING SO BIOCHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTORS; SIGNAL TRANSDUCTION; EGF RECEPTOR; PHOSPHOLIPASE-C; PDGF RECEPTOR; TYROSINE PHOSPHORYLATION; KINASE-ACTIVITY; PROTEIN; GAP; PHOSPHOTYROSINE AB We have developed a competition binding assay to quantify relative affinities of isolated Src-homology 2 (SH2) domains for phosphopeptide sequences. Eleven synthetic 11-12-amino acid phosphopeptides containing YMXM or YVXM recognition motifs bound to a PI 3-kinase p85 SH2 domain with highest affinities, including sequences surrounding phosphorylated tyrosines of the PDGF, CSF-1/c-Fms, and kit-encoded receptors, IRS-1, and polyoma middle T antigens; matched, unphosphorylated sequences did not bind. A scrambled YMXM phosphopeptide or sequences corresponding to the GAP or PLC-gamma SH2 domain binding motifs of the PDGF, FGF, and EGF receptors bound to the p85 SH2 domain with 30-100-fold reduced affinity, indicating that this affinity range confers specificity. Binding specificity was appropriately reversed with an SH2 domain from PLC-gamma: a phosphopeptide corresponding to the site surrounding PDGF receptor Tyr1021 binds with almost-equal-to 40-fold higher affinity than a YMXM-phosphopeptide. We conclude that essential features of specific phosphoprotein/SH2 domain interactions can be reconstituted using truncated versions of both the phosphoprotein (a phosphopeptide) and cognate SH2 domain-containing protein (the SH2 domain). SH2 domain binding specificity results from differences in affinity conferred by the linear sequence surrounding phosphotyrosine. C1 JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. NYU MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. NR 49 TC 132 Z9 132 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 6 PY 1993 VL 32 IS 13 BP 3197 EP 3202 DI 10.1021/bi00064a001 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KW112 UT WOS:A1993KW11200001 PM 8384875 ER PT J AU SPIEGELMAN, BM CHOY, L HOTAMISLIGIL, GS GRAVES, RA TONTONOZ, P AF SPIEGELMAN, BM CHOY, L HOTAMISLIGIL, GS GRAVES, RA TONTONOZ, P TI REGULATION OF ADIPOCYTE GENE-EXPRESSION IN DIFFERENTIATION AND SYNDROMES OF OBESITY DIABETES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ENHANCER BINDING-PROTEIN; PREADIPOCYTE CLONAL LINE; MESSENGER-RNA; 3T3-L1 PREADIPOCYTES; INSULIN; ADIPSIN; C/EBP; IDENTIFICATION; INVOLVEMENT; CULTURE C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP SPIEGELMAN, BM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 52 TC 211 Z9 221 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 1993 VL 268 IS 10 BP 6823 EP 6826 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KV141 UT WOS:A1993KV14100001 PM 8463205 ER PT J AU SGROI, D VARKI, A BRAESCHANDERSEN, S STAMENKOVIC, I AF SGROI, D VARKI, A BRAESCHANDERSEN, S STAMENKOVIC, I TI CD22, A B-CELL-SPECIFIC IMMUNOGLOBULIN SUPERFAMILY MEMBER, IS A SIALIC ACID-BINDING LECTIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYELIN-ASSOCIATED GLYCOPROTEIN; MOLECULE N-CAM; ADHESION MOLECULE; LEUKOCYTE ADHESION; MEMBRANE-PROTEIN; SPERM RECEPTOR; CDNA; ENDOTHELIUM; CLONING; FAMILY AB The B lymphocyte cell surface receptor CD22 is an adhesion molecule that can mediate binding to several leukocyte subsets. The first CD22 ligand to be identified was the receptor-linked phosphotyrosine phosphatase CD45, but several lines of evidence suggest that CD22 may interact with multiple counter receptors on adjacent lymphocytes. In the present work, we show that in addition to CD45, a soluble CD22-immunoglobulin fusion protein (CD22Rg) recognizes several other distinct lymphocyte sialoglycoproteins. CD22-mediated adhesion is dependent upon the presence of sialic acids on ligands. CD22Rg is observed to bind specifically to a 115-kDa sialoglycoprotein in COS cells transfected with an alpha-2,6-sialyltransferase cDNA, but not in COS cells transfected with unrelated cDNA clones, indicating that at least some CD22-mediated interactions require presentation of sialic acid in an alpha-2,6 linkage by CD22 ligands. In all cases, truncation of the side chain of sialic acids by mild periodate oxidation abolishes recognition by CD22Rg. Direct binding of CD22Rg to lymphoid cells also requires sialic acids and their side chains. Taken together, these observations indicate that CD22 is a sialic acid-binding lectin and may define a novel functional subset of immunoglobulin superfamily adhesion molecules. C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. UNIV CALIF SAN DIEGO, DIV CELLULAR & MOLEC MED, CTR CANC, GLYCOBIOL PROGRAM, LA JOLLA, CA 92093 USA. FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM32373, GM43257] NR 58 TC 194 Z9 197 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 1993 VL 268 IS 10 BP 7011 EP 7018 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KV141 UT WOS:A1993KV14100033 PM 8463234 ER PT J AU POWELL, LD SGROI, D SJOBERG, ER STAMENKOVIC, I VARKI, A AF POWELL, LD SGROI, D SJOBERG, ER STAMENKOVIC, I VARKI, A TI NATURAL LIGANDS OF THE B-CELL ADHESION MOLECULE CD22-BETA CARRY N-LINKED OLIGOSACCHARIDES WITH ALPHA-2,6-LINKED SIALIC ACIDS THAT ARE REQUIRED FOR RECOGNITION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GALACTOSIDE ALPHA-2,6-SIALYLTRANSFERASE; GLYCOPROTEIN OLIGOSACCHARIDES; ANTIGEN CD22; SIALYLTRANSFERASE; EXPRESSION; RECEPTOR; CHROMATOGRAPHY; GANGLIOSIDES; SPECTROSCOPY; SIALYLATION AB CD22beta is a glycoprotein found on the surface of B cells during restricted stages of development. It is believed to play a role in cell-cell interactions and B cell activation. The accompanying paper (Sgroi, D., Varki, A., Braesch-Andersen, S., and Stamenkovic, I. (1993) J. Biol. Chem. 268, 7011-7018) shows that CD22beta recognizes multiple glycoproteins on the surfaces of T and B cells and that sialylation of these ligands is essential for binding. To identify the structure(s) of the sialylated oligosaccharide(s) recognized by CD22beta, [H-3]glucosamine-labeled glycoproteins were purified from Daudi cells by adsorption onto a CD22beta recombinant immunoglobulin (CD22betaRg) chimera attached to protein A-Sepharose (PAS), and the N-linked oligosaccharides were released by peptide N-glycosidase F. These released oligosaccharides failed to bind to CD22betaRg-PAS under the conditions used initially to adsorb the glycoproteins, but their elution from a column of CD22betaRg-PAS was significantly retarded. Populations of oligosaccharides with different affinities could be identified by their order of elution. Specific sialidases were used to determine the content of alpha-2,3- and alpha-2,6-linked sialic acid in these different populations and their contribution to binding. Multiantennary oligosaccharides with one alpha-2,6-linked residue bound marginally, and those with two or more bound more tightly. Alpha-2,3-linked sialic acid residues were without effect. Binding did not require divalent cations and was abrogated by mild periodate oxidation of the outer side chain of sialic acid. No marked differences in size or fucose content were found between the populations of high and low affinity oligosaccharides. However, the low affinity population could be partially converted into higher affinity by treatment with beta-galactoside alpha-2,6 sialyltransferase and CMP-sialic acid. Thus, CD22beta is a mammalian lectin that can recognize specific N-linked oligosaccharide structures containing alpha-2,6-linked sialic acids. C1 UNIV CALIF SAN DIEGO, CTR CANC, GLYCOBIOL PROGRAM, LA JOLLA, CA 92093 USA. UNIV CALIF SAN DIEGO, DIV CELLULAR & MOLEC MED, LA JOLLA, CA 92093 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. FU NCI NIH HHS [R01CA55735]; NIGMS NIH HHS [R01GM32373, R01GM43257] NR 47 TC 191 Z9 193 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 1993 VL 268 IS 10 BP 7019 EP 7027 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KV141 UT WOS:A1993KV14100034 PM 8463235 ER PT J AU PARKER, CM PUJADES, C BRENNER, MB HEMLER, ME AF PARKER, CM PUJADES, C BRENNER, MB HEMLER, ME TI ALPHA(4/180), A NOVEL FORM OF THE INTEGRIN ALPHA(4)-SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION MOLECULE-1; MONOCLONAL-ANTIBODY; T-CELLS; BIOCHEMICAL-CHARACTERIZATION; FIBRONECTIN MOLECULES; CHEMICAL MODIFICATION; POLYACRYLAMIDE GELS; MELANOMA ADHESION; VLA PROTEINS; RECEPTOR AB The integrin alpha4beta1 (VLA-4) is a versatile cell-cell and cell-extracellular matrix adhesion receptor. The alpha4 subunit can be expressed on the cell surface in two forms: an intact form (alpha4/150) and a cleaved form (alpha4/80, 70). Here we have characterized a third form of alpha4, called alpha3/180. Although alpha4/180 (M(r) 180, nonreduced) is different in size than alpha4/150 (M(r) 150, nonreduced), these two forms are clearly related, as they (i) shared the same amino- terminal sequence, (ii) were both recognized in Western blots by an anti-alpha4 COOH-terminal antiserum, (iii) migrated with the same apparent size and charge when reduced, and (iv) were both immunoprecipitated using anti-VLA-4 reagents. In pulse-chase experiments, precursors to both forms appeared simultaneously and matured at the same rate, indicating that one is most likely not the biosynthetic precursor of the other. Although reduction of alpha4/180 to yield alpha4/150 suggested the release of a cysteine-linked 30-kDa fragment, seven different biochemical techniques failed to identify such a fragment. Also, alpha4/180 was converted to alpha4/150 by incubation at pH 11, by treatment with EDTA at 56-degrees-C, or by heating in the presence of elevated SDS levels. Together our findings suggest that alpha4/180 and alpha4/150 represent different conformations of the same alpha4 polypeptide, with the former having anomalous slower migration in SDS-polyacrylamide gel electrophoresis. This unusual biochemical feature of alpha4 is not shared by other beta1-associated integrin alpha subunits and suggests that VLA-4 has unique structural properties. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RP PARKER, CM (reprint author), BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,SEELEY G MUDD BLDG,RM 504,BOSTON,MA 02115, USA. RI Pujades, Cristina/F-7908-2014 OI Pujades, Cristina/0000-0001-6423-7451 FU NIAID NIH HHS [K11AI00903]; NIGMS NIH HHS [GM38903] NR 56 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 1993 VL 268 IS 10 BP 7028 EP 7035 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KV141 UT WOS:A1993KV14100035 PM 8463236 ER PT J AU PEREIRA, BJG MILFORD, EL KIRKMAN, RL LEVEY, AS TOMFORD, WW LEIBOWITZ, H RHODES, M QUAN, S WILBER, JC AF PEREIRA, BJG MILFORD, EL KIRKMAN, RL LEVEY, AS TOMFORD, WW LEIBOWITZ, H RHODES, M QUAN, S WILBER, JC TI LOW-RISK OF LIVER-DISEASE AFTER TISSUE-TRANSPLANTATION FROM DONORS WITH HCV SO LANCET LA English DT Letter ID HEPATITIS-C VIRUS; RNA C1 MASSACHUSETTS GEN HOSP,BONE BANK,BOSTON,MA 02114. NEW ENGLAND EYE BANK,BOSTON,MA. CHIRON CORP,EMERYVILLE,MA. RP PEREIRA, BJG (reprint author), NEW ENGLAND ORGAN BANK INC,NEWTON,MA 02158, USA. NR 5 TC 26 Z9 26 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 3 PY 1993 VL 341 IS 8849 BP 903 EP 904 DI 10.1016/0140-6736(93)93118-K PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KV811 UT WOS:A1993KV81100058 PM 7681921 ER PT J AU MELTZER, PC LIANG, AY BROWNELL, AL ELMALEH, DR MADRAS, BK AF MELTZER, PC LIANG, AY BROWNELL, AL ELMALEH, DR MADRAS, BK TI SUBSTITUTED 3-PHENYLTROPANE ANALOGS OF COCAINE - SYNTHESIS, INHIBITION OF BINDING AT COCAINE RECOGNITION SITES, AND POSITRON EMISSION TOMOGRAPHY IMAGING SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DOPAMINE UPTAKE SITES; PARKINSONS-DISEASE; HIGH-AFFINITY; NONHUMAN-PRIMATES; LIGAND-BINDING; BRAIN; RECEPTORS; PUTAMEN; TRANSPORTERS; STRIATUM AB It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3beta-phenyltropane-2beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [H-3]-3beta-(4-fluorophenyl)tropane-2beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3beta-(3,4-dichlorophenyl)tropane-2beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated. C1 HARVARD UNIV,SCH MED,SOUTHBOROUGH,MA 01772. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP MELTZER, PC (reprint author), ORGANIX INC,65 CUMMINGS PK,WOBURN,MA 01801, USA. FU NCRR NIH HHS [RR00168]; NIDA NIH HHS [DA06303] NR 34 TC 136 Z9 139 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 2 PY 1993 VL 36 IS 7 BP 855 EP 862 DI 10.1021/jm00059a010 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KV705 UT WOS:A1993KV70500010 PM 8464040 ER PT J AU STANDAERT, DG TESTA, CM PENNEY, JB YOUNG, AB AF STANDAERT, DG TESTA, CM PENNEY, JB YOUNG, AB TI ALTERNATIVELY SPLICED ISOFORMS OF THE NMDAR1 GLUTAMATE RECEPTOR SUBUNIT - DIFFERENTIAL EXPRESSION IN THE BASAL GANGLIA OF THE RAT SO NEUROSCIENCE LETTERS LA English DT Article DE N-METHYL-D-ASPARTATE RECEPTOR; MESSENGER RNA; LIGAND-GATED ION CHANNEL; BASAL GANGLIA; SUBTHALAMIC NUCLEUS ID H-3 MK-801 BINDING; REGIONAL DISTRIBUTION; GLYCINE; SITES; AUTORADIOGRAPHY; BRAIN AB Several isoforms of the NMDAR1 glutamate receptor subunit are produced by alternative mRNA splicing of three cassette sequences. Using in situ hybridization with exon-specific probes, we have observed differential regional expression of a cassette in the amino terminus of the NMDAR1 subunit, Insertion I, which confers distinct structural and physiologic properties. The differential distribution of expression is most prominent in the basal ganglia, where only the subthalamic nucleus expresses the insertion at high levels. RP STANDAERT, DG (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,FRUIT ST,BOSTON,MA 02114, USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS19613] NR 20 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 2 PY 1993 VL 152 IS 1-2 BP 161 EP 164 DI 10.1016/0304-3940(93)90508-I PG 4 WC Neurosciences SC Neurosciences & Neurology GA KX376 UT WOS:A1993KX37600041 PM 8515871 ER PT J AU REBECK, GW MARZLOFF, K HYMAN, BT AF REBECK, GW MARZLOFF, K HYMAN, BT TI THE PATTERN OF NADPH-DIAPHORASE STAINING, A MARKER OF NITRIC-OXIDE SYNTHASE ACTIVITY, IS ALTERED IN THE PERFORANT PATHWAY TERMINAL ZONE IN ALZHEIMERS-DISEASE SO NEUROSCIENCE LETTERS LA English DT Article DE NADPH-DIAPHORASE; HUMAN HIPPOCAMPUS; DENTATE GYRUS; ALZHEIMERS DISEASE; NITRIC OXIDE SYNTHASE ID HIPPOCAMPAL-FORMATION; POTENTIATION; MESSENGER AB NADPH-diaphorase positive neurons aw relatively spared in Alzheimer's disease (AD). We show here, however, that the pattern of NADPH-diaphorase staining in the neuropil of the hippocampus changes dramatically in the brains of patients with AD. Control individuals displayed a striking band of NADPH-diaphorase staining in the middle 1/3 of the molecular layer of the dentate gyrus; this band was absent in AD. Staining in the molecular layer was reduced 18-31% in AD (P < 0.001) with the greatest loss in the most severely affected cases. NADPH diaphorase is thought to reflect the presence of nitric oxide synthase. Because nitric oxide has been implicated in long-term potentiation, changes in its expression could reflect loss of synapses important for memory formation. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,WARREN 408,BOSTON,MA 02114. FU NIA NIH HHS [AG08487, AG05598-01] NR 19 TC 31 Z9 34 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 2 PY 1993 VL 152 IS 1-2 BP 165 EP 168 DI 10.1016/0304-3940(93)90509-J PG 4 WC Neurosciences SC Neurosciences & Neurology GA KX376 UT WOS:A1993KX37600042 PM 7685863 ER PT J AU MCGINNIS, HD DELUCA, SA AF MCGINNIS, HD DELUCA, SA TI SPLENIC ARTERY ANEURYSMS SO AMERICAN FAMILY PHYSICIAN LA English DT Article AB Splenic artery aneurysms are potentially life-threatening lesions with an uncertain propensity for serious consequences. These aneurysms are most often discovered incidentally in asymptomatic patients. Current practice standards suggest that definitive treatment should be undertaken in female patients in their childbearing years with lesions larger than 1 cm in diameter, in patients with lesions greater than 2 cm in diameter, in symptomatic patients and in patients with enlarging lesions. Patients with splenic artery aneurysms should be referred to vascular surgeons or vascular interventional radiologists for surgery or percutaneous embolization therapy. RP MCGINNIS, HD (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD APR PY 1993 VL 47 IS 5 BP 1199 EP 1202 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA KW264 UT WOS:A1993KW26400019 PM 8465715 ER PT J AU CHANG, A HUNT, M PARKINSON, DR HOCHSTER, H SMITH, TJ AF CHANG, A HUNT, M PARKINSON, DR HOCHSTER, H SMITH, TJ TI PHASE-II TRIAL OF CARBOPLATIN IN PATIENTS WITH METASTATIC MALIGNANT-MELANOMA - A REPORT FROM THE EASTERN-COOPERATIVE-ONCOLOGY GROUP SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE CARBOPLATIN; METASTATIC MELANOMA ID NSC-241240; CISPLATIN AB Thirty patients with pathologically proven, measurable metastatic melanoma without prior chemotherapy were treated with carboplatin 400 mg/m2 by intravenous infusion for 30 minutes every 4 weeks. Twenty-seven patients were evaluable for response and toxicity. Two complete responses and one partial response (3 of 27 = 11%, 90% confidence intervals: 3-26%) were documented. The median survival was 4.7 months. The most common toxicity was myelosuppression. One drug-related death was observed due to renal failure. Prior radiotherapy and liver metastasis were the poor prognostic indicators identified in our study. Carboplatin in the dose and schedule reported in our trial has only modest antitumor activity in patients with advanced malignant melanoma. C1 UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. NYU MED CTR,NEW YORK,NY 10016. FU NCI NIH HHS [CA 07190, CA 11083, CA 2318] NR 18 TC 17 Z9 17 U1 0 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 APR PY 1993 VL 16 IS 2 BP 152 EP 155 DI 10.1097/00000421-199304000-00015 PG 4 WC Oncology SC Oncology GA KT616 UT WOS:A1993KT61600015 PM 8452109 ER PT J AU STONE, RM SPRIGGS, DR ARTHUR, KA MAYER, RJ GRIFFIN, J KUFE, DW AF STONE, RM SPRIGGS, DR ARTHUR, KA MAYER, RJ GRIFFIN, J KUFE, DW TI RECOMBINANT HUMAN GAMMA-INTERFERON ADMINISTERED BY CONTINUOUS INTRAVENOUS-INFUSION IN ACUTE MYELOGENOUS LEUKEMIA AND MYELODYSPLASTIC SYNDROMES SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE BIOLOGICAL RESPONSE MODIFIER; ACUTE MYELOID LEUKEMIA; MYELODYSPLASTIC SYNDROME; INTERFERON-GAMMA ID PHASE-I; CANCER-PATIENTS; MONOCYTIC DIFFERENTIATION; IMMUNE INTERFERON; CELL-LINES; ALPHA; EXPRESSION; TOXICITY; THERAPY; TRIAL AB Nine patients (median age, 58; range: 37-74) with relapsed de novo acute myeloid leukemia (AML) (3), AML after prior myelodysplastic syndrome (MDS) (4), or MDS (2) were treated with 2-20 X 10(6) U/m2/day (1-10 mg/m2/day) of recombinant human interferon gamma (rIFNgamma; Biogen) on a 14-day continuous intravenous infusion schedule. The two patients who received the initial dose of 20 X 10(6) U/m2/day (1.0 mg/m2/day) could only tolerate 6 days of therapy because of severe hepatotoxicity. Two patients who received the revised starting dose of 10 X 10(6) U/m2/day also could not complete a full course of rIFNgamma due to renal failure in one case and pulmonary deterioration in the other. A reversible dose-related rise in SGOT was seen in six patients. All patients developed a severe flu-like syndrome characterized by myalgias and fevers. These toxicities were not associated with detectable serum levels of tumor necrosis factor (TNF). Although blasts from three of five assessable patients displayed increased expression of the Ia (HLA-DR) antigen, there were no hematological responses. Steady-state rIFNgamma plasma levels in patients who tolerated a complete infusion were <40 U/ml, a concentration below that required to induce differentiation of myeloid leukemic cell lines in vitro. We conclude that continuous infusions of rIFNgamma at doses as low as 2 X 10(6) U/m2/day are poorly tolerated in patients with AML and MDS; the maximum tolerated dose is approximately 2 X 10(6) U/m2/day. RP STONE, RM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 42802, CA 34183] NR 25 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 1993 VL 16 IS 2 BP 159 EP 163 DI 10.1097/00000421-199304000-00017 PG 5 WC Oncology SC Oncology GA KT616 UT WOS:A1993KT61600017 PM 8452111 ER PT J AU SANGUEZA, OP HYDER, DM BAKKE, AC WHITE, CR AF SANGUEZA, OP HYDER, DM BAKKE, AC WHITE, CR TI DNA DETERMINATION IN DYSPLASTIC NEVI - A COMPARATIVE-STUDY BETWEEN FLOW-CYTOMETRY AND IMAGE-ANALYSIS SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE DYSPLASTIC NEVUS; DNA DETERMINATION; FLOW CYTOMETRY; IMAGE ANALYSIS ID MALIGNANT-MELANOMA; LESIONS AB Dysplastic nevi (DN), described in 1978, have been associated with increased risk of melanoma, but the role of DN as precursors of melanoma is still controversial. Recent studies have shown that DN are very common in the general population, bringing into question this purported association. Numerous investigations have attempted to correlate the presence of DN in individuals with specific phenotypic and genotypic features, including the presence of abnormal DNA content. Because the occurrence of such abnormal DNA stemlines in neoplasms may be associated with malignant behavior, we studied 38 biopsies from 19 patients that histologically fulfilled criteria for DN in order to ascertain characteristics of DNA content. Nuclear suspensions made from paraffin-embedded tissue were evaluated by both flow cytometry and image analysis techniques. All cases demonstrated diploid populations by both DNA measurement methods. Our results contradict previous reports of aneuploid populations in these melanocytic lesions. C1 OREGON HLTH SCI UNIV,DEPT DERMATOL,3181 S W SAM JACKSON PK RD,PORTLAND,OR 97201. SW WASHINGTON MED CTR,DEPT PATHOL,VANCOUVER,WA. PORTLAND VET AFFAIRS MED CTR,DERMATOL SERV,PORTLAND,OR. OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201. NR 16 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 1993 VL 15 IS 2 BP 99 EP 105 DI 10.1097/00000372-199304000-00001 PG 7 WC Dermatology SC Dermatology GA KV592 UT WOS:A1993KV59200001 PM 8494124 ER PT J AU FERGUSON, DR HARIG, JM KOZAREK, RA KELSEY, PB PICHA, GJ AF FERGUSON, DR HARIG, JM KOZAREK, RA KELSEY, PB PICHA, GJ TI PLACEMENT OF A FEEDING BUTTON (ONE-STEP BUTTON) AS THE INITIAL PROCEDURE SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; COMPLICATIONS; SUCCESS AB The procedure of choice for enteral feeding access is now percutaneous endoscopic gastrostomy (PEG). Standard PEG tubes have the disadvantages of clogging, stomal enlargement, and external bulkiness. Button replacement tubes can convert the more cumbersome PEG tubes to low external profile devices. A procedure and an early experience is described for placement of a button as a single-step procedure. This procedure is an over-the-wire, ''push'' procedure. Sixty-nine buttons were placed, 47 (61%) for neurologic reasons and 22 (32%) for cancer and other reasons. In 49 of the 69 (71%), there was no difficulty at all with insertion, and in only two (3%) could the button not be placed. Complications were assessed at 48 h and at 3 wk. No complications were found in 61 (90%). In only two patients (3%) were there serious complications (gastro-colon-cutaneous fistula and ''peritonitis''). The One-Step Button' represents a rapid, safe procedure for the placement of a low-profile PEG with its attendant advantages. C1 CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. UNIV ILLINOIS,CHICAGO,IL 60680. VIRGINIA MASON,SEATTLE,WA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. APPL MED TECHNOL INC,INDEPENDENCE,OH. NR 10 TC 29 Z9 29 U1 1 U2 1 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 APR PY 1993 VL 88 IS 4 BP 501 EP 504 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KW463 UT WOS:A1993KW46300006 PM 8470628 ER PT J AU CHAMBERLAIN, JS BOEHNKE, M FRANK, TS KIOUSIS, S XU, JX GUO, SW HAUSER, ER NORUM, RA HELMBOLD, EA MARKEL, DS KESHAVARZI, SM JACKSON, CE CALZONE, K GARBER, J COLLINS, FS WEBER, BL AF CHAMBERLAIN, JS BOEHNKE, M FRANK, TS KIOUSIS, S XU, JX GUO, SW HAUSER, ER NORUM, RA HELMBOLD, EA MARKEL, DS KESHAVARZI, SM JACKSON, CE CALZONE, K GARBER, J COLLINS, FS WEBER, BL TI BRCA1 MAPS PROXIMAL TO D17S579 ON CHROMOSOME-17Q21 BY GENETIC-ANALYSIS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BREAST-CANCER; RISK AB Previous studies have demonstrated linkage between early-onset breast cancer and ovarian cancer and genetic markers on chromosome 17q21. These markers define the location of a gene (BRCA1) which appears to be inherited as an autosomal dominant susceptibility allele. We analyzed five families with multiple affected individuals for evidence of linkage to the BRCA1 region. Two of the five families appear to be linked to BRCA1. One apparently linked family contains critical recombinants, suggesting that the gene is proximal to the marker D17S579 (Mfd188). These findings are consistent with the maximum-likelihood position estimated by the Breast Cancer Linkage Consortium and with recombination events detected in other linked families. Linkage analysis was greatly aided by PCR-based analysis of paraffin-embedded normal breast tissue from deceased family members, demonstrating the feasibility and importance of this approach. One of the two families with evidence of linkage between breast cancer and genetic markers flanking BRCA1 represents the first such family of African-American descent to be reported in detail. C1 UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48104. UNIV MICHIGAN,SCH MED,DEPT INTERNAL MED,ANN ARBOR,MI 48104. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48104. UNIV NANCY 1,SCH PUBL HLTH,DEPT BIOSTAT,F-54506 VANDOEUVRE NANCY,FRANCE. UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109. HOWARD HUGHES MED INST,ANN ARBOR,MI. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HENRY FORD HOSP,DETROIT,MI 48202. FU NCI NIH HHS [CA32280, CA57601]; NHGRI NIH HHS [HG00209] NR 16 TC 47 Z9 47 U1 0 U2 2 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 APR PY 1993 VL 52 IS 4 BP 792 EP 798 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA KY059 UT WOS:A1993KY05900020 PM 8460646 ER PT J AU WYANDT, HE MILUNSKY, J LERNER, T GUSELLA, JF HOU, A MACDONALD, M ADEKUNLE, S MILUNSKY, A AF WYANDT, HE MILUNSKY, J LERNER, T GUSELLA, JF HOU, A MACDONALD, M ADEKUNLE, S MILUNSKY, A TI CHARACTERIZATION OF A DUPLICATION IN THE TERMINAL BAND OF 4P BY MOLECULAR CYTOGENETICS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE DUP(4P) SYNDROME; CHROMOSOME ANALYSIS; PARTIAL DUPLICATION ID WOLF-HIRSCHHORN SYNDROME; HIGH-RESOLUTION; TRISOMY 4P; COSMID CLONES; CHROMOSOME-4; REGION AB An infant with multiple anomalies including small head, large apparently low-set ears, beaked nose, micrognathia, choanal stenosis, proptosis, atrial-septal defect, and left inguinal hernia was found, on chromosome analysis, to have a longer than normal terminal band 4p16 by G and R-banding. In situ hybridization of biotin-labeled DNA probes C39, BJ14, BJ54, BJ19, BJ7, and BJ11 showed them to be duplicated. Probes 114, A157.1, and the telomeric sequence, (TTAGGG)n, which hybridized to the more distal part of 4p16.3, were not duplicated. These results confirm the impression by G and R-banding of a duplication within band 4p16, a region extending from approximately 2.1 Mb from the telomere, proximally, to the junction of 4p16.1 and 4p15.3. This is the smallest confirmed duplication of distal 4p reported to date, with many of the classical findings of dup(4p) syndrome. C1 BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. BOSTON UNIV,DEPT BIOL,BOSTON,MA 02215. RP WYANDT, HE (reprint author), BOSTON UNIV,SCH MED,CTR HUMAN GENET,80 E CONCOR ST,BOSTON,MA 02118, USA. NR 17 TC 16 Z9 16 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 APR 1 PY 1993 VL 46 IS 1 BP 72 EP & DI 10.1002/ajmg.1320460112 PG 0 WC Genetics & Heredity SC Genetics & Heredity GA KV048 UT WOS:A1993KV04800011 PM 7684190 ER PT J AU HIBNER, CS MOSELEY, MJ SHANK, TL AF HIBNER, CS MOSELEY, MJ SHANK, TL TI WHAT IS TRANSESOPHAGEAL ECHOCARDIOGRAPHY SO AMERICAN JOURNAL OF NURSING LA English DT Article RP HIBNER, CS (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 1993 VL 93 IS 4 BP 74 EP & PG 0 WC Nursing SC Nursing GA KV594 UT WOS:A1993KV59400037 ER PT J AU ANTONIADES, HN GALANOPOULOS, T NEVILLEGOLDEN, J KIRITSY, CP LYNCH, SE AF ANTONIADES, HN GALANOPOULOS, T NEVILLEGOLDEN, J KIRITSY, CP LYNCH, SE TI EXPRESSION OF GROWTH-FACTOR AND RECEPTOR MESSENGER-RNAS IN SKIN EPITHELIAL-CELLS FOLLOWING ACUTE CUTANEOUS INJURY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FACTOR-I IMMUNOREACTIVITY; HUMAN-TUMOR CELLS; FACTOR-ALPHA; NUCLEOTIDE-SEQUENCE; ENDOTHELIAL-CELLS; BOVINE BRAIN; FACTOR-BETA; PROTEIN; INVIVO; RATS AB We report that acute injury induces the expression of selective growth factor and growth factor receptors in the epithelial cells of the wounded tissue. In situ hybridization analysis of skin biopsy specimens obtained after cutaneous injury in swine demonstrated the induction of the expression of transforming growth factor-alpha, its receptor, epidermal growth factor-R, acidic fibroblast growth factor, and basic fibroblast growth factor messenger RNAs in the skin epithelial cells of the wounded tissue. There was no significant expression in the epithelial cells of control, uninjured tissues. The expression levels were maximal during the period of active tissue repair (1 to 5 days after injury) and were totally suppressed upon the healing of the wounded tissues. In contrast. insulin like growth factor-I, (IGF-I), IGF-I receptor, and IGF-II receptor messenger RNAs were expressed in the epithelial cells of both the control, uninjured tissues and in tissue specimens obtained after injury. There was no significant expression of IGF-II messenger RNA in the epithelial cells before or after injury. It seems that injury induces the coordinated expression of selective growth factor and growth factor receptor genes whose products contribute to the regulation of the complex processes involved in tissue repair and remodelling. C1 HARVARD UNIV,SCH ENGN MATH,DEPT MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH ENGN MATH,DEPT PERIODONTOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. RP ANTONIADES, HN (reprint author), HARVARD UNIV,SCH PUBL HLTH,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA30101] NR 46 TC 41 Z9 44 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1993 VL 142 IS 4 BP 1099 EP 1110 PG 12 WC Pathology SC Pathology GA KY014 UT WOS:A1993KY01400017 PM 8386442 ER PT J AU HOERR, RA MATTHEWS, DE BIER, DM YOUNG, VR AF HOERR, RA MATTHEWS, DE BIER, DM YOUNG, VR TI EFFECTS OF PROTEIN RESTRICTION AND ACUTE REFEEDING ON LEUCINE AND LYSINE KINETICS IN YOUNG MEN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE METABOLIC ADAPTATION; HUMANS; TRACER STUDIES ID ALPHA-KETOISOCAPROATE; OBESE SUBJECTS; METABOLISM; INFUSION; L-<1-C-13>LEUCINE; INGESTION; TURNOVER; PLASMA; LIVER; GUT AB To explore the effects of altered protein intake on the uptake and utilization of dietary amino acids in human subjects, six healthy male Massachusetts Institute of Technology students were studied during three dietary periods each of 9 days, with tracer infusion studies conducted on days 8 and 9. During one period the diet provided a generous protein intake (1.5 g . kg- 1 . day- 1) and during the other two a low-protein intake (0.1 g-kg-1.day-1). Tracer infusions (fed state) were given while subjects received either a liquid formula, supplying the prior protein intake or (on day 9) a generous intake. Combinations of [H-2(3)]Leu and [C-13]Leu and of [N-15]Lys and [H-2(3)]Lys were given via continuous intravenous or intragastric infusion for 4 h to estimate leucine kinetics and the first-pass splanchnic uptake of tracer. Dietary-induced changes in leucine flux and oxidation were similar irrespective of the tracer and/or route of administration and sampled pool (leucine or KIC) used for calculation. Estimates of absolute changes in the rates of leucine disappearance via nonoxidative metabolism (protein synthesis) and of appearance via protein breakdown depended on the route of [C-13]Leu administration. However, it appears that both altered rates of protein synthesis and breakdown contribute to the adaptations required in the body nitrogen economy when protein intakes are restricted and subsequently resupplied. From the intragastric [C-13]Leu protocol, the first-pass splanchnic uptake of tracer was the same (approximately 30%) for generous, low-protein, and refed conditions. Hence, it is tentatively concluded that when protein intake is low the splanchnic region does not remove indispensable amino acids to a disproportionate extent, permitting a balanced mix of amino acids to reach the peripheral circulation. C1 MIT,SCH SCI,CTR CLIN,HUMAN NUTR LAB,E18-613,50 AMES ST,CAMBRIDGE,MA 02142. SHRINERS BURNS INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,CTR BURN TRAUMA,BOSTON,MA 02114. CORNELL UNIV,MED CTR,COLL MED,DEPT MED,NEW YORK,NY 10021. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. FU NCRR NIH HHS [RR-88]; NIDDK NIH HHS [DK-15856, DK-38429] NR 28 TC 74 Z9 75 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1993 VL 264 IS 4 BP E567 EP E575 PN 1 PG 9 WC Physiology SC Physiology GA KZ603 UT WOS:A1993KZ60300052 PM 8476035 ER PT J AU SALORANTA, C KOIVISTO, V WIDEN, E FALHOLT, K DEFRONZO, RA HARKONEN, M GROOP, L AF SALORANTA, C KOIVISTO, V WIDEN, E FALHOLT, K DEFRONZO, RA HARKONEN, M GROOP, L TI CONTRIBUTION OF MUSCLE AND LIVER TO GLUCOSE-FATTY ACID CYCLE IN HUMANS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE FREE FATTY ACIDS; HEPATIC GLUCOSE PRODUCTION; GLYCOGEN SYNTHASE; PYRUVATE DEHYDROGENASE; CARNITINE PALMITOYLTRANSFERASE ID DEPENDENT DIABETES-MELLITUS; PERFUSED SKELETAL-MUSCLE; PYRUVATE-DEHYDROGENASE; INSULIN RESISTANCE; GLYCOGEN-SYNTHASE; METABOLISM; INFUSION; CARBOHYDRATE; AVAILABILITY; STARVATION AB To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin. Suppression of HGP by insulin was impaired by elevated plasma FFA levels. Furthermore, the increase in plasma FFA was associated with a 20% reduction in total glucose metabolism (P < 0.01), which was completely accounted for by a reduction in the rate of glucose oxidation. Although the fractional activity of GS was increased by insulin, elevation of plasma FFA had no influence on this key enzyme of glycogen synthesis. In addition, the activities of PDH and CPT were uninfluenced by the elevation of FFA, suggesting that oxidative processes in skeletal muscle were not a major target for the operative glucose-fatty acid cycle under the current conditions. Taken together, the data indicate that the interaction between FFA and glucose metabolism also involves impaired suppression of HGP by insulin. C1 HELSINKI UNIV HOSP,DEPT MED 4,UNIONINKATU 38,SF-00170 HELSINKI,FINLAND. HELSINKI UNIV HOSP,DEPT MED 2,SF-00170 HELSINKI,FINLAND. NOVO RES INST,COPENHAGEN,DENMARK. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM-24092] NR 37 TC 92 Z9 92 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1993 VL 264 IS 4 BP E599 EP E605 PN 1 PG 7 WC Physiology SC Physiology GA KZ603 UT WOS:A1993KZ60300056 PM 8476039 ER PT J AU MATALON, S BAUER, ML BENOS, DJ KLEYMAN, TR LIN, CM CRAGOE, EJ OBRODOVICH, H AF MATALON, S BAUER, ML BENOS, DJ KLEYMAN, TR LIN, CM CRAGOE, EJ OBRODOVICH, H TI FETAL LUNG EPITELIAL CELLS CONTAIN 2 POPULATIONS OF AMILORIDE-SENSITIVE NA+ CHANNELS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE 5-(N-ETHYL-N-ISOPROPYL)-2'-4'-AMILORIDE; BENZAMIL; BINDING SITES; IMMUNOFLUORESCENCE; POLYCLONAL ANTIBODIES; ANTIIDIOTYPIC ANTIBODIES; PLASMA MEMBRANE VESICLES, ALVEOLAR TYPE-II PNEUMOCYTES ID EPITHELIAL SODIUM-CHANNEL; WATER CLEARANCE; II PNEUMOCYTES; BINDING; PROTEIN; ANTIBODIES; AFFINITY AB Active Na+ transport by the alveolar epithelium plays a major role in reabsorption of the fetal lung fluid after birth. We characterized the biochemical and physiological characteristics of Na+ conductive pathways in distal fetal lung epithelial (FLE) cells isolated from 20-day-old rat fetuses. We demonstrated that a polyclonal antibody to Na+ channel protein (NaAb) binds to the plasma membranes of FLE cells. In Western blot studies, this NaAb and an anti-idiotypic monoclonal antibody to the amiloride-binding subunit of the Na+ channel protein recognized 150- and 90-kDa polypeptides in plasma membrane vesicles of FLE. Na-22+ flux measurements across plasma membrane vesicles of FLE revealed the existence of electrogenic Na+ transport, which was twice as high as the corresponding adult value. One hundred micromolars of amiloride, benzamil, and 5-(N-ethyl-N-isopropyl)-2'-4'-amiloride inhibited 30, 40, and 70% of the electrogenic Na+ transport across plasma membrane vesicles of FLE cells, respectively. The half-maximum inhibition of electrogenic Na+ transport by these substances occurred between 0.3 and 1 muM. [H-3]benzamil equilibrium binding studies in membrane vesicles of FLE cells revealed the existence of two binding sites that had dissociation constant values of 19 and 1,525 nM, respectively. These data indicate the presence of both high- and low-amiloride affinity Na+ conductive pathways (channels) in FLE cells. C1 UNIV ALABAMA,DEPT ANAESTHESIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PEDIAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV TORONTO,HOSP SICK CHILDREN,DEPT PEDIAT RESP RES DIV,TORONTO M5G 1X8,ONTARIO,CANADA. FU NHLBI NIH HHS [HL-31197]; NIDDK NIH HHS [DK-37206] NR 31 TC 50 Z9 50 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1993 VL 264 IS 4 BP L357 EP L364 PN 1 PG 8 WC Physiology SC Physiology GA KZ603 UT WOS:A1993KZ60300101 PM 8386466 ER PT J AU CHEW, FS HUANGHELLINGER, F AF CHEW, FS HUANGHELLINGER, F TI BROWN TUMOR SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 HARVARD UNIV,BOSTON,MA 02114. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 22 Z9 24 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1993 VL 160 IS 4 BP 752 EP 752 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KU602 UT WOS:A1993KU60200010 PM 8456657 ER PT J AU HULKA, CA HALL, DA AF HULKA, CA HALL, DA TI ENDOMETRIAL ABNORMALITIES ASSOCIATED WITH TAMOXIFEN THERAPY FOR BREAST-CANCER - SONOGRAPHIC AND PATHOLOGICAL CORRELATION SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID RECEIVING TAMOXIFEN; ULTRASONOGRAPHY AB OBJECTIVE. Tamoxifen is widely used to treat breast carcinoma in postmenopausal women. Previous studies have suggested an increased prevalence of endometrial carcinoma and polyps after treatment with tamoxifen. We correlated findings on pelvic sonograms with pathologic findings in a group of patients treated with tamoxifen. MATERIALS AND METHODS. We reviewed the pelvic sonograms and medical histories of 14 postmenopausal women with breast carcinoma who were being treated with tamoxifen. Pathologic correlation was available in the 11 cases in which adequate tissue was obtained. Coexisting pathologic changes were found in seven patients. Pathologic examination showed a total of 18 endometrial abnormalities, including nine cases of uterine polyps, four cases of hyperplasia, two cases of endometritis, one proliferative endometrium, one inactive endometrium, and one case of carcinoma. RESULTS. Sagittal sonograms of all 11 patients with pathologic correlation showed abnormal endometrial thickening measuring more than 7 mm. The sonographic appearance of the endometrium in these patients included hyperechoic, homogeneous tissue; hyperechoic tissue with multiple, small cystic spaces; heterogeneous tissue with small cystic spaces; and solid tissue that was heterogeneous. Small cystic spaces were seen in all cases of polyps. Six of the nine cases of polyps were associated with other endometrial abnormalities also. The single case of endometrial carcinoma appeared solid and heterogeneous on sonography; however, further pathologic examination of the surgical specimen showed a coexisting polyp. CONCLUSION. Tamoxifen therapy is associated with several findings on sonograms of the uterus. Because several pathologic findings frequently coexist, sonography is of limited use in the diagnosis of specific abnormalities. RP HULKA, CA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 57 Z9 57 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1993 VL 160 IS 4 BP 809 EP 812 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KU602 UT WOS:A1993KU60200023 PM 8456669 ER PT J AU BOLAND, GW LEE, MJ DAWSON, SL MUELLER, PR AF BOLAND, GW LEE, MJ DAWSON, SL MUELLER, PR TI INTERVENTIONAL RADIOLOGY CASE CONFERENCE - PERCUTANEOUS CHOLECYSTOSTOMY FOR ACUTE ACALCULOUS CHOLECYSTITIS IN A CRITICALLY ILL PATIENT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DIAGNOSTIC-ACCURACY; GALLBLADDER; CHOLESCINTIGRAPHY; SCINTIGRAPHY; ASPIRATION C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02114. NR 20 TC 8 Z9 8 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1993 VL 160 IS 4 BP 871 EP 874 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KU602 UT WOS:A1993KU60200040 PM 8456684 ER PT J AU ANDRADE, F ANZUETO, A GREENE, KE LEVINE, SM SILMAN, JB ROODMAN, GD MAXWELL, LC JENKINSON, SG BRYAN, CL AF ANDRADE, F ANZUETO, A GREENE, KE LEVINE, SM SILMAN, JB ROODMAN, GD MAXWELL, LC JENKINSON, SG BRYAN, CL TI DIAPHRAGM MUSCLE IMPAIRMENT IN MICE CHRONICALLY EXPOSED TO TUMOR-NECROSIS-FACTOR-ALPHA SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RI Andrade, Francisco/F-1258-2011 OI Andrade, Francisco/0000-0002-2460-5798 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A235 EP A235 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14900876 ER PT J AU ANZUETO, A BRYAN, CL LEVINE, SM PETERS, JI CRONIN, T CALHOON, JH JENKINSON, SG AF ANZUETO, A BRYAN, CL LEVINE, SM PETERS, JI CRONIN, T CALHOON, JH JENKINSON, SG TI PANEL REACTIVE ANTIBODIES AS A PREDICTOR OF GRAFT COMPLICATIONS IN SINGLE-LUNG TRANSPLANT RECIPIENTS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A339 EP A339 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14901270 ER PT J AU ARAPE, IS BEAGLE, J BURTON, M KAZEMI, H AF ARAPE, IS BEAGLE, J BURTON, M KAZEMI, H TI EFFECTS OF SUBSTANCE-P AND GLUTAMATE ANTAGONIST DURING HYPOXIA IN ANESTHETIZED RATS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A282 EP A282 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14901045 ER PT J AU BIGATELLO, LM HURFORD, WE KACMAREK, RM ROBERTS, JD ZAPOL, WM AF BIGATELLO, LM HURFORD, WE KACMAREK, RM ROBERTS, JD ZAPOL, WM TI THE HEMODYNAMIC AND RESPIRATORY RESPONSE OF ARDS PATIENTS TO PROLONGED NITRIC-OXIDE INHALATION SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RESP CARE,BOSTON,MA 02114. NR 2 TC 4 Z9 4 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A720 EP A720 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14902761 ER PT J AU BIGATELLO, LM HURFORD, WE KACMAREK, RM ROBERTS, JD ZAPOL, WM AF BIGATELLO, LM HURFORD, WE KACMAREK, RM ROBERTS, JD ZAPOL, WM TI THE HEMODYNAMIC AND RESPIRATORY RESPONSE OF ARDS PATIENTS TO PROLONGED NITRIC-OXIDE INHALATION SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & RESP CARE,BOSTON,MA 02114. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A718 EP A718 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14902751 ER PT J AU BRASSARD, JM ANZUETO, A LEVINE, SM ANDRADE, F MAXWELL, LC LAWRENCE, RA JENKINSON, SG AF BRASSARD, JM ANZUETO, A LEVINE, SM ANDRADE, F MAXWELL, LC LAWRENCE, RA JENKINSON, SG TI EFFECTS OF HYPEROXIA ON RAT DIAPHRAGM FUNCTION SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. BROOKE ARMY MED CTR,FT SAM HOUSTON,TX 78234. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A236 EP A236 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14900878 ER PT J AU BRYAN, CL LEVINE, SM ANZUETO, A PETERS, JI COALSON, JJ TRINKLE, JK JENKINSON, SG AF BRYAN, CL LEVINE, SM ANZUETO, A PETERS, JI COALSON, JJ TRINKLE, JK JENKINSON, SG TI ISCHEMIC PRESERVATION TIME AS A PREDICTOR OF LUNG GRAFT COMPLICATIONS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A339 EP A339 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14901271 ER PT J AU BUKOWSKI, DM LAWRENCE, RA DENEKE, SM JENKINSON, SG AF BUKOWSKI, DM LAWRENCE, RA DENEKE, SM JENKINSON, SG TI EFFECT OF GAMMA-GLUTAMYL-TRANSPEPTIDASE INHIBITION ON GLUTATHIONE UPTAKE AND METABOLISM IN RAT TYPE-II EPITHELIAL-CELLS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A149 EP A149 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14900540 ER PT J AU BUKOWSKI, DM DENEKE, SM LAWRENCE, RA JENKINSON, SG AF BUKOWSKI, DM DENEKE, SM LAWRENCE, RA JENKINSON, SG TI CHARACTERISTICS OF SODIUM-DEPENDENT CYSTINE UPTAKE IN RAT ALVEOLAR TYPE-II EPITHELIAL-CELLS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A1005 EP A1005 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14903862 ER PT J AU BURTON, MD NOURI, K SAMUELSTOYLOY, N KAZEMI, H AF BURTON, MD NOURI, K SAMUELSTOYLOY, N KAZEMI, H TI VESAMICOL, AN INHIBITOR OF ACETYLCHOLINE VESICULAR TRANSPORT, DEPRESSES RESPIRATORY NEURONAL OUTPUT IN THE NEONATAL RAT SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A162 EP A162 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14900591 ER PT J AU CHIANG, YY ZACHMAN, RD THET, LA AF CHIANG, YY ZACHMAN, RD THET, LA TI CHANGES IN RETINOIC ACID RECEPTORS (RAR) IN TYPE-I AND TYPE-2 ALVEOLAR EPITHELIAL-CELLS DURING REPAIR OF HYPEROXIC LUNG INJURY SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Meeting Abstract C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. UNIV WISCONSIN,SCH MED,MADISON,WI 53706. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1993 VL 147 IS 4 SU S BP A150 EP A150 PG 1 WC Respiratory System SC Respiratory System GA LB149 UT WOS:A1993LB14900546 ER EF